Clear micellized formulations of beta-carotene and method of treating leukoplakia

Abstract

A clear aqueous formulation for topical application in the oral cavity of humans to treat leukoplakia contains water, β-carotene, a water miscible polyol, an unsaturated fatty acid ester, and a surfactant, preferably polyethoxylated castor oil. The formulation preferably also contains a pharmaceutically acceptable anti-oxidant, preferably d-alpha-tocopherol (vitamin E), and is in the form of an oral rinse or as a gel well suited for spreading on gums or other parts of the oral cavity. The formulation is applied in a gel form on a substantially regular daily basis to areas in the oral cavity where leukoplakia lesions are present. Persistent application of the gel results in substantial diminution or total elimination of the leukoplakia lesions.

1 - 20 . (canceled).  
     
     
         21 . A clear aqueous composition for topical application in the oral cavity of humans, the composition comprising: 
 water;    a water miscible pharmaceutically acceptable polyol;    a pharmaceutically acceptable unsaturated fatty acid ester;    a pharmaceutically acceptable surfactant, and    β-carotene, said β-carotene being in a micellized form within said composition.    
     
     
         22 . A composition in accordance with  claim 21  wherein the composition additionally comprises a pharmaceutically acceptable anti-oxidant.  
     
     
         23 . A composition in accordance with  claim 22  wherein the pharmaceutically acceptable anti-oxidant is d-alpha-tocopherol or a pharmaceutically acceptable derivative of d-alpha tocopherol having vitamin E activity.  
     
     
         24 . A composition in accordance with  claim 21  wherein the composition additionally comprises a compound having vitamin A activity.  
     
     
         25 . A composition in accordance with  claim 21  wherein the surfactant is polyethoxylated castor oil.  
     
     
         26 . A composition in accordance with  claim 21  wherein the polyol is glycerol.  
     
     
         27 . A composition in accordance with  claim 21  wherein the unsaturated fatty acid ester is ethyl linoleate.  
     
     
         28 . A composition in accordance with  claim 21  wherein the composition is a gel.  
     
     
         29 . A composition in accordance with  claim 21  wherein the composition comprises: 
 10 to 50% by weight water;  
 5 to 40% by weight of the water miscible pharmaceutically acceptable polyol;  
 1 to 20% by weight of the pharmaceutically acceptable unsaturated fatty acid ester;  
 10 to 60% by weight of the pharmaceutically acceptable surfactant, and  
 0.03 to 9.0% by weight of β-carotene.  
 
     
     
         30 . A composition in accordance with  claim 29  wherein the water miscible pharmaceutically acceptable polyol is glycerol; 
 the pharmaceutically acceptable unsaturated fatty acid ester is ethyl linoleate, and  
 the pharmaceutically acceptable surfactant is polyethoxylated castor oil.  
 
     
     
         31 . A composition in accordance with  claim 21  wherein the composition comprises: 
 20 to 40% by weight water;  
 10 to 30% by weight of the water miscible pharmaceutically acceptable polyol;  
 1 to 15% by weight of the pharmaceutically acceptable unsaturated fatty acid ester;  
 20 to 40% by weight of the pharmaceutically acceptable surfactant, and  
 0.3 to 3.0% by weight of β-carotene.  
 
     
     
         32 . A composition in accordance with  claim 31  wherein the water miscible pharmaceutically acceptable polyol is glycerol; 
 the pharmaceutically acceptable unsaturated fatty acid ester is ethyl linoleate, and  
 the pharmaceutically acceptable surfactant is polyethoxylated castor oil.  
 
     
     
         33 . A composition in accordance with  claim 32  wherein the composition additionally comprises d-alpha-tocopherol and a compound having vitamin A activity.  
     
     
         34 . A composition in accordance with  claim 33  wherein the composition is a gel.  
     
     
         35 . A composition in accordance with  claim 21  wherein the composition comprises: 
 50 to 95% by weight water;  
 1 to 10% by weight of the water miscible pharmaceutically acceptable polyol;  
 0.01 to 2% by weight of the pharmaceutically acceptable unsaturated fatty acid ester;  
 0.01 to 5% by weight of the pharmaceutically acceptable surfactant, and  
 0.003 to 1.2% by weight of β-carotene,  
 1 to 10% by weight of a pharmaceutically acceptable sweetener;  
 0.01 to 2% of a pharmaceutically acceptable antibacterial agent;  
 d-alpha tocopherol or a pharmaceutically acceptable derivative of d-alpha tocopherol having vitamin E activity;  
 vitamin A palmitate or a pharmaceutically acceptable derivative of vitamin A palmitate having vitamin A activity;  
 a pharmaceutically acceptable chelating agent;  
 a pharmaceutically acceptable antifoaming agent;  
 a flavoring agent, and  
 a preservative.  
 
     
     
         36 . A composition in accordance with  claim 35  wherein the water miscible pharmaceutically acceptable polyol is glycerol; 
 the pharmaceutically acceptable unsaturated fatty acid ester is ethyl linoleate;  
 the pharmaceutically acceptable surfactant is polyethoxylated castor oil;  
 the pharmaceutically acceptable sweetener is xylitol;  
 the pharmaceutically acceptable antibacterial agent is cetyl pyridinium chloride;  
 the pharmaceutically acceptable chelating agent is disodium EDTA, and  
 the preservative is sodium benzoate.  
 
     
     
         37 . A composition in accordance with  claim 36  wherein the composition is an oral rinse.  
     
     
         38 . A composition in accordance with  claim 37  wherein the composition comprises: 
 75 to 95% by weight water;  
 2 to 7% by weight of glycerol;  
 0.01 to 0.5% by weight ethyl linoleate;  
 0.01 to 1% by weight polyethoxylated castor oil;  
 0.003 to 10.6% by weight of β-carotene,  
 2 to 7% by weight of xylitol;  
 0.01 to 1% of cetyl pyridinium chloride;  
 0.005 to 0.05% by weight of disodium EDTA;  
 0.2 to 1.5% by weight of flavoring agent, and  
 0.01 to 0.5% by weight of sodium benzoate.  
 
     
     
         39 . A clear aqueous gel composition for topical application in the oral cavity of humans, the composition having been prepared by a process comprising the steps of: admixing a suspension of β-carotene in edible oil with polyethoxylated castor oil and heating said admixture to approximately 160 to 180° C. and agitating said admixture in said temperature range of 160 to 180° C. until a clear homogeneous solution is obtained; thereafter cooling said admixture to approximately 130 to 135° C. and adding d-alpha-tocopherol, glycerol and ethyl linoleate to said admixture, the d-alpha-tocopherol, glycerol and ethyl linoleate being added to the admixture at such a rate of addition that the temperature of the resulting mixture is cooled to approximately 85 to 95° C.; maintaining the resulting mixture under agitation at 85 to 95° C. until a clear homogeneous mixture is obtained; 
 thereafter adding under agitation water of approximately 55 to 60° C. temperature and cooling the mixture under agitation until a clear homogenous product is obtained.  
 
     
     
         40 . A clear aqueous gel composition in accordance with  claim 39  comprising: 
 20 to 40% by weight water;  
 10 to 30% by weight of glycerol;  
 1 to 15% by weight of ethyl linoleate;  
 20 to 40% by weight of polyethoxylated castor oil;  
 0.3 to 3.0% by weight of β-carotene.