CN109498831A - A kind of negatively charged injectable type gelatine microsphere base gel hemostatic material and its preparation method and application - Google Patents
A kind of negatively charged injectable type gelatine microsphere base gel hemostatic material and its preparation method and application Download PDFInfo
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- CN109498831A CN109498831A CN201811291055.7A CN201811291055A CN109498831A CN 109498831 A CN109498831 A CN 109498831A CN 201811291055 A CN201811291055 A CN 201811291055A CN 109498831 A CN109498831 A CN 109498831A
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- gelatin
- gelatine microsphere
- hemostatic material
- oil
- base gel
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- 229920000159 gelatin Polymers 0.000 title claims abstract description 135
- 235000019322 gelatine Nutrition 0.000 title claims abstract description 135
- 239000004005 microsphere Substances 0.000 title claims abstract description 68
- 230000002439 hemostatic effect Effects 0.000 title claims abstract description 65
- 239000000463 material Substances 0.000 title claims abstract description 52
- 239000001828 Gelatine Substances 0.000 title claims description 64
- 238000002360 preparation method Methods 0.000 title claims description 16
- 108010010803 Gelatin Proteins 0.000 claims abstract description 71
- 239000008273 gelatin Substances 0.000 claims abstract description 71
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 71
- 239000000499 gel Substances 0.000 claims abstract description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 230000036571 hydration Effects 0.000 claims abstract 2
- 238000006703 hydration reaction Methods 0.000 claims abstract 2
- 208000032843 Hemorrhage Diseases 0.000 claims description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 239000006210 lotion Substances 0.000 claims description 12
- 238000010907 mechanical stirring Methods 0.000 claims description 12
- 239000002504 physiological saline solution Substances 0.000 claims description 11
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 10
- 238000004132 cross linking Methods 0.000 claims description 10
- 239000003995 emulsifying agent Substances 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 235000019441 ethanol Nutrition 0.000 claims description 8
- 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 claims description 7
- 230000000887 hydrating effect Effects 0.000 claims description 7
- 239000003921 oil Substances 0.000 claims description 7
- 235000019198 oils Nutrition 0.000 claims description 7
- 239000008367 deionised water Substances 0.000 claims description 6
- 229910021641 deionized water Inorganic materials 0.000 claims description 6
- 239000005457 ice water Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 4
- 239000012459 cleaning agent Substances 0.000 claims description 4
- 239000012024 dehydrating agents Substances 0.000 claims description 4
- 125000005909 ethyl alcohol group Chemical group 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 239000010773 plant oil Substances 0.000 claims description 4
- 239000012890 simulated body fluid Substances 0.000 claims description 4
- 239000003760 tallow Substances 0.000 claims description 4
- 235000019483 Peanut oil Nutrition 0.000 claims description 2
- 235000019484 Rapeseed oil Nutrition 0.000 claims description 2
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 claims description 2
- 235000014121 butter Nutrition 0.000 claims description 2
- 239000004359 castor oil Substances 0.000 claims description 2
- 235000019438 castor oil Nutrition 0.000 claims description 2
- 230000008859 change Effects 0.000 claims description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 2
- 239000004006 olive oil Substances 0.000 claims description 2
- 235000008390 olive oil Nutrition 0.000 claims description 2
- 239000000312 peanut oil Substances 0.000 claims description 2
- 239000008363 phosphate buffer Substances 0.000 claims description 2
- 230000001376 precipitating effect Effects 0.000 claims description 2
- 239000003549 soybean oil Substances 0.000 claims description 2
- 235000012424 soybean oil Nutrition 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 abstract description 32
- 239000008280 blood Substances 0.000 abstract description 32
- 230000023597 hemostasis Effects 0.000 abstract description 26
- 208000027418 Wounds and injury Diseases 0.000 abstract description 22
- 206010052428 Wound Diseases 0.000 abstract description 19
- 208000014674 injury Diseases 0.000 abstract description 5
- 230000006378 damage Effects 0.000 abstract description 4
- 210000004204 blood vessel Anatomy 0.000 abstract description 3
- 230000017531 blood circulation Effects 0.000 abstract description 2
- 208000034158 bleeding Diseases 0.000 description 24
- 230000000740 bleeding effect Effects 0.000 description 21
- 239000000047 product Substances 0.000 description 19
- 239000012530 fluid Substances 0.000 description 17
- 210000004185 liver Anatomy 0.000 description 14
- 230000000025 haemostatic effect Effects 0.000 description 13
- 206010053567 Coagulopathies Diseases 0.000 description 12
- 230000035602 clotting Effects 0.000 description 12
- 108010063195 Surgiflo Proteins 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 238000011587 new zealand white rabbit Methods 0.000 description 8
- 239000002994 raw material Substances 0.000 description 8
- 229910021536 Zeolite Inorganic materials 0.000 description 6
- 229940030225 antihemorrhagics Drugs 0.000 description 6
- 210000001772 blood platelet Anatomy 0.000 description 6
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000010457 zeolite Substances 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 230000023555 blood coagulation Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000004945 emulsification Methods 0.000 description 5
