Thiol-aldehyde group cross-linked hydrogel material, preparation method and applications thereof

A cross-linked hydrogel and aldehyde-based technology, which is applied in pharmaceutical formulations, medical preparations of non-active ingredients, medical science, etc., can solve problems such as insufficient clinical operation time, plugging of pipette tips, and gel displacement.

Active Publication Date: 2019-08-16
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in clinical practice, the above two methods often have some shortcomings: 1) The preformed hydrogel does not have good wound tissue shaping, and it is difficult to completely cover irregularly shaped wounds; in addition, the surface is smooth, The fragile hydrogel cannot be fixed on the wound surface by surgical means, causing the gel to displace and slip in the wound tissue and affect the use effect. Although the negative pressure wound therapy technology can make the gel closely fit the wound, the operation is cumbersome and easy Break the hydrogel; 2) Although the gel precursor solution of the in situ formed hydrogel can penetrate into various parts of the wound tissue well, it has high requirements on the crosslinking speed of the gel, and the gelation speed Too slow tends to cause the gel precursor to be diluted or washed away by the blood or exudate of the wound. The speed of gelation is too fast and there is not enough time for clinical operation, especially when the sample is applied by spraying glue. Once the glue is sprayed, the middle cannot Stop, otherwise the excessively fast cross-linking speed will lead to the plugging of the tip of the pipette; in addition, the existing in-situ formed medical gels all use two-component cross-linking, which requires complicated and expensive two-component cross-linking in clinical use. Serving Syringes
The above deficiencies limit the clinical application of hydrogel materials

Method used

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  • Thiol-aldehyde group cross-linked hydrogel material, preparation method and applications thereof
  • Thiol-aldehyde group cross-linked hydrogel material, preparation method and applications thereof
  • Thiol-aldehyde group cross-linked hydrogel material, preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0186] Example 1: Synthesis of thiol-modified hyaluronic acid derivatives (HA-SH)

[0187]

[0188] Synthesis of HA-SH: Dissolve hyaluronic acid (0.5g, 48kDa) in 50mL distilled water until completely dissolved, add hydroxybenzotriazole (HOBt, 0.2g), 1-ethyl-(3-dimethyl Aminopropyl) carbodiimide hydrochloride (EDC-HCl, 0.1g), 3,3'-dithiobis(propionohydrazide) (DTP, 0.1g), adjust the pH to 4.75, react for 24 hours, then add DTT to continue the reaction for 5 hours, pour the reaction solution into a dialysis bag (MWCO 3500), dialyze with deionized water for 2-3 days, and freeze-dry to obtain HA-SH (0.46g). From the hydrogen spectrogram, it can be calculated that the content of mercapto groups is about 24%.

Embodiment 2

[0189] Example 2: Synthesis of thiol-modified dextran derivatives (Dex-SH)

[0190]

[0191] Synthesis of Dex-SH: Dissolve 40kDa dextran Dextran (12g, 0.3mmol) in 50mL DMSO until completely dissolved, add 3-mercaptopropionic acid (636.8mg, 6.0mmol), 1,3-dicyclohexylcarbodi Imine (910.7mg, 9.0mmol), 4-(dimethylamino)pyridine (1099.5mg, 9.0mmol), reacted at room temperature for 48h, then reprecipitated in acetone, dissolved the crude product in water and poured it into dialysis Dex-SH (11.5g) can be obtained by dialysis with deionized water for 2-3 days in a bag (MWCO 3500), and freeze-dried. According to the H NMR spectrum, the content of sulfhydryl groups can be calculated to be about 16%.

Embodiment 3

[0192]Example 3: Synthesis of thiol-modified heparin derivatives (Hep-SH)

[0193]

[0194] Synthesis of Hep-SH: Dissolve Heparin (0.5g, 12kDa) in 50mL of distilled water until completely dissolved, add hydroxybenzotriazole (HOBt, 0.2g), 1-ethyl-(3-dimethylamino Propyl) carbodiimide hydrochloride (EDC-HCl, 0.1g), mercaptoethylamine (0.1g), adjust the pH to 5-6 with dilute hydrochloric acid solution, after reacting for 24h, pour the reaction solution into the dialysis bag ( MWCO 3500), dialyzed with deionized water for 2-3 days, and freeze-dried to obtain Hep-SH (0.45 g). According to the H NMR spectrum, the content of sulfhydryl groups can be calculated to be about 29%.

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Abstract

The invention relates to a thiol-aldehyde group cross-linked hydrogel material, a preparation method and applications thereof. The preparation method comprises: dissolving a component A thiol-containing polymer derivative in a biocompatible medium to obtain a solution A; dissolving a component B aldehyde group-containing polymer derivative in a biocompatible medium to obtain a solution B; and mixing with the solution A and the solution B to obtain the hydrogel, wherein the hydrogel has plasticity at the initial stage of cross-linking, can form a removable hydrogel system at the later stage ofcross-linking, and can form an interpenetrating network hydrogel system with enhanced mechanical property, a component C and / or a component D can be added to the hydrogel precursor solution, the component C is a double bond-containing substance or an amino-containing substance or a substance containing a double bond and amino, and the component D is a tissue repairing beneficial ingredient. The invention further provides a kit for preparing the hydrogel, applications of the hydrogel in tissue engineering and regenerative medicine, 3D cell culture, 3D printing, and applications of the hydrogelas cell carriers, protein carriers or drug carriers.

Description

technical field [0001] The invention relates to a hydrogel material, in particular to a mercapto-aldehyde group crosslinked hydrogel material and a preparation method and application thereof, belonging to the technical field of biomaterials. Background technique [0002] Hydrogel is a kind of highly water-containing polymer material with a three-dimensional network cross-linked structure. Due to its excellent biocompatibility, degradability and certain mechanical strength, it has been used as a scaffold material in the field of tissue engineering and has been applied in the skin. , Cartilage, bone, myocardium, corneal repair, etc. have made important breakthroughs. In addition, it also has unique advantages in clinical wound treatment, such as hemostasis, protection, isolation, and repair. Currently, hydrogels are applied in clinical operations in two ways: preformed hydrogels and in-situ formed hydrogels. Preformed hydrogels refer to gels that have been cross-linked into a ...

Claims

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Application Information

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IPC IPC(8): C08J3/24C08J3/075C08L71/02C08L5/02C08L5/08C08L89/00C08L1/28A61K47/36A61K47/38A61K47/08A61K47/14A61K47/16A61L27/52A61L27/54A61L27/20A61L27/22A61L27/16A61L27/50A61L26/00
CPCA61K47/08A61K47/14A61K47/16A61K47/36A61K47/38A61K47/42A61L26/0019A61L26/0023A61L26/0038A61L26/0061A61L26/0066A61L26/008A61L27/16A61L27/20A61L27/222A61L27/50A61L27/52A61L27/54A61L2430/02A61L2430/38C08J3/075C08J3/246C08J2301/28C08J2305/02C08J2305/08C08J2371/02C08J2389/00C08J2401/28C08J2405/02C08J2405/08C08J2471/02C08J2489/00C08L5/08C08L5/02C08L5/10C08L1/286C08L5/04
Inventor 林秋宁华宇杰朱麟勇张依晴包春燕钟学鹏
Owner EAST CHINA UNIV OF SCI & TECH
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