CN111320770A - Biological gel for burn department for accelerating wound healing and preparation method thereof - Google Patents

Biological gel for burn department for accelerating wound healing and preparation method thereof Download PDF

Info

Publication number
CN111320770A
CN111320770A CN202010310035.0A CN202010310035A CN111320770A CN 111320770 A CN111320770 A CN 111320770A CN 202010310035 A CN202010310035 A CN 202010310035A CN 111320770 A CN111320770 A CN 111320770A
Authority
CN
China
Prior art keywords
wound healing
cellulose
solution
burn department
bacterial
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202010310035.0A
Other languages
Chinese (zh)
Other versions
CN111320770B (en
Inventor
张丙起
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Affiliated Hospital of University of Qingdao
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to CN202010310035.0A priority Critical patent/CN111320770B/en
Publication of CN111320770A publication Critical patent/CN111320770A/en
Application granted granted Critical
Publication of CN111320770B publication Critical patent/CN111320770B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00Processes of treating or compounding macromolecular substances
    • C08J3/02Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
    • C08J3/03Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
    • C08J3/075Macromolecular gels
    • 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
    • A61L26/0004Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing inorganic materials
    • 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
    • A61L26/0023Polysaccharides
    • 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
    • A61L26/0061Use 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
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08BPOLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B15/00Preparation of other cellulose derivatives or modified cellulose, e.g. complexes
    • C08B15/02Oxycellulose; Hydrocellulose; Cellulosehydrate, e.g. microcrystalline cellulose
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00Processes of treating or compounding macromolecular substances
    • C08J3/24Crosslinking, e.g. vulcanising, of macromolecules
    • C08J3/246Intercrosslinking of at least two polymers
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J7/00Chemical treatment or coating of shaped articles made of macromolecular substances
    • C08J7/12Chemical modification
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J7/00Chemical treatment or coating of shaped articles made of macromolecular substances
    • C08J7/12Chemical modification
    • C08J7/14Chemical modification with acids, their salts or anhydrides
    • 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23Carbohydrates
    • A61L2300/232Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
    • 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/418Agents promoting blood coagulation, blood-clotting agents, embolising agents
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2305/00Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
    • C08J2305/04Alginic acid; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2389/00Characterised by the use of proteins; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2401/00Characterised by the use of cellulose, modified cellulose or cellulose derivatives
    • C08J2401/02Cellulose; Modified cellulose
    • C08J2401/04Oxycellulose; Hydrocellulose
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2405/00Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2401/00 or C08J2403/00
    • C08J2405/04Alginic acid; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2489/00Characterised by the use of proteins; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08KUse of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00Use of inorganic substances as compounding ingredients
    • C08K3/16Halogen-containing compounds
    • C08K2003/162Calcium, strontium or barium halides, e.g. calcium, strontium or barium chloride
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08KUse of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00Use of inorganic substances as compounding ingredients
    • C08K3/38Boron-containing compounds

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Polymers & Plastics (AREA)
  • Dispersion Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

The invention provides a biological gel for a burn department for accelerating wound healing and a preparation method thereof. Firstly, carrying out oxidation reaction on bacterial nano-cellulose by adopting sodium periodate to prepare modified bacterial nano-cellulose; then dispersing the bacterial nano cellulose into water to prepare modified bacterial nano cellulose dispersion liquid, and mixing the modified bacterial nano cellulose dispersion liquid with a sodium alginate solution to obtain a mixed solution; then, mixing and stirring the mixed solution and the collagen swelling solution, and then placing the mixture in a mixed crosslinking aqueous solution of boric acid and calcium chloride for crosslinking reaction to prepare composite biogel; and finally, soaking the composite biogel in a polyhexamethylene hydrochloric acid solution to prepare the biogel for the burn department, which can accelerate wound healing. The biological gel for the burn department, which is used for accelerating the healing of the wound surface, has excellent stability and thermal reversible self-repairing performance, and also has excellent biocompatibility, water absorption swelling property and broad-spectrum antibacterial performance.

