Oleaginous pharmaceutical and cosmetic foam

• US 8,518,378 B2
• Filed: 09/14/2010
• Issued: 08/27/2013
• Est. Priority Date: 08/04/2003
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix 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:
  US12/881,856
• Publication Number:
  US 20110002857A1
• Time in Patent Office: 1,078 Days
• Field of Search: None
• US Class Current: 424/45
• 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. An oleaginous foamable therapeutic composition, comprising:

a. about 70% to about 96.5% of a solvent phase, wherein the solvent phase is selected from the group consisting of a hydrophobic solvent, a silicone oil, and mixtures thereof;

b. at least one non-ionic surface-active agent at a concentration of about 0.1% to about 10% by weight of the total composition;

c. at least one gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition;

d. at least one active agent;

e. at least one potent solvent selected from the group consisting of a hydrophobic solvent other than mineral oil;

a co-solvent;

an emollient; and

mixtures thereof, wherein the potent solvent solubilizes the active agent substantially better than mineral oil solubilizes the active agent; and

f. at least one liquefied or compressed gas propellant, wherein the composition forms a thermally stable breakable foam upon release from a pressurized container that collapses upon application of shear force; and

wherein the water content of the composition is less than about 30% by weight.

2. The oleaginous composition of claim 1, wherein the potent solvent solubilizes the active agent at least 5-fold better than mineral oil solubilizes the active agent.

3. The oleaginous composition of claim 1, wherein the potent solvent solubilizes the active agent at least 10-fold better than mineral oil solubilizes the active agent.

4. The oleaginous composition of claim 1, wherein the potent solvent is one or more potent solvents selected from the group consisting of polyethylene glycol, a polyol, benzyl alcohol, DMSO, ethyl oleate, ethyl caprylate, diisopropyl adipate, dimethylacetamide, N-methylpyrrolidone, N-hydroxyethylpyrrolidone, polyvinylpyrrolidone, isosorbide derivatives, dimethyl isosorbide, glycofurol, ethoxydiglycol, and mixtures thereof.

5. The oleaginous foamable therapeutic composition of claim 4, wherein said polyol is selected from the group consisting of glycerol, ethylene glycol, propylene glycol, hexylene glycol, diethylene glycol, a propylene glycol n-alkanol, a terpene, a di-terpene, a tri-terpene, a terpen-ol, limonene and I-menthol dioxolane.

6. The oleaginous foamable therapeutic composition of claim 4, wherein said polyethylene glycol is a liquid selected from the group consisting of PEG200, PEG300, PEG400 and PEG600.

7. The oleaginous composition of claim 1, further comprising at least one foam adjuvant selected from the group consisting of fatty alcohols having greater than or equal to 15 carbons, fatty acids having greater than or equal to 16 carbons, and mixtures thereof.

8. The oleaginous composition of claim 1, wherein the hydrophobic solvent is one or more hydrophobic solvents selected from the group consisting of mineral oil, triglyceride oil, silicone oil, an ester of a dicarboxylic acid, an ester of a fatty acid, a polyunsaturated oil, an unsaturated oil, an essential oil, and mixtures thereof.

9. The oleaginous composition of claim 1, wherein the solvent phase comprises at least one hydrophobic solvent and the potent solvent is at least one co-solvent.

10. The oleaginous composition of claim 9, wherein the mixture of the hydrophobic solvent and the one co-solvent comprises a weight ratio of about 1:

8 to about 8;

1.

11. The oleaginous composition of claim 1, wherein the composition is an emulsion.

12. The oleaginous composition of claim 1, further comprising at least one ionic surface-active agent, wherein the mixture of the non-ionic surface-active agent and the ionic surface-active agent is present at a weight ratio of about 20:

1 to about 1;

1 non-ionic surfactant surface-active agent to ionic surfactant surface-active agent.

13. The oleaginous composition of claim 1, wherein the concentration of the nonionic surfactant surface-active agent is from about 0.1% to about 2%.

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

15. The oleaginous composition of claim 1, wherein the water content is less than about 20% by weight.

16. The oleaginous composition of claim 1 wherein the specific gravity of the foam is about 0.01 g/mL to about 0.3 g/mL.

17. The oleaginous composition of claim 1, wherein the active agent is selected to treat a dermatological or mucosal disorder that is bacterial, fungal, viral, parasitic, inflammatory, autoimmune, allergic, hormonal, malignant and combinations thereof.

