Oligopeptides And Their Use In Cosmetics

Abstract

The present invention relates to the cosmetic use of oligopeptides, cosmetic preparations which comprise such oligopeptides as well as certain oligopeptide derivatives themselves.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation of U.S. application Ser. No. 11/665,810 filed Apr. 18, 2007, which claims priority to International Application No. PCT/EP2005/010893 filed Oct. 10, 2005, and published in English on Apr. 27, 2006, as WO 2006/042661 A3, which claims priority from European Application No. 04292475.3 filed Oct. 18, 2004, each of which is incorporated herein by reference in its entirety.

REFERENCE TO SEQUENCE LISTING

[0002] The Sequence Listing submitted on Oct. 29, 2008, in parent application U.S. application Ser. No. 11/665,810, (85 pages containing 375 oligopeptide sequences) is incorporated herein by reference.

FIELD OF THE INVENTION

[0003] The present invention relates to the cosmetic use of oligopeptides, cosmetic preparations which comprise such oligopeptides as well as certain oligopeptide derivatives themselves.

BACKGROUND OF THE INVENTION

[0004] Cosmetic preparations are available nowadays to the consumer in a large number of combinations. In this regard, it is not only expected that these cosmetics exhibit a particular care effect or overcome a certain deficiency, but there is an evermore frequent requirement for products which have several properties at the same time and thus exhibit an improved performance spectrum. Of particular interest are substances which both favourably influence the technical properties of the cosmetic product, such as storage stability, photostability and ability to be formulated, and also at the same time constitute active ingredients which confer care, irritation suppressing and/or photoprotective properties for skin and/or hair for example. Additionally, good skin compatibility and particularly the use of natural products are requested by the customer. There is a further need for effective protection of the skin against environmental ageing effects.

[0005] The human skin expresses a number of antimicrobially effective peptides, such as, for example, cathelicidin and 13-defensin, during inflammation processes of the skin such as wound healing, contact dermatitis and psoriasis. It is known that these peptides in the skin construct a barrier for protecting the endogenous skin cells against microbial pathogenesis (Gallo R L & Huttner K M. J. Invest. Dermatol. 1998, 111, 739-43). The peptide cathelicidin PR39 was identified for the first time in wound fluid of pigs through the induction of syndecan (Gallo R-L., Proc Natl. Acad. Sci. USA, 1994, 91, 11035-11039). Supplementary to this prior art, it is reported that in the case of fragment 1-15 of PR39 the antimicrobial properties of the peptide remain completely intact. It was shown that the interaction of the fragment with the lipid double layer is identical to the complete peptide and that the fragment binds with SH3-containing proteins (Chan Y. R, Gallo R L., J. Biol. Chem. 1998, 273, 2897-28985). The same team was then able to show that the N-terminal region is important for peptide activity and specifically for the syndecan induction and the antimicrobial activity and that the C-terminal region is of greater importance for the antibacterial properties (Chan Y. R., Gallo R. L., J. Invest. Dermat. 2001, 116, 230-235).

[0006] WO 01/47540 describes a method for selectively inhibiting degradation of IkBa using oligopeptides of PR-39. The following oligopeptides of PR-39 are disclosed: the oligopeptide consisting of the 15 aminoterminal amino acids, the oligopeptide consisting of the 11 aminoterminal amino acids, and the oligopeptide consisting of the 8 aminoterminal amino acids. WO 01/30368 describes a method for stimulating angiogenesis with oligopeptides of PR-39 using the oligopeptides as described in WO 01/47540. Gallo R L et al. PNAS 91, 11035-39 (1994) describes the antibacterial activity of the peptide PR39 and its ability to induce syndecan. Gaczynska M. et al Biochemistry, 2003, 42, 8663-8670 describes that the shortest functional derivative from PR 39 to still show allosteric inhibitory effects consist of eleven amino-terminal residues. Zaiou M & Gallo R L J Mol Med 80, 549-61 (2002) review the different know activities of PR-39, e.g. induction of syndecan expression, chemoattractant activity etc. Gudmundsson G. et al PCNAS 92, 7085-89 (1995) describes the gene for PR-39.

[0007] U.S. Pat. No. 6,713,605 (WO 96/32129) describes PR-39 and truncated analogs consisting of 26, 23, 19, 16, 15, 14, 7 and 6 amino acids of PR-39 and their use as medicaments for inhibiting leucocyte superoxide anion production. WO 00/43417 describes peptides H-Arg-Pro-(AA)n-OH or H-Pro-Arg-(AA)n-OH, wherein n=0 to 3. WO 00/43317 describes the use of these penta-petides for the regulation of immunological dysfunction and in cutaneous inflammation. Specifically disclosed are the following peptides: Arg Pro Arg (SEQ ID NO. 366), Arg Lys Pro Arg (SEQ ID NO. 367), Thr Lys Pro Arg (SEQ ID NO. 368), N-Palmitoyl-Thr Lys Pro Arg (SEQ ID NO. 369), Gly Gln Pro Arg (SEQ ID NO. 370), N-Palmitoyl-Gly Gln Pro Arg (SEQ ID NO 371), Phe-Tyr-Arg-Pro-Arg (SEQ ID NO. 372), Ala-Arg-Asp-Pro-Arg (SEQ ID NO. 373).

[0008] Cosmetic preparations comprising peptides with a large number of amino acids, such as, for example, the entire cathelicidin PR-39, are not practicable and sometimes also not realizable because the production of this type of peptides on an industrial scale is very difficult and very expensive.

[0009] The object of the present patent application was to provide cosmetic preparations which lead to protection of the skin, scalp, mucosa and/or hair against environmental effects, oxidative stress, toxic substances or UV radiation and to a stimulation of the renewal rate of skin and/or hair and can thus be used effectively in cosmetics for topical application. It was also an object of the present invention to provide oligopeptides as well as cosmetic preparations having the above mentioned specified profile of requirements and at the same time the shortest possible number of amino acids.

[0010] Surprisingly, it has now been found that oligopeptides comprising amino acids of the peptide cathelicidin PR-39 satisfy the requirements made. None of the document of the prior art describes oligopeptides of the invention nor the cosmetic use of the claimed oligopeptides. None of the documents describes oligopeptides which can be used for stimulating the renewal rate of skin and/or hair or cosmetic compositions comprising oligopeptides with such a profile.

DESCRIPTION OF THE INVENTION

Cosmetic Use of Oligopeptide of Formula (I)

[0011] The current invention relates to the cosmetic use of oligopeptides with the structure of formula (I)

R1-[AA]_n-R2 (I)

wherein [AA] comprises at least 4 consecutive amino acids, which are identical compared to 4 consecutive amino acids of SEQ ID NO.1 and/or wherein [AA] comprises at least 6 amino acids, of which 4, preferably 5 are identical compared to 6 consecutive amino acids of SEQ ID NO. 1 wherein n=4 to 15, preferably n=4 to 10 wherein R1 is linked to the NH₂ group of the amino-terminal part of [AA] and is chosen from the group which is formed from [0012] a) --H, [0013] b) a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24 carbon atoms, which may be functionalized by a --OH, --SH, --COOH or --CONH₂ group, [0014] c) a sterol or a spingolipid group which is joined to the amino terminal part of [AA] via a bifunctional linker wherein R2 is linked to the 0=0 group of the carboxy-terminal part of [AA] and is chosen from the group which is formed from [0015] a) --OH, [0016] b) --NH₂ [0017] c) a linear saturated or unsaturated or branched saturated or unsaturated alkoxy group having 1 to 24 carbon atoms [0018] d) or a sterol or a sphingolipid group.

[0019] The term "oligopeptide" encompasses single species of formula (I) as well as mixtures of at least 2, at least 3 or more oligopeptides of formula (I).

Oligopeptide (I)

[0020] A further embodiment of the invention is directed to oligopeptides with the structure of formula (I)

R1-[AA]_n-R2 (I)

wherein [AA] comprises at least 4 consecutive amino acids, which are identical compared to 4 consecutive amino acids of SEQ ID NO.1 and/or wherein [AA] comprises at least 6 amino acids, of which 4, preferably 5, more preferably 6 are identical compared to 6 consecutive amino acids of SEQ ID NO.1 wherein n=4 to 15 wherein R1 is linked to the NH₂ group of the amino-terminal part of [AA] and is chosen from the group consisting of [0021] a) --H, [0022] b) is a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24 carbon atoms, which may be functionalised by a --OH, --SH, --COOH or --CONH₂ group, [0023] c) a sterol or a spingolipid group which is joined to the amino terminal part of [AA] via a bifunctional linker wherein R2 is linked to the C═O group of the carboxy-terminal part of [AA] and is chosen from the group which is formed from [0024] a) --OH, [0025] b) --NH₂ [0026] c) is a linear saturated or unsaturated or branched saturated or unsaturated alkoxy group having 1 to 24 carbon atoms, which may be functionalised by a --OH, --SH, --COOH or --CONH₂ group, or [0027] d) a sterol or a sphingolipid group, with the proviso that if R1 is --H, R2 is not --OH; or that if R2 is --OH, R1 is not --H, and with the proviso that if R1 is --H, R2 is chosen form the group which is formed from [0028] b) --NH₂ [0029] c) a linear saturated or unsaturated or branched saturated or unsaturated alkoxy group having 2 to 24 carbon atoms, or [0030] d) a sterol or a sphingolipid group.

[0031] These oligopeptides are especially useful in cosmetic preparations.

[0032] The total number of amino acids in the oligopeptide (=n) be any number between 4 and 15, thus n can be 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15. In a preferred embodiment the total number of amino acids is at most 15, preferably at most 12, preferably at most 10, preferably at most 8, preferably at most 6, preferably at most 5.

[0033] The terms "oligopeptide" and "oligopeptides" are used synonymously to encompass single oligopeptide species of formula (I) as well as mixtures of at least 2, at least 3, or more oligopeptides according to formula (I). In case where at least R1 is not ═H or R2 is not --OH, the term "oligopeptide derivative" would be a more precise term. As used in this description, the term "oligopeptide" or "oligopeptides" encompasses oligopeptides as well as oligopeptide derivatives as well as salt of the oligopeptides as well as salts of the oligopeptide derivatives.

[0034] In a further embodiment of the invention, oligopeptides which are able to stimulate the growth of human keratinocytes in-vitro are preferred.

[0035] This ability can be tested in standard assays using human primary keratinocytes, which can be obtained by trypsinization of human skin biopsis. These are cultured in standard medium under standard conditions prior to the cultivation of the oligopeptide to be tested. Usual cultivation with the oligopeptide to be tested is 37° C., 4 or 5 days.

[0036] The stimulation of the proliferation can be determined by measuring the number of living cells in a sample cultivated with the oligopeptide to be tested in comparison to control (=no peptide). The number of living cells can for example be determined by measuring the DNA content, e.g. by fluorescence methods.

[0037] A stimulation of the proliferation is preferably achieved, if 5% more DNA is detected, preferably 10% more, even more preferably 15% more, even more preferably 20% more DNA when compared to the DNA content of the control.

Cosmetic Use

[0038] It has been found that the oligopeptides according to the invention are especially useful for producing a preparation which is effective against the formation of wrinkles and/or for reducing the severity of wrinkles and/or against the loss of elasticity of the skin and/or for strengthening the cutaneous barrier and/or dermis and/or the dermalepidermal junction (DEJ) and/or for reducing the skin dryness and/or for reducing the "orange skin" phenomenon of subcutaneous tissue. The oligopeptides according to formula (I) are preferably used for stimulating the renewal rate of skin and/or hair. They are preferably useful in cosmetic preparations against the reduction in cell numbers in human skin or for stimulating and/or regenerating hair growth and against hair loss.

[0039] It has surprisingly been found that the oligopeptides according to the invention are useful in strengthening of the cutaneous barrier and reducing the skin dryness at the same time.

[0040] In one embodiment, the oligopeptide according to the invention are useful for the cosmetic treatment of [0041] a. human skin or hair ageing and/or [0042] b. for preventing against ageing symptoms, such as wrinkles, and/or [0043] c. decrease of the epidermal and dermal skin layers, and/or [0044] d. alterations of the extracellular matrix and/or decrease in the renewal of epidermal and dermal cells and/or [0045] e. modifications of the dermal epidermal junctions and/or [0046] f. loss of elasticity and/or [0047] g. hair damages and/or hair losses.

[0048] In one embodiment, the oligopeptide according to the invention are preferably useful for [0049] h. stimulation of the renewal rate of human skin and/or hair.

[0050] In a preferred embodiment, the oligopeptide according to the invention are used for cosmetic preparations which are effective [0051] i. for stimulating the production of mRNA and/or [0052] j. for stimulation of matrix proteins such as collagen, elastin or proteoglycans and/or [0053] k. for stimulation of syndecan-1 synthesis

[0054] It has surprisingly been found, that the oligopeptides according to this invention are especially useful in cosmetic compositions for stimulating syndecan-1 synthesis.

[0055] In a preferred embodiment, the oligopeptides according to the invention, are used for producing a preparation which is effective against the formation of wrinkles and for reducing the severity of wrinkles or against the loss of elasticity of the skin or for strengthening the cutaneous barrier and/or the dermis and/or the dermal-epidermal junction (DEJ) or for reducing the "orange skin" phenomenon of subcutaneous tissue or for improved wound healing or against the reduction in cell numbers in human skin.

[0056] In one embodiment of the invention the oligopeptides according to the invention are used for stimulating and/or regenerating hair growth and against hair loss. In a preferred embodiment of the invention the oligopeptides are used in cosmetic preparations which stimulate the growth and the differentiation of human primary keratinocytes, which strenghten the skin barrier function. Preferably the oligopeptides according to the invention can be used effectively as inhibitors of elastase, the enzyme which degrades elastin.

[AA] Moiety: Tetrapeptide

[0057] In one embodiment of the invention, [AA] consists of 4 consecutive amino acids, which are identical to 4 consecutive amino acids of SEQ ID NO.1.

Table 1 lists these tetra-peptides:

TABLE-US-00001 36 tetra peptides of 4 consecutive amino acids of SEQ ID NO. 1 Seq. ID NO. Column I Seq. ID NO. 2 Arg Arg Arg Pro Seq. ID NO. 3 Arg Arg Pro Arg Seq. ID NO. 4 Arg Pro Arg Pro Seq. ID NO. 5 Pro Arg Pro Pro Seq. ID No. 6 Arg Pro Pro Tyr Seq. ID NO. 7 Pro Pro Tyr Leu Seq. ID NO. 8 Pro Tyr Leu Pro Seq. ID NO. 9 Tyr Leu Pro Arg Seq. ID NO. 10 Leu Pro Arg Pro Seq. ID NO. 11 Pro Arg Pro Arg Seq. ID NO. 12 Arg Pro Arg Pro Seq. ID NO. 13 Pro Arg Pro Pro Column II Seq. ID NO. 14 Arg Pro Pro Pro Seq. ID NO. 15 Pro Pro Pro Phe Seq. ID NO. 16 Pro Pro Phe Phe Seq. ID NO. 17 Pro Phe Phe Pro Seq. ID NO. 18 Phe Phe Pro Pro Seq. ID NO. 19 Phe Pro Pro Arg Seq. ID NO. 20 Pro Pro Arg Leu Seq. ID NO. 21 Pro Arg Leu Pro Seq. ID NO. 22 Arg Leu Pro Pro Seq. ID NO. 23 Leu Pro Pro Arg Seq. ID NO. 24 Pro Pro Arg Ile Seq. ID NO. 25 Pro Arg Ile Pro Column III Seq. ID NO. 26 Arg Ile Pro Pro Seq. ID NO. 27 Ile Pro Pro Glu Seq. ID NO. 28 Pro Pro Glu Phe Seq. ID NO. 29 Pro Glu Phe Pro Seq. ID NO. 30 Glu Phe Pro Pro Seq. ID NO. 31 Phe Pro Pro Arg Seq. ID NO. 32 Pro Pro Arg Phe Seq. ID NO. 33 Pro Arg Phe Pro Seq. ID NO. 34 Arg Phe Pro Pro Seq. ID NO. 35 Phe Pro Pro Arg Seq. ID NO. 36 Pro Pro Arg Phe Seq. ID NO. 37 Pro Arg Phe Pro

[0058] In a preferred embodiment [AA] consists of a tetra-peptide as specified in column I of table 1.

[0059] In a preferred embodiment [AA] consists of a tetra-peptide selected from the group consisting of [0060] i) Arg Arg Arg Pro (SEQ ID NO. 2); Arg Arg Pro Arg (SEQ ID NO. 3); [0061] ii) Arg Pro Pro Tyr (SEQ ID NO. 6); Pro Pro Tyr Leu (SEQ ID NO. 7); preferably Pro Pro Tyr Leu (SEQ ID NO. 7); [0062] iii) Pro Tyr Leu Pro (SEQ ID NO. 8); Tyr Leu Pro Arg (SEQ ID NO. 9); or [0063] iv) Tyr Leu Pro Arg (SEQ ID NO. 9); Leu Pro Arg Pro (SEQ ID NO. 10).

[0064] In a further embodiment the oligopeptide consists of at most 15, preferably at most 10, more preferably at most 5 amino acids, of which at least 4 consecutive amino acids are identical to 4 consecutive amino acids of SEQ ID NO.1. Thus in one embodiment of the invention, [AA] comprises 4 consecutive amino acids which are identical to 4 consecutive amino acids of SEQ ID NO.1 and has up to 11 further amino acids (resulting in a total number of 15 amino acids), preferably up to 6 further amino acids (resulting in a total number of 10 amino acids), more preferably up to 1 further amino acid (resulting in a total number of 5 amino acids), whereas the further amino acids need not be identical to or even present in SEQ ID NO.1.

[0065] In this embodiment [AA] is thus [X_m-aa-Y_o], wherein aa is a tetra-peptide of table 1 and X and Y are further amino acids, m and 0 being numbers from 0 to 11, with the proviso that m+o is ≦11. In a preferred embodiment, aa is selected from the tetrapeptides as specified in column 1 of table 1. In a further preferred embodiment m+o is ≦6, preferably =1.

[0066] In a preferred embodiment [AA] comprises a tetra-peptide as specified in column I of table 1.

[0067] In a preferred embodiment [AA] comprises a tetra-peptide selected from the group consisting of [0068] i) Arg Arg Arg Pro (SEQ ID NO. 2); Arg Arg Pro Arg (SEQ ID NO. 3); [0069] ii) Arg Pro Pro Tyr (SEQ ID NO. 6); Pro Pro Tyr Leu (SEQ ID NO. 7), preferably Pro Pro Tyr Leu (SEQ ID NO. 7) [0070] iii) Pro Tyr Leu Pro (SEQ ID NO. 8); Tyr Leu Pro Arg (SEQ ID NO. 9); or [0071] iv) Tyr Leu Pro Arg (SEQ ID NO. 9); Leu Pro Arg Pro (SEQ ID NO. 10).

[0072] The further amino acids can be any of the known proteinogenic amino acids including selenocystein (Sec) and L-pyrrolysine, derivatives of the proteinogenic amino acids or non-proteinogenic amino acids, e.g. L-citrullin. L-homocysteine, L-homoserine, (4R)-4-hydroxy-L-prolin, L-Homoserin (Hse), (4R)-4-Hydroxy-L-proline (Hyp), (5R)-5Hydroxy-L-lysine (Hyl), L-ornithine (am), sarkosine to name only a few. Functional groups of the further amino acids can be derivatised, e.g. by linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24 carbon atoms, by functional groups such as a --OH, --SH, --COOH or --CONH₂ group.

[0073] The amino acids can be either in D- or in L-configuration.

[0074] In a further embodiment of the invention [AA] comprises at most 14, preferably at most 13, preferably at most 13, preferably at most 12, more preferably at most 10, preferably at most 9, preferably at most 8, preferably at most 7, preferably at most 6, preferably at most 5 consecutive amino acids identical to the respective amino acids of the amino acid sequence of SEQ ID NO.1.

[0075] In a preferred embodiment of the invention [AA] consists of at most 15, preferably at most 14, preferably at most 13, preferably at most 13, preferably at most 12, more preferably at most 10, preferably at most 9, preferably at most 8, preferably at most 7, preferably at most 6, preferably at most 5 consecutive amino acids identical to the respective amino acids of the amino acid sequence of SEQ ID NO.1.

[AA] Moiety: Pentapeptide

[0076] In a further embodiments of the invention [AA] comprises at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14 or consists of 15 consecutive amino acids which are identical to the respective number of amino acids of SEQ ID NO.1.

[0077] In a further embodiments of the invention [AA] consists of at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14 consecutive amino acids which are identical to the respective number of amino acids of SEQ ID NO.1.

[0078] In one embodiment of the invention, [AA] consists of 5 consecutive amino acids, which are identical to 5 consecutive amino acids of SEQ ID NO.1.

TABLE-US-00002 TABLE 2 35 penta-peptides of 5 consecutive amino acids of SEQ ID NO. 1 Seq. ID NO. Column I Seq. ID NO. 38 Arg Arg Arg Pro Arg Seq. ID NO. 39 Arg Arg Pro Arg Pro Seq. ID NO. 40 Arg Pro Arg Pro Pro Seq. ID NO. 41 Pro Arg Pro Pro Tyr Seq. ID NO. 42 Arg Pro Pro Tyr Leu Seq. ID NO. 43 Pro Pro Tyr Leu Pro Seq. ID NO. 44 Pro Tyr Leu Pro Arg Seq. ID NO. 45 Tyr Leu Pro Arg Pro Seq. ID NO. 46 Leu Pro Arg Pro Arg Seq. ID NO. 47 Pro Arg Pro Arg Pro Seq. ID NO. 48 Arg Pro Arg Pro Pro Column II Seq. ID NO. 49 Pro Arg Pro Pro Pro Seq. ID NO. 50 Arg Pro Pro Pro Phe Seq. ID NO. 51 Pro Pro Pro Phe Phe Seq. ID NO. 52 Pro Pro Phe Phe Pro Seq. ID NO. 53 Pro Phe Phe Pro Pro Seq. ID NO. 54 Phe Phe Pro Pro Arg Seq. ID NO. 55 Phe Pro Pro Arg Leu Seq. ID NO. 56 Pro Pro Arg Leu Pro Seq. ID NO. 57 Pro Arg Leu Pro Pro Seq. ID NO. 58 Arg Leu Pro Pro Arg Seq. ID NO. 59 Leu Pro Pro Arg Ile Column III Seq. ID NO. 60 Pro Pro Arg Ile Pro Seq. ID NO. 61 Pro Arg Ile Pro Pro Seq. ID NO. 62 Arg Ile Pro Pro Glu Seq. ID NO. 63 Ile Pro Pro Glu Phe Seq. ID NO. 64 Pro Pro Glu Phe Pro Seq. ID NO. 65 Pro Glu Phe Pro Pro Seq. ID NO. 66 Glu Phe Pro Pro Arg Seq. ID NO. 67 Phe Pro Pro Arg Phe Seq. ID NO. 68 Pro Pro Arg Phe Pro Seq. ID NO. 69 Pro Arg Phe Pro Pro Seq. ID NO. 70 Arg Phe Pro Pro Arg Seq. ID NO. 71 Phe Pro Pro Arg Phe Seq. ID NO. 72 Pro Pro Arg Phe Pro

[0079] In a preferred embodiment [AA] consists of a penta-peptide as specified in column I of table 2.

[0080] In a preferred embodiment [AA] consists of a penta-peptide selected from the group consisting of Arg Arg Arg Pro Arg (SEQ ID NO. 38); Arg Pro Pro Tyr Leu (Seq. ID NO. 42); Pro Tyr Leu Pro Arg (Seq. ID NO. 44); and Tyr Leu Pro Arg Pro (SEQ ID NO. 45).

[0081] In a further embodiment the oligopeptide consists of at most 15, preferably at most 10, more preferably at most 7 amino acids, of which 5 consecutive amino acids are identical to 5 consecutive amino acids of SEQ ID NO.1; Thus in one embodiment of the invention, [AA] comprises 5 consecutive amino acids which are identical to 5 consecutive amino acids of SEQ ID NO.1 and has up to 10 further amino acids (resulting in a total number of 15 amino acids), preferably up to 5 further amino acids (resulting in a total number of 10 amino acids), preferably up to 2 further amino acids (resulting in a total number of 7 amino acids) whereas the further amino acids need not be identical to or even present in SEQ ID NO.1.

[0082] In this embodiment [AA] is thus [X_m-aa-Y_o], wherein aa is a penta-peptide of table 2, and X and Y are further amino acids, m and 0 being numbers from 0 to 10, with the proviso that m+o is ≦10. In a preferred embodiment, aa is selected from the pentapeptide as specified in column 1 of table 2. In a further preferred embodiment m+o is ≦5, more preferably ≦2.

[0083] In a preferred embodiment [AA] comprises a penta-peptide as specified in column I of table 2.

[0084] In a preferred embodiment [AA] comprises a penta-peptide selected from the group consisting of Arg Arg Arg Pro Arg (SEQ ID NO. 38); Arg Pro Pro Tyr Leu (Seq. ID NO. 42); Pro Tyr Leu Pro Arg (SEQ ID NO. 44) and Tyr Leu Pro Arg Pro (SEQ ID NO. 45).

[AA] Moiety: Hexapapetide

[0085] In one embodiment of the invention, [AA] consists of 6 consecutive amino acids, which are identical to 6 consecutive amino acids of SEQ ID NO.1.

