CN117599236B - Preparation method of absorbable tissue adhesive for blood vessels and organs - Google Patents
Preparation method of absorbable tissue adhesive for blood vessels and organs Download PDFInfo
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- CN117599236B CN117599236B CN202410097102.3A CN202410097102A CN117599236B CN 117599236 B CN117599236 B CN 117599236B CN 202410097102 A CN202410097102 A CN 202410097102A CN 117599236 B CN117599236 B CN 117599236B
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- chitosan
- tissue adhesive
- absorbable tissue
- gelatin
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- 239000003106 tissue adhesive Substances 0.000 title claims abstract description 102
- 238000002360 preparation method Methods 0.000 title claims abstract description 85
- 210000004204 blood vessel Anatomy 0.000 title claims abstract description 18
- 210000000056 organ Anatomy 0.000 title claims abstract description 16
- 108010010803 Gelatin Proteins 0.000 claims abstract description 140
- 229920000159 gelatin Polymers 0.000 claims abstract description 140
- 239000008273 gelatin Substances 0.000 claims abstract description 140
- 235000019322 gelatine Nutrition 0.000 claims abstract description 140
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 140
- 239000004005 microsphere Substances 0.000 claims abstract description 117
- 229920001661 Chitosan Polymers 0.000 claims abstract description 113
- 239000002131 composite material Substances 0.000 claims abstract description 108
- 239000000243 solution Substances 0.000 claims abstract description 92
- 239000003094 microcapsule Substances 0.000 claims abstract description 59
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims abstract description 28
- 238000000034 method Methods 0.000 claims abstract description 22
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims abstract description 19
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims abstract description 19
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims abstract description 19
- 239000007864 aqueous solution Substances 0.000 claims abstract description 17
- 238000003756 stirring Methods 0.000 claims abstract description 16
- 238000002156 mixing Methods 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims description 41
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 41
- 229920001577 copolymer Polymers 0.000 claims description 40
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 20
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 6
- 238000004108 freeze drying Methods 0.000 claims description 4
- 238000002791 soaking Methods 0.000 claims description 4
- 239000004310 lactic acid Substances 0.000 claims description 3
- 235000014655 lactic acid Nutrition 0.000 claims description 3
- 239000002504 physiological saline solution Substances 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 2
- 230000001070 adhesive effect Effects 0.000 abstract description 17
- 239000000853 adhesive Substances 0.000 abstract description 9
- 206010052428 Wound Diseases 0.000 description 47
- 208000027418 Wounds and injury Diseases 0.000 description 47
- 230000000052 comparative effect Effects 0.000 description 41
- 230000035876 healing Effects 0.000 description 28
- 230000015556 catabolic process Effects 0.000 description 22
- 238000006731 degradation reaction Methods 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 239000000017 hydrogel Substances 0.000 description 17
- 210000001519 tissue Anatomy 0.000 description 17
- 208000024891 symptom Diseases 0.000 description 15
- 206010061218 Inflammation Diseases 0.000 description 13
- 230000003247 decreasing effect Effects 0.000 description 13
- 230000004054 inflammatory process Effects 0.000 description 13
- 230000000694 effects Effects 0.000 description 10
- 230000029663 wound healing Effects 0.000 description 10
- 230000002757 inflammatory effect Effects 0.000 description 9
- 229920000747 poly(lactic acid) Polymers 0.000 description 9
- 239000004626 polylactic acid Substances 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
- 238000004132 cross linking Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000011259 mixed solution Substances 0.000 description 7
- 239000003995 emulsifying agent Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
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- 238000011084 recovery Methods 0.000 description 6
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- 241000699670 Mus sp. Species 0.000 description 5
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- 238000012360 testing method Methods 0.000 description 5
- 241001391944 Commicarpus scandens Species 0.000 description 4
- 102000016942 Elastin Human genes 0.000 description 4
- 108010014258 Elastin Proteins 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 229920002549 elastin Polymers 0.000 description 4
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 241000191967 Staphylococcus aureus Species 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical group CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 2
- 125000003172 aldehyde group Chemical group 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000005336 cracking Methods 0.000 description 2
- 230000006196 deacetylation Effects 0.000 description 2
- 238000003381 deacetylation reaction Methods 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010018833 Haematocoele Diseases 0.000 description 1
- 208000005873 Hematocele Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010048038 Wound infection Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 201000004920 hematocele of tunica vaginalis testis Diseases 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/10—Polypeptides; Proteins
- A61L24/108—Specific proteins or polypeptides not covered by groups A61L24/102 - A61L24/106
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0015—Medicaments; Biocides
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0042—Materials resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/10—Polypeptides; Proteins
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- 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
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
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- A—HUMAN NECESSITIES
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- 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
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
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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
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
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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
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
- A61L2300/622—Microcapsules
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- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Surgery (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
Abstract
The application relates to the technical field of medical adhesives, and particularly discloses a preparation method of an absorbable tissue adhesive for blood vessels and organs. A method for preparing absorbable tissue adhesive for blood vessels and organs, comprising the following steps: preparation of solution a: adding trehalose into the elastin-like aqueous solution, stirring for 5-15min, adding chitosan/gelatin composite microspheres and hydrolase microcapsules, and stirring for 10-20min to obtain solution A, wherein the concentration of elastin-like in the solution A is 50-650mg/L, and the concentration of trehalose in the solution A is 5-20%; preparation of solution B: dissolving glutaraldehyde in water to form a glutaraldehyde aqueous solution of 1-3 wt%; mixing: the absorbable tissue adhesive can be prepared by mixing the solution A and the solution B according to the mass ratio of 1 (0.5-2.0), and has the advantage of improving the mechanical strength of the medical adhesive.
Description
Technical Field
The application relates to the technical field of medical adhesives, in particular to a preparation method of an absorbable tissue adhesive for blood vessels and organs.
Background
Along with the development of medical technology, how to allow a wound to stop bleeding and heal quickly in an operation and reduce complications such as postoperative incision infection, wound cracking, hematocele and the like becomes a concern, and at present, a common method for closing an incision clinically is mechanical fixation such as needle and line suturing or suturing nails, and the like, and when the fixation is carried out, secondary damage is easily caused to fragile human tissues, so that postoperative recovery of a patient is affected.
The medical adhesive can adhere the incisions of patients by using the self-adhesive, has good biocompatibility and degradability, has no irritation to human bodies when in use, seals the incisions under the condition of not affecting the self-healing of human tissues, can be gradually absorbed and metabolized by human bodies, but still has the defects that the existing adhesive for mucous membranes or tissues is mainly carboxymethyl cellulose products, can play a biological barrier role when in use, prevents seepage, has lower mechanical strength, is easy to crack and affects healing effect.
