Surfactant-free water-free foamable compositions, breakable foams and gels and their uses

Abstract

A substantially surface active agent free composition which includes a hydrophobic solvent, and/or a petrolatum, a paraffin wax and/or a fatty alcohol, a fatty acid and/or a wax and/or shea butter, with and without a propellant. A substantially surface active agent free composition, further comprising, a tetracycline antibiotic, or a vitamin D derivative, or one or more other active agents. A method of treatment using a substantially surface active agent free composition.

1 . (canceled) 
     
     
         2 . A composition comprising a tetracycline and a hydrophobic carrier, wherein the hydrophobic carrier comprises:
 i) about 60% to about 95% by weight of the carrier comprising a gelled oil; and   ii) a liquid oil;   wherein the composition is essentially waterless;   wherein the tetracycline is suspended or partially suspended in the composition;   wherein the composition does not contain one or more of a substance selected from the group consisting of dimethyl sulfoxide (DMSO), dimethylformamide (DMF), acetonitrile, acetone, methyl ethyl ketone, 1,4-dioxane, tetrahydrofuran (THF), N-methylpyrrolidone, pyridine, piperidine, dimethylformamide, N-methyl-2-pyrrolidone and 1-methyl-2-pyrrolidinone), azone (1-dodecylazacycloheptan-2-one), dimethyl isosorbide, glycerin, ethanol, propylene glycol, butylene glycol, PEG 200, hexylene glycol, PEG 400, diethylene glycol monoethyl ether, pomegranate seed oil, isostearic acid, and ethocel; and   wherein the carrier is free of or contains less than 0.1% by weight of a surfactant.   
     
     
         3 . The composition of  claim 2 , wherein after storage at 25° C. for at least six months, the composition retains at least 90% of the tetracycline initially present in the composition. 
     
     
         4 . The composition of  claim 2 , wherein the viscosity of the composition is at least 30% higher than the viscosity of the carrier without the tetracycline antibiotic, and is higher than the viscosity of the liquid oil and the tetracycline antibiotic without the gelled oil. 
     
     
         5 . The composition of  claim 2 , wherein when packaged in an aerosol container and pressurized with a propellant, the composition affords upon release from the container a foam that breaks upon application of shear force. 
     
     
         6 . The composition of  claim 2 , wherein the gelled oil is a gelled mineral oil. 
     
     
         7 . The composition of  claim 2 , wherein the tetracycline antibiotic is selected from the group consisting of a tetracycline, an oxytetracycline, a demeclocycline, a doxycycline, a lymecycline, a meclocycline, a methacycline, aminocycline, a rolitetracycline, a chlorotetracycline, a tigecycline, and mixtures of any two or more thereof. 
     
     
         8 . The composition of  claim 2 , wherein the tetracycline antibiotic is hydrophobic. 
     
     
         9 . The composition of  claim 2 , wherein the tetracycline antibiotic is present in a free base form, a hydrate form, a salt form, or a complex form. 
     
     
         10 . The composition of  claim 2 , wherein the Log of the distribution constant of the tetracycline antibiotic at pH 7.0 (buffer/chloroform) is equal to or less than 0.2. 
     
     
         11 . The composition of  claim 2 , wherein the tetracycline antibiotic does not comprise a hydroxy group at one or more of carbons 5, 6, and 7. 
     
     
         12 . The composition of  claim 2 , wherein the tetracycline antibiotic is selected from the group consisting of aminocycline, a doxycycline, and mixtures thereof. 
     
     
         13 . The composition of  claim 2 , further comprising an additional active agent. 
     
     
         14 . The composition of  claim 2 , wherein the liquid oil comprises a mineral oil, a triglyceride oil, or a mixture thereof. 
     
     
         15 . The composition of  claim 2 , wherein the liquid oil comprises a mixture of one or more liquid oil and one or more solid oils or comprises a mixture of two or more liquid oils. 
     
