CN111686297A - Antibacterial active dressing and preparation method thereof - Google Patents
Antibacterial active dressing and preparation method thereof Download PDFInfo
- Publication number
- CN111686297A CN111686297A CN202010379148.6A CN202010379148A CN111686297A CN 111686297 A CN111686297 A CN 111686297A CN 202010379148 A CN202010379148 A CN 202010379148A CN 111686297 A CN111686297 A CN 111686297A
- Authority
- CN
- China
- Prior art keywords
- dressing
- carboxymethyl cellulose
- sericin
- clindamycin
- stirring
- 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.)
- Pending
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/425—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/28—Polysaccharides or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/23—Carbohydrates
- A61L2300/232—Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
- A61L2300/406—Antibiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
- A61L2300/622—Microcapsules
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention relates to an antibacterial active dressing which comprises the following components in percentage by mass: 1 to 4 percent of sodium carboxymethylcellulose, 0.2 to 2 percent of sericin, 0.01 to 0.2 percent of carboxymethyl cellulose microsphere containing clindamycin and the balance of deionized water. According to the invention, clindamycin is loaded on carboxymethyl Cellulose Microspheres (CMs) to obtain carboxymethyl cellulose microspheres (CMs @ CLDM) with uniform particle size, so as to develop synergistically effective antibacterial microspheres, thereby reducing the addition of antibiotics without reducing antibacterial performance and simultaneously increasing the biocompatibility of the material; and based on the sericin/carboxymethyl cellulose dressing, the easy-degradation performance of the single carboxymethyl cellulose dressing can be improved, and the water stability and the cell adhesion performance of the CMC dressing are improved by adding the sericin.
Description
Technical Field
The invention relates to an antibacterial active dressing and a preparation method thereof, belonging to the technical field of medical biomaterials.
Background
The skin plays a key role in protecting the body from external invasion. The skin, which is the first layer in contact with the surrounding environment, is the largest layer and is more vulnerable to injury. Thus, the use of effective wound dressings has been considered as an effective way to accelerate the healing process. A suitable wound dressing should be able to provide optimal conditions around the wound, which best mimic the extracellular matrix (ECM) of the skin, to help allow epithelial cell movement, properly transfer oxygen, allow a moist environment, drain wound secretions, and largely prevent wound infection.
Sodium carboxymethylcellulose (CMC) -based dressings have received particular attention in this regard due to their richness, transparency, and low cost. The high hydrophilicity of CMC leads to a high absorption of wound exudate; it also provides a moist environment around the wound and prevents tissue desiccation, which is important in burn and diabetic wounds. Despite these improvements, CMC dressings have relatively poor cell adhesion and have been reported in previous studies. In addition, the lower antimicrobial activity and water stability limit their practical applicability as wound dressings. To compensate for this drawback, the mixing of CMC with other polymers is a viable solution. In addition to selecting CMC, selecting a naturally based protein may be closer to making a structure similar to natural ECM when making a dressing.
Sericin is a natural biomaterial derived from silk, and has excellent biocompatibility, low immunogenicity, natural cell adhesion, proliferation promoting effect and adjustable mechanical properties. Previous studies have demonstrated that sericin or a sericin derivative does not stimulate inflammatory responses in vitro and in vivo. In addition, the sericin has the advantages of simple preparation, low cost, convenient storage and long shelf life. Sericin-coated substrate L929 fibroblasts had better attachment and growth than collagen-coated substrate, sericin extracted from silkworm cocoon was more effective in healing wound because epithelial cells were almost completely regenerated.
The chitosan microsphere is a drug carrier material with wide application. However, chitosan has poor water solubility, and hydrochloric acid or acetic acid is added to increase the solubility during dissolution, and the acids are difficult to completely remove during cleaning and have certain irritation to cells. Compared with chitosan, the water solubility of sodium carboxymethylcellulose is greatly improved, so that the application range of the chitosan is expanded, and the characteristics of biocompatibility and the like of the chitosan are maintained.
Clindamycin is a potent antibiotic used to treat severe skin and soft tissue infections, particularly infections caused by staphylococcus aureus (s.
Aiming at the problem that the traditional antibiotic dressing dose can generate drug resistance greatly, the invention loads clindamycin on carboxymethyl Cellulose Microspheres (CMs) so as to improve antibacterial performance and biocompatibility and ensure that the dressing is suitable for healing skin wound surfaces. Also, in the preparation of dressings, the selection of a naturally based protein (sericin) may more closely resemble the structure of a natural cytoplasmic matrix, in addition to the selection of pure sodium carboxymethyl cellulose. The system is fully expandable to any other soluble drug, thereby achieving the effect of slow release of the drug in the dressing.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide an antibacterial active dressing and a preparation method thereof.
In order to achieve the purpose, the invention adopts the technical scheme that: an antibacterial active dressing comprises the following components in percentage by mass: 1 to 4 percent of sodium carboxymethylcellulose, 0.2 to 2 percent of sericin, 0.01 to 0.2 percent of carboxymethyl cellulose microsphere containing clindamycin and the balance of deionized water.
