US3880995A - Treatment of arthritis with mycophenolic acid and derivatives - Google Patents
Treatment of arthritis with mycophenolic acid and derivatives Download PDFInfo
- Publication number
- US3880995A US3880995A US360292A US36029273A US3880995A US 3880995 A US3880995 A US 3880995A US 360292 A US360292 A US 360292A US 36029273 A US36029273 A US 36029273A US 3880995 A US3880995 A US 3880995A
- Authority
- US
- United States
- Prior art keywords
- arthritis
- mycophenolic acid
- treatment
- derivatives
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 206010003246 arthritis Diseases 0.000 title claims abstract description 27
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 title abstract description 22
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 title abstract description 22
- 229960000951 mycophenolic acid Drugs 0.000 title abstract description 22
- 238000011282 treatment Methods 0.000 title description 9
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 12
- 208000024891 symptom Diseases 0.000 claims abstract description 7
- 230000002917 arthritic effect Effects 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 6
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 241000282412 Homo Species 0.000 claims description 2
- 229930182480 glucuronide Natural products 0.000 abstract description 3
- 150000008134 glucuronides Chemical class 0.000 abstract description 3
- 150000003839 salts Chemical class 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 3
- 210000000707 wrist Anatomy 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 241000228143 Penicillium Species 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940124599 anti-inflammatory drug Drugs 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 2
- 239000011591 potassium Chemical group 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011734 sodium Chemical group 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000027932 Collagen disease Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 206010023232 Joint swelling Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000228145 Penicillium brevicompactum Species 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 208000018631 connective tissue disease Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 210000003811 finger Anatomy 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 229940098377 penicillium brevicompactum Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000003813 thumb Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
Definitions
- MYCOPIIENOLIC ACID AND DERIVATIVES [75] Inventor: E. Linn Jones, Indianapolis, Ind. Primary ExamInerQEIbert Roberts Attorney, Agent, or FzrmJames L. Rowe; Everet F. [73] Assrgnee: Eli Lilly and Company, Indianapolis, S i h Ind.
- Inflammatory arthritis is a fairly common problem 5 M h nolic acid fl-D-glucuronide is described by usually attacking the older segment of the pop l ion Ando et a]. in J. Antibiotics, 23, 408 (1970) and its analthough extremely severe cases of inflammatory arti-tumor activity is set forth in that same article.
- It is an object of this invention to provide anew drug SOHS- for the treatment of arthritis and for the alleviation of lnflammatory arthritis may be classified into two 1() arthritic symptoms which is devoid ofcertain ofthe del based on the Presence of absence of a Serum ficiencies of other drugs employed in the past for these rheumatoid factor.
- the sero-positive group includes purposes rheumatoid arthritis and arthritis associated with connective tissue or collagen disease including systemic SUMMARY OF THE INVENTION lupus erythematosus and polyarteritis (periarteritis no- I f lfill f h above d other bj hi i
- the Seromegatlve group includes p' vention provides a method of treating inflammatory arthritis, ankylosing spondylitis and arthritis associated h i i comprising administering to a human suffering with ulcerative colitis, regional ileitis and Whipples h efrom an arthritic symptom relieving amount of a disease.
- arthritis other forms of arthritis such as degenerative compound of the formula 9 joint disease (osteoarthritis) and arthritis caused by wherein M is hydrogen, potassium, sodium or ammometabolic or endocrine disorders, are also seronegative but are not classified with inflammatory arthritis.
- Osteoarthritis degenerative compound of the formula 9 joint disease
- M is hydrogen, potassium, sodium or ammometabolic or endocrine disorders
- Section 13 particularly pages -l Inflammatory arthritis, generally, and rheumatoid and psoriatic arthritis in particular have been subject to more or less successful drug therapy for a number of years, the most acceptable of the drug treatments being either gold therapy or the use of the anti-inflammatory drugs aspirin, indomethacin and butazolidine. Neither of these treatment methods are free from defects.
- Gold therapy and aspirin administration are not uniformly successful and the two more recently introduced antiinflammatory drugs, indomethacin and butazolidine, are frequently toxic at therapeutic levels, usually necessitating a dose reduction, if not outright withdrawal, of the drug followed by a return of the arthritic symptoms.
