Method and composition for treating inflammatory disorders

• US 4,309,415 A
• Filed: 04/11/1979
• Issued: 01/05/1982
• Est. Priority Date: 04/11/1978
• Status: Expired due to Term

• Current Assignee: Verronmay Limited
• Original Assignee: Verronmay Limited
• Inventors: Horrobin, David F.
• Primary Examiner(s): WADDELL, FREDERICK
• Application Number:
  US06/029,058
• Time in Patent Office: 1,000 Days
• Field of Search: 424/312, 424/270, 424/145, 424/85, 424/289, 424/274, 424/256, 424/285, 424/271, 424/246, 424/318
• US Class Current: 424/85.4
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/23 of acids having a carboxyl group bound to a chain of seven or more carbon atoms
• CPC Class Codes: A61K 31/34 having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/425 Thiazoles
• CPC Class Codes: A61K 31/43 Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula , e.g. penicillins, penems
• CPC Class Codes: A61K 31/475 having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine vincamine A61K31/4375
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 33/30 Zinc; Compounds thereof
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Compositions and use of γ-linolenic acid and related materials with (i) zinc, β-lactam antibiotics or other materials enhancing physiological 1-series PG synthesis and/or (ii) colchicine, Vinca alkaloids or other materials enhancing physiological synthesis of thromboxane A2, for treatment of inflammatory disorders.

Claims

1. A pharmaceutical composition useful for the treatment of inflammatory disorders comprising:

(a) an effective amount of γ

-linolenic acid or physiologically functional derivative thereof and/or dihomo-γ

-linolenic acid or physiologically functional derivative thereof, and (b) an effective, conjoint amount of another material enhancing the synthesis or action of thromoboxane A2, alone or in an acceptable pharmaceutical vehicle.

3. The composition of claim 1 or 2, presented for administration in doses comprising 0.05 to 10 g of (a) calculated as γ

-linolenic acid, or one half one third or one quarter of said amount.

4. The composition of claim 1 or 2, presented for administration in doses comprising 0.1 to 1 g of (a) calculated as γ

-linolenic acid or one half one third or one quarter of said amount.

10. The composition of claim 1, comprising further (c) a conjoint amount of a material influencing the 1-series/2-series PG balance in the body in favor of the 1-series PG'"'"'s.

2. A pharmaceutical composition useful for the treatment of inflammatory disorders comprising:

(a) an effective amount of γ

-linolenic acid or physiologically functional derivative thereof and/or dihomo-γ

-linolenic acid or physiologically functional derivative thereof, and (b) an effective, conjoint amount of a material selected from colchicine, vinblastine, vincristine, and other Vinca alkaloids, griseofulvin, amantadine, melatonin, and interferon, alone or in an acceptable pharmaceutical vehicle.

5. The composition of claim 2, presented in daily or where specified weekly doses for administration in doses comprising:

0.3 to 15 mg colchicine or

100 to 1000 mg amantidine or

0.5 to 5 g griseofulvin or

35 to 350 mg vinblastine (weekly) or

7 to 70 mg vincristine (weekly) or

1×

10⁵ to 1×

10⁸ units interferon or

10 mg to 5 g melatonin

or one half one third or one quarter of said amount.

11. The composition of claim 2, comprising further (c) a conjoint amount of physiologically assimilable zinc, penicillamine, phenformin, levamisole or a β

-lactam antibiotic.

12. The composition of claim 11, wherein the antibiotic is a natural or semi-synthetic penicillin or cephalosporin antibiotic.

13. The composition of claim 11, wherein the antibiotic is selected from penicillin G, penicillin N, penicillin V, cephalothin, ampicillin, amoxycillin, cloxacillin, cephalexin and cephaloglycin.

14. The composition of claim 11, 12 or 13 presented for administration in doses comprising 0.5 to 3 g of the antibiotic or one half one third or one quarter of said amount.

15. The composition of claim 11, presented for administration in doses comprising:

50 mg to 10 g;

penicillamine or

10 mg to 5 g;

phenformin or

10 mg to 2 g;

levamisole

or one half one third or one quarter of said amount.

16. The composition of claim 11, presented for administration in doses comprising 2.5 to 800 mg assimilable zinc calculated as the metal, or one half one third or one quarter thereof.

17. The composition of claim 11, presented for administration in doses comprising 10 to 200 mg assimilable zinc calculated as the metal, or one half one third or one quarter thereof.

18. The composition of claim 11, presented for administration in doses comprising 10 to 80 mg assimilable zinc calculated as the metal, or one half one third or one quarter thereof.

19. A composition according to claim 11 wherein the zinc is present as a zinc oleate, γ

-linolenate or dihomo-γ

-linolenate.

