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Irinotecan and chloroquine pharmaceutical composition and common carrier liposome and preparation thereof

A technology of irinotecan and liposome, which is applied in the direction of drug combination, liposome delivery, antineoplastic drugs, etc., can solve the unreported problems of the combined use of irinotecan and chloroquine, and achieve the reduction of drug usage, Reduce toxic side effects, good controllability and reproducibility

Active Publication Date: 2015-10-14
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] Although the combination of irinotecan and doxorubicin or sunitinib has achieved better therapeutic effect, the combination of irinotecan and chloroquine has not been reported

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Weigh 500mg of soybean lecithin (purity of phosphatidylcholine>76%) and 100mg of cholesterol and dissolve in 6mL of anhydrous ether, mix well after fully dissolving, then distill off the organic solvent ether under reduced pressure, so that film-forming materials such as phospholipids are at the bottom of the flask Form a uniform lipid film, then add 5mL of 0.2mol / L ammonium sulfate aqueous solution, hydrate in a water bath at 50°C for 30 minutes, vortex for 5 minutes, and then use a cell disruptor to sonicate for 10 minutes to uniform particle size, and the blank liposomes after sonication The suspension was transferred to a dialysis bag and dialyzed for 6 hours with distilled water as the dialysis medium to remove ammonium sulfate in the outer water phase, resulting in a gradient of ammonium sulfate, and 5 mL blank liposomes were obtained for future use. The average particle diameter (number average) of the blank liposomes was measured to be 78.6 nm.

Embodiment 2

[0049] Weigh 400mg of lecithin (purity of phosphatidylcholine>76%) and 120mg of cholesterol and dissolve in 6mL of anhydrous ether, mix well after fully dissolving, then evaporate the organic solvent ether under reduced pressure, so that the film-forming materials such as phospholipids are at the bottom of the flask Form a uniform lipid film, then add 5mL of 0.3mol / L ammonium sulfate aqueous solution, hydrate in a water bath at 50°C for 30 minutes, vortex for 5 minutes, and then use a cell smasher to sonicate for 10 minutes to uniform particle size, and the blank liposomes after sonication The suspension was transferred to a dialysis bag and dialyzed for 10 h with distilled water as the dialysis medium to remove ammonium sulfate in the outer water phase, resulting in a gradient of ammonium sulfate, and 5 mL blank liposomes were obtained for future use. The average particle diameter (number average) of the blank liposomes was measured to be 69.4 nm.

Embodiment 3

[0051] Weigh 2000mg of soybean lecithin (purity of phosphatidylcholine >76%), 1000mg of DMPC (purity of phosphatidylcholine >76%) and 750mg of cholesterol and dissolve them in 6mL of anhydrous ether. Solvent diethyl ether to make phospholipids and other film-forming materials form a uniform lipid film at the bottom of the flask, then add 5mL of 0.4mol / L ammonium sulfate aqueous solution, hydrate in a water bath at 50°C for 30 minutes, vortex for 5 minutes, and then use a cell disruptor to sonicate for 10 minutes. Uniform particle size, transfer the blank liposome suspension after ultrasound to a dialysis bag, and use distilled water as the dialysis medium for dialysis for 15 hours to remove ammonium sulfate in the external water phase, resulting in a gradient of ammonium sulfate, and obtain 5mL blank liposomes for future use. The average particle diameter (number average) of the blank liposomes was measured to be 88.6 nm.

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Abstract

The invention discloses an irinotecan and chloroquine pharmaceutical composition, and a common carrier liposome and preparation thereof. The irinotecan and chloroquine in the pharmaceutical composition are in the weight ratio of 1-100:1-00. The irinotecan and chloroquine pharmaceutical composition common carrier liposome comprises the drug, phospholipid, cholesterol compound and an aqueous phase, wherein the weight ratio of the drug, phospholipid and cholesterol compound is 1:2-100:0.8-35, and the drug is irinotecan drug and chloroquine drug. Synergic effect of irinotecan and chloroquine enhances the killing effect of irinotecan drug on sensitive strain cells of colon cancer. The preparation method of the common carrier liposome uses a pH gradient method or ammonium sulfate gradient method, has the advantages of simple preparation process, few parameter control and lower reaction conditions, and is helpful to reduce production cost and easy for industrial production.

Description

technical field [0001] The invention relates to the technical field of drug combination and liposome medicament, in particular to a combination of irinotecan drug and chloroquine drug and its co-carried liposome and preparation. Background technique [0002] In recent years, in the field of tumor chemotherapy, researchers have found that using one chemotherapy drug alone can rarely achieve better tumor suppression effect. The two drugs are co-delivered using nanocarriers, so that they can be targeted to the lesion in the body. It is also considered to have great potential for tumor treatment. Liposome carrier has even entered the stage of clinical trials (First-in-man study of CPX-351: aliposomal carrier containing cytarabine and daunorubicin in a fixed 5:1molar ratio for the treatment of relapsed and refractory acute 5myeloid leukemia, [J ] Journal of Clinical Oncology, 2011, Vol.29, 979-985). Liposome is widely used as a carrier of chemotherapy drugs. It can not only imp...

Claims

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Application Information

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IPC IPC(8): A61K31/4745A61K9/127A61P35/00A61K31/4706
Inventor 邱利焱高梦华许玉珍
Owner ZHEJIANG UNIV
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