CN107929795A - A kind of preparation and its application of antibacterial anti hemorrhagic material - Google Patents
A kind of preparation and its application of antibacterial anti hemorrhagic material Download PDFInfo
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- CN107929795A CN107929795A CN201711137277.9A CN201711137277A CN107929795A CN 107929795 A CN107929795 A CN 107929795A CN 201711137277 A CN201711137277 A CN 201711137277A CN 107929795 A CN107929795 A CN 107929795A
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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
- A61L15/20—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing organic materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
- A61L15/42—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
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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
- 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
- A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
- A61L2300/208—Quaternary ammonium compounds
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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
- 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
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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
- 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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- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
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Abstract
The present invention relates to a kind of preparation and its application of antibacterial anti hemorrhagic material, belong to biomaterial and medicine and hygiene fields.The invention particularly discloses a kind of preparation and its application of antibacterial anti hemorrhagic material, material is with collagen, based on organosilicon quaternary ammonium salt and chitosan, through following steps：The extraction of collagen, the preparation of three kinds of solution, solution freeze, and the process such as crosslinking and sterilizing is made.Gained antibacterial anti hemorrhagic material has tridimensional network, mechanical performance is high, imbibition ability is strong, and rate of liquid aspiration is fast, good biocompatibility, degrade the advantages that controllable, additionally due to the presence of organosilicon quaternary ammonium salt and chitosan, product of the present invention also has good bacteriostasis antibiosis, has a broad antifungal spectrum, it is a kind of excellent antibacterial anti hemorrhagic, tissue bulking material.
Description
Technical field
The invention belongs to biomaterial and medicine and hygiene fields, be specifically related to a kind of antibacterial anti hemorrhagic material preparation and its
Using.
Background technology
Wound bleeding is the problem of being difficult to avoid that in human lives, such as surgical procedure, injured in war, traffic accident,
Natural calamity and other people be or accident can cause the appearance of bleeding, can not fast and effective hemostasis be dead master
Influence factor is wanted, therefore effectively hemostasis seems particularly critical.Hemostasis is a complicated process in itself, except blood itself blood
Platelet is assembled outside itself solidification, and other factors may also function as key effect, such as hemostasis by compression, electrosurgical and hemostatic material
Deng.Hemostatic material not only needs to have that common bleeding stopping period is short, and haemostatic effect is obvious, has and promotes wound healing and treatment
Effect, material should also have good biocompatibility, have no adverse reaction with body in itself, good with wound tissue adhesion, spy
It is not that should not produce secondary insult again, increases pain and medical treatment cost to patient for no reason.Current clinically common hemostatic material
Species is various, and Various Functions, quality is uneven, such as gauze, sponge kind, styptic powder and gel etc..Above-mentioned hemostatic material base
Instinct meets clinical practice, but in surgical procedure, particularly in war, or cannot hospitalier immediately, easily hinder
Mouthfeel contaminates, severe patient's even threat to life.Therefore a kind of good biocompatibility is urgently developed, anthemorrhagic speed is fast, promotes wound to be cured
Have the multifunctional and composite type hemostatic material in medical use of bacteriostasis antibiosis during contract concurrently.
Collagen is bioabsorbable polymer material, is the spirality fiber shape protein for having three peptide chains to twist into, three phases
Mutually independent collagen peptide chain relies on the hydrogen bond formed between glycine to maintain the structure that triple helix is mutually wound, collagen this
The special triple helix structure of kind ensure that its mechanical strength.Collagen is the important protein of animal connective tissue, about
Account for its 20% ~ 30%, be mammal in-vivo content at most, the most wide functional protein of distribution.Collagen species is more, common
Type is I type, II type, III type, V type and Ⅺ type.Collagen is good biocompatibility, degradable because of its extensive source
Property and bioactivity, obtain extensive use and concern in fields such as food, medicine, organizational project, cosmetics.
