TOPICAL TETRACYCLINE COMPOSITIONS

• US 20180193468A1
• Filed: 03/06/2018
• Published: 07/12/2018
• Est. Priority Date: 10/02/2009
• Status: Active Grant

• Current Assignee: Journey Medical Corp. (Fortress Biotech, Inc.)
• Original Assignee: Foamix Pharmaceuticals, Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Tamarkin, Dov, Gazal, Elana, Papiashvili, Irakliy, Hazot, Yohan, Schuz, David, Keynan, Rita
• Granted Patent: US 10,086,080 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2800/31 Anhydrous
• CPC Class Codes: A61K 2800/33 Free of surfactant
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/593 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/02 Inorganic compounds
• 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 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: 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
• CPC Class Codes: A61K 8/31 Hydrocarbons
• CPC Class Codes: A61K 8/342 Alcohols having more than seven atoms in an unbroken chain
• CPC Class Codes: A61K 8/361 Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
• 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 9/0048 : Eye, e.g. artificial tears
• 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: A61K 9/124 : characterised by the propellant
• CPC Class Codes: A61P 1/00 : Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 15/00 : Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/02 : for disorders of the vagina
• 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 17/04 : Antipruritics
• CPC Class Codes: A61P 17/06 : Antipsoriatics
• CPC Class Codes: A61P 17/08 : Antiseborrheics
• CPC Class Codes: A61P 17/10 : Anti-acne agents
• CPC Class Codes: A61P 17/12 : Keratolytics, e.g. wart or anti-corn preparations
• 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 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 23/00 : Anaesthetics
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/20 : Hypnotics; Sedatives
• CPC Class Codes: A61P 25/24 : Antidepressants
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 27/06 : Antiglaucoma agents or miotics
• 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 31/14 : for RNA viruses
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 33/10 : Anthelmintics
• CPC Class Codes: A61P 33/14 : Ectoparasiticides, e.g. scabicides
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• 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 39/06 : Free radical scavengers or antioxidants
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications
• 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 19/10 : Washing or bathing preparations

Abstract

A topical therapeutic hydrophobic breakable composition includes a carrier comprising (a) about 60% to about 90% by weight of at least one hydrophobic oil; (b) at least one viscosity-modifying agents selected from the group consisting of a fatty alcohol, a fatty acid and a wax; and (c) a tetracycline antibiotic, characterized in that at least part of the tetracycline antibiotic is suspended in the composition; the viscosity of the composition is at least about 30% higher than the viscosity of the carrier without the tetracycline antibiotic; and is higher than the viscosity of the hydrophobic oil and the tetracycline antibiotic without the viscosity modifying agents. The tetracycline is chemically stable to the composition for at least six months; wherein more than about 90% of the tetracycline has not broken down. The composition is packaged as a breakable foam that breaks easily upon application of shear force.

Claims

1. (canceled)

2. A method of treating acne vulgaris, comprising administering a waterless foam composition comprising

a minocycline and a foamable carrier, the carrier comprising:

a) at least one hydrophobic oil; and

b) an agent comprising (i) at least one fatty alcohol and at least one wax;

(ii) at least one fatty acid and at least one wax;

(iii) at least one fatty alcohol, at least one fatty acid, and at least one wax;

(iv) a wax comprising a hydrogenated oil;

or (v) a combination of two or more waxes;

wherein the composition does not contain one or more minocycline incompatible 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, 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 composition does not contain a polyol and/or polyethylene

glycol.

3. The method of claim 2, wherein the at least one hydrophobic oil comprises a mineral oil, a cocoglyceride, a silicone oil, a liquid paraffin, a caprylic/capric triglyceride, a coconut oil, a soybean oil, a cyclomethicone, disopropyl adipate isododecane, cetearyl octanoate, a gelled mineral oil, isopropyl myristate, PPG 15 stearyl ether, octyl dodecanol, a petrolatum, a calendula oil, a grape seed oil, an almond oil, a jojoba oil. an avocado oil, a peanut oil, a wheat germ oil, or a mixture of any two or more thereof.

4. The method of claim 2, wherein at least one or both of the fatty alcohol or the fatty acid has at least 12 carbon atoms in its carbon backbone.

5. The method of claim 2, wherein the agent comprises at least one fatty alcohol, at least one fatty acid, and least one wax, wherein the at least one wax comprises a beeswax, a hydrogenated oil, or both.