- 239000005995 Aluminium silicate Substances 0.000 description 4
- 229920001661 Chitosan Polymers 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 241000256856 Vespidae Species 0.000 description 4
- 230000003187 abdominal effect Effects 0.000 description 4
- 235000012211 aluminium silicate Nutrition 0.000 description 4
- 230000003444 anaesthetic effect Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000010253 intravenous injection Methods 0.000 description 4
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 4
- 239000006101 laboratory sample Substances 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 210000000115 thoracic cavity Anatomy 0.000 description 4
- 239000002569 water oil cream Substances 0.000 description 4
- 238000000733 zeta-potential measurement Methods 0.000 description 4
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 3
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 3
- 108010080379 Fibrin Tissue Adhesive Proteins 0.000 description 3
- 235000010443 alginic acid Nutrition 0.000 description 3
- 229920000615 alginic acid Polymers 0.000 description 3
- 239000003114 blood coagulation factor Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000035479 physiological effects, processes and functions Effects 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 108010073385 Fibrin Proteins 0.000 description 2
- 102000009123 Fibrin Human genes 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000005611 electricity Effects 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
- 102000000429 Factor XII Human genes 0.000 description 1
- 108010080865 Factor XII Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 241000165940 Houjia Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004317 Lyases Human genes 0.000 description 1
- 108090000856 Lyases Proteins 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 240000002853 Nelumbo nucifera Species 0.000 description 1
- 235000006508 Nelumbo nucifera Nutrition 0.000 description 1
- 235000006510 Nelumbo pentapetala Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical group [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 229940045110 chitosan Drugs 0.000 description 1
- 230000006448 coagulant property Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- DHRRIBDTHFBPNG-UHFFFAOYSA-L magnesium dichloride hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[Cl-].[Cl-] DHRRIBDTHFBPNG-UHFFFAOYSA-L 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000003634 thrombocyte concentrate Substances 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000010148 water-pollination 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
- A61L24/001—Use of materials characterised by their function or physical properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0031—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0042—Materials resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/10—Polypeptides; Proteins
- A61L24/104—Gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
-
- 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
- A61L2400/06—Flowable or injectable implant compositions
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Surgery (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明公开了一种带负电荷可注射型明胶微球基凝胶止血材料。该明胶微球基凝胶止血材料通过明胶微球与水发生水合作用制成明胶微球基凝胶，赋予其可注射性，通过普通注射器就能进行注射；满足在深出血点和腔内出血时达到将止血凝胶准确快速送达止血点的要求；同时基于明胶自身吸水膨胀和可被吸收降解的特性，注入的止血凝胶吸收血液膨胀压迫创口血管，实现血流量减少达到止血，且止血凝胶不必取出，从而减少对患者的二次伤害。
The invention discloses a negatively charged injectable gelatin microsphere-based gel hemostatic material. The gelatin microsphere-based gel hemostatic material is made into a gelatin microsphere-based gel through the hydration of gelatin microspheres and water, which gives it injectability and can be injected through a common syringe; At the same time, based on the characteristics of gelatin itself, which absorbs water and can be absorbed and degraded, the injected hemostatic gel absorbs blood and swells and compresses the wound blood vessels, reducing blood flow to achieve hemostasis and hemostasis. The gel does not have to be taken out, thereby reducing the secondary injury to the patient.
Description
Technical field
The invention belongs to field of biomedical materials, and in particular to a kind of for clinical operation medium and deep and intracavitary bleeding
Negatively charged injectable type gelatine microsphere base gel hemostatic material and its preparation method and application.
Background technique
In surgical procedures, quickly and effectively stop blooding to patient's bleeding position, is conducive to shorten operating time propulsion
Operation goes on smoothly raising success rate of operation, to save more life.Currently, the material that can be used for trauma hemostasis mainly wraps
Include inorganic hemostatic materials and organic hemostatic material.
Inorganic hemostatic materials mainly have zeolite and kaolin etc..Zeolite has good anthemorrhagic performance, can be significantly shorter only
Blood time and reduction amount of bleeding.Zeolite can absorb blood rapidly in hemostasis to agglomerate blood platelet and coagulation factor, reach
To the purpose of quick-acting haemostatic powder.U.S. army's equipmentBleeding-stopping dressing, main component are exactly zeolite, since its is excellent
Haemostatic effect,Bleeding-stopping dressing has saved the life of many wounded in the war in Iraq and Afghanistan.But
Zeolite can discharge a large amount of heat in hemostasis, this is possible to burn tissue, so as to cause inflammation.Kaolin has and zeolite
Similar hemostatic function.2008, kaolin hemostatic gauze was selected in U.S. army " ten big top army materials ", became rare
First choice of fighting hemostasia products.But kaolin does not have biodegradability, needs to move back in hemostasis and remove, this is possible to impaired
Taeniae telarum comes secondary injury and secondary bleeding.
