Claims for Patent: 9,868,103

Summary for Patent: 9,868,103

Title:	Metal oxide coating of water insoluble ingredients
Abstract:	The invention relates to process for coating a solid, water-insoluble particulate matter, with a metal oxide comprising: (a) contacting the solid water-insoluble particulate matter with a cationic additive in an aqueous medium to obtain a dispersion of said particulate matter having a positive zeta potential; (b) coating the solid water-insoluble particulate matter by precipitation of a metal oxide salt onto the surface of the particulate matter, forming a metal oxide layer thereon; and (c) aging said coating layer. The invention further relates to coated particulate matter obtained by the process and to compositions comprising solid, water-insoluble particulate matter, coated by a metal oxide layer, the particulate matter being a dermatological active agent or a pesticide. The invention additionally relates to methods of treating a surface condition in a subject using compositions comprising solid, water insoluble dermatologically active agent, coated by a metal oxide layer.
Inventor(s):	Toledano; Ofer (Kfar Saba, IL), Sertchook; Hanan (Gedera, IL), Loboda; Natalia (Jerusalem, IL), Bar-Simantov; Haim (Modiin, IL)
Assignee:	SOL-GEL TECHNOLOGIES LTD. (Ness Ziona, IL)
Application Number:	11/997,823
Patent Claims:	1. A process for coating an organic pharmaceutically active material in the form of a solid, water-insoluble particulate matter with a metal oxide coating, comprising: (a) contacting, in a medium consisting of an aqueous medium, the solid, water-insoluble organic pharmaceutically active particulate matter with a cationic additive to obtain a dispersion of said particulate matter in said aqueous medium, said particulate matter having a positive zeta potential; (b) adding an aqueous solution of a metal oxide salt to said dispersion of said particulate matter, under conditions wherein said metal oxide salt precipitates onto the surface of the particulate matter, and acidifying to thereby form a solid, water-insoluble particulate matter that has a metal oxide layer coated thereon; and (c) aging said metal oxide layer to form an aged, coated, solid, water-insoluble particulate matter having a coating thickness in the range of about 0.3-10 micron; and (d) after said aging step (c), subjecting the aged, coated, solid, water-insoluble particulate matter to one or more steps of precipitation of metal oxide salt onto the surface of the particulate matter in the presence of a cationic additive, and acidifying to thereby form a solid, water-insoluble particulate matter that has a metal oxide layer coated thereon, followed by aging treatment. 2. The process of claim 1, comprising: (a) contacting, in a medium consisting of an aqueous medium, the solid, water-insoluble particulate matter, with a cationic additive to obtain a dispersion of said particulate matter in said aqueous medium, said particulate matter having a positive zeta potential, wherein said solid, water-insoluble particulate matter is an organic pharmaceutically active ingredient; (b) adding an aqueous solution of a metal oxide salt to said dispersion of said particulate matter, under conditions wherein said metal oxide salt precipitates onto the surface of the particulate matter, and acidifying to thereby form solid, water-insoluble particulate matter that has a metal oxide layer coated thereon; (c) aging said metal oxide layer to form an aged, coated, solid, water-insoluble particulate matter; (d) contacting the aged, coated particulate matter of the immediately preceding step with a cationic additive in a medium consisting of an aqueous medium to obtain a dispersion of said aged, coated particulate matter having a positive zeta potential; (e) adding an aqueous solution of a metal oxide salt to said dispersion obtained in the immediately preceding step, under conditions wherein said metal oxide salt precipitates onto the surface of the particulate matter, and acidifying to thereby form solid, water-insoluble particulate matter that has a metal oxide layer coated thereon; and (f) aging said metal oxide layer formed in the immediately preceding step to form an aged, coated, solid, water-insoluble particulate matter. 3. The process of claim 2, comprising, after step (f), repeating steps (d), (e) and (f) one or two additional times. 4. The process of claim 2, wherein the cationic additive used in step (a) and the cationic additive used in step (d) are the same. 5. The process of claim 2, wherein the cationic additive used in step (a) and the cationic additive used in step (d) are different. 6. The process of claim 2, wherein said cationic additive of step (a) is a cationic surfactant selected from the group consisting of monoalkylquaternary ammonium salts, dialkyl quaternary ammonium salts, and mixtures thereof. 7. The process of claim 2, wherein said cationic additive of step (d) is a cationic polymer. 8. The process of claim 2, wherein said cationic additive of step (d) is selected from the group consisting of colloidal alumina, colloidal ceria (CeO.sub.2), colloidal alumina coated silica, and mixtures thereof. 9. The process of claim 1, further comprising, after said step (c), separating the coated particulate matter from the dispersing aqueous medium and optionally rinsing and redispersing the obtained coated active ingredient in an aqueous medium. 10. The process of claim 1, wherein, in step (b) the conditions wherein said metal oxide salt precipitates onto the surface of the particulate matter are those that cause a pH of 7-11 to be yielded in the aqueous medium, and said acidifying is to an extent that yields a pH of 1-3. 11. The process of claim 1, wherein, in step (b), the conditions wherein said metal oxide salt precipitates onto the surface of the particulate matter are obtained by adjusting the pH of the dispersion obtained in (a) to a value in the range 5.5-8 and then adding the aqueous solution of the metal oxide salt. 12. The process of claim 1, wherein the aging of step (c) comprises adjusting the pH to a value in the range 6.5-9.5 and mixing for a period of at least 12 h. 13. The process of claim 1, wherein said positive zeta potential in step (a) is less than +150 mV. 14. The process of claim 1, wherein said organic pharmaceutically active material is a dermatologically active agent. 