CN112535761A - Antibacterial hemostatic healing-promoting gel, preparation method and application thereof - Google Patents

Antibacterial hemostatic healing-promoting gel, preparation method and application thereof Download PDF

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CN112535761A
CN112535761A CN202011578552.2A CN202011578552A CN112535761A CN 112535761 A CN112535761 A CN 112535761A CN 202011578552 A CN202011578552 A CN 202011578552A CN 112535761 A CN112535761 A CN 112535761A
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gel
double bond
hemostatic
active double
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梁晓飞
宋萍
周健
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Suzhou Jujian Biotechnology Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0028Polypeptides; Proteins; Degradation products thereof
    • A61L26/0033Collagen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
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    • AHUMAN NECESSITIES
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    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0057Ingredients of undetermined constitution or reaction products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • A61L26/008Hydrogels or hydrocolloids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/04Materials for stopping bleeding

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Abstract

The invention provides an antibacterial hemostatic healing-promoting gel, a preparation method and application thereof, wherein the gel comprises the following raw materials: 4-18 parts of carboxylic acid or carboxylic acid sodium salt with an active double bond, 2-10 parts of amide with an active double bond, 1-3 parts of aldehyde with an active double bond, 30-100 parts of fish collagen peptide and 2-3 parts of heparin sodium; 1-5 parts of modified guanidine salt with active double bonds, 3-10 parts of chitosan, 1-5 parts of modified diamine with active double bonds, 0.4-0.8 part of double bond cross-linking agent, 4-7 parts of L-arginine, 50-200 parts of aloe raw gel, 5-10 parts of beta-sodium glycerophosphate and 600 parts of deionized water. The antibacterial hemostatic and healing promoting gel has various wound healing effects, promotes the generation of skin capillaries, is beneficial to tissue growth and protects wound nerves, achieves the hemostatic effect by rapidly plugging damaged blood vessels, has excellent antibacterial property, and is beneficial to wound antibacterial hemostatic and healing promotion by forming a protective isolation layer on a wound part.

Description

Antibacterial hemostatic healing-promoting gel, preparation method and application thereof
Technical Field
The invention relates to the field of biomedical materials, in particular to an antibacterial hemostatic healing-promoting gel, a preparation method and application thereof.
Background
People inevitably cause injuries and generate hemorrhagic wounds in daily work and life, and the quick and effective hemostasis effect cannot be achieved by physiological hemostasis of the organism alone, so that the introduction of exogenous substances to accelerate the hemostasis of the wounds is very necessary. The hemostatic material is always a research hotspot in the field of biological medicine, the traditional hemostatic material is easy to adhere to the wound surface, the wound surface which is just recovered is likely to be damaged again when the hemostatic material is removed, the current frontier hotspot is an absorbable hemostatic material, the current main absorbable hemostatic materials at home and abroad comprise fibrin glue, gelatin, collagen, oxidized cellulose, chitosan, calcium alginate and the like, the hemostatic effect of the products can meet the requirement of quick hemostasis of general wounds, but the clinical wound wounds are changeable and complex in form and shape, the products cannot completely meet the requirements of different wound parts, sizes, exudative fluid volumes and the like of patients due to poor plasticity, and the application range is narrowed.
Gels are a class of polymers having a three-dimensional network structure, which swell by absorbing a large amount of water or physiological saline as compared with conventional water-absorbent materials, and after swelling, can continue to maintain their original structure without being dissolved. It becomes a fibrous structure when it comes into contact with blood, locking the blood cells like a large net and not allowing them to flow freely, and thus has received much attention. The hemostatic gel has the function of coagulating wounds, the viscous colloid has certain sealing effect on bleeding wounds, and the effect is better than that of a common bandage, even if the blood is gushed out from arterial blood vessels. The gel contains components that rapidly activate platelets, allowing them to promote blood clotting, bind fibrin, and complete the seal. However, the following problems still remain: the existing hemostatic material has single efficacy, narrow application range, no good elasticity and air permeability, easy inflammation and other adverse reactions, and low hemostatic speed, which leads to poor hemostatic effect; and the wound surface is easy to adhere to the wound surface, and the wound surface which is just recovered is likely to be damaged again when the wound surface is removed.
