Fusidate sodium composition and preparation of its freeze-drying preparations

Abstract

The invention relates to a sodium fusidate combination and the preparation method of freeze dried formulation. Weight ratio of the sodium fusidate, the excipient and the stabilizing agent / pH regulator in the sodium fusidate combination is 25 to 100 : 2 to 100 : 1 to 50, wherein, preferred excipient is glucose and / or mannitol; the stabilizing agent / pH regulator is one from arginine, ethylene diamine tetraacetic acid disodium and EDTA calcium disodium or the mixture. The preparation method is characterized in that: water is used as solvent; the sodium fusidate, the excipient and the stabilizing agent / pH regulator are made into clear and transparent solution before filtered and subpacked, thereby producing freeze dried formulation being suitable for requirement of injection through drying by sublimation, wherein, pH value of the formulation is 7.5 to 9.0 and the formulation of each unit dose comprises 125 to 500mg sodium fusidate. The sodium fusidate combination and the preparation method of freeze dried formulation have the advantages of good stability, convenient use, improvement of drugs tolerance upon patients and simple medical operation, strong practicability, simple technology and good stability of finished product.

Description

technical field [0001] The invention relates to a pharmaceutical preparation, in particular to a sodium fusidate composition for treating severe staphylococcus infection and a method for preparing the freeze-dried preparation thereof. Background technique [0002] Fusidic acid (Fusidic Acid, also known as brown mycin), the chemical name is 16α-acetoxy-3β, 11β-dihydroxy-4β, 8β, 14α-trimethyl-18-nor-5β, 10α- Cholesta-(17Z)-17(20),24-dien-21-oic acid. In 1962, it was first extracted from the Fusidate coccus fungus in the fermentation broth by the Danish Leo Pharmaceutical Company, and it is now widely used in severe staphylococcal infections, such as sepsis, endocarditis, osteomyelitis, pneumonia, trauma infection and skin infections (impetigo, boils, carbuncles, etc.). In recent years, due to the increasing resistance of staphylococci to antibiotics, the incidence of serious infections is increasing, and the treatment is becoming more and more difficult. Fusidic acid has bee...

AI Technical Summary

Problems solved by technology

At present, the preparation process of Sodium Fusidate for Injection produced in China is freeze-drying method. There is only Sodium Fusidate as the main drug in its formulation prescription. Each Sodium Fusidate for Injection preparation is attached with a special solvent. The ingredients are disodium hydrogen phosphate and citric acid. During the quality tracking process, it was found that the quality of this product was unstable, and the related substances changed greatly. After compatibility, there were different degrees of opalescence, visible foreign matter increased, and the blood vessels of patients were stimulated. Significantly increased sex and reduced patient tolerance

In addition, Chinese patent application CN1817340A discloses a freeze-dried preparation containing sodium fusidate, in which disodium hydrogen phosphate and citric acid are added, and fusidic acid, disodium hydrogen phosphate, citron The weight ratio of acid is 500: 78~108: 4.5~5.7, and the sodium fusidate lyophilized preparation of this patent application is compared with existing preparation of the same kind, only the buffer pair ( Disodium hydrogen phosphate, citric acid) are added in the prescription of sodium fusidate preparation, and it has no novelty in essence, also does not fundamentally solve the problem of drug stability and the occurrence of irritation and pain at the venipuncture site during clinical use, so , compared with the currently commercially available sodium fusidate for injection (sodium fusidate + special solvent), there is no essential difference between the preparation obtained according to the prescription of the patent application

And according to the preparation that the prescription of this patent application makes, under high temperature (60 ℃) condition, also there is the phenomenon that related substance significantly increases (over 3%) after 5 days, and content significantly reduces (over 5%); Poor, after 6 months of storage at room temperature, not only the color of the sample changed, but also the related substances increased significantly, and the content decreased significantly; after 60 days of storage at room temperature, it appeared flocculent after being compatible with glucose or sodium chloride injection. The phenomenon of precipitation is not conducive to its long-term storage and clinical use

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