CN109620999A - A kind of preparation method of compound hemostatic medical tissue glue - Google Patents
A kind of preparation method of compound hemostatic medical tissue glue Download PDFInfo
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- CN109620999A CN109620999A CN201910029272.7A CN201910029272A CN109620999A CN 109620999 A CN109620999 A CN 109620999A CN 201910029272 A CN201910029272 A CN 201910029272A CN 109620999 A CN109620999 A CN 109620999A
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- solution
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- chitosan
- tissue glue
- compound hemostatic
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- 239000003106 tissue adhesive Substances 0.000 title claims abstract description 38
- 230000002439 hemostatic effect Effects 0.000 title claims abstract description 34
- 150000001875 compounds Chemical class 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 30
- 108010010803 Gelatin Proteins 0.000 claims abstract description 29
- 239000008273 gelatin Substances 0.000 claims abstract description 29
- 229920000159 gelatin Polymers 0.000 claims abstract description 29
- 235000019322 gelatine Nutrition 0.000 claims abstract description 29
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 29
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000001263 FEMA 3042 Substances 0.000 claims abstract description 27
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 claims abstract description 27
- 229920002258 tannic acid Polymers 0.000 claims abstract description 27
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 claims abstract description 27
- 229940033123 tannic acid Drugs 0.000 claims abstract description 27
- 235000015523 tannic acid Nutrition 0.000 claims abstract description 27
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 9
- 239000000243 solution Substances 0.000 claims description 109
- 229920001661 Chitosan Polymers 0.000 claims description 66
- CFFZDZCDUFSOFZ-UHFFFAOYSA-N 3,4-Dihydroxy-phenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C(O)=C1 CFFZDZCDUFSOFZ-UHFFFAOYSA-N 0.000 claims description 64
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 53
- 108010073385 Fibrin Proteins 0.000 claims description 52
- 102000009123 Fibrin Human genes 0.000 claims description 52
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims description 51
- 229950003499 fibrin Drugs 0.000 claims description 51
- 239000008367 deionised water Substances 0.000 claims description 40
- 229910021641 deionized water Inorganic materials 0.000 claims description 40
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- 229940012952 fibrinogen Drugs 0.000 claims description 34
- 239000000499 gel Substances 0.000 claims description 33
- 230000004048 modification Effects 0.000 claims description 27
- 238000012986 modification Methods 0.000 claims description 27
- 235000006226 Areca catechu Nutrition 0.000 claims description 24
- 238000003756 stirring Methods 0.000 claims description 22
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- 244000080767 Areca catechu Species 0.000 claims description 19
- 239000002504 physiological saline solution Substances 0.000 claims description 19
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 16
- 239000003643 water by type Substances 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 11
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 11
- 239000000835 fiber Substances 0.000 claims description 9
- 102000005525 fibrillarin Human genes 0.000 claims description 8
- 108020002231 fibrillarin Proteins 0.000 claims description 8
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 7
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 7
- 244000269722 Thea sinensis Species 0.000 claims description 6
- 150000001298 alcohols Chemical class 0.000 claims description 6
- 108090000190 Thrombin Proteins 0.000 claims description 5
- 235000011148 calcium chloride Nutrition 0.000 claims description 5
- -1 carbodiimide salt Chemical class 0.000 claims description 5
- 238000004132 cross linking Methods 0.000 claims description 5
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- 108010080379 Fibrin Tissue Adhesive Proteins 0.000 claims description 2
- 210000004369 blood Anatomy 0.000 abstract description 9
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- 239000001257 hydrogen Substances 0.000 abstract description 7
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- 230000001070 adhesive effect Effects 0.000 abstract description 6
- 239000000853 adhesive Substances 0.000 abstract description 5
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- 210000001772 blood platelet Anatomy 0.000 abstract description 4
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- 239000001648 tannin Substances 0.000 abstract description 3
- 229940030225 antihemorrhagics Drugs 0.000 abstract description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 2
- 210000004204 blood vessel Anatomy 0.000 abstract description 2
- 230000000025 haemostatic effect Effects 0.000 abstract description 2
- 125000001165 hydrophobic group Chemical group 0.000 abstract description 2
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- 125000001151 peptidyl group Chemical group 0.000 abstract description 2
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- 239000002994 raw material Substances 0.000 abstract description 2
- 239000000376 reactant Substances 0.000 abstract description 2
- 235000018553 tannin Nutrition 0.000 abstract 1
- 206010052428 Wound Diseases 0.000 description 8
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- 229920001436 collagen Polymers 0.000 description 5
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000003292 glue Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XDQGMXYCBZNEAG-UHFFFAOYSA-N C(C)[C]CCCN(C)C Chemical compound C(C)[C]CCCN(C)C XDQGMXYCBZNEAG-UHFFFAOYSA-N 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000002242 deionisation method Methods 0.000 description 3
- 230000023597 hemostasis Effects 0.000 description 3
- 206010020718 hyperplasia Diseases 0.000 description 3
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- 238000001356 surgical procedure Methods 0.000 description 3
- FBPFZTCFMRRESA-ZXXMMSQZSA-N D-iditol Chemical compound OC[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-ZXXMMSQZSA-N 0.000 description 2
- 206010018910 Haemolysis Diseases 0.000 description 2
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- 208000007536 Thrombosis Diseases 0.000 description 2
- 238000004026 adhesive bonding Methods 0.000 description 2
- 239000003364 biologic glue Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical class OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
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- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
