Purification method of morphine base crude product

Abstract

The invention relates to a morphine base crude product purification method, which comprises: (1) sequentially adding L(+)-tartaric acid, sodium hydrogen sulfite and a morphine base crude product to purified water under nitrogen protection, and carrying out a stirring reaction to obtain a first treatment liquid; (2) carrying out acid regulation, stirring crystallization, cooling, stirring re-crystallization and cold filtration on the first treatment liquid to respectively obtain a crystallized solid substance and a second treatment liquid; (3) sequentially adding purified water, sodium hydrogensulfite and n-butyl alcohol into the crystallized solid substance, adjusting the pH value, and filtering and drying the solution to respectively obtain a product and a third treatment solution; (4) adjusting the pH value of the second treatment solution, and filtering the second treatment solution to obtain a solid substance and a fourth treatment solution; (5) adjusting the acidity of the fourthtreatment liquid twice, and filtering the fourth treatment liquid to respectively obtain recycled crude morphine and fifth treatment liquid; and (6) mixing the fifth treatment liquid and the third treatment liquid to recover residual morphine. The method is low in cost and high in yield, industrial large-scale production can be achieved, the content of the obtained morphine base can reach 94%-95%, and the yield reaches 90%.

Description

technical field [0001] The invention relates to the field of separation and purification of plant extracts, in particular to a method for purification of crude morphine base. Background technique [0002] Morphine (MOP) is an important part of opiate drugs. In 1806, German chemist Zeltina first separated it from opium. Its derivative, morphine hydrochloride, is a commonly used anesthetic in clinical practice and has a strong sedative effect. Pain effect, mostly used for severe pain caused by trauma, surgery, burns, etc., also used for angina pectoris caused by myocardial infarction, and can also be used as an analgesic, antitussive and antidiarrheal agent. [0003] Pure morphine is colorless crystal or white crystalline powder, odorless, easy to deteriorate when exposed to light, and will slowly oxidize when exposed to air for a long time. Slightly soluble in water, slightly soluble in ethanol, almost insoluble in chloroform or ether. Commercially available products genera...

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Problems solved by technology

However, compared to the large amount of solvents used in this patent, the content of the obtained product is too low, and qualified products cannot be directly obtained in production, so it is of little significance

[0008] (3) Junming MA reported another purification method in US6054584. Firstly, an alkaline alcohol solution was used to extract morphine from opium, and after acid adjustment, it was concentrated. The concentrate was dissolved in alkali, and sodium acetate was added as a buffer, and toluene was used to extract and remove impurities. , acid crystallization with alkali solution to obtain morphine, the content of morphine obtained by this method is 84-86%, and the yield is 86-88%. Although the content and yield of this method are improved, the morphine obtained still cannot meet the market demand. And in the process of operation, the time is too long under the alkaline environment, which will easily cause the destruction of morphine. With the enlargement of production scale, the yield will gradually decline.

[0009] (4) People such as Ai Lin announced a kind of method that uses cation exchange resin to extract and separate morphine in CN1597039A, and it uses water or the aqueous solution containing alcohol to extract PCS or opium, filter, go up cation exchange resin, after washing, use again Alkaline or alkali-containing alcohol solution is eluted, and the eluent is concentrated and adjusted to pH=8.5~9.5, and then crystallized to obtain morphine base. This method has a much higher yield than the above-mentioned methods. The morphine base produced by this method The highest content can reach 91%, and the content can reach 94%, but the disadvantages of this method are also very obvious. First, the extract obtained according to this method is very easy to block the column in the link of resin adsorption. Secondly, the analysis efficiency of morphine is low, and often requires The huge amount of lye can be completely resolved, and the morphine is obviously destroyed in the final concentration process, so although higher yield and content can be obtained in small batch production, it is difficult to apply in production

[0010] (5) Li Rong and Piao Meishan disclosed a method of using cation exchange resin to obtain total alkaloids of poppy in CN101491588A, but this method did not mention how to separate the alkaloids, so the reference significance is not great

Compared with other literatures, the yield and content of this method are greatly improved. Among them, the yield of morphine can reach up to 97.6%, and the content can reach 98.87%. The fixed investment is huge. For large-scale production enterprises, the fixed cost will be raised invisibly, which is not conducive to enterprises to participate in market competition.