CN111135340A - Biological cellulose composite gel material and application thereof as wound dressing - Google Patents

Biological cellulose composite gel material and application thereof as wound dressing Download PDF

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Publication number
CN111135340A
CN111135340A CN201811311462.XA CN201811311462A CN111135340A CN 111135340 A CN111135340 A CN 111135340A CN 201811311462 A CN201811311462 A CN 201811311462A CN 111135340 A CN111135340 A CN 111135340A
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protein
gel material
composite gel
biological cellulose
preparing
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CN111135340B (en
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钟春燕
钟宇光
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Hainan Guangyu Biotechnology Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use 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
    • 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
    • A61L26/0052Mixtures of macromolecular compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • A61L26/0066Medicaments; 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
    • 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
    • A61L2300/252Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
    • 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
    • A61L2300/41Anti-inflammatory agents, e.g. NSAIDs
    • 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
    • A61L2300/412Tissue-regenerating or healing or proliferative agents

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

The invention relates to a new material of a biological cellulose composite gel and a new application thereof in preparing wound dressing products. The composite gel provided by the invention is formed by compounding a biological cellulose hydrogel and a protein thixotropic gel. The biological cellulose hydrogel has high water content, good water retention and enough mechanical strength. And protein gel is formed in the space structure of the biological cellulose, which can maintain the space structure of the biological cellulose hydrogel and promote the adhesion and proliferation of cells. The adhesive can also form a protein thixotropic gel, and the protein thixotropic gel is converted into protein sol from the protein gel by mechanical pressing before or during use to further promote the adhesion and proliferation of cells, slowly release globulin which is not converted into gel, further improve the antibacterial and anti-inflammatory properties of the dressing and promote wound healing.