As a preferred embodiment of the dressing of the present invention, the dressing comprises the following components by mass: 2% of sodium carboxymethylcellulose, 1% of sericin, 0.1% of carboxymethyl cellulose microspheres containing clindamycin and the balance of deionized water.
As a preferred embodiment of the dressing of the present invention, the preparation method of the carboxymethyl cellulose microsphere containing clindamycin comprises:
(1) adding sodium carboxymethylcellulose and clindamycin into deionized water, then adding liquid paraffin and span 80, heating in a water bath, dropwise adding a gelatin solution to form a mixed solution, adding a cross-linking agent, and stirring for reaction;
(2) and after the reaction is finished, centrifuging the reaction solution to obtain a precipitate, washing, and freeze-drying the precipitate to obtain the carboxymethyl cellulose microsphere containing the clindamycin.
As a preferred embodiment of the dressing, the mass ratio of the sodium carboxymethyl cellulose to the clindamycin is (10-30): 1. preferably 20: 1.
As a preferred embodiment of the dressing, the rotation speed of the stirring reaction is 400-1000 rmp, the time of the stirring reaction is 2 hours, the centrifugation time is 1-10 min, and the cross-linking agent is glutaraldehyde. Preferably, the rotation speed of the stirring reaction is 600rmp and the centrifugation time is 3 min.
As a preferred embodiment of the dressing of the present invention, the preparation method of the clindamycin-containing carboxymethyl cellulose microsphere (CMs @ CLDM) comprises the following steps:
(1) weighing 0.3g of sodium carboxymethylcellulose and 0.03g of clindamycin, dissolving in 10mL of deionized water, then adding 10mL of liquid paraffin, adding magnetons, stirring, then adding 2mL of span 80 serving as an emulsifier, and heating in a water bath at 40 ℃;
(2) transferring 10mL of 3% prepared gelatin solution into a dropping funnel, and slowly dropping the gelatin solution into the reaction solution at the rotating speed of 400rmp until the dropping is finished (about 4h) to obtain a mixed solution;
(3) then adding 0.2mL of 5 wt% glutaraldehyde (20 uL each time and once every 20 minutes) as a cross-linking agent, keeping the rotating speed of 400rmp, and continuing stirring for reaction for 2 hours;
(4) centrifuging the reaction solution at the rotating speed of 4000rmp for 3min to obtain a precipitate, alternately washing the precipitate with isopropanol and absolute ethyl alcohol for 3 times, and freeze-drying the washed precipitate to obtain the carboxymethyl cellulose microsphere (CMs @ CLDM) containing clindamycin.
As a preferred embodiment of the dressing, the preparation method of the sericin comprises the following steps: cutting silkworm cocoon into pieces, washing with deionized water, and soaking in Na2CO3Boiling the solution, centrifuging, filtering to remove insoluble residue, dialyzing with deionized water, and lyophilizing to obtain sericin.
In a preferred embodiment of the dressing of the present invention, the boiling time is 0.5 to 2 hours, the rotation speed of the centrifugation is 1000 to 5000rpm, and the time of the centrifugation is 5 to 15 min. Preferably, the boiling time is 1h, the rotation speed of the centrifugation is 3500rpm, and the centrifugation time is 10 min.
As a preferred embodiment of the dressing of the present invention, the preparation method of sericin (Ser) comprises: extracting sericin from Bombyx Bombycis by hot and alkaline degumming, cutting 5.0g Bombyx Bombycis into pieces, washing with deionized water, soaking in 200mL of 0.02MNa2CO3Boiling the solution for 1 hour, then removing insoluble residues by centrifugation (3500rpm, 10 minutes) and filtration, dialyzing the reaction solution (MWCO 3.5kDa) against deionized water to remove Na2CO3Dialyzing for 2 days, and freeze-drying to obtain sericin.
In a second aspect, the present invention provides a method for preparing the dressing, comprising the steps of: adding sodium carboxymethylcellulose and sericin into deionized water, stirring until completely dissolving, adding carboxymethyl cellulose microspheres containing clindamycin, stirring to uniformly disperse the microspheres, pouring the reaction solution into a mold, freezing overnight, drying, and crosslinking to obtain the antibacterial active dressing.
As a preferable embodiment of the preparation method of the present invention, the time for stirring until complete dissolution is 3 hours, the time for stirring to uniformly disperse the microspheres is 15 minutes, and the temperature for freezing overnight is-70 ℃.
As a preferred embodiment of the preparation method of the invention, the temperature of the cross-linking is 70 ℃, and the time of the cross-linking is 72 h.
Compared with the prior art, the invention has the beneficial effects that:
(1) the invention takes sericin, sodium carboxymethylcellulose and carboxymethyl cellulose microspheres loaded by clindamycin as raw materials, prepares the three-dimensional antibacterial wound dressing with obviously interconnected porous structures by freeze drying, simulates an extracellular matrix structure, and has good mechanical properties and biocompatibility.
