阅读说明：本技术 一种七叶皂苷钠的制备方法 (Preparation method of sodium aescinate ) 是由 刘骞 于 2018-08-28 设计创作，主要内容包括：本发明公开了一种七叶皂苷钠的制备方法,以娑罗子为起始原料,经挑选粉碎,提取、萃取、洗涤、蒸馏、层析、成盐、浓缩、结晶、烘包工序生产而成。本发明工艺简单,采用简单的提取纯化工艺,可达到生产药用级七叶皂苷钠的质量要求。本发明工艺总收率可高达4.32～6.18％,比传统工艺收率提高了35～90％。本发明生产周期约28～36h,比传统工艺减少了约16h,提高了生产效率。本发明未采用毒性试剂或大量金属盐,有机溶剂都可回收处理后再利用,产生的少量含钠盐废水可经简单的离子交换进行水处理,彻底解决了传统方法的环境污染问题。(The invention discloses a preparation method of aescine sodium, which is prepared by using buckeye seeds as a starting raw material through the processes of selecting, crushing, extracting, washing, distilling, carrying out chromatography, salifying, concentrating, crystallizing and baking. The invention has simple process, adopts simple extraction and purification process, and can meet the quality requirement of producing the medical-grade sodium aescinate. The total yield of the process can reach 4.32-6.18%, and is improved by 35-90% compared with the yield of the traditional process. The production cycle of the invention is about 28-36 h, which is reduced by about 16h compared with the traditional process, and the production efficiency is improved. The method does not adopt toxic reagents or a large amount of metal salts, the organic solvent can be recycled and reused after being recycled, and the generated small amount of wastewater containing sodium salt can be subjected to water treatment by simple ion exchange, thereby thoroughly solving the problem of environmental pollution of the traditional method.)

1. A method for preparing aescine sodium is prepared from semen Aesculi as a starting raw material by selecting, pulverizing, extracting, washing, distilling, chromatography, salifying, concentrating, crystallizing, and baking, and specifically comprises the following steps:

1) after the buckeye is picked, crushing the buckeye by using a crusher, and collecting buckeye powder for later use;

2) extracting; buckeye powder is prepared by mixing 1-10 parts of Chinese buckeye powder in a solid-liquid ratio: 1, adding an alcohol extraction solution, standing and soaking for 2-8 hours, and then stirring and extracting for 4-5 hours; filtering the extract by a centrifuge and then filtering the extract by a bag filter to obtain an extract, transferring the extract into the extraction process, and carrying out secondary extraction on filter residues, wherein the secondary extract is recycled;

3) extracting the extractive solution with chloroform or dichloromethane for 2 times, mixing, and washing with purified water for 3 times;

4) concentrating the extracting solution under reduced pressure, dissolving the extracting solution with 75% ethanol, adding 1-2% activated carbon for decolorization, adjusting the pH of the filtrate to 5.5-7, and purifying by chromatography with a neutral alumina layer, wherein the amount of the neutral alumina filler is 1/20-1/10 of the weight of the seven-leaf solution;

5) and concentrating the purified solution under reduced pressure, and concentrating according to the following concentrated solution: diluting with absolute ethyl alcohol at a ratio of 1: 10-15, filtering the diluted solution, cooling to-10-18 ℃, crystallizing for 8-12 h, filtering the crystal, washing with absolute ethyl alcohol, and drying in vacuum for 4h to obtain the sodium aescinate.

2. The preparation method of aescine sodium as claimed in claim 1, wherein the buckeye is crushed by a water-cooling crusher in the step 1), and the crushed buckeye has 20-100 meshes.

3. The method for preparing sodium aescinate according to claim 1, wherein the alcohol solution in the step 2) is an aqueous solution of methanol and ethanol, and the volume ratio of the alcohol to the water is 1-5: 1.

