CN102633911B - Method for preparing hydroxypropyl-beta-cyclodextrin by catalysis of starch microsphere supported calcium hydroxides - Google Patents

Abstract

The invention discloses a method for preparing hydroxypropyl-β-cyclodextrin by catalyzing calcium hydroxide loaded on starch microspheres. Adding β-cyclodextrin, propylene oxide, catalyst and reaction solvent water into the reaction equipment, The reaction is carried out under pressure conditions, and the reaction temperature is controlled, which can effectively improve the yield and purity of the product, and the final product is obtained by rapid drying with a spray dryer. The product has the advantages of low water content, uniform particle size distribution, high whiteness, appropriate degree of substitution, moderate fluffy feeling, etc. The purity of the product is over 99%, and the total reaction yield is over 95%.

Description

Catalyzed preparation method of hydroxypropyl-β-cyclodextrin supported by starch microspheres with calcium hydroxide

technical field

The invention relates to a method for preparing hydroxypropyl-β-cyclodextrin, in particular to a method for preparing hydroxypropyl-β-cyclodextrin by catalyzing starch microsphere-loaded calcium hydroxide.

Background technique

β-cyclodextrin is composed of 7 glucose units, and the hydrogen atoms in the 2-, 3-, and 6-position hydroxyl groups of each glucose residue can be replaced by hydroxypropyl groups to obtain hydroxypropyl-β-cyclodextrin. Hydroxypropyl-β-cyclodextrin is mainly used as an excipient drug in the medical field, and its main features are: ①Increase the water solubility of insoluble drugs; ②Increase drug stability and improve drug bioavailability; ③Reduce the toxic and side effects of drugs. Hydroxypropyl-β-cyclodextrin can be used in oral drugs, injections, mucosal drug delivery systems, transdermal drug delivery systems, carriers of lipophilic targeted drugs, and can also be used as protein protectants and stabilizers.

As a derivative of starch, a natural polymer product, starch microspheres have good environmental compatibility and have no toxic effects on the human body. Their porous structure makes them a catalyst carrier with excellent performance.

Contents of the invention

The purpose of the present invention is to provide a method for the preparation of hydroxypropyl-β-cyclodextrin catalyzed by calcium hydroxide loaded on starch microspheres, which can overcome the disadvantages of difficult handling of alkali catalysts in the traditional production process of hydroxypropyl-β-cyclodextrin , but does not affect the purity and yield of the product, and is a production method of hydroxypropyl-β-cyclodextrin with simple process and low cost.

In order to achieve the above object, the technical scheme adopted in the present invention is:

1) First, add 100L deionized water and 100-160g calcium hydroxide to the reaction equipment, stir for 0.5-2 hours, then add 2-4kg of porous starch microspheres, control the stirring speed to 100-300r/min, at room temperature Stir and react for 1-5 hours, filter, and rinse the filter cake 3 times with deionized water to obtain a porous starch microsphere-supported calcium hydroxide catalyst;

2) Next, add β-cyclodextrin, the catalyst of 3%-8% of β-cyclodextrin quality in reaction equipment, and add reaction solvent by the mass ratio of β-cyclodextrin: water=1:5-10 water, stirred evenly to obtain a mixed solution;

3) Then, fill the mixed solution with a pressure of 0.5Mpa-5Mpa at 15-25°C, control the temperature of the reaction system at 15-25°C, according to the molar ratio of β-cyclodextrin:propylene oxide=1:3-7 Add propylene oxide dropwise, control the drop rate, and complete the dropwise addition in 5-10 hours;

4) Finally, keep the reaction at 15-25°C for 12-36 hours. After the reaction is completed, filter and separate the starch microspheres, adjust the solid content of the obtained liquid to 5%-10%, and spray powder with a spray dryer to obtain Product Hydroxypropyl-β-cyclodextrin.

The present invention adopts an adsorption method to prepare the porous starch microsphere-loaded calcium hydroxide catalyst, that is, the porous starch microsphere is added to the aqueous solution of calcium hydroxide, so that the calcium hydroxide is adsorbed in the interior of the starch microsphere, thereby meeting the loading requirement. The preparation of hydroxypropyl-β-cyclodextrin by using starch microsphere-loaded calcium hydroxide catalyst, and taking into account the application of a certain pressure for the reaction, can effectively improve the yield and purity of the product, and the final product is quickly dried by a spray dryer. . The product has the advantages of low water content, uniform particle size distribution, high whiteness, appropriate degree of substitution, and moderate fluffy feeling. This is a green, simple process, high yield, high purity, and low-cost production method.