Description

Biological gel for burn department for accelerating wound healing and preparation method thereof
Technical Field
The invention relates to the technical field of medical dressings, in particular to a biological gel for a burn department for accelerating wound healing and a preparation method thereof.
Background
Burns are skin injuries caused by contact with flames, hot liquids, vapors, hot surfaces, electricity, extreme acids, or extreme basic chemicals. Burns destroy the skin barrier which maintains homeostasis and prevents the invasion of pathogens, and in addition, the presence of a large amount of denatured and necrotic tissue and the exudation of protein-rich body fluids, bacteria multiply on the wound surface in large numbers, causing sepsis with bloody infections. It is still one of the leading causes of burn death, and the wound is the major source of burn infection.
The most common complication in the care of skin burn wounds is wound infection, a process accompanied by massive exudate, resulting in the breakdown of various growth factors and extracellular matrix, and the processes of epidermal growth and wound healing are hindered. The dressing is a medical material widely used in clinic for treating skin wounds, and can provide a moist environment for the wounds so as to accelerate the healing of the wounds. The traditional dressing mainly comprises dry gauze, oil gauze, a bandage and the like, is mainly woven by cotton fibers, has no antibacterial effect on infectious wounds, has limited seepage management capability and cannot promote wound healing.
Alginate has the characteristics of wide source, biocompatibility and no toxicity. The wound dressing prepared from the calcium alginate hydrogel has the advantages of providing a moist healing environment for wounds, stopping bleeding, being low in cost and the like, but has a single function, no antibacterial activity, insufficient mechanical properties of the gel and no self-repairing performance, and further application of the wound dressing is limited.
Collagen as a tissue component of an organism has a plurality of advantages when being used as a tissue scaffold material, but the application of the collagen is limited by the defects that the collagen has low mechanical strength, is easy to be hydrolyzed by protease when entering the organism and the like.
The bacterial nano-cellulose has wide source and low cost, and has unique natural nano-fiber three-dimensional network structure, ultrahigh water holding capacity, excellent mechanical strength in a wet state and good biocompatibility. The dressing can provide a moist environment for wounds, accords with the current wet therapy concept, and can be used as a novel medical dressing to replace traditional gauze.
The invention patent with the application number of CN201610020947.8 discloses a medical bacterial cellulose gel. The gel is prepared into seed liquid by selecting bacterial strains capable of secreting bacterial cellulose and activating the bacterial strains; adding gelatin into water, heating and stirring to prepare a gelatin solution with the mass percentage concentration of 5-15%; heating and dissolving alginic acid by using a sodium hydroxide solution with the concentration of 0.1mol/L to prepare a yellow sodium alginate milky solution with the mass percentage concentration of 5-10%; mixing the prepared seed liquid, gelatin solution and sodium alginate solution, and stirring uniformly; and adding glycerol into the mixed solution, blending for 0.5-1 h at 50-60 ℃, filtering the blended solution, and standing to obtain the glycerol-modified polypropylene composite material. However, the gel has the defects of poor structural stability, no antibacterial activity and single function.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a multifunctional biological gel for a burn department for accelerating wound healing and a preparation method thereof.
In order to achieve the above object, the present invention provides a method for preparing a biological gel for burn department, which accelerates the healing of a wound surface, comprising the following steps:
s1, preparing a gel-like bacterial nano cellulose wet film through fermentation culture, placing the bacterial nano cellulose wet film in deionized water, and performing high-speed shearing for 3-5 min to obtain bacterial nano cellulose pulp with a preset mass concentration; shading the bacterial nano-cellulose pulp, adding a predetermined amount of sodium periodate, carrying out oxidation reaction for 12-18 h at 35-45 ℃, and carrying out suction filtration washing and freeze drying after reaction to prepare modified bacterial nano-cellulose;
s2, adding deionized water into the modified bacterial nano-cellulose prepared in the step S1 and homogenizing at a high speed to prepare modified bacterial nano-cellulose dispersion liquid with a preset mass concentration; adding the modified bacterial nano cellulose dispersion liquid into a sodium alginate solution with a preset mass concentration, and stirring for 10-14 hours to obtain a uniformly mixed solution;
s3, adding collagen into deionized water, slowly stirring in a water bath at 35-40 ℃ until the collagen is uniformly swelled, and standing for 1-2 hours to obtain a collagen swelling solution; uniformly mixing the collagen swelling solution and the mixed solution prepared in the step S2, slowly stirring the mixture in one direction for 20-30 min at the temperature of 35-45 ℃ in a water bath, then soaking the mixture in a mixed crosslinking solution of boric acid and calcium chloride for 2-3 h, and washing the mixture to prepare the composite biological hydrogel;
s4, soaking the composite biological hydrogel prepared in the step S3 in a poly (hexamethylene) hydrochloric acid solution with a preset mass fraction for 0.5-1 h, taking out and removing excessive surface water, and preparing the biological gel for the burn department, which can accelerate wound healing.
Preferably, in the bacterial nanocellulose slurry of step S1, the mass concentration of the bacterial nanocellulose is 0.5 to 2 wt%.
Preferably, in step S1, the mass ratio of the sodium periodate to the bacterial nanocellulose is (2-3): 5.
preferably, in the mixed solution of step S2, the mass ratio of the modified bacterial nanocellulose to the sodium alginate is 1: (3-6).
