Pharmaceutical spray composition comprising a vitamin D analogue and a corticosteroid

Patent metadata

Field	Value
Publication number	US-10660908-B2
Application number	US-201816135366-A
Country	US
Kind code	B2
Filing date	Sep 19, 2018
Priority date	Jun 11, 2010
Publication date	May 26, 2020
Grant date	May 26, 2020

Abstract

The present invention relates to a topical spray composition comprising a biologically active vitamin D derivative or analogue and a corticosteroid, and its use in the treatment of dermal diseases and conditions.

First claim

The invention claimed is:

1. A substantially anhydrous topical composition comprising
calcipotriol or calcipotriol monohydrate,
betamethasone dipropionate,
a pharmaceutically acceptable propellant, and
a pharmaceutically acceptable lipid carrier,
wherein the calcipotriol or calcipotriol monohydrate and the betamethasone dipropionate are dissolved in the pharmaceutically acceptable propellant,
wherein upon application of the composition to skin and evaporation of the pharmaceutically acceptable propellant, the pharmaceutically acceptable lipid carrier forms a semi-solid and occlusive layer at the site of application, and
wherein the composition does not include propylene glycol.

2. The composition of claim 1 , wherein the pharmaceutically acceptable propellant is present in an amount sufficient to completely dissolve the calcipotriol or calcipotriol monohydrate, and the betamethasone dipropionate.

3. The composition of claim 1 , wherein the content of free water in the composition does not exceed about 1% by weight of the composition.

4. The composition of claim 1 , wherein the calcipotriol or calcipotriol monohydrate is present in an amount of about 0.00001-0.05% w/w of the composition and the betamethasone dipropionate is present in an amount of about 0.0005-1% w/w of the composition.

5. The composition of claim 4 , wherein the calcipotriol or calcipotriol monohydrate is present in amount of about 0.002% w/w of the composition and the betamethasone dipropionate is present in an amount of about 0.02-0.03% w/w of the composition.

6. The composition of claim 1 , wherein no more than about 10% of the calcipotriol or calcipotriol monohydrate and no more than about 10% of the betamethasone dipropionate degrades during storage of the composition at 40° C. for at least two months.

7. The composition of claim 6 , wherein no more than about 10% of the calcipotriol or calcipotriol monohydrate and no more than about 10% of the betamethasone dipropionate degrades during storage of the composition at 40° C. for three months.

8. The composition of claim 1 wherein the calcipotriol or calcipotriol monohydrate, and the betamethasone dipropionate do not precipitate from the pharmaceutically acceptable propellant during storage of the composition for at least 12 months at 25° C.

9. The composition of claim 1 , wherein the pharmaceutically acceptable propellant comprises dimethyl ether, methylethyl ether, or both.

10. The composition of claim 1 , wherein the pharmaceutically acceptable propellant comprises dimethyl ether.

11. The composition of claim 1 , wherein the pharmaceutically acceptable lipid carrier comprises at least one hydrocarbon.

12. The composition of claim 1 , wherein the pharmaceutically acceptable lipid carrier comprises a paraffin.

13. The composition of claim 1 , wherein the pharmaceutically acceptable lipid carrier comprises a wax.

14. A substantially anhydrous topical composition comprising
calcipotriol or calcipotriol monohydrate,
betamethasone dipropionate,
a first pharmaceutically acceptable propellant and a second pharmaceutically acceptable propellant, and
a pharmaceutically acceptable lipid carrier,
wherein the calcipotriol or calcipotriol monohydrate and the betamethasone dipropionate are dissolved in the first propellant, or are dissolved in the first propellant and in the second propellant,
wherein upon application of the composition to skin and evaporation of the first propellant and the second propellant, the lipid carrier forms a semi-solid and occlusive layer at the site of application, and
wherein the composition does not include propylene glycol.

15. The composition of claim 14 , wherein the first pharmaceutically acceptable propellant comprises dimethyl ether and the calcipotriol or calcipotriol monohydrate, and the betamethasone dipropionate are dissolved in the dimethyl ether.

