Preparation method of nalmefene hydrochloride injection and nalmefene hydrochloride injection prepared with method

Abstract

The invention discloses a preparation method of a nalmefene hydrochloride injection. When the nalmefene hydrochloride injection is prepared with a conventional method, a certain quantity of citric acid or citrate auxiliary material is added to the preparation, and 5-15 g of the citric acid or citrate auxiliary material is added in each liter of the injection. During preparation, the prescription quantity of the auxiliary material is dissolved in water for injection firstly, then activated carbon is added with stirring for adsorption, and filtration is performed for impurity removal; the prescription amount of nalmefene hydrochloride is added under the nitrogen protection, after full dissolution, the solution is metered to the designated volume with water, the pH value is adjusted to 3.5-4.5, and finally, the solution is filtered by a filter, sub-packaged, filled with nitrogen, sealed and sterilized. With the adoption of the method, the expiry date of the nalmefene hydrochloride injection can be obviously prolonged, the stability is good due to adoption of a specific citric acid pH value stabilizer, the sample appearance properties, pH value, effective ingredient content, related substances and the like are relatively stable, and the medication safety is guaranteed.

Description

technical field [0001] The invention relates to a pharmaceutical dosage form, in particular to a preparation method of nalmefene hydrochloride injection and the prepared nalmefene hydrochloride injection. Background technique [0002] Nalmefene hydrochloride was synthesized in 1975. It is a new generation of pure opioid receptor antagonist synthesized after naloxone and naltrexone. It has no agonistic effect on opioid receptors and does not produce dependence. Compared with naltrexone, it has the advantages of long action time, high oral bioavailability, small dosage, and wide safety range. [0003] Chinese patent document CN1813739 discloses a nalmefene hydrochloride injection, wherein the content of nalmefene hydrochloride in each unit dose ranges from 0.1 to 4.5 mg; the pharmaceutical carrier can be mannitol, glucose, β-cyclodextrin, chloride One or more of sodium, dextran, fructose, sorbitol, etc., preferably mannitol and glucose, whose content in the preparation ranges...

AI Technical Summary

Problems solved by technology

[0004] Chinese patent document CN1895251 discloses a stable nalmefene hydrochloride injection and its preparation method. The preparation is composed of a pharmaceutically effective amount of nalmefene hydrochloride and an appropriate amount of pharmaceutical carrier, and its core is the addition of hydrogen sulfite to the prescription. Inorganic antioxidants such as sodium, sodium sulfite, pyrosulfite, vitamin C, and a certain amount of antioxidant synergist disodium ethylenediaminetetraacetate were added, but the results of the stability test according to this prescription showed that it could not reach its The stabilizing effect in the instructions, the relevant substances also changed significantly during the investigation period (increased from 0.7% to 1.4%), and the pH value also changed significantly (increased from 3.9 to 5.3). Although the results did not exceed the standard, they were close to the upper limit. There are certain risks in the safety and effectiveness of the drug

[0005] Several nalmefene hydrochloride injections currently on the market are valid for 12 to 18 months, indicating that the stability of the drug is not good, which brings certain risks to the clinical use and drug safety of the drug