Disclosure of Invention
The invention aims to provide an antibacterial hemostasis healing-promoting gel, a preparation method and application thereof, which have various wound healing efficacies, promote the generation of skin capillaries, are beneficial to tissue growth and the protection of wound nerves, achieve the hemostatic effect by rapidly plugging damaged blood vessels, have excellent antibacterial property, and form a protective isolation layer at the wounded part to be beneficial to the antibacterial hemostasis healing-promoting of wounds.
The technical scheme adopted by the invention is as follows: an antibacterial hemostatic healing promoting gel comprises the following raw materials in parts by weight: 4-18 parts of carboxylic acid or carboxylic acid sodium salt with an active double bond, 2-10 parts of amide with an active double bond, 1-3 parts of aldehyde with an active double bond, 30-100 parts of fish collagen peptide and 2-3 parts of heparin sodium; 1-5 parts of modified guanidine salt with active double bonds, 3-10 parts of chitosan, 1-5 parts of modified diamine with active double bonds, 0.4-0.8 part of double bond cross-linking agent, 4-7 parts of L-arginine, 50-200 parts of aloe raw gel, 5-10 parts of beta-sodium glycerophosphate and 600 parts of deionized water.
As a preferable scheme of the invention, the carboxylic acid or carboxylic acid sodium salt with the activated double bond is any one or more of acrylic acid, sodium acrylate, methacrylic acid, sodium methacrylate, undecylenic acid and oleic acid; the amide with the active double bond is any one or more of acrylamide, methacrylamide, oleamide and derivatives; the aldehyde with the activated double bond is any one or more of undecenal, citronellal, 2, 4-hexadienal and derivatives.
As a preferable scheme of the invention, the modified diamine with the active double bond is any one or more of ethylenediamine, N' -bis (3-aminopropyl) ethylenediamine and hexamethylenediamine, and the double bond crosslinking agent is any one or more of divinylbenzene, glutaraldehyde, epichlorohydrin and genipin.
As a preferred embodiment of the present invention, the preparation method of the aloe vera raw gel comprises: cleaning fresh Aloe, sterilizing, peeling off leaf, taking pulp, mechanically crushing, centrifuging, and collecting supernatant to obtain Aloe crude gel.
As a preferred embodiment of the present invention, the preparation method of the fish collagen peptide comprises: performing enzymolysis on macromolecular raw material aqueous solution such as fish skin and fish scale with biological enzyme, and decolorizing with active carbon; then nano-filtering, desalting and freeze-drying to obtain the fish collagen peptide.
As a preferred scheme of the invention, drug-loaded drug molecules with the effects of stopping bleeding, relieving pain, relieving itching, diminishing inflammation, reducing swelling and the like are also added into the gel.
A preparation method of an antibacterial hemostatic healing promoting gel comprises the following steps:
step 1): dissolving fish collagen peptide, carboxylic acid or sodium carboxylate with an active double bond, amide with an active double bond and aldehyde with an active double bond in deionized water at the temperature of 2-10 ℃ in parts by weight, fully stirring and mixing, and standing for 30min at the temperature of 15-25 ℃;
step 2): adding heparin sodium, L-arginine, aloe raw gel and carboxylic acid or anhydride with an active double bond into the solution obtained in the step (1), dissolving the mixture in deionized water, fully stirring and mixing, dissolving chitosan and modified guanidinium with a double bond in deionized water, slowly adding beta-sodium glycerophosphate into the deionized water at 15-30 ℃ for reaction, and standing for 15min after the reaction is finished;
step 3): swelling the product obtained in the step 2) with distilled water, changing water for many times, screening out redundant components, adding a double-bond cross-linking agent to initiate polymerization, adjusting the pH value of the solution to 7.0-8.0, and solidifying and regenerating at 0-10 ℃ to form gel, thus obtaining the antibacterial hemostatic multifunctional composite hydrogel.
