CN116983466A - Medical gel dressing and preparation method and application thereof - Google Patents

Medical gel dressing and preparation method and application thereof Download PDF

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Publication number
CN116983466A
CN116983466A CN202311040584.0A CN202311040584A CN116983466A CN 116983466 A CN116983466 A CN 116983466A CN 202311040584 A CN202311040584 A CN 202311040584A CN 116983466 A CN116983466 A CN 116983466A
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China
Prior art keywords
dressing
gel dressing
polyethylene glycol
medical gel
medical
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CN202311040584.0A
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Chinese (zh)
Inventor
吴德成
杨宇
张冲
冉竞超
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Shenzhen Ningju Biological New Material Technology Co ltd
Southwest University of Science and Technology
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Shenzhen Ningju Biological New Material Technology Co ltd
Southwest University of Science and Technology
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Priority to CN202311040584.0A priority Critical patent/CN116983466A/en
Publication of CN116983466A publication Critical patent/CN116983466A/en
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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
    • A61L26/0019Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/26Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives 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
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • A61L15/44Medicaments
    • 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001Use of materials characterised by their function or physical properties
    • A61L24/0015Medicaments; Biocides
    • 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001Use of materials characterised by their function or physical properties
    • A61L24/0031Hydrogels 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/046Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L26/0066Medicaments; Biocides
    • 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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04Macromolecular materials
    • A61L31/06Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/145Hydrogels 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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16Biologically active materials, e.g. therapeutic substances
    • 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
    • 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
    • A61L2400/06Flowable or injectable implant compositions

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Abstract

The application discloses a medical gel dressing, and a preparation method and application thereof. The medical gel dressing is mainly formed by solidifying polyethylene glycol derivatives and polylysine. The medical gel dressing has the advantages of high gel forming speed, excellent mechanical property, strong tissue adhesiveness, good biocompatibility, biodegradability and the like, and can be effectively used for plugging wound bleeding. The medical gel dressing can be used as a tissue wound plugging and repairing material, a hemostatic agent, a medical adhesive, a tissue adhesion preventing material, a drug slow-release material, a tissue regeneration bracket or a chronic wound dressing, and has good clinical application value. In addition, the medical gel dressing has rich sources of raw materials and low cost.

Description

Medical gel dressing and preparation method and application thereof
Technical Field
The application relates to the technical field of medical gel, in particular to a medical gel dressing and a preparation method and application thereof.
Background
Various hemostatic sealing materials have been developed, including hemostatic bandages, hemostatic powders, hemostatic gels, and the like. Hemostatic bandages are difficult to apply to irregularly shaped wounds and cannot seal deep wounds; the adhesion and mechanical strength of the hemostatic powder are weak, and the hemostatic powder is easy to be washed away and lost by blood flow. The commercial fibrin glue has good biocompatibility and biodegradability, but has insufficient tissue adhesion and mechanical strength, poor hemostatic effect on massive hemorrhage, inconvenient storage, potential immunogenicity and allergic reaction and other problems.
The hydrogel is a soft material which is obtained by crosslinking a hydrophilic polymer and contains a large amount of water, and has good biocompatibility, high elasticity, softness, soft tissue water content-like property, three-dimensional porous network structure similar to a natural extracellular matrix and cell behavior regulation effect. In addition, the injectable gel can be applied to irregular wounds, effectively maintains the required moist environment of the wounds, promotes gas exchange, simultaneously isolates external infection, and has advantages in wound hemostasis and subsequent tissue healing modification.
Wound healing is particularly important after hemostasis is complete. Although human skin has the ability to regenerate itself after loss, this ability can be compromised under specific conditions such as extensive skin loss, deep burns, scalds, chronic wounds, pressure sores, arterial ulcers and injuries in diabetics. With the aging of the world population, there is an increasing demand for the treatment of chronic wounds such as decubitus ulcers and ulcers that are closely related thereto. The traditional gauze is used for treating wounds, so that patients need to change dressings frequently, the hospitalization time is long, the medical cost is high, and the compliance of the patients is poor. An ideal medical dressing should have the following conditions: (1) excellent tissue compatibility and non-toxicity; (2) suitable biodegradability; (3) good antibacterial activity; (4) good moisturizing ability to promote cell and tissue regeneration; (5) sufficient mechanical strength. The proper medical dressing is selected according to the type of the wound, so that the functions of stopping bleeding, preventing bacterial infection, debridement and the like can be realized in time, and the wound is promoted to be repaired as soon as possible according to the ordered wound healing process. However, the existing wound dressing has the disadvantages of higher cost, single function, insufficient antibacterial and anti-infection capabilities, and unsatisfactory effect when treating chronic wound surfaces which are difficult to heal.
Although, studies have shown that functional gel dressings can be prepared by loading bioactive components into the gel dressing or delivering functional drugs, which can accelerate healing of chronic wounds; however, how to prepare the multifunctional medical gel dressing with low cost, fast gelling speed, excellent mechanical property, strong tissue adhesiveness, good biocompatibility and biodegradability is still the research focus and difficulty in the field.
