Injectable intelligent response hydrogel and preparation method and application thereof

A hydrogel and intelligent technology, applied in pharmaceutical formulations, medical science, prostheses, etc., can solve the problems of poor tissue adhesion, the inability of hydrogels to self-repair, etc., achieving easy operation, good injectability, Controllable effect

Pending Publication Date: 2019-07-05
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The technical problem solved by the present invention is to provide an injectable intelligent response hydrogel, which solves the problems in the prior art that the traditional hydrogel cannot be self-repaired after being broken and has poor adhesion to the original tissue

Method used

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  • Injectable intelligent response hydrogel and preparation method and application thereof
  • Injectable intelligent response hydrogel and preparation method and application thereof
  • Injectable intelligent response hydrogel and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] This embodiment discloses the preparation method of aldylated hyaluronic acid, the specific steps are as follows:

[0061] (1) Dissolve sodium hyaluronate with a molecular weight of 0.01MDa to 3.0MDa in deionized water, fully dissolve sodium periodate in advance, and then add it dropwise to the sodium hyaluronate solution. After a period of reaction in the dark, add 200ul~500ul of ethylene glycol reacted for 1~2h to stop sodium periodate and continue to oxidize.

[0062] In this step, the oxidation time is 2-24 hours, and the molar ratio of hyaluronic acid and sodium periodate is 1:0.3-1:5, which are recorded as experimental groups ①, ②, ③, ④, and ⑤ respectively.

[0063] (2) The reaction solution obtained in step (1) was dialyzed in deionized water for 3 to 4 days, and freeze-dried to obtain aldylated hyaluronic acid (HA-CHO). The oxidation degrees in the HA-CHO were 10.3% and 19.8% respectively. , 32.9%, 46.1%, 79.2%.

[0064] The molecular weight of sodium hyaluron...

Embodiment 2

[0075] This example discloses a preparation method of hydrazidated hyaluronic acid, and the specific steps are as follows:

[0076] (1) Dissolve sodium hyaluronate with a molecular weight of 0.01MDa~3.0MDa in 0.01~1mol / l Mes buffer solution, add N-hydroxysuccinimide (NHS), fully dissolve, and then add 1-ethyl -(3-Dimethylaminopropyl) carbodiimide hydrochloride (EDC·HCl), fully dissolved, with 0.1~1mol / L NaOH solution and 0.1~1mol / L HCl solution to adjust the mixture When the pH value reaches 4.75-5.5, react at room temperature for 1-2 hours, then add 3,3'-dithiobis(hydrazine propionate) (TPH) solution, and react overnight at room temperature.

[0077] In this step, sodium hyaluronate, N-hydroxysuccinimide (NHS), 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC·HCl), 3 , 3'-dithiobis(hydrazine propionate) (TPH) molar ratio is 1:0.3:1.5:5~1:2:5:10.

[0078] (2) The reaction solution obtained in step (1) was dialyzed in deionized water for 3 to 4 days, and freeze...

Embodiment 3

[0084] In this example, an injectable smart responsive hydrogel is prepared, and the steps are as follows:

[0085] (1) Dissolve the aldylated hyaluronic acid and hydrazide hyaluronic acid obtained by dialysis and freeze-drying in PBS solution respectively, the concentration is 1-50mg / ml, and use 0.1-1mol / L NaoH and 0.1-1mol / L The HCl solution adjusts the pH value to 7.0-8.0.

[0086] (2) At room temperature, add the aldylated hyaluronic acid and hydrazide hyaluronic acid respectively into the barrel of the double syringe, push out at the same time to ensure uniform mixing, inject into the mold, and stand at room temperature to form a gel.

[0087] Specifically as shown in Table 4:

[0088] Table 4

[0089]

[0090]

[0091] image 3 It is the gelation diagram of experimental group ①~⑤ in embodiment 3, adopts the method for test tube inversion to determine its gelation time, specifically as shown in table 5:

[0092] table 5

[0093] Experimental group① ...

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Abstract

The invention discloses injectable intelligent response hydrogel and a preparation method and application thereof and solves the problems that traditional hydrogel cannot achieve self-repairing afterbeing broken and is poor in adhesive capacity to original tissue in the prior art. The structure of the injectable intelligent response hydrogel is as shown in formula I. The preparation method includes: allowing an aldehyde group modified natural material or synthetic polymer to have Schiff base reaction with a hydrazide natural material or synthetic polymer with a disulfide bond to prepare the injectable intelligent response hydrogel. The injectable intelligent response hydrogel can be used as a drug carrier or / and a biological material. The injectable intelligent response hydrogel is scientific in design, simple to operate, good in injectability and biocompatibility and degradable, has certain adhesive capacity to original tissue, has self-healing performance, pH sensitivity and redox property and is an ideal drug carrier and biological repairing material.

Description

technical field [0001] The invention belongs to the technical field of biological materials, and in particular relates to an injectable intelligent response hydrogel and its preparation method and application. Background technique [0002] Tissue engineering has developed by leaps and bounds since it was first proposed. Not only have various tissue-engineered tissues been constructed in animals, but they have also been widely used clinically and have achieved lasting curative effects. Tissue engineering technology can avoid immune rejection and insufficient donor sources in traditional autologous or allogeneic tissue and organ transplantation, and it is hopeful to realize tissue and organ reconstruction to solve clinical difficulties. The study of tissue engineering includes methods and techniques for seeding cells, scaffolding materials, and constructing tissues and organs. Its core is to establish a three-dimensional space complex composed of cells and biological material...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/52A61L27/18A61L27/20A61L27/58C08J3/075C08L5/08C08B37/08
CPCA61L27/18A61L27/20A61L27/52A61L27/58A61L2400/06C08B37/0072C08J3/075C08J2305/08C08J2405/08C08L5/08
Inventor 孙勇樊渝江徐扬张兴栋
Owner SICHUAN UNIV
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