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Topotecan hydrochloride targeted liposome preparation and preparation method thereof

A technology of topotecan hydrochloride and targeted liposomes, which can be used in liposome delivery, antineoplastic drugs, drug combinations, etc., and can solve problems such as shortening the elimination time

Inactive Publication Date: 2012-11-07
SHANGHAI MODERN PHARMA ENG INVESTIGATION CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, since integrins are not only present in tumor cells, but also expressed in spleen mononuclear macrophages, RGD peptides are easily taken up by the spleen, shortening the elimination time in vivo, and the elimination half-life of cyclic RGD peptides in vivo is only a few minutes

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035]Weigh 40 mg (50 μmol) of hydrogenated soybean lecithin HSPC, 9.7 mg (25 μmol) of cholesterol and 2.23 mg (2.5 μmol) of maleimidated phosphatidylethanolamine (MBPE) into an eggplant-shaped bottle, add chloroform, and dissolve by ultrasonic , remove the organic solvent by rotary evaporation, add 4 mL of 0.200 mol / L ammonium sulfate solution, hydrate at 60 ° C for 1 h, disperse ultrasonically, and extrude 15 times each through 400, 200, 100 and 50 nm polycarbonate films with a film extruder to obtain lipid Plastid, then with 0.9% NaCl solution as eluent, the outer aqueous phase is replaced by Sephadex G-50 to obtain blank liposomes containing MBPE; the resulting blank liposomes and topotecan hydrochloride solution ( 2mg / mL) and 2mL were mixed, incubated at 65°C for 20min, loaded with topotecan; then mixed with cyclic RGD peptide solution (1.45mg / mL) 1mL (ie 2.5μmol), incubated at 37°C for 1h, and then mixed with DSPE-PEG2000 Solution (7mg / mL) 1mL (ie 2.5μmol) was incubated ...

Embodiment 2

[0037] Weigh 40 mg (50 μmol) of soybean lecithin S100, 19.3 mg (50 μmol) of cholesterol and 2.23 mg (2.5 μmol) of MBPE into an eggplant-shaped bottle, add 2 mL of dichloromethane and 8 mL of ethanol to dissolve, remove the organic solvent by rotary evaporation, add 0.125 mol / L ammonium sulfate solution 4mL was hydrated at 60°C for 30min, ultrasonically dispersed, extruded 15 times through 400, 200, 100 and 50nm polycarbonate membranes with a film extruder, and then 0.9% NaCl solution was used as eluent, passed Sephadex G-50 replaced the outer aqueous phase to obtain blank liposomes containing MBPE; the resulting blank liposomes were mixed with 0.5 mL (0.5 μmol) of the cyclic RGD peptide solution (0.58 mg / mL) at 37 Incubate at ℃ for 1 h, then incubate with 1 mL (1.25 μmol) of PEG-SC solution (3.5 mg / mL) at 37 °C for 1 h, then mix with 2 mL of topotecan hydrochloride solution (2 mg / mL) and incubate at 60 °C for 20 min. The ultrafiltration tube was concentrated to 4 mL to obtain...

Embodiment 3

[0039] Weigh 40 mg (50 μmol) of hydrogenated soybean lecithin HSPC, 3.9 mg (10 μmol) of cholesterol and 4.45 mg (5 μmol) of MBPE into an eggplant-shaped bottle, add 8 mL of chloroform and 2 mL of methanol to dissolve, remove the organic solvent by rotary evaporation, add 0.150 mol / L ammonium sulfate solution 4mL was hydrated at 60°C for 30min, ultrasonically dispersed, extruded 15 times through 400, 200, 100 and 50nm polycarbonate membranes with a film extruder, and then 5% glucose solution was used as eluent, The outer aqueous phase was replaced by dialysis to obtain blank liposomes containing MBPE; the resulting blank liposomes were mixed with 0.5 mL (0.5 μmol) of cyclic RGD peptide solution (0.58 mg / mL), incubated at 37 ° C for 1 h, and then mixed with PEG -1mL (0.63μmol) of SC solution (1.75mg / mL) was incubated at 37°C for 1h, then 4mg of topotecan hydrochloride powder was added, and then incubated at 60°C for 30min, concentrated to 4mL with an ultrafiltration tube to obtai...

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Abstract

The invention provides a topotecan hydrochloride targeted liposome preparation and a preparation method of the topotecan hydrochloride targeted liposome preparation. According to the topotecan hydrochloride targeted liposome preparation, antitumor drug topotecan hydrochloride is encapsulated into a targeted long-circulating liposome modified by hydrophilic polymer polyethylene glycol and targeted ligand RGD cyclopeptide, and the lipsome is capable of prolonging the circulating time of the medicine in the body, thereby the tumor targeting is achieved, the curative effect is improved and the toxic and side effects are reduced.

Description

technical field [0001] The invention relates to targeted liposome preparations, in particular to targeted liposomes containing topotecan hydrochloride and a preparation method thereof. Background technique [0002] Cancer is a serious threat to human health. Tumor-targeted long-circulating liposomes are an ideal drug delivery system to improve the efficacy of chemotherapy and reduce the toxicity of anti-tumor drugs. It has significant clinical significance and application prospects. It can direct the drug carrier to the tumor tissue through the specific recognition mechanism of the targeting ligand to the tumor cell, so that the anticancer drug loaded can be concentrated in the cancerous part, improve the chemotherapy effect, and reduce the damage of the cytotoxic drug to the normal cell tissue . Polyethylene glycol on the surface of long-circulation liposomes can form a layer of hydration film on the surface of liposomes, avoiding the intake of liposomes by the reticuloend...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K31/4745A61K47/34A61K47/18A61P35/00
Inventor 陶涛赵雁陈中亚邓家欣柴旭煜印玺璟高大林
Owner SHANGHAI MODERN PHARMA ENG INVESTIGATION CENT
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