Compositions, gels and foams with rheology modulators and uses thereof

• US 8,618,081 B2
• Filed: 05/04/2011
• Issued: 12/31/2013
• Est. Priority Date: 10/02/2009
• Status: Active Grant

• Current Assignee: Journey Medical Corp. (Fortress Biotech, Inc.)
• Original Assignee: Foamix Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Tamarkin, Dov, Gazal, Elana, Hazot, Yohan, Schuz, David, Papiashvili, Irakliy
• Primary Examiner(s): Padmanabhan, Sreeni
• Assistant Examiner(s): Neagu, Irina
• Application Number:
  US13/100,724
• Publication Number:
  US 20110281827A1
• Time in Patent Office: 972 Days
• Field of Search: 514/152, 514/937, 514/945, 514/947, 424/400, 424/401, 424/502, 424/731, 424/727
• US Class Current: 514/152
• 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

The present disclosure relates generally to compositions for cosmetic or pharmaceutical application. The compositions include a carrier and rheology modulators.

Claims

1. A therapeutic composition comprising:

a first rheology modulator comprising a pharmaceutical or a cosmetic active agent at least part of which is suspended in the therapeutic composition; and

a carrier comprising;

a) a second rheology modulator selected from the group consisting of (i) a combination of at least one fatty alcohol and at least one wax;

(ii) a combination of at least one fatty acid and at least one wax; and

(iii) a combination of;

at least one fatty alcohol, at least one fatty acid, and at least one wax; and

b) at least one hydrophobic solvent;

the carrier being otherwise free of or containing less than 0.1% by weight of surfactant;

wherein the at least one wax comprises a hydrogenated castor oil;

wherein the viscosity of the therapeutic composition is at least about 30% higher than the viscosity of a first partial composition comprising the carrier without the first rheology modulator; and

is higher than the viscosity of the first rheology modulator and the at least one hydrophobic solvent without the second rheology modulator; and

wherein the viscosity of the first partial composition is less than about 25,000 cPs at room temperature.

2. The composition of claim 1 wherein the first rheology modulator comprises at least one tetracycline antibiotic.

3. The composition of claim 2, wherein the tetracycline antibiotic is compatible with the carrier and with the second rheology modulator.

4. The composition of claim 2, wherein the tetracycline antibiotic is selected from the group consisting of tetracycline, oxytetracycline, demeclocycline, doxycycline, lymecycline, meclocycline, methacycline, minocycline, rolitetracycline, chlorotetracycline, and tigecycline;

wherein the tetracycline antibiotic is present in a free base form, a hydrate form, a salt form, or a complex form; and

wherein at least part of the tetracycline antibiotic is not soluble and is suspended in the carrier composition.

5. The composition of claim 3, wherein the tetracycline antibiotic is minocycline or doxycycline or a mixture of both.

6. The composition of claim 1, wherein the therapeutic composition is waterless.

7. The composition of claim 1, wherein the second rheology modulator comprises a compound selected from the group consisting of:

i) at least one fatty alcohol selected from the group consisting of;

(a) a fatty alcohol having 14 or more carbons in its carbon chain, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, cetostearyl alcohol, oleyl alcohol, erucyl alcohol, arachidyl alcohol, behenyl alcohol, tetracosanol, hexacosanol, octacosanol, triacontanol, tetratriacontanol, 1-triacontanol, and a fatty alcohol having a carbon chain between C30 and C50;

(b) a fatty alcohol mixture derived from beeswax; and

(c) a therapeutically-active fatty alcohol;

ii) at least one fatty acid selected from the group consisting of;

(a) a fatty acid having 12 or more carbons in its carbon chain, dodecanoic acid, myristic acid, hexadecanoic acid, heptadecanoic acid, palmitic acid, stearic acid, oleic acid, arachidic acid, behenic acid, tetracosanoic acid, hexacosanoic acid, heptacosanoic acid, octacosanoic acid, triacontanoic acid, dotriacontanoic acid, tritriacontanoic acid, tetratriacontanoic acid, pentatriacontanoic acid, and a fatty acid having a carbon chain between C30 and C50; and

(b) a hydroxy fatty acid;

iii) at least one wax, having the properties of (i) plastic behavior at ambient temperatures, (ii) a melting point above approximately 45°

C., (iii) a relatively low viscosity when melted; and

(iv) hydrophobic nature, or selected from the group consisting of a beeswax, a hard fat, a paraffin and a hydrogenated castor oil.

8. The composition of claim 7, wherein the second rheology modulator comprises a combination of (i) at least one fatty alcohol, (ii) at least one fatty acid;

and (iii) at least one wax.

9. The composition of claim 7, wherein the ratio of fatty alcohol to wax or fatty acid to wax or fatty alcohol and fatty acid to wax is between about 1:

10 to about 10;

1.

10. The composition of claim 1, wherein the carrier composition is essentially free of at least one of water, polymeric agents, short chain alcohols, and polyols.

11. The composition of claim 1, wherein the carrier composition is essentially free of water, polymeric agents, short chain alcohols, and polyols.

12. The composition of claim 1, wherein the viscosity of the therapeutic composition is at least about 50% more than the viscosity of the carrier without the first rheology modulator.

