# US 2014/0193502 A1 · Foam Prepared From Nanoemulsions And Uses

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- Number: US 2014/0193502 A1
- Document ID: US20140193502A1
- Status: Published application
- Kind: A1
- Application number: 14/172,466
- Filed: 2014-02-04
- Published: 2014-07-10
- Earliest claimed: 2002-10-25
- Assignees: Foamix Ltd.
- Applicants: Foamix Ltd.
- Inventors: Dov Tamarkin; Alex Besonov; Meir Eini; Jorge Danziger
- Web page: https://patentgrep.com/patent/US20140193502A1

## CPC

- A61K 9/122: {Foams; Dry foams (edible foams A61K9/0056)}
- A01N 25/16: Foams
- A61K 8/046: {Aerosols; Foams}
- A61K 8/06: Emulsions
- A61K 8/062: {Oil-in-water emulsions}
- A61K 8/068: {Microemulsions}
- A61K 8/342: {Alcohols having more than seven atoms in an unbroken chain}
- A61K 8/375: {the alcohol moiety containing more than one hydroxy group}
- A61K 8/39: Derivatives containing from 2 to 10 oxyalkylene groups
- A61K 8/498: {having 6-membered rings or their condensed derivatives, e.g. coumarin}
- A61K 8/4993: {Derivatives containing from 2 to 10 oxyalkylene groups}
- A61K 8/602: {Glycosides, e.g. rutin}
- A61K 8/73: Polysaccharides
- A61K 8/731: {Cellulose; Quaternized cellulose derivatives}
- A61K 8/737: {Galactomannans, e.g. guar; Derivatives thereof}
- A61K 8/8141: {Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers}
- A61K 8/8147: {Homopolymers or copolymers of acids; Metal or ammonium salts thereof, e.g. crotonic acid, (meth)acrylic acid; Compositions of derivatives of such polymers}
- A61K 8/86: Polyethers
- A61K 8/87: Polyurethanes
- 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)}
- A61K 9/1075: {Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence)}
- A61K 47/06: Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61K 47/18: Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- 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
- A61K 47/38: Cellulose; Derivatives thereof
- A61Q 19/00: Preparations for care of the skin
- A61K 2800/21: Emulsions characterized by droplet sizes below 1 micron
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS

## Abstract

The present invention provides a foamable composition for administration to the skin, body surface, body cavity or mucosal surface, e.g., the mucosa of the nose, mouth, eye, ear, respiratory system, vagina or rectum, and methods of using such a composition to treat, alleviate, or prevent a disorder of the skin, body cavity, or mucosal surface. The foamable oil in water nano emulsion composition includes: (a) a nano oil globule system, comprising substantially of sub-micron oil globules; (b) about 0.1% to about 5% by weight of at least one stabilizing agent selected from (i) a non-ionic surfactant, (ii) an ionic surfactant, or (iii) a polymeric agent; and (c) a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition, water and optional ingredients. Upon release from an aerosol container, the foamable composition forms and expanded foam suitable for topical administration.

## Claims

### Claim 1

A foamable oil in water nano emulsion composition comprising:
(a) a nano oil globule system, comprising substantially of sub-micron oil globules;
(b) about 0.1% to about 5% by weight of at least one stabilizing agent, selected from the group consisting of
i. a non-ionic surfactant,
ii. an ionic surfactant, and
iii. a polymeric agent;
(c) water; and
(d) a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition
wherein the oil, stabilizer and water are selected to provide a composition that is substantially homogenous and resistant to aging;
wherein the composition is contained in a pressurized container is substantially flowable and provides a breakable foam upon release, which is thermally stable, yet breaks under sheer force; and
wherein the bubble size of the resultant foam is significantly greater than the bubble size of the resultant foam from a composition with the same ingredients which has not been subject to nano processing.

### Claim 2 (depends on 1)

The foamable composition of claim 1, wherein the oil globule system consists of oil globules with an average diameter size in the range of about 1000 nanometers to about 10 nanometers; and the stabilizing agent consists of a polymeric agent.

### Claim 3 (depends on 2)

The foamable composition of claim 2, further comprising a non-ionic surfactant having an HLB value between 9 and 16; and/or an ionic surfactant.