Organosilicon quaternary ammonium salt is a kind of Novel Cationic Surfactants, it has high temperature resistant, water-fastness, lasting effect
Fruit, scope of restraining fungi are wide, can effectively inhibit gram-positive bacteria, Gram-negative bacteria, saccharomycete and fungi.Organosilicon quaternary ammonium salt
Excellent antibacterial bacteriostasis property by facts have proved.Some researches show that use it for pure cotton fabric arrangement, find to golden yellow
Bacteriostasis rate after 24 h of color staphylococcus, Escherichia coli and candida albicans respectively reaches 98.12 %, 96.86 %, 95.14
%, show broad-spectrum antimicrobial effect and higher antibiotic rate and it is safe and non-toxic, without cause enzyme reaction.Its sterilization mechanism is：With organosilicon
As medium, ammonium cation group with bactericidal property is forcefully adsorbed in the surface of object, positively charged quaternary ammonium
Salt ion firmly adsorbs the microorganisms such as the bacterium with negative electrical charge, fungi, by varying the permeability of bacteria cell wall, makes thalline
Interior enzyme, coenzyme and metabolic intermediate overflow, and cause microorganism to cease breathing function and lethal, so as to reach sterilization, antibacterial
Effect.In addition organosilicon quaternary ammonium salt is water solubility, can be mixed with multi-solvents and solute, and have good stability.
Alkaline polysaccharide of the chitosan as the unique positively charged of nature, it can adsorb the negative electrical charge on red blood cell, make
Red blood cell is largely assembled, and produces blood coagulation, accelerates hemostasis；In addition chitosan also has excellent anti-microbial property, its Antibacterial Mechanism point
It is several below：（1）The chitosan that molecular weight is less than 5000 dalton can be with penetration cell film, and the chitosan of small-molecular-weight is into a subtle way
In biological cell, because chitosan it is positively charged its with intracellular electronegative material（Mainly protein and nucleic acid）With reference to making
The normal physiological function of cell is affected, and causes microorganism dead；（2）The chitosan of macromolecule is adsorbed in microbial cell
Surface, forms a floor height molecular film, nutriment is prevented to intracellular transport, so as to play sterilization and bacteriostasis effect；（3）Shell
Interaction between the positive charge of glycan and the negative electrical charge of microbial cell film surface, changes the penetrating of microbial cell film
Property, cause microbial cell dead；（4）Chitosan has optionally grown microorganism pass as a kind of chelating agent to chelating
The metal ion of key effect, so as to suppress the growth of microorganism, produces toxic death.
In view of this, the present invention provides with collagen, organosilicon quaternary ammonium salt and chitosan are the compound of basic material
The preparation method and applications of hemostatic material.
The content of the invention
To solve the above problems, the present invention provides a kind of preparation and its application of antibacterial anti hemorrhagic material, particular technique side
Case is as follows.
The preparation of 1 collagen
（1）Choose collagen-rich tissue, remove it after undesired residues that at least 6 are freezed in the environment of -20 DEG C is small
When more than；Then the tissue after freezing carries out slicing treatment.It is collagen-rich to be organized as ox heel string, cow hoof, ox-hide, trotter
With pigskin etc..
（2）By the tissue of well cutting, 5 ~ 30min of soaking flushing, drains unnecessary water into the water；Prepare phosphate-buffered
Liquid, after the completion of weigh a certain amount of enzyme and be added thereto, the concentration of enzyme is 0.001% ~ 5%, is fully mixed.It is described in the present invention
Phosphate buffer is by NaCl, Na2HPO4And NaH2PO4Composition or NaCl, Na2HPO4And KH2PO4Composition, phosphate buffer
Concentration is 0.01-0.1mol/L；PH value is 5 ~ 7.The enzyme is pepsin, ficin, cysteine proteases
And the one or more of other acid proteases.
（3）The tissue completed will be rinsed to add in above-mentioned enzyme solutions, be put into shaking table, keep 0.5 at 10 ~ 50 DEG C ~
24h；The ratio of wherein tissue and enzyme solutions is 0.01:100~20:100（As mass fraction）.
（4）Enzyme-deactivating：Reactant is taken out out of shaking table, is rinsed several times with water, is drained excessive moisture, be added to advance preparation
In good salting liquid, shaking table is opened, 0.5 ~ 5h is kept at 10 ~ 50 DEG C；Heretofore described salting liquid is sodium nitrate, nitric acid
Ammonium, potassium nitrate, sodium hypochlorite, sodium hydroxide, the one or more in potassium hydroxide；Concentration is 0.01% ~ 20%；Reactant and salt
Solution proportion is 0.1:100~30:100.
（5）Inactivation of virus：Reactant is taken out out of shaking table, is rinsed several times with water, drains excessive moisture, then solid is added
Into prepared salting liquid, shaking table is opened, 15 ~ 40 DEG C of design temperature, cultivates 20 ~ 60h.Salting liquid described in this step is
Sodium hydrogensulfite, sodium thiosulfate, ammonium sulfate, sodium sulphate, the one or more in sodium hydroxide and potassium hydroxide, concentration are
0.01%~20%；Reactant and salting liquid ratio are 0.1:100~30:100.