- Other drug therapy of arthritis such as the hormonal approach employing corticoids, has fallen into relative disuse, either for failure to alleviate the symptoms to the degree thought desirable or because of the extreme severity of the side effects accompanying their administration.
- Mycophenolic acid is produced by various strains of fungi of th'e Penicillium brevicompactum, Penicillium stolomferum and Penicillium urtic/zae groups.
- pound was the first biologically-active compound iso-' lated from a mold.
- the initial isolation was carried out by Gosio in 1896 (Gosio, Rivista d lgiene e Sanita pubblica, Ann., 7 825, 869, 961 [1896]). Structure work was effected largely through the efforts of Raistrick et a]. from 1932 to 1935 (Raistrick et al., Biochem. .I. 26, 1441 [1932]; Biochem J. 27, 654 [1933]).
- nium and R is hydrogen or B-D-glucuronidyl COOH
- M hydrogen and R is hydrogen
- the above compound is named systematically as 6-[4-hydroxy-7- methyl-6-methoxy-3-oxo-5-phthalanyl]-4-methyl-4- hexenoic acid or mycophenolic acid.
- R is B-D- glucuronidyl and M is hydrogen
- the resulting compound is mycophenolic acid B-D-glucuronide or, systematically, 6-[ 4-( ,B-D-glucopyranosylglucuronate )-4- methyl-6-methoxy-3-oxo-5-phthalanyl]-4-methyl-4- hexenoic acid.
- Other non-toxic salts than those listed above can also be employed.
- Mycophenolic acid, mycophenolic acid B-D- glucuronide or salts thereof are administered by the oral route to a human suffering from inflammatory arthritis, such as rheumatoid or psoriatic arthritis.
- mycophenolic acid, its B-D-glucuronide, or salts thereof are administered in the form of tablets or capsules or as a liquid solution or suspension.
- a preferred mode for oral administration is via telescoping gelatin capsules.
- a typical useful formulation employing capsules is prepared as follows:
- mycophenolic acid isolated from a fermentation medium is thoroughly mixed with 4.7 kg. of starch and the mixture loaded into empty telescoping gelatin capsules.
- Each capsule contains the following ingredients 400 mg. mycophenolic acid 200 mg. starch
- mycophenolic acid [3-D- glucuronide, prepared by the method of Ando et al. (supra) can be substituted for mycophenolic acid.
- patients diagnosed as suffering from inflammatory arthritis are treated with from 2 to 5 g. of mycophenolic acid or an equivalent amount of its glucuronide or of a salt thereof per day.
- the daily dosage should be divided into either 2 or 3 doses.
- An example of the use of the treatment method of this invention is as follows: A male subject 22 years old who had been diagnosed as suffering from psoriatic arthritis two years previously was found to have the following joints involved in his arthritis: shoulders, hips, right wrist, right hand, proximal interphalangial joints of third and fourth fingers and distal interphalangial joint of the thumb. The rheumatoid factor was negative indicating that the disease involved was psoriatic arthritis.
- Mycophenolic acid was administered to the patient at the rate of 1200 to 2400 mg every 12 hours over a 6 week period. Improvement was noticed at the end of 3 weeks as follows: The patient mentioned that there was improved comfort, decreased morning stiffness and he no longer needed to take aspirin.
- a second, female patient of 46 years was diagnosed as suffering from psoriatic arthritis with hips, left wrist, and sacroiliac involved. She was given from 800 to 1600 mg of mycophenolic acid every eight hours for a 12-week period. Subjective improvement was noticed at the end of one week with the following comments: There was less pain in wrist and hips, less swelling of wrists (an objective improvement) and increased range of rotation. Again, in this instance, the need for aspirin was eliminated.
- Mycophenolic acid B-glucuronide as well as cationic salts of mycophenolic acid can be employed in the treatment of inflammatory arthritis at dose levels equivalent to those specified above for mycophenolic acid itself.
- equivalent dose levels is meant the same weight of mycophenolic acid per dose.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Mycophenolic acid or its glucuronide is administered to patients suffering from inflammatory arthritis for the alleviation of their arthritic symptoms.
