# US 10,946,101 B2 · Surfactant-free water-free foamable compositions, breakable foams and gels and their uses

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- Number: US 10,946,101 B2
- Document ID: US10946101B2
- Status: Granted
- Kind: B2
- Application number: 16/235,986
- Filed: 2018-12-28
- Published: 2019-05-09
- Granted: 2021-03-16
- Earliest claimed: 2009-10-02
- Assignees: Vyne Therapeutics Inc.
- Applicants: Vyne Pharmaceuticals Ltd.
- Inventors: Dov Tamarkin; Elana Gazal; Irakliy Papiashvili; Yohan Hazot; David Schuz; Rita Keynan
- Web page: https://patentgrep.com/patent/US10946101B2

## CPC

- A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14)
- A61K 8/31: Hydrocarbons
- A61K 8/342: {Alcohols having more than seven atoms in an unbroken chain}
- A61K 8/361: {Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof}
- 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 9/0048: {Eye, e.g. artificial tears}
- A61K 9/12: Aerosols; Foams {(A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015)}
- A61K 9/122: {Foams; Dry foams (edible foams A61K9/0056)}
- A61K 9/124: {characterised by the propellant}
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 31/192: having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid {(cannabinoids A61K31/658)}
- A61K 31/4164: 1,3-Diazoles
- A61K 31/57: substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 31/593: 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
- A61K 31/65: Tetracyclines
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/02: Inorganic compounds
- 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 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 5/00: Drugs for disorders of the endocrine system
- A61P 7/10: Antioedematous agents; Diuretics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/08: Vasodilators for multiple indications
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 15/02: for disorders of the vagina
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 17/04: Antipruritics
- A61P 17/06: Antipsoriatics
- A61P 17/08: Antiseborrheics
- A61P 17/10: Anti-acne agents
- A61P 17/12: Keratolytics, e.g. wart or anti-corn preparations
- A61P 17/14: for baldness or alopecia
- A61P 17/16: Emollients or protectives, e.g. against radiation
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 23/00: Anaesthetics
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/24: Antidepressants
- A61P 27/02: Ophthalmic agents
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 31/10: Antimycotics
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/18: for HIV
- A61P 31/20: for DNA viruses
- A61P 31/22: for herpes viruses
- A61P 33/00: Antiparasitic agents
- A61P 33/10: Anthelmintics
- A61P 33/14: Ectoparasiticides, e.g. scabicides
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 39/06: Free radical scavengers or antioxidants
- A61Q 17/04: Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
- A61Q 19/00: Preparations for care of the skin
- A61Q 19/10: Washing or bathing preparations
- A61K 2800/31: Anhydrous
- A61K 2800/33: Free of surfactant
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS

## 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.

## Claims

### Claim 1

A method of treating rosacea, consisting of administering a surfactant free foam composition, obtained from a foamable composition dispensed from a container, to a subject in need thereof, wherein the foamable composition consists of:
i) a carrier consisting of:
a) about 60% to about 95% by weight of the carrier of a hydrophobic solvent;
b) about 0.1% to about 20% by weight of the carrier of at least one fatty alcohol, wherein the fatty alcohol has a carbon chain length of 14 to 22 carbons;
c) about 0.1% to about 20% by weight of the carrier of at least one fatty acid, at least one wax, at least one shea butter, or mixtures of two or more thereof, wherein the fatty acid has a carbon chain length of 12 to 28 carbons, and the wax is selected from the group consisting of a beeswax, a hydrogenated castor oil, a paraffin wax, a wax that is solid at room temperature, and a mixture of any two or more thereof; and
d) one active agent, wherein the one active agent is minocycline or a salt thereof; and
ii) a liquefied or compressed gas propellant;
wherein the foamable composition comprises 15% or less of petrolatum by weight of the carrier;
wherein the foamable composition is essentially waterless;
wherein the foamable composition is free of polymeric agent;
wherein, upon dispensing, the foamable composition forms a foam; and
wherein the subject in need thereof has rosacea.

### Claim 2 (depends on 1)

The method of claim 1, wherein the fatty alcohol is selected from the group consisting of stearyl alcohol, cetyl alcohol, behenyl alcohol, myristyl alcohol, and a mixture of any two or more thereof; and
wherein the hydrophobic solvent is selected from the group consisting of: an avocado oil, a calendula oil, cocoglycerides, a coconut oil, a cyclomethicone, a grape seed oil, a heavy mineral oil, a jojoba oil, a light mineral oil, medium chain triglyceride (MCT) oil, octyldodecanol, a peanut oil, a PPG-15 stearyl ether, a soybean oil, a wheat germ oil, and a mixture of any two or more thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the hydrophobic solvent is selected from the group consisting of an avocado oil, a calendula oil, cocoglycerides, a coconut oil, a cyclomethicone, a grape seed oil, a heavy mineral oil, a jojoba oil, a light mineral oil, medium chain triglyceride (MCT) oil, octyldodecanol, a peanut oil, a PPG-15 stearyl ether, a soybean oil, a wheat germ oil, and a mixture of any two or more thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein the fatty acid comprises stearic acid.

