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A kind of amphiphilic hydroxyethyl starch coupled cholesterol polymer and nano drug loading system

A technology of hydroxyethyl starch and nano-drug loading, applied in the directions of drug combination, powder delivery, drug delivery, etc., can solve the problem of poor tumor deep penetration effect, etc., and achieve good tumor deep penetration effect and biocompatibility. Good, structurally stable effect

Active Publication Date: 2022-04-22
XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The present invention aims to provide an amphiphilic hydroxyethyl starch-coupled cholesterol polymer and a nano-drug loading system to solve the problem of poor deep tumor penetration of existing nano-drug-loaded carriers

Method used

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  • A kind of amphiphilic hydroxyethyl starch coupled cholesterol polymer and nano drug loading system
  • A kind of amphiphilic hydroxyethyl starch coupled cholesterol polymer and nano drug loading system
  • A kind of amphiphilic hydroxyethyl starch coupled cholesterol polymer and nano drug loading system

Examples

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Effect test

Embodiment 1

[0035] A kind of amphiphilic hydroxyethyl starch coupled cholesterol polymer (HES-CH), is synthesized according to the following steps:

[0036] Step 1, amination of hydroxyethyl starch (HES)

[0037] Blend 1g of bromopropylamine hydrobromic acid with 1g of hydroxyethyl starch, add 4mL of sodium hydroxide solution, the equivalent concentration is 6.17N, and react at 4°C for 20 minutes, add 37% concentrated hydrochloric acid to adjust the pH value to 7 , Obtain aminated hydroxyethyl starch (HES-NH2), aminated hydroxyethyl starch (HES-NH2) removes impurities by dialysis, and then obtain purified aminated hydroxyethyl starch (HES-NH2) powder by lyophilization.

[0038]Step 2, dissolving 1g of cholesterol and 1g of succinic anhydride in 10ml of pyridine. The mixture was heated to 70° C. and stirred for 3 hours, then dried by rotary evaporation to obtain a precipitate, which was dissolved in ethanol, and the white precipitate was obtained by rotary evaporation as carboxylated chol...

Embodiment 2

[0049] According to the synthesis steps of the amphiphilic hydroxyethyl starch-coupled cholesterol polymer in Example 1, the amphiphilic hydroxyethyl starch-coupled cholesterol polymer (HES-CH) with a cholesterol grafting ratio of 0.21 was synthesized.

[0050] Preparation of a nano-drug delivery system for deep tumor penetration: Dissolve the purified amphiphilic hydroxyethyl starch-coupled cholesterol polymer (HES-CH) in water, and use a sonicator in an ice bath while Add indocyanine green (ICG) and paclitaxel (PTX) blended dichloromethane solution at a ratio of 1:1 while ultrasonicating. Ultrasonic for a total of 5 minutes. After ultrasonication, add the emulsion to a high-pressure homogenizer and homogenize twice at 600 bar Finally, the suspension of indocyanine green / paclitaxel@hydroxyethyl starch conjugated cholesterol (ICG / PTX@HES-CH) and indocyanine green (ICG) and paclitaxel (PTX) was obtained, followed by centrifugation at 5000rpm for 20min, To remove the unencapsula...

Embodiment 3

[0058] According to the synthesis steps of the amphiphilic hydroxyethyl starch-coupled cholesterol polymer (HES-CH) in Example 1, a hydroxyethyl starch-coupled cholesterol polymer (HES-CH) with a cholesterol grafting ratio of 0.21 was synthesized.

[0059] Preparation of a nano-drug delivery system for deep tumor penetration: Dissolve the purified amphiphilic hydroxyethyl starch-coupled cholesterol polymer (HES-CH) in water, and use a sonicator in an ice bath while Add indocyanine green (ICG) and paclitaxel (PTX) blended dichloromethane solution at a ratio of 1:1 while ultrasonicating. Ultrasonic for a total of 5 minutes. After ultrasonication, add the emulsion to a high-pressure homogenizer and homogenize twice at 600 bar Finally, the suspension of indocyanine green / paclitaxel@hydroxyethyl starch conjugated cholesterol (ICG / PTX@HES-CH) and indocyanine green (ICG) and paclitaxel (PTX) was obtained, followed by centrifugation at 5000rpm for 20min, To remove unencapsulated pacli...

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Abstract

The invention provides an amphiphilic hydroxyethyl starch-coupled cholesterol polymer, which is formed by the acylation reaction of carboxylated cholesterol and aminated hydroxyethyl starch. The invention also provides a Penetrating nano drug-carrying system and its preparation method. An amphiphilic hydroxyethyl starch-coupled cholesterol copolymer provided by the present invention can be prepared into spherical nanoparticles loaded with indocyanine green by ultrasonic emulsification and high-pressure homogenization, and then continue Illuminate it with a near-infrared laser to prepare a "sea urchin-shaped" nanocarrier with stable structure, good biocompatibility, and good deep tumor penetration effect.

Description

Technical field: [0001] The invention relates to the technical field of polymer drug carriers, in particular to an amphiphilic hydroxyethyl starch-coupled cholesterol polymer, a nanometer drug-carrying system, and a preparation method for the two. Background technique: [0002] Nano-carriers are an important part of the nano-drug delivery system. Nano-carriers are loaded with drugs to obtain pharmaceutical preparations between 0-1000 nanometers, which can increase the accumulation of drugs in tumor sites by enhancing the retention and penetration effects, and increase the efficacy and attenuation of drugs; at the same time Increase the blood stability of the drug, prevent the drug from being excreted too quickly by the kidneys and prolong the half-life of the loaded drug, so as to improve the bioavailability of the drug. After the nanocarriers are accumulated in the tumor tissue, the next step is the deep penetration of the tumor. The rapid proliferation of tumor cells can ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08B31/12A61K47/61A61K47/55A61K47/69A61K31/337A61K41/00A61P35/00
CPCC08B31/125A61K47/61A61K47/554A61K47/6939A61K31/337A61K41/0057A61P35/00A61K2300/00
Inventor 梅恒胡豫唐宇翔陈钊钊姚惟琪
Owner XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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