As a preferable embodiment of the preparation method of the present invention, the swelling ratio of the product in the step 3) is controlled to be between 150-300%.
An antibacterial gel for stopping bleeding and promoting healing is prepared by uniformly applying the gel on the injured part after injury to form a protective isolation layer to help wound antibacterial stop bleeding and promote healing.
Has the advantages that: the invention relates to an antibacterial hemostatic and healing promoting gel, a preparation method and application thereof, the gel has various wound healing effects, achieves the hemostatic effect by rapidly swelling and absorbing a large amount of water in blood, promotes the generation of skin capillaries, is beneficial to tissue growth and protects the nerves of a wound surface, drug-loaded drug molecules can be added into the gel, and the gel has the effects of stopping bleeding, relieving pain, relieving itching, diminishing inflammation and diminishing swelling, achieves the hemostatic effect by rapidly plugging damaged blood vessels, achieves the effects of rapidly stopping bleeding, promoting wound healing and efficiently resisting bacteria, has excellent antibacterial property, and forms a protective isolation layer at a wound part to help the wound to achieve the antibacterial hemostatic and healing promoting.
Drawings
In order to more clearly illustrate the embodiments of the present application or technical solutions in the prior art, the drawings needed to be used in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments described in the present invention, and other drawings can be obtained by those skilled in the art according to the drawings.
FIG. 1 is a flow chart of the preparation of the antibacterial hemostatic and healing promoting gel according to the embodiment of the present invention;
FIG. 2 is a flow chart of the preparation of aloe vera raw gel according to an embodiment of the present invention;
FIG. 3 is a flow chart of the preparation of fish collagen peptide according to the embodiment of the present invention.
Detailed Description
The antibacterial hemostatic and healing promoting gel of the present invention and the preparation method thereof are further described in detail below.
Example 1
An antibacterial hemostasis healing promotion gel and a preparation method thereof, the antibacterial hemostasis healing promotion gel comprises the following raw materials by mass: 4 parts of carboxylic acid or carboxylic acid sodium salt with an active double bond, 10 parts of amide with an active double bond, 1 part of aldehyde with an active double bond, 30 parts of fish collagen peptide and 3 parts of heparin sodium; 1 part of modified guanidine salt with an active double bond, 3 parts of chitosan, 1 part of modified diamine with an active double bond, 0.4 part of double bond cross-linking agent, 7 parts of L-arginine, 50 parts of aloe raw gum, 5 parts of beta-sodium glycerophosphate and 600 parts of deionized water.
As a preferred embodiment of the invention, the carboxylic acid or carboxylic acid sodium salt with an activated double bond is any one or more of acrylic acid, sodium acrylate, methacrylic acid, sodium methacrylate, undecylenic acid and oleic acid; the amide with the active double bond is any one or more of acrylamide, methacrylamide, oleamide and derivatives; the aldehyde with the activated double bond is any one or more of undecenal, citronellal, 2, 4-hexadienal and derivatives.
As a preferable scheme of the invention, the modified diamine with the active double bond is any one or more of ethylenediamine, N' -bis (3-aminopropyl) ethylenediamine and hexamethylenediamine, and the double bond crosslinking agent is any one or more of divinylbenzene, glutaraldehyde, epichlorohydrin and genipin.
As a preferred embodiment of the present invention, the preparation method of the aloe vera raw gel comprises: cleaning fresh Aloe, sterilizing, peeling off leaf, taking pulp, mechanically crushing, centrifuging, and collecting supernatant to obtain Aloe crude gel.
