CN107970486A - A kind of preparation method of chitosan-based compound hemostatic film - Google Patents

A kind of preparation method of chitosan-based compound hemostatic film Download PDF

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CN107970486A
CN107970486A CN201711316988.2A CN201711316988A CN107970486A CN 107970486 A CN107970486 A CN 107970486A CN 201711316988 A CN201711316988 A CN 201711316988A CN 107970486 A CN107970486 A CN 107970486A
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chitosan
film
parts
based compound
liquid
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高玉梅
许蘅
张琳
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Zhou Rong
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Changzhou Kai Heng Textile 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
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/28Polysaccharides or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/18Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing inorganic materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/26Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/32Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/40Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing ingredients of undetermined constitution or reaction products thereof, e.g. plant or animal extracts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • A61L15/425Porous materials, e.g. foams or sponges
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/04Materials for stopping bleeding

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Abstract

The invention discloses a kind of preparation method of chitosan-based compound hemostatic film, belong to medical film technical field.The present invention first mixes chitosan liquid and gelatin solution, and adds polyethylene glycol and crosslinking agent, stirring reaction, film liquid is made into, then through casting film-forming, obtains chitosan-based film, inorganic powder dispersion liquid is sprayed on chitosan-based film surface again, it is cold-pressed after naturally dry, obtains cold pressing film, after cold pressing film surface coating nutrition homogenate, spray acetobacter xylinum bacterium solution, after constant temperature and humidity culture, sterilizing, washing and drying, up to chitosan-based compound hemostatic film.The chitosan-based compound hemostatic film haemostatic effect of gained of the invention is effectively improved, and after wound healing, easy to be peeled off from wound, the situation of pain and secondary injury is produced when being conducive to avoid removing haemostatic membrane.

Description

A kind of preparation method of chitosan-based compound hemostatic film
Technical field
The invention discloses a kind of preparation method of chitosan-based compound hemostatic film, belong to medical film technical field.
Background technology
Bleeding is major complications after wound, and adult's amount of bleeding will cause shock more than 0.8~1.0L, threat to life, Therefore timely and effective hemostasis acquires a special sense to saving life.
Biomedical material be it is a kind of there are property and features, for artificial organs, surgical repair, diagnosis and Treatment, the material having no adverse effects to tissue.With going deep into for correlative study, various new medical biological hemostatic materials are not It is disconnected to occur.Clinical common biological hemostatic material has oxycellulose and polysaccharide at present, its haemostatic effect is definite, but price is held high It is expensive, using being subject to a definite limitation.Chitosan biological hemostatic material is because with good biocompatibility, biodegradability, resisting Bacterium, anti-inflammatory, hemostasis, reduction surface of a wound exudation, promote wound tissue's regeneration, repair, heal, be easily formed gel, derive from a wealth of sources, valency The advantages that lattice are cheap, becomes the research hotspot of new medical biological hemostatic material.The stopping blooding, is antibacterial of chitosan, antibiotic property, biology Compatibility, promote wound healing and be easily formed the property of gel, and it is good as bleeding-stopping dressing or hemostat all to impart it Good performance, itself has antibacterial, antibacterial action.The material absorbs in vivo, degrade after end-product have it is nontoxic, nonantigenic Property.
Chitosan(chitosan,CS)With good biocompatibility, degradability, unique antibacterial, antibiotic property with And promote the function of hemostasis and wound healing, it has also become the research hotspot of hemostatic material.The CS haemostatic membranes hemostasis effect studied at present Fruit is undesirable, CS/ carboxymethyl chitosans(carboxymethyl chitosan,CMCS)Haemostatic membrane pliability is poor, and rate of film build is low. Therefore, also need to strengthen the research to chitosan haemostatic membrane.
The content of the invention
The present invention solves the technical problem of:For traditional chitosan haemostatic membrane haemostatic effect it is bad the problem of, carry A kind of preparation method of chitosan-based compound hemostatic film is supplied.