13. The composition of claim 12, wherein the increase in viscosity is at least about 100%.

14. The composition of claim 13, wherein the viscosity of the carrier without the first rheology modulator is

i) less than about 12,000 cPs;

or

ii) less than about 8,000 cPs;

or

iii) less than about 2,000 cPs.

15. The composition of claim 1, wherein the concentration of the first rheology modulator in the composition is from about 0.01% to about 25% by weight of the therapeutic composition.

16. The composition of claim 1, wherein the hydrophobic solvent is selected from the group consisting of:

a diglyceride, a therapeutic oil, acetylated lanolin alcohol, alexandria laurel tree oil, alkyl benzoate, alkyl octanoate, almond oil, an essential oil, an unsaturated or polyunsaturated oil, apricot stone oil, arachidyl behenate, arachidyl propionate, avocado oil, barley oil, basil oil, beeswax, benzyl laurate, benzyl myristate, benzyl palmitate, bis (octyldodecyl stearoyl) dimer dilinoleate, borage seed oil, butyl myristate, butyl stearate, C12-C15 alkyl benzoate, C12-C15 alkyl octanoate, calendula oil, camphor oil, canelle nut tree oil, canola oil, capric/caprylic triglycerides, caprylyl methicone, cardamom oil, carrot oil, castor oil, cetearyl ethylhexanoate, cetearyl isononanoate, cetearyl octanoate, cetyl acetate, cetyl dimethicone, cetyl ethylhexanoate, cetyl lactate, cetyl myristate, cetyl octanoate, cetyl palmitate, cetyl ricinoleate, citronella oil, clary sage oil, clove oil, cocoglycerides, coconut oil, cod-liver oil, corn oil, cotton oil, cottonseed oil, cyclohexasiloxane, cyclomethicone, Cyclomethicone 5-NF (cyclopentasiloxane), cyclotetrasiloxane, cypress oil, decyl oleate, diethyleneglycol diethylhexanoate, diethyleneglycol diisononanoate, diethyleneglycol dioctanoate, diethylhexanoate, diethylhexyl adipate, diethylhexyl malate, diethylhexyl succinate, diisopropyl adipate, diisopropyl dimerate, diisopropyl sebacate, diisosteary dimer dilinoleate, diisostearyl fumerate, dimethicone, dimethyl polysiloxane, dioctyl malate, dioctyl sebacate, diisopropyl adipate, dodecyl oleate, Dow Corning 244 Fluid (cyclotetrasiloxane), Dow corning 246 Fluid (d6+d5) (cyclohexasiloxane &

