CN106344960B - The hemostasis gel prepared using microcrystalline cellulose graft modification abortive calfskin collagenous fibres - Google Patents
The hemostasis gel prepared using microcrystalline cellulose graft modification abortive calfskin collagenous fibres Download PDFInfo
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- CN106344960B CN106344960B CN201610834678.9A CN201610834678A CN106344960B CN 106344960 B CN106344960 B CN 106344960B CN 201610834678 A CN201610834678 A CN 201610834678A CN 106344960 B CN106344960 B CN 106344960B
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- 230000023597 hemostasis Effects 0.000 title claims abstract description 18
- 229920000168 Microcrystalline cellulose Polymers 0.000 title claims abstract description 14
- 235000019813 microcrystalline cellulose Nutrition 0.000 title claims abstract description 14
- 239000008108 microcrystalline cellulose Substances 0.000 title claims abstract description 12
- 229940016286 microcrystalline cellulose Drugs 0.000 title claims abstract description 12
- 238000012986 modification Methods 0.000 title claims abstract description 11
- 230000004048 modification Effects 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 23
- 102000008186 Collagen Human genes 0.000 claims abstract description 20
- 108010035532 Collagen Proteins 0.000 claims abstract description 20
- 229920001436 collagen Polymers 0.000 claims abstract description 20
- 238000000605 extraction Methods 0.000 claims abstract description 18
- 239000002904 solvent Substances 0.000 claims abstract description 15
- 239000000835 fiber Substances 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 9
- 230000008569 process Effects 0.000 claims abstract description 5
- 239000000243 solution Substances 0.000 claims description 37
- 238000010992 reflux Methods 0.000 claims description 16
- 229920002125 Sokalan® Polymers 0.000 claims description 15
- 239000004584 polyacrylic acid Substances 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000008367 deionised water Substances 0.000 claims description 8
- 229910021641 deionized water Inorganic materials 0.000 claims description 8
- 235000019832 sodium triphosphate Nutrition 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 7
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 claims description 6
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims description 6
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 6
- 229920000148 Polycarbophil calcium Polymers 0.000 claims description 6
- 229920000954 Polyglycolide Polymers 0.000 claims description 6
- 229960002684 aminocaproic acid Drugs 0.000 claims description 6
- 229960005261 aspartic acid Drugs 0.000 claims description 6
- 229950005134 polycarbophil Drugs 0.000 claims description 6
- 239000002994 raw material Substances 0.000 claims description 6
- 235000021283 resveratrol Nutrition 0.000 claims description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 6
- 238000004381 surface treatment Methods 0.000 claims description 6
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims description 5
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 5
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 5
- 239000002202 Polyethylene glycol Substances 0.000 claims description 5
- 229930003448 Vitamin K Natural products 0.000 claims description 5
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 claims description 5
- CBMPTFJVXNIWHP-UHFFFAOYSA-L disodium;hydrogen phosphate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].OP([O-])([O-])=O.OC(=O)CC(O)(C(O)=O)CC(O)=O CBMPTFJVXNIWHP-UHFFFAOYSA-L 0.000 claims description 5
- 239000007981 phosphate-citrate buffer Substances 0.000 claims description 5
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 claims description 5
- 229920001223 polyethylene glycol Polymers 0.000 claims description 5
- 238000004659 sterilization and disinfection Methods 0.000 claims description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 5
- 235000019168 vitamin K Nutrition 0.000 claims description 5
- 239000011712 vitamin K Substances 0.000 claims description 5
- 150000003721 vitamin K derivatives Chemical class 0.000 claims description 5
- 229940046010 vitamin k Drugs 0.000 claims description 5
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 claims description 4
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- LKXYJYDRLBPHRS-UHFFFAOYSA-N bromocyclopropane Chemical compound BrC1CC1 LKXYJYDRLBPHRS-UHFFFAOYSA-N 0.000 claims description 4
- 230000001680 brushing effect Effects 0.000 claims description 4
- 238000005138 cryopreservation Methods 0.000 claims description 4
- 235000019441 ethanol Nutrition 0.000 claims description 4
- 239000005457 ice water Substances 0.000 claims description 4
- 229960003511 macrogol Drugs 0.000 claims description 4
- 239000002245 particle Substances 0.000 claims description 4
- 239000004633 polyglycolic acid Substances 0.000 claims description 4
- 229950008885 polyglycolic acid Drugs 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 239000003755 preservative agent Substances 0.000 claims description 4
- 230000002335 preservative effect Effects 0.000 claims description 4
- 229940016667 resveratrol Drugs 0.000 claims description 4
