CN108619560A - A kind of preparation method of tissue adhension hemostatic and antibacterial nanometer film - Google Patents
A kind of preparation method of tissue adhension hemostatic and antibacterial nanometer film Download PDFInfo
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/10—Polypeptides; Proteins
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- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0015—Medicaments; Biocides
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- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0028—Polypeptides; Proteins; Degradation products thereof
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- A—HUMAN NECESSITIES
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0028—Polypeptides; Proteins; Degradation products thereof
- A61L26/0038—Gelatin
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/0066—Medicaments; Biocides
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- 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
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- 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
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Abstract
The invention discloses a kind of preparation methods of tissue adhension hemostatic and antibacterial nanometer film, including step:1) preparation of tissue adhension hemostatic and antibacterial basis material;2) that step 1) is obtained basis material is soluble in water, obtains nano thin-film by spin-coating method, then dries and removes solvent after UV photocurings, obtain required tissue adhension hemostatic and antibacterial nanometer film;Water soluble polymer is dissolved in water, sacrificial layer is built in nanometer film by spin-coating method, this layer of sacrificial layer facilitates practical operation and follow-up in use, can be removed by washing.The biological safety of tissue adhension hemostatic and antibacterial nanometer film obtained is good by the method for the invention, easy to use comfortable, and for energy secure adhesion in the tissue of different-shape, hemostatic and antibacterial effect is good and not will produce bacterial resistance.
Description
Technical field
The present invention relates to the technical field of wound repair material, a kind of tissue adhension hemostatic and antibacterial nanometer film is referred in particular to
Preparation method.
Background technology
Huge market and lasting demand, the research and development of soft tissue repair material are always bio-medical material
The hot spot in field.Traditional soft-tissue trauma repair materials mainly have medical adhesive tape, suture and biological glue, they are invented certainly
Since just always be the mankind existence and health make significant contribution.
Medical adhesive tape mainly has gauze, adhesive bandage etc., be now price it is most cheap, using most convenient, widest wound
Wrapper material.But in the complicated surface of a wound of reply, show slightly weak on sealing effect.Closure strength of the operation suture thread to wound
It is very high, and have successively develop degradable operation suture thread recently, cause patient's trouble and pain without postoperative dismounting.But
Wound secondary damage and infection caused by when needing medical practitioner to be operated, and using, postoperative-scar is also inevitable
's.Commercial biological glue mainly has a-cyanoacrylate medical adhesive, can be used for skin surface or sub-layer wound repair, possesses solid
The advantages that change speed is fast, and intensity is high, easy to use.But it is in brittleness after the solidification of cyanoacrylate biological glue, it is difficult to human body
Organize modulus matching, when use that wound is caused to generate heat, degradation product has the shortcomings that cytotoxicity also limits its extensive use.
It is rare in view of being subsequently likely to occur moreover, traditional repair mode only stops blooding to being closed after wound debridement mostly
A series of problems that bacterium infection is brought.Based on the flexibility that nano thin-film dimensional effect assigns, may be implemented to different-shape
The surface of a wound carries out physical adhesion;Based on the good biocompatibility of gelatin modified object (GelMA) and bioactivity, we first will tool
The DOPA of adhesiveness is amine-modified in a organized way arrives gelatin modified object skeleton, assigns its tissue adherence;Then that antibacterial effect is excellent,
Bacterial resistance, the modification of avirulent antibacterial polypeptide are not generated to gelatin modified object skeleton, assign its antibiotic property;By with blood coagulation because
Muon physics mix, and assign its coagulant property, finally obtain a kind of tissue adhension hemostatic and antibacterial basis material.By this basis material
It is prepared into nano thin-film by spin-coating method, and structure facilitates the water soluble polymer sacrificial layer of practical operation on it, in use,
This sacrificial layer can be removed by the method for washing, finally leave that tissue adherence is good, nanometer film of hemostatic and antibacterial in wound.
This hemostatic and antibacterial film can be used for soft tissue repair, and a wide range of epidermis for being especially used to not suturing, adhesive tape can not be closed lacks
Damage is repaired, it will is a kind of completely new, efficient scheme.
Invention content
The shortcomings that it is an object of the invention to overcome the prior art and deficiency, it is proposed that a kind of effective, scientific and reasonable
Tissue adhension hemostatic and antibacterial nanometer film preparation method, pass through the life of tissue adhension hemostatic and antibacterial nanometer film made from this method
Object safety is good, easy to use comfortable, and for energy secure adhesion in the tissue of different-shape, hemostatic and antibacterial effect is good and not will produce thin
Bacterium resistance.