As a preferred embodiment of the present invention, the preparation method of the fish collagen peptide comprises: performing enzymolysis on macromolecular raw material aqueous solution such as fish skin and fish scale with biological enzyme, and decolorizing with active carbon; then nano-filtering, desalting and freeze-drying to obtain the fish collagen peptide.
As a preferred scheme of the invention, drug-loaded drug molecules with the effects of stopping bleeding, relieving pain, relieving itching, diminishing inflammation, reducing swelling and the like are also added into the gel.
A preparation method of an antibacterial hemostatic healing promoting gel comprises the following steps:
step 1): dissolving fish collagen peptide, carboxylic acid or sodium carboxylate with active double bond, amide with active double bond and aldehyde with active double bond in deionized water at 2 deg.c, stirring and mixing, and stilling at 15 deg.c for 30 min;
step 2): adding heparin sodium, L-arginine, aloe raw gel and carboxylic acid or anhydride with an active double bond into the solution obtained in the step (1), dissolving the mixture in deionized water, fully stirring and mixing, dissolving chitosan and modified guanidinium with a double bond in the deionized water, slowly adding beta-sodium glycerophosphate into the deionized water at 15 ℃ for reaction, and standing for 15min after the reaction is finished;
step 3): swelling the product obtained in the step 2) with distilled water, changing water for many times, screening out redundant components, adding a double-bond cross-linking agent to initiate polymerization, adjusting the pH value of the solution to 8.0, and solidifying and regenerating at 10 ℃ to form gel, thus obtaining the antibacterial hemostatic multifunctional composite hydrogel.
As a preferred embodiment of the preparation method of the present invention, the swelling ratio of the product in the step 3) is controlled to be between 150%.
An antibacterial gel for stopping bleeding and promoting healing is prepared by uniformly applying the gel on the injured part after injury to form a protective isolation layer to help wound antibacterial stop bleeding and promote healing. Referring to fig. 1-3, the preparation method comprises the steps of dissolving carboxylic acid or sodium carboxylate with active double bonds and fish collagen peptide in deionized water, adding amide with active double bonds and aldehyde with active double bonds, fully stirring and mixing, standing at 15 ℃ for 30min, and carrying out amino carboxyl reaction to obtain the fish collagen peptide. Then dissolving the prepared aloe raw gel, heparin sodium, L-arginine and carboxylic acid or anhydride with active double bonds in deionized water and fully stirring and mixing, wherein the heparin sodium plays a role in preventing the adhesion between the wound and the gel during hemostasis by utilizing the anticoagulation property of the heparin sodium or the adhesion between the wound when the hemostasis healing-promoting gel is used during healing, and simultaneously accelerates the blood to be quickly adsorbed by the hemostasis healing-promoting gel by utilizing a mode of preventing the coagulation of the outflowing blood; and then adding chitosan and modified guanidine salt with double bonds into the solution, fully stirring, filtering and sterilizing by using a filter membrane in the process of preparing the beta-sodium glycerophosphate to obtain a sterile beta-sodium glycerophosphate solution, adding the beta-sodium glycerophosphate slowly into a reaction system to initiate reaction, swelling by using distilled water, removing unreacted monomers and a crosslinking agent, adding a double bond crosslinking agent to initiate polymerization, adjusting the pH value of the solution to be 8.0, and solidifying and regenerating at 10 ℃ to obtain the gel.
Example 2
An antibacterial hemostasis healing promotion gel and a preparation method thereof, the antibacterial hemostasis healing promotion gel comprises the following raw materials by mass: 12 parts of carboxylic acid or carboxylic acid sodium salt with an active double bond, 6 parts of amide with an active double bond, 2 parts of aldehyde with an active double bond, 70 parts of fish collagen peptide and 2.5 parts of heparin sodium; 3 parts of modified guanidine salt with an active double bond, 6 parts of chitosan, 3 parts of modified diamine with an active double bond, 0.6 part of double bond cross-linking agent, 6 parts of L-arginine, 150 parts of aloe raw gum, 7 parts of beta-sodium glycerophosphate and 400 parts of deionized water.