Disclosure of Invention
In order to improve the mechanical strength of the medical adhesive, the application provides a preparation method of an absorbable tissue adhesive for blood vessels and organs, which adopts the following technical scheme:
A method for preparing absorbable tissue adhesive for blood vessels and organs, which is characterized by comprising the following steps: the method comprises the following steps:
Preparation of solution a: adding trehalose into the elastin-like aqueous solution, stirring for 5-15min, adding chitosan/gelatin composite microspheres and hydrolase microcapsules, and stirring for 10-20min to obtain solution A, wherein the concentration of elastin-like in the solution A is 50-650mg/L, and the concentration of trehalose in the solution A is 5-20%;
preparation of solution B: dissolving glutaraldehyde in water to form a glutaraldehyde aqueous solution of 1-3 wt%;
Mixing: mixing the solution A and the solution B according to the mass ratio of 1 (0.5-2.0) to obtain the absorbable tissue adhesive.
Through adopting above-mentioned technical scheme, the amino functional group of class elastin reacts with glutaraldehyde's aldehyde, amino on the human biological tissue protein also reacts with active aldehyde simultaneously for solution A and solution B crosslinked formation gel, cover on the wound, the gel has excellent inter-tissue adhesive strength, can carry out quick adhesion with human blood vessel and viscera, the trehalose molecule can form strong hydrogen bond with many polar groups in the gel, through the hydrogen bond interact of introducing class covalent bond, can effectively improve the ductility and the toughness of hydrogel, thereby the mechanical strength of absorbable tissue adhesive has been improved, the healing effect of wound has been guaranteed.
The chitosan/gelatin composite microsphere is a macromolecular microsphere, when the hydrogel is deformed by external force, the microsphere can deform along with the deformation, energy is dissipated, and the hydrogel is endowed with good deformability, so that the mechanical property of the absorbable tissue adhesive in use is improved, the degradation rate of gelatin in a human body is slower, the hydrolase microcapsule can slowly release the hydrolase, and the degradation rate of the chitosan/gelatin composite microsphere is accelerated, so that the degradation rate of the absorbable tissue adhesive is moderate, and the self-healing of biological tissues of the human body is not easy to be hindered.
Preferably, the concentration of the chitosan/gelatin composite microspheres in the absorbable tissue adhesive is 0.1-10 mug/mL, and the concentration of the hydrolase microcapsules in the absorbable tissue adhesive is 0.1-10 mug/mL.
By adopting the technical scheme, the addition amount of the chitosan/gelatin composite microsphere is controlled, so that the chitosan/gelatin composite microsphere can enhance the strength of the absorbable tissue adhesive, the strength of the absorbable tissue adhesive is easily reduced due to excessive or insufficient addition amount, and the addition amount of the hydrolase microcapsule is controlled, so that the hydrolase microcapsule can degrade the chitosan/gelatin composite microsphere, the degradation period of the chitosan/gelatin composite microsphere is similar to the healing period of human biological tissues, and meanwhile, the degradation is not easy and too fast, so that the strength of the absorbable tissue adhesive is reduced to cause fracture.
Preferably, the mass ratio of the chitosan/gelatin composite microspheres to the hydrolase microcapsules in the absorbable tissue adhesive is 1 (0.9-1).
By adopting the technical scheme, the mass ratio of the chitosan/gelatin composite microsphere to the hydrolase microcapsule is controlled, and the concentration of the hydrolase microcapsule is controlled, so that the degradation rate of the chitosan/gelatin composite microsphere is moderate, and the recovery effect of the wound is not influenced easily and quickly.
Preferably, the chitosan/gelatin composite microsphere comprises chitosan and gelatin with a mass ratio of 1 (1.8-2.2).
By adopting the technical scheme, when the raw materials of the chitosan/gelatin composite microsphere comprise chitosan and gelatin with the mass ratio of 1 (1.8-2.2), the spherical diameter of the formed chitosan/gelatin composite microsphere is moderate, no adhesion exists between the chitosan/gelatin composite microsphere, and the formed microsphere is better in state, so that the chitosan/gelatin composite microsphere can be uniformly dispersed in various places of the absorbable tissue adhesive after being added.
Preferably, the chitosan/gelatin composite microsphere is subjected to the following treatment before being added: dissolving FGF and G-CSF in physiological saline to form FGF/G-CSF solution, dripping the FGF/G-CSF solution on chitosan/gelatin composite microsphere, fully soaking and expanding at 4-6 ℃ for 24-26h, centrifuging, taking centrifugate, freeze-drying under sterile condition, wherein the concentration of FGF is 150-250 mug/mL, and the concentration of G-CSF is 150-250 mug/mL.
By adopting the technical scheme, the FGF/G-CSF solution is dripped on the chitosan/gelatin composite microsphere, so that the chitosan/gelatin composite microsphere can load FGF and G-CSF, promote the growth of biological tissues of a human body, reduce the occurrence of complications such as wound infection and the like, and further improve the healing effect and the healing speed of wounds.
Preferably, the mass ratio of the chitosan/gelatin composite microsphere to the FGF/G-CSF solution is 1 (0.4-0.6).
By adopting the technical scheme, the mass ratio of the chitosan/gelatin composite microsphere to the FGF/G-CSF solution is 1 (0.4-0.6), the FGF and the G-CSF can fully enter the chitosan/gelatin composite microsphere to finish the loading of the growth factors on the composite microsphere, so that the growth factors can be dispersed in various positions of the absorbable tissue adhesive along with the dispersion of the composite microsphere, and the growth factors are released slowly, thereby promoting the growth and healing of wound tissues.
Preferably, the wall of the hydrolase microcapsule is polylactic acid-glycolic acid copolymer, and the core is gelatin hydrolase.
By adopting the technical scheme, the capsule wall is the polyacetic acid-glycolic acid copolymer, the degradation rate of the polyacetic acid-glycolic acid copolymer is similar to the healing rate of the wound, a metabolic chain exists in a human body as a degraded product, and along with the degradation of the capsule wall, gelatin hydrolase is slowly released, and the chitosan/gelatin composite microsphere is degraded, so that the degradation period of the composite microsphere is shortened, and the influence of the chitosan/gelatin composite microsphere on wound self-healing is reduced.
Preferably, in the polylactic acid-glycolic acid copolymer, the mass ratio of lactic acid to glycolic acid is (45-55): 50.
