Body cavity foams

• US 8,840,869 B2
• Filed: 04/28/2005
• Issued: 09/23/2014
• Est. Priority Date: 10/25/2002
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Friedman, Doron, Besonov, Alex, Tamarkin, Dov, Eini, Meir
• Primary Examiner(s): ZISKA, SUZANNE E
• Application Number:
  US11/116,761
• Publication Number:
  US 20050271598A1
• Time in Patent Office: 3,435 Days
• Field of Search: 424/47
• US Class Current: 424/47
• CPC Class Codes: A01N 25/16 Foams
• CPC Class Codes: A61K 2800/24 Thermal properties
• CPC Class Codes: A61K 2800/242 Exothermic; Self-heating; Heating sensation
• CPC Class Codes: A61K 2800/244 Endothermic; Cooling; Cooling sensation
• CPC Class Codes: A61K 2800/30 Characterized by the absence of a particular group of ingredients
• CPC Class Codes: A61K 2800/75 Anti-irritant
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/351 not condensed with another ring
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/4174 Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/535 having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
• CPC Class Codes: A61K 31/567 substituted in position 17 alpha, e.g. mestranol, norethandrolone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/212 IFN-alpha
• CPC Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• 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 47/20 : containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• 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 47/34 : 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 47/38 : Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/46 : Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
• CPC Class Codes: A61K 8/046 : Aerosols; Foams
• CPC Class Codes: A61K 8/34 : Alcohols
• CPC Class Codes: A61K 8/345 : containing more than one hydroxy group
• CPC Class Codes: A61K 8/362 : Polycarboxylic acids
• CPC Class Codes: A61K 8/37 : Esters of carboxylic acids
• CPC Class Codes: A61K 8/42 : Amides
• CPC Class Codes: A61K 8/4993 : Derivatives containing from 2 to 10 oxyalkylene groups
• CPC Class Codes: A61K 8/60 : Sugars; Derivatives thereof
• CPC Class Codes: A61K 8/731 : Cellulose; Quaternized cellulose derivatives
• CPC Class Codes: A61K 8/736 : Chitin; Chitosan; Derivatives thereof
• CPC Class Codes: A61K 8/8152 : Homopolymers or copolymers of esters, e.g. (meth)acrylic acid esters; Compositions of derivatives of such polymers
• CPC Class Codes: A61K 8/8158 : Homopolymers or copolymers of amides or imides, e.g. (meth) acrylamide; Compositions of derivatives of such polymers
• CPC Class Codes: A61K 8/86 : Polyethers
• CPC Class Codes: A61K 8/87 : Polyurethanes
• CPC Class Codes: A61K 8/922 : of vegetable origin
• CPC Class Codes: A61K 9/0007 : Effervescent A61K9/0065 takes precedence
• 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 9/0034 : 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 1/00 : Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 17/00 : Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/14 : for baldness or alopecia
• CPC Class Codes: A61P 17/16 : Emollients or protectives, e.g. against radiation
• CPC Class Codes: A61P 23/00 : Anaesthetics
• 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 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• 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: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61Q 17/02 : containing insect repellants
• CPC Class Codes: A61Q 17/04 : Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin
• CPC Class Codes: A61Q 19/007 : Preparations for dry skin
• CPC Class Codes: A61Q 19/02 : for chemically bleaching or whitening the skin
• CPC Class Codes: A61Q 19/04 : for chemically tanning the skin topical sun or radiation screening or tanning preparations A61Q17/04
• CPC Class Codes: A61Q 19/08 : Anti-ageing preparations
• CPC Class Codes: A61Q 7/00 : Preparations for affecting hair growth
• CPC Class Codes: A61Q 7/02 : Preparations for inhibiting or slowing hair growth

Abstract

The invention relates to an alcohol-free cosmetic or therapeutic foam carrier comprising water, a hydrophobic organic carrier, a foam adjuvant agent, a surface-active agent and a gelling agent. The cosmetic or therapeutic foam carrier does not contain aliphatic alcohols, making it non-irritating and non-drying. The alcohol-free foam carrier is suitable for inclusion of both water-soluble and oil soluble therapeutic and cosmetic agents.

Claims

1. A device for administration of a foamable composition into a body cavity, comprising an aerosol container, a valve, an insert applicator and a foamable composition for application into said body cavity, which upon release from said aerosol container provides an expanded foam suitable for topical administration;

wherein the foamable composition comprises a propellant and a therapeutic composition being substantially free of lower alcohols wherein the therapeutic composition comprises;

at least one organic carrier selected from a hydrophobic organic carrier, an emollient, a polar solvent, and mixtures thereof, at a concentration of about 70% to about 99% by weight of the therapeutic composition;

at least one surface active agent at a concentration of about 0.2% to about 5% by weight of the therapeutic composition;

at least one active agent; and

at least one polymeric gelling agent at a concentration of about 0.01% to about 5% by weight of the therapeutic composition;

wherein the propellant is a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the foamable composition;

wherein the surface active agent is a non-ionic surface active agent or a mixture of at least one non ionic surface active agent and at least one ionic surface active agent in a ratio of about 20;

1 or greater than 20;

1.

wherein upon release from the container the composition forms a breakable foam that collapses upon application of shear force; and

wherein the breakable foam stays stable as a foam for at least about 3 minutes at about 37°

C. after being dispensed from the container.

2. The device of claim 1, wherein the valve is a metered dose valve and the metered dose is adjusted to afford a dose between about 10 μ

L and about 1000 μ

L.

