CN112384255A - 止血材料 - Google Patents
止血材料 Download PDFInfo
- Publication number
- CN112384255A CN112384255A CN201980013232.1A CN201980013232A CN112384255A CN 112384255 A CN112384255 A CN 112384255A CN 201980013232 A CN201980013232 A CN 201980013232A CN 112384255 A CN112384255 A CN 112384255A
- Authority
- CN
- China
- Prior art keywords
- chitosan
- hemostatic
- composition
- agent
- bioadhesive
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000463 material Substances 0.000 title claims abstract description 63
- 230000002439 hemostatic effect Effects 0.000 title claims abstract description 57
- 230000017531 blood circulation Effects 0.000 claims abstract description 12
- 229940030225 antihemorrhagics Drugs 0.000 claims description 65
- 229920001661 Chitosan Polymers 0.000 claims description 62
- 239000002874 hemostatic agent Substances 0.000 claims description 47
- 239000000203 mixture Substances 0.000 claims description 45
- 239000000227 bioadhesive Substances 0.000 claims description 38
- 239000000504 antifibrinolytic agent Substances 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 21
- 239000012876 carrier material Substances 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 17
- 230000000025 haemostatic effect Effects 0.000 claims description 12
- 230000023597 hemostasis Effects 0.000 claims description 11
- 239000000499 gel Substances 0.000 claims description 10
- 229920000058 polyacrylate Polymers 0.000 claims description 8
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 7
- 108010039627 Aprotinin Proteins 0.000 claims description 6
- 229920002125 Sokalan® Polymers 0.000 claims description 6
- 229960004405 aprotinin Drugs 0.000 claims description 6
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 239000006260 foam Substances 0.000 claims description 5
- 229920001184 polypeptide Polymers 0.000 claims description 5
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 5
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 4
- RFIMISVNSAUMBU-UHFFFAOYSA-N 2-(hydroxymethyl)-2-(prop-2-enoxymethyl)propane-1,3-diol Chemical compound OCC(CO)(CO)COCC=C RFIMISVNSAUMBU-UHFFFAOYSA-N 0.000 claims description 4
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 claims description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 4
- 229910021536 Zeolite Inorganic materials 0.000 claims description 4
- 229960002684 aminocaproic acid Drugs 0.000 claims description 4
- 239000010408 film Substances 0.000 claims description 4
- KUQWZSZYIQGTHT-UHFFFAOYSA-N hexa-1,5-diene-3,4-diol Chemical compound C=CC(O)C(O)C=C KUQWZSZYIQGTHT-UHFFFAOYSA-N 0.000 claims description 4
- 229920001519 homopolymer Polymers 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 239000010457 zeolite Substances 0.000 claims description 4
- 102000008186 Collagen Human genes 0.000 claims description 3
- 108010035532 Collagen Proteins 0.000 claims description 3
- 108010010803 Gelatin Proteins 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 229920001400 block copolymer Polymers 0.000 claims description 3