In order to solve the above-mentioned technical problem, the technical solution adopted in the present invention is:
(1)It is 1 in mass ratio:80~1:120 mix acetobacter xylinum with fluid nutrient medium, obtain acetobacter xylinum bacterium solution;
(2)It is 8 in mass ratio by chitosan liquid and gelatin solution:1~10:After 1 is stirred, pH is adjusted to 5.2~5.4, then add Enter the polyethylene glycol of 0.6~0.8 times of chitosan liquid quality, under constant temperature stirring, dropwise addition chitosan liquid quality 0.01~ 0.03 times of crosslinking agent, treats completion of dropwise addition, continues constant temperature stirring 45~60min of reaction, then through vacuum defoamation, obtain it is chitosan-based into Film liquid;
(3)To be formed a film liquid casting film-forming, dry, obtain chitosan-based film;
(4)Inorganic powder dispersion liquid is sprayed on chitosan-based film surface, it is 100~150g/m2 to control fountain height, is dried in the air naturally After dry, 5~10min is cold-pressed, obtains cold pressing film;
(5)The nutrition that a layer thickness is 0.1~0.3mm is coated in cold pressing film surface to be homogenized, and obtains composite cold press mold;
(6)Acetobacter xylinum bacterium solution is sprayed on composite cold press mold surface, it is 15~30mL/m2 to control fountain height, and constant temperature and humidity is trained Support 8~15 days, sterilize, wash, it is dry, up to chitosan-based compound hemostatic film.
Step(1)The fluid nutrient medium is made of the raw material of following parts by weight:10~15 portions of mannitol, 3~5 parts Sucrose, 2~3 portions of beef extracts, 4~10 parts of peptones, 500~600 parts of water.
Step(2)The chitosan liquid configuration process is:It is 1 in mass ratio by chitosan and water:50~1:After 60 mixing, Swelling is stood, constant temperature stirring and dissolving, obtains chitosan liquid.
Step(2)The gelatin solution configuration process is:It is 1 in mass ratio by gelatin and water:30~1:After 40 mixing, stand Swelling, constant temperature stirring and dissolving, obtains gelatin solution.
Step(2)The polyethylene glycol is polyethylene glycol 400, any one in polyethylene glycol 500 or Macrogol 600 Kind.
Step(2)The crosslinking agent is any one in terephthalaldehyde, hexandial or glutaraldehyde.
Step(4)The inorganic powder dispersion liquid is made of the raw material of following parts by weight:3~5 parts of magnesia, 10~ 20 parts of calcium hydroxy phosphates, 8~10 parts of pearl powders, 10~20 parts of pounces, 100~120 parts of mass fractions are molten for 75% ethanol Liquid.
Step(5)The nutrition homogenate is formed by the raw material configuration of following parts by weight:40~60 parts of honey, 3~5 parts Glycerine, 2~4 parts of sodium alginates, 6~8 portions of mannitol, 40~50 parts of water.
The beneficial effects of the invention are as follows:
Technical solution of the present invention using chitosan it is excellent stop blooding, be antibacterial, antibacterial and the advantages that biocompatibility, made with chitosan For base film, inorganic powder is added then at film surface, in cold pressure procedure, inorganic powder can be embedded in chitosan-based body thin film , can be in chitosan-based body thin film table in incubation in hole, then by spraying nutrient source and bacterial solution in film surface Face forms one layer of porous bacterial cellulose gel film, and in the drying process, bacterial cellulose gel film syneresis, gathers in shell Sugared film surface forms pleated structure, improves surface roughness, in use, has benefited from inorganic particle, the bacterium of addition The excellent water absorbing properties such as cellulose membrane, can quickly absorb the moisture in blood, and the porous pleated structure of bacteria cellulose film The macromolecular substances such as the haemocyte in blood can be shut off, and condense upon pleated structure surface, make blood rapid concentration, so that Wound part blood coagulation concentration of substrate rapid increase, accelerates clotting factor inside human activin, promotes itself blood coagulation, shortens blood coagulation It is time, and bacteria cellulose film moderate strength, preferable with human-body biological compatibility, can be with concentration with blood clotting after use Blood afterwards is collectively forming thrombus and gradually from chitosan basal body sur-face peeling, after wound healing, easy to by haemostatic membrane from wound Mouth is removed, and mitigates patient suffering.
