Oleaginous pharmaceutical and cosmetic foam

• US 9,050,253 B2
• Filed: 04/07/2014
• Issued: 06/09/2015
• Est. Priority Date: 08/04/2003
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Pharmaceuticals, Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Tamarkin, Dov, Friedman, Doron, Eini, Meir, Besonov, Alex
• Primary Examiner(s): Desai, Anand
• Assistant Examiner(s): MERCIER, MELISSA S
• Application Number:
  US14/246,533
• Publication Number:
  US 20140219929A1
• Time in Patent Office: 428 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A01N 25/16 Foams
• CPC Class Codes: A61K 31/351 not condensed with another ring
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 38/13 Cyclosporins
• 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 8/046 Aerosols; Foams
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• 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: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• 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 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin

Abstract

The invention relates to stable oleaginous cosmetic or therapeutic foam compositions containing certain active agents, having unique therapeutic properties and methods of treatment using such compositions. The foamable composition includes at least one solvent selected from a hydrophobic solvent, a silicone oil, an emollient, a co-solvent, and mixtures thereof, wherein the solvent is present at a concentration of about 70% to about 96.5% by weight of the total composition, at least a non-ionic surface-active agent at a concentration of about 0.1% to less than about 10% by weight of the total composition; at least one gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition; a therapeutically effective amount of at least one active agent; and at least one liquefied or compressed gas propellant, at a concentration of about 3% to about 25% by weight of the total composition.

Claims

1. A foamable composition, comprising a carrier comprising:

a) about 70% to about 96.5% by weight of the carrier of a solvent selected from the group consisting of a co-solvent, a hydrophobic solvent, and mixtures thereof;

b) at least one gelling agent at a concentration of about 0.1% to about 5% by weight of the carrier; and

c) a surface-active agent;

wherein when mixed with a propellant in a canister, the composition is released as a breakable foam which collapses on application of shear force, and the breakable foam does not readily collapse at 37°

C.

2. The composition of claim 1, further comprising a therapeutically effective amount of at least one active agent.

3. The composition of claim 1, wherein the composition has less than about 5% by weight of the carrier of lower alcohols having up to 5 carbon atoms in their carbon chain skeleton.

4. The composition of claim 1, wherein the composition further comprises at least one liquefied or compressed gas propellant, at a concentration of about 3% to about 25% by weight of the carrier.

5. The composition of claim 1, wherein the composition is contained within a pressurized container.

6. The composition of claim 1, wherein the co-solvent is selected from the group consisting of a polyol, a sulfoxide, and mixtures thereof.

7. The composition of claim 1, wherein the co-solvent is selected from the group consisting of glycerol, propylene glycol, hexylene glycol, diethylene glycol, propylene glycol n-alkanols, terpenes, di-terpenes, tri-terpenes, terpen-ols, limonene, terpene-ol, 1-menthol, dioxolane, ethylene glycol, dimethylsulfoxide, dimethylformamide, methyl dodecyl sulfoxide, dimethylacetamide, a monooleate of ethoxylated glycerides with 8 to 10 ethylene oxide units, azone, 2-n-nonyl-1,3-dioxolane, isopropyl myristate, isopropyl palmitate, ethyl acetate, butyl acetate, methyl proprionate, capric/caprylic triglycerides, octyl-myristate, dodecyl-myristate, lauryl alcohol, lauric acid, lauryl lactate, ketones, amides, acetamide, oleates, triolein, alkanoic acids, caprylic acid, lactam compounds, alkanols, dialkylamino acetates, and mixtures of any two or more thereof.

8. The composition of claim 1, wherein the co-solvent is an organic solvent, other than a short chain alcohol, which is soluble in both water and oil.

9. The composition of claim 2, wherein the co-solvent solubilizes the active agent at least 5-fold better than mineral oil.

10. The composition of claim 2, wherein the co-solvent is present in a sufficient amount to solubilize at least 95% of the active agent in the composition.

