An amphiphilic polysaccharide derivative/poloxamer thermosensitive in-situ hydrogel and its preparation method

A technology of amphiphilic polysaccharides and poloxamers, which is applied in the field of biomedical materials, can solve the problems of less research and great influence on the properties of poloxamer thermosensitive hydrogels, so as to increase the gelation temperature, Effects of improving drug bioavailability and shortening gelation time

Inactive Publication Date: 2019-02-01
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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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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  • An amphiphilic polysaccharide derivative/poloxamer thermosensitive in-situ hydrogel and its preparation method
  • An amphiphilic polysaccharide derivative/poloxamer thermosensitive in-situ hydrogel and its preparation method
  • An amphiphilic polysaccharide derivative/poloxamer thermosensitive in-situ hydrogel and its preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] 1. Preparation method

[0042] (1) Weigh 10 mg of cholesterol-containing amphiphilic sodium alginate derivatives, put them in a serum bottle, add 1 ml of disodium hydrogen phosphate-sodium dihydrogen phosphate buffer (pH7.4), and store at 45°C Stir (rotate at 300 rpm) and dissolve for 12 hours to prepare an amphiphilic sodium alginate derivative solution;

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

[0044] (3) Take by weighing 20 mg of prednisone, place it in a serum bottle, add 2 milliliters of acetone, stir and dissolve at room temperature for 10 minutes, slowly add dropwise (30 drops / minute) to S2 gained mixed system I, stir at 8°C ( Rotating speed 300 rpm) dissolved for 12 hours to obtain the mixed system II;

[0045] (4) Put th...

Embodiment 2

[0055] 1. Preparation method

[0056] (1) Weigh 60 mg of amphiphilic hyaluronic acid derivatives containing cholesterol groups, place in a serum bottle, add 5 ml of citric acid-sodium citrate buffer solution (pH7.2), stir at 25°C (speed 100 revs / min) dissolving for 24 hours to prepare the amphiphilic hyaluronic acid derivative solution;

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

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

[0059] (4) Put th...

Embodiment 3

[0064] 1. Preparation method

[0065] (1) Weigh 130 mg of amphiphilic pullulan derivatives containing cholesterol groups, place it in a serum bottle, add 8 ml of disodium hydrogen phosphate-sodium dihydrogen phosphate buffer solution (pH7.4), and Stir at ℃ (1000 rpm) and dissolve for 24 hours to prepare an amphiphilic pullulan derivative solution;

[0066] (2) Weigh 267 mg of poloxamer 407 and 26 mg of poloxamer 108 respectively, place them in a stoppered test tube, add the amphiphilic pullulan derivative solution obtained in step S1, stir at 15°C (speed 1000 RPM) was dissolved for 24 hours to obtain the mixed system I;

[0067] (3) Weigh 38 mg of triamcinolone acetonide acetate, place it in a serum bottle, add 8 ml of acetone, stir and dissolve at room temperature for 15 minutes, slowly add dropwise (drop rate 40 drops / min) to the resulting mixed system I of S2, and stir at 12°C (rotating speed 1000 revs / min) dissolved for 36 hours, and mixed system II was obtained;

[006...

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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 gel) refers to a class of liquid preparations in which a polymer material containing a drug undergoes a phase transition under external stimuli to form a semi-solid gel after administration in the form of a solution (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 mu...

Claims

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Application Information

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Patent Type & Authority Patents(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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