CN106344951B - A kind of bleeding stopping and adherence preventing biomembrane and preparation method thereof - Google Patents
A kind of bleeding stopping and adherence preventing biomembrane and preparation method thereof Download PDFInfo
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- CN106344951B CN106344951B CN201610593557.XA CN201610593557A CN106344951B CN 106344951 B CN106344951 B CN 106344951B CN 201610593557 A CN201610593557 A CN 201610593557A CN 106344951 B CN106344951 B CN 106344951B
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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
- 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
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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
- 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
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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
- 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
- A61L15/325—Collagen
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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
- 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
- A61L15/62—Compostable, hydrosoluble or hydrodegradable materials
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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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/042—Polysaccharides
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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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/043—Proteins; Polypeptides; Degradation products thereof
- A61L31/044—Collagen
-
- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/043—Proteins; Polypeptides; Degradation products thereof
- A61L31/045—Gelatin
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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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L89/00—Compositions of proteins; Compositions of derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L89/00—Compositions of proteins; Compositions of derivatives thereof
- C08L89/04—Products derived from waste materials, e.g. horn, hoof or hair
- C08L89/06—Products derived from waste materials, e.g. horn, hoof or hair derived from leather or skin, e.g. gelatin
Abstract
The invention discloses a kind of bleeding stopping and adherence preventing biomembranes and preparation method thereof, raw material selects carboxymethyl chitosan or carboxymethyl chitosan and gelatin/collagen mixture soluble in water, the mode of foamed, plasticising, frozen drying, hot setting, last machinery press mold is prepared.Biological membrane biological safety produced by the present invention is good, and hemostasis rapidly, and can effectively prevent wound adhesion, promotes wound healing.
Description
Technical field
The present invention relates to pharmaceutical technology field, in particular to a kind of bleeding stopping and adherence preventing biomembrane and preparation method thereof,
Specifically using natural biologic material as raw material, biomembrane made of crosslinked, foaming, curing molding and mechanical pressure.With
In the local hemostasis of surgery and wounded patient and prevent each section's post-operation adhesion preventing effect of Clinical Surgery.
Background technique
Clinically there is very big requirement to local hemostasis and post-operation adhesion preventing at present, clinically hemostasia products are various,
Dosage form multiplicity, has liquid, pulvis, gelling agent and film etc., wherein natural biological hemostatic material can be dropped with its unique biology
Solution sexual clorminance occupies leading position in clinical hemostasis application field.The adhesion of part will will lead to serious clinical complication,
Surgical effect and patients ' life quality have been seriously affected, the economy and mental burden of patient have been aggravated.In Surgery of spinal cord, due to art
Focal adhesion can cause the complication such as patient and dyskinesia afterwards；The focal adhesion of tendon Orthopeadic Surgery can cause movement to hinder
Hinder；The adhesion of gynemetrics can cause infertility, so post-operation adhesion preventing clinically has extensive purposes, can significantly reduce
Postoperative complications and second operation.
In clinical field, biological tissue will appear the bad adhesion unrelated with tissue repair, bad adhesion after surgery
It will cause metaplasia, obstruction, distortion, cause serious consequence.For example, postoperative bad adhesion can cause pain or biological group
The dysfunction knitted also needs to carry out in severe cases other operation for removing bad adhesion.Moreover, postoperative generation
Bad adhesion can also become very difficult to the operation again of original disease.It is existing that postoperative bad adhesion is generated in order to prevent
As generally being covered and protected using the Antiadhesive film with excellent biocompatibility and bioresorbable may stick together
Tissue.
Chitosan and its derivative is natural polymers, belongs to glycosaminoglycan, be find up to now it is unique
Alkaline polysaccharide with cationic charge.It is widely present in unicellular lower eukaryote mushroom in nature, the cell of algae, section branch animal shrimp,
In the shell of crab, insect etc..Good biocompatibility, toxicity are low, biodegradable, are widely used in food, medicine, health care, life
The fields such as object engineering.Chitosan itself has anastalsis, meanwhile, chitosan passes through its phase interaction between erythrocyte membrane
With mainly realizing hemostasis to the agglutination of red blood cell.
