Stable compound coenzyme preparation as well as preparation method and applications thereof

Abstract

The invention provides a stable compound coenzyme preparation and a preparation method thereof. The main compositions and proportions of the stable compound coenzyme preparation are as follows: 90-120 U of coenzyme A (CoA), 0.1-0.3 mg / ml coenzyme I (NAD), 1-5 mg / ml glutathione (GSH), 1-2.5 mg / ml adenosine triphosphate (ATP), 1.8-12 mu g / ml flavin mononucleotide (FMN), 3-13 mu g / ml flavin adenine dinucleotide (FAD), 0.1-0.4 mg / ml adenosine diphosphate (ADP), 0.2-0.4 mg / ml adenosine monophosphate (AMP), 1.2-15 mu g / ml of adenosine methionine (SAM), 1-5 mg / ml calcium gluconate, 0.5-1.5 mg / ml cysteine hydrochloride, and 0.6-5 mg / ml mannitol. The preparation method overcomes the defects that high-speed centrifugalization is adopted, freeze-drying conditions are not clear and the product stability is poor in the existing method, and the stable compound coenzyme preparation is widely applied to the practices of preparing drugs for treating cardia-cerebrovascular diseases and digestive system diseases.

Description

[0001] This application is a divisional application of the application number 201310298764.9 and the title of the invention "a stable compound coenzyme preparation, its preparation method and application" submitted on July 17, 2013. technical field [0002] The invention belongs to the field of pharmaceutical preparations, and the core of the invention is to provide a stable compound coenzyme pharmaceutical preparation, its preparation method and application. Background technique [0003] Coenzymes are important and indispensable cofactors in human substance metabolism. The coenzyme complex is rich in various active ingredients (coenzyme A, coenzyme I, GSH, ATP, etc.) It has an important promotion effect and is an important adjuvant drug for the clinical treatment of acute and chronic hepatitis, idiopathic thrombocytopenic purpura, coronary arteriosclerosis, renal insufficiency and other diseases (Qin Bangyong, Yu Zhihao, etc., 2009; Shen Zhongming, Zhu Junyi, etc., 20071003...

AI Technical Summary

Problems solved by technology

However, for compound coenzyme, a small molecule polypeptide drug that is sensitive to heat and has a certain surface activity, it is not easy to find the appropriate temperature and time during the freeze-drying process, and the freeze-drying conditions are not well controlled. , not only will lead to poor appearance of the drug, but more importantly, it will cause the product to shrink after freeze-drying, which will lead to a high scrap rate in commercial production, and the quality of the batch is unstable, making it difficult to prepare and store for a long time

[0007] In addition, as far as the methods involved in the above two authorized patents are concerned, there are certain disadvantages in the production and application process: first, high-speed centrifugation (20000-35000CPM and 10000-15000G) is used in the two methods, and the centrifugation The time is long (30-60 minutes), and such conditions have very high requirements on the quality of instruments and equipment, and consume a lot of energy, which is difficult to realize in production and causes serious pollution to the environment; secondly, "the preparation of a compound coenzyme drug In the "method" patent, the centrifuge is directly subjected to ultrafiltration, which may easily cause blockage of the ultrafiltration column in the actual production process, greatly reduce the filtration speed, or even stop the filtration, resulting in a great waste of fillers; again, small-scale production according to this method The stability of the compound coenzyme raw material produced by the patent is also difficult to control, and the reproducibility between batches is poor; finally, the freeze-drying process conditions in the two patents are not clear, and it is difficult to obtain stable freeze-dried products repeatedly according to conventional methods

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