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- 238000013517 stratification Methods 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 3
- 235000002374 tyrosine Nutrition 0.000 claims description 3
- 238000007385 chemical modification Methods 0.000 claims description 2
- 238000007710 freezing Methods 0.000 claims description 2
- 230000008014 freezing Effects 0.000 claims description 2
- 238000012545 processing Methods 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 239000007853 buffer solution Substances 0.000 claims 1
- 235000019262 disodium citrate Nutrition 0.000 claims 1
- 239000002526 disodium citrate Substances 0.000 claims 1
- 229940079896 disodium hydrogen citrate Drugs 0.000 claims 1
- CEYULKASIQJZGP-UHFFFAOYSA-L disodium;2-(carboxymethyl)-2-hydroxybutanedioate Chemical compound [Na+].[Na+].[O-]C(=O)CC(O)(C(=O)O)CC([O-])=O CEYULKASIQJZGP-UHFFFAOYSA-L 0.000 claims 1
- 238000002791 soaking Methods 0.000 claims 1
- 230000000025 haemostatic effect Effects 0.000 abstract description 5
- 230000000740 bleeding effect Effects 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 239000000499 gel Substances 0.000 abstract 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 3
- 230000002439 hemostatic effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 108091029865 Exogenous DNA Proteins 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 231100000899 acute systemic toxicity Toxicity 0.000 description 2
- 239000012752 auxiliary agent Substances 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000005238 degreasing Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 230000003328 fibroblastic effect Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-I triphosphate(5-) Chemical compound [O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O UNXRWKVEANCORM-UHFFFAOYSA-I 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
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
- A61L24/102—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
-
- 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
- A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- 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
- A61L2300/418—Agents promoting blood coagulation, blood-clotting agents, embolising 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Surgery (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses a kind of hemostasis gels prepared using microcrystalline cellulose graft modification abortive calfskin collagenous fibres, it is related to hemostasis gel technical field, include the following steps: that (1) abortive calfskin pre-processes, (2) preparation of collagenous fibres Extraction solvent, (3) preparation of collagenous fibres solution, (4) preparation of modified collagen fiber solution, the preparation of (5) hemostasis gel.Hemostasis gel of the present invention can directly overlie bleed site, play haemostatic effect, and stop blooding rapidly, promote the reparation of the surface of a wound while effectively reducing amount of bleeding；There is excellent biocompatibility and biological degradability simultaneously, it is safe to use, using rear without any side effects.
Description
Technical field:
The present invention relates to hemostasis gel technical fields, and in particular to a kind of to utilize microcrystalline cellulose graft modification abortive calfskin glue
The hemostasis gel of fibrinogen preparation.
Background technique:
Often the bleeding profusely along with the surface of a wound in surgery and trauma operation, so that patient be made to face great life
Danger, therefore prepare the research hotspot that quickly and effectively hemostatic material is used as always medical field.Traditional hemostatic material exists
The shortcomings that not portable and disinfection saves, and stop blooding and almost lean on mechanism, haemostatic effect is bad.In recent years, people develop
Biological absorbable hemostatic material, wherein Animal Skin Collagen sill is as a kind of good medical material of biological property, with human body
It is biodegradable and have no toxic side effect with good histocompatbility, while adherency, proliferation and the wound of cell can be promoted
It is compound；And by its distinctive microcellular structure and good adhesiveness, promotes the growth of biotic factor to spread, induce and promote
Into fibroblastic growth, to promote the healing of wound.
Currently, it is sour enzyme combination extraction method that universal Animal Skin Collagen, which extracts preparation method, main includes the pre- place of raw material
Reason, degreasing enzymolysis, digestion, are saltoutd, are centrifuged and purified, but there is gained collagen purity and low yield, at high cost etc.
Problem, and collagen can be made to reduce or lose biomechanical property because dealing with improperly in extraction process, stop to influence it
Blood effect.For this problem, our company starts with from the extracting method of collagen, and combines the modification to collagen is extracted
And the addition of auxiliary agent prepares hemostasis gel material, improves haemostatic effect, biocompatibility, biology drop on a low-cost basis
Solution property and safety in utilization.
