Claims for Patent: 6,753,013

Summary for Patent: 6,753,013

Title:	Pharmaceutical composition
Abstract:	A pharmaceutical composition for dermal use, wherein the composition has a first pharmacologically active component A consisting of at least one vitamin D or vitamin D analogue, and a second pharmacologically active component B consisting of at least one corticosteroid, wherein the difference between the maximum stability pH of said first component A and the maximum stability pH of said second component B is at least 1. The composition can also have at least one solvent component C, where component C is compounds of the general formula R.sup.3 (OCH.sub.2 C(R.sup.1)H).sub.x OR.sup.2 (I), wherein x is in the range of 2-60, R.sup.1 in each of the x units independently is H or CH.sub.3, R.sup.2 is straight chain or branched C.sub.1-20 alkyl or benzoyl, and R.sup.3 is H or phenylcarbonyloxy; di-(straight or branched)-C.sub.4-10 alkyl esters of C.sub.4 -C.sub.8 dicarboxylic acids; straight or branched C.sub.12-18 -alkyl benzoates; straight or branched C.sub.2-4 -alkyl esters of straight or branched C.sub.10-18 -alkanoic or -alkenoic acids; propylenglycol diesters with C.sub.8-14 -alkanoic acids; and branched primary C.sub.18-24 alkanols.
Inventor(s):	Didriksen; Erik (Ballerup, DK), H.o slashed.y; Gert (Ballerup, DK)
Assignee:	Leo Pharmaceutical Products, Ltd. A/S (Ballerup, DK)
Application Number:	09/959,367
Patent Claims:	1. A pharmaceutical composition for dermal use, said composition comprising: a first pharmacologically active component A consisting of at least one vitamin D or vitamin D analogue selected from the group consisting of seocalcitol, calcipotriol, calcitriol, tacalcitol, maxacalcitol, paricalcitol, falecalcitriol, 1.alpha.,24S-dihydroxy-vitamin D2, 1(S),3(R)-dihydroxy-20(R)-[((3-(2-hydroxy-2-propyl)-phenyl)-methoxy)-methy l]-9,10-seco-pregna-5(Z),7(E),10(19)-triene and mixtures thereof; and a second pharmacologically active component B consisting of at least one corticosteroid, wherein the difference between the maximum stability pH of said first component A and the maximum stability pH of said second component B is at least 1; and at least one solvent component C selected from the group consisting of: (i) compounds of the general formula R.sup.3 (OCH.sub.2 C(R.sup.1)H).sub.x OR.sup.2 (I) wherein x is in the range of 2-60, R.sup.1 in each of the x units independently is H or CH.sub.3, R.sup.2 is straight chain or branched C.sub.1-20 alkyl or benzoyl, and R.sup.3 is H or phenylcarbonyloxy; (ii) di-(straight or branched)-C.sub.4-10 alkyl esters of C.sub.4 -C.sub.8 dicarboxylic acids; (iii) straight or branched C.sub.12-18 -alkyl benzoates; (iv) straight or branched C.sub.2-4 -alkyl esters of straight or branched C.sub.10-18 -alkanoic or -alkenoic acids; (v) propylenglycol diesters with C.sub.8-14 -alkanoic acids; and (vi) branched primary C.sub.18-24 alkanols. 2. The composition according to claim 1, wherein said vitamin D analogue is selected from the group consisting of calcipotriol, calcitriol, tacalcitol, maxacalcitol, 1(S),3(R)-dihydroxy-20(R)-[((3-(2-hydroxy-2-propyl)-phenyl)-methoxy)-methy l]-9,10-seco-pregna-5(Z),7(E),10(19)-triene, and mixtures thereof. 3. The composition according to claim 1 or 2, wherein the vitamin D analogue is effective against psoriasis and related disorders of the skin in humans and other mammals. 4. The composition according to claim 3, wherein said vitamin D analogue is calcipotriol or its hydrate thereof. 5. The composition according to claim 1 or 2, wherein said corticosteroid is selected from the group consisting of Betamethasone, Clobetasol, Clobetasone, Desoximethasone, Diflucortolon, Diflorasone, Fluocinonid, Flumethasone, Fluocinolon, Fluticasone, Fluprednidene, Halcinonide, Hydrocortisone, Momethasone, Triamcinolon, and pharmaceutically acceptable esters and acetonides as well as mixtures thereof. 