Description
United States Patent Jones Apr. 29, 1975 TREATMENT OF ARTHRITIS WITH [58] Field of Search 424/180; 260/210, 343.2 R
MYCOPIIENOLIC ACID AND DERIVATIVES [75] Inventor: E. Linn Jones, Indianapolis, Ind. Primary ExamInerQEIbert Roberts Attorney, Agent, or FzrmJames L. Rowe; Everet F. [73] Assrgnee: Eli Lilly and Company, Indianapolis, S i h Ind.
[22] Filed: May 14, 1973 [57] ABSTRACT [21] A N 360,292 Mycophenolic acid or its glucuronide is administered to patients suffering from inflammatory arthritis for th ll 'tfth th 't t 52 us. Cl 424/180; 260/210; 260/343.2 R e a em o ar Symp 0m [51] lm. Cl. A01N 9/00 4 Claims, N0 Drawings TREATMENT OF ARTHRITIS WITH MYCOPIIENOLIC ACID AND DERIVATIVES BACKGROUND OF THE INVENTION Mycophenolic acid is known to exhibit antifungal, antiviral and antibacterial activity. [See for example, J. Gen. Virol. 4, 629 (1969); J. Antibiotics 22, 297 (1969).]
Inflammatory arthritis is a fairly common problem 5 M h nolic acid fl-D-glucuronide is described by usually attacking the older segment of the pop l ion Ando et a]. in J. Antibiotics, 23, 408 (1970) and its analthough extremely severe cases of inflammatory arti-tumor activity is set forth in that same article. thritis are found, through infrequently, in younger per- It is an object of this invention to provide anew drug SOHS- for the treatment of arthritis and for the alleviation of lnflammatory arthritis may be classified into two 1() arthritic symptoms which is devoid ofcertain ofthe del based on the Presence of absence of a Serum ficiencies of other drugs employed in the past for these rheumatoid factor. The sero-positive group includes purposes rheumatoid arthritis and arthritis associated with connective tissue or collagen disease including systemic SUMMARY OF THE INVENTION lupus erythematosus and polyarteritis (periarteritis no- I f lfill f h above d other bj hi i The Seromegatlve group includes p' vention provides a method of treating inflammatory arthritis, ankylosing spondylitis and arthritis associated h i i comprising administering to a human suffering with ulcerative colitis, regional ileitis and Whipples h efrom an arthritic symptom relieving amount of a disease. Other forms of arthritis such as degenerative compound of the formula 9 joint disease (osteoarthritis) and arthritis caused by wherein M is hydrogen, potassium, sodium or ammometabolic or endocrine disorders, are also seronegative but are not classified with inflammatory arthritis. [For a discussion and classification of arthritis, see for example Harrisons Principles of lnternal Medicine, Ed. Wintrobe et al., 6th Edition (McGraw-Hill Book Co., New, NY. 1970) Section 13, particularly pages -l Inflammatory arthritis, generally, and rheumatoid and psoriatic arthritis in particular have been subject to more or less successful drug therapy for a number of years, the most acceptable of the drug treatments being either gold therapy or the use of the anti-inflammatory drugs aspirin, indomethacin and butazolidine. Neither of these treatment methods are free from defects. Gold therapy and aspirin administration are not uniformly successful and the two more recently introduced antiinflammatory drugs, indomethacin and butazolidine, are frequently toxic at therapeutic levels, usually necessitating a dose reduction, if not outright withdrawal, of the drug followed by a return of the arthritic symptoms. Other drug therapy of arthritis, such as the hormonal approach employing corticoids, has fallen into relative disuse, either for failure to alleviate the symptoms to the degree thought desirable or because of the extreme severity of the side effects accompanying their administration.