By adopting the technical scheme, the mass ratio of lactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is (45-55): 50, the degradation rate of the polylactic acid-glycolic acid copolymer is faster, and the polylactic acid-glycolic acid copolymer is similar to the wound healing period, so that the absorbable tissue adhesive has good mechanical property in the healing process, the residue of the absorbable tissue adhesive in a human body during healing can be reduced, and the influence on self-healing of biological tissues of the human body is reduced.
Alternatively, the average molecular weight of the polylactic acid-glycolic acid copolymer is 9-11kDa.
By adopting the technical scheme, the average molecular weight of the polylactic acid-glycolic acid copolymer is controlled, and the degradation rate of the polylactic acid-glycolic acid copolymer can be effectively controlled, so that the rate of outwards slow-release gelatin hydrolase of the hydrolase microcapsule is controlled, the degradation rate of the chitosan/gelatin composite microsphere is regulated and controlled, and the degradation rate of the absorbable tissue adhesive is ensured to be similar to the healing rate of biological tissues.
In summary, the application has the following beneficial effects:
1. As the trehalose is added, the trehalose molecules can form strong hydrogen bonds with a plurality of polar groups in the hydrogel, and the strength of the hydrogel formed by the elastin-like aqueous solution and glutaraldehyde aqueous solution is effectively improved through the hydrogen bond interaction of the introduced covalent bond, so that the ductility and the stretch resistance of the absorbable tissue adhesive are improved, the wound is not easy to crack, and the healing effect of the wound is ensured.
2. According to the application, the chitosan/gelatin composite microsphere and the hydrolase microcapsule are preferably adopted, when the hydrogel is stressed, the macromolecular microsphere deforms, energy is dissipated, good deformability is provided for the hydrogel, the ductility and toughness of the absorbable tissue adhesive are improved, and the hydrolase microcapsule can regulate and control the degradation rate of the chitosan/gelatin composite microsphere in a human body, so that the self-healing capacity of biological tissues is not easily affected.
3. According to the application, the chitosan/gelatin composite microsphere is treated, so that growth factors such as FGF and G-CSF are loaded, and the FGF and the G-CSF are released slowly when the absorbable tissue adhesive acts, so that the healing of human tissues can be effectively promoted, the occurrence of complications such as inflammation is reduced, and the recovery effect and recovery rate of wounds are improved.
Detailed Description
The present application will be described in further detail with reference to examples.
Preparation examples 1-10 of Chitosan/gelatin composite microspheres
Preparation example 1
The preparation method of the chitosan/gelatin composite microsphere comprises the following steps: dissolving 3mg of chitosan in an acetic acid solution to obtain 10mL of acetic acid solution of chitosan, wherein the deacetylation degree of the chitosan is 95%, dissolving gelatin in water to obtain 10mL of gelatin water solution, mixing the acetic acid solution of the chitosan with 10mL of gelatin water solution to obtain a mixed solution, mixing liquid paraffin with an emulsifying agent, wherein the emulsifying agent is span80, the adding amount of the emulsifying agent is 6mL to obtain oil liquid, dripping the mixed solution into the oil liquid, the volume ratio of the mixed solution to the oil liquid is 1:7, stirring and heating to 60 ℃ for emulsification for 35min, adding 25% glutaraldehyde for curing for 1h, adding acetone for stirring for 10min, centrifuging, washing with acetone, and drying to obtain the chitosan/gelatin composite microsphere.
Preparation example 2
The preparation method of the chitosan/gelatin composite microsphere comprises the following steps: dissolving 4.4mg of chitosan in an acetic acid solution to obtain 10mL of acetic acid solution of chitosan, wherein the deacetylation degree of the chitosan is 95%, dissolving gelatin in water to obtain 10mL of gelatin water solution, mixing the acetic acid solution of the chitosan with 10mL of gelatin water solution to obtain a mixed solution, mixing liquid paraffin with an emulsifying agent, wherein the emulsifying agent is span80, the adding amount of the emulsifying agent is 6mL, obtaining oil liquid, dripping the mixed solution into the oil liquid, the volume ratio of the mixed solution to the oil liquid is 1:7, stirring and heating to 60 ℃ for 45min, adding 25% glutaraldehyde for curing for 1h, adding acetone for stirring for 15min, centrifuging, washing with acetone, and drying to obtain the chitosan/gelatin composite microsphere.
Preparation example 3
Preparation 3 differs from preparation 1 in that the mass ratio of chitosan to gelatin is 1:3.5.
Preparation example 4
Preparation 4 differs from preparation 1 in that the mass ratio of chitosan to gelatin is 1:0.8.
Preparation example 5
Preparation example 5 differs from preparation example 1 in that the chitosan/gelatin composite microsphere is subjected to the following treatment: dropping FGF/G-CSF solution on chitosan/gelatin composite microsphere, fully soaking and expanding for 24h at 4 ℃, centrifuging, taking centrifugate, freeze-drying under aseptic condition, wherein in FGF/G-CSF solution, the concentration of FGF is 150 mug/mL, the concentration of G-CSF is 150 mug/mL, and the mass ratio of chitosan/gelatin composite microsphere to FGF/G-CSF solution is 1:0.4.
Preparation example 6
Preparation example 6 differs from preparation example 1 in that the chitosan/gelatin composite microsphere is subjected to the following treatment: dropping FGF/G-CSF solution on chitosan/gelatin composite microsphere, fully soaking and expanding for 26h at 6 ℃, centrifuging, taking centrifugate, freeze-drying under aseptic condition, wherein in FGF/G-CSF solution, the concentration of FGF is 250 mug/mL, the concentration of G-CSF is 250 mug/mL, and the mass ratio of chitosan/gelatin composite microsphere to FGF/G-CSF solution is 1:0.6.
Preparation example 7
Preparation 7 differs from preparation 5 in that the concentration of FGF is 25. Mu.g/mL.
Preparation example 8
Preparation 8 differs from preparation 5 in that the concentration of G-CSF is 25. Mu.g/mL.
Preparation example 9
Preparation example 9 differs from preparation example 5 in that the mass ratio of chitosan/gelatin composite microspheres to FGF/G-CSF solution is 1:0.1.
Preparation example 10
Preparation 10 differs from preparation 5 in that the mass ratio of chitosan/gelatin composite microspheres to FGF/G-CSF solution is 1:1.2.
