Transdermal treatment for pain and inflammation with 2-amino-3-aroylbenzeneacetic acids, salts and esters

• US 4,683,242 A
• Filed: 10/28/1985
• Issued: 07/28/1987
• Est. Priority Date: 10/28/1985
• Status: Expired due to Term

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: A. H. Robins Company, Incorporated
• Inventors: Poser, Richard G.
• Primary Examiner(s): Friedman, Stanley J.
• Application Number:
  US06/792,269
• Time in Patent Office: 638 Days
• Field of Search: 514/562, 514/539
• US Class Current: 514/539
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

A method is disclosed for treating pain and/or inflammation by transdermal administration of 2-amino-3-benzoylbenzeneacetic acids, salts and esters having the formula ##STR1## wherein R¹ is hydrogen, loweralkyl or a pharmaceutically acceptable cation; R² is hydrogen, halogen, loweralkyl or loweralkoxy; R³, R⁴ and R⁵ are hydrogen or loweralkyl; X is hydrogen, halogen, loweralkyl, hydroxy, loweralkoxy, nitro, trifluoromethyl or loweralkylthio; Y is hydrogen, loweralkyl, loweralkoxy, nitro or trifluoromethyl and hydrates and alcoholates thereof.

Claims

1. A method of treating animals or humans to alleviate pain or inflammation by applying to the skin of said animals or humans a transdermal preparation comprised of a pharmaceutical carrier containing therein a pain or inflammation alleviating amount of compound of the formula:

##STR4## wherein;

R¹ is hydrogen, loweralkyl or a pharmaceutically acceptable cation;

R² is hydrogen, halogen, loweralkyl or loweralkoxy;

R³, R⁴ and R⁵ are hydrogen or loweralkyl;

X is hydrogen, halogen, loweralkyl, hydroxy, loweralkoxy, nitro, trifluoromethyl or S-loweralkyl; and

Y is hydrogen, loweralkyl, loweralkoxy, nitro or trifluoromethyl; and

the hydrates thereof.

2. The method of claim 1 wherein the transdermal preparation is a cream and the pH of said cream is 6.5-8.0.

3. The method of claim 1 wherein the transdermal preparation is contained in an occlusive device.

4. The method of claim 1 wherein R¹ is sodium ion.

5. The method of claim 1 wherein the compound is 2-amino-3-benzoylacetic acid or a pharmaceutically acceptable salt thereof.

6. The method of claim 1 wherein the compound is 2-amino-3-benzoyl-5-chlorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

7. The method of claim 1 wherein the compound is 2-amino-3-benzoyl-5-methoxybenzeneacetic acid or a pharmaceutically acceptable salt thereof.

8. The method of claim 1 wherein the compound is 2-amino-3-benzoylbenzeneacetic acid, sodium salt, dihydrate.

9. The method of claim 1 wherein the compound is 2-amino-3-benzoylbenzeneacetic acid, ethyl ester.

10. The method of claim 1 wherein the compound is 2-amino-3-(4-chlorobenzoyl)benzeneacetic acid or a pharmaceutically acceptable salt thereof.

11. The method of claim 1 wherein the compound is 2-amino-3-benzoylbenzeneacetic acid, potassium salt, monohydrate.

12. The method of claim 1 wherein the compound is 2-amino-3-(4-chlorobenzoyl)benzeneacetic acid, ethyl ester.

13. The method of claim 1 wherein the compound is 2-amino-3-(4-fluorobenzoyl)benzeneacetic acid or a pharmaceutically acceptable salt thereof.

14. The method of claim 1 wherein the compound is 2-amino-3-(4-fluorobenzoyl)benzeneacetic acid, sodium salt, monohydrate.

15. The method of claim 1 wherein the compound is 2-amino-3-(4-methoxybenzoyl)benzeneacetic acid or a pharmaceutically acceptable salt thereof.

16. The method of claim 1 wherein the compound is 2-amino-3-benzoylbenzeneacetic acid, megnesium salt, trihydrate.

17. The method of claim 1 wherein the compound is 2-amino-3-benzoylbenzeneacetic acid, calcium salt, dihydrate.

18. The method of claim 1 wherein the compound is 2-amino-3-benzoylbenzeneacetic acid sodium salt, monohydrate.

19. The method of claim 1 wherein the compound is 2-amino-3-(4-fluorobenzoyl)-5-methylbenzeneacetic acid, sodium salt, monohydrate.

