Patent application title: METHOD FOR DIAGNOSING AND TREATING BRONCHIAL ASTHMA
Fatema Salem Al-Thallab (Jahra, KW)
IPC8 Class: AA61K4904FI
Class name: Drug, bio-affecting and body treating compositions in vivo diagnosis or in vivo testing x-ray contrast imaging agent (e.g., computed tomography, angiography, etc.)
Publication date: 2008-12-25
Patent application number: 20080317673
A method for diagnosing and treating a bronchial asthma by classifying a
patient's asthma as Type I, Type II or Type III based on the patient's
symptoms is disclosed. The symptoms for the three types of asthma are
disclosed together with recommended treatment guidelines for each type to
optimize treatment regiments based on symptoms.
1. A method for diagnosing and treating a patient with bronchial asthma
comprising the steps of:establishing three types of bronchial asthma,
namely Type I or a wet type, Type II or a dry type and Type III or a
mixed type and wherein the wet type is characterized by more production
of mucus than bronchi constriction while the dry type presents more
evidence of bronchi spasms than mucus production and Type III, the mixed
type is between the Type I and Type II asthmas;diagnosing a patients
asthma as a Type I, Type II or Type III asthma based on an examination of
a patient; andtreating the patient for the type of asthma diagnosed
wherein the Type I asthma is treated with a mucolytic more than a bronco
dilator and in which the Type II is treated with a bronco dilator as a
major part of the treatment.
2. A method for diagnosing and treating a patient with bronchial asthma according to claim 1 in which the diagnoses of a patient's asthma is based on an initial physical examination.
3. A method for diagnosing and treating a patient with bronchial asthma according to claim 2 in which the diagnoses is also based on a patient's age.
4. A method for diagnosing and treating a patient with bronchial asthma according to claim 3 in which the diagnoses is also based on the severity of the symptoms during an initial attack.
5. A method for diagnosing and treating a patient with bronchial asthma according to claim 4 in which the diagnoses is also based on chest findings.
6. A method for diagnosing and treating a patient with bronchial asthma according to claim 5 in which the diagnoses is also based on a presentation of other allergies symptoms.
7. A method for diagnosing and treating a patient with bronchial asthma according to claim 6 in which the diagnoses is also based on X-ray findings.
8. A method for diagnosing and treating a patient with bronchial asthma according to claim 7 in which the diagnosis is also based on triggering factors.
9. A method for diagnosing and treating a patient with bronchial asthma according to claim 8 in which the diagnoses is also based on a patient's response to treatment.
10. A method for diagnosing and treating a patient with bronchial asthma according to claim 1 in which the criteria for diagnoses includes the age at onset; the severity at onset; chest findings; other allergic symptoms; treatments used namely medication used, use of nebulizers or oral bronco dilators, use of cortisone and need for prophylactics, X-ray findings, triggering factors, responses to treatment and wherein a diagnoses of the Type I or Type II of asthma is also based on the age of the patient.
11. A method for diagnosing and treating a patient with bronchial asthma according to claim 10 wherein the diagnoses of a Type I asthma is based on chest findings and bubbled lungs and wheezes.
12. A method for diagnosing and treating a patient with bronchial asthma according to claim 1 in which the diagnoses of a Type II asthma is based on a lot of wheezes and an X-ray showing hyperinflation and a dark lung.
13. A method for diagnosing and treating a patient with bronchial asthma according to claim 11 which includes the step of treating the patient with a mucus dissolving agent and a mild bronco dilator.
14. A method for diagnosing and treating a patient with bronchial asthma according to claim 13 which includes the step of:prescribing a nebulizer with an addition of a synthetic derivative of vasicine to dissolve the mucus.
15. A method for diagnosing and treating a patient with bronchial asthma according to claim 12 which includes the step of treating the patient with Atrovert®, Adrenalin (4) and Pulmicort (5).
FIELD OF THE INVENTION
This invention relates to a method for diagnosing and treating bronchial asthma and more particularly to a method and treatment based on categorizing bronchial asthma into three types and optimizing treatment based on the type of asthma encountered.
BACKGROUND FOR THE INVENTION
It has been reported that asthma is the number one chronic illness for children and is a significant cause of infants' deaths. It has also been reported that over twenty million Americans have asthma. It addition, it is well known that asthma is adversely affected by pollution. For this reason, there has been a significant increase in asthma cases in Kuwait since the Gulf War and the fire set in the Kuwait oil fields by the retreating Iraqi troops.