TABLE-US-00003 TABLE 3 34 hexa-peptides of 6 consecutive amino acids of SEQ ID NO. 1 Column I Seq. ID NO. 73 Arg Arg Arg Pro Arg Pro Seq. ID NO. 74 Arg Arg Pro Arg Pro Pro Seq. ID NO. 75 Arg Pro Arg Pro Pro Tyr Seq. ID NO. 76 Pro Arg Pro Pro Tyr Leu Seq. ID NO. 77 Arg Pro Pro Tyr Leu Pro Seq. ID No. 78 Pro Pro Tyr Leu Pro Arg Seq. ID NO. 79 Pro Tyr Leu Pro Arg Pro Seq. ID NO. 80 Tyr Leu Pro Arg Pro Arg Seq. ID NO. 81 Leu Pro Arg Pro Arg Pro Seq. ID No. 82 Pro Arg Pro Arg Pro Pro Column II Seq. ID NO. 83 Arg Pro Arg Pro Pro Pro Seq. ID NO. 84 Pro Arg Pro Pro Pro Phe Seq. ID NO. 85 Arg Pro Pro Pro Phe Phe Seq. ID NO. 86 Pro Pro Pro Phe Phe Pro Seq. ID NO. 87 Pro Pro Phe Phe Pro Pro Seq. ID NO. 88 Pro Phe Phe Pro Pro Arg Seq. ID NO. 89 Phe Phe Pro Pro Arg Leu Seq. ID NO. 90 Phe Pro Pro Arg Leu Pro Seq. ID NO. 91 Pro Pro Arg Leu Pro Pro Seq. ID NO. 92 Pro Arg Leu Pro Pro Arg Column III Seq. ID NO. 93 Arg Leu Pro Pro Arg Ile Seq. ID NO. 94 Leu Pro Pro Arg Ile Pro Seq. ID NO. 95 Pro Pro Arg Ile Pro Pro Seq. ID NO. 96 Pro Arg Ile Pro Pro Glu Seq. ID NO. 97 Arg Ile Pro Pro Glu Phe Seq. ID NO. 98 Ile Pro Pro Glu Phe Pro Seq. ID NO. 99 Pro Pro Glu Phe Pro Pro Seq. ID NO. 100 Pro Glu Phe Pro Pro Arg Seq. ID NO. 101 Glu Phe Pro Pro Arg Phe Seq. ID NO. 102 Phe Pro Pro Arg Phe Pro Seq. ID NO. 103 Pro Pro Arg Phe Pro Pro Seq. ID NO. 104 Pro Arg Phe Pro Pro Arg Seq. ID NO. 105 Arg Phe Pro Pro Arg Phe Seq. ID NO. 106 Phe Pro Pro Arg Phe Pro

[0086] In a preferred embodiment [AA] consists of a hexa-peptide as specified in column I of table 3.

[0087] In a further embodiment of the oligopeptide consists of at most 15, preferably at most 10, more preferably at most 8 amino acids, of which 6 consecutive amino acids are identical to 6 consecutive amino acids of SEQ ID NO.1; Thus in one embodiment of the invention, [AA] comprises 6 consecutive amino acids which are identical to 6 consecutive amino acids of SEQ ID NO.1 and has up to 9 further amino acids (resulting in a total number of 15 amino acids), preferably up to 5 further amino acids (resulting in a total number of 10 amino acids), preferably up to 2 further amino acids (resulting in a total number of 8 amino acids) whereas the further amino acids need not be identical to or even present in SEQ ID NO.1.

[0088] In this embodiment [AA] is thus [X_m-aa-Y_o], wherein aa is a hexa-peptide of table 3, and X and Yare further amino acids, m and 0 being numbers from 0 to 9, with the proviso that m+o is ≦9. In a preferred embodiment, aa is selected from the hexapeptide as specified in column 1 of table 3. In a further preferred embodiment m+o is ≦4, more preferably ≦2.

[AA] Moiety: Heptapeptide

[0089] In one embodiment of the invention, [AA] consists of 7 consecutive amino acids, which are identical to 7 consecutive amino acids of SEQ ID NO.1.

[0090] Table 4 lists these hepta-peptides:

TABLE-US-00004 33 hepta-peptides of 7 consecutive amino acids of SEQ ID NO. 1 Seq. ID NO. Column I Seq. ID NO. 107 Arg Arg Arg Pro Arg Pro Pro Seq. ID NO. 108 Arg Arg Pro Arg Pro Pro Tyr Seq. ID NO. 109 Arg Pro Arg Pro Pro Tyr Leu Seq. ID NO. 110 Pro Arg Pro Pro Tyr Leu Pro Seq. ID NO. 111 Arg Pro Pro Tyr Leu Pro Arg Seq. ID NO. 112 Pro Pro Tyr Leu Pro Arg Pro Seq. ID NO. 113 Pro Tyr Leu Pro Arg Pro Arg Seq. ID NO. 114 Tyr Leu Pro Arg Pro Arg Pro Seq. ID NO. 115 Leu Pro Arg Pro Arg Pro Pro Column II Seq. ID NO. 116 Pro Arg Pro Arg Pro Pro Pro Seq. ID NO. 117 Arg Pro Arg Pro Pro Pro Phe Seq. ID NO. 118 Pro Arg Pro Pro Pro Phe Phe Seq. ID NO. 119 Arg Pro Pro Pro Phe Phe Pro Seq. ID NO. 120 Pro Pro Pro Phe Phe Pro Pro Seq. ID NO. 121 Pro Pro Phe Phe Pro Pro Arg Seq. ID NO. 122 Pro Phe Phe Pro Pro Arg Leu Seq. ID NO. 123 Phe Phe Pro Pro Arg Leu Pro Seq. ID NO. 124 Phe Pro Pro Arg Leu Pro Pro Column III Seq. ID NO. 125 Pro Prro Arg Leu Pro Pro Arg Seq. ID NO. 126 Pro Arg Leu Pro Pro Arg Ile Seq. ID NO. 127 Arg Leu Pro Pro Arg Ile Pro Seq. ID NO. 128 Leu Pro Pro Arg Ile Pro Pro Seq. ID NO. 129 Pro Pro Arg Ile Pro Pro Glu Seq. ID NO. 130 Pro Arg Ile Pro Pro Glu Phe Seq. ID NO. 131 Arg Ile Pro Pro Glu Phe Pro Seq. ID NO. 132 Ile Pro Pro Glu Phe Pro Pro Seq. ID NO. 133 Pro Pro Glu Phe Pro Pro Arg Seq. ID NO. 134 Pro Glu Phe Pro Pro Arg Phe Seq. ID NO. 135 Glu Phe Pro Pro Arg Phe Pro Seq. ID NO. 136 Phe Pro Pro Arg Phe Pro Pro Seq. ID No. 137 Pro Pro Arg Phe Pro Pro Arg Seq. ID NO. 138 Pro Arg Phe Pro Pro Arg Phe Seq. ID NO. 139 Arg Phe Pro Pro Arg Phe Pro

[0091] In a preferred embodiment [AA] consists of a heptapeptide as specified in column I of table 4.

[0092] In a further embodiment the oligopeptide consists of at most 15, preferably at most 10, more preferably at most 9 amino acids, of which at least 7 consecutive amino acids are identical to 7 consecutive amino acids of SEQ ID NO.1. Thus in one embodiment of the invention, [AA] comprises 7 consecutive amino acids which are identical to 7 consecutive amino acids of SEQ ID NO.1 and has up to 8 further amino acids (resulting in a total number of 15 amino acids), preferably up to 3 further amino acids (resulting in a total number of 10 amino acids), more preferably up to 2 further amino acid (resulting in a total number of 9 amino acids), whereas the further amino acids need not be identical to or even present in SEQ ID NO.1.

[0093] In this embodiment [AA] is thus [X_m-aa-Y_o], wherein aa is a hepta-peptide of table 4 and X and Y are further amino acids, m and 0 being numbers from 0 to 8, with the proviso that m+o is ≦8. In a preferred embodiment, aa is selected from the heptapeptides as specified in column 1 of table 4. In a further preferred embodiment m+o is ≦3, preferably =2.

[AA] Moiety: Octapeptide

[0094] In one embodiment of the invention, [AA] consists of 8 consecutive amino acids, which are identical to 8 consecutive amino acids of SEQ ID NO.1.

[0095] Table 5 lists these octa-peptides:

TABLE-US-00005 32 octa-peptides of 8 consecutive amino acids of SEQ ID NO. 1 Seq. ID NO. Column I Seq. ID Arg Arg Arg Pro Arg Pro Pro Tyr NO. 140 Seq. ID Arg Arg Pro Arg Pro Pro Tyr Leu NO. 141 Seq. ID Arg Pro Arg Pro Pro Tyr Leu Pro NO. 142 Seq. ID Pro Arg Pro Pro Tyr Leu Pro Arg NO. 143 Seq. ID Arg Pro Pro Tyr Leu Pro Arg Pro NO. 144 Seq. ID Pro Pro Tyr Leu Pro Arg Pro Arg NO. 145 Seq. ID Pro Tyr Leu Pro Arg Pro Arg Pro NO. 146 Seq. ID Tyr Leu Pro Arg Pro Arg Pro Pro NO. 147 Column II Seq. ID Leu Pro Arg Pro Arg Pro Pro Pro NO. 148 Seq. ID Pro Arg Pro Arg Pro Pro Pro Phe NO. 149 Seq. ID Arg Pro Arg Pro Pro Pro Phe Phe NO. 150 Seq. ID Pro Arg Pro Pro Pro Phe Phe Pro NO. 151 Seq. ID Arg Pro Pro Pro Phe Phe Pro Pro NO. 152 Seq. ID Pro Pro Pro Phe Phe Pro Pro Arg NO. 153 Seq. ID Pro Pro Phe Phe Pro Pro Arg Leu NO. 154 Seq. ID Pro Phe Phe Pro Pro Arg Leu Pro NO. 155 Seq. ID Phe Phe Pro Pro Arg Leu Pro Pro NO. 156 Seq. ID Phe Pro Pro Arg Leu Pro Pro Arg NO. 157 Seq. ID Pro Pro Arg Leu Pro Pro Arg Ile NO. 158 Seq. ID Pro Arg Leu Pro Pro Arg Ile Pro NO. 159 Seq. ID Arg Leu Pro Pro Arg Ile Pro Pro NO. 160 Seq. ID Leu Pro Pro Arg Ile Pro Pro Glu NO. 161 Seq. ID Pro Pro Arg Ile Pro Pro Glu Phe NO. 162 Seq. ID Pro Arg Ile Pro Pro Glu Phe Pro NO. 163 Seq. ID Arg Ile Pro Pro Glu Phe Pro Pro NO. 164 Seq. ID Ile Pro Pro Glu Phe Pro Pro Arg NO. 165 Seq. ID Pro Pro Glu Phe Pro Pro Arg Phe NO. 166 Seq. ID Pro Glu Phe Pro Pro Arg Phe Pro NO. 167 Seq. ID Glu Phe Pro Pro Arg Phe Pro Pro NO. 168 Seq. ID Phe Pro Pro Arg Phe Pro Pro Arg NO. 169 Seq. ID Pro Pro Arg Phe Pro Pro Arg Phe NO. 170 Seq. ID Pro Arg Phe Pro Pro Arg Phe Pro NO. 171

[0096] In a preferred embodiment [AA] consists of an octapeptide as specified in column 1 of table 5. In a further embodiment the oligopeptide consists of at most 15, preferably at most 10 amino acids, of which at least 8 consecutive amino acids are identical to 8 consecutive amino acids of SEQ ID NO.1. Thus in one embodiment of the invention, [AA] comprises 8 consecutive amino acids which are identical to 8 consecutive amino acids of SEQ ID NO.1 and has up to 7 further amino acids (resulting in a total number of 15 amino acids), preferably up to 2 further amino acids (resulting in a total number of 10 amino acids), whereas the further amino acids need not be identical to or even present in SEQ ID NO.1.

[0097] In this embodiment [AA] is thus [X_m-aa-Y_o], wherein aa is a octa-peptide of table 5 and X and Y are further amino acids, m and 0 being numbers from 0 to 7, with the proviso that m+o is ≦7. In a preferred embodiment, aa is selected from the octapeptides as specified in column I of table 5. In a further preferred embodiment m+o is ≦2.

[AA] Moiety: Nonapeptide

[0098] In one embodiment of the invention, [AA] consists of 9 consecutive amino acids, which are identical to 9 consecutive amino acids of SEQ ID NO.1.

[0099] Table 6 list these nona-peptides:

TABLE-US-00006 31 nona peptides of 9 consecutive amino acids of SEQ ID NO. 1 Seq. ID NO. Column I Seq. ID Arg Arg Arg Pro Arg Pro Pro Tyr Leu NO. 172 Seq. ID Arg Arg Pro Arg Pro Pro Tyr Leu Pro NO. 173 Seq. ID Arg Pro Arg Pro Pro Tyr Leu Pro Arg NO. 174 Seq. ID Pro Arg Pro Pro Tyr Leu Pro Arg Pro NO. 175 Seq. ID Arg Pro Pro Tyr Leu Pro Arg Pro Arg NO. 176 Seq. ID Pro Pro Tyr Leu Pro Arg Pro Arg Pro NO. 177 Seq. ID Pro Tyr Leu Pro Arg Pro Arg Pro Pro NO. 178 Column II Seq. ID Tyr Leu Pro Arg Pro Arg Pro Pro Pro NO. 179 Seq. ID Leu Pro Arg Pro Arg Pro Pro Pro Phe NO. 180 Seq. ID Pro Arg Pro Arg Pro Pro Pro Phe Phe NO. 181 Seq. ID Arg Pro Arg Pro Pro Pro Phe Phe Pro NO. 182 Seq. ID Pro Arg Pro Pro Pro Phe Phe Pro Pro NO. 183 Seq. ID Arg Pro Pro Pro Phe Phe Pro Pro Arg NO. 184 Seq. ID Pro Pro Pro Phe Phe Pro Pro Arg Leu NO. 185 Seq. ID Pro Pro Phe Phe Pro Pro Arg Leu Pro NO. 186 Seq. ID Pro Phe Phe Pro Pro Arg Leu Pro Pro NO. 187 Seq. ID Phe Phe Pro Pro Arg Leu Pro Pro Arg No. 188 Seq. ID Phe Pro Pro Arg Leu Pro Pro Arg Ile No. 189 Seq. ID Pro Pro Arg Leu Pro Pro Arg Ile Pro NO. 190 Seq. ID Pro Arg Leu Pro Pro Arg Ile Pro Pro NO. 191 Seq. ID Arg Leu Pro Pro Arg Ile Pro Pro Glu NO. 192 Seq. ID Leu Pro Pro Arg Ile Pro Pro Glu Phe NO. 193 Seq. ID Pro Pro Arg Ile Pro Pro Glu Phe Pro No. 194 Seq. ID Pro Arg Ile Pro Pro Glu Phe Pro Pro NO. 195 Seq. ID Arg Ile Pro Pro Glu Phe Pro Pro Arg No. 196 Seq. ID Ile Pro Pro Glu Phe Pro Pro Arg Phe No. 197 Seq. ID Pro Pro Glu Phe Pro Pro Arg Phe Pro NO. 198 Seq. ID Pro Glu Phe Pro Pro Arg Phe Pro Pro NO. 199 Seq. ID Glu Phe Pro Pro Arg Phe Pro Pro Arg NO. 200 Seq. ID Phe Pro Pro Arg Phe Pro Pro Arg Phe No. 201 Seq. ID Pro Pro Arg Phe Pro Pro Arg Phe Pro NO. 202

[0100] In a preferred embodiment [AA] consists of a nona-peptide as specified in column I of table 6.

[0101] In a further embodiment the oligopeptide consists of at most 15, preferably at most 10 amino acids, of which at least 9 consecutive amino acids are identical to 9 consecutive amino acids of SEQ ID NO.1. Thus in one embodiment of the invention, [AA] comprises 9 consecutive amino acids which are identical to 9 consecutive amino acids of SEQ ID NO.1 and has up to 6 further amino acids (resulting in a total number of 15 amino acids), preferably up to 1 further amino acid (resulting in a total number of 10 amino acids), whereas the further amino acids need not be identical to or even present in SEQ ID NO.1.

[0102] In this embodiment [AA] is thus [X_m-aa-Y_o], wherein aa is a nona-peptide of table 9 and X and Y are further amino acids, m and 0 being numbers from 0 to 5, with the proviso that m+o is ≦5. In a preferred embodiment, aa is selected from the nonapeptides as specified in column I of table 6. In a further preferred embodiment m+o is =1.

[AA] Moiety: Decapeptide

[0103] In one embodiment of the invention, [AA] consists of 10 consecutive amino acids, which are identical to 10 consecutive amino acids of SEQ ID NO.1.

[0104] Table 7 list these deca-peptides:

TABLE-US-00007 30 deca peptides of 10 consecutive amino acids of SEQ ID NO. 1 SEQ ID NO. Column I SEQ ID Arg Arg Arg Pro Arg Pro Pro Tyr Leu NO. 203 Pro SEQ ID Arg Arg Pro Arg Pro Pro Tyr Leu Pro NO. 204 Arg SEQ ID Arg Pro Arg Pro Pro Tyr Leu Pro Arg NO. 205 Pro SEQ ID Pro Arg Pro Pro Tyr Leu Pro Arg Pro NO. 206 Arg SEQ ID Arg Pro Pro Tyr Leu Pro Arg Pro Arg NO. 207 Pro SEQ ID Pro Pro Tyr Leu Pro Arg Pro Arg Pro NO. 208 Pro Column II SEQ ID Pro Tyr Leu Pro Arg Pro Arg Pro Pro NO. 209 Pro SEQ ID Tyr Leu Pro Arg Pro Arg Pro Pro Pro NO. 210 Phe SEQ ID Leu Pro Arg Pro Arg Pro Pro Pro Phe NO. 211 Phe SEQ ID Pro Arg Pro Arg Pro Pro Pro Phe Phe NO. 212 Pro SEQ ID Arg Pro Arg Pro Pro Pro Phe Phe Pro NO. 213 Pro SEQ ID Pro Arg Pro Pro Pro Phe Phe Pro Pro NO. 214 Arg SEQ ID Arg Pro Pro Pro Phe Phe Pro Pro Arg NO. 215 Leu SEQ ID Pro Pro Pro Phe Phe Pro Pro Arg Leu NO. 216 Pro SEQ ID Pro Pro Phe Phe Pro Pro Arg Leu Pro NO. 217 Pro SEQ ID Pro Phe Phe Pro Pro Arg Leu Pro Pro NO. 218 Arg SEQ ID Phe Phe Pro Pro Arg Leu Pro Pro Arg NO. 219 Ile SEQ ID Phe Pro Pro Arg Leu Pro Pro Arg Ile NO. 220 Pro SEQ ID Pro Pro Arg Leu Pro Pro Arg Ile Pro NO. 221 Pro SEQ ID Pro Arg Leu Pro Pro Arg Ile Pro Pro NO. 222 Glu SEQ ID Arg Leu Pro Pro Arg Ile Pro Pro Glu NO. 223 Phe SEQ ID Leu Pro Pro Arg Ile Pro Pro Glu Phe NO. 224 Pro SEQ ID Pro Pro Arg Ile Pro Pro Glu Phe Pro NO. 225 Pro SEQ ID Pro Arg Ile Pro Pro Glu Phe Pro Pro NO. 226 Arg SEQ ID Arg Ile Pro Pro Glu Phe Pro Pro Arg NO. 227 Phe SEQ ID Ile Pro Pro Glu Phe Pro Pro Arg Phe NO. 228 Pro SEQ ID Pro Pro Glu Phe Pro Pro Arg Phe Pro NO. 229 Pro SEQ ID Pro Glu Phe Pro Pro Arg Phe Pro Pro NO. 230 Arg SEQ ID Glu Phe Pro Pro Arg Phe Pro Pro Arg NO. 231 Phe SEQ ID Phe Pro Pro Arg Phe Pro Pro Arg Phe NO. 232 Pro

[0105] In a preferred embodiment [AA] consists of a deca-peptide as specified in column I of table 7.

[0106] In a further embodiment the oligopeptide consists of at most 15, preferably at most 12 amino acids, of which at least 10 consecutive amino acids are identical to 10 consecutive amino acids of SEQ ID NO.1. Thus in one embodiment of the invention, [AA] comprises 10 consecutive amino acids which are identical to 10 consecutive amino acids of SEQ ID NO.1 and has up to 4 further amino acids (resulting in a total number of 15 amino acids), preferably up to 2 further amino acids (resulting in a total number of 12 amino acids), whereas the further amino acids need not be identical to or even present in SEQ ID NO.1.

[0107] In this embodiment [AA] is thus [X_m-aa-Y_o], wherein aa is a deca-peptide of table 7 and X and Y are further amino acids, m and 0 being numbers from 0 to 5, with the proviso that m+o is ≦5.

[0108] In a preferred embodiment, aa is selected from the decapeptides as specified in column 1 of table 7. In a further preferred embodiment m+o is ≦2.

[AA] Moiety: Undecapeptide

[0109] In one embodiment of the invention, [AA] consists of 11 consecutive amino acids, which are identical to 11 consecutive amino acids of SEQ ID NO.1.

[0110] Table 8 lists these undeca-peptides:

TABLE-US-00008 29 undeca-peptides of 11 consecutive amino acids of SEQ ID NO. 1 Seq. ID NO. Column I Seq. ID Arg Arg Arg Pro Arg Pro Pro Tyr Leu NO. 233 Pro Arg Seq. ID Arg Arg Pro Arg Pro Pro Tyr Leu Pro NO. 234 Arg Pro Seq. ID Arg Pro Arg Pro Pro Tyr Leu Pro Arg NO. 235 Pro Arg Seq. ID Pro Arg Pro Pro Tyr Leu Pro Arg Pro NO. 236 Arg Pro Seq. ID Arg Pro Pro Tyr Leu Pro Arg Pro Arg NO. 237 Pro Pro Column II SEQ ID Pro Pro Tyr Leu Pro Arg Pro Arg Pro NO. 238 Pro Pro SEQ ID Pro Tyr Leu Pro Arg Pro Arg Pro Pro NO. 239 Pro Phe SEQ ID Tyr Leu Pro Arg Pro Arg Pro Pro Pro NO. 240 Phe Phe Seq. ID Leu Pro Arg Pro Arg Pro Pro Pro Phe NO. 241 Phe Pro SEQ ID Pro Arg Pro Arg Pro Pro Pro Phe Phe NO. 242 Pro Pro SEQ ID Arg Pro Arg Pro Pro Pro Phe Phe Pro NO. 243 Pro Arg Seq. ID Pro Arg Pro Pro Pro Phe Phe Pro Pro NO. 244 Arg Leu SEQ ID Arg Pro Pro Pro Phe Phe Pro Pro Arg NO. 245 Leu Pro SEQ ID Pro Pro Pro Phe Phe Pro Pro Arg Leu NO. 246 Pro Pro SEQ ID Pro Pro Phe Phe Pro Pro Arg Leu Pro NO. 247 Pro Arg SEQ ID Pro Phe Phe Pro Pro Arg Leu Pro Pro NO. 248 Arg Ile SEQ ID Phe Phe Pro Pro Arg Leu Pro Pro Arg NO. 249 Ile Pro SEQ ID Phe Pro Pro Arg Leu Pro Pro Arg Ile NO. 250 Pro Pro Seq. ID Pro Pro Arg Leu Pro Pro Arg Ile Pro NO. 251 Pro Glu Seq. ID Pro Arg Leu Pro Pro Arg Ile Pro Pro NO. 252 Glu Phe SEQ ID Arg Leu Pro Pro Arg Ile Pro Pro Glu NO. 253 Phe Pro SEQ ID Leu Pro Pro Arg Ile Pro Pro Glu Phe NO. 254 Pro Pro SEQ ID Pro Pro Arg Ile Pro Pro Glu Phe Pro NO. 255 Pro Arg SEQ ID Pro Arg Ile Pro Pro Glu Phe Pro Pro NO. 256 Arg Phe SEQ ID Arg Ile Pro Pro Glu Phe Pro Pro Arg NO. 257 Phe Pro SEQ ID Ile Pro Pro Glu Phe Pro Pro Arg Phe NO. 258 Pro Pro SEQ ID Pro Pro Glu Phe Pro Pro Arg Phe Pro NO. 259 Pro Arg SEQ ID Pro Glu Phe Pro Pro Arg Phe Pro Pro NO. 260 Arg Phe SEQ ID Glu Phe Pro Pro Arg Phe Pro Pro Arg NO. 261 Phe Pro

[0111] In a preferred embodiment [AA] consists of an undeca-peptide as specified in column I of table 8.

[0112] In a further embodiment the oligopeptide consists of at most 15, preferably at most 12 amino acids, of which at least 11 consecutive amino acids are identical to 11 consecutive amino acids of SEQ ID NO.1. Thus in one embodiment of the invention, [AA] comprises 11 consecutive amino acids which are identical to 11 consecutive amino acids of SEQ ID NO. 1 and has up to 4 further amino acids (resulting in a total number of 15 amino acids), preferably up to 1 further amino acids (resulting in a total number of 12 amino acids), whereas the further amino acids need not be identical to or even present in SEQ ID NO.1.

[0113] In this embodiment [AA] is thus [X_m-aa-Y_o], wherein aa is an undeca-peptide of table 8 and X and Yare further amino acids, m and 0 being numbers from 0 to 4, with the proviso that m+o is ≦4. In a preferred embodiment, aa is selected from the undecapeptides as specified in column I of table 8. In a further preferred embodiment m+o is =1.

[AA] Moiety: Dodecapeptide

[0114] In one embodiment of the invention, [AA] consists of 12 consecutive amino acids, which are identical to 12 consecutive amino acids of SEQ ID NO. 1.

[0115] Table 9 lists these dodeca-peptides:

TABLE-US-00009 28 dodeca-peptides of 12 consecutive amino acids of SEQ ID No. 1 SEQ ID NO. Column I SEQ ID NO. 262 Arg Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro SEQ ID NO. 263 Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg SEQ ID NO. 264 Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro SEQ ID NO. 265 Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Column II SEQ ID NO. 266 Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Seq. ID NO. 267 Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe SEQ ID NO. 268 Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe SEQ ID NO. 269 Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro SEQ ID NO. 270 Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro SEQ ID NO. 271 Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg SEQ ID NO. 272 Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu SEQ ID NO. 273 Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Seq. ID NO. 274 Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro SEQ ID NO. 275 Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg SEQ ID NO. 276 Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile SEQ ID NO. 277 Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro SEQ ID NO. 278 Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro SEQ ID NO. 279 Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu SEQ ID NO. 280 Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe SEQ ID NO. 281 Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro SEQ ID NO. 282 Arg Leu Pro Pro Arg Ile Pro Pro Giu Phe Pro Pro SEQ ID NO. 283 Leu Pro Pro Arg lie Pro Pro Glu Phe Pro Pro Arg SEQ ID NO. 284 Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe SEQ ID NO. 285 Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro SEQ ID NO. 286 Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro SEQ ID NO. 287 Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Seq. ID NO. 288 Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe SEQ ID NO. 289 Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe Pro

[0116] In a preferred embodiment [AA) consists of a dodeca-peptide as specified in column I of table 9.