In the prior art, the Antiadhesive film of various material has been disclosed, is mentioned in Chinese patent CN104208758 A
It has supplied one is polylactic acid-based Antiadhesive film, polylactic acid-based Antiadhesive film has good mechanical property, biodegradable and biofacies
The advantages that capacitive is good, but there is also inevitable disadvantages, wherein most important problem is to be easy to become fragile after implanting to be hardened,
Preventing adhesiving effect is influenced, therefore use is very restricted.Chinese patent literature CN101052425A discloses one kind
The Antiadhesive film of the copolymer of lactide and caprolactone, the molar ratio of lactide and caprolactone in the copolymer is 65: 35~
80:20.A kind of preventing adhesion for the copolymer preparation of polycarbonate and lactide is provided in 102327651 A of Chinese patent CN
Film, compared with polylactic acid-based Antiadhesive film, the advantages of such contains Antiadhesive film made of the mixture of polycarbonate is elasticity
It is good, but the disadvantage is that mechanical strength is low, raw materials used poor biocompatibility easily causes organism immune response, therefore uses
It is limited by very large.
Summary of the invention
It is an object of the invention to overcome the shortcomings of above-mentioned technology, a kind of bleeding stopping and adherence preventing biomembrane and its preparation side are provided
Method.
A kind of bleeding stopping and adherence preventing biomembrane and preparation method thereof, component includes: carboxymethyl chitosan or carboxymethyl chitosan
With one of gelatin/collagen mixture, moisturizer, crosslinking agent, foaming agent and water.It takes water as a solvent, each component presses quality
Than are as follows: carboxymethyl chitosan or carboxymethyl chitosan/gelatin/collagen 0.5%~5%；Moisturizer 0.5%~5%；Crosslinking agent
0.01%~1%；Foaming agent 0.1%~2%.
On the basis of above scheme, the moisturizer be glycerine, propylene glycol, polyethylene glycol, one or more of；
Crosslinking agent is sodium alginate, potato starch, tapioca, glucose, dopamine, hyaluronic acid；Foaming agent is poloxamer.
On the basis of above scheme, the preparation method of bleeding stopping and adherence preventing biomembrane a kind of the following steps are included:
1) preparation of crosslinking agent: the sodium alginate aqueous solution of suitable concentration is prepared, it is molten to be then slowly added to sodium metaperiodate
Mechanical stirring in liquid, then with deionized water dialysis for 24 hours~48h, vacuum freeze is freeze-dried reaction solution, cold
Freezing the time is that for 24 hours, drying time is 48h~72h；
2) preparation of reaction solution: described to be selected from containing carboxymethyl chitosan solution: carboxymethyl chitosan sugar aqueous solution, carboxymethyl
One of chitosan and gelatin/collagen mixed solution；Solution containing carboxymethyl chitosan is soluble in water, moisturizer is added
10min~90min is stirred to react with above-mentioned crosslinking agent；Foaming agent is soluble in water, it is slowly dropped in above-mentioned mixed liquor, high speed
Stirring foaming 30min~90min；
3) frozen drying: above-mentioned reaction solution is poured into mold, -20 DEG C~-80 DEG C freezings, and the rear vacuum that carries out is done
It is dry, it is soft cavernous body after dry；
4) hot setting is plasticized: the material after freeze-drying being moved into reaction kettle and carries out 20 DEG C~100 DEG C high temperature plasticization reactions；
5) mechanical press mold: after curing molding, material is taken out from reaction kettle, is demoulded first, then machinery pressure
Compel film forming.
On the basis of above scheme, the preparation method of the carboxymethyl chitosan sugar aqueous solution are as follows: according to concentration be 0.5%
~5% weighs a certain amount of carboxymethyl chitosan, dissolves in dissolution 15min~120min in water while stirring.