Organic hemostatic material mainly has chitosan, alginate, Fibrin Glue and gelatin etc..Chitosan is in hemostasis
In can assemble blood platelet and red blood cell, while chitosan can also inhibit the activity of body inner fibrin lyase so that
The thrombus of formation is more secured.The chitosan class bleeding-stopping dressing being approved by the FDA in the United States at present has Clo-SurWithChitosan bandage.But it has been reported that due to both bleeding-stopping dressing slabbings, so being used for intracavitary and deep
Effect is unobvious when wound hemostasis.Alginates hemostatic material (such as:Comfeel) have
Stronger water absorbing capacity, in hemostasis can rapid aggregation blood platelet and coagulation factor, while by the sodium ion exchange in body fluid
Calcium ion out can participate in rapidly blood coagulation.But single alginates hemostatic material adhesiveness is poor, and when use needs other
Dressing fix.Fibrin Glue class hemostatic material such as Fibrin Glue foam, is a kind of spray, to surface injury hemostasis have compared with
Good effect, but there is correlative study to show to imitate intracavitary hemostasis due to its poor dispersed and weaker adhesive capacity
Fruit is unsatisfactory.Gelatin class hemostatic material has very strong hydrophily, itself expansion compressing damaged blood vessels reaches hemostasis after water suction
Purpose, while gelatin can also assemble haemocyanin and blood platelet and activate intra platelet free calcium coagulation factor, application at present and face
Most of product on bed be absorbable gelatin sponge (such as:With), this kind of hemostatic material is suitable for hand
Open wound hemostasis and postoperative closing seepage-proof liquid in art, can not be applied to the hemostasis of intracavitary and deep wound.
Due to current hemostatic material or biocompatibility and biological degradability difference or it is applied to intracavitary and deep wound
Mouth haemostatic effect is undesirable.Therefore it is good to need to develop a kind of biocompatibility, there is biodegradability, and for clinical hand
Art medium and deep and the hemostatic material of intracavitary bleeding.
Summary of the invention
The purpose of the present invention is prepare it is a kind of possess excellent anthemorrhagic performance be suitable for the negatively charged of deep and intracavitary bleeding
Lotus injectable type gelatine microsphere base gel hemostatic material, while the gelatine microsphere base gel hemostatic material has good biofacies
Capacitive and biological absorbable degradation property, can stay in the body after hemostasis need not take out.
The present invention is a kind of solidifying for clinical operation medium and deep and the negatively charged injectable type gelatine microsphere base of intracavitary bleeding
Glue hemostatic material:
It is to obtain gelatine microsphere and hydrating agents by the way that aquation occurs after physical mixed；
Wherein, the hydrating agents are deionized water, phosphate buffer, simulated body fluid, one of physiological saline or more
The mixture of kind composition；The gelatine microsphere partial size is 1~500 μm.
The essence of aquation is that hydrone integrally enters mineral lattice, thus the effect for increasing mineral volume.And
After aquation refers to that hydrone enters gelatine microsphere inside in the present invention, make the effect of gelatine microsphere volume increase.
Phosphate-buffered is commonly used for a buffer solution of biological study, and osmotic pressure and ion concentration are usually and people
Body pH is close, and preparation method is as follows: 8g NaCl, 0.2g KCl, 1.44g disodium hydrogen phosphate and 0.24g are dissolved in 1L deionized water
Potassium dihydrogen phosphate adjusts solution ph to 7.4 with HCl.
Simulated body fluid is the component of simulated body fluid and a kind of solution of pH value.Preparation method is as follows: 1L deionized water
In dissolve 8.035g NaCl, 0.355g NaHCO in order3, 0.225g KCl, 0.231g K2HPO4.3H2O, 0.311g
MgCl2.6H2O, 39mL 1.0M HCl, 0.292g CaCl2, 0.072g Na2SO4, 6.118g Tris, 0~5mL 1.0M HCl
Adjust pH to 7.4.
Further, the proportion of the gelatine microsphere and hydrating agents is 1:2~1:3 (g/mL).
