Penetrating pharmaceutical foam

• US 9,492,412 B2
• Filed: 04/22/2014
• Issued: 11/15/2016
• Est. Priority Date: 10/25/2002
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Pharmaceuticals, Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Tamarkin, Dov, Friedman, Doron, Eini, Meir
• Primary Examiner(s): FISHER, ABIGAIL L
• Application Number:
  US14/258,700
• Publication Number:
  US 20140227199A1
• Time in Patent Office: 938 Days
• US Class Current: 1/1
• CPC Class Codes: A01N 25/16 Foams
• CPC Class Codes: A01N 53/00 Biocides, pest repellants or attractants, or plant growth regulators containing cyclopropane carboxylic acids or derivatives thereof
• CPC Class Codes: A61K 2800/75 Anti-irritant
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/17 having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine isoureas, isothioureas A61K31/155; sulfonylureas A61K31/64
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61K 45/00 Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 8/046 : Aerosols; Foams
• CPC Class Codes: A61K 8/06 : Emulsions
• CPC Class Codes: A61K 8/062 : Oil-in-water emulsions
• CPC Class Codes: A61K 8/31 : Hydrocarbons
• CPC Class Codes: A61K 8/365 : Hydroxycarboxylic acids; Ketocarboxylic acids
• CPC Class Codes: A61K 8/42 : Amides
• 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 9/107 : Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61K 9/12 : Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• 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: A61P 15/00 : Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/02 : for disorders of the vagina
• CPC Class Codes: A61P 17/00 : Drugs for dermatological disorders
• CPC Class Codes: A61P 17/10 : Anti-acne agents
• CPC Class Codes: A61P 17/18 : Antioxidants, e.g. antiradicals preparations for protection against sunlight A61Q17/00
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61Q 17/02 : containing insect repellants
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin
• CPC Class Codes: A61Q 19/08 : Anti-ageing preparations
• CPC Class Codes: A61Q 19/10 : Washing or bathing preparations

Abstract

The invention relates to an alcohol-free cosmetic or pharmaceutical foam composition comprising water, a hydrophobic solvent, a surface-active agent, a gelling agent, an active component selected from the group of urea, hydroxy acid and a therapeutic enhancer and a propellant. The foam further comprises active agents and excipients with therapeutic properties having enhanced skin penetration.

Claims

1. A foamable composition comprising a carrier and a liquefied or a compressed gas propellant, the carrier comprising:

i) a surface-active agent, wherein the surface-active agent is a non-ionic surface-active agent, an ionic surface-active agent, or mixtures thereof, wherein the surface-active agent is selected from the group consisting of a polysorbate, a polyoxyethylene fatty acid ester, a polyoxyethylene alkyl ether, a sucrose ester, a partial ester of sorbitol, a partial ester of sorbitol anhydride, sodium methyl cocoyl taurate, sodium methyl oleoyl taurate, sodium lauryl sulfate, triethanolamine lauryl sulfate, a betaine, a mono-, di- or tri-ester of sucrose with food fatty acids (sucrose esters), a monoglyceride, a diglyceride, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan monooleate, polyoxyethylene (8) stearate, polyoxyethylene (20) stearate, polyoxyethylene (100) stearate, a polyoxyethylene cetyl ether, a polyoxyethylene palmityl ether, a polyethylene oxide hexadecyl ether, polyoxyethylene (2) cetyl ether, polyoxyethylene (10) cetyl ether, sorbitan monolaurate, isoceteth-20, cocamidopropyl betaine, polyoxyethylene (40) stearate, and mixtures of any two or more thereof;

ii) about 2% to about 75% by weight of the carrier of a liquid, non-volatile hydrophobic solvent, wherein the hydrophobic solvent is a mixture of octyldodecanol and isopropyl myristate;

iii) a foam adjuvant; and

iv) water;

wherein a breakable foam forms upon dispensing of the foamable composition.

2. The foamable composition of claim 1, wherein the carrier further comprises a therapeutically effective amount of at least one active agent.

3. The foamable composition of claim 2, wherein the active agent is selected from the group consisting of an antibacterial agent, an anti-fungal agent, an anti-viral agent, an anti-inflammatory agent, a steroid, a corticosteroid, an anti-histamine, a nonsteroidal anti-inflammatory agent, an immunomodulating agent, an immunosuppressant, an anti-allergic agent, a local anesthetic agent, a retinoid, an insecticide, an insect repellent, an anti-cancer drug, a photodynamic therapy agent, an active agent for burns, wounds, cuts and ulcers, an anti-acne active agent, an anti-wrinkle active agent, an anti-atrophy active agent, an anti-oxidant, a radical scavenger, a self-tanning active agent, a skin lightening or whitening agent, an agent suitable for the treatment of a hair growth disorder, an agent for treating cellulite, and mixtures of any two or more thereof.