On the basis of above scheme, the preparation method of the carboxymethyl chitosan/gelatin solution includes: to prepare gelatin water
Solution: medical gelatin is added in distilled water, and 30~60 DEG C of heating obtain aqueous gelatin solution, and 30 points are stood at 0~10 DEG C
Clock to 2h, the mass concentration of institute's gelatin water solution is 0.01~20%；Then according to the quality of carboxymethyl chitosan and gelatin
Than being 100: 2~20, carboxymethyl chitosan sugar aqueous solution and aqueous gelatin solution are mixed, carboxymethyl chitosan and gelatin is prepared
Mixed solution.
On the basis of above scheme, the preparation method of the carboxymethyl chitosan/collagen solution includes: that configuration concentration is
0.01%~2% collagen acetic acid solution, and 30 minutes to 2 hours are stood at 0~10 DEG C；Then according to carboxymethyl shell
The mass ratio of glycan and collagen is 100: 2~20, mixes carboxymethyl chitosan sugar aqueous solution and collagenic aqueous solution, carboxylic first is prepared
The mixed solution of base enclosure glycan and collagen.
On the basis of above scheme, sodium alginate aqueous solution and sodium metaperiodate volume ratio are 1 in crosslinking agent preparation process
~10:1.
On the basis of above scheme, the expanding foam solution cryogenic freezing time be 12h~72h, vacuum drying time be 12h~
72h。
On the basis of above scheme, the reaction kettle of hot setting plasticising selects air dry oven, vacuum desiccator, constant temperature
Incubator, high temperature plasticization reaction temperature are 20 DEG C~100 DEG C, and the reaction time is 5h~72h.
On the basis of above scheme, the molding mode of biomembrane is that soft cavernous body is carried out to mechanical compression film forming, raw
The thickness of object film is in 0.1~3mm.
Due to the application of the above technical scheme, compared with the prior art, the invention has the following advantages:
1) due to preparation process be all water environment with facilitate operation at a temperature of carry out, prepared process is mild, easily-controllable,
It will not cause the reduction of the biological membrane biological compatibility；
2) crosslinking for carrying out biomembrane in the present invention using macromolecules cross-linking substance, instead of small molecule toxic chemical
The use of (such as formaldehyde, glutaraldehyde) has better histocompatbility；
3) present invention is using the biomaterials such as carboxymethyl chitosan, gelatin and collagen, enough film formings and is suitable for
Crosslinking guarantees that the liquid-absorbent and biodegradability of finished product, chitosan itself have the function of sorptivety of stopping blooding, machining
After film forming, mechanical property is improved, adhesion inhibiting properties enhancing avoids secondary insult, inhibits scar, healing acceleration to reach
Effect；
It 4) during the preparation process, can be by adjusting cryogenic temperature, the parameters such as solution concentration, solidification plasticising time, control
The microstructure of biomembrane meets the requirement of different application to easily reach control biomembrane hemostasis rate.
Specific embodiment:
Embodiment 1:
1) preparation of crosslinking agent: weighing 1.0g sodium alginate and be dissolved in 140mL water, and it is molten that 10mL sodium metaperiodate is added dropwise thereto
Liquid (40mg/mL) is often protected from light electromagnetic agitation and reacts 4 hours.0.200mL ethylene glycol is added dropwise thereto again, is stirred to react 1 hour
Afterwards, it is then dialysed 24 hours in deionized water with the bag filter leaching of molecular cut off 3500, changes a water within during which every 4 hours,
Vacuum equipment is freeze-dried 48 hours, obtains the sodium alginate solid of hydroformylation.
2) preparation of reaction solution: 1.0g carboxymethyl chitosan is weighed again and is dissolved in 30mL water, ultrasound is needed in the process or stirs
Dissolution 30min is mixed, be formulated as follows solution at the same time: the sodium alginate of the above-mentioned hydroformylation of 50mg is dissolved in 10mL water；1.50g glycerol
It is dissolved in 1mL water, 0.30g poloxamer188 is dissolved in 9mL water and 10mL PBS.Next, carboxylic is added in the glycerol after preparation
In methyl chitosan solution, 10min is stirred, dissolved sodium alginate soln is finally added dropwise, is stirred to react 30min.Finally will
Poloxamer188 solution is added in above-mentioned reaction solution, high-speed stirred 60min.