3. The device of claim 1, wherein the valve is a metered dose valve and the metered dose is adjusted to afford a final volume of foam between about 0.17 mL and about 17 mL.

4. The device of claim 1, wherein the thickness of said insert applicator is selected from the group consisting of (1) between about 0.2 cm and about 0.4 cm;

(2) between about 0.4 cm and about 0.8 cm; and

(3) between about 0.8 cm and about 1 cm.

5. The device of claim 1, wherein the length of said insert applicator is between about 1 cm and about 20 cm.

6. The device of claim 1, wherein the thickness and length of said insert applicator are designed to match the dimensions of the target body cavity.

7. The device of claim 1, wherein the body cavity is selected from the group consisting of cranial cavity, the thoracic cavity, the abdominal cavity, the ventral cavity, the vagina, the rectum cavity, the penile cavity, the urinary tract, bladder, the cavity between the uterus and the fallopian tubes, the ovaries, the nasal cavity, the mouth, the eye, the ear, the peritoneum, the large and small bowel, the caecum, bladder, stomach, and other body cavities or spaces, which may accept topically-applied products.

8. The device of claim 1, wherein the gelling agent is selected from the group consisting of a locust bean gum, sodium alginate, sodium caseinate, egg albumin, a gelatin agar, a carrageenin gum, a xanthan gum, a quince seed extract, a tragacanth gum, a guar gum, a starch, a chemically modified starch, cellulose ethers, a hydroxyethyl cellulose, a methyl cellulose, a carboxymethyl cellulose, a hydroxy propylmethyl cellulose, a hydroxypropyl guar gum, a soluble starch, cationic celluloses, cationic guars, carboxyvinyl polymers, a polyvinylpyrrolidone, a polyvinyl alcohol, polyacrylic acid polymers, polymethacrylic acid polymers, polyvinyl acetate polymers, polyvinyl chloride polymers, polyvinylidene chloride polymers, acrylic acid/ethyl acrylate copolymers, carboxyvinyl polymers, a carbopol and mixtures thereof.

9. The device of claim 1, wherein the foamable composition further includes about 0.1% to about 5% by weight of a therapeutically active foam adjuvant is selected from the group consisting of a fatty alcohol having 15 or more carbons in their carbon chain;

a fatty acid having 16 or more carbons in their carbon chain;

fatty alcohols, derived from beeswax and including a mixture of alcohols, a majority of which has at least 20 carbon atoms in their carbon chain;

a fatty alcohol having at least one double bond;

a fatty acid having at least one double bond;

a branched fatty alcohol;

a branched fatty acid;

a fatty acid substituted with a hydroxyl group;

cetyl alcohol;

stearyl alcohol;

arachidyl alcohol;

behenyl alcohol;

1-triacontanol;

hexadecanoic acid;

stearic acid;

arachidic acid;

behenic acid;

octacosanoic acid;

12-hydroxy stearic acid and mixtures thereof.

10. The device of claim 1, wherein the organic carrier comprises a mixture of mineral oil and an emollient in a ratio between 1:

4 and 4;

1 on a weight basis.

11. The device of claim 1, wherein the surface active agent is selected from a non ionic surfactant, a cationic surfactant, an amphoteric surface active agent and an ionic surface active agent.

12. The device of claim 11, wherein the surface active agent is non-ionic.

13. The device of claim 1, wherein the surface active agent is a non-ionic surface active agent in a concentration of below 1% by weight of the therapeutic composition.

14. The device of claim 9, wherein the combined amount of foam adjuvant, surface active agent and gelling agent is less than about 8% by weight of the therapeutic composition.

15. The device of claim 9, wherein the combined amount of foam adjuvant, surface active agent and gelling agent is less than about 5% by weight of the therapeutic composition.

16. The device of claim 1, wherein the active agent is selected for the treatment of a disease or disorder, wherein the etiology of the disease is bacterial, fungal, viral, parasitic, inflammatory, autoimmune, allergic, hormonal, malignant, and combinations thereof or wherein the disorder is selected from of inflammation, bacterial infections, fungal infections, parasitic infections, viral infections, benign tumors, malignant tumors, pain, itch, allergy, dryness, wound, cut, a tissue adhesion abnormality, a hormonal abnormality, chlamydia infection, gonorrhea infection, hepatitis B, herpes, a neoplasm, a benign tumor, HIV/AIDS, human papillomavirus (HPV), genital warts, bacterial vaginosis, candidiasis, chancroid, granuloma Inguinale, lymphogranloma 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, post-surgical adhesions, disorders that respond to hormone therapy and birth control.