Further, the gelatine microsphere base gel hemostatic material preparation method the following steps are included:
(1) it is mutually mixed oily with the emulsifier of 0.01~0.1 times of oil phase volume, is heated to 40~60 DEG C, mechanical stirring is equal
The concentration that 0.01~0.02 times of oil phase volume is slowly added to after even is the gelatin solution of 5wt%~40wt%, then is stirred by machinery
Mix emulsification, mechanical stirring 300~5000rpm of speed, 15~120min of mechanical stirring time；
(2) whole system after stirring is put into progress 10~60min of ice bath in ice water, 0.05~0.5 times is added later
1~5% glutaraldehyde solution of gelatin solution volume is crosslinked 0.5~5h, and dehydrating agent is added after crosslinking and makes in lotion
Gelatine microsphere precipitating；
(3) lotion is filtered, then cleans gelatine microsphere for several times with cleaning agent, except phase and unreacted penta 2 of deoiling
Aldehyde is dried at room temperature, obtains gelatine microsphere.
Further, in the step (1), oil be mutually plant oil, animal tallow oil and one of atoleine or
The miscella of a variety of compositions；Wherein, plant oil is rapeseed oil, peanut oil, soybean oil, olive oil, one of castor oil or
It is a variety of；Animal tallow oil is lard and/or butter；
In the step (1), the hydrophilic lipophilic balance of the emulsifier is 3~6；Wherein hydrophilic lipophilic balance is 3
~6 emulsifier is Span-80 and/or Span -60；
In the step (1), gelatin solution is type A gelatin, the mixing gelatin of type B gelatin or two kinds of gelatin composition 40~
It is dissolved in deionized water and obtaining at 60 DEG C；
In the step (2), dehydrating agent is ethyl alcohol, acetone, isopropanol, one of n,N-Dimethylformamide or a variety of
The mixture of composition；
In the step (3), cleaning agent is ethyl alcohol, acetone, isopropanol, one of n,N-Dimethylformamide or a variety of
The mixture of composition.
The present invention provides a kind of method for preparing aforementioned gelatine microsphere base gel hemostatic material, it the following steps are included:
By gelatine microsphere and hydrating agents physical mixed occur aquation to get.
Application the present invention also provides gelatine microsphere base gel above-mentioned as hemostatic material.
Further, the hemostatic material can be injected with ordinary syringe.
Further, the hemostatic material is the hemostatic material of clinical operation medium and deep and intracavitary bleeding.
The present invention has following prominent characteristics:
1) gelatin is prepared into microballoon, increases specific surface area, increase the contact area of material and blood；Increase material simultaneously
Water absorbing capacity, enable in hemostasis material to absorb the water in blood rapidly, assemble blood platelet concentrate blood formation
Rationality blocks matrix, realizes quick-acting haemostatic powder.
2) by the method modified gelatin of chemical crosslinking, the thermal stability of gelatin is improved, is made it for body temperature ring
Border；Keep gelatine microsphere surface negatively charged by modification simultaneously, surface negative charge can activate Hageman factor, generate fibrin ferment
And intrinsic coagulation access is activated, achieve the purpose that rapidly and effectively to stop blooding.
3) aquation is occurred by gelatine microsphere and water and gelatine microsphere base gel is made, assigned its syringeability, pass through
Ordinary syringe just can be carried out injection；Satisfaction reaches at deep blutpunkte and intracavitary bleeding stops the accurate rapid delivery of hemostasis gel
The requirement of blood point；Simultaneously based on gelatin itself water swelling and the characteristic that can be absorbed degradation, the hemostasis gel of injection absorbs blood
Liquid expansion compressing wound blood vessel, realizes that blood flow reduction reaches hemostasis, and hemostasis gel need not take out, to reduce to patient's
Secondary injury.
Obviously, above content according to the present invention is not being departed from according to the ordinary technical knowledge and customary means of this field
Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification, replacement or change of other diversified forms can also be made.
The specific embodiment of form by the following examples remakes further specifically above content of the invention
It is bright.But the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to example below.It is all to be based on above content of the present invention
The technology realized all belongs to the scope of the present invention.
Detailed description of the invention
Fig. 1 is the scanning electron microscope (SEM) photograph of gelatine microsphere obtained by embodiment 1, and the amplification factor in figure is 200 times.
Fig. 2 is the outside drawing of gelatine microsphere base gel made from embodiment 1.
Fig. 3 is type B gelatin microballoon base gel obtained by embodiment 2 for rabbit liver wound hemostasis Experimental Optical figure.
Specific embodiment
The preparation of the hemostatic material of the present invention of embodiment 1
1, preparation method
Gelatine microsphere is prepared using water oil emulsion process.By 300mL atoleine and 9ml emulsifier Span-80 (Span-80)
It is added in round bottom three-necked bottle and is heated to 45 DEG C, the type B gelatin solution (10wt%) of 10mL is slowly added to after mechanical stirring is uniform,
Emulsion is obtained after 1000rpm mechanical stirring 15min.Whole system is then put into progress ice bath 15min, Zhi Houjia in ice water
The glutaraldehyde cross-linking 2h for entering the 2.5% of 3mL is added ethanol in proper amount and is dehydrated and keeps the gelatine microsphere in lotion heavy after crosslinking
It forms sediment.Lotion is filtered, then alternately clean for several times, to remove atoleine and unreacted penta with acetone and isopropanol
Dialdehyde is dried at room temperature, obtains type B gelatin microballoon.Type B gelatin microballoon mixes that (gelatin is micro- with a certain amount of physiological saline
Ball: physiological saline=1:2.5 (g/mL)) aquation occurs, form type B gelatin microballoon base gel.
