Novel method of producing strontium ranelate heptahydrate

Abstract

The invention relates to a method for preparing strontium ranelate heptahydrate. The product prepared by the method has a water content of 19.0-20.4%, and related substances are less than 0.5%. The strontium ranelate heptahydrate prepared by the method is stable at room temperature, the difference in water content between batches is small, and its water content, content and related substances remain unchanged when stored in a natural environment for a long time. It is characterized in that: 1. 2-[N, N-bis(carboxymethyl)amino]-3-cyano-4-carboxymethylthiophene-5-carboxylic acid tetraester (b) in an appropriate amount of sodium hydroxide hydroalcohol Reflux the solution for 5 to 6 hours, and keep the pH value above 10 during the hydrolysis process; ② Then add 20-60% ethanol, and then directly add 2-2.5 times the molar amount of strontium chloride aqueous solution, precipitate crystals, filter, and dry; ③ Add water Reflux, remove a small amount of salt wrapped in the crude product, heat filter, and collect the product. The invention also discloses a pharmaceutical composition containing strontium ranelate heptahydrate, which is used for treating postmenopausal women's osteoporosis.

Description

technical field [0001] The present invention relates to a new preparation method of strontium ranelate heptahydrate and a pharmaceutical composition containing it. The compound has activity in the treatment of osteoporosis in postmenopausal women. Background technique [0002] The structural formula of strontium ranelate heptahydrate is as follows: [0003] [0004] Strontium ranelate heptahydrate chemical name: [0005] 3-Thiopheneacetic acid, 5-[bis(carboxymethyl)amino]-2-carboxy-4-cyano, strontium salt(1:2)heptahydrate [0006] That is, 5-[di(carboxymethyl)amino]-2-carboxy-4-cyano-3-thiophene acetate distrontium salt heptahydrate, which has very valuable pharmacological activities, especially in anti-osteoporotic properties On the one hand, it can both inhibit bone resorption and promote bone formation, making this compound useful in the treatment of osteoporosis in postmenopausal women. [0007] EP0415850 has described the preparation and therapeutic use of stront...

AI Technical Summary

Problems solved by technology

In this way, the octahydrate of distrontium ranelate can be produced, dried under a dry air stream to generate the heptahydrate, and dried under reduced pressure (10mmHg) at 55°C to obtain the corresponding tetrahydrate, but the preparation method is cumbersome

[0014] The second method: Add 2-[N,N-bis(carboxymethyl)amino]-3-cyano-4-carboxymethylthiophene-5-carboxylic acid tetraethyl ester to the sodium hydroxide solution mixed with alcohol and water Medium hydrolysis, after hydrolysis, the alcohol and water are evaporated to dryness to obtain a tetrasodium salt solid, and then strontium chloride is added to form a salt, but the tetrasodium salt has strong hygroscopicity, and the actual operation is also troublesome;

[0016] The applicant uses these methods, the related substance of the product that makes is higher (more than 2%), and the hydrate water content of generation is unstable, brings difficulty to the formulation of raw material quality standard and the preparation of preparation

Strontium ranelate is insoluble in most solvents, and the purification operation is quite difficult, so the products prepared by these methods are not qualified as pharmaceutical raw materials

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