Fusidate sodium composition and preparation of its freeze-drying formulation

Abstract

The invention relates to a sodium fusidate composition and a method for preparing a freeze-dried preparation thereof. In the sodium fusidate composition, the weight ratio of sodium fusidate, excipient, stabilizer / pH regulator is 25 ~100:2~100:1~50. Wherein the excipient is preferably glucose and / or mannitol, and the stabilizer / pH regulator is preferably one of arginine, disodium edetate and calcium sodium edetate or a mixture thereof. Its preparation method is to use water for injection as a solvent, make sodium fusidate, excipients, stabilizers / pH regulators into a clear and transparent solution, filter and subpackage, and freeze-dry to make a freeze-dried preparation that meets the requirements of injections . The pH value of the preparation is 7.5-9.0. The preparation per unit dose contains 125-500 mg of sodium fusidate. The freeze-dried powder preparation of the sodium fusidate composition of the present invention has good stability, is convenient to use, improves the drug tolerance of patients and the convenience of medical operation, and has strong practicability. The preparation method of the invention has the advantages of simple process and good stability of finished products.

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 Staphylococcus to antibiotics, the incidence of serious infections is increasing, and the treatment is becoming more and more difficult. Fusidic acid has be...

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 the acid is 500:78~108:4.5~5.7. Compared with the existing preparations of the same kind, the freeze-dried preparation of sodium fusidate in this patent application only uses the buffer pair in the special solvent attached to the original preparation ( 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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