[0117] In a further embodiment the oligopeptide consists of at most 15, of which at least 12 consecutive amino acids are identical to 12 consecutive amino acids of SEQ ID NO. 1. Thus in one embodiment of the invention, [AA] comprises 12 consecutive amino acids which are identical to 12 consecutive amino acids of SEQ ID NO.1 and has up to 3 further amino acids (resulting in a total number of 15 amino acids), preferably up to 2 further amino acids (resulting in a total number of 14 amino acids), more preferably up to 1 further amino acid (resulting in a total number of 13 amino acids), whereas the further amino acids need not be identical to or even present in SEQ ID NO.1.

[0118] In this embodiment [AA] is thus [X_m-aa-Y_o), wherein aa is a dodeca-peptide of table 9 and X and Y are further amino acids, m and 0 being numbers from a to 3, with the proviso that m+o is ≦3. In a preferred embodiment, aa is selected from the dodecapeptides as specified in column I of table 9. In a further preferred embodiment m+o is ≦2, preferably =1.

[AA] Moiety: Tridecapeptide

[0119] In one embodiment of the invention, [AA] consists of 13 consecutive amino acids, which are identical to 13 consecutive amino acids of SEQ ID NO.1.

[0120] Table 10 lists these trideca-peptides:

TABLE-US-00010 27 trideca peptides of 13 consecutive amino acids of SEQ ID NO. 1 SEQ ID NO. Column I Seq. ID NO. 290 Arg Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg SEQ ID NO. 291 Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro SEQ ID NO. 292 Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Column II Seq. ID NO. 293 Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Seq. ID NO. 294 Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Seq. ID NO. 285 Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Seq. ID NO. 296 Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Seq. ID NO. 297 Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Seq. ID NO. 298 Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Seq. ID NO. 299 Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Seq. ID NO. 300 Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Seq. ID NO. 301 Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Seq. ID NO. 302 Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Seq. ID NO. 303 Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Seq. ID NO. 304 Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Seq. ID NO. 305 Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Seq. ID NO. 306 Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Seq. ID NO. 307 Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Seq. ID NO. 308 Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Seq. ID NO. 309 Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Seq. ID NO. 310 Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Seq. ID NO. 311 Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Seq. ID NO. 312 Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Seq. ID NO. 313 Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Seq. ID NO. 314 Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Seq. ID NO. 315 Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe Seq. ID NO. 316 Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe Pro

[0121] In a preferred embodiment [AA] consists of a trideca-peptide as specified in column I of table 10.

[0122] In a further embodiment the oligopeptide consists of at most 15, preferably at most 14 amino acids, of which at least 13 consecutive amino acids are identical to 13 consecutive amino acids of SEQ ID NO.1. Thus in one embodiment of the invention, [AA] comprises 13 consecutive amino acids which are identical to 13 consecutive amino acids of SEQ ID NO.1 and has up to 2 further amino acids (resulting in a total number of 15 amino acids), preferably up to 1 further amino acids (resulting in a total number of 14 amino acids), whereas the further amino acids need not be identical to or even present in SEQ ID NO.1.

[0123] In this embodiment [AA] is thus [X_m-aa-Y_o] wherein aa is a trideca-peptide of table 10 and X and Yare further amino acids, m and o being numbers from 0 to 2, with the proviso that m+o is ≦2. In a preferred embodiment, aa is selected from the trdecapeptides as specified in column I of table 10. In a further preferred embodiment m+o is =1.

[AA] Moiety: Tetradecapeptide

[0124] In one embodiment of the invention, [AA] consists of 14 consecutive amino acids, which are identical to 14 consecutive amino acids of SEQ ID NO.1.

[0125] Table 11 lists these tetradeca-peptides:

TABLE-US-00011 26 tetradeca peptides of 14 consecutive amino acids of SEQ ID NO. 1 SEQ ID NO. Column I Seq. ID No. 317 Arg Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Seq. ID NO. 318 Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Column II Seq. ID NO. 319 Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Seq. ID NO. 320 Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Seq. ID NO. 321 Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Seq. ID NO. 322 Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Seq. ID NO. 323 Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Seq. ID NO. 324 Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Seq. ID NO. 325 Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Seq. ID NO. 326 Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Seq. ID NO. 327 Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Seq. ID NO. 328 Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg He Seq. ID NO. 329 Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg He Pro Seq. ID NO. 330 Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Seq. ID NO. 331 Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Seq. ID NO. 332 Phe Phe Pro Pro Arg Leu Pro Pro Arg He Pro Pro Glu Phe Seq. ID NO. 333 Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Seq. ID NO. 334 Pro Arg Leu Pro Pro Arg He Pro Pro Glu Phe Pro Pro Arg Seq. ID NO. 335 Arg Leu Pro Pro Arg He Pro Pro Glu Phe Pro Pro Arg Phe Seq. ID NO. 336 Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Seq. ID NO. 337 Pro Pro Arg He Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Seq. ID NO. 338 Pro Arg He Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg SEQ ID NO. 339 Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe Seq. ID NO. 340 Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe Pro

[0126] In a preferred embodiment [AA] consists of a tetradeca-peptide as specified in column I of table 11.

[0127] In a further embodiment the oligopeptide consists of at most 15, of which at least 14 consecutive amino acids are identical to 14 consecutive amino acids of SEQ ID NO. 1. Thus in one embodiment of the invention, [AA] comprises 14 consecutive amino acids which are identical to 14 consecutive amino acids of SEQ ID NO.1 and has up to 1 further amino acids (resulting in a total number of 15 amino acids), whereas the further amino acids need not be identical to or even present in SEQ ID NO.1.

[0128] In this embodiment [AA] is thus [X_m-aa-Y_o], wherein aa is a tetradeca-peptide of table 1 and X and Y are further amino acids, m and 0 being numbers from a to 1, with the proviso that m+o is =1. In a preferred embodiment, aa is selected from the tetradeca-peptides as specified in column I of table 11.

[AA] Moiety: Pentadecapeptide

[0129] In one embodiment of the invention, [AA] consists of 15 consecutive amino acids, which are identical to 15 consecutive amino acids of SEQ ID NO.1.

[0130] Table 12 lists these pentadeca peptides:

TABLE-US-00012 25 pentadeca-peptides of 15 consecutive amino acids of SEQ ID NO. 1 SEQ ID NO. Column I SEQ ID NO. 341 Arg Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Column II SEQ ID NO. 342 Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Seq. ID NO. 343 Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe SEQ ID NO. 344 Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe SEQ ID NO. 345 Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro SEQ ID NO. 346 Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro SEQ ID NO. 347 Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg SEQ ID NO. 348 Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu SEQ ID NO. 349 Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro SEQ ID NO. 350 Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro SEQ ID NO. 351 Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg SEQ ID NO. 352 Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile SEQ ID NO. 353 Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro SEQ ID NO. 354 Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Seq. ID NO. 355 Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu SEQ ID NO. 356 Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe SEQ ID NO. 357 Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro SEQ ID NO. 358 Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro SEQ ID NO. 359 Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg SEQ ID NO. 360 Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe SEQ ID NO. 361 Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro SEQ ID NO. 362 Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro SEQ ID NO. 363 Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg SEQ ID NO. 364 Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe SEQ ID NO. 365 Ar~ Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe Pro

[0131] In a preferred embodiment [AA] consists of the pentadeca-peptide as specified in column I of table 12.

[AA] Moiety: Hexapeptides

[0132] In an embodiment [AA] comprises at least 6 amino acids, of which 4, preferably 5, more preferably 6 are identical compared to 6 consecutive amino acids of SEQ ID NO.1. Any possible 6 consecutive amino acids of SEQ ID NO.1 are listed in Table 3.

[0133] Thus in this embodiment of the invention, [AA] comprises at least 6 amino acids, of which at least 66.6%, preferably at least 83.3%, preferably 100% are identical to 6 consecutive amino acids of SEQ ID NO.1.

[0134] In a preferred embodiment [AA] comprises at least 6 amino acids, of which 4 amino acids, preferably 5 amino acids are identical compared to 6 consecutive amino acids of SEQ ID NO.1 and the position of the 4, respective 5 identical amino acids is also identical when compared to the respective positions of the 6 amino acids of SEQ ID NO.1.

[0135] Thus in this embodiment of the invention [AA] comprises at least 6 amino acids, of which at least 66.6%, preferably at least 83.3% are identical to 6 consecutive amino acids of SEQ ID NO.1 and the position of the 4, respective 5 identical amino acids is also identical when compared to the respective positions of the 6 amino acids of SEQ ID NO.1.

[0136] The following chart illustrates this embodiment of the invention. X and Yare further amino acids.

TABLE-US-00013 Position No. 1 2 3 4 5 6 SEQ Arg Arg Arg Pro Arg Pro ID NO. 1 [AAI Arg X Arg Y Arg Pro [AA] Arg Arg Arg Y Arg Pro

[0137] In a preferred embodiment [AA] comprises at least 6 amino acids, of which 4, preferably 5 are identical to 6 consecutive amino acids of column I of table 3.

[0138] In a further embodiment [AA] consists of 6 amino acids, of which 4, preferably 5, more preferably 6 are identical compared to 6 consecutive amino acids of SEQ ID NO.1. Any possible 6 consecutive amino acids of SEQ ID NO.1 are listed in Table 3.

[0139] Thus in this embodiment of the invention, [AA] consists of 6 amino acids, of which at least 66.6%, preferably at least 83.3%, more preferably 100% are identical to 6 consecutive amino acids of SEQ ID NO.1.

[0140] In a preferred embodiment [AA] consists of 6 amino acids, of which 4 amino acids, preferably 5 amino acids are identical compared to 6 consecutive amino acids of SEQ ID NO.1 and the position of the 4, respective 5 identical amino acids is also identical when compared to the respective position of the 6 amino acids of SEQ ID NO.1.

[0141] In a preferred embodiment [AA] consists of least 6 amino acids, of which 4, preferably 5 are identical to 6 consecutive amino acids of column I of table 3.

[0142] In a further embodiment [AA] consists of at most 15, preferably at most 10, more preferably at most 8 amino acids, of which 4 amino acids, preferably 5 amino acids, more preferably 6, are identical to 6 consecutive amino acids of SEQ ID NO.1.

[0143] In a further embodiment [AA] consists of at most 15, preferably at most 10, more preferably at most 8 amino acids, of which 4 amino acids, preferably 5 amino acids, are identical to 6 consecutive amino acids of SEQ ID NO.1 and the position of the 4, respective 5 amino acids is identical to the positions of respective amino acids of the 6 amino acids of SEQ ID NO. 1. In this embodiment of the invention, also the position of the 4, respective 5 amino acids is identical when compared to the respective positions of 6 consecutive amino acids of SEQ ID NO.1.

[AA] Moiety: Heptapeptides

[0144] In a further embodiment [AA] comprises at least 7 amino acids, of which 5, preferably 6, more preferably 7 are identical compared to 7 consecutive amino acids of SEQ ID NO.1. Any possible 7 consecutive amino acids of SEQ ID NO.1 are listed in Table 4.

[0145] Thus in this embodiment of the invention, [AA] comprises at least 7 amino acids, of which at least 71.4%, preferably at least 85.7%, preferably 100% are identical to 7 consecutive amino acids of SEQ ID NO.1.

[0146] In a preferred embodiment [AA] comprises at least 7 amino acids, of which 5 amino acids, preferably 6 amino acids are identical compared to 7 consecutive amino acids of SEQ ID NO.1 and the position of the 5, respective 6 identical amino acids is also identical when compared to the respective positions of the 7 amino acids of SEQ ID NO.1.

[0147] Thus in this embodiment of the invention [AA] comprises at least 7 amino acids, of which at least 71.4%, preferably at least 85.7% are identical to 7 consecutive amino acids of SEQ ID NO.1 and the position of the 5, respective 6 identical amino acids is also identical when compared to the respective positions of the 7 amino acids of SEQ ID NO.1.

[0148] In a preferred embodiment [AA] comprises at least 7 amino acids, of which 5, preferably 6 are identical to 7 consecutive amino acids of column I of table 4.

[0149] In a further embodiment [AA] consists of 7 amino acids, of which 5, preferably 6, preferably 7 are identical compared to 7 consecutive amino acids of SEQ ID NO.1. Any possible 7 consecutive amino acids of SEQ ID NO.1 are listed in table 4.

[0150] Thus in this embodiment of the invention, [AA] consists of 7 amino acids, of which at least 71.4%, preferably at least 85.7%, preferably 100% are identical to 7 consecutive amino acids of SEQ ID NO.1.

[0151] In a preferred embodiment [AA] consists of 7 amino acids, of which 5 amino acids, preferably 6 amino acids are identical compared to 7 consecutive amino acids of SEQ ID NO.1 and the position of the 5, respective 6 identical amino acids is also identical when compared to the respective position of the 7 amino acids of SEQ ID NO.1.

[0152] In a preferred embodiment (AA] consists of least 7 amino acids, of which 5, preferably 6 are identical to 7 consecutive amino acids of column I of table 4.

[0153] In a further embodiment [AA] consists of at most 15, preferably at most 10, more preferably at most 8 amino acids, of which 5, preferably 6, preferably 7 amino acids, are identical to 7 consecutive amino acids of SEQ ID NO.1.

[0154] In a further embodiment [AA] consists of at most 15, preferably at most 10, more preferably at most 8 amino acids, of which 5 amino acids, preferably 6 amino acids, are identical to 7 consecutive amino acids of SEQ ID NO.1 and the position of the 5, respective 6 amino acids is identical to the positions of respective amino acids of the 7 amino acids of SEQ ID no. 1. In this embodiment of the invention, also the position of the 5, respective 6 amino acids is identical when compared to the respective positions of 7 consecutive amino acids of SEQ ID NO.1.

[AA] Moiety: Octapeptides

[0155] In a further embodiment [AA] comprises at least 8 amino acids, of which 6, preferably 7, preferably 8 are identical compared to 8 consecutive amino acids of SEQ ID NO.1. Any possible 8 consecutive amino acids of SEQ ID NO.1 are listed in Table 5.

[0156] Thus in this embodiment of the invention, [AA] comprises at least 8 amino acids, of which at least 75%, preferably at least 87.5%, preferably 100% are identical to 8 consecutive amino acids of SEQ ID NO.1.

[0157] In a preferred embodiment [AA] comprises at least 8 amino acids, of which 6 amino acids, preferably 7 amino acids are identical compared to 8 consecutive amino acids of SEQ ID NO. 1 and the position of the 6, respective 7 identical amino acids is also identical when compared to the respective positions of the 8 amino acids of SEQ ID NO.1.

[0158] Thus in this embodiment of the invention [AA] comprises at least 8 amino acids, of which at least 75%, preferably at least 87.5% are identical to 8 consecutive amino acids of SEQ ID NO.1 and the position of the 6, respective 7 identical amino acids is also identical when compared to the respective positions of the 8 amino acids of SEQ ID NO.1.

[0159] In a preferred embodiment [AA] comprises at least 8 amino acids, of which 6, preferably 7 are identical to 8 consecutive amino acids of column I of table 5.

[0160] In a further embodiment [AA] consists of 8 amino acids, of which 6, preferably 7, preferably 8 are identical compared to 8 consecutive amino acids of SEQ ID NO.1. Any possible 8 consecutive amino acids of SEQ ID NO.1 are listed in table 5.

[0161] Thus in this embodiment of the invention, [AA] consists of 8 amino acids, of which at least 75%, preferably at least 87.5%, preferably 100% are identical to 8 consecutive amino acids of SEQ ID NO.1.

[0162] In a preferred embodiment [AA] consists of 8 amino acids, of which 6 amino acids, preferably 7 amino acids are identical compared to 8 consecutive amino acids of SEQ ID NO.1 and the position of the 6, respective 7 identical amino acids is also identical when compared to the respective position of the 8 amino acids of SEQ ID NO.1.

[0163] In a preferred embodiment [AA] consists of least 8 amino acids, of which 6, preferably 7 are identical to 8 consecutive amino acids of column I of table 5.

[0164] In a further embodiment [AA] consists of at most 15, preferably at most 10, more preferably at most 9 amino acids, of which 6, preferably 7, preferably 8 amino acids, are identical to 8 consecutive amino acids of SEQ ID NO.1.

[0165] In a further embodiment [AA] consists of at most 15, preferably at most 10, more preferably at most 9 amino acids, of which 6 amino acids, preferably 7 amino acids, are identical to 8 consecutive amino acids of SEQ ID NO.1 and the position of the 6, respective 7 amino acids is identical to the positions of respective amino acids of the 8 amino acids of SEQ ID no. 1. In this embodiment of the invention, also the position of the 6, respective 7 amino acids is identical when compared to the respective positions of 8 consecutive amino acids of SEQ ID NO.1.

[AA] Moiety: Nonapeptides

[0166] In a further embodiment [AA] comprises at least 9 amino acids, of which 6, preferably 7, more preferably 8, more preferably 9 amino acids are identical compared to 9 consecutive amino acids of SEQ ID NO.1. Any possible 9 consecutive amino acids of SEQ ID NO.1 are listed in Table 6.

[0167] Thus in this embodiment of the invention, [AA] comprises at least 9 amino acids, of which at least 66.6%, preferably at least 77.7%, more preferably at least 88.8%, more preferably 100% are identical to 9 consecutive amino acids of SEQ ID NO.1.

[0168] In a preferred embodiment [AA] comprises at least 9 amino acids, of which 6 amino acids, preferably 7 amino acids, more preferably 8 amino acids are identical compared to 9 consecutive amino acids of SEQ ID NO.1 and the position of the 6, respective 7 or 8 identical amino acids is also identical when compared to the respective positions of the 9 amino acids of SEQ ID NO.1.

[0169] Thus in this embodiment of the invention [AA] comprises at least 9 amino acids, of which at least 66.6%, preferably at least 77.7%, more preferably at least 88.8% are identical to 9 consecutive amino acids of SEQ ID NO.1 and the position of the 6, respective 7 or 8 identical amino acids is also identical when compared to the respective positions of the 9 amino acids of SEQ ID NO.1.

[0170] In a preferred embodiment [AA] comprises at least 9 amino acids, of which 6, preferably 7, more preferably 8 are identical to 9 consecutive amino acids of column I of table 6.

[0171] In a further embodiment [AA] consists of 9 amino acids, of which 6, preferably 7, more preferably 8, more preferably 9, are identical compared to 9 consecutive amino acids of SEQ ID NO.1. Any possible 9 consecutive amino acids of SEQ ID NO.1 are listed in table 6.

[0172] Thus in this embodiment of the invention, [AA] consists of 9 amino acids, of which at least 66.6%, preferably at least 77.7%, more preferably at least 88.8%, more preferably 100% are identical to 9 consecutive amino acids of SEQ ID NO.1.

[0173] In a preferred embodiment [AA] consists of 9 amino acids, of which 6 amino acids, preferably 7 amino acids, more preferably 8 amino acids are identical compared to 9 consecutive amino acids of SEQ ID NO.1 and the position of the 6, respective 7 or 8 identical amino acids is also identical when compared to the respective position of the 9 amino acids of SEQ ID NO.1.

[0174] In a preferred embodiment [AA] consists of least 9 amino acids, of which 6, preferably 7, more preferably 8 are identical to 9 consecutive amino acids of column I of table 6.

[0175] In a further embodiment [AA] consists of at most 15, preferably at most 12, more preferably at most 10 amino acids, of which 6, preferably 7, more preferably 8, more preferably 9 amino acids are identical to 9 consecutive amino acids of SEQ ID NO.1.

[0176] In a further embodiment [AA] consists of at most 15, preferably at most 12, more preferably at most 10 amino acids, of which 6 amino acids, preferably 7, more preferably 8 amino acids, are identical to 9 consecutive amino acids of SEQ ID NO. 1 and the position of the 6, respective 7 or 8 amino acids is identical to the positions of respective amino acids of the 9 amino acids of SEQ ID NO.1. In this embodiment of the invention, also the position of the 6, respective 7 or 8 amino acids is identical when compared to the respective positions of 9 consecutive amino acids of SEQ ID NO.1.

[AA] Moiety: Decapeptides

[0177] In a further embodiment [AA] comprises at least 10 amino acids, of which 7, preferably 8, more preferably 9, more preferably 10 amino acids are identical compared to 10 consecutive amino acids of SEQ ID NO.1. Any possible 10 consecutive amino acids of SEQ ID NO.1 are listed in Table 7.

[0178] Thus in this embodiment of the invention, [AA] comprises at least 10 amino acids, of which at least 70%, preferably at least 80%, more preferably at least 90%, more preferably 100% are identical to 10 consecutive amino acids of SEQ ID NO.1.

[0179] In a preferred embodiment [AA] comprises at least 10 amino acids, of which 7 amino acids, preferably 8 amino acids, more preferably 9 amino acids are identical compared to 10 consecutive amino acids of SEQ ID NO.1 and the position of the 7, respective 8 or 9 identical amino acids is also identical when compared to the respective positions of the 10 amino acids of SEQ ID NO.1.

[0180] Thus in this embodiment of the invention [AA] comprises at least 10 amino acids, of which at least 70%, preferably at least 80%, more preferably at least 90% are identical to 10 consecutive amino acids of SEQ ID NO.1 and the position of the 7, respective 8 or 9 identical amino acids is also identical when compared to the respective positions of the 10 amino acids of SEQ ID NO.1.

[0181] In a preferred embodiment [AA] comprises at least 10 amino acids, of which 7, preferably 8, more preferably 9 are identical to 10 consecutive amino acids of column I of table 7.

[0182] In a further embodiment [AA] consists of 10 amino acids, of which 7, preferably 8, more preferably 9, more preferably 10 are identical compared to 10 consecutive amino acids of SEQ ID NO.1. Any possible 10 consecutive amino acids of SEQ ID NO.1 are listed in table 7.

[0183] Thus in this embodiment of the invention, [AA] consists of 10 amino acids, of which at least 70%, preferably at least 80%, more preferably at least 90%, more preferably 100% are identical to 10 consecutive amino acids of SEQ ID NO.1.

[0184] In a preferred embodiment [AA] consists of 10 amino acids, of which 7 amino acids, preferably 8 amino acids, more preferably 9 amino acids are identical compared to 10 consecutive amino acids of SEQ ID NO.1 and the position of the 7, respective 8 or 9 identical amino acids is also identical when compared to the respective position of the 10 amino acids of SEQ ID NO.1.

[0185] In a preferred embodiment [AA] consists of least 10 amino acids, of which 7, preferably 8, more preferably 9 are identical to 10 consecutive amino acids of column I of table 7.

[0186] In a further embodiment [AA] consists of at most 15, preferably at most 14, more preferably at most 12 amino acids, of which, preferably 8, more preferably 9, more preferably 10 amino acids, are identical to 10 consecutive amino acids of SEQ ID NO. 1.

[0187] In a further embodiment [AA] consists of at most 15, preferably at most 14, more preferably at most 12 amino acids, of which 7 amino acids, preferably 8, more preferably 9 amino acids, are identical to 10 consecutive amino acids of SEQ ID NO. 1 and the position of the 7, respective 8 or 9 amino acids is identical to the positions of respective amino acids of the 10 amino acids of SEQ ID NO.1. In this embodiment of the invention, also the position of the 7, respective 8 or 9 amino acids is identical when compared to the respective positions of 10 consecutive amino acids of SEQ ID NO.1.

[AA] Moiety: Undecapeptides

[0188] In a further embodiment [AA] comprises at least 11 amino acids, of which 8, preferably 9, more preferably 10, more preferably 11 amino acids are identical compared to 11 consecutive amino acids of SEQ ID NO.1. Any possible 11 consecutive amino acids of SEQ ID NO.1 are listed in Table 8.

[0189] Thus in this embodiment of the invention, [AA] comprises at least 11 amino acids, of which at least 72.7%, preferably at least 81.8%, more preferably at least 90.9%, more preferably 100% are identical to 11 consecutive amino acids of SEQ ID NO.1.

[0190] In a preferred embodiment [AA] comprises at least 11 amino acids, of which 8 amino acids, preferably 9 amino acids, more preferably 10 amino acids are identical compared to 11 consecutive amino acids of SEQ ID NO.1 and the position of the 8, respective 9 or 10 identical amino acids is also identical when compared to the respective positions of the 11 amino acids of SEQ ID NO.1.

[0191] Thus in this embodiment of the invention [AA] comprises at least 11 amino acids, of which at least 72.7%, preferably at least 81.8%, more preferably at least 90.9% are identical to 11 consecutive amino acids of SEQ ID NO.1 and the position of the 8, respective 9 or 10 identical amino acids is also identical when compared to the respective positions of the 11 amino acids of SEQ ID NO.1.

[0192] In a preferred embodiment [AA] comprises at least 11 amino acids, of which 8, preferably 9, more preferably 10 are identical to 11 consecutive amino acids of column I of table 8.

[0193] In a further embodiment [AA] consists of 11 amino acids, of which 8, preferably 9, more preferably 10, more preferably 11 are identical compared to 11 consecutive amino acids of SEQ ID NO.1. Any possible 11 consecutive amino acids of SEQ ID NO.1 are listed in table 8.

[0194] Thus in this embodiment of the invention, [AA] consists of 11 amino acids, of which at least 72.7%, preferably at least 81.8%, more preferably at least 90.9%, more preferably 100% are identical to 11 consecutive amino acids of SEQ ID NO.1.

[0195] In a preferred embodiment [AA] consists of 11 amino acids, of which 8 amino acids, preferably 9 amino acids, more preferably 10 amino acids are identical compared to 11 consecutive amino acids of SEQ ID NO. 1 and the position of the 8, respective 9 or 10 identical amino acids is also identical when compared to the respective position of the 11 amino acids of SEQ ID NO.1.

[0196] In a preferred embodiment [AA] consists of least 11 amino acids, of which 8, preferably 9, more preferably 10 are identical to 11 consecutive amino acids of column I of table 8.

[0197] In a further embodiment [AA] consists of at most 15, preferably at most 14, more preferably at most 12 amino acids, of which 8, preferably 9, more preferably 10, more preferably 11 amino acids, are identical to 11 consecutive amino acids of SEQ ID NO. 1.

[0198] In a further embodiment [AA] consists of at most 15, preferably at most 14, more preferably at most 12 amino acids, of which 8 amino acids, preferably 9, more preferably 10 amino acids, are identical to 11 consecutive amino acids of SEQ ID NO. 1 and the position of the 8, respective 9 or 10 amino acids is identical to the positions of respective amino acids of the 11 amino acids of SEQ ID NO.1. In this embodiment of the invention, also the position of the 8, respective 9 or 10 amino acids is identical when compared to the respective positions of 11 consecutive amino acids of SEQ ID NO.1.