Mycophenolic acid is produced by various strains of fungi of th'e Penicillium brevicompactum, Penicillium stolomferum and Penicillium urtic/zae groups. The com; 60
pound was the first biologically-active compound iso-' lated from a mold. The initial isolation was carried out by Gosio in 1896 (Gosio, Rivista d lgiene e Sanita pubblica, Ann., 7 825, 869, 961 [1896]). Structure work was effected largely through the efforts of Raistrick et a]. from 1932 to 1935 (Raistrick et al., Biochem. .I. 26, 1441 [1932]; Biochem J. 27, 654 [1933]).
nium and R is hydrogen or B-D-glucuronidyl COOH When M is hydrogen and R is hydrogen, the above compound is named systematically as 6-[4-hydroxy-7- methyl-6-methoxy-3-oxo-5-phthalanyl]-4-methyl-4- hexenoic acid or mycophenolic acid. When R is B-D- glucuronidyl and M is hydrogen, the resulting compound is mycophenolic acid B-D-glucuronide or, systematically, 6-[ 4-( ,B-D-glucopyranosylglucuronate )-4- methyl-6-methoxy-3-oxo-5-phthalanyl]-4-methyl-4- hexenoic acid. Other non-toxic salts than those listed above can also be employed.
Mycophenolic acid, mycophenolic acid B-D- glucuronide or salts thereof are administered by the oral route to a human suffering from inflammatory arthritis, such as rheumatoid or psoriatic arthritis. For oral use, mycophenolic acid, its B-D-glucuronide, or salts thereof are administered in the form of tablets or capsules or as a liquid solution or suspension. A preferred mode for oral administration is via telescoping gelatin capsules. A typical useful formulation employing capsules is prepared as follows:
9.4 kg. of mycophenolic acid isolated from a fermentation medium is thoroughly mixed with 4.7 kg. of starch and the mixture loaded into empty telescoping gelatin capsules. Each capsule contains the following ingredients 400 mg. mycophenolic acid 200 mg. starch In the above formulation, mycophenolic acid [3-D- glucuronide, prepared by the method of Ando et al. (supra) can be substituted for mycophenolic acid.
In the above formulation it has been stated that it is preferred to employ the drug in the form of the free acid; however, the sodium, potassium or ammonium l salts are also effective. Formulations employed for the salts are substantially the same as those indicated above for the free acid.
In carrying out my novel treatment method, patients diagnosed as suffering from inflammatory arthritis are treated with from 2 to 5 g. of mycophenolic acid or an equivalent amount of its glucuronide or of a salt thereof per day. The daily dosage should be divided into either 2 or 3 doses.
An example of the use of the treatment method of this invention is as follows: A male subject 22 years old who had been diagnosed as suffering from psoriatic arthritis two years previously was found to have the following joints involved in his arthritis: shoulders, hips, right wrist, right hand, proximal interphalangial joints of third and fourth fingers and distal interphalangial joint of the thumb. The rheumatoid factor was negative indicating that the disease involved was psoriatic arthritis. Mycophenolic acid was administered to the patient at the rate of 1200 to 2400 mg every 12 hours over a 6 week period. Improvement was noticed at the end of 3 weeks as follows: The patient mentioned that there was improved comfort, decreased morning stiffness and he no longer needed to take aspirin.
A second, female patient of 46 years was diagnosed as suffering from psoriatic arthritis with hips, left wrist, and sacroiliac involved. She was given from 800 to 1600 mg of mycophenolic acid every eight hours for a 12-week period. Subjective improvement was noticed at the end of one week with the following comments: There was less pain in wrist and hips, less swelling of wrists (an objective improvement) and increased range of rotation. Again, in this instance, the need for aspirin was eliminated.
Mycophenolic acid B-glucuronide as well as cationic salts of mycophenolic acid can be employed in the treatment of inflammatory arthritis at dose levels equivalent to those specified above for mycophenolic acid itself. By equivalent dose levels is meant the same weight of mycophenolic acid per dose.
I claim:
I. The process of treating inflammatory arthritis in humans which comprises administering by the oral route to a human suffering therefrom an arthritis symptom relieving amount of mycophenolic acid or a derivative thereof represented by the following formula UNITED STATES PATENT AND TRADEMARK OFFICE CETHICATE OF CORRECTION PATENT N0. 5,880,995
DATED April 29, 1975 INVENTOR(S) E Linn Jones It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
Column 1, line 8, "through" should read --though--,
Column 4, line 36, delete "[or B-D-glucuron1dyl].".