2, the characterization result of hemostatic material
The gelatine microsphere that the present invention is obtained carries out granularmetric analysis, counts number 300.Average grain diameter is 14.97 μm.
The gelatine microsphere that the present invention is obtained carries out Zeta potential analysis, and control group is absorbable hemostatic fluid gelatin
SURGIFLOTMProduct, blank control group are type B gelatin raw material.The gelatine microsphere Zeta potential that the present invention obtains is -24.8mV,
Control group Zeta potential is 6.1mV, and blank control group Zeta potential is -0.1mV.Illustrate the gelatine microsphere surface that the present invention obtains
It is negatively charged, absorbable hemostatic fluid gelatin SURGIFLOTMProduct is positively charged, and type B gelatin raw material is negatively charged, but its electricity is negative
Property the microballoon that is prepared into lower than its.
3, the haemostatic effect of hemostatic material
The type B gelatin microballoon base gel (experimental group) that the present invention is obtained is used for the measurement in external clotting time, tests institute
It is fresh new zealand white rabbit arteria auricularis blood with blood, control group is the absorbable hemostatic fluid gelatin SURGIFLO of equivalentTMIt produces
Product, blank control group are the physiological saline of equivalent.Method: being respectively charged into general blood collection tube for 0.2g laboratory sample, then respectively
The fresh new zealand white rabbit arteria auricularis blood of 1mL is added, shakes up rear timing rapidly, blood clotting situation is checked every 15s, to blood
Liquid records its clotting time after solidifying completely.Experimental result: experimental group, control group, the external clotting time point of blank control group
It Wei not 57.8s, 112s, 137.6s.
The type B gelatin microballoon base gel (experimental group) that the present invention is obtained is for rabbit liver deep wound (Φ 4*5mm)
Measurement, control group are the absorbable hemostatic fluid gelatin SURGIFLO of equivalentTMProduct, blank control group is with no treatment.Side
Method: the intravenous injection of yellow Jackets anesthetic anaesthetizes it, and the disinfection of abdominal operation area preserved skin, ventrimeson row 5cm is left under thoracic cavity
Right long notch, exposure liver, makees the cylindrical blutpunkte of a depth 0.5cm using orthopaedics drill bit (Φ 4) on its liver, certainly to it
After right bleeding 5s, injection experiments sample and timing record its bleeding stopping period.Wound situation after observing hemostasis simultaneously, if wound
Keeping haemostatic state is more than 3min, then it is assumed that bleeding stopping period is effective.Experimental result: experimental group, control group, blank control group are stopped
The blood time is respectively 36.4s, 51.5s, 309.8s.
The preparation of the hemostatic material of the present invention of embodiment 2
1, preparation method
Gelatine microsphere is prepared using water oil emulsion process.Round bottom is added in 300mL atoleine and 9mL emulsifier Span-80
It is heated to 45 DEG C in three-necked bottle, the type B gelatin solution (10wt%) of 10mL is slowly added to after mechanical stirring is uniform, 300rpm is mechanical
Emulsion is obtained after stirring 15min.Whole system is then put into progress ice bath 15min in ice water, is added 3mL's later
2.5% glutaraldehyde cross-linking 2h is added ethanol in proper amount and is dehydrated and precipitates the gelatine microsphere in lotion after crosslinking.To lotion
It is filtered, then alternately clean for several times, to remove atoleine and unreacted glutaraldehyde, room temperature with acetone and isopropanol
Lower drying process, obtains type B gelatin microballoon.Type B gelatin microballoon mixes (gelatine microsphere: physiology salt with a certain amount of physiological saline
Water=1:2.5 (g/mL)) aquation occurs, form type B gelatin microballoon base gel.
2, the characterization result of hemostatic material
The gelatine microsphere that the present invention is obtained carries out granularmetric analysis, counts number 300.Average grain diameter is 80.19 μm.
The gelatine microsphere that the present invention is obtained carries out Zeta potential analysis, and control group is absorbable hemostatic fluid gelatin
SURGIFLOTMProduct, blank control group are type B gelatin raw material.The gelatine microsphere Zeta potential that the present invention obtains is -17.5mV,
Control group Zeta potential is 6.1mV, and blank control group Zeta potential is -0.1mV.Illustrate the gelatine microsphere surface that the present invention obtains
It is negatively charged, absorbable hemostatic fluid gelatin SURGIFLOTMProduct is positively charged, and type B gelatin raw material is negatively charged, but its electricity is negative
Property the microballoon that is prepared into lower than its.
