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Melphalan multi-targeted drug carrying system, and preparation method and application thereof

A drug-carrying system, the technology of melphalan, applied in the field of medicine, can solve the problems of poor cell selectivity, high toxicity and side effects, etc., achieve wide applicability, expand the scope of application, and improve the effect of drug invisibility

Active Publication Date: 2012-05-30
WUHAN NUOAN PHARMACY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Therefore, aiming at and strengthening the basic research on common problems such as poor cell selectivity, large toxic and side effects, and serious adverse reactions, especially tumor cell MDR, which are common in this type of chemotherapeutic drug preparations, it is important to develop new drug delivery systems for chemotherapeutic drugs and improve the treatment of malignant tumors. The effect has important theoretical and practical significance

Method used

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  • Melphalan multi-targeted drug carrying system, and preparation method and application thereof
  • Melphalan multi-targeted drug carrying system, and preparation method and application thereof
  • Melphalan multi-targeted drug carrying system, and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0041] 1. Preparation of PEG-HA-MEL Components

[0042] (1) Synthesis and purification of carboxyl-terminated polyethylene glycol

[0043] 10g (5mmol) PEG-2000 was placed in a 250mL three-necked flask with a condenser, a stirrer and a thermometer, and 100mL of chloroform (CaH 2 After the dissolution, add 2.5g (25mmol) succinic anhydride, heat to dissolve, add 2mL of dry pyridine at the same time, reflux reaction under stirring for 6 hours, stop the reaction and cool to room temperature, and the reaction mixture is decompressed Evaporate until it becomes viscous, add a large amount of anhydrous ether to the residue to precipitate a white product, filter it with suction, dissolve the product with 30 mL of dichloromethane, filter off the insoluble matter, add anhydrous ether to precipitate a white product, repeat several times. After suction filtration, vacuum-dry to constant weight to obtain carboxyl-terminated polyethylene glycol, which is weighed;

[0044] (2) Preparation of...

Embodiment 2

[0063] 1. Preparation of PEG-HA-MEL Components

[0064] (1) Synthesis and purification of carboxyl-terminated polyethylene glycol

[0065] Put 20g (5mmol) PEG-2000 in a 500mL three-necked flask with a condenser, a stirrer and a thermometer, add 200mL chloroform (distilled out in the presence of CaH2) to dissolve, and add 5g (50mmol) succinic anhydride after the dissolution is complete, Heat to dissolve, add 4mL of dry pyridine at the same time, reflux reaction under stirring for 6 hours, stop the reaction and cool to room temperature, the reaction mixture is evaporated under reduced pressure until it becomes viscous, the residue is added with a large amount of anhydrous ether to precipitate a white product, and suction filtered , Dissolve the product with 60 mL of dichloromethane, filter off the insoluble matter, add anhydrous ether to precipitate a white product, repeat several times. After suction filtration, vacuum-dry to constant weight to obtain carboxyl-terminated polye...

Embodiment 3

[0087] 1. Preparation of PEG-HA-MEL Components

[0088] (1) Synthesis and purification of carboxyl-terminated polyethylene glycol

[0089] Put 40g (5mmol) PEG-2000 in a 1000mL three-necked flask with a condenser, a stirrer and a thermometer, add 400mL chloroform (steamed out in the presence of CaH2) to dissolve, add 10g (100mmol) succinic anhydride after the dissolution is complete, Heat to dissolve, add 8 mL of dry pyridine at the same time, reflux for 6 hours under stirring, stop the reaction and cool to room temperature, the reaction mixture is evaporated under reduced pressure until it becomes viscous, the residue is added with a large amount of anhydrous ether to precipitate a white product, and suction filtered , Dissolve the product with 120 mL of dichloromethane, filter off the insoluble matter, add anhydrous ether to precipitate a white product, repeat several times. After suction filtration, vacuum-dry to constant weight to obtain carboxyl-terminated polyethylene gl...

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Abstract

The invention relates to a tumor cell multi-targeted drug carrying system, and a preparation method of the drug carrying system and application of the drug carrying system in the aspect of antitumor drugs. The drug carrying system is prepared by mixing a PEG (Polyethylene Glycol)-HA (Hyaluronic Acid)-MEL (Melamine) component and a Fe3O4 magnetic fluid component according to a weight ratio of 1:1-5, wherein the PEG-HA-MEL component comprises the following components in parts by weight: 20-100 parts of melphalan, 500-1500 parts of PEG, 100-500 parts of HA, 10-50 parts of DCC (dicyclohexylcarbodiimide), 1-10 parts of DMAP (Dimethylamino Pyridine), 100-500 parts of succinic anhydride, 10-50 parts of EDC (ethylene dichloride) and 20-100 parts of sodium hydrogensulfite. The invention has the advantages of drug release intelligence of the system, multi-targeted property and good reverse drug resistance action of the system, drug release control of the system, good blood circulation stabilityof the system, good invisibility of the system, and wide applicability of the system.

Description

technical field [0001] The invention relates to the field of medicines, in particular to a tumor cell multi-targeting drug-carrying system, a preparation method of the drug-carrying system and the application of the drug-carrying system in antitumor drugs. Background technique [0002] At present, the treatment of malignant tumors is mainly combined with surgery and chemotherapy. Chemotherapy is a necessary treatment method. However, the existing chemotherapeutic drugs have poor selectivity for normal cells and tumor cells, and are prone to serious adverse reactions and multidrugs. Drug resistance (Multi-drug resistance, MDR), resulting in unsatisfactory chemotherapy effect. At present, any method that can increase the effective concentration of chemotherapy drugs in tumor cells is a feasible method to overcome MDR, such as using new preparations such as liposomes and targeted drug delivery systems for treatment. Therefore, aiming at and strengthening the basic research on ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/19A61K47/02A61K47/48A61K31/198A61P35/00A61K47/52A61K47/60A61K47/69
Inventor 徐海星许沛虎黄志军郑化刘霞姜晓晔李冉王玲
Owner WUHAN NUOAN PHARMACY
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