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Recombinant collagen injectable hydrogel and preparation method thereof

A technology for recombining collagen and water for injection, which is applied in pharmaceutical formulations, prostheses, aerosol delivery, etc., can solve problems such as human injury and achieve high cross-linking rate, excellent biocompatibility and biodegradability

Active Publication Date: 2021-02-05
SHAANXI GIANT BIOTECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the need to use chemical cross-linking agents such as 1,4-butanediol diglycidyl ether and β-sodium glycerophosphate during the cross-linking process, if the residue is not complete, it will cause damage to the human body

Method used

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  • Recombinant collagen injectable hydrogel and preparation method thereof
  • Recombinant collagen injectable hydrogel and preparation method thereof
  • Recombinant collagen injectable hydrogel and preparation method thereof

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preparation example Construction

[0035] The application provides a method for preparing recombinant collagen injectable hydrogel, which is characterized in that it comprises the following steps:

[0036] Respectively adding a certain concentration of p-hydroxyphenylpropionic acid, an activator and a recombinant collagen solution into the solvent to form a mixed solution, under the action of the activator, the recombinant collagen and p-hydroxyphenylpropionic acid undergo a dehydration condensation reaction;

[0037] Separating the mixed solution after the above reaction - removing unreacted components and then lyophilizing to obtain a recombinant collagen-p-hydroxyphenylpropionic acid conjugate;

[0038] Dispersing the above-mentioned recombinant collagen-p-hydroxyphenylpropionate conjugate in an aqueous phase to obtain a precursor solution; and

[0039] adding hydrogen peroxide and peroxidase to catalyze the precursor solution to form a hydrogel in situ;

[0040] Wherein, the recombinant collagen consists o...

Embodiment 1

[0066] Step 1: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N-hydroxysuccinimide and p-hydroxyphenylpropionic acid were mixed with 2.5% (w / v) , 3.0% (w / v) and 1.3% (w / v) were dissolved in 250mL of 40% (v / v) aqueous solution of dimethylformamide, stirred at room temperature for 12 hours;

[0067] Step 2: Add 150 mL of 8.5% (w / v) recombinant collagen solution to the above solution, and stir overnight;

[0068] Step 3: Transfer the above reaction solution to a dialysis bag with a cut-off molecular weight of 8000-12000 Da, lyophilize after dialysis to obtain a recombinant collagen-p-hydroxyphenylpropionic acid conjugate;

[0069] Step 4: Dissolve the recombinant collagen-p-hydroxyphenylpropionic acid conjugate in water for injection at a concentration of 50mg / mL, add hydrogen peroxide and horseradish peroxide to make the final concentrations 1.5mmol / L and 1.0mmol / L respectively U / mL, hydrogels formed in situ.

Embodiment 2

[0071] Step 1: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N-hydroxysuccinimide and p-hydroxyphenylpropionic acid were added at 5.0% (w / v) , 2.5% (w / v) and 0.8% (w / v) were dissolved in 200mL of 40% (v / v) dimethylformamide aqueous solution, stirred at room temperature for 10 hours;

[0072] Step 2: Add 150 mL of 10.0% (w / v) recombinant collagen solution to the above solution, and stir overnight;

[0073] Step 3: Transfer the above reaction solution to a dialysis bag with a cut-off molecular weight of 8000-12000 Da, lyophilize after dialysis to obtain a recombinant collagen-p-hydroxyphenylpropionic acid conjugate;

[0074] Step 4: Dissolve the recombinant collagen-p-hydroxyphenylpropionic acid conjugate in water for injection at a concentration of 50mg / mL, add hydrogen peroxide and horseradish peroxidase to make the final concentrations 2.0mmol / L and 1.0U / mL, form hydrogel in situ.

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Abstract

The invention relates to recombinant collagen injectable hydrogel and a preparation method thereof, and aims to solve the problems that materials such as animal collagen and sodium hyaluronate and thelike used in the field of soft tissue filling at present still have rejection problems such as chronic inflammation and allergy and the like although having good effects, and the cross-linking agentsused are mostly chemical cross-linking agents, such as 1, 4-butanediol diglycidyl ether, beta-sodium glycerophosphate, and the like. If the residual amount of the cross-linking agent exceeds a limitvalue, toxicity is generated to a human body. In order to solve the problems of the existing hydrogel material, the recombinant collagen injectable hydrogel is constructed, the recombinant collagen isselected as a hydrogel main body, and enzyme is used as a catalyst. Compared with the traditional hydrogel, the hydrogel prepared by the invention has excellent biocompatibility, can be molded in situ and has the effects of promoting cell growth and resisting inflammation.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and in particular relates to a recombinant collagen injectable hydrogel and a preparation method thereof. Background technique [0002] Hydrogel is a three-dimensional network biomaterial composed of hydrophilic polymer chains. Its hydrophilic network can absorb and retain a large amount of water, and it has good biocompatibility and extracellular matrix-like properties. It is widely used It is used in a variety of fields, including biopharmaceutical fields such as implantable medical devices, medical wound dressings, and drug release carriers as biomedical materials. Among them, as a soft tissue filling material, hydrogel can repair soft tissue damage or pathologically caused cavities and defective tissues, as well as remove wrinkles or improve facial contours in the plastic surgery industry. [0003] Hydrogels are formed by chemical or physical cross-linking of water-soluble or hydrophilic ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/52A61L27/58A61L27/50A61L27/24A61K9/06A61K47/42
CPCA61L27/52A61L27/58A61L27/50A61L27/24A61K9/06A61K47/42A61L2400/06Y02A50/30
Inventor 范代娣高尚段志广
Owner SHAANXI GIANT BIOTECHNOLOGY CO LTD
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