Saccharide foamable compositions

• US 7,645,803 B2
• Filed: 05/09/2006
• Issued: 01/12/2010
• Est. Priority Date: 05/09/2005
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Besonov, Alex, Friedman, Doron, Tamarkin, Dov
• Primary Examiner(s): Arnold; Ernst V
• Application Number:
  US11/430,437
• Publication Number:
  US 20060275221A1
• Time in Patent Office: 1,344 Days
• Field of Search: None
• US Class Current: 424/43
• 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 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 8/046 Aerosols; Foams
• CPC Class Codes: A61K 8/39 Derivatives containing from 2 to 10 oxyalkylene groups
• CPC Class Codes: A61K 8/60 Sugars; Derivatives thereof
• CPC Class Codes: A61K 8/988 Honey; Royal jelly, Propolis
• 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 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61K 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin

Abstract

A foamable composition, containing a saccharide for use in the treatment of various disorders including: water, a saccharide, about 0.2% to about 5% by weight of a surface-active agent, about 0.01% to about 5% by weight of at least one polymeric agent selected from a bio-adhesive agent, a gelling agent, a film forming agent and a phase change agent, and a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition.

Claims

1. A foamable saccharide composition for topical administration to the skin or vaginal body cavity including:

(i) water;

(ii) about 50% to about 80% by weight of a saccharide selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a sugar alcohol and mixtures thereof;

or honey, in an amount that provides about 50% to about 80% by weight of a mixture of saccharides in the composition;

(iii) about 0.2% to about 5% by weight of a surface-active agent;

(iv) about 0.01% to about 5% by weight of at least one polymeric agent selected from a bioadhesive agent, a gelling agent, a film forming agent and phase change agent; and

(v) a foam adjuvant, the foam adjuvant comprising a fatty alcohol or a fatty acid, or a mixture thereof; and

a liquefied hydrocarbon propellant or compressed gas propellant at a concentration of about 3% to about 25% of the total composition;

wherein the saccharide composition is hygroscopic; and

wherein the composition forms a breakable foam upon dispensing.

2. The saccharide composition of claim 1, further containing a hydrophobic solvent.

3. The saccharide composition of claim 2, wherein the composition is in the form of an oil in water emulsion.

4. The saccharide composition of claim 2, wherein the composition is in the form of a water in oil emulsion.

5. The saccharide composition of claim 1, further containing an additive selected from the group of a keratolytic agent and a polar solvent.

6. The saccharide composition of claim 1, further containing at least one active agent selected from the group of an active herbal extract, an acaricide, an age spot and keratose removing agent, an allergen, an analgesic agent, a local anesthetic, an antiacne agent, an antiallergic agent, an antiaging agent, an antibacterial agent, an antibiotic agent, an antiburn agent, an anticancer agent, an antidandruff agent, an antidepressant, an antidermatitis agent, an antiedemic agent, an antihistamine, an antihyperkeratolyte agent, an antiinflammatory agent, an antiirritant, an antilipemic agent, an antimicrobial agent, an antimycotic agent, an antiproliferative agent, an antioxidant, an anti-wrinkle agent, an antipruritic agent, 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 insecticide, an insect repellent, a keratolytic agent, a lactam, a metal, a metal oxide, a mitocide, a neuropeptide, a non-steroidal anti-inflammatory agent, an oxidizing agent, a pediculicide, a photodynamic therapy agent, a retinoid, a scabicide, a self tanning agent, a skin whitening agent, a vasoconstrictor, a vasodilator, a vitamin, a vitamin D derivative, a wound healing agent and a wart remover.

7. The saccharide composition of claim 1, wherein the concentration of the saccharide is sufficient to provide a Aw value less than 0.9 or about 0.9.

8. The saccharide composition of claim 1, further containing a therapeutically effective concentration of an anti-infective agent.

9. The saccharide composition of claim 8, wherein the anti-infective agent is selected from the group consisting of an antibiotic agent, an antibacterial agent, an antifungal agent, an agent that controls yeast, an antiviral agent and an antiparasitic agent.

10. The saccharide composition of claim 9, wherein the antibiotic agent is selected from the group consisting of a beta-lactam antibiotic, an aminoglycoside, an ansa-type antibiotic, an anthraquinone, an azole, metronidazole, an antibiotic glycopeptide, a macrolide, erythromycin, clindamycin, an antibiotic nucleoside, an antibiotic peptide, polymyxin B, an antibiotic polyene, an antibiotic polyether, an antibiotic quinolone, an antibiotic steroid, fucidic acid, mupirocin, chloramphenicol, a sulfonamide, tetracycline, an antibiotic metal, silver, copper, zinc, mercury, tin, lead, bismuth, cadmium, chromium, an oxidizing agent, iodine, iodate, a periodate, a hypochlorite, a permanganate, a cationic antimicrobial agent, a quaternary ammonium compound, a biguanide, chlorohexidine, a triguanide, a bisbiguanide, a polymeric biguanide, a naturally occurring antibiotic compound and salts, ions and complexes thereof.