Summary of the invention:
Technical problem to be solved by the present invention lies in providing, one kind is easy to use, haemostatic effect is good and has superior bio
The hemostasis gel of compatibility and biological degradability prepared using microcrystalline cellulose graft modification abortive calfskin collagenous fibres.
The following technical solution is employed for the technical problems to be solved by the invention to realize:
The hemostasis gel prepared using microcrystalline cellulose graft modification abortive calfskin collagenous fibres, is included the following steps:
(1) abortive calfskin pre-processes: purifying abortive calfskin as raw material can trace to the source, is wrapped up after being fully deployed with preservative film
It is good, it is placed in 5~8h of freezing in -5~0 DEG C of environment, then with 10-15 DEG C of temperature, the sodium bicarbonate and tripolyphosphate of mass fraction 5%
Sodium mixed aqueous solution impregnates 10~15min, then uses sponge brush brushing surface 2~3 times under deionized water shower；
(2) preparation of collagenous fibres Extraction solvent: according to the ratio of 1.2~1.5:1 of molar ratio by Cyclopropyl Bromide and 2- pyrrole
Pyrrolidone is sufficiently mixed, prior to being ultrasonically treated 15~30min under supersonic frequency 40kHz, power 50W, then at microwave frequency
3~5min of microwave treatment under 2450MHz, power 700W is then heated to 30~60min of reflux state insulated and stirred, to be mixed
5-10 DEG C of deionized water of the weight such as addition, is sufficiently stirred rear stratification after solution naturally cools to 50-55 DEG C, phase of fetching water,
Up to Extraction solvent；
(3) preparation of collagenous fibres solution: the abortive calfskin after above-mentioned scrub is sent into freeze drier, dry to aqueous
Amount using onal machine is ground into the particle that granularity is 2-3mm after being 10-15%, adds in above-mentioned made Extraction solvent, sufficiently
10~15min is stood after dispersion, is transferred in ball mill after standing, is milled to fineness less than 50 μm, is then added pH=3's
Disodium hydrogen phosphate-citrate buffer solution utilizes the Surface Treatment with Plasma machine of working frequency 40Hz, power 600W after being sufficiently mixed
10~15s is handled to gained mixture, after treatment is transferred to 3~5h of standing in 0~5 DEG C of environment, polyacrylic acid is then added
And polyethylene glycol oxide, and it is heated to reflux state 15~30min of insulated and stirred, 270 meshes are finally crossed, gained filtrate is collagen
Fiber solution；
(4) microcrystalline cellulose, poly- second the preparation of modified collagen fiber solution: are added into above-mentioned made collagenous fibres solution
Glycol 6000 and L-Aspartic acid are sufficiently mixed, in 35~40 DEG C of 1~2h of sealing and standing after being uniformly dispersed then in Microwave Frequency
2~3min of microwave treatment under rate 2450MHz, power 700W, is sufficiently mixed again, and utilizes working frequency 40Hz, power 600W
Surface Treatment with Plasma machine handle 10~15s, gained mixture is under ice-water bath with the cooling drop of the speed of 10~15 DEG C/min
Temperature, 10~15min of insulated and stirred is after temperature is down to 0~5 DEG C to get modified collagen fiber solution；
(5) preparation of hemostasis gel: into above-mentioned made modified collagen fiber solution be added polyglycolic acid, Polycarbophil,
Vitamin K and aminocaproic acid are distributed into mold after being sufficiently mixed uniformly, and utilize gamma-rays sterilization, are finally packaged
The cryo-conservation under the conditions of 0~5 DEG C afterwards.
The dosage mass ratio of sodium bicarbonate and sodium tripolyphosphate is 2~3:1 in the step (1).
Abortive calfskin, Extraction solvent, disodium hydrogen phosphate-citrate buffer solution, polyacrylic acid and polyoxygenated in the step (3)
10~15:40 of dosage mass ratio~50:0.5~1:0.5~1:0.5~1 of ethylene.
Polyacrylic acid passes through chemical modification, method of modifying are as follows: by polyacrylic acid and junket ammonia using preceding in the step (3)
Acid be added double weight part ethyl alcohol in, reflux state insulated and stirred 10min is heated to after being uniformly dispersed, add resveratrol and
Disodium ethylene diamine tetraacetate continues at insulated and stirred 30min under reflux state, after gained mixture naturally cools to 35-40 DEG C
It is transferred in 0-5 DEG C of environment immediately and stands 8h, be then fed into spray dryer, obtained solid is ground after drying is made powder.