- 229920001436 collagen Polymers 0.000 claims description 3
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 claims description 3
- 239000008273 gelatin Substances 0.000 claims description 3
- 229920000159 gelatin Polymers 0.000 claims description 3
- 235000019322 gelatine Nutrition 0.000 claims description 3
- 235000011852 gelatine desserts Nutrition 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 229920000642 polymer Polymers 0.000 claims description 3
- 238000003825 pressing Methods 0.000 claims description 3
- 239000000758 substrate Substances 0.000 claims description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 3
- 229960000401 tranexamic acid Drugs 0.000 claims description 3
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 2
- 239000005995 Aluminium silicate Substances 0.000 claims description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 2
- 102000008946 Fibrinogen Human genes 0.000 claims description 2
- 108010049003 Fibrinogen Proteins 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 125000005250 alkyl acrylate group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229940086737 allyl sucrose Drugs 0.000 claims description 2
- 235000012211 aluminium silicate Nutrition 0.000 claims description 2
- 229960003375 aminomethylbenzoic acid Drugs 0.000 claims description 2
- QCTBMLYLENLHLA-UHFFFAOYSA-N aminomethylbenzoic acid Chemical compound NCC1=CC=C(C(O)=O)C=C1 QCTBMLYLENLHLA-UHFFFAOYSA-N 0.000 claims description 2
- 229910001424 calcium ion Inorganic materials 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 229940012952 fibrinogen Drugs 0.000 claims description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000004627 regenerated cellulose Substances 0.000 claims description 2
- 229920000536 2-Acrylamido-2-methylpropane sulfonic acid Polymers 0.000 claims 1
- XHZPRMZZQOIPDS-UHFFFAOYSA-N 2-Methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid Chemical compound OS(=O)(=O)CC(C)(C)NC(=O)C=C XHZPRMZZQOIPDS-UHFFFAOYSA-N 0.000 claims 1
- 229920006158 high molecular weight polymer Polymers 0.000 claims 1
- KQCBYLOBOGMDSY-OMCTUWBCSA-N n-[(2r,3r,4r,5r,6r)-5-[(2s,3r,4r,5r,6r)-3-acetamido-5-[(2s,3r,4r,5s,6r)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2,4-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide;2-hydroxybutanedioic acid Chemical compound OC(=O)C(O)CC(O)=O.O[C@@H]1[C@@H](NC(=O)C)[C@H](O)O[C@H](CO)[C@@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 KQCBYLOBOGMDSY-OMCTUWBCSA-N 0.000 claims 1
- 238000007906 compression Methods 0.000 abstract description 19
- 230000006835 compression Effects 0.000 abstract description 19
- 239000012530 fluid Substances 0.000 abstract description 7
- 230000002829 reductive effect Effects 0.000 abstract description 4
- 230000003902 lesion Effects 0.000 abstract description 2
- 208000027418 Wounds and injury Diseases 0.000 description 35
- 206010052428 Wound Diseases 0.000 description 32
