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):	Harmenberg; Johan (Stockholm, SE), Kristofferson; Ann Harriet Margareta (Sodertaklje, SE)
Assignee:	Medivir AB (Huddinge, SE)
Application Number:	10/771,259
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 .Iadd.to treat recurrent herpes infections .Iaddend.comprising.Iadd., as sole active drug substances, .Iaddend.a .[.synergistic.]. combination of a.Iadd.n .Iaddend..[.topically acceptable.]. antiviral .[.substance.]. .Iadd.ingredient .Iaddend.selected from the group consisting of .Iadd.foscarnet, .Iaddend.acyclovir, .[.cidofovir, desciclovir, famciclovir, ganciclovir, lobucavir,.]. penciclovir, .[.PMEA, valacyclovir, 2242, PAA, PFA.]. and .Iadd.9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine .Iaddend.(H2G).Iadd., .Iaddend.or .[.an ester,.]. .Iadd.a .Iaddend.salt .[.or solvate.]. thereof and an antiinflammatory glucocorticoid .Iadd.ingredient selected from the group consisting of hydrocortisone and esters thereof, .Iaddend.in a pharmaceutically acceptable carrier.Iadd., wherein said combination of antiviral and glucocorticoid is more effective in treating said herpes infections than either ingredient alone.Iaddend.. .[.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.]. .Iadd.The .Iaddend.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.]. .Iadd.The .Iaddend.pharmaceutical composition according to claim .[.1.]. .Iadd.2.Iaddend., 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.]. .Iadd.2.Iaddend., 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.]. .Iadd.wherein said foscarnet is contained in an amount of .Iaddend.0.1-10% .[.foscarnet.]. .Iadd.(w/w) .Iaddend.and .Iadd.said hydrocortisone is contained in an amount of .Iaddend.0.005-3% .[.hydrocortisone.]. .Iadd.(w/w) based on the weight of the pharmaceutical composition.Iaddend.. 9. The pharmaceutical composition according to claim 8 .[.comprising.]. .Iadd.wherein said foscarnet is contained in an amount of .Iaddend.1-5% .[.foscarnet.]. .Iadd.(w/w) based on the weight of the pharmaceutical composition.Iaddend.. 10. The pharmaceutical composition according to claim 8 .[.comprising.]. .Iadd.wherein said foscarnet is contained in an amount of .Iaddend.0.3-3% .[.foscarnet.]. .Iadd.(w/w) .Iaddend.and .Iadd.said hydrocortisone is contained in an amount of .Iaddend.0.25-1% .[.hydrocortisone.]. .Iadd.(w/w) based on the weight of the pharmaceutical composition.Iaddend.. .[.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.]. .Iadd.wherein said acyclovir is contained in an amount of .Iaddend.0.1-10% .[.acyclovir.]. .Iadd.(w/w) .Iaddend.and .Iadd.said hydrocortisone is contained in an amount of .Iaddend.0.005-3% .[.hydrocortisone.]. .Iadd.(w/w) based on the weight of the pharmaceutical composition.Iaddend.. 14. The pharmaceutical composition according to claim 13 .[.comprising.]. .Iadd.wherein said acyclovir is contained in an amount of .Iaddend.1-5% .[.acyclovir.]. .Iadd.(w/w) based on the weight of the pharmaceutical composition.Iaddend.. 15. The pharmaceutical composition according to claim 14 .[.comprising.]. .Iadd.wherein said hydrocortisone is contained in an amount of .Iaddend.0.25-1% .[.hydrocortisone.]. .Iadd.(w/w) based on the weight of the pharmaceutical composition.Iaddend.. 16. A cream, lotion, gel, ointment, plaster, stick or pen containing a pharmaceutical composition according to any one of claims .Iadd.2, 4, 5, 7-10 and 13.Iaddend..[.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.]. .Iadd.treating recurrent .Iaddend.herpesvirus infections of the skin or mucous membranes in mammals .Iadd.having or identified as being at risk of developing said infections .Iaddend.comprising topical.Iadd.ly .Iaddend.administ.[.ration.]. .Iadd.ring thereto, as sole active drug substances and .Iaddend.in combination or in sequence, .[.of a therapeutically synergistic dose of.]. .[.a topically acceptable.]. .Iadd.an .Iaddend.antiviral .[.substance.]. .Iadd.ingredient .Iaddend.selected from the group consisting of .Iadd.foscarnet, .Iaddend.acyclovir, .[.cidofovir, desciclovir, famciclovir, ganciclovir, lobucavir,.]. penciclovir, .[.PMEA, valacyclovir, 2242, PAA, PFA.]. and .Iadd.9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (.Iaddend.H2G.Iadd.), .Iaddend.or .[.an ester,.]. .Iadd.a .Iaddend.salt .[.or solvate.]. thereof and an antiinflammatory glucocorticoid .Iadd.ingredient selected from the group consisting of hydrocortisone and esters thereof, .Iaddend.in a pharmaceutically acceptable carrier.Iadd., wherein said antiviral and glucocorticoid are more effective in treating said herpesvirus infections than either ingredient alone.Iaddend.. .[.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.]. .Iadd.The .Iaddend.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.]. .Iadd.18.Iaddend., 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.]. .Iadd.18.Iaddend., 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.]. .Iadd.treating recurrent .Iaddend.herpes virus infections of the skin or mucous membranes in mammals .Iadd.having or identified as being at risk of developing said infections .Iaddend.comprising topical.Iadd.ly .Iaddend.administ.[.ration.]. .Iadd.ring thereto a therapeutic dose .Iaddend.of a .Iadd.topically acceptable .Iaddend.composition according to anyone of claims .[.1-.]. .Iadd.2, 4, 5, 7-10 and 13-.Iaddend.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-.]. .Iadd.18, 20, 21 and .Iaddend.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-.]. .Iadd.18, 20, 21 and .Iaddend.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. .Iadd.37. The method according to claim 18, wherein said antiviral is acyclovir and said anti-inflammatory glucocorticoid is hydrocortisone..Iaddend.