Disclosure of Invention
The application aims to provide a novel multifunctional medical gel dressing, and a preparation method and application thereof.
In order to achieve the above purpose, the present application adopts the following technical scheme:
one aspect of the application discloses a medical gel dressing which is mainly formed by solidifying polyethylene glycol derivatives and polylysine.
The medical gel dressing has the advantages of high gelling speed, excellent mechanical property, strong tissue adhesiveness, good biocompatibility, biodegradability and the like, and can be effectively used for plugging wound bleeding. In one implementation mode of the application, the medical gel dressing can load bioactive components and/or medicines, and has excellent functions of resisting bacteria and inflammation, promoting wound healing and repairing and the like. The medical gel dressing can be used as a tissue wound plugging and repairing material, a hemostatic agent, a medical adhesive, a tissue adhesion preventing material, a drug slow-release material, a tissue regeneration bracket, a chronic wound dressing and the like, and has good clinical application value. In addition, the medical gel dressing has the advantages of abundant raw material sources and low cost, and is suitable for large-scale industrialized mass production.
In one implementation of the application, the chemical bond formed by the chemical reaction in the curing process is a beta-carbonyl amide bond or a Schiff base bond.
In one implementation of the application, the medical gel dressing has a three-dimensional gel skeleton structure.
In one implementation mode of the application, the structural formula of the polylysine is at least one of the formula I, the formula II, the formula III and the formula IV;
wherein, m is an integer between 2 and 10000.
Preferably, the molecular weight of the polylysine is 292-300000, preferably 3500-10000.
In the application, polylysine with a structural formula I is epsilon-polylysine (EPL), polylysine with a structural formula II is poly-L-lysine (PLL), polylysine with a structural formula III is Hyperbranched Polylysine (HPL), and polylysine with a structural formula IV is Dendritic Polylysine (DPL).
In one implementation of the application, the polyethylene glycol derivative is a succinimide ester functionalized polyethylene glycol.
In one implementation of the application, the structural formula of the succinimide ester functionalized polyethylene glycol is at least one of formula V, formula VI, formula VII and formula VIII;
wherein n is an integer between 2 and 10000.
Preferably, the molecular weight of the succinimide ester-functionalized polyethylene glycol is 2000-20000, preferably 2000-10000.
In the application, the succinimide ester functionalized polyethylene glycol with the structural formula V is double-arm polyethylene glycol succinimide ester (PEG) 2 -NHS), the succinimide ester functionalized polyethylene glycol of formula VI is a four-arm polyethylene glycol succinimide ester (PEG) 4 -NHS), the succinimide ester functionalized polyethylene glycol of formula VII is a six-arm polyethylene glycol succinimide ester (PEG) 6 -NHS), the succinimide ester functionalized polyethylene glycol of formula VIII is an eight-arm polyethylene glycol succinimide ester (PEG) 8 -NHS)。
In one implementation of the application, the polyethylene glycol derivative is aldehyde modified polyethylene glycol.
In one implementation of the application, the structural formula of the aldehyde-modified polyethylene glycol is at least one of formula IX, formula X, formula XI and formula XII;
wherein z is an integer between 2 and 10000.
Preferably, the molecular weight of the aldehyde-modified polyethylene glycol is 2000-20000, preferably 2000-12000.
In the present application, the aldehyde-modified polyethylene glycol having the structural formula IX is a double-arm terminal aldehyde-modified polyethylene glycol (PEG) 2 -CHO), the aldehyde-modified polyethylene glycol of formula X being a four-armTerminal aldehyde modified polyethylene glycol (PEG 4 -CHO), the aldehyde-modified polyethylene glycol of formula XI is a six-arm terminal aldehyde-modified polyethylene glycol (PEG) 6 -CHO), the aldehyde-modified polyethylene glycol of formula XII is an eight-arm terminal aldehyde-modified polyethylene glycol (PEG) 8 -CHO)。
In one implementation of the application, the mass ratio of polyethylene glycol derivative to polylysine is 1 (0.1-500), preferably 1 (0.25-10).
In one implementation of the application, the medical gel dressing is an injectable gel or gel patch dressing.
The medical gel dressing of the present application may be an injectable gel or a gel patch dressing according to the need. In the case of injectable gels, the polyethylene glycol derivative and polylysine are placed separately and mixed and cured when needed to form the medical gel dressing of the present application. In the case of a gel patch dressing, the dressing may be a previously cured medical gel dressing.
In one implementation of the application, the medical gel dressing of the application is loaded with bioactive components and/or drugs.