(2) According to the invention, clindamycin is loaded on carboxymethyl Cellulose Microspheres (CMs) to obtain carboxymethyl cellulose microspheres (CMs @ CLDM) with uniform particle size, so as to develop synergistically effective antibacterial microspheres, thereby reducing the addition of antibiotics without reducing antibacterial performance and simultaneously increasing the biocompatibility of the material; and based on the sericin/carboxymethyl cellulose dressing, the easy-degradation performance of the single carboxymethyl cellulose dressing can be improved, and the water stability and the cell adhesion performance of the CMC dressing are improved by adding the sericin.
(3) Aiming at the problem that the traditional antibiotic dressing dose can generate drug resistance greatly, clindamycin is loaded on carboxymethyl Cellulose Microspheres (CMs), so that the antibacterial performance and the biocompatibility can be improved, and the dressing is suitable for healing skin wound surfaces. The clindamycin releasing time of the composite dressing can reach 14 days, and the composite dressing has a good antibacterial effect on staphylococcus aureus and escherichia coli. Compared with the traditional dressing containing antibiotics, the carboxymethyl cellulose microsphere dressing loaded with clindamycin has very high bactericidal performance.
Drawings
FIG. 1 is an external view of dressings prepared in example 5 and comparative example 2; in which the left side is an appearance view of the dressing prepared in comparative example 2 and the right side is an appearance view of the dressing prepared in example 5.
FIG. 2 is a scanning electron micrograph of the dressings prepared in example 5 and comparative example 2; wherein, A is the scanning electron microscope image of the dressing prepared in comparative example 2, and B is the scanning electron microscope image of the dressing prepared in example 5.
Fig. 3 is a graph of the release profile of clindamycin from the dressings prepared in example 5 and comparative example 2.
FIG. 4 is a statistical graph of cell viability for the dressings prepared in examples 4-6 and comparative examples 1-2.
Detailed Description
To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to the accompanying drawings and specific embodiments.
Example 1
A carboxymethyl cellulose/sericin dressing (CMC/Ser) is prepared by the following steps: sodium carboxymethylcellulose powder (2g) and sericin (0.2g) were gradually added to 100mL of deionized water, followed by gentle stirring until complete dissolution, 0.1g of 5 wt.% citric acid (polymer weight) as a crosslinking agent and 0.06g of 3 wt.% glycerin (polymer weight) as a crosslinking extender were added, and then the mixture was poured into a polytetrafluoroethylene mold; subsequently, the molds were stored at-70 ℃ overnight, freeze-dried; then, crosslinking the sample at 70 ℃ for 72h to obtain the carboxymethyl cellulose/sericin dressing (CMC/Ser).
The preparation method of the sericin comprises the following steps: extracting sericin from Bombyx Bombycis by hot and alkaline degumming, cutting 5.0g Bombyx Bombycis into pieces, washing with deionized water, and soaking in 200mL 0.02M Na2CO3Boiling the solution for 1 hour, then removing insoluble residues by centrifugation (3500rpm, 10 minutes) and filtration, dialyzing the reaction solution (MWCO 3.5kDa) against deionized water to remove Na2CO3Dialyzing for 2 days, and freeze-drying to obtain sericin.
Example 2
A carboxymethyl cellulose/sericin dressing (CMC/Ser) is prepared by the following steps: sodium carboxymethylcellulose powder (2g) and sericin (1g) were gradually added to 100mL of deionized water, followed by gentle stirring until completely dissolved, 0.1g of 5 wt.% citric acid (polymer weight) as a crosslinking agent and 0.06g of 3 wt.% glycerin (polymer weight) as a crosslinking extender were added, and then the mixture was poured into a polytetrafluoroethylene mold; subsequently, the molds were stored at-70 ℃ overnight, freeze-dried; then, crosslinking the sample at 70 ℃ for 72h to obtain the carboxymethyl cellulose/sericin dressing (CMC/Ser).
Sericin was prepared by the same method as in example 1.
Example 3
A carboxymethyl cellulose/sericin dressing (CMC/Ser) is prepared by the following steps: sodium carboxymethylcellulose powder (2g) and sericin (2g) were gradually added to 100mL of deionized water, followed by gentle stirring until completely dissolved, 0.1g of 5 wt.% citric acid (polymer weight) as a crosslinking agent and 0.06g of 3 wt.% glycerin (polymer weight) as a crosslinking extender were added, and then the mixture was poured into a polytetrafluoroethylene mold; subsequently, the molds were stored at-70 ℃ overnight, freeze-dried; then, crosslinking the sample at 70 ℃ for 72h to obtain the carboxymethyl cellulose/sericin dressing (CMC/Ser).
Sericin was prepared by the same method as in example 1.
Example 4
A carboxymethyl cellulose/sericin/clindamycin microsphere dressing (CMC/Ser/CMs @ CLDM-01) comprises the following components in percentage by mass: 2% of sodium carboxymethylcellulose, 1% of sericin, 0.01% of carboxymethyl cellulose microspheres containing clindamycin and the balance of deionized water.