' Signed and Scaled this eighth Day of June 1976 ismu Arrest:
Claims (4)
1. A PROCESS OF TREATING INFLAMMATORY ARTHRITIS IN HUMANS WHICH COMPRISES ADMISTERING BY THE ORAL ROUTE TO A HUMAN SUFFERING THEREFROM AN ARTHRITIS SYMPTOM RELIEVING AMOUNT OF MYCOPHENLIC ACTA OR A DERIVATIVE THEREOR REPRESENTED BY THE FOLLOWING FORMULA
2. A process according to claim 1 in which the arthritis treated is rheumatoid arthritis.
3. A process according to claim 1 in which the arthritis treated is psoriatic arthritis.
4. A process according to claim 1 in which from 2-5 g. per day of drug is administered to the arthritic patient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US360292A US3880995A (en) | 1973-05-14 | 1973-05-14 | Treatment of arthritis with mycophenolic acid and derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US360292A US3880995A (en) | 1973-05-14 | 1973-05-14 | Treatment of arthritis with mycophenolic acid and derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3880995A true US3880995A (en) | 1975-04-29 |
Family
ID=23417382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US360292A Expired - Lifetime US3880995A (en) | 1973-05-14 | 1973-05-14 | Treatment of arthritis with mycophenolic acid and derivatives |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3880995A (en) |
Cited By (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1980000791A1 (en) * | 1978-10-13 | 1980-05-01 | Schwimmer A | B-glucuronidase activity and/or ph-dependent pharmaceuticals and their methods of production and use for selective treatment of diseases |
| US4327074A (en) * | 1978-10-13 | 1982-04-27 | Adolf W. Schwimmer | Method for diagnosis and selective treatment of infections of bacteria having β-glucuronidase activity |
| US4584368A (en) * | 1978-10-13 | 1986-04-22 | Adolf W. Schwimmer | β-Glucuronidase activity and/or pH-dependent pharmaceuticals and thier methods of production |
| US4686234A (en) * | 1985-11-27 | 1987-08-11 | Syntex (U.S.A) Inc. | Mycophenolic acid derivatives in the treatment of inflammatory diseases, in particular rheumatoid arthritis |
| US4725622A (en) * | 1986-01-23 | 1988-02-16 | Syntex (U.S.A.) Inc. | Mycophenolic acid derivatives in the treatment of rheumatoid arthritis |
| US4808592A (en) * | 1987-01-30 | 1989-02-28 | Syntex (U.S.A.) Inc. | Method of treating diseases by administering morpholinoethylester of mycophenolic acid and derivatives thereof |
| US4959387A (en) * | 1986-01-23 | 1990-09-25 | Syntex (U.S.A.) Inc. | Mycophenolic acid derivatives in the treatment of rheumatoid arthritis |
| US5177072A (en) * | 1987-01-30 | 1993-01-05 | Syntex (U.S.A.) Inc. | Treatment of autoimmune inflammatory, and psoriatic diseases with heterocyclic aminoalkyl esters of mycophenolic acid and derivatives |
| WO1994001105A1 (en) * | 1992-07-10 | 1994-01-20 | The Board Of Trustees Of The Leland Stanford Junior University | Method of treating hyperproliferative vascular disease |
| US5346997A (en) * | 1992-08-26 | 1994-09-13 | Murphy James G | Agents for complexing sodium under biological conditions |
| WO1995009626A1 (en) * | 1993-10-01 | 1995-04-13 | Syntex (U.S.A.) Inc. | Mycophenolate mofetil high dose oral suspensions |
| US5472707A (en) * | 1993-05-13 | 1995-12-05 | Syntex (U.S.A.) Inc. | High dose ranolazine formulations |
| US6025391A (en) * | 1996-04-12 | 2000-02-15 | Novartis Ag | Enteric-coated pharmaceutical compositions of mycophenolate |
| US6471980B2 (en) | 2000-12-22 | 2002-10-29 | Avantec Vascular Corporation | Intravascular delivery of mycophenolic acid |
| US20030139801A1 (en) * | 2000-12-22 | 2003-07-24 | Avantec Vascular Corporation | Delivery of therapeutic capable agents |