[AA] Moiety: Dodecapeptides

[0199] In a further embodiment [AA] comprises at least 12 amino acids, of which 8, preferably 9, more preferably 10, most preferably 11, most preferably 12 amino acids are identical compared to 12 consecutive amino acids of SEQ ID NO.1. Any possible 12 consecutive amino acids of SEQ ID NO.1 are listed in Table 9.

[0200] Thus in this embodiment of the invention, [AA] comprises at least 12 amino acids, of which at least 66.6%, preferably at least 75%, more preferably at least 83.3%, most preferably at least 91.6%, most preferably 100% are identical to 12 consecutive amino acids of SEQ ID NO.1.

[0201] In a preferred embodiment [AA] comprises at least 12 amino acids, of which 8 amino acids, preferably 9 amino acids, more preferably 10, most preferably 11 amino acids are identical compared to 12 consecutive amino acids of SEQ ID NO. 1 and the position of the 8, respective 9 or 10 or 11 identical amino acids is also identical when compared to the respective positions of the 12 amino acids of SEQ ID NO.1.

[0202] Thus in this embodiment of the invention [AA] comprises at least 12 amino acids, of which at least 66.6%, preferably at least 75%, more preferably at least 83.3%, most preferably at least 91.6% are identical to 12 consecutive amino acids of SEQ ID NO.1 and the position of the 8, respective 9 or 10 or 11 identical amino acids is also identical when compared to the respective positions of the 12 amino acids of SEQ ID NO.1.

[0203] In a preferred embodiment [AA] comprises at least 12 amino acids, of which 8, preferably 9, more preferably 10, most preferably 11 are identical to 12 consecutive amino acids of column I of table 9.

[0204] In a further embodiment [AA] consists of 12 amino acids, of which 8, preferably 9, more preferably 10, most preferably 11, most preferably 12 are identical compared to 12 consecutive amino acids of SEQ ID NO.1. Any possible 12 consecutive amino acids of SEQ ID NO.1 are listed in table 9.

[0205] Thus in this embodiment of the invention, [AA] consists of 12 amino acids, of which at least 66.6%, preferably at least 75%, more preferably at least 83.3%, most preferably at least 91.6%, most preferably 100% are identical to 12 consecutive amino acids of SEQ ID NO.1.

[0206] In a preferred embodiment [AA] consists of 12 amino acids, of which 8 amino acids, preferably 9 amino acids, more preferably 10 amino acids, most preferably 11 amino acids are identical compared to 12 consecutive amino acids of SEQ ID NO. 1 and the position of the 8, respective 9 or 10 or 11 identical amino acids is also identical when compared to the respective position of the 12 amino acids of SEQ ID NO.1.

[0207] In a preferred embodiment [AA] consists of least 12 amino acids, of which 8, preferably 9, more preferably 10, most preferably 11 are identical to 12 consecutive amino acids of column I of table 9.

[0208] In a further embodiment [AA] consists of at most 15, preferably at most 14, more preferably at most 13 amino acids, of which 8, preferably 9, more preferably 10, most preferably 11, most preferably 12 amino acids, are identical to 12 consecutive amino acids of SEQ ID NO.1.

[0209] In a further embodiment [AA] consists of at most 15, preferably at most 14, more preferably at most 13 amino acids, of which 8 amino acids, preferably 9, more preferably 10, most preferably 11 amino acids, are identical to 12 consecutive amino acids of SEQ ID NO.1 and the position of the 8, respective 9 or 10 or 11 amino acids is identical to the positions of respective amino acids of the 12 amino acids of SEQ ID NO.1. In this embodiment of the invention, also the position of the 8, respective 9 or 10 or 11 amino acids is identical when compared to the respective positions of 12 consecutive amino acids of SEQ ID NO.1.

[AA] Moiety: Tridecapeptides

[0210] In a further embodiment [AA] comprises at least 13 amino acids, of which 9, preferably 10, more preferably 11, most preferably 12, most preferably 13 amino acids are identical compared to 13 consecutive amino acids of SEQ ID NO.1. Any possible 13 consecutive amino acids of SEQ ID NO.1 are listed in Table 10.

[0211] Thus in this embodiment of the invention, [AA] comprises at least 13 amino acids, of which at least 69.2%, preferably at least 76.9%, more preferably at least 84.6%, most preferably at least 92.3%, most preferably 100% are identical to 13 consecutive amino acids of SEQ ID NO.1.

[0212] In a preferred embodiment [AA] comprises at least 13 amino acids, of which 9 amino acids, preferably 10 amino acids, more preferably 11, most preferably 12 amino acids are identical compared to 13 consecutive amino acids of SEQ ID NO.1 and the position of the 9, respective 10, 11 or 12 identical amino acids is also identical when compared to the respective positions of the 13 amino acids of SEQ ID NO.1.

[0213] Thus in this embodiment of the invention [AA] comprises at least 13 amino acids, of which at least 69.2%, preferably at least 76.9%, more preferably at least 84.6%, most preferably at least 92.3% are identical to 13 consecutive amino acids of SEQ ID NO.1 and the position of the 9, respective 10 or 11 or 12 identical amino acids is also identical when compared to the respective positions of the 13 amino acids of SEQ ID NO.1.

[0214] In a preferred embodiment [AA] comprises at least 13 amino acids, of which 9, preferably 10, more preferably 11, most preferably 12 are identical to 13 consecutive amino acids of column I of table 10.

[0215] In a further embodiment [AA] consists of 13 amino acids, of which 9, preferably 10, more preferably 11, most preferably 12, more preferably 13 are identical compared to 13 consecutive amino acids of SEQ ID NO.1. Any possible 13 consecutive amino acids of SEQ ID NO.1 are listed in table 10.

[0216] Thus in this embodiment of the invention, [AA] consists of 13 amino acids, of which at least 69.2%, preferably at least 76.9%, more preferably at least 84.6%, most preferably at least 92.3%, most preferably 100% are identical to 13 consecutive amino acids of SEQ ID NO.1.

[0217] In a preferred embodiment [AA] consists of 13 amino acids, of which 9 amino acids, preferably 10 amino acids, more preferably 11 amino acids, most preferably 12 amino acids are identical compared to 13 consecutive amino acids of SEQ ID NO.1 and the position of the 9, respective 10 or 11 or 12 identical amino acids is also identical when compared to the respective position of the 13 amino acids of SEQ ID NO.1.

[0218] In a preferred embodiment [AA] consists of least 13 amino acids, of which 9, preferably 10, more preferably 11, most preferably 12 are identical to 13 consecutive amino acids of column I of table 10.

[0219] In a further embodiment [AA] consists of at most 15, preferably at most 14, of which 9, preferably 10, more preferably 11, most preferably 12, most preferably 13 amino acids, are identical to 13 consecutive amino acids of SEQ ID NO.1.

[0220] In a further embodiment [AA] consists of at most 15, preferably at most 14, of which 9 amino acids, preferably 10, more preferably 11, most preferably 12 amino acids, are identical to 13 consecutive amino acids of SEQ ID NO.1 and the position of the 9, respective 10 or 11 or 12 amino acids is identical to the positions of respective amino acids of the 13 amino acids of SEQ ID NO.1. In this embodiment of the invention, also the position of the 9, respective 10 or 11 or 12 amino acids is identical when compared to the respective positions of 13 consecutive amino acids of SEQ ID NO.1.

[AA] Moiety: Tetradecapeptides

[0221] In a further embodiment [AA] comprises at least 14 amino acids, of which 10, preferably 11, more preferably 12, most preferably 13, most preferably 14 amino acids are identical compared to 14 consecutive amino acids of SEQ ID NO.1. Any possible 14 consecutive amino acids of SEQ ID NO.1 are listed in Table 11.

[0222] Thus in this embodiment of the invention, [AA] comprises at least 14 amino acids, of which at least 71.4%, preferably at least 78.6%, more preferably at least 85.7%, most preferably at least 92.9%, most preferably 100% are identical to 14 consecutive amino acids of SEQ ID NO.1.

[0223] In a preferred embodiment [AA] comprises at least 14 amino acids, of which 10 amino acids, preferably 11 amino acids, more preferably 12, most preferably 13 amino acids are identical compared to 14 consecutive amino acids of SEQ ID NO.1 and the position of the 10, respective 11, 12 or 13 identical amino acids is also identical when compared to the respective positions of the 14 amino acids of SEQ ID NO.1.

[0224] Thus in this embodiment of the invention [AA] comprises at least 14 amino acids, of which at least 71.4%, preferably at least 78.6%, more preferably at least 85.7%, most preferably at least 92.9% are identical to 14 consecutive amino acids of SEQ ID NO.1 and the position of the 10, respective 11, 12 or 13 identical amino acids is also identical when compared to the respective positions of the 14 amino acids of SEQ ID NO.1.

[0225] In a preferred embodiment [AA] comprises at least 14 amino acids, of which 10, preferably 11, more preferably 12, most preferably 13 are identical to 14 consecutive amino acids of column I of table 11.

[0226] In a further embodiment [AA] consists of 14 amino acids, of which 10, preferably 11, more preferably 12, most preferably 13, most preferably 14 are identical compared to 14 consecutive amino acids of SEQ ID NO.1. Any possible 14 consecutive amino acids of SEQ ID NO.1 are listed in table 11.

[0227] Thus in this embodiment of the invention, [AA] consists of 14 amino acids, of which at least 71.4%, preferably at least 78.6%, more preferably at least 85.7%, most preferably at least 92.9%, most preferably 100% are identical to 14 consecutive amino acids of SEQ ID NO.1.

[0228] In a preferred embodiment [AA] consists of 14 amino acids, of which 10 amino acids, preferably 11 amino acids, more preferably 12 amino acids, most preferably 13 amino acids are identical compared to 14 consecutive amino acids of SEQ ID NO.1 and the position of the 10, respective 11 or 12 or 13 identical amino acids is also identical when compared to the respective position of the 14 amino acids of SEQ ID NO.1.

[0229] In a preferred embodiment [AA] consists of 14 amino acids, of which 10, preferably 11, more preferably 12, most preferably 13 are identical to 14 consecutive amino acids of column I of table 11.

[0230] In a further embodiment [AA] consists of at most 15, preferably at most 14, of which 10 amino acids, preferably 11, more preferably 12, most preferably 13, most preferably 14 amino acids, are identical to 14 consecutive amino acids of SEQ ID NO. 1.

[0231] In a further embodiment [AA] consists of at most 15, preferably at most 14, of which 10 amino acids, preferably 11, more preferably 12, most preferably 13 amino acids, are identical to 14 consecutive amino acids of SEQ ID NO.1 and the position of the 10, respective 11, 12 or 13 amino acids is identical to the positions of respective amino acids of the 14 amino acids of SEQ ID NO.1. In this embodiment of the invention, also the position of the 10, respective 11 or 12 or 13 amino acids is identical when compared to the respective positions of 14 consecutive amino acids of SEQ ID NO.1.

[AA] Moiety: Pentadecapeptides

[0232] In a further embodiment [AA] consists of 15 amino acids, of which 10, preferably 11, more preferably 12, most preferably 13, most preferably 14, most preferably 15 amino acids are identical compared to 15 consecutive amino acids of SEQ ID NO.1.

[0233] Any possible 15 consecutive amino acids of SEQ ID NO.1 are listed in Table 12. Thus in this embodiment of the invention, [AA] consists of 15 amino acids, of which at least 66.6%, preferably at least 73.3%, more preferably at least 80%, most preferably at least 86.7%, most preferably at least 93.3%, most preferably 100% are identical to 15 consecutive amino acids of SEQ ID NO.1.

[0234] In a preferred embodiment [AA] consists of 15 amino acids, of which 10 amino acids, preferably 11 amino acids, more preferably 12, most preferably 13, most preferably 14 amino acids are identical compared to 15 consecutive amino acids of SEQ ID NO.1 and the position of the 10, respective 11, 12, 13 or 14 identical amino acids is also identical when compared to the respective positions of the 15 amino acids of SEQ ID NO.1.

[0235] Thus in this embodiment of the invention [AA] consists of 15 amino acids, of which at least 66.6%, preferably at least 73.3%, more preferably at least 80%, most preferably at least 86.7%, most preferably at least 93.3% are identical to 15 consecutive amino acids of SEQ ID NO.1 and the position of the 10, respective 11, 12, 13 or 14 identical amino acids is also identical when compared to the respective positions of the 15 amino acids of SEQ ID NO.1.

[0236] In a preferred embodiment [AA] consists of 15 amino acids, of which 10, preferably 11, more preferably 12, most preferably 13, most preferably 14, most preferable 15 are identical to 15 consecutive amino acids of column I of table 12.

[AA] Moiety Pentapeptides

[0237] In a preferred embodiment [AA] comprises at least 5 amino acids, of which 4 amino acids, preferably 5 amino acids are identical compared to 5 consecutive amino acids of SEQ ID NO.1 and the position of the 4, respective 5 identical amino acids is also identical when compared to the respective positions of the 5 amino acids of SEQ ID NO.1. Any possible 5 consecutive amino acids of SEQ ID NO.1 are listed in Table 2.

[0238] Thus in this embodiment of the invention [AA] comprises at least 5 amino acids, of which at least 70%, preferably 100% are identical to 5 consecutive amino acids of SEQ ID NO.1 and the position of the 4, respective 5 identical amino acids is also identical when compared to the respective positions of the 5 amino acids of SEQ ID NO.1, preferably when compared to 5 consecutive amino acids of column I of table 2.

[0239] In a preferred embodiment [AA] consists of 5 amino acids, of which 4 amino acids, preferably 5 amino acids are identical compared to 5 consecutive amino acids of SEQ ID NO.1 and the position of the 4, respective 5 identical amino acids is also identical when compared to the respective position of the 6 amino acids of SEQ ID NO.1, preferably when compared to 5 consecutive amino acids of column I of table 2.

[0240] In a further embodiment [AA] consists of at most 15, preferably at most 10, more preferably at most 8 amino acids, of which 4 amino acids, preferably 5 amino acids, are identical to 5 consecutive amino acids of SEQ ID NO.1 and the position of the 4, respective 5 identical amino acids is also identical when compared to the respective positions of the 5 amino acids of SEQ ID NO.1, preferably when compared to 5 consecutive amino acids of column I of table 2.

[0241] In a further embodiment [AA] consists of at most 15, preferably at most 10, more preferably at most 8 amino acids, of which 4 amino acids, preferably 5 amino acids, are identical to 5 consecutive amino acids of SEQ ID NO.1 and the position of the 4, respective 5 amino acids is identical to the positions of respective amino acids of the 5 amino acids of SEQ ID NO. 1, preferably when compared to 5 consecutive amino acids of column I of table 2.

R1 Moiety

[0242] The amino-terminal part of [AA] is linked via R1. R1 is chosen from the group consisting of [0243] a) --H [0244] b) is a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24 carbon atoms, which may be functionalised by a --OH, SH, --COOH or --CONH₂ group, or [0245] c) a sterol or a sphingolipid group which is joined to the amino terminal part of [AA] via a bifunctional linker.

[0246] In embodiment a) the amino terminal is not substituted but consists of an amino group. It is within the scope of the invention that, in case R1=H, the oligopeptide of the invention can be protonated, and be present as salt, e.g. as chloride, bromide, fluoride or iodide.

[0247] In a preferred embodiment of the invention R1 is a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24 carbon atoms, preferably 1 to 6, preferably 1 to 12, preferably 10 to 20, more preferably 12 to 18 carbon atoms.

[0248] The radical R1 is preferably chosen from the group which is formed by acetyl (CH₃CO--), ethanoyl (CH₃--CH₂--CO--), propionyl, butanoyl (=butyryl; CH₃--(CH₂)₂--CO--), decanoyl, palmitoyl (CH₃--(CH₂)₁₄--CO--), stearoyl (CH₃--(CH₂)₁₆--CO--), oleyl, lipoyl, linoleyl or conjugated linoleyl, particularly preferable the group is acetyl.

[0249] In one embodiment of the invention the acyl group can be further functionalised by one or more of the functional groups selected from the group consisting of --OH, --SH, --COOH and --CONH₂.

[0250] In one embodiment of the invention R1 is a sterol group. The sterol group can be selected from plant sterol or from sterol of animal origin.

[0251] Sterols in the context of the invention are steroids which only contain a hydroxyl group but no other functional groups at C-3. Formally, therefore, they are alcohols which is why this group of compounds is also referred to occasionally as sterols. In general, sterols contain from about 27 to about 30 carbon atoms and one double bond in the 5/6 position and occasionally in the 7/8, 8/9 or other positions. Sterols which may be used for the purposes of the invention are those obtained from natural products such as, for example, soya, rapeseed, sunflower, coconut, palm kernel and palm oil. Preferred sterols are sigmasterol, campesterol, sitosterol, brassicasterots, stigmasterol, D5 avenasterol, D7 avenasterol, ergosterol, citrostadienol, cholesterol, lanosterols, spongosterols, fungisterols, stellasterols, zymosterols and mixtures thereof and, more particularly, phytosterols based on ergosterols, avenasterols (D5 and D7 avenasterol), campesterols, stigmasterols, sitosterols, brassicasterols, citrosdandiols, sigmastandiols and mixtures thereof. Any other phytosterols known to the expert may also be used.

[0252] In a preferred embodiment the sterol group is selected from the group consisting of cholesterol, stigmasterol, sitosterol, or brassicasterol.

[0253] In one embodiment R1 is a sphingolipid, preferably sphingolipids are selected from the group consisting of sphingosine, phytosphingosine, dehydrosphingosine or deshuydrophytosphingosine.

##STR00001##

[0254] The sterol or the sphingolipide are linked to the oligopeptides using a bifunctional linker such as a diacid, for example succinic acid. The sterol hydroxyl group at C-3 can be linked via an ester bond to the bifunctional linker, with can be linked via an amide bond to the amino-terminal part of [AA]. The sphingolipid amino group at C-1 can be linked via an amide bond to the bifunctional linker, which can be linked via an amide bond to the amino-terminal part of [AA].

R2 Moiety

[0255] The carboxy terminal part of [AA] is linked via the 0=0 group of the carboxy terminal amino acids of [AA] and is chosen from the group which consists of [0256] a) --OH [0257] b) --NH₂ [0258] c) a linear saturated or unsaturated or branched saturated or unsaturated alkoxy group having 1 to 24 carbon atoms, which may be functionalised by a --OH, --SH, --COOH or --CONH₂ group, or [0259] d) a sterol or a sphingolipid group.

[0260] In embodiment a) the carboxy terminal is not substituted but consists of a free carboxy group. It is within the scope of the invention that, in case R2=OH, the carboxygroup of the oligopeptide of the invention can be deprotonated, and be present as salt, e.g. as potassium or sodium salt.

[0261] In embodiment b) the carboxy terminal is linked to an amino group. It is within the scope of the invention, that, in case R2=NH₂, the NH₂ group of can be protonated, and be present as a salt, e.g. as chloride, bromide, fluoride or iodide.

[0262] In a preferred embodiment of the invention R2 is a linear saturated or unsaturated or branched saturated or unsaturated alkoxy group having 1 to 24 carbon atoms, preferably 1 to 6, preferably 10 to 20, more preferably 12 to 18 carbon atoms.

[0263] In one embodiment of the invention the alkoxy group can be further functionalised by one or more of the functional groups selected from the group consisting of --OH, --SH, --COOH and --CONH₂.

[0264] In one embodiment of the invention R2 is a sterol. Suitable sterols are described under "R1 moieties". The sterol is linked to the C═O group of the carboxy terminus of [AA] via the 3-hydroxy group, thus resulting in an ester.

[0265] In one embodiment of the invention R1 is a sphingolipid. Suitable sphingolipids are described under "R2 moieties". The sphingolipid is linked to via its amino group to the terminal 0=0 group of the carboxy terminus of [AA], resulting in an amide.

Preferred Oligopeptides

[0266] Preferred oligopeptides according to the invention are oligopeptides with the structure of formula (I) wherein R1=a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl), which may be functionalised by a --OH, --SH, --COOH or --CONH₂ group.

[0267] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a tetra peptide as specified in table 1, preferably column I of table 1 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl).

[0268] Especially preferred are oligopeptides of formula (I), wherein [AA] consist of a tetrapeptide selected from the group consisting of [0269] i) Arg Arg Arg Pro (SEQ ID NO. 2); Arg Arg Pro Arg (SEQ ID NO. 3); [0270] ii) Arg Pro Pro Tyr (SEQ ID NO. 6); Pro Pro Tyr Leu (SEQ ID NO. 7); preferably Pro Pro Tyr Leu (SEQ ID NO.7); [0271] iii) Pro Tyr Leu Pro (Seq. ID NO. 8); Tyr Leu Pro Arg (SEQ ID NO. 9); or [0272] iv) Tyr Leu Pro Arg (Seq. ID NO. 9); Leu Pro Arg Pro (SEQ ID NO. 10); and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl).

[0273] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a tetra peptide as specified in table 1, preferably column I of table 1 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl) and R2=--OH.

[0274] Especially preferred are oligopeptides of formula (I), wherein [AA] consist of a tetrapeptide selected from the group consisting of [0275] i) Arg Arg Arg Pro (SEQ ID NO.2); Arg Arg Pro Arg (SEQ ID NO.3); [0276] ii) Arg Pro Pro Tyr (SEQ ID NO.6); Pro Pro Tyr Leu (SEQ ID NO.7); preferably Pro Pro Tyr Leu (SEQ ID NO.7); [0277] iii) Pro Tyr Leu Pro (Seq. ID NO. 8); Tyr Leu Pro Arg (SEQ ID NO. 9); or [0278] iv) Tyr Leu Pro Arg (SEQ ID NO. 9); Leu Pro Arg Pro (SEQ ID NO. 10); and wherein R1=acetyl and R2=OH.

[0279] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a penta peptide as specified in table 2, preferably column I of table 2 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl).

[0280] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] is selected from the group consisting of Arg Arg Arg Pro Arg (SEQ ID NO. 38); Arg Pro Pro Tyr Leu (SEQ ID NO. 42); Pro Tyr Leu Pro Arg (SEQ ID NO. 44); or Tyr Leu Pro Arg Pro (SEQ ID NO. 45); and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl).

[0281] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a penta peptide as specified in table 2, preferably column I of table 2 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl) and R2=--OH.

[0282] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] is selected from the group consisting of Arg Arg Arg Pro Arg (SEQ ID NO. 38); Arg Pro Pro Tyr Leu (SEQ ID NO. 42); Pro Tyr Leu Pro Arg (SEQ ID NO. 44); and Tyr Leu Pro Arg Pro (SEQ ID NO. 45); and wherein R1=acetyl and R2=OH.

[0283] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a hexa peptide as specified in table 3, preferably column I of table 3 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl).

[0284] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a hexa peptide as specified in table 3, preferably column I of table 3 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl) and R2=--OH.

[0285] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a hepta peptide as specified in table 4, preferably column I of table 4 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl).

[0286] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a hepta peptide as specified in table 4, preferably column I of table 4 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl) and R2=--OH.

[0287] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of an octa peptide as specified in table 5, preferably column I of table 5 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl).

[0288] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of an acta peptide as specified in table 5, preferably column I of table 5 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl) and R2=--OH.

[0289] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a nona peptide as specified in table 6, preferably column I of table 6 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl).

[0290] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a nona peptide as specified in table 6, preferably column I of table 6 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl) and R2=--OH.

[0291] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a deca peptide as specified in table 7, preferably column I of table 7 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl).

[0292] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a deca peptide as specified in table 7, preferably column I of table 7 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl) and R2=--OH.

[0293] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of an undeca peptide as specified in table 8, preferably column I of table 8 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl).

[0294] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of an undeca peptide as specified in table 8, preferably column I of table 8 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl) and R2=--OH.

[0295] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of an dodeca peptide as specified in table 9, preferably column I of table 9 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl).

[0296] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of an dodeca peptide as specified in table 9, preferably column I of table 9 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl) and R2=--OH.

[0297] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a trideca peptide as specified in table 10, preferably column I of table 10 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl).

[0298] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a trideca peptide as specified in table 10, preferably column I of table 10 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl) and R2=--OH.

[0299] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a tetradeca peptide as specified in table 11, preferably column I of table 11 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl).

[0300] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a tetradeca peptide as specified in table 11, preferably column I of table 11 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl) and R2=--OH.

[0301] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a pentadeca peptide as specified in table 12, preferably column I of table 11 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl).

[0302] Preferred according to the invention are oligopeptides of formula (I), wherein [AA] consists of a pentadeca peptide as specified in table 12, preferably column I of table 12 and R1 is selected from a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24, preferably 1 to 12 carbon atoms, preferably 1 to 6, most preferably 2 (=acetyl) and R2=--OH.

[0303] In a preferred embodiment of the invention n is at least 4, preferably at least 5; [AA] is selected from the amino acids no. 1 to 15 of SEQ ID NO.1, preferably from the amino acids no. 1-5, preferably from the amino acids 5-9, more preferably from the amino acids 6-9, preferably from the amino acids 7-11, more preferably from the amino acids 8-12 of SEQ ID NO.1.

Oligopeptides of Formula (II)

[0304] One embodiment of the invention is directed to the cosmetic use of oligopeptides of structure (II) for stimulating the renewal rate of skin and/or hair. They are preferably useful cosmetic preparations against the reduction in cell numbers in human skin or for stimulating and/or regenerating hair growth and against hair loss.

[0305] In one embodiment, the oligopeptide according to the formula (II) are especially useful for the cosmetic treatment of [0306] l. human skin or hair ageing and/or [0307] m. for preventing against ageing symptoms, such as wrinkles, and/or [0308] n. decrease of the epidermal and dermal skin layers, and/or [0309] o. alterations of the extracellular matrix and/or decrease in the renewal of epidermal and dermal cells and/or [0310] p. modifications of the dermal epidermal junctions and/or [0311] q. loss of elasticity and/or [0312] r. hair damages and/or hair losses.

[0313] In one embodiment, the oligopeptides are preferably useful for [0314] s. stimulation of the renewal rate of human skin and/or hair.

