Application of citric acid in preparing parecoxib sodium freeze-drying preparation compound, compound and preparation method thereof

Abstract

The invention discloses application of citric acid in preparing a parecoxib sodium freeze-drying preparation compound, a compound and a preparation method thereof. A photo-stable parecoxib sodium freeze-drying preparation compound comprises a pharmaceutically acceptable amount of parecoxib sodium, a pharmaceutically acceptable amount of pH regulator, a pharmaceutically acceptable amount of sodiumphosphate and a pharmaceutically acceptable amount of photo-stabilizer, wherein citric acid serves as the photo-stabilizer. The citric acid disclosed by the invention can be used as the photo-stabilizer for preparing the parecoxib sodium freeze-drying preparation compound, and meanwhile, a more stable parecoxib sodium freeze-drying preparation compound is supplied. The compound is capable of preventing or delaying generation of impurities U and T when the parecoxib sodium freeze-drying preparation compound is exposed to light source during the processes of production, storage, transportation and clinic use, and the compound is capable of obviously promoting product quality and clinic use safety.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to the application of citric acid in the preparation of a parenteral administration liquid preparation parecoxib sodium freeze-dried preparation composition and its composition and preparation method. The specific cyclooxygenase-2 (COX-2) inhibitor for intravenous administration and intramuscular injection is mainly used clinically for the short-term treatment of postoperative pain, and can also be used for the treatment of moderate or severe postoperative acute pain. Background technique [0002] Parecoxib sodium is a water-soluble drug, which is the active prodrug of Valdecoxib (Valdecoxib), which itself does not inhibit COX-1 and COX-2, but after injection, parecoxib sodium is rapidly hydrolyzed by liver enzymes, Transformed into valdecoxib N-{[4-(5-methyl-3-benzisoxazole-4-yl)benzenesulfonamide] and propionic acid. Valdecoxib is a selective COX-2 inhibitor. At ther...

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Problems solved by technology

[0010] Inquiring literature information, most of the photodegradation impurities introduced mainly involve the conversion of sulfonamide (ammonia) and propionamide active functional groups, including oxidation, hydrolysis and other pathways, and the photodegradation pathway and photodegradation impurities of parecoxib sodium have not been investigated. Research

Moreover, up to now, there is no information on the photodegradation impurities of parecoxib sodium for in-depth research, and there is also no public report on the photodegradation impurities of parecoxib sodium formulations.

[0011] Patents CN201310412213.0, CN201410016516.5, CN02810765.9, etc. all disclose the formulation patents of the preparation, but none of them propose to solve the problem of how to solve the problem of photodegradation impurities on the product during the production, storage, transportation and clinical use of the parecoxib sodium preparation. Quality Impact and Clinical Safety Issues

[0012] From the analysis of the above patents, it can be seen that photodegradation impurities in preparations cannot be avoided. These invention defects obviously bring very high risks to product quality and clinical administration.

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