Pharmaceutical spray composition comprising a vitamin D analogue and a corticosteroid

Patent metadata

Field	Value
Publication number	US-10688108-B2
Application number	US-201916554539-A
Country	US
Kind code	B2
Filing date	Aug 28, 2019
Priority date	Jun 11, 2010
Publication date	Jun 23, 2020
Grant date	Jun 23, 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 method of treating psoriasis, comprising administering to a patient a therapeutically effective amount of a sprayable, substantially anhydrous topical composition comprising
calcipotriol or calcipotriol monohydrate,
betamethasone dipropionate,
a pharmaceutically acceptable propellant, present in amount between 45-95% w/w of the total composition,
a pharmaceutically acceptable lipid carrier, present in an amount between 5-55% w/w of the total composition, and
a pharmaceutically acceptable antioxidant,
wherein the composition does not include propylene glycol, and
wherein no more than 10% by weight of the calcipotriol or calcipotriol monohydrate has degraded after storage of the composition for 3 months at about 40° C.

2. The method of treatment of claim 1 , wherein the composition comprises calcipotriol monohydrate, and
the pharmaceutically acceptable lipid carrier comprises petrolatum,
the calcipotriol monohydrate is present in an amount of 0.00522% w/w of the composition, excluding any mass contributed by any pharmaceutically acceptable propellant,
the betamethasone dipropionate is present in an amount of 0.064% w/w of the composition, excluding any mass contributed by any pharmaceutically acceptable propellant, and
the composition further comprises a pharmaceutically acceptable oily co-solvent, which is present in an amount between 0.1-10% w/w of the total composition.

3. The method of treatment of claim 1 , wherein each gram of the composition, excluding any mass contributed by any pharmaceutically acceptable propellant, comprises 52.2 mcg of calcipotriol monohydrate and 0.643 mg betamethasone dipropionate, wherein the pharmaceutically acceptable lipid carrier comprises petrolatum, and wherein the composition further comprises a pharmaceutically acceptable oily co-solvent.

4. The method of treatment of claim 3 wherein the pharmaceutically acceptable oily co-solvent is myristyl alcohol.

5. The method of treatment of claim 3 , wherein no more than 6% by weight of the calcipotriol monohydrate has degraded after storage of the composition for 3 months at about 40° C.

6. The method of claim 1 , wherein the pharmaceutically acceptable propellant comprises dimethyl ether; and the pharmaceutically acceptable lipid carrier is a mixture of liquid paraffin and petrolatum.

7. The method of claim 3 , wherein the pharmaceutically acceptable propellant comprises dimethyl ether; the pharmaceutically acceptable lipid carrier is a mixture of liquid paraffin and petrolatum.

8. A method of treating psoriasis, comprising administering to a patient a therapeutically effective amount of a sprayable, substantially anhydrous topical composition comprising
calcipotriol or calcipotriol monohydrate,
betamethasone dipropionate,
a pharmaceutically acceptable propellant, present in amount between 45-95% w/w of the total composition,
a pharmaceutically acceptable lipid carrier, present in an amount between 5-55% w/w of the total composition, and
a pharmaceutically acceptable antioxidant,
wherein the composition does not include propylene glycol, and
wherein visible crystals of the calcipotriol or calcipotriol monohydrate or the betamethasone dipropionate are not observed, as determined by polarized light microscopy, after storage of the composition for 12 months at about 25° C.

9. The method of treatment of claim 8 , wherein the composition comprises calcipotriol monohydrate, and
the pharmaceutically acceptable lipid carrier comprises petrolatum,
the calcipotriol monohydrate is present in an amount of 0.00522% w/w of the total composition, excluding any mass contributed by any pharmaceutically acceptable propellant,
the betamethasone dipropionate is present in an amount of 0.064% w/w of the total composition, excluding any mass contributed by any pharmaceutically acceptable propellant, and
the composition further comprises a pharmaceutically acceptable oily co-solvent, which is present in an amount between 0.1-10% w/w of the total composition.