Bronchial Asthma typically causes decreased lung function, bronchial inflammation, coughing, wheezing and tightness in the chest. These problems are often exasperated by air born irritants such as smoke, exercise, viral infections etc. When a patient encounters such problems, it means that the individual's airway is obstructed and the lungs are not receiving sufficient air. Typically, the airways become obstructed due to the lining of the airways becoming irritated and swollen and because the airways tighten causing them to narrow.
With modern medicine, there are many treatments for asthma. However, most of the drugs prescribed have the potential for negative side effects. For example, asthma treatment can cause depression, dizziness, fatigue, impotence, liver damage etc. In addition, some medications are effective for some patients but less effective with others. Therefore, it is highly desirable to select the right treatment for the right patient.
The main idea of the new invention is to categorize the patient with Bronchial Asthma so you can give the right medication to the right patient thereby reducing side effects of the medication.
BRIEF SUMMARY OF THE INVENTION
In essence the present invention contemplates a method for diagnosing and treating a patient with Bronchial Asthma. The method includes the step of classifying a patient's asthma into three types, namely Type I (a wet type), Type II (a dry type) and Type III (a mixed type). The Type I asthma is characterized by more production of mucus than bronco constriction while the dry type has more bronco spasm than mucus production. The mixed type is a mixture of the two i.e. Type I and Type II. A patient is then diagnosed as Type I, Type II or Type III based on an examination of the patient. For Type I, a patient is treated with a mucolyptic more than a bronco dilator or with a bronco dilator if Type II or some combination of the two if Type III.
In a preferred embodiment of the invention, the diagnosis is based on the onset of symptoms, severity of symptoms at the onset of the symptoms, chest findings, other allergy symptoms, X-ray findings, trigger factors and to a degree response to treatment and age of the patient. The treatment for the Type I asthma includes more use of a mucolyptic than a broncho dilator, and if a nebulizer is used it should include Bisolvon®, a bromhexine that is a synthetic derivative of vasicine. In essence the Bisolvon® is an expectorant i.e. mucus or phlem dissolving preparation. Small doses of a bronco dilator may also be used to open the passages to let the mucus pass. Cortisone is seldom used for such patients.
For those patients with the Type II asthma, they are treated with a bronco dilator and/or nebulizer with the addition of Atrovert, adrenaline and pulmicort if needed in measured amounts. This combination has given relatively quick response and is often effective in decreasing the use of a nebulizer. The treatment for Type III includes a combination of the treatments for Types I and II and is derived based on the physician's experience.
DESCRIPTION OF THE DRAWINGS
FIG. 1 a block diagram illustrating a method for categorizing different types of asthma in accordance with the present invention;
FIG. 2 is a block diagram illustrating a method for treating different types of asthma in accordance with the present invention;
FIG. 3 is a block diagram illustrating a method for diagnosing and treating asthma in accordance with the present invention; and
FIG. 4 is a block diagram illustrating the method for diagnosing and treating asthma in accordance with the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION
A diagnostic method and method for treating patients with Bronchial Asthma will now be described in connection with FIGS. 1-3. As illustrated in FIG. 1, a diagnostic method 20 includes a step 22 of dividing or categorizing asthma into three types i.e. Type I (wet type) as indicated by box 24, Type II (dry type) as indicated by box 26 and Type III (mixed type) as indicated by box 28. The division of the three types is based on differences in symptoms.
The criteria for diagnosing the different types of asthma were developed based on the examination and treatment of numerous patients. The criteria are based on the age of the patient, the age at initial attack (onset of the presentation) or the severity of the initial attack(s), chest findings, evidence of other symptoms as well as the results of any previous treatments tried and used.
Differences in chest findings for the different types of Bronchial Asthma are described as follows: Type I (wet type)--chest examination will reveal a bubbled sound,
Type II (dry type)--there will be flaring of alae nasi, and using accessory muscles of respiration, prolonged expiratory phase and wheezes and in Type III (mixed type), we could find the mixture of symptoms of both types.