- 230000000740 bleeding effect Effects 0.000 description 31
- 208000032843 Hemorrhage Diseases 0.000 description 30
- 239000008280 blood Substances 0.000 description 18
- 210000004369 blood Anatomy 0.000 description 18
- 229920002101 Chitin Polymers 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 239000004094 surface-active agent Substances 0.000 description 12
- 206010053567 Coagulopathies Diseases 0.000 description 10
- 239000002245 particle Substances 0.000 description 10
- 230000020764 fibrinolysis Effects 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 208000015294 blood coagulation disease Diseases 0.000 description 7
- 210000001105 femoral artery Anatomy 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 5
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 5
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000002035 prolonged effect Effects 0.000 description 5
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 4
- 229920000297 Rayon Polymers 0.000 description 4
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- -1 zeolite compound Chemical class 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229960001631 carbomer Drugs 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000006196 deacetylation Effects 0.000 description 3
- 238000003381 deacetylation reaction Methods 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- MSWZFWKMSRAUBD-IVMDWMLBSA-N glucosamine group Chemical group OC1[C@H](N)[C@@H](O)[C@H](O)[C@H](O1)CO MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 3
- 238000013310 pig model Methods 0.000 description 3
- 239000003001 serine protease inhibitor Substances 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 108010088842 Fibrinolysin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 108060005987 Kallikrein Proteins 0.000 description 2
- 102000001399 Kallikrein Human genes 0.000 description 2
- 239000005639 Lauric acid Substances 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229940122055 Serine protease inhibitor Drugs 0.000 description 2
- 101710102218 Serine protease inhibitor Proteins 0.000 description 2
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 2
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
- 239000003114 blood coagulation factor Substances 0.000 description 2
- 230000036760 body temperature Effects 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 230000035602 clotting Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 229960002442 glucosamine Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 229940012957 plasmin Drugs 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000004576 sand Substances 0.000 description 2
- 238000004513 sizing Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229960000187 tissue plasminogen activator Drugs 0.000 description 2
- LZPMXOHEHLXPNA-UHFFFAOYSA-N 2-methyl-2-(prop-2-enoylamino)propane-1-sulfonic acid Chemical compound CC(CS(=O)(=O)O)(C)NC(C=C)=O.CC(CS(=O)(=O)O)(C)NC(C=C)=O LZPMXOHEHLXPNA-UHFFFAOYSA-N 0.000 description 1
