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.
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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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