Evidences of other symptoms are likewise outlined here. In Wet Type I, the baby will usually present with a blocked nose, less likely to have allergic symptoms and cough throughout the day. In Dry Type II, the child will be very distress, manifesting allergic symptoms like allergic rhinitis, eczema which may precede or come later and continuous cough throughout the day but usually more severe during the night.
To expound further on the result of any previous treatment tried and used, it is understood that Bronchial Asthma was not recognized before as a heterogenous disease thus it was treated as only one disease using cough syrup and a bronchodilator. Although some authors were against giving mucolytics, some others were giving mucolytics because it was not clear to them that Bronchial Asthma is not just one disease. As some were against, others may be giving mucolytic with a bronchodilator. Most of available medications for treatment of Bronchial Asthma is recategorize according to the types of Bronchial Asthma and this gives good results because the right treatment id given to the right patient.
Before the new invention, all kinds of bronchial asthma were treated the same and it is divided into its Acute Stages:
During Acute Stage: For a child in acute stage: 1. mostly nebulizer Bronchodilator--mainly Ventolin (6) and Atrovent (3) use of mucolytic like Bisolvon (1) was controversial. Inhaled Steroid--less likely to be used, its used mainly as a prophylaxis. 2. Injected Steroid--can be used if the case needed. 3. Some authors add IV aminophylline (7) which is not currently recommended. 4. Once the Acute Stage passes they gave: Bronchodilator like Ventolin (6) syrup or Bricanyl (8) or Berotec (9) and some used oral cortisone.
This is decided according to severity, age of patient and available medication 1. Either Pulmicort (5) or Flixotide (10) inhaler (inhaled steroid) 2. Singular (1)--either sachet 4 mg or 4-5 mg label
These were what were used to be given before for all children with Bronchial Asthma but with the new invention:
The Wet Type:
During Acute Stage:
Need more mucolytic to dissolve the mucus like Bisolvon (1) and you can add bronchodilator to help open the closed bronchioles If you do so you will not need to use cortisone either inhaled or injectable. When the Acute Stage subsides, I will give any mucolytic like Mucosolvan (12) and Prospan (13) to dissolve the sputum which will give dramatic and marvelous result. This group of patient since you treated the cause they're less likely to get prophylaxis
The Dry Type:
During Acute Stage: Inhalation: Use Ventolin (6) Nebulization Solution, Adrenalin (4) and inhaled Steroid like Pulmicort (5) No need for inhaled mucolytic Some need to be given injectable steroids and they gave dramatic response Once patient's acute stage subsides, I will give cough syrup and bronchodilator like Bricanyl (8) +/-oral cortisone (2) This group of patient may need prophylaxis either inhaled steroid or singular
In addition to the above X-ray findings, trigger factors and responses to further treatment are considered. The following are the usual x-ray findings: In Wet Type:--the x-ray will be hazy, white lung In Dry Type:--signs of hyperinflation, and a dark lung
The Type I asthma sometimes referred to as the Wet Type and is typically characterized by the following symptoms as indicated by box 32. The symptoms include the age of the patient. For example, Type I asthma is typically found in younger patients from 0 to 1 year old. The type I asthma is also characterized by less distress during an attack (presentation) and chest findings that show bubbled lungs, few wheezes during an attack and lack of allergic symptoms. Additional symptoms include the finding that the patient rarely need prophylactics like Singular (11) if needed and their x-rays show a hazy white lung field. Further, there are no clear triggering factors and the patient usually shows a relatively quick response to proper treatment for Type I asthma.
The symptoms for Type II asthma are typically found in an older age group i.e. those are usually from 1 to 5 years of age but can also occur later on and are further characterized by prolonged expiratory phases and lots of wheezes. Additional symptoms of the Type II asthma relate to the use of accessory muscles for breathing and evidence of other allergies.
A number of patients that exhibit evidence of both Type I and Type II asthma are categorized as Type III i.e. a Mixed Type of asthma. Unless patients' symptoms that are predominantly categorized as Type I or Type II they are classified as a Type III or mixed type asthmatic. Usually the following symptoms occur for the Dry Type II patients; severe distress on presentation, flaring alae nasi, using accessory muscles of respiration, with or without cyanosis, inability to continue the sentences spoken, cough mainly at night, runny nose and could be preceded by a viral infection, exercise and they could also have eczema.