11. The composition of claim 1, wherein the at least one gelling agent is selected from the group consisting of natural polymeric materials, semi-synthetic polymeric materials, synthetic polymeric materials, inorganic gelling agents, and mixtures of any two or more thereof.

12. The composition of claim 11, wherein the at least one gelling agent is selected from the group consisting of locust bean gum, sodium alginate, sodium caseinate, egg albumin, gelatin agar, carrageenan gum, xanthan gum, quince seed extract, tragacanth gum, starch, chemically modified starches, cellulose ethers, hydroxyethyl cellulose, methyl cellulose, carboxymethyl cellulose, hydroxy propylmethyl cellulose, polyvinylpyrrolidone, polyvinylalcohol, guar gum, hydroxypropyl guar gum, soluble starch, cationic celluloses, cationic guars, carboxyvinyl polymers, polyvinyl alcohol, polyacrylic acid polymers, polymethacrylic acid polymers, polyvinyl acetate polymers, polyvinyl chloride polymers, polyvinylidene chloride polymers, acrylic acid/ethyl acrylate copolymers, carboxyvinyl polymers, carbopols, and mixtures of any two or more thereof.

13. The composition of claim 1, wherein the surface-active agent is selected from the group consisting of sorbitan derivatives, alkoxylated alcohols, hydroxylated derivatives of polymeric silicones, alkylated derivatives of hydroxylated polymeric silicones, glyceryl esters, beeswax derivatives, lecithin, polysorbates, polyoxyethylene fatty acid esters, polyoxyethylene alkyl ethers, sucrose esters, partial esters of sorbitol and its anhydrides, mono and diglycerides, isoceteth-20, sodium methyl cocoyl taurate, sodium methyl oleoyl taurate, sodium lauryl sulfate, triethanolamine lauryl sulfate, betaines, and mixtures of any two or more thereof.

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

15. The composition of claim 1, wherein the carrier further comprises a fatty acid, a fatty alcohol, or a mixture thereof.

16. The composition of claim 15, wherein the fatty acid is selected from the group consisting of fatty acids having greater than or equal to 16 carbons and wherein the fatty alcohol is selected from the group consisting of fatty alcohols having greater than or equal to 15 carbons.

17. The composition of claim 1, wherein the carrier further comprises an emollient.

18. The composition of claim 17, wherein the emollient is selected from the group consisting of hexylene glycol, propylene glycol, isostearic acid derivatives, isopropyl palmitate, isopropyl isostearate, diisopropyl adipate, diisopropyl dimerate, maleated soybean oil, octyl palmitate, cetyl lactate, cetyl ricinoleate, tocopheryl acetate, acetylated lanolin alcohol, cetyl acetate, phenyl trimethicone, glyceryl oleate, tocopheryl linoleate, wheat germ glycerides, arachidyl propionate, myristyl lactate, decyl oleate, propylene glycol ricinoleate, isopropyl lanolate, pentaerythrityl tetrastearate, neopentylglycol dicaprylate/dicaprate, isononyl isononanoate, isotridecyl isononanoate, myristyl myristate, triisocetyl citrate, octyl dodecanol, sucrose esters of fatty acids, octyl hydroxystearate, and mixtures of any two or more thereof.

