Pharmaceutical composition for topical application

• US 8,512,718 B2
• Filed: 02/12/2010
• Issued: 08/20/2013
• Est. Priority Date: 07/03/2000
• Status: Expired due to Fees

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Eini, Meir, Tamarkin, Dov
• Primary Examiner(s): Haghighatian, Mina
• Application Number:
  US12/705,219
• Publication Number:
  US 20100137198A1
• Time in Patent Office: 1,285 Days
• Field of Search: 424/401, 424/78.03, 424/78.06, 424/78.07, 424/70.1, 514/724, 514/859, 514/861, 514/863, 514/864, 514/880, 514/887
• US Class Current: 424/401
• CPC Class Codes: A21D 2/14 Organic oxygen compounds
• CPC Class Codes: A21D 2/16 Fatty acid esters
• CPC Class Codes: A23C 11/04 containing non-milk fats but no non-milk proteins A23C11/08, A23C11/10 take precedence
• CPC Class Codes: A23C 13/12 Cream preparations
• CPC Class Codes: A23C 15/16 Butter having reduced fat content
• CPC Class Codes: A23C 19/055 Addition of non-milk fats or non-milk proteins , polyol fatty acid polyesters or mineral oils
• CPC Class Codes: A23C 19/093 Addition of non-milk fats or non-milk proteins
• CPC Class Codes: A23C 9/1315 Non-milk proteins or fats; Seeds, pulses, cereals or soja; Fatty acids, phospholipids, mono- or diglycerides or derivatives therefrom; Egg products
• CPC Class Codes: A23D 7/0053 Compositions other than spreads
• CPC Class Codes: A23D 7/0056 Spread compositions
• CPC Class Codes: A23D 7/011 Compositions other than spreads
• CPC Class Codes: A23D 7/013 Spread compositions
• CPC Class Codes: A23D 9/007 characterised by ingredients other than fatty acid triglycerides
• CPC Class Codes: A23G 1/305 Products for covering, coating, finishing, decorating
• CPC Class Codes: A23G 1/36 characterised by the fats used containing dairy products A23G1/46
• CPC Class Codes: A23G 1/38 Cocoa butter substitutes
• CPC Class Codes: A23G 2200/08 containing cocoa fat if specifically mentioned or containing products of cocoa fat or containing other fats, e.g. fatty acid, fatty alcohol, their esters, lecithin, paraffins
• CPC Class Codes: A23G 3/346 Finished or semi-finished products in the form of powders, paste or liquids A23G3/343 takes precedence
• CPC Class Codes: A23J 3/227 Meat-like textured foods meat extenders A23L13/00
• CPC Class Codes: A23L 13/43 Addition of vegetable fats or oils; Addition of non-meat animal fats or oils; Addition of fatty acids
• CPC Class Codes: A23L 19/18 : Roasted or fried products, e.g. snacks or chips
• CPC Class Codes: A23L 23/10 : Soup concentrates, e.g. powders or cakes
• CPC Class Codes: A23L 33/115 : Fatty acids or derivatives thereof; Fats or oils
• CPC Class Codes: A23L 7/109 : Types of pasta, e.g. macaroni or noodles
• CPC Class Codes: A23L 7/122 : Coated, filled, multilayered or hollow ready-to-eat cereals
• CPC Class Codes: A23L 7/183 : by heating without using a pressure release device
• CPC Class Codes: A23P 20/11 : Coating with compositions containing a majority of oils, fats, mono/diglycerides, fatty acids, mineral oils, waxes or paraffins
• CPC Class Codes: A61K 2300/00 : Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/225 : Polycarboxylic acids
• CPC Class Codes: A61K 31/351 : not condensed with another ring
• CPC Class Codes: A61K 31/43 : Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula , e.g. penicillins, penems
• CPC Class Codes: A61K 31/496 : Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/545 : Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: , e.g. cephalosporins, cefaclor, or cephalexine
• CPC Class Codes: A61K 31/573 : substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/65 : Tetracyclines
• CPC Class Codes: A61K 36/738 : Rosa (rose)
• CPC Class Codes: A61K 36/899 : Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
• CPC Class Codes: A61K 45/06 : Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 47/14 : Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• 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 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 8/342 : Alcohols having more than seven atoms in an unbroken chain
• CPC Class Codes: A61K 8/922 : of vegetable origin
• 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: A61P 1/10 : Laxatives
• CPC Class Codes: A61P 1/14 : Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 13/12 : of the kidneys
• 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 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/02 : Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin

Abstract

A pharmaceutical or cosmetic carrier or composition for topical application characterized by rheological properties which render the carrier or composition semi-solid at rest and a liquid upon application of shear forces thereto. The composition or carrier are prepared by mixing 1-25 percent of a solidifying agent and 75-99 percent of a hydrophobic solvent, by weight, wherein at least one of them has therapeutic or cosmetic benefits, in the presence or absence of a biologically active substance.