| US20040127435A1 (en) * | 2002-08-02 | 2004-07-01 | Regents Of The University Of California | Uses for inhibitors of inosine monophosphate dehydrogenase |
| US20050013859A1 (en) * | 2001-10-17 | 2005-01-20 | Dederichs Juergen | Pharmaceutical compositions comprising mycophenolic acid or mycophenolate salt |
| US20050107869A1 (en) * | 2000-12-22 | 2005-05-19 | Avantec Vascular Corporation | Apparatus and methods for controlled substance delivery from implanted prostheses |
| US20050125054A1 (en) * | 2000-12-22 | 2005-06-09 | Avantec Vascular Corporation | Devices delivering therapeutic agents and methods regarding the same |
| US20050203612A1 (en) * | 2000-12-22 | 2005-09-15 | Avantec Vascular Corporation | Devices delivering therapeutic agents and methods regarding the same |
| US20060106453A1 (en) * | 2000-12-22 | 2006-05-18 | Avantec Vascular Corporation | Delivery of therapeutic capable agents |
| US20060212109A1 (en) * | 2001-02-13 | 2006-09-21 | Avantec Vascular Corporation | Delivery of therapeutic capable agents |
| US20070032483A1 (en) * | 2003-09-11 | 2007-02-08 | Julia Greil | Process for the production of mycophenolate mofetil |
| US20070111949A1 (en) * | 2001-01-11 | 2007-05-17 | Duke University | Inhibiting GS-FDH to modulate no bioactivity |
| US20100010082A1 (en) * | 2008-07-09 | 2010-01-14 | Aspreva International Ltd. | Formulations for treating eye disorders |
| CN107897186A (en) * | 2017-11-20 | 2018-04-13 | 华南农业大学 | Application of the mycophenolic acid in lichee frost epidemic disease is suppressed |
-
1973
- 1973-05-14 US US360292A patent/US3880995A/en not_active Expired - Lifetime
Cited By (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4327074A (en) * | 1978-10-13 | 1982-04-27 | Adolf W. Schwimmer | Method for diagnosis and selective treatment of infections of bacteria having β-glucuronidase activity |
| US4584368A (en) * | 1978-10-13 | 1986-04-22 | Adolf W. Schwimmer | β-Glucuronidase activity and/or pH-dependent pharmaceuticals and thier methods of production |
| WO1980000791A1 (en) * | 1978-10-13 | 1980-05-01 | Schwimmer A | B-glucuronidase activity and/or ph-dependent pharmaceuticals and their methods of production and use for selective treatment of diseases |
| US4686234A (en) * | 1985-11-27 | 1987-08-11 | Syntex (U.S.A) Inc. | Mycophenolic acid derivatives in the treatment of inflammatory diseases, in particular rheumatoid arthritis |
| US4959387A (en) * | 1986-01-23 | 1990-09-25 | Syntex (U.S.A.) Inc. | Mycophenolic acid derivatives in the treatment of rheumatoid arthritis |
| US4725622A (en) * | 1986-01-23 | 1988-02-16 | Syntex (U.S.A.) Inc. | Mycophenolic acid derivatives in the treatment of rheumatoid arthritis |
| US4992467A (en) * | 1987-01-30 | 1991-02-12 | Syntex (U.S.A.) Inc. | Treatment of autoimmune diseases with mycophenolic acid, and derivatives and formulations thereof |
| US4948793A (en) * | 1987-01-30 | 1990-08-14 | Syntex (U.S.A.) Inc. | Treatment of autoimmune diseases with the morpholinoethyl ester of mycophenolic acid, and derivatives thereof |
| US4952579A (en) * | 1987-01-30 | 1990-08-28 | Syntex (U.S.A.) Inc. | Method of treating diseases by administering morpholino-ethylester of mycophenolic acid or derivatives thereof |
| US4868153A (en) * | 1987-01-30 | 1989-09-19 | Syntex (U.S.A.) Inc. | Treatment of allograft rejection with mycophenolic acid, its morpholinoethylester and derivatives thereof |
| US4808592A (en) * | 1987-01-30 | 1989-02-28 | Syntex (U.S.A.) Inc. | Method of treating diseases by administering morpholinoethylester of mycophenolic acid and derivatives thereof |