The polyacrylic acid, tyrosine, resveratrol and disodium ethylene diamine tetraacetate dosage mass ratio be 10~15:1
~2:3~6:0.5~1.
The dosage matter of collagenous fibres solution, microcrystalline cellulose, Macrogol 6000 and L-Aspartic acid in the step (4)
Measure ratio 25~30:3~6:1~2:0.5~1.
The use of modified collagen fiber solution, polyglycolic acid, Polycarbophil, vitamin K and aminocaproic acid in the step (5)
Measure 25~30:2 of mass ratio~3:1~2:0.5~1:0.5~1.
The beneficial effects of the present invention are: the present invention purifies abortive calfskin as raw material can trace to the source, it is molten that extraction prepares collagenous fibres
Liquid, and the extracted collagenous fibres of microcrystalline cellulose graft modification are utilized, and be aided with a variety of auxiliary agents and hemostasis gel is made, it should be only
Blood clotting glue can directly overlie bleed site, play haemostatic effect, and stop blooding rapidly, promote wound while effectively reducing amount of bleeding
The reparation in face；There is excellent biocompatibility and biological degradability simultaneously, it is safe to use, without the secondary work of any poison after use
With.
Specific embodiment:
In order to be easy to understand the technical means, the creative features, the aims and the efficiencies achieved by the present invention, tie below
Specific embodiment is closed, the present invention is further explained.
Embodiment 1
(1) abortive calfskin pre-processes: purifying abortive calfskin as raw material can trace to the source, is wrapped up after being fully deployed with preservative film
It is good, it is placed in -5~0 DEG C of environment and freezes 8h, then with 10-15 DEG C of temperature, the sodium bicarbonate and sodium tripolyphosphate of mass fraction 5%
(sodium bicarbonate, sodium tripolyphosphate dosage mass ratio be 3:1) mixed aqueous solution impregnate 15min, then under deionized water shower
With sponge brush brushing surface 2 times.
(2) preparation of collagenous fibres Extraction solvent: according to the ratio of molar ratio 1.2:1 by Cyclopropyl Bromide and 2-Pyrrolidone
It is sufficiently mixed, prior to being ultrasonically treated 30min under supersonic frequency 40kHz, power 50W, then at microwave frequency 2450MHz, power
Microwave treatment 5min under 700W, is then heated to reflux state insulated and stirred 60min, and solution to be mixed naturally cools to 50-55
5-10 DEG C of deionized water of the weight such as addition after DEG C, is sufficiently stirred rear stratification, water intaking is mutually to get Extraction solvent.
(3) preparation of collagenous fibres solution: 15 parts of abortive calfskins after above-mentioned scrub are sent into freeze drier, and drying is extremely
Water content using onal machine is ground into the particle that granularity is 2-3mm after being 10-15%, adds above-mentioned made 50 parts of Extraction solvents
In, 15min is stood after fully dispersed, is transferred in ball mill after standing, is milled to fineness less than 50 μm, is then added 0.5
Disodium hydrogen phosphate-citrate buffer solution of part pH=3, utilizes the plasma of working frequency 40Hz, power 600W after being sufficiently mixed
Surface treating machine handles 15s to gained mixture, and after treatment is transferred in 0~5 DEG C of environment and stands 5h, is then added 1 part and gathers
Acrylic acid and 0.5 part of polyethylene glycol oxide, and it is heated to reflux state insulated and stirred 30min, finally cross 270 meshes, gained filtrate
As collagenous fibres solution.
(4) 3 parts of microcrystalline celluloses the preparation of modified collagen fiber solution: are added into above-mentioned made 25 parts of collagenous fibres solution
Element, 1 part of Macrogol 6000 and 0.5 part of L-Aspartic acid are sufficiently mixed in 35~40 DEG C of sealing and standing 2h after being uniformly dispersed,
Then the microwave treatment 3min under microwave frequency 2450MHz, power 700W, is sufficiently mixed again, and utilization working frequency 40Hz,
The Surface Treatment with Plasma machine of power 600W handles 15s, and gained mixture is cold with the speed of 10~15 DEG C/min under ice-water bath
But cool down, the insulated and stirred 15min after temperature is down to 0~5 DEG C.
