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Composite micelle carrying anti-tumor medicine and preparation method thereof

A technology of anti-tumor drugs and composite micelles, which is applied in the field of composite micelles carrying anti-tumor drugs and its preparation. It can solve the problems of poor stability of micelles, easy leakage of drugs, and low encapsulation efficiency, and achieve high encapsulation efficiency. High, increase intracellular accumulation, good stability

Inactive Publication Date: 2012-04-25
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the small proportion of the hydrophobic segment of pluronic, the encapsulation efficiency of many drugs, especially insoluble drugs, is low, and the stability of the micelles formed is poor, and the drugs are easily leaked, resulting in inactivation, which makes it a micelle carrier material. have certain defects

Method used

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  • Composite micelle carrying anti-tumor medicine and preparation method thereof
  • Composite micelle carrying anti-tumor medicine and preparation method thereof
  • Composite micelle carrying anti-tumor medicine and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Take 1 mg of P105 (molecular weight 6500 Da) and 10 mg of PEG-PLGA with a molecular weight of 6500 Da (the molar ratio of PEG to PLGA is 1), dissolve them in 2 ml of chloroform, add 1 mg of doxorubicin hydrochloride after alkalization, and vortex until After all the materials are dissolved, under ultrasonic conditions, add to 10ml of water at a rate of 5 seconds per drop, place the solution on a magnetic stirrer, stir at 700r / min for 2h, 100r / min for 24h, and vacuum for 120min to remove trichlor methane, the liquid was concentrated to about 5ml, and a transparent composite micellar solution was obtained, wherein the concentration of doxorubicin was 200 μg / mL, and the encapsulation efficiency was 52.3%.

Embodiment 2

[0049] Take 10 mg of P105 (molecular weight 6500 Da) and 10 mg of PEG-PCL with a molecular weight of 5000 Da (the molar ratio of PEG to PCL is 7.08), dissolve them in 2 ml of chloroform, add 2 mg of doxorubicin hydrochloride after alkalization, and vortex until After all the materials are dissolved, under ultrasonic conditions, add to 20ml of water at a rate of 5 seconds per drop, place the solution on a magnetic stirrer, stir at 1000r / min for 60min, slowly stir at 300r / min for 8h, and vacuum for 120min to remove three Methyl chloride was used to prepare a transparent complex micellar solution, in which the concentration of doxorubicin was 100 μg / mL, and the encapsulation efficiency was 56.5%.

Embodiment 3

[0051] Take 50 mg of P105 (molecular weight 6500 Da) and 10 mg of PEG-PCL with a molecular weight of 16000 Da (the molar ratio of PEG to PCL is 3.19), dissolve them in 4 ml of chloroform, add 5 mg of doxorubicin hydrochloride after alkalization, and vortex until After all the materials are dissolved, under ultrasonic conditions, add to 30ml of water at a rate of 5 seconds per drop, place the solution on a magnetic stirrer, stir at 1500r / min for 30min, slowly stir at 300r / min for 12h, and vacuum for 60min to remove three Methyl chloride was used to prepare a transparent complex micellar solution, in which the concentration of doxorubicin was 250 μg / mL and the encapsulation efficiency was 55.5%.

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Abstract

The invention discloses composite micelle carrying an anti-tumor medicine and a preparation method thereof. The composite micelle is prepared from the following raw materials: pluronic, an amphiphilic block copolymer, an anti-tumor medicine, an organic solvent and water, wherein the mass ratio of the pluronic to the amphiphilic block copolymer is 1-1000:10; the mass ratio of the total mass of thepluronic and the amphiphilic block copolymer to the anti-tumor medicine is 2-100:1. The invention combines the advantages of the pluronic and the amphiphilic block copolymer, and the prepared composite micelle has uniform particle diameter and can overcome a multidrug resistance action. Fluorescent HPLC proves that the composite micelle can obviously increase the intracellular accumulation of themedicine and can be applied to the field of the reversion of the multidrug resistance of tumors. The invention has simple preparation method and very good application prospect.

Description

technical field [0001] The invention relates to the preparation and application of a micellar drug delivery system, in particular to a composite micelle carrying an antitumor drug and a preparation method thereof. Background technique [0002] Chemotherapy plays a very important role in the clinical treatment of tumors. However, multidrug resistance (MDR) produced by tumor cells to chemotherapy drugs is an important reason for the failure of clinical treatment. MDR is an important cellular defense mechanism for tumor cells to avoid drug attacks. It is a phenomenon that tumor cells are resistant to one chemotherapeutic drug and also have cross-resistance to other drugs (with different chemical structures and mechanisms of action). The mechanism is very important. complex. In recent years, drug delivery system (DDS), as a new MDR reversal strategy, has shown good results and attracted the attention of pharmaceutical researchers. [0003] As a material for preparing micelles,...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/34A61K47/32A61K9/00A61K45/00A61K31/704A61K31/337A61K31/4745A61P35/00
Inventor 高建青韩旻刁媛媛
Owner ZHEJIANG UNIV
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