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- 206010063560 Excessive granulation tissue Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
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- 230000000711 cancerogenic effect Effects 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
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- 210000001126 granulation tissue Anatomy 0.000 description 1
- 230000037313 granulation tissue formation Effects 0.000 description 1
- 230000001894 hemadsorption Effects 0.000 description 1
- DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
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- 206010034754 petechiae Diseases 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/10—Polypeptides; Proteins
- A61L24/104—Gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0031—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0042—Materials resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/08—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/10—Polypeptides; Proteins
- A61L24/106—Fibrin; Fibrinogen
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Surgery (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
Abstract
The present invention relates to a kind of preparation methods of compound hemostatic medical tissue glue, belong to medical adhesive technical field.The present invention is using gelatin as raw material, prepare compound hemostatic medical tissue glue, gelfoam has loose porous structure, it is absorbable to overweight itself 10~12 times of blood, and attachment and the coagulation factor of blood platelet can be activated, generate release and aggreation, sludged blood is promoted to be formed, form nerve and blood vessel tight structure, realize quick-acting haemostatic powder, the present invention is using tannic acid as crosslinking agent, prepare compound hemostatic medical tissue glue, the association reaction of gelatin and tannic acid is multiple spot hydrophobic bond and the coefficient result of hydrogen bond between the two, tannin acid molecule containing hydrophobic group is in the form of hydrophobic reactant in conjunction with gelatin, two o'clock Hydrogenbond occurs for the phenolic hydroxyl group of tannic acid and the polar group of gelatin, phenolic hydroxyl group is as hydrogen bond donor, ketonic oxygen on peptidyl is as receptor, form gelatin-tannin acid complex, to improve compound hemostatic medical tissue glue Gumminess.
Description
Technical field
The present invention relates to a kind of preparation methods of compound hemostatic medical tissue glue, belong to medical adhesive technical field.
Background technique
All the time, handle that wound is widely used in surgical field is suture.Traditional surgical operation suturing
It is not only operationally time-consuming with the hemostasis on organ-tissue, increase the difficulty of operation and tissue repair, is brought animally to patient
Suture pain, while being also easy bacterial infection and causing some inflammatory reactions, infection, hyperplasia, the rupture of tissue, to group occur
The case where knitting the damage, necrosis or even disunion of organ.On the other hand, most of surgery operating wound generally all injures true
Skin and skin corium are hereinafter, the fibre composition of wound skin corium during reparation carries out hyperplasia, in the compact of operation suture thread
Under pulling force, therefore the interstitial space for providing cytothesis and hyperplasia is blocked, fibre composition just by fibrosis and forms granulation
Tissue, granulation tissue formation while, directly influence the secretion and absorption of collagen, cause collagen, pigment it is heavy
Product, collagen deposition abundant and its it is structural get muddled, be exactly the principal structural component of cicatricial tissue, it final
As a result scar is shown as.
Scar is for the tissue before damage, an always incomplete replacement.From the point of view of aesthetical point, skin is caused
The destruction of skin is two degree of shades on numerous patients ' psychologicals, eternal mental wound, because having scar confident, entirely
The world has ten hundreds of people to live in the shade of scar.It flows in nowadays material desire, U.S.A has become essential in life
Not part, certainly, people to operation also proposed higher more perfect requirement, i.e., to mitigate surgical procedure to the greatest extent
In and postoperative pain, the fastest progresss wound tissue's reparation and while heal, be reduced as far as opening operation knife wound mouth institute
Bring scar proliferation problem.
Part of the medical tissue glue in clinic in surgical operation for certain organs is binded and repairing, in bone surgery
The combination and positioning of bone, joint, gear division operation in be used for tooth repairing etc., in the fields such as caesarean operation and beauty,
Medical tissue glue more has the unrivaled superiority of other methods, not only, mitigates the operation stitching pain of patient, reaches promotion
Wound healing and the effect repaired more reduce the generation of complication, can also effectively reduce the formation of scar, this is for numerous
It is all a perfect for patient especially the gynemetrics's caesarean birth women and the medical professional of surgical operation suturing of liking to be beautiful
Message.
Adhesive effect of the medical tissue glue in human-body biological cell and tissue generally relates to bonding between cell, nothing
It is active with it is active between bonding, three aspects of bonding between inner body and ectosome, be specifically also manifested in soft tissue, ability to speak
On section, bone cement and skin binder, and what tissue glue also exactly put forward on the basis of this, between soft tissue
Bonding, it is understood that the bonding between cell and cell.As a kind of medical instrument consumptive material, directly with tissue, blood
Liquid, cell and each internal organs are contacted, and everyway should have high security, and ideal medical adhesive should have:
(1) safe and nontoxic, non-stimulated, nothing three causes (carcinogenic, teratogenesis, mutagenesis)；
(2) good biocompatibility, biological absorbable degradation；
(3) rapid curing, bonding action are high；
(4) stability is preferable, easily stored.
Medical adhesive can be generally divided into two major classes: chemical binder and biological adhesive.Wherein chemical binder accounts for
Main body comes under chemical binder such as a-cyanoacrylate class, gelatin system class and polyurethanes, and clinically normal at present
Several prods；Biological adhesive is then based on fibrinogen (FS).