### Claim 4 (depends on 1)

The foamable composition of claim 1, wherein:
i. the oil globule system consists of sub-micron oil globules; and
ii. the stabilizing agent consists of a surfactant, having an HLB value or a mean HLB value between 9 and 16.

### Claim 5 (depends on 1)

The foamable composition of claim 1 wherein the ratio of the surfactant to oil is high being in the range of the order of about 1:1 to about 1:10

### Claim 6 (depends on 1)

The foamable composition of claim 1, wherein the sub-micron oil globules contain at least one organic carrier selected from the group consisting of a hydrophobic organic carrier, a polar solvent, an emollient and mixtures thereof.

### Claim 7 (depends on 1)

The foamable composition of claim 1, wherein said submicron oil globules are about 50% to about 100% of the composition.

### Claim 8 (depends on 1)

The foamable composition of claim 1, wherein the sub-micron oil globules have a number-average size range, selected from (i) 40 nm to 1,000 nm. (ii) 40 nm to 500 nm; (iii) 40 nm to 200 nm; (iv) 40 nm to 100 nm (v) less than 500 nm; (vi) less than 200 nm; and (vii) less than 100 nm.

### Claim 9 (depends on 1)

The foamable composition of claim 1, further comprising about 0.1% to about 5% by weight of a foam adjuvant 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; and a fatty acid substituted with a hydroxyl group and mixtures thereof.

### Claim 10 (depends on 1)

The foamable composition of claim 1, wherein said foamable composition is substantially alcohol-free.

### Claim 11 (depends on 1)

The foamable composition of claim 1, further containing at least one therapeutic agent.

### Claim 12 (depends on 11)

The foamable composition of claim 11, wherein the therapeutic agent is selected from the group consisting of an anti-infective, an antibiotic, an antibacterial agent, an antifungal agent, an antiviral agent, an antiparasitic agent, an steroidal antiinflammatory agent, an immunosuppressive agent, an immunomodulator, an immunoregulating agent, a hormonal agent, vitamin A, a vitamin A derivative, vitamin B, a vitamin B derivative, vitamin C, a vitamin C derivative, vitamin D, a vitamin D derivative, vitamin E, a vitamin E derivative, vitamin F, a vitamin F derivative, vitamin K, a vitamin K derivative, a wound healing agent, a disinfectant, an anesthetic, an antiallergic agent, an alpha hydroxyl acid, lactic acid, glycolic acid, a beta-hydroxy acid, a protein, a peptide, a neuropeptide, a allergen, an immunogenic substance, a haptene, an oxidizing agent, an antioxidant, a dicarboxylic acid, azelaic acid, sebacic acid, adipic acid, fumaric acid, a retinoid, an antiproliferative agent, an anticancer agent, a photodynamic therapy agent, an anti-wrinkle agent, a radical scavenger, a metal oxide (e.g., titanium dioxide, zinc oxide, zirconium oxide, iron oxide), silicone oxide, an anti wrinkle agent, a skin whitening agent, a skin protective agent, a masking agent, an anti-wart agent, a refatting agent, a lubricating agent and mixtures thereof.

### Claim 13 (depends on 12)

The foamable composition of claim 12, wherein the therapeutic agent is suitable to treat a disorder, selected from a dermatological disorder, a cosmetic disorder, a gynecological disorder, a disorder of a body cavity, wound and burn.

### Claim 14 (depends on 1)

The foamable composition of claim 1, wherein the HLB or mean HLB value of said non-ionic surfactant is between about 2 and about 9.

### Claim 15 (depends on 1)

The foamable composition of claim 1, wherein the stabilizing agent is a polymeric agent selected from the group consisting of a water-soluble cellulose ether naturally-occurring polymeric material, microcrystalline cellulose, hydrophobically-modified ethoxylated urethane, and a carbomer and wherein said water-soluble cellulose ether is selected from the group consisting of methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose (Methocel), hydroxyethyl cellulose, methylhydroxyethylcellulose, methylhydroxypropylcellulose, hydroxyethylcarboxymethylcellulose, carboxymethylcellulose, carboxymethylhydroxyethylcellulose, xanthan gum, guar gum, carrageenin gum, locust bean gum and tragacanth gum.

