Wax foamable vehicle and pharmaceutical compositions thereof

• US 9,662,298 B2
• Filed: 01/22/2014
• Issued: 05/30/2017
• Est. Priority Date: 08/07/2007
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Pharmaceuticals, Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Keynan, Rita, Schuz, David, Tamarkin, Dov, Berman, Tal
• Primary Examiner(s): FALKOWITZ, ANNA R
• Application Number:
  US14/161,134
• Publication Number:
  US 20140271494A1
• Time in Patent Office: 1,224 Days
• Field of Search: 424400, 424 45, 424401, 424 47
• 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 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• 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 8/31 Hydrocarbons
• CPC Class Codes: A61K 8/342 Alcohols having more than seven atoms in an unbroken chain
• CPC Class Codes: A61K 8/361 Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
• CPC Class Codes: A61K 8/4993 Derivatives containing from 2 to 10 oxyalkylene groups
• CPC Class Codes: A61K 8/86 Polyethers
• CPC Class Codes: A61K 9/0031 Rectum, anus
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/0046 Ear
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• 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 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin
• CPC Class Codes: A61Q 19/02 : for chemically bleaching or whitening the skin
• CPC Class Codes: A61Q 19/08 : Anti-ageing preparations
• CPC Class Codes: A61Q 5/006 : Antidandruff preparations
• CPC Class Codes: A61Q 7/00 : Preparations for affecting hair growth

Abstract

Unique foamable vehicles or carriers comprising at least one wax, waxy substance, counterpart or derivative, a stabilizer, water, and a propellant are provided. In some embodiments, the wax is a liquid wax. In some embodiments, the wax includes a solid wax and a liquid wax. The compositions are substantially free of crystals. The components are selected to provide a composition that is substantially resistant to aging and to phase separation, and/or can substantially solubilize and or stabilize active ingredients. Pharmaceutical and cosmetic compositions with potentially enhanced skin delivery and their uses are also provided.

Claims

1. A foamable composition for a pharmaceutical comprising:

A. a carrier comprising;

a. at least about 20% by weight of a liquid wax comprising one or more free fatty acids, wherein at least one free fatty acid is oleic acid and wherein the oleic acid is at least about 20% by weight of the carrier;

b. a surface-active agent;

c. a polymeric agent; and

d. a solid wax comprising a solid paraffin wax;

wherein the ratio of liquid wax to solid wax is about 3;

1 to about 10;

1, and

B. a liquefied hydrocarbon gas propellant at a concentration of about 3% to about 35% by weight of the foamable composition;

wherein the composition has a water content less than about 5% by weight;

wherein the composition is not an emulsion; and

wherein, upon release from a pressurized container, a breakable foam is produced.

2. The foamable composition of claim 1, wherein the solid wax further comprises a solid wax selected from the group consisting of a fatty acid, a fatty alcohol, a microcrystalline wax, a petroleum wax, a polyethylene wax, a beeswax, a candelilla wax, a castor wax, a Chinese wax, a Fischer-Tropsch wax, a rice bran wax, a tallow, a wool wax, and a mixture of any two or more thereof.

3. The foamable composition of claim 2, wherein the solid wax further comprises a solid wax selected from the group consisting of stearic acid, cetyl alcohol, behenyl alcohol, stearyl alcohol, and a mixture of any two or more thereof.

4. The foamable composition of claim 1, wherein the liquid wax enables the solid wax to solubilize.

5. The foamable composition of claim 1, wherein solid wax crystals are not visible and the composition is flowable through an aerosol valve.

6. The foamable composition of claim 1, wherein the polymeric agent is present in the composition at a concentration of about 0.01% to about 5% by weight of the carrier and is selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent, and a phase change agent.

7. The foamable composition of claim 1, wherein the surface-active agent is selected from the group consisting of a polysorbate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan monooleate, a polyoxyethylene fatty acid ester, polyoxyethylene (8) stearate, polyoxyethylene (20) stearate, polyoxyethylene (40) stearate, polyoxyethylene (100) stearate, a polyoxyethylene alkyl ether, a polyoxyethylene cetyl ether, polyoxyethylene (23) cetyl ether, polyoxyethylene (2) cetyl ether, polyoxyethylene (10) cetyl ether, a sucrose ester, a partial ester of sorbitol, sorbitan monolaurate, a monoglyceride, a diglyceride, isoceteth-20, steareth 2, glyceryl stearate, steareth-21, sorbitan stearate, laureth 4, sorbitan monooleate, ceteareth 20, steareth 20, ceteth 20, macrogol cetostearyl ether, PEG-30 dipolyhydroxystearate, sucrose distearate, cetomacrogol ether, cetearyl glucoside, polysorbate 20;

methyl glucose sesquistearate, a sucrose stearic acid ester, a phospholipid, and a mixture of any two or more thereof.