3, the haemostatic effect of hemostatic material
The type B gelatin microballoon base gel (experimental group) that the present invention is obtained is used for the measurement in external clotting time, tests institute
It is fresh new zealand white rabbit arteria auricularis blood with blood, control group is the absorbable hemostatic fluid gelatin SURGIFLO of equivalentTMIt produces
Product, blank control group are the physiological saline of equivalent.Method: being respectively charged into general blood collection tube for 0.2g laboratory sample, then respectively
The fresh new zealand white rabbit arteria auricularis blood of 1mL is added, shakes up rear timing rapidly, blood clotting situation is checked every 15s, to blood
Liquid records its clotting time after solidifying completely.Experimental result: experimental group, control group, the external clotting time point of blank control group
It Wei not 50.8s, 112s, 137.6s.
The type B gelatin microballoon base gel (experimental group) that the present invention is obtained is for rabbit liver deep wound (Φ 4*5mm)
Measurement, control group are the absorbable hemostatic fluid gelatin SURGIFLO of equivalentTMProduct, blank control group is with no treatment.Side
Method: the intravenous injection of yellow Jackets anesthetic anaesthetizes it, and the disinfection of abdominal operation area preserved skin, ventrimeson row 5cm is left under thoracic cavity
Right long notch, exposure liver, makees the cylindrical blutpunkte of a depth 0.5cm using orthopaedics drill bit (Φ 4) on its liver, certainly to it
After right bleeding 5s, injection experiments sample and timing record its bleeding stopping period.Wound situation after observing hemostasis simultaneously, if wound
Keeping haemostatic state is more than 3min, then it is assumed that bleeding stopping period is effective.Experimental result: experimental group, control group, blank control group are stopped
The blood time is respectively 32.2s, 51.5s, 309.8s.
The preparation of the hemostatic material of the present invention of embodiment 3
1, preparation method
Gelatine microsphere is prepared using water oil emulsion process.Round bottom is added in 300mL atoleine and 9mL emulsifier Span-80
It is heated to 45 DEG C in three-necked bottle, the type A gelatin solution (10wt%) of 10mL, 1000rpm machine are slowly added to after mechanical stirring is uniform
Emulsion is obtained after tool stirring 15min.Whole system is then put into progress ice bath 15min in ice water, 3mL is added later
2.5% glutaraldehyde cross-linking 2h is added ethanol in proper amount and is dehydrated and precipitates the gelatine microsphere in lotion after crosslinking.To lotion
It is filtered, then alternately clean for several times, to remove atoleine and unreacted glutaraldehyde, room temperature with acetone and isopropanol
Lower drying process, obtains type A gelatin microballoon.Type A gelatin microballoon mixes (gelatine microsphere: physiology salt with a certain amount of physiological saline
Water=1:2.5 (g/mL)) aquation occurs, form type A gelatin microballoon base gel.
2, the characterization result of hemostatic material
The gelatine microsphere that the present invention is obtained carries out granularmetric analysis, counts number 300.Average grain diameter is 23.86 μm.
The gelatine microsphere that the present invention is obtained carries out Zeta potential analysis, and control group is absorbable hemostatic fluid gelatin
SURGIFLOTMProduct, blank control group are type A gelatin raw material.The gelatine microsphere Zeta potential that the present invention obtains is -4.2mV, right
It is 6.1mV according to group Zeta potential, blank control group Zeta potential is 5.8mV.Illustrate the gelatine microsphere surface band that the present invention obtains
Negative electrical charge, absorbable hemostatic fluid gelatin SURGIFLOTMProduct is positively charged, and type A gelatin raw material is positively charged.
3, the haemostatic effect of hemostatic material
The type A gelatin microballoon base gel (experimental group) that the present invention is obtained is used for the measurement in external clotting time, tests institute
It is fresh new zealand white rabbit arteria auricularis blood with blood, control group is the absorbable hemostatic fluid gelatin SURGIFLO of equivalentTMIt produces
Product, blank control group are the physiological saline of equivalent.Method: being respectively charged into general blood collection tube for 0.2g laboratory sample, then respectively
The fresh new zealand white rabbit arteria auricularis blood of 1mL is added, shakes up rear timing rapidly, blood clotting situation is checked every 15s, to blood
Liquid records its clotting time after solidifying completely.Experimental result: experimental group, control group, the external clotting time point of blank control group
It Wei not 111.67s, 112s, 137.6s.