11. The saccharide composition of claim 9, wherein the antifungal agent is useful in the treatment of an infection of dermatophytosis, microsporum, trichophyton and epidermophyton infections, candidiasis, oral candidiasis (thrush), yeast and candida.

12. The saccharide composition of claim 9, wherein the antifungal agent is selected from the group consisting of a polyene, natamycin, nystatin;

an allylamine, naftifine, terbinafine;

an imidazole, bifonazole, clotrimazole, econazole, fenticonazole, ketocanazole, miconazole, oxiconazole;

a diazole, a triazoles, fluconazole, itraconazole, terconazole, tolnaftate, ciclopirox, undecylenic acid, sulbentine, griseofulvin, Amphotericin B, flucytosine (5FC), a morpholine compound, amorolfine, and the related morpholines and salts thereof, and any combination thereof at a therapeutically effective concentration.

13. The saccharide composition of claim 5, wherein the keratolytic agent is selected from the group consisting of urea, an alpha-hydroxy acid, lactic acid, phenol, resorcinol, salicylic acid, a keratolytic enzyme, a proteolytic enzyme and papain.

19. The saccharide composition of claim 7, wherein the concentration of the saccharide is selected to provide a Aw value less than 0.7 or about 0.7.

20. The saccharide composition of claim 1 wherein the HLB of the surface-active agent is between about 2 and about 9.

21. The saccharide composition of claim 1, wherein the HLB of the surface-active agent is between about 9 and about 14.

22. The saccharide composition of claim 1, wherein the composition has an Aw value of less than 0.9 or about 0.9.

14. A method of treatment of a disorder of a target site comprising:

administering to a target site in need of treatment, said target site selected from the group consisting of the skin, a body surface, a body cavity or mucosal surface, the nasal cavity, the mouth, the eye, the ear canal, the vagina and the rectum;

a saccharide composition comprising;

(i) water;

(ii) about 50% to about 80% by weight of a saccharide selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a sugar alcohol and mixtures thereof;

or honey, in an amount that provides about 50% to about 80% by weight of a mixture of saccharides in the composition;

(iii) about 0.2% to about 5% by weight of a surface-active agent;

(iv) about 0.01% to about 5% by weight of at least one polymeric agent selected from a bio-adhesive agent, a gelling agent, a film forming agent and a phase change agent; and

(v) a foam adjuvant, the foam adjuvant comprising a fatty alcohol or a fatty acid, or a mixture thereof; and

a liquefied hydrocarbon propellant or compressed gas propellant at a concentration of about 3% to about 25% of the total composition;

wherein the saccharide composition is hygroscopic; and

wherein the composition forms a breakable foam upon administration.

15. The method of claim 14, wherein the disorder comprises an infection.

16. The method of claim 15, wherein the infection is selected from the group consisting of a bacterial infection, a fungal infection, a yeast infection, a viral infection and a parasitic infection.