Summary of the invention
The technical problems to be solved by the invention: it for the problem that existing medical tissue glue bonding action is poor, provides
A kind of preparation method of compound hemostatic medical tissue glue.
In order to solve the above technical problems, the technical solution adopted by the present invention is that:
(1) gelatin, fibrin gel are added in deionized water, with 180~200r/min stirring in 37~40 DEG C of water-baths
15~20min, heat preservation, obtains colloidal solution；
(2) catechu phenolic group modification of chitosan is slowly added in colloidal solution, with 220~260r/min under 37~40 DEG C of water-baths
Revolving speed stirs 50~60min, obtains mixed solution；
(3) by tannic acid be added mixed solution in, in 37~40 DEG C of water-baths with 100~120r/min revolving speed crosslinking 15~
20min stands 1.5~2h, 30~40min of ultraviolet-sterilization, obtains compound hemostatic medical tissue glue.
The gelatin, fibrin gel, catechu phenolic group modification of chitosan, tannic acid, the ratio between deionized water
Are as follows: according to parts by weight, 30~40 parts of gelatin, 10~20 parts of fibrin gels, 5~10 share tea phenolic group are weighed respectively and is changed
Property chitosan, 1~3 part of tannic acid, 80~100 parts of deionized waters.
The specific preparation step of fibrin gel described in step (1) are as follows:
(1) fibrinogen is added in physiological saline, 10~15min is stirred with 150~160r/min revolving speed under room temperature, is obtained fine
Fibrillarin original solution；
(2) by fibrin ferment, anhydrous calcium chloride be added deionized water in, under room temperature with 120~140r/min revolving speed stirring 20~
30min obtains thrombin solution；
(3) fibrinogen solution is slowly dropped on six orifice plates with disposable needle tubing, keeps solution evenly laid out in bottom, then will
Thrombin solution is added dropwise in fibrinogen solution, is come into full contact with, uniformly mix, be placed on 36~38 DEG C of shaking tables stand 20~
30min obtains fibrin gel.
The fibrinogen, physiological saline, fibrin ferment, anhydrous calcium chloride, the ratio between deionized water are as follows: by weight
Number meter is measured, weighs 1~3 part of fibrinogen, 10~20 parts of physiological saline, 3~5 parts of fibrin ferments, 2~4 parts of anhydrous chlorine respectively
Change calcium, 20~30 parts of deionized waters.
The content of fibrinogen described in step (1) is 2~4g/L.
The specification of fibrin ferment described in step (2) is 500~2000IU.
The specific preparation step of catechu phenolic group modification of chitosan described in step (2) are as follows:
(1) 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride, n-hydroxysuccinimide, dehydrated alcohol are added
Enter in deionized water, with 100~120r/min revolving speed 20~30min of stir-activating under room temperature, obtains mixed solution；
(2) chitosan solution is added in mixed solution, 15~20min is stirred with 160~180r/min revolving speed under room temperature, is obtained mixed
Close liquid；
(3) 3,4-Dihydroxyphenylacetic acid solution is slowly added dropwise into mixed liquor, dropwise addition 5~10min of the world, with 200 under room temperature
~220r/min revolving speed 1~2h of stirring, standing reaction 22~for 24 hours, it is freeze-dried 5~7 days, obtains catechu phenolic group modification of chitosan.
The chitosan solution, 3,4-Dihydroxyphenylacetic acid solution, 1- ethyl-(3- dimethylaminopropyl) carbon two are sub-
Amine hydrochlorate, n-hydroxysuccinimide, dehydrated alcohol, the ratio between deionized water are as follows: according to parts by weight, weigh respectively
20~30 parts of chitosan solutions, 20~30 parts of 3,4-Dihydroxyphenylacetic acid solution, 5~10 parts of 1- ethyls-(3- dimethylamino third
Base) carbodiimide hydrochloride, 5~10 parts of n-hydroxysuccinimides, 20~30 parts of dehydrated alcohols, 40~50 parts of deionized waters.
The specific preparation step of chitosan solution described in step (2) are as follows: deionized water is added in chitosan by mass ratio 1: 5
In, 30~40min is stirred with 200~220r/min revolving speed under room temperature, obtains chitosan solution.
The specific preparation step of 3,4-Dihydroxyphenylacetic acid solution described in step (3) are as follows: in mass ratio 1: 5 by 3,4- dihydroxy
Base phenylacetic acid is placed in deionized water, is stirred 15~20min under room temperature with 120~140r/min revolving speed, is obtained 3,4- dihydroxy benzenes
Acetic acid solution.