The preparation method comprises the following steps: gradually adding sodium carboxymethylcellulose powder (2g) and sericin (1g) into 100mL of deionized water, and then gently stirring until completely dissolved; stirring for about 3h, adding 50mg of carboxymethyl cellulose microsphere containing clindamycin, and stirring for 15min to uniformly disperse the microsphere on the carboxymethyl cellulose microsphere; pouring the mixture into a polytetrafluoroethylene mold, storing the mold at-70 ℃ overnight, and freeze-drying; then, crosslinking the sample at 70 ℃ for 72h to obtain the carboxymethyl cellulose/sericin/clindamycin microsphere dressing (CMC/Ser/CMs @ CLDM-01).
The preparation method of the carboxymethyl cellulose microsphere (CMs @ CLDM) containing clindamycin comprises the following steps:
(1) weighing 0.3g of sodium carboxymethylcellulose and 0.03g of clindamycin, dissolving in 10mL of deionized water, then adding 10mL of liquid paraffin, adding magnetons, stirring, then adding 2mL of span 80 serving as an emulsifier, and heating in a water bath at 40 ℃;
(2) transferring 10mL of 3% prepared gelatin solution into a dropping funnel, and slowly dropping the gelatin solution into the reaction solution at the rotating speed of 400rmp until the dropping is finished (about 4h) to obtain a mixed solution;
(3) then adding 0.2mL of 5 wt% glutaraldehyde (20 uL each time and once every 20 minutes) as a cross-linking agent, keeping the rotating speed of 400rmp, and continuing stirring for reaction for 2 hours;
(4) centrifuging the reaction solution at the rotating speed of 4000rmp for 3min to obtain a precipitate, alternately washing the precipitate with isopropanol and absolute ethyl alcohol for 3 times, and freeze-drying the washed precipitate to obtain the carboxymethyl cellulose microsphere (CMs @ CLDM) containing clindamycin.
Example 5
A carboxymethyl cellulose/sericin/clindamycin microsphere dressing (CMC/Ser/CMs @ CLDM-02) comprises the following components in percentage by mass: 2% of sodium carboxymethylcellulose, 1% of sericin, 0.1% of carboxymethyl cellulose microspheres containing clindamycin and the balance of deionized water.
The preparation method comprises the following steps: gradually adding sodium carboxymethylcellulose powder (2g) and sericin (1g) into 100mL of deionized water, and then gently stirring until completely dissolved; stirring for about 3h, adding 50mg of carboxymethyl cellulose microsphere containing clindamycin, and stirring for 15min to uniformly disperse the microsphere on the carboxymethyl cellulose microsphere; pouring the mixture into a polytetrafluoroethylene mold, storing the mold at-70 ℃ overnight, and freeze-drying; then, crosslinking the sample at 70 ℃ for 72h to obtain the carboxymethyl cellulose/sericin/clindamycin microsphere dressing (CMC/Ser/CMs @ CLDM-02).
The preparation of carboxymethyl cellulose microspheres (CMs @ CLDM) containing clindamycin was performed as described in example 4.
Example 6
A carboxymethyl cellulose/sericin/clindamycin microsphere dressing (CMC/Ser/CMs @ CLDM-03) comprises the following components in percentage by mass: 2% of sodium carboxymethylcellulose, 1% of sericin, 0.2% of carboxymethyl cellulose microspheres containing clindamycin and the balance of deionized water.
The preparation method comprises the following steps: gradually adding sodium carboxymethylcellulose powder (2g) and sericin (1g) into 100mL of deionized water, and then gently stirring until completely dissolved; stirring for about 3h, adding 50mg of carboxymethyl cellulose microsphere containing clindamycin, and stirring for 15min to uniformly disperse the microsphere on the carboxymethyl cellulose microsphere; pouring the mixture into a polytetrafluoroethylene mold, storing the mold at-70 ℃ overnight, and freeze-drying; then, crosslinking the sample at 70 ℃ for 72h to obtain the carboxymethyl cellulose/sericin/clindamycin microsphere dressing (CMC/Ser/CMs @ CLDM-03).
The preparation of carboxymethyl cellulose microspheres (CMs @ CLDM) containing clindamycin was performed as described in example 4.
Example 7
A carboxymethyl cellulose/sericin/clindamycin microsphere dressing (CMC/Ser/CMs @ CLDM-04) comprises the following components in percentage by mass: 1% of sodium carboxymethylcellulose, 0.2% of sericin, 0.01% of carboxymethyl cellulose microspheres containing clindamycin and the balance of deionized water.
The preparation method comprises the following steps: gradually adding sodium carboxymethylcellulose powder (1g) and sericin (0.2g) into 100mL of deionized water, and then gently stirring until completely dissolved; stirring for about 3h, adding 10mg of carboxymethyl cellulose microsphere containing clindamycin, and stirring for 15min to uniformly disperse the microsphere on the carboxymethyl cellulose microsphere; pouring the mixture into a polytetrafluoroethylene mold, storing the mold at-70 ℃ overnight, and freeze-drying; then, crosslinking the sample at 70 ℃ for 72h to obtain the carboxymethyl cellulose/sericin/clindamycin microsphere dressing (CMC/Ser/CMs @ CLDM-04).