Description

Biological cellulose composite gel material and application thereof as wound dressing
Technical Field
The application relates to a new material, in particular to a new biological cellulose composite gel material and a new application thereof in preparing wound dressing products.
Background
Wound dressings, generally referred to as wound dressings, are used to cover wounds or other wounds, to protect the wound from external mechanical, contamination and chemical stimuli, to prevent secondary infections, to prevent desiccation and loss of body fluids and heat. Traditional wound dressings are primarily dry gauze and oil gauze. However, dry gauze cannot be used for infected wounds, has no promoting effect on wound healing, has limited exudate management capacity, also adheres to the wound, causes re-damage to the neoepithelium and causes bleeding. The oil gauze contains vaseline or triglyceride, which can play a role in preventing the wound from being adhered, but also has no promotion effect on the wound healing and limited liquid seepage management capability. Modern medicine has developed many new types of wound dressings, such as interactive dressings, antimicrobial dressings, foam dressings, gel dressings, and the like.
Biocellulose (Biocellulose) is a hydrogel produced by the metabolism of certain microorganisms of the Acetobacter genus. Compared with plant cellulose, the biological cellulose does not contain associated products such as lignin, pectin, hemicellulose and the like, and has high crystallinity and high polymerization degree. The biological cellulose also has a hyperfine spatial network structure, so the elastic modulus and the tensile strength are high. In addition, the biological cellulose also has excellent water retention property. CN101586309A discloses a preparation method of a bacterial cellulose membrane compounded with simple substance nano silver in situ, and discloses that the bacterial cellulose membrane is used for preparing large-area wound dressings. The specific mode is that a purified bacterial cellulose membrane is immersed in a silver ammonia solution, and after being washed by water, the bacterial cellulose membrane is immersed in a chemical reagent solution containing aldehyde groups for reaction, and the obtained Ag is attached to a grid structure of the bacterial cellulose membrane, so that the bacterial cellulose membrane containing the simple substance nano silver is obtained. CN101708341A also discloses a silver-loaded bacterial cellulose hydrogel antibacterial dressing, which is prepared by soaking a bacterial cellulose hydrogel film in a silver metal precursor solution, then autoclaving, washing, partially dehydrating, packaging and sterilizing. The obtained silver-loaded bacterial cellulose hydrogel antibacterial dressing has the characteristics of good antibacterial performance, high water content, good water retention, strong toughness, good air permeability and the like, and can meet the requirements of wet treatment of various wounds.
However, since the space structure of the biocellulose hydrogel is dense, it is not easily absorbed by the human body, and the dense mesh often limits the adhesion and proliferation of cells during the use process. This limits the use of bio-cellulose in wound dressings.
Protein gels are a phenomenon of aggregation of protein molecules. After the protein molecules are denatured by heating, under specific conditions, such as pH, temperature, ionic environment, etc., an aqueous gel is formed. The gel can also obtain thixotropic gel due to different external environments, and the thixotropic gel has thixotropy and can be changed into sol without heating as long as mechanical force such as shaking and the like is applied; it can be left standing for a certain time without cooling, and can be changed from sol to gel.
Disclosure of Invention
Aiming at the defects, the invention provides a novel composite gel material which is compounded by biological cellulose hydrogel and protein gel.
The above-mentioned biocellulose hydrogels can be prepared by conventional methods in the art, for example, using coconut water medium or artificially prepared medium; prepared by using microorganisms such as gluconacetobacter xylinus, acetobacter xylinus and the like; the membrane may be cultured by static fermentation or dynamic culture in a tray, but it is preferably a biological cellulose hydrogel membrane obtained by using a coconut water medium and culturing gluconacetobacter xylinus by static fermentation in a tray.
The protein gel described above is preferably a protein thixotropic gel.
The invention also provides application of the composite gel material in preparing wound dressings.
The protein for preparing the protein gel is selected from various animal proteins and vegetable proteins, such as globulin, ovalbumin, lactalbumin, collagen, and soybean protein. Preferably, globulin is used.
The invention also provides a preparation method of the composite gel material, which comprises the following steps:
1) preparing a biological cellulose hydrogel film;
2) dehydrating the biological cellulose hydrogel membrane, soaking the membrane in a protein solution, ultrasonically vibrating for 3-24 hours, taking out the membrane, and cleaning the membrane with clear water for later use;
3) taking a salt solution, adjusting the pH value to 3-6, heating to 60-100 ℃, immersing the film obtained in the step 2), and heating and preserving heat for 1-36 hours;
4) taking out the clean water and cleaning.
In the above method, the biocellulose hydrogel membrane is preferably cultured by static fermentation, and the biocellulose hydrogel membrane is preferably partially dehydrated to a water content of 40-60%.
In the above method, the protein solution is an animal protein solution or a plant protein solution. More preferably an animal protein solution. More preferably selected from the group consisting of globulin, ovalbumin, lactalbumin, collagen. Most preferably, a solution of globulin having a concentration of 0.1-3wt% in the protein solution is used.
In the above method, the time of the ultrasonic oscillation may be selected according to the frequency of the ultrasonic wave, and is preferably 5 to 10 hours, more preferably 6 to 8 hours.
In the above method, the salt solution is preferably a sodium chloride solution or a calcium chloride solution. More preferably a sodium chloride solution with a concentration of 0.01-0.5M.
In the above method, the salt solution is preferably adjusted to a pH of 4.