| US5177072A (en) * | 1987-01-30 | 1993-01-05 | Syntex (U.S.A.) Inc. | Treatment of autoimmune inflammatory, and psoriatic diseases with heterocyclic aminoalkyl esters of mycophenolic acid and derivatives |
| US5283257A (en) * | 1992-07-10 | 1994-02-01 | The Board Of Trustees Of The Leland Stanford Junior University | Method of treating hyperproliferative vascular disease |
| WO1994001105A1 (en) * | 1992-07-10 | 1994-01-20 | The Board Of Trustees Of The Leland Stanford Junior University | Method of treating hyperproliferative vascular disease |
| US5346997A (en) * | 1992-08-26 | 1994-09-13 | Murphy James G | Agents for complexing sodium under biological conditions |
| US5472707A (en) * | 1993-05-13 | 1995-12-05 | Syntex (U.S.A.) Inc. | High dose ranolazine formulations |
| WO1995009626A1 (en) * | 1993-10-01 | 1995-04-13 | Syntex (U.S.A.) Inc. | Mycophenolate mofetil high dose oral suspensions |
| LT4099B (en) | 1993-10-01 | 1997-01-27 | Syntex Inc | Oral pharmaceutical compositions, processes for preparation and use thereof |
| US5688529A (en) * | 1993-10-01 | 1997-11-18 | Syntex (U.S.A) Inc. | Mycophenolate mofetil high dose oral suspensions |
| EP1475091A1 (en) * | 1993-10-01 | 2004-11-10 | Roche Palo Alto LLC | Mycophenolate mofetil - high dose oral suspensions |
| RU2150942C1 (en) * | 1993-10-01 | 2000-06-20 | Синтекс (Ю.ЭС.ЭЙ.) Инк. | Oral suspension containing high dose of mofetil mycophenolate |
| US6306900B1 (en) | 1996-04-12 | 2001-10-23 | Novartis Ag | Enteric coated pharmaceutical compositions |
| US6025391A (en) * | 1996-04-12 | 2000-02-15 | Novartis Ag | Enteric-coated pharmaceutical compositions of mycophenolate |
| US6172107B1 (en) | 1996-04-12 | 2001-01-09 | Novartis Ag | Entric-coated pharmaceutical compositions |
| US7077859B2 (en) | 2000-12-22 | 2006-07-18 | Avantec Vascular Corporation | Apparatus and methods for variably controlled substance delivery from implanted prostheses |
| US20050203612A1 (en) * | 2000-12-22 | 2005-09-15 | Avantec Vascular Corporation | Devices delivering therapeutic agents and methods regarding the same |
| US20030139801A1 (en) * | 2000-12-22 | 2003-07-24 | Avantec Vascular Corporation | Delivery of therapeutic capable agents |
| US20050131532A1 (en) * | 2000-12-22 | 2005-06-16 | Avantec Vascular Corporation | Apparatus and methods for controlled substance delivery from implanted prostheses |
| US6858221B2 (en) | 2000-12-22 | 2005-02-22 | Avantec Vascular Corporation | Intravascular delivery of mycophenolic acid |
| US20050107869A1 (en) * | 2000-12-22 | 2005-05-19 | Avantec Vascular Corporation | Apparatus and methods for controlled substance delivery from implanted prostheses |
| US20050125054A1 (en) * | 2000-12-22 | 2005-06-09 | Avantec Vascular Corporation | Devices delivering therapeutic agents and methods regarding the same |
| US6471980B2 (en) | 2000-12-22 | 2002-10-29 | Avantec Vascular Corporation | Intravascular delivery of mycophenolic acid |
| US7083642B2 (en) | 2000-12-22 | 2006-08-01 | Avantec Vascular Corporation | Delivery of therapeutic capable agents |
| US20060106453A1 (en) * | 2000-12-22 | 2006-05-18 | Avantec Vascular Corporation | Delivery of therapeutic capable agents |
| EP1349562A4 (en) * | 2001-01-11 | 2008-08-06 | Univ Duke | INHIBITION OF GS-FDH TO MODULATE THE BIOACTIVITY OF NITROGEN MONOXIDE |
| US20070111949A1 (en) * | 2001-01-11 | 2007-05-17 | Duke University | Inhibiting GS-FDH to modulate no bioactivity |
| US7615535B2 (en) | 2001-01-11 | 2009-11-10 | Duke University | Inhibiting GS-FDH to modulate no bioactivity |