The medical gel dressing of the present application may be loaded with bioactive components or deliver functional drugs according to the prior art, including but not limited to natural polyphenols, small molecule drugs, inorganic nanoparticles, growth factors, functional proteins, active polysaccharides, exosomes, liposomes, stem cells, probiotics, genes, RNAs, nucleic acids, active peptides, and modifications of these substances. Wherein the natural polyphenols include, but are not limited to, puerarin, curcumin, myricetin, procyanidins, catechin, quercetin, kaempferol, quercetin, caffeic acid, gallic acid, ellagic acid, and arbutin. The bioactive components loaded on the medical gel dressing of the present application include, but are not limited to, insulin-like growth factors, epidermal growth factors, platelet-derived proliferation factors, nerve growth factors, colony stimulating factors, transforming growth factor-alpha, bone morphogenic proteins, fibroblast growth factors, platelet-derived growth factors, erythropoietin, interleukin-like growth factors, and growth hormone release-inhibiting factors.
In another aspect, the application discloses the application of the medical gel dressing in preparing a tissue wound plugging and repairing material, a hemostatic agent, a medical adhesive, a tissue adhesion preventing material, a drug sustained-release material, a tissue regeneration bracket or a chronic wound dressing.
It can be understood that the medical gel dressing of the application has the advantages of high gelling speed, excellent mechanical property, strong tissue adhesiveness, good biocompatibility and biodegradability; therefore, the composite material can be used as a tissue wound blocking and repairing material, a hemostatic agent, a medical adhesive, a tissue adhesion preventing material, a drug slow release material, a tissue regeneration bracket or a chronic wound dressing.
In another aspect, the application discloses a method for preparing the medical gel dressing of the application, comprising the following steps:
(1) Preparing a polylysine solution, and marking the polylysine solution as a solution A;
(2) Preparing polyethylene glycol derivative solution, and marking as solution B;
(3) And mixing the solution A and the solution B, and curing the mixture at room temperature to form gel to obtain the medical gel dressing.
In the preparation method, the polyethylene glycol derivative and the polylysine can be rapidly solidified at room temperature to form the medical gel dressing, and the whole preparation method has the advantages of simple steps, easy operation, low cost of preparation raw materials and abundant sources, and is suitable for large-scale industrialized mass production.
In one embodiment of the application, the solution a and/or the solution B contains bioactive components and/or drugs.
When the medical gel dressing is loaded with the bioactive components and/or the medicines, the bioactive components and/or the medicines can be dissolved or dispersed in the solution A and/or the solution B, namely the bioactive components and/or the medicines can be independently dissolved in the solution A or the solution B, or the loading materials are partially dissolved in the solution A and partially dissolved in the solution B, and then the solution A and the solution B are mixed and cured at room temperature, so that the medical gel dressing loaded with the bioactive components and/or the medicines is obtained.
In one implementation of the application, the mass concentration of the solution A is 0.1% -50%, preferably 1% -10%.
In one implementation of the application, the mass concentration of the solution B is 1% -50%, preferably 5% -20%.
Due to the adoption of the technical scheme, the application has the beneficial effects that:
the medical gel dressing has the advantages of high gel forming speed, excellent mechanical property, strong tissue adhesiveness, good biocompatibility, biodegradability and the like, and can be effectively used for plugging wound bleeding. The medical gel dressing can be used as a tissue wound plugging and repairing material, a hemostatic agent, a medical adhesive, a tissue adhesion preventing material, a drug slow-release material, a tissue regeneration bracket or a chronic wound dressing, and has good clinical application value. In addition, the medical gel dressing has rich sources of raw materials and low cost.
Drawings
FIG. 1 is a graph showing statistics of gel forming time of a gel dressing for traditional Chinese medicine in accordance with an embodiment of the present application;
FIG. 2 is a graph showing the results of adhesive strength test of a gel dressing for medical use in the examples of the present application;
FIG. 3 is an observation result of the traditional Chinese medicine gel dressing according to the embodiment of the application after bending, twisting and extrusion at 0-90 degrees on pigskin;
FIG. 4 is a graph showing the results of compressive strength testing of a gel dressing for use in the present application;
FIG. 5 is an electron microscope image of a gel dressing for medical use in an embodiment of the application;
FIG. 6 is a swelling picture of a gel dressing for use in the present application;
FIG. 7 is a graph showing the results of an antibacterial property test of a gel dressing for medical use according to an embodiment of the present application;
FIG. 8 is a graph showing the results of a cell compatibility test of a gel dressing for medical use in accordance with an embodiment of the present application;
FIG. 9 is a graph showing liver hemostasis test results of a medical gel dressing in accordance with an embodiment of the present application;
FIG. 10 is a view showing the observation result of the healing effect of a traditional Chinese medical gel dressing according to the embodiment of the application;
fig. 11 is a view showing the observation result of the wound repair effect of the gel dressing for treating diabetic ulcers in the embodiment of the application.
