Irinotecan hydrochloride-containing drug composition and preparation method thereof

Abstract

The invention provides an irinotecan hydrochloride-containing drug composition and a preparation method thereof. The preparation method comprises the following steps: before irinotecan hydrochloride is added into a lactic acid aqueous solution, adjusting the lactic acid aqueous solution to a specific pH range at first, and then after the irinotecan hydrochloride, sorbitol and injection water are added, adjusting medicinal liquid to the specific pH range. Through twice pH value adjustment, the long-term stability of the injection can be obviously improved, and impurities can be reduced; the drug use risk of a patient is greatly lowered; meanwhile, the preparation method is simple; no special equipment requirement is needed; the production cost is obviously reduced.

Description

Technical field [0001] The present invention relates to a pharmaceutical composition, and more specifically, to a pharmaceutical composition containing irinotecan hydrochloride and a preparation method thereof. Background technique [0002] Irinotecan hydrochloride (Irinotecan), chemical name (+)-(4S)-4,11-diethyl-4-hydroxy-9[(4-piperidinylpiperidine) carbonyl]-1H-pyrano [3',4': 6,7] Indoleazine [1,2-b] Quinoline-3,14-(4H,12H)-dione hydrochloride, is a semi-synthetic water-soluble camptothecin Class derivatives. The drug and its metabolite SN38 are DNA topoisomerase I inhibitors. The complex formed with topoisomerase I and DNA can cause DNA single-strand breaks, prevent DNA replication and inhibit RNA synthesis. The first-line medication for advanced colorectal cancer also has certain effects on lung cancer, breast cancer, and pancreatic cancer. [0003] Because irinotecan hydrochloride is slightly soluble in water, and the resulting aqueous solution is easily degraded by environ...

AI Technical Summary

Problems solved by technology

[0005] CN102885765A discloses an injection containing lactic acid, sorbitol, and irinotecan hydrochloride. During preparation, a metal filter element is used for decarbonization, and a rotating water bath is used for sterilization, so as to more effectively control the amount of related substances, but the preparation method requires equipment Very high, and the applicant of the present invention prepared the sample according to the prescription and preparation method described in its embodiment 1, placed it for 36 months for a long time, found that the content of other individual impurities was 0.15%, the total impurity content was 1.58%, and the impurity level was still high , unable to meet the requirements of the registration standards for imported drugs

[0006] In addition, we also studied the impurity levels of the reference preparation of irinotecan injection listed by the original research company Pfizer in different periods, and found that although the impurities of the original research product can meet the requirements of the registration standards for imported drugs within the shelf life (36 months), the samples were tested. After the accelerated test, it was found that the content of other individual impurities in some batches of samples exceeded 0.1% and reached 0.39% when accelerated for 6 months, indicating that the stability of the original research product was poor under accelerated conditions, and the content of other individual impurities increased rapidly, and the product quality still needs to be improved. further improvement

[0007] The impurity level in medicines can reflect the stability of product quality. Lower impurity level means better product stability, higher safety, and is more conducive to patient drug safety. However, the existing technology has not yet solved the problem of hydrochloric acid. The stability of irinotecan injection still requires in-depth research on the prescription and preparation method of the injection to provide a low-cost irinotecan hydrochloride injection with long-term stability and no special requirements for production equipment

Images