The present invention is compared with other methods, and advantageous effects are:
(1) present invention prepares compound hemostatic medical tissue glue, gelatin is a kind of collagen from Animal Skin using gelatin as raw material
The fat-free component protein matter obtained after partially hydrolysed, gelfoam has loose porous structure, absorbable to overweight itself
10~12 times of blood, and attachment and the coagulation factor of blood platelet can be activated, release and aggreation are generated, sludged blood is promoted
It is formed, forms nerve and blood vessel tight structure, realize quick-acting haemostatic powder, gelfoam is neutral in pH, can be 4~6 in human body
Week can degrade；
(2) present invention prepares compound hemostatic medical tissue glue using tannic acid as crosslinking agent, and tannic acid is a kind of common chemical combination
Object can degrade in vivo, in generally existing bark and fruit, due to containing unique polyphenol hydroxyl structure, Ke Yiyu in tannic acid
The large biological molecules such as protein-polysaccharide, which combine, complexing occurs with metal ion, there is good reproducibility, bright
The association reaction of glue and tannic acid is that multiple spot hydrophobic bond and hydrogen bond are coefficient as a result, the tannic acid containing hydrophobic group point between the two
In the form of hydrophobic reactant in conjunction with gelatin, two o'clock Hydrogenbond, phenol occur son for the phenolic hydroxyl group of tannic acid and the polar group of gelatin
Hydroxyl is as hydrogen bond donor, and the ketonic oxygen on peptidyl is as receptor.Multiple spot hydrophobic bond and hydrogen bond is common between gelatin and tannic acid
Effect forms gelatin-tannin acid complex, to improve the gumminess of compound hemostatic medical tissue glue；
(3) present invention prepares compound hemostatic medical tissue glue, chitosan is a kind of band by addition catechu phenolic group modification of chitosan
Positive electricity alkaline polysaccharide has good biocidal property, has hemostatic function, can degrade in vivo, since chitosan surface is positively charged,
The rapid aggregation of blood platelet and erythrocyte can be effectively facilitated into blood clot or certain polymerization effect itself can also occur
It answers, generates network structure to assemble free red blood cell, chitosan has certain viscosity after meeting blood, is woven with certain glue to group
Attached property, wound closure promote hemostasis to complete；
(4) present invention is grafted catechol group in chitosan molecule structure by coupling reaction, prepares the modified shell of catechu phenolic group
Glycan, catechu phenolic group are a kind of very strong polar groups, can be with the protein and polysaccharide polymer formation hydrogen bond in organism
Interaction, catechu phenolic group are easily oxidized, and can form ortho position quinoid structure, quinoid structure in alkalinity or under conditions of containing oxidant
Very not quietly, it can continue to react between any two with active hydrogen reaction, the quinoid structure after oxidation, be formed very strong
The chemical bond of active force, ultimately forms cross-linked structure, further enhances compound hemostatic medical tissue gluing knotting strength；
(5) present invention prepares compound hemostatic medical tissue glue, fibrin gel is fiber egg by addition fibrin gel
Bai Danti polymerize the biological macromolecule material of formation, the fiber egg in fibrin gel under fibrin ferment and catalytic factor effect
White original can quickly form insoluble fibrin polymer, and the networking that further interweaves under the action of calcium ion and fibrin ferment
Blood platelet and hemadsorption are formed blood clot by shape, complete hemostasis seals effect.Its anastalsis is small independent of blood simultaneously
Plate or coagulation factor are applicable in the capillary hemorrhage patient of coagulation disorders or substantial viscera, fibrin gel very much
As a kind of Biodegradable material, the treatment of wound healing can be widely used in.Since fibrin gel can promote carefully
The adherency and proliferation of born of the same parents, and be natural biologic material, good biocompatibility can be used as drug, cell or cell factor
Slow-released carrier.
Specific embodiment
In mass ratio 1: 5 by chitosan be added deionized water in, under room temperature with 200~220r/min revolving speed stirring 30~
40min obtains chitosan solution, and in mass ratio 1: 5 is placed in 3,4-Dihydroxyphenylacetic acid in deionized water, under room temperature with 120~
140r/min revolving speed stirs 15~20min, obtains 3,4-Dihydroxyphenylacetic acid solution, according to parts by weight, weighs 20~30 respectively
Part chitosan solution, 20~30 parts of 3,4-Dihydroxyphenylacetic acid solution, 5~10 parts of 1- ethyls-(3- dimethylaminopropyl) carbon
Diimmonium salt hydrochlorate, 5~10 parts of n-hydroxysuccinimides, 20~30 parts of dehydrated alcohols, 40~50 parts of deionized waters, by 1- second
Base-(3- dimethylaminopropyl) carbodiimide hydrochloride, n-hydroxysuccinimide, dehydrated alcohol are added in deionized water,
With 100~120r/min revolving speed 20~30min of stir-activating under room temperature, mixed solution is obtained, it is molten that mixing is added in chitosan solution
In liquid, 15~20min is stirred with 160~180r/min revolving speed under room temperature, mixed liquor is obtained, 3,4-Dihydroxyphenylacetic acid solution is delayed
Slowly it is added dropwise in mixed liquor, dropwise addition 5~10min of the world, 1~2h is stirred with 200~220r/min revolving speed under room temperature, stands reaction
22~for 24 hours, it is freeze-dried 5~7 days, obtains catechu phenolic group modification of chitosan, then according to parts by weight, weigh 1~3 part of fiber respectively
Proteinogen, 10~20 parts of physiological saline, 3~5 parts of fibrin ferments, 2~4 parts of anhydrous calcium chlorides, 20~30 parts of deionized waters, by fiber
Proteinogen is added in physiological saline, stirs 10~15min under room temperature with 150~160r/min revolving speed, obtains fibrinogen solution,
Fibrin ferment, anhydrous calcium chloride are added in deionized water, 20~30min is stirred with 120~140r/min revolving speed under room temperature, is obtained solidifying
Fibrinogen solution is slowly dropped on six orifice plates with disposable needle tubing, keeps solution evenly laid out in bottom by hemase solution, then
Thrombin solution is added dropwise in fibrinogen solution, is come into full contact with, is uniformly mixed, is placed on 36~38 DEG C of shaking tables and stands 20
~30min obtains fibrin gel, then according to parts by weight, respectively the gelatin, 10~20 parts of fibrins of 30~40 parts of weighing
Gel, 5~10 share tea phenolic group modification of chitosan, 1~3 difference tannic acid, 80~100 parts of deionized waters, by gelatin, fiber egg
White gel is added in deionized water, stirs 15~20min in 37-40 DEG C of water-bath with 180~200r/min, and heat preservation obtains colloid
Catechu phenolic group modification of chitosan is slowly added in colloidal solution by solution, is turned under 37~40 DEG C of water-baths with 220-260r/min
Speed 50~60min of stirring, obtains mixed solution, tannic acid is added in mixed solution, in 37~40 DEG C of water-baths with 100~
120r/min revolving speed is crosslinked 15~20min, stands 1.5~2h, obtains compound hemostatic medical tissue glue.