3) reaction solution is injected into mold, is freezed at -20 DEG C for 24 hours, obtains carboxymethyl chitosan Frozen Body, be then placed in
In vacuum drier, through 48h freeze-drying process, soft cavernous body is obtained.
4) this cavernous body is put into air dry oven, through for 24 hours, during which 60 DEG C of hot setting plasticizing reactions keep sponge
Body is not fallen off with mold.
5) after solidification plasticising, cavernous body is taken out from reaction kettle, is demoulded first, restores 30min under room temperature, so
Afterwards mechanical pressure form a film, film with a thickness of 0.5mm.
Embodiment 2:
1) preparation of crosslinking agent is the same as the 1) preparation of crosslinking agent in embodiment 1.
2) preparation of reaction solution: taking water as a solvent, and each component is in mass ratio are as follows: carboxymethyl chitosan: gelatin: polyethylene
Alcohol: crosslinking agent: poloxamer188=1:1:0.5:0.03:0.3 ratio is weighed.Carboxymethyl chitosan and gelatin first
It is mixed, sequentially adds crosslinking agent and be stirred to react 30min, poloxamer188 reacts 30min.
3) reaction solution is injected into mold, in -40 DEG C of freezing 12h, obtains carboxymethyl chitosan/gelatin Frozen Body, so
After be put into vacuum drier, through 48h freeze-drying process, obtain soft cavernous body.
4) this cavernous body is put into vacuum oven, vacuum drying, temperature is 80 DEG C, plasticizing reaction 12h.
5) after solidification plasticising, cavernous body is taken out from reaction kettle, is demoulded first, restores 30min under room temperature, so
Afterwards mechanical pressure form a film, film with a thickness of 1mm.
Embodiment 3:
1) preparation of crosslinking agent: weighing 3g potato starch and be dissolved in the sodium hydroxide solution (1mol/L) of 25mL, then
10mL DMSO and 10mL isopropanol is added dropwise thereto.Then 4mL epoxychloropropane is added dropwise thereto, reaction is stirred at room temperature in exhaust
48h.Then with hydrochloric acid adjust pH=7, then with excess acetone precipitation.High speed centrifugation is carried out after precipitating, product is on a small quantity after centrifugation
Purified water dissolves 1h, dialyses 24 hours in water, changes within during which every 4 hours a water, and vacuum equipment is freeze-dried 48 hours.
2) preparation of reaction solution: weighing 3g carboxymethyl chitosan again and be dissolved in 100mL water, needs ultrasound or stirring in the process
30min is dissolved, be formulated as follows solution at the same time: the above-mentioned epoxy starch of 100mg is dissolved in 20mL water；3g glycerol is dissolved in 10mL water
In, 1g poloxamer188 is dissolved in 50mL water.Then the glycerol after preparation is added in carboxymethyl chitosan solution, stirring
300min is finally added dropwise dissolved epoxy starch solution, is stirred to react 1h.Finally poloxamer188 solution is added above-mentioned
In reaction solution, high-speed stirred 1h.
3) reaction solution is injected into mold, in -40 DEG C of freezing 12h, obtains carboxymethyl chitosan Frozen Body, be then placed in
In vacuum drier, through 48h freeze-drying process, soft cavernous body is obtained.
4) this cavernous body is put into constant temperature and humidity drying case, through 72h, during which 50 DEG C of hot setting plasticizing reactions are kept
Cavernous body is not fallen off with mold.
5) after solidification plasticising, cavernous body is taken out from reaction kettle, is demoulded first, then mechanical pressure forms a film,
Film with a thickness of 1mm.