20. The method of claim 1 wherein the compound is 2-amino-3-(4-chlorobenzoyl)-5-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

21. The method of claim 1 wherein the compound is 2-amino-3-[(4-methylthio)benzoyl]benzene acetic acid or a pharmaceutically acceptable salt thereof.

22. The method of claim 1 wherein the compound is 2-amino-3-[(4-methylthio)benzoyl]-5-chlorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

23. The method of claim 1 wherein the compound is 2-amino-3-[(4-methylthio)benzoyl]-5-fluorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

24. The method of claim 1 wherein the compound is 2-amino-3-benzoyl-4-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

25. The method of claim 1 wherein the compound is 2-amino-3-(4-bromobenzoyl)benzeneacetic acid or a pharmaceutically acceptable salt thereof.

26. The method of claim 1 wherein the compound is 2-amino-3-benzoyl-6-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

27. The method of claim 1 wherein the compound is 2-amino-3-benzoyl-5-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

28. The method of claim 1 wherein the compound is 2-amino-3-(2,4-dichlorobenzoyl)benzeneacetic acid or a pharmaceutically acceptable salt thereof.

29. The method of claim 1 wherein the compound is 2-amino-3-[4-(methylthio)benzoyl]-5-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

30. The method of claim 1 wherein the compound is 2-amino-3-(4-methylbenzoyl)-5-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

31. The method of claim 1 wherein the compound is 2-amino-3-(4-chlorobenzoyl)-5-fluorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

32. The method of claim 1 wherein the compound is 2-amino-3-(2,4-dichlorobenzoyl)-5-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

33. The method of claim 1 wherein the compound is 2-amino-3-(4-bromobenzoyl)-5-chlorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

34. The method of claim 1 wherein the compound is 2-amino-3-(4-chlorobenzoyl)-5-methoxybenzeneacetic acid or a pharmaceutically acceptable salt thereof.

35. The method of claim 1 wherein the compound is 2-amino-3-(4-bromo-2-chlorobenzoyl)benzeneacetic acid or a pharmaceutically acceptable salt thereof.

36. The method of claim 1 wherein the compound is 2-amino-3-(4-bromo-2-chlorobenzoyl)-5-chlorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

37. The method of claim 1 wherein the compound is 2-amino-3-(4-bromobenzoyl)-5-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

38. The method of claim 1 wherein the compound is 2-amino-3-(4-iodobenzoyl)-5-chlorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

39. The method of claim 1 wherein the compound is 2-amino-3-(4-bromobenzoyl)-5-fluorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

40. The method of claim 1 wherein the compound is 2-amino-3-(4-bromobenzoyl)-5-bromobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

41. The method of claim 1 wherein the compound is 2-amino-3-(4-bromobenzoyl)-5-methoxybenzeneacetic acid or a pharmaceutically acceptable salt thereof.

42. The method of claim 1 wherein the compound is 2-amino-3-(3,4-dichlorobenzoyl)benzeneacetic acid or a pharmaceutically acceptable salt thereof.

43. The method of claim 1 wherein the compound is 2-amino-3-(4-fluorobenzoyl)benzeneacetic acid, sodium salt.

44. The method of claim 1 wherein the compound is 2-amino-3-(4-methoxybenzoyl)benzeneacetic acid, sodium salt, hemihydrate.

45. The method of claim 1 wherein the compound is 2-amino-3-benzoyl-5-chlorobenzeneacetic acid, sodium salt.

46. The method of claim 1 wherein the compound is 2-amino-3-(2-chlorobenzoyl)benzeneacetic acid or a pharmaceutically acceptable salt thereof.

47. The method of claim 1 wherein the compound is 2-amino-3-(3-chlorobenzoyl)benzeneacetic acid or a pharmaceutically acceptable salt thereof.

48. The method of claim 1 wherein the compound is 2-amino-3-benzoyl-5-fluorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

49. The method of claim 1 wherein the compound is 2-amino-3-(4-methylbenzoyl)benzeneacetic acid or a pharmaceutically acceptable salt thereof.