15. The process of claim 14, wherein said dermatologically active agent is selected from the group consisting of antifungal agents, antibacterial agents, antiinflammatory agents, antipuritic agents, antipsoriatic agent, anti-acne agents, and combinations of any of the above. 16. The process of claim 15, wherein said dermatologically active agent is an anti-acne agent selected from the group consisting of benzoyl peroxide, retinoid, and mixtures thereof. 17. The process of claim 16, wherein said anti-acne agent is benzoyl peroxide. 18. The process of claim 1, wherein said cationic additive is selected from the group consisting of a cationic surfactant, a cationic polymer, and mixtures thereof. 19. The process of claim 18, wherein said cationic additive is a cationic polymer selected from the group consisting of poly(ethyleneimine), poly(dimethyldiallylammonium chloride), poly(acrylamide-co-diallyl-dimethylammonium chloride), poly(allylamine hydrochloride), Chitosan, poly lysine, and mixtures thereof. 20. The process according to claim 1, further comprising, after step (c), chemically modifying the surface of the aged, coated, solid, water-insoluble particulate matter. 21. An aged, solid, water-insoluble organic pharmaceutically active particulate matter that has a metal oxide layer coated thereon, obtained by the process of claim 1. 22. A composition comprising coated particulate matter in accordance with claim 21 and a carrier. 23. The composition according to claim 22, wherein said coated particulate matter has a surface area of about 20-400 m.sup.2/g, and wherein said metal oxide layer has a thickness in the range of about 0.3-10 micron. 24. The composition of claim 23, wherein the weight ratio of said metal oxide to said solid, water-insoluble particulate matter, is in the range of about 3:97 to about 50:50. 25. The composition of claim 24, wherein the weight ratio of said metal oxide to said solid, water-insoluble particulate matter, is in the range of about 10:90 to about 20:80. 26. The composition of claim 23, wherein said coated particulate matter has a diameter of about 0.5-100 micron. 27. The composition of claim 22, wherein said metal oxide is selected from the group consisting of silica, titania, alumina, ZnO, and mixtures thereof. 28. The composition of claim 22, further comprising hydrophobic groups attached to the surface of the metal oxide layer. 29. The composition of claim 28, wherein said hydrophobic groups are selected from the group consisting of alkyl silane, aryl silane, and mixtures thereof. 30. A method for treating a surface condition in a subject, comprising topically administering onto the surface a composition according to claim 22. 31. The method of claim 30, wherein said surface is skin or mucosal membrane. 32. The method of claim 31, wherein said surface condition is a disease or disorder selected from the group consisting of acne, infection, inflammation, pruritus, psoriasis, seborrhea, contact dermatitis, rosacea, and a combination thereof. 33. The method of claim 30, wherein said solid, water insoluble organic dermatologically active agent is benzoyl peroxide or retinoid. 34. The process of claim 1, wherein the metal oxide salt is a salt of a silicate, an aluminate, a titanate or a zirconate. 35. The process of claim 1, wherein said solid, water-insoluble particulate matter has a particle size of about 0.5-100 microns. 36. A composition for topical administration, comprising: a plurality of particles, each of said particles comprising a solid, water insoluble organic dermatologically active agent, having a metal oxide layer coated on the surface of the solid, water insoluble organic dermatologically active agent, wherein said coated particles have a surface area of about 20-400 m.sup.2/g and said metal oxide layer has a thickness in the range of about 0.3-10 micron; and a carrier; said composition having reduced side effects and at least essentially the same therapeutic effect as compared to a reference composition, the difference between said composition and the reference composition being that in the latter the active agent is not coated. 37. The composition of claim 36, wherein said dermatologically active agent is selected from the group consisting of antifungal agents, antibacterial agents, antiinflammatory agents, antipruritic agents, antipsoriatic agent, and anti-acne agents. 38. The composition of claim 37, wherein said anti-acne agent is selected from the group consisting of benzoyl peroxide, retinoid, and mixtures thereof. 39. The composition of claim 37, wherein said anti-acne agent is benzoyl peroxide and said side effects are irritation, erythema, scaling, dryness, and stinging. 40. The composition of claim 37, wherein said anti-acne agent is benzoyl peroxide. 41. The composition of claim 36, wherein and said dermatological agent is an anti-acne agent, said composition yielding a therapeutic effect manifested in a colony reduction of P. acnes. 42. The composition of claim 41, wherein said therapeutic effect is at least a 0.5 logarithmic colony reduction of P. acnes in at least 90% of the subjects treated. 43. The composition of claim 41, wherein said therapeutic effect is at least 1 logarithmic colony reduction of P. acnes in at least 60% of the subjects treated. 44. A method for treating a surface condition in a subject, comprising topically administering onto the surface the composition of claim 36. 45. The method of claim 44, wherein said surface is skin or mucosal membrane. 46. The method of claim 44, wherein said surface condition is a disease or disorder selected from the group consisting of acne, infection, inflammation, pruritus, psoriasis, seborrhea, contact dermatitis, rosacea, and a combination thereof. 47. The method of claim 44, wherein said solid, water insoluble particulate matter, is benzoyl peroxide or retinoid.