The preparation of carboxymethyl cellulose microspheres (CMs @ CLDM) containing clindamycin was performed as described in example 4.
Example 8
A carboxymethyl cellulose/sericin/clindamycin microsphere dressing (CMC/Ser/CMs @ CLDM-05) comprises the following components in percentage by mass: 4% of sodium carboxymethylcellulose, 2% of sericin, 0.2% of carboxymethyl cellulose microspheres containing clindamycin and the balance of deionized water.
The preparation method comprises the following steps: gradually adding sodium carboxymethylcellulose powder (4g) and sericin (2g) into 100mL of deionized water, and then gently stirring until completely dissolved; stirring for about 3h, adding 200mg of carboxymethyl cellulose microspheres containing clindamycin, and stirring for 15min to uniformly disperse the microspheres on the carboxymethyl cellulose microspheres; pouring the mixture into a polytetrafluoroethylene mold, storing the mold at-70 ℃ overnight, and freeze-drying; then, crosslinking the sample at 70 ℃ for 72h to obtain the carboxymethyl cellulose/sericin/clindamycin microsphere dressing (CMC/Ser/CMs @ CLDM-05).
The preparation of carboxymethyl cellulose microspheres (CMs @ CLDM) containing clindamycin was performed as described in example 4.
Comparative example 1
A carboxymethyl cellulose dressing (CMC) is prepared by the following steps: CMC powder (2g) was gradually added to 100mL of deionized water, then gently stirred until completely dissolved, 0.1g of 5 wt% (polymer weight) citric acid as a cross-linking agent and 0.06g of 3 wt.% glycerol (polymer weight) as a cross-linking extender were added, and the mixture was poured into a teflon mold; subsequently, the molds were stored at-70 ℃ overnight, freeze-dried; then, the sample is crosslinked for 72h at 70 ℃ to obtain the carboxymethyl cellulose dressing (CMC).
Comparative example 2
A carboxymethyl cellulose/sericin/clindamycin (CMC/Ser/CLDM) dressing is prepared by the following steps: gradually adding CMC (2g) and sericin (1g) into 100mL of deionized water, and then gently stirring until completely dissolved; stirring for about 3h, adding 50mg of clindamycin, stirring for about 15min to make the solution uniform, and pouring the mixture into a polytetrafluoroethylene mold; subsequently, the molds were stored at-70 ℃ overnight, freeze-dried; then, the sample was crosslinked at 70 ℃ for 72 hours to obtain a carboxymethylcellulose/sericin/clindamycin (CMC/Ser/CLDM) dressing.
Examples of effects
(1) Dressing appearance
The appearance of the dressings prepared in example 5 and comparative example 2 is shown in fig. 1, and it can be seen that the dressings prepared in example 5 and comparative example 2 each exhibited a white, smooth-surfaced appearance.
(2) Scanning electron microscope image
And spraying gold on the prepared dressing, and then observing the dressing under a scanning electron microscope. The test conditions were: 5kV electron beam. Scanning electron micrographs of the dressings prepared in example 5 and comparative example 2 are shown in fig. 2, where a is the scanning electron micrograph of the dressing prepared in comparative example 2, and B is the scanning electron micrograph of the dressing prepared in example 5. As can be seen from FIG. 2, the dressing prepared in comparative example 2 has a porous network structure and a diameter of 50-60 μm. Furthermore, the embedding of the CMs @ CLDM microspheres within the dressing can be seen in the electron micrograph of the dressing prepared in example 5.
(3) Water absorption, water vapor transmission, porosity, tensile strength
Water absorption: water absorption is another characteristic of biological materials and should be considered especially when used as a wound dressing. To obtain the initial weight (W) of the sampleo) The dressing was weighed before soaking in deionized water. After soaking and incubation at 37 ℃ for about 24 hours, the swollen dressing is weighed again (W)s) While gently wiping off excess water with filter paper. The water absorption is obtained from the following equation:
water absorption (%) - (Ws-W)0)/W0
Water vapor transmission rate: water Vapor Transmission Rate (WVTR) is the ability of the prepared composite to control water loss. Briefly, the sample was mounted on top of a glass bottle (13 mm diameter) filled with deionized water. The edges are completely sealed by adhesive tapes, and the mixture is weighed and then placed into a constant temperature and humidity incubator with the relative humidity of 37 percent and the temperature of 32 +/-1 ℃. After 24 hours, the weight loss of the assembly was measured and plotted against time. The Water Vapor Transmission Rate (WVTR) is calculated according to the following formula:
WVTR＝(△m/△t)/A
wherein, Deltam/△ t is the moisture loss weight loss (g/day) for 24 hours, and A is the surface area (mm) of the bottle mouth2)。
Porosity: filling a pycnometer with ethanol, weighing its mass W1, immersing a sample with mass Ws in ethanol, degassing the ethanol in order to fill the pores of the porous dressing, and then filling with ethanol, weighing its mass W2After the ethanol-impregnated sample was taken out, the remaining ethanol and the weight of the pycnometer W3 were weighed. The assay was repeated 3 times for each sample and averaged. The porosity p is calculated as:
P＝(W2-W3-Ws)/(W1-W3)
tensile strength: the mechanical strength of the composite dressing is tested according to a testing method of pharmaceutical industry standard YY/T0471.4-2004, an electronic tensile testing machine is adopted to test the tensile strength and the elongation at break of the dressing, the bearing capacity is 500N, and the efficiency is within +/-1%. The method comprises the following specific steps: the sample was cut into a strip-shaped sample having a length of 90mm and a width of 25 mm. The thickness was measured with a vernier caliper and recorded. The sample was stretched under constant temperature and humidity conditions (temperature 25 ℃ C., relative humidity 70%) at a holding distance of 50mm and a stretching rate of 300 mm/min. The procedure was set up as specified in the test method, testing was performed, and the Tensile Strength (TS) of the dressing was recorded, with 5 sets of validation data per test.