4. The method for preparing sodium aescinate according to claim 1, wherein the pH of the extract solution in the step 3) is adjusted to 2.2 to 3.0 before extraction, and the amount of the extract solution is 1/6 to 1/3 of the extract solution.

5. The method for preparing sodium aescinate according to claim 1, wherein the concentration temperature in step 4) is < 60 ℃.

6. The method for preparing sodium aescinate according to claim 1, wherein kaolin is added for filtration in the step 4).

Technical Field

The invention relates to the field of extraction and purification of natural compounds, in particular to a preparation and purification method of sodium aescinate.

Background

Chinese buckeye is one of the traditional Chinese medicines collected in Chinese pharmacopoeia, and is dry mature fruit or seed of Aesculus hippocastanum, Aesculus zhejiang or Chinese chestnut of Hippocastanaceae. Aescin sodium extracted from semen Aesculi is a pure natural sodium salt of triterpene saponin containing multiple ester bonds, contains aescin sodium A, B, C and D, and contains aescin sodium A and aescin sodium B as main components.

Aescin A, B, C, D has the following chemical structure:

madus pharmaceutical factory in germany conducted intensive studies on aescin first. Preparations of Aesculus hippocastanum such as Repand (injection) and Qes-cusan germd (sugar-coated tablet and suppository) in Germany are widely used in clinic. Japanese horse chestnut, the seeds of which are used in folk to treat sore throat and eye diseases, is sold in the current commercial preparations of Venostacin (injection, capsule, ointment) and Tochikinon (tablet).

In 1980, the national institute of medicine and drug has published Hu run in the "Manual of pharmacy and botanical drug abroad", which describes the European horse chestnut formulation, seven-leaf soap. The extraction and purification process of aescine sodium in buckeye, the aescine sodium preparation and the clinical application thereof are researched by Wuhanaimin pharmaceutical limited company at home at first. In 1984, the Chinese buckeye saponin extraction, preparation process and surgical clinical application pass through the scientific committee identification of Hubei province, and more than ten manufacturers producing aescine sodium for injection at present are in China.

Buckeye seeds are widely distributed in China, aescine sodium extracted from buckeye seeds has good curative effect and good application prospect, and is one of a few pure natural plant medicines which are known to be stable and exact in curative effect and less in side effect, so that the clinical application range of the buckeye seed is continuously expanded. The pharmacological activity of the sodium aescinate is mainly shown as follows: (1) has strong anti-inflammatory and anti-exudation effects; (2) reducing or eliminating the formation of edema or hematoma; (3) has effect in protecting nerve against oxygen free radicals. Therefore, the sodium aescinate is widely applied clinically, is mainly used for swelling caused by cerebral edema, trauma or operation, and is also used for venous return disturbance diseases. In recent years, the aescine sodium is considered to be used for treating various diseases such as pulmonary heart disease, Hunt's syndrome, tumor, anal edema, facial neuritis, nephrotic syndrome I and the like. Therefore, the number of manufacturers engaged in the production of the drug and preparing to develop the drug is increasing at home and abroad.

At present, most of domestic manufacturers adopt macroporous adsorption resin for primary purification and then purify the macroporous adsorption resin by neutral alumina or polyamide resin. However, the method has the advantages of long production period, low product yield, low purity, insufficient quality control of intermediates, low content of sodium aescinate A and B in the original process and poor clinical application effect. In addition, because the raw material buckeye is different according to the production place, climate and annual scene, the quality has larger difference, and meanwhile, the method can not adjust the composition, and the applicability is poor.

Chinese patent CN104804060 discloses a preparation method of sodium aescinate. Extracting with 0-80% methanol or ethanol solution, decolorizing, performing gradient elution with ion exchange column, extracting with ethanol, and precipitating with acid to obtain sodium aescinate. The method has simple process, short production period and less pollutant. However, the method adopts reflux extraction of the aescin, and the fact that the aescin is unstable when the temperature reaches above 60 ℃ and the glycosidic bond is easy to break to cause the rise of related substances is found in practical application.