Detailed Description
Polyethylene glycol (polyethylene glycol, PEG) is a class of synthetic polymers licensed for use in humans by the U.S. food and drug administration and has excellent biosafety. Another polymer material polylysine is a water-soluble polypeptide, contains rich amino groups, has the advantages of antibacterial activity, biodegradability and the like, and is regarded as a biological material with larger potential in the biomedical field. The medical gel dressing is obtained by creatively mixing and curing at least one polyethylene glycol in a formula V, a formula VI, a formula VII and a formula VIII, or at least one polyethylene glycol in a formula IX, a formula X, a formula XI and a formula XII with at least one polylysine in a formula I, a formula II, a formula III and a formula IV at room temperature.
Compared with the existing medical gel dressing, the medical gel dressing has the following advantages:
(1) The medical gel dressing has the advantages of simple preparation steps, easy operation, low cost of preparation raw materials and rich sources, and is suitable for large-scale industrialized mass production.
(2) The medical gel dressing can be formed in situ, can be prepared into any shape in different grinding tools, and can be applied to irregular wounds.
(3) The medical gel dressing has controllable gel forming speed and excellent mechanical property.
(4) The medical gel dressing can be covered on the wound of epidermis or viscera, can absorb tissue fluid, can be rapidly degraded in vivo and on the body surface after being used, is beneficial to dressing change of the wound and reduces the pain of wounded.
(5) The medical gel dressing has excellent hemostatic and visceral occlusion effects.
(6) The medical gel dressing has excellent anti-tissue adhesion effect.
(7) The medical gel dressing has good biocompatibility.
(8) The medical gel dressing can destroy cell membranes of bacteria and has a natural broad-spectrum antibacterial effect.
(9) The medical gel dressing has remarkable anti-inflammatory effect.
(10) The medical gel dressing has the effect of accelerating wound healing.
(11) The medical gel dressing can be used as a medical adhesive or a chronic wound healing dressing.
The application is described in further detail below with reference to specific examples and figures. The following examples are merely illustrative of the present application and should not be construed as limiting the application.
The terms used in the present application generally have meanings commonly understood by those of ordinary skill in the art unless otherwise indicated.
In the following examples, various processes and methods, which are not described in detail, are conventional methods well known in the art.
Example 1
The gel forming time of the medical gel dressing is tested in the embodiment, and the medical gel dressing formed by crosslinking succinimidyl ester functionalized or aldehyde modified polyethylene glycol with different arm numbers and polylysine with different structures through beta-carbonyl amide bonds or Schiff base bonds is prepared by the specific preparation method as follows:
(1) 5.0mg of linear polylysine was precisely weighed and dissolved in 1.0mL of PBS (pH 7.4) to obtain a mixture A. In this example, two 5.0mg portions of epsilon-polylysine (EPL) and two 5.0mg portions of poly-L-lysine (PLL) were weighed out to prepare solution A.
(2) 20.0mg of four-arm polyethylene glycol succinimidyl ester (PEG) was accurately weighed out respectively 4 -NHS), 20.0mg of four-arm terminal aldehyde modified polyethylene glycol (PEG) 4 -CHO), dissolved in 1.0mL PBS (pH 7.4), respectively, to give solution B.
(3) And respectively adding the solution A and the solution B into a double-tube syringe, extruding two liquids into a sample bottle at the same time, observing the flowing state of the liquids by inverting the sample bottle to judge the formation of gel, and recording the gel forming time.
EPL and PEG were specifically observed and recorded in this example 4 Gel time of NHS curing to form medical gel dressing, EPL and PEG 4 Gel time for CHO curing to form medical gel dressing, PLL and PEG 4 Gel time, PLL and PEG for curing NHS to form a medical gel dressing 4 Gel time for CHO curing to form a medical gel dressing, the results are shown in fig. 1.
The results in FIG. 1 show that EPL+PEG 4 -NHS、EPL+PEG 4 -CHO、PLL+PEG 4 -NHS、PLL+PEG 4 CHO forms hydrogels within 10 seconds. EPL+PEG 4 -NHS and PLL+PEG 4 Compared with EPL+PEG, the NHS hydrogel 4 -CHO and pll+peg 4 The gel formation time of CHO hydrogels is shorter.
Example two
The adhesive strength of the medical gel dressing is tested in this example, and the specific steps are as follows:
50. Mu.L of the solution A and the solution B of the first embodiment are respectively and uniformly coated on one end of a fresh back pigskin, the coating area is 1cm multiplied by 1cm, then the two ends of the pigskin are rapidly overlapped in opposite directions, the pigskin is fixed for 1min by a 100g weight at room temperature, and then the pigskin is stretched at a speed of 5mm/min until fracture occurs. The maximum shear adhesion strength of the medical gel dressing was recorded. Meanwhile, 100 mu L of hydrogel is coated on pigskin, and is bent, twisted and extruded at 0-90 degrees, so that the condition that the hydrogel adheres to the pigskin is observed. At the same time, the same test was performed using Fibrin glue (Fibrin glue) as a control. The results of the adhesion strength test are shown in FIG. 2, and the photographed results of the partial hydrogel adhered pigskin are shown in FIG. 3. In FIG. 3, (a) behavior EPL+PEG 4 Test pattern of NHS gel, (b) row and (c) row EPL+PEG 4 Test pattern of CHO gels, fig. 3 provides a graphic representation of only two gels, the remaining two gels also having similar effects.