Embodiment 4:
The biomembrane prepared in embodiment 1 promotes Rat Wound Healing experiment:
The depilation of rat back depilatory agent, area about 5cm × 5cm tie four limbs with rubber band, are fixed on rat in ventral decubitus
In fixed plate.Lcm is opened on the selection back middle part each side in backbone two sides, away from preparing the surface of a wound at 2cm below shoulder blade.In above-mentioned traumatic part processed
Position respectively extrudes 1 round trace (2.54cm2) with the trepan of diameter 18mm perpendicular to skin, and bend surgical is cut to be cut off entirely along impression
Layer skin (reaches deep fascia), and round full thickness dermal wounds are made, and stops blooding spare.Every rat prepares 2 surface of a wound, i.e. back
Two sides respectively prepare 1 surface of a wound.
Experimental group: diffraction patterns for biomembrane samples covering；Positive control: sterile gauze covering.
Observe rat animation, healing state, infection conditions, scar shape etc..The sample of replacement covering daily.After wound
3rd day, 5 days, 7 days, 11 days, 14 days, transparent membrane flap coverage is used respectively, film is drawn along edge of wound, cuts film, setting scale division value is
The assay balance of 0.1mg weighs quality and is converted to area, records each group surface of a wound area, calculates healing rate.Healing rate=(former face
Product-non-repaired area)/original area × 100%.
Experimental result:
A) behaviouristics result: during the experiment, rat diet, drinking-water situation are normal, and behavior is without exception, and no fur is extremely de-
It falls, it is not intended to the outer phenomena of mortality.There was no significant difference for biofilm experiments group and rat body weight.
B) inflammatory reaction: biofilm experiments group is sliced without obvious redness, physiology the result shows that postoperative one week visible obvious inflammation
Property intrusion, inflammatory is remarkably decreased after 2 weeks.The decline of sterile gauze group inflammation is unobvious.
C) wound bleeding adhesion situation: sterile gauze group adhesion is serious, has resulted in secondary injury to wound, with sterile yarn
Cloth control group is compared, and oozing of blood situation is significantly less than control group when biofilm experiments group dressing, and without any adhesion.
D) healing state: the surface of a wound of sections observation to biomembrane test group is substantially better than sterile gauze group, granulation tissue
Well-grown, it is obvious at fibrosis, and have angeogenesis.
Attached drawing 1 is wound healing situation map, and attached drawing 2 is wound healing rate figure.
Claims (2)
1. a kind of bleeding stopping and adherence preventing biomembrane, which is characterized in that component include: carboxymethyl chitosan or carboxymethyl chitosan with it is bright
One of glue/collagen mixture, moisturizer, crosslinking agent, foaming agent and water；It takes water as a solvent, each component is in mass ratio are as follows:
Carboxymethyl chitosan or one of carboxymethyl chitosan and gelatin/collagen mixture 0.5%~5%；Moisturizer 0.5%~
5%；Crosslinking agent 0.01%~1%；Foaming agent 0.1%~2%；
The moisturizer is one or more of glycerine, propylene glycol, polyethylene glycol；Crosslinking agent is sodium alginate；Foaming agent
For poloxamer；
A kind of preparation method of the bleeding stopping and adherence preventing biomembrane the following steps are included:
1) preparation of crosslinking agent: the sodium alginate aqueous solution of suitable concentration is prepared, is then slowly added in sodium periodate solution
Mechanical stirring, then with deionized water dialysis for 24 hours~48h, vacuum freeze is freeze-dried reaction solution, when freezing
Between for for 24 hours, drying time is 48h~72h；
2) preparation of reaction solution: the solution containing carboxymethyl chitosan is soluble in water, moisturizer is added and above-mentioned crosslinking agent stirs
Mix reaction 10min~90min；Foaming agent is soluble in water, it is slowly dropped in above-mentioned mixed liquor, high-speed stirred foaming 30min
~90min；It is described to be selected from containing carboxymethyl chitosan solution: carboxymethyl chitosan sugar aqueous solution, carboxymethyl chitosan and gelatin/glue
One of former mixed solution；
3) frozen drying: above-mentioned reaction solution is poured into mold, -20 DEG C~-80 DEG C freezing, after be dried in vacuo, do
