Claims for Patent: RE39264

Summary for Patent: RE39264

Title:	Pharmaceutical combination
Abstract:	The invention relates to pharmaceutical compositions for topical administration comprising a topically acceptable antiviral substance and an antiinflammatory glucocorticoid in a pharmaceutically acceptable carrier. The pharmaceutical composition can be used in the prophylactic and curative treatment of herpesvirus infections in mammals including man. The invention also relates to the use of a combination of a topically acceptable antiviral substance and an antiinflammatory glucocorticoid for the manufacture of a medicament for said prophylactic and curative treatment.
Inventor(s):	Johan Harmenberg, Ann Harriet Margareta Kristofferson
Assignee:	Medivir AB
Application Number:	US10/771,259
Patent Claims:	1. A pharmaceutical composition for topical administration comprising a synergistic combination of a topically acceptable antiviral substance which is 1) a herpes-specific nucleoside analogue or an ester, salt or solvate thereof that is preferentially phosphorylated in virus-infected cells or 2) selected from the group consisting of cidofovir, PMEA, PAA and PFA or an ester, salt or solvate thereof, and an antiinflammatory glucocorticoid in a pharmaceutically acceptable carrier. 2. A pharmaceutical composition for topical administration to treat recurrent herpes infections comprising, as sole active drug substances, a synergistic combination of an topically acceptable antiviral substance ingredient selected from the group consisting of foscarnet, acyclovir, cidofovir, desciclovir, famciclovir, ganciclovir, lobucavir, penciclovir, PMEA, valacyclovir, 2242, PAA, PFA and 9-[ 4 -hydroxy- 2 -(hydroxymethyl)butyl]guanine (H2G), or an ester, a salt or solvate thereof and an antiinflammatory glucocorticoid ingredient selected from the group consisting of hydrocortisone and esters thereof, in a pharmaceutically acceptable carrier, wherein said combination of antiviral and glucocorticoid is more effective in treating said herpes infections than either ingredient alone. 3. A pharmaceutical composition according to claim 1, wherein the antiinflammatory glucocorticoid is selected from the group consisting of hydrocortisone, alclometasone, desonide, fluprednidene, flumethasone, hydrocortisone butyrate, clobetasone, triamcinolone acetonide, betamethasone, budesonide, desoximethasone, diflorosane, fluocinolone, fluocortolone, fluticasone, methylprednisolone aceponate, mometasone and rofleponide or an ester, salt or solvate thereof. 4. A The pharmaceutical composition according to claim 2, wherein the antiinflammatory glucocorticoid is selected from the group consisting of hydrocortisone, alclometasone, desonide, fluprednidene, flumethasone, hydrocortisone butyrate, clobetasone, triamcinolone acetonide, betamethasone, budesonide, desoximethasone, diflorosane, fluocinolone, fluocortolone, fluticasone, methylprednisolone aceponate, mometasone and rofleponide or an ester, salt or solvate thereof . 5. A The pharmaceutical composition according to claim 1 2, wherein the antiviral substance is foscarnet and the antiinflammatory glucocorticoid is hydrocortisone, or an ester thereof . 6. A pharmaceutical composition according to claim 1, wherein the antiviral substance is foscarnet and the antiinflammatory glucocorticoid is budesonide, or an ester thereof. 7. A pharmaceutical composition according to claim 1 2, wherein the antiviral substance is acyclovir, or an ester, salt or solvate thereof, and the antiinflammatory glucocorticoid is hydrocortisone, or an ester thereof . 8. The pharmaceutical composition according to claim 5 comprising wherein said foscarnet is contained in an amount of 0.1-10% foscarnet (w/w) and said hydrocortisone is contained in an amount of 0.005-3% hydrocortisone (w/w) based on the weight of the pharmaceutical composition. 9. The pharmaceutical composition according to claim 8 comprising wherein said foscarnet is contained in an amount of 1-5% foscarnet (w/w) based on the weight of the pharmaceutical composition. 10. The pharmaceutical composition according to claim 8 comprising wherein said foscarnet is contained in an amount of 0.3-3% foscarnet (w/w) and said hydrocortisone is contained in an amount of 0.25-1% hydrocortisone (w/w) based on the weight of the pharmaceutical composition. 11. The pharmaceutical composition according to claim 6 comprising 0.1-10% foscarnet and 0.005-3% budesonide. 12. The pharmaceutical composition according to claim 11 comprising 1-5% foscarnet . 13. The pharmaceutical composition according to claim 7 comprising wherein said acyclovir is contained in an amount of 0.1-10% acyclovir (w/w) and said hydrocortisone is contained in an amount of 0.005-3% hydrocortisone (w/w) based on the weight of the pharmaceutical composition. 14. The pharmaceutical composition according to claim 13 comprising wherein said acyclovir is contained in an amount of 1-5% acyclovir (w/w) based on the weight of the pharmaceutical composition. 15. The pharmaceutical composition according to claim 14 comprising wherein said hydrocortisone is contained in an amount of 0.25-1% hydrocortisone (w/w) based on the weight of the pharmaceutical composition. 