(5) 2 parts of polyglycolic acids, 2 parts the preparation of hemostasis gel: are added into above-mentioned made 25 parts of modified collagen fiber solutions
Polycarbophil, 0.5 part of vitamin K and 0.5 part of aminocaproic acid are distributed into mold after being sufficiently mixed uniformly, and utilize gamma-rays
Sterilization, after being finally packaged under the conditions of 0~5 DEG C cryo-conservation.
The modification of polyacrylic acid: 15 parts of polyacrylic acid and 1 part of tyrosine are added in double weight part ethyl alcohol, are uniformly dispersed
After be heated to reflux state insulated and stirred 10min, add 5 parts of resveratrols and 0.5 part of disodium ethylene diamine tetraacetate, continue at
Insulated and stirred 30min under reflux state, gained mixture are transferred in 0-5 DEG C of environment immediately after naturally cooling to 35-40 DEG C and stand
8h is then fed into spray dryer, and obtained solid is ground after drying is made powder.
Embodiment 2
(1) abortive calfskin pre-processes: purifying abortive calfskin as raw material can trace to the source, is wrapped up after being fully deployed with preservative film
It is good, it is placed in -5~0 DEG C of environment and freezes 8h, then with 10-15 DEG C of temperature, the sodium bicarbonate and sodium tripolyphosphate of mass fraction 5%
(sodium bicarbonate, sodium tripolyphosphate dosage mass ratio be 3:1) mixed aqueous solution impregnate 15min, then under deionized water shower
With sponge brush brushing surface 2 times.
(2) preparation of collagenous fibres Extraction solvent: according to the ratio of molar ratio 1.2:1 by Cyclopropyl Bromide and 2-Pyrrolidone
It is sufficiently mixed, prior to being ultrasonically treated 30min under supersonic frequency 40kHz, power 50W, then at microwave frequency 2450MHz, power
Microwave treatment 5min under 700W, is then heated to reflux state insulated and stirred 60min, and solution to be mixed naturally cools to 50-55
5-10 DEG C of deionized water of the weight such as addition after DEG C, is sufficiently stirred rear stratification, water intaking is mutually to get Extraction solvent.
(3) preparation of collagenous fibres solution: 15 parts of abortive calfskins after above-mentioned scrub are sent into freeze drier, and drying is extremely
Water content using onal machine is ground into the particle that granularity is 2-3mm after being 10-15%, adds above-mentioned made 45 parts of Extraction solvents
In, 15min is stood after fully dispersed, is transferred in ball mill after standing, is milled to fineness less than 50 μm, is then added 0.5
Disodium hydrogen phosphate-citrate buffer solution of part pH=3, utilizes the plasma of working frequency 40Hz, power 600W after being sufficiently mixed
Surface treating machine handles 15s to gained mixture, and after treatment is transferred in 0~5 DEG C of environment and stands 5h, is then added 0.5 part
Polyacrylic acid and 0.5 part of polyethylene glycol oxide, and it is heated to reflux state insulated and stirred 30min, finally cross 270 meshes, gained filter
Liquid is collagenous fibres solution.
(4) 3 parts of microcrystalline celluloses the preparation of modified collagen fiber solution: are added into above-mentioned made 30 parts of collagenous fibres solution
Element, 1.5 parts of Macrogol 6000s and 0.5 part of L-Aspartic acid, it is sufficiently mixed in 35~40 DEG C of sealing and standing 2h after being uniformly dispersed
It closes, then the microwave treatment 3min under microwave frequency 2450MHz, power 700W, is sufficiently mixed again, and utilizes working frequency
The Surface Treatment with Plasma machine processing 15s of 40Hz, power 600W, gained mixture is under ice-water bath with the speed of 10~15 DEG C/min
Degree cools, the insulated and stirred 15min after temperature is down to 0~5 DEG C.
(5) 2 parts of polyglycolic acids, 1 part the preparation of hemostasis gel: are added into above-mentioned made 25 parts of modified collagen fiber solutions
Polycarbophil, 0.5 part of vitamin K and 0.5 part of aminocaproic acid are distributed into mold after being sufficiently mixed uniformly, and utilize gamma-rays
Sterilization, after being finally packaged under the conditions of 0~5 DEG C cryo-conservation.