The results in FIG. 2 show that EPL+PEG 4 -NHS and PLL+PEG 4 The adhesive strength of the formed NHS hydrogel is about 30kPa, EPL+PEG 4 -CHO and pll+peg 4 The adhesion strength of the CHO hydrogel is about 17kPa, which is far higher than that of commercial control fibrinAdhesive strength (4 kPa) of glue (Fibrin glue).
The observation result that the medical gel dressing is bent, twisted and extruded on the pigskin by 0-90 degrees shows that EPL+PEG 4 -NHS、EPL+PEG 4 -CHO、PLL+PEG 4 -NHS、PLL+PEG 4 All four gels-CHO-were able to adhere to pig skin as initially without falling off and had excellent adhesion properties, and the partial results are shown in FIG. 3.
Example III
The compressive strength of the medical gel dressing is tested in this example, and is specifically as follows:
the procedure for preparing the medical gel dressing of this example was the same as in example one, except that: the polylysine of solution A added was Hyperbranched Polylysine (HPL), i.e.the EPL of example one was replaced with an equal amount of HPL.
The solution A of this example was separately compared with the two solutions B of example one, PEG 4 -NHS and PEG 4 CHO, added separately to a double syringe, while extruding two liquids into a disc mold 15mm in diameter and 7.5mm in height, compression performance testing was performed using a dual column universal tester, compressing the hydrogel to 80% deformation or fracture at a compression rate of 1 mm/min.
The present example specifically tested HPL and PEG 4 Compressive Strength of NHS formed hydrogels, HPL and PEG 4 Compression strength of CHO formed hydrogels, test results are shown in fig. 4.
The results in FIG. 4 show that HPL+PEG 4 NHS to HPL+PEG 4 CHO hydrogels with higher compression modulus, hpl+peg 4 -NHS、HPL+PEG 4 The compression modulus of the CHO hydrogel compressed to 80% strain is 350.4 + -8.2 kPa and 327.5 + -4.4 kPa respectively, and the compression modulus of the medical gel dressing of this example is superior to that of physiological soft tissue, and has excellent mechanical properties.
Example IV
In this example, the medical gel dressing is observed by electron microscopy, and the specific steps are as follows:
the procedure for preparing the medical gel dressing of this example was the same as in example one, except that: the polylysine of solution A added was Dendritic Polylysine (DPL), i.e. the EPL of example one was replaced with an equal amount of DPL.
The solution A of this example was separately compared with the two solutions B of example one, PEG 4 -NHS and PEG 4 CHO, added separately to a double syringe, and simultaneously squeeze out both liquids into an orifice plate to obtain a hydrogel. Before the test, the hydrogel is subjected to freeze drying treatment, brittle fracture is carried out by liquid nitrogen, and the internal section is selected for observation by a scanning electron microscope. And (3) carrying out metal spraying treatment before testing, wherein the accelerating voltage is 5kV, and the amplification factor is 300 times and 500 times.
The present example is specific to DPL and PEG 4 Hydrogels formed by NHS, DPL and PEG 4 The hydrogel formed by CHO was subjected to electron microscopy and the results are shown in FIG. 5.
The results of FIG. 5 show that DPL+PEG at different magnification 4 -NHS and DPL+PEG 4 The CHO hydrogels all have three-dimensional porous network structure, which is favorable for permeation of water molecules and drug molecules, DPL+PEG 4 -NHS vs DPL+PEG 4 The pore structure of CHO hydrogels is denser.
Example five
The swelling test of the medical gel dressing is carried out in this example, and the specific steps are as follows:
the procedure for preparing the medical gel dressing of this example was the same as in example one, except that: the polyethylene glycol derivatives of the added solution B were respectively double arm polyethylene glycol succinimidyl esters (PEG 2 -NHS) and double arm terminal aldehyde modified polyethylene glycol (PEG 2 CHO), i.e. with equal amounts of PEG respectively 2 -NHS and PEG 2 CHO, PEG of alternative example one 4 -NHS and PEG 4 -CHO。
The EPL solution a of example one and the two solutions B of this example were added separately to a double syringe while two liquids were extruded and injected into a cylindrical glass mold. The weighed sample was put into 10mL of PBS, and the sample was taken out according to a set time, the surface water was sucked dry with filter paper, and the image was taken.
The present example separately observed EPL and PEG 2 Swelling of hydrogels formed by NHS, EPL and PEG 2 -CHO formationThe swelling of the hydrogels, and the results are shown in FIG. 6.