In the above method, the salt solution is preferably heated to 70 to 80 ℃ and preferably kept at the temperature for 2 to 8 hours, more preferably 3 to 6 hours.
The composite gel provided by the invention is formed by compounding a biological cellulose hydrogel and a protein thixotropic gel. The biological cellulose hydrogel has high water content, good water retention and enough mechanical strength. And protein gel is formed in the space structure of the biological cellulose, which can maintain the space structure of the biological cellulose hydrogel and promote the adhesion and proliferation of cells. The adhesive can also form a protein thixotropic gel, and the protein thixotropic gel is converted into protein sol from the protein gel by mechanical pressing before or during use to further promote the adhesion and proliferation of cells, slowly release globulin which is not converted into gel, further improve the antibacterial and anti-inflammatory properties of the dressing and promote wound healing.
Detailed Description
To further illustrate the present invention, reference is made to the following examples:
example 1: preparation example 1 of composite gel Material
1) Preparing a biological cellulose hydrogel membrane by a static fermentation method: using coconut water culture medium, gluconacetobacter xylinus, fermenting and culturing for 7 days at 28 ℃ in a shallow tray, and collecting the biological cellulose hydrogel membrane on the liquid surface. Cleaning and purifying for later use;
2) dehydrating the biological cellulose hydrogel membrane by mechanical pressure until the water content is 60 percent, then soaking the biological cellulose hydrogel membrane in 0.7 weight percent of globulin solution, ultrasonically vibrating for 6 hours, taking out the biological cellulose hydrogel membrane, and washing the biological cellulose hydrogel membrane by clear water;
3) taking 0.05M sodium chloride solution, adjusting the pH value to 4 by using dilute hydrochloric acid, heating to 80 ℃, immersing the biological cellulose hydrogel film obtained in the step 2) into the solution, and heating and preserving heat for 5 hours;
4) taking out the clean water and cleaning.
Thus obtaining the composite gel material of the invention.
Example 2: preparation example 2 of composite gel Material
1) Preparing a biological cellulose hydrogel membrane by a static fermentation method: artificially prepared culture medium, gluconacetobacter xylinus, shallow tray fermentation at 29 ℃ for 9 days, and collecting the biological cellulose hydrogel membrane on the liquid surface. Cleaning and purifying for later use;
2) dehydrating the biological cellulose hydrogel membrane by mechanical pressure until the water content is 40 percent, then soaking the biological cellulose hydrogel membrane in an ovalbumin solution with the weight percent of 1 percent, ultrasonically vibrating for 8 hours, taking out the biological cellulose hydrogel membrane, and cleaning the biological cellulose hydrogel membrane with clear water;
3) taking 0.2M calcium chloride solution, adjusting the pH value to 5 by using dilute hydrochloric acid, heating to 70 ℃, immersing the biological cellulose hydrogel film obtained in the step 2) into the solution, and heating and preserving heat for 4 hours;
4) taking out the clean water and cleaning.
Example 3: preparation example 3 of composite gel Material
1) Preparing the biological cellulose hydrogel by a shaking table dynamic fermentation method: artificially preparing a culture medium, performing dynamic fermentation culture on acetobacter xylinum at 27 ℃ for 5 days by using a shaking table, collecting the biological cellulose hydrogel, and cleaning and purifying the biological cellulose hydrogel for later use;
2) pressing the collected biological cellulose hydrogel into a film by mechanical pressure, dehydrating the film to the water content of 70 percent, then soaking the film in 3 weight percent of soybean protein solution, ultrasonically vibrating the film for 16 hours, taking out the film and washing the film by clean water;
3) taking 0.1M sodium chloride solution, adjusting the pH value to 3 by using dilute hydrochloric acid, heating to 65 ℃, immersing the biological cellulose hydrogel film obtained in the step 2) into the solution, and heating and preserving heat for 6 hours;
4) taking out the clean water and cleaning.
Experimental example: wound healing promotion test of composite gel material in the invention
1) Wound healing: after anaesthesia, 25 adult mice were removed and a 2cm by 2cm wound was made by cutting the entire skin from the back of each mouse. Every 5 mice were divided into one group, and gauze soaked in physiological saline was used as dressing in the control group 1; the control group 2 had a biocellulose hydrogel as a dressing; example 1 group the composite gel material prepared in example 1 was used as a dressing; example 2 group composite gel material prepared in example 2 was used as dressing; example 3 group the composite gel material prepared in example 3 was used as a dressing. Dressing change was performed once a day for each mouse, the time to wound healing was recorded for each mouse, the mean values were taken for each group, and the results are recorded in table 1 below;
2) and (3) burn healing: after anaesthetizing 25 adult mice, the area of 2cm x 2cm was marked on the back of each mouse using gentian violet as marking water, 0.2ml of solidified gasoline was applied to the area, and the area was ignited for 15 seconds and extinguished, thus producing a shallow II degree burn wound. Every 5 mice were divided into one group, and gauze soaked in physiological saline was used as dressing in the control group 1; the control group 2 had a biocellulose hydrogel as a dressing; example 1 group the composite gel material prepared in example 1 was used as a dressing; example 2 group composite gel material prepared in example 2 was used as dressing; example 3 group the composite gel material prepared in example 3 was used as a dressing. Dressing change was performed once a day for each mouse, the time to wound healing was recorded for each mouse, the mean values were taken for each group, and the results are recorded in table 1 below;
TABLE 1 mouse wound healing test results
Figure 529686DEST_PATH_IMAGE001
It is apparent from the test results that the composite gel material of the present invention can promote wound healing, particularly the group of example 1 containing globulin, which can shorten the healing time by about one week compared to the control.