The modification of polyacrylic acid: 15 parts of polyacrylic acid and 2 parts of tyrosine are added in double weight part ethyl alcohol, are uniformly dispersed
After be heated to reflux state insulated and stirred 10min, add 5 parts of resveratrols and 0.5 part of disodium ethylene diamine tetraacetate, continue at
Insulated and stirred 30min under reflux state, gained mixture are transferred in 0-5 DEG C of environment immediately after naturally cooling to 35-40 DEG C and stand
8h is then fed into spray dryer, and obtained solid is ground after drying is made powder.
Performance measurement is carried out to hemostasis gel prepared by Examples 1 and 2, as a result as follows:
Appearance: gel, surface is smooth, the impurity being visible by naked eyes；
Moisture content :≤80% (wt)；
Gel strength: 100~500g/cm2；
Content of beary metal :≤10 μ g/g (m/m)；
Liposome :≤1% (m/m)；
Ash content :≤2% (m/m)；
PH value: >=4.0；
Biological degradability: it all degrades in internal January；
Antibacterial/bacteriostasis property: equal to the bacteriostasis rate of Escherichia coli, gold goal bacterium, Candida albicans and Pseudomonas aeruginosa >=50%；
Hemolysis rate :≤5%；
Cytotoxicity: cell-cytotoxic reaction is not more than 1 grade；
Sterility test: sterile；
Sensitization test (STT): without delayed type hypersensitivity, DTH；
Intradermal reaction test: primary stimulus index PII < 0.4；
Exogenous DNA content: Residual exogenous DNA amount answers≤10ng/ml (m/v)
Heat source: without heat source；
Acute systemic toxicity: without Acute systemic toxicity；
Genetoxic: hereditary-less toxicity；
Gel time :≤30s；
Bleeding stopping period :≤1min.
The above shows and describes the basic principles and main features of the present invention and the advantages of the present invention.The technology of the industry
Personnel are it should be appreciated that the present invention is not limited to the above embodiments, and the above embodiments and description only describe this
The principle of invention, without departing from the spirit and scope of the present invention, various changes and improvements may be made to the invention, these changes
Change and improvement all fall within the protetion scope of the claimed invention.The claimed scope of the invention by appended claims and its
Equivalent thereof.
Claims (1)
1. utilizing the hemostasis gel of microcrystalline cellulose graft modification abortive calfskin collagenous fibres preparation, which is characterized in that including as follows
Step:
(1) abortive calfskin pre-processes: abortive calfskin is purified as raw material can trace to the source, and is wrapped after being fully deployed with preservative film, and
It is placed in 5~8h of freezing in -5~0 DEG C of environment, then mixed with 10-15 DEG C of temperature, the sodium bicarbonate of mass fraction 5% and sodium tripolyphosphate
10~15min of aqueous solution soaking is closed, is then used sponge brush brushing surface 2~3 times under deionized water shower；
(2) preparation of collagenous fibres Extraction solvent: according to the ratio of 1.2~1.5:1 of molar ratio by Cyclopropyl Bromide and 2- pyrrolidines
Ketone is sufficiently mixed, prior under supersonic frequency 40kHz, power 50W be ultrasonically treated 15~30min, then at microwave frequency 2450MHz,
3~5min of microwave treatment under power 700W, is then heated to 30~60min of reflux state insulated and stirred, and solution to be mixed is natural
5-10 DEG C of deionized water of the weight such as addition after being cooled to 50-55 DEG C, is sufficiently stirred rear stratification, water intaking is mutually to get extraction
Solvent；
(3) preparation of collagenous fibres solution: the abortive calfskin after above-mentioned scrub is sent into freeze drier, and drying to water content is
It is ground into the particle that granularity is 2-3mm using onal machine after 10-15%, is added in above-mentioned made Extraction solvent, it is fully dispersed
10~15min is stood afterwards, is transferred in ball mill after standing, is milled to fineness less than 50 μm, the phosphoric acid of pH=3 is then added
Disodium hydrogen-citrate buffer solution utilizes the Surface Treatment with Plasma machine of working frequency 40Hz, power 600W to institute after being sufficiently mixed