（6）Culture is taken out out of shaking table, it is 4 ~ 8 to adjust ph, collects product, washes with water, drain, that is, obtain collagen egg
In vain.
The preparation of 2 slurries
（1）Collagen obtained by the step 1 of certain amount is weighed, is added to purified water, stirring makes its dispersed, molten with acid
Liquid adjusts pH to 4 ~ 7, and quick stirring makes it mix completely, spare；The ratio of collagen and purified water is 0.01:100~10:
100, acid solution is acetic acid, hydrochloric acid, at least one of sulfuric acid or lactic acid.
（2）A certain number of commercially available organosilicon quaternary ammonium salts are measured, are added to purified water, quick stirring makes to be uniformly mixed, standby
With；The ratio of organosilicon quaternary ammonium salt and purified water is 0.01:100~50:100.
（3）A certain number of commercially available chitosans are weighed, are added to purified water, quick stirring makes to be uniformly mixed, and uses acid solution
PH to 4 ~ 7 is adjusted, it is spare；The ratio of chitosan and purified water is 0.01:100~50:100；Chitosan of the present invention is carboxylic first
Base enclosure glycan, chitosan, at least one of hydroxyl butyl chitosan and other modification of chitosan；Acid used is acetic acid, hydrochloric acid,
At least one of sulfuric acid or lactic acid.
（4）By step（1）Gained collagen slurry, step（2）Gained organosilicone quaternary ammonium salting liquid and step（3）Gained
Chitosan solution is mixed in a certain ratio, and is quickly stirred and evenly mixed, and through vacuum deaerator, is stood, is obtained mixed serum, spare；This hair
Bright middle collagen slurry, organosilicone quaternary ammonium salting liquid, the ratio of chitosan solution are（1~10）：（1~10）:（1~10）(V/V/
V)。
The preparation of 3 antibacterial anti hemorrhagic materials
（1）Above-mentioned obtained mixed liquor is poured slowly into stainless steel to freeze in mould, slurries thickness 1mm ~ 50mm, sets lyophilized ginseng
Number is freeze-dried.
（2）After the completion of lyophilized, product is taken out, is crosslinked using physically and/or chemically method, cuts packaging, sterilizing, that is, obtain
Antibacterial anti hemorrhagic material of the present invention.Product Physical cross linking methods are heat cross-linking in the present invention；Chemical Crosslinking Methods are formaldehyde,
Glutaraldehyde, Geniposide and EDC etc.；Used sterilization method includes ethylene oxide sterilizing, ray sterilizing and high-temperature sterilization, wherein
Ray sterilizing divides cobalt -60 and electron beam again, and sterilizing dose is 5KGy ~ 40KGy.
The antibacterial anti hemorrhagic material obtained by above step has following clear advantage：
First, antibacterial anti hemorrhagic material provided by the present invention, has a three-dimensional aperture structure, high mechanical strength, low immunogenicity and pure
Spend the advantages that high；
2nd, antibacterial anti hemorrhagic material provided by the present invention, has excellent anti-microbial property, has a broad antifungal spectrum, antibacterial bacteriostatic rate height；
3rd, antibacterial anti hemorrhagic material provided by the present invention, good biocompatibility can be degradable, can be real by adjusting the degree of cross linking
Now degrade controllable；
4th, antibacterial anti hemorrhagic material provided by the present invention, it is strong with tissue adhesiveness, promote tissue repair, superpower imbibition
Ability, accelerates hemostasis, promotes wound healing, the generation of scar is significantly reduced for the wound dressing moment.
Embodiment
To make technical scheme clearer, below embodiment of the present invention is described further in detail.
Embodiment one
The acquisition of collagen
1st, collagen-rich ox heel string is chosen, rejects fascia, when freezing 20 is small in the environment of -20 DEG C.After freezing
Tissue carries out slicing treatment；
2nd, ox heel string section 5000g is weighed, soaking flushing 15min, drains unnecessary water into the water；Prepare 0.06mol/L's
Phosphate buffer 40L, it is 7 to adjust ph, after the completion of weigh 60g pepsin enzymes and be added thereto, fully mix；
3rd, the tissue for rinsing completion is added in above-mentioned enzyme solutions, is put into shaking table, 10h is kept at 30 DEG C；Wherein ox heel string
The ratio of section and enzyme solutions is 8:100；
4th, enzyme-deactivating：Reactant is taken out out of shaking table, with water rinse several times, drain excessive moisture, be added to 3% sodium nitrate and
In 0.4% sodium hydroxide solution, liquor capacity 40L, opens shaking table, 2h is kept at 30 DEG C；
5th, inactivation of virus：Reactant is taken out out of shaking table, is rinsed several times with water, is drained excessive moisture, it is molten to be added to 2% ammonium sulfate
In liquid, liquor capacity 35L, opens shaking table, 10h is kept at 25 DEG C；
6th, culture is taken out out of shaking table, it is 5.5 to adjust ph, collects product, washes with water, drain, that is, obtain collagen.