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010060964 Arterial haemorrhage Diseases 0.000 description 1
- 206010003162 Arterial injury Diseases 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 108010071241 Factor XIIa Proteins 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 229920002201 Oxidized cellulose Polymers 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 102000010752 Plasminogen Inactivators Human genes 0.000 description 1
- 108010077971 Plasminogen Inactivators Proteins 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- GYDJEQRTZSCIOI-UHFFFAOYSA-N Tranexamic acid Chemical compound NCC1CCC(C(O)=O)CC1 GYDJEQRTZSCIOI-UHFFFAOYSA-N 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001567 anti-fibrinolytic effect Effects 0.000 description 1
- 229940082620 antifibrinolytics Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 238000001266 bandaging Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010894 electron beam technology Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000004362 fungal culture Methods 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 108091006086 inhibitor proteins Proteins 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000006623 intrinsic pathway Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229940107304 oxidized cellulose Drugs 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002797 plasminogen activator inhibitor Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 239000004632 polycaprolactone Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000002910 solid waste Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/00051—Accessories for dressings
- A61F13/00063—Accessories for dressings comprising medicaments or additives, e.g. odor control, PH control, debriding, antimicrobic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/01—Non-adhesive bandages or dressings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/765—Polymers containing oxygen
- A61K31/78—Polymers containing oxygen of acrylic acid or derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/28—Polysaccharides or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/58—Adhesives
-
- 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
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/08—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F2013/00361—Plasters
- A61F2013/00365—Plasters use
- A61F2013/00463—Plasters use haemostatic
- A61F2013/00472—Plasters use haemostatic with chemical means
-
- 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
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/21—Acids
- A61L2300/214—Amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/23—Carbohydrates
- A61L2300/232—Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Hematology (AREA)
- Materials Engineering (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Surgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Materials For Medical Uses (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明涉及止血材料,其有效地控制来自标准伤口损伤和凝血病伤口损伤二者的血流,同时保持降低的压迫时间,使对复苏流体的需求最小化,并且使用起来容易且安全。