Gelatin, fibrin gel are added in deionized water, 15min is stirred with 180r/min in 37 DEG C of water-baths, is protected
Temperature obtains colloidal solution；Catechu phenolic group modification of chitosan is slowly added in colloidal solution, is turned under 37 DEG C of water-baths with 220r/min
Speed stirring 50min, obtains mixed solution；Tannic acid is added in mixed solution, with the crosslinking of 100r/min revolving speed in 37 DEG C of water-baths
15min stands 1.5h, ultraviolet-sterilization 30min, obtains compound hemostatic medical tissue glue.Gelatin, fibrin gel, catechu phenolic group
Modification of chitosan, tannic acid, the ratio between deionized water are as follows: according to parts by weight, weigh respectively 30 parts gelatin, 10 parts of fibres
Fibrillarin gel, 5 share tea phenolic group modification of chitosan, 1 part of tannic acid, 80 parts of deionized waters.Fibrin gel is specifically prepared
Step are as follows: fibrinogen is added in physiological saline, 10min is stirred with 150r/min revolving speed under room temperature, obtains fibrinogen
Solution；Fibrin ferment, anhydrous calcium chloride are added in deionized water, 20min is stirred with 120r/min revolving speed under room temperature, obtains fibrin ferment
Solution；Fibrinogen solution is slowly dropped on six orifice plates with disposable needle tubing, keeps solution evenly laid out in bottom, then will coagulate
Hemase solution is added dropwise in fibrinogen solution, is come into full contact with, and is uniformly mixed, is placed on 36 DEG C of shaking tables and stands 20min, obtain fine
Fibrillarin gel.Fibrinogen, physiological saline, fibrin ferment, anhydrous calcium chloride, the ratio between deionized water are as follows: by weight
Number meter weighs 1 part of fibrinogen, 10 parts of physiological saline, 3 parts of fibrin ferments, 2 parts of anhydrous calcium chlorides, 20 parts of deionizations respectively
Water.The content of fibrinogen is 2g/L.The specification of fibrin ferment is 500IU.The specific preparation step of catechu phenolic group modification of chitosan
Are as follows: 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride, n-hydroxysuccinimide, dehydrated alcohol addition are gone
In ionized water, with 100r/min revolving speed stir-activating 20min under room temperature, mixed solution is obtained；It is molten that mixing is added in chitosan solution
In liquid, 15min is stirred with 160r/min revolving speed under room temperature, obtains mixed liquor；By 3,4-Dihydroxyphenylacetic acid solution be slowly added dropwise to
In mixed liquor, world 5min is added dropwise, is freeze-dried 5 days, obtains with 200r/min revolving speed stirring 1h, standing reaction 22h under room temperature
Tea phenolic group modification of chitosan.Chitosan solution, 3,4-Dihydroxyphenylacetic acid solution, 1- ethyl-(3- dimethylaminopropyl) carbon
Diimmonium salt hydrochlorate, n-hydroxysuccinimide, dehydrated alcohol, the ratio between deionized water are as follows: according to parts by weight, respectively
Weigh 20 parts of chitosan solutions, 20 parts of 3,4-Dihydroxyphenylacetic acid solution, 5 parts of 1- ethyls-(3- dimethylaminopropyl) carbon two
Inferior amine salt hydrochlorate, 5 parts of n-hydroxysuccinimides, 20 parts of dehydrated alcohols, 40 parts of deionized waters.Chitosan solution specifically prepares step
Suddenly are as follows: in mass ratio 1: 5 chitosan is added in deionized water, stirs 30min under room temperature with 200r/min revolving speed, obtains chitosan
Solution.The specific preparation step of 3,4-Dihydroxyphenylacetic acid solution are as follows: in mass ratio 1: 5 by 3,4-Dihydroxyphenylacetic acid be placed in from
In sub- water, 15min is stirred with 120r/min revolving speed under room temperature, obtains 3,4-Dihydroxyphenylacetic acid solution.