Having characterized the types of asthma and the symptoms of each type, a physician is better prepared to examine and treat a patient, which is defined as a treatment method 40. In the treatment method 40, a physician reviews a patient's medical history and examines the patient and conducts a conventional examination of the patient in step 42. After examining the patient, the physician characterizes the patient's asthma as Type I in box 44, Type II in box 46 or Type III as indicated by box 48. After characterizing the type of asthma experienced by the patient in boxes 44, 46 and 48, the physician considers the appropriate treatment as set forth in boxes 50, 52 and 54 and prescribes an appropriate regime for the patient as indicated by box 56.
The treatment for Type I Asthma includes the use of mucolytic such as Mucosolvan (12), Prospan (13), Bisolvon (1) and Tuscalman (14) more so than bronchodilators. Bronchodilators which acts as mainstay on nebulization are Ventolin (6) and Atrovent (3). In those cases where a nebulizer is called for, an addition of Bisolvon (I) (bromhexine or its equivalent) to dissolve the mucus may be added based on the physician's experience. The physician may also add small doses of a bronchodilator such as Atrovent (3) and Ventolin (6) to let the mildly constricted airways open up and let the mucus pass. In Type I asthma, cortisone is rarely used as re prophylactics.
Hypothetical Patient Type I Mariam is 2 months of age with weight of 5.4 kg, height 52 cm and presented with cough, noisy breathing and blocked nose for the last 3 days after her father smoke cigarettes near the baby. She was afebrile, mildly distress on examination, no cyanosis, respiratory rales is mildly distress and no dysmorphic feature.
TABLE-US-00001 Mouth: oral trash Ear: no abnormality detected Nose: blocked Chest: bubbled lung, no wheezes Abdomen: intact CVS: intact CNS: intact
Baby was diagnosed to have Bronchial Asthma Type I. She was given the following treatment: Tuscalman (14) Prospan drops (13)
The treatment of Type II asthma typically includes the use of a bronchodilator as a cornerstone of treatment. Such bronchodilators may be administered orally but mostly by nebulizers particularly in an acute stage. These bronchodilators are given either thru nebulization such as Atrovent (3), Ventolin (6) or Adrenalin (4) or as orally using Bricanyl (8), Berotec (9) or Ventolin (6). Cortisones may also be used through inhalation using Pulmicort (5) and oral steroid such as Decadron (2). Prophylactics used for this type are inhaled steroid and Singular (11).
An example of a Hypothetical patient having Type II asthma and their treatment follows:
Hypothetical Case, Type II
Mosa is a 5 year old boy, he was presented to my clinic with distress, severe cough that he could not sleep last night after he was exposed to a sandstorm. Last night, the child is restless with flaring alae nasi, using his accessory muscles or respiration, mildly cyanotic, afebrile, HR (100/min), high RR and a congested throat
Chest prolonged expiratory phase a lot of wheezes
Others system intact
He was given hydrocortisone injection with a dose of 50 mg new nebulization are Atrovent (3) and Pulmicort (5) with Adrenalin (4). He was diagnosed to have attacks of Bronchial Asthma, Type II (Dry Type) he was given cough syrup.
Bronchodilator in nebulization for 2-3 days followed by oral Bronchodilator like Bricanyl (8) or Berotec (9) and cortisone (Decadron) (2). This boy used to have a frequent attacks of Bronchial Asthma. Last attack was before 2 weeks so he needs to take prophylaxis like Singular (11) tablets or Pulmicort (5) nebulization solution according to the discussion with the mother.
The treatment of Type III asthma presents a greater challenge to the physician. With symptoms of Type I and Type II asthma present, it is necessary to use a balance treatments from each type and find a treatment that fits the need of a specific patient. For example, a treatment of a hypothetical patient based on a compilation of studies of patients with Type III asthma is as follows:
Hypothetical Case Type III
Mohesen is 1.2 month old boy who was presented with a cough and running nose for one week. Clinical presentation mild to moderate distress, afebrile, chest findings is a mix of bubble lung and wheezes. He took 2 doses of nebulization (Atrovent (3), Ventolin (6)) and continued a bronchodilator and cough syrup like Sinecod (15).