Preparation examples 11 to 16 of hydrolase microcapsules
PREPARATION EXAMPLE 11
The wall of the hydrolase microcapsule is polylactic acid-glycolic acid copolymer, the mass ratio of polylactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is 45:50, the molecular weight of the polylactic acid-glycolic acid copolymer is 9kDa, the core of the hydrolase microcapsule is gelatin hydrolase, and the gelatin hydrolase is selected from Shanghai Fengshi biotechnology Co.
Adding gelatin hydrolase into PBS buffer solution, wherein the PBS buffer solution is pH7.4, 0.02% NaN3 is contained to form gelatin hydrolase solution with the gelatin hydrolase concentration of 100mg/mL, adding 1mL of gelatin hydrolase solution into 10mL of methylene dichloride solution of polylactic acid-glycolic acid copolymer, wherein the concentration of the polylactic acid-glycolic acid copolymer is 30mg/mL, immersing in ice water bath, emulsifying into white emulsion under the ultrasonic condition, immediately pouring into 100mL of 10mg/mL polyvinyl alcohol solution, dispersing uniformly, magnetically stirring for 4h, centrifuging after the methylene dichloride is completely volatilized, taking the centrifugate for washing, cooling and drying to obtain the hydrolase microcapsule.
Preparation example 12
The wall of the hydrolase microcapsule is polylactic acid-glycolic acid copolymer, the mass ratio of polylactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is 55:50, the molecular weight of the polylactic acid-glycolic acid copolymer is 11kDa, the core of the hydrolase microcapsule is gelatin hydrolase, and the gelatin hydrolase is selected from Shanghai Fengshi biotechnology Co.
Adding gelatin hydrolase into PBS buffer solution, wherein the PBS buffer solution is pH7.4, 0.02% NaN3 is contained to form gelatin hydrolase solution with the gelatin hydrolase concentration of 100mg/mL, adding 1mL of gelatin hydrolase solution into 10mL of methylene dichloride solution of polylactic acid-glycolic acid copolymer, wherein the concentration of the polylactic acid-glycolic acid copolymer is 30mg/mL, immersing in ice water bath, emulsifying into white emulsion under the ultrasonic condition, immediately pouring into 100mL of 10mg/mL polyvinyl alcohol solution, dispersing uniformly, magnetically stirring for 4h, centrifuging after the methylene dichloride is completely volatilized, taking the centrifugate for washing, cooling and drying to obtain the hydrolase microcapsule.
Preparation example 13
Preparation example 13 differs from preparation example 11 in that the mass ratio of polylactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is 75:50.
PREPARATION EXAMPLE 14
Preparation example 14 differs from preparation example 11 in that the mass ratio of polylactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is 25:50.
Preparation example 15
Preparation example 15 differs from preparation example 11 in that the molecular weight of the polylactic acid-glycolic acid copolymer is 5kDa.
PREPARATION EXAMPLE 16
Preparation example 16 differs from preparation example 11 in that the molecular weight of the polylactic acid-glycolic acid copolymer is 20kDa.
Examples
Example 1
A method for preparing absorbable tissue adhesive for blood vessels and organs, comprising the following steps:
Preparation of solution a: adding trehalose into the elastin-like aqueous solution, stirring for 5min, adding chitosan/gelatin composite microspheres and hydrolase microcapsules, and stirring for 10min to obtain solution A, wherein the concentration of elastin-like in the solution A is 50mg/L, and the concentration of trehalose in the solution A is 5%;
Preparation of solution B: glutaraldehyde is dissolved in water to form a 1% glutaraldehyde aqueous solution;
mixing: the absorbable tissue adhesive can be prepared by mixing the solution A and the solution B according to the mass ratio of 1:0.5.
Wherein the concentration of the chitosan/gelatin composite microsphere in the absorbable tissue adhesive is 0.1 mug/mL, the concentration of the hydrolase microcapsule in the absorbable tissue adhesive is 0.1 mug/mL, the chitosan/gelatin composite microsphere in the embodiment is prepared in preparation example 1, and the hydrolase microcapsule is prepared in preparation example 11.
The elastin is selected from Beijing instant biotechnology Co., ltd, and has the model of SEQ ID NO. 6 and the gene sequence as follows ：VPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGVGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGVGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGVGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGVGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGVGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGVGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGVGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKG.
Example 2
A method for preparing absorbable tissue adhesive for blood vessels and organs, comprising the following steps:
preparation of solution a: adding trehalose into the elastin-like aqueous solution, stirring for 15min, adding chitosan/gelatin composite microspheres and hydrolase microcapsules, and stirring for 20min to obtain solution A, wherein the concentration of elastin-like in the solution A is 650mg/L, and the concentration of trehalose in the solution A is 20%;
preparation of solution B: dissolving glutaraldehyde in water to form a 3% glutaraldehyde aqueous solution;
Mixing: and mixing the solution A and the solution B according to the mass ratio of 1:2 to obtain the absorbable tissue adhesive.
Wherein the concentration of the chitosan/gelatin composite microsphere in the absorbable tissue adhesive is 10 mug/mL, the concentration of the hydrolase microcapsule in the absorbable tissue adhesive is 10 mug/mL, the chitosan/gelatin composite microsphere in the embodiment is prepared in preparation example 1, and the hydrolase microcapsule is prepared in preparation example 11.
The elastin is selected from Beijing instant biotechnology Co., ltd, and has the model of SEQ ID NO. 6 and the gene sequence as follows ：VPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGVGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGVGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGVGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGVGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGVGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGVGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGVGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKGVPGKG.
Example 3
Example 3 differs from example 1 in that the chitosan/gelatin composite microspheres were present at a concentration of 0.01 μg/mL in the absorbable tissue adhesive and the hydrolase microcapsules were present at a concentration of 0.01 μg/mL in the absorbable tissue adhesive.
Example 4
Example 4 differs from example 1 in that the concentration of chitosan/gelatin composite microspheres in the absorbable tissue adhesive is 20 μg/mL and the concentration of hydrolase microcapsules in the absorbable tissue adhesive is 20 μg/mL.
Example 5
Example 5 differs from example 1 in that the chitosan/gelatin composite microspheres were present at a concentration of 0.1 μg/mL in the absorbable tissue adhesive and the hydrolase microcapsules were present at a concentration of 20 μg/mL in the absorbable tissue adhesive.
Example 6
Example 6 differs from example 1 in that the concentration of chitosan/gelatin composite microspheres in the absorbable tissue adhesive is 20 μg/mL and the concentration of hydrolase microcapsules in the absorbable tissue adhesive is 0.1 μg/mL.
