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Natural polysaccharide-based injectable in-situ formed hydrogel as well as preparation method and application thereof

A natural polysaccharide and in-situ molding 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 gelation time, good mechanical stability and Effects of biocompatibility and mild reaction conditions

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

AI Technical Summary

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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  • Natural polysaccharide-based injectable in-situ formed hydrogel as well as preparation method and application thereof
  • Natural polysaccharide-based injectable in-situ formed hydrogel as well as preparation method and application thereof
  • Natural polysaccharide-based injectable in-situ formed hydrogel as well as preparation method and application thereof

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Experimental program
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Effect test

Embodiment 1

[0045] The preparation method of the natural polysaccharide-based injectable in situ forming hydrogel of the present embodiment comprises the following steps:

[0046] 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;

[0047] 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;

[0048] 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;

[0049] 4) Mix the solutions in the above step 1), step 2) and step 3) according to the volume ratio of 6:1:1, incubate in a constant temperature incubator at 37°C for 30 minutes to make it gel , to obtain chitosan oligosaccharide-based injectab...

Embodiment 2

[0051] The preparation method of the natural polysaccharide-based injectable in situ forming hydrogel of the present embodiment comprises the following steps:

[0052] 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;

[0053] 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;

[0054] 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;

[0055] 4) Mix the solutions in the above step 1), step 2) and step 3) according to the volume ratio of 9:1:1, incubate in a constant temperature incubator at 37°C for 5 minutes to make it gel , to obtain chitosan oligosaccharide-based i...

Embodiment 3

[0057] The preparation method of the natural polysaccharide-based injectable in situ forming hydrogel of the present embodiment comprises the following steps:

[0058] 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;

[0059] 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;

[0060] 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;

[0061] 4) Mix the solutions in the above step 1), step 2) and step 3) according to the volume ratio of 8:1:1, incubate in a constant temperature incubator at 37°C for 1min to make it gel , to obtain chitosan oligosaccharide-based inje...

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Abstract

The invention discloses natural polysaccharide-based injectable in-situ formed hydrogel as well as a preparation method and application thereof. The preparation method comprises the following steps: 1) dissolving a natural polysaccharide material in a neutral or acidic solution to prepare a natural polysaccharide material solution; 2) dissolving glycerophosphate in water or dilute acid to preparea glycerophosphate solution; (3) dissolving four-arm polyethylene glycol succinimide carbonate in a PBS to prepare a four-arm polyethylene glycol succinimide carbonate solution; and 4) uniformly mixing the solutions prepared in the step 1), the step 2) and the step 3), and performing incubating to obtain the natural polysaccharide-based injectable in-situ formed hydrogel. According to the preparation method, rapid forming is achieved through a click chemical reaction, gelation can be achieved through operation under physiological conditions, the gelation time is short, the reaction conditionsare mild, and the gelation performance is controllable. The hydrogel prepared by the method 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, and relates to a natural polysaccharide-based injectable in-situ forming hydrogel and a preparation method and application thereof. Background technique [0002] Natural polysaccharide materials have been widely studied in tissue engineering due to their good biocompatibility and biodegradability, such as chitosan, chitin and its derivatives, sodium alginate and its derivatives, hyaluronic acid, etc. Acids and their derivatives, etc., have a wide range of sources and low prices, and have become one of the ideal choices for constructing injectable hydrogels. Therefore, tissue engineering research using natural polysaccharide materials as raw materials is an effective method for simulating natural tissues. [0003] Hydrogel is a colloidal material with a water content of up to 90% and a tight three-dimensional network structure. In recent years, injectable hydrogels have been widely use...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/52A61L27/56A61L27/50A61L27/20A61L27/18
CPCA61L27/52A61L27/56A61L27/50A61L27/20A61L27/18A61L2400/06A61L2430/02C08L5/08C08L71/02
Inventor 彭松林谭宝玉陈欣鲍志腾唐榕泽王尚
Owner SHENZHEN PEOPLES HOSPITAL
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