6. The method of claim 2, wherein the composition contains less than 0.4% by weight of a protic solvent, a polar aprotic solvent, and a silicone thickening agent.

7. The method of claim 2, wherein the composition contains less than 0.4% by weight of a polymeric gelling agent, a polyol, a short chain alcohol, and a silicone thickening agent.

8. The method of claim 2, wherein the minocycline is minocycline hydrochloride.

9. The method of claim 2, wherein the foamable carrier comprises:

a) 45% to 55% by weight of a soybean oil;

b) 21.2% to 28% by weight of a coconut oil;

c) 4.5% to 5.5% by weight of a cyclomethicone;

d) 0.85% to 4.8% by weight of a light mineral oil;

e) 3.2% to 3.9% by weight of cetostearyl alcohol;

f) 2.7% to 3.3% by weight of stearic acid;

g) 2.3% to 2.8% by weight of myristyl alcohol;

h) 1.8% to 2.2% by weight of hydrogenated castor oil;

i) 1.8% to 2.2% by weight of beeswax;

j) 1.4% to 1.7% by weight of stearyl alcohol; and

k) 1 % to 1.2% by weight of behenyl alcohol.

10. The method of claim 2, wherein the minocycline is present at about 1% to about 10% of the composition.

11. The method of claim 2, wherein the minocycline is present at about 4% of the composition.

12. The method of claim 2, further comprising an additional active agent.

13. The method of claim 2, wherein the carrier is free of or contains less than 0.1% by weight of surfactant.

14. The method of claim 2, wherein the composition is free of or comprises less than 10% petrolatum by weight of the composition.

15. The method of claim 2, wherein the at least one hydrophobic oil is about 60% to about 99% by weight of the composition.

16. The method of claim 2, wherein the composition comprises less than 0.4% by weight of a polymeric gelling agent.

17. The method of claim 2, wherein the composition is administered at least once daily.

18. The method of claim 2, wherein the composition is administered at least once daily and the minocycline is present at about 4% of the composition.

19. The method of claim 2, wherein the foam composition is produced with a liquefied or compressed gas propellant.

20. The method of claim 2, comprising a hydrocarbon oil, an ester oil, an ester of a dicarboxylic acid, a triglyceride oil, an unsaturated or polyunsaturated oil, an essential oil, a canola oil, a castor oil, a corn oil, a cotton oil, a cottonseed oil, glycerol, an olive oil, a palm oil, a dimethicone, a fatty acid-modified silicone oil, or a mixture of any two or more thereof.

21. A method of treating acne vulgaris, comprising administering a waterless composition comprising

a carrier and 1% to 10% by weight of the composition of a minocycline, wherein the carrier comprises:

a) at least one hydrophobic oil; and

b) an agent comprising (i) at least one fatty alcohol and at least one wax;

(ii) at least one fatty acid and at least one wax;

(iii) at least one fatty alcohol, at least one fatty acid, and at least one wax;

(iv) a wax comprising a hydrogenated oil;

or (v) a combination of two or more waxes;

wherein the composition does not contain a polyol and/or polyethylene glycol.

22. The method of claim 21, wherein the minocycline is minocycline hydrochloride and is present at an amount of about 4% by weight of the composition.

23. The method of claim 21, wherein the agent comprises at least one fatty alcohol, at least one fatty acid, and at least one wax.

24. The method of claim 21, wherein the composition is a foam composition, and wherein the foam composition is produced upon addition of a liquefied or compressed gas propellant to the carrier.

25. The method of claim 21, wherein the carrier comprises.

a) 45% to 55% by weight of a soybean oil;

b) 21.2% to 26% by weight of a coconut oil;

c) 4.5% to 5.5% by weight of a cyclomethicone;

d) 0.85% to 4.8% by weight of a light mineral oil;

e) 3.2% to 3.9% by weight of cetostearyl alcohol;

f) 2.7% to 3.3% by weight of stearic acid;

g) 2.3% to 2.8% by weight of myristyl alcohol;

h) 1.8% to 2.2% by weight of hydrogenated castor oil;

i) 1.8% to 2.2% by weight of beeswax;

j) 1.4% to 1.7% by weight of stearyl alcohol; and

k) 1 % to 1.2% by weight of behenyl alcohol.