Therapeutic treatment

• US 20060160896A1
• Filed: 01/17/2006
• Published: 07/20/2006
• Est. Priority Date: 02/04/2002
• Status: Abandoned Application

• Current Assignee: Jallal Messadek
• Original Assignee: Jallal Messadek
• Inventors: Messadek, Jallal
• Application Number:
  US11/333,514
• Publication Number:
  US 20060160896A1
• Time in Patent Office: Days
• US Class Current: 514/554
• CPC Class Codes: A61K 31/205 Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine

Abstract

The invention describes the use of betaine for treating and preventing arterites. The invention also describes an orally administered composition for treating arterites and, in particular, intermittent claudication, said composition containing, as an active ingredient, an active therapeutic quantity of betaine glycine by single dose. The invention particularly describes a medicament provided for treating a patient suffering from an intermittent claudication caused by peripheral circulatory disorders such as arteriosclerosis obliterans or by thromboangiitis obliterans.

Claims

1. A method for increasing the absolute claudication distance in a patient suffering of peripheral arterial diseases and/or intermittent claudication, said method comprising administering to said patient, as therapeutically active agent for increasing the maximal walking distance, a therapeutically effective amount of at least one therapeutically active compound selected from the group consisting of betaine of formula (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof.

2. The method of claim 1, for increasing the absolute claudication distance of said patient by at least 10% with respect to the average walking distance of said patient before his treatment, whereby said walking distance is increased by at least 20 meters and whereby the walking distance is determined by assessing the patient by a constant-load treadmill testing at a 12% grade inclination and speed of 3.2 km/h.

3. The method of claim 1, in which a therapeutically effective amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient for at least 4 weeks.

4. The method of claim 1, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is orally administered to said patient.

5. The method of claim 1, in which the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient with a dosage form selected from the group consisting of the once daily administration forms and the twice daily administration forms.

6. The method of claim 1, in which the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient with an extended release dosage form.

7. The method of claim 1, in which at least 1000 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂) COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an immediate release dosage form.

8. The method of claim 1, in which at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂) COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an extended release dosage form.

9. The method of claim 1, in which from 250 mg to 3000 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an extended release dosage form.

10. The method of claim 1, in which from 250 mg to 1000 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an extended release dosage form.

11. The method of claim 1, in which at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂) COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an extended release dosage form, while at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an immediate release dosage form.

12. The method of claim 11, in which at least one unit dosage form comprising an immediate release dosage portion of at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof and an extended release dosage portion of at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient.

13. A method for increasing the initial claudication distance in a patient suffering from peripheral arterial diseases and/or intermittent claudication, said method comprising administering to said patient, as therapeutically active agent for increasing the initial walking distance, a therapeutically effective amount of at least one therapeutically active compound selected from the group consisting of betaine of formula (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof.

14. A method for increasing the absolute claudication distance and for preventing stroke in a patient suffering of peripheral arterial diseases and/or intermittent claudication, said method comprising administering to said patient, as therapeutically active agent for increasing the absolute walking distance, a therapeutically effective amount of at least one therapeutically active compound selected from the group consisting of betaine of formula (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof.

15. A method for increasing the absolute claudication distance and preventing stroke in a patient suffering of peripheral arterial diseases and/or intermittent claudication and at risk from suffering of thrombosis, said method comprising administering to said patient, as therapeutically active agent for increasing the absolute walking distance, a therapeutically effective amount of at least one therapeutically active compound selected from the group consisting of betaine of formula (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof.

16. A method for increasing the absolute claudication distance and preventing stroke in a patient suffering of peripheral arterial diseases and/or intermittent claudication and at risk from suffering of headaches due to a treatment for his peripheral arterial disease, said method comprising administering to said patient, as therapeutically active agent for increasing the absolute walking distance, a therapeutically effective amount of at least one therapeutically active compound selected from the group consisting of betaine of formula (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof.

17. A method for increasing the initial claudication distance without headache side effect in a patient suffering from peripheral arterial diseases and/or intermittent claudication and at risk from suffering headache due to a treatment for his peripheral arterial occlusive disease, said method comprising administering to said patient a therapeutically effective amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof.