Preferably, in step S3, the mass ratio of the collagen to the modified bacterial nanocellulose in the mixed solution is (1 to 3): 1.
preferably, in the mixed crosslinked aqueous solution of step S3, the boric acid is 0.5 to 2% by mass, and the calcium chloride is 1 to 2% by mass.
Preferably, in the polyhexamethylene hydrochloride solution of step S4, the mass fraction of the polyhexamethylene hydrochloride is 0.001 to 0.005%.
In order to achieve the purpose, the invention also provides a biological gel for the burn department, which is prepared by the preparation method and used for accelerating the healing of the wound surface. The biological gel for accelerating wound healing in the department of burns is prepared by carrying out double cross-linking reaction on modified bacteria nano cellulose, sodium alginate and collagen. The biological gel for the burn department for accelerating wound healing has self-healing capacity and antibacterial performance.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a preparation method of biological gel for accelerating wound healing in a burn department, which adopts modified bacteria nano cellulose, sodium alginate and collagen to carry out double cross-linking reaction to prepare the multifunctional biological gel for the burn department with self-repairing capability and excellent antibacterial property, and the mechanism is as follows:
1) the method takes sodium periodate as an oxidant, oxidizes and cracks the bacterial nano-cellulose, oxidizes hydroxyl on 2 and 3 positions of the bacterial nano-cellulose molecule, and prepares the modified bacterial nano-cellulose (dialdehyde bacterial nano-cellulose); and then, two aldehyde groups on the dialdehyde bacterial nano-cellulose react with amino groups on collagen molecules by using Schiff base crosslinking reaction to form a heat reversible imine bond, so that the modified nano-cellulose/collagen composite biological gel with certain self-repairing capability and stable thermodynamic structure is prepared.
2) The dialdehyde bacterial nano-cellulose and the sodium alginate are blended, and the blended solution is placed into boric acid/calcium chloride mixed crosslinking aqueous solution containing a predetermined amount of boric acid antibacterial agent for calcium crosslinking, so that the uniformly crosslinked ionic hydrogel with certain antibacterial performance is prepared. And then by an impregnation method, a cationic antibacterial agent polyhexamethylene hydrochloride solution with excellent spectrum antibacterial performance is introduced into the hydrogel, and boric acid and polyhexamethylene hydrochloride are cooperated to further remarkably improve the antibacterial performance of the composite hydrogel, so that the modified nano-cellulose/sodium alginate composite biogel with excellent antibacterial performance is prepared.
3) According to the invention, the Schiff base crosslinking reaction and the calcium crosslinking reaction are combined to prepare the composite biological hydrogel of a double crosslinking system, imine bond reversible crosslinking and ionic crosslinking are combined, and a sodium calcium alginate crosslinking network is taken as a support structure, so that the Schiff base crosslinking hydrogel with a three-dimensional nano-network structure and the calcium crosslinking ionic hydrogel support are mixed with each other to form a double crosslinking interpenetrating network structure, the mechanical property of the composite biological hydrogel is promoted, and the composite biological hydrogel also has excellent stability and thermal reversible self-repairing performance.
4) The preparation method provided by the invention integrates the excellent performances of the modified bacteria nano-cellulose/sodium alginate/collagen, and the prepared multifunctional composite biological hydrogel has a three-dimensional micro-nano-sized reticular structure, excellent biocompatibility and water-absorbing swelling property, can create a good wet healing environment for the burn wound, effectively prevents wound adhesion, and promotes the absorption and drainage of wound exudate of the burn wound; meanwhile, the mechanical property of the composite biological hydrogel is enhanced, the broad-spectrum antibacterial property is stable, the procoagulant property is obviously improved, pathogen invasion can be reduced, the forming speed of granulation tissues and re-epithelization is accelerated, and various functional multiple factors in the multifunctional composite hydrogel are combined, so that the function of accelerating the healing of burn wounds is cooperatively achieved.
Detailed Description
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a preparation method of biological gel for accelerating wound healing in a burn department, which comprises the following steps:
s1, preparing a gel-like bacterial nano cellulose wet film through fermentation culture, placing the bacterial nano cellulose wet film in deionized water, and performing high-speed shearing for 3-5 min to obtain bacterial nano cellulose pulp with a preset mass concentration; shading the bacterial nano-cellulose pulp, adding a predetermined amount of sodium periodate, carrying out oxidation reaction for 12-18 h at 35-45 ℃, and carrying out suction filtration washing and freeze drying after reaction to prepare modified bacterial nano-cellulose;
s2, adding deionized water into the modified bacterial nano-cellulose prepared in the step S1 and homogenizing at a high speed to prepare modified bacterial nano-cellulose dispersion liquid with a preset mass concentration; adding the modified bacterial nano cellulose dispersion liquid into a sodium alginate solution with a preset mass concentration, and stirring for 10-14 hours to obtain a uniformly mixed solution;
s3, adding collagen into deionized water, slowly stirring in a water bath at 35-40 ℃ until the collagen is uniformly swelled, and standing for 1-2 hours to obtain a collagen swelling solution; uniformly mixing the collagen swelling solution and the mixed solution prepared in the step S2, slowly stirring the mixture in one direction for 20-30 min at the temperature of 35-45 ℃ in a water bath, then soaking the mixture in a mixed cross-linking aqueous solution of boric acid and calcium chloride for 2-3 h, and washing the mixture to prepare the composite biological hydrogel;
