(S)-4-hydroxyl-2-oxo-1-pyrrolidine acetamide freeze-dried powder injection and preparation method thereof

Abstract

(S)-4-hydroxyl-2-oxo-1-pyrrolidine acetamide freeze-dried powder injection is prepared from (S)-4-hydroxyl-2-oxo-1-pyrrolidine acetamide, L-serine, mannitol, sodium glutamate and benzyl alcohol which serve as raw materials and auxiliary materials through the steps of performing concentrated preparation, performing dilute preparation, freeze-drying and capping, wherein the use amount of the raw materials and the auxiliary materials are as follows: the (S)-4-hydroxyl-2-oxo-1-pyrrolidine acetamide is 36 to 43 percent, the L-serine is 21 to 28 percent, the mannitol is 30 to 35 percent, the sodium glutamate is 4 to 10 percent and the benzyl alcohol is 1 to 3 percent; and the (S)-4-hydroxyl-2-oxo-1-pyrrolidine acetamide freeze-dried powder injection prepared according to the invention has the advantages that the shape is fixed, spray bottle phenomenon is avoided in the freeze-drying preparation process, the product has high uniformity, consistent characters of upper and lower layers and few impurities, the total impurities are less than 0.26 percent, the product has high stability, the shelf life is up to 24 months, the pain of a patient in the injection process is less, and the patient compliance is high.

Description

technical field [0001] The invention mainly relates to the field of pharmaceutical technology, in particular to (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide freeze-dried powder injection and a preparation method thereof. Background technique [0002] The chemical name of levo-oxiracetam is: S-(-)-4-hydroxy-2-oxopyrrolidine-N-acetamide. It is a white microcrystalline powder with a melting point of 135-136°C and an optical rotation of -36°( C=1.00in water), the solubility of levoxiracetam is obviously better than that of racemate. The chemical structural formula is as follows: [0003] [0004] The drug was launched in Italy in 1987, and the listed dosage forms are tablets, 800mg; capsules, 800mg; injection, 1g / 5ml. At present, only oxiracetam capsules and injections are on the market in China, and the main active ingredients used are racemates. Ye Lei et al. mentioned in the patent publication No. CN 103735545A that levoxiracetam has an obvious effect of promoting awakeni...

AI Technical Summary

Problems solved by technology

[0005] The existing (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide freeze-dried powder mainly has no fixed shape, is not easy to form a skeleton, and is prone to spray bottle phenomenon during the freeze-drying process. The product has poor stability and shelf life. Short period, poor product uniformity, inconsistent properties of upper and lower layers, obvious pain during injection, poor patient compliance, etc.

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