Embodiment
It is 1 in mass ratio:80~1:Acetobacter xylinum is mixed and poured into beaker by 120 with fluid nutrient medium, is stirred with glass bar 15~20min of mixing is mixed, obtains acetobacter xylinum bacterium solution;It is again 8 in mass ratio by chitosan liquid and gelatin solution:1~10:After 1 mixing, 45~60min is stirred for 300~500r/min rotating speeds in rotating speed, obtains chitosan gelatin mixed liquor, then by chitosan gelatin PH of mixed is adjusted to 5.2~5.4, obtains faintly acid chitosan gelatin mixed liquor, then gained faintly acid chitosan gelatin is mixed Liquid is moved into reaction kettle, and the polyethylene glycol of 0.6~0.8 times of chitosan liquid quality is added into reaction kettle, in temperature for 55~ 65 DEG C, under the conditions of rotating speed is 400~600r/min, the crosslinking of 0.01~0.03 times of chitosan liquid quality is added dropwise into reaction kettle Agent, treats crosslinking agent completion of dropwise addition, continues constant temperature stirring 45~60min of reaction, then through vacuum defoamation, discharging, obtain it is chitosan-based into Film liquid;Casting machine hopper then is transferred into film liquid by gained is chitosan-based, adjusts scraper knife away from for 0.2~0.3mm, casting film-forming Afterwards, it is 4~8% to dry to moisture content, obtains chitosan-based film;Shell obtained by inorganic powder dispersion liquid is sprayed on as watering can gathers Glycosyl film surface, it is 100~150g/m to control fountain height2, after 6~8h of naturally dry, in pressure be 10~20MPa conditions Under, 5~10min is cold-pressed, obtains cold pressing film;The nutrition that a layer thickness is 0.1~0.3mm is coated then at cold pressing film surface to be homogenized, and is obtained Composite cold press mold, is then sprayed on composite cold press mold surface, the bacterium solution spray of control acetobacter xylinum by acetobacter xylinum bacterium solution by watering can The amount of spilling is 15~30mL/m2, then by spray acetobacter xylinum bacterium solution after composite cold press mold move into greenhouse in, in temperature be 30~35 DEG C, relative air humidity be 65~75% under the conditions of, constant temperature and humidity culture 8~15 days, in incubation, every 12~24h to Spray the composite cold press mold surface after acetobacter xylinum bacterium solution and spray 30~50mL/m2Water, is waited after cultivating, ultraviolet sterilization 45~ 60min, obtains sterilizing composite membrane, and gained sterilizing composite membrane is washed until cleaning solution is in neutrality, then is incited somebody to action with aseptic deionized water Sterilizing composite membrane drying to moisture content after washing is 8~10%, up to chitosan-based compound hemostatic film.The fluid nutrient medium It is made of the raw material of following parts by weight:10~15 portions of mannitol, 3~5 portions of sucrose, 2~3 portions of beef extracts, 4~10 parts of albumen Peptone, 500~600 parts of water.The chitosan liquid configuration process is:It is 1 in mass ratio by chitosan and water:50~1:60 mixing Afterwards, swelling is stood, constant temperature stirring and dissolving, obtains chitosan liquid.The gelatin solution configuration process is:It is in mass ratio with water by gelatin 1:30~1:After 40 mixing, swelling is stood, constant temperature stirring and dissolving, obtains gelatin solution.The polyethylene glycol is polyethylene glycol 400, is gathered Any one in ethylene glycol 500 or Macrogol 600.The crosslinking agent is in terephthalaldehyde, hexandial or glutaraldehyde Any one.The inorganic powder dispersion liquid is made of the raw material of following parts by weight:3~5 parts of magnesia, 10~20 parts of hydroxyls Base calcium phosphate, 8~10 parts of pearl powders, 10~20 parts of pounces, 80~120 parts of mass fractions are 75% ethanol solution.The battalion Foster homogenate is formed by the raw material configuration of following parts by weight:40~60 parts of honey, 3~5 parts of glycerine, 2~4 parts of sodium alginates, 6 ~8 portions of mannitol, 40~50 parts of water.
