Preparation of sterol and stanol-esters

#This invention relates to the preparation of discrete sterol and stanol-esters through a highly efficient catalyzed route in the presence of a color deactivating agent.

#It has been shown that the addition of plant sterols, such as β-sitosterol, to diets will reduce serum cholesterol levels. The sterols reduce serum cholesterol through the disruption of intestinal absorption of dietary cholesterol by displacing it from bile acid micelli. More recently, β-sitosterol's saturated derivative, β-sitostanol, has been shown to be more effective in the reduction of intestinal cholesterol absorption. The sitostanol itself is virtually unabsorbed, so it does not contribute at all to in vivo serum sterol concentration upon consumption. Unfortunately, typical sterols and stanols are insoluble in the micelli phase of the alimentary canal and have only limited solubility in oils and/or fats or water. Hence, free sterols or stanols themselves are not optimum candidates for use in typical pharmaceutical or dietary dosage forms as cholesterol reducing agents.

#U.S. Pat. No. 5,502,045 discloses the interesterification of stanols with a fatty acid ester from an edible oil to produce a waxy sterol-ester mixture with improved fat solubility characteristics. Specifically, this patent discloses the reaction of sitostanol interesterified with fatty acids from methyl esters of an edible oil such as rapeseed oil specifically via a base catalyzed transesterification reaction. This is a process that is widely used in the food industry. From a pharmaceutical standpoint, however, interesterification processes such as this have some distinct disadvantages. Primarily, the composition profile of the sterol-ester products are difficult to control since the profile is dependent on the array of fatty acids present in the edible oil employed in the reaction. In addition methanol a by-product of this reaction must be carefully removed and the use of methyesters requires large excesses to be used making recycle difficult.

#The term acid used herein to describe acid used as a reactant is understood to include fatty acids, saturated including polyunsaturated and polyunsaturated acids as is set forth herein. The following examples are provided to further illustrate the claimed invention, but not limit the invention to the examples provided below.

#The stanol-fatty acid-esters of the invention were prepared by the acid catalyzed esterification reaction method as follows: stanol (10 mmol), fatty acid (12 mmol) and sodium bisulfate (0.12 mmol) were stirred neat under vacuum for 16 hours, at 150° C. The resulting stanol-ester products were isolated using either the technique described above as Method A (employing both water and an organic solvent) or Method B (an aqueous separation process). When glass-like products were formed in method A, they were converted into free flowing solids upon cooling below 0° C. Gas chromatography analysis of crude reaction product indicated that the reactions proceed to greater than 95% completion. Final work-up was performed according to methods A or B as described above.

#Analytical data for five representative stanol-esters are described below. Analytical data for an ester of cholestanol, as an additional model is also included.