Cellulose-polylactic acid amphiphilic drug-loading micelle preparation method and product thereof, and applications of product

A technology of drug-loaded micelles and amphiphilicity, which is applied in the preparation of cellulose-polylactic acid amphiphilic drug-loaded micelles and the preparation of drug-loaded amphiphilic nanomicelles, which can solve the problems of underutilization of renewable resources , to achieve good biodegradability, meet production and application requirements, and good biocompatibility

Inactive Publication Date: 2019-01-25
SHANGHAI NAT ENG RES CENT FORNANOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, this cheap and inexhaustible renewa

Method used

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  • Cellulose-polylactic acid amphiphilic drug-loading micelle preparation method and product thereof, and applications of product
  • Cellulose-polylactic acid amphiphilic drug-loading micelle preparation method and product thereof, and applications of product
  • Cellulose-polylactic acid amphiphilic drug-loading micelle preparation method and product thereof, and applications of product

Examples

Experimental program
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Example Embodiment

[0033] Example 1

[0034] First, 1g of hydroxypropyl methylcellulose (Mn=7000 g / mol) and 0.2g of sodium cyanoborohydride reducing agent were dissolved in 50 mL of dimethyl sulfoxide (DMSO) at 60 ℃ and 10×10 -3 M NaCl mixed solution (3 / 1 v / v), add 0.1g mercaptoethylamine after the dissolution is complete, the above mixed solution is slowly stirred and refluxed at 60 ºC for 6 days, the solution is cooled to room temperature, and deionized water Dialysis in a dialysis bag with a molecular weight cut-off of 3500 g / mol for 3 days. After freeze-drying, add excess dithiothreitol (DTT), react for 12 hours at room temperature under argon atmosphere, and then dialyze again for 3 days, freeze-dry Then obtain the mercapto-terminated hydroxypropyl methylcellulose;

[0035] Secondly, 7.2g L-lactide, 168.78 mg propargyl alcohol, 0.2g stannous octoate (Sn(Oct) 2 ) The three substances were added to a 30 mL Schlenk bottle of anhydrous toluene solution, and the resulting mixture solution was stirre...

Example Embodiment

[0048] Example 2

[0049] First, 1g of hydroxypropyl methylcellulose (Mn=5000 g / mol) and 0.13g of sodium cyanoborohydride reducing agent were dissolved in 50 mL of dimethyl sulfoxide (DMSO) at 60 ℃ and 10×10 -3 In the mixed solution of M NaCl (3 / 1 v / v), add 0.15g mercaptoethylamine after the dissolution is complete, the above mixed solution is slowly stirred and refluxed for 6 days at 60 ºC, the solution is cooled to room temperature, and deionized water Dialysis in a dialysis bag with a molecular weight cut-off of 3500 g / mol for 3 days. After freeze-drying, add excess dithiothreitol (DTT), react for 12 hours at room temperature under argon atmosphere, and then dialyze again for 3 days, freeze-dry Then obtain the mercapto-terminated hydroxypropyl methylcellulose;

[0050] Secondly, 7.2g L-lactide, 168.78 mg propargyl alcohol, 0.2g stannous octoate (Sn(Oct) 2 ) The three substances were added to a 30 mL Schlenk bottle of anhydrous toluene solution, and the resulting mixture solutio...

Example Embodiment

[0052] Example 3

[0053] First, 1g of hydroxypropyl methylcellulose (Mn=10000 g / mol) and 0.06g of sodium cyanoborohydride reducing agent were dissolved in 50 mL of dimethyl sulfoxide (DMSO) at 60℃ and 10×10 -3 In the mixed solution of M NaCl (3 / 1 v / v), add 0.08g of mercaptoethylamine after the dissolution is complete, the above mixed solution is slowly stirred and refluxed at 60 ºC for 6 days, the solution is cooled to room temperature, and deionized water Dialysis in a dialysis bag with a molecular weight cut-off of 3500 g / mol for 3 days. After freeze-drying, add excess dithiothreitol (DTT), react for 12 hours at room temperature under argon atmosphere, and then dialyze again for 3 days, freeze-dry Then obtain the mercapto-terminated hydroxypropyl methylcellulose;

[0054] Secondly, 7.2g L-lactide, 168.78 mg propargyl alcohol, 0.2g stannous octoate (Sn(Oct) 2 ) The three substances were added to a 30 mL Schlenk bottle of anhydrous toluene solution, and the resulting mixture solu...

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Abstract

The invention relates to a cellulose-polylactic acid amphiphilic drug-loading micelle preparation method and a product thereof, and applications of the product. According to the method, the active aldehyde group of hydroxypropylmethylcellulose is reduced with mercapto-ethylamine to obtain thiol-terminated hydroxypropylmethylcellulose, alkynyl-terminal poly(L-lactic acid) is synthesis by initiatingwith propargyl alcohol through a ring-opening polymerization method, and finally a thiol alkyne click reaction is initiated under ultraviolet light irradiation so as to obtain a series of hydroxypropylmethylcellulose-poly(L-lactic acid) block copolymers with different molecular weights. According to the present invention, the product is the amphiphilic block nano-micelles using hydroxypropylmethylcellulose as the hydrophilic chain segment and using poly(L-lactic acid) as the hydrophobic chain segment; the preparation method has characteristics of wide raw material source, simple process and strong operability; and the obtained product has good popularization and application value in drug controlled slow release carriers, bio-intelligent switches and nano-scale reactors.

Description

technical field [0001] The invention relates to a preparation method of drug-loaded amphiphilic nano micelles, in particular to a preparation method of cellulose-polylactic acid amphiphilic drug-loaded micelles as well as its products and applications. The invention belongs to the field of macromolecular materials and nano biomedical materials. Background technique [0002] Because amphiphilic block copolymers can self-assemble into aggregates of different shapes in selective solvents, they are widely used in the fields of nano templates, nanoreactors and drug carriers. Among them, the most focused ones are nanoparticles or micelles composed of amphiphilic front-end copolymers as nanocarriers for carrying bioactive molecules. Compared with traditional drug delivery systems, nanometer-sized polymer micelles have excellent properties, such as: selective targeting, prolonging the residence time of drugs in blood circulation, etc., so it can reduce drug dosage, drug delivery f...

Claims

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Application Information

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IPC IPC(8): C08G81/00C08G63/08C08B15/00A61K9/107A61K47/34A61K47/38
CPCA61K9/1075A61K47/34A61K47/38C08B15/00C08G63/08C08G81/00
Inventor 何丹农王杰林王萍金彩虹
Owner SHANGHAI NAT ENG RES CENT FORNANOTECH
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