6. A pharmaceutical composition useful for the treatment of inflammatory disorders comprising (a) an effective amount of γ

-linolenic acid or physiologically functional derivative thereof and/or dihomo-γ

-linolenic acid or physiologically functional derivative thereof, and (b) an effective, conjoint amount of a material selected from penicillamine, phenformin and levamisole, alone or in an acceptable pharmaceutical vehicle.

7. The composition of claim 6, presented for administration in doses comprising 0.05 to 10 g of (a) calculated as γ

-linolenic acid, or one half one third or one quarter of said amounts.

8. The composition of claim 6, presented for administration in doses comprising 0.1 to 1 g of (a) calculated as γ

-linolenic acid, or one half one third or one quarter of said amounts.

9. The composition of claim 6, presented for administration in doses comprising:

50 mg to 10 g;

penicillamine or

10 mg to 5 g;

phenformin or

10 mg to 2 g;

levamisole

or one half one third or one quarter of said amount.

20. A method of treating inflammation, comprising administering to a person suffering therefrom an effective amount of γ

-linolenic acid or a physiologically functional derivative thereof and/or dihomo-γ

-linolenic acid or a physiologically functional derivative thereof, and an effective conjoint amount of a material influencing the 1-series/2-series PG balance in the body in factor of the 1-series PG'"'"'s.

27. A method according to claim 20, wherein the daily amount of said acid or derivative is 0.05 to 10 g calculated as γ

-linolenic acid.

28. A method according to claim 27, wherein the daily amount of said acid or derivative is 0.1 to 5 g.

21. A method of treating inflammation, comprising administering to a person suffering therefrom an effective amount of γ

-linolenic acid or a physiologically functional derivative thereof and/or dihomo-γ

-linolenic acid or a physiologically functional derivative thereof, and an effective conjoint amount of a material selected from physiologically assimilible zinc, penicillamine, phenformin, levamisole, or a β

γ

-lactam antibiotic.

25. A method according to claim 21, wherein said antibiotic is a natural or semi-synthetic penicillin or cephalosporin antibiotic.

26. A method according to claim 25, wherein said antibiotic is selected from penicillin G, penicillin N, penicillin V, cephalothin, ampicillin, amoxycillin, cloxacillin, cephalexin and cephaloglycin.

29. A method according to claim 21, wherein the daily amount of said zinc is 2.5 to 800 mg calculated as the metal.

30. A method according to claim 29, wherein the amount of zinc is 10 to 200 mg.

31. A method according to claim 29, wherein the amount of zinc is 10 to 80 mg.

32. A method according to claim 21, wherein the daily amount of said penicillamine, phenformin or levamisole ismg to 10 g pencillamine ormg to 5 g phenformin ormg to 2 g levamisole.

33. A method according to claim 21, 25, or 26, wherein the daily amount of said antibiotic is 0.3 to 5 g.

37. A method according to claim 21 in which said zinc is in the form of zinc oleate, γ

-linolenate or dihomo-γ

-linolenate.

22. A method of treating inflammation, comprising administering to a person suffering therefrom an effective amount of γ

-linolenic acid or a physiologically functional derivative thereof and/or dihomo-γ

-linolenic acid or a physiologically functional derivative thereof and an effective conjoint amount of a material enhancing synthesis or action of thromboxane A2.

34. A method according to claim 22, further comprising administering an effective, conjoint amount of a material influencing the 1-series/2-series PG balance in the body in favor of 1-series PG'"'"'s.

23. A method of treating inflammation, comprising administering to a person suffering therefrom an effective amount of γ

-linolenic acid or a physiologically functional derivative thereof and/or dihomo-γ

-linolenic acid or a physiologically functional derivative thereof and/or dihomo-γ

-linolenic acid or a physiologically functional derivative thereof and an effective conjoint amount a material selected from colchicine, vinblastine, vincristine and other Vinca alkalodis, griseofulvin, amantadine, melatonin, and interferon.

35. A method according to claim 23, further comprising administering an effective, conjoint amount of a material influencing the 1-series/2-series PG balance in the body in favor of 1-series PG'"'"'s.

36. A method according to claim 23 or 35 when said selected material is administered in a daily or where specified weekly amount of:

0.3 to 15 mg colchicine or

100 to 1000 mg amantadine or

0.5 to 5 g griseofulvin or

35 to 350 mg vinblastine (weekly) or

7 to 70 mg vincristine (weekly) or

1×

10⁵ to 1×

10⁸ units interferon or 10 mg to 5 g melatonin

24. A method of treating inflammation, comprising administering to a person suffering therefrom (1) an effective amount of γ

-linolenic acid or a physiologically functional derivative thereof and/or dihomo-γ

-linolenic acid or physiologically functional derivative thereof, (2) an effective conjoint amount of physiologically assimilable zinc, penicillamine, phenformin, levamisole, or a β

-lactam antibiotic, and (3) an effective conjoint amount of a material selected from colchicine, vinblastine, vincristine and other Vinca alkaloids, griseofulvin, amantadine, melatonin, and interferon.