     
         16 . The composition of  claim 15 , wherein the oil or mixture of oils is selected from the group consisting of a mineral oil, a hydrocarbon oil, an ester oil, an ester of a dicarboxylic acid, a triglyceride oil, an oil of plant origin, an oil from animal origin, an unsaturated or polyunsaturated oil, a diglyceride, a PPG alkyl ether, an essential oil, a silicone oil, liquid paraffin, an isoparaffin, a polyalphaolefin, a polyolefin, polyisobutylene, a synthetic isoalkane, isohexadecane, isododecane, alkyl benzoate, alkyl octanoate, C12-C15 alkyl benzoate, C12-C15 alkyl octanoate, arachidyl behenate, arachidyl propionate, benzyl laurate, benzyl myristate, benzyl palmitate, bis(octyldodecyl stearoyl) dimer dilinoleate, butyl myristate, butyl stearate, cetearyl ethylhexanoate, cetearyl isononanoate, cetyl acetate, cetyl ethylhexanoate, cetyl lactate, cetyl myristate, cetyl octanoate, cetyl palmitate, cetyl ricinoleate, decyl oleate, diethyleneglycol diethylhexanoate, diethyleneglycol dioctanoate, diethyleneglycol diisononanoate, diethyleneglycol diisononanoate, diethylhexanoate, diethylhexyl adipate, diethylhexyl malate, diethylhexyl succinate, diisopropyl adipate, diisopropyl dimerate, diisopropyl sebacate, diisosteary dimer dilinoleate, diisostearyl fumerate, dioctyl malate, dioctyl sebacate, dodecyl oleate, ethylhexyl palmitate, ester derivatives of lanolic acid, ethylhexyl cocoate, ethylhexyl ethylhexanoate, ethylhexyl hydroxystarate, ethylhexyl isononanoate, ethylhexyl palmytate, ethylhexyl pelargonate, ethylhexyl stearate, hexadecyl stearate, hexyl laurate, isoamyl laurate, isocetyl isocetyl behenate, isocetyl lanolate, isocetyl palmitate, isocetyl stearate, isocetyl salicylate, isocetyl stearate, isocetyl stearoyl stearate, isocetearyl octanoate, isodecyl ethylhexanoate, isodecyl isononanoate, isodecyl oleate, isononyl isononanoate, isodecyl oleate, isohexyl decanoate, isononyl octanoate, isopropyl isostearate, isopropyl lanolate, isopropyl laurate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isostearyl behenate, isosteary citrate, isostearyl erucate, isostearyl glycolate, isostearyl isononanoate, isostearyl isostearate, isostearyl lactate, isostearyl linoleate, isostearyl linolenate, isostearyl malate, isostearyl neopentanoate, isostearyl palmitate, isosteary salicylate, isosteary tartarate, isotridecyl isononanoate, isotridecyl isononanoate, lauryl lactate, myristyl lactate, myristyl myristate, myristyl neopentanoate, myristyl propionate, octyldodecyl myristate, neopentylglycol dicaprate, octyl dodecanol, octyl stearate, octyl palmitate, octyldodecyl