Example 7
Example 7 differs from example 1 in that the chitosan/gelatin composite microsphere of this example was prepared from preparation example 2 and the hydrolase microcapsule was prepared from preparation example 12.
Example 8
Example 8 differs from example 1 in that the chitosan/gelatin composite microsphere of this example was prepared from preparation example 3 and the hydrolase microcapsule was prepared from preparation example 11.
Example 9
Example 9 differs from example 1 in that the chitosan/gelatin composite microsphere of this example was prepared from preparation example 4 and the hydrolase microcapsule was prepared from preparation example 11.
Example 10
Example 10 differs from example 1 in that the chitosan/gelatin composite microsphere of this example was prepared from preparation 5 and the hydrolase microcapsule was prepared from preparation 11.
Example 11
Example 11 differs from example 1 in that the chitosan/gelatin composite microsphere in this example was prepared from preparation example 6 and the hydrolase microcapsule was prepared from preparation example 11.
Example 12
Example 12 differs from example 1 in that the chitosan/gelatin composite microsphere of this example was prepared from preparation 7 and the hydrolase microcapsule was prepared from preparation 11.
Example 13
Example 13 differs from example 1 in that the chitosan/gelatin composite microsphere of this example was prepared from preparation 8 and the hydrolase microcapsule was prepared from preparation 11.
Example 14
Example 14 differs from example 1 in that the chitosan/gelatin composite microsphere of this example was prepared from preparation example 9 and the hydrolase microcapsule was prepared from preparation example 11.
Example 15
Example 15 differs from example 1 in that the chitosan/gelatin composite microsphere of this example was prepared from preparation 10 and the hydrolase microcapsule was prepared from preparation 11.
Example 16
Example 16 differs from example 1 in that the chitosan/gelatin composite microsphere of this example was prepared from preparation example 1 and the hydrolase microcapsule was prepared from preparation example 13.
Example 17
Example 17 differs from example 1 in that the chitosan/gelatin composite microsphere of this example was prepared from preparation example 1 and the hydrolase microcapsule was prepared from preparation example 14.
Example 18
Example 18 differs from example 1 in that the chitosan/gelatin composite microsphere of this example was prepared from preparation example 1 and the hydrolase microcapsule was prepared from preparation example 15.
Example 19
Example 19 differs from example 1 in that the chitosan/gelatin composite microsphere of this example was prepared from preparation example 1 and the hydrolase microcapsule was prepared from preparation example 16.
Comparative example
Comparative example 1
Comparative example 1 differs from example 1 in that the last one of solution a was free of trehalose.
Comparative example 2
Comparative example 2 differs from example 1 in that the chitosan/gelatin composite microspheres and hydrolase microcapsules were not added to solution a.
Comparative example 3
Comparative example 3 differs from example 1 in that the glutaraldehyde concentration in solution B is 0.1%.
Comparative example 4
Comparative example 4 differs from example 1 in that the glutaraldehyde concentration in solution B is 10%.
Comparative example 5
Comparative example 5 differs from example 1 in that the mass ratio of solution A to solution B was 1:0.1 when solution B was mixed with solution A.
Comparative example 6
Comparative example 6 differs from example 1 in that the mass ratio of solution a to solution B was 1:3 when solution B was mixed with solution a.
Test method
1. Mechanical property test of absorbable tissue adhesive: the solutions B prepared in examples 1 to 9 and comparative examples 1 to 6 and the corresponding solutions A or mixed solutions were respectively packed into A, B syringes of two-component syringes, and were injected onto glass plates, cured to form absorbable tissue adhesives having a thickness of 2mm, the curing times of the absorbable tissue adhesives were recorded in Table 1, the absorbable tissue adhesives were cut into samples having a length of 30mm and a width of 10mm, the tensile strength and tensile properties of each sample were measured using a universal tester, and the results were recorded in Table 1.
TABLE 1 mechanical Properties of absorbable tissue adhesive
Compared with comparative example 1, the embodiment 1-2 has the advantages that trehalose is added into the solution A, the tensile strength and the tensile property of the embodiment 1-2 are improved greatly compared with those of the comparative example 1, the addition of the trehalose can greatly improve the mechanical property of the hydrogel, the amino functional group of the elastin reacts with the aldehyde group of glutaraldehyde, and the aldehyde group reacts with the amino group on the human tissue protein, so that the gel formed by crosslinking the solution A and the solution B can be adhered to human tissues, the trehalose molecule has good water retention property and hydrophilicity, a large number of active groups in the trehalose molecule form strong hydrogen bonds with a plurality of polar groups in the gel, and the ductility and the toughness of the hydrogel are effectively improved through the hydrogen bond interaction of introducing the covalent bond, so that the tensile strength and the tensile property of the absorbable tissue adhesive are improved, the mechanical strength of the absorbable tissue adhesive is improved, the absorbable tissue adhesive is not easy to break and fall off during use, the adhesive effect of the absorbable tissue adhesive is ensured, and the curing time of the embodiment 1-2 is between 30 and 40 seconds, and accords with the operation speed in a comparatively high operation speed.
Compared with comparative example 2, examples 1-2 and 7 are prepared by adding chitosan/gelatin composite microspheres and hydrolase microcapsules into absorbable tissue adhesive, and the tensile strength and tensile property of examples 1-2 and 7 are greatly improved compared with those of comparative example 2, which means that the chitosan/gelatin composite microspheres and hydrolase microcapsules can improve the mechanical property of the absorbable tissue adhesive, and the chitosan/gelatin composite microspheres belong to macromolecular microspheres, and when the absorbable tissue adhesive is stressed, the macromolecular microspheres deform and dissipate energy, so that the absorbable tissue adhesive has good deformability, and the tensile property and tensile strength of the absorbable tissue adhesive are improved.
Example 5 shows an increase in the concentration of hydrolase microcapsules in example 5 as compared to example 1, but the tensile strength and tensile properties of the absorbable tissue adhesive in example 5 are not significantly altered as compared to example 1, indicating an improvement in the tensile strength and tensile properties of the absorbable tissue adhesive, which is not a major contributor.