Embodiment two
Collagen raw material obtains
1st, collagen-rich pigskin is chosen, removes impurity, when freezing 20 is small in the environment of -20 DEG C.Then after freezing
Pigskin carries out slicing treatment；
2nd, pigskin section 1000g is weighed, soaking flushing 25min, drains unnecessary water into the water；Prepare the phosphorus of 0.08mol/L
Phthalate buffer 15L, it is 6 to adjust ph, after the completion of weigh 4g ficins and be added thereto, fully mix；
3rd, the tissue for rinsing completion is added in above-mentioned enzyme solutions, is put into shaking table, 18h is kept at 40 DEG C；Wherein pigskin is cut
The ratio of piece and enzyme solutions is 1:30；
4th, enzyme-deactivating：Reactant is taken out out of shaking table, is rinsed several times with water, is drained excessive moisture, be added to 5% ammonium nitrate solution
In, liquor capacity 10L, opens shaking table, 4h is kept at 20 DEG C；
5th, inactivation of virus：Reactant is taken out out of shaking table, with water rinse several times, drain excessive moisture, be added to 6% ammonium sulfate and
In 1% sodium hydroxide solution, liquor capacity 15L, opens shaking table, 50h is kept at 20 DEG C；
6th, culture is taken out out of shaking table, it is 5 to adjust ph, collects product, washes with water, drain, that is, obtain collagen.
Embodiment three
1 weigh the embodiment one of 50g obtained by collagen, be added to 1L purified waters, stirring makes its dispersed, uses hydrochloric acid
Solution adjusts pH to 5.5, and quick stirring makes it mix completely, spare；
2 measure certain 500mL organosilicon quaternary ammonium salts, are added to 2L purified waters, and quick stirring makes to be uniformly mixed, spare；
3 weigh 100g chitosans, are added to 1L purified waters, and quick stirring makes to be uniformly mixed, standby with acetum tune pH to 6.0
With；
4 measure above-mentioned 500mL collagen solutions respectively, 800mL organosilicone quaternary ammoniums salting liquid and 800mL chitosan solutions in
In one clean reaction kettle, quickly stir and evenly mix, open vacuum pump and carry out vacuum deaerator, stand, it is spare；
Above-mentioned obtained mixed liquor is poured slowly into stainless steel by 5 to be freezed in mould, slurries thickness 4mm, is set lyophilized parameter and is carried out
Freeze-drying；
6 lyophilized end, take out product, are crosslinked with formalin；Sample after crosslinking is subjected to cutting packaging, send irradiation
Center carries out cobalt -60 and sterilizes, and sterilizing dose 15KGy, obtains antibacterial anti hemorrhagic material of the present invention.
Example IV
1 weigh the embodiment one of 400g obtained by collagen, be added to 2L purified waters, stirring makes its dispersed, uses sulfuric acid
Solution adjusts pH to 5.9, and quick stirring makes it mix completely, spare；
2 measure certain 500mL organosilicon quaternary ammonium salts, are added to 1L purified waters, and quick stirring makes to be uniformly mixed, spare；
3 weigh 200g chitosans, are added to 1L purified waters, and quick stirring makes to be uniformly mixed, standby with lactic acid solution tune pH to 6.0
With；
4 measure above-mentioned 1000mL collagen solutions respectively, 500mL organosilicone quaternary ammoniums salting liquid and 200mL chitosan solutions in
In one clean reaction kettle, quickly stir and evenly mix, open vacuum pump and carry out vacuum deaerator, stand, it is spare；
Above-mentioned obtained mixed liquor is poured slowly into stainless steel by 5 to be freezed in mould, slurries thickness 5mm, is set lyophilized parameter and is carried out
Freeze-drying；
6 lyophilized end, take out product, are crosslinked with glutaraldehyde；Sample after crosslinking is subjected to cutting packaging, send epoxy second
Alkane sterilizing station sterilizes, and after parsing, obtains antibacterial anti hemorrhagic material of the present invention.
