CN113845607A

CN113845607A - Preparation method of hydroxypropyl-gamma-cyclodextrin

Info

Publication number: CN113845607A
Application number: CN202111246629.0A
Authority: CN
Inventors: 王哲; 崔丽艳; 许维成; 刘涛
Original assignee: Potofino Hainan Industrial Co ltd
Current assignee: Potofino Hainan Industrial Co ltd
Priority date: 2021-10-26
Filing date: 2021-10-26
Publication date: 2021-12-28

Abstract

The invention relates to a preparation method of hydroxypropyl-gamma-cyclodextrin, belonging to the technical field of preparation of etherified derivatives of cyclodextrin in organic high molecular compounds. The method simplifies post-treatment process, greatly reduces impurity content while improving product quality and yield, and is suitable for industrial production.

Description

Preparation method of hydroxypropyl-gamma-cyclodextrin

Technical Field

The invention relates to the technical field of preparation of etherified derivatives of organic macromolecular compounds, in particular to a preparation method of hydroxypropyl-gamma-cyclodextrin.

Background

The cyclodextrin has the advantages of natural and wide source, proper price, good biocompatibility and wide inclusion range, and can be widely applied to a plurality of industries such as the pharmaceutical industry, the food industry, the daily chemical industry, the environmental protection industry, the agriculture and the like. The matrix cyclodextrin produced in large scale at present comprises three types of alpha, beta and gamma-cyclodextrin, which are respectively prepared by connecting 6, 7 and 8D-glucopyranose units end to form a ring. Hydroxypropyl cyclodextrin is an etherified derivative of cyclodextrin, and the introduction of hydroxypropyl opens intramolecular hydrogen bonds of cyclodextrin to form an amorphous mixture, so that the water solubility is greatly improved while the main cavity structure is maintained.

The water solubility of the hydroxypropyl-gamma-cyclodextrin product after hydroxypropylation is further improved to 80g/100ml (25 ℃), and meanwhile, the gamma-cyclodextrin after hydroxypropylation is not a single pure product but a mixture with various substitutions, so that an inclusion compound is not easy to generate and crystallize out when being included with guest molecules. In general, hydroxypropyl- γ -cyclodextrin has higher solubility in water and stronger resistance to crystallization.

In the existing preparation method of hydroxypropyl-gamma-cyclodextrin, a high-concentration sodium hydroxide solution is generally adopted to participate in reaction, liquid acid is used for neutralization, an organic solvent or a membrane separation mode is used for removing impurities, the post-treatment process is complex, new byproduct impurities are easily introduced while various chemical reagents are harmful to human bodies, and if the impurities are removed by adopting the membrane separation mode, a large amount of wastewater is generated, and the impurities are not easily removed completely, so that the existing preparation method has low efficiency, and the finally obtained finished product has high impurity content.

Disclosure of Invention

In order to overcome the defects in the prior art, the invention provides a preparation method of hydroxypropyl-gamma-cyclodextrin, which has simple post-treatment and low impurity content, and comprises the following specific steps:

(1) preparing a sodium hydroxide solution with the mass concentration of 1-5%, adding gamma-cyclodextrin at room temperature, and stirring until the gamma-cyclodextrin is completely dissolved; and (3) dropwise adding propylene oxide, controlling the temperature to be 25-35 ℃, and continuously stirring and reacting for 3-5 h after the dropwise adding. Wherein the molar ratio of sodium hydroxide, gamma-cyclodextrin and propylene oxide is 0.5-1.5: 1: 5 to 6.5.

(2) Neutralizing the reaction liquid obtained in the step (1) with solid acid, filtering, performing membrane separation, and drying to obtain the hydroxypropyl-gamma-cyclodextrin. Wherein, the solid acid used for neutralizing the reaction solution comprises strong acid ion exchange resin, a molecular sieve and a load-type acid compound; the time of membrane separation is 1-3 h.

According to the preparation method, the substitution degree of the finally obtained hydroxypropyl-gamma-cyclodextrin is 4-6, and impurities such as gamma-cyclodextrin and 1, 2-propylene glycol are not contained.