cyclopentasiloxane), epoxy-modified silicone oil, ester derivatives of lanolic acid, ester oils, ethylhexyl cocoate, ethylhexyl ethylhexanoate, ethylhexyl hydroxystarate, ethylhexyl isononanoate, ethylhexyl palmitate, ethylhexyl palmytate, ethylhexyl pelargonate, ethylhexyl stearate, evening primrose oil, fatty acid-modified silicone oil, flaxseed oil, fluoro group-modified silicone oil, frankincense oil, gelled mineral oil, ginger oil, glycereth triacetate, glycerol triheptanoate, glyceryl oleate, glyceryl trioctanoate, glyceryl triundecanoate, grape seed oil, grapefruit oil, groundnut oil, hard fat , hazelnut oil, heavy mineral oil, hempseed oil, herring oil, hexadecyl stearate, hexyl laurate, hydrocarbon oils, hyssop oil, isoamyl laurate, isocetearyl octanoate, isocetyl behenate, isocetyl lanolate, isocetyl palmitate, isocetyl salicylate, isocetyl stearate, isocetyl stearoyl stearate, isodecyl ethylhexanoate, isodecyl isononanoate, isodecyl oleate, isododecane, isohexadecane, isododecane, isohexadecanol, isohexyl decanoate, isononyl isononanoate, isononyl octanoate, isoparaffin, isopropyl isostearate, isopropyl lanolate, isopropyl laurate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isostearyl citrate, isostearyl salicylate, isostearyl tartarate, isostearyl behenate, isostearyl erucate, isostearyl glycolate, isostearyl isononanoate, isostearyl isostearate, isostearyl lactate, isostearyl linoleate, isostearyl linolenate, isostearyl malate, isostearyl neopentanoate, isostearyl palmitate, isotridecyl isononanoate, jasmine oil, jojoba oil, lauryl lactate, lavender oil, lemon oil, light mineral oil, liquid paraffin, liquid triglycerides, lucerne oil, maize germ oil, maleated soybean oil, mandarin oil, manuka oil, marjoram oil, marrow oil, MCT oil, methylphenylpolysiloxane, millet oil, mineral oil, myristyl lactate, myristyl myristate, myristyl neopentanoate, myristyl propionate, myrrh oil, neopentylglycol dicaprate, neopentylglycol dicaprylate/dicaprate, neroli oil, nutmeg oil, octyl palmitate, octyl stearate, octyldodecanol, octyldodecyl behenate, octyldodecyl hydroxystearate, octyldodecyl myristate, octyldodecyl stearoyl stearate, oils from animal origin, oils of plant origin, oleyl erucate, oleyl lactate, oleyl oleate, olive oil, dimethiconol, palm oil, passionflower oil, peanut oil, PEG/PPG 18/18 dimethicone, pentaerythrityl tetrastearate, petitgrain oil, phenyl trimethicone, phenyltrimethicone, poly(dimethylsiloxane)-(diphenyl-siloxane) copolymer, polyalkyl siloxane, polyalkylaryl siloxane, polyalphaolefin, polyaryl siloxane, polyaryl siloxanes, polyether group-modified silicone oil cyclomethicone, polyether siloxane copolymer, polyether siloxane copolymers, polyisobutylene, polyolefin, poppy oil, PPG alkyl ether, PPG-10 cetyl ether, PPG-10 oleyl ether, PPG-11 stearyl ether, PPG-12 butyl ether, PPG-14 butyl ether, PPG-15 butyl ether, PPG-15 stearyl ether, PPG-16 butyl ether, PPG-17 butyl ether, PPG-18 butyl ether, PPG-2 butyl ether, PPG-2 methyl ether, PPG-20 butyl ether, PPG-20 oleyl ether, PPG-22 butyl ether, PPG-23 oleyl ether, PPG-24 butyl ether, PPG-26 butyl ether, PPG-28 cetyl ether, PPG-3 methyl ether, PPG-3 myristyl ether, PPG-30 butyl ether, PPG-30 cetyl ether, PPG-30 isocetyl ether, PPG-30 oleyl ether, PPG-33 butyl ether, PPG-37 oleyl ether, PPG-4 butyl ether, PPG-4 lauryl ether, PPG-4 myristyl ether, PPG-40 butyl ether, PPG-5 butyl ether, PPG-50 cetyl ether, PPG-50 oleyl ether, PPG-52 butyl ether, PPG-53 butyl ether, PPG-7 lauryl ether, PPG-9 butyl ether, PPG-9-13 butyl ether, propyl myristate, propylene glycol dicaprate, propylene glycol dicaprylate, propylene glycol myristyl ether acetate, propylene glycol ricinoleate, rapeseed oil, rosehip oil, rye oil, safflower oil, sage oil, salmon oil, sesame oil, shea butter, silicone oils, soya oil, soybean oil, stearyl caprate, stearyl dimethicone, stearyl heptanoate, stearyl propionate, sunflower oil, sweet almond oil, synthetic isoalkane, sysymbrium oil, syzigium aromaticum oil, tangerine oil, tea tree oil, therapeutic oils, tocopheryl acetate, tocopheryl linoleate, tridecyl ethylhexanoate, tridecyl isononanoate, triisocetyl citrate, unsaturated or polyunsaturated oils, vanilla oil, verbena oil, walnut oil, wheat germ glycerides, wheat germ oil, white petrolatum, and mixtures of any two or more thereof.

17. The composition of claim 16, wherein the carrier composition further comprises a petrolatum or a paraffin.

18. The composition of claim 7, further comprising a liquefied or compressed gas propellant, wherein the composition is a foamable composition;

wherein the second rheology modulator is about 0.1% to about 20% by weight of the carrier composition;

wherein the hydrophobic solvent is about 60% to about 95% by weight of the carrier composition;

wherein the ratio of carrier composition to propellant is from about 100;

1 to about 100;

30; and

wherein upon dispensing, the foamable composition forms a breakable foam that breaks upon application of shear force.

19. The composition of claim 1, wherein the carrier composition further comprises about 1% to about 25% by weight of the carrier composition of a polar solvent or a penetration enhancer.

20. The composition of claim 1, wherein the increase in viscosity is a synergistic increase such that the combined viscosity of the first partial composition and the viscosity of the first rheology modulator and the hydrophobic solvent without the second rheology modulator is less than the viscosity of the therapeutic composition.

21. The composition of claim 1, wherein the fatty alcohol is selected from the group consisting of isostearyl alcohol, behenyl alcohol, stearyl alcohol, cetyl alcohol, oleyl alcohol, myristyl alcohol, and cetostearyl alcohol;

the fatty acid is selected from the group consisting of palmitic acid, stearic acid, and oleic acid; and

the wax is selected from the group consisting of a beeswax, a hard fat, a paraffin, and a hydrogenated castor oil.

22. The composition of claim 21, wherein the fatty alcohol is selected from the group consisting of behenyl alcohol, stearyl alcohol, cetyl alcohol, myristyl alcohol, and cetostearyl alcohol;

the fatty acid is stearic acid; and

the wax is selected from the group consisting of a beeswax, and a hydrogenated castor oil.

23. The composition of claim 22 comprising behenyl alcohol, stearyl alcohol, myristyl alcohol, cetostearyl alcohol, stearic acid, a beeswax, and a hydrogenated castor oil.

24. The composition of claim 16, wherein the hydrophobic solvent comprises mineral oil.

25. The composition of claim 1, wherein the hydrophobic solvent is selected from the group consisting of a vegetable oil, a mineral oil, a silicone oil, and mixtures of any two or more thereof.