Non-aqueous liquid and semi-solid formulations of amorphous calcium carbonate

Abstract

The present invention provides stabilized amorphous calcium carbonate (ACC) formulations, comprising ACC and a non-aqueous liquid carrier in which the ACC is dispersed. The present invention further provides cosmetic and pharmaceutical compositions comprising ACC.

1 . A liquid or semi-solid non-aqueous composition in the form of a dispersion or suspension of amorphous calcium carbonate (ACC) particles, the liquid or semi-solid non-aqueous comprising:
 a plurality of ACC particles comprising:
 ACC as an active agent; 
 at least one agent stabilizing the ACC in amorphous form; and 
 a non-aqueous liquid carrier in which the ACC particles are insoluble and are substantially uniformly dispersed or suspended; 
   wherein the liquid or semi-solid non-aqueous composition has a viscosity of above 40 centipoise (cP) at 25° C.   
     
     
         2 . The liquid or semi-solid non-aqueous composition of  claim 1 , wherein the liquid or semi-solid non-aqueous composition is selected from the group consisting of a toothpaste, gel, emulsion, cream, ointment, lotion, paste, suppository, and patch. 
     
     
         3 . The liquid or semi-solid non-aqueous composition of  claim 1 , wherein the liquid or semi-solid non-aqueous composition is a topical composition. 
     
     
         4 . The liquid or semi-solid non-aqueous composition of  claim 1 , further comprising less than 20% or less than 5% by weight water of the total composition. 
     
     
         5 . The liquid or semi-solid non-aqueous composition of  claim 1 , further comprising from 0.01 to 40% by weight ACC particles. 
     
     
         6 . The liquid or semi-solid non-aqueous composition of  claim 1 , wherein the non-aqueous liquid carrier is selected from the group consisting of organic polyols, water-immiscible lipids, synthetic oils, and mixtures thereof. 
     
     
         7 . The liquid or semi-solid non-aqueous composition of  claim 6 , having one or more of the following:
 the organic polyol is selected from the group consisting of propylene glycol (PG), polyethylene glycol (PEG), PEG derivative, glycerol, glycerol, and combinations thereof;   the water-immiscible lipid is selected from the group consisting of natural oils, medium-chain triglycerides, and combinations thereof; or   the synthetic oil is selected from the group consisting of a polydimethylsiloxane, a functionally modified dimethylsiloxane, a polydimethylsiloxane-copolyol, a polydimethylsiloxane-crosspolymer, and combinations thereof.   
     
     
         8 . The liquid or semi-solid non-aqueous composition of  claim 7 , having one or more of the following:
 the PEG is selected from the group consisting of PEG 300, PEG 400, and combinations thereof;   the natural oil is selected from the group consisting of castor oil, corn oil, cottonseed oil, olive oil, peanut oil, peppermint oil, sunflower oil, sesame oil, soybean oil, hydrogenated vegetable oils, hydrogenated soybean oil, and combinations thereof;   the medium-chain triglyceride comprises medium-chain triglycerides of coconut oil or palm seed oil;   the polydimethylsiloxane is selected from the group consisting of a cyclopentasiloxane, a cyclotetrasiloxane, and combinations thereof;   the functionally modified dimethylsiloxane is a siloxane monomer modified by independently replacing one or two methyl groups with an H, OH, phenyl, propyl, octyl, amino-propyl, or vinyl;   the polydimethylsiloxane-copolyol is a mixture of 70-90% cyclopentasiloxane and 10-30% PEG/PPG-18/18; or   the polydimethylsiloxane-crosspolymer is a mixture of 70-90% cyclopentasiloxane and 10-30% crosspolymer.   
     
     
         9 . The liquid or semi-solid non-aqueous composition of  claim 1 , further comprising at least one excipient selected from the group consisting of a surfactant, an emollient, a thickening agent, and a dispersing agent. 
     
     
         10 . The liquid or semi-solid non-aqueous composition of  claim 9 , having one or more of the following:
 the surfactant is a non-ionic organic surfactant or an anionic organic surfactant;   the emollient is selected from the group consisting of a wax, a solid fat, a glyceride, an ethoxylated fatty alcohol, and combinations thereof;   the thickening agent is selected from the group consisting of a cellulose polymer, silsesquioxane, silica, and combinations thereof; or   the dispersing agent is a cyclodextrin.   
     
     
         11 . The liquid or semi-solid non-aqueous composition of  claim 10 , having one or more of the following:
 the non-ionic organic surfactant is selected from the group consisting of polysorbates, sorbitan esters, fatty acid esters, wax esters, poloxamers, and phospholipids;   the anionic organic surfactant is sodium lauryl sulfate;   the cellulose polymer is selected from the group consisting of hydroxypropylethylcellulose, sodium carboxymethyl cellulose, and combinations thereof; or   the cyclodextrin is selected from the group consisting of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and combinations thereof.   
     
     
         12 . The liquid or semi-solid non-aqueous composition of  claim 11 , having one or more of the following:
 the polysorbates are selected from the group consisting of Tween 80, Tween 60, Tween 20, and combinations thereof;   the fatty acid esters are selected from the group consisting of polyoxyethylene fatty acid esters, sucrose esters of fatty acids, glycerol monostearate, and combinations thereof;   the fatty acid esters are selected from the group consisting of Span 80, Span 60, Sisterna, Cutina, MYRJ 52, solutol HS15, and combinations thereof; or   the wax ester is isostearyl isostearate.   
     
     
         13 . The liquid or semi-solid non-aqueous composition of  claim 1 , further comprising from 2 to 7 wt % of ACC, Glycerin, Precipitated silica, Sodium lauryl sulfate, a flavor, and sodium carboxymethyl cellulose-1.5%. 
     
     
         14 . A pharmaceutical or cosmeceutical composition comprising the liquid or semi-solid non-aqueous composition of  claim 1 . 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein said pharmaceutical composition is formulated for a topical administration. 
     
     
         16 . A method of preparing a liquid or semi-solid non-aqueous composition in the form of a dispersion or suspension of amorphous calcium carbonate (ACC) particles, the method comprising:
 i. mixing at least one non-aqueous liquid carrier with at least one additional agent selected from the group consisting of a dispersing agent, a surfactant, a thickening agent and an emollient; and   ii. adding ACC to the mixture.   
     
     
         17 . The method of  claim 16 , further comprising preparing two separate non-aqueous liquid carriers, wherein the ACC is added to one of the non-aqueous liquid carriers before it is mixed with the other non-aqueous liquid carrier. 
     
     
         18 . The method of  claim 16 , further comprising one or more of:
 mixing comprises high shear mixing or using a micro-fluidizer; or
 mixing continues until all non-liquid agents are dissolved in the non-aqueous liquid carrier. 
   
     
     
         19 . The method of  claim 16 , wherein the ACC is dry, stabilized ACC. 
     
     
         20 . The method of  claim 16 , further comprising heating the non-aqueous liquid carrier.