Claims for Patent: 4,349,563

Summary for Patent: 4,349,563

Title:	Pharmaceutical compositions
Abstract:	An anti-inflammatory pharmaceutical composition is described which is adapted for topical application to the eye and contains as active principle a compound of formula ##STR1## or a pharmaceutically acceptable salt thereof where R.sub.1 is a chlorine atom or a methyl group, R.sub.2 is a hydrogen atom or a methyl group and R.sub.3 is a hydrogen atom or a methyl group. The composition may be used to treat ocular inflammation.
Inventor(s):	Gilbert; David J. (Bishops Stortford, GB2), Hollingsbee; Derek A. (Essex, GB2)
Assignee:	Smith and Nephew Associated Companies Limited (GB2)
Application Number:	06/253,184
Patent Claims:	1. A method of treating ocular inflammation which comprises topically administering to the eye an anti-inflammatory amount of a composition which comprises an anti-inflammatory effective amount of a compound of the formula (I): ##STR3## or a pharmaceutically acceptable salt thereof wherein R.sub.1 is chloro or methyl; R.sub.2 is hydrogen or methyl; and R.sub.3 is hydrogen or methyl, in combination with an ocularly acceptable carrier. 2. A method according to claim 1 wherein the composition contains from 0.1 to 10% wt/wt of said compound in the form of a pharmaceutically acceptable salt. 3. A method according to claim 1 wherein the composition contains from 0.4 to 7% wt/wt of said compound in the form of a pharmaceutically acceptable salt. 4. A method according to claim 1 wherein the composition contains from 0.5 to 5% wt/wt of said compound in the form of a pharmaceutically acceptable salt. 5. A method according to claim 1 wherein the composition contains from 1 to 2% wt/wt of said compound in the form of a pharmaceutically acceptable salt. 6. A method according to claim 1 wherein the composition contains from 2 to 5% wt/wt of said compound in the form of a pharmaceutically acceptable salt. 7. A method according to claim 1 wherein the composition contains 2% wt of said compound in the form of a pharmaceutically acceptable salt. 8. A method according to claim 1 wherein the composition contains 5% wt of said compound in the form of a pharmaceutically acceptable salt. 9. A method according to claim 1 wherein the composition has been rendered substantially isotonic. 10. A method according to claim 1 wherein the composition contains from 0.01 to 2.5% of an antioxidant. 11. A method according to claim 1 wherein the composition contains from 0.05 to 2% of an antioxidant. 12. A method according to claim 1 wherein the composition contains from 0.5 to 1.5% of an antioxidant. 13. A method according to claim 1 wherein the composition contains 1% of an antioxidant. 14. A method according to claim 10 wherein the antioxidant is a citrate salt, anacetylcysteine, sodium thiosulphate, sodium metabisulphate or thiourea. 15. A method according to claim 14 wherein the antioxidant is a citrate salt. 16. A method according to claim 15 wherein the citrate salt is tri-sodium citrate. 17. A method according to claim 1 wherein the composition contains from 0.001 to 2% of a metal ion sequestering agent. 18. A method according to claim 1 wherein the composition contains from 0.5 to 1.5% of a metal ion sequestering agent. 19. A method according to claim 17 wherein the composition also contains from 0.01 to 2.5% of an antioxidant. 20. A method according to claim 19 wherein the antioxidant and the metal ion sequestering agent is trisodium citrate. 21. A method according to claim 1 wherein the pH of the composition is 6.0 to 8.6. 22. A method according to claim 1 wherein the composition contains a preservative. 23. A method according to claim 22 wherein the preservative is phenylethanol and thiomersal. 24. A method according to claim 23 wherein the composition contains from 0.1 to 1% phenylethanol and from 0.001 to 0.025% thiomersal. 25. A method according to claim 2 wherein the compound is the sodium or potassium salt of tolemetin. 26. A method according to claim 4 wherein the compound is the sodium salt of tolemetin. 27. A method according to claim 26 wherein the composition is in the form of a clear, sterile aqueous solution. 28. A method according to claim 1 wherein the composition is in the form of a sterile emulsion. 29. A method according to claim 1 wherein the composition is in the form of a sterile ointment. 30. A method according to claim 1 wherein the composition is in the form of a clear, sterile aqueous solution which comprises 0.5 to 5% wt/wt of the sodium salt of tolmetin, 0.5 to 2% of an antioxidant or sequestering agent and a preservative, the pH of said solution being from 7.0 to 8.0. 31. A method according to claim 30 wherein the antioxidant or sequestering agent is a citrate salt. 32. A method according to claim 31 wherein the citrate salt is tri-sodium citrate. 33. A method according to claim 32 wherein the preservative is a mixture of 0.5% phenylethanol and 0.01% thiomersal. 34. A method according to claim 1 wherein the composition is in the form of a sterile water-in-oil emulsion which comprises from 0.5 to 5.0% wt/wt of the sodium salt of tolmetin, 0.05 to 2% of an antioxidant or sequestering agent, 40 to 65% of a pharmacologically acceptable oil, 1 to 20% of an emulsifying agent, a preservative and water to 100%. 35. A method according to claim 34 wherein the antioxidant or sequestering agent is a citrate salt. 36. A method according to claim 34 wherein the citrate salt is tri-sodium citrate. 37. A method according to claim 36 wherein the emulsifier is selected from the group consisting of glyceryl monoisostearate, cetostearyl alcohol, hydrogenated castor oil, sorbitan sesquioleate and mixtures thereof. 