TABLE 1
The water absorption, porosity, water vapor transmission rate, and tensile strength of the dressings prepared in examples 1 to 8 and comparative examples 1 to 2 are shown in table 1. As can be seen from Table 1, the water absorption of the prepared dressing in PBS buffer solution is 2000-3200%. This high water absorption is mainly due to the high hydrophilicity of carboxymethyl cellulose and the porous structure of the dressing. From the perspective of application of the dressing to a wound, the greater the water absorption rate, the more beneficial it is to rapidly absorb wound exudate and maintain a suitably moist healing environment. It can be seen that the dressing has the greatest water absorption at CMC carboxymethyl cellulose (2g) and sericin (1 g).
Water Vapor Transmission Rate (WVTR) is a key parameter for evaluating the effectiveness of a wound dressing. As can be seen from Table 1, the water vapor transmission rate of the blank control was 13391.52g/m224h, the water vapor permeability of the dressing is 1800-2800 g/m224 h. Compared with a blank control group without the dressing, the composite dressing can effectively reduce the loss of water vapor. Research shows that WVTR is 2000-2500 g/m2The dressing with 24h or so can keep better moisture content, thereby promoting the proliferation of epidermal cells and fibroblasts. It can be seen that the dressing has a suitable water vapour transmission rate at CMC carboxymethyl cellulose (2g) and sericin (1 g).
As can be seen from table 1, the porosity of the dressing ranged from 70% to 90%. In general, dressings with a porosity of 80% to 90% are considered to be dressings with better functionality. It can be seen that the porosity of the material is best at CMC carboxymethyl cellulose (2g) and sericin (1 g).
As can be seen from Table 1, the tensile strength of the dressing is in the range of 0.21 to 0.33 MPa. It is known that CMC carboxymethyl cellulose (2g) and sericin (1g) have the highest tensile strength and are suitable for application to skin wounds.
(4) Drug delivery
The 2 × 2cm dressings were cut out and placed in 50mL centrifuge tubes, 20mL PBS (pH 7.4) was added to each sample, and then the centrifuge tubes were placed in a 37 ℃ water bath, and samples were taken at the set time points, 1mL of supernatant was taken and collected in sterile centrifuge tubes, and assayed at-80 ℃. And (3) checking the sustained-release solution collected at each time point by using an ultraviolet spectrophotometer, measuring the absorbance (A) of the sustained-release solution at the maximum absorption wavelength of 210nm at each time point, and calculating the concentration of clindamycin contained in the corresponding sustained-release solution according to a standard curve so as to calculate the drug release amount at each time point.
The drug release profiles of the dressing systems prepared in example 5 and comparative example 2 are shown in figure 3. As can be seen from fig. 3, the dressing prepared in comparative example 2 was released substantially completely on day 2. The dressing prepared in example 5 showed a slow release tendency, and the total release rate of the antimicrobial peptide was about 87.21% by day 11, and it was not completely released, which was suspected that some of the drug was encapsulated by the CMs microspheres. The dressing prepared by the method has the function of continuously delivering the medicine.
(5) Antibacterial experiments
Zone of inhibition experiments adopted standards established by the american Clinical and Laboratory Standards Institute (CLSI), detailed procedures: sterilizing a laboratory clean bench, and starting ultraviolet irradiation for 30min before operation. Cutting dressing with size of 1C × 1cm with a puncher, dripping 100 μ L of the above bacterial suspension into solid LB culture medium, spreading uniformly with a spreading rod, sequentially sticking the above cut samples on the culture medium, standing for 15min, and placing the culture dish back into a 37 deg.C biochemical incubator for inverted culture for 24 h. Taking out the culture medium, observing the size of the inhibition zone and the growth condition of bacteria, and making three parallel samples in each group.