Example 1
It is 1 in mass ratio:Acetobacter xylinum is mixed and poured into beaker by 120 with fluid nutrient medium, is stirred with glass bar 20min, obtains acetobacter xylinum bacterium solution;It is again 10 in mass ratio by chitosan liquid and gelatin solution:1 mixing after, in rotating speed be 500r/ Min rotating speeds are stirred 60min, obtain chitosan gelatin mixed liquor, then chitosan gelatin pH of mixed is adjusted to 5.4, obtain weak Acidic chitosan gelatin mixed liquor, then gained faintly acid chitosan gelatin mixed liquor is moved into reaction kettle, and into reaction kettle Add the polyethylene glycol of 0.8 times of chitosan liquid quality, in temperature be 65 DEG C, under the conditions of rotating speed is 600r/min, into reaction kettle The crosslinking agent of 0.03 times of chitosan liquid quality is added dropwise, treats crosslinking agent completion of dropwise addition, continues constant temperature stirring reaction 60min, then through true Empty deaeration, discharging, obtains chitosan-based into film liquid;Casting machine hopper then is transferred into film liquid by gained is chitosan-based, adjusts scraper Knife is away from for 0.3mm, and after casting film-forming, dry to moisture content is 8%, obtains chitosan-based film;Inorganic powder is disperseed by watering can Liquid is sprayed on the chitosan-based film surface of gained, and it is 150g/m to control fountain height2, after naturally dry 8h, in pressure be 20MPa bars Under part, 10min is cold-pressed, obtains cold pressing film;The nutrition that a layer thickness is 0.3mm is coated then at cold pressing film surface to be homogenized, and obtains composite cold Press mold, is then sprayed on composite cold press mold surface by acetobacter xylinum bacterium solution by watering can, controls the acetobacter xylinum bacterium solution fountain height to be 30mL/m2, then by spray acetobacter xylinum bacterium solution after composite cold press mold move into greenhouse in, in temperature be 35 DEG C, air is relatively wet Spend under the conditions of 75%, constant temperature and humidity culture 15 days, in incubation, every 24h to compound after sprinkling acetobacter xylinum bacterium solution It is cold-pressed film surface sprinkling 50mL/m2Water, is waited after cultivating, ultraviolet sterilization 60min, obtains sterilizing composite membrane, and gained is sterilized Composite membrane is washed with aseptic deionized water until cleaning solution is in neutrality, then is by sterilizing composite membrane drying to the moisture content after washing 10%, up to chitosan-based compound hemostatic film.The fluid nutrient medium is made of the raw material of following parts by weight:15 parts of sweet dews Alcohol, 5 portions of sucrose, 3 portions of beef extracts, 10 parts of peptones, 600 parts of water.The chitosan liquid configuration process is:Chitosan and water are pressed Mass ratio is 1:After 60 mixing, swelling is stood, constant temperature stirring and dissolving, obtains chitosan liquid.The gelatin solution configuration process is:Will be bright Glue is 1 in mass ratio with water:After 40 mixing, swelling is stood, constant temperature stirring and dissolving, obtains gelatin solution.The polyethylene glycol is poly- second Glycol 400.The crosslinking agent is terephthalaldehyde.The inorganic powder dispersion liquid is made of the raw material of following parts by weight:5 Part magnesia, 20 parts of calcium hydroxy phosphates, 10 parts of pearl powders, 20 parts of pounces, 120 parts of mass fractions are 75% ethanol solution.Institute Stating nutrition homogenate is formed by the raw material configuration of following parts by weight:60 parts of honey, 5 parts of glycerine, 4 parts of sodium alginates, 8 parts of sweet dews Alcohol, 50 parts of water.