### Claim 16 (depends on 1)

The foamable composition of claim 1, wherein surfactant is selected from the group consisting of steareth 2, steareth 21, ceteth-20, span 80, behenyl alcohol, glyceryl monostearate, PEG 40 stearate, polyoxyl 100 monostearate, methyl glucose seasquit stearate and polysorbate 80.

### Claim 17 (depends on 1)

The foamable composition of claim 1, wherein the density of the foam is selected from the group consisting of (1) less than 0.12 g/mL; (2) the range between 0.02 and 0.12; (3) the range between 0.04 and 0.10; (4) the range between 0.06 and 0.10.

### Claim 18

A foamable oil in water nano emulsion composition comprising:
(a) a nano oil globule system, comprising substantially of sub-micron oil globules;
(b) about 0.1% to about 5% by weight of at least one stabilizing agent, selected from the group consisting of
i. a non-ionic surfactant,
ii. an ionic surfactant, and
iii. a polymeric agent; and
(c) water;
wherein the oil, stabilizer and water are selected to provide a composition that is substantially homogenous and resistant to aging;
wherein the composition prior to addition of propellant is translucent with a blue tint;
wherein if the composition is contained in a pressurized container and further comprises a liquefied hydrocarbon gas propellant at a concentration of about 3% to about 35% by weight of the total composition it is substantially flowable and provides a breakable foam upon release, which is thermally stable, yet breaks under sheer force; and
wherein the bubble size of the resultant foam is significantly greater than the bubble size of the resultant foam from a composition with the same ingredients which has not been subject to nano processing.

### Claim 19

A method of promoting the penetration of an active agent into the surface layers of the skin and mucosal membranes, comprising: apply a foamable composition to the surface layers of a stem or mucosal membrane, the foamable composition comprising:
(a) a nano oil globule system, comprising substantially of sub-micron oil globules;
(b) about 0.1% to about 5% by weight of at least one stabilizing agent, selected from the group consisting of
i. a non-ionic surfactant,
ii. an ionic surfactant, and
iii. a polymeric agent; and
(c) water;
wherein the oil, stabilizer and water are selected to provide a composition that is substantially homogenous and resistant to aging;
wherein the composition prior to addition of propellant is translucent with a blue tint;
wherein if the composition is contained in a pressurized container and further comprises a liquefied hydrocarbon gas propellant at a concentration of about 3% to about 35% by weight of the total composition it is substantially flowable and provides a breakable foam upon release, which is thermally stable, yet breaks under sheer force; and
wherein the bubble size of the resultant foam is significantly greater than the bubble size of the resultant foam from a composition with the same ingredients which has not been subject to nano processing.

### Claim 20 (depends on 19)

The method of claim 19, wherein the active agent is selected from the group consisting of an anti-infective, an antibiotic, an antibacterial agent, an antifungal agent, an antiviral agent, an antiparasitic agent, an steroidal antiinflammatory agent, an immunosuppressive agent, an immunomodulator, an immunoregulating agent, a hormonal agent, vitamin A, a vitamin A derivative, vitamin B, a vitamin B derivative, vitamin C, a vitamin C derivative, vitamin D, a vitamin D derivative, vitamin E, a vitamin E derivative, vitamin F, a vitamin F derivative, vitamin K, a vitamin K derivative, a wound healing agent, a disinfectant, an anesthetic, an antiallergic agent, an alpha hydroxyl acid, lactic acid, glycolic acid, a beta-hydroxy acid, a protein, a peptide, a neuropeptide, a allergen, an immunogenic substance, a haptene, an oxidizing agent, an antioxidant, a dicarboxylic acid, azelaic acid, sebacic acid, adipic acid, fumaric acid, a retinoid, an antiproliferative agent, an anticancer agent, a photodynamic therapy agent, an anti-wrinkle agent, a radical scavenger, a metal oxide (e.g., titanium dioxide, zinc oxide, zirconium oxide, iron oxide), silicone oxide, an anti wrinkle agent, a skin whitening agent, a skin protective agent, a masking agent, an anti-wart agent and a refatting agent.