Biocompatible quick-gelatinizing hydrogels and method for preparing spray thereof
A biocompatible, hydrogel technology, applied in the preparation of biocompatible rapid gelling hydrogel spray, the field of preparation of biocompatible rapid gelling hydrogel, can solve the problem of expensive, high cost, Problems such as unstable solution of multi-armed polyethylene glycol mercapto derivatives
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Embodiment 1
[0111] Example 1 Preparation of mercapto-modified hyaluronic acid (HA-DTPH)
[0112] It was prepared by the method reported by Shu et al. (Shu et al., Biomacromolecules, 3, 1304, 2002).
[0113] 20 grams of sodium hyaluronate (molecular weight: about 1.5 million) was dissolved in 2 liters of distilled water, and concentrated hydrochloric acid was added to adjust the pH of the solution to about 0.5, and then degraded in a shaker at 37 degrees Celsius and 150 revolutions per minute for 24 hours. Dialysis purification freeze-drying to obtain low molecular weight hyaluronic acid (weight average molecular weight 246,000, number average molecular weight 120,000).
[0114] 20 grams of the aforementioned low molecular weight hyaluronic acid was dissolved in 2 liters of distilled water. Add 23.8 g of dithiodimalonyl hydrazide (prepared according to the method disclosed by Shu et al. in Biomacromolecules, 3, 1304, 2002) into the above solution, and stir to dissolve. Then the pH value of the ...
Embodiment 2
[0117] Example 2 Preparation of sulfhydryl reactive biocompatible crosslinking agent
[0118] Polyethylene glycol diacrylate, polyethylene glycol di(meth)acrylate, polyethylene glycol diacrylamide and polyethylene glycol di(meth)acrylamide are composed of the corresponding polyethylene glycol (molecular weight) 3,400 or 10,000, Sigma-Aldrich, U.S.) and polyethylene glycol diamine (molecular weight 3400, Nektar Therapeutics, U.S.), multi-arm (4 and 8 arms) polyethylene glycol diacrylate and polyethylene glycol Di(meth)acrylates are prepared from the corresponding multi-arm polyethylene glycol (molecular weight 10,000). The general process of its preparation is that polyethylene glycol or polyethylene glycol diamine reacts with acryloyl chloride or methacryloyl chloride under the action of triethylamine, and the product can be obtained after purification. For details, see Shu et al., Biomaterials, 25, 1339, 2004.
[0119] Replace the corresponding acryloyl chloride with halogenated...
Embodiment 3
[0120] Example 3 Preparation of biocompatible fast gelling hydrogel
[0121] The HA-DTPH solution (2.0% w / v, pH 5.0) prepared in Example 1 was thawed at room temperature for use. Polyethylene glycol diacrylate (molecular weight 3400, Nektar Therapeutics, USA) was dissolved in 0.3 mol / L sodium phosphate / sodium carbonate buffer to obtain a 2.0% w / v solution (pH 9.6), which was filtered and sterilized for later use. Under electromagnetic stirring, the above one solution (5ml) was quickly added to another solution (5ml), the stirring was continued for 3 seconds and then the stirring was stopped. The pH value of the reactive mixture was about 9.4, and the mixed solution was lost after about 17 seconds. The fluidity forms a gel.
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