Prefreezing method in preparing injection-used reduced glutathione with freeze drying method

Abstract

The invention discloses a prefreezing method in preparing injection-used reduced glutathione with a freeze drying method, comprising the following steps: (1) quantitatively split charging reduced glutathione solution into each tube-type bottle according to the specification of a final product, lowering the temperature below -40 DEG C in 1.5-2 hours, and keeping the temperature for 1 hour to obtaina reduced glutathione solution freezing body; (2) rising the temperature of the reduced glutathione solution freezing body obtained in step (1) to -17 DEG C in two hours, and keeping the temperaturefor one hour; (3) lowering the temperature of the reduced glutathione solution freezing body obtained in step (2) below -40 DEG C within 1-1.5 hours, and keeping the temperature for one hour. After the prefreezing method of the invention is adopted, the obtained substance is sublimated and dried to obtain a white loose block product, and surface has no appearance defect. The product obtained by the prefreezing method of the invention has small possibility of erupting in the production process, and the quality of the final product conforms to the national standard.

Description

technical field [0001] The invention specifically relates to a prefreezing method when preparing reduced glutathione for injection by a freeze-drying method. Background technique [0002] Reduced glutathione (GSH) is widely distributed in the cells of mammals, plants and microorganisms. It is an important antioxidant component in the biochemical system and plays an important role in maintaining the biological functions of cells. It is often used in chemotherapy patients, radiation therapy patients, various hypoxemia, liver disease and liver damage caused by toxicity of other chemicals. [0003] Reduced glutathione is unstable in water and sensitive to heat, so it is generally made into powder injection by freeze-drying method for clinical application. [0004] The process of preparing powder injections by freeze-drying method is generally divided into two stages: first, the product to be freeze-dried is divided into suitable containers and placed on a metal plate suitable f...

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Problems solved by technology

[0012] The technical problems to be solved by the present invention are: 1. In the preparation process of the existing reduced glutathione freeze-dried powder injection, it is necessary to first freeze-dry the raw material and then pulverize it, and then carry out aseptic packaging according to the specifications, resulting in the product The defects of poor appearance, unstable quality, and high scrap rate; 2. Overcome the defects in the prior art that the preparation of reduced glutathione freeze-dried powder injection requires the addition of excipients as the crystal skeleton proppant to bring quality risks; 3. To overcome the defect in the prior art that it is necessary to control the temperature of the shelf and the product during the pre-freezing stage of the preparation of the reduced glutathione freeze-dried powder injection, resulting in difficult control defects, and discovered the formation and composition of reduced glutathione crystals The key control parameters of the skeleton structure, and the oxidized glutathione formed by controlling the oxidative denaturation of the reduced glutathione pre-freezing stage, that is, the key factor for the increase of related substances, thus providing a method for preparing injections by lyophilization. The pre-freezing method when reducing glutathione makes the control indicators clear and easy to control; improves product quality and ensures drug safety

[0013] The inventor has confirmed through a large number of experimental studies and various comparative tests that the reduced glutathione for injection can be prepared by quantitative filling method, which overcomes the prior art (invention patent application No. 200610054295.6) that requires the raw materials to be freeze-dried and crushed Repackaging causes defects in product appearance, quality, and yield; and without adding crystal skeleton proppant, through a specific re-temperature pre-freezing method, reduced glutathione itself forms crystals and forms and maintains stability The crystal skeleton structure obtains products whose appearance and internal quality meet national standards, and overcomes the quality risk caused by the addition of auxiliary materials in the prior art (invention patent application number 200510123876.6).

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