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Multi-purpose synergistic active targeting drug delivery system as well as preparation and applications thereof

A targeted drug delivery, multi-functional technology, applied in the direction of antineoplastic drugs, drug combinations, pharmaceutical formulations, etc., can solve the problems of lymphocyte decline, liver function damage, whole blood decline, etc., to reduce toxic and side effects, reduce toxic and side effects , the effect of reducing dosage

Inactive Publication Date: 2017-08-11
WUHAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in addition to killing tumor cells, it can also cause side effects such as lymphocyte drop, whole blood drop, liver function damage, and jaundice.

Method used

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  • Multi-purpose synergistic active targeting drug delivery system as well as preparation and applications thereof
  • Multi-purpose synergistic active targeting drug delivery system as well as preparation and applications thereof
  • Multi-purpose synergistic active targeting drug delivery system as well as preparation and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] 1. Preparation of HA-PLA-RGD-CLB / Ce6 Components

[0035] 1) Preparation of HA-TBA

[0036]After activating the cation exchange resin, add 300 mg of sodium hyaluronate, and stir for 12 hours. At this time, the pH of the solution is about 3. Add a small amount of TBA-OH solution dropwise to the solution to make the pH 7, and stir for 2 hours. The solution is freeze-dried to obtain white floc HA-TBA, characterized by FTIR and NMR.

[0037] 2) Preparation of polylactic acid active ester

[0038] Weigh 3.967g of polylactic acid and dissolve it in 30ml of anhydrous dichloromethane, protect it under nitrogen at room temperature, and add 0.204g of N,N'-dicyclohexylcarbodiimide and 0.114g of N-hydroxysuccinimide to activate for 24h ( PLA / DCC / NHS=1:2:2), the reacted solution was added to glacial ether for precipitation, the precipitate was filtered and vacuum-dried to obtain white powder PLA-NHS;

[0039] 3) Preparation of HA-PLA

[0040] Weigh 300 mg of the above-prepared HA...

Embodiment 2

[0054] 1. Preparation of HA-PLA-RGD-CLB / Ce6 Components

[0055] 1) Preparation of HA-TBA

[0056] After activating the cation exchange resin, add 300 mg of sodium hyaluronate and stir for 12 hours. At this time, the solution is acidic. Add a small amount of TBA-OH solution to the solution so that the pH is 7. Stir for 2 hours and freeze the solution after reaction. Dry to obtain white floc HA-TBA;

[0057] 2) Preparation of polylactic acid active ester

[0058] Weigh 3.174g of polylactic acid and dissolve it in 30ml of anhydrous dichloromethane, protect it under nitrogen at room temperature, and add 0.2163g of N,N'-dicyclohexylcarbodiimide and 0.091g of N-hydroxysuccinimide to activate for 24h (PLA / DCC / NHS=1:2:2), the reacted solution was added to glacial ether for precipitation, the precipitate was filtered and vacuum-dried to obtain white powder PLA-NHS;

[0059] 3) Preparation of HA-PLA

[0060] Weigh 300 mg of the above-prepared HA-TBA and dissolve it in anhydrous dim...

Embodiment 3

[0074] 1. Preparation of HA-PLA-RGD-CLB / Ce6 Components

[0075] 1) Preparation of HA-TBA

[0076] After activating the cation exchange resin, add 300 mg of sodium hyaluronate and stir for 12 hours. At this time, the solution is acidic. Add a small amount of TBA-OH solution to the solution so that the pH is 7. Stir for 2 hours and freeze the solution after reaction. Dry to obtain white floc HA-TBA;

[0077] 2) Preparation of polylactic acid active ester

[0078] Weigh 2.380g of polylactic acid and dissolve it in 30ml of anhydrous dichloromethane, under nitrogen protection at room temperature, and add 0.098g of N,N'-dicyclohexylcarbodiimide and 0.068g of N-hydroxysuccinimide to activate for 24h ( PLA / DCC / NHS=1:2:2), the reacted solution was added to glacial ether for precipitation, the precipitate was filtered and vacuum-dried to obtain white powder PLA-NHS;

[0079] 3) Preparation of HA-PLA

[0080] Weigh 300 mg of the above-prepared HA-TBA and dissolve it in anhydrous dime...

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Abstract

The invention relates to a double-receptor targeting drug delivery system realizing the synergistic effect of phototherapy and chemotherapy, as well as preparation and applications of the double-receptor targeting drug delivery system. The system is a compound containing hyaluronic acid, polylactic acid, polypeptide, and chlorambucil / chlorin e6, wherein the molecular weight of polylactic acid is 8000Da, specifically, the compound comprises the following components in parts by weight: 100-2000 parts of hyaluronic acid, 1500-10000 parts of polylactic acid, 21-450 parts of N,N'-dicyclohexylcarbodiimide, 12-240 parts of N-hydroxy succinimide, 1-30 parts of polypeptide, 20-400 parts of 1-(3-(Dimethylaminopropyl)-3-ethylcarbodiimide, 100-1000 parts of chlorambucil, and 50-600 parts of chlorin e6. The double-receptor targeting drug delivery system has the beneficial effects that (1) the synergistic effect of phototherapy and chemotherapy is realized; (2) the multiple targeting properties are realized; (3) the good blood stability is realized; (4) the system has small toxicity and high safety.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a dual-receptor targeted drug delivery system with synergistic effects of phototherapy and chemotherapy, as well as its preparation and application. Background technique [0002] Nowadays, malignant tumors have seriously threatened human life and health. Effective treatment and improvement of the quality of life of cancer patients are currently hot issues in the field of global cancer research. At present, the traditional treatment of cancer is mainly based on the comprehensive treatment of surgery and chemotherapy, among which chemotherapy is an indispensable treatment method. It plays an important role in clinical treatment because of its strong drug potency and its ability to rapidly kill or kill tumor cells. However, chemotherapy drugs generally have problems such as poor cell selectivity, large toxic and side effects, severe adverse reactions, and mult...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K47/61A61K47/64A61K31/196A61P35/00C08G81/00C08B37/08
Inventor 许沛虎张希徐海星黄志军马慧郭兴蕾布颖梁鹏李意璇
Owner WUHAN UNIV OF TECH
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