To achieve the above object, technical solution provided by the present invention is:A kind of tissue adhension hemostatic and antibacterial nanometer film
Preparation method includes the following steps:
1) preparation of tissue adhension hemostatic and antibacterial basis material
1.1) methacrylic acid anhydridization gelatin GelMA is dissolved in water, it is 10-20%'s to be added and account for GelMA mass percents
The N- hydroxysuccinimide NHS of 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides EDC and 20-30%, and adjust
It is 5.0~6.0 to save pH, is activated 30 minutes at 37 DEG C, obtains A systems;It is 50-70% that GelMA mass percents, which will then be accounted for,
Dopamine hydrochloride DA A systems are added, react at least 12 hours, obtain sample B;By sample B dialysis, then freeze-drying obtains white
To light grey solid, it is named as GelMA-DA;
1.2) GelMA-DA that step 1.1) obtains is dissolved in water, it is 2 to be charged with and account for GelMA-DA mass percents
The dimethylacetylamide DMAC solution of the triphenylphosphine catalysis of~4% sulfydryl antibacterial polypeptide PT and 0.1~0.2%;Room temperature is lazy
Terminate after being reacted 1 hour under property atmosphere, obtains sample C;By sample C dialysis, then freeze-drying obtains white to light grey solid, life
Entitled GelMA-DA-PT;
1.3) by obtained by step 1.2) GelMA-DA-PT and account for the calcium chloride CaCl of its mass ratio 2.0~3.0%2
Physical mixed obtains product and is named as GelMA-DA-PT/CaCl2;
2) step 1.3) is obtained into GelMA-DA-PT/CaCl2It is soluble in water, with the molten of obtained 5~10% mass fractions
Liquid, addition account for GelMA-DA-PT/CaCl2The initiator i2595 that mass fraction is 0.5~1.0%, is received by spin-coating method
Rice film, dries and removes solvent after UV photocurings, obtains required tissue adhension hemostatic and antibacterial nanometer film.
By mass fraction be 20~30% 1788 type aqueous solution of PVAC polyvinylalcohol by spin-coating method, obtained in step 2)
Tissue adhension hemostatic and antibacterial nanometer film on build one layer of sacrificial layer, to facilitate later stage practical operation, and follow-up in use, energy
It is enough to be removed by washing.
In step 2), the thickness of tissue adhension hemostatic and antibacterial nanometer film obtained is 50nm~100nm.
Sacrificial layer thickness obtained is 0.2~0.5mm.
Compared with prior art, the present invention having the following advantages that and advantageous effect:
Can obtain by the method for the invention a kind of biological safety it is good, it is easy to use it is comfortable, can cope with the complex topography surface of a wound,
Adhering soft tissues effect is good, hemostatic and antibacterial excellent effect and the film that not will produce bacterial resistance, can be used for avoiding because hurting, piercing
Hinder class external form acute injury, bacterium infection caused by part visceral injury and diabetes class chronic wounds etc. has practical
Promotional value.
Specific implementation mode
The present invention is further explained in the light of specific embodiments.
Embodiment 1
The preparation method for the tissue adhension hemostatic and antibacterial nanometer film that the present embodiment is provided, includes the following steps:
1) preparation of tissue adhension hemostatic and antibacterial basis material
1.1) GelMA is dissolved in water, the NHS for accounting for the EDC and 20% that its mass fraction is 10% is added, and adjust pH and be
It is activated 30 minutes at 5.0,37 DEG C and obtains system A;The Dopamine hydrochloride that GelMA mass fractions are 50% will then be accounted for, system is added
A, reaction obtain sample B at least 12 hours;By sample B dialysis, then freeze-drying obtains white to light grey solid, is named as
GelMA-DA。
1.2) GelMA-DA that step 1.1) obtains is dissolved in water, is charged with that account for its mass fraction anti-for 2% sulfydryl
The DMAC solution of the triphenylphosphine catalysis of bacterium polypeptide PT and 0.1%;Terminate to obtain sample after reacting 1 hour under room temperature inert atmosphere
Product C;By sample C dialysis, then freeze-drying obtains white to light grey solid, is named as GelMA-DA-PT.