TABLE 2
The bacteriostatic effects of the dressings prepared in examples 4 to 8 and comparative example 2 on escherichia coli and staphylococcus aureus are shown in table 2. As can be seen from Table 2, the dressings prepared in examples 4 to 8 have an inhibitory zone against both Escherichia coli and Staphylococcus aureus. The dressing prepared in the embodiment 6 and the dressing prepared in the embodiment 8 have the largest antibacterial performance, the dressing prepared in the embodiment 5, the dressing prepared in the embodiments 6-8 and the dressing prepared in the comparative example 2 have no obvious difference in bacteriostasis zone, and the dressing prepared in the embodiment 5 is selected as the optimal group in consideration of certain cytotoxicity caused by high clindamycin concentration. In-vitro antibacterial experiments show that the dressing has good antibacterial property on staphylococcus epidermidis (gram positive) and escherichia coli (gram negative).
(6) Cytotoxicity
Leaching the leaching liquor of medical instruments according to the national standard GB/T16886.12 according to the surface area of 1.25cm2leaching the leaching solution at a ratio of 100uL mouse fibroblast-containing 3T3(1 × 10), adding the leaching solution according to national standard, culturing in a shaker at 37 deg.C for 24 + -2h, and standing the rest in a refrigerator at 4 deg.C4pieces/mL) of the medium were inoculated in a 96-well plate. After 12h of inoculation, the original culture solution was taken out, and 100. mu.L of the test material leaching solution was added to each well dish. Each group is provided with at least 5 holes. The culture medium was changed once every 2 days. After culturing the cells for 1 day, 2 days, and 3 days, the culture medium was removed, and the cells were washed 2 times with PBS. A50 ul amount of CCK8 solution was added to each well and a negative control (blank medium) was set and incubated for 1h-2h in a cell incubator. According to the color change judgment, the culture plate is taken out, and the liquid in the corresponding hole is sucked into a 96-well plate. And detecting the absorbance value (OD value) under the wavelength of 450nm of a microplate reader, recording and calculating data. The dressings prepared in examples 4 to 6 and comparative examples 1 to 2 were subjected to a biocompatibility test, and the test results are shown in fig. 4.
As can be seen from fig. 4, the relative cell survival rate of the CMC dressing group prepared in comparative example 1 (about 96%) was comparable to that of the control group, indicating that the CMC dressing group was not cytotoxic. The CMC/Ser/CLDM dressing group prepared in comparative example 2 had a cell survival rate of only about 70%, a cytotoxicity of grade 2, and a mild cytotoxicity.
When CLDM was loaded into carboxymethyl chitosan microspheres, the CMC/Ser/CMs @ CLDM-01 dressing prepared in example 4 and the CMC/Ser/CMs @ CLDM-02 dressing prepared in example 4 all showed greater than 90% cell viability, indicating that the dressing group with microspheres loaded with clindamycin was substantially free of cytotoxicity. The cell survival rate of the CMC/Ser/CMs @ CLDM-03 dressing is reduced by about 85 percent. The result shows that the designed dressing has zero-order cytotoxicity through the technology of loading clindamycin on microspheres, and can be applied to implant materials.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention and not for limiting the protection scope of the present invention, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (10)
1. The dressing with the antibacterial activity is characterized by comprising the following components in percentage by mass: 1 to 4 percent of sodium carboxymethylcellulose, 0.2 to 2 percent of sericin, 0.01 to 0.2 percent of carboxymethyl cellulose microsphere containing clindamycin and the balance of deionized water.
2. The dressing of claim 1, wherein the dressing comprises the following components in percentage by mass: 2% of sodium carboxymethylcellulose, 1% of sericin, 0.1% of carboxymethyl cellulose microspheres containing clindamycin and the balance of deionized water.
3. The dressing of claim 1 or 2, wherein the preparation method of the clindamycin-containing carboxymethyl cellulose microsphere comprises the following steps:
(1) adding sodium carboxymethylcellulose and clindamycin into deionized water, then adding liquid paraffin and span 80, heating in a water bath, dropwise adding a gelatin solution to form a mixed solution, adding a cross-linking agent, and stirring for reaction;
(2) and after the reaction is finished, centrifuging the reaction solution to obtain a precipitate, washing, and freeze-drying the precipitate to obtain the carboxymethyl cellulose microsphere containing the clindamycin.
4. The dressing of claim 3, wherein the mass ratio of the sodium carboxymethylcellulose to the clindamycin is (10-30): 1.
5. the dressing of claim 3, wherein the rotation speed of the stirring reaction is 400-1000 rmp, the time of the stirring reaction is 2h, the centrifugation time is 1-10 min, and the cross-linking agent is glutaraldehyde.
6. The dressing of claim 1 or 2, wherein the sericin is prepared by a method comprising: cutting silkworm cocoon into pieces, washing with deionized water, and soaking in Na2CO3Boiling the solution, centrifuging, filtering to remove insoluble residue, dialyzing with deionized water, and lyophilizing to obtain sericin.
7. The dressing of claim 6, wherein the boiling time is 0.5-2 h, the rotation speed of the centrifugation is 1000-5000 rpm, and the time of the centrifugation is 5-15 min.