Examples 3-4 and 6 show that the concentration of the chitosan/gelatin composite microspheres in example 3 is reduced compared with example 1, the concentration of the chitosan/gelatin composite microspheres in example 4 and example 6 is increased, the tensile strength and tensile properties of the absorbable tissue adhesive in examples 3-4 and 6 are reduced compared with example 1, which means that the addition amount of the chitosan/gelatin composite microspheres has an influence on the tensile strength of the absorbable tissue adhesive, the concentration of the chitosan/gelatin composite microspheres in the absorbable tissue adhesive is reduced, the energy dissipated by the macromolecular microspheres when the hydrogel is stressed is reduced, the tensile strength and tensile properties of the macromolecular microspheres are reduced, the chitosan/gelatin composite microspheres belong to semi-rigid microspheres, and when the concentration of the chitosan/gelatin composite microspheres in the absorbable tissue adhesive is increased, the rigid brittle structure in the hydrogel is excessive, the tensile strength and tensile properties of the absorbable tissue adhesive are reduced when stressed.
Examples 8-9 compared with example 1, the ratio of gelatin in the chitosan/gelatin composite microspheres in example 8 was increased, the ratio of gelatin in the chitosan/gelatin composite microspheres in example 9 was decreased, both the tensile strength and tensile properties of the absorbable tissue adhesive in examples 8 and 9 were decreased, which means that the mass ratio of gelatin in the composite microspheres had an effect on the mechanical properties of the absorbable tissue adhesive, when the concentration of gelatin was low, the diameters of the composite microspheres formed by chitosan and gelatin were smaller, the elasticity of the composite microspheres was decreased, the deformation properties were decreased, and the dissipated energy was decreased, so that the tensile strength and tensile properties of the hydrogel were decreased, and when the concentration of gelatin was high, adhesion and irregular shape were occurred between the composite microspheres, thereby decreasing the mechanical properties of the composite microspheres, and decreasing the tensile strength and tensile properties of the absorbable tissue adhesive.
Comparative examples 3 to 4 have a lower glutaraldehyde concentration in comparative example 3 and an increased glutaraldehyde concentration in comparative example 4, and the tensile strength and tensile properties of comparative example 3 are both decreased, while the tensile strength and tensile properties of comparative example 4 are slightly increased, indicating that the glutaraldehyde concentration has an effect on the mechanical properties of the hydrogel formed after crosslinking, the glutaraldehyde concentration in comparative example 3 is lower, and the degree of crosslinking of glutaraldehyde with elastin-like is lower, thereby affecting the curing time and the tensile strength of the hydrogel after curing, while the glutaraldehyde concentration in comparative example 4 is higher, and although the tensile strength and tensile properties are increased compared with example 1, the curing speed is too fast, the operation time is too short in practical use, and is not suitable for clinical use.
Comparative examples 5-6 compared with example 1, the comparative example 5 had a smaller amount of glutaraldehyde aqueous solution, the comparative example 6 had a larger amount of glutaraldehyde aqueous solution, the comparative example 5 had a lower tensile strength and tensile properties, and the comparative example 6 had a slightly improved tensile strength and tensile properties, indicating that the ratio of solution A to solution B had an effect on the mechanical properties of the hydrogels, the comparative example 5 had a smaller amount of glutaraldehyde aqueous solution, the hydrogels had a lower degree of crosslinking, and the crosslinking time was longer, affecting the tensile strength of the absorbable tissue adhesive, and the comparative example 6 had a larger amount of glutaraldehyde aqueous solution, but the crosslinking speed was too fast, the curing time was shorter, and was unsuitable for use.
2. Healing efficacy test of absorbable tissue adhesive: 26 mice were cut on the backs of the mice, wounds 2.5cm long and 5mm deep were respectively smeared with staphylococcus aureus bacterial liquid at the wounds, the wounds were treated with the absorbable tissue adhesives prepared in examples 1-2, 7, 10-19 and comparative example 2 and the same amount of clear water (blank group), recovery of the wounds was observed for 4 and7 days, wound healing was expressed as wound length (mm), wound inflammation was progressively divided into grade I, grade II, grade III and grade IV according to the severity of redness, grade I was no inflammation, grade II was slight inflammation, grade III was normal inflammation, grade IV was severe inflammation, and wound healing and wound inflammation were recorded in table 2.
TABLE 2 recovery of mouse wounds
As can be seen from table 2, comparative example 2 showed normal inflammation symptoms at 0 day, slight inflammation symptoms at 4 days, no inflammation symptoms at 7 days, and severe inflammation symptoms at the early stage, and slight inflammation symptoms at 7 days, indicating that the absorbable tissue adhesive can inhibit staphylococcus aureus infected by the wound, reduce bacterial infection and inflammation symptoms of the wound, and the wound length of comparative example 2 was reduced at 4 days and 7 days, compared to the blank, indicating that the absorbable tissue adhesive can promote wound healing. The absorbable tissue adhesive covers the wound, can closely attach the section of the wound by means of the adhesive force between the absorbable tissue adhesive and biological tissues, has the effect of replacing suture, has good water-retaining property and biocompatibility, and can be slowly decomposed and absorbed by organisms.
The chitosan/gelatin composite microspheres and the hydrolase microcapsules are added in the examples 1-2 and 7, the wound length of the examples 1-2 and 7 is slightly shortened compared with that of the comparative example 2, the chitosan/gelatin composite microspheres can further enhance the tensile strength and tensile property of the absorbable tissue adhesive, so that the absorbable tissue adhesive is not easy to break during use, the adhesive effect of the absorbable tissue adhesive on the wound is guaranteed, the wound is not easy to break due to the movement of a mouse, the healing effect and the healing speed of the wound are further improved, the hydrolase microcapsules can slowly release the gelatin hydrolase, the degradation speed of the chitosan/gelatin composite microspheres is accelerated, the degradation speed of the absorbable tissue adhesive is similar to that of the wound, and the gelatin composite microspheres are not easy to remain to influence the self-healing function of the wound.
Examples 10-11 compared to example 1, the chitosan/gelatin composite microspheres were treated and loaded with FGF and G-CSF, examples 10-11 exhibited slight inflammatory symptoms at day 0 and no inflammatory symptoms at day 4, and the wound length of examples 10-11 was also shortened compared to example 1, demonstrating that FGF and G-CSF could promote wound healing rate and reduce inflammatory symptoms during wound healing; FGF can promote the formation of new blood vessels and repair damaged endothelial cells, has the effect of promoting healing, G-CSF can promote proliferation, differentiation and activation of neutrophil hematopoietic cells, neutrophils can effectively inhibit and kill the growth of bacteria, infection complications in the wound healing process are reduced, and the addition of FGF and G-CSF is beneficial to improving the healing effect of mouse wounds.