[0315] In a preferred embodiment, the oligopeptides are used for [0316] t. producing cosmetic preparations which are effective for stimulating the production of mRNA and/or [0317] u. for stimulation of matrix proteins such as collagen, elastin or proteoglycans and/or [0318] v. for stimulation of syndecan-1 synthesis

[0319] Oligopeptides of formula (II):

R1-[AA]_n-R2 (II)

wherein [AA] comprises at least 4 amino acids of which at least 3, are identical compared to 4 consecutive amino acids of SEQ ID NO. 1 and/or wherein [AA] comprises at least 5 amino acids of which at least 4 are identical to 5 consecutive amino acids of SEQ ID NO. 1 wherein n=4 to 15 wherein R1 is linked to the NH₂-group of the amino-terminal part of [AA] and is chosen from the group which is formed from [0320] a) --H [0321] b) a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24 carbon atoms, which may be functionalized by a --OH, --SH, --COOH or --CONH₂ group, [0322] c) a sterol or a sphingolipid group which is joined to the amino terminal part of [AA] via a bifunctional linker wherein R2 is linked to the C═O group of the carboxy-terminal part of [AA] and is chosen from the group which is formed from [0323] a) --OH, [0324] b) --NH₂ [0325] c) a linear saturated or unsaturated or branched saturated or unsaturated alkoxy group having 1 to 24 carbon atoms [0326] d) or a sterol or a sphingolipid group.

[0327] In this embodiment [AA] comprises at least 4 amino acids, of which at least 3 are identical compared to 4 consecutive amino acids of SEQ ID NO.1. Any possible 4 consecutive amino acids of SEQ ID NO.1 are listed in Table 1.

[0328] Thus in this embodiment of the invention, [AA] comprises at least 4 amino acids, of which at least 75%, preferably 100% are identical to 4 consecutive amino acids of SEQ ID NO.1.

[0329] In a preferred embodiment [AA] comprises at least 4 amino acids, of which at least 3 amino acids are identical compared to 4 consecutive amino acids of SEQ ID NO. 1 and the position of the 3 identical amino acids is also identical when compared to the respective positions of the 4 amino acids of SEQ ID NO.1.

[0330] Thus in this embodiment of the invention [AA] comprises at least 4 amino acids, of which at least 75%, are identical to 4 consecutive amino acids of SEQ ID NO.1 and the position of the 3 identical amino acids is also identical when compared to the respective positions of the 4 amino acids of SEQ ID NO.1.

[0331] In following chart illustrates this embodiment of the invention. X and Yare further amino acids.

TABLE-US-00014 Position No. 1 2 3 4 SEQ 10 No. 1 Arg Arg Arg Pro [AA] Arg X Arg Pro [AA] Arg Arg Arg Y

[0332] In a preferred embodiment [AA] comprises at least 4 amino acids, of which at least 3, are identical to 4 consecutive amino acids of column I of table 1.

[0333] In a further embodiment [AA] consists of 4 amino acids, of which at least 3 are identical compared to 4 consecutive amino acids of SEQ ID NO.1. Any possible 4 consecutive amino acids of SEQ ID NO.1 are listed in Table 1.

[0334] Thus in this embodiment of the invention, [AA] consists of 4 amino acids, of which at least 75%, preferably 100% are identical to 4 consecutive amino acids of SEQ ID NO.1.

[0335] In a preferred embodiment [AA] consists of 4 amino acids, of which at least 3 amino acids, are identical compared to 4 consecutive amino acids of SEQ ID NO.1 and the position of the 3 identical amino acids is also identical when compared to the respective position of the 4 amino acids of SEQ ID NO.1.

[0336] In this embodiment [AA] comprises at least 5 amino acids, of which at least 4 are identical compared to 5 consecutive amino acids of SEQ ID NO.1. Any possible 5 consecutive amino acids of SEQ ID NO.1 are listed in Table 2.

[0337] Thus in this embodiment of the invention, [AA] comprises at least 5 amino acids, of which at least 80%, preferably 100% are identical to 4 consecutive amino acids of SEQ ID NO.1.

[0338] In a preferred embodiment [AA] comprises at least 5 amino acids, of which at least 4 amino acids are identical compared to 5 consecutive amino acids of SEQ ID NO.1 and the position of the 4 identical amino acids is also identical when compared to the respective positions of the 5 amino acids of SEQ ID NO.1.

[0339] Thus in this embodiment of the invention [AA] comprises at least 5 amino acids, of which at least 80%, are identical to 5 consecutive amino acids of SEQ ID NO.1 and the position of the 4 identical amino acids is also identical when compared to the respective positions of the 5 amino acids of SEQ ID NO.1.

[0340] In a preferred embodiment [AA] comprises at least 5 amino acids, of which at least 4, are identical to 5 consecutive amino acids of column I of table 1.

[0341] In a further embodiment [AA] consists of 5 amino acids, of which at least 4 are identical compared to 5 consecutive amino acids of SEQ ID NO.1. Any possible 5 consecutive amino acids of SEQ ID NO.1 are listed in Table 2.

[0342] Thus in this embodiment of the invention, [AA] consists of 5 amino acids, of which at least 80%, preferably 100% are identical to 5 consecutive amino acids of SEQ ID NO.1.

[0343] In a preferred embodiment [AA] consists of 5 amino acids, of which at least 4 amino acids, are identical compared to 5 consecutive amino acids of SEQ ID NO.1 and the position of the 4 identical amino acids is also identical when compared to the respective position of the 5 amino acids of SEQ ID NO.1.

Oligopeptides

[0344] A further embodiment of the invention relates to oligopeptides of formula (II)

R1-[AA]_n-R2 (II)

wherein [AA] comprises at least 4 amino acids of which at least 3, are identical compared to 4 consecutive amino acids of SEQ ID NO. 1 and/or wherein [AA] comprises at least 5 amino acids of which at least 4 are identical to 5 consecutive amino acids of SEQ ID NO.1 wherein n=4 to 15, preferably n=4, n=5. wherein R1 is linked to the NH₂ group of the amino-terminal part of [AA] and is chosen from the group which is formed from [0345] a) --H, [0346] b) a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24 carbon atoms, which may be functionalized by a --OH, --SH, --COOH or --CONH₂ group, [0347] c) a sterol or a sphingolipid group which is joined to the amino terminal part of [AA] via a bifunctional linker wherein R2 is linked to the C═O group of the carboxy-terminal part of [AA] and is chosen from the group which is formed from [0348] a) --OH, [0349] b) --NH₂ [0350] c) a linear saturated or unsaturated or branched saturated or unsaturated alkoxy group having 1 to 24 carbon atoms [0351] d) or a sterol or a sphingolipid group with the proviso that if R1 is --H, R2 is not --OH; or that if R2 is --OH, R1 is not --H; and with the proviso that [AA] is not Arg Lys Pro Arg (SEQ ID NO. 367), Phe-Tyr-Arg-Pro-Arg (SEQ ID NO. 372), Ala-Arg-Asp-Pro-Arg (SEQ ID NO. 373).

[0352] Surprisingly it has been found that these oligopeptides can be used in cosmetic compositions, preferably for stimulating the renewal rate of skin and/or hair.

Synthesis of Oligopeptides

[0353] The oligogpeptides according to the invention can be obtained by chemical or enzymatic synthesis or by controlled hydrolysis of natural proteins of microorganisms, plants or animals which contain the sequence as in SEQ ID NO.1. The hydrolysate comprising the sequence as in SEQ ID NO.1 or at least one fragment of at least four amino acids of SEQ ID NO.1 or the position 1-15 or 1-5, or 5-9, or 6-9, or 7-11, or 8-12 of SEQ ID NO.1 obtained by hydrolysis of natural proteins can be purified by known techniques such as membrane filtration, chromatography or immunoprecipitation. The oligopeptides can also be produced by microorganisms, which either naturally form the oligopeptides, or have possibly been genetically modified or are manipulated in some other way during fermentation through fermentation conditions such that they form the oligopeptides according to the invention. The amino acids can either occur in the L, the D, or the DL form in the peptide fragment.

Cosmetic Compositions

[0354] One embodiment of the invention is directed to cosmetic compositions comprising at least one oligopeptide of the structure of formula (I).

[0355] The oligopeptide are preferably used in a concentration from 0.05 to 500 ppm, preferably from 0.5 to 100 ppm.

[0356] The oligopeptides are preferably dissolved in one or more solvents which are approved for cosmetic preparations, such as, for example, water, glycerin, propylene glycol, butylene glycol, ethoxylated or propoxylated diglycols, ethanol, propanol, isopropanol or mixtures of said solvents. Furthermore, it is possible to use the oligopeptides solubilized in liposomes or adsorbed to organic polymers or similar material which is acceptable for topical application. Besides the solvents, further auxiliaries and additives may also be present in the preparations which are used according to the invention.

Cosmetic and/or Dermatological Preparations

[0357] The oligopeptides and the cosmetic uses according to the invention can serve for producing cosmetic preparations, such as, for example, hair shampoos, hair lotions, foam baths, shower baths, creams, gels, lotions, alcoholic and aqueous/alcoholic solutions, emulsions, wax/fat masses, stick preparations, powders or ointments. These preparations can also comprise, as further auxiliaries and additives, mild surfactants, oil bodies, emulsifiers, pearlescent waxes, consistency regulators, thickeners, superfatting agents, stabilizers, polymers, silicone compounds, fats, waxes, lecithins, phospholipids, UV photoprotective factors, biogenic active ingredients, antioxidants, deodorants, antiperspirants, antidandruff agents, film formers, swelling agents, insect repellents, self-tanning agents, tyrosine inhibitors (depigmentation agents), hydrotropes, solubilizers, preservatives, perfume oils, dyes and the like.

Surfactants

[0358] Surface-active substances which may be present are anionic, nonionic, cationic and/or amphoteric or zwitterionic surfactants, the content of which in the compositions is usually about 1 to 70% by weight, preferably 5 to 50% by weight and in particular 10 to 30% by weight. Typical examples of anionic surfactants are soaps, alkylbenzenesulphonates, alkanesulphonates, olefinsulphonates, alkyl ether sulphonates, glycerol ether sulphonates, a-methyl ester sulphonates, sulpho fatty acids, alkyl sulphates, alkyl ether sulphates, glycerol ether sulphates, fatty acid ether sulphates, hydroxy mixed ether sulphates, monoglyceride (ether) sulphates, fatty acid amide (ether) sulphates, mono- and dialkyl sulphosuccinates, mono- and dialkyl sulphosuccinamates, sulphotriglycerides, amide soaps, ether carboxylic acids and salts thereof, fatty acid isethionates, fatty acid sarcosinates, fatty acid taurides, Nacylaminoacids, such as, for example, acyl lactylates, acyl tartrates, acyl glutamates and acyl aspartates, alkyl oligoglucoside sulphates, protein fatty acid condensates (in particular wheat-based vegetable products) and alkyl (ether) phosphates. If the anionic surfactants comprise polyglycol ether chains, these can have a conventional homologue distribution, but preferably have a narrowed homologue distribution. Typical examples of nonionic surfactants are fatty alcohol polyglycol ethers, alkylphenol polyglycol ethers, fatty acid polyglycol esters, fatty acid amide polyglycol ethers, fatty amine polyglycol ethers, alkoxylated triglycerides, mixed ethers and mixed formals, optionally partially oxidized alk(en)yl oligoglycosides and glucoronic acid derivatives, fatty acid N-alkylglucamides, protein hydrolysates (in particular wheat-based vegetable products), polyol fatty acid esters, sugar esters, sorbitan esters, polysorbates and amine oxides. If the nonionic surfactants contain polyglycol ether chains, these can have a conventional homologue distribution, but preferably have a narrowed homologue distribution. Typical examples of cationic surfactants are quaternary ammonium compounds, such as, for example, dimethyldistearylammonium chloride, and ester quats, in particular quaternized fatty acid trialkanolamine ester salts. Typical examples of amphoteric and zwitterionic surfactants are alkylbetaines, alkylamidobetaines, aminopropionates, aminoglycinates, imidazoliniumbetaines and sulphobetaines. The specified surfactants are exclusively known compounds. Typical examples of particularly suitable mild, i.e. particularly skin-compatible, surfactants are fatty alcohol polyglycol ether sulphates, monoglyceride sulphates, mono- and/or dialkyl sulphosuccinates, fatty acid isethionates, fatty acid sarcosinates, fatty acid taurides, fatty acid glutamates, u-olefinsulphonates, ether carboxylic acids, alkyl oligoglucosides, fatty acid glucamides, alkylamidobetaines, amphoacetals and/or protein fatty acid condensates, the latter preferably being based on wheat proteins.

Oil Bodies

[0359] Suitable oil bodies are, for example, Guerbet alcohols based on fatty alcohols having 6 to 18, preferably 8 to 10, carbon atoms, esters of linear C₆-C₂2-fatty acids with linear or branched C₆-C₂2 fatty alcohols and/or esters of branched C₆-C₁₃ carboxylic acids with linear or branched C₆-C₂2 fatty alcohols, such as, for example, myristyl myristate, myristyl palmitate, myristyl stearate, myristyl isostearate, myristyl oleate, myristyl behenate, myristyl erucate, cetyl myristate, cetyl palmitate, cetyl stearate, cetyl isostearate, cetyl oleate, cetyl behenate, cetyl erucate, stearyl myristate, stearyl palmitate, stearyl stearate, stearyl isostearate, stearyl oleate, stearyl behenate, stearyl erucate, isostearyl myristate, isostearyl palmitate, isostearyl stearate, isostearyl isostearate, isostearyl oleate, isostearyl behenate, isostearyl oleate, oleyl myristate, oleyl palmitate, oleyl stearate, oleyl isostearate, oleyl oleate, oleyl behenate, oleyl erucate, behenyl myristate, behenyl palmitate, behenyl stearate, behenyl isostearate, behenyl oleate, behenyl behenate, behenyl erucate, erucyl myristate, erucyl palmitate, erucyl stearate, erucyl isostearate, erucyl oleate, erucyl behenate and erucyl erucate. Also suitable are esters of linear C₆C₂2-fatty acids with branched alcohols, in particular 2-ethylhexanol, esters of C₁₈-C₃8-alkyl hydroxycarboxylic acids with linear or branched C₆-C₂2 fatty alcohols (cf. DE 19756377 A1), in particular dioctyl malates, esters of linear and/or branched fatty acids with polyhydric alcohols (such as, for example, propylene glycol, dimerdiol or trimertriol) and/or Guerbet alcohols, triglycerides based on C₆-C₁₀-fatty acids, liquid mono-/di-/triglyceride mixtures based on C₆-C₁₈-fatty acids, esters of C₆-C₂2-fatty alcohols and/or Guerbet alcohols with aromatic carboxylic acids, in particular benzoic acid, esters of C₂-C₁₂-dicarboxylic acids with linear or branched alcohols having 1 to 22 carbon atoms or polyols having 2 to 10 carbon atoms and 2 to 6 hydroxyl groups, vegetable oils, branched primary alcohols, substituted cyclohexanes, linear and branched C₆-C₂2-fatty alcohol carbonates, such as, for example, dicaprylyl carbonate (Cetiol® CC), Guerbet carbonates based on fatty alcohols having 6 to 18, preferably 8 to 10, carbon atoms, esters of benzoic acid with linear and/or branched C₆-C₂2 alcohols (e.g. Fins® Iv® TN), linear or branched, symmetrical or unsymmetrical dialkyl ethers having 6 to 22 carbon atoms per alkyl group, such as, for example, dicaprylyl ether (Cetiol® OE), ring-opening products of epoxidized fatty acid esters with polyols, silicone oils (cyclomethicones, silicon methicone types, inter alia) and/or aliphatic or naphthenic hydrocarbons, such as, for example, squalane, squalene or dialkylcyclohexanes.

Emulsifiers

[0360] Suitable emulsifiers are, for example, nonionogenic surfactants from at least one of the following groups: [0361] addition products of from 2 to 30 mol of ethylene oxide and/or a to 5 mol of propylene oxide to linear fatty alcohols having 8 to 22 carbon atoms, to fatty acids having 12 to 22 carbon atoms, to alkylphenols having 8 to 15 carbon atoms in the alkyl group, and alkylamines having 8 to 22 carbon atoms in the alkyl radical; [0362] alkyl and/or alkenyl oligoglycosides having 8 to 22 carbon atoms in the alk(en)yl radical and the ethoxylated analogues thereof; [0363] addition products of from 1 to 15 mol of ethylene oxide to castor oil and/or hydrogenated castor oil; [0364] addition products of from 15 to 60 mol of ethylene oxide to castor oil and/or hydrogenated castor oil; [0365] partial esters of glycerol and/or sorbitan with unsaturated, linear or saturated, branched fatty acids having 12 to 22 carbon atoms and/or hydroxycarboxylic acids having 3 to 18 carbon atoms, and the adducts thereof with 1 to 30 mol of ethylene oxide; [0366] partial esters of polyglycerol (average degree of self-condensation 2 to 8), polyethylene glycol (molecular weight 400 to 5 000), trimethylolpropane, pentaerythritol, sugar alcohols (e.g. sorbitol), alkyl glucosides (e.g. methyl glucoside, butyl glucoside, lauryl glucoside), and polyglucosides (e.g. cellulose) with saturated and/or unsaturated, linear or branched fatty acids having 12 to 22 carbon atoms and/or hydroxycarboxylic acids having 3 to 18 carbon atoms, and the adducts thereof with 1 to 30 mol of ethylene oxide; [0367] mixed esters of pentaerythritol, fatty acids, citric acid and fatty alcohol and/or mixed esters of fatty acids having 6 to 22 carbon atoms, methylglucose and polyols, preferably glycerol or polyglycerol, [0368] mono-, di- and trialkyl phosphates, and mono-, di- and/or tri-PEG alkyl phosphates and salts thereof; [0369] wool wax alcohols; [0370] polysiloxane-polyalkyl-polyether copolymers and corresponding derivatives; [0371] block copolymers, e.g. polyethylene glycol-30 dipolyhydroxystearates; [0372] polymer emulsifiers, e.g. Pemulen grades (TR-1, TR-2) from Goodrich; [0373] polyalkylene glycols, and [0374] glycerol carbonate.

[0375] Ethylene Oxide Addition Products

[0376] The addition products of ethylene oxide and/or of propylene oxide to fatty alcohols, fatty acids, alkylphenols or to castor oil are known, commercially available products. These are homologue mixtures whose average degree of alkoxylation corresponds to the ratio of the amounts of substance of ethylene oxide and/or propylene oxide and substrate with which the addition reaction is carried out. C12118-fatty acid mono- and diesters of addition products of ethylene oxide to glycerol are known as refatting agents for cosmetic preparations.

[0377] Alkyl and/or Alkenyl Oligoglycosides

[0378] Alkyl and/or alkenyl oligoglycosides, their preparation and their use are known from the prior art. They are prepared, in particular, by reacting glucose or oligosaccharides with primary alcohols having 8 to 18 carbon atoms. With regard to the glycoside radical, both monoglycosides, in which a cyclic sugar radical is glycosidically bonded to the fatty alcohol, and also oligomeric glycosides having a degree of oligomerization of up to, preferably, about 8, are suitable. The degree of oligomerization here is a statistical average value which is based on a homologue distribution customary for such technical-grade products.

[0379] Partial Glycerides

[0380] Typical examples of suitable partial glycerides are hydroxystearic acid monoglyceride, hydroxystearic acid diglyceride, isostearic acid monoglyceride, isostearic acid diglyceride, oleic acid monoglyceride, oleic acid diglyceride, ricinoleic acid monoglyceride, ricinoleic acid diglyceride, linoleic acid monoglyceride, linoleic acid diglyceride, linolenic acid monoglyceride, linolenic acid diglyceride, erucic acid monoglyceride, erucic acid diglyceride, tartaric acid monoglyceride, tartaric acid diglyceride, citric acid monoglyceride, citric acid diglyceride, malic acid monoglyceride, malic acid diglyceride, and the technicalgrade mixtures thereof which may also comprise small amounts of triglyceride as a minor product of the preparation process. Likewise suitable are addition products of 1 to 30 mol, preferably 5 to 10 mol, of ethylene oxide to said partial glycerides.

[0381] Sorbitan Esters

[0382] Suitable sorbitan esters are sorbitan monoisostearate, sorbitan sesquiisostearate, sorbitan diisostearate, sorbitan triisostearate, sorbitan monooleate, sorbitan sesquioleate, sorbitan dioleate, sorbitan trioleate, sorbitan monoerucate, sorbitan sesquierucate, sorbitan dierucate, sorbitan trierucate, sorbitan monoricinoleate, sorbitan sesquiricinoleate, sorbitan diricinoleate, sorbitan triricinoleate, sorbitan monohydroxystearate, sorbitan sesquihydroxystearate, sorbitan dihydroxystearate, sorbitan trihydroxystearate, sorbitan monotartrate, sorbitan sesquitartrate, sorbitan ditartrate, sorbitan tritartrate, sorbitan monocitrate, sorbitan sesquicitrate, sorbitan dicitrate, sorbitan tricitrate, sorbitan monomaleate, sorbitan sesquimaleate, sorbitan dimaleate, sorbitan trimaleate, and technicalgrade mixtures thereof. Likewise suitable are addition products of from 1 to 30 mol, preferably 5 to 10 mol, of ethylene oxide to said sorbitan esters.

[0383] Polyglycerol Esters

[0384] Typical examples of suitable polyglycerol esters are polyglyceryl-2 dipolyhydroxystearate (Dehymuls® PGPH), polyglycerol-3 diisostearate (Lameform® TGI), polyglyceryl-4 isostearate (Isolan® GI 34), polyglyceryl-3 oleate, diisostearoyl polyglyceryl-3 diisostearate (Isolan® PDI), polyglyceryl-3 methylglucose distearate (Tego Care® 450), polyglyceryl-3 beeswax (Cera Bellina®), polyglyceryl-4 caprate (Polyglycerol Caprate T201 0/90), polyglyceryl-3 cetyl ether (Chimexane® NL), polyglyceryl-3 distearate (Cremophor® GS 32) and polyglyceryl polyricinoleate (Admul® WOL 1403), polyglyceryl dimerate isostearate, and mixtures thereof. Examples of further suitable polyol esters are the mono-, di- and triesters, optionally reacted with 1 to 30 mol of ethylene oxide, of trimethylolpropane or pentaerythritol with lauric acid, coconut fatty acid, tallow fatty acid, palmitic acid, stearic acid, oleic acid, behenic acid and the like.

[0385] Anionic Emulsifiers

[0386] Typical anionic emulsifiers are aliphatic fatty acids having 12 to 22 carbon atoms, such as, for example, palmitic acid, stearic acid or behenic acid, and dicarboxylic acids having 12 to 22 carbon atoms, such as, for example, azelaic acid or sebacic acid.

[0387] Amphoteric and Cationic Emulsifiers

[0388] Furthermore, zwitterionic surfactants can be used as emulsifiers. The term "zwitterionic surfactants" refers to those surface-active compounds which carry at least one quaternary ammonium group and at least one carboxylate and one sulphonate group in the molecule. Particularly suitable zwitterionic surfactants are the so-called betaines, such as N-alkyl-N,N-dimethylammonium glycinates, for example cocoalkyldimethylammonium glycinate, N-acylaminopropyl-N,N-dimethylammonium glycinates, for example cocoacylaminopropyldimethylammonium glycinate, and 2-alkyl-3-carboxymethyl3-hydroxyethylimidazolines having in each case 8 to 18 carbon atoms in the alkyl or acyl group, and cocoacylaminoethylhydroxyethylcarboxymethyl glycinate. Particular preference is given to the fatty acid amide derivative known under the CTFA name Cocamidopropyl Betaine. Likewise suitable emulsifiers are ampholytic surfactants. The term "ampholytic surfactants" means those surfaceactive compounds which, apart from a C8/18-alkyl or -acyl group, contain at least one free amino group and at least one --COOH or --SO₃H group in the molecule and are capable of forming internal salts. Examples of suitable ampholytic surfactants are N-alkylglycines, N-alkylaminopropionic acids, N-alkylaminobutyric acids, N-alkyliminodipropionic acids, N-hydroxyethyl-N-alkylamidopropylglycines, N-alkyltaurines, N-alkylsarcosines, 2-alkylaminopropionic acids and alkylaminoacetic acids having in each case about 8 to 18 carbon atoms in the alkyl group. Particularly preferred ampholytic surfactants are N-cocoalkylaminopropionate, cocoacylaminoethylaminopropionate and C₁₂/18-acylsarcosine. Finally, cationic surfactants are also suitable as emulsifiers, those of the ester quat type, preferably methyl-quaternized difatty acid triethanolamine ester salts, being particularly preferred.

Fats and Waxes

[0389] Typical examples of fats are glycerides, i.e. solid or liquid vegetable or animal products which consist essentially of mixed glycerol esters of higher fatty acids, suitable waxes are inter alia natural waxes, such as, for example, candelilla wax, carnauba wax, Japan wax, esparto grass wax, cork wax, guaruma wax, rice germ oil wax, sugarcane wax, ouricury wax, montan wax, beeswax, shellac wax, spermaceti, lanolin (wool wax), uropygial grease, ceresin, ozokerite (earth wax), petrolatum, paraffin waxes, microcrystalline waxes; chemically modified waxes (hard waxes), such as, for example, montan ester waxes, sasol waxes, hydrogenated jojoba waxes, and synthetic waxes, such as, for example, polyalkylene waxes and polyethylene glycol waxes. In addition to the fats, suitable additives are also fat-like substances, such as lecithins and phospholipids. The term lecithins is understood by the person skilled in the art as meaning those glycerophospholipids which are founded from fatty acids, glycerol, phosphoric acid and choline by esterification. Lecithins are thus also often as phosphatidylcholines (PC) in the specialist world. Examples of natural lecithins which may be mentioned are the cephalins, which are also referred to as phosphatidic acids and constitute derivatives of 1,2-diacyl-sn-glycerol-3-phosphoric acids. By contrast, phospholipids are usually understood as meaning mono- and preferably diesters of phosphoric acid with glycerol (glycerol phosphates), which are generally classed as fats. In addition, sphingosines or sphingolipids are also suitable.

Pearlescent Waxes

[0390] Examples of suitable pearlescent waxes are: alkylene glycol esters, specifically ethylene glycol distearate; fatty acid alkanolamides, specifically coconut fatty acid diethanolamide; partial glycerides, specifically stearic acid monoglyceride; esters of polybasic, optionally hydroxy-substituted carboxylic acids with fatty alcohols having 6 to 22 carbon atoms, specifically long-chain esters of tartaric acid; fatty substances, such as, for example, fatty alcohols, fatty ketones, fatty aldehydes, fatty ethers and fatty carbonates, which have a total of at least 24 carbon atoms, specifically laurone and distearyl ether; fatty acids, such as stearic acid, hydroxystearic acid or behenic acid, ring-opening products of olefin epoxides having 12 to 22 carbon atoms with fatty alcohols having 12 to 22 carbon atoms and/or polyols having 2 to 15 carbon atoms and 2 to 10 hydroxyl groups, and mixtures thereof.