Example 2
It is 1 in mass ratio:Acetobacter xylinum is mixed and poured into beaker by 80 with fluid nutrient medium, and 15min is stirred with glass bar, Obtain acetobacter xylinum bacterium solution;It is again 8 in mass ratio by chitosan liquid and gelatin solution:After 1 mixing, stirred in rotating speed for 300r/min rotating speeds Mixing 45min is mixed, obtains chitosan gelatin mixed liquor, then chitosan gelatin pH of mixed is adjusted to 5.2, obtains faintly acid chitosan Gelatin mixed liquor, then gained faintly acid chitosan gelatin mixed liquor is moved into reaction kettle, and chitosan is added into reaction kettle The polyethylene glycol that 0.6 times of liquid quality, is 55 DEG C in temperature, under the conditions of rotating speed is 400r/min, chitosan is added dropwise into reaction kettle The crosslinking agent that 0.01 times of liquid quality, treats crosslinking agent completion of dropwise addition, continues constant temperature stirring reaction 45min, then through vacuum defoamation, go out Material, obtains chitosan-based into film liquid;Then be transferred to casting machine hopper into film liquid by gained is chitosan-based, adjust scraper knife away from for 0.2mm, after casting film-forming, dry to moisture content is 4%, obtains chitosan-based film;Inorganic powder dispersion liquid is sprayed by watering can In the chitosan-based film surface of gained, it is 100g/m to control fountain height2, after naturally dry 6h, under the conditions of pressure is 10MPa, 5min is cold-pressed, obtains cold pressing film;The nutrition that a layer thickness is 0.1mm is coated then at cold pressing film surface to be homogenized, and obtains composite cold press mold, with Acetobacter xylinum bacterium solution is sprayed on composite cold press mold surface by watering can afterwards, it is 15mL/m to control acetobacter xylinum bacterium solution fountain height2, The composite cold press mold after sprinkling acetobacter xylinum bacterium solution is moved into greenhouse again, is 30 DEG C in temperature, relative air humidity is 65% Under part, constant temperature and humidity culture 8 days, in incubation, every 12h to sprinkling acetobacter xylinum bacterium solution after composite cold press mold surface Spray 30mL/m2Water, is waited after cultivating, ultraviolet sterilization 45min, obtains sterilizing composite membrane, and gained is sterilized composite membrane nothing Bacterium deionized water washing until cleaning solution be in neutrality, then by the sterilizing composite membrane drying after washing to moisture content be 8%, up to shell Glycan base compound hemostatic film.The fluid nutrient medium is made of the raw material of following parts by weight:10 portions of mannitol, 3 portions of sucrose, 2 portions of beef extracts, 4 parts of peptones, 500 parts of water.The chitosan liquid configuration process is:It is 1 in mass ratio by chitosan and water:50 After mixing, swelling is stood, constant temperature stirring and dissolving, obtains chitosan liquid.The gelatin solution configuration process is:Gelatin and water are pressed into quality Than for 1:After 30 mixing, swelling is stood, constant temperature stirring and dissolving, obtains gelatin solution.The polyethylene glycol is polyethylene glycol 400.It is described Crosslinking agent is terephthalaldehyde.The inorganic powder dispersion liquid is made of the raw material of following parts by weight:3 parts of magnesia, 10 Part calcium hydroxy phosphate, 8 parts of pearl powders, 10 parts of pounces, 80 parts of mass fractions are 75% ethanol solution.The nutrition is homogenized Formed by the raw material configuration of following parts by weight:40 parts of honey, 3 parts of glycerine, 2 parts of sodium alginates, 6 portions of mannitol, 40 parts of water.
