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Method for preparing injectable aquagel with cohesion enhancing characteristic

A technology for injecting water and properties, which is applied in the field of medical biomaterials and can solve problems such as gel cohesion enhancement

Active Publication Date: 2019-03-22
SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In summary, for injectable hydrogels, there are many reports in the literature and patents, but none of the reports mentioned that the gel will have cohesion enhancement after sterilization

Method used

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  • Method for preparing injectable aquagel with cohesion enhancing characteristic
  • Method for preparing injectable aquagel with cohesion enhancing characteristic

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] This example describes the preparation of hyaluronic acid-chitosan oligomeric cohesion-enhanced injectable hydrogels.

[0044]Weigh 0.8g chitosan oligosaccharide and dissolve in 100g 1.8% NaCl solution, then add 2g sodium hyaluronate and stir at low temperature (2-8°C) for 12 hours to fully mix. Then 1M HCl solution was added dropwise to adjust the pH of the system to 4.5-6, and 0.48 g of EDC and 0.29 g of NHS were added in sequence. At 2-8°C, stir for 1 hour and then let stand for reaction for 7 hours. Then add 300g of 0.1M NaOH solution for alkalization, stir at 2-8°C for 18 hours, and then settle with 1200mL of ethanol. The obtained powder was thoroughly washed with 800 mL of ethanol, and the washing step was repeated 3 times. Then drain the ethanol in the powder, reconstitute the powder with 100g of PBS, and stir well. The uniformly reconstituted system was placed in a dialysis bag (MWCO=16000), dialyzed in 1000 g of PBS for a total of 4 days, and the dialysate w...

Embodiment 2

[0046] This example describes the preparation of sodium alginate-chitosan oligomeric cohesion-reinforced injectable hydrogels.

[0047] Weigh 2.8g chitosan oligosaccharide and dissolve in 100g 0.1M PBS solution, then add 3g sodium alginate and stir at room temperature for 24 hours to fully dissolve and mix. Then 1M HCl solution was added dropwise to adjust the pH of the system to 4.5-6, 0.73g EDC and 0.44g NHS were added in sequence, and the mixture was fully stirred and reacted at 2-8°C for 24 hours. Then, 275 g of 0.08 M KOH solution was added for alkalinization, and after stirring at room temperature for 12 hours, 1500 mL of ethanol was used for precipitation. The obtained powder was thoroughly washed with 500 mL of ethanol, and the washing step was repeated 3 times. It was then vacuum dried overnight in a vacuum oven. The obtained powder was reconstituted with 200 g of 0.9% NaCl solution, stirred well and then dialyzed in a dialysis bag (MWCO=16000), with 1500 g of 0.9% ...

Embodiment 3

[0049] This example describes the preparation of carboxymethylchitin-polyarginine cohesion-enhanced injectable hydrogels.

[0050] Weigh 3.3g polyarginine and dissolve it in 100g 0.1M PBS solution, then add 3g carboxymethyl chitin and stir at room temperature for 6 hours to fully dissolve and mix. Then add 0.88g DMTMM, stir well and react at -20°C for 120 hours. Then add 200g of 0.08M NaOH solution for alkalization, stir at room temperature for 4 hours, then transfer to 2-8°C and let stand for 12 hours. Then settle with 1800 mL of ethanol. The obtained powder was thoroughly washed with 600 mL of ethanol, and the washing step was repeated 3 times. After the powder was drained, it was reconstituted with 150g of PBS solution, stirred well and then dialyzed in a dialysis bag (MWCO=16000), with 1200g of PBS solution as the external fluid for dialysis. Dialysis was performed at 2-8°C for 6 days, and the dialysate was changed once a day. After the dialysis, it was filled into a g...

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Abstract

The invention provides a method for preparing injectable aquagel with cohesion enhancing characteristic after autoclaving sterilization. Due to a chemical crosslinked amido bond in a system, the gel can have relatively high capacity for resisting short-time high-pressure high-temperature destruction; free carboxyl and amino will form ionic bonds through electrostatic force attraction due to slow movement of molecular chains, so that the kinetic viscosity of the system in a period of time after sterilization is continuously enhanced, and the kinetic viscosity of plateau and exceeding sterilization is achieved finally. The gel is endowed with good stability due to cohesion enhancing and can keep a form for a long time in a liquid environment without dispersion. The gel is endowed with injectability due to proper cross-linking degree. Due to cohesion enhancing property and injectability, the gel system has very strong application prospect in the field of biomedicine, particularly in-vivoimplantation, such as drug carrying, filling and tissue repair.

Description

technical field [0001] The invention relates to the field of medical biomaterials, in particular to the preparation of a class of injectable hydrogels, which are characterized in that they have cohesion-enhancing properties after high-pressure steam sterilization, that is, the dynamic viscosity after sterilization will increase after a period of time before sterilization. Background technique [0002] Injectable hydrogel refers to a type of hydrogel that has fluidity and can be applied by injection, and can be used in minimally invasive applications. Such as encapsulating drugs to prepare injectable drug carriers, injectable bare stents or encapsulating growth factors or cells to prepare injectable composite stents. There are a large number of literature and patents reporting such hydrogel systems. [0003] Wu (Zhang, W.; Jin, X.; Li, H.; Zhang, R.-r.; Wu, C.-w., Injectable and bodytemperature sensitive hydrogels based on chitosan and hyaluronic acid for pHsensitive drug r...

Claims

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Application Information

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IPC IPC(8): C08J3/075C08L5/08C08L5/04C08L77/04
CPCC08J3/075C08J2305/04C08J2305/08C08J2377/04C08J2405/08C08J2477/04
Inventor 魏长征曹彬陆婷婷
Owner SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD
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