8. The foamable composition of claim 7, wherein the surface-active agent is selected from the group consisting of sorbitan stearate, glyceryl monostearate, and a mixture thereof.

9. The foamable composition of claim 1, wherein the surface active agent also functions as a solvent.

10. The foamable composition of claim 1, wherein the polymeric agent is selected from the group consisting of a cross-linked polyacrylate polymer, acrylates/C10-30 alkyl acrylate crosspolymers, a locust bean gum, sodium alginate, sodium caseinate, an egg albumin, a gelatin agar, a carrageenin gum, a xanthan gum, a quince seed extract, a tragacanth gum, a guar gum, a cationic guar, a hydroxypropyl guar gum, a starch, an amine-bearing polymer, a chitosan, an alginic acid, a hyaluronic acid, a chemically modified starch, a carboxyvinyl polymer, a polyvinylpyrrolidone, a polyvinyl alcohol, a polyacrylic acid polymer, a polymethacrylic acid polymer, a polyvinyl acetate, a polyvinyl chloride polymer, a polyvinylidene chloride polymer, a methylcellulose, a hydroxypropyl cellulose, a hydroxypropyl methylcellulose, a hydroxyethyl cellulose, a methylhydroxyethylcellulose, a carboxymethylcellulose, a hydroxyethylcarboxymethylcellulose, a cationic cellulose, an aluminum starch octenylsuccinate, a sodium starch octenylsuccinate, and a mixture of any two or more thereof.

11. The foamable composition of claim 1, wherein the composition further comprises a solvent selected from the group consisting of an organic carrier, a hydrophilic solvent, a hydrophobic solvent, a potent solvent, a polar solvent, a silicone, an emollient, and a mixture thereof.

12. The foamable composition of claim 11, wherein the solvent comprises dimethyl sulfoxide.

13. The foamable composition of claim 11, wherein the solvent comprises a polyethylene glycol.

14. The foamable composition of claim 1, wherein the surface active agent is between about 0.2% to about 8% by weight.

15. The foamable composition of claim 1, further comprising an additional component selected from the group consisting of a modulating agent, a polar solvent, an anti perspirant, an anti-static agent, a buffering agent, a bulking agent, a chelating agent, a colorant, a conditioner, a deodorant, a diluent, a dye, an emollient, fragrance, a humectant, an occlusive agent, a penetration enhancer, a perfuming agent, a permeation enhancer, a pH-adjusting agent, a preservative, a skin penetration enhancer, a sunscreen, a sun blocking agent, a sunless tanning agent, a vitamin, and a mixture of any two or more thereof.

16. The foamable composition of claim 1, further comprising an active agent.

17. The foamable composition of claim 16, wherein at least 95% of the active ingredient has been solubilized.

18. The foamable composition of claim 16, wherein the active agent is selected from the group consisting of an active herbal extract, an acaricide, an age spot and keratose removing agent, an allergen, an analgesic, a local anesthetic, an antiacne agent, an antiallergic agent, an antiaging agent, an antibacterial, an antibiotic, an antiburn agent, an anticancer agent, an antidandruff agent, an antidepressant, an antidermatitis agent, an antiedemic, an antihistamine, an antihelminth, an antihyperkeratolyte agent, an antiinflammatory agent, an antiirritant, an antilipemic, an antimicrobial, an antimycotic, an antiproliferative agent, an antioxidant, an anti-wrinkle agent, an antipruritic, an antipsoriatic agent, an antirosacea agent, an antiseborrheic agent, an antiseptic agent, an antiswelling agent, an antiviral agent, an antiyeast agent, an astringent, a topical cardiovascular agent, a chemotherapeutic agent, a corticosteroid, a dicarboxylic acid, a disinfectant, a fungicide, a hair growth regulator, a hormone, a hydroxy acid, an immunosuppressant, an immunoregulating agent, an immunomodulatory, an insecticide, an insect repellent, a keratolytic agent, a lactam, a metal oxide, a mitocide, a neuropeptide, a steroid, a non-steroidal anti-inflammatory agent, an oxidizing agent, a pediculicide, a photodynamic therapy agent, a retinoid, a sanative, a scabicide, a vasoconstrictor, a vasodilator, a vitamin, a vitamin D derivative, a wound healing agent, a wart remover;

