Pharmaceutical composition containing beta-lactamase restrainer and piperacillin sodium with steady content and preparation method thereof

Abstract

The invention provides a stable-content drug compound containing Beta-lactamases inhibitors and piperacillin sodium and the preparation method thereof. The drug compound consists of piperacillin sodium, Beta-lactamases inhibitors and pH-value regulators with the weight proportion of 1 to 100:1:0.001 to 2. Diluted and delivered in any proportion with conventional clinical transfusions, the drug compound can have a stable piperacillin sodium content, dissolve rapidly, generate no crystallization or degradation products and receive no effect from the temperature. The preparation method of the stable-content drug compound containing Beta-lactamases inhibitors and piperacillin sodium has simple preparing method and high efficiency and is fit for a large-scale industrial production.

Description

technical field [0001] The invention relates to a pharmaceutical composition with stable content of active ingredients. Specifically, it relates to a drug that can maintain stable content of piperacillin sodium when it is diluted with all clinical routine infusion solutions in any ratio, and dissolves quickly, does not produce crystals and degradation products, and is not affected by temperature. A pharmaceutical composition comprising a beta-lactamase inhibitor and piperacillin sodium. Background technique [0002] Piperacillin sodium is a semi-synthetic penicillin antibiotic with broad antibacterial spectrum and few side effects, and is widely used in clinic. However, in the course of clinical application, it was found that the compound preparation containing piperacillin sodium and β-lactamase inhibitor dissolved in the infusion would often appear turbid, and the content of piperacillin sodium decreased, so the use was terminated. Especially in winter and spring in the ...

AI Technical Summary

Problems solved by technology

This invention has the following disadvantages: the composite preparation of piperacillin sodium and tazobactam sodium must be dissolved in a diluent for clinical use, and the most commonly used diluent for dissolving clinically is 5% or The pH value of 10% glucose injection and 5% glucose saline solution is about 3.8, both of which are slightly acidic. After using this infusion solution to dissolve the compound preparation of piperacillin sodium and tazobactam sodium, the pH value of the infusion solution at this time is 4.0 Left or right, piperacillin sodium will reversibly precipitate and produce insoluble or milky white turbidity. medical malpractice

But there are following problems in this method: 1, this method just accelerates dissolution speed with physical method, when ambient temperature is low 10 degrees, can not solve the dissolution problem of piperacillin sodium completely; 2, must select water for injection or 0.9 % sodium chloride solution instead of acidic glucose solution or 5% glucose saline, otherwise it will still not dissolve

3. It does not help to solve the problem that the content of piperacillin sodium in the solution decreases and the potency decreases

But no matter how it is packed, one bottle or two bottles still have following deficiencies that cannot be solved: 1, because the pH value of the pharmaceutical composition of β-lactamase inhibitor and piperacillin sodium is the most stable when 4.5~6.5, The range is very narrow, as long as a small amount of alkali can make the pH of the solution exceed 6.5, thereby destroying the lactam ring structure of piperacillin sodium, producing by-products, and causing adverse reactions

Therefore the consumption of alkali must be strictly controlled, and such a small amount (a few tenths of milligrams) is difficult to be produced into a separate bottle of B under current production conditions; It is very troublesome, and the back-and-forth puncture of the needle increases the chance of drug contamination; 3. During the dissolving process of dispensing, the commonly used co-solvent sodium carbonate or sodium bicarbonate will generate gas, which will increase the pressure in the bottle

Due to the high internal pressure of the bottle, it is easy to push the needle piston out during the drug pumping process, or there is liquid overflow from the ventilation tube in the early stage of infusion, resulting in insufficient dosage or drug contamination; 4. Sodium carbonate or carbonic acid as a cosolvent Sodium hydrogen is a weak acid and strong base compound. When dissolved in an acidic solution, it can react to release CO 2

However, commonly used clinical infusions such as 5% glucose solution, 10% glucose injection, and 5% glucose saline are acidic, so sodium carbonate or sodium bicarbonate is used as a cosolvent, and CO will be continuously produced during the dilution process. 2 Gas, if the exhaust operation is improper, it may contaminate the liquid medicine, and the CO in the process of infusion to the patient 2 Air bubbles entering the patient's blood may form a gas embolism. If the blockage occurs in the main blood vessels of the heart and brain, it will cause great danger to the patient.

[0007] The above problems have seriously affected the clinical use of the compound preparation of piperacillin sodium and β-lactamase inhibitors, and have not been fundamentally and effectively solved so far.

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