s4, soaking the composite biological hydrogel prepared in the step S3 in a poly (hexamethylene) hydrochloric acid solution with a preset mass fraction for 0.5-1 h, taking out and removing excessive surface water, and preparing the biological gel for the burn department, which can accelerate wound healing.
Further, in the bacterial nano cellulose pulp of the step S1, the mass concentration of the bacterial nano cellulose is 0.5-2 wt%.
Further, in step S1, the mass ratio of the sodium periodate to the bacterial nanocellulose is (2-3): 5.
further, in the mixed solution of step S2, the mass ratio of the modified bacterial nanocellulose to the sodium alginate is 1: (3-6).
Further, in step S3, the mass ratio of the collagen to the modified bacterial nanocellulose in the mixed solution is (1-3): 1.
further, in the mixed crosslinked aqueous solution of step S3, the boric acid is 0.5 to 2% by mass, and the calcium chloride is 1 to 2% by mass.
Further, in the polyhexamethylene hydrochloride solution of step S4, the mass fraction of the polyhexamethylene hydrochloride is 0.001-0.005%.
The present invention is described in further detail below with reference to specific examples.
Example 1
A preparation method of biological gel for burn department for accelerating wound healing comprises the following steps:
s1, inoculating the activated strain into a liquid fermentation culture medium, standing and culturing at 30 ℃ for 10 days to prepare a bacterial nano cellulose membrane, taking out the bacterial nano cellulose membrane, washing with deionized water, immersing the bacterial nano cellulose membrane into a 1% NaOH solution, treating at 80 ℃ for 4 hours, repeating for many times to remove residual bacteria and the culture medium, washing with deionized water to neutrality, and sterilizing at 121 ℃ for 20 min to obtain a white semi-transparent gelatinous bacterial nano cellulose wet membrane; placing the wet bacterial nano cellulose membrane in deionized water, and carrying out high-speed shearing for 3-5 min to obtain bacterial nano cellulose pulp with the mass concentration of 1.2 wt%; and (2) carrying out light-resistant treatment on the bacterial nano cellulose pulp, adding sodium periodate, carrying out oxidation reaction for 18h at 40 ℃, carrying out suction filtration washing and freeze drying after the reaction is finished, and preparing the modified bacterial nano cellulose. Wherein the mass ratio of the sodium periodate to the bacterial nanocellulose is 1: 2.
s2, adding deionized water into the modified bacterial nano-cellulose prepared in the step S1, and homogenizing at a high speed to prepare 100ml of modified bacterial nano-cellulose dispersion liquid with the mass concentration of 2.0 wt%; adding the modified bacterial nano cellulose dispersion liquid into 400ml of sodium alginate solution with the mass concentration of 2.0wt%, and stirring for 14h to obtain a uniformly mixed liquid;
s3, adding collagen into deionized water, slowly stirring in a water bath at 40 ℃ until the collagen is uniformly swelled, and standing for 1h to obtain 200ml of collagen swelling solution with the mass concentration of 2.0 wt%; uniformly mixing the collagen swelling solution and the mixed solution prepared in the step S2, slowly stirring the mixture in one direction for 25min in a water bath at 40 ℃, then putting the mixture into a mixed cross-linking aqueous solution of boric acid and calcium chloride for soaking for 2.5h, and washing the mixture to be neutral by deionized water to prepare the composite biological hydrogel; wherein, in the mixed crosslinking aqueous solution, the mass fraction of the boric acid is 2 percent, and the mass fraction of the calcium chloride is 2 percent.
S4, soaking the composite biological hydrogel prepared in the step S3 in 0.005% by mass of polyhexamethylene hydrochloride solution for 1 hour, taking out and removing excessive surface water, and preparing the biological gel for the burn department, which can accelerate wound healing.
In this embodiment, in step S1, sodium periodate (NaIO) is used4) As an oxidant, carrying out oxidative cracking on hydroxyl groups on 2 and 3 positions of a bacterial nano-cellulose molecule to prepare dialdehyde bacterial nano-cellulose, wherein the reaction is as follows:
Figure DEST_PATH_IMAGE002
in step S3, first, two aldehyde groups on the dialdehyde bacterial nanocellulose are reacted with amino groups on the collagen molecule by schiff base crosslinking reaction to form the thermo-reversible imine linkage crosslinked hydrogel. Then, carrying out calcium crosslinking reaction on sodium alginate to obtain the ionic hydrogel. According to the invention, imine bond crosslinked hydrogel and calcium crosslinked ionic hydrogel are subjected to combined reaction, so that Schiff base crosslinked hydrogel with a three-dimensional nano-network structure and calcium crosslinked ionic hydrogel are mixed with each other to form a double-crosslinked interpenetrating network structure, the mechanical property of the composite biological hydrogel is promoted, and the composite biological hydrogel is stable in structure. Meanwhile, the composite biological hydrogel has more pores which are communicated with each other, thereby being beneficial to the transportation of nutrients and gas transmission required by the survival of cells.
The preparation method provided by the invention integrates the excellent performances of the modified bacteria nano-cellulose/sodium alginate/collagen, and the prepared multifunctional composite biological hydrogel has a three-dimensional nano-mesh structure, excellent biocompatibility and water-absorbing swelling property, can create a good wet healing environment for the burn wound, effectively prevents wound adhesion, and promotes the absorption and drainage of wound exudates of the burn wound; meanwhile, the mechanical property of the composite biological hydrogel is enhanced, the broad-spectrum antibacterial property is stable, the procoagulant property is obviously improved, pathogen invasion can be reduced, the forming speed of granulation tissues and re-epithelization is accelerated, and all functions in the multifunctional composite hydrogel are combined, so that the function of accelerating the healing of burn wounds is cooperatively achieved.
Examples 2 to 5
The difference from example 1 is that: the mass ratio of collagen to modified bacterial nanocellulose was set differently, and the mass ratio of modified bacterial nanocellulose to sodium alginate was set differently, and the other steps were the same as in example 1, and are not repeated here, and the parameter settings are shown in table 1.