17. The device of claim 1, wherein the active agent is selected for the treatment of a mucosal disorder, a vaginal disorder, a vulvar disorder, an anal disorder, the vagina, the rectum and penile cavities, the urinary tract, bladder, the cavity between the uterus and the fallopian tubes, the ovaries, a disorder of the respiratory system, or post- surgical adhesion.

18. The device of claim 1, wherein the active agent is selected from the group consisting of antibacterial agents, anti-parasitic agents, antifungal agents, antiviral agents, steroidal anti-inflammatory agents, non-steroidal immunomodulating agents, immunosuppressants, anti-allergic agents, anticancer agents, hormones, androgens, estrogens, progesterones, contraceptive agents, retinoids, vitamin A, vitamin B, vitamin D, local anesthetic agents, lubricating agents and immunizing agents.

19. The device of claim 1, wherein the composition further comprises an active agent selected from the group consisting of negatively charged sulfated polymers, hyaluronic acid, dextrin sulphate, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, carrageenans, naphthalene sulfonate polymer, sodium alginate, a cationic polymer, and chitosan.

20. The device of claim 1, wherein the active agent is intended for trans-mucosal delivery.

21. The device of claim 20, wherein the active agent is intended for the treatment of a systemic disease, which responds to administration of the active agent.

22. The device of claim 1, wherein the oleaginous foamable composition contains more than 50% of a potent solvent.

23. The device of claim 22, wherein the potent solvent is selected from polyethylene glycol, propylene glycol, hexylene glycol, butane-diol and isomers thereof, glycerol, benzyl alcohol, DMSO, ethyl oleate, ethyl caprylate, dimethylacetamide, N-methylpyrrolidone, N-hydroxyethylpyrrolidone, polyvinylpyrrolidone, isosorbide derivatives, dimethyl isosorbide, glycofurol and ethoxydiglycol (transcutol).

24. The device of claim 1, wherein the body cavity is selected from the group consisting of cranial cavity, the thoracic cavity, the abdominal cavity, the ventral cavity, the vagina, the rectum cavity the penile cavity, the urinary tract, bladder, the cavity between the uterus and the fallopian tubes, the ovaries, the nasal cavity, the mouth, the eye, the ear, the peritoneum, the large and small bowel, the caecum, bladder, stomach, and other body cavities or spaces which may accept topically-applied products.

25. The device of claim 8, wherein the gelling agent comprises a bioadhesive agent.

26. The device of claim 16, wherein the etiology of the disease is selected from the group consisting of a viral infection, human papillomavirus (HPV), genital warts, genital cancer, cancer of the cervix, cancer of the vulva, cancer of the vagina, anal cancer, anal fissure, and anal warts;

and the active agent is selected from the group consisting of antiviral agents and non-steroidal immunomodulating agents.

27. The device of claim 1, wherein the foamable composition comprises less than about 2% of one or more lower alcohols by weight of the therapeutic composition.

28. The device of claim 1, wherein the foamable composition comprises less than about 1% of one or more lower alcohols by weight of the therapeutic composition.

29. The device of claim 1, wherein the gelling agent is a mucoadhesive agent.

30. The device of claim 1, further comprising a mucoadhesive agent selected from the group consisting of acidic synthetic polymers, a poly(acrylic)- and/or poly(methacrylic) acid, a poly(methylvinyl ether/maleic anhydride) copolymer, acidic synthetically modified natural polymers, a carboxymethylcellulose, neutral synthetically modified natural polymers, a hydroxypropylmethylcellulose, basic amine-bearing polymers, a chitosan, acidic polymers obtainable from natural sources, an alginic acid, a hyaluronic acid, pectin, a gum tragacanth, a karaya gum, neutral synthetic polymers, a polyvinyl alcohol, a cyclodextrin, a hydroxypropyl-β

-cyclodextrin, silicon dioxide and mixtures thereof.

31. The device of claim 1, wherein the foam is delivered into the body cavity with no or minimal overflow.

32. The device of claim 3, wherein the foam is delivered into the body cavity with no or minimal overflow.

33. The device of claim 1, wherein the device is adapted to provide a metered dose and the foam is delivered into the body cavity with no or minimal overflow.

34. The device of claim 1, wherein the device is adapted to provide a metered dose of a size suitable for the target body cavity and wherein the foam is deliverable into the body cavity with no or minimal overflow.

35. The device of claim 1, wherein the foam provides no or low irritation to the body cavity.

36. The device of claim 1, wherein the foam expands in the cavity.

37. The device of claim 1, wherein the foam provides no or low itching or itching potential to the body cavity surface.

38. The device of claim 1, wherein the foam can be retained in the body cavity for at least fifteen minutes after administration.