| US8217006B2 (en) | 2001-01-11 | 2012-07-10 | Duke University | Inhibiting GS-FDH to modulate no bioactivity |
| US20100015121A1 (en) * | 2001-01-11 | 2010-01-21 | Duke University | Inhibiting gs-fdh to modulate no bioactivity |
| US20060212109A1 (en) * | 2001-02-13 | 2006-09-21 | Avantec Vascular Corporation | Delivery of therapeutic capable agents |
| US20100210717A1 (en) * | 2001-10-17 | 2010-08-19 | Dederichs Juergen | Pharmaceutical compositions comprising mycophenolic acid or mycophenolate salt |
| US20050013859A1 (en) * | 2001-10-17 | 2005-01-20 | Dederichs Juergen | Pharmaceutical compositions comprising mycophenolic acid or mycophenolate salt |
| US20040127435A1 (en) * | 2002-08-02 | 2004-07-01 | Regents Of The University Of California | Uses for inhibitors of inosine monophosphate dehydrogenase |
| US20070032483A1 (en) * | 2003-09-11 | 2007-02-08 | Julia Greil | Process for the production of mycophenolate mofetil |
| US20100010082A1 (en) * | 2008-07-09 | 2010-01-14 | Aspreva International Ltd. | Formulations for treating eye disorders |
| CN107897186A (en) * | 2017-11-20 | 2018-04-13 | 华南农业大学 | Application of the mycophenolic acid in lichee frost epidemic disease is suppressed |
| CN107897186B (en) * | 2017-11-20 | 2020-08-07 | 华南农业大学 | Application of mycophenolic acid in inhibiting lychee frost blight |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US3880995A (en) | Treatment of arthritis with mycophenolic acid and derivatives | |
| Lémann et al. | Methotrexate in Crohn's disease: long-term efficacy and toxicity | |
| Huskisson et al. | Trial comparing D-penicillamine and gold in rheumatoid arthritis. Preliminary report | |
| Pasquier et al. | “Hemicrania continua”: the first bilateral case? | |
| US4438138A (en) | Reduction of cholesterol with meta-chloro α-t-butylaminopropiophenone | |
| Schlesinger et al. | Observations on the clinical course and treatment of one hundred cases of Still's disease | |
| Berry et al. | Indomethacin and naproxen suppositories in the treatment of rheumatoid arthritis. | |
| US4425363A (en) | Treatment of tardive dyskinesia in mammals | |
| CN1173134A (en) | Uses of Boswellia for Alzheimer's Disease | |
| GB2110532A (en) | Bendazac compositions for treatment of cataract | |
| JPS5942649B2 (en) | Myasthenia gravis treatment agent | |
| JPH08512311A (en) | Arsenic medicine for treating chronic fatigue syndrome | |
| US4952594A (en) | Reagents and method for therapeutic treatment of multiple sclerosis | |
| Tyson et al. | The value of penicillin in the treatment of agranulocytosis caused by thiouracil | |
| CA2371393C (en) | Use of bismuth subgallate in inhibition of production of nitric oxide synthase | |
| US4355029A (en) | Combination therapy for rheumatoid arthritis | |
| HEJTMANCIK et al. | A clinical study of gitalin | |
| US4612303A (en) | Therapeutic and/or preventive agent for obstructive respiratory diseases | |
| Sokolow et al. | Clinical evaluation of Cedilanid | |
| US3773937A (en) | Method of treatment | |
| EP0369088B1 (en) | Use of zinc acexamate in the prophylaxis of gastropathy induced by non-steroidal anti-inflammatory drugs | |
| EP0911031B1 (en) | Use of arsenic for preparing a medicament for the treatment of premenstrual syndrome | |
| Uddenfeldt et al. | A double-blind comparison of oral ketoprofen ‘controlled release’and indomethacin suppository in the treatment of rheumatoid arthritis with special regard to morning stiffness and pain on awakening | |
| Kothari et al. | Reduction of gastric acid secretion on a low-salt diet and furosemide | |
| Harris | Subacute bacterial endocarditis presenting with meningitis |