(S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide sterile powder and preparation method thereof

Abstract

The present invention discloses (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide sterile powder and a preparation method thereof, wherein the sterile powder contains the following raw materials and the auxiliary materials by weight: 50-59% of (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide, 20-25% of L-serine, 10-17% of mannitol, 5-7% of sodium glutamate, 5-10% of sodium hydrogen sulfite, and 1-3% of benzyl alcohol. According to the present invention, by using the specific excipient combination, the prepared (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide sterile powder has the fixed shape, and cannot be sprayed out of the bottle during the freeze drying, the stability of the product is good, the insoluble particles are obviously reduced and the size of the insoluble particles is obviously reduced, the pain of patients during the injection is less, the patient compliance is good, the drug use safety can be easily improved, and the adverse reaction of the drug can be reduced.

Description

technical field [0001] The invention belongs to the field of pharmacy, and in particular relates to a sterile powder of (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide and a preparation method thereof. Background technique [0002] The chemical name of levo-oxiracetam is: (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide, which 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 103735545 A that levoxiracetam has an obvious wake-promoting effect on coma caused by alcohol...

AI Technical Summary

Problems solved by technology

[0005] However, the existing (S)-4-hydroxyl-2-oxo-1-pyrrolidineacetamide aseptic powder has no fixed shape, is not easy to form a skeleton, is prone to spray bottle phenomenon in the freeze-drying process, and has product The problem of poor stability, before clinical use, it needs to be dissolved in 5% glucose injection or 0.9% sodium chloride injection 100 ~ 250ml, prepared as an intravenous infusion solution for use, after being prepared as an intravenous infusion solution, with time The extension of its insoluble particles increases, which brings great safety hazards to clinical use

In addition, the existing sterile powder of (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide still has problems such as obvious pain during injection and poor patient compliance.

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