Compared with example 10, the chitosan/gelatin composite microsphere in example 12 has the advantages that the concentration of FGF is reduced during treatment, and the wound length in example 12 is slightly longer than that in example 10 in 4 days, which indicates that the content of FGF can influence the healing speed of the wound, and the wound healing speed is increased and has direct influence on the concentration of FGF; example 13 the concentration of G-CSF was reduced at treatment compared to example 10, example 13 showed slight inflammatory symptoms at day 0, and slight inflammatory symptoms remained at day 4 until no inflammatory symptoms were observed at the wound until day 7, indicating that G-CSF was associated with infectious complications during wound healing, and that G-CSF promoted expression of neutrophils in mice, thereby increasing the rate of killing staphylococcus aureus at the wound.
Example 14 showed a reduced mass of FGF/G-CSF solution treated with the chitosan/gelatin composite microspheres compared to example 10, such that the FGF and G-CSF loaded in the chitosan/gelatin composite microspheres was reduced, and example 14 showed a longer wound length at 4 days and 7 days, and a common inflammatory symptom at 0 day, a slight inflammatory symptom at 4 days, and no inflammatory symptom at 7 days, indicating that a small amount of FGF and G-CSF had effects of promoting healing and reducing infectious complications, but had a weaker effect compared to example 10, compared to example 10.
Example 15 shows an increase in mass of FGF/G-CSF solution treated with the chitosan/gelatin composite microspheres compared to example 10, but example 15 is similar to the wound healing case of example 10, indicating that the amount of physiological saline used for FGF/G-CSF is excessive, and that part of FGF and G-CSF are not successfully loaded into the chitosan/gelatin composite microspheres, resulting in waste.
In example 16, compared with example 10, the mass ratio of polylactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer was increased, so that the content of polylactic acid in the copolymer was increased, and the healing rate of example 16 was decreased compared with example 10, probably because the content of polylactic acid in the polylactic acid-glycolic acid copolymer was too high, the degradation rate of the polylactic acid-glycolic acid copolymer was decreased, and the release rate and release amount of gelatin hydrolase were decreased, affecting the self-healing function of mice and decreasing the healing rate of wounds.
In example 17, compared with example 10, the mass ratio of polylactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is reduced, the healing rate of example 17 is reduced compared with example 10, the content of polylactic acid in the copolymer is increased, the degradation rate of the polylactic acid-glycolic acid copolymer is accelerated, but the hydrophilicity of the copolymer is improved due to the increase of the content of the glycolic acid, when preparing the hydrolase microcapsule, the encapsulation effect of the capsule wall formed by the polylactic acid-glycolic acid copolymer on the gelatin hydrolase with the capsule core is poor, the encapsulation rate of the hydrolase microcapsule is reduced, the content of the gelatin hydrolase contained in the hydrolase microcapsule is less, the degradation rate of the chitosan/gelatin composite microsphere is reduced, the self-healing function of the mouse is affected, and the healing rate of the wound is reduced.
Compared with example 10, the molecular weight of the polylactic acid-glycolic acid copolymer in example 18 is reduced, the healing rate of example 18 is reduced compared with that of example 10, the smaller the molecular weight of the polylactic acid-glycolic acid copolymer is, the faster the degradation rate is, and the degradation rate of the chitosan/gelatin composite microsphere is accelerated due to the fact that the rate of outwards slowly releasing gelatin hydrolase by the hydrolase microcapsule is accelerated, the mechanical property of the absorbable tissue adhesive is gradually reduced, the adhesive effect is affected, a slight cracking phenomenon of a wound possibly occurs in the healing process, and the healing effect of the wound is finally affected.
The molecular weight of the polylactic acid-glycolic acid copolymer in example 19 is increased compared with that in example 10, the healing rate of example 19 is reduced compared with that in example 10, the larger the molecular weight of the polylactic acid-glycolic acid copolymer is, the slower the degradation rate is, and the slow release rate of gelatin hydrolase is reduced, so that the decomposition rate of chitosan/gelatin composite microspheres is reduced, the self-healing function of mice is affected, and finally the healing rate of wounds is reduced.
3. Adhesive performance test of absorbable tissue adhesive: the absorbable tissue adhesives prepared in examples 1-2, 7, 10-11 and comparative examples 1-2 were subjected to adhesive property test by referring to YY/T0729.4-2009, "tissue adhesive property test method part 4: wound closure strength, and the results are recorded in table 3.
TABLE 3 adhesive properties of absorbable tissue adhesives
As can be seen from table 3, the closing strength of examples 1-2, 7 and 10-11 all meet the clinical requirement, which indicates that the hydrogel formed by crosslinking the elastin-like aqueous solution and glutaraldehyde has good adhesion with biological tissues, and the absorbable tissue adhesive has good mechanical properties, and is not easy to break, so that the adhesive effect of the absorbable tissue adhesive on wounds is ensured, and the chitosan/gelatin composite microsphere, the hydrolase microcapsule, the FGF and the G-CSF added in the absorbable tissue adhesive do not affect the adhesive property of the absorbable tissue adhesive.
Comparative example 1 was compared with example 1, trehalose was not added, comparative example 2 was compared with example 1, chitosan/gelatin composite microspheres and hydrolase microcapsules were not added, the wound closure strength of comparative example 1-2 was low, and in the test process, the broken portion of the test sample was an adhesion area, i.e., the absorbable tissue adhesive itself was broken, but the non-absorbable tissue adhesive was peeled off from the biological tissue, indicating that the absorbable tissue adhesive of comparative example 1-2 had good adhesion properties, but the mechanical strength of itself was low, and breakage was likely to occur, thereby affecting the adhesive effect of the absorbable tissue adhesive on the wound.
The present embodiment is only for explanation of the present application and is not to be construed as limiting the present application, and modifications to the present embodiment, which may not creatively contribute to the present application as required by those skilled in the art after reading the present specification, are all protected by patent laws within the scope of claims of the present application.
Claims (7)
1. A method for preparing absorbable tissue adhesive for blood vessels and organs, which is characterized by comprising the following steps: the method comprises the following steps:
Preparation of solution a: adding trehalose into the elastin-like aqueous solution, stirring for 5-15min, adding chitosan/gelatin composite microspheres and hydrolase microcapsules, and stirring for 10-20min to obtain solution A, wherein the concentration of elastin-like in the solution A is 50-650mg/L, and the concentration of trehalose in the solution A is 5-20%;
preparation of solution B: dissolving glutaraldehyde in water to form a glutaraldehyde aqueous solution of 1-3 wt%;
Mixing: mixing the solution A and the solution B according to the mass ratio of 1 (0.5-2.0) to obtain the absorbable tissue adhesive, wherein the concentration of the chitosan/gelatin composite microspheres in the absorbable tissue adhesive is 0.1-10 mug/mL, and the concentration of the hydrolase microcapsules in the absorbable tissue adhesive is 0.1-10 mug/mL;
Before the chitosan/gelatin composite microsphere is added, the following treatment is carried out: dissolving FGF and G-CSF in physiological saline to form FGF/G-CSF solution, dripping the FGF/G-CSF solution on chitosan/gelatin composite microsphere, fully soaking and expanding at 4-6 ℃ for 24-26h, centrifuging, taking centrifugate, freeze-drying under sterile condition, wherein the concentration of FGF is 150-250 mug/mL, and the concentration of G-CSF is 150-250 mug/mL.