Gelatin, fibrin gel are added in deionized water, 18min is stirred with 190r/min in 39 DEG C of water-baths, is protected
Temperature obtains colloidal solution；Catechu phenolic group modification of chitosan is slowly added in colloidal solution, is turned under 39 DEG C of water-baths with 240r/min
Speed stirring 55min, obtains mixed solution；Tannic acid is added in mixed solution, with the crosslinking of 110r/min revolving speed in 39 DEG C of water-baths
18min stands 1.8h, ultraviolet-sterilization 35min, obtains compound hemostatic medical tissue glue.Gelatin, fibrin gel, catechu phenolic group
Modification of chitosan, tannic acid, the ratio between deionized water are as follows: according to parts by weight, weigh respectively 35 parts gelatin, 15 parts of fibres
Fibrillarin gel, 8 share tea phenolic group modification of chitosan, 2 parts of tannic acid, 90 parts of deionized waters.Fibrin gel is specifically prepared
Step are as follows: fibrinogen is added in physiological saline, 12min is stirred with 155r/min revolving speed under room temperature, obtains fibrinogen
Solution；Fibrin ferment, anhydrous calcium chloride are added in deionized water, 25min is stirred with 130r/min revolving speed under room temperature, obtains fibrin ferment
Solution；Fibrinogen solution is slowly dropped on six orifice plates with disposable needle tubing, keeps solution evenly laid out in bottom, then will coagulate
Hemase solution is added dropwise in fibrinogen solution, is come into full contact with, and is uniformly mixed, is placed on 37 DEG C of shaking tables and stands 25min, obtain fine
Fibrillarin gel.Fibrinogen, physiological saline, fibrin ferment, anhydrous calcium chloride, the ratio between deionized water are as follows: by weight
Number meter weighs 2 parts of fibrinogens, 15 parts of physiological saline, 4 parts of fibrin ferments, 3 parts of anhydrous calcium chlorides, 25 parts of deionizations respectively
Water.The content of fibrinogen is 3g/L.The specification of fibrin ferment is 1250IU.The specific preparation step of catechu phenolic group modification of chitosan
Are as follows: 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride, n-hydroxysuccinimide, dehydrated alcohol addition are gone
In ionized water, with 110r/min revolving speed stir-activating 25min under room temperature, mixed solution is obtained；It is molten that mixing is added in chitosan solution
In liquid, 18min is stirred with 170r/min revolving speed under room temperature, obtains mixed liquor；By 3,4-Dihydroxyphenylacetic acid solution be slowly added dropwise to
In mixed liquor, world 8min is added dropwise, is freeze-dried 6 days, obtains with 210r/min revolving speed stirring 1h, standing reaction 23h under room temperature
Tea phenolic group modification of chitosan.Chitosan solution, 3,4-Dihydroxyphenylacetic acid solution, 1- ethyl-(3- dimethylaminopropyl) carbon
Diimmonium salt hydrochlorate, n-hydroxysuccinimide, dehydrated alcohol, the ratio between deionized water are as follows: according to parts by weight, respectively
Weigh 25 parts of chitosan solutions, 25 parts of 3,4-Dihydroxyphenylacetic acid solution, 8 parts of 1- ethyls-(3- dimethylaminopropyl) carbon two
Inferior amine salt hydrochlorate, 8 parts of n-hydroxysuccinimides, 25 parts of dehydrated alcohols, 45 parts of deionized waters.Chitosan solution specifically prepares step
Suddenly are as follows: in mass ratio 1: 5 chitosan is added in deionized water, stirs 35min under room temperature with 210r/min revolving speed, obtains chitosan
Solution.The specific preparation step of 3,4-Dihydroxyphenylacetic acid solution are as follows: in mass ratio 1: 5 by 3,4-Dihydroxyphenylacetic acid be placed in from
In sub- water, 18min is stirred with 130r/min revolving speed under room temperature, obtains 3,4-Dihydroxyphenylacetic acid solution.
Gelatin, fibrin gel are added in deionized water, 20min is stirred with 200r/min in 40 DEG C of water-baths, is protected
Temperature obtains colloidal solution；Catechu phenolic group modification of chitosan is slowly added in colloidal solution, is turned under 40 DEG C of water-baths with 260r/min
Speed stirring 60min, obtains mixed solution；Tannic acid is added in mixed solution, with the crosslinking of 120r/min revolving speed in 40 DEG C of water-baths
20min stands 2h, ultraviolet-sterilization 40min, obtains compound hemostatic medical tissue glue.Gelatin, fibrin gel, catechu phenolic group change
Property chitosan, tannic acid, the ratio between deionized water are as follows: according to parts by weight, weigh respectively 40 parts gelatin, 20 parts of fibers
Protein gel, 10 share tea phenolic group modification of chitosan, 3 parts of tannic acid, 100 parts of deionized waters.Fibrin gel is specifically prepared
Step are as follows: fibrinogen is added in physiological saline, 15min is stirred with 160r/min revolving speed under room temperature, obtains fibrinogen
Solution；Fibrin ferment, anhydrous calcium chloride are added in deionized water, 30min is stirred with 140r/min revolving speed under room temperature, obtains fibrin ferment
Solution；Fibrinogen solution is slowly dropped on six orifice plates with disposable needle tubing, keeps solution evenly laid out in bottom, then will coagulate
Hemase solution is added dropwise in fibrinogen solution, is come into full contact with, and is uniformly mixed, is placed on 38 DEG C of shaking tables and stands 30min, obtain fine