The practice of a preferred embodiment of the present invention will now be described in connection with FIG. 3. As shown in FIG. 3, a physician characterizes the three types of asthma as indicated in box 60 based on the symptoms for each of the three types as indicated in box 62. The physician also identifies the treatment which were generally most effective for each of the three types of asthma as indicated by box 64. As indicated by box 66, with the above mental background, the physician conducts a conventional examination of a patient including review of the patient's medical history and prescribes an appropriate treatment as indicated by box 68. Following this, the physician follows up on the results of the treatment as indicated in box 70 and if necessary modifies the treatment.
1. Bisolvon (Bromhexine Hydrochloride)--
Mucolytics Concentration: 4 mg/2 ml for inhalation and oral administration containing 8 mg Bromhexine is a synthetic derivative of a herbal active ingredient vasicine Enhances mucous transport by reducing mucous viscosity, mucociliary clearance Doses: Children 6-12: 1 ml 2 times daily 2-6: 10 drops 2 times daily <2.yo: 5 drops 2 times daily But usually we add 2-3 drops which is more than enough
2. Decadron (Dexamethasone)
 A synthetic glucocorticoid used for its anti-inflammatory effects It has 25 to 30 times the anti-inflammatory activity of hydrocortisone 0.5 mg tablet: blister pack of 30's, 0.5 mg/5 ml: bottle of 100 ml as elixir Doses: In acute, self-limited allergic disorders or acute exacerbations of chronic allergic disorders (e.g. bronchial asthma) Dosage requirements are variable and must be individualized according to the severity of the disease and the response of the patient The usual initial dosage varies from 0.75 to 15 mg a day depending on the disease being treated For infants and children, the recommended doses usually will have to be reduced, but dosage should be dictated by the severity of the condition rather than by age or body weight.)
3. Atrovent (Ipatropium Bromide)
 Anti muscarinic bronchodilator Doses of child: 100-500 microgram (0.4-2 ml at 0.02% solution) 1 ml (20 drops) 0.025% solution for inhalation with nebulising devices contain: 261 mcgg (=1 ipatropium bromide) corresponding to 250 mg ipatropium bromide anhydrose bronchodilator Doses 6-12 years old: 1 ml (20 drops=0.25 ml) 3 to 4 times daily <6 y.o.: 0-0.4-1 ml (8-20 drops=0.1-0.25 mg) 3 to 4 times daily
5. Pulmicort nebulizer solution (budesonide) Concentration: 0.25 mg/ml-0.5 mg/ml Budesonide is a gluco corticosteroid with a high local anti inflammatory effect to prevent the release of inflammatory mediator Studies have shown that the earlier budesonide treatment is initiated after the onset of asthma, the better lung function can be expected Doses: Acute: from 6 months: 0.25-0.5 mg per day, may increase up to 1 mg/day Prophylaxis: from 6 months: 0.25-2 mg/day
6. Ventolin Respiratory Solution
 Provide 5 mg/ml of salbutamol sulphate of nebulization It is selective Beta 2 agonist that provides short acting (4-6 ml) bronchodilator with fast onset (5 minutes) Dose in children under the age of 12 years old Minimum: 0.5 ml (2.5 mg of salbutamol) diluted to 2-2.5 ml with normal saline However, higher dose of up to 5 mg could be used
8. Bricanyl (Terbutaline Sulphate)
 1 ml contains Terbutaline sulphate 0.3 mg Should be used as a maintenance therapy in asthma and other pulmonary diseases where bronchospasm is a complicating factor Doses: Children: 0.075 mg (0.25 ml)/kg Body weight 3 times daily
TABLE-US-00002 Suitable Doses: (Kg) Dosage 4 1 ml × 3 6 1.5 ml × 3 8 2 ml × 3 10 2.5 ml × 3 12 3 ml × 3 14 3.5 ml × 3 16 4 ml × 3 18 4.5 ml × 3 20 5 ml × 3 24 6 ml × 3 28 7 ml × 3 32 8 ml × 3 36 9 ml × 3 40 10 ml × 3
If an adequate response is not obtained with this dose, the dose may be doubled, provided adverse reactions are not pronounced