The type A gelatin microballoon base gel (experimental group) that the present invention is obtained is for rabbit liver deep wound (Φ 4*5mm)
Measurement, control group are the absorbable hemostatic fluid gelatin SURGIFLO of equivalentTMProduct, blank control group is with no treatment.Side
Method: the intravenous injection of yellow Jackets anesthetic anaesthetizes it, and the disinfection of abdominal operation area preserved skin, ventrimeson row 5cm is left under thoracic cavity
Right long notch, exposure liver, makees the cylindrical blutpunkte of a depth 0.5cm using orthopaedics drill bit (Φ 4) on its liver, certainly to it
After right bleeding 5s, injection experiments sample and timing record its bleeding stopping period.Wound situation after observing hemostasis simultaneously, if wound
Keeping haemostatic state is more than 3min, then it is assumed that bleeding stopping period is effective.Experimental result: experimental group, control group, blank control group are stopped
The blood time is respectively 42.92s, 51.5s, 309.8s.
The preparation of the hemostatic material of the present invention of embodiment 4
1, preparation method
Gelatine microsphere is prepared using water oil emulsion process.Round bottom is added in 300mL atoleine and 9mL emulsifier Span-80
It is heated to 45 DEG C in three-necked bottle, the type A gelatin solution (10wt%) of 10mL is slowly added to after mechanical stirring is uniform, 300rpm is mechanical
Emulsion is obtained after stirring 15min.Whole system is then put into progress ice bath 15min in ice water, is added 3mL's later
2.5% glutaraldehyde cross-linking 2h is added ethanol in proper amount and is dehydrated and precipitates the gelatine microsphere in lotion after crosslinking.To lotion
It is filtered, then alternately clean for several times, to remove atoleine and unreacted glutaraldehyde, room temperature with acetone and isopropanol
Lower drying process, obtains type A gelatin microballoon.Type A gelatin microballoon mixes (gelatine microsphere: physiology salt with a certain amount of physiological saline
Water=1:2.5 (g/mL)) aquation occurs, form type A gelatin microballoon base gel.
2, the characterization result of hemostatic material
The gelatine microsphere that the present invention is obtained carries out granularmetric analysis, counts number 300.Average grain diameter is 105.03 μm.
The gelatine microsphere that the present invention is obtained carries out Zeta potential analysis, and control group is absorbable hemostatic fluid gelatin
SURGIFLOTMProduct, blank control group are type A gelatin raw material.The gelatine microsphere Zeta potential that the present invention obtains is -0.5mV, right
It is 6.1mV according to group Zeta potential, blank control group Zeta potential is 5.8mV.Illustrate the gelatine microsphere surface band that the present invention obtains
Negative electrical charge, absorbable hemostatic fluid gelatin SURGIFLOTMProduct is positively charged, and type A gelatin raw material is positively charged.
3, the haemostatic effect of hemostatic material
The type A gelatin microballoon base gel (experimental group) that the present invention is obtained is used for the measurement in external clotting time, tests institute
It is fresh new zealand white rabbit arteria auricularis blood with blood, control group is the absorbable hemostatic fluid gelatin SURGIFLO of equivalentTMIt produces
Product, blank control group are the physiological saline of equivalent.Method: being respectively charged into general blood collection tube for 0.2g laboratory sample, then respectively
The fresh new zealand white rabbit arteria auricularis blood of 1mL is added, shakes up rear timing rapidly, blood clotting situation is checked every 15s, to blood
Liquid records its clotting time after solidifying completely.Experimental result: experimental group, control group, the external clotting time point of blank control group
It Wei not 107s, 112s, 137.6s.
The type A gelatin microballoon base gel (experimental group) that the present invention is obtained is for rabbit liver deep wound (Φ 4*5mm)
Measurement, control group are the absorbable hemostatic fluid gelatin SURGIFLO of equivalentTMProduct, blank control group is with no treatment.Side
Method: the intravenous injection of yellow Jackets anesthetic anaesthetizes it, and the disinfection of abdominal operation area preserved skin, ventrimeson row 5cm is left under thoracic cavity
Right long notch, exposure liver, makees the cylindrical blutpunkte of a depth 0.5cm using orthopaedics drill bit (Φ 4) on its liver, certainly to it
After right bleeding 5s, injection experiments sample and timing record its bleeding stopping period.Wound situation after observing hemostasis simultaneously, if wound
Keeping haemostatic state is more than 3min, then it is assumed that bleeding stopping period is effective.Experimental result: experimental group, control group, blank control group are stopped
The blood time is respectively 51.1s, 51.5s, 309.8s.
To sum up, the external coagulant property of the gelatine microsphere base gel prepared by the present invention and liver anthemorrhagic performance are better than to inhale
Receive hemostasis fluid gelatin SURGIFLOTMProduct has good haemostatic effect.
Claims (8)
1. a kind of negatively charged injectable type gelatine microsphere base gel hemostatic material, it is characterised in that: it be by gelatine microsphere with
After hydrating agents mixing；The hydrating agents are deionized water, phosphate buffer, simulated body fluid, one of physiological saline
Or the mixture of a variety of compositions；The gelatine microsphere partial size is 1~500 μm.
