Doxorubicin hydrochloride liposome injection and preparation technology thereof

Abstract

The invention discloses a doxorubicin hydrochloride liposome injection and a preparation technology thereof. The injection comprises the following components by weight percent: 0.05-0.5% of doxorubicin hydrochloride, 0.025-3% of hydrogenated soybean phosphatidylcholine, 0.001-1.5% of cholesterol, 0.01-1% of PEG-lipid, 0.0025-2.5% of organic acid or ammonium sulfate, 2.8-20% of sugar, 0.1-10% of buffering agent and the balance water for injection. The preparation technology comprises the following steps: 1) freeze-drying lipid phase; 2) hydrating lipid phase; 3) straightening the granules of lipid phase; 4) forming transmembrane gradient inside and outside phospholipid membrane; 5) loading medicine with liposome; and 6) degerming, subpackaging and storing.

Description

technical field [0001] The invention relates to a doxorubicin hydrochloride liposome injection and a preparation process thereof. Background technique [0002] Doxorubicin (doxorubicin, adriamycin, also known as doxorubicin) is an anthracycline antibiotic with a structure similar to daunorubicin and belongs to a broad-spectrum antineoplastic drug. Clinically applicable to acute leukemia, malignant lymphoma, multiple myeloma, lung cancer, breast cancer, bladder cancer, testicular cancer, thyroid cancer, soft tissue tumors, osteosarcoma, etc. Although doxorubicin hydrochloride has a broad anti-tumor spectrum and high curative effect, it has a strong cytotoxic effect and poor selectivity. It can kill both tumor cells and normal cells, which limits its clinical application. [0003] The doxorubicin hydrochloride liposome preparation method adopted in the patent CN100376249C and CN100431525C of Taiwan Dongyang Pharmaceutical Industry Co., Ltd. is similar, and the lipid component...

AI Technical Summary

Problems solved by technology

[0008] Compared with mitoxantrone with two dissociable groups under the raw pH, after the doxorubicin with one dissociable group is made into small particle size (60nm) liposomes, the release is too fast in vitro, which will cause High toxicity in vivo (see Example 9 of WO2008080367A1)

In addition, in this patented method, a water / tert-butanol mixed solvent is used to dissolve the lipid phase components, and the obtained solution has a certain viscosity, the sublimation speed is slow, and the time required for freeze-drying is long.

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