(S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide sterile powder for injection

Abstract

The invention discloses an (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide sterile powder for injection. The sterile powder contains (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide, methionine, lactose, triethanolamine and sodium bisulfite according to a mass ratio of 1:(0.4-0.6):(0.5-0.9):(0.2-0.4):(0.1-0.2). A specific excipient combination and a freeze-drying curve are used to improve the sublimation temperature of a secondary drying stage, shorten the production period of the above preparation, avoid the scattering phenomenon of the powder and makes the content and other indexes meet regulations; and the above product has a good stability, and can be dissolved in a glucose injection or a sodium chloride injection to prepare an intravenous drip solution, so insoluble particles are remarkably reduced, the improvement of the drug use safety is facilitated, and the untoward effects of the drug are reduced.

Description

technical field [0001] The invention belongs to the field of pharmacy, in particular to a sterile powder of (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide for injection. 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 alcoholism, while dextro-oxiracetam ha...

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Problems solved by technology

[0005] However, during the preparation of the existing sterile powder of (S)-4-hydroxyl-2-oxo-1-pyrrolidineacetamide for injection, the inventors found that in the secondary drying stage, the sublimation temperature was lower, and the temperature It cannot be higher than 20°C, which greatly prolongs the production cycle of the preparation. If the temperature in the secondary drying stage is increased, powder scattering will occur in the preparation, and its content will drop significantly

In addition, when the existing (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide sterile powder for injection is prepared as an intravenous infusion solution, the insoluble particles increase with the prolongation of the storage time , which brings a great potential safety hazard to the clinical use

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