Blood protein responsive type gamma-PGA (polyglutamic acid) hydrogel hemostasis material as well as preparation method and application thereof

A technology of polyglutamic acid and blood protein, applied in application, medical science, surgery, etc., can solve the problems of poor blood responsiveness and poor integration ability of wet bleeding wounds, achieve high hemostasis efficiency and solve poor integration ability of wet bleeding wounds , good biocompatibility

Active Publication Date: 2018-01-19
NANJING SHINEKING BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to provide a blood protein response type γ-polyglutamic acid hydrogel hemostatic material, which effectively overcomes the limitations of the application field of traditional pressing hemostasis, and solves the problem of poor blood responsiveness of many hemostatic materials at present. It has the advantages of high hemostatic efficiency, good biocompatibility, in situ injection matching complex wound types, etc. due to poor integration ability of wet bleeding wounds.

Method used

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  • Blood protein responsive type gamma-PGA (polyglutamic acid) hydrogel hemostasis material as well as preparation method and application thereof
  • Blood protein responsive type gamma-PGA (polyglutamic acid) hydrogel hemostasis material as well as preparation method and application thereof
  • Blood protein responsive type gamma-PGA (polyglutamic acid) hydrogel hemostasis material as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Dissolve γ-polyglutamic acid (γ-PGA, molecular weight 100,000 Daltons) in a mixed solution of MES buffer (pH=4.8, 0.1M) and methanol (MES / MeOH=1 / 1, v / v), the mass volume ratio of γ-PGA to the mixed solution is 10g / L, stir and mix evenly; then add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) And N-hydroxysuccinimide (NHS), stirred and activated in ice bath for 2h. Add 3-phenylpropanamide (PHPA) and dopamine (DA) respectively, and stir the reaction for 5 hours at room temperature; the molar ratio of each substance is as follows, EDC:γ-PGA (-COOH)=1:1, EDC:NHS=1 :1, γ-PGA(-COOH):PHPA=1:1, γ-PGA(-COOH):DA=1:1. The obtained system was transferred to a dialysis bag, and placed in deionized water for dialysis for 3 days; the purified solution obtained after dialysis was freeze-dried to obtain γ-polyglutamic acid-3-phenylpropanamide-dopamine (γ-PGA-PHPA -DA) polymer, PHPA and DA grafting rates were 6% and 11%, respectively.

Embodiment 2

[0040]Dissolve γ-PGA (molecular weight: 300,000 Daltons) in a mixed solution of MES buffer (pH=5.0, 0.05M) and methanol (MES / MeOH=1 / 1, v / v), γ-PGA and The mass volume ratio of the mixed solution is 10g / L, stir and mix evenly; then add EDC and NHS, stir and activate in ice bath for 3h. Add PHPA and DA respectively, stir and react at room temperature for 10 h; the molar ratio of each substance is as follows, EDC: γ-PGA (-COOH) = 2: 1, EDC: NHS = 1: 1, γ-PGA (-COOH): PHPA=1:2, γ-PGA(-COOH):DA=1:1. The obtained system was transferred to a dialysis bag, and placed in deionized water for dialysis for 5 days; the purified solution obtained after dialysis was freeze-dried to obtain a γ-PGA-PHPA-DA polymer, and the grafting rates of PHPA and DA were 13% and 10%, respectively. 9%.

Embodiment 3

[0042] Dissolve γ-PGA (molecular weight: 700,000 Daltons) in a mixed solution of MES buffer (pH=5.5, 0.12M) and methanol (MES / MeOH=1 / 1, v / v), γ-PGA and The mass volume ratio of the mixed solution is 15g / L, stir and mix evenly; then add EDC and NHS, stir and activate in ice bath for 6h. Add PHPA and DA respectively, stir and react at room temperature for 8h; the molar ratio of each substance is as follows, EDC:γ-PGA(-COOH)=3:1, EDC:NHS=1:1,γ-PGA(-COOH): PHPA=1:3, γ-PGA(-COOH):DA=1:1. The obtained system was transferred to a dialysis bag, placed in deionized water and dialyzed for 7 days; the obtained purified solution after dialysis was freeze-dried to obtain a γ-PGA-PHPA-DA polymer, and the grafting rates of PHPA and DA were 17% and 10%, respectively. 6%.

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Abstract

The invention provides a blood protein responsive type gamma-PGA (polyglutamic acid) hydrogel hemostasis material as well as a preparation method and an application thereof. The hemostasis material isprepared from a PHPA and DA (dopamine) molecule functionalized gamma-PGA polymer, a solvent with water as a main body, horseradish peroxidase and hydrogen peroxide, the synergetic enhancement effectof gamma-PGA, PHPA and DA on integration of wet high-strength wound is realized and the efficient blocking and hemostasis effect is achieved through Fe<3+> in gamma-PGA complexing blood, adsorption and blood coagulation of blood protein under the inducing action of benzene ring hydrophobic functional groups in PHPA and gel forming through oxidation and crosslinking by catechol groups in DA. The provided gamma-PGA hydrogel hemostasis material can effectively overcome the limitation of conventional pressing hemostasis method in application fields, besides, the problems that numerous hemostasis materials have poor blood responsiveness, poor integration capability for the wet bleeding wound and the like at present are solved, and the blood protein responsive type gamma-PGA hydrogel hemostasismaterial has the advantages of being high in hemostasis efficiency, good in biocompatibility, capable of allowing orthotopic injection of matched complicated wound types and the like and has broad market application prospects.

Description

technical field [0001] The invention belongs to the field of biomedical polymer materials, and in particular relates to a blood protein-responsive gamma-polyglutamic acid hydrogel hemostatic material, its preparation method and application. Background technique [0002] Control of bleeding is an urgent problem in emergency trauma and surgery. Hemorrhage is also the second leading cause of death from everyday trauma. Problems such as wound infection, hypothermia, coagulation dysfunction or multiple organ failure caused by bleeding cannot be ignored. At the same time, blood oozing from large wounds during surgery can easily block the doctor's surgical field of view, prolong the operation time, and delay the best time for surgery, thereby increasing the risk of surgery. In recent decades, with the advancement of human science and technology and the rapid development of medical level, a lot of progress has been made in the research and development of hemostatic products. [0...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L24/02A61L24/04A61L24/10A61L24/00C08G69/48
Inventor 徐虹王瑞任战坤殷文锋詹伊婧冯小海
Owner NANJING SHINEKING BIOTECH CO LTD
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