6. The composition according to claim 5, wherein said esters or acetonides are selected from the group consisting of 17-valerate, 17-propionate, 17,21-dipropionate, acetonide, acetonide-21-N-benzoyl-2-methyl-.beta.-alaninate, acetonide-21-(3,3-dimethylbutyrate) and 17-butyrate. 7. The composition according to claim 1 or 2, wherein said corticosteroid is selected from the group consisting of group I topical steroid, group II topical steroid and group III topical steroid. 8. The composition according to claim 1 or 2, wherein said composition is in the form of a non-aqueous composition. 9. The composition according to claim 1 or 2, wherein said composition is in the form of a non-aqueous composition. 10. The composition according to claim 9, wherein said composition is an ointment. 11. The composition according to claim 10, wherein said composition has the following composition: 12. A lotion comprising the composition according to claim 1 or 2. 13. The composition according to claim 12, said composition having the following composition: 14. The composition according to claim 1, wherein said component C is selected from the group consisting of a compound of the general formula H(OCH.sub.2 C(R.sup.1)H).sub.x OR.sup.2 (II) and mixtures thereof, wherein where R.sup.1, x, and R.sup.2 are as defined in claim 1. 15. The composition according to claim 14, wherein where R.sup.1 in the general formula is CH.sub.3. 16. The composition according to claim 14, wherein said component C is polyoxypropylene-15-stearyl ether. 17. The composition according to claim 1 or containing 0.001-0.25 mg/g or ml of said component A and 0.005-0.1% w/w of said component B. 18. A method of treating psoriasis, sebopsoriasis or seborrhoic dermatitis, the method comprising topically administering an effective amount of the composition of claim 1 or 2, to a patient in need of such treatment. 19. The method of claim 18 comprising topical administration once or twice daily of a medically sufficient dosage of said composition. 20. The method of claim 18, wherein application of the composition results in a higher efficacy in the treatment of psoriasis, sebopsoriasis or seborrhoic dermatitis than the efficacy attainable when using any composition comprising said components A or B alone. 21. The method of claim 18, wherein the efficacy of said treatment is measured, and said efficacy is measured as a percentage change in Psoriasis Area and Severity Index score. 22. A pharmaceutical composition comprising: a first pharmacologically active component A consisting of at least one vitamin D or vitamin D analogue selected from the group consisting of seocalcitol, calcipotriol, calcitriol, tacalcitol, maxacalcitol, paricalcitol, falecalcitriol, 1.alpha.,24S-dihydroxy-vitamin D2, 1(S),3(R)-dihydroxy-20(R)-[((3-(2-hydroxy-2-propyl)-phenyl)-methoxy)-methy l]-9,10-seco-pregna-5(Z),7(E),10(19)-triene and mixtures thereof; and a second pharmacologically active component B consisting of at least one corticosteroid, wherein the difference between the maximum stability pH of said first component A and the maximum stability pH of said second component B is at least 1; and at least one solvent component C selected from the group consisting of: (i) compounds of the general formula R.sup.3 (OCH.sub.2 C(R.sup.1)H).sub.x OR.sup.2 (I) wherein x is in the range of 2-60, R.sup.1 in each of the x units independently is H or CH.sub.3, R.sup.2 is straight chain or branched C.sub.1-20 alkyl or benzoyl, and R.sup.3 is H or phenylcarbonyloxy; (ii) straight or branched C.sub.2-4 -alkyl esters of straight or branched C.sub.10-18 -alkanoic or -alkenoic acids; (iii) propylenglycol diesters with C.sub.8-14 -alkanoic acids; and (iv) branched primary C.sub.18-24 alkanols; wherein said pharmaceutical composition is storage stable, non-aqueous and in a single container. 23. The pharmaceutical composition of claim 22, wherein said pharmaceutical composition is stable when stored at 40.degree. C. for 3 months.