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Temperature-sensitive polymer, synthesis method thereof and temperature-sensitive injectable hydrogel

A synthesis method and polymer technology, applied in medical science, prosthesis, etc., can solve the problems of unstable gel mechanical properties, limited application range, and low strength of cross-linking points, achieve good biocompatibility, and avoid surgery The trouble of taking out, the effect of easy preparation

Active Publication Date: 2019-05-10
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Similar to the existing thermosensitive hydrogels based on the low critical phase transition temperature, mainly rely on the hydrophobic aggregation of polymers above the low critical phase transition temperature to form a cross-linked structure, and the strength of the cross-linking points formed by this hydrophobic aggregation is low, resulting in unstable The mechanical properties of the gel and the cross-linked structure that is not resistant to swelling greatly limit its application range

Method used

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  • Temperature-sensitive polymer, synthesis method thereof and temperature-sensitive injectable hydrogel
  • Temperature-sensitive polymer, synthesis method thereof and temperature-sensitive injectable hydrogel
  • Temperature-sensitive polymer, synthesis method thereof and temperature-sensitive injectable hydrogel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] 1. Synthesis of Thermosensitive Polymers

[0047] (1) Synthesis of GelMA (methacrylic acylated gelatin) using gelatin and methacrylic acid anhydride:

[0048] ①Put 6g of solid gelatin and 60ml of 1×PBS into a 250ml round-bottomed flask with a 4cm double-tip PTFE magnetic rotor, seal the container, stir at a constant speed of 300rpm, and dissolve it in a water bath at 40°C for 1 hour until the contents of the container are pale. yellow clear liquid;

[0049] ②Heating step ①The gelatin solution obtained in ① was brought to 50°C, kept stirring at 300rpm, and then slowly injected and dropped 12ml of methacrylic anhydride therein at a rate of 0.2ml / min;

[0050] ③ After the dropwise addition, fully react for 4 hours in a 50°C water bath with a stirring rate of 300rpm;

[0051] ④ Stop the reaction, dissolve the product, dilute the reaction system with 10 times the volume with 1×PBS, and then dissolve it in a water bath at 40°C for 1 hour;

[0052] ⑤Purify the product, 5 li...

Embodiment 2

[0083] 1. Synthesis of Thermosensitive Polymers

[0084] (1) Synthesis of GelMA (methacrylic acylated gelatin) using gelatin and methacrylic acid anhydride

[0085] ①Put 10g of solid gelatin and 100ml of 0.3M (0.09M Na 2 CO 3 , 0.21M NaHCO 3 )Na 2 CO 3 -NaHCO 3 Sodium bicarbonate aqueous solution, in a closed container, stirred at a constant speed of 300rpm, dissolved in a water bath at 40°C for 1 hour until the substance in the container is a light yellow clear liquid, and the pH value is adjusted to 9.0 with 5M NaOH aqueous solution;

[0086] ②Heating step ①The gelatin solution obtained in ① was brought to 50°C, kept stirring at 300rpm, and then slowly injected and dropped 1ml of methacrylic acid anhydride therein at a rate of 0.2ml / min;

[0087] ③ After the dropwise addition, fully react for 2 hours in a 50°C water bath with a stirring rate of 300rpm;

[0088] ④ Stop the reaction, dissolve the product, adjust the pH to 7.4 with 5M HCl aqueous solution, and then disso...

Embodiment 3

[0105] 1. Synthesis of Thermosensitive Polymers

[0106] (1) Synthesis of GelMA from gelatin and methacrylic acid anhydride

[0107] ①Put 10g of solid gelatin and 100ml of 0.2M (0.03M Na 2 CO 3 , 0.17M NaHCO 3 )Na 2 CO 3 -NaHCO 3 Sodium bicarbonate aqueous solution, in a closed container, stirred at a constant speed of 300rpm, dissolved in a water bath at 40°C for 1 hour until the substance in the container is a light yellow clear liquid, and the pH value is adjusted to 9.0 with 5M NaOH aqueous solution;

[0108] ②Heating step (1) ①The gelatin solution obtained is brought to 50°C, kept stirring at 300rpm, and then slowly injects 1ml of methacrylic anhydride therein dropwise, with a dropping rate of 0.2ml / min;

[0109] ③After the dropwise addition, fully react for 2 hours in a water bath at 50°C and a stirring rate of 300rpm (1)②The obtained system;

[0110] ④ Stop the reaction, dissolve the product, adjust the pH to 7.4 with 6M HCl aqueous solution, and then dissolve it...

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Abstract

The invention discloses temperature-sensitive polymer, a synthesis method thereof and temperature-sensitive injectable hydrogel. A temperature-sensitive polymer is obtained by synthesizing GelMA and UPyMA, dispersing UPyMA, GelMA and MEOnMA monomers in an alkaline water solution of 8-11 in pH, removing oxygen, adding an oxidative reduction initiator or a water soluble initiator at room temperaturefor polymerization reaction until reaction is sufficient, purifying a product, and removing a solvent to obtain the temperature-sensitive polymer. The temperature-sensitive polymer can be prepared into injectable aqueous-phase temperature-sensitive polymer sol when being not higher than corresponding low critical phase transition temperature and not lower than water freezing point in a normal-pressure environment, and the sol can immediately form gel when being higher than the corresponding low critical phase transition temperature. The temperature-sensitive injectable hydrogel has dynamic mechanical performance and high biocompatibility and can be applied in the field of biomedicine like tissue engineering, drug controlled release and cell three-dimensional culture.

Description

technical field [0001] The invention belongs to the technical fields of polymer physics, polymer chemistry, biomedical materials and tissue engineering, and specifically relates to the synthesis of a temperature-sensitive polymer with good biocompatibility and the preparation and preparation of a corresponding temperature-sensitive injectable hydrogel. application method. Background technique [0002] Hydrogel is a gel in which the aqueous phase system is used as the dispersion medium. The molecular composition and structure in the gel network are complex and changeable, and have good designability; the aqueous phase dispersion system can endow the gel with good biocompatibility. Due to the above characteristics, hydrogel can provide cells with an environment for retention or proliferation, and can also contain drugs or proteins for controlled release. After the task is completed, it can be biodegraded and excreted as metabolic waste. It has great potential in biomedicine. ...

Claims

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Application Information

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IPC IPC(8): C08F289/00C08F220/36C08F220/28C08H1/00A61L27/22A61L27/38A61L27/52A61L27/54A61L27/58
CPCA61L27/22A61L27/38A61L27/52A61L27/54A61L27/58C08F220/28C08F220/36C08F289/00C08H1/00
Inventor 任力齐大卫陈云华刘卅
Owner SOUTH CHINA UNIV OF TECH
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