16. A cream, lotion, gel, ointment, plaster, stick or pen containing a pharmaceutical composition according to any one of claims 2, 4, 5, 7-10 and 13 1 -15. 17. A method for the prophylaxis and/or treatment of herpesvirus infections of the skin or mucous membranes in mammals comprising topical administration, in combination or in sequence, of a therapeutically synergistic dose of a topically acceptable antiviral substance which is 1) a herpes-specific nucleoside analogue or an ester, salt or solvate thereof that is preferentially phosphorylated in virus-infected cells or 2) selected from the group consisting of cidofovir, PMEA, PAA and PFA or an ester, salt or solvate thereof and an antiinflammatory glucocorticoid. 18. A method for the prophylaxis and/or treatment of treating recurrent herpesvirus infections of the skin or mucous membranes in mammals having or identified as being at risk of developing said infections comprising topically administration ring thereto, as sole active drug substances and in combination or in sequence, of a therapeutically synergistic dose of a topically acceptable an antiviral substance ingredient selected from the group consisting of foscarnet, acyclovir, cidofovir, desciclovir, famciclovir, ganciclovir, lobucavir, penciclovir, PMEA, valacyclovir, 2242, PAA, PFA and 9-[ 4 -hydroxy- 2 -(hydroxymethyl)butyl]guanine (H2G), or an ester, a salt or solvate thereof and an antiinflammatory glucocorticoid ingredient selected from the group consisting of hydrocortisone and esters thereof, in a pharmaceutically acceptable carrier, wherein said antiviral and glucocorticoid are more effective in treating said herpesvirus infections than either ingredient alone. 19. A method according to claim 17, wherein the antiinflammatory glucocorticoid is selected from the group consisting of hydrocortisone, alclometasone, desonide, fluprednidene, flumethasone, hydrocortisone butyrate, clobetasone, triamcinolone acetonide, betamethasone, budesonide, desoximethasone, diflorosane, fluocinolone, fluocortolone, fluticasone, methylprednisolone aceponate, mometasone and rofleponide or an ester, salt or solvate thereof. 20. A The method according to claim 18, wherein the antiinflammatory glucocorticoid is selected from the group consisting of hydrocortisone, alclometasone, desonide, fluprednidene, flumethasone, hydrocortisone butyrate, clobetasone, triamcinolone acetonide, betamethasone, budesonide, desoximethasone, diflorosane, fluocinolone, fluocortolone, fluticasone, methylprednisolone aceponate, mometasone and rofleponide or an ester, salt or solvate thereof . 21. A method according to claim 17 18, wherein the antiviral substance is foscarnet and the antiinflammatory glucocorticoid is hydrocortisone, or an ester thereof. 22. A method according to claim 17, wherein the antiviral substance is foscarnet and the antiinflammatory glucocorticoid is budesonide, or an ester thereof. 23. A method according to claim 17 18, wherein the antiviral substance is acyclovir, or an ester, salt or solvate thereof , and the antiinflammatory glucocorticoid is hydrocortisone, or an ester thereof. 24. A method for the prophylaxis and/or treatment of treating recurrent herpes virus infections of the skin or mucous membranes in mammals having or identified as being at risk of developing said infections comprising topically administration ring thereto a therapeutic dose of a topically acceptable composition according to anyone of claims 1- 2, 4, 5, 7-10 and 13-15. 25. A method according to claim 24 wherein the composition is contained in a cream, lotion, gel, ointment, plaster, stick or pen. 26. A method according to anyone of claims 17-23, wherein the herpesvirus infection is a recurrent herpesvirus infection. 27. A method according to any one of claims 17- 18, 20, 21 and 23, wherein the antiviral substance and the glucocorticoid are administered 1 to 10 times per day. 28. A method according to claim 27, wherein the antiviral substance and the glucocorticoid are administered 3 to 4 times per day. 29. A method according to claim 26 40, wherein the antiviral substance and the glucocorticoid are administered 1 to 10 times per day. 30. A method according to claim 29, wherein the antiviral substance and the glucocorticoid are administered 3 to 4 times per day. 31. A method according to anyone of claims 17- 18, 20, 21 and 23 wherein the antiviral substance and the glucocorticoid are administered in combination and are contained in a cream, lotion, gel, ointment, plaster, stick or pen. 32. A method according to claim 24, wherein the herpesvirus infection is a recurrent herpesvirus infection. 33. A method according to claim 24, wherein the antiviral substance and the glucocorticoid are administered 1 to 10 times per day. 34. A method according to claim 33, wherein the antiviral substance and the glucocorticoid are administered 3 to 4 times per day. 35. A method according to claim 31, wherein the antiviral substance and the glucocorticoid are administered 1 to 10 times per day. 36. A method according to claim 35, wherein the antiviral substance and the glucocorticoid are administered 3 to 4 times per day. 37. The method according to claim 18, wherein said antiviral is acyclovir and said anti-inflammatory glucocorticoid is hydrocortisone.