1.3) by obtained by step 1.2) GelMA-DA-PT and account for its mass fraction be 2.0% CaCl2Physical mixed,
It obtains product and is named as GelMA-DA-PT/CaCl2。
2) step 1.3) is obtained into GelMA-DA-PT/CaCl2It is soluble in water, it is 5% solution with mass fraction is made, adds
Enter to account for GelMA-DA-PT/CaCl2The initiator i2595 that mass fraction is 0.5% obtains nano thin-film, UV light by spin-coating method
Solvent is dried and removed after solidification, obtains the tissue adhension hemostatic and antibacterial nanometer film that thickness is 50nm or so.
3) by mass fraction be 20% PVA1788 types aqueous solution by spin-coating method, in the tissue adhension that step 2) obtains
The sacrificial layer of thickness 0.2mm or so is built in hemostatic and antibacterial nanometer film, this layer of sacrificial layer facilitates practical operation and subsequently make
In, it can be removed by washing.
Embodiment 2
The preparation method for the tissue adhension hemostatic and antibacterial nanometer film that the present embodiment is provided, includes the following steps:
1) preparation of tissue adhension hemostatic and antibacterial basis material
1.1) GelMA is dissolved in water, the NHS for accounting for the EDC and 30% that its mass fraction is 20% is added, and adjust pH and be
It is activated 30 minutes at 6.0,37 DEG C and obtains system A;The Dopamine hydrochloride that GelMA mass fractions are 75% will then be accounted for, system is added
A, reaction obtain sample B at least 12 hours;By sample B dialysis, then freeze-drying obtains white to light grey solid, is named as
GelMA-DA。
1.2) GelMA-DA that step 1.1) obtains is dissolved in water, is charged with that account for its mass fraction anti-for 4% sulfydryl
The DMAC solution of the triphenylphosphine catalysis of bacterium polypeptide PT and 0.2%;Terminate to obtain sample after reacting 1 hour under room temperature inert atmosphere
Product C;By sample C dialysis, then freeze-drying obtains white to light grey solid, is named as GelMA-DA-PT.
1.3) by obtained by step 1.2) GelMA-DA-PT and account for its mass fraction be 3.0% CaCl2Physical mixed,
It obtains product and is named as GelMA-DA-PT/CaCl2。
2) step 1.3) is obtained into GelMA-DA-PT/CaCl2It is soluble in water, it is 10% solution with mass fraction is made, adds
Enter to account for GelMA-DA-PT/CaCl2The initiator i2595 that mass fraction is 1.0% obtains nano thin-film, UV light by spin-coating method
Solvent is dried and removed after solidification, obtains the tissue adhension hemostatic and antibacterial nanometer film that thickness is 100nm or so.
3) by mass fraction be 30% PVA1788 types aqueous solution by spin-coating method, in the tissue adhension that step 2) obtains
A thickness 0.5mm or so sacrificial layer is built in hemostatic and antibacterial nanometer film, this layer of sacrificial layer facilitates practical operation and subsequently using
In, it can be removed by washing.
Embodiment 3
The preparation method for the tissue adhension hemostatic and antibacterial nanometer film that the present embodiment is provided, includes the following steps:
1) preparation of tissue adhension hemostatic and antibacterial basis material
1.1) GelMA is dissolved in water, the NHS for accounting for the EDC and 25% that its mass fraction is 15% is added, and adjust pH and be
It is activated 30 minutes at 5.5,37 DEG C and obtains system A;The Dopamine hydrochloride that GelMA mass fractions are 60% will then be accounted for, system is added
A, reaction obtain sample B at least 12 hours;By sample B dialysis, then freeze-drying obtains white to light grey solid, is named as
GelMA-DA。
1.2) GelMA-DA that step 1.1) obtains is dissolved in water, is charged with that account for its mass fraction anti-for 3% sulfydryl
The DMAC solution of the triphenylphosphine catalysis of bacterium polypeptide PT and 0.15%;Terminate to obtain after reacting 1 hour under room temperature inert atmosphere
Sample C;By sample C dialysis, then freeze-drying obtains white to light grey solid, is named as GelMA-DA-PT.
1.3) by obtained by step 1.2) GelMA-DA-PT and account for its mass fraction be 2.5% CaCl2Physical mixed,
It obtains product and is named as GelMA-DA-PT/CaCl2。
2) step 1.3) is obtained into GelMA-DA-PT/CaCl2It is soluble in water, it is 7.5% solution with mass fraction is made,
Addition accounts for GelMA-DA-PT/CaCl2The initiator i2595 that mass fraction is 0.75% obtains nano thin-film by spin-coating method,
Solvent is dried and removed after UV photocurings, obtains the tissue adhension hemostatic and antibacterial nanometer film that thickness is 78nm or so.