As a preferred embodiment of the invention, the carboxylic acid or carboxylic acid sodium salt with an activated double bond is any one or more of acrylic acid, sodium acrylate, methacrylic acid, sodium methacrylate, undecylenic acid and oleic acid; the amide with the active double bond is any one or more of acrylamide, methacrylamide, oleamide and derivatives; the aldehyde with the activated double bond is any one or more of undecenal, citronellal, 2, 4-hexadienal and derivatives.
As a preferable scheme of the invention, the modified diamine with the active double bond is any one or more of ethylenediamine, N' -bis (3-aminopropyl) ethylenediamine and hexamethylenediamine, and the double bond crosslinking agent is any one or more of divinylbenzene, glutaraldehyde, epichlorohydrin and genipin.
As a preferred embodiment of the present invention, the preparation method of the aloe vera raw gel comprises: cleaning fresh Aloe, sterilizing, peeling off leaf, taking pulp, mechanically crushing, centrifuging, and collecting supernatant to obtain Aloe crude gel.
As a preferred embodiment of the present invention, the preparation method of the fish collagen peptide comprises: performing enzymolysis on macromolecular raw material aqueous solution such as fish skin and fish scale with biological enzyme, and decolorizing with active carbon; then nano-filtering, desalting and freeze-drying to obtain the fish collagen peptide.
As a preferred scheme of the invention, drug-loaded drug molecules with the effects of stopping bleeding, relieving pain, relieving itching, diminishing inflammation, reducing swelling and the like are also added into the gel.
A preparation method of an antibacterial hemostatic healing promoting gel comprises the following steps:
step 1): dissolving fish collagen peptide, carboxylic acid or sodium carboxylate with active double bond, amide with active double bond and aldehyde with active double bond in deionized water at 5 deg.C, stirring and mixing, and standing at 20 deg.C for 30 min;
step 2): adding heparin sodium, L-arginine, aloe raw gel and carboxylic acid or anhydride with an active double bond into the solution obtained in the step (1), dissolving the mixture in deionized water, fully stirring and mixing, dissolving chitosan and modified guanidinium with a double bond in the deionized water, slowly adding beta-sodium glycerophosphate into the deionized water at 25 ℃ for reaction, and standing for 15min after the reaction is finished;
step 3): swelling the product obtained in the step 2) with distilled water, changing water for many times, screening out redundant components, adding a double-bond cross-linking agent to initiate polymerization, adjusting the pH value of the solution to 7.5, and solidifying and regenerating at 5 ℃ to form gel, thus obtaining the antibacterial hemostatic multifunctional composite hydrogel.
As a preferred embodiment of the preparation method of the present invention, the swelling ratio of the product in the step 3) is controlled to be between 200%.
An antibacterial gel for stopping bleeding and promoting healing is prepared by uniformly applying the gel on the injured part after injury to form a protective isolation layer to help wound antibacterial stop bleeding and promote healing. Referring to fig. 1-3, the preparation method comprises the steps of dissolving carboxylic acid or sodium carboxylate with active double bonds and fish collagen peptide in deionized water, adding amide with active double bonds and aldehyde with active double bonds, fully stirring and mixing, standing at 20 ℃ for 30min, and carrying out amino carboxyl reaction to obtain the fish collagen peptide. Then dissolving the prepared aloe raw gel, heparin sodium, L-arginine and carboxylic acid or anhydride with active double bonds in deionized water and fully stirring and mixing, wherein the heparin sodium plays a role in preventing the adhesion between the wound and the gel during hemostasis by utilizing the anticoagulation property of the heparin sodium or the adhesion between the wound when the hemostasis healing-promoting gel is used during healing, and simultaneously accelerates the blood to be quickly adsorbed by the hemostasis healing-promoting gel by utilizing a mode of preventing the coagulation of the outflowing blood; and then adding chitosan and modified guanidine salt with double bonds into the solution, fully stirring, filtering and sterilizing by using a filter membrane in the process of preparing the beta-sodium glycerophosphate to obtain a sterile beta-sodium glycerophosphate solution, adding the beta-sodium glycerophosphate slowly into a reaction system to initiate reaction, swelling by using distilled water, removing unreacted monomers and a crosslinking agent, adding a double bond crosslinking agent to initiate polymerization, adjusting the pH value of the solution to be 7.5, and solidifying and regenerating at 5 ℃ to obtain the gel.