Bronchodilator 2.5 mg tablet, liquid 2.5 mg 5 ml 1 teaspoonful liquid contains 1-(3,5-dihydroxyphenyl)-2-hydroxy-benzyl)-ethyl-amino athanol hydrobromide (=fenoterol hydrobromide) Doses: Infants up to 1 y.o.--(below 10 kg BW)=2.5 ml liquid 2 to 3 times daily Children 1-6 y.o--(ca. 10-22 kg BW)=0.5-1 tablet/2.5-5 ml liquid 3× daily Children 6-14 y.o.--=1 tablet or 5 ml liquid 3 times daily
10. Flixotide Evohaler 125 mcg
 Fllixotide Evohaler is a pressurized inhalation, suspension delivering 125 micrograms of fluticasone propionate per actuation Given by inhalation offers prophylactic treatment of asthma Doses: Mild Asthma:--100 to 250 mcgs twice daily Moderate Asthma:--250 to 500 mcgs twice daily Severe Asthma:--500 to 1,000 mcgs twice daily Administration of doses>1000 mcgs (500 mcgs twice daily) should be via spacer device to help reduce side-effects in the mouth and throat
The dose should be titrated to the lowest dose t which effective control of asthma is maintained
It should be taken regularly even when asymptomatic. Onset of therapeutic effect is within 4 to 7 days
11. Singular (Montelukast Sodium)
4 mg sachet, 4 mg, 5 mg chewable tablet It is a leukotriene receptor antagonist so it blocks the receptos of leukotriene (naturally occurring chemicals that cause narrowing of the airway and inflammation) Doses: From 6 months-5 years=4 mg either sachet or chewable tablet From 6-12 years=5 mg once daily or at bedtime
 Preclinically, ambroxol, the active ingredianet of Mucosolvan, has been shown to increase respiratory tract secretion. It enhances pulmonary surfactant production and stimulate ciliary activity liquid 15 mg/5 ml, solution for oral or inhalation use 15 mg/2 ml Doses: Liquid 15 mg/5 ml <2 y. o.--2.5 ml (1/2 teaspoon) 2 times daily 2-6 y.o.--2.5 ml (1/2 teaspoon) 3 times daily 6-12 y.o.--5 ml (1 teaspoon) 2-3 times daily Solution 15 mg/2 ml for oral and inhalation use <2 y. o.--1 ml (=25 drops) 2 times daily 2-6 y.o.--1 ml (=25 drops) 3 times daily >6 y.o.--2 ml (=50 drops) 2-3 times daily
13. Prospan (Herbal Drops)
 Mucolytic, spasmolytic, cough relieving 100 ml bottle Composition: 100 ml solution contains 2 g of dried ivy leaf extract (5-7.5:1); extractive agent: ethanol 30% (w/w):Herbal Drops contains 47% vol. alcohol Herbal Drops is a natural product and contains an active ingredient. which is purely herbal Doses: Infants--10 to 15 drops 3 to 5 times daily Small children--15 drops 3 to 5 times daily Adults and schoolchildren--20 drops 3 to 5 times daily
 Antitussive Tuscalman contains noscapine as the effective principle. This substance exerts a reliable, suppressive action on the cough center Drops: 15 mg Noscapini Hydrochloridium, 100 mg Guaifenesinum Syrup: 15 mg, 100 mg, 250 mg Suppositories: 10 mg, 50 mg Packings: 20 ml dropper-bottle, 120 ml bottle, Suppositories A and B=boxes of 10 suppositories Doses: Drops for Children--10-20 drops for 2 to 3 times daily Syrup: 6-12 y.o.--1 teaspoonful 3 to 5 times daily Suppositories A: --0-8 months 2 suppositories daily 9-18 months 3 suppositories daily Suppositories B:--1.5 to 3 y.o--2 suppositories daily 4-8 y.o.--3 to 4 suppositories daily
 Antitussive Active Principle: Butamirate citrate, a central cough suppressant which is chemically and pharmacologically unrelated to the opium alkaloids. It reduce airway resistance Drops for children: pack of 20 ml, syrup: pack of 200 ml Doses: Drops for Children: 2 months--1 year--10 drops 4 times daily 1-3 y.o.--15 drops 4 times daily <3 y.o.--25 drops 4 times daily Syrup: 3 to 6 y.o.--5 ml 3 times daily 6 to 12 y.o.--10 ml 3 times daily
While the invention has been described in connection with its preferred embodiment it should be recognized that changes and modifications can be made therein without departing from the scope of the appended claims.
Patent applications in class X-ray contrast imaging agent (e.g., computed tomography, angiography, etc.)
Patent applications in all subclasses X-ray contrast imaging agent (e.g., computed tomography, angiography, etc.)