18. A method for increasing the absolute claudication distance in a patient suffering of peripheral arterial diseases and/or intermittent claudication, said method comprising administering to said patient a therapeutically effective amount of a first active agent effective for treating peripheral arterial diseases and/or intermittent claudication and a therapeutically effective amount of a second active agent different from the first active agent, whereby said second effective agent is selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof.

19. The method of claim 18, in which the first active agent is selected from the group consisting of cilostazol, pentoxifylline, prostaglandins, naftidrofuryl, aspirin, clopidogrel, levocarnitine, propionyl levocarnitine, and mixtures thereof.

20. A method for increasing the absolute claudication distance in a patient suffering of peripheral arterial diseases and/or intermittent claudication, said method comprising administering to said patient a therapeutically effective amount of a first active agent effective for treating peripheral arterial diseases and/or intermittent claudication, said first active agent having at least one side effect selected from the group consisting of thrombosis, stroke, palpitation, headache, loose stool samples, soft stool samples, and a therapeutically effective amount of a second active agent different from the first active agent for preventing said at least one side effect of the first active agent, whereby said second effective agent is selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof.

21. The method of claim 20, in which the first active agent is selected from the group consisting of Cilostazol, pentoxifylline, prostaglandins, naftidrofuryl, aspirin, clopidogrel, levocarnitine, propionyl levocarnitine, and mixtures thereof.

22. A method for increasing the absolute claudication distance in a patient suffering of peripheral arterial diseases and/or intermittent claudication, said method comprising administering to said patient a therapeutically effective amount of a first active agent effective for treating peripheral arterial diseases and/or intermittent claudication for increasing the absolute claudication distance, and a therapeutically effective amount of a second active agent different from the first active agent, whereby said second effective agent is selected from the group consisting of betaine of formula (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof, said second agent improving at least one effect selected from the group consisting of the absolute claudication distance achieved by the first active agent taken alone, the initial claudication distance achieved by the first active agent taken alone, the time onset for achieving a 10% improvement of the walking distance with respect to the walking distance achieved without pain by the patient not treated for his peripheral arterial occlusive diseases, the time onset for achieving a 20 m improvement of the walking distance with respect to the walking distance achieved without pain by the patient not treated for his peripheral arterial occlusive disease, and combinations thereof.

23. The method of claim 22, in which the first active agent is selected from the group consisting of cilostazol, pentoxifylline, prostaglandins, naftidrofuryl, aspirin, clopidogrel, levocarnitine, propionyl levocarnitine, and mixtures thereof.

24. A pharmaceutical combination for increasing at least one walking distance selected from the group consisting of absolute claudication distance and initial claudication distance, in a patient suffering of peripheral arterial diseases and/or intermittent claudication, said combination comprising administering to said patient a therapeutically effective amount of a first active agent effective for treating peripheral arterial occlusive diseases and a therapeutically effective amount of a second active agent different from the first active agent, whereby said second effective agent is selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof.

25. The combination of claim 24, in which the weight ration first active agent/second active agent is comprised between 1:

100 and 100;

1.

26. The combination of claim 25, in which the weight ration first active agent/second active agent is comprised between 1:

20 and 1;

1.

27. The combination of claim 24, in which the second active agent is at least partly in a extended release form.

28. The combination of claim 24, in which the first active agent is at least partly in an immediate release form.

29. The combination of claim 24, in which the first active agent is selected from the group consisting of cilostazol, pentoxifylline, prostaglandins, naftidrofuryl, aspirin, clopidogrel, levocarnitine, propionyl levocarnitine, and mixtures thereof.

30. The combination of claim 24, comprising from 10 to 200 mg of first active agent and from 250 mg to 3000 mg of second active agent.