Mixture 10~15s of processing is obtained, after treatment is transferred to 3~5h of standing in 0~5 DEG C of environment, and polyacrylic acid is then added and gathers
Ethylene oxide, and it is heated to reflux state 15~30min of insulated and stirred, 270 meshes are finally crossed, gained filtrate is collagenous fibres
Solution；
(4) microcrystalline cellulose, polyethylene glycol the preparation of modified collagen fiber solution: are added into above-mentioned made collagenous fibres solution
6000 and L-Aspartic acid be sufficiently mixed, in 35~40 DEG C of 1~2h of sealing and standing after being uniformly dispersed then in microwave frequency
2~3min of microwave treatment under 2450MHz, power 700W, is sufficiently mixed again, and utilization working frequency 40Hz, power 600W
Surface Treatment with Plasma machine handles 10~15s, and gained mixture is cooled under ice-water bath with the speed of 10~15 DEG C/min,
10~15min of insulated and stirred is after temperature is down to 0~5 DEG C to get modified collagen fiber solution；
(5) polyglycolic acid, Polycarbophil, dimension life the preparation of hemostasis gel: are added into above-mentioned made modified collagen fiber solution
Plain K and aminocaproic acid are distributed into mold after being sufficiently mixed uniformly, and utilize gamma-rays sterilization, in 0 after being finally packaged
Cryo-conservation under the conditions of~5 DEG C；
The dosage mass ratio of sodium bicarbonate and sodium tripolyphosphate is 2~3:1 in the step (1)；
Abortive calfskin, Extraction solvent, disodium hydrogen phosphate-citrate buffer solution, polyacrylic acid and polyethylene glycol oxide in the step (3)
10~15:40 of dosage mass ratio~50:0.5~1:0.5~1:0.5~1；
Polyacrylic acid passes through chemical modification, method of modifying are as follows: add polyacrylic acid and tyrosine using preceding in the step (3)
Enter in double weight part ethyl alcohol, reflux state insulated and stirred 10min is heated to after being uniformly dispersed, adds resveratrol and second two
Amine tetraacethyl disodium, continues at insulated and stirred 30min under reflux state, gained mixture naturally cool to 35-40 DEG C after immediately
It is transferred in 0-5 DEG C of environment and stands 8h, be then fed into spray dryer, obtained solid is ground after drying is made powder；It is described
Polyacrylic acid, tyrosine, resveratrol and disodium ethylene diamine tetraacetate dosage mass ratio be 10~15:1~2:3~6:0.5
~1；
The dosage mass ratio of collagenous fibres solution, microcrystalline cellulose, Macrogol 6000 and L-Aspartic acid in the step (4)
25~30:3~6:1~2:0.5~1；
The dosage matter of modified collagen fiber solution, polyglycolic acid, Polycarbophil, vitamin K and aminocaproic acid in the step (5)
Measure ratio 25~30:2~3:1~2:0.5~1:0.5~1.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1140235A1 (en) * | 1998-12-23 | 2001-10-10 | Aventis Behring GmbH | Fibrin-based glue granulate and corresponding production method |
| CN1502375A (en) * | 2002-11-26 | 2004-06-09 | hemostatic wound dressing containing aldehyde-modified polysaccharide and hemostatic agents | |
| EP2809365A1 (en) * | 2012-02-01 | 2014-12-10 | Haemostatix Limited | Haemostatic wound dressing |
| CN104661708A (en) * | 2012-09-19 | 2015-05-27 | 尤法玛私人有限公司 | Viscous haemostatic compostions and method of treatment |
-
2016
- 2016-09-20 CN CN201610834678.9A patent/CN106344960B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1140235A1 (en) * | 1998-12-23 | 2001-10-10 | Aventis Behring GmbH | Fibrin-based glue granulate and corresponding production method |
| CN1502375A (en) * | 2002-11-26 | 2004-06-09 | hemostatic wound dressing containing aldehyde-modified polysaccharide and hemostatic agents | |
| EP2809365A1 (en) * | 2012-02-01 | 2014-12-10 | Haemostatix Limited | Haemostatic wound dressing |
| CN104661708A (en) * | 2012-09-19 | 2015-05-27 | 尤法玛私人有限公司 | Viscous haemostatic compostions and method of treatment |
Non-Patent Citations (1)
| Title |
|---|
| 胶原蛋白肽接枝羧甲基纤维素及其衍生物制备及性能研究;彭敏;《中国优秀硕士学位论文全文库》;20150430;B016-348 |
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