### Claim 5 (depends on 1)

The method of claim 1, wherein the foamable composition comprises at least one fatty alcohol and at least one wax, or at least one fatty alcohol and at least one fatty acid, or at least one fatty alcohol, at least one fatty acid, and at least one wax.

### Claim 6 (depends on 1)

The method of claim 1, wherein the wax comprises a combination of a beeswax and a hydrogenated castor oil, wherein the ratio of beeswax to hydrogenated castor oil is between about 1:1 and about 5:1.

### Claim 7 (depends on 1)

The method of claim 1, wherein the ratio of fatty alcohol to wax is between about 4:1 and about 1:4.

### Claim 8 (depends on 1)

The method of claim 1, wherein the foamable composition is free of short chain alcohols.

### Claim 9 (depends on 1)

The method of claim 1, wherein the hydrophobic solvent is a liquid oil.

### Claim 10 (depends on 1)

The method of claim 1, wherein the foamable composition comprises about 10% or less of petrolatum by weight of the carrier.

### Claim 11 (depends on 1)

The method of claim 1, wherein the foamable composition comprises a fatty acid and a fatty alcohol at a ratio of between about 1:10 and about 10:1.

### Claim 12 (depends on 1)

The method of claim 1, wherein the fatty alcohol comprises stearyl alcohol, cetyl alcohol, or both.

### Claim 13 (depends on 1)

The method of claim 1, wherein the fatty alcohol comprises one or more of stearyl alcohol, cetyl alcohol, behenyl alcohol, or myristyl alcohol.

### Claim 14 (depends on 1)

The method of claim 1, wherein the minocycline antibiotic is present at about 0.5% to about 6% by weight of the carrier.

### Claim 15 (depends on 1)

The method of claim 1, wherein the hydrophobic solvent is selected from the group consisting of an alexandria laurel tree oil, an almond oil, an essential oil, an unsaturated or polyunsaturated oil, an apricot stone oil, an avocado oil, a barley oil, a basil oil, a borage seed oil, a calendula oil, a camphor oil, a canelle nut tree oil, a canola oil, a cardamom oil, a carrot oil, a castor oil, a citronella oil, a clary sage oil, a clove oil, a coconut oil, a cod-liver oil, a corn oil, a cotton oil, a cottonseed oil, a cypress oil, an epoxy-modified silicone oil, an ester oil, an evening primrose oil, a fatty acid-modified silicone oil, a flaxseed oil, a fluoro group-modified silicone oil, a frankincense oil, a ginger oil, a grape seed oil, a grapefruit oil, a groundnut oil, a hazelnut oil, a heavy mineral oil, a hempseed oil, a herring oil, hydrocarbon oils, a hyssop oil, a jasmine oil, a jojoba oil, a lavender oil, a lemon oil, a light mineral oil, a lucerne oil, a maize germ oil, a maleated soybean oil, a mandarin oil, a manuka oil, a marjoram oil, a marrow oil, medium chain triglyceride (MCT) oil, a millet oil, a mineral oil, a myrrh oil, a neroli oil, a nutmeg oil, oils from animal origin, oils of plant origin, an olive oil, a palm oil, a passionflower oil, a peanut oil, a petitgrain oil, a polyether group-modified silicone oil, a poppy oil, a rapeseed oil, a rosehip oil, a rye oil, a safflower oil, a sage oil, a salmon oil, a sesame oil, a silicone oil, a soya oil, a soybean oil, a sunflower oil, a sweet almond oil, a sysymbrium oil, a syzigium aromaticum oil, a tangerine oil, a tea tree oil, unsaturated or polyunsaturated oils, a vanilla oil, a verbena oil, a walnut oil, a wheat germ oil, and a mixture of any two or more thereof.