Description
本发明涉及用于控制出血的止血材料。
存在很多其中动物(人和非人二者)可受损或受伤而造成出血的情况。在伤口较小的情况下,出血可通过机体的天然止血机制而被阻止,该机制导致血液凝结形成固体凝块,其防止出血并有助于受损血管的恢复。
传统上,对于阻止来自伤口的血流所采用的主要技术是对伤口施加持续的压力。这使得凝血因子能够聚集在伤口部位并形成凝结的血块(blood mass)以阻止血流。然而,该技术不适用于严重的伤口和具有多个出血点的伤口。因此,出血仍然是死亡的一个主要原因。
出血造成的死亡是战场上的一个特殊问题。通常来说,在这种情况下出现的伤口伴有大量出血,并且许多导致死亡。出血也是平民群体创伤后死亡的一个重要原因。
尽管有效,但这些组合物并非没有问题,如其需要持续的压力以控制出血。在2009年11月由战术作战伤员救护(Tactical Combat Casualty Care,TCCC)提供的指南指出,当使用止血绷带(特别是Combat)时,最少应施加三分钟的压迫。需要最少三分钟压迫的止血产品的另一些实例包括但不限于Gauze(Medtrade Products Ltd)和(Hemcon)。
最近,如专利US 2014/105950中所述,已经使用生物黏合剂并将其并入到上述止血敷料中以降低压迫时间,从而潜在地降低失血和总体治疗时间。
医护人员强调的该工作的另一方面为:由于凝血病,机体控制出血的能力受损。凝血病可被定义为血液凝结(形成凝块)的能力受损的病症。该病症可导致可在受损或医学操作之后发生的延长或过量的出血的倾向。使用上述止血产品对治疗所产生的影响是延长了压力所需的时间,即与未患凝血病的人相比,需要进一步延长的压迫时间。
在人患有凝血病的情况下,这可导致治疗之后出血延长,这将需要在外科手术医院治疗(战地或民用)之前的另外的医疗干预。当在炮火中进行治疗时,延迟治疗时间以在患凝血病的人中实现止血还可导致进一步危及医护人员的生命,或者可导致对其他伤亡或损伤的反应延迟。
出血损伤的另一方面是需要施用流体(fluid)和复苏流体(resuscitationfluid)。
美国外科手术研究所(Institute for Surgical Research in the USA)进行的测试报告了使用体内凝血病模型的数个现有产品或针对含有生物黏合剂的产品的延长压迫缺乏止血作用。
因此,本发明的一个目的是提供止血材料,其有效地控制来自标准伤口损伤和凝血病伤口损伤二者的血流,同时保持降低的压迫时间,使对复苏流体的需求最小化,并且使用起来容易且安全。
因此,根据本发明的第一方面,提供了包含止血剂、生物黏合剂和抗纤维蛋白溶解剂或其衍生物的止血组合物。
本发明的组合物可以是数种形式,包括但不限于:颗粒、粉末、片状物(flake)、泡沫、溶液或凝胶,这些可直接施加于伤口或涂覆、运载或递送于载体材料上。
“止血剂”在本文中意指促进止血的物质。当止血剂与血液接触时可以能够产生凝块或栓(plug)以阻止或减轻出血。
止血材料的生理目标部位可以是动物身体内或身体上的任何部位。动物可以是人或非人动物。生理目标部位可以是伤口,或者其可以是在医学操作期间(例如在外科手术期间)造成的身体的开口。在下文中,仅出于方便和举例说明的目的,生理目标部位是指伤口。
有益地,本发明的止血材料可以由仅具有基础医学训练的人施加。这是一个简单地将材料施加到生理目标部位然后施加压力的问题。
此外,止血材料易于处理和施加。通常在施加之前将其干燥保存。
利用生物过程的产品倾向于是温度依赖性的。通常来说,遭受失血的患者由于在战场上尽力而非常热,或者由于他们暴露于寒冷条件而非常冷。在这样的极端温度下目前可用的产品不太有效。有利地,本发明的材料基本上不受温度波动的影响,并因此在高于和低于正常体温的温度下均能等同地良好地工作。“正常体温”意指约37℃。
在正常条件和凝血病条件二者下,与使用止血绷带包扎之后压迫最少三分钟的TCCC指南相比,本发明的止血组合物能够在降低的治疗时间下有效地控制出血。有利地,这导致对象在被部署到医疗区域之前在较短的时间段内稳定。“治疗”意指用止血组合物包扎和填充伤口或切口所花费的时间,这包括压迫出血部位。
与TCCC指南中指出的至少三分钟相比,本发明能够在约45秒的治疗下有效地控制出血。
止血剂可以是具有止血特性的任何材料。止血剂可包含其中含有一个或更多个葡糖胺单元的聚合物。止血剂的一些实例包括但不限于:氧化再生纤维素、高岭土、明胶、钙离子、沸石、胶原、壳多糖(chitin)、壳聚糖(chitosan)或壳聚糖盐、壳聚糖衍生物、壳多糖衍生物,及其任意组合。葡糖胺无疑是壳聚糖和壳多糖结构的一部分。止血剂优选地是壳聚糖盐。
本文中使用的术语“衍生物”是指来自于壳聚糖或壳多糖接着进行一种或更多种化学反应或修饰的化合物。所述一种或更多种化学反应或修饰可包括壳聚糖或壳多糖中一个或更多个氨基或羟基质子的替代;或壳多糖的部分脱乙酰化。例如,壳多糖衍生物可包括部分脱乙酰化的壳多糖,其可以根据需要具有不同脱乙酰化的百分比。通常来说,适用于本发明的部分脱乙酰化壳多糖的脱乙酰化程度高于约50%,更通常高于约75%,并且最通常高于约85%。术语“壳聚糖或壳多糖衍生物”中还包括壳聚糖或壳多糖与其他化合物的反应产物。这样的反应产物包括但不限于羧甲基壳聚糖、羟丁基壳多糖、N-酰基壳聚糖、O-酰基壳聚糖、N-烷基壳聚糖、O-烷基壳聚糖、N-亚烷基壳聚糖、O-磺酰基壳聚糖、硫酸化壳聚糖、磷酸化壳聚糖、硝化壳聚糖、碱壳多糖(alkalichitin)、碱壳聚糖(alkalichitosan)或与壳聚糖的金属螯合物,等。
壳聚糖是来自水生有壳动物(shell fish)加工的固体废物的衍生物,并且可以从真菌培养物中提取。壳聚糖是水不溶性聚合物材料。因此,首先将用于本发明的壳聚糖转化为水溶性盐。该壳聚糖盐可溶于血液以形成阻止血流的凝胶。
壳聚糖盐理想地适合于本文中描述的应用,因为壳聚糖在体内容易分解。壳聚糖通过溶菌酶转化成葡糖胺,并因此可以从身体自然地排出。无需采取任何措施从身体去除壳聚糖。
此外,壳聚糖盐表现出温和的抗菌特性,并且因此,使用它们降低了感染的风险。
适用于本发明的示例性壳聚糖盐包括但不限于单独或组合的以下的任一种:乙酸盐、乳酸盐、琥珀酸盐、苹果酸盐、硫酸盐或丙烯酸盐。它们通常为粉末形式。
已经观察到良好的结果,其中壳聚糖盐包含壳聚糖乳酸盐或为壳聚糖乳酸盐。
壳聚糖盐是通过将壳聚糖与适当的酸组合来制备的。应理解,酸可以是产生在与人或动物机体相关的条件下(特别是血液中)可溶的壳聚糖盐的任何无机或有机酸。合适的酸可被技术人员所识别。例如,壳聚糖磷酸盐在这样的条件下是不溶的,因此磷酸是不合适的。
止血剂可占止血材料按重量计的至少20%,或更通常按重量计的至少约80%。通常来说,止血剂占止血材料按重量计的20%至99%,优选止血材料按重量计的45%至95%。
