Penetrating pharmaceutical foam

• US 8,435,498 B2
• Filed: 04/01/2010
• Issued: 05/07/2013
• Est. Priority Date: 10/25/2002
• Status: Expired due to Term

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Tamarkin, Dov, Friedman, Doron, Eini, Meir
• Primary Examiner(s): FISHER, ABIGAIL L
• Application Number:
  US12/752,718
• Publication Number:
  US 20100284938A1
• Time in Patent Office: 1,132 Days
• Field of Search: 424/47, 424/43, 424/401, 514/945, 514/588, 514/557
• US Class Current: 424/47
• 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 method of skin or mucosal surface application comprising spreading or collapsing a breakable thermally stable foam by mechanical force at or about a target site of a subject, the breakable thermally stable foam obtained by dispensing a foamable emulsion composition comprising

(i) about 0.1 to about 5% by weight of a surface-active agent;

(ii) about 5 to about 50% by weight of a liquid, non-volatile hydrophobic solvent;

(iii) about 0.1 to about 5% by weight of a gelling agent; and

(iv) a component selected from the group consisting of urea, a hydroxy acid, a therapeutic enhancer, and mixtures of two or more thereof;

(v) water; and

(vi) a liquefied or a compressed gas propellant;

wherein the foamable emulsion composition contains no more than 7.5% by weight methyl alcohol, ethyl alcohol, isopropyl alcohol, butyl alcohol, or mixtures thereof.

2. The method of claim 1, wherein the foam has a specific gravity of between about 0.01 g/mL and about 0.1 g/mL.

3. The method of claim 1, wherein the surface-active agent has an HLB in the range of about 9 to 14.

4. The method of claim 1, wherein the surface-active agent is a non-ionic surfactant.

5. The method of claim 1, wherein the gelling agent comprises an amphiphilic copolymer.

6. The method of claim 1, wherein the component consists of about 1% to about 50% by weight of urea.

7. The method of claim 1, wherein the component consists of about 10% to about 20% by weight of urea.

8. The method of claim 1, wherein the component consists of about 20% to about 50% by weight of urea.

9. The method of claim 1, wherein the component consists of about 1% to about 30% by weight of at least one hydroxy acid.

10. The method of claim 1, wherein the component consists of about 1% to about 10% by weight of at least one hydroxy acid.

11. The method of claim 1, wherein the component consists of a combination of about 1% to about 50% by weight of urea and about 1% to about 30% by weight of at least one hydroxy acid.

12. The method of claim 1, wherein the component consists of at about 1% to about 30% by weight of at least one therapeutic enhancer selected from the group consisting of propylene glycol, butylene glycols, glycerol, pentaerythritol, sorbitol, mannitol, oligosaccharides, dimethyl isosorbide, monooleate of ethoxylated glycerides (with 8 to 10 ethylene oxide units), polyethylene glycol 200-600, transcutol (diethylene glycol monoethyl ether), glycofurol (tetrahydrofurfuryl alcohol), PEG ether, and a cyclodextrin.

13. The method of claim 1, wherein the component comprises at least one humectant or moisture-retaining agent.

14. The method of claim 1, wherein the composition further comprises a foam adjuvant.

15. The method of claim 1, wherein the composition further comprises a therapeutically effective concentration of at least one active agent.

16. The method of claim 15, wherein the active agent is at least one agent 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, anti-histamine, a nonsteroidal anti-inflammatory agent, an immonumodulating agent, an immunosuppressant, an anti-allergic agent, a local anesthetic agent, a keratolytically active agent, a retinoid, an insecticide, an insect repellent, an anti-cancer drug, a photodynamic therapy agent, an active agents 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, a humectant, a moisture-retaining agent, a hydroxy acid, and an agent for treating cellulite.

17. The method of claim 1, wherein the ratio between the surface active agent and the hydrophobic solvent is between about 1:

8 and about 1;

16.

18. The method of claim 1, wherein the ratio between the surface active agent and the hydrophobic solvent is between about 1:

16 and about 1;

32.

19. The method of claim 1, wherein the emulsion is an oil in water emulsion.

20. The method of claim 6, wherein the skin or mucosal surface application is for ameliorating a skin or mucosal disorder selected from the group consisting of one or more of pain, wounds, burns, cuts, ulcers, ear channel disorders, vaginal disorders, rectal disorders, penile disorders, and urethra disorders.

21. The method of claim 9, wherein the skin or mucosal surface application is for ameliorating a skin or mucosal disorder selected from the group consisting of one or more of pain, wounds, burns, cuts, ulcers, ear channel disorders, vaginal disorders, rectal disorders, penile disorders, and urethra disorders.

22. The method of claim 15, wherein the skin or mucosal application is for ameliorating a disorder that is known to be responsive to the at least one active agent, wherein the disorder is selected from the group consisting of contact dermatitis, atopic dermatitis, seborrheic dermatitis, nummular dermatitis, chronic dermatitis of the hands or feet, generalized exfoliative dermatitis, stasis dermatitis, diaper rash, bacterial infections, cellulitis, fungal infections, parasitic infections, scabies, pediculosis, viral infections, disorders of hair follicles, disorders of sebaceous glands, acne, rosacea, perioral dermatitis, psoriasis, basal cell carcinoma, squamous cell carcinoma, melanoma reactions to sunlight, sunburn, photosensitivity, bullous diseases, vitiligo, hyperpigmentation, ichthyosis, actinic keratosis, pressure sores, disorders of sweating, non-dermatological disorders which respond to topical or transdermal delivery of an active agent, localized pain, joint pain, muscle pain, back pain, ostheoarthritis, conditions which respond to hormone therapy, pelvic pain, vulvovaginal infections, bacterial vaginosis, candidal vaginitis, trichomonas vaginalis, herpes simplex, genital ulcers, genital warts, sexually transmitted diseases, sexual dysfunction disorders that respond to pharmacological topical therapy, erectile dysfunction, anal fistula, anal warts, haemorrhoids, and anal fissures.

24. The method of claim 15, wherein the skin or mucosal surface application is for ameliorating a disorder selected from the group consisting of one or more of pain, wounds, burns, cuts, ulcers, ear channel disorders, vaginal disorders, rectal disorders, penile disorders, and urethra disorders.

23. A method of skin or mucosal surface application comprising spreading or collapsing a breakable thermally stable foam by mechanical force at or about a target site of a subject, the breakable thermally stable foam obtained by dispensing a foamable emulsion composition comprising:

about 0.1 to about 5% by weight of a surface-active agent, wherein the surface active agent comprises one or more of a polysorbate, a polyoxyethylene fatty acid ester, a poly(oxyethylene) alkyl ether, a sucrose ester, a partial ester of sorbitol, a sorbitol anhydride, isoceteth-20, 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, and polyoxyethylene 40 stearate;

(ii) about 0.1 to about 5% by weight of a gelling agent;

(iii) a therapeutic enhancer and a component selected from the group consisting of urea, hydroxyl acid, an active agent, and combinations of two or more thereof;

(iv) water; and

(v) a liquefied or a compressed gas propellant;

wherein the composition contains no more than 7.5% by weight methyl alcohol, ethyl alcohol, isopropyl alcohol, butyl alcohol, or mixtures thereof.