Chinese patent CN104402963 discloses a preparation method of sodium aescinate. And (3) extracting semen aesculi with alcohol, purifying by using a column after ultrafiltration, and crystallizing to obtain aescine sodium. The total yield of the method can reach 2.6-3.2%, and the purification period is about 45 hours. The method can obtain sodium aescinate meeting the medicinal requirements, but has long production period and low yield, and restricts the production efficiency of sodium aescinate.

Disclosure of Invention

The invention aims to solve the technical problems of long production cycle and low product yield of the preparation method of sodium aescinate, and provides the preparation method of sodium aescinate.

In order to solve the technical problems, the invention provides the following technical scheme:

a method for preparing aescine sodium is prepared from semen Aesculi as a starting raw material by selecting, pulverizing, extracting, washing, distilling, chromatography, salifying, concentrating, crystallizing, and baking, and specifically comprises the following steps:

1) after the buckeye is picked, crushing the buckeye by using a crusher, and collecting buckeye powder for later use;

2) extracting; buckeye powder is prepared by mixing 1-10 parts of Chinese buckeye powder in a solid-liquid ratio: 1, adding an alcohol extraction solution, standing and soaking for 2-8 hours, and then stirring and extracting for 4-5 hours; filtering the extract by a centrifuge and then filtering the extract by a bag filter to obtain an extract, transferring the extract into the extraction process, and carrying out secondary extraction on filter residues, wherein the secondary extract is recycled;

3) extracting the extractive solution with chloroform or dichloromethane for 2 times, mixing, and washing with purified water for 3 times;

4) concentrating the extracting solution under reduced pressure, dissolving the extracting solution with 75% ethanol, adding 1-2% activated carbon for decolorization, adjusting the pH of the filtrate to 5.5-7, and purifying by chromatography with a neutral alumina layer, wherein the amount of the neutral alumina filler is 1/20-1/10 of the weight of the seven-leaf solution;

5) and concentrating the purified solution under reduced pressure, and concentrating according to the following concentrated solution: diluting with absolute ethyl alcohol at a ratio of 1: 10-15, filtering the diluent, cooling to-10-18 ℃, crystallizing for 8-12 h, filtering the crystal, washing with absolute ethyl alcohol, and drying in vacuum for 4h to obtain the finished product of sodium aescinate.

Further, the buckeye in the step 1) is crushed by a water-cooling crusher, and the crushed buckeye is 20-100 meshes.

Further, the alcohol solution in the step 2) is an aqueous solution of methanol and ethanol, and the volume ratio of the alcohol to the water is 1-5: 1.

Further, before the extraction of the extracting solution in the step 3), the pH value is adjusted to 2.2-3.0, and the amount of the extracting solution is 1/6-1/3 of the extracting solution.

Further, the concentration temperature in the step 4) is less than 60 ℃.

Further, kaolin is added for assisting filtration during filtration in the step 4).

The invention has the following beneficial effects: the invention has simple process, adopts simple extraction and purification process, and can meet the quality requirement of producing the medical-grade sodium aescinate. The total yield of the process can reach 4.32-6.18%, and is improved by 35-90% compared with the yield of the traditional process. The production cycle of the invention is about 28-36 h, which is reduced by about 16h compared with the traditional process, and the production efficiency is improved. The method does not adopt toxic reagents or a large amount of metal salts, the organic solvent can be recycled and reused after being recycled, and the generated small amount of wastewater containing sodium salt can be subjected to water treatment by simple ion exchange, thereby thoroughly solving the problem of environmental pollution of the traditional method.

Drawings

The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention and not to limit the invention. In the drawings:

FIG. 1 is a process flow diagram of the present invention.

Detailed Description

The following description of the preferred embodiments of the present invention is provided for the purpose of illustration and description, and is in no way intended to limit the invention.