초록 ▼

Novel analgesic and anti-inflammatory compositions of matter for use in eliciting an analgesic or anti-inflammatory response, said compositions comprising xanthine together with a selected non-narcotic analgesic/nonsteroidal anti-inflammatory drug or a selected narcotic analgesic, or both, are discl

Novel analgesic and anti-inflammatory compositions of matter for use in eliciting an analgesic or anti-inflammatory response, said compositions comprising xanthine together with a selected non-narcotic analgesic/nonsteroidal anti-inflammatory drug or a selected narcotic analgesic, or both, are disclosed. When used in combination with the selected drugs, such xanthine enhances the analgesic or anti-inflammatory response and also hastens its onset.

대표청구항 ▼

1. A pharmaceutical composition of matter adapted to elicit an onset hastened and enhanced analgesic and anti-inflammatory response in a mammaliam organism in need of such treatment, said composition comprising an analgesically and anti-inflammatory effective amount of an active drug component and a

1. A pharmaceutical composition of matter adapted to elicit an onset hastened and enhanced analgesic and anti-inflammatory response in a mammaliam organism in need of such treatment, said composition comprising an analgesically and anti-inflammatory effective amount of an active drug component and an active drug potentiating adjuvant therefor, said active drug comprising ibuprofen, naproxen, fenoprofen, indoprofen, diflunisal or pharmaceutically acceptable salts thereof and said adjuvant comprising an active drug analgesic and anti-inflammatory onset hastening and enhancing amount of a xanthine derivative of the formula ##STR## or a pharmaceutically acceptable non-toxic salt thereof wherein R 1 -R 3, inclusive, independently represent hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, hydroxy(C 1 -C 6 )alkyl, halogen, hydroxy(C 1 -C 4 )alkylamino(C 1 -C 4 )alkyl, C 1 -C 4 (dialkyl) amino(C 1 -C 4 )alkyl, C 1 -C 4 alkylcarbonyl (C 1 -C 4 )alkyl, C 1 -C 6 alkylamino, C 1 -C 6 (dialkyl)amino, indolyl, phenyl or allyl; R 4 is hydrogen, C 1 -C 6 alkyl, halo(C 1 -C 6 ) alkyl, C 1 -C 6 alkylamino, C 1 -C 6 alkylthio, nitro, carboxy C 1 -C 6 (dialkyl)amino, C 3 -C 6 cycloalkyl, phenyl, naphthyl, ar(C 1 -C 4 )alkyl, or a group of the formula ##STR## where R 5 is halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, notro or C 1 -C 6 alkylamino and n is 1, 2 or 3, with the proviso that R 1, R 2 and R 3 cannot all be C 1 alkyl when R 4 is hydrogen 2. A composition according to claim 1, wherein said active drug is ibuprofen or a pharmaceutically acceptable salt thereof. 3. A composition according to claim 1, wherein said active drug is naproxen or a pharmaceutically acceptable salt thereof. 4. A composition according to claim 1, wherein said active drug is fenoprofen or a pharmaceutically acceptable salt thereof. 5. A composition according to claim 1, wherein said active drug is indoprofen or a pharmaceutically acceptable salt thereof. 6. A composition according to claim 1, wherein said active drug is diflunisal or a pharmaceutically acceptable salt thereof. 7. The xanthine derivative of the composition according to claim 1, wherein R 1, R 2 and R 3 represent C 1 -C 6 alkyl, halo (C 1 -C 6 )alkyl, C 1 -C 4 (dialkyl)amino (C 1 -C 4 ) alkyl or hydroxy (C 1 -C 6 ) alkyl and R 4 represents C 1 -C 6 (dialkyl)amino, C 1 -C 6 alkylthio, phenyl or the group of formula (II). 8. The xanthine derivative according to claims 1 or 7, wherein R 1 and R 2 are the same and represent C 1 -C 6 alkyl, R 3 represents hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy or halo (C 1 -C 6 ) alkyl and R 4 represents hydrogen, C 1 -C 6 alkylthio, C 1 -C 6 alkylamino or phenyl. 9. The xanthine derivative according to claims 1 or 7, wherein R 1 represents hydrogen, R 2 and R 3 represent C 1 -C 6 alkyl, and R 4 represents hydrogen, C 1 -C 6 alkyl, halo (C 1 -C 6 )alkyl, phenyl or the group of formula (II). 10. The xanthine derivative according to claims 1 or 7, wherein R 1 and R 2 are the same and represent C 1 -C 6 alkyl, R 3 is hydrogen and R 4 represents halo, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkylthio, nitro, C 1 -C 6 alkylamino, C 1 -C 6 (dialkyl)amino, ar(C 1 -C 4 )alkyl, phenyl or the group of formula (II). 11. The xanthine derivative according to claims 1 or 7, wherein R 1 and R 2 represent hydrogen, methyl, ethyl, propyl, butyl, isobutyl, propenyl or isopropenyl, R 3 represents hydrogen, methyl, ethyl, butyl, 2-haloethyl, or 2-hydroxyethyl and R 4 represents hydrogen, methyl, ethyl, propyl, cyclopropyl, cyclohexyl, methylthio, ethylthio, nitro, methylamino, dimethylamino, phenyl, naphthyl, halophenyl, methoxy, phenyl, nitrophenyl, dimethylaminophenyl, dichlorophenyl or hydroxy phenyl. 12. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-phenyl-1,3-dimethylxanthine. 13. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-phenyl-1,3,-diethylxanthine. 14. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-methylthio-1,3-dimethyl xanthine. 15. The xanthine derivative of the composition according to claim 12, wherein said derivative is 8-methylamino-1,3-dimethyl xanthine. 16. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-dimethylamino-1,3-dimethyl xanthine. 17. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-methyl-1,3-dimethyl xanthine. 18. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-ethyl-1,3-dimethyl xanthine. 19. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-propyl-1,3-dimethyl xanthine. 20. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-cyclopropyl-1,3-dimethyl xanthine. 21. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-cyclopentyl-1,3-dimethyl xanthine. 22. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-(chlorophenyl)-1,3-dimethyl xanthine. 23. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-(bromophenyl)-1,3-dimethyl xanthine. 24. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-(methoxyphenyl)-1,3-dimethyl xanthine. 25. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-(nitrophenyl)-1,3-dimethyl xanthine. 26. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-(dimethylaminophenyl)-1,3-dimethyl xanthine. 27. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-(2,6-dimethyl-4-hydroxyphenyl)-1,3-dimethyl xanthine. 28. The xanthine derivative of the composition according to claim 1, wherein said derivative is xanthine. 29. The xanthine derivative of the composition according to claim 1, wherein said derivative is 3,7-dimethyl xanthine. 30. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-phenyl-1-methyl xanthine. 31. The xanthine derivative of the composition according to claim 1, wherein said derivative is 1,7-dimethyl xanthine. 32. The xanthine derivative of the composition according to claim 1, wherein said derivative is 1-methyl xanthine. 33. The xanthine derivative of the composition according to claim 1, wherein said derivative is 1,3-dimethyl xanthine. 34. The xanthine derivative of the composition according to claim 1, wherein said derivative is 8-ethyl-1,3,7-trimethyl xanthine. 35. The xanthine derivative of the composition according to claim 1, wherein said derivative is 7-methoxy-8-phenyl-1,3-dimethyl xanthine. 36. The xanthine derivative of the composition according to claim 1, wherein said derivative is 1-methyl-3-isobutyl xanthine. 37. The xanthine derivative of the composition according to claim 1, wherein said derivative is 1-ethyl-3,7-dimethyl xanthine. 38. The xanthine derivative of the composition according to claim 1, wherein said derivative is 1,3-diethyl xanthine. 39. The xanthine derivative of the composition according to claim 1, wherein said derivative is 1,3,7-triethyl xanthine. 40. The xanthine derivative of the composition according to claim 1, wherein said derivative is 1,3-dipropyl xanthine. 41. The xanthine derivative of the composition according to claim 1, wherein said derivative is 1,3-diallyl xanthine. 42. The xanthine derivative of the composition according to claim 1, wherein said derivative is 1-butyl-3,7-dimethyl xanthine. 43. The xanthine derivative of the composition according to claim 1, wherein said derivative is 1-hexyl-3,7-dimethyl xanthine. 44. A composition according to claim 1, comprising from about 60 to 200 mg of said xanthine derivative. 45. A composition according to claim 1, comprising from about 20 to 100 mg of said xanthine derivative. 46. A composition according to claim 1, comprising from about 125 mg to 500 mg diflunisal and from about 65 to 150 mg of said xanthine derivative. 47. A composition according to claim 1, comprising from about 50 to 400 mg ibuprofen. 48. A composition according to claim 1, comprising from about 125 to about 500 mg naproxen and from about 65 to about 150 mg of said xanthine derivative in sustained release form. 49. A composition according to claim 1, comprising from about 50 to about 200 mg fenoprofen. 50. A composition according to claim 1, further comprising a nontoxic pharmaceutically acceptable inert carrier. 51. A composition according to claim 1, said composition being adapted for oral administration. 52. A composition according to claim 1, said composition being adapted for rectal administration. 53. A composition according to claim 1, said composition being formulated as a suppository. 54. A method of eliciting an onset hastened and enhanced analgesic and anti-inflammatory response in a mammalian organism in need of such treatment comprising administering to such organism an analgesically and anti-inflammatorily effective amount of a pharmaceutical composition of matter comprising an analgesically and anti-inflammatorily effective amount of an active drug component and an active drug potentiating adjuvant therefor, said active drug comprising ibuprofen, naproxen, fenoprofen, indoprofen, diflunisal or pharmaceutically acceptable salts thereof and said adjuvant comprising an active drug analgesic and anti-inflammatory onset hastening and enhancing amount of a xanthine derivative of the formula ##STR## or a pharmaceutically acceptable non-toxic salt thereof wherein R 1 -R 3, inclusive, independently represent hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, hydroxy (C 1 -C 6 )alkyl, halogen, hydroxy(C 1 -C 4 )-alkylamino(C 1 -C 4 )alkyl, C 1 -C 4 (dialkyl)amino(C 1 -C 4 )alkyl, C 1 -C 4 alkylcarbonyl(C 1 -C 4 )alkyl, C 1 -C 6 alkylamino, C 1 -C 6 (dialkyl)amino, indolyl, phenyl or allyl; R 4 is hydrogen, C 1 -C 6 alkyl, halo(C 1 -C 6 )alkyl, C 1 -C 6 alkylamino, C 1 -C 6 alkylthio, nitro, carboxy, C 1 -C 6 (dilakyl)amino, C 3 -C 6 cycloalkyl, phenyl, naphthyl, ar(C 1 -C 4 )alkyl, or a group of the formula ##STR## where R 5 is halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, nitro, or C 1 -C 6 -alkylamino and n is 1, 2 or 3 with the proviso that R 1, R 2 and R 3 cannot all be C 1 alkyl when R 4 is hydrogen.