Claims

1. An oleaginous pharmaceutical carrier comprising:

a mixture comprising, by weight;

75-99 percent of a hydrophobic solvent, and

1-25 percent of a solidifying agent, wherein said solidifying agent is selected from the group consisting of (i) at least one long chain fatty alcohol having at least 15 carbon atoms in its carbon backbone (ii) at least one fatty acid having at least 18 carbons in its carbon backbone, and (iii) a mixture thereof

wherein the pharmaceutical carrier is semi-solid at rest and liquefies upon application of shear forces thereto; and

wherein the carrier is free of a netted framework of solidifying agent.

2. A pharmaceutical composition, comprising the carrier of claim 1, further comprising a therapeutically effective amount of a biologically active substance.

3. The pharmaceutical composition of claim 2, wherein the biologically active substance is selected from the group of consisting of an antibiotic agent, a free radical generating agent, an antifungal agent, an antiviral agent, a non-steroidal anti-inflammatory drug, an immunosuppressant, an antihistamine agent, an anti-inflammatory agent, a retinoid agent, a tar agent, an antipruritics agent and a scabicide agent.

4. The pharmaceutical composition of claim 3, wherein the antibiotic agent comprises a tetracycline antibiotic.

5. The pharmaceutical composition of claim 2, wherein said hydrophobic solvent includes an oil selected from the group consisting of olive oil, soybean oil, canola oil, rapeseed oil, cottonseed oil, coconut oil, palm oil, sesame oil, sunflower oil, safflower oil, rice bran oil, borage seed oil, syzigium aromaticum oil, hempseed oil, herring oil, cod-liver oil, salmon oil, corn oil, flaxseed oil, wheat germ oil, rape seed oil, evening primrose oil, rosehip oil, tea tree oil, melaleuca oil and jojoba oil.

6. The pharmaceutical composition of claim 2, wherein said hydrophobic solvent includes an oil selected from the group consisting of marine animal derived oils, terrestrial animal derived oils, mineral oils, silicone oils and plant-derived oils.

7. The pharmaceutical composition of claim 2, wherein said hydrophobic solvent includes an oil selected from the group consisting of omega-3 oil and omega-6 oil.

8. The pharmaceutical composition of claim 2, wherein the hydrophobic solvent comprises a silicone oil.

9. The pharmaceutical composition of claim 2, wherein the carrier provides a protective moisture barrier.

10. The pharmaceutical composition of claim 2, wherein the composition spreads easily and is non sticky.

11. The pharmaceutical composition of claim 2, wherein said solidifying agent includes a 12-hydroxy fatty acid and or behenyl alcohol.

12. The pharmaceutical composition of claim 2,

wherein the solidifying agent is solid at ambient temperature;

and

wherein the biologically active substance comprises a tetracycline antibiotic in a therapeutically effective amount to treat a disease or disorder of the skin or mucosal membrane.

30. The pharmaceutical composition of claim 2, wherein the biologically active substance is selected from the group consisting of chloramphenicol, a tetracyclines, a synthetic penicillin, semi-synthetic penicillins, a beta-lactam, a quinolone, a fluoroquinolone, a macrolide antibiotic, a peptide antibiotic, a cyclosporine, erythromycin, clyndamycin and mixtures thereof.

13. A method of applying:

a pharmaceutical composition to a skin or a mucosal membrane having a disease or disorder, comprising topically administering the pharmaceutical composition to the skin or the mucosal membrane surface, said pharmaceutical composition comprising, by weight, a mixture of;

75-99 percent of a hydrophobic solvent,

1-25 percent of a solidifying agent, wherein said solidifying agent is selected from the group consisting of (i) at least one long chain fatty alcohol having at least 15 carbon atoms in its carbon backbone (ii) at least one fatty acid having at least 18 carbons in its carbon backbone and (iii) a mixture thereof; and

a biologically active agent,

wherein the composition is semi-solid at rest and liquefies upon application of shear forces thereto; and

wherein the composition is free of a netted framework of solidifying agent.

14. The method of claim 13, wherein on application the composition freely spreads on the skin surface or mucosal membrane and is rapidly absorbed.

15. The method of claim 14, wherein the composition spreads without film formation.

16. The method of claim 13, wherein the composition is adapted to facilitate enhanced penetration of the active agent.

17. The method of claim 13, wherein the disease or disorder is selected from the group consisting of psoriasis, acne, seborrhea, seborrheic dermatitis, alopecia and excessive hair growth, ichthyosis, wounds, burns, cuts, ulcers, psoriasis, seborrheic dermatitis of the face and trunk, seborrheic blepharitis, contact dermatitis, stasis dermatitis and exfoliative dermatitis.