8. A method of manufacturing a dressing according to any of claims 1 to 7, comprising the steps of: adding sodium carboxymethylcellulose and sericin into deionized water, stirring until completely dissolving, adding carboxymethyl cellulose microspheres containing clindamycin, stirring to uniformly disperse the microspheres, pouring the reaction solution into a mold, freezing overnight, drying, and crosslinking to obtain the antibacterial active dressing.
9. The method of claim 8, wherein the stirring is performed for a period of 3 hours until complete dissolution, the stirring is performed for a period of 15 minutes to uniformly disperse the microspheres, and the freezing is performed at-70 ℃ overnight.
10. The method of claim 8, wherein the temperature of the crosslinking is 70 ℃ and the time of the crosslinking is 72 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010379148.6A CN111686297A (en) | 2020-05-07 | 2020-05-07 | Antibacterial active dressing and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010379148.6A CN111686297A (en) | 2020-05-07 | 2020-05-07 | Antibacterial active dressing and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111686297A true CN111686297A (en) | 2020-09-22 |
Family
ID=72476626
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010379148.6A Pending CN111686297A (en) | 2020-05-07 | 2020-05-07 | Antibacterial active dressing and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111686297A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114541133A (en) * | 2022-03-21 | 2022-05-27 | 浙江隆腾医用新材料有限公司 | Preparation method of cross-linked sodium carboxymethylcellulose fiber |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108042841A (en) * | 2017-12-11 | 2018-05-18 | 罗卫 | A kind of biological dressing and preparation method thereof and purposes |
| CN110448544A (en) * | 2019-07-29 | 2019-11-15 | 同济大学 | Perfluocarbon oxygen carrying microballoon with anti-microbial property and its preparation method and application |
-
2020
- 2020-05-07 CN CN202010379148.6A patent/CN111686297A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108042841A (en) * | 2017-12-11 | 2018-05-18 | 罗卫 | A kind of biological dressing and preparation method thereof and purposes |
| CN110448544A (en) * | 2019-07-29 | 2019-11-15 | 同济大学 | Perfluocarbon oxygen carrying microballoon with anti-microbial property and its preparation method and application |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114541133A (en) * | 2022-03-21 | 2022-05-27 | 浙江隆腾医用新材料有限公司 | Preparation method of cross-linked sodium carboxymethylcellulose fiber |
| CN114541133B (en) * | 2022-03-21 | 2024-05-07 | 浙江隆腾医用新材料有限公司 | Preparation method of crosslinked sodium carboxymethyl cellulose fiber |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Cao et al. | Double crosslinked HLC-CCS hydrogel tissue engineering scaffold for skin wound healing | |
| Aramwit | Introduction to biomaterials for wound healing | |
| Zhu et al. | Novel enzymatic crosslinked hydrogels that mimic extracellular matrix for skin wound healing | |
| US20120215149A1 (en) | Chitosan tissue dressing | |
| CN102380129B (en) | Sodium hyaluronate and KGM porous bracket material and method for preparing same | |
| CN107261195B (en) | Preparation method and application of antibacterial biomass gel net for sports wound rehabilitation dressing | |
| CN115154642B (en) | Bionic asymmetric sponge dressing and preparation method thereof | |
| Augustine et al. | Stromal cell-derived factor loaded co-electrospun hydrophilic/hydrophobic bicomponent membranes for wound protection and healing | |
| US20080254088A1 (en) | Shaped bodies based on a cross-linked, gelatinous material, method for producing such bodies and use of the bodies | |
| CN115487337B (en) | Dressing patch for skin repair and preparation method thereof | |
| Archana et al. | Chitosan: a potential therapeutic dressing material for wound healing | |
| CN112646204A (en) | Sericin hydrogel and preparation method and application thereof | |
| Rasouli et al. | Bacterial cellulose as potential dressing and scaffold material: toward improving the antibacterial and cell adhesion properties | |
| CN107198794B (en) | Natural polymer bioactive wound repair material with active ion release function and preparation method thereof | |
| Seifi et al. | A novel multifunctional chitosan-gelatin/carboxymethyl cellulose-alginate bilayer hydrogel containing human placenta extract for accelerating full-thickness wound healing | |
| CN112870451B (en) | Nerve sheath tube and preparation method and application thereof | |
| Latańska et al. | The use of chitin and chitosan in manufacturing dressing materials | |
| CN111686297A (en) | Antibacterial active dressing and preparation method thereof | |
| CN111001041B (en) | Anti-inflammatory and antibacterial composite skin scaffold material and preparation method thereof | |
| CN107349456B (en) | Preparation method of collagen sponge with pore size self-adaptive adjusting capacity and collagen sponge | |
| EP3148599B1 (en) | Method for preparing neutralized matrix of non-antigenic collagenous material | |
| Denkbas et al. | EGF loaded chitosan sponges as wound dressing material | |
| Rezaei et al. | Highly Absorbent Egg White/Carbomer‐940 Hydrofilm as a Potential Diabetic Wound Dressing | |
| CN112023108A (en) | Three-dimensional dressing and preparation method thereof | |
| CN111214710A (en) | Composite scaffold for promoting skin regeneration 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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200922 |