Preparation of a class of injectable hydrogels with cohesion-enhancing properties

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: 2021-06-29
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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  • Preparation of a class of injectable hydrogels with cohesion-enhancing properties
  • Preparation of a class of injectable hydrogels with cohesion-enhancing properties

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

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

[0044]Weigh 0.8 g of chitosan oligosaccharide and dissolve it in 100 g of 1.8% NaCl solution, then add 2 g of sodium hyaluronate and stir at low temperature (2-8° C.) for 12 hours to mix well. Then 1M HCl solution was added dropwise to adjust the pH of the system to 4.5-6, and 0.48g EDC and 0.29g NHS were added in sequence. After stirring for 1 hour at 2 to 8°C, the reaction was allowed to stand for 7 hours. Then 300g of 0.1M NaOH solution was added for alkalization, and the mixture was stirred at 2-8°C for 18 hours, and then sedimented 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 100 g PBS, and stir well. The reconstituted homogeneous system was placed in a dialysis bag (MWCO=16000) and placed in 1000 g PBS...

Embodiment 2

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

[0047] Weigh 2.8g of chitosan oligosaccharide and dissolve it in 100g of 0.1M PBS solution, then add 3g of 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, 0.73 g EDC and 0.44 g NHS were added in sequence, and the mixture was fully stirred and reacted at 2-8° C. for 24 hours. Next, 275 g of a 0.08 M KOH solution was added for alkalization, and after stirring at room temperature for 12 hours, sedimentation was carried out with 1500 mL of ethanol. The obtained powder was thoroughly washed with 500 mL of ethanol, and the washing step was repeated 3 times. It was then vacuum dried in a vacuum oven overnight. The obtained powder was reconstituted with 200 g of 0.9% NaCl solution, fully stirred and then dialyzed in a dialysis bag (MWCO=16000). The out...

Embodiment 3

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

[0050] 3.3g of polyarginine was weighed and dissolved in 100g of 0.1M PBS solution, and then 3g of carboxymethyl chitin was added and stirred at room temperature for 6 hours to fully dissolve and mix. Then, 0.88 g of DMTMM was added, and the mixture was fully stirred and reacted at -20° C. for 120 hours. Then, 200 g of 0.08M NaOH solution was added for alkalization, and the mixture was stirred at room temperature for 4 hours, and then transferred to 2-8° C. for 12 hours. Settling was then performed 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 PBS solution, fully stirred and then dialyzed in a dialysis bag (MWCO=16000), and the outer dialysate solution was 1200g PBS solution. Dialysis was performed at 2-8°...

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Abstract

The present invention provides a method for the preparation of a class of injectable gels having cohesion-enhancing properties after autoclaving. The chemically cross-linked amide bond in the system makes the gel have a strong ability to resist short-term high-temperature and high-pressure damage, and the free carboxyl and amino groups will form ionic bonds through electrostatic attraction due to the slow movement of the molecular chain, making the system sterilized. After a period of time, the dynamic viscosity continued to increase, and finally reached a plateau and exceeded the dynamic viscosity before sterilization. The enhanced cohesion endows the gel with good stability, which can maintain its shape for a long time without dispersion in a liquid environment. A suitable degree of crosslinking confers injectability to the gel. The enhanced cohesion and injectability make the gel system have strong application prospects in the field of biomedicine, especially in the direction of implantation in vivo, such as drug loading, filling, tissue repair, etc.

Description

technical field [0001] The invention relates to the field of medical biomaterials, in particular to the preparation of a type of injectable hydrogel, which is characterized in that it has cohesive enhancement properties after being sterilized by high pressure steam, 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 is fluid and can be applied by injection, and can be used in the field of minimally invasive applications. For example, a drug can be encapsulated into an injectable drug carrier, a bare stent can be injected, or a growth factor or cell can be encapsulated into an injectable composite scaffold. There are numerous 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...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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