Example 3
It is 1 in mass ratio:Acetobacter xylinum is mixed and poured into beaker by 100 with fluid nutrient medium, is stirred with glass bar 17min, obtains acetobacter xylinum bacterium solution;It is again 9 in mass ratio by chitosan liquid and gelatin solution:1 mixing after, in rotating speed be 400r/min Rotating speed is stirred 52min, obtains chitosan gelatin mixed liquor, then chitosan gelatin pH of mixed is adjusted to 5.3, obtains faintly acid Chitosan gelatin mixed liquor, then gained faintly acid chitosan gelatin mixed liquor is moved into reaction kettle, and added into reaction kettle The polyethylene glycol of 0.7 times of chitosan liquid quality, is 60 DEG C in temperature, under the conditions of rotating speed is 500r/min, is added dropwise into reaction kettle The crosslinking agent of 0.02 times of chitosan liquid quality, treats crosslinking agent completion of dropwise addition, continues constant temperature stirring reaction 52min, then take off through vacuum Bubble, discharging, obtains chitosan-based into film liquid;Then be transferred to casting machine hopper into film liquid by gained is chitosan-based, adjust scraper knife away from For 0.2mm, after casting film-forming, dry to moisture content is 6%, obtains chitosan-based film;Inorganic powder dispersion liquid is sprayed by watering can Spill in the chitosan-based film surface of gained, it is 125g/m to control fountain height2, after naturally dry 7h, in pressure be 15MPa conditions Under, 8min is cold-pressed, obtains cold pressing film;The nutrition that a layer thickness is 0.2mm is coated then at cold pressing film surface to be homogenized, and obtains compound cold pressing Film, is then sprayed on composite cold press mold surface by acetobacter xylinum bacterium solution by watering can, controls the acetobacter xylinum bacterium solution fountain height to be 22mL/m2, then by spray acetobacter xylinum bacterium solution after composite cold press mold move into greenhouse in, in temperature be 32 DEG C, air is relatively wet Spend under the conditions of 70%, constant temperature and humidity culture 12 days, in incubation, every 18h to compound after sprinkling acetobacter xylinum bacterium solution It is cold-pressed film surface sprinkling 40mL/m2Water, is waited after cultivating, ultraviolet sterilization 52min, obtains sterilizing composite membrane, and gained is sterilized Composite membrane is washed with aseptic deionized water until cleaning solution is in neutrality, then is by sterilizing composite membrane drying to the moisture content after washing 9%, up to chitosan-based compound hemostatic film.The fluid nutrient medium is made of the raw material of following parts by weight:13 parts of sweet dews Alcohol, 4 portions of sucrose, 3 portions of beef extracts, 7 parts of peptones, 550 parts of water.The chitosan liquid configuration process is:Chitosan and water are pressed Mass ratio is 1:After 55 mixing, swelling is stood, constant temperature stirring and dissolving, obtains chitosan liquid.The gelatin solution configuration process is:Will be bright Glue is 1 in mass ratio with water:After 35 mixing, swelling is stood, constant temperature stirring and dissolving, obtains gelatin solution.The polyethylene glycol is poly- second Glycol 400.The crosslinking agent is terephthalaldehyde.The inorganic powder dispersion liquid is made of the raw material of following parts by weight:4 Part magnesia, 15 parts of calcium hydroxy phosphates, 9 parts of pearl powders, 15 parts of pounces, 100 parts of mass fractions are 75% ethanol solution.Institute Stating nutrition homogenate is formed by the raw material configuration of following parts by weight:50 parts of honey, 4 parts of glycerine, 3 parts of sodium alginates, 7 parts of sweet dews Alcohol, 45 parts of water.
Comparative example:The chitosan haemostatic membrane of Beijing bio tech ltd production.
The gained of example 1 to 3 haemostatic membrane and comparative example product are subjected to performance detection, specific detection method is as follows:
Anthemorrhagic performance:The phleborrhagia surface of a wound of 1cm × 1cm is prepared in the hard of hearing artery both sides of rabbit with scalpel, respectively by preparation Chitosan haemostatic membrane directly covers the bleeding surface of a wound, is oozed out with no blood for stopped bleeding standard.Observation each group haemostatic membrane solidified Journey;Bleeding stopping period is recorded, is subject to haemostatic membrane flap coverage to stopped bleeding;And using stop blooding forward and backward haemostatic membrane weight difference with It is amount of bleeding to solidify the sum of clot weight.Testing result is as shown in table 1:
Table 1:
Detection content Example 1 Example 2 Example 3 Comparative example
Bleeding stopping period/s 48 49 52 120
Amount of bleeding/mg 90.1 93.4 98.3 121.5
From 1 testing result of table, the chitosan-based compound hemostatic film haemostatic effect of present invention gained is effectively improved, and After wound healing, easy to be peeled off from wound, the situation of pain and secondary injury is produced when being conducive to avoid removing haemostatic membrane.