4. The foamable composition of claim 1, wherein the liquefied or compressed gas propellant is at a concentration of about 3% to about 18% by weight of the carrier.

5. The foamable composition of claim 1, wherein the surface-active agent is a mixture of the non-ionic surface-active agent and the ionic surface-active agent.

6. The foamable composition of claim 5, wherein the ratio of the non-ionic surface-active agent to the ionic surface-active agent is between 1:

1to 20;

1.

7. The foamable composition of claim 1, wherein the surface-active agent is a non-ionic surface-active agent.

8. The foamable composition of claim 1, wherein the surface-active agent is present at about 0.3% to about 6.25% by weight of the carrier.

9. The foamable composition of claim 1, wherein the carrier is an oil-in-water emulsion.

10. The foamable composition of claim 1, wherein the carrier further comprises a preservative, a pH adjusting agent, or a mixture thereof.

11. The foamable composition of claim 1, wherein the carrier further comprises about 2% to about 30% by weight of the carrier of a therapeutic enhancer.

12. The foamable composition of claim 11, wherein the therapeutic enhancer is selected from the group consisting of a polyhydric alcohol, propylene glycol, butylene glycol, glycerol, pentaerythritol, sorbitol, mannitol, an oligosaccharide, dimethyl isosorbide, monooleate of ethoxylated glycerides with 8 to 10 ethylene oxide units, a polyethylene glycol 200-600, diethylene glycol monoethyl ether, glycofurol, a cyclodextrin, and mixtures of any two or more thereof.

13. The foamable composition of claim 12, wherein therapeutic enhancer is contained in the foamable composition in an amount from about 2% to about 10% by weight of the carrier.

14. The foamable composition of claim 1, wherein the breakable foam has a specific gravity of between about 0.01 and about 0.1.

15. The foamable composition of claim 1, wherein the carrier further comprises a gelling agent at a concentration of less than 1% by weight of the carrier.

16. The foamable composition of claim 15, wherein the gelling agent is a carbomer, a hypromellose, or mixtures thereof.

17. The foamable composition of claim 15, wherein the ratio between the foam adjuvant and the hydrophobic solvent is selected from a group consisting of about 1:

12, about 1;

24, about 1;

44, about 1;

60, about 1;

25, and about 1;

220.

18. The foamable composition of claim 1, wherein the hydrophobic solvent is included at a concentration of 5% to about 10% or 10% to about 20% by weight of the carrier.

19. The foamable composition of claim 1, wherein the ratio between the surface-active agent and the hydrophobic solvent is between about 1:

8 and about 1;

16 or is between about 1;

16 and about 1;

32.

20. The foamable composition of claim 1, wherein the surface-active agent is about 0.1% to about 5% by weight of the carrier.

21. The foamable composition of claim 1, wherein the ratio between the surface-active agent and the hydrophobic solvent is selected from a group consisting of about 3:

8, about 2;

7, about 2;

5, about 2;

13, about 1;

5, about 1;

6, about 1;

8, about 1;

16, about 1;

32, about 1;

36, between about 1;

8 and about 1;

16, and between about 1;

16, about 1;

32.

22. The foamable composition of claim 1, wherein the ratio between the gelling agent and the hydrophobic solvent is selected from a group consisting of about 1:

10, about 1;

16 about 2;

15, about 1;

24, about 1;

20, about 1;

55, about 1;

41, and about 1;

50.

23. The foamable composition of claim 1, wherein the ratio between the gelling agent and the surface-active agent is selected from a group consisting of about 1:

3, about 3;

10, about 1;

7, about 3;

28, about 1;

10, about 1;

5, about 1;

8, and about 2;

1.

24. The foamable composition of claim 1, further comprising a gelling agent.

25. The foamable composition of claim 24, wherein the carrier further comprises a therapeutically effective amount of at least one active agent.

26. The foamable composition of claim 25, wherein the active agent is selected from the group consisting of an anti-fungal agent, an anti-viral agent, a steroid, a corticosteroid, an anti-histamine, an immunomodulating agent, an immunosuppressant, an anti-allergic agent, a local anesthetic agent, an insecticide, an insect repellent, an anti-cancer drug, a photodynamic therapy agent, an active agent for burns, wounds, cuts and ulcers, an anti-wrinkle active agent, an anti-atrophy active agent, an anti-oxidant, a radical scavenger, a self-tanning active agent, a skin lightening or whitening agent, an agent suitable for the treatment of a hair growth disorder, an agent for treating cellulite, and mixtures of any two or more thereof.