behenate, octyldodecyl hydroxystearate, octyldodecyl myristate, octyldodecyl stearoyl stearate, oleyl erucate, oleyl lactate, oleyl oleate, propyl myristate, propylene glycol myristyl ether acetate, propylene glycol dicaprate, propylene glycol dicaprylate, maleated soybean oil, stearyl caprate, stearyl heptanoate, stearyl propionate, tocopheryl acetate, tocopheryl linoleate, glyceryl oleate, tridecyl ethylhexanoate, tridecyl isononanoate, triisocetyl citrate, an alexandria laurel tree oil, an avocado oil, an apricot stone oil, a barley oil, a borage seed oil, a calendula oil, a canelle nut tree oil, a canola oil, caprylic/capric triglycerides, a castor oil, a coconut oil, a corn oil, a cotton oil, a cottonseed oil, an evening primrose oil, a flaxseed oil, a groundnut oil, a hazelnut oil, glycereth triacetate, glycerol triheptanoate, glyceryl trioctanoate, glyceryl triundecanoate, a hempseed oil, a jojoba oil, a lucerne oil, a maize germ oil, a marrow oil, a millet oil, a neopentylglycol dicaprylate/dicaprate, an olive oil, a palm oil, a passionflower oil, pentaerythrityl tetrastearate, a poppy oil, propylene glycol ricinoleate, a rapeseed oil, a rye oil, a safflower oil, a sesame oil, a shea butter, a soya oil, a soybean oil, a sweet almond oil, a sunflower oil, a sysymbrium oil, a syzigium aromaticum oil, a tea tree oil, a walnut oil, wheat germ glycerides, a wheat germ oil, a PPG-2 butyl ether, a PPG-4 butyl ether, a PPG-5 butyl ether, a PPG-9 butyl ether, a PPG-12 butyl ether, a PPG-14 butyl ether, a PPG-15 butyl ether, a PPG-15 stearyl ether, a PPG-16 butyl ether, a PPG-17 butyl ether, a PPG-18 butyl ether, a PPG-20 butyl ether, a PPG-22 butyl ether, a PPG-24 butyl ether, a PPG-26 butyl ether, a PPG-30 butyl ether, a PPG-33 butyl ether, a PPG-40 butyl ether, a PPG-52 butyl ether, a PPG-53 butyl ether, a PPG-10 cetyl ether, a PPG-28 cetyl ether, a PPG-30 cetyl ether, a PPG-50 cetyl ether, a PPG-30 isocetyl ether, a PPG-4 lauryl ether, a PPG-7 lauryl ether, a PPG-2 methyl ether, a PPG-3 methyl ether, a PPG-3 myristyl ether, a PPG-4 myristyl ether, a PPG-10 oleyl ether, a PPG-20 oleyl ether, a PPG-23 oleyl ether, a PPG-30 oleyl ether, a PPG-37 oleyl ether, a PPG-40 butyl ether, a PPG-50 oleyl ether, a PPG-11 stearyl ether, a herring oil, a cod-liver oil, a salmon oil, a cyclomethicone, a dimethyl polysiloxane, a dimethicone, an epoxy-modified silicone oil, a fatty acid-modified silicone oil, a fluoro group-modified silicone oil, a methylphenylpolysiloxane, phenyl trimethicone, a polyether group-modified silicone oil, and mixtures of any two or more thereof. 
     
