FI63948C - FOERFARANDE FOER SEPARERING AV BETA-SITOSTEROL FRAON EN STEROLBLANDNING UTVUNNEN UR RAOSAOPANS NEUTRALFRAKTION - Google Patents

Description

, 63948

Method for separating 0-sitosterol from a sterol mixture isolated from a crude neutral neutralizer

By division separated from application 810216.

The invention relates to a process for isolating O-sitosterol from a sterol mixture isolated from a crude neutral fraction.

This gives O-sitosterol containing not more than A X, preferably less than 2 X, 0 (-s-sitosterol and less than 7 X of campester o-5. The total proportion of other impurities is less than 0.5 X.

In the pharmaceutical industry, O-sitosterol can be used per se for pharmaceutical purposes, as well as as a starting material for the preparation of steroid intermediates. However, an important condition is that β-sitosterol meets certain quality requirements. For example, it is necessary to obtain 13-sitosterol with the lowest possible X-sitosterol content, i.e. at least less than A%. Natural sources of 3-sitosterol, such as a mixture of sitosterol separated from the neutral fraction of sulphate pulp crude, may be rich in 0-sitosterol , i.e. about 20% or more.

The separation of β- and β-sitosterol is thus an important task in practice. The following methods have been proposed to solve this problem: U.S. Patent No. 2,573,265 describes a method for separating 13-sitosterol-like sitosterols from other 20 sterols, that the starting material is dissolved in a hydrocarbon or halogenated hydrocarbon, after which the β-sitosterols and sitosterols of the same type are crystallized with HClO 2 or HPF 2.

6 3 9 4 8 1 In Sei.Res. (Dhaka, Pak.) 1969, p. 162, describes e.g.

Separation of O- and β-sitosterol by chromatography on alumina.

Finnish Patent Publication No. 57956 describes a method for isolating 50 O-sitosterol from mixtures containing e.g.

. also (X-binders. This method is characterized in that the starting material is treated with a strong, inorganic or organic acid in an organic solvent. After the acid treatment, the reaction product obtained, e.g. by cooling solution 10 or evaporating the solvent, is crystallized from a suitable organic solvent. a sterol mixture separated from the neutral fraction, according to this method a final product is obtained which contains about 90 X β-sitosterol, about 6% campesterol, sitosterol degradation products and possibly water-cleavage products The actual X-sitosterol is very low in the final product; 2 X if suitable conditions are selected.

Finnish Patent Publication No. 58333 describes a process for removing? - acids and water.

the fact that the yield of 3-sitosterol remains rather low, less than 55 X, 25 as well as the O 2 -costerosterol content of the final product remains above 2%.

The process according to the invention for isolating 3-sitosterol from a crude sterol mixture containing, in addition to 13-sitosterol, O (-itosterol and campesterol) seeks to eliminate the above-mentioned drawbacks. β-sitosterol has a 0 (sitosterol content of 0-4.0% and a campesterol content of 6.0-7.0%).

'3' 63948 1 The process according to the invention uses an aqueous mixture of acetone to crystallize O-sitosterol from a crude sterol mixture as a hydrate. The crystallized sterol contains 2-4% water of crystal, which is not removed from the product until a temperature of 80-100 ° C.

5 Acetone is a cheap solvent and can be reused for the same purpose after distillation. The process of the invention is economical and easy to perform because the process does not use complex solvent mixtures typical of other purification processes. The use of only one solvent is a significant advantage on a technical scale in carrying out the process. The solvent used, acetone, is also advantageous from the point of view of occupational safety. It can also be considered an advantage that the final product does not contain impurities other than the above-mentioned campesterol and β-sitostero-1511 in addition to O-sitosterol.

The process according to the invention is characterized in that the crude sterol mixture containing O-sitosterol, campesterol and sitosterol is boiled with acetone for 1/2 to 1 hour in a reactor 20 under vertical cooling until the precipitate has dissolved. Water is added to the solution, whereupon O-sitosterol forms a hydrate which crystallizes on cooling. O (sitosterol) and other neutral components present as a harmful impurity remain selectively in the mother liquor. The crystallized fraction contains more than 90% O-sitosterol, 6-7% campesterol and up to 4% δ (-sitosterol. The mother liquor readily gives the solvent. Thus, there are no problems in the purification process with respect to solvent recycling.The concentration of campesterol has no effect on the success of the process, since campesterol also crystallizes as a hydrate almost quantitatively.

-4- 63948 1 The method according to the invention can be described in more detail by the following examples. The examples use as starting material a crude roll mixture isolated from the crude neutral fraction and having the following composition:

5-sitosterol 76.2 Z

q (-sitosterol 17.7 Z

Campesterol 6.1%

Example 1 10 g of crude 13-sitosterol containing 76.2 Z O-sitosterol, 17.7 Z-sitosterol and 6.1 Z campesterol were dissolved in 10 100 ml hot acetone. 5 ml of water were added and the mixture was cooled to 10 ° C. The resulting precipitate was filtered off and dried. The precipitate, weighing 7.9 g, contained 91.5 Z O-sitosterol, 2.0 Z-sitosterol and 6.5 Z campesterol.

Example 2 10 g of crude O-sitosterol (same as e.g. 1) were dissolved in 100 ml of hot acetone. To the solution was added 1 ml of water, and the mixture was cooled to 10 ° C. The resulting precipitate was filtered off and dried. The precipitate weighing 8.2 g contained 89.0 Z O-sitosterol, 4.0 Z ≤ (sitosterol) and 7 Z campesterol.

Claims (1)

A process for separating β-sitosterol from a sterol mixture isolated from the crude neutral fraction of the sulphate cellulose process as a hydrate in good yield, preferably in more than 90% yield, to obtain purified O-sitosterol-5 containing up to A% sitosterols and 7X campesterol, and soil impurities not exceeding 0.5%, by treating said sterol mixture with a mixture containing only one solvent and water, characterized in that 10 a) the β-sitosterol-containing mixture is dissolved in acetone so that the solids-solvent ratio is preferably 1: 8 to 1:13, 'and the volume ratio of water to acetone is 1:20 to 1: 100 b) heating the solvent to boiling point until the 0-sitosterol-containing mixture dissolves 15 c) adding water to the solution before cooling the solution to 15 ° C or below, whereupon the product crystallizes on freezing as a hydrate , and d) separating the doped β-sitosterol-rich product which is substantially free of CX-sitosterol, including up to 20 X of the O 2 -citosterol content of the starting sterol mixture by filtration.