31. The combination of claim 24, in the form of an unitary dosage form.

32. The combination of claim 24, which is an oral formulation.

33. A method for treating a human suffering from at least one trouble selected from the group consisting of trouble of Horton, varices, Raynaud'"'"'s disease, Burger'"'"'s diseases, heavy leg, leg swelling, leg oedema, ankle swelling, ankle oedema, claudication, vision function losses, occlusive central arterial, retinal ischemia, erectile dysfunction, temporal gigantic cell trouble, oedemas, blood flow disturbances due to oedemas and combinations thereof, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

34. The method of claim 33 for treating a human suffering from the disease of Horton, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

35. The method of claim 33 for treating a human suffering from at least one trouble selected from the group consisting of varices, blood flow disturbances due to varices and combinations thereof, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

36. The method of claim 33 for treating a human suffering from at least one trouble selected from the group consisting of oedemas, blood flow disturbances due to oedemas and combinations thereof, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

37. The method of claim 33 for treating a human suffering from one trouble selected from the group consisting of heavy leg, leg swelling, leg oedema, ankle swelling, ankle oedema, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

38. The method of claim 33 for treating a human suffering from at least one disease selected from the group consisting of Raynaud'"'"'s diseases, Burger'"'"'s disease and combination thereof, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

39. The method of claim 33 for treating a human suffering from at least one trouble selected from the group consisting of intermittent claudication, erectile dysfunctions, retinal ischemia, occlusive central arterial troubles, vision function losses and combinations thereof, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

40. The method of claim 33 for treating a human suffering from at least two different troubles selected from the group consisting of trouble of Horton, arteritis, varices, Raynaud'"'"'s disease, Burger'"'"'s disease, heavy leg, leg swelling, leg oedema, ankle swelling, ankle oedema, claudication, vision function losses, occlusive central arterial, retinal ischemia, erectile dysfunction, temporal gigantic cell trouble, oedemas, blood flow disturbances, blood flow disturbances due to oedemas and combinations thereof, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

41. The method of claim 33, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

42. The method of claim 33, in which the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient with a dosage form selected from the group consisting of the once daily administration forms and the twice daily administration forms.

43. The method of claim 33, in which the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient with an extended release dosage form

44. The method of claim 33, in which at least 1000 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂) COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an immediate release dosage form.

45. The method of claim 33, in which at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂) COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an extended release dosage form.

46. The method of claim 33, in which from 250 mg to 3000 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an extended release dosage form.

47. The method of claim 33, in which from 250 mg to 1000 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an extended release dosage form.

48. The method of claim 33, in which at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂) COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an extended release dosage form, while at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an immediate release dosage form.

49. The method of claim 33, in which at least one unit dosage form comprising an immediate release dosage portion of at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof and an extended release dosage portion of at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient.

50. The method of claim 33, which is suitable for treating at least one arteritis selected from the group consisting of common arteritis, degenerative arteritis, and combinations thereof.

51. A method for treating a human at risk of suffering from at least one trouble selected from the group consisting of trouble of Horton, varices, Raynaud'"'"'s disease, Burger'"'"'s disease, heavy leg, leg swelling, leg oedema, ankle swelling, ankle oedema, claudication, vision function losses, occlusive central arterial, retinal ischemia, erectile dysfunction, temporal gigantic cell trouble, oedemas, blood flow disturbances due to oedemas and combinations thereof, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

52. The method of claim 51 for treating a human suffering from the disease of Horton, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

53. The method of claim 51 for treating a human at risk of suffering from at least one trouble selected from the group consisting of varices, blood flow disturbances due to varices and combinations thereof, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

54. The method of claim 51 for treating a human at risk of suffering from at least one trouble selected from the group consisting of oedemas, blood flow disturbances due to oedemas and combinations thereof, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

55. The method of claim 51 for treating a human at risk of suffering from at least one trouble selected from the group consisting of heavy leg, leg swelling, leg oedema, ankle swelling, ankle oedema, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

56. The method of claim 51 for treating a human at risk of suffering from at least one disease selected from the group consisting of Raynaud'"'"'s disease, Burger'"'"'s disease and combinations thereof, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

57. The method of claim 51 for treating a human at risk of suffering from at least one trouble selected from the group consisting of intermittent claudication, erectile dysfunctions, retinal ischemia, occlusive central arterial troubles, vision function losses and combinations thereof, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

58. The method of claim 51 for treating a human at risk of suffering from at least two different troubles selected from the group consisting of trouble of Horton, arteritis, varices, Raynaud'"'"'s disease, Burger'"'"'s disease, heavy leg, leg swelling, leg oedema, ankle swelling, ankle oedema, claudication, vision function losses, occlusive central arterial, retinal ischemia, erectile dysfunction, temporal gigantic cell trouble, oedemas, blood flow disturbances due to oedemas and combinations thereof, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

59. The method of claim 51, in which an effective therapeutic amount of at least one therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient.