The results in FIG. 6 show that EPL+PEG 2 -NHS and EPL+PEG 2 CHO hydrogels achieve a swelling balance within 48h and the swelling volume is not very pronounced.
Example six
The antibacterial performance of the medical gel dressing is tested in the embodiment, and the specific steps are as follows:
the procedure for preparing the medical gel dressing of this example was the same as in example one, except that: the polyethylene glycol derivatives of the added solution B are respectively six-arm polyethylene glycol succinimidyl esters (PEG 6 -NHS) and six-arm terminal aldehyde modified polyethylene glycols (PEG 6 CHO), i.e. with equal amounts of PEG respectively 6 -NHS and PEG 6 CHO, PEG of alternative example one 4 -NHS and PEG 4 -CHO。
The EPL solution a of example one and the two solutions B of this example were separately added to a double syringe, and simultaneously two liquids were extruded and injected into an orifice plate to obtain a hydrogel. Respectively soaking 50mg of multifunctional hydrogel in 1mL of bacterial solution of Escherichia coli, staphylococcus aureus and Pseudomonas aeruginosa, wherein the concentration of bacterial solution is 1×10 7 CFU/mL, incubated with shaking at 37℃for 12h. By measuring OD 600 To determine the bacteriostatic action of the multifunctional hydrogel on bacteria.
The present example tested EPL and PEG, respectively 6 The antibacterial properties of the NHS-formed hydrogel against E.coli, staphylococcus aureus, pseudomonas aeruginosa were tested for EPL and PEG, respectively 6 The antibacterial properties of CHO-formed hydrogels against e.coli, staphylococcus aureus, pseudomonas aeruginosa are shown in fig. 7.
In FIG. 7, FIG. E.coil is EPL and PEG 6 NHS-formed hydrogels, EPL and PEG 6 Test results of antibacterial Properties of CHO-formed hydrogels against E.coli, FIG. P. Aeromonas EPL and PEG 6 NHS-formed hydrogels, EPL and PEG 6 Results of antibacterial property test of CHO-formed hydrogels against Pseudomonas aeruginosa, S.aureus is EPL and PEG 6 NHS-formed hydrogels, EPL and PEG 6 CHO-formed waterThe results of the antibacterial performance test of the gel against staphylococcus aureus are shown.
The results in FIG. 7 show EPL+PEG 6 -NHS and EPL+PEG 6 The antibacterial rate of the CHO hydrogel to the escherichia coli, staphylococcus aureus and pseudomonas aeruginosa is more than 95%, so that the multifunctional hydrogel can realize broad-spectrum antibacterial effect and has stronger antibacterial performance.
Example seven
The cell compatibility of the medical gel dressing is tested in this example, and the specific steps are as follows:
the procedure for preparing the medical gel dressing of this example was the same as in example one, except that: the polyethylene glycol derivatives of the added solution B are respectively eight-arm polyethylene glycol succinimidyl esters (PEG 8 -NHS) and octa-terminal aldehyde modified polyethylene glycol (PEG 8 CHO), i.e. with equal amounts of PEG respectively 8 -NHS and PEG 8 CHO, PEG of alternative example one 4 -NHS and PEG 4 -CHO。
The EPL solution a of example one and the two solutions B of this example were separately added to a double syringe, and simultaneously two liquids were extruded and injected into an orifice plate to obtain a hydrogel. Preparing a culture medium leaching solution of the aqueous gel according to the proportion of 10mg/mL, namely 10mg EPL+PEG 8 NHS hydrogel and 1mL of high sugar complete medium (brand Vison, cat No. C11995500BT, DMEM medium, 10% fetal bovine serum and 100IU/mL penicillin, streptomycin). Soaking for 24 hours at 37 ℃ in a cell culture box, then, discarding the common culture medium of the mouse fibroblast 3T3 inoculated on a tissue culture plate for 24 hours, replacing the common culture medium with a culture medium leaching solution containing aqueous gel, and culturing for 24 hours in the cell culture box at 37 ℃ and a carbon dioxide concentration of 5%, so as to obtain monolayer cells with good adhesion. Cell activity was measured using CCK-8 reagent, cell activity (%) = (OD) Hydrogel -OD Blank space )/(OD Culture plate -OD Blank space )。OD Hydrogel Refers to OD after 24h of culture in a medium containing hydrogel 600 A value; OD (optical density) Blank space Represents OD after 24h incubation with equal amounts of cell culture medium and CCK-8 solution without cells 600 A value; OD (optical density) Culture plate Representative of a non-aqueous gel extractOD after 24h culture in DMEM medium 600 Values.
EPL+PEG was tested separately in this example 8 -NHS and EPL+PEG 8 Cell compatibility of CHO two hydrogels, the results are shown in fig. 8. In FIG. 8, the Control group refers to the reference of the culture plate of the cells cultured in the normal DMEM medium without the hydrogel extract.