Consistency Regulators and Thickeners

[0391] Suitable consistency regulators are primarily fatty alcohols or hydroxy fatty alcohols having 12 to 22, and preferably 16 to 18, carbon atoms, and also partial glycerides, fatty acids or hydroxy fatty acids. Preference is given to a combination of these substances with alkyl oligoglucosides and/or fatty acid N-methylglucamides of identical chain length and/or polyglycerol poly-12-hydroxystearates. Suitable thickeners are, for example, Aerosil grades (hydrophilic silicas), polysaccharides, in particular xanthan gum, guar guar, agar agar, alginates and tyloses, carboxymethylcellulose, hydroxyethylcellulose and hydroxypropylcellulose, and also relatively high molecular weight polyethylene glycol mono- and diesters of fatty acids, polyacrylates (e.g. Carbopols® and Pemulen grades from Goodrich; Synthalens® from Sigma; Keltrol grades from Kelco; Sepigel grades from Seppic; Salcare grades from Allied Colloids), polyacrylamides, polymers, polyvinyl alcohol and polyvinylpyrrolidone. Bentonites, such as, for example, Bentone® Gel VS 5PC (Rheox), which is a mixture of cyclopentasiloxane, disteardimonium hectorite and propylene carbonate, have also proven to be particularly effective. Also suitable are surfactants, such as, for example, ethoxylated fatty acid glycerides, esters of fatty acids with polyols such as, for example, pentaerythritol or trimethylolpropane, fatty alcohol ethoxylates having a narrowed homologue distribution or alkyl oligoglucosides, and electrolytes such as sodium chloride and ammonium chloride.

Superfatting Agents

[0392] Superfatting agents which can be used are substances such as, for example, lanolin and lecithin, and polyethoxylated or acylated lanolin and lecithin derivatives, polyol fatty acid esters, monoglycerides and fatty acid alkanolamides, the latter also serving as foam stabilizers.

Stabilizers

[0393] Stabilizers which can be used are metal salts of fatty acids, such as, for example, magnesium, aluminium and/or zinc stearate or ricinoleate.

Polymers

[0394] Suitable cationic polymers are, for example, cationic cellulose derivatives, such as, for example, a quaternized hydroxyethylcellulose obtainable under the name Polymer JR 400® from Amerchol, cationic starch, copolymers of diallylammonium salts and acrylamides, quaternized vinylpyrrolidone-vinylimidazole polymers, such as, for example, Luviquat® (BASF), condensation products of polyglycols and amines, quaternized collagen polypeptides, such as, for example, lauryldimonium hydroxypropyl hydrolyzed collagen (Lamequat@UGrunau), quaternized wheat polypeptides, polyethyleneimine, cationic silicone polymers, such as, for example, amodimethicones, copolymers of adipic acid and dimethylaminohydroxypropyldiethylenetriamine (Cartaretins@/Sandoz), copolymers of acrylic acid with dimethyldiallylammonium chloride (Merquat® 550/Chemviron), polyaminopolyamides, as described, for example, in FR 2252840 A, and crosslinked water-soluble polymers thereof, cationic chitin derivatives, such as, for example, quaternized chitosan, optionally in microcrystalline dispersion, condensation products from dihaloalkyls, such as, for example, dibromobutane with bisdialkylamines, such as, for example, bis-dimethylamino-1,3-propane, cationic guar gum, such as, for example, Jaguar® CBS, Jaguar® C-17, Jaguar® C-16 from Celanese, quaternized ammonium salt polymers, such as, for example, Mirapol® A-15, Mirapol® AD-1, Mirapol® AZ-1 from Miranol.

[0395] Suitable anionic, zwitterionic, amphoteric and nonionic polymers are, for example, vinyl acetate-crotonic acid copolymers, vinylpyrrolidone-vinyl acrylate copolymers, vinyl acetate-butyl. maleate-isobornyl acrylate copolymers, methyl vinyl ether-maleic anhydride copolymers and esters thereof, uncrosslinked polyacrylic acids and polyacrylic acids crosslinked with polyols, acrylamidopropyltrimethylammonium chloride-acrylate copolymers, octylacrylamide-methyl methacrylate-tert-butylaminoethyl methacrylate-2-hydroxypropyl methacrylate copolymers, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymers, vinylpyrrolidone-dimethylaminoethyl methacrylate-vinylcaprolactam terpolymers, and optionally derivatized cellulose ethers and silicones.

Silicone Compounds

[0396] Suitable silicone compounds are, for example, dimethylpolysiloxanes, methylphenylpolysiloxanes, cyclic silicones, and amino-, fatty acid-, alcohol-, polyether-, epoxy-, fluorine-, glycoside- and/or alkyl-modified silicone compounds, which can either be liquid or in resin form at room temperature. Also suitable are simethicones, which are mixtures of dimethicones having an average chain length of from 200 to 300 dimethylsiloxane units and hydrogenated silicates.

UV Photoprotective Filters

[0397] UV photoprotective factors are, for example, to be understood as meaning organic substances (photoprotective filters) which are liquid or crystalline at room temperature and which are able to absorb ultraviolet rays and give off the absorbed energy again in the form of longer-wavelength radiation, e.g. heat. UVB filters can be oil-soluble or water-soluble. Examples of oil-soluble substances are: [0398] 3-benzylidenecamphor or 3-benzylidenenorcamphor and derivatives thereof, e.g. 3-(4-methylbenzylidene)camphor; [0399] 4-aminobenzoic acid derivatives, preferably 2-ethylhexyl 4(dimethylamino)benzoate, 2-octyl 4-(dimethylamino)benzoate and amyl 4(dimethylamino)benzoate; [0400] esters of cinnamic acid, preferably 2-ethylhexyl 4-methoxycinnamate, propyl 4-methoxycinnamate, isoamyl 4-methoxycinnamate, 2-ethylhexyl 2-cyano-3,3-phenylcinnamate (octocrylene); [0401] esters of salicylic acid, preferably 2-ethylhexyl salicylate, 4-isopropylbenzyl salicylate, homomethyl salicylate; [0402] derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone, 2hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone; [0403] esters of benzalmalonic acid, preferably di-2-ethylhexyl 4-methoxybenzalmalonate; [0404] triazine derivatives, such as, for example, 2,4,6-trianilino(p-carbo-2¹-ethyl-1' hexyloxy)-1,3,5-triazine and octyltriazone or dioctylbutamidotriazone (Uvasorb® HEB); [0405] propane-1,3-diones, such as, for example, 1-(4-tert-butylphenyl)-3-(4'methoxyphenyl) propane-1,3-dione; [0406] ketotricyclo(5.2.1.0)decane derivatives. [0407] Suitable water-soluble substances are: [0408] 2-phenylbenzimidazole-5-sulphonic acid and the alkali metal, alkaline earth metal, ammonium, alkylammonium, alkanolammonium and glucammonium salts thereof; [0409] sulphonic acid derivatives of benzophenones, preferably 2-hydroxy-4-methoxybenzophenone-5-sulphonic acid and its salts; [0410] sulphonic acid derivatives of 3-benzylidenecamphor, such as, for example, 4-(2oxo-3-bornylidenemethyl)benzenesulphonic acid and 2-methyl-5-(2-oxo-3-bornylidene) sulphonic acid and salts thereof.

[0411] Suitable typical UV-A filters are, in particular, derivatives of benzoylmethane, such as, for example, 1-(4'-tert-butylphenyl)-3-(4'-methoxyphenyl)propane-1,3-dione, 4tert-butyl-4'-methoxydibenzoylmethane (Parsol® 1789), 1-phenyl-3-(4' isopropylphenyl) propane-1,3-dione, and enamine compounds. The UV-A and UV-B filters can of course also be used in mixtures. Particularly favourable combinations consist of the derivatives of benzoylmethane, e.g. 4-tert-butyl-4'-methoxydibenzoylmethane (Parsol® 1789) and 2-ethylhexyl 2-cyano-3,3-cinnamate (octocrylene) in combination with esters of cinnamic acid, preferably 2-ethylhexyl 4-methoxycinnamate and/or propyl 4-methoxycinnamate and/or isoamyl 4-methoxycinnamate. Advantageously, such combinations are combined with watersoluble filters such as, for example, 2-phenylbenzimidazole-5-sulphonic acid and their alkali metal, alkaline earth metal, ammonium, alkylammonium, alkanolammonium and glucammonium salts.

[0412] As well as said soluble substances, insoluble light protection pigments, namely finely dispersed metal oxides or salts, are also suitable for this purpose. Examples of suitable metal oxides are, in particular, zinc oxide and titanium dioxide and also oxides of iron, zirconium, silicon, manganese, aluminium and cerium, and mixtures thereof. Salts which may be used are silicates (talc), barium sulphate or zinc stearate. The oxides and salts are used in the form of the pigments for skincare and skin-protective emulsions and decorative cosmetics. The particles here should have an average diameter of less than 100 nm, preferably between 5 and 50 nm and in particular between 15 and 30 nm. They can have a spherical shape, but it is also possible to use particles which have an ellipsoidal shape or a shape deviating in some other way from the spherical form. The pigments can also be surface-treated, i.e. hydrophilicized or hydrophobicized. Typical examples are coated titanium dioxides, such as, for example, titanium dioxide T 805 (Degussa) or Eusolex® T2000 (Merck). Suitable hydrophobic coating agents are here primarily silicones and, specifically in this case, trialkoxyoctylsilanes or simethicones. In sunscreens, preference is given to using so-called micro- or nanopigments. Preference is given to using micronized zinc oxide.

Biogenic Active Ingredients and Antioxidants

[0413] Biogenic active ingredients are understood as meaning, for example, tocopherol, tocopherol acetate, tocopherol palmitate, ascorbic acid, (deoxy)ribonucleic acid and fragmentation products thereof, f3-glucans, retinol, bisabolol, allantoin, phytantriol, panthenol, AHA acids, amino acids, ceramides, pseudoceramides, essential oils, plant extracts, such as, for example, prunus extract, bambara nut extract and vitamin complexes.

[0414] Antioxidants interrupt the photochemical reaction chain which is triggered when UV radiation penetrates the skin. Typical examples thereof are amino acids (e.g. glycine, histidine, tyrosine, tryptophan) and derivatives thereof, imidazoles (e.g. urocanic acid) and derivatives thereof, peptides, such as D,L-carnosine, D-carnosine, Lcarnosine and derivatives thereof (e.g. anserine), carotenoids, carotenes (e.g. acarotene, I3-carotene, lycopene) and derivatives thereof, chlorogenic acid and derivatives thereof, lipoic acid and derivatives thereof (e.g. dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (e.g. thioredoxin, glutathione, cysteine, cystine, cystamine and the glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, γ-linoleyl, cholesteryl and glyceryl esters thereof) and salts thereof, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts), and sulphoximine compounds (e.g. buthionine sulphoximines, homocysteine sulphoximine, buthionine suiphones, penta-, hexa-, heptathionine sulphoximine) in very low tolerated doses (e.g. pmol to).Imol/kg), and also (metal) chelating agents (e.g. a-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), a-hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and derivatives thereof, unsaturated fatty acids and derivatives thereof (e.g. y-linolenic acid, linoleic acid, oleic acid), folic acid and derivatives thereof, ubiquinone and ubiquinol and derivatives thereof, vitamin C and derivatives (e.g. ascorbyl palmitate, Mg ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (e.g. vitamin E acetate), vitamin A and derivatives (vitamin A palmitate), and coniferyl benzoate of gum benzoin, rutic acid and derivatives thereof, a-glycosylrutin, ferulic acid, furfurylideneglucitol, carnosine, butylhydroxytoluene, butylhydroxyanisole, nordihydroguaiacic acid, nordihydroguaiaretic acid, trihydroxybutyrophenone, uric acid and derivatives thereof, mannose and derivatives thereof, superoxide dismutase, zinc and derivatives thereof (e.g. ZnO, ZnS04) selenium and derivatives thereof (e.g. selenomethionine), stilbenes and derivatives thereof (e.g. stilbene oxide, trans-stilbene oxide) and the derivatives (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of said active ingredients which are suitable according to the invention.

Deodorants and Antimicrobial Agents

[0415] Cosmetic deodorants counteract, mask or remove body odours. Body odours arise as a result of the effect of skin bacteria on apocrine perspiration, with the formation of degradation products which have an unpleasant odour. Accordingly, deodorants comprise active ingredients which act as antimicrobial agents, enzyme inhibitors, odour absorbers or odour masking agents.

[0416] Antimicrobial Agents

[0417] Suitable antimicrobial agents are, in principle, all substances effective against gram-positive bacteria, such as, for example, 4-hydroxybenzoic acid and its salts and esters, N-(4-chlorophenyl)-N'-(3,4-dichlorophenyl)urea, 2,4,4'-trichloro-2' hydroxydiphenyl ether (triclosan), 4-chloro-3,5-dimethylphenol, 2,2'-methylenebis(6-bromo-4-chlorophenol), 3-methyl-4-(1-methylethyl)phenol, 2-benzyl-4-chlorophenol, 3-(4-chlorophenoxy)-1,2-propanediol, 3-iodo-2-propynyl butylcarbamate, chlorhexidine, 3,4,4'-trichlorocarbanilide (TTC), antibacterial fragrances, thymol, thyme oil, eugenol, oil of cloves, menthol, mint oil, famesol, phenoxyethanol, glycerol monocaprate, glycerol monocaprylate, glycerol monolaurate (GML), diglycerol monocaprate (DMC), salicylic acid N-alkylamides, such as, for example, N-octylsalicylamide or N-decylsalicylamide.

[0418] Enzyme Inhibitors

[0419] Suitable enzyme inhibitors are, for example, esterase inhibitors. These are preferably trialkyl citrates, such as trimethyl citrate, tripropyl citrate, triisopropyl citrate, tributyl citrate and, in particular, triethyl citrate (Hydagen@ CAT). The substances inhibit enzyme activity, thereby reducing the formation of odour. Other substances which are suitable esterase inhibitors are sterol sulphates or phosphates, such as, for example, lanosterol, cholesterol, campesterol, stigmasterol and sitosterol sulphate or phosphate, dicarboxylic acids and esters thereof, such as, for example, glutaric acid, monoethyl glutarate, diethyl glutarate, adipic acid, monoethyl adipate, diethyl adipate, malonic acid and diethyl malonate, hydroxycarboxylic acids and esters thereof, such as, for example, citric acid, malic acid, tartaric acid or diethyl tartrate, and zinc glycinate.

[0420] Odour Absorbers

[0421] Suitable odour absorbers are substances which are able to absorb and largely retain odour-forming compounds. They lower the partial pressure of the individual components, thus also reducing their rate of diffusion. It is important that in this process perfumes must remain unimpaired. Odour absorbers are not effective against bacteria. They comprise, for example, as main constituent, a complex zinc salt of ricinoleic acid or specific, largely odour-neutral fragrances which are known to the person skilled in the art as "fixatives", such as, for example, extracts of labdanum or styrax or certain abietic acid derivatives. The odour masking agents are fragrances or perfume oils, which, in addition to their function as odour masking agents, give the deodorants their respective fragrance note. Perfume oils which may be mentioned are, for example, mixtures of natural and synthetic fragrances. Natural fragrances are extracts from flowers, stems and leaves, fruits, fruit peels, roots, woods, herbs and grasses, needles and branches, and resins and balsams. Also suitable are animal raw materials, such as, for example, civet and castoreum. Typical synthetic fragrance compounds are products of the ester, ether, aldehyde, ketone, alcohol and hydrocarbon type. Fragrance compounds of the ester type are, for example, benzyl acetate, p-tert-butylcyclohexyl acetate, linalyl acetate, phenylethyl acetate, linalyl benzoate, benzyl formate, allyl cyclohexylpropionate, styrallyl propionate and benzyl salicylate. The ethers include, for example, benzyl ethyl ether, and the aldehydes include, for example, the linear alkanals having 8 to 18 carbon atoms, citral, citronellal, citronellyloxyacetaldehyde, cyclamen aldehyde, hydroxycitronellal, lilial and bourgeonal, the ketones include, for example, the ionones and methyl cedryl ketone, the alcohols include anethole, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol and terpineol, and the hydrocarbons include mainly the terpenes and balsams. Preference is, however, given to using mixtures of different fragrances which together produce a pleasing fragrance note. Essential oils of relatively low volatility, which are mostly used as aroma components, are also suitable as perfume oils, e.g. sage oil, camomile oil, oil of cloves, melissa oil, mint oil, cinnamon leaf oil, linden blossom oil, juniper berry oil, vetiver oil, olibanum oil, galbanum oil, labdanum oil and lavandin oil. Preference is given to using bergamot oil, dihydromyrcenol, lilial, lyral, citronellol, phenylethyl alcohol, 0.hexylcinnamaldehyde, geraniol, benzylacetone, cyclamen aldehyde, linalool, boisambrene forte, ambroxan, indole, hedione, sandelice, lemon oil, mandarin oil, orange oil, allyl amyl glycolate, cyclovertal, lavandin oil, clary sage oil, f3damascone, geranium oil bourbon, cyclohexyl salicylate, Vertofix coeur, iso-Esuper, Fixolide NP, evernyl, iraldein gamma, phenylacetic acid, geranyl acetate, benzyl acetate, rose oxide, romilat, irotyl and floramat alone or in mixtures.

[0422] Antiperspirants

[0423] Antiperspirants reduce the formation of perspiration by influencing the activity of the eccrine sweat glands, thus counteracting underarm wetness and body odor. Aqueous or anhydrous formulations of antiperspirants typically comprise the following ingredients: [0424] astringent active ingredients, [0425] oil components, [0426] nonionic emulsifiers, [0427] coemulsifiers, [0428] consistency regulators, [0429] auxiliaries, such as, for example, thickeners or complexing agents and/or [0430] nonaqueous solvents, such as, for example, ethanol, propylene glycol and/or glycerol.

[0431] Suitable astringent antiperspirant active ingredients are primarily salts of aluminium, zirconium or of zinc. Such suitable antihydrotic active ingredients are, for example, aluminium chloride, aluminium chlorohydrate, aluminium dichlorohydrate, aluminium sesquichlorohydrate and complex compounds thereof, e.g. with 1,2-propylene glycol, aluminium hydroxyallantoinate, aluminium chloride tartrate, aluminium zirconium trichlorohydrate, aluminium zirconium tetrachlorohydrate. aluminium zirconium pentachlorohydrate and complex compounds thereof, e.g. with amino acids, such as glycine. In addition, customary oil-soluble and water-soluble auxiliaries may be present in antiperspirants in relatively small amounts. Such oil-soluble auxiliaries may, for example, be: [0432] anti-inflammatory, skin-protective or perfumed essential oils, [0433] synthetic skin-protective active ingredients and/or [0434] oil-soluble perfume oils.

[0435] Customary water-soluble additives are, for example, preservatives, water-soluble fragrances, pH regulators, e.g. buffer mixtures, water-soluble thickeners. e.g. water-soluble natural or synthetic polymers, such as, for example, xanthan gum, hydroxyethylcellulose, polyvinylpyrrolidone or high molecular weight polyethylene oxides.

Film Formers

[0436] Customary film formers are, for example, chitosan, microcrystalline chitosan, quaternized chitosan, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymers, polymers of the acrylic acid series, quaternary cellulose derivatives, collagen, hyaluronic acid and salts thereof, and similar compounds.

Antidandruff Active Ingredients

[0437] Suitable antidandruff active ingredients are piroctone olamine (1-hydroxy-4-methyl6-(2,4,4-trimythylpentyl)-2-(1H)-pyridinone monoethanolamine salt), Baypival® (c1 imbazole), Ketoconazole®, (4-acetyl-1-{-4-[2-(2,4-dichlorophenyl) r-2-(1H-imidazo1'-ylmethyl)-1,3-dioxylan-c-4-ylmethoxyphenyl}piperazine, ketoconazole, elubiol, selenium disulphide, sulphur colloidal, sulphur polyethylene glycol sorbitan monooleate, sulphur ricinole polyethoxylate, sulphur tar distillates, salicylic acid (or in combination with hexachlorophene), undecylenic acid monoethanolamide sulphosuccinate Na salt, Lamepon® UD (protein undecylenic acid condensate), zinc pyrithione, aluminium pyrithione and magnesium pyrithione/dipyrithione magnesium sulphate.

Swelling Agents

[0438] The swelling agents for aqueous phases may be montmorillonites, clay mineral substances, Pemulen, and alkyl-modified Carbopol grades (Goodrich). Other suitable polymers and swelling agents are given in the review by R. Lochhead in Cosm. Toil. 108, 95 (1993).

Insect Repellents

[0439] Suitable insect repellents are N,N-diethyl-m-toluamide, 1,2-pentanediol or ethyl butylacetylaminopropionate.

Self-Tanning Agents and Depigmentation Agents

[0440] A suitable self-tanning agent is dihydroxyacetone. Suitable tyrosine inhibitors, which prevent the formation of melanin and are used in depigmentation agents, are, for example, arbutin, ferulic acid, kojic acid, coumaric acid and ascorbic acid (vitamin C).

Hydrotropic Agents

[0441] To improve the flow behaviour, it is also possible to use hydrotropic agents, such as, for example, ethanol, isopropyl alcohol, or polyols. Polyols which are suitable here preferably have 2 to 15 carbon atoms and at least two hydroxyl groups. The polyols can also contain further functional groups, in particular amino groups, or be modified with nitrogen. Typical examples are [0442] glycerol; [0443] alkylene glycols, such as, for example, ethylene glycol, diethylene glycol, propylene glycol, butylene glycol, hexylene glycol, and polyethylene glycols with an average molecular weight of from 100 to 1 000 daltons; [0444] technical-grade oligoglycerol mixtures with a degree of self-condensation of from 1.5 to 10, such as, for example, technical-grade diglycerol mixtures with a diglycerol content of from 40 to 50% by weight; [0445] methylol compounds, such as, in particular, trimethylolethane, trimethylolpropane, trimethylolbutane, pentaerythritol and dipentaerythritol; [0446] lower alkyl glucosides, in particular those having 1 to 8 carbon atoms in the alkyl radical, such as, for example, methyl and butyl glucoside; [0447] sugar alcohols having 5 to 12 carbon atoms, such as, for example, sorbitol or mannitol, [0448] sugars having 5 to 12 carbon atoms, such as, for example, glucose or sucrose; [0449] amino sugars, such as, for example, glucamine; [0450] dialcohol amines, such as diethanolamine or 2-amino-1,3-propanediol.

Preservatives

[0451] Suitable preservatives are, for example, phenoxy ethanol, formaldehyde solution, parabens, pentanediol or sorbic acid, and the silver complexes known under the name Surfacins®, and also the other classes of substance listed in Annex 6, Part A and B of the Cosmetics Directive.

Perfume Oils and Aromas

[0452] Perfume oils which may be mentioned are mixtures of natural and synthetic fragrances. Natural fragrances are extracts from flowers (lily, lavender, rose, jasmine, neroli, ylang-ylang), stems and leaves (geranium, patchouli, petitgrain), fruits (aniseed, coriander, cumin, juniper), fruit peels (bergamot, lemon, orange), roots (mace, angelica, celery, cardamon, costus, iris, calmus), woods (pinewood, sandalwood, guaiac wood, cedarwood, rosewood), herbs and grasses (tarragon, lemongrass, sage, thyme), needles and branches (spruce, fir, pine, dwarf-pine), resins and balsams (galbanum, elemi, benzoin, myrrh, olibanum, opoponax). Also suitable are animal raw materials, such as, for example, civet and castoreum. Typical synthetic fragrance compounds are products of the ester, ether, aldehyde, ketone, alcohol and hydrocarbon type. Fragrance compounds of the ester type are, for example, benzyl acetate, phenoxyethyl isobutyrate, p-tert-butylcyclohexyl acetate, linalyl acetate, dimethylbenzylcarbinyl acetate, phenylethyl acetate, linalyl benzoate, benzyl formate, ethylmethylphenyl glycinate, allyl cyclohexylpropionate, styrallyl propionate and benzyl salicylate. The ethers include, for example, benzyl ethyl ether, the aldehydes include, for example, the linear alkanals having 8 to 18 carbon atoms, citral, citronellal, citronellyloxyacetaldehyde, cyclamen aldehyde, hydroxycitronellal, lilial and bourgeonal, and the ketones include, for example, the ionones, aisomethylionone and methyl cedryl ketone, the alcohols include anethole, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol and terpineol, and the hydrocarbons include mainly the terpenes and balsams. Preference is, however, given to using mixtures of different fragrances which together produce a pleasing fragrance note. Essential oils of relatively low volatility, which are mostly used as aroma components, are also suitable as perfume oils, e.g. sage oil, camomile oil, oil of cloves, melissa oil, mint oil, cinnamon leaf oil, linden blossom oil, juniper berry oil, vetiver oil, olibanum oil, galbanum oil, labolanum oil and lavandin oil. Preference is given to using bergamot oil, dihydromyrcenol, lilial, lyral, citronellol, phenylethyl alcohol, a-hexylcinnamaldehyde, geraniol, benzylacetone, cyclamen aldehyde, linalool, boisambrene forte, ambroxan, indole, hedione, sandelice, lemon oil, mandarin oil, orange oil, allyl amyl glycolate, cyclovertal, lavandin oil, clary sage oil, 13-damascone, geranium oil bourbon, cyclohexyl salicylate, Vertofix coeur, iso-Esuper, Fixolide NP, evernyl, iraldein gamma, phenylacetic acid, geranyl acetate, benzyl acetate, rose oxide, romilat, irotyl and floramat alone or in mixtures.

[0453] Suitable aromas are, for example, peppermint oil, spearmint oil, anise oil, star anise oil, caraway oil, eucalyptus oil, fennel oil, lemon oil, wintergreen oil, oil of cloves, menthol and the like.

Dyes

[0454] Dyes which can be used are the substances which are approved and suitable for cosmetic purposes, as are summarized, for example, in the publication "Kosmetische Farbemittel" [Cosmetic Colorants] from the Farbstoffkommission der Deutschen Forschungsgemeinschaft [Dyes Commission of the German Research Council], Verlag Chemie, Weinheim, 1984, pp. 81-106. Examples are cochineal red A (C.1.16255), patent blue V (C.1.42051), indigotin (C.1.73015), chlorophyllin (C.1.75810), quinoline yellow (C.1.47005), titanium dioxide (C.1.77891), indanthrene blue RS (C.1.69800) and madder lake (C.1.58000). As a luminescent dye, it is also possible for luminol to be present. These dyes are customarily used in concentrations of from 0.001 to 0.1% by weight, based on the total mixture.