### Claim 16 (depends on 1)

The method of claim 1, wherein the hydrophobic solvent comprises
(i) a diglyceride, capric/caprylic triglycerides, glycereth triacetate, glycerol triheptanoate, glyceryl oleate, glyceryl trioctanoate, liquid triglycerides, or a wheat germ glyceride;
(ii) a PPG alkyl ether, a PPG-10 cetyl ether, a PPG-10 oleyl ether, a PPG-11 stearyl 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-2 butyl ether, a PPG-2 methyl ether, a PPG-20 butyl ether, a PPG-20 oleyl ether, a PPG-22 butyl ether, a PPG-23 oleyl ether, a PPG-24 butyl ether, a PPG-26 butyl ether, a PPG-28 cetyl ether, a PPG-3 methyl ether, a PPG-3 myristyl ether, a PPG-30 butyl ether, a PPG-30 cetyl ether, a PPG-30 isocetyl ether, a PPG-30 oleyl ether, a PPG-33 butyl ether, a PPG-37 oleyl ether, a PPG-4 butyl ether, a PPG-4 lauryl ether, a PPG-4 myristyl ether, a PPG-40 butyl ether, a PPG-5 butyl ether, a PPG-50 cetyl ether, a PPG-50 oleyl ether, a PPG-52 butyl ether, a PPG-53 butyl ether, a PPG-7 lauryl ether, a PPG-9 butyl ether, or a PPG-9-13 butyl ether;
(iii) benzyl laurate, benzyl myristate, benzyl palmitate, bis dimer dilinoleate, butyl myristate, butyl stearate, propyl myristate, propylene glycol dicaprate, propylene glycol dicaprylate, propylene glycol myristyl ether acetate, propylene glycol ricinoleate, stearyl caprate, stearyl propionate, tocopheryl acetate, tocopheryl linoleate, triisocetyl citrate, decyl oleate, diethylhexyl adipate, diethylhexyl malate, diethylhexyl succinate, diisopropyl adipate, diisopropyl dimerate, diisopropyl sebacate, diisosteary dimer dilinoleate, diisostearyl fumerate, dioctyl malate, dioctyl sebacate, disopropyl adipate, dodecyl oleate, ester derivatives of lanolic acid, ethylhexyl hydroxystearate, ethylhexyl palmitate, ethylhexyl pelargonate, ethylhexyl stearate, hexyl laurate, isoamyl laurate, isocetyl behenate, isocetyl lanolate, isocetyl palmitate, isocetyl salicylate, isocetyl stearate, isocetyl stearoyl stearate, isodecyl oleate, isododecane, isohexadecane, isohexadecanol, isopropyl isostearate, isopropyl lanolate, isopropyl laurate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isosteary citrate, isosteary salicylate, isosteary tartarate, isostearyl behenate, isostearyl erucate, isostearyl glycolate, isostearyl isostearate, isostearyl lactate, isostearyl linoleate, isostearyl linolenate, isostearyl malate, isostearyl palmitate, lauryl lactate, myristyl lactate, myristyl myristate, myristyl propionate, neopentylglycol dicaprate, neopentylglycol dicaprylate/dicaprate, octyl palm itate, octyl stearate, octyldodecyl behenate, octyldodecyl hydroxystearate, octyldodecyl myristate, octyldodecyl stearoyl stearate, oleyl erucate, oleyl lactate, oleyl oleate, or pentaerythrityl tetrastearate;
(iv) alkyl benzoate, alkyl octanoate, C12-C15 alkyl benzoate, C12-C15 alkyl octanoate, stearyl heptanoate, tridecyl ethyl hexanoate, tridecyl isononanoate, a cetearyl ethyl hexanoate, cetearyl isononanoate, cetearyl octanoate, cetyl ethyl hexanoate, cetyl octanoate, diethyleneglycol diethylhexanoate, diethyleneglycol diisononanoate, diethyleneglycol dioctanoate, diethylhexanoate, ethylhexyl cocoate, ethylhexyl ethyl hexanoate, ethylhexyl isononanoate, isocetearyl octanoate, isodecyl ethylhexanoate, isodecyl isononanoate, isohexyl decanoate, isononyl isononanoate, isononyl octanoate, isostearyl isononanoate, isostearyl neopentanoate, isotridecyl isononanoate, or myristyl neopentanoate;
(v) a caprylyl methicone, cetyl dimethicone, stearyl dimethicone, a cyclohexasiloxane, a cyclomethicone, cyclopentasiloxane, a cyclotetrasiloxane, dimethicone, dimethyl polysiloxane, methylphenylpolysiloxane, PEG/PPG 18/18 dimethicone, phenyl trimethicone, a poly-diphenyl-siloxane copolymer, a polyalkyl siloxane, a polyalkylaryl siloxane, a polyaryl siloxane, or a polyether siloxane copolymer;
(vi) an acetylated lanolin alcohol, a liquid paraffin, octyldodecanol, a polyalphaolefin, a polyisobutylene, a polyolefin, or a synthetic isoalkane; or
(vii) a mixture of any two or more thereof.

### Claim 17 (depends on 1)

The method of claim 1, wherein the foamable composition is administered at least once daily.

### Claim 18 (depends on 1)

The method of claim 1, wherein the foamable composition is administered at least once daily and the minocycline is present at about 3% by weight of the carrier.

### Claim 19 (depends on 1)

The method of claim 1, wherein the foamable composition is administered at least once daily and the minocycline is present at about 1.5% by weight of the carrier.

### Claim 20 (depends on 1)

The method of claim 1, wherein the foamable composition comprises at least one fatty alcohol, at least one fatty acid, and at least one wax.

### Claim 21 (depends on 1)

The method of claim 1, wherein the ratio of fatty alcohol to fatty acid is about 1:7 to about 16:3.

### Claim 22 (depends on 1)

The method of claim 1, wherein the ratio of fatty alcohol to fatty acid is about 3:17 to about 2:1.

### Claim 23 (depends on 1)

The method of claim 1, wherein the foamable composition is free of petrolatum.

### Claim 24 (depends on 1)

The method of claim 1, wherein the salt of minocycline is minocycline hydrochloride.