38. A method according to claim 37 wherein the pharmacologically acceptable oil is a vegetable or mineral oil. 39. A method according to claim 37 wherein the pharmacologically acceptable oil is a mixture of liquid paraffin, white soft paraffin and castor oil. 40. A method according to claim 39 wherein the preservative is 0.5% phenylethanol. 41. An anti-inflammatory pharmaceutical composition in a form suitable for topical administration to the eye which comprises an anti-inflammatory effective amount of a compound of the formula (I): ##STR4## or a pharmaceutically acceptable salt thereof wherein R.sub.1 is chloro or methyl; R.sub.2 is hydrogen or methyl; and R.sub.3 is hydrogen or methyl, in combination with an occularly acceptable carrier. 42. A composition according to claim 41 which contains from 0.1 to 10% wt/wt of said compound in the form of a pharmaceutically acceptable salt. 43. A composition according to claim 41 which contains from 0.4 to 7% wt/wt of said compound in the form of a pharmaceutically acceptable salt. 44. A composition according to claim 41 which contains from 0.5 to 5% wt/wt of said compound in the form of a pharmaceutically acceptable salt. 45. A composition according to claim 41 which contains from 1 to 2% wt/wt of said compound in the form of a pharmaceutically acceptable salt. 46. A composition according to claim 41 which contains from 2 to 5% wt/wt of said compound in the form of a pharmaceutically acceptable salt. 47. A composition according to claim 41 which contains 2% wt of said compound in the form of a pharmaceutically acceptable salt. 48. A composition according to claim 41 which contains 5% wt of said compound in the form of a pharmaceutically acceptable salt. 49. A composition according to claim 41 which has been rendered substantially isotonic. 50. A composition according to claim 41 which contains from 0.01 to 2.5% of an antioxidant. 51. A composition according to claim 41 which contains from 0.05 to 2% of an antioxidant. 52. A composition according to claim 41 which contains from 0.5 to 1.5% of an antioxidant. 53. A composition according to claim 41 which contains 1% of an antioxidant. 54. A composition according to claim 50 wherein the antioxidant is a citrate salt, anacetylcysteine, sodium thiosulphate, sodium metabisulphate or thiourea. 55. A composition according to claim 54 wherein the antioxidant is a citrate salt. 56. A composition according to claim 55 wherein the citrate salt is tri-sodium citrate. 57. A composition according to claim 41 which contains from 0.001 to 2% of a metal ion sequestering agent. 58. A composition according to claim 41 which contains from 0.5 to 1.5% of a metal ion sequestering agent. 59. A composition according to claim 57 which also contains from 0.01 to 2.5% of an antioxidant. 60. A composition according to claim 59 wherein the antioxidant and the metal ion sequestering agent is trisodium citrate. 61. A composition according to claim 41 wherein the pH of the composition is 6.0 to 8.6. 62. A composition according to claim 41 which contains a preservative. 63. A composition according to claim 62 wherein the preservative is phenylethanol and thiomersal. 64. A composition according to claim 63 which contains from 0.1 to 1% phenylethanol from 0.001 to 0.025% thiomersal. 65. A composition according to claim 42 wherein the compound is the sodium or potassium salt of tolemetin. 66. A composition according to claim 44 wherein the compound is the sodium salt of tolemetin. 67. A composition according to claim 66 wherein the composition is in the form of a clear, sterile aqueous solution. 68. A composition according to claim 41 in the form of a sterile ointment. 69. A composition according to claim 41 in the form of a sterile emulsion. 70. A composition according to claim 41 in the form of a clear, sterile aqueous solution which comprises 0.5 to 5% wt/wt of the sodium salt of tolmetin, 0.5 to 2% of an antioxidant or sequestering agent and a preservative, the pH of said solution being from 7.0 to 8.0. 71. A composition according to claim 70 wherein the antioxidant or sequestering agent is a citrate salt. 72. A composition according to claim 71 wherein the citrate salt is tri-sodium citrate. 73. A composition according to claim 72 wherein the preservative is a mixture of 0.5% phenylethanol and 0.01% thiomersal. 74. A composition according to claim 41 in the form of a sterile water-in-oil emulsion which comprises from 0.5 to 5.0% wt/wt of the sodium salt of tolmetin, 0.05 to 2% of an antioxidant or sequestering agent, 40 to 65% of a pharmacologically acceptable oil, 1 to 20% of an emulsifying agent, a preservative and water to 100%. 75. A composition according to claim 74 wherein the antioxidant or sequestering agent is a citrate salt. 76. A composition according to claim 74 wherein the citrate salt is tri-sodium citrate. 77. A composition according to claim 76 wherein the emulsifier is selected from the group consisting of glyceryl monoisostearte, cetostearyl alcohol, hydrogenated castor oil, sorbitan sesquiolesate and mixtures thereof. 78. A composition according to claim 77 wherein the pharmacologically acceptable oil is a vegetable or mineral oil. 79. A composition according to claim 77 wherein the pharmacologically acceptable oil is a mixture of liquid paraffin, white soft paraffin and castor oil. 80. A composition according to claim 79 wherein the preservative is 0.5% phenylethanol.

Details for Patent 4,349,563

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2000-04-18