2. gelatine microsphere base gel hemostatic material according to claim 1, it is characterised in that: the gelatine microsphere and hydration
The proportion of agent is 1:2~1:3 (g/mL).
3. gelatine microsphere base gel hemostatic material according to claim 1, it is characterised in that: the preparation of the gelatine microsphere
Method the following steps are included:
(1) it is mutually mixed oily with the emulsifier of 0.01~0.1 times of oil phase volume, is heated to 40~60 DEG C, after mechanical stirring is uniform
The concentration for being slowly added to 0.01~0.02 times of oil phase volume is the gelatin solution of 5wt%~40wt%, then passes through mechanical stirring cream
Change, mechanical stirring 300~5000rpm of speed, 15~120min of mechanical stirring time；
(2) whole system after stirring is put into progress 10~60min of ice bath in ice water, 0.05~0.5 times of gelatin is added later
1~5% glutaraldehyde solution of liquor capacity is crosslinked 0.5~5h, and dehydrating agent is added after crosslinking and makes the gelatin in lotion
Microballoon precipitating；
(3) lotion is filtered, then cleans gelatine microsphere for several times with cleaning agent, to remove deoil phase and unreacted glutaraldehyde,
It is dried at room temperature, obtains gelatine microsphere.
4. gelatine microsphere base gel hemostatic material according to claim 3, it is characterised in that:
In the step (1), oil is mutually the mixing of one of plant oil, animal tallow oil and atoleine or a variety of compositions
Oil；Wherein, plant oil is rapeseed oil, peanut oil, soybean oil, olive oil, one of castor oil or a variety of；Animal tallow oil
For lard and/or butter；
In the step (1), the hydrophilic lipophilic balance of the emulsifier is 3~6；Wherein hydrophilic lipophilic balance is 3~6
Emulsifier is Span-80 and/or Span -60；
In the step (1), gelatin solution is type A gelatin, and the mixing gelatin that type B gelatin or two kinds of gelatin form is at 40~60 DEG C
Under be dissolved in deionized water and obtaining；
In the step (2), dehydrating agent is ethyl alcohol, acetone, isopropanol, one of n,N-Dimethylformamide or a variety of compositions
Mixture；
In the step (3), cleaning agent is ethyl alcohol, acetone, isopropanol, one of n,N-Dimethylformamide or a variety of compositions
Mixture.
5. the preparation method of gelatine microsphere base gel hemostatic material described in Claims 1 to 4 any one, it is characterised in that:
It the following steps are included:
By gelatine microsphere and hydrating agents physical mixed occur aquation to get.
6. application of the gelatine microsphere base gel as hemostatic material described in Claims 1 to 4 any one.
7. application according to claim 6, it is characterised in that: the hemostatic material can be injected with ordinary syringe.
8. application according to claim 6 or 7, it is characterised in that: the hemostatic material is clinical operation medium and deep and chamber
The hemostatic material of internal haemorrhage.
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| CN201910381084.0A CN110124093A (en) | 2018-10-31 | 2018-10-31 | A kind of preparation method of negatively charged injectable type gelatine microsphere base gel hemostatic material |
| CN201811291055.7A CN109498831A (en) | 2018-10-31 | 2018-10-31 | A kind of negatively charged injectable type gelatine microsphere base gel hemostatic material and its preparation method and application |
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| CN201910381095.9A Division CN110201214A (en) | 2018-10-31 | 2018-10-31 | A kind of purposes of negatively charged injectable type gelatine microsphere base gel as hemostatic material |
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| CN110251727A (en) * | 2019-05-31 | 2019-09-20 | 上海欧邦医疗管理有限公司 | A kind of nutrient solution forming three-dimensional collagenous fiber network at eye tail socket of the eye bone edge |
| CN110698692A (en) * | 2019-10-28 | 2020-01-17 | 四川大学 | Preparation method and application of self-healing sodium alginate/gelatin-based hydrogel material capable of spraying to form film |
| CN112354000A (en) * | 2020-11-30 | 2021-02-12 | 中国人民解放军联勤保障部队第九〇九医院 | Gelatin compound hemostatic and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110251727A (en) * | 2019-05-31 | 2019-09-20 | 上海欧邦医疗管理有限公司 | A kind of nutrient solution forming three-dimensional collagenous fiber network at eye tail socket of the eye bone edge |
| CN110698692A (en) * | 2019-10-28 | 2020-01-17 | 四川大学 | Preparation method and application of self-healing sodium alginate/gelatin-based hydrogel material capable of spraying to form film |
| CN112354000A (en) * | 2020-11-30 | 2021-02-12 | 中国人民解放军联勤保障部队第九〇九医院 | Gelatin compound hemostatic and preparation method thereof |
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