10. The method of treatment of claim 8 , wherein each gram of the composition, excluding any mass contributed by any pharmaceutically acceptable propellant, comprises 52.2 mcg of calcipotriol monohydrate and 0.643 mg betamethasone dipropionate, wherein the pharmaceutically acceptable lipid carrier comprises petrolatum, and wherein the composition further comprises a pharmaceutically acceptable oily co-solvent.

11. The method of treatment of claim 10 wherein the pharmaceutically acceptable oily co-solvent is myristyl alcohol.

12. The method of treatment of claim 10 , wherein the pharmaceutically acceptable propellant comprises dimethyl ether; the pharmaceutically acceptable lipid carrier is a mixture of liquid paraffin and petrolatum.

13. A method of treating psoriasis, comprising administering to a patient a therapeutically effective amount of a sprayable, substantially anhydrous topical composition comprising
calcipotriol or calcipotriol monohydrate,
betamethasone dipropionate,
a pharmaceutically acceptable propellant, present in amount between 45-95% w/w of the total composition,
a pharmaceutically acceptable lipid carrier, present in an amount between 5-55% w/w of the total composition, and
a pharmaceutically acceptable antioxidant,
wherein the composition does not include propylene glycol, and
wherein said composition results in increased skin permeation of calcipotriol, as measured by the percent of applied dose of calcipotriol that reaches the receptor fluid of a Franz cell using full thickness pig ear skin after 21 hours of exposure, compared to an ointment lacking a propellant and comprising 0.005% w/w calcipotriol as monohydrate, 0.05% w/w betamethasone as betamethasone dipropionate, 0.002% w/w alpha-tocopherol, 5% w/w polyoxypropylene-11-stearyl ether, 3% w/w liquid paraffin, and white soft paraffin up to 100% w/w.

14. The method of treatment of claim 13 , wherein the composition comprises calcipotriol monohydrate, and
the pharmaceutically acceptable lipid carrier comprises petrolatum,
the calcipotriol monohydrate is present in an amount of 0.00522% w/w of the total composition, excluding any mass contributed by any pharmaceutically acceptable propellant,
the betamethasone dipropionate is present in an amount of 0.064% w/w of the composition excluding any mass contributed by any pharmaceutically acceptable propellant, and
the composition further comprises a pharmaceutically acceptable oily co-solvent, which is present in an amount between 0.1-10% w/w of the total composition.

15. The method of treatment of claim 13 , wherein each gram of the composition, excluding any mass contributed by any pharmaceutically acceptable propellant, comprises 52.2 mcg of calcipotriol monohydrate and 0.643 mg betamethasone dipropionate, wherein the pharmaceutically acceptable lipid carrier comprises petrolatum, and wherein the composition further comprises a pharmaceutically acceptable oily co-solvent.

16. The method of treatment of claim 15 , wherein the pharmaceutically acceptable oily co-solvent is myristyl alcohol.

17. The method of treatment of claim 14 , wherein said increased skin permeation of calcipotriol is at least about 2-fold.

18. The method of treatment of claim 14 , wherein said composition results in increased skin penetration of betamethasone diproprionate compared to the ointment, as measured by an increase in the percent of applied dose of betamethasone dipropionate in the dermis and epidermis after 21 hours of exposure using a Franz cell using full thickness pig

Assignees

• Leo Pharma As

Inventors

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

Classifications

• B65D83/164

  Actuators comprising a manually operated valve and being attachable to the aerosol container, e.g. downstream a valve fitted to the container; Actuators associated to container valves with valve seats located outside the aerosol container · CPC title

• B65D83/141

  specially adapted for specific contents or propellants · CPC title

• A61K31/593 Primary

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

• A61K9/12 Primary

  Aerosols; Foams {(A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015)} · CPC title

• A61K47/06

  Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite · CPC title