止血剂通常为颗粒状的,但可包含短纤维、海绵、织物、膜、粉末、液体、凝胶或液体涂层。短纤维的长度可以不超过约7.5mm,更通常地长度不超过约5mm。
止血剂的pH通常为约3.5至约8.0。pH主要取决于所使用的特定止血剂,因为它们各自具有不同的pH。
“生物黏合剂”意指与生物基质结合的天然或合成的生物相容性物质。生物基质可以是例如伤口部位处的湿润组织。实际上,生物黏合剂可以促进两种材料之间的黏附,其中一种材料本质上是生物材料,使得这些材料长时间保持在一起。生物黏合剂通常表现出对干燥表面(例如手套或完整皮肤)的低黏附,以及对湿/湿润表面(例如伤口或内脏器官)的高黏附。因此,包含生物黏合剂和止血剂的止血材料应优选地表现出对干燥表面的低黏附和对湿/湿润表面的高黏附。优选地,止血材料不表现出对干燥表面的黏附。有益地,生物黏合剂的这种特性提供了这样的止血材料:既易于处理,又使得能够使止血材料在与压迫最少三分钟的TCCC指南相比降低的压迫时间内有效地控制出血。
生物黏合剂应优选地与止血剂相容,且不干扰止血材料的效力。生物黏合剂通常是固体、干燥的材料。
“低黏附”意指以每25mm材料0.05N(表示为0.05N/25mm)或低于此的剥离力黏附至表面。无黏附有效地测量为0.0N/25mm。
“高黏附”意指以0.25N/25mm或高于此的剥离力黏附至表面。优选地,对湿/湿润表面的黏附表现出0.7N/25mm或高于此的剥离力,并且更优选地1.0N/25mm或高于此的剥离力。对湿/湿润表面的黏附通常表现出0.6至2.0N/25mm的剥离力。
因此,生物黏合剂可促进止血剂与伤口部位处的湿润组织的黏附。有益地,这允许降低了凝血所需的压迫时间,而没有迫使止血剂离开伤口部位的血压。
生物黏合剂可占止血材料按重量计的多至90%。优选地,生物黏合剂可占止血材料按重量计的多至20%,更优选地占止血材料按重量计的2%至20%,甚至更优选地占止血材料按重量计的5%至10%,最优选地占止血材料按重量计的7%至8%。在这些优选范围内,生物黏合剂被优化用于黏附至湿或湿润组织,而不在去除之后造成不利影响,例如伤口重新打开。
生物黏合剂应是当施加于湿/湿润基质时产生高黏附的材料。生物黏合剂可选自单独或组合的以下的任一种:卡波姆(carbomer)、聚乙烯醇(polyvinyl alcohol,PVA)、聚乙烯吡咯烷酮(polyvinylpyrrolidone,PVP)、2-丙烯酰胺基-2-甲基丙磺酸(2-acrylamido-2-methylpropane sulfonic acid)或高分子量的与二乙烯基二醇交联的丙烯酸聚合物或与二乙烯基二醇交联的聚丙烯酸盐。优选地,生物黏合剂包含高分子量的交联的丙烯酸聚合物。“高分子量”意指分子量为至少50,000g/mol。优选地,分子量为至少60,000g/mol,更优选地为100,000至300,000g/mol。在这样的实施方案中,生物黏合剂可以是包含与烯丙基蔗糖或烯丙基季戊四醇交联的丙烯酸聚合物的均聚物;包含与烯丙基季戊四醇交联的丙烯酸和C10-C30烷基丙烯酸盐/酯聚合物的共聚物;包含聚乙二醇和长链烷基酸酯的嵌段共聚物的卡波姆均聚物或共聚物;或其混合物。这样的聚合物的一些实例包括NF934、NF974、NF971和NF980。
生物黏合剂提供了具有优异的湿黏特性的本发明组合物。“湿黏”意指黏附至湿或湿润组织。这使生物黏合剂促进止血剂与伤口部位处的湿润组织之间的黏附。
在一些实施方案中,止血剂和生物黏合剂通常以至少3∶1的比例存在。通常来说,止血剂和生物黏合剂以至少4∶1的比例存在,更优选地以至少9∶1的比例存在。
“抗纤维蛋白溶解剂”意指抑制纤维蛋白溶解的天然或合成物质。纤维蛋白溶解是防止凝块增大的过程。该过程有两种类型:初级纤维蛋白溶解和次级纤维蛋白溶解。初级类型是正常的机体过程,而次级纤维蛋白溶解是由于药物、医学病症或一些其他原因导致的凝块分解。因此,抗纤维蛋白溶解剂防止凝块的分解,该凝块与不存在抗纤维蛋白溶解剂时相比应更坚固且持续更久。
抗纤维蛋白溶解剂可以与止血剂化学键合、与其形成盐或与其缔合,或者可独立于止血剂和生物黏合剂。
抗纤维蛋白溶解剂可包含纤溶酶原激活物抑制剂,例如丝氨酸蛋白酶抑制剂。这样的丝氨酸蛋白酶抑制剂的一些非限制性实例包括纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor-1,PAI-1),其也被称为内皮纤溶酶原激活物抑制剂或丝酶抑制蛋白E1(serpin E1),或抑蛋白酶多肽(aprotinin)。PAI-1是一种丝氨酸蛋白酶抑制剂,其作为组织型纤溶酶原激活物(tissue plasminogen activator,tPA)和尿激酶(uPA)(其为纤溶酶原的激活物并因此引起纤维蛋白溶解)的主要抑制剂发挥作用。抑蛋白酶多肽是数种丝氨酸蛋白酶,特别是浓度为约125,000IU/ml的胰蛋白酶、胰凝乳蛋白酶和纤溶酶以及300,000IU/ml的激肽释放酶的竞争性抑制剂。抑蛋白酶多肽对激肽释放酶的作用导致对因子XIIa形成的抑制。因此,凝结和纤维蛋白溶解的内源性途径二者均被抑制。抑蛋白酶多肽对纤溶酶的作用独立地减慢了纤维蛋白溶解。
或者,抗纤维蛋白溶解剂可包含糖蛋白,例如纤维蛋白原或氨甲环酸。
或者,抗纤维蛋白溶解剂可包含C2-C12氨基羧酸、C4-C8氨基羧酸或C5-C7氨基羧酸,例如C6氨基羧酸,例如氨基己酸或ε-氨基己酸。
或者,抗纤维蛋白溶解剂可包含氨基苯甲酸,例如氨甲苯酸。
这些抗纤维蛋白溶解剂中的任何一种或更多种或其衍生物可单独或组合使用。
本文中使用的关于抗纤维蛋白溶解剂的术语“衍生物”是指直接来自于或可来自于任一种上述所列化合物并且还表现出抗纤维蛋白溶解行为的任何化合物。
抗纤维蛋白溶解剂通常以以下量存在:止血剂组合物的约0.01至约99.9wt%;更通常约0.1至约90wt%,更通常约1至约80wt%,更通常约2至约70wt%,更通常约5至约60wt%,更通常约10至约50wt%,更通常约12至约40wt%,更通常约15至约35wt%,更通常约20至约30wt%,更通常约22至约28wt%,例如约25wt%。
止血剂还可包含惰性材料。“惰性”意指具有非止血特性或差止血特性并对湿/湿润表面具有低黏附的材料,即,单独在施加于出血部位之后约三分钟、五分钟的时间内或甚至十分钟内不表现出任何显著止血的材料。
一些示例性的惰性材料包括但不限于:非止血纤维素、非止血砂(non-haemostatic sand)、非止血黏土、非止血藻酸类(non-haemostatic alginate)、微晶纤维素、瓜尔胶、黄原胶、非止血壳聚糖、非止血壳多糖、右旋糖酐、蔗糖、乳糖、果胶、羧甲基纤维素、羟乙基纤维素、磨碎的玉米粉、聚丙烯酸、硫酸钡、淀粉或其任意两种或更多种的组合。通常来说,使用选自非止血壳聚糖、非止血壳多糖和羧甲基纤维素的一种或更多种惰性材料。