The results in FIG. 8 show that EPL+PEG 8 -NHS and EPL+PEG 8 The CHO hydrogel extract and the cells are incubated together for 24 hours, the cells treated by the hydrogel group show cell viability similar to that of the cells of the normal group, and the survival rate of each group is higher than 90 percent, so that the hydrogel has excellent cell compatibility.
Example eight
The liver hemostatic performance of the medical gel dressing is tested in this example, and the specific steps are as follows:
in this example, new Zealand white rabbits, males, 2-3kg were anesthetized with isoparaffin and tested. The rabbits were fixed on an operating table, the liver was exposed by carefully cutting the skin of the abdominal cavity, and a liver perforation bleeding model was produced on the liver of the rabbits using a 5mm punch. The solution A (EPL) of example one and the solution B (PEG) of example one were mixed 4 -NHS) and extruding two liquids simultaneously, 200. Mu.L (ES), EPL+PEG 4 NHS hydrogel is injected into the bleeding site, photographed and the hemostatic condition recorded. In addition, fibrin glue (Fibrin glue), a commercial product, was selected as a control group. The wound conditions were observed and photographed for 0min, 1s, 6s, and 5min after injection, respectively, and the results are shown in fig. 9. In fig. 9, the upper case is where ES is injected, and the lower case is where Fibrin glue is injected.
The results of fig. 9 show that in a rabbit liver perforation bleeding model, blood leakage occurs 5min after fibrin glue group hemostasis, and rapid blocking hemostasis is difficult; the ES hydrogel group of this example can complete hemostasis by only 6.+ -.1 s without any blood leakage, and can be used as a rapid hemostatic material.
Example nine
The scald wound healing effect of the medical gel dressing is tested by the embodiment, and the method is as follows:
the procedure for preparing the medical gel dressing of this example was the same as in example one, except that: the solution B contains puerarin with concentration of 0.1%.
20 SD rats, male, 250-300g, were selected, and after anesthesia with isoparaffin, deep II-degree scalding was performed on the backs of the rats with round metal copper blocks, further creating a round skin full-layer defect model with a diameter of 15 mm. Then the solution A (EPL) of example one and the solution B (PEG) of example one 4 -NHS), into double syringes, two liquids were simultaneously extruded, 200. Mu.L (ESM), EPL+PEG, was injected 4 The NHS+puerarin hydrogel dressing can rapidly cover and fill the wound, and the wound is photographed at 3, 7, 14, 21 and 28 days to observe the wound healing condition. Saline group (Control) and commercial product tergaderm TM The transparent dressing served as negative and positive control groups, respectively. The results are shown in FIG. 10. In FIG. 10, the top row is the photographed result of the Control of the normal saline group, and the middle row is the commercial product Tegaderm TM The bottom of the photographed results after the treatment is the photographed results after the hydrogel treatment in this example.
The results of fig. 10 show that the healing area of all groups of back wounds gradually decreased with increasing days, but ESM hydrogels were significantly more useful for treating scalded wounds than the saline group and the commercial control Tegaderm TM The healing area of the transparent dressing group is smaller, and almost no scar is left after healing, so that the medical gel dressing of the embodiment can obviously accelerate the repair of scalded wounds.
Examples ten
The repairing effect of the medical gel dressing on the diabetic ulcer wound surface is tested in the embodiment, and the repairing effect is specifically as follows:
the procedure for preparing the medical gel dressing of this example was the same as in example one, except that: the solution A contains insulin-like growth factor, and the solution B contains puerarin. Wherein the concentration of the insulin-like growth factor is 2.5%, and the concentration of puerarin is 0.1%.
40 SD rats, male, 250-300g, were selected, fasted and not water forbidden for 14h, weighed one by one, and were intraperitoneally injected with streptozotocin (60 mg/mL) to construct a model of type I diabetes rats. After the successful construction of the model by blood glucose determination, the model is determined to be sufficientThe sections create a circular model of a full-thickness defect of skin with a diameter of 5 mm. Then the solution A (EPL) of example one and the solution B (PEG) of example one 4 -CHO), separately added to a double syringe, simultaneously expressing two liquids, 200 μl (ESMP), i.e. epl+peg, is injected 4 The cho+puerarin+insulin-like growth factor hydrogel dressing rapidly covers and fills the wound, photographs the wound at regular intervals, measures the wound area with Image J software, and calculates the wound healing rate. Wound healing rate (%) = (S) 0 -S t )/S 0 ×100%,S 0 And S is t Represents the initial area of the wound and the area at time t, respectively, saline group (Control) and commercial Tegaderm TM The transparent dressing was used as negative and positive control groups, respectively, in this example, on days 7, 14 and 21, the tissue of the wound site was obtained and fixed in 4% paraformaldehyde solution, and after paraffin embedding, the sections were used and pathological analysis was performed on the sections. The wound healing rate statistics are shown in FIG. 11, and the Control group, commercial Tegaderm, is shown in the order from left to right in FIG. 11 on the abscissa TM Group and ESMP hydrogel group.
