镇咳药咳必定的质量研究

为了推广工业生产并鉴于我们合成所得咳必定[2-甲基-2-苯氧基丙酸-2-(4-吗啉)-乙酯盐酸盐]熔点154～155℃,与文献⁽¹⁾报道熔点143～145℃不一致,因此,进行了咳必定的质量研究。经2-甲基-2-苯氧基丙酰氯与4-吗啉乙醇酯化或2-甲基-2苯氧基丙酸与4-吗啉乙醇直接酯化的途径合成所得咳必定,熔点154～155℃,杂质检查合格,含量测定在99%左右,合乎药用要求。低熔点物(熔点143～145℃)与文献⁽¹⁾一致,根据干燥失重、含量测定、薄层层析及氧化铝柱层析的研究,证明其中含有杂质,C₁₆H₂₄O₄NCl含量仅93%左右,不适于药用。低熔点物以丙酮(1:30)处理,可将其中所含杂质除去,得到合格产品(熔点154～155℃)。

STUDIES ON THE QUALITY OF THE ANTITUSSIVE DRUG KEBIDING (4-MORPHOLINO-ETHYL ESTER OF 2-METHYL-2-PHENOXY-PROPANOIC ACID HYDROCHLORIDE)

There is a difference in melting point between the product Kěbiding (4-morpholino-ethyl ester of 2-methyl-2-phenoxypropanoic acid hydrochloride) with mp 154～155℃ synthesized in this laboratory and the product morphethylbutyne with mp 143～145℃ reported in the Iiterature(1). Therefore, the quality of the drug was studied.Kěbiding was synthesized by esterification of 4-morpholinoethanol with 2-methyl-2-phenoxypropanoyl chloride or 2-methyl-2-phenoxypropanoic acid by the authors. It possesses mp 154～155℃. This product is up to standard: It contains less than 200 ppm sulfates; less than 20 ppm heavy metals; the loss on ignition not more than 0.03%; ultraviolet absorption λ_max 268 nm; the theloss on drying less than 0.2%; pH of its solution 3.8～4.1. An analysis by thin layer chromatographic method was also completed. It contains approximately 99% C₁₆H₂₄O4NCl. In view of these facts, this product may be used as a medical preparation.The product with mp 143～145℃, reported in literature showed a loss on drying of more than 2%. It contains approximately 93% C₁₆H₂₄O₄NGl. This substance was found to be impure. The impurity was also observed by thin-layer chromatography and column chromatography on aluminum oxide. It cannot therefore be used as a medical preparation. The impurity may, however, be removed by treatment with acetone (1: 30) to obtain a product (rap 154～155℃) which meets the specifications required.