Composition and method for reparation and prevention of fibrotic lesions

• US 5,310,562 A
• Filed: 09/21/1992
• Issued: 05/10/1994
• Est. Priority Date: 11/22/1989
• Status: Expired due to Term

• Current Assignee: Intermune Incorporated (Roche Holding AG)
• Original Assignee: Solomon B. Margolin
• Inventors: Margolin, Solomon B.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Spear, James M.
• Application Number:
  US07/947,995
• Time in Patent Office: 596 Days
• Field of Search: 424/435, 424/423, 424/427, 424/436, 424/451, 424/461, 424/489, 514/851, 514/838, 514/824, 514/866
• US Class Current: 424/489
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof

Abstract

In a preferred embodiment, drugs having heretofore unknown pharmacological properties which are useful in the medicinal therapy of fibrotic disease for the reparation and prevention of fibrotic lesional tissues, such drugs including as the active ingredient 5-methyl-1-phenyl-2-(1H)-pyridone. The pharmaceutical composition of this invention is novel as an anti-fibrotic drug, namely, as an agent for treating fibrosis. Any existing compounds have not been shown to be effective for the reparation and prevention of fibrotic lesions.

Claims

1. A pharmaceutical composition for reparation and prevention of fibrotic lesional tissue in a mammal, comprising 5-methyl-1-phenyl-2-(1H)-pyridone as an active anti-fibrotic ingredient present in an internally administered dosage form in an amount of from about 25 mg per kilogram of body weight per day to about 150 mg per kilogram of body weight per day.

2. A pharmaceutical composition, as defined in claim 1, wherein said 5-methyl-1-phenyl-2-(1H)-pyridone is present in said composition in an amount of from about 100 mg to about 1600 mg.

3. A pharmaceutical composition, as defined in claim 1, wherein said 5-methyl-1-phenyl-2-(1H)-pyridone is present in said pharmaceutical composition in an amount of from about 800 mg to about 1600 mg.

5. A pharmaceutical composition, as defined in claim 1, wherein said fibrotic lesional tissue is associated with a condition in the group consisting of pulmonary fibrosis, benign prostate hypertrophy, coronary infarcts, cerebral infarcts, myocardiac fibrosis, musculoskeletal fibrosis, post-surgical adhesions, liver cirrhosis, renal fibrotic disease, fibrotic vascular disease, scleroderma, Alzheimer'"'"'s disease, diabetic retinopathy, and skin lesions.

6. A pharmaceutical composition, as defined in claim 1, wherein said pharmaceutical composition is contained in an article for administration thereof selected from the group consisting of capsules, tablets, powders, granules, syrups, injectable fluids, and pills.

4. A method for the reparation and prevention of fibrotic lesional tissue in a mammal, comprising administering topically to said mammal a pharmaceutical composition containing 5-methyl-1-phenyl-2-(1H)-pyridone as an active anti-fibrotic ingredient in an amount of from about 5% to about 10%.

11. A method, as defined in claim 4, wherein said fibrotic lesional tissue is associated with a condition in the group consisting of musculoskeletal fibrosis, post-surgical adhesions, scleroderma, glaucoma, and skin lesions.

7. A method for the reparation and prevention of fibrotic lesional tissue in a mammal, comprising administering internally to said mammal a pharmaceutical composition containing 5-methyl-1-phenyl-2-(1H)-pyridone as an active anti-fibrotic ingredient, said composition being administered to said mammal at a rate of from about 25 mg per kilogram of body weight per day to about 150 mg per kilogram of body weight per day.

8. A method, as defined in claim 7, wherein said 5-methyl-1-phenyl-2-(1H)-pyridone is administered in an amount of from about 100 mg to about 4800 mg per day.

9. A method, as defined in claim 7, wherein said 5-methyl-1-phenyl-2-(1H)-pyridone is administered in an amount of from about 300 mg to about 4800 mg per day.

10. A method, as defined in claim 7, wherein said 5-methyl-1-phenyl-2-(1H)-pyridone is administered in an amount of from about 100 mg to about 1600 mg contained in a capsule.

12. A method, as defined in claim 7, wherein said fibrotic lesional tissue is associated with a condition in the group consisting of pulmonary fibrosis, benign prostate hypertrophy, coronary infarcts, cerebral infarcts, myocardiac fibrosis, musculoskeletal fibrosis, post-surgical adhesions, liver cirrhosis, renal fibrotic disease, fibrotic vascular disease, scleroderma, Alzheimer'"'"'s disease, diabetic retinopathy, and skin lesions.

13. A method, as defined in claim 7, wherein said pharmaceutical composition is administered by means selected from the groups consisting of capsules, tablets, powders, granules, syrups, injectable fluids, creams, ointments, inhalable fluids, eye drops, suppositories, and pills.

14. A method, as defined in claim 7, wherein said pharmaceutical composition is administered by means selected from the group consisting of creams, ointments, hydrophillic ointments, inhalable fluids, eye drops, and suppositories.

15. A method, as defined in claim 7, wherein said mammal is a human.

16. A pharmaceutical composition for reparation and prevention of fibrotic lesional tissue in a mammal, comprising 5-methyl-1-phenyl-2-(1H)-pyridone as an active anti-fibrotic ingredient present in a topically administered dosage form in an amount of from about 5% to about 10%.

17. A pharmaceutical composition, as defined in claim 16, wherein said fibrotic lesional tissue is associated with a condition in the group consisting of musculoskeletal fibrosis, post-surgical adhesions, scleroderma, glaucoma, and skin lesions.

18. A pharmaceutical composition, as defined in claim 16, wherein said pharmaceutical composition is contained in an article for administration thereof selected from the group consisting of creams, ointments, hydrophillic ointments, inhalable fluids, eye drops, and suppositories.