Detailed ways

Example 1:

1) First, add 100L deionized water and 100g calcium hydroxide to the reaction equipment, stir for 0.5 hours, then add 4kg of porous starch microspheres, control the stirring speed to 300r/min, stir and react at room temperature for 3 hours, filter, The filter cake was rinsed three times with deionized water to obtain porous starch microsphere-loaded calcium hydroxide catalyst;

2) Next, add β-cyclodextrin, 5% catalyst of β-cyclodextrin mass in reaction equipment, and add reaction solvent water by the mass ratio of β-cyclodextrin: water=1:8, stir to obtain mixture;

3) Then, fill the mixed solution with a pressure of 3Mpa at 25°C, control the temperature of the reaction system at 25°C, add propylene oxide dropwise according to the molar ratio of β-cyclodextrin:propylene oxide=1:7, and control the rate of addition , the dropwise addition was completed in 5 hours;

4) Finally, keep the reaction at 25°C for 36 hours. After the reaction is completed, filter and separate the starch microspheres. After adjusting the solid content of the obtained liquid to 5%, use a spray dryer to spray powder to obtain the product hydroxypropyl-β- Cyclodextrin. The purity detected by high performance liquid chromatography was 99%, and the yield was 95%.

Example 2:

1) First, add 100L deionized water and 160g calcium hydroxide to the reaction equipment, stir for 1 hour, then add 2kg of porous starch microspheres, control the stirring speed to 100r/min, stir and react at room temperature for 1 hour, filter, The filter cake was rinsed three times with deionized water to obtain porous starch microsphere-loaded calcium hydroxide catalyst;

2) Next, add β-cyclodextrin, 3% catalyst of β-cyclodextrin quality in reaction equipment, and add reaction solvent water by the mass ratio of β-cyclodextrin: water=1: 10, stir to obtain mixture;

3) Then, fill the mixed solution with a pressure of 0.5Mpa at 20°C, control the temperature of the reaction system at 20°C, add propylene oxide dropwise according to the molar ratio of β-cyclodextrin:propylene oxide=1:5, and control the temperature of the dropwise Acceleration, 8 hours dropwise completed;

4) Finally, keep the reaction at 20°C for 24 hours. After the reaction is completed, filter and separate the starch microspheres. After adjusting the solid content of the obtained liquid to 8%, use a spray dryer to spray powder to obtain the product hydroxypropyl-β- Cyclodextrin. The purity detected by high performance liquid chromatography was 99%, and the yield was 96%.

Example 3:

1) First, add 100L deionized water and 140g calcium hydroxide to the reaction equipment, stir for 2 hours, then add 3kg of porous starch microspheres, control the stirring speed to 200r/min, stir and react at room temperature for 5 hours, filter, The filter cake was rinsed three times with deionized water to obtain porous starch microsphere-loaded calcium hydroxide catalyst;

2) Next, add β-cyclodextrin, 8% catalyst of β-cyclodextrin mass in reaction equipment, and add reaction solvent water by the mass ratio of β-cyclodextrin: water=1:5, stir to obtain mixture;

3) Then, fill the mixed solution with a pressure of 5Mpa at 15°C, control the temperature of the reaction system to be 15°C, add propylene oxide dropwise according to the molar ratio of β-cyclodextrin: propylene oxide=1:3, and control the drop rate , the dropwise addition was completed in 10 hours;

4) Finally, keep the reaction at 15°C for 12 hours. After the reaction is completed, filter and separate the starch microspheres. After adjusting the solid content of the obtained liquid to 10%, use a spray dryer to spray powder to obtain the product hydroxypropyl-β- Cyclodextrin. The purity detected by high performance liquid chromatography was 99%, and the yield was 98%.

The present invention uses starch microspheres loaded with calcium hydroxide as a reaction catalyst. During the entire reaction process, the catalyst always exists in the apparent form of starch microspheres. After the reaction is completed, it is directly removed by solid-liquid separation, thereby eliminating the need for traditional alkalis. The ion exchange equipment or ion permeation equipment required by the liquid as a reaction catalyst simplifies the production process. The product purity can reach more than 99%, and the total yield is more than 95%.

Claims (1)

1. a starch microsphere loaded calcium hydroxide catalyzes the method for preparing hydroxypropyl-beta-cyclodextrin, is characterized in that: 1) First, add 100L deionized water and 100-160g calcium hydroxide to the reaction equipment, stir for 0.5-2 hours, then add 2-4kg of porous starch microspheres, control the stirring speed to 100-300r/min, at room temperature Stir and react for 1-5 hours, filter, and rinse the filter cake 3 times with deionized water to obtain a porous starch microsphere-supported calcium hydroxide catalyst; 2) Next, add β-cyclodextrin and a catalyst with 3%-8% mass of β-cyclodextrin in the reaction equipment, and add the reaction solvent according to the mass ratio of β-cyclodextrin:water=1:5-10 water, stirred evenly to obtain a mixed solution; 3) Then, fill the mixed solution with a pressure of 0.5MPa-5MPa at 15-25℃, control the temperature of the reaction system at 15-25℃, according to the molar ratio of β-cyclodextrin:propylene oxide=1:3-7 Add propylene oxide dropwise, control the drop rate, and complete the dropwise addition in 5-10 hours; 4) Finally, keep the reaction at 15-25°C for 12-36 hours. After the reaction is completed, filter and separate the starch microspheres, adjust the solid content of the obtained liquid to 5%-10%, and spray powder with a spray dryer to obtain Product Hydroxypropyl-β-cyclodextrin.