Claims (8)

1. a kind of preparation method of chitosan-based compound hemostatic film, it is characterised in that specifically preparation process is:
(1)It is 1 in mass ratio:80~1:120 mix acetobacter xylinum with fluid nutrient medium, obtain acetobacter xylinum bacterium solution;
(2)It is 8 in mass ratio by chitosan liquid and gelatin solution:1~10:After 1 is stirred, pH is adjusted to 5.2~5.4, then add Enter the polyethylene glycol of 0.6~0.8 times of chitosan liquid quality, under constant temperature stirring, dropwise addition chitosan liquid quality 0.01~ 0.03 times of crosslinking agent, treats completion of dropwise addition, continues constant temperature stirring 45~60min of reaction, then through vacuum defoamation, obtain it is chitosan-based into Film liquid;
(3)To be formed a film liquid casting film-forming, dry, obtain chitosan-based film;
(4)Inorganic powder dispersion liquid is sprayed on chitosan-based film surface, it is 100~150g/m to control fountain height2, dry in the air naturally After dry, 5~10min is cold-pressed, obtains cold pressing film;
(5)The nutrition that a layer thickness is 0.1~0.3mm is coated in cold pressing film surface to be homogenized, and obtains composite cold press mold;
(6)Acetobacter xylinum bacterium solution is sprayed on composite cold press mold surface, it is 15~30mL/m to control fountain height2, constant temperature and humidity culture 8~15 days, sterilize, wash, it is dry, up to chitosan-based compound hemostatic film.
A kind of 2. preparation method of chitosan-based compound hemostatic film according to claim 1, it is characterised in that:Step(1) The fluid nutrient medium is made of the raw material of following parts by weight:10~15 portions of mannitol, 3~5 portions of sucrose, 2~3 parts of beef Cream, 4~10 parts of peptones, 500~600 parts of water.
A kind of 3. preparation method of chitosan-based compound hemostatic film according to claim 1, it is characterised in that:Step(2) The chitosan liquid configuration process is:It is 1 in mass ratio by chitosan and water:50~1:After 60 mixing, swelling is stood, constant temperature stirs Dissolving is mixed, obtains chitosan liquid.
A kind of 4. preparation method of chitosan-based compound hemostatic film according to claim 1, it is characterised in that:Step(2) The gelatin solution configuration process is:It is 1 in mass ratio by gelatin and water:30~1:After 40 mixing, swelling is stood, constant temperature stirring is molten Solution, obtains gelatin solution.
A kind of 5. preparation method of chitosan-based compound hemostatic film according to claim 1, it is characterised in that:Step(2) The polyethylene glycol is polyethylene glycol 400, any one in polyethylene glycol 500 or Macrogol 600.
A kind of 6. preparation method of chitosan-based compound hemostatic film according to claim 1, it is characterised in that:Step(2) The crosslinking agent is any one in terephthalaldehyde, hexandial or glutaraldehyde.
A kind of 7. preparation method of chitosan-based compound hemostatic film according to claim 1, it is characterised in that:Step(4) The inorganic powder dispersion liquid is made of the raw material of following parts by weight:3~5 parts of magnesia, 10~20 parts of calcium hydroxy phosphates, 8~10 parts of pearl powders, 10~20 parts of pounces, 100~120 parts of mass fractions are 75% ethanol solution.
A kind of 8. preparation method of chitosan-based compound hemostatic film according to claim 1, it is characterised in that:Step(5) The nutrition homogenate is formed by the raw material configuration of following parts by weight:40~60 parts of honey, 3~5 parts of glycerine, 2~4 portions of seaweed Sour sodium, 6~8 portions of mannitol, 40~50 parts of water.
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