可将惰性材料以以下量添加至止血剂:总组合物按重量计的多至约95%,通常按重量计的多至约80%,并且更通常按重量计的多至约50%。惰性材料通常与止血剂共混,但也可以分散在含有止血剂的溶液中并干燥。
通常来说,惰性材料是颗粒状的,但也可以是粉末、泡沫、纤维或膜的形式。
止血剂还可包含医用表面活性剂。“医用表面活性剂”意指对于与人或动物机体接触或施用于人或动物机体是可药用的且不对人或动物机体造成任何显著有害作用的任何表面活性剂。用于本发明的一些示例性医用表面活性剂包括单独或组合的以下的任一种:基于环氧乙烷和环氧丙烷的嵌段共聚物(例如BASF)、甘油、聚乙二醇、丙二醇、脂肪酸(例如月桂酸、油酸、其他脂肪酸和脂肪酸盐)、基于硅酮的表面活性剂和乳化剂。通常来说,医用表面活性剂包括月桂酸和油酸。
医用表面活性剂通常可占止血剂按重量计的约0.001%至约10%。
更有利地,医用表面活性剂占止血剂按重量计的约0.5%至约1%。有利地,表面活性剂的存在产生优异的润湿特性。止血剂润湿的方式对其性能很重要。也就是说,止血剂可以过快地吸收血液且与血液简单混合而未发生足够的胶凝作用以致于无法形成能够阻止血流的凝胶凝块。在另一方面,如果止血剂吸收血液过慢,则仅少量止血剂(通常是最接近伤口部位的止血剂的前几毫米深度)发生胶凝作用。在这种情况下,形成的凝胶凝块不够稠密而无法阻止血流持续足够的时间以允许将患者移动到医疗中心。通常来说,这样的凝胶凝块将随着患者移动而破裂,并且出血将重新开始。
已经发现,通过向止血剂中添加一定量的惰性材料和/或一定量的医用表面活性剂,即实际上稀释了止血剂的量,事实上进一步增强了止血剂的性能。惰性材料和医用表面活性剂一起的组合特别有利,因为惰性材料的存在进一步增强了医用表面活性剂的性能,反之亦然。
止血剂的粒径可以影响本发明止血材料的性能。粒径是由筛的尺寸测量的,颗粒将经由该筛而通过或被保留。
例如,当止血剂为微粒或颗粒形式时,其平均粒径可大于约200目,使得其不能通过200目的筛。平均粒径通常可大于约100目,更通常大于约50目,并且不期望粒或颗粒能够通过40目的筛。
更有利地,惰性材料的粒径基本上等于止血剂的粒径。“基本上等于”意指颗粒的相对尺寸相差不超过约25%,更通常不超过约10%。通过研磨止血剂并通过任何合适的方法(例如筛选)进行分选,达到了最优粒径。这样的定径过程(sizing process)对于本领域技术人员而言是公知的,并将不再另外描述。
止血组合物可以以任何特定形式,例如以干粉末、溶液、泡沫或凝胶的形式施用于伤口。
止血组合物可施加于载体材料以施加于伤口部位。载体材料可包含织造材料(woven material)或黏胶非织造材料(non-woven material),或者作为替代地,载体材料可包含薄的柔性基质、织造纱布(woven gauze)、膜、泡沫、溶液或片状凝胶。本发明的组合物也可以是冷冻干燥的形式。
组合物在与人或动物身体内或身体上的伤口相关的条件下可降解或可不降解。在一个实例中,载体材料的材料可在合理的时间段(例如约30天)内在体内安全地降解,使得在外科手术使用或治疗之后可将整个止血材料片留在原处。用于组合物的安全且可降解的材料的一些实例包括但不限于:氧化纤维素、明胶、右旋糖酐、胶原、聚己内酯、聚乳酸、聚交酯-co-乙交酯、聚乙交酯、壳多糖等。
止血剂可通过多种方法施加到载体材料上。这些方法包括:使用黏合剂使止血剂与载体材料粘合(bonding);将包含止血剂的溶液施加到载体材料上,涂覆载体材料并干燥溶液;或通过热粘合。止血剂也可在载体材料加工期间并入到载体材料中。
组合物可采取任何合适的形式,并且可以以处理伤口所需的一系列不同尺寸、形状(例如正方形、矩形、圆形或椭圆形)和厚度提供。例如,材料可以是相对于其宽度/深度具有小的高度的大体上扁平的形状。可采用任何规则或不规则的形状。材料可以以可切成所需尺寸的大的片提供。
止血组合物可以以无菌或非无菌形式提供。当材料以无菌形式提供时,可以使用任一种常规已知的方法,例如γ辐照、电子束处理、热处理、环氧乙烷(ethylene oxide,EtO)灭菌等进行灭菌。非无菌形式的材料可以与一种或更多种防腐剂或抗微生物剂(例如银及其盐组合)组合提供。
当使用环氧乙烷对止血组合物进行灭菌时,其可包括将中间装置暴露于气态环氧乙烷中。灭菌阶段可以在腔室中进行,该腔室优选地是密封的。
根据本发明的另一方面,提供了止血方法,该方法包括以下步骤:向生理目标部位施加如本文中所述的包含止血剂、生物黏合剂和抗纤维蛋白溶解剂或其衍生物的止血组合物;以及向止血材料施加压力,持续少于约一分钟、或少于约55秒、或少于约50秒、或少于约45秒的时间。
根据本发明的另一方面,提供了包含止血剂、生物黏合剂和抗纤维蛋白溶解剂或其衍生物的止血组合物,其用于阻止来自生理目标部位的血流。
可向目标部位施加压力,持续约30秒至一分钟的时间。在一些实施方案中,可向伤口部位施加压力持续约35秒至约55秒;或约40秒至约50秒;或约45秒。本发明的一个优点是使从伤口部位流出的血液充分凝结所花费的快速的时间。因此,在约一分钟内形成足够的凝块,使得可向目标部位施加压力持续较短的时间以获得期望的效果。在一些实施方案中,可向伤口部位施加压力持续少于约55秒以具有期望的效果,并且优选地少于约50秒。
根据本发明的另一方面,提供了载体材料,其包含施加到该载体材料上的止血组合物,该止血组合物包含止血剂、生物黏合剂和抗纤维蛋白溶解剂或其衍生物。
载体材料可包含上文中所述的载体材料的任一种特征。优选地,载体材料包含黏胶纱布(viscose gauze)。
根据本发明的另一方面,提供了制造包含止血剂、生物黏合剂和抗纤维蛋白溶解剂或其衍生物的止血组合物的方法,该方法包括将止血剂与生物黏合剂和抗纤维蛋白溶解剂或其衍生物组合的步骤。
优选地,制造止血材料的方法包括以下步骤:(1)将预定重量的止血剂和任选的惰性材料分配到混合容器中;(2)将预定重量的生物黏合剂分配到含有止血剂和任选的惰性材料的混合容器中;(3)分配预定重量的抗纤维蛋白溶解剂或其衍生物;以及(4)将止血剂、生物黏合剂和抗纤维蛋白溶解剂或其衍生物混合。
现在将参考以下实施例进一步描述本发明,所述实施例旨在仅是举例说明性的,并不限制本发明的范围。
实施例1
将7wt%的生物黏合剂(高分子量交联的丙烯酸聚合物(980NF))与壳聚糖衍生物/非止血壳聚糖共混物共混。壳聚糖衍生物由壳聚糖乳酸盐和壳聚糖氨甲环酸盐组成,其中使用壳聚糖、乳酸和氨甲环酸的组合来使壳聚糖形成盐。将混合物以45gsm的涂覆重量双层涂覆在黏胶纱布上。这提供了根据本发明的止血组合物。
体内
为了证实本发明在压迫时间上表现出真实优势,并提供在45秒的总包扎和压迫时间的情况下的效力的证据,在正常条件和凝血病条件二者下,根据ISR模型,在猪模型中使用6mm股动脉切割模型,对实施例1的组合物进行了测试。
对于正常条件,对猪模型的股动脉手术地进行6mm的切割。使动脉出血持续45秒的时间,然后将止血材料施加于出血部位,并使用45秒的总的组合包扎和压迫时间。在压迫期之后,评估伤口的出血。如果出血再次发生,则再压迫止血材料持续施压一分钟。此后的任何再次出血都归类为失败。