16. The composition of claim 14 , wherein the first pharmaceutically acceptable propellant comprises dimethyl ether and the calcipotriol or calcipotriol monohydrate, and the betamethasone dipropionate are dissolved in the mixture of dimethyl ether and the second propellant.

17. The composition of claim 14 , wherein the second propellant comprises a C 3-5 alkane, hydrofluoroalkane, hydrochloroalkane, fluoroalkane, or chlorofluoroalkane.

18. The composition of claim 17 , wherein the second propellant comprises a C 3-5 alkane.

19. The composition of claim 18 , wherein the C 3-5 alkane is propane, isopropane, n-butane, or isobutane.

20. The composition of claim 19 , wherein the C 3-5 alkane is n-butane.

21. The composition of claim 1 , wherein the pharmaceutically acceptable lipid carrier is solubilized or suspended in the pharmaceutically acceptable propellant.

22. The composition of claim 1 , wherein the pharmaceutically acceptable lipid carrier comprises white soft paraffin.

23. The composition of claim 1 wherein the pharmaceutically acceptable lipid carrier further comprises liquid paraffin.

24. The composition of claim 1 , wherein the composition further comprises an oily co-solvent.

25. The composition of claim 24 , wherein the oily co-solvent comprises one or more of:
(a) a compound of general formula I: H(OCH 2 C(CH 3 )H) x OR 1 wherein R 1 is a straight or branched chain C 1-20 alkyl, and x is an integer from 2 to 60 inclusive;
(b) an isopropyl ester of a straight or branched chain C 10-18 alkanoic or alkenoic acid;
(c) a propylene glycol diester of a C 8-14 alkanoic or alkenoic acid;
(d) a straight or branched C 8-24 alkanol or alkenol;
(e) a highly purified vegetable oil; or
(f) an N-alkylpyrrolidone or N-alkylpiperidone.

26. The composition of claim 25 , wherein the compound of general formula I is polyoxypropylene-15-stearyl ether, polyoxypropylene-11-stearyl ether, polyoxypropylene-14-butyl ether, polyoxypropylene-10-cetyl ether, or polyoxypropylene-3-myristyl ether.

27. The composition of claim 25 , wherein the isopropyl ester of a straight or branched chain C 10-18 alkanoic or alkenoic acid is isopropyl myristate, isopropyl palmitate, isopropyl isostearate, isopropyl linolate, or isopropyl monooleate.

28. The composition of claim 25 , wherein the propylene glycol diester of a C 8-14 alkanoic acid is propylene glycol dipelargonate.

29. The composition of claim 25 , wherein: the straight C 8-24 alkanol is capryl alcohol, lauryl alcohol, cetyl alcohol, stearyl alcohol, or myristyl alcohol; the straight C 8-24 alkenol is oleyl alcohol or linoleyl alcohol; or the branched C 8-24 alkanol is a branched C 18-24 alkanol.

30. The composition of claim 29 , wherein the straight C 8-24 alkanol is myristyl alcohol, or the straight C 8-24 alkenol is oleyl alcohol.

31. The composition of claim 25 , wherein the N-alkylpyrrolidone is N-methylpyrrolidone.

32. The composition of claim 25 , wherein the highly purified vegetable oil comprises medium chain triglycerides.

33. The composition of claim 25 , wherein the oily co-solvent comprises polyoxypropylene-11-stearyl ether.

34. The composition of claim 1 , wherein the pharmaceutically acceptable propellant comprises dimethyl ether and wherein the pharmaceutically acceptable lipid carrier comprises white soft paraffin and liquid paraffin, wherein the calcipotriol

Assignees

• Leo Pharma As

Inventors

• Lind Marianne
• Rasmussen Gritt
• Sonne Mette Rydahl
• Hansen Jens
• Petersson Karsten

Classifications

• A61K9/0014

  Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00) · CPC title

• A61K31/59

  Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems · CPC title

• A61K9/122

  Foams; Dry foams (edible foams A61K9/0056) · CPC title

• A61K31/593 Primary

  9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3 · CPC title

• A61K47/14

  Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters · CPC title