The invention has the technical effects and advantages that:

1. the invention adopts the reaction of low-concentration alkali liquor and gamma-cyclodextrin, reduces the cost of raw materials, and simultaneously avoids the harm of high-concentration alkali liquor to human bodies;

2. the invention adopts solid acid to replace the traditional liquid acid, and because the solid acid has a special structure with macropores and multiple pores, the solid acid can also play a role in adsorbing small molecular impurities while neutralizing alkali, thereby effectively reducing the content of the impurities in the product;

3. the method adopts the mode of solid acid neutralization combined with membrane separation to remove trace impurities, can avoid the use of organic solvents, effectively remove impurities, reduce the use of waste acid and avoid the generation of a large amount of wastewater.

4. The hydroxypropyl-gamma-cyclodextrin product prepared by the invention has low impurity content, moderate degree of substitution, high product quality and high subsequent application safety.

Drawings

FIG. 1 is a nuclear magnetic spectrum of hydroxypropyl-gamma-cyclodextrin obtained in example 1 of the present invention.

Detailed Description

The present invention will be described in further detail with reference to specific examples.

Example 1:

s1, weighing 1.6g of sodium hydroxide, preparing into 1% alkali liquor by mass, adding 100g of gamma-cyclodextrin, stirring until the gamma-cyclodextrin is completely dissolved, controlling the temperature at 30 ℃, slowly dripping 23g of propylene oxide, controlling the dripping time at 30min, and continuing to react for 3h after the dripping is finished.

And S2, after the reaction is finished, adding strong acid ion exchange resin to adjust the pH value to be neutral, filtering to remove insoluble substances, carrying out membrane separation on the feed liquid for 1 hour, and drying to obtain white amorphous powder, namely hydroxypropyl-gamma-cyclodextrin. The product substitution degree is 5.3, the residue of gamma-cyclodextrin is not detected, and the residue of 1, 2-propylene glycol is not detected. The nuclear magnetic spectrum of the hydroxypropyl-gamma-cyclodextrin obtained in the example is shown in fig. 1, and the peak map is clean and has no impurity peak, which indicates that the hydroxypropyl-gamma-cyclodextrin obtained by the preparation method has high purity.

Example 2:

s1, weighing 3.0g of sodium hydroxide, preparing into alkali liquor with the mass fraction of 3%, adding 100g of gamma-cyclodextrin, stirring until the gamma-cyclodextrin is completely dissolved, controlling the temperature at 25 ℃, slowly dripping 23g of propylene oxide, controlling the dripping time at 20min, and continuing to react for 4h after the dripping is finished.

And S2, after the reaction is finished, adding a molecular sieve to adjust the pH value to be neutral, filtering to remove insoluble substances, carrying out membrane separation on the feed liquid for 2 hours, and drying to obtain white amorphous powder, namely hydroxypropyl-gamma-cyclodextrin. The product substitution degree is 4.8, the residue of gamma-cyclodextrin is not detected, and the residue of 1, 2-propylene glycol is not detected.

Claims

1. The preparation method of the hydroxypropyl-gamma-cyclodextrin is characterized by comprising the following steps:

(1) preparing a sodium hydroxide solution with the mass concentration of 1-5%, adding gamma-cyclodextrin at room temperature, and stirring until the gamma-cyclodextrin is completely dissolved; dropwise adding epoxypropane, controlling the temperature at 25-35 ℃, and continuously stirring and reacting for 3-5 h after the dropwise adding;

(2) and (2) neutralizing the reaction liquid obtained in the step (1) with solid acid, filtering, performing membrane separation, and drying to obtain the hydroxypropyl-gamma-cyclodextrin.

2. The preparation method of hydroxypropyl-gamma-cyclodextrin according to claim 1, wherein the molar ratio of sodium hydroxide, gamma-cyclodextrin and propylene oxide is 0.5-1.5: 1: 5 to 6.5.

3. The method of claim 1, wherein the solid acid used for neutralizing the reaction solution comprises one or more of a strongly acidic ion exchange resin, a molecular sieve, and a supported acid compound.

4. The preparation method of hydroxypropyl-gamma-cyclodextrin according to claim 1, wherein the time of membrane separation is 1-3 h.

5. The preparation method of hydroxypropyl-gamma-cyclodextrin according to claim 1, wherein the substitution degree of the obtained hydroxypropyl-gamma-cyclodextrin is 4-6.