The results of FIG. 11 show that ESMP hydrogels when used to treat full-thickness defect wounds of foot ulcers and skin in diabetic rats, the 21-day wound healing rate reached 100%, had healed completely, whereas saline treated groups and commercial control Tegaderm TM The 21-day wound healing rates for the transparent dressing set were only 75% and 80%, respectively. The medical gel dressing of the example can obviously accelerate wound repair of diabetic foot ulcers.
The foregoing is a further detailed description of the application in connection with specific embodiments, and it is not intended that the application be limited to such description. It will be apparent to those skilled in the art that several simple deductions or substitutions can be made without departing from the spirit of the application.

Claims (10)

1. A medical gel dressing, characterized in that: mainly prepared by solidifying polyethylene glycol derivatives and polylysine.
2. The medical gel dressing of claim 1, wherein: in the curing process, the chemical bond formed by chemical reaction is a beta-carbonyl amide bond or a Schiff base bond;
preferably, the medical gel dressing has a three-dimensional gel skeleton structure.
3. The medical gel dressing of claim 1, wherein: the structural formula of the polylysine is at least one of a formula I, a formula II, a formula III and a formula IV;
wherein, m is an integer between 2 and 10000;
preferably, the molecular weight of the polylysine is 292-300000, preferably 3500-10000.
4. The medical gel dressing of claim 1, wherein: the polyethylene glycol derivative is succinimide ester functionalized polyethylene glycol;
preferably, the structural formula of the succinimide ester-functionalized polyethylene glycol is at least one of formula V, formula VI, formula VII and formula VIII;
wherein n is an integer between 2 and 10000;
preferably, the molecular weight of the succinimide ester-functionalized polyethylene glycol is 2000-20000, preferably 2000-10000.
5. The medical gel dressing of claim 1, wherein: the polyethylene glycol derivative is aldehyde modified polyethylene glycol;
preferably, the aldehyde group-modified polyethylene glycol has at least one of the structural formulas IX, X, XI and XII;
wherein z is an integer between 2 and 10000;
preferably, the molecular weight of the aldehyde-modified polyethylene glycol is 2000-20000, preferably 2000-12000.
6. The medical gel dressing according to any one of claims 1-5, wherein: the mass ratio of the polyethylene glycol derivative to the polylysine is 1 (0.1-500), preferably 1 (0.25-10);
preferably, the medical gel dressing is an injectable gel or gel patch type dressing.
7. The medical gel dressing according to any one of claims 1-5, wherein: the medical gel dressing is filled with bioactive components and/or medicines;
preferably, the bioactive component and/or drug comprises natural polyphenols, small molecule drugs, inorganic nanoparticles, growth factors, functional proteins, active polysaccharides, exosomes, liposomes, stem cells, probiotics, genes, RNAs, nucleic acids, active peptides, and modifications of at least one of these substances;
preferably, the natural polyphenol is at least one of puerarin, curcumin, myricetin, procyanidine, catechin, quercetin, kaempferol, quercetin, caffeic acid, gallic acid, ellagic acid and arbutin;
preferably, the bioactive component is at least one of insulin-like growth factor, epidermal growth factor, platelet-derived proliferation factor, nerve growth factor, colony stimulating factor, transforming growth factor-alpha, bone morphogenic protein, fibroblast growth factor, platelet-derived growth factor, erythropoietin, interleukin-like growth factor, and growth hormone release-inhibiting factor.
8. Use of a medical gel dressing according to any one of claims 1-7 for the preparation of a tissue wound plugging and repair material, a hemostatic agent, a medical adhesive, a tissue adhesion preventing material, a drug release material, a tissue regeneration scaffold or a chronic wound dressing.
9. A method of preparing a medical gel dressing according to any one of claims 1 to 7, characterized in that: comprises the steps of,
(1) Preparing a polylysine solution, and marking the polylysine solution as a solution A;
(2) Preparing polyethylene glycol derivative solution, and marking as solution B;
(3) And mixing the solution A and the solution B, and curing to form gel at room temperature to obtain the medical gel dressing.
10. The method of manufacturing according to claim 9, wherein: the solution A and/or the solution B contains bioactive components and/or medicines;
preferably, the mass concentration of the solution A is 0.1% -50%, preferably 1% -10%;
preferably, the mass concentration of the solution B is 1% -50%, preferably 5% -20%.
CN202311040584.0A 2023-08-16 2023-08-16 Medical gel dressing and preparation method and application thereof Pending CN116983466A (en)

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Publication number Priority date Publication date Assignee Title
CN104307052A (en) * 2014-10-27 2015-01-28 北京爱美客生物科技有限公司 Medicinal injectable anti-adhesive gel and preparation method thereof
CN105169469A (en) * 2015-08-29 2015-12-23 北京诺康达医药科技有限公司 Tissue sealant and preparation method and application thereof
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