19. The composition of claim 2, wherein the active agent is selected from the group consisting of an anti-infective, an antibiotic agent, an antibacterial agent, a macrolide, erythromycin, clindamycin, a sulfonamide, sulfanilamide, sulfadiazine, sulfacetamide, mupirocin, a tetracycline, tetracycline, doxycycline, a semi-synthetic penicillin, a beta-lactam, cloramphenicol, a dicarboxylic acid, azelaic acid, a peptide antibiotic, a cyclic peptide, cyclosporine, an oxidant, a free radical liberating compound, an iodine compound, benzoyl peroxide, an antifungal agent, an imidazole, a triazole, miconazole, fluconazole, ketoconazole, clotrimazole, itraconazole griseofulvin, ciclopirox, amorolfine, terbinafine, amphotericin B, potassium iodide, flucytosine, an antiviral agent, an antiparasitic agent, an anti-inflammatory agent, a nonsteroidal anti-inflammatory agent, an oxicam, piroxicam, isoxicam, tenoxicam, sudoxicam, a salicylate, salicylic acid, ethyl salicylate, methyl salycilate, aspirin, disalcid, benorylate, trilisate, safapryn, solprin, diflunisal, fendosal, an acetic acid derivative, diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, isoxepac, furofenac, tiopinac, zidometacin, acematacin, fentiazac, zomepirac, clindanac, oxepinac, felbinac, ketorolac, a fenamate, mefenamic, meclofenamic, flufenamic, niflumic, tolfenamic acid, a propionic acid derivative, ibuprofen, naproxen, benoxaprofen, flurbiprofen, ketoprofen, fenoprofen, fenbufen, indopropfen, pirprofen, carprofen, oxaprozin, pranoprofen, miroprofen, tioxaprofen, suprofen, alminoprofen, tiaprofenic, a pyrazole, phenylbutazone, oxyphenbutazone, feprazone, azapropazone, trimethazone, an antihistamine, doxepin, phrilamine maleate, chlorpheniramine, tripelennamine, phenothiazines, promethazine hydrochloride, dimethindene maleate, an anesthetic agent, benzocaine, lidocaine, bupivacaine, chlorprocaine, dibucaine, etidocaine, mepivacaine, tetracaine, dyclonine, hexylcaine, procaine, cocaine, ketamine, pramoxine, an analgesic agent, an antiallergic agent, a corticosteroid, clobetasol proprionate, halobetasol proprionate, betamethasone, betamethasone diproprionate, betamethasone valerate, fluocinolone, halcinonide, etamethasone valerate, fluocinolone acetonide, hydrocortisone, triamcinolone, a cortisone, an immunosuppressant, an immunoregulating agent, an immunomodulator, tacrolimus, tresperimus, pimecrolimus, sirolimus, verolimus, laflunimus, laquinimod, imiquimod, a keratolytic agent, an alpha-hydroxy acid, lactic acid, glycolic acid, a beta-hydroxy acid, urea, a retinoid, retinol, retinal, retinoic acid, etretinate, actiretin, isotretinoin, adapalene, tazarotene, an anti-acne agent, an azelaic acid derivative, an anti cancer agent, an antiproliferative drug, 5-fluorouracil, a photodynamic therapy agent, a vitamin, a vitamin derivative, an anti-wrinkle agent, a radical scavenger, a self-tanning agent, a skin whitening agent, a skin protective agent, an anti-cellulite agent, an anti-wart agent, and mixtures of any two or more thereof.

20. The composition of claim 1, wherein the surface-active agent is at a concentration of about 0.1% to about 10% by weight of the carrier.

21. The composition of claim 1, wherein the hydrophobic solvent is an oil.

22. The composition of claim 1, wherein the solvent is a mixture of the hydrophobic solvent and the co-solvent, and wherein the ratio of the hydrophobic solvent to the co-solvent is about 1:

8 to about 8;

1.

23. The composition of claim 1, wherein the water content of the composition is less than about 30% by weight.

24. The composition of claim 23, wherein the composition is an emulsion.

25. The composition of claim 2 further comprising a potent solvent.

26. A method of treating or alleviating a disorder of the skin, a mucosal membrane, a body cavity, the rectum, the vagina, the penile urethra, or the ear canal, comprising administering topically to a subject having the disorder a therapeutically effective amount of a foamable composition according to claim 2.

