COMPOSITION EXHIBITING ENHANCED FORMULATION STABILITY AND DELIVERY OF TOPICAL ACTIVE INGREDIENTS

• US 20100255107A1
• Filed: 06/18/2010
• Published: 10/07/2010
• Est. Priority Date: 04/21/2000
• Status: Active Grant

• Current Assignee: Sol-Gel Technologies Ltd.
• Original Assignee: Sol-Gel Technologies Ltd.
• Inventors: Gans, Orit, Magdassi, Shlomo, Rottman, Claudio, Lapidot, Noa, Seri-Levy, Alon, Avnir, David
• Granted Patent: US 8,039,020 B2
• Time in Patent Office: Days
• US Class Current: 424/490
• CPC Class Codes: A61K 2800/412 Microsized, i.e. having sizes between 0.1 and 100 microns
• CPC Class Codes: A61K 2800/75 Anti-irritant
• CPC Class Codes: A61K 8/042 Gels
• CPC Class Codes: A61K 8/11 Encapsulated compositions
• CPC Class Codes: A61K 8/25 Silicon; Compounds thereof
• CPC Class Codes: A61K 8/37 Esters of carboxylic acids
• CPC Class Codes: A61K 8/38 Percompounds, e.g. peracids
• CPC Class Codes: A61K 8/602 Glycosides, e.g. rutin
• CPC Class Codes: A61K 8/671 Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
• CPC Class Codes: A61K 9/501 Inorganic compounds
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5115 Inorganic compounds
• CPC Class Codes: A61K 9/5138 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61P 17/06 Antipsoriatics
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61Q 1/00 Make-up preparations; Body powders; Preparations for removing make-up
• CPC Class Codes: A61Q 11/00 : Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
• 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 5/02 : Preparations for cleaning the hair
• CPC Class Codes: A61Q 5/12 : Preparations containing hair conditioners
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

A therapeutic, cosmetic or cosmeceutic composition for topical application, capable of stabilizing an active ingredient and delivering the active ingredient, comprising a plurality of microcapsules having a core-shell structure. The microcapsules have a diameter of approximately 0.1 to 100 micron. The core of each microcapsule includes at least one active ingredient, and is encapsulated within a microcapsular shell. The shell is comprised of at least one inorganic polymer obtained by a sol-gel process, and the shell protects the active ingredient before topical application and is designed to release the active ingredient from the microcapsules following application. The composition is useful in encapsulating active ingredients, such as benzoyl peroxide, that are unstable in other formulation, or are irritating to the skin.

Claims

1. A composition for topical application comprising as an active ingredient at least one of benzoyl peroxide and retinoid encapsulated in microcapsules having a core-shell structure, wherein said core includes said active ingredient, and wherein said shell comprises at least one metal oxide inorganic polymer obtained by a sol-gel process.

2. The composition of claim 1, comprising benzoyl peroxide and retinoid, wherein the benzoyl peroxide is encapsulated and the retinoid is non-encapsulated.

3. The composition of claim 1, comprising benzoyl peroxide and retinoid encapsulated in separate microcapsules.

4. The composition of claim 1, comprising benzoyl peroxide and retinoid, wherein the retinoid is encapsulated and the benzoyl peroxide is non-encapsulated.

5. The composition of claim 1, wherein said active ingredient is stabilized prior to said topical application.

6. The composition of claim 1, wherein said active ingredient is released from said microcapsules following said topical application.

7. The composition of claim 1, wherein said microcapsules have an average diameter between 0.1 micron and 100 microns.

8. The composition of claim 1, wherein said microcapsules are non-scratching both prior and following disintegration.

9. The composition of claim 1, wherein said at least one inorganic polymer comprises at least one organically-modified inorganic polymer prepared by the sol-gel process.

10. The composition of claim 1, further comprising at least one other type of microcapsules, each of said at least one other type of microcapsules contain at least one active ingredient other than benzoyl peroxide or retinoid.

11. The composition of claim 10, wherein said at least one active ingredient is selected from the group consisting of erythromycin, synthomycin clindamycin, tetracycline, an alpha hydroxy acid, a salt thereof, a derivative thereof, and mixtures thereof.

12. The composition of claim 1, further comprising a pharmaceutically, cosmetically or cosmeceutically acceptable carrier.

13. The composition of claim 1, wherein said composition comprises at least one non-encapsulated active ingredient.

14. The composition of claim 13, wherein said non-encapsulated active ingredient is selected from the group consisting of erythromycin, synthomycin, clindamycin, tetracycline, a retinoid, an alpha hydroxy acid, a salt thereof, a derivative thereof and mixtures thereof.

15. The composition of claim 1, wherein an amount of said active ingredient is between about 0.001% and about 95% by weight of said microcapsules.

16. The composition of claim 1, wherein said core is in a form selected from the group consisting of a solid, an oil solution, an emulsion, an aqueous solution and a dispersion.

17. The composition of claim 1, wherein said inorganic polymer is prepared from a sol-gel precursor selected from the group consisting of a metal alkoxide monomer, a semi-metal alkoxide monomer, a metal ester monomer, a semi-metal ester monomer, a silazane monomer, a monomer of the formula M(R)_nP)_m, wherein M is a metallic or a semi metallic element, R is a hydrolyzable substituent, n is an integer from 2 to 6, P is a non polymerizable substituent and m is an integer from 0 to 6, a partially hydrolyzed and partially condensed polymer thereof, and mixtures thereof.