     
         17 . The composition of  claim 2 , wherein the composition contains less than 0.4% by weight of protic solvents, polar aprotic solvents, and silicone thickening agents. 
     
     
         18 . The composition of  claim 2 , wherein the composition contains less than 0.4% by weight of polymeric gelling agents, polyols, short chain alcohols, and silicone thickening agents. 
     
     
         19 . The composition of  claim 2 , wherein the composition is free of one or more of protic solvents, polar aprotic solvents, polymeric gelling agents, polyols, short chain alcohols, and silicone thickening agents. 
     
     
         20 . The composition of  claim 2 , wherein the tetracycline antibiotic is about 0.001% to about 10% by weight of the composition. 
     
     
         21 . The composition of  claim 2 , wherein the tetracycline antibiotic is about 0.025% to about 6% by weight of the composition. 
     
     
         22 . The composition of  claim 2 , wherein the carrier is essentially free of surfactant. 
     
     
         23 . The composition of  claim 2 , wherein the composition comprises less than 10% petrolatum by weight of the composition. 
     
     
         24 . The composition of  claim 2 , wherein the composition is free of petrolatum. 
     
     
         25 . The composition of  claim 12 , wherein the additional active agent is selected form the group consisting of an active herbal extract, an acaricide, an age spot and keratose removing agent, an allergen, an alpha hydroxyl acid, an analgesic agent, an androgen, an antiacne agent, an antiallergic agent, an antiaging agent, an antibacterial agent, an antibiotic, an antiburn agent, an anticancer agent, an antidandruff agent, an antidepressant, an antidermatitis agent, an antiedemic agent, an antifungal agent, an antihistamine, an antihelminth agent, an anti-hyperkeratosis agent, an anti-infective agent, an antiinflammatory agent, an antiirritant, an antilipemic agent, an antimicrobial agent, an antimycotic agent, an antioxidant, an antiparasitic agent, an antiproliferative agent, an antipruritic agent, an antipsoriatic agent, an antirosacea agent, an antiseborrheic agent, an antiseptic agent, an antiswelling agent, an antiviral agent, an anti-wart agent, an anti-wrinkle agent, an antiyeast agent, an astringent, a beta-hydroxy acid, benzoyl peroxide, a topical cardiovascular agent, a chemotherapeutic agent, a corticosteroid, an immunogenic substance, a dicarboxylic acid, a disinfectant, an estrogen, a fungicide, a hair growth regulator, a haptene, a hormone, a hydroxy acid, an immunosuppressant, an immunoregulating agent, an immunomodulator, an immunostimulant, an insecticide, an insect repellent, a keratolytic agent, a lactam, a local anesthetic agent, a lubricating agent, a masking agent, a metal, a metal oxide, a mitocide, a neuropeptide, a non-steroidal anti-inflammatory agent, an oxidizing agent, a pediculicide, a peptide, a pesticide, a protein, a photodynamic therapy agent, a progesterone, a radical scavenger, a refatting agent, a retinoid, a sanative, a scabicide, a sedative, a self tanning agent, a skin protective agent, a skin whitening agent, a steroid, a steroid hormone, a vasoactive agent, a vasoconstrictor, a vasodilator, a vitamin, a vitamin A, a vitamin A derivative, a vitamin B, a vitamin B derivative, a vitamin C, a vitamin C derivative, a vitamin D, a vitamin D derivative, a vitamin D analog, a vitamin F, a vitamin F derivative, a vitamin K, a vitamin K derivative, a wound healing agent, a wart remover, and mixtures of any two or more thereof. 
     
     
         26 . The composition of  claim 2 , wherein the composition is in the form of a gel and wherein the gel liquefies and spreads upon application of shear force. 
     
     
         27 . The composition of  claim 5 , wherein the weight ratio of composition other than propellant to propellant is from 100:1 to 100:25. 
     
     
         28 . The composition of  claim 5 , wherein the propellant comprises a liquefied or compressed gas propellant and or wherein the propellant is selected form the group consisting of butane, propane, isobutene, a fluorocarbon, and mixtures of any two or more thereof. 
     
     
         29 . The composition of  claim 12 , wherein the composition is capable of inhibiting the growth of one or more of  streptococcus pyogenes, pseudomonas aeruginosa, staphylococcus aureus , methicillin-resistant strain of  staphylococcus aureus  (MRSA), and  propionbacterium acnes.    
     
     
         30 . The composition of  claim 2 , wherein the composition has an Aw value selected from the ranges of (1) about 0.8 and about 0.9; (2) about 0.7 and about 0.8; and (3) less than about 0.7. 
     
     
         31 . The composition of  claim 2 , wherein the tetracycline antibiotic is present in a crystalline form. 
     
     
         32 . The composition of  claim 14 , wherein the triglyceride oil comprises capric/caprylic triglycerides. 
     
     
         33 . The composition of  claim 31 , wherein the liquid oil is about 15% to about 34% by weight of the carrier. 
     
     
         34 . The composition of  claim 2 , wherein the tetracycline antibiotic is about 0.2% to about 20% by weight of the composition. 
     
     
         35 . The composition of  claim 2 , wherein the carrier is free of surfactant. 
     
     
         36 . A method of treating or alleviating the symptoms of a dermatological, an opthalmological, a gynecological, or mucosal disorder, comprising: applying to a target area a composition of  claim 1 , wherein the disorder includes at least one etiological factor selected from the group consisting of an infection, an inflammation, oxidative stress, neurodegeneration, and apoptosis. 
     