27. The method of claim 26, wherein the disorder is selected from the group consisting of a dermatitis, contact dermatitis, atopic dermatitis, seborrheic dermatitis, nummular dermatitis, chronic dermatitis, generalized exfoliative dermatitis, stasis dermatitis, lichen simplex chronicus, diaper rash, a bacterial infection, cellulitis, acute lymphangitis, lymphadenitis, erysipelas, cutaneous abscess, a necrotizing subcutaneous infection, staphylococcal scalded skin syndrome, folliculitis, furuncles, hidradenitis suppurativa, carbuncles, a fungal infection, a dermatophyte infection, a yeast infection, a parasitic infection, scabies, pediculosis, creeping eruption, a viral infection, a disorder of hair follicles, a disorder of sebaceous glands, acne, rosacea, perioral dermatitis, hypertrichosis, hirsutism, alopecia, male pattern baldness, alopecia areata, alopecia universalis, alopecia totalis, pseudofolliculitis barbae, keratinous cyst, a scaling papular diseases, psoriasis, pityriasis rosea, lichen planus, pityriasis rubra pilaris, a benign tumor, moles, dysplastic nevi, skin tags, lipomas, angiomas, pyogenic granuloma, seborrheic keratoses, dermatofibroma, keratoacanthoma, keloid, a malignant tumor, basal cell carcinoma, squamous cell carcinoma, melanoma, paget'"'"'s disease of the nipples, kaposi'"'"'s sarcoma, reactions to sunlight, sunburn, photosensitivity, a bullous disease, pemphigus, bullous pemphigoid, dermatitis herpetiformis, a pigmentation disorder, hypopigmentation, vitiligo, albinism, postinflammatory hypopigmentation, hyperpigmentation, melasma, chloasma, drug-induced hyperpigmentation, postinflammatory hyperpigmentation, a disorder of cornification, ichthyosis, keratosis pilaris, calluses, corns, actinic keratosis, pressure sores, a disorder of sweating, an inflammatory reaction, toxic epidermal necrolysis, erythema multiforme, erythema nodosum, granuloma annulare, pelvic pain, dysmenorrhea, endometriosis, pelvic congestion syndrome, vulvodynia, a vulvovaginal infection, bacterial vaginosis, candidal vaginitis, trichomonas vaginalis, herpes simplex, genital ulcers, genital warts, pelvic inflammatory disease, cervicitis, acute and chronic salpingitis, a gynecological neoplasm, endometrial cancer, cervical cancer, vulvar cancer, vaginal cancer, fallopian tube cancer, gestational trophoblastic disease, a benign tumor, a sexually transmitted disease, a sexual dysfunction disorder that respond to pharmacological therapy, sexual arousal disorder, female orgasmic disorder, dyspareunia, vaginismus, a gynecological disorder that responds to hormonal therapy, anal abscess, anal fistula, anal cancer, anal warts, Crohn'"'"'s disease, haemorrhoids, anal pruritus, perianal pruritus, perianal thrush, anal fissures, fecal incontinence, constipation, polyps of the colon, and polyps of the rectum.

28. A method of treating or alleviating a non-dermatological disorder, which responds to topical or transdermal delivery of an active agent, comprising administering topically to a subject having the disorder a therapeutically effective amount of a foam composition according to claim 2, wherein the disorder is selected from the group consisting of pelvic pain, premenstrual syndrome, mittelschmerz, dysmenorrhea, endometriosis, ectopic pregnancy, ovarian cysts, ovarian masses, acute pelvic inflammatory disease, pelvic congestion syndrome and vulvodynia, vulvovaginal infections, bacterial vaginosis, candidal vaginitis, trichomonas vaginalis, herpes simplex genital ulcers and warts, pelvic inflammatory disease, cervicitis, acute and chronic salpingitis, endometriosis, gynecological neoplasms, endometrial cancer, ovarian cancer, cervical cancer, vulvar cancer, vaginal cancer, fallopian tube cancer, gestational trophoblastic disease, benign tumors, sexually transmitted diseases, sexual dysfunction disorders that respond to pharmacological therapy, sexual arousal disorder, female orgasmic disorder, dyspareunia and vaginismus, gynecological disorders that respond to hormonal therapy, abscess, fistula, anal cancer, anal warts, Crohn'"'"'s disease, haemorrhoids, anal and perianal pruritus, soreness, excoriation, perianal thrush, anal fissures, fecal incontinence, constipation, polyps of the colon and of the rectum.

29. The method of claim 26, comprising collapsing the foam by application of a mechanical force to the foam such that it is spread at or about a target site on the subject.