[0455] The total amount of auxiliaries and additives can be 1 to 50% by weight, preferably 5 to 40% by weight, based on the compositions. The compositions can be prepared by customary cold or hot processes; preference is given to using the phase-inversion temperature method.

EXAMPLES

Effects on the Growth of Human Primary Keratinocytes

[0456] The aim of this test was to analyse the revitalizing and regenerating activities of oligpopeptides according to the invention on human keratinocyte cultures in vitro.

[0457] Human keratinocytes were obtained by trypsinization of skin biopsies. They were incubated in standard medium for cell cultures with foetal calf serum (FCS) and growth factors (EGF 10 ng/ml). After cultivation for 2 days at 37° C. and a CO₂ content of 5%, the medium was replaced by standard medium with varying concentrations of peptides. After a further incubation of 4 or 5 days at 37° C. and a CO₂ content of 5%, the number of living cells was determined by determining the cellular DNA content using an ethidium bromide fluorescent sample. The fluorescence was determined using a fluorimeter (excitation at 538 nm and emission at 590 nm). The foetal calf serum forms a positive control because it comprises many growth factors, such as, for example, IGF (insulin-like growth factor) and PDGF (platelet derived growth factor).

[0458] The results are shown in Table 1 and 2 as the average value from 3 assays in triplicate in % based on a control in which the standard medium comprised no additives.

TABLE-US-00015 TABLE 1 DNA after Concentration culture Oligopeptide % (w/v) for 4-5 days Control -- 100 Foetal calf serum 1 117 +/- 13 Example 1 Arg-Arg-Arg-Pro-Arg-Pro-Pro- 0.001 124 +/- 15 Tyr-Leu-Pro-Arg-Pro-Arg-Pro- 0.003 131 +/- 11 Pro (SEQ ID NO. 341) Example 2 0.001 119 +/- 6 Arg-Arg-Arg-Pro-Arg (SEQ ID NO. 38) 0.003 126 +/- 8 Example 3 0.001 97 +/- 1 Arg-Pro-Pro-Tyr-Leu (SEQ ID NO. 42) 0.003 118 +/- 10 Example 4 0.001 150 +/- 26 Pro-Pro-Tyr-Leu (SEQ ID NO. 7) 0.003 166 +/- 7 Example 5 0.001 118 +/- 3 Pro-Tyr-Leu-Pro-Arg (SEQ ID NO. 44) 0.003 112 +/- 5 Example 6 0.001 110 +/- 6 Tyr-Leu-Pro-Arg-Pro (SEQ ID NO. 45) 0.003 146 +/- 24

TABLE-US-00016 TABLE 2 Concentration DNA after culture Peptide % (w/v) for 3 days Control -- 100 Foetal calf serum 1 126 +/- 17 Example 7 0.00005 136 +/- 13 N-Palmitoyl-Pro-Pro-Tyr-Leu 0.00015 135 +/- 8 (SEQ ID NO. 374)

[0459] The oligopeptide consisting of 15 consecutive amino acids of SEQ ID NO.1 (Example 1, R1=H, R2=OH) as well as the oligopeptides consisting of 5 consecutive amino acids, which are identical to 5 consecutive amino acids of SEQ ID NO.1 (examples 2, 3, 5 and 6, R1=H, R2=OH) as well as the oligopeptides consisting of 4 consecutive amino acids, which are identical to 4 consecutive amino acids of SEQ ID NO.1 (example 4, R1=H, R2=OH) stimulate the growth of human keratinocytes cultivated from biopsies of adult subjects. The activity can still be detected after 5 days even without changing the cell culture medium.

[0460] The same is true for an oligopeptide according to formula (I), wherein [AA] is Pro-Pro-Tyr-Leu (SEQ ID NO.7); , R1 is Palmitoyl and R2 is OH (=example 7).

Stimulation of the Synthesis of Syndecan-1 on Human Keratinocytes

[0461] Monoclonal antibody anti-syndecan-1 and secondary antibody FITC conjugated were obtained from TEBU, Le Perray en Yvelines and BIO-RAD, Marnes-1a-Coquette; KGF (Keratinocyte Growth Factor) (positive control) was obtained from SIGMA, L'Isle d'Abeau Chesnes.

[0462] Human keratinocytes were seeded in DMEM standard medium for 2 days at 37° C., CO₂=5%. Then, N-Acetyl-Pro-Pro-Tyr-Leu (SEQ ID NO. 375) or positive control KGF are introduced and after 5 days of incubation at 37° C., CO₂=5%, the synthesis of syndecan-1 was evaluated on glass slides by immunocytochemistry. Quantification of the staining was carried out by image analysis.

[0463] The results are shown in table 3 as the mean of the sum ±SEM of the product of number of pixels by green detected values (arbitrary unit).

TABLE-US-00017 TABLE 3 Control Treated with without KGF at 10 Treated with N-Acetyl- treatment ng/ml (positive Pro-Pro-Tyr-Leu (DMEM) control) 1 μg/ml 3 μg/ml Sum of product of 1 545 10³ ± 2408 10³ ± 2791 10³ ± 3344 10³ ± number of pixel by 374 10³ 549 10³ 573 10³ 359 10³ (*) green detected values for syndecan-1 (arbitrary unit) Statistics: Test PLSD of Fisher (*)/control, p < 0.01

[0464] Without treatment, human keratinocytes in culture expressed a small amount of syndecan-1. The treatment with the positive control KGF has induced an increase of syndecan-1 expression in the keratinocytes culture.

[0465] The oligopeptide according formula (I) wherein [AA] is Pro-Pro-Tyr-Leu (SEQ ID NO. 7); R1 is Acetyl and R2 is OH stimulates the synthesis of syndecan-1 in human keratinocytes cultivated from biopsies of adult subjects.

TABLE-US-00018 % by weight Cosmetic emulsion: Trade Name [INCI] Emulgade SE-PF (2) 6.00 [Glyceryl Stearate (and) Ceteareth-20 (and) Ceteareth-12 (and) Cethaeryl Alcohol (and) Cetyl palmitate] Lanette 0.sup.(2) 2.50 [Cetearyl Alcohol] Cegesoft C24.sup.(2) 6.00 [Ethyl hexyl palmitate] Cetiol PGL.sup.(2) 5.00 [Hexyldecanol (and) Hexyldecyl laurate] Myritol 312.sup.(2) 3.00 [Caprylic/Capric Triglyceride] DC 200-50cts.sup.(3) 1.00 [Dimethicone] Deioinzed water add 100 Keltrol T.sup.(4) 0.20 [Xantham Gum] Elestab 50J.sup.(1) 0.40 [Chlorphensin (and) Methylparaben] Glycerine 4.00 Carbopol 980.sup.(5) 2% 15.00 [Carbomer] NaOH 10% 0.60 Perfume Champaline G10415611.sup.(6) 0.10 N-Acetyl-Pro-Pro-Tyr-Leu-OH 0.0003 Cosmetic fluid serum Trade Name Deionized water add 100 Elestab 50J.sup.(1) 0.35 [Chlorphenesin (and) Methylparaben] H-Tyr-Leu-Pro-Arg-Pro-OH 0.001 Keltrol CGT.sup.(4) 0.10 [Xantham gum] Cosmedia SP.sup.(2) 0.25 [Sodium Polyacrylate] Suppliers .sup.(1)Laboratoires Serobiologiques .sup.(2)Cognis .sup.(3)Dow Corning .sup.(4)Kelco .sup.(5)Noveon .sup.(6)Robertet

[0466] SEQ 10 No.1 consisting of 39 amino acids:

(=1)Arg Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg He Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe Pro (=39)

Sequence CWU 1

375139PRTArtificialpeptide derived from cathelicidin PR-39 1Arg Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro1 5 10 15Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro 20 25 30Arg Phe Pro Pro Arg Phe Pro 3524PRTArtificialpeptide derived from cathelicidin PR-39 2Arg Arg Arg Pro134PRTArtificialpeptide derived from cathelicidin PR-39 3Arg Arg Pro Arg144PRTArtificialpeptide derived from cathelicidin PR-39 4Arg Pro Arg Pro154PRTArtificialpeptide derived from cathelicidin PR-39 5Pro Arg Pro Pro164PRTArtificialpeptide derived from cathelicidin PR-39 6Arg Pro Pro Tyr174PRTArtificialpeptide derived from cathelicidin PR-39 7Pro Pro Tyr Leu184PRTArtificialpeptide derived from cathelicidin PR-39 8Pro Tyr Leu Pro194PRTArtificialpeptide derived from cathelicidin PR-39 9Tyr Leu Pro Arg1104PRTArtificialpeptide derived from cathelicidin PR-39 10Leu Pro Arg Pro1114PRTArtificialpeptide derived from cathelicidin PR-39 11Pro Arg Pro Arg1124PRTArtificialpeptide derived from cathelicidin PR-39 12Arg Pro Arg Pro1134PRTArtificialpeptide derived from cathelicidin PR-39 13Pro Arg Pro Pro1144PRTArtificialpeptide derived from cathelicidin PR-39 14Arg Pro Pro Pro1154PRTArtificialpeptide derived from cathelicidin PR-39 15Pro Pro Pro Phe1164PRTArtificialpeptide derived from cathelicidin PR-39 16Pro Pro Phe Phe1174PRTArtificialpeptide derived from cathelicidin PR-39 17Pro Phe Phe Pro1184PRTArtificialpeptide derived from cathelicidin PR-39 18Phe Phe Pro Pro1194PRTArtificialpeptide derived from cathelicidin PR-39 19Phe Pro Pro Arg1204PRTArtificialpeptide derived from cathelicidin PR-39 20Pro Pro Arg Leu1214PRTArtificialpeptide derived from cathelicidin PR-39 21Pro Arg Leu Pro1224PRTArtificialpeptide derived from cathelicidin PR-39 22Arg Leu Pro Pro1234PRTArtificialpeptide derived from cathelicidin PR-39 23Leu Pro Pro Arg1244PRTArtificialpeptide derived from cathelicidin PR-39 24Pro Pro Arg Ile1254PRTArtificialpeptide derived from cathelicidin PR-39 25Pro Arg Ile Pro1264PRTArtificialpeptide derived from cathelicidin PR-39 26Arg Ile Pro Pro1274PRTArtificialpeptide derived from cathelicidin PR-39 27Ile Pro Pro Glu1284PRTArtificialpeptide derived from cathelicidin PR-39 28Pro Pro Glu Phe1294PRTArtificialpeptide derived from cathelicidin PR-39 29Pro Glu Phe Pro1304PRTArtificialpeptide derived from cathelicidin PR-39 30Glu Phe Pro Pro1314PRTArtificialpeptide derived from cathelicidin PR-39 31Phe Pro Pro Arg1324PRTArtificialpeptide derived from cathelicidin PR-39 32Pro Pro Arg Phe1334PRTArtificialpeptide derived from cathelicidin PR-39 33Pro Arg Phe Pro1344PRTArtificialpeptide derived from cathelicidin PR-39 34Arg Phe Pro Pro1354PRTArtificialpeptide derived from cathelicidin PR-39 35Phe Pro Pro Arg1364PRTArtificialpeptide derived from cathelicidin PR-39 36Pro Pro Arg Phe1374PRTArtificialpeptide derived from cathelicidin PR-39 37Pro Arg Phe Pro1385PRTArtificialpeptide derived from cathelicidin PR-39 38Arg Arg Arg Pro Arg1 5395PRTArtificialpeptide derived from cathelicidin PR-39 39Arg Arg Pro Arg Pro1 5405PRTArtificialpeptide derived from cathelicidin PR-39 40Arg Pro Arg Pro Pro1 5415PRTArtificialpeptide derived from cathelicidin PR-39 41Pro Arg Pro Pro Tyr1 5425PRTArtificialpeptide derived from cathelicidin PR-39 42Arg Pro Pro Tyr Leu1 5435PRTArtificialpeptide derived from cathelicidin PR-39 43Pro Pro Tyr Leu Pro1 5445PRTArtificialpeptide derived from cathelicidin PR-39 44Pro Tyr Leu Pro Arg1 5455PRTArtificialpeptide derived from cathelicidin PR-39 45Tyr Leu Pro Arg Pro1 5465PRTArtificialpeptide derived from cathelicidin PR-39 46Leu Pro Arg Pro Arg1 5475PRTArtificialpeptide derived from cathelicidin PR-39 47Pro Arg Pro Arg Pro1 5485PRTArtificialpeptide derived from cathelicidin PR-39 48Arg Pro Arg Pro Pro1 5495PRTArtificialpeptide derived from cathelicidin PR-39 49Pro Arg Pro Pro Pro1 5505PRTArtificialpeptide derived from cathelicidin PR-39 50Arg Pro Pro Pro Phe1 5515PRTArtificialpeptide derived from cathelicidin PR-39 51Pro Pro Pro Phe Phe1 5525PRTArtificialpeptide derived from cathelicidin PR-39 52Pro Pro Phe Phe Pro1 5535PRTArtificialpeptide derived from cathelicidin PR-39 53Pro Phe Phe Pro Pro1 5545PRTArtificialpeptide derived from cathelicidin PR-39 54Phe Phe Pro Pro Arg1 5555PRTArtificialpeptide derived from cathelicidin PR-39 55Phe Pro Pro Arg Leu1 5565PRTArtificialpeptide derived from cathelicidin PR-39 56Pro Pro Arg Leu Pro1 5575PRTArtificialpeptide derived from cathelicidin PR-39 57Pro Arg Leu Pro Pro1 5585PRTArtificialpeptide derived from cathelicidin PR-39 58Arg Leu Pro Pro Arg1 5595PRTArtificialpeptide derived from cathelicidin PR-39 59Leu Pro Pro Arg Ile1 5605PRTArtificialpeptide derived from cathelicidin PR-39 60Pro Pro Arg Ile Pro1 5615PRTArtificialpeptide derived from cathelicidin PR-39 61Pro Arg Ile Pro Pro1 5625PRTArtificialpeptide derived from cathelicidin PR-39 62Arg Ile Pro Pro Glu1 5635PRTArtificialpeptide derived from cathelicidin PR-39 63Ile Pro Pro Glu Phe1 5645PRTArtificialpeptide derived from cathelicidin PR-39 64Pro Pro Glu Phe Pro1 5655PRTArtificialpeptide derived from cathelicidin PR-39 65Pro Glu Phe Pro Pro1 5665PRTArtificialpeptide derived from cathelicidin PR-39 66Glu Phe Pro Pro Arg1 5675PRTArtificialpeptide derived from cathelicidin PR-39 67Phe Pro Pro Arg Phe1 5685PRTArtificialpeptide derived from cathelicidin PR-39 68Pro Pro Arg Phe Pro1 5695PRTArtificialpeptide derived from cathelicidin PR-39 69Pro Arg Phe Pro Pro1 5705PRTArtificialpeptide derived from cathelicidin PR-39 70Arg Phe Pro Pro Arg1 5715PRTArtificialpeptide derived from cathelicidin PR-39 71Phe Pro Pro Arg Phe1 5725PRTArtificialpeptide derived from cathelicidin PR-39 72Pro Pro Arg Phe Pro1 5736PRTArtificialpeptide derived from cathelicidin PR-39 73Arg Arg Arg Pro Arg Pro1 5746PRTArtificialpeptide derived from cathelicidin PR-39 74Arg Arg Pro Arg Pro Pro1 5756PRTArtificialpeptide derived from cathelicidin PR-39 75Arg Pro Arg Pro Pro Tyr1 5766PRTArtificialpeptide derived from cathelicidin PR-39 76Pro Arg Pro Pro Tyr Leu1 5776PRTArtificialpeptide derived from cathelicidin PR-39 77Arg Pro Pro Tyr Leu Pro1 5786PRTArtificialpeptide derived from cathelicidin PR-39 78Pro Pro Tyr Leu Pro Arg1 5796PRTArtificialpeptide derived from cathelicidin PR-39 79Pro Tyr Leu Pro Arg Pro1 5806PRTArtificialpeptide derived from cathelicidin PR-39 80Tyr Leu Pro Arg Pro Arg1 5816PRTArtificialpeptide derived from cathelicidin PR-39 81Leu Pro Arg Pro Arg Pro1 5826PRTArtificialpeptide derived from cathelicidin PR-39 82Pro Arg Pro Arg Pro Pro1 5836PRTArtificialpeptide derived from cathelicidin PR-39 83Arg Pro Arg Pro Pro Pro1 5846PRTArtificialpeptide derived from cathelicidin PR-39 84Pro Arg Pro Pro Pro Phe1 5856PRTArtificialpeptide derived from cathelicidin PR-39 85Arg Pro Pro Pro Phe Phe1 5866PRTArtificialpeptide derived from cathelicidin PR-39 86Pro Pro Pro Phe Phe Pro1 5876PRTArtificialpeptide derived from cathelicidin PR-39 87Pro Pro Phe Phe Pro Pro1 5886PRTArtificialpeptide derived from cathelicidin PR-39 88Pro Phe Phe Pro Pro Arg1 5896PRTArtificialpeptide derived from cathelicidin PR-39 89Phe Phe Pro Pro Arg Leu1 5906PRTArtificialpeptide derived from cathelicidin PR-39 90Phe Pro Pro Arg Leu Pro1 5916PRTArtificialpeptide derived from cathelicidin PR-39 91Pro Pro Arg Leu Pro Pro1 5927PRTArtificialpeptide derived from cathelicidin PR-39 92Pro Arg Leu Pro Pro Pro Arg1 5936PRTArtificialpeptide derived from cathelicidin PR-39 93Arg Leu Pro Pro Arg Ile1 5946PRTArtificialpeptide derived from cathelicidin PR-39 94Leu Pro Pro Arg Ile Pro1 5956PRTArtificialpeptide derived from cathelicidin PR-39 95Pro Pro Arg Ile Pro Pro1 5966PRTArtificialpeptide derived from cathelicidin PR-39 96Pro Arg Ile Pro Pro Glu1 5976PRTArtificialpeptide derived from cathelicidin PR-39 97Arg Ile Pro Pro Glu Phe1 5986PRTArtificialpeptide derived from cathelicidin PR-39 98Ile Pro Pro Glu Phe Pro1 5996PRTArtificialpeptide derived from cathelicidin PR-39 99Pro Pro Glu Phe Pro Pro1 51006PRTArtificialpeptide derived from cathelicidin PR-39 100Pro Glu Phe Pro Pro Arg1 51016PRTArtificialpeptide derived from cathelicidin PR-39 101Glu Phe Pro Pro Arg Phe1 51026PRTArtificialpeptide derived from cathelicidin PR-39 102Phe Pro Pro Arg Phe Pro1 51036PRTArtificialpeptide derived from cathelicidin PR-39 103Pro Pro Arg Phe Pro Pro1 51046PRTArtificialpeptide derived from cathelicidin PR-39 104Pro Arg Phe Pro Pro Arg1 51056PRTArtificialpeptide derived from cathelicidin PR-39 105Arg Phe Pro Pro Arg Phe1 51066PRTArtificialpeptide derived from cathelicidin PR-39 106Phe Pro Pro Arg Phe Pro1 51077PRTArtificialpeptide derived from cathelicidin PR-39 107Arg Arg Arg Pro Arg Pro Pro1 51087PRTArtificialpeptide derived from cathelicidin PR-39 108Arg Arg Pro Arg Pro Pro Tyr1 51097PRTArtificialpeptide derived from cathelicidin PR-39 109Arg Pro Arg Pro Pro Tyr Leu1 51107PRTArtificialpeptide derived from cathelicidin PR-39 110Pro Arg Pro Pro Tyr Leu Pro1 51117PRTArtificialpeptide derived from cathelicidin PR-39 111Arg Pro Pro Tyr Leu Pro Arg1 51127PRTArtificialpeptide derived from cathelicidin PR-39 112Pro Pro Tyr Leu Pro Arg Pro1 51137PRTArtificialpeptide derived from cathelicidin PR-39 113Pro Tyr Leu Pro Arg Pro Arg1 51147PRTArtificialpeptide derived from cathelicidin PR-39 114Tyr Leu Pro Arg Pro Arg Pro1 51157PRTArtificialpeptide derived from cathelicidin PR-39 115Leu Pro Arg Pro Arg Pro Pro1 51167PRTArtificialpeptide derived from cathelicidin PR-39 116Pro Arg Pro Arg Pro Pro Pro1 51177PRTArtificialpeptide derived from cathelicidin PR-39 117Arg Pro Arg Pro Pro Pro Phe1 51187PRTArtificialpeptide derived from cathelicidin PR-39 118Pro Arg Pro Pro Pro Phe Phe1 51197PRTArtificialpeptide derived from cathelicidin PR-39 119Arg Pro Pro Pro Phe Phe Pro1 51207PRTArtificialpeptide derived from cathelicidin PR-39 120Pro Pro Pro Phe Phe Pro Pro1 51217PRTArtificialpeptide derived from cathelicidin PR-39 121Pro Pro Phe Phe Pro Pro Arg1 51227PRTArtificialpeptide derived from cathelicidin PR-39 122Pro Phe Phe Pro Pro Arg Leu1 51237PRTArtificialpeptide derived from cathelicidin PR-39 123Phe Phe Pro Pro Arg Leu Pro1 51247PRTArtificialpeptide derived from cathelicidin PR-39 124Phe Pro Pro Arg Leu Pro Pro1 51257PRTArtificialpeptide derived from cathelicidin PR-39 125Pro Pro Arg Leu Pro Pro Arg1 51267PRTArtificialpeptide derived from cathelicidin PR-39 126Pro Arg Leu Pro Pro Arg Ile1 51277PRTArtificialpeptide derived from cathelicidin PR-39 127Arg Leu Pro Pro Arg Ile Pro1 51287PRTArtificialpeptide derived from cathelicidin PR-39 128Leu Pro Pro Arg Ile Pro Pro1 51297PRTArtificialpeptide derived from cathelicidin PR-39 129Pro Pro Arg Ile Pro Pro Glu1 51307PRTArtificialpeptide derived from cathelicidin PR-39 130Pro Arg Ile Pro Pro Glu Phe1 51317PRTArtificialpeptide derived from cathelicidin PR-39 131Arg Ile Pro Pro Glu Phe Pro1 51327PRTArtificialpeptide derived from cathelicidin PR-39 132Ile Pro Pro Glu Phe Pro Pro1 51337PRTArtificialpeptide derived from cathelicidin PR-39 133Pro Pro Glu Phe Pro Pro Arg1 51347PRTArtificialpeptide derived from cathelicidin PR-39 134Pro Glu Phe Pro Pro Arg Phe1 51357PRTArtificialpeptide derived from cathelicidin PR-39 135Glu Phe Pro Pro Arg Phe Pro1 51367PRTArtificialpeptide derived from cathelicidin PR-39 136Phe Pro Pro Arg Phe Pro Pro1 51377PRTArtificialpeptide derived from cathelicidin PR-39 137Pro Pro Arg Phe Pro Pro Arg1 51387PRTArtificialpeptide derived from cathelicidin PR-39 138Pro Arg Phe Pro Pro Arg Phe1 51397PRTArtificialpeptide derived from cathelicidin PR-39 139Arg Phe Pro Pro Arg Phe Pro1 51408PRTArtificialpeptide derived from cathelicidin PR-39 140Arg Arg Arg Pro Arg Pro Pro Tyr1 51418PRTArtificialpeptide derived from cathelicidin PR-39 141Arg Arg Pro Arg Pro Pro Tyr Leu1 51428PRTArtificialpeptide derived from cathelicidin PR-39 142Arg Pro Arg Pro Pro Tyr Leu Pro1 51438PRTArtificialpeptide derived from cathelicidin PR-39 143Pro Arg Pro Pro Tyr Leu Pro Arg1 51448PRTArtificialpeptide derived from cathelicidin PR-39 144Arg Pro Pro Tyr Leu Pro Arg Pro1 51458PRTArtificialpeptide derived from cathelicidin PR-39 145Pro Pro Tyr Leu Pro Arg Pro Arg1 51468PRTArtificialpeptide derived from cathelicidin PR-39 146Pro Tyr Leu Pro Arg Pro Arg Pro1 51478PRTArtificialpeptide derived from cathelicidin PR-39 147Tyr Leu Pro Arg Pro Arg Pro Pro1 51488PRTArtificialpeptide derived from cathelicidin PR-39 148Leu Pro Arg Pro Arg Pro Pro Pro1 51498PRTArtificialpeptide derived from cathelicidin PR-39 149Pro Arg Pro Arg Pro Pro Pro Phe1 51508PRTArtificialpeptide derived from cathelicidin PR-39 150Arg Pro Arg Pro Pro Pro Phe Phe1 51518PRTArtificialpeptide derived from cathelicidin PR-39 151Pro Arg Pro Pro Pro Phe Phe Pro1 51528PRTArtificialpeptide derived from cathelicidin PR-39 152Arg Pro Pro Pro Phe Phe Pro Pro1 51538PRTArtificialpeptide derived from cathelicidin PR-39 153Pro Pro Pro Phe Phe Pro Pro Arg1 51548PRTArtificialpeptide derived from cathelicidin PR-39 154Pro Pro Phe Phe Pro Pro Arg Leu1 51558PRTArtificialpeptide derived from cathelicidin PR-39 155Pro Phe Phe Pro Pro Arg Leu Pro1 51568PRTArtificialpeptide derived from cathelicidin PR-39 156Phe Phe Pro Pro Arg Leu Pro Pro1 51578PRTArtificialpeptide derived from cathelicidin PR-39 157Phe Pro Pro Arg Leu Pro Pro Arg1 51588PRTArtificialpeptide derived from cathelicidin PR-39 158Pro Pro Arg Leu Pro Pro Arg Ile1 51598PRTArtificialpeptide derived from cathelicidin PR-39 159Pro Arg Leu Pro Pro Arg Ile Pro1 51608PRTArtificialpeptide derived from cathelicidin PR-39 160Arg Leu Pro Pro Arg Ile Pro Pro1 51618PRTArtificialpeptide derived from cathelicidin PR-39 161Leu Pro Pro Arg Ile Pro Pro Glu1 51628PRTArtificialpeptide derived from cathelicidin PR-39 162Pro Pro Arg Ile Pro Pro Glu Phe1 51638PRTArtificialpeptide derived from cathelicidin PR-39 163Pro Arg Ile Pro Pro Glu Phe Pro1 51648PRTArtificialpeptide derived from cathelicidin PR-39 164Arg Ile Pro Pro Glu Phe Pro Pro1 51658PRTArtificialpeptide derived from cathelicidin PR-39 165Ile Pro Pro Glu Phe Pro Pro Arg1 51668PRTArtificialpeptide derived from cathelicidin PR-39 166Pro Pro Glu Phe Pro Pro Arg Phe1 51678PRTArtificialpeptide derived from cathelicidin PR-39 167Pro Glu Phe Pro Pro Arg Phe Pro1 51688PRTArtificialpeptide derived from cathelicidin PR-39 168Glu Phe Pro Pro Arg Phe Pro Pro1 51698PRTArtificialpeptide derived from cathelicidin PR-39 169Phe Pro Pro Arg Phe Pro Pro Arg1 51708PRTArtificialpeptide derived from cathelicidin PR-39 170Pro Pro Arg Phe Pro Pro Arg Phe1 51718PRTArtificialpeptide derived from cathelicidin PR-39 171Pro Arg Phe Pro Pro Arg Phe Pro1 51729PRTArtificialpeptide derived from cathelicidin PR-39 172Arg Arg Arg Pro Arg Pro Pro Tyr Leu1 51739PRTArtificialpeptide derived from cathelicidin PR-39 173Arg Arg Pro Arg Pro Pro Tyr Leu Pro1 51749PRTArtificialpeptide derived from cathelicidin PR-39 174Arg Pro Arg Pro Pro Tyr Leu Pro Arg1 51759PRTArtificialpeptide derived from cathelicidin PR-39 175Pro Arg Pro Pro Tyr Leu Pro Arg Pro1 51769PRTArtificialpeptide derived from cathelicidin PR-39 176Arg Pro Pro Tyr Leu Pro Arg Pro Arg1 51779PRTArtificialpeptide derived from cathelicidin PR-39 177Pro Pro Tyr Leu Pro Arg Pro Arg Pro1 51789PRTArtificialpeptide derived from cathelicidin PR-39 178Pro Tyr Leu Pro Arg Pro Arg Pro Pro1 51799PRTArtificialpeptide derived from cathelicidin PR-39 179Tyr Leu Pro Arg Pro Arg Pro Pro Pro1 51809PRTArtificialpeptide derived from cathelicidin PR-39 180Leu Pro Arg Pro Arg Pro Pro Pro Phe1 51819PRTArtificialpeptide derived from cathelicidin PR-39 181Pro Arg Pro Arg Pro Pro Pro Phe Phe1