Embodiment five
1 weigh the embodiment two of 200g obtained by collagen, be added to 2L purified waters, stirring makes its dispersed, uses hydrochloric acid
Solution adjusts pH to 5.5, and quick stirring makes it mix completely, spare；
2 measure certain 100mL organosilicon quaternary ammonium salts, are added to 1L purified waters, and quick stirring makes to be uniformly mixed, spare；
3 weigh 30g hydroxyl butyl chitosans, are added to 1L purified waters, and quick stirring makes to be uniformly mixed, with hydrochloric acid solution tune pH extremely
6.0, it is spare；
4 measure above-mentioned 800mL collagen solutions respectively, 500mL organosilicone quaternary ammoniums salting liquid and 1000mL chitosan solutions in
In one clean reaction kettle, quickly stir and evenly mix, open vacuum pump and carry out vacuum deaerator, stand, it is spare；
Above-mentioned obtained mixed liquor is poured slowly into stainless steel by 5 to be freezed in mould, slurries thickness 3mm, is set lyophilized parameter and is carried out
Freeze-drying；
6 lyophilized end, take out product, are crosslinked with EDC；Sample after crosslinking is subjected to cutting packaging, send Radiation Center into
Row electron beam sterilization, sterilizing dose 35KGy., obtain antibacterial anti hemorrhagic material of the present invention.
Embodiment six
By embodiment three, example IV, obtained antibacterial anti hemorrhagic material carries out water absorbing properties detection, each implementation in embodiment five
Example takes three samples as follows as parallel sample, detection：
Detection process：Sample three pieces in each embodiment are randomly selected, weighs and records respectively, be denoted as m1.Sample is soaked respectively
Enter in the beaker for filling 20 DEG C of water for injection, with antimagnetic type tweezer softly up to soaking saturation completely, and all air are removed,
Pay attention to not making breakage, after moisture is suctioned, one jiao is gently clamped with tweezers and takes out it from water, tweezers is gently held and is arranged on the water surface
After water 1min, record is weighed again, is denoted as m2.Liquid absorption amount is calculated according to formula（Times）=(m2-m1)/m1；Leaching completely is recorded at the same time
The time required to wet saturation（Second）；
Result of calculation is shown in Table 1
Table 1
Unit：Liquid absorption amount（Times）, saturation time（Second）
By upper table as can be seen that antibacterial anti hemorrhagic material obtained by the present invention has extremely strong imbibition ability, its liquid absorption amount all reaches
To more than 60 times of own wt, rate of liquid aspiration is fast, and average saturation time is 5 seconds or so, therefore product of the present invention is a kind of excellent
Good hemostatic material, can meet the needs of various bleedings.
The above is for only for ease of it will be understood by those skilled in the art that technical scheme, not limiting
The present invention.Within the spirit and principles of the invention, any modification, equivalent replacement, improvement and so on, should be included in this
Within the protection domain of invention.
Claims (10)
1. a kind of preparation and its application of antibacterial anti hemorrhagic material, it is characterised in that preparation process includes step：
（1）Choose collagen-rich tissue, remove it after undesired residues that at least 6 are freezed in the environment of -20 DEG C is small
When more than；Then the tissue after freezing carries out slicing treatment；
（2）By the tissue of well cutting, 5 ~ 30min of soaking flushing, drains unnecessary water into the water；Prepare phosphate-buffered at the same time
Liquid, after the completion of weigh a certain amount of enzyme and be added thereto, the concentration of enzyme is 0.001% ~ 5%, is fully mixed；
（3）The tissue for rinsing completion is added in above-mentioned enzyme solutions, is put into shaking table, 0.5 ~ 24h is kept at 10 ~ 50 DEG C；Its
The ratio of middle tissue and enzyme solutions is 0.01:100~20:100（As mass fraction）；
（4）Enzyme-deactivating：Reactant is taken out out of shaking table, is rinsed several times with water, drains excessive moisture, is added to prepared in advance
In salting liquid, shaking table is opened, 0.5 ~ 5h is kept at 10 ~ 50 DEG C；
（5）Inactivation of virus：Reactant is taken out out of shaking table, is rinsed several times with water, drains excessive moisture, then solid is added to and is matched somebody with somebody
In the salting liquid made, shaking table is opened, 15 ~ 40 DEG C of design temperature, cultivates 20 ~ 60h；
（6）Culture is taken out out of shaking table, it is 4 ~ 8 to adjust ph, collects product, washes with water, drain, that is, obtain collagen；