18. The composition of claim 1, further comprising an auxiliary vehicle, said auxiliary vehicle is added to the composition prior to said topical application to trigger the release of said active ingredient from said microcapsules.

19. The composition of claim 1, wherein said microcapsules release said active ingredient upon disintegration.

20. The composition of claim 19, wherein said disintegration is effectable by a rubbing or spreading action or by drying.

21. The composition of claim 1, designed to release said active ingredient upon extraction.

22. A method for treating a skin condition in a subject in need thereof, the method comprising topically applying onto the skin a composition comprising as an active ingredient at least one of benzoyl peroxide and retinoid encapsulated in microcapsules having a core-shell structure, wherein said core includes said active ingredient, and wherein said shell comprises at least one metal oxide inorganic polymer obtained by a sol-gel process.

23. The method of claim 22, wherein said composition comprises as an active ingredient benzoyl peroxide and retinoid, wherein said benzoyl peroxide is encapsulated and said retinoid is non-encapsulated.

24. The method of claim 22, wherein said benzoyl peroxide and said retinoid are encapsulated in separate microcapsules.

25. The method of claim 22, wherein said composition comprises as an active ingredient benzoyl peroxide and retinoid, wherein said retinoid is encapsulated and said benzoyl peroxide is non-encapsulated.

26. The method of claim 22, wherein said skin condition comprises a disease or disorder selected from the group consisting of acne, psoriasis, seborrea, bacteria, virus, or fungus infection, and inflammation.

27. The method of claim 22, wherein said at least one inorganic polymer comprises at least one organically-modified inorganic polymer prepared by a sol-gel process.

28. The method of claim 22, wherein said composition further comprising at least one other type of microcapsules, each of said at least other type of microcapsules containing at least one active ingredient other than benzoyl peroxide or retinoid.

29. The method of claim 28, wherein said at least one active ingredient is selected from the group consisting of erythromycin, synthomycin, clindamycin, tetracycline, an alpha hydroxy acid, a salt thereof, a derivative thereof and mixtures thereof.

30. The method of claim 22, wherein said composition further comprising a pharmaceutically, cosmetically or cosmeceutically acceptable carrier.

31. The method of claim 30, wherein said composition comprises at least one non-encapsulated active ingredient.

32. The method of claim 31, wherein said non-encapsulated active ingredient is selected from the group consisting of erythromycin, synthomycin, clindamycin, tetracycline, a retinoid, an alpha hydroxy acid, a salt thereof, a derivative thereof, and mixtures thereof.

33. The method of claim 22, wherein said inorganic polymer is prepared from a sol-gel precursor selected from the group consisting of a metal alkoxide monomer, a semi-metal alkoxide monomer, a metal ester monomer, a semi-metal ester monomer, a silazane monomer, a monomer of the formula M(R)_n(P)_m, wherein M is a metallic or a semi metallic element, R is a hydrolyzable substituent, n is an integer from 2 to 6, P is a non polymerizable substituent and m is an integer from 0 to 6, a partially hydrolyzed and partially condensed polymer thereof, and a mixture thereof.

34. A process for preparing a composition for topical application that comprises, as active ingredient, one or both of benzoyl peroxide and a retinoid, the process comprising encapsulating the active ingredient in microcapsules having a core-shell structure, wherein said core includes said active ingredient, and wherein said shell comprises at least one inorganic polymer, the microcapsules being obtained by a sol-gel process that comprises:

preparing a hydrophobic solution or a hydrophobic dispersion comprising at least one sol-gel precursor and said active ingredient;

emulsifying said hydrophobic solution or dispersion in an aqueous solution under high shear forces, so as to obtain an emulsion containing said active ingredient; and

(c) mixing and stirring said emulsion, with a second aqueous solution, at a selected pH, so as to obtain said active ingredient encapsulated in said microcapsules.

35. The process of claim 34, wherein said emulsion is an oil-in-water emulsion.

36. The process of claim 34, wherein said microcapsules have an average diameter between 0.1 micron and 100 microns.

37. The process of claim 34, wherein said at least one inorganic polymer comprises at least one organically-modified inorganic polymer prepared by said sol-gel process.

38. The process of claim 34, wherein said hydrophobic solution or dispersion further comprises a surfactant, a polymer, a polymeric surfactant, a suspending agent or mixtures thereof.

39. The process of claim 34, wherein said at least one sol-gel precursor is selected from the group consisting of a metal alkoxide monomer, a semi-metal alkoxide monomer, a metal ester monomer, a semi-metal ester monomer, a silazane monomer, a monomer of the formula M(R)n(P)m, wherein M is a metallic or a semi metallic element R is a hydrolyzable substituent, n is an integer from 2 to 6, P is a non polymerizable substituent and m is an integer from 0 to 6, a partially hydrolyzed and partially condensed polymer thereof, and any mixture thereof.

40. The process of claim 34, wherein said hydrophobic dispersion is prepared by a method comprising:

wetting and mixing said active ingredient to be encapsulated within said microcapsules with at least one additive selected from the group consisting of a liquid, a wetting agent and a combination thereof; and

micronizing said active ingredient by grinding or milling, so as to obtain a micronized active ingredient.

41. The process of claim 34, further comprising adding and mixing at least one dispersing phase selected from the group consisting of an oil, a sol-gel precursor and a combination thereof, so as to obtain a dispersion of said active ingredient in said dispersing phase.

42. The process of claim 34, wherein an average particle size of said active ingredient is between about 0.1 micron and about 20 microns.