Example 3
An antibacterial hemostasis healing promotion gel and a preparation method thereof, the antibacterial hemostasis healing promotion gel comprises the following raw materials by mass: 18 parts of carboxylic acid or carboxylic acid sodium salt with an active double bond, 2 parts of amide with an active double bond, 3 parts of aldehyde with an active double bond, 100 parts of fish collagen peptide and 2 parts of heparin sodium; 5 parts of modified guanidine salt with active double bonds, 10 parts of chitosan, 5 parts of modified diamine with active double bonds, 0.8 part of double bond cross-linking agent, 4 parts of L-arginine, 200 parts of aloe raw gel, 10 parts of beta-sodium glycerophosphate and 200 parts of deionized water.
As a preferred embodiment of the invention, the carboxylic acid or carboxylic acid sodium salt with an activated double bond is any one or more of acrylic acid, sodium acrylate, methacrylic acid, sodium methacrylate, undecylenic acid and oleic acid; the amide with the active double bond is any one or more of acrylamide, methacrylamide, oleamide and derivatives; the aldehyde with the activated double bond is any one or more of undecenal, citronellal, 2, 4-hexadienal and derivatives.
As a preferable scheme of the invention, the modified diamine with the active double bond is any one or more of ethylenediamine, N' -bis (3-aminopropyl) ethylenediamine and hexamethylenediamine, and the double bond crosslinking agent is any one or more of divinylbenzene, glutaraldehyde, epichlorohydrin and genipin.
As a preferred embodiment of the present invention, the preparation method of the aloe vera raw gel comprises: cleaning fresh Aloe, sterilizing, peeling off leaf, taking pulp, mechanically crushing, centrifuging, and collecting supernatant to obtain Aloe crude gel.
As a preferred embodiment of the present invention, the preparation method of the fish collagen peptide comprises: performing enzymolysis on macromolecular raw material aqueous solution such as fish skin and fish scale with biological enzyme, and decolorizing with active carbon; then nano-filtering, desalting and freeze-drying to obtain the fish collagen peptide.
As a preferred scheme of the invention, drug-loaded drug molecules with the effects of stopping bleeding, relieving pain, relieving itching, diminishing inflammation, reducing swelling and the like are also added into the gel.
A preparation method of an antibacterial hemostatic healing promoting gel comprises the following steps:
step 1): dissolving fish collagen peptide, carboxylic acid or sodium carboxylate with active double bond, amide with active double bond and aldehyde with active double bond in deionized water at 10 deg.c, stirring and mixing, and standing at 25 deg.c for 30 min;
step 2): adding heparin sodium, L-arginine, aloe raw gel and carboxylic acid or anhydride with an active double bond into the solution obtained in the step (1), dissolving the mixture in deionized water, fully stirring and mixing, dissolving chitosan and modified guanidinium with a double bond in the deionized water, slowly adding beta-sodium glycerophosphate into the deionized water at 30 ℃ for reaction, and standing for 15min after the reaction is finished;
step 3): swelling the product obtained in the step 2) with distilled water, changing water for many times, screening out redundant components, adding a double-bond cross-linking agent to initiate polymerization, adjusting the pH value of the solution to 7.0, and solidifying and regenerating at 0 ℃ to form gel, thus obtaining the antibacterial hemostatic multifunctional composite hydrogel.
