Preparation method of polysulfated chondroitin sulfate

Abstract

The invention discloses a preparation method of polysulfated chondroitin sulfate, which comprises the steps of preparation of polysulfated chondroitin sulfate, separation and purification, formamide removal, decolorization, precipitation, lyophilization and the like. According to the invention, a chlorosulfonic acid- formamide mixed solution is adopted to performing sulfonation and heat degradation on chondroitin sulfate, then alcohol precipitation, filtration, decolorization and the like are carried out, and further purificatoion is conducted to obtain polysulfated chondroitin sulfate which can improve bone and joint function. The sulfonation and the degradation reaction are separated, firstly chlorosulfonic acid and formamide are added for sulfonation, and then heating is carried out fordegradation, and then through multi-step alcohol precipitation and filtration, polysulfated chondroitin sulfate meeting key quality indexes such as the molecular weight, the sulfur-carboxyl ratio, glucuronic acid and free sulfate content is obtained, has a high sulfonated chondroitin content of more than 70%. The chondroitin sulfate has a high degree of sulfation and is stable in nature and is not easily degraded by natural chondrosulphatase. The weight average molecular weight Mw is 7300-9300 Da, and the prepared polysulfated chondroitin sulfate has a good joint function improvement effect and can be used to maintain the joint cartilage integrity of humans and animals.

Description

technical field [0001] The present invention relates to the preparation method of polysulfated chondroitin sulfate. Background technique [0002] As the world's population is aging, the prevalence of osteoarthritis diseases, including (Osteoarthritis, OA), is increasing, and the number of patients is increasing. OA can cause pain, disease, and seriously affect the patient's ability to work. The treatment of OA is currently commonly used non-steroidal anti-inflammatory drugs and polysulfate chondroprotectants. Polysaccharide chondroprotective agents are generally heparin drugs, such as polysulfated aminoglycans, polysulfated pentose sodium, polysulfated chondroitin sulfate, etc. [0003] Chondroitin sulfate (CS) is an important component of articular cartilage. When OA occurs, cartilage is damaged and CS content decreases. Supplementing CS can effectively relieve symptoms, reduce swelling in the inflammatory area and reduce OA damage to cartilage; it may also reduce morbi...

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Problems solved by technology

[0004] Petitou et al once disclosed sulfated chondroitin sulfate derivatives in the U.S. patent "Sulfated glycosaminoglycanoid derivatives of the dermatan sulfate and chondroitin sulfate type, patent No. US5382570" However, this method has the characteristics of complex process, high reagent cost, unfavorable industrial production and different structures and activities of the obtained products, which limits its application.

[0005] CN1789287A discloses a kind of polysulfated chondroitin sulfate and its preparation method, which discloses the method of using chlorosulfonic acid and concentrated sulfuric acid to prepare polysulfated chondroitin sulfate, but because concentrated sulfuric acid is highly dangerous, the operation is difficult, and the industrial High equipment requirements in production, so the application is limited

[0006] In 2008, Yuan Shi of Shandong University used chlorosulfonic acid-formamide to prepare sulfated sulfated chondroitin in his master's thesis "Preparation, Properties and Oral Preparation of Polysulfated Chondroitin Sulfate and its Oral Preparation for Rabbit Knee Osteoarthritis". However, according to experiments, the disclosed method is that the sulfonation reaction and the degradation reaction are carried out simultaneously, and highly sulfated polysulfated chondroitin sulfate cannot be obtained. Not higher than 10%, thiocarboxylate ratio higher than 3 and containing highly sulfonated polysulfated chondroitin content higher than 70%

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