18. The oleaginous composition of claim 1, wherein at least one active agent is hydrophobic, having solubility in distilled water at ambient temperature of less than about 1 gm per 100 mL.

19. The oleaginous composition of claim 1, wherein at least one active agent is hydrophobic, having solubility in distilled water at ambient temperature of less than about 0.1 gm per 100 mL.

20. The oleaginous composition of claim 1, wherein at least one active agent is one or more therapeutic agents 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 salicylate, a peptide antibiotic, a cyclic peptide, cyclosporine, an oxidant, a free radical liberating compound, a bleaching agent, 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, anonsteroidal 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, and 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 pyrazoles, 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 lubricating agent, an antiproliferative, a cortisone, an immunosuppressant, an immunoregulating agent, an immunomodulator, tacrolimus, tresperimus, pimecrolimus, sirolimus, verolimus, laflunimus, laquinimod, Imiquimod, a keratolytic agent, a alpha-hydroxy acid, lactic acid, glycolic acid, a betahydroxy acids, urea, a retinoid, retinol, retinal, retinoic acid, etretinate, actiretin, isotretinoin, adapalene, tazarotene, an anti-acne agent, azelaic acid, an azelaic acid derivative an anti cancer agent, an antiproliferative drugs, 5-fluorouracil, a photodynamic therapy agent, a vitamin or 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, a massaging oil, an anti-wart agent, a lubricating agent_. and mixtures thereof.

21. The oleaginous composition of claim 20, wherein the therapeutic agent is selected for the treatment of a disorder of the skin, mucosal membrane, ear channel, vagina, penile urethra, colon, and rectum.

22. A method of treating, alleviating or preventing a dermatological, mucosal or cosmetic disorder or disease, comprising administering topically to a subject having said disorder a therapeutically effective amount of an oleaginous foam composition according to claim 1.

23. The method of claim 22, wherein the composition is applied topically to a target selected from the group consisting of the skin, mucosal membrane, ear channel, vagina, penile urethra, colon and rectum.

24. The method of claim 22, wherein the disorder or disease is selected from the group consisting of

a. 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, necrotizing subcutaneous infections, staphylococcal scalded skin syndrome, folliculitis, furuncles, hidradenitis suppurativa, carbuncles, paronychial infection, erythrasma, a fungal infection, a dennatophyte 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 disease, psoriasis, pityriasis rosea, lichen planus, pityriasis rubra pilaris, a benign tumor, moles, dysplastic nevi, skin tags, lipomas, angiomas, pyogenic granuloma, seborrheic keratoses, dennatofibroma, 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, chronic effects of sunlight, photosensitivity, a bullous disease, pemphigus, bullous pemphigoid, dermatitis herpetiformis, linear immunoglobulin A disease, 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, drug eruption, toxic epidermal necrolysis, erythema multifonne, erythema nodosum, granuloma annulare;

b. a non dermatological disorder which responds to topical or transdermal delivery of an active agent, localized pain in general, joint pain, muscle pain, back pain, rheumatic pain, arthritis, ostheoarthritis, acute soft tissue injury, sports injuries;

c. a condition which responds to hormone therapy, a disorder which responds to hormone replacement therapy, a disorder which responds to transdermal nicotine administration;

d. a disorder of a body cavity, the rectum, vagina, penile urethra, or ear canal;

e. pelvic pain, premenstrual syndrome, mittelschmerz, midcycle pain, midcycle pain due to ovulation, dysmenorrhea, endometriosis, ectopic pregnancy, ovarian cysts and masses, acute pelvic inflammatory disease, pelvic congestion syndrome, vulvodynia, a vulvovaginal infection, bacterial vaginosis, candidal vaginitis, trichomonas vaginalis, herpes simplex, genital ulcer, genital 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, a benign tumor, a sexually transmitted disease, a sexual dysfunction disorder, sexual arousal disorder, female orgasmic disorder, dyspareunia, vaginismus, a gynecological disorder that respond to hormonal therapy;

f. rectal abscess, rectal fistula, anal cancer, anal warts, Crohn'"'"'s disease, haemorrhoids, anal pruritus, perianal pruritus, anal soreness, anal excoriation, perianal thrush, anal fissures, fecal incontinence, constipation, polyps of the colon and rectum; and

g. an intra-vaginal or rectal sexually-transmitted and non-sexually-transmitted infectious disease.