As a preferred embodiment of the preparation method of the present invention, the swelling ratio of the product in the step 3) is controlled to be between 300%.
An antibacterial gel for stopping bleeding and promoting healing is prepared by uniformly applying the gel on the injured part after injury to form a protective isolation layer to help wound antibacterial stop bleeding and promote healing. Referring to fig. 1-3, the preparation method comprises the steps of dissolving carboxylic acid or sodium carboxylate with active double bonds and fish collagen peptide in deionized water, adding amide with active double bonds and aldehyde with active double bonds, fully stirring and mixing, standing at 25 ℃ for 30min, and carrying out amino carboxyl reaction to obtain the fish collagen peptide. Then dissolving the prepared aloe raw gel, heparin sodium, L-arginine and carboxylic acid or anhydride with active double bonds in deionized water and fully stirring and mixing, wherein the heparin sodium plays a role in preventing the adhesion between the wound and the gel during hemostasis by utilizing the anticoagulation property of the heparin sodium or the adhesion between the wound when the hemostasis healing-promoting gel is used during healing, and simultaneously accelerates the blood to be quickly adsorbed by the hemostasis healing-promoting gel by utilizing a mode of preventing the coagulation of the outflowing blood; and then adding chitosan and modified guanidine salt with double bonds into the solution, fully stirring, filtering and sterilizing by using a filter membrane in the process of preparing the beta-sodium glycerophosphate to obtain a sterile beta-sodium glycerophosphate solution, adding the beta-sodium glycerophosphate slowly into a reaction system to initiate reaction, swelling by using distilled water, removing unreacted monomers and a crosslinking agent, adding a double bond crosslinking agent to initiate polymerization, adjusting the pH value of the solution to be 7.0, and solidifying and regenerating at 0 ℃ to obtain the gel.
The curative effect experiment:
the method comprises the following steps of taking about 30 white rabbits of 400g, randomly dividing the white rabbits into experimental groups 1, 2 and 3 and a blank group, carrying out unhairing treatment on the backs of the two groups of white rabbits, disinfecting the skin with 75% alcohol, then respectively making 2 x 2.5cm wounds on two sides of the back, enabling the blank group to heal automatically, smearing the antibacterial hemostasis healing promoting gel of the embodiments 1-3 of the invention on the wound bottom surface of the experimental group, and respectively recording the hemostasis time and the wound healing rates of 1,3 and 10 days, which are shown in the following table.
Figure BDA0002864157260000081
The result shows that after the skin wound repair hydrogel disclosed by the invention is applied, the healing rate of the wound is remarkably improved, the hemostatic effect is achieved by rapidly swelling and absorbing a large amount of water in blood, the generation of skin capillaries is promoted, the tissue growth is facilitated, the nerves of the wound are protected, drug-loaded drug molecules can be added into the gel, the gel has the effects of stopping bleeding, relieving pain, relieving itching, diminishing inflammation and diminishing swelling, the hemostatic effect is achieved by rapidly plugging damaged blood vessels, the effects of rapidly stopping bleeding, promoting wound healing and efficiently resisting bacteria are achieved, the antibacterial property is excellent, and the wound antibacterial hemostatic effect is facilitated by forming a protective isolation layer on the wounded part.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.

Claims (9)

1. An antibacterial hemostatic healing promoting gel, which is characterized in that: the gel comprises the following raw materials in parts by weight: 4-18 parts of carboxylic acid or carboxylic acid sodium salt with an active double bond, 2-10 parts of amide with an active double bond, 1-3 parts of aldehyde with an active double bond, 30-100 parts of fish collagen peptide and 2-3 parts of heparin sodium; 1-5 parts of modified guanidine salt with active double bonds, 3-10 parts of chitosan, 1-5 parts of modified diamine with active double bonds, 0.4-0.8 part of double bond cross-linking agent, 4-7 parts of L-arginine, 50-200 parts of aloe raw gel, 5-10 parts of beta-sodium glycerophosphate and 600 parts of deionized water.