18. The method of claim 13, wherein said biologically active substance is selected from the group of consisting of an antibiotic agent, a free radical generating agent, an antifungal agent, an antiviral agent, a non-steroidal anti-inflammatory drug, an immunosuppressant, an antihistamine agent, an anti-inflammatory agent, a retinoid agent, a tar agent, an antipruritic agent and a scabicide agent.

19. The method of claim 13, wherein the biologically active agent comprises a tetracycline antibiotic.

20. The method of claim 13, wherein said hydrophobic solvent includes an oil selected from the group consisting of olive oil, soybean oil, canola oil, rapeseed oil, cottonseed oil, coconut oil, palm oil, sesame oil, sunflower oil, safflower oil, rice bran oil, borage seed oil, syzigium aromaticum oil, hempseed oil, herring oil, cod-liver oil, salmon oil, corn oil, flaxseed oil, wheat germ oil, rape seed oil, evening primrose oil, rosehip oil, tea tree oil, melaleuca oil and jojoba oil.

21. The method of claim 13, wherein said hydrophobic solvent includes an oil selected from the group consisting of marine animal derived oils, terrestrial animal derived oils, mineral oils, silicone oils and plant-derived oils.

22. The method of claim 13, wherein said hydrophobic solvent includes an oil selected from the group consisting of omega-3 oil and omega-6 oil.

23. The method of claim 13, wherein the composition provides a protective moisture barrier.

24. The method of claim 15, wherein the composition is delivered by means of a dermal patch or as a suppository.

25. The method of claim 13, wherein said solidifying agent includes a 12-hydroxy fatty acid and or behenyl alcohol.

26. The method of claim 13, wherein the solidifying agent is solid at ambient temperature;

wherein the biologically active substance comprises a tetracycline antibiotic in a therapeutically effective amount to treat a disease or disorder of the skin or mucosal membrane.

29. The method of claim 18, wherein the antibiotic agent is selected from the group consisting of chloramphenicol, a tetracyclines, a synthetic penicillins, a semi-synthetic penicillin, a beta-lactam, a quinolone, a fluoroquinolone, a macrolide antibiotic, a peptide antibiotic, a cyclosporine, erythromycin clyndamycin and mixtures thereof.

27. A method of preparing an oleaginous pharmaceutical carrier, the method comprising the steps of mixing a hydrophobic solvent and a solidifying agent at a temperature above a melting temperature of the solidifying agent so as to obtain a mixture containing 75-99 percent of the hydrophobic solvent by weight and 1-25 percent of the solidifying agent by weight;

and cooling the mixture,

wherein said solidifying agent is selected from the group consisting of (i) at least one long chain fatty alcohol having at least 15 carbon atoms in its carbon backbone (ii) at least one fatty acid having at least 18 carbons in its carbon backbone, and (iii) a mixture thereof; and

wherein the pharmaceutical carrier is semi-solid at rest and liquefies upon application of shear forces thereto.

28. The method of claim 27, further comprising:

mixing into the mixture a therapeutically or cosmetically effective amount of a biologically active substance.

31. A method of treating a disease or disorder of a skin or a mucosal membrane comprising:

topically administering a pharmaceutical composition to the skin or the mucosal membrane, said pharmaceutical composition comprising, by weight, a mixture of;

75-99 percent of a hydrophobic solvent,

1-25 percent of a solidifying agent, wherein said solidifying agent is selected from the group consisting of (i) at least one long chain fatty alcohol having at least 15 carbon atoms in its carbon backbone (ii) at least one fatty acid having at least 18 carbons in its carbon backbone and (iii) a mixture thereof; and

a biologically active agent selected from the group consisting of an antibiotic agent, a free radical generating agent, an antifungal agent, an antiviral agent, a non-steroidal anti-inflammatory drug, an immunosuppressant, an antihistamine agent, an anti-inflammatory agent, a retinoid agent, a tar agent, an antipruritics agent, and a scabicide agent and wherein the antibiotic agent is selected from the group consisting of chloramphenicol, tetracyclines, synthetic and semi-synthetic penicillins, beta-lactams, quinolones, fluoroquinolones, macrolide antibiotics, peptide antibiotics, cyclosporines, erythromycin, clyndamycin, and mixtures thereof;

wherein the composition is semi-solid at rest and liquefies upon application of shear forces thereto;

wherein the composition is free of a netted framework of solidifying agent; and

wherein the disease or disorder is selected from the group consisting of psoriasis, acne, seborrhea, seborrheic dermatitis, alopecia, excessive hair growth, ichthyosis, infection, inflammation, wounds, burns, cuts, ulcers, psoriasis, seborrheic dermatitis of the face and trunk, seborrheic blepharitis, contact dermatitis, stasis dermatitis, and exfoliative dermatitis.