Table 1 shows the parameter settings of examples 1 to 5
Examples M (collagen): m (modified bacteria nanocellulose) M (sodium alginate): m (modified bacteria nanocellulose)
Example 1 2:1 4:1
Example 2 1:1 4:1
Example 3 3:1 4:1
Example 4 2:1 3:1
Example 5 2:1 6:1
According to the invention, amino groups in collagen and aldehyde groups of modified bacteria nano-cellulose are subjected to Schiff base reaction, the consumption rate of the aldehyde groups of the modified bacteria nano-cellulose is increased and then is stable and basically unchanged along with the increase of the mass ratio of the collagen to the modified bacteria nano-cellulose, the aldehyde groups on the surface modified bacteria nano-cellulose molecules are reacted with the amino groups on the collagen thoroughly, and the Schiff base crosslinking reaction hydrogel generated by the method has a stable structure, has more excellent stability compared with hydrogel maintained through hydrogen bonding, and has a certain thermal reversible self-repairing function.
In the invention, the sodium calcium alginate crosslinked hydrogel is of a support structure, and the Schiff base crosslinked hydrogel with a three-dimensional nano-network structure and the calcium crosslinked hydrogel form a double-crosslinked interpenetrating network structure, thereby playing an internal supporting role and enabling the hydrogel structure to be more stable. With the reduction of the mass ratio of the sodium alginate to the modified bacteria nano-cellulose, the average pore diameter in the hydrogel is reduced and more uniform, the compactness of the hydrogel is enhanced, the probability of pathogen invasion is favorably reduced, and the air permeability is slightly reduced.
Comparative example 1
The difference from example 1 is that: in step S1, the sodium periodate was not subjected to the oxidative modification reaction, and bacterial nanocellulose without modification treatment was prepared.
Compared with the embodiment 1, the hydrogel generated by the bacterial nano cellulose and the collagen in the comparative example 1 is maintained only by the action of hydrogen bonds, the structure is extremely unstable, the hydrogel is easily damaged by the action of external force, and the hydrogel does not have the thermal reversible self-repairing performance.
Comparative example 2
The difference from example 1 is that: in step S3, a calcium crosslinking aqueous solution containing 2% by mass of calcium chloride is used.
Comparative example 3
The difference from example 1 is that: the immersion step of the polyhexamethylene hydrochloride solution of step S4 is not performed.
Comparative example 4
The difference from example 1 is that: a blank control was run without using the boric acid solution and the polyhexamethylene hydrochloride solution.
Bacteriostatic tests of Staphylococcus aureus and Escherichia coli were performed for example 1 and comparative examples 2 to 4, and the results are shown in Table 2. (qualitative detection method of antibacterial property of material adopts antibacterial ring method, according to GB/T20944.1-2007 standard, Staphylococcus aureus and Escherichia coli are selected for testing.)
Table 2 shows the antibacterial performance parameters of example 1 and comparative examples 2 to 4
Examples Staphylococcus aureus antibacterial band width Width of bacteriostatic band for colibacillus
Example 1 3.0mm 2.0mm
Comparative example 2 2.5mm 1.5mm
Comparative example 3 2.5mm 1.0mm
Comparative example 4 Without bacteriostatic zone Without bacteriostatic zone
The composite biological hydrogel prepared in comparative example 4 without the antibacterial agent treatment has no inhibition zone in the culture dish of staphylococcus aureus and escherichia coli, and bacteria below the hydrogel are not inhibited, i.e. the composite hydrogel does not show antibacterial performance.
In comparative example 2, after the poly hexamethylene hydrochloric acid solution is adopted for soaking, the hydrogel shows obvious antibacterial performance, and the antibacterial broadband of staphylococcus aureus and escherichia coli reaches 2.5mm and 1.5mm respectively.
In comparative example 3, after boric acid is adopted, the bacteriostatic broad bands of staphylococcus aureus and escherichia coli of the hydrogel reach 2.5mm and 1.0mm respectively.
In the embodiment 1, the boric acid and polyhexamethylene hydrochloride solution is adopted to treat the hydrogel, and when combined antibiosis is carried out, the bacteriostatic broad bands of staphylococcus aureus and escherichia coli respectively reach 3.0mm and 2.0mm, which shows that the two are synergistic, the antibacterial performance of the composite hydrogel is effectively improved, pathogen invasion and bacterial infection can be effectively prevented, and the healing speed of burn wounds is further accelerated.
In conclusion, the invention provides biological gel for the burn department for accelerating wound healing and a preparation method thereof. Firstly, carrying out oxidation reaction on bacterial nano-cellulose by adopting sodium periodate to prepare modified bacterial nano-cellulose; then dispersing the bacterial nano cellulose into water to prepare modified bacterial nano cellulose dispersion liquid, and mixing the modified bacterial nano cellulose dispersion liquid with a sodium alginate solution to obtain a mixed solution; then, mixing and stirring the mixed solution and the collagen swelling solution, and then placing the mixture in a mixed crosslinking aqueous solution of boric acid and calcium chloride for crosslinking reaction to prepare composite biogel; and finally, soaking the composite biogel in a polyhexamethylene hydrochloric acid solution to prepare the biogel for the burn department, which can accelerate wound healing. The biological gel for the burn department, which is used for accelerating the healing of the wound surface, has excellent stability and thermal reversible self-repairing performance, and also has excellent biocompatibility, water absorption swelling property and broad-spectrum antibacterial performance.
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions deviate from the technical solutions of the embodiments of the present invention.