51829PRTArtificialpeptide derived from cathelicidin PR-39 182Arg Pro Arg Pro Pro Pro Phe Phe Pro1 51839PRTArtificialpeptide derived from cathelicidin PR-39 183Pro Arg Pro Pro Pro Phe Phe Pro Pro1 51849PRTArtificialpeptide derived from cathelicidin PR-39 184Arg Pro Pro Pro Phe Phe Pro Pro Arg1 51859PRTArtificialpeptide derived from cathelicidin PR-39 185Pro Pro Pro Phe Phe Pro Pro Arg Leu1 51869PRTArtificialpeptide derived from cathelicidin PR-39 186Pro Pro Phe Phe Pro Pro Arg Leu Pro1 51879PRTArtificialpeptide derived from cathelicidin PR-39 187Pro Phe Phe Pro Pro Arg Leu Pro Pro1 51889PRTArtificialpeptide derived from cathelicidin PR-39 188Phe Phe Pro Pro Arg Leu Pro Pro Arg1 51899PRTArtificialpeptide derived from cathelicidin PR-39 189Phe Pro Pro Arg Leu Pro Pro Arg Ile1 51909PRTArtificialpeptide derived from cathelicidin PR-39 190Pro Pro Arg Leu Pro Pro Arg Ile Pro1 51919PRTArtificialpeptide derived from cathelicidin PR-39 191Pro Arg Leu Pro Pro Arg Ile Pro Pro1 51929PRTArtificialpeptide derived from cathelicidin PR-39 192Arg Leu Pro Pro Arg Ile Pro Pro Glu1 51939PRTArtificialpeptide derived from cathelicidin PR-39 193Leu Pro Pro Arg Ile Pro Pro Glu Phe1 51949PRTArtificialpeptide derived from cathelicidin PR-39 194Pro Pro Arg Ile Pro Pro Glu Phe Pro1 51959PRTArtificialpeptide derived from cathelicidin PR-39 195Pro Arg Ile Pro Pro Glu Phe Pro Pro1 51969PRTArtificialpeptide derived from cathelicidin PR-39 196Arg Ile Pro Pro Glu Phe Pro Pro Arg1 51979PRTArtificialpeptide derived from cathelicidin PR-39 197Ile Pro Pro Glu Phe Pro Pro Arg Phe1 51989PRTArtificialpeptide derived from cathelicidin PR-39 198Pro Pro Glu Phe Pro Pro Arg Phe Pro1 51999PRTArtificialpeptide derived from cathelicidin PR-39 199Pro Glu Phe Pro Pro Arg Phe Pro Pro1 52009PRTArtificialpeptide derived from cathelicidin PR-39 200Glu Phe Pro Pro Arg Phe Pro Pro Arg1 52019PRTArtificialpeptide derived from cathelicidin PR-39 201Phe Pro Pro Arg Phe Pro Pro Arg Phe1 52029PRTArtificialpeptide derived from cathelicidin PR-39 202Pro Pro Arg Phe Pro Pro Arg Phe Pro1 520310PRTArtificialpeptide derived from cathelicidin PR-39 203Arg Arg Arg Pro Arg Pro Pro Tyr Leu Pro1 5 1020410PRTArtificialpeptide derived from cathelicidin PR-39 204Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg1 5 1020510PRTArtificialpeptide derived from cathelicidin PR-39 205Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro1 5 1020610PRTArtificialpeptide derived from cathelicidin PR-39 206Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg1 5 1020710PRTArtificialpeptide derived from cathelicidin PR-39 207Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro1 5 1020810PRTArtificialpeptide derived from cathelicidin PR-39 208Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro1 5 1020910PRTArtificialpeptide derived from cathelicidin PR-39 209Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro1 5 1021010PRTArtificialpeptide derived from cathelicidin PR-39 210Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe1 5 1021110PRTArtificialpeptide derived from cathelicidin PR-39 211Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe1 5 1021210PRTArtificialpeptide derived from cathelicidin PR-39 212Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro1 5 1021310PRTArtificialpeptide derived from cathelicidin PR-39 213Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro1 5 1021410PRTArtificialpeptide derived from cathelicidin PR-39 214Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg1 5 1021510PRTArtificialpeptide derived from cathelicidin PR-39 215Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu1 5 1021610PRTArtificialpeptide derived from cathelicidin PR-39 216Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro1 5 1021710PRTArtificialpeptide derived from cathelicidin PR-39 217Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro1 5 1021810PRTArtificialpeptide derived from cathelicidin PR-39 218Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg1 5 1021910PRTArtificialpeptide derived from cathelicidin PR-39 219Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile1 5 1022010PRTArtificialpeptide derived from cathelicidin PR-39 220Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro1 5 1022110PRTArtificialpeptide derived from cathelicidin PR-39 221Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro1 5 1022210PRTArtificialpeptide derived from cathelicidin PR-39 222Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu1 5 1022310PRTArtificialpeptide derived from cathelicidin PR-39 223Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe1 5 1022410PRTArtificialpeptide derived from cathelicidin PR-39 224Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro1 5 1022510PRTArtificialpeptide derived from cathelicidin PR-39 225Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro1 5 1022610PRTArtificialpeptide derived from cathelicidin PR-39 226Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg1 5 1022710PRTArtificialpeptide derived from cathelicidin PR-39 227Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe1 5 1022810PRTArtificialpeptide derived from cathelicidin PR-39 228Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro1 5 1022910PRTArtificialpeptide derived from cathelicidin PR-39 229Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro1 5 1023010PRTArtificialpeptide derived from cathelicidin PR-39 230Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg1 5 1023110PRTArtificialpeptide derived from cathelicidin PR-39 231Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe1 5 1023210PRTArtificialpeptide derived from cathelicidin PR-39 232Phe Pro Pro Arg Phe Pro Pro Arg Phe Pro1 5 1023311PRTArtificialpeptide derived from cathelicidin PR-39 233Arg Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg1 5 1023411PRTArtificialpeptide derived from cathelicidin PR-39 234Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro1 5 1023511PRTArtificialpeptide derived from cathelicidin PR-39 235Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg1 5 1023611PRTArtificialpeptide derived from cathelicidin PR-39 236Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro1 5 1023711PRTArtificialpeptide derived from cathelicidin PR-39 237Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro1 5 1023811PRTArtificialpeptide derived from cathelicidin PR-39 238Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro1 5 1023911PRTArtificialpeptide derived from cathelicidin PR-39 239Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe1 5 1024011PRTArtificialpeptide derived from cathelicidin PR-39 240Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe1 5 1024111PRTArtificialpeptide derived from cathelicidin PR-39 241Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro1 5 1024211PRTArtificialpeptide derived from cathelicidin PR-39 242Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro1 5 1024311PRTArtificialpeptide derived from cathelicidin PR-39 243Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg1 5 1024411PRTArtificialpeptide derived from cathelicidin PR-39 244Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu1 5 1024511PRTArtificialpeptide derived from cathelicidin PR-39 245Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro1 5 1024611PRTArtificialpeptide derived from cathelicidin PR-39 246Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro1 5 1024711PRTArtificialpeptide derived from cathelicidin PR-39 247Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg1 5 1024811PRTArtificialpeptide derived from cathelicidin PR-39 248Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile1 5 1024911PRTArtificialpeptide derived from cathelicidin PR-39 249Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro1 5 1025011PRTArtificialpeptide derived from cathelicidin PR-39 250Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro1 5 1025111PRTArtificialpeptide derived from cathelicidin PR-39 251Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu1 5 1025211PRTArtificialpeptide derived from cathelicidin PR-39 252Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe1 5 1025311PRTArtificialpeptide derived from cathelicidin PR-39 253Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro1 5 1025411PRTArtificialpeptide derived from cathelicidin PR-39 254Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro1 5 1025511PRTArtificialpeptide derived from cathelicidin PR-39 255Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg1 5 1025611PRTArtificialpeptide derived from cathelicidin PR-39 256Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe1 5 1025711PRTArtificialpeptide derived from cathelicidin PR-39 257Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro1 5 1025811PRTArtificialpeptide derived from cathelicidin PR-39 258Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro1 5 1025911PRTArtificialpeptide derived from cathelicidin PR-39 259Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg1 5 1026011PRTArtificialpeptide derived from cathelicidin PR-39 260Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe1 5 1026111PRTArtificialpeptide derived from cathelicidin PR-39 261Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe Pro1 5 1026212PRTArtificialpeptide derived from cathelicidin PR-39 262Arg Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro1 5 1026312PRTArtificialpeptide derived from cathelicidin PR-39 263Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg1 5 1026412PRTArtificialpeptide derived from cathelicidin PR-39 264Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro1 5 1026512PRTArtificialpeptide derived from cathelicidin PR-39 265Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro1 5 1026612PRTArtificialpeptide derived from cathelicidin PR-39 266Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro1 5 1026712PRTArtificialpeptide derived from cathelicidin PR-39 267Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe1 5 1026812PRTArtificialpeptide derived from cathelicidin PR-39 268Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe1 5 1026912PRTArtificialpeptide derived from cathelicidin PR-39 269Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro1 5 1027012PRTArtificialpeptide derived from cathelicidin PR-39 270Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro1 5 1027112PRTArtificialpeptide derived from cathelicidin PR-39 271Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg1 5 1027212PRTArtificialpeptide derived from cathelicidin PR-39 272Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu1 5 1027312PRTArtificialpeptide derived from cathelicidin PR-39 273Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro1 5 1027412PRTArtificialpeptide derived from cathelicidin PR-39 274Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro1 5 1027512PRTArtificialpeptide derived from cathelicidin PR-39 275Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg1 5 1027612PRTArtificialpeptide derived from cathelicidin PR-39 276Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile1 5 1027712PRTArtificialpeptide derived from cathelicidin PR-39 277Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro1 5 1027812PRTArtificialpeptide derived from cathelicidin PR-39 278Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro1 5 1027912PRTArtificialpeptide derived from cathelicidin PR-39 279Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu1 5 1028012PRTArtificialpeptide derived from cathelicidin PR-39 280Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe1 5 1028112PRTArtificialpeptide derived from cathelicidin PR-39 281Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro1 5 1028212PRTArtificialpeptide derived from cathelicidin PR-39 282Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro1 5 1028312PRTArtificialpeptide derived from cathelicidin PR-39 283Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg1 5 1028412PRTArtificialpeptide derived from cathelicidin PR-39 284Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe1 5 1028512PRTArtificialpeptide derived from cathelicidin PR-39 285Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro1 5 1028612PRTArtificialpeptide derived from cathelicidin PR-39 286Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro1 5 1028712PRTArtificialpeptide derived from cathelicidin PR-39 287Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg1 5 1028812PRTArtificialpeptide derived from cathelicidin PR-39 288Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe1 5 1028912PRTArtificialpeptide derived from cathelicidin PR-39 289Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe Pro1 5 1029013PRTArtificialpeptide derived from cathelicidin PR-39 290Arg Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg1 5 1029113PRTArtificialpeptide derived from cathelicidin PR-39 291Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro1 5 1029213PRTArtificialpeptide derived from cathelicidin PR-39 292Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro1 5 1029313PRTArtificialpeptide derived from cathelicidin PR-39 293Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro1 5 1029413PRTArtificialpeptide derived from cathelicidin PR-39 294Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe1 5 1029513PRTArtificialpeptide derived from cathelicidin PR-39 295Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe1 5 1029613PRTArtificialpeptide derived from cathelicidin PR-39 296Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro1 5 1029713PRTArtificialpeptide derived from cathelicidin PR-39 297Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro1 5 1029813PRTArtificialpeptide derived from cathelicidin PR-39 298Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg1 5 1029913PRTArtificialpeptide derived from cathelicidin PR-39 299Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu1 5 1030013PRTArtificialpeptide derived from cathelicidin PR-39 300Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro1 5 1030113PRTArtificialpeptide derived from cathelicidin PR-39 301Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro1 5 1030213PRTArtificialpeptide derived from cathelicidin PR-39 302Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg1 5 1030313PRTArtificialpeptide derived from cathelicidin PR-39 303Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile1 5 1030413PRTArtificialpeptide derived from cathelicidin PR-39 304Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro1 5 1030513PRTArtificialpeptide derived from cathelicidin PR-39 305Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro1 5 1030613PRTArtificialpeptide derived from cathelicidin PR-39 306Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu1 5 1030713PRTArtificialpeptide derived from cathelicidin PR-39 307Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe1 5 1030813PRTArtificialpeptide derived from cathelicidin PR-39 308Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro1 5 1030913PRTArtificialpeptide derived from cathelicidin PR-39 309Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro1 5

1031013PRTArtificialpeptide derived from cathelicidin PR-39 310Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg1 5 1031113PRTArtificialpeptide derived from cathelicidin PR-39 311Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe1 5 1031213PRTArtificialpeptide derived from cathelicidin PR-39 312Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro1 5 1031313PRTArtificialpeptide derived from cathelicidin PR-39 313Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro1 5 1031413PRTArtificialpeptide derived from cathelicidin PR-39 314Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg1 5 1031513PRTArtificialpeptide derived from cathelicidin PR-39 315Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe1 5 1031613PRTArtificialpeptide derived from cathelicidin PR-39 316Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe Pro1 5 1031714PRTArtificialpeptide derived from cathelicidin PR-39 317Arg Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro1 5 1031814PRTArtificialpeptide derived from cathelicidin PR-39 318Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro1 5 1031914PRTArtificialpeptide derived from cathelicidin PR-39 319Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro1 5 1032014PRTArtificialpeptide derived from cathelicidin PR-39 320Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe1 5 1032114PRTArtificialpeptide derived from cathelicidin PR-39 321Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe1 5 1032214PRTArtificialpeptide derived from cathelicidin PR-39 322Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro1 5 1032314PRTArtificialpeptide derived from cathelicidin PR-39 323Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro1 5 1032414PRTArtificialpeptide derived from cathelicidin PR-39 324Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg1 5 1032514PRTArtificialpeptide derived from cathelicidin PR-39 325Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu1 5 1032614PRTArtificialpeptide derived from cathelicidin PR-39 326Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro1 5 1032714PRTArtificialpeptide derived from cathelicidin PR-39 327Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg1 5 1032814PRTArtificialpeptide derived from cathelicidin PR-39 328Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile1 5 1032914PRTArtificialpeptide derived from cathelicidin PR-39 329Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro1 5 1033014PRTArtificialpeptide derived from cathelicidin PR-39 330Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro1 5 1033114PRTArtificialpeptide derived from cathelicidin PR-39 331Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu1 5 1033214PRTArtificialpeptide derived from cathelicidin PR-39 332Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe1 5 1033314PRTArtificialpeptide derived from cathelicidin PR-39 333Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro1 5 1033414PRTArtificialpeptide derived from cathelicidin PR-39 334Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg1 5 1033514PRTArtificialpeptide derived from cathelicidin PR-39 335Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe1 5 1033614PRTArtificialpeptide derived from cathelicidin PR-39 336Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro1 5 1033714PRTArtificialpeptide derived from cathelicidin PR-39 337Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro1 5 1033814PRTArtificialpeptide derived from cathelicidin PR-39 338Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg1 5 1033914PRTArtificialpeptide derived from cathelicidin PR-39 339Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe1 5 1034014PRTArtificialpeptide derived from cathelicidin PR-39 340Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe Pro1 5 1034115PRTArtificialpeptide derived from cathelicidin PR-39 341Arg Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro1 5 10 1534215PRTArtificialpeptide derived from cathelicidin PR-39 342Arg Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro1 5 10 1534315PRTArtificialpeptide derived from cathelicidin PR-39 343Arg Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe1 5 10 1534415PRTArtificialpeptide derived from cathelicidin PR-39 344Pro Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe1 5 10 1534515PRTArtificialpeptide derived from cathelicidin PR-39 345Arg Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro1 5 10 1534615PRTArtificialpeptide derived from cathelicidin PR-39 346Pro Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro1 5 10 1534715PRTArtificialpeptide derived from cathelicidin PR-39 347Pro Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg1 5 10 1534815PRTArtificialpeptide derived from cathelicidin PR-39 348Tyr Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu1 5 10 1534915PRTArtificialpeptide derived from cathelicidin PR-39 349Leu Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro1 5 10 1535015PRTArtificialpeptide derived from cathelicidin PR-39 350Pro Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro1 5 10 1535115PRTArtificialpeptide derived from cathelicidin PR-39 351Arg Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg1 5 10 1535215PRTArtificialpeptide derived from cathelicidin PR-39 352Pro Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile1 5 10 1535315PRTArtificialpeptide derived from cathelicidin PR-39 353Arg Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro1 5 10 1535415PRTArtificialpeptide derived from cathelicidin PR-39 354Pro Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro1 5 10 1535515PRTArtificialpeptide derived from cathelicidin PR-39 355Pro Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu1 5 10 1535615PRTArtificialpeptide derived from cathelicidin PR-39 356Pro Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe1 5 10 1535715PRTArtificialpeptide derived from cathelicidin PR-39 357Phe Phe Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro1 5 10 1535815PRTArtificialpeptide derived from cathelicidin PR-39 358Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg1 5 10 1535915PRTArtificialpeptide derived from cathelicidin PR-39 359Pro Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg1 5 10 1536015PRTArtificialpeptide derived from cathelicidin PR-39 360Pro Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe1 5 10 1536115PRTArtificialpeptide derived from cathelicidin PR-39 361Arg Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro1 5 10 1536215PRTArtificialpeptide derived from cathelicidin PR-39 362Leu Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro1 5 10 1536315PRTArtificialpeptide derived from cathelicidin PR-39 363Pro Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg1 5 10 1536415PRTArtificialpeptide derived from cathelicidin PR-39 364Pro Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe1 5 10 1536515PRTArtificialpeptide derived from cathelicidin PR-39 365Arg Ile Pro Pro Glu Phe Pro Pro Arg Phe Pro Pro Arg Phe Pro1 5 10 153663PRTArtificialpeptide derived from cathelicidin PR-39 366Arg Pro Arg13674PRTArtificialpeptide derived from cathelicidin PR-39 367Arg Lys Pro Arg13684PRTArtificialpeptide derived from cathelicidin PR-39 368Thr Lys Pro Arg13694PRTArtificialpeptide derived from cathelicidin PR-39 369Thr Lys Pro Arg13704PRTArtificialpeptide derived from cathelicidin PR-39 370Gly Gln Pro Arg13714PRTArtificialpeptide derived from cathelicidin PR-39 371Gly Gln Pro Arg13725PRTArtificialpeptide derived from cathelicidin PR-39 372Phe Tyr Arg Pro Arg1 53735PRTArtificialpeptide derived from cathelicidin PR-39 373Ala Arg Asp Pro Arg1 53744PRTArtificialpeptide derived from cathelicidin PR-39 374Pro Pro Tyr Leu13754PRTArtificialpeptide derived from cathelicidin PR-39 375Pro Pro Tyr Leu1

Claims

1. A cosmetic composition comprising oligopeptides with the structure of formula (I) R1-[AA]_n-R2 (I) wherein [AA] comprises at least 5 consecutive amino acids, which are identical compared to 5 consecutive amino acids of SEQ 10 NO. 1, wherein n is the total number of amino acids in the oligopeptide, wherein n=5; wherein R1 is linked to the amino-terminal part of [AA] and is selected from the group consisting of a) --H, b) a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24 carbon atoms, wherein said acyl group is optionally functionalised by a --OH, --SH, --COOH or --CONH₂ group, and c) a sterol or a sphingolipid group which is joined to the amino terminal part of [AA] via a bifunctional linker, and wherein R2 is linked to the C═O group of the carboxy terminal part of [AA] and is selected from the group consisting of d) --OH, e) --NH₂, f) a linear saturated or unsaturated or branched saturated or unsaturated alkoxy group having 1 to 24 carbon atoms, wherein said acyl group is optionally functionalised by a --OH, --SH, --COOH or CONH₂ group, and g) a sterol or a sphingolipid group.

2. The composition of claim 1, wherein [AA] comprises at least 5 consecutive amino acids identical to amino acids no. 1 to 15 of SEQ ID0 NO.1.

3. The composition of claim 1, wherein R1=H or a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 12 carbon atoms.

4. The composition of claim 3, wherein R1=H and R2=OH.

5. The composition of claim 1, wherein the oligopeptides are present in a concentration of from 0.05 to 500 ppm.

6. The composition of claim 5, wherein the oligopeptides are present in a concentration of from 0.5 to 100 ppm.

7. The composition of claim 1 which is selected from the group consisting of shampoos, hair lotions, foam baths, shower baths, creams, gels, lotions, alcoholic and aqueous/alcoholic solutions, emulsions, wax/fat masses, stick preparations, powders and ointments.

8. The composition of claim 1, wherein said oligopeptides are present in an amount effective to stimulate the growth of human keratinocytes in-vitro.

9. The composition of claim 1, wherein said at least 5 consecutive amino acids is selected from the group consisting of Arg-Arg-Arg-Pro-Arg (SEQ ID NO. 38), Arg-Pro-Pro-Tyr-Leu (SEQ ID NO. 42), Pro-Tyr-Leu-Pro-Arg (SEQ ID NO. 44), and Tyr-Leu-Pro-Arg-Pro (SEQ ID NO. 45).

10. A cosmetic composition comprising oligopeptides with the structure of formula (I) R1-[AA]_n-R2 (I) wherein [AA] comprises at least 5 consecutive amino acids, which are identical compared to 5 consecutive amino acids of SEQ ID NO. 1, wherein n is the total number of amino acids in the oligopeptide, wherein n=5, wherein R1 is linked to the amino-terminal part of [AA] and is selected from the group consisting of a. --H, b. a linear saturated or unsaturated or branched saturated or unsaturated acyl group having 1 to 24 carbon atoms, which may be functionalised by a --OH, --SH, --COOH or --CONH₂ group, or c. a sterol or a sphingolipid group which is joined to the amino terminal part of [AA] via a bifunctional linker, wherein R2 is linked to the C═O group of the carboxy terminal part of [AA] and is selected from the group consisting of d) --OH, e) --NH₂, f) a linear saturated or unsaturated or branched saturated or unsaturated alkoxy group having 1 to 24 carbon atoms, which may be functionalised by a --OH, SH, --COOH or --CONH₂ group, and g) a sterol or a sphingolipid group, with the proviso that if R1 is --H, R2 is not --OH; or that if R2 is --OH, R1 is not --H; and with the further proviso that if R1 is --H, R2 is selected from the group consisting of h) --NH₂, i) a linear saturated or unsaturated or branched saturated or unsaturated alkoxy group having 2 to 24 carbon atoms, and j) a sterol or a sphingolipid group.

11. The composition of claim 10, wherein the oligopeptides are present in a concentration of from 0.05 to 500 ppm.

12. The composition of claim 11, wherein the oligopeptides are present in a concentration of from 0.5 to 100 ppm.

13. A method for strengthening the cutaneous barrier of human skin comprising contacting the skin with the cosmetic composition of claim 1 in an amount effective to stimulate the growth and differentiation of human keratinocytes.

14. A method for strengthening the cutaneous barrier of human skin comprising contacting the skin with the cosmetic composition of claim 1 in an amount effective to stimulate syndecan-1 synthesis.

15. A method for delaying and preventing skin aging and strengthening firmness, epidermal cohesion, and dermo-epidermal junction of human skin comprising contacting the skin with the cosmetic composition of claim 1 in an amount effective to stimulate the growth and differentiation of human keratinoctyes.

16. A method for delaying and preventing skin aging and strengthening firmness, epidermal cohesion, and dermo-epidermal junction of human skin comprising contacting the skin with the cosmetic composition of claim 1 in an amount effective to stimulate syndecan-1 synthesis.

17. An oligopeptide selected from the group consisting of Arg-Arg-Arg-Pro-Arg (SEQ ID NO. 38), Arg-Pro-Pro-Tyr-Leu (SEQ ID NO. 42), Pro-Tyr-Leu-Pro-Arg (SEQ ID NO. 44), and Tyr-Leu-Pro-Arg-Pro (SEQ ID NO. 45).

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