3) by mass fraction be 25% PVA1788 types aqueous solution by spin-coating method, in the tissue adhension that step 2) obtains
A thickness 0.35mm or so sacrificial layer is built in hemostatic and antibacterial nanometer film, this layer of sacrificial layer facilitates practical operation and subsequently using
In, it can be removed by washing.
Embodiment described above is only the preferred embodiments of the invention, and but not intended to limit the scope of the present invention, therefore
Change made by all shapes according to the present invention, principle, should all cover within the scope of the present invention.
Claims (4)
1. a kind of preparation method of tissue adhension hemostatic and antibacterial nanometer film, which is characterized in that include the following steps:
1) preparation of tissue adhension hemostatic and antibacterial basis material
1.1) methacrylic acid anhydridization gelatin GelMA is dissolved in water, the 1- (3- for accounting for that GelMA mass percents are 10-20% is added
Dimethylamino-propyl) -3- ethyl-carbodiimide hydrochlorides EDC and 20-30% N- hydroxysuccinimide NHS, and adjust pH
It is 5.0~6.0, is activated 30 minutes at 37 DEG C, obtain A systems;The salt that GelMA mass percents are 50-70% will then be accounted for
A systems are added in sour dopamine D A, react at least 12 hours, obtain sample B;Sample B dialysis and then freeze-drying are obtained white to light
Gray solid is named as GelMA-DA;
1.2) GelMA-DA that step 1.1) obtains is dissolved in water, it is 2~4% to be charged with and account for GelMA-DA mass percents
The dimethylacetylamide DMAC solution of the triphenylphosphine catalysis of sulfydryl antibacterial polypeptide PT and 0.1~0.2%;Room temperature inert atmosphere
Lower reaction terminates after 1 hour, obtains sample C;By sample C dialysis, then freeze-drying obtains white to light grey solid, is named as
GelMA-DA-PT;
1.3) by obtained by step 1.2) GelMA-DA-PT and account for the calcium chloride CaCl of its mass ratio 2.0~3.0%2Physics is mixed
It closes, obtains product and be named as GelMA-DA-PT/CaCl2;
2) step 1.3) is obtained into GelMA-DA-PT/CaCl2It is soluble in water, with the solution that 5~10% mass fractions are made, it is added
Account for GelMA-DA-PT/CaCl2The initiator i2595 that mass fraction is 0.5~1.0% obtains nano thin-film by spin-coating method,
Solvent is dried and removed after UV photocurings, obtains required tissue adhension hemostatic and antibacterial nanometer film.
2. a kind of preparation method of tissue adhension hemostatic and antibacterial nanometer film according to claim 1, it is characterised in that:By matter
The 1788 type aqueous solution of PVAC polyvinylalcohol that score is 20~30% is measured by spin-coating method, is stopped in the tissue adhension that step 2) obtains
One layer of sacrificial layer is built on blood antimicrobial nano film, to facilitate later stage practical operation, and follow-up in use, can be removed by washing
It goes.
3. a kind of preparation method of tissue adhension hemostatic and antibacterial nanometer film according to claim 1, it is characterised in that:In step
It is rapid 2) in, the thickness of tissue adhension hemostatic and antibacterial nanometer film obtained is 50nm~100nm.
4. a kind of preparation method of tissue adhension hemostatic and antibacterial nanometer film according to claim 2, it is characterised in that:It is made
Sacrificial layer thickness be 0.2~0.5mm.
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CN110917392A (en) * | 2019-12-31 | 2020-03-27 | 广州贝奥吉因生物科技股份有限公司 | Hemostatic and antibacterial hydrogel with adhesiveness and preparation method thereof |
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CN110755676A (en) * | 2019-10-21 | 2020-02-07 | 浙江大学 | Composite dressing for promoting wound healing and regeneration and loading traditional Chinese medicine exosomes and preparation method thereof |
CN110755676B (en) * | 2019-10-21 | 2021-06-15 | 浙江大学 | Composite dressing for promoting wound healing and regeneration and loading traditional Chinese medicine exosomes and preparation method thereof |
CN110917392A (en) * | 2019-12-31 | 2020-03-27 | 广州贝奥吉因生物科技股份有限公司 | Hemostatic and antibacterial hydrogel with adhesiveness and preparation method thereof |
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