17. The method of claim 14, wherein the disorder is selected from the group consisting of wound, ulcer and burn.

18. The method of claim 14, wherein the disorder is selected from the group consisting of dermatological pain, dermatological inflammation, acne, acne vulgaris, inflammatory acne, non-inflammatory acne, acne fulminans, nodular papulopustular acne, acne conglobata, dermatitis, bacterial skin infections, fungal skin infections, viral skin infections, parasitic skin infections, skin neoplasia, skin neoplasms, pruritis, cellulitis, acute lymphangitis, lymphadenitis, erysipelas, cutaneous abscesses, necrotizing subcutaneous infections, scalded skin syndrome, folliculitis, furuncles, hidradenitis suppurativa, carbuncles, paronychial infections, rashes, erythrasma, impetigo, ecthyma, yeast skin infections, warts, molluscum contagiosum, trauma or injury to the skin, post-operative or post-surgical skin conditions, scabies, pediculosis, creeping eruption, eczemas, psoriasis, pityriasis rosea, lichen planus, pityriasis rubra pilaris, edematous, erythema multiforme, erythema nodosum, granuloma annulare, epidermal necrolysis, sunburn, photosensitivity, pemphigus, bullous pemphigoid, dermatitis herpetiformis, keratosis pilaris, callouses, corns, ichthyosis, skin ulcers, ischemic necrosis, miliaria, hyperhidrosis, moles, Kaposi'"'"'s sarcoma, melanoma, malignant melanoma, basal cell carcinoma, squamous cell carcinoma, poison ivy, poison oak, contact dermatitis, atopic dermatitis, rosacea, purpura, moniliasis, candidiasis, baldness, alopecia, Behcet'"'"'s syndrome, cholesteatoma, Dercum disease, ectodermal dysplasia, gustatory sweating, nail patella syndrome, lupus, hives, hair loss, Hailey-Hailey disease, chemical or thermal skin burns, scleroderma, aging skin, wrinkles, sun spots, necrotizing fasciitis, necrotizing myositis, gangrene, scarring, vitiligo, chlamydia infection, gonorrhea infection, herpes, HIV/AIDS, human papillomavirus (HPV), genital warts, bacterial vaginosis, candidiasis, chancroid, granuloma Inguinale, lymphogranuloma venereum, mucopurulent cervicitis (MPC), molluscum contagiosum, nongonococcal urethritis (NGU), trichomoniasis, vulvar disorders, vulvodynia, vulvar pain, yeast infection, vulvar dystrophy, vulvar intraepithelial neoplasia (VIN), contact dermatitis, pelvic inflammation, endometritis, salpingitis, oophoritis, genital cancer, cancer of the cervix, cancer of the vulva, cancer of the vagina, vaginal dryness, dyspareunia, anal and rectal disease, anal abscess/fistula, anal cancer, anal fissure, anal warts, Crohn'"'"'s disease, hemorrhoids, anal itch, pruritus ani, fecal incontinence, constipation, polyps of the colon and rectum.

23. A foamable saccharide composition for topical administration comprising:

(i) water;

(ii) about 50% to about 80% by weight of a saccharide selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a sugar alcohol and mixtures thereof;

or honey in an amount that provides about 50% to about 80% by weight of a mixture of saccharides in the composition;

(iii) about 0.2% to about 5% by weight of a surface-active agent; and

(iv) a liquefied hydrocarbon propellant or compressed gas propellant at a concentration of about 3% to about 25% of the total composition,

wherein the saccharide composition is hygroscopic; and

wherein the composition forms a breakable foam upon dispensing.

24. A foamable saccharide composition for topical administration including:

(i) water;

(ii) about 50% to about 80% by weight of a saccharide selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a sugar alcohol and mixtures thereof;

or honey in an amount that provides about 50% to about 80% by weight of a mixture of saccharides in the composition;

(iii) about 0.2% to about 5% by weight of a surface-active agent; and

(iv) a liquefied hydrocarbon propellant or compressed gas propellant at a concentration of about 3% to about 25% of the total composition,

wherein the foam is capable of providing an Aw value of less than about 9; and

wherein the foam forms a breakable foam upon dispensing.

25. A method for delivering a saccharide composition, comprising

(a) charging a container with a composition comprising a foamable carrier and a liquefied or compressed gas hydrocarbon propellant, wherein the propellant is present at a concentration of about 3% to about 25% by weight of the total composition, and wherein the carrier comprises

(i) water;

(ii) about 50% to about 80% by weight of a saccharide selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a sugar alcohol and mixtures thereof;

(iii) optionally honey, in an amount that provides about 50% to about 80% by weight of a mixture of saccharides in the composition;

(iv) about 0.2% to about 5% by weight of a surface-active agent;

(v) about 0.01% to about 5% by weight of at least one polymeric agent selected from a bioadhesive agent, a gelling agent, a film forming agent and a phase change agent; and

(vi) a foam adjuvant, the foam adjuvant comprising a fatty alcohol or a fatty acid, or a mixture thereof; and

(b) dispensing the composition onto a body surface or in a body cavity, wherein the composition is dispensed as a breakable foam.

26. The method of claim 25, wherein the breakable foam creates a semi-occlusive layer on the surface or body cavity.

27. A foamable composition for topical administration to the skin or vaginal body cavity including:

(i) water;

(ii) about 50% to about 80% by weight of a sugar alcohol;

(iii) about 0.2% to about 5% by weight of a surface-active agent;

(iv) about 0.01% to about 5% by weight of at least one polymeric agent selected from a bioadhesive agent, a gelling agent, a film forming agent and phase change agent; and

(v) a liquefied hydrocarbon propellant or compressed gas propellant at a concentration of about 3% to about 25% of the total composition, and

wherein the saccharide composition is hygroscopic; and

wherein the composition forms a breakable foam upon dispensing.

28. The foamable composition of claim 27, further comprising a foam adjuvant, the foam adjuvant comprising a fatty alcohol or a fatty acid, or a mixture thereof.