Claims (8)

1. A preparation method of biological gel for burn department for accelerating wound healing is characterized in that: the method comprises the following steps:
s1, preparing a gel-like bacterial nano cellulose wet film through fermentation culture, placing the bacterial nano cellulose wet film in deionized water, and performing high-speed shearing for 3-5 min to obtain bacterial nano cellulose pulp with a preset mass concentration; shading the bacterial nano-cellulose pulp, adding a predetermined amount of sodium periodate, carrying out oxidation reaction for 12-18 h at 35-45 ℃, and carrying out suction filtration washing and freeze drying after reaction to prepare modified bacterial nano-cellulose;
s2, adding deionized water into the modified bacterial nano-cellulose prepared in the step S1 and homogenizing at a high speed to prepare modified bacterial nano-cellulose dispersion liquid with a preset mass concentration; adding the modified bacterial nano cellulose dispersion liquid into a sodium alginate solution with a preset mass concentration, and stirring for 10-14 hours to obtain a uniformly mixed solution;
s3, adding collagen into deionized water, slowly stirring in a water bath at 35-40 ℃ until the collagen is uniformly swelled, and standing for 1-2 hours to obtain a collagen swelling solution; uniformly mixing the collagen swelling solution and the mixed solution prepared in the step S2, slowly stirring the mixture in one direction for 20-30 min at the temperature of 35-45 ℃ in a water bath, then soaking the mixture in a mixed cross-linking aqueous solution of boric acid and calcium chloride for 2-3 h, and washing the mixture to prepare the composite biological hydrogel;
s4, soaking the composite biological hydrogel prepared in the step S3 in a poly (hexamethylene) hydrochloric acid solution with a preset mass fraction for 0.5-1 h, taking out and removing excessive surface water, and preparing the biological gel for the burn department, which can accelerate wound healing.
2. The method for preparing a biogel for burn department for accelerating wound healing according to claim 1, which is characterized in that: in the bacterial nano cellulose pulp obtained in the step S1, the mass concentration of the bacterial nano cellulose is 0.5-2 wt%.
3. The method for preparing a biogel for burn department for accelerating wound healing according to claim 2, which is characterized in that: in step S1, the mass ratio of the sodium periodate to the bacterial nanocellulose is (2-3): 5.
4. the method for preparing a biogel for burn department for accelerating wound healing according to claim 1, which is characterized in that: in the mixed solution of step S2, the mass ratio of the modified bacterial nanocellulose to the sodium alginate is 1: (3-6).
5. The method for preparing a biogel for burn department for accelerating wound healing according to claim 4, which is characterized in that: in step S3, the mass ratio of the collagen to the modified bacterial nanocellulose in the mixed solution is (1-3): 1.
6. the method for preparing a biogel for burn department for accelerating wound healing according to claim 1, which is characterized in that: in the mixed crosslinking aqueous solution of step S3, the boric acid is 0.5 to 2% by mass, and the calcium chloride is 1 to 2% by mass.
7. The method for preparing a biogel for burn department for accelerating wound healing according to claim 1, which is characterized in that: in the polyhexamethylene hydrochloride solution of step S4, the mass fraction of the polyhexamethylene hydrochloride is 0.001-0.005%.
8. The biological gel for burn department for accelerating wound healing, which is prepared by the preparation method of the biological gel for burn department for accelerating wound healing according to any one of claims 1 to 7, and is characterized in that: the biological gel for accelerating wound healing in the department of burns is prepared by carrying out double cross-linking reaction on modified bacteria nano cellulose, sodium alginate and collagen.
CN202010310035.0A 2020-04-20 2020-04-20 Biological gel for burn department for accelerating wound healing and preparation method thereof Expired - Fee Related CN111320770B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010310035.0A CN111320770B (en) 2020-04-20 2020-04-20 Biological gel for burn department for accelerating wound healing and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010310035.0A CN111320770B (en) 2020-04-20 2020-04-20 Biological gel for burn department for accelerating wound healing and preparation method thereof