It is soft cavernous body after dry；
4) hot setting is plasticized: the material after freeze-drying being moved into reaction kettle and carries out 20 DEG C~100 DEG C high temperature plasticization reactions；
5) mechanical press mold: after curing molding, material being taken out from reaction kettle, is demoulded first, then mechanical pressure at
Film；
The preparation method of the carboxymethyl chitosan sugar aqueous solution are as follows: weigh a certain amount of carboxymethyl according to concentration for 0.5%~5%
Chitosan dissolves in dissolution 15min~120min in water while stirring；
The preparation method of the carboxymethyl chitosan/gelatin solution includes: preparation aqueous gelatin solution: medical gelatin being added and is distilled
In water, 30~60 DEG C of heating obtain aqueous gelatin solutions, and stand at 0~10 DEG C 30 minutes to 2h, institute's gelatin water solution
Mass concentration is 0.01~20%；Then it is 100: 2~20 according to the mass ratio of carboxymethyl chitosan and gelatin, mixes carboxymethyl
The mixed solution of carboxymethyl chitosan and gelatin is prepared in chitosan aqueous solution and aqueous gelatin solution；
The preparation method of the carboxymethyl chitosan/collagen solution includes: the collagen second that configuration concentration is 0.01%~2%
Acid solution, and 30 minutes to 2 hours are stood at 0~10 DEG C；It then is 100 according to the mass ratio of carboxymethyl chitosan and collagen
: 2~20, it mixes carboxymethyl chitosan sugar aqueous solution and collagenic aqueous solution, the mixing that carboxymethyl chitosan and collagen is prepared is molten
Liquid；
Sodium alginate aqueous solution and sodium metaperiodate volume ratio are 1~10:1 in crosslinking agent preparation process；
The reaction solution cryogenic freezing time is 12h~72h, and vacuum drying time is 12h~72h；
The reaction kettle of hot setting plasticising selects one of air dry oven, vacuum desiccator, constant incubator, high temperature plasticization
Reaction temperature is 20 DEG C~100 DEG C, and the reaction time is 5h~72h；
The molding mode of biomembrane is that soft cavernous body is carried out mechanical compression film forming, and the thickness of biomembrane is in 0.1~3mm.
2. a kind of bleeding stopping and adherence preventing biomembrane, which is characterized in that be prepared by following methods:
1) it the preparation of crosslinking agent: weighs 3g potato starch and is dissolved in the 1mol/L sodium hydroxide solution of 25mL, then thereto
10mL DMSO and 10mL isopropanol is added dropwise, 4mL epoxychloropropane is then added dropwise thereto, reaction 48h is stirred at room temperature, so in exhaust
PH=7 is adjusted with hydrochloric acid afterwards, then with excess acetone precipitation, carries out high speed centrifugation after precipitating, a small amount of purified water of product after centrifugation
1h is dissolved, is dialysed 24 hours in water, a water is changed within during which every 4 hours, vacuum equipment is freeze-dried 48 hours；
2) preparation of reaction solution: weighing 3g carboxymethyl chitosan again and be dissolved in 100mL water, needs ultrasound or stirring and dissolving in the process
30min is formulated as follows solution at the same time: the above-mentioned epoxy starch of 100mg is dissolved in 20mL water；3g glycerol is dissolved in 10mL water,
1g poloxamer188 is dissolved in 50mL water, and then the glycerol after preparation is added in carboxymethyl chitosan solution, stirring
300min is finally added dropwise dissolved epoxy starch solution, is stirred to react 1h, finally poloxamer188 solution is added above-mentioned
In reaction solution, high-speed stirred 1h；
3) reaction solution is injected into mold, in -40 DEG C of freezing 12h, obtains carboxymethyl chitosan Frozen Body, be then placed in vacuum
In drying machine, through 48h freeze-drying process, soft cavernous body is obtained；
4) above-mentioned soft cavernous body is put into constant temperature and humidity drying case, through 72h, during which 50 DEG C of hot setting plasticizing reactions are protected
Cavernous body is held not fall off with mold；
5) after solidification plasticising, cavernous body is taken out from reaction kettle, is demoulded first, then mechanical pressure forms a film, film
With a thickness of 1mm.
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