2. The antibacterial, hemostatic and healing promoting gel according to claim 1, wherein: the carboxylic acid or carboxylic acid sodium salt with the activated double bond is any one or more of acrylic acid, sodium acrylate, methacrylic acid, sodium methacrylate, undecylenic acid and oleic acid; the amide with the active double bond is any one or more of acrylamide, methacrylamide, oleamide and derivatives; the aldehyde with the activated double bond is any one or more of undecenal, citronellal, 2, 4-hexadienal and derivatives.
3. The antimicrobial, hemostatic and healing promoting gel of claim 2, wherein: the modified diamine with active double bonds is one or more of ethylenediamine, N' -bis (3-aminopropyl) ethylenediamine and hexamethylenediamine, and the double bond cross-linking agent is one or more of divinylbenzene, glutaraldehyde, epichlorohydrin and genipin.
4. The antibacterial, hemostatic and healing promoting gel according to claim 1, wherein: the preparation method of the aloe vera raw gel comprises the following steps: cleaning fresh Aloe, sterilizing, peeling off leaf, taking pulp, mechanically crushing, centrifuging, and collecting supernatant to obtain Aloe crude gel.
5. The antibacterial, hemostatic and healing promoting gel according to claim 1, wherein: the preparation method of the fish collagen peptide comprises the following steps: performing enzymolysis on macromolecular raw material aqueous solution such as fish skin and fish scale with biological enzyme, and decolorizing with active carbon; then nano-filtering, desalting and freeze-drying to obtain the fish collagen peptide.
6. The antimicrobial, hemostatic and healing promoting gel of claim 1, wherein: the gel also contains drug-carrying molecules with hemostatic, analgesic, antipruritic, antiinflammatory, and repercussive effects.
7. A preparation method of an antibacterial hemostatic healing promoting gel is characterized by comprising the following steps:
step 1): dissolving fish collagen peptide, carboxylic acid or sodium carboxylate with an active double bond, amide with an active double bond and aldehyde with an active double bond in deionized water at the temperature of 2-10 ℃ in parts by weight, fully stirring and mixing, and standing for 30min at the temperature of 15-25 ℃;
step 2): adding heparin sodium, L-arginine, aloe raw gel and carboxylic acid or anhydride with an active double bond into the solution obtained in the step (1), dissolving the mixture in deionized water, fully stirring and mixing, dissolving chitosan and modified guanidinium with a double bond in deionized water, slowly adding beta-sodium glycerophosphate into the deionized water at 15-30 ℃ for reaction, and standing for 15min after the reaction is finished;
step 3): swelling the product obtained in the step 2) with distilled water, changing water for many times, screening out redundant components, adding a double-bond cross-linking agent to initiate polymerization, adjusting the pH value of the solution to 7.0-8.0, and solidifying and regenerating at 0-10 ℃ to form gel, thus obtaining the antibacterial hemostatic multifunctional composite hydrogel.
8. The antimicrobial, hemostatic and healing promoting gel of claim 7, wherein: the swelling ratio of the product in the step 3) is controlled to be between 150 and 300 percent.
9. The use of an antibacterial haemostatic healing promoting gel according to claims 1-8, wherein: after injury, the gel is uniformly coated on the injured part to form a protective isolation layer, which is helpful for wound antibiosis, hemostasis and healing promotion.
CN202011578552.2A 2020-12-28 2020-12-28 Antibacterial hemostatic healing-promoting gel, preparation method and application thereof Pending CN112535761A (en)

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CN102698312A (en) * 2012-05-24 2012-10-03 南方医科大学 Skin wound repair hydrogel and preparation method thereof
CN103599558A (en) * 2013-07-16 2014-02-26 汪贤宗 Rapid hemostatic dressing and preparation method thereof
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