Publications (2)

Publication Number Publication Date
CN111320770A true CN111320770A (en) 2020-06-23
CN111320770B CN111320770B (en) 2021-01-12

Family

ID=71166429

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010310035.0A Expired - Fee Related CN111320770B (en) 2020-04-20 2020-04-20 Biological gel for burn department for accelerating wound healing and preparation method thereof

Country Status (1)

Country Link
CN (1) CN111320770B (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112442200A (en) * 2020-11-29 2021-03-05 宁波工程学院 Preparation method of bacterial cellulose composite collagen self-assembly material
CN115337464A (en) * 2022-08-15 2022-11-15 成都斐洛智凝生物科技有限公司 Preparation method of modified bacterial cellulose membrane for periodontal tissue repair
CN115721767A (en) * 2022-12-12 2023-03-03 广东省人民医院 Antibacterial healing-promoting porous medical dressing and preparation method thereof
CN115970040A (en) * 2022-12-16 2023-04-18 北京科技大学 Hydrogel patch capable of being bonded on wet surface and being easily replaced and promoted to repair and preparation method thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102924613A (en) * 2012-11-01 2013-02-13 海南大学 Preparation method of dialdehyde bacterial cellulose
CN103536954A (en) * 2013-10-22 2014-01-29 山东颐诺生物科技有限公司 Crosslinked alginate-bacterial cellulose sponge and preparation method thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102924613A (en) * 2012-11-01 2013-02-13 海南大学 Preparation method of dialdehyde bacterial cellulose
CN103536954A (en) * 2013-10-22 2014-01-29 山东颐诺生物科技有限公司 Crosslinked alginate-bacterial cellulose sponge and preparation method thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HUIQIONG YAN, ET AL.: "A novel and homogeneous scaffold material: preparation and evaluation of alginate/bacterial cellulose nanocrystals/collagen composite hydrogel for tissue engineering", 《POLYM. BULL.》 *
I. SULAEVA, ET AL.: "Fabrication of bacterial cellulose-based wound dressings with improved performance by impregnation with alginate", 《MATERIALS SCIENCE & ENGINEERING C》 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112442200A (en) * 2020-11-29 2021-03-05 宁波工程学院 Preparation method of bacterial cellulose composite collagen self-assembly material
CN115337464A (en) * 2022-08-15 2022-11-15 成都斐洛智凝生物科技有限公司 Preparation method of modified bacterial cellulose membrane for periodontal tissue repair
CN115337464B (en) * 2022-08-15 2023-12-15 成都斐洛智凝生物科技有限公司 Preparation method of modified bacterial cellulose membrane for periodontal tissue repair
CN115721767A (en) * 2022-12-12 2023-03-03 广东省人民医院 Antibacterial healing-promoting porous medical dressing and preparation method thereof
CN115721767B (en) * 2022-12-12 2024-03-12 广东省人民医院 Antibacterial healing-promoting porous medical dressing and preparation method thereof
CN115970040A (en) * 2022-12-16 2023-04-18 北京科技大学 Hydrogel patch capable of being bonded on wet surface and being easily replaced and promoted to repair and preparation method thereof