50. The method of claim 1 wherein the compound is 2-amino-3-[4-(trifluoromethyl)benzoyl]benzeneacetic acid or a pharmaceutically acceptable salt thereof.

51. The method of claim 1 wherein the compound is 2-amino-3-(2-methylbenzoyl)benzeneacetic acid or a pharmaceutically acceptable salt thereof.

52. The method of claim 1 wherein the compound is 2-amino-3-benzoyl-4-chlorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

53. The method of claim 1 wherein the compound is 2-amino-3-(4-chlorobenzoyl)-5-chlorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

54. The method of claim 1 wherein the compound is 2-amino-3-(4-fluorobenzoyl)-5-fluorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

55. The method of claim 1 wherein the compound is 2-amino-3-(4-methylbenzoyl)-5-fluorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

56. The method of claim 1 wherein the compound is 2-amino-3-(2,4-dichlorobenzoyl)-5-fluorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

57. The method of claim 1 wherein the compound is 2-amino-3-(2,4-dimethylbenzoyl)benzeneacetic acid or a pharmaceutically acceptable salt thereof.

58. The method of claim 1 wherein the compound is 2-amino-3-(4-hydroxybenzoyl)-5-chlorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

59. The method of claim 1 wherein the compound is 2-amino-3-(4-methylbenzoyl)-5-chlorobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

60. The method of claim 1 wherein the compound is 2-amino-3-(4-chlorobenzoyl)-5-bromobenzeneacetic acid or a pharmaceutically acceptable salt thereof.

61. The method of claim 1 wherein the compound is 2-amino-3-(4-iodobenzoyl)benzeneacetic acid or a pharmaceutically acceptable salt thereof.

62. The method of claim 1 wherein the compound is 2-dimethylamino-3-benzoylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

63. The method of claim 1 wherein the compound is 2-amino-3-benzoyl-α

-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

64. The method of claim 1 wherein the compound is 2-amino-3-benzoyl-α

-methylbenzeneacetic acid, zinc salt, hemihydrate.

65. The method of claim 1 wherein the compound is 2-amino-3-benzoyl-5-chlorobenzeneacetic acid, ethyl ester.

66. The method of claim 1 wherein the compound is 2-amino-3-(4-chlorobenzoyl)-α

-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

67. The method of claim 1 wherein the compound is 2-amino-3-(4-chlorobenzoyl)-5-fluoro-α

-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

68. The method of claim 1 wherein the compound is 2-amino-3-(4-bromobenzoyl)-5-chloro-α

-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

69. The method of claim 1 wherein the compound is 2-amino-3-(4-chlorobenzoyl)-α

-ethylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

70. The method of claim 1 wherein the compound is 2-amino-3-(4-bromobenzoyl)-α

-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

71. The method of claim 1 wherein the compound is 2-amino-3-(2,4-dichlorobenzoyl)-α

-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

72. The method of claim 1 wherein the compound is 2-amino-3-(4-chlorobenzoyl)-5-chloro-α

-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

73. The method of claim 1 wherein the compound is 2-amino-3-(4-bromobenzoyl)benzeneacetic acid, ethyl ester.

74. The method of claim 1 wherein the compound is 2-amino-3-(4-bromobenzoyl)-5-fluoro-α

-methylbenzeneacetic acid or a pharmaceutically acceptable salt thereof.

75. The method of claim 1 wherein the compound is 2-amino-3-benzoylbenzeneacetic acid, zinc salt.

76. The method of claim 1 wherein the compound is 2-amino-3-benzoylbenzeneacetic acid, dihydroxyaluminum salt, monohydrate.

77. The method of claim 1 wherein the compound is 2-amino-3-benzoylbenzeneacetic acid copper salt, monohydrate.

78. The method of claim 1 wherein the compound is 2-amino-3-(4-bromobenzoyl)benzeneacetic acid, sodium salt, sesquihydrate.

79. The method of claim 1 wherein the compound is 2-amino-3-(4-bromobenzoyl)-5-chlorobenzeneacetic acid, sodium salt, monohydrate.

80. The method of claim 1 wherein the compound is 2-amino-3-(4-bromobenzoyl)-5-chlorobenzeneacetic acid, ethyl ester.