Fibrillarin gel.Fibrinogen, physiological saline, fibrin ferment, anhydrous calcium chloride, the ratio between deionized water are as follows: by weight
Number meter weighs 3 parts of fibrinogens, 20 parts of physiological saline, 5 parts of fibrin ferments, 4 parts of anhydrous calcium chlorides, 30 parts of deionizations respectively
Water.The content of fibrinogen is 4g/L.The specification of fibrin ferment is 2000IU.The specific preparation step of catechu phenolic group modification of chitosan
Are as follows: 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride, n-hydroxysuccinimide, dehydrated alcohol addition are gone
In ionized water, with 120r/min revolving speed stir-activating 30min under room temperature, mixed solution is obtained；It is molten that mixing is added in chitosan solution
In liquid, 20min is stirred with 180r/min revolving speed under room temperature, obtains mixed liquor；By 3,4-Dihydroxyphenylacetic acid solution be slowly added dropwise to
In mixed liquor, world 10min is added dropwise, 2h is stirred with 220r/min revolving speed under room temperature, stands reaction for 24 hours, is freeze-dried 7 days, obtains
Catechu phenolic group modification of chitosan.Chitosan solution, 3,4-Dihydroxyphenylacetic acid solution, 1- ethyl-(3- dimethylaminopropyl)
Carbodiimide hydrochloride, n-hydroxysuccinimide, dehydrated alcohol, the ratio between deionized water are as follows: according to parts by weight, point
Also known as amount 30 parts of chitosan solutions, 30 parts of 3,4-Dihydroxyphenylacetic acid solution, 10 parts of 1- ethyls-(3- dimethylaminopropyl) carbon
Diimmonium salt hydrochlorate, 10 parts of n-hydroxysuccinimides, 30 parts of dehydrated alcohols, 50 parts of deionized waters.Chitosan solution is specifically made
Standby step are as follows: in mass ratio 1: 5 chitosan is added in deionized water, stirs 40min under room temperature with 220r/min revolving speed, obtains shell
Glycan solution.The specific preparation step of 3,4-Dihydroxyphenylacetic acid solution are as follows: in mass ratio 1: 5 is placed in 3,4-Dihydroxyphenylacetic acid
In deionized water, 20min is stirred with 140r/min revolving speed under room temperature, obtains 3,4-Dihydroxyphenylacetic acid solution.
Reference examples: the compound hemostatic medical tissue glue of Dongguan company production.
The compound hemostatic medical tissue glue that example and reference examples are prepared is detected, specific detection is as follows:
Bonding action: it is one layer thin to be coated on sheet glass formation by structure and ingredient in order to simulate bonding wound for gelatin solution
Thin collagen film, with the Optical instrument of test organization glue.The specific method is as follows: the filtered hot gelatin of a certain concentration is molten
Drop is added on glass sheet surface, and glass bar is uniformly smeared and opened, the specification of sheet glass 6cm × 2cm, surpasses under natural conditions in clean
Net workbench is dry for 24 hours, and it is several must to be covered with a thin layer of gelatin film sheet glass.The area band of test be center S=2cm ×
2cm, the tissue sol solution of 50uL is added dropwise to one piece of sheet glass middle ground band, and 20uL is added dropwise in another piece of sheet glass center 2cm × 2cm
Crosslinking agent carbodiimides solution, central 2cm × 2cm contact surface bonding of two blocks of sheet glass avoids intermediate residue gas as far as possible
Bubble, presses 10min or 5min(a certain regular time in 37 DEG C of baking ovens of 100g counterweight), weight beam tests adhesive
Optical instrument, the maximum, force F, F/S that writing down weight beam two blocks of sheet glass of stretching can bear then are to organize on unit area
The bonding action of glue.
Blood compatibility: subject material is one group of experiment of four ratios: taking 6 Boiling tubes, it is numbered 1-4, a
And b, wherein 1-4 is respectively 9/1,8/1,7/1,6/1 experimental group of gelatin/carboxymethyl chitosan mass ratio, and a is negative control, and b is
Positive control, three parallel groups of every group of setting.Freeze-dried material sample 0.05g, the physiological saline of each ratio is added in 1-4 test tube
10ml；A test tube adds physiological saline 10ml；B adds deionized water 10ml；37 DEG C of water bath with thermostatic control 0.5h；It is again 10-200uL with specification
Liquid-transfering gun be added to every test tube and dilute fresh anticoagulation 200uL, mix well, be transferred to 37 DEG C of warmed-up constant temperature at this time
Water-bath vibrator, with speed water bath with thermostatic control 1h appropriate；Each test tube solution is successively transferred to centrifuge tube, in centrifuge 1000r/
Min is centrifuged 5min, and the supernatant 200uL after taking centrifugation is in 96 orifice plates, wherein 96 orifice plate peripheries make a circle and remove ionized water
200uL, absorbance value of the measurement at 540nm in microplate reader.Take the mean value of three parallel groups as experimental result, according to public affairs
Formula calculates hemolysis rate.
Specific test result such as table 1.
1 performance characterization contrast table of table
| Detection project | Example 1 | Example 2 | Example 3 | Reference examples |
| Bonding action/N | 2.50 | 2.45 | 2.55 | 0.70 |
| Hemolysis rate/% | 0.33 | 0.43 | 0.35 | 1.55 |
As shown in Table 1, compound hemostatic medical tissue glue prepared by the present invention has good bonding action and blood compatibility, is
The medical tissue glue of function admirable.