60. The method of claim 51, in which the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient with a dosage form selected from the group consisting of the once daily administration forms and the twice daily administration forms.

61. The method of claim 51, in which the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is administered to said patient with an extended release dosage form

62. The method of claim 51, in which at least 1000 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂) COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an immediate release dosage form.

63. The method of claim 51, in which at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂) COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an extended release dosage form.

64. The method of claim 51, in which from 250 mg to 3000 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an extended release dosage form.

65. The method of claim 51, in which from 250 mg to 1000 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an extended release dosage form.

66. The method of claim 51, in which at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂) COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an extended release dosage form, while at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient as an immediate release dosage form.

67. The method of claim 51, in which at least one unit dosage form comprising an immediate release dosage portion of at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof and an extended release dosage portion of at least 250 mg of the therapeutically active compound selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof is daily administered to said patient.

68. The method of claim 51, which is suitable for treating at least one arteritis selected from the group consisting of common arteritis, degenerative arteritis, and combinations thereof.

69. A method for increasing the initial claudication distance in a patient suffering of peripheral arterial diseases and/or intermittent claudication, said method comprising administering to said patient a therapeutically effective amount of a first active agent effective for treating peripheral arterial diseases and/or intermittent claudication for increasing a claudication distance selected from the group consisting of the absolute claudication distance and the initial claudication distance, and a therapeutically effective amount of a second active agent different from the first active agent, whereby said second effective agent is selected from the group consisting of betaine of formula (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof, said second agent improving at least one effect selected from the group consisting of the absolute claudication distance achieved by the first active agent taken alone, the initial claudication distance achieved by the first active agent taken alone, the time onset for achieving a 10% improvement of the walking distance with respect to the walking distance achieved without pain by the patient not treated for his peripheral arterial occlusive diseases, the time onset for achieving a 20 m improvement of the walking distance with respect to the walking distance achieved without pain by the patient not treated for his peripheral arterial occlusive disease, and combinations thereof.

71. The method of claim 69, in which the first active agent is selected from the group consisting of cilostazol, pentoxifylline, prostaglandins, naftidrofuryl, aspirin, clopidogrel, levocarnitine, propionyl levocarnitine, and mixtures thereof.

70. A method for increasing the initial claudication distance and the absolute walking distance in a patient suffering of peripheral arterial diseases and/or intermittent claudication, said method comprising administering to said patient a therapeutically effective amount of a first active agent effective for treating peripheral arterial diseases and/or intermittent claudication a claudication distance selected from the group consisting of the absolute claudication distance and the initial claudication distance, and a therapeutically effective amount of a second active agent different from the first active agent, whereby said second effective agent is selected from the group consisting of betaine of formula (CH₃)₃N⁺(CH₂) COO⁻

, pharmaceutically active salts thereof and mixtures thereof, said second agent improving at least one effect selected from the group consisting of the absolute claudication distance achieved by the first active agent taken alone, the initial claudication distance achieved by the first active agent taken alone, the time onset for achieving a 10% improvement of the walking distance with respect to the walking distance achieved without pain by the patient not treated for his peripheral arterial occlusive diseases, the time onset for achieving a 20 m improvement of the walking distance with respect to the walking distance achieved without pain by the patient not treated for his peripheral arterial occlusive disease, and combinations thereof.

72. A pharmaceutical combination for increasing the initial claudication distance in a patient suffering of peripheral arterial diseases and/or intermittent claudication, said combination comprising administering to said patient a therapeutically effective amount of a first active agent effective for treating peripheral arterial occlusive diseases and a therapeutically effective amount of a second active agent different from the first active agent, whereby said second effective agent is selected from the group consisting of (CH₃)₃N⁺(CH₂)COO⁻

, pharmaceutically active salts thereof and mixtures thereof.