an agent having activity against superficial basal cell carcinomas, actinic keratoses, Bowen'"'"'s disease, or other squamous cell carcinomas and molluscum contagiosum;

an agent having activity against herpes simplex virus infections, other viral infections, or eczema;

a vaccine adjuvant, and a mixture of any two or more thereof.

19. The foamable composition of claim 18, wherein the active agent is an anti-cancer agent.

20. A method of treating or ameliorating a skin, mucosal or body cavity cancer disorder of a mammalian subject, comprising administering the foamable composition of claim 19 to the skin, a mucosal surface, or a body cavity of said mammalian subject.

21. The method of claim 20, wherein the cancer disorder is selected from the group consisting of skin neoplasia, skin neoplasms, skin cancer, ischemic necrosis, moles, Kaposi'"'"'s sarcoma, melanoma, basal cell carcinoma, squamous cell carcinoma, scleroderma, vulvar intraepithelial neoplasia, genital cancer, cancer of the cervix, cancer of the vulva, cancer of the vagina, anal cancer, polyps of the colon and rectum, superficial basal cell carcinomas, and Bowen'"'"'s disease.

23. The foamable composition of claim 1, wherein the solid wax comprises a paraffin wax, stearyl alcohol, behenyl alcohol, or a mixture of any two or more thereof;

wherein the surface-active agent comprises glyceryl monostearate, sorbitan monostearate, or a mixture thereof;

wherein the polymeric agent comprises a methylcellulose;

wherein the composition further comprises a polar solvent comprising dimethyl sulfoxide, polyethylene glycol, or a mixture thereof; and

wherein the composition further comprises an anti-cancer agent.

24. The foamable composition of claim 1, wherein the surface active agent is between about 0.2% to about 8% by weight;

wherein the polymeric agent is present in the composition at a concentration of about 0.01% to about 5% by weight, and wherein the composition further comprises a polar solvent at a concentration of about 40% to about 80% by weight.

28. The foamable composition of claim 1, wherein the composition has a water content of less than about 2%.

29. The foamable composition of claim 1, wherein the composition has a water content of less than about 1.5%.

22. A foamable composition for a pharmaceutical comprising:

A. a carrier comprising;

a. a solvent comprising;

i. at least about 20% by weight of a liquid wax comprising one or more free fatty acids, wherein at least one free fatty acid is oleic acid and wherein the oleic acid is at least about 20% by weight of the carrier; and

ii. at least one potent solvent, wherein the concentration of the potent solvent is more than about 60% by weight of the solvent;

b. a surface-active agent;

c. a polymeric agent; and

d. a solid wax comprising a solid paraffin wax;

wherein the ratio of liquid wax to solid wax is about 3;

1 to about 10;

1, and

B. a liquefied hydrocarbon gas propellant at a concentration of about 3% to about 35% by weight of the foamable composition;

wherein,

the foamable composition a water content less than about 5% by weight;

wherein the foamable composition is not an emulsion; and

upon release from a pressurized container, a breakable foam is produced.

25. The foamable composition of claim 22, wherein the solid wax further comprises stearyl alcohol, behenyl alcohol, or a mixture thereof;

wherein the surface-active agent comprises glyceryl monostearate, sorbitan monostearate, or a mixture thereof;

wherein the polymeric agent comprises a methylcellulose;

wherein the potent solvent comprises dimethyl sulfoxide, polyethylene glycol, or a mixture thereof; and

wherein the composition further comprises an anti-cancer agent.

26. The foamable composition of claim 22, wherein the surface active agent is between about 0.2% to about 8% by weight;

wherein the polymeric agent is present in the composition at a concentration of about 0.01% to about 5% by weight.

27. The foamable composition of claim 22, wherein the composition is waterless.

30. The foamable composition of claim 22, wherein the composition has a water content of less than about 2%.

31. The foamable composition of claim 22, wherein the composition has a water content of less than about 1.5%.