（7）The step of weighing certain amount（6）In collagen, be added to purified water, stirring makes its dispersed, molten with acid
Liquid adjusts pH to 4 ~ 7, and quick stirring makes it mix completely, spare；The ratio of collagen and purified water is 0.01:100~10:
100；
（8）A certain number of commercially available organosilicon quaternary ammonium salts are measured, are added to purified water, quick stirring makes to be uniformly mixed, spare；Have
The ratio of machine silicon quaternary ammonium salt and purified water is 0.01:100~50:100；
（9）A certain number of commercially available chitosans are weighed, are added to purified water, quick stirring makes to be uniformly mixed, with acid solution tune pH
It is spare to 4 ~ 7；The ratio of chitosan and purified water is 0.01:100~50:100；
（10）By step（7）Gained collagen slurry, step（8）Gained organosilicone quaternary ammonium salting liquid and step（9）Gained shell
Glycan solution is mixed in a certain ratio, and is quickly stirred and evenly mixed, and through vacuum deaerator, is stood, is obtained mixed serum, spare；
（11）Above-mentioned obtained mixed liquor is poured slowly into stainless steel to freeze in mould, slurries thickness 1mm ~ 50mm, sets lyophilized
Parameter is freeze-dried；
（12）After the completion of lyophilized, product is taken out, is crosslinked using physically and/or chemically method, cuts packaging, sterilizing, that is, obtain this
The invention antibacterial anti hemorrhagic material.
2. preparation process step according to claim 1（1）In, it is characterised in that described collagen-rich group
It is woven to ox heel string, cow hoof, ox-hide, trotter and pigskin etc..
3. preparation process step according to claim 1（2）In, it is characterised in that the phosphate buffer by
NaCl、Na2HPO4And NaH2PO4Composition or NaCl, Na2HPO4And KH2PO4Composition, the concentration of phosphate buffer is 0.01-
0.1mol/L；PH value is 5 ~ 7；The enzyme is pepsin, ficin, cysteine proteases and other acid eggs
The one or more of white enzyme.
4. preparation process step according to claim 1（4）In, it is characterised in that the salting liquid is sodium nitrate, nitre
Sour ammonium, potassium nitrate, sodium hypochlorite, sodium hydroxide, the one or more in potassium hydroxide；Concentration is 0.01% ~ 20%；Reactant with
Salting liquid ratio is 0.1:100~30:100.
5. preparation process step according to claim 1（5）In, it is characterised in that the salting liquid is bisulfite
Sodium, sodium thiosulfate, ammonium sulfate, sodium sulphate, the one or more in sodium hydroxide and potassium hydroxide, concentration are 0.01% ~ 20%；
Reactant and salting liquid ratio are 0.1:100~30:100.
6. preparation process step according to claim 1（9）In, it is characterised in that chitosan of the present invention is carboxylic
Methyl chitosan, chitosan, at least one of hydroxyl butyl chitosan and other modification of chitosan；Preparation process step（7）With
（9）In used acid be acetic acid, hydrochloric acid, at least one of sulfuric acid or lactic acid.
7. preparation process step according to claim 1（10）In, it is characterised in that collagen slurry in the present invention,
Organosilicone quaternary ammonium salting liquid, the ratio of chitosan solution are（1~10）：（1~10）:（1~10）(by volume, V：V：V).
8. preparation process step according to claim 1（12）In, it is characterised in that product physical crosslinking side in the present invention
Method is heat cross-linking；Chemical Crosslinking Methods are formaldehyde, glutaraldehyde, Geniposide and EDC etc.；Used sterilization method includes epoxy second
Alkane sterilizes, and ray sterilizing and high-temperature sterilization, wherein ray sterilizing divide cobalt -60 and electron beam again, and sterilizing dose is 5KGy ~ 40KGy.
9. a kind of antibacterial anti hemorrhagic material according to claim 1, it is characterised in that the antibacterial anti hemorrhagic material has three
Net structure is tieed up, high mechanical strength, washing lotion speed is fast, ability is strong, and controllable, good biocompatibility of degrading, and also has well
Broad-spectrum antiseptic bacteriostasis property.
10. a kind of antibacterial anti hemorrhagic material according to claim 1, it is characterised in that the antibacterial anti hemorrhagic material, can use
Stop blooding in operative incision, cavity filling, exedens wound repair regeneration.
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| CN114316350A (en) * | 2021-12-31 | 2022-04-12 | 南京神奇科技开发有限公司 | Organosilicon quaternary ammonium salt blood-sucking sponge with antibacterial function and preparation method thereof |
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