US 12,257,348 B2
Stabilized microcapsules, method of their preparation and uses thereof
Ofer Toledano, Kfar Saba (IL); Karine Neimann, Ness Ziona (IL); Danil Finkel-Moiseev, Rehovot (IL); Maya Erlich, Ness Ziona (IL); and Dorit Marco, Rehovot (IL)
Assigned to Sol-Gel Technologies Ltd., Ness Ziona (IL)
Filed by Sol-Gel Technologies Ltd., Ness Ziona (IL)
Filed on May 23, 2021, as Appl. No. 17/327,724.
Claims priority of provisional application 63/028,599, filed on May 22, 2020.
Prior Publication US 2021/0361586 A1, Nov. 25, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 9/48 (2006.01); A61K 9/00 (2006.01); A61K 9/50 (2006.01); A61K 31/202 (2006.01); A61K 31/203 (2006.01); A61K 31/235 (2006.01); A61K 31/327 (2006.01); A61K 31/336 (2006.01)
CPC A61K 9/4808 (2013.01) [A61K 9/0014 (2013.01); A61K 9/4841 (2013.01); A61K 9/4858 (2013.01); A61K 9/4875 (2013.01); A61K 9/501 (2013.01); A61K 9/5084 (2013.01); A61K 9/5089 (2013.01); A61K 31/202 (2013.01); A61K 31/203 (2013.01); A61K 31/235 (2013.01); A61K 31/327 (2013.01); A61K 31/336 (2013.01)] 32 Claims
 
1. A microcapsule comprising a core encapsulated by a silica based shell, wherein said core comprises solid benzoyl peroxide (BPO), wherein said benzoyl peroxide is released at a dissolution rate of between 12%-60% weight/h as measured in a medium of 55%:45% mixture of water and acetonitrile at ambient temperature, and wherein said microcapsule is prepared by a process comprising:
a) contacting solid benzoyl peroxide particulate matter, with a first cationic additive being a cationic surfactant, to obtain a dispersion in an aqueous medium, said particulate matter having positive charges on its surface;
b) adding an aqueous solution comprising silicate salt to said dispersion of said particulate matter, under conditions wherein said silicate 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;
c) contacting, in a medium consisting of an aqueous medium, the particulate matter coated with a silica based layer of the preceding step with a surface adhering additive being one or both of (i) a second cationic additive being a cationic polymer and (ii) a non-ionic additive, to obtain a dispersion of said coated particulate matter having an adhering additive on the surface thereof in said aqueous medium;
d) bringing the dispersion obtained in step (c) into contact with an aqueous solution of a sodium silicate, under conditions wherein said sodium silicate precipitates onto the surface of said coated particulate matter, and acidifying to thereby form a solid, water-insoluble particulate matter that has a further silica based layer coated thereon;
e) repeating steps (c) and (d) between 3-50 times at a temperature of between 28° C. to 40° C.; and
f) optionally, after completion of step (e), aging the dispersion to obtain said encapsulated benzoyl peroxide.