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A kind of preparation method of ester

A technology of glyceryl behenate and behenic acid, which is applied in the preparation of pharmaceutical excipients and the field of glyceryl behenate, can solve the problem that glyceryl behenate is difficult to meet the quality requirements of pharmaceutical excipients, and achieve cost Low, easy to operate and control, the effect of low reaction temperature

Active Publication Date: 2019-01-04
SUNSHINE LAKE PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The glyceryl behenate obtained by the method of the prior art is difficult to meet the quality requirements of pharmaceutical excipients

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] In the reactor, add 136.40g behenic acid, 44.60g glycerin, 4.60g p-toluenesulfonic acid monohydrate, 200mL mixed solvent of cyclohexane and n-heptane (volume ratio 1:4), add The same mixed solvent is 32mL, stirred, heated to reflux; the water separator is divided into water, refluxed for 11 hours to 12 hours, and the reaction is stopped; the reaction mixture is cooled to 60°C, added to 400mL of ice water, stirred for 1 hour, and a solid is precipitated , filtered; the obtained solid was vacuum dried at 40°C for 8 hours to 10 hours; the obtained solid was mixed with 1000mL isopropyl ether, stirred at 20°C to 30°C for 0.5 hour to 1 hour, filtered, and the solid was vacuum dried at 35°C for 20 hours to 24 hours ; Obtain white product 150.35g, HPLC detects, and ester content meets the requirements.

Embodiment 2

[0027] In the reactor, add 136.40g behenic acid, 44.60g glycerol, 4.60g p-toluenesulfonic acid monohydrate, add 225mL of mixed solvent of cyclohexane and n-heptane (volume ratio 1:4), in the water separator Add 30mL of the same mixed solvent, stir, and heat to reflux; the water separator divides the water, reflux for 12-13 hours, and stop the reaction; cool the mixed solution to 60°C, add 450mL of cold acetone and water mixed solution ( Volume ratio 1:4), stirred for 1 hour, filtered; the obtained solid was vacuum-dried at 40°C for 8 hours; the obtained solid was mixed with 900mL isopropyl ether, stirred for 1 hour at 25°C-30°C, filtered, and the solid was vacuum-dried at 35°C for 24 hours ; Obtain 150.08g of white product, and HPLC detects that the ester content meets the requirements.

Embodiment 3

[0029] In the reactor, add 136.40g behenic acid, 50.00g glycerol, 3.90g p-toluenesulfonic acid monohydrate, add 180mL of mixed solvent of cyclohexane and n-heptane (volume ratio 1:5), in the water separator Add 25mL of the same mixed solvent, stir, and heat to reflux; divide the water with the water separator, reflux for 13-14 hours, and stop the reaction; cool the mixed solution to 60°C, add it to 400mL of cold water, and stir for 1-1.5 hours , filtered; the obtained solid was vacuum-dried at 40°C for 8 hours to 10 hours; the obtained solid was mixed with 1100mL isopropyl ether, stirred at 20°C for 45 minutes, filtered, and the solid was dried at 35°C for 24 hours; 149.78g of white product was obtained, which was detected by HPLC. The content meets the requirements.

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Abstract

The invention provides a method for preparing a pharmaceutical adjuvant glyceryl behenate. The method comprises: reacting in a mixed reaction solvent of cyclohexane and n-heptane in the presence of an acid catalyst to prepare glyceryl behenate. According to the method provided by the invention, by controlling such reaction conditions as the use amount and proportion of the mixed solvent, the reaction temperature and the like, products meeting the quality standard of pharmaceutical adjuvants can be obtained; moreover, the method is easy to operate and control, low in cost and suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical excipient, in particular to a preparation method of glyceryl behenate, and belongs to the technical field of pharmacy. Background technique [0002] Glyceryl behenate is a mixture mainly of glyceryl monobehenate (monoester), glyceryl dibehenate (diester), and glyceryl tribehenate (trieser) Glycerides of long-chain fatty acids; it is a nonionic surfactant with excellent biocompatibility and can be used as a lubricant or sustained-release agent for tablets, capsules, and oral liquids, which can improve the quality of tablets and capsules. Compressibility in production; also has the characteristics of odor masking, chemical protection, anti-oxidation, anti-hydrolysis; widely used in food, medicine, cosmetics and other fields. [0003] In the prior art, the methods for preparing glyceryl behenate mainly include: first protect the hydroxyl group of glycerol with a protective agent, then reac...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C67/08C07C69/30
CPCC07C67/08C07C69/30
Inventor 王振国黄扬兵陈勇钟少伟
Owner SUNSHINE LAKE PHARM CO LTD