Antibiotics composition with stable content and rapid solubility

Abstract

The invention discloses an antibiotics combination with stable content and rapid dissolution and the preparation method, which comprises cefoperazone sodium, Beta- lactamase inhibitor and pH regulator with weight proportion of 1 to 100 : 1 : 0.001 to 1. When the antibiotics combination is dilutedly administrated with clinical conventional infusion according to certain proportion, wherein, the content of the cefoperazone sodium can be kept stable and the dissolution is rapid without crystallization and degradation product and without influence of temperature, thereby solving the problems of content lowering of cefoperazone sodium and low solubility when similar drugs are used clinically. The antibiotics combination has the advantages of simple preparation method and high efficiency and easy industrialization.

Description

technical field [0001] The present invention relates to an antibiotic composition, more specifically, the present invention relates to an antibiotic composition with stable content and rapid dissolution. Meanwhile, the present invention also relates to a preparation method of the antibiotic composition. Background technique [0002] Cefoperazone sodium (cefoperazone) and its compound preparation with β-lactamase inhibitors are third-generation cephalosporins with broad antibacterial spectrum and strong effect. They have strong antibacterial effect on Pseudomonas aeruginosa and have a high concentration in bile. Years of clinical application have shown that it has obvious clinical curative effect, low incidence of adverse reactions, enzyme resistance, broad spectrum, and low price. Therefore, it is widely used by doctors and patients and is currently the most commonly used third-generation cephalosporin. Bacteroid antibiotics. However, in the process of clinical application...

AI Technical Summary

Problems solved by technology

But the problem that occurs is, one, because there is no detection equipment and standardized measurement tool on the spot, there is no definite regulation when the concentration of sodium bicarbonate solution is used, and the amount of adding sodium bicarbonate solution has no quantitative control, so the pH value cannot be accurately regulated; And in order to make the content of cefoperazone sodium stable, the pH value of the solution is required to be very precise. When the pH value of the solution was less than 4.5, a small amount of sodium cefoperazone would reversibly separate out to produce turbid appearance. However, if the addition of 5% sodium bicarbonate solution exceeds a few tenths of milliliters, the pH value> 6.5 will be made, and cefoperazone sodium is easily decomposed at this pH, destroying the lactam ring of cefoperazone sodium, causing the content of cefoperazone sodium to decrease and produce by-products , leading to adverse reactions

2. There is no sterile environment in the clinical department of the hospital for on-site preparation of sterile sodium bicarbonate solution

3. Most of the clinical nurses do not have the operational skills in pharmacy

This solution brings great trouble to the timely preparation of drugs, and also increases the chance of drug contamination, which has great risks and is very prone to medical accidents.

[0006] The Chinese patent literature with application number 200610034315.3 discloses a stable cefoperazone-sulbactam drug compound preparation, which is composed of cefoperazone acid as raw material, sulbactam acid and sodium bicarbonate, and proposes a solution to cefoperazone acid The problem of insufficient solubility in the solution, but the invention has the following obvious shortcomings: 1. The raw materials do not meet the requirements of the Pharmacopoeia and injection preparations. Cefoperazone acid contains a large amount of impurities harmful to the human body, and cannot reach the Chinese Pharmacopoeia standard without purification. The specified content, clarity and pH value, etc., cannot be directly used as medicinal raw materials, otherwise the impurities contained in it will cause great harm to the human body; 2. There is no scientific theoretical basis for prescription design

For example, according to the method of this patent, the pharmaceutical composition containing β-lactamase inhibitor and cefoperazone sodium is made into bottle A, and the salt of water-soluble alkali metal or alkaline earth metal is made into bottle B, and the two bottles are placed in a packing box. Combined into a combined injection, but still have the following disadvantages: 1. Because the pH value of the pharmaceutical composition is the most stable at 4.5 to 6.5, the range is very narrow, as long as a trace of alkali can make the pH value of the solution greater than 6.5, it will destroy The lactam ring of cefoperazone acid produces by-products, leading to adverse reactions

Therefore must strictly control the amount of alkali, and such a small amount (tens of milligrams), it is difficult to produce a separate bottle under the current production conditions

2. The combination of two bottles not only increases the packaging cost but also is very troublesome for clinical use. The back and forth puncture of the needle also increases the chance of drug contamination

3. During the process of adding liquid to dissolve the medicine, the commonly used co-solvent sodium carbonate or sodium bicarbonate will generate gas, which will increase the pressure in the bottle

However, these problems that plague clinical use, such as the often unstable content of cefoperazone sodium, which affects the clinical efficacy, the solubility is too low, and the problems that the pH value cannot be accurately controlled in the solid state, have not been resolved so far.

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