Also Published As

Publication number Publication date
CN111320770B (en) 2021-01-12

Similar Documents

Publication Publication Date Title
CN111320770B (en) Biological gel for burn department for accelerating wound healing and preparation method thereof
CN112724459B (en) Preparation method of antibacterial hydrogel with uniformly dispersed and controllable release antibacterial agent
CN111632190B (en) Preparation method of medical biogel hemostatic dressing
CN110507842B (en) Bacterial cellulose/hyaluronic acid/epsilon-polylysine functional dressing and preparation method thereof
CN113817181B (en) Carbon quantum dot modified double-network hydrogel and preparation method thereof
CN110639050A (en) Silk fibroin nanofiber and preparation method of silver-loaded antibacterial dressing based on silk fibroin nanofiber
CN114000349A (en) Alginate-encapsulated bacterial cellulose composite photo-thermal antibacterial medical dressing and preparation method thereof
CN110747534A (en) Antibacterial polysaccharide fiber material and preparation method thereof
CN112480434A (en) Copper ion antibacterial hydrogel and preparation method and application thereof
Fan et al. The novel alginate/N‐succinyl‐chitosan antibacterial blend fibers
CN106344954A (en) Bio-antimicrobial bacterial cellulose dressing and preparation method thereof
CN113456877A (en) Organosilicon foam medical dressing and preparation method and application thereof
CN112587717A (en) Metal cation crosslinked alginate/bacterial cellulose composite hydrogel antibacterial dressing
CN104606710B (en) A kind of preparation method of high antibiotic property alginate dressing
Hassabo et al. Natural polymers in medical textiles
CN111118878A (en) Silver ion alginate wound dressing and preparation method thereof
CN115850733B (en) Nanoclay hydrogel for injection and preparation method and application thereof
CN101700408A (en) Novel gluconacetobacter xylinus cellulose hydrogel dressing and manufacturing method thereof
CN107496971B (en) Bacterial cellulose/lactoferrin antibacterial dressing and preparation method thereof
CN116407674A (en) Preparation method of tannic acid-loaded high-strength self-healing antibacterial hydrogel
CN110947022A (en) Preparation method of chitosan-based composite antibacterial dressing
CN113069590B (en) Preparation method of regenerated bacterial cellulose composite hydrogel dressing
CN113005633A (en) Antibacterial nanofiber membrane and preparation method and application thereof
CN107080856B (en) Bacterial cellulose-chitosan-laponite composite wound dressing and preparation method thereof
CN115531603B (en) Multifunctional polymer hydrogel dressing and preparation method thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
CB02 Change of applicant information

Address after: No.29-31 Huancheng North Road, Panlong District, Kunming City, Yunnan Province

Applicant after: Zhang Bingqi

Address before: 350005 No. 102, Gudong Road, Gulou District, Fuzhou City, Fujian Province

Applicant before: Zhang Bingqi

CB02 Change of applicant information
CB03 Change of inventor or designer information
CB03 Change of inventor or designer information

Inventor after: Chen Lei

Inventor after: Jiang Lili

Inventor after: Fang Jing

Inventor after: Zhang Bingqi

Inventor before: Zhang Bingqi

TA01 Transfer of patent application right

Effective date of registration: 20201222

Address after: 266000 Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Southern District of Qingdao City, Shandong Province

Applicant after: THE AFFILIATED HOSPITAL OF QINGDAO University

Address before: No. 29-31, Huancheng North Road, Panlong District, Kunming City, Yunnan Province

Applicant before: Zhang Bingqi

TA01 Transfer of patent application right
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20210112

Termination date: 20210420

CF01 Termination of patent right due to non-payment of annual fee