Amphipathic polysaccharide derivative/poloxamer thermo-sensitive type in-situ hydrogel and preparation method thereof

A technology of amphiphilic polysaccharides and poloxamers, which is applied in the field of biomedical materials, can solve the problems that the properties of poloxamer thermosensitive hydrogels are greatly affected, and there are few studies, so as to improve the bioavailability of drugs, Effect of increasing gelation temperature, good biocompatibility and degradability

Inactive Publication Date: 2015-09-09
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are still too few related studies. Different types of poloxamers and different modification methods have a great influence on the properties of poloxamer thermosensitive hydrogels. Poloxamer thermosensitive hydrogels with excellent properties need further research

Method used

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  • Amphipathic polysaccharide derivative/poloxamer thermo-sensitive type in-situ hydrogel and preparation method thereof
  • Amphipathic polysaccharide derivative/poloxamer thermo-sensitive type in-situ hydrogel and preparation method thereof
  • Amphipathic polysaccharide derivative/poloxamer thermo-sensitive type in-situ hydrogel and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] 1. Preparation method

[0042] (1) Weigh 10 mg of the amphiphilic sodium alginate derivative containing cholesterol group, put it in a serum bottle, add 1 ml of disodium hydrogen phosphate-sodium dihydrogen phosphate buffer (pH 7.4), and at 45 ℃ Stir (rotation speed 300 r / min) to dissolve for 12 hours to obtain amphiphilic sodium alginate derivative solution;

[0043] (2) Weigh 126 mg of poloxamer 407 and 10 mg of poloxamer 188 respectively, put them in a stoppered test tube, add the amphiphilic sodium alginate derivative solution obtained in step S1, and stir at 4°C (rotation speed 300 rpm) / min) dissolved for 12 hours to obtain Mixed System I;

[0044] (3) Weigh 20 mg of prednisone, put it in a serum bottle, add 2 ml of acetone, stir and dissolve at room temperature for 10 minutes, slowly add it dropwise (drop rate 30 drops / min) to the mixed system I obtained from S2, stir at 8°C ( Rotation speed 300 rpm) and dissolved for 12 hours to obtain Mixed System II;

[004...

Embodiment 2

[0055] 1. Preparation method

[0056] (1) Weigh 60 mg of amphiphilic hyaluronic acid derivative containing cholesterol group, put it in a serum bottle, add 5 ml of citric acid-sodium citrate buffer (pH 7.2), and stir at 25°C (rotation speed) 100 rpm) for 24 hours to obtain amphiphilic hyaluronic acid derivative solution;

[0057] (2) Weigh 100 mg of poloxamer 407 and 70 mg of poloxamer 338 respectively, put them in a test tube with a stopper, add the solution of the amphiphilic hyaluronic acid derivative obtained in step S1, and stir at 8°C (rotation speed 100 rpm) / min) dissolved for 36 hours to obtain Mixed System I;

[0058] (3) Weigh 1 mg of indomethacin, put it in a serum bottle, add 1 ml of ethanol, stir and dissolve at room temperature for 25 minutes, slowly add it dropwise (drop rate 10 drops / min) to the mixed system I obtained from S2, stir at 10 °C (Rotation speed 100 rpm) and dissolved for 12 hours to obtain Mixed System II;

[0059] (4) The mixed system II obtai...

Embodiment 3

[0064] 1. Preparation method

[0065] (1) Weigh 130 mg of the amphiphilic pullulan derivative containing cholesterol group, put it in a serum bottle, add 8 ml of disodium hydrogen phosphate-sodium dihydrogen phosphate buffer solution (pH 7.4), at 38 ℃ stirring (rotation speed 1000 r / min) to dissolve for 24 hours to obtain amphiphilic pullulan derivative solution;

[0066] (2) Weigh 267 mg of poloxamer 407 and 26 mg of poloxamer 108 respectively, put them in a stoppered test tube, add the amphiphilic pullulan derivative solution obtained in step S1, and stir at 15°C (rotation speed 1000 rev / min) to dissolve for 24 hours to obtain Mixed System I;

[0067] (3) Weigh 38 mg of triamcinolone acetonide acetate, put it in a serum bottle, add 8 ml of acetone, stir and dissolve at room temperature for 15 minutes, slowly add it dropwise (drop rate 40 drops / min) to the mixed system I obtained from S2, stir at 12°C (Rotation speed 1000 rpm) and dissolved for 36 hours to obtain Mixed Syst...

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Abstract

The invention discloses amphipathic polysaccharide derivative/poloxamer thermo-sensitive type in-situ hydrogel and a preparation method thereof. The thermo-sensitive type in-situ hydrogel is prepared in the mode that amphipathic polysaccharide series derivatives, poloxamer polymer and hydrophobic drugs interact to form stable in-situ hydrogel, the gelatinization temperature of the thermo-sensitive type in-situ hydrogel ranges from 34 DEG C to 37 DEG C, and the gelatinization time for forming the in-situ hydrogel at the gelatinization temperature ranges from one to three minutes. The poloxamer polymer is the mixture of poloxamer 407 and any one kind of poloxamer of other types. Compared with common amphipathic/poloxamer in-situ hydrogel, the in-situ hydrogel is higher in stability and longer in drug sustained release time, parenteral drug delivery and improving of drug bioavailability are made possible, and the in-situ hydrogel can be applied to mucous membrane drug delivery, transdermal drug delivery and parenteral drug delivery systems; the preparation method of the mphipathic polysaccharide derivative/poloxamer thermo-sensitive type in-situ hydrogel is convenient to operate, simple in process and cheap in needed equipment and raw material.

Description

technical field [0001] The invention belongs to the field of biomedical materials. More specifically, it relates to an amphiphilic polysaccharide derivative / poloxamer temperature-sensitive in-situ hydrogel and a preparation method thereof. Background technique [0002] In situ gel (in situ gel1) refers to a type of liquid preparation in which the polymer material containing the drug is administered in the form of a solution and undergoes a phase transition under external stimuli to form a semi-solid gel (Wang Lijuan et al., Chinese Journal of Pharmaceutical Sciences, 2009, 44(4), 245-248). Among them, thermosensitive in situ hydrogels are the most extensively studied. They take advantage of the difference between human body temperature and ambient temperature to inject drugs, form gels under physiological temperature conditions, and maintain their integrity for a required time. [0003] In recent years, the temperature-sensitive in situ hydrogel of Poloxamer has attracted ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/34A61K47/36
Inventor 杨立群赖欣宜胡亦清龙茜罗嘉浩冯子乐张黎明
Owner SUN YAT SEN UNIV
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