Claims (10)

1. The composite gel material for preparing the wound dressing is characterized by being compounded by biological cellulose hydrogel and protein gel.
2. The composite gel material of claim 1, wherein: the protein gel is a protein thixotropic gel.
3. The composite gel material according to claim 1 or 2, characterized in that: the protein from which the protein gel is made is selected from the group consisting of globulin, ovalbumin, lactalbumin, collagen, and soy protein.
4. The composite gel material of claim 3, wherein: the protein from which the protein gel is made is globulin.
5. A method of preparing a composite gel material as claimed in any preceding claim, characterised in that: the method comprises the following steps:
preparing a biological cellulose hydrogel film;
dehydrating the biological cellulose hydrogel membrane, soaking the membrane in a protein solution, ultrasonically vibrating for 3-24 hours, taking out the membrane, and cleaning the membrane with clear water for later use;
taking a salt solution, adjusting the pH value to 3-6, heating to 60-100 ℃, immersing the film obtained in the step 2), and heating and preserving heat for 1-36 hours;
taking out the clean water and cleaning.
6. The method for preparing a composite gel material according to claim 5, wherein: the biocellulose hydrogel membrane is cultured by static fermentation, and is partially dehydrated to a water content of 40-60%.
7. The method of preparing a composite gel material according to claim 6, wherein: the protein solution is 0.1-3wt% globulin solution.
8. The method for preparing a composite gel material according to claim 7, wherein: the salt solution is sodium chloride solution or calcium chloride solution with concentration of 0.01-0.5M.
9. The method for preparing a composite gel material according to claim 8, wherein: the salt solution is heated to 70-80 ℃ and is heated and insulated for 3-6 hours.
10. Use of a composite gel material as claimed in any one of claims 1 to 4 in the manufacture of a wound dressing.
CN201811311462.XA 2018-11-06 2018-11-06 Biological cellulose composite gel material and application thereof as wound dressing Active CN111135340B (en)

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CN113940898A (en) * 2020-07-17 2022-01-18 海南光宇生物科技有限公司 High-rehydration dry facial mask sheet
CN115382003A (en) * 2021-05-24 2022-11-25 海南光宇生物科技有限公司 Biological cellulose surgical suture without stitches taking off

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Publication number Priority date Publication date Assignee Title
CN113940898A (en) * 2020-07-17 2022-01-18 海南光宇生物科技有限公司 High-rehydration dry facial mask sheet
CN115382003A (en) * 2021-05-24 2022-11-25 海南光宇生物科技有限公司 Biological cellulose surgical suture without stitches taking off
CN115382003B (en) * 2021-05-24 2024-01-30 海南光宇生物科技有限公司 Biological cellulose operation suture line without disconnecting

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