Claims (10)
1. a kind of preparation method of compound hemostatic medical tissue glue, which is characterized in that specific preparation step are as follows:
(1) gelatin, fibrin gel are added in deionized water, with 180~200r/min stirring in 37~40 DEG C of water-baths
15~20min, heat preservation, obtains colloidal solution；
(2) catechu phenolic group modification of chitosan is slowly added in colloidal solution, with 220~260r/min under 37~40 DEG C of water-baths
Revolving speed stirs 50~60min, obtains mixed solution；
(3) by tannic acid be added mixed solution in, in 37~40 DEG C of water-baths with 100~120r/min revolving speed crosslinking 15~
20min stands 1.5~2h, 30~40min of ultraviolet-sterilization, obtains compound hemostatic medical tissue glue.
2. a kind of preparation method of compound hemostatic medical tissue glue according to claim 1, which is characterized in that described is bright
Glue, fibrin gel, catechu phenolic group modification of chitosan, tannic acid, the ratio between deionized water are as follows: according to parts by weight,
30~40 parts of gelatin, 10~20 parts of fibrin gels, 5~10 share tea phenolic group modification of chitosan, 1~3 part are weighed respectively
Tannic acid, 80~100 parts of deionized waters.
3. a kind of preparation method of compound hemostatic medical tissue glue according to claim 1, which is characterized in that step (1)
The specific preparation step of the fibrin gel are as follows:
(1) fibrinogen is added in physiological saline, 10~15min is stirred with 150~160r/min revolving speed under room temperature, is obtained fine
Fibrillarin original solution；
(2) by fibrin ferment, anhydrous calcium chloride be added deionized water in, under room temperature with 120~140r/min revolving speed stirring 20~
30min obtains thrombin solution；
(3) fibrinogen solution is slowly dropped on six orifice plates with disposable needle tubing, keeps solution evenly laid out in bottom, then will
Thrombin solution is added dropwise in fibrinogen solution, is come into full contact with, uniformly mix, be placed on 36~38 DEG C of shaking tables stand 20~
30min obtains fibrin gel.
4. a kind of preparation method of compound hemostatic medical tissue glue according to claim 3, which is characterized in that the fibre
Fibrillarin original, physiological saline, fibrin ferment, anhydrous calcium chloride, the ratio between deionized water are as follows: according to parts by weight, claim respectively
Amount 1~3 part of fibrinogen, 10~20 parts of physiological saline, 3~5 parts of fibrin ferments, 2~4 parts of anhydrous calcium chlorides, 20~30 parts go
Ionized water.
5. a kind of preparation method of compound hemostatic medical tissue glue according to claim 3, which is characterized in that step (1)
The content of the fibrinogen is 2~4g/L.
6. a kind of preparation method of compound hemostatic medical tissue glue according to claim 3, which is characterized in that step (2)
The specification of the fibrin ferment is 500~2000IU.
7. a kind of preparation method of compound hemostatic medical tissue glue according to claim 1, which is characterized in that step (2)
The specific preparation step of catechu phenolic group modification of chitosan are as follows:
(1) 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride, n-hydroxysuccinimide, dehydrated alcohol are added
Enter in deionized water, with 100~120r/min revolving speed 20~30min of stir-activating under room temperature, obtains mixed solution；
(2) chitosan solution is added in mixed solution, 15~20min is stirred with 160~180r/min revolving speed under room temperature, is obtained mixed
Close liquid；
(3) 3,4-Dihydroxyphenylacetic acid solution is slowly added dropwise into mixed liquor, dropwise addition 5~10min of the world, with 200 under room temperature
~220r/min revolving speed 1~2h of stirring, standing reaction 22~for 24 hours, it is freeze-dried 5~7 days, obtains catechu phenolic group modification of chitosan.
8. a kind of preparation method of compound hemostatic medical tissue glue according to claim 6, which is characterized in that the shell
Glycan solution, 3,4-Dihydroxyphenylacetic acid solution, 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride, N- hydroxyl
Succinimide, dehydrated alcohol, the ratio between deionized water are as follows: according to parts by weight, weigh 20~30 parts of chitosans respectively
Solution, 20~30 parts of 3,4-Dihydroxyphenylacetic acid solution, 5~10 parts of 1- ethyls-(3- dimethylaminopropyl) carbodiimide salt
Hydrochlorate, 5~10 parts of n-hydroxysuccinimides, 20~30 parts of dehydrated alcohols, 40~50 parts of deionized waters.
9. a kind of preparation method of compound hemostatic medical tissue glue according to claim 6, which is characterized in that step (2)
The specific preparation step of the chitosan solution are as follows: in mass ratio 1: 5 chitosan is added in deionized water, with 200 under room temperature
~220r/min revolving speed stirs 30~40min, obtains chitosan solution.
10. a kind of preparation method of compound hemostatic medical tissue glue according to claim 6, which is characterized in that step (3)
The specific preparation step of 3,4-Dihydroxyphenylacetic acid solution are as follows: in mass ratio 1: 5 is placed in 3,4-Dihydroxyphenylacetic acid
In ionized water, 15~20min is stirred with 120~140r/min revolving speed under room temperature, obtains 3,4-Dihydroxyphenylacetic acid solution.
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