Pharmaceutical spray composition comprising a vitamind D analogue and a corticosteroid

• US 10,682,364 B2
• Filed: 08/28/2019
• Issued: 06/16/2020
• Est. Priority Date: 06/11/2010
• Status: Active Grant

• Current Assignee: Leo Pharma A/S (10 Pharmaceuticals) (Leo Fondet)
• Original Assignee: Leo Pharma A/S (10 Pharmaceuticals) (Leo Fondet)
• Inventors: Lind, Marianne, Rasmussen, Gritt, Sonne, Mette Rydahl, Hansen, Jens, Petersson, Karsten
• Primary Examiner(s): Stevens, Mark V
• Application Number:
  US16/554,603
• Publication Number:
  US 20200009160A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 31/593 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
• CPC Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• CPC Class Codes: A61K 47/08 containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 9/0014 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 Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61K 9/124 characterised by the propellant
• CPC Class Codes: A61M 11/00 Sprayers or atomisers specially adapted for therapeutic purposes in general B05B; aerosol containers B65D83/14
• CPC Class Codes: A61M 2210/04 Skin
• CPC Class Codes: A61M 35/003 Portable hand-held applicators having means for dispensing or spreading integral media hand-held massage devices with liquid delivery A61H7/003
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/08 Antiseborrheics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: B65D 83/207 : 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 portable spraying apparatus comprising pressurised supply containers B05B7/2402, B05B9/0805; manually actuated controlling means for spraying apparatus B05B12/002; actuators connected to the aerosol container by a flexible tube B65D83/756
• CPC Class Codes: B65D 83/752 : characterised by the use of specific products or propellants

Abstract

A Pharmaceutical Spray Composition Comprising a Vitamin D Analogue and a Corticosteroid

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.

Claims

1. 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 composition of claim 1, wherein no more than 6% by weight of the calcipotriol or calcipotriol monohydrate has degraded after storage of the composition for 3 months at about 40°

C.

3. The composition 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.

4. The composition of claim 3, wherein the composition further comprises a pharmaceutically acceptable lipophilic viscosity increasing ingredient.

5. The composition of claim 1, wherein the pharmaceutically acceptable propellant comprises a C_3-5 alkane.

6. The composition of claim 5, wherein the C_3-5 alkane is propane, isopropane, n-butane, isobutane, or mixtures thereof.

7. The composition of claim 6, wherein the C_3-5 alkane is n-butane.

8. The composition of claim 3, wherein the pharmaceutically acceptable propellant comprises dimethyl ether.

9. The composition of claim 1, wherein the pharmaceutically acceptable lipid carrier comprises petrolatum.

10. The composition of claim 9, wherein the composition further comprises a pharmaceutically acceptable oily cosolvent.

11. The composition 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, and wherein the pharmaceutically acceptable lipid carrier comprises petrolatum, and wherein the composition further comprises a pharmaceutically acceptable oily cosolvent.

12. The composition of claim 10, wherein the oily co-solvent comprises a compound of general formula I:

H(OCH₂C(CH₃)H)_xOR¹ wherein R¹ is a straight or branched chain C_1-20 alkyl, and x is an integer from 2 to 60 inclusive.

13. The composition of claim 12, 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.

14. The composition of claim 10, wherein the oily co-solvent comprises an isopropyl ester of a straight or branched chain C_10-18 alkanoic or alkenoic acid.

15. The composition of claim 14, 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.

16. The composition of claim 10, wherein the oily co-solvent comprises a straight or branched C_8-24 alkanol or alkenol.

17. The composition of claim 16, wherein (i) the straight C_8-24 alkanol is capryl alcohol, lauryl alcohol, cetyl alcohol, stearyl alcohol, or myristyl alcohol, (ii) the straight C_8-24 alkenol is oleyl alcohol or linoleyl alcohol, and/or (iii) the branched C_8-24 alkanol is a branched C_18-24 alkanol.

18. The composition of claim 17, wherein the straight C_8-24 alkanol is myristyl alcohol.

19. The composition of claim 9, wherein

(a) the calcipotriol or calcipotriol monohydrate is present in an amount between 0.001-0.05% w/w of the total composition,

(b) the betamethasone dipropionate is present in an amount between 0.0005-1% w/w of the total composition, and

(c) a pharmaceutically acceptable oily co-solvent, which is present in an amount between 0.1-10% w/w of the total composition.

20. The composition of claim 19, wherein the composition comprises calcipotriol, wherein

(a) the calcipotriol is present in an amount of 0.005% w/w of the composition, excluding any mass contributed by any pharmaceutically acceptable propellant , and

(b) 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.

21. The composition of claim 19, wherein the composition comprises calcipotriol monohydrate, wherein

(a) 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, and

(b) 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.

22. The composition of claim 21 wherein the pharmaceutically acceptable oily co-solvent is myristyl alcohol.

23. The composition of claim 3, wherein the pharmaceutically acceptable propellant comprises dimethyl ether;

the pharmaceutically acceptable lipid carrier is a mixture of liquid paraffin and petrolatum.

24. The composition of claim 23, further comprising a pharmaceutically acceptable oily co-solvent.

25. The composition of claim 9, wherein the petrolatum is white soft paraffin.

26. The composition of claim 11, wherein the petrolatum is white soft paraffin.

27. The composition of claim 23, wherein the petrolatum is white soft paraffin.