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Injectable composite hydrogel and preparation method and application of hydrogel

A composite hydrogel and solution technology, which is applied in the fields of pharmaceutical formulation, medical science, prosthesis, etc., can solve the problems of poor mechanical strength and long curing time of cross-linking agents, and achieve short gel time, good mechanical stability and Biocompatibility, growth-promoting effect

Active Publication Date: 2020-11-17
SHENZHEN PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The performance of the hydrogel of the invention is controllable, and it can be gelled under human physiological conditions without adding other chemical cross-linking agents. It can be used as a tissue engineering material, especially suitable for conjunctival repair, and has injectability. And quick response, gelation within 5-15 minutes, in-situ molding, strong surgical operability, automatic bonding during the operation, no need for suture fixation, and effective protection for wounds of any shape and position; but using this The invented cross-linking agent has long curing time, poor mechanical strength, and requires a relatively high concentration of β-sodium glycerophosphate. When β-sodium glycerophosphate exceeds a certain value, it has certain toxicity to the body, for example, the concentration is 800mg / mL The osmotic pressure of β-glycerophosphate sodium solution is about 1080mOsm, which is much higher than the normal osmotic pressure of human cells

Method used

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  • Injectable composite hydrogel and preparation method and application of hydrogel
  • Injectable composite hydrogel and preparation method and application of hydrogel
  • Injectable composite hydrogel and preparation method and application of hydrogel

Examples

Experimental program
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Embodiment 1

[0052] The preparation method of the injectable composite hydrogel of the present embodiment comprises the following steps:

[0053] 1) Weigh chitosan oligosaccharide and dissolve it in PBS solution, stir at room temperature for 0.5h, make a solution with a concentration of 40mg / mL, and store it at 4°C for later use;

[0054] 2) Weigh β-sodium glycerophosphate and dissolve it in water, fully dissolve it, prepare a solution with a concentration of 50mg / mL, and store it at 4°C for later use;

[0055] 3) Weigh four-arm polyethylene glycol succinimide carbonate and dissolve it in PBS solution, fully dissolve, and prepare a solution with a concentration of 5 mg / mL, which is prepared and used immediately;

[0056] 4) the purified T4 lysozyme / Zn 2+ Dilute protein in buffer to prepare T4 lysozyme / Zn at a concentration of 1 mg / mL 2+ Protein solution, stored at -20°C for later use;

[0057] 5) Mix the solutions of step 1), step 2), step 3) and step 4) according to the volume ratio of...

Embodiment 2

[0059] The preparation method of the injectable composite hydrogel of the present embodiment comprises the following steps:

[0060] 1) Weigh chitosan oligosaccharide and dissolve it in PBS solution, stir at room temperature for 1 hour, prepare a solution with a concentration of 85mg / mL, and store it at 4°C for later use;

[0061] 2) Weigh β-sodium glycerophosphate and dissolve it in water, fully dissolve it, prepare a solution with a concentration of 500mg / mL, and store it at 4°C for later use;

[0062] 3) Weigh four-arm polyethylene glycol succinimide carbonate and dissolve it in PBS solution, fully dissolve, and prepare a solution with a concentration of 100 mg / mL, which is prepared and used immediately;

[0063] 4) the purified T4 lysozyme / Zn 2+ Protein was diluted in buffer to prepare T4 lysozyme / Zn at a concentration of 10mg / mL 2+ Protein solution, stored at -20°C for later use;

[0064] 5) Mix the solutions of the above step 1), step 2), step 3) and step 4) according...

Embodiment 3

[0066] The preparation method of the injectable composite hydrogel of the present embodiment comprises the following steps:

[0067] 1) Weigh chitosan oligosaccharide and dissolve it in PBS solution, stir at room temperature for 2 hours, prepare a solution with a concentration of 100mg / mL, and store it at 4°C for later use;

[0068] 2) Weigh β-sodium glycerophosphate and dissolve it in water, fully dissolve it, prepare a solution with a concentration of 800mg / mL, and store it at 4°C for later use;

[0069] 3) Weigh four-arm polyethylene glycol succinimide carbonate and dissolve it in PBS solution, fully dissolve, and prepare a solution with a concentration of 200 mg / mL, which is prepared and used immediately;

[0070] 4) the purified T4 lysozyme / Zn 2+ The protein was diluted in buffer to prepare T4 lysozyme / Zn at a concentration of 20mg / mL 2+ Protein solution, stored at -20°C for later use;

[0071] 5) Mix the solutions of the above step 1), step 2), step 3) and step 4) acc...

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Abstract

The invention discloses an injectable composite hydrogel, a preparation method and application of the hydrogel. The preparation method of the invention comprises the following steps: (1) preparing a solution of natural polysaccharide material; (2) preparing a glycerophosphate solution; (3) preparing a solution of four-arm polyethylene glycol succinimide carbonate; (4) preparing a solution of T4 lysozyme / Zn < 2 + > protein; and (5) uniformly mixing the solutions prepared in step (1), step (2), step (3) and step (4), and performing incubation to obtain the injectable composite hydrogel. According to the preparation method of the invention, rapid forming is achieved through a click chemical reaction, gelation can be achieved through operation under physiological conditions, the gelation timeis short, the reaction conditions are mild, and the gelation performance is controllable. The hydrogel prepared by the method of the invention can be applied to tissue engineering materials, and is particularly suitable for local cavity filling materials for bone defects.

Description

technical field [0001] The invention relates to the technical field of tissue engineering, relates to an injectable composite hydrogel and its preparation method and application, in particular to an injectable T4 lysozyme / Zn 2+ Protein complex hydrogels. Background technique [0002] Using porous scaffold materials to load cells and / or bone growth-promoting factors is one of the research hotspots in bone tissue engineering. The polymer hydrogel has the characteristics of high water content (70-99%) and water retention. Its three-dimensional The network structure is very similar to the extracellular matrix, has good biocompatibility and biodegradability, and has good research prospects and application potential in bone tissue engineering. Injectable hydrogels have emerged as an effective alternative implant material in the field of bone tissue engineering research. The injectable hydrogel is solidified in situ at the target point by injection, and can fill any irregular bon...

Claims

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Application Information

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IPC IPC(8): A61L27/52A61L27/50A61L27/54A61L27/22A61L27/02A61L27/56C08J3/24C08J3/075C08L5/08
CPCA61L27/52A61L27/50A61L27/54A61L27/227A61L27/025A61L27/56C08J3/24C08J3/075A61L2400/06A61L2430/02A61L2300/102A61L2300/602A61L2300/414C08J2305/08C08L89/00
Inventor 陈欣彭松林谭宝玉唐榕泽鲍志腾王尚
Owner SHENZHEN PEOPLES HOSPITAL
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