2. The method for preparing the absorbable tissue adhesive for blood vessels and organs according to claim 1, wherein the method comprises the following steps: the mass ratio of the chitosan/gelatin composite microsphere to the hydrolase microcapsule in the absorbable tissue adhesive is 1 (0.9-1).
3. The method for preparing the absorbable tissue adhesive for blood vessels and organs according to claim 1, wherein the method comprises the following steps: the chitosan/gelatin composite microsphere comprises the raw materials of chitosan and gelatin with the mass ratio of 1 (1.8-2.2).
4. The method for preparing the absorbable tissue adhesive for blood vessels and organs according to claim 1, wherein the method comprises the following steps: the mass ratio of the chitosan/gelatin composite microsphere to the FGF/G-CSF solution is 1 (0.4-0.6).
5. The method for preparing the absorbable tissue adhesive for blood vessels and organs according to claim 1, wherein the method comprises the following steps: the wall of the hydrolase microcapsule is polylactic acid-glycolic acid copolymer, and the core is gelatin hydrolase.
6. The method for preparing an absorbable tissue adhesive for blood vessels and organs according to claim 5, wherein the method comprises the steps of: in the polylactic acid-glycolic acid copolymer, the mass ratio of lactic acid to glycolic acid is (45-55): 50.
7. The method for preparing an absorbable tissue adhesive for blood vessels and organs according to claim 5, wherein the method comprises the steps of: the average molecular weight of the polylactic acid-glycolic acid copolymer is 9-11kDa.
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6699470B1 (en) * | 1999-10-12 | 2004-03-02 | Massachusetts Institute Of Technology | Mesh-gel constructs for cell delivery containing enzymes and/or enzyme inhibitors to control gel degradation |
| CN105879109A (en) * | 2016-03-31 | 2016-08-24 | 武汉华同信生物科技有限公司 | Medical adhesive and preparation method thereof |
| CN109432488A (en) * | 2018-12-14 | 2019-03-08 | 武汉理工大学 | A kind of preparation method of chitosan/gelatin-compounded hemostatic microsphere |
| CN110452662A (en) * | 2019-08-22 | 2019-11-15 | 中国科学院长春应用化学研究所 | A kind of bioadhesive and preparation method thereof based on bioengineered proteins |
| KR20220084885A (en) * | 2020-12-14 | 2022-06-21 | 주식회사 넥스트바이오메디컬 | Adhesive composition for in-body absorbable reinforcement materials comprising chitosan and gelatin and manufacturing method thereof |
| CN115192776A (en) * | 2022-07-21 | 2022-10-18 | 西北大学 | Method for preparing tenacious hydrogel for repairing tendon injury |
| CN116421772A (en) * | 2023-04-28 | 2023-07-14 | 北京瞬行生物科技有限公司 | Bi-component instantaneous in-situ adhesive based on bioengineering protein, and preparation method and application thereof |
| CN116535565A (en) * | 2023-05-29 | 2023-08-04 | 河北工业大学 | Trehalose modified photo-thermal water gel and preparation method and application thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7837986B2 (en) * | 2004-12-01 | 2010-11-23 | E. I. Du Pont De Nemours And Company | Protein-based polymer tissue adhesives for medical use |
| US20140220136A1 (en) * | 2013-02-05 | 2014-08-07 | Bordoloi Biotech, Llc | System and method for delivering protease inhibitors |
-
2024
- 2024-01-24 CN CN202410097102.3A patent/CN117599236B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6699470B1 (en) * | 1999-10-12 | 2004-03-02 | Massachusetts Institute Of Technology | Mesh-gel constructs for cell delivery containing enzymes and/or enzyme inhibitors to control gel degradation |
| CN105879109A (en) * | 2016-03-31 | 2016-08-24 | 武汉华同信生物科技有限公司 | Medical adhesive and preparation method thereof |
| CN109432488A (en) * | 2018-12-14 | 2019-03-08 | 武汉理工大学 | A kind of preparation method of chitosan/gelatin-compounded hemostatic microsphere |
| CN110452662A (en) * | 2019-08-22 | 2019-11-15 | 中国科学院长春应用化学研究所 | A kind of bioadhesive and preparation method thereof based on bioengineered proteins |
| KR20220084885A (en) * | 2020-12-14 | 2022-06-21 | 주식회사 넥스트바이오메디컬 | Adhesive composition for in-body absorbable reinforcement materials comprising chitosan and gelatin and manufacturing method thereof |
| CN115192776A (en) * | 2022-07-21 | 2022-10-18 | 西北大学 | Method for preparing tenacious hydrogel for repairing tendon injury |
| CN116421772A (en) * | 2023-04-28 | 2023-07-14 | 北京瞬行生物科技有限公司 | Bi-component instantaneous in-situ adhesive based on bioengineering protein, and preparation method and application thereof |
| CN116535565A (en) * | 2023-05-29 | 2023-08-04 | 河北工业大学 | Trehalose modified photo-thermal water gel and preparation method and application thereof |
Non-Patent Citations (4)
| Title |
|---|
| Covalently antibacterial alginate-chitosan hydrogel dressing integrated gelatin microspheres containing tetracycline hydrochloride for wound healing;Chen H, et al;Materials Science and Engineering: C;20170101;第70卷;摘要 * |
| 张伟忠 ; 黄惠民 ; 苏肇伉 ; .纤维蛋白粘合剂在小儿心脏外科中的应用.国际心血管病杂志.(01),全文. * |
| 顾其胜等.海藻酸盐基生物医用材料与临床医学.上海科学技术出版社,2015,212-213. * |
| 黄丽 ; 叶群丽 ; 陈玉玲 ; 朱仁庆 ; 王碧 ; .2,4-D-明胶/壳聚糖/葡甘聚糖复合微球的制备及其性能.皮革科学与工程.2008,(06),全文. * |
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