     
         37 . The method of  claim 36 , wherein the dermatological disorder is selected from the group consisting of an abscess, acne, acne conglobata, acne fulminans, acne vulgaris, acne scars, acute febrile neutrophilic dermatosis, acute lymphangitis, allergic contact dermatitis, alopecia, athlete's foot, atopic dermatitis, bacterial skin infections, bullous pemphigoid, burn, calluses candidiasis, carbuncles, cellulitis, chemical burns, chicken pox, cholinergic urticaria, chronic effects of sunlight, comedones, corns, creeping eruption, cutaneous abscess, cutaneous myiasis, delusional parasitosis, dermatitis, dermatitis herpetiformis, dermatological inflammation, dermatophytoses, drug eruptions and reactions, dyshidrotic eczema, eczema, epidermoid cyst, epidermal necrolysis, exfoliative dermatitis, erythema multiforme, folliculitis, fungal nail infections, fungal skin infections, furuncles, gangrene, genital herpes, head lice, impetigo, inflammatory acne, ingrown nails, intertrigo, irritant contact dermatitis, ischemic necrosis, itching, jock itch, Kaposi's sarcoma, molluscum contagiosum, MRSA, necrotizing subcutaneous infection, necrotizing fasciitis, necrotizing myositis, nodular papulopustular acne, non-inflammatory acne, nummular dermatitis, parapsoriasis paronychia, parasitic skin infections, pemphigus, photo-allergy, photo-damage, photo-irritation, photosensitivity, papules, pediculosis, perioral dermatitis, pimples, pityriasis rosea, pityriasis rosea, pityriasis rubra pilaris, poison ivy, post-operative or post-surgical skin conditions, pressure ulcers, pressure urticaria, pruritis, pseudofolliculitis barbae, psoriasis, pustules, rosacea, scabies, scarring, scleroderma, sebaceous cyst, seborrheic dermatitis, seborrheic keratosis, shingles, skin aging, skin rash, skin ulcers, staphylococcal scalded skin syndrome, sunburn, thermal burns, tinea corporis, tinea cruris, tinea pedis, tinea versicolor, toxic epidermal necrolysis, trauma or injury to the skin, varicella zoster virus, viral skin infections, wrinkles, and yeast skin infections; wherein the gynecological or mucosal disorder is selected from the group consisting of a disorder of a body cavity or mucosal surface, a disorder of the nose, mouth, eye, ear, respiratory system, vagina, urethra, or rectum, chlamydia infection, gonorrhea infection, herpes, human papillomavirus (HPV), genital warts, bacterial vaginosis, candidiasis, molluscum contagiosum, nongonococcal urethritis (NGU), trichomoniasis, vulvodynia, yeast infection, pelvic inflammation, anal abscess/fistula, anal fissure, and hemorrhoids; and wherein the opthalmological disorder is selected from the group consisting of an eye infection, an eye redness, eyelid problems, ophthalmic allergy, blepharitis, corneal abrasion, corneal edema, corneal ulcer, conjunctivitis, contact lens complications, dry eye, eyelid cellulitis, glaucoma, macular degeneration, macular edema, ocular cicatricial pemphigoid, obstructed tear duct, ocular rosacea, optic neuritis, orbital cellulitis, recurrent corneal erosion, trachoma, and uveitis. 
     
     
         38 . The method of  claim 37 , wherein the disorder is acne and or rosacea, the tetracycline is aminocycline, and the gelled oil is a gelled mineral oil. 
     
     
         39 . A method of treating or alleviating the symptoms of acne and or rosacea, comprising applying to a target area a topical composition comprising:
 a) aminocycline; and   b) about 60% to about 95% by weight of a hydrophobic carrier comprising a gelled mineral oil;   wherein less than 10% of the minocycline breaks down over a period of at least six months at 25° C.;   wherein the topical composition is essentially waterless;   wherein the minocycline is suspended or partially suspended in the composition;   wherein the composition does not contain one or more of a substance selected from the group consisting of dimethyl sulfoxide (DMSO), dimethylformamide (DMF), acetonitrile, acetone, methyl ethyl ketone, 1,4-dioxane, tetrahydrofuran (THF), N-methylpyrrolidone, pyridine, piperidine, dimethylformamide, N-methyl-2-pyrrlidone and 1-methyl-2-pyrrlidinone), azone (1-dodecylazacycloheptan-2-one), dimethyl isosorbide, glycerin, ethanol, propylene glycol, butylene glycol, PEG 200, hexylene glycol, PEG 400, diethylene glycol monoethyl ether, pomegranate seed oil, isostearic acid, and ethocel; and   wherein the topical composition is free of or contains less than 0.1% by weight of a surfactant.