对于凝血病条件,将猪血量的25%替换为Hextend流体(25%血液稀释),并在动脉损伤和出血之前在猪中诱导低体温(体核温度为34℃至35℃)。对猪模型的股动脉手术地进行6mm的切割。使动脉出血持续45秒的时间,然后将止血组合物施加于出血部位,并使用45秒的总的组合包扎和压迫时间。在压迫期之后,评估伤口的出血。如果出血再次发生,则再压迫止血材料持续施压一分钟。此后的任何再次出血都归类为失败。
结果表明,在正常条件下和在凝血病条件下处理的模型的66%在股动脉模型的方案中在最初45秒的时间内实现了止血。在再施压一分钟之后,在正常条件下处理的模型的82%在股动脉模型的方案中实现了止血,而在凝血病条件下处理的模型的83%在股动脉模型的方案中实现了止血。
在正常条件下,当前市售的Celox Rapid止血剂产品需要进行1分钟的持续压迫接着再进行1分钟的压迫(如果需要的话)的护理方案来实现止血,而根据最近的ISR结果,在凝血病条件下,Celox Rapid需要2分钟的持续压迫来实现止血。
相比之下,本发明的组合物在多数情况下(在正常条件和凝血病条件二者下均为66%)能够在仅45秒的时间内实现止血,且在正常条件下的82%和在凝血病条件下的83%在再施压一分钟之后实现止血。这示出了显著的改善,尤其是在阻止伤口出血所需的时间至关重要并且对于患者来说可能是生与死的差别的技术领域中。
当然,应理解,本发明不旨在限制于仅通过举例描述的前述实施例。
Claims (17)
1.止血组合物,其包含止血剂、生物黏合剂和抗纤维蛋白溶解剂或其衍生物。
2.根据权利要求1所述的组合物,其中所述抗纤维蛋白溶解剂包含选自以下的一种或更多种:氨甲环酸、氨基己酸、氨甲苯酸、抑蛋白酶多肽、ε-氨基己酸和纤维蛋白原。
3.根据权利要求1或权利要求2所述的组合物,其中所述止血剂包含选自以下的一种或更多种:氧化再生纤维素、高岭土、明胶、钙离子、沸石、胶原、壳聚糖或壳聚糖盐。
4.根据权利要求3所述的组合物,其中所述止血剂包含壳聚糖盐。
5.根据权利要求4所述的组合物,其中所述壳聚糖盐包含选自以下的一种或更多种:壳聚糖乙酸盐、壳聚糖乳酸盐、壳聚糖琥珀酸盐、壳聚糖苹果酸盐、壳聚糖硫酸盐或壳聚糖丙烯酸盐。
6.根据权利要求5所述的组合物,其中所述壳聚糖盐包含乳酸盐和/或壳聚糖琥珀酸盐。
7.根据前述权利要求中任一项所述的组合物,其中所述生物黏合剂包含选自以下的一种或更多种:卡波姆、聚乙烯醇(PVA)、聚乙烯吡咯烷酮(PVP)、2-丙烯酰胺基-2-甲基丙磺酸或高分子量的与二乙烯基二醇交联的丙烯酸聚合物或与二乙烯基二醇交联的聚丙烯酸盐。
8.根据权利要求7所述的组合物,其中所述生物黏合剂包含交联的丙烯酸聚合物,所述聚合物的分子量为至少约50,000g/mol。
9.根据权利要求8所述的组合物,其中所述生物黏合剂包含选自以下的一种或更多种:包含与烯丙基蔗糖或烯丙基季戊四醇交联的丙烯酸聚合物的均聚物;包含与烯丙基季戊四醇交联的丙烯酸和C10-C30烷基丙烯酸盐/酯聚合物的共聚物;和/或包含聚乙二醇和长链烷基酸酯的嵌段共聚物的卡波姆均聚物或共聚物。
10.根据前述权利要求中任一项所述的组合物,其中所述组合物施加于载体材料。
11.根据权利要求10所述的组合物,其中所述载体材料选自:织造材料、非织造材料、柔性基质、膜、泡沫或片状凝胶。
12.根据权利要求1至10中任一项所述的止血组合物,其用于阻止来自生理目标部位的血流。
13.制造根据权利要求1至11中任一项所述的止血组合物的方法,所述方法包括将止血剂与生物黏合剂和抗纤维蛋白溶解剂或其衍生物组合的步骤。
14.根据权利要求13所述的方法,其中所述方法包括以下步骤:(1)将预定重量的止血剂和任选的惰性材料分配到混合容器中;(2)将预定重量的生物黏合剂分配到含有所述止血剂和任选的惰性材料的所述混合容器中;(3)分配预定重量的抗纤维蛋白溶解剂或其衍生物;以及(4)将所述止血剂、生物黏合剂和抗纤维蛋白溶解剂或其衍生物混合。
15.止血方法,所述方法包括以下步骤:将根据权利要求1至11中任一项所述的止血组合物施加于生理目标部位;以及对止血材料施加压力。
16.根据权利要求15所述的方法,其中施加所述压力不超过约1分钟。
17.载体材料,其包含施加于所述载体材料的根据权利要求1至11中任一项所述的止血组合物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB1802380.4 | 2018-02-14 | ||
GB1802380.4A GB2571080A (en) | 2018-02-14 | 2018-02-14 | Haemostatic material |
PCT/GB2019/050396 WO2019158926A1 (en) | 2018-02-14 | 2019-02-14 | Haemostatic material |
Publications (1)
Publication Number | Publication Date |
---|---|
CN112384255A true CN112384255A (zh) | 2021-02-19 |
Family
ID=61731341
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201980013232.1A Pending CN112384255A (zh) | 2018-02-14 | 2019-02-14 | 止血材料 |
Country Status (12)
Country | Link |
---|---|
US (1) | US20200376157A1 (zh) |
EP (1) | EP3752210A1 (zh) |
JP (1) | JP2021514394A (zh) |
CN (1) | CN112384255A (zh) |
AU (1) | AU2019220619A1 (zh) |
BR (1) | BR112020016382A2 (zh) |
CA (1) | CA3090350A1 (zh) |
GB (1) | GB2571080A (zh) |
MX (1) | MX2020008368A (zh) |
RU (1) | RU2020127558A (zh) |
WO (1) | WO2019158926A1 (zh) |
ZA (1) | ZA202004802B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115814149A (zh) * | 2022-12-30 | 2023-03-21 | 东华大学 | 一种改性羧甲基壳聚糖止血材料及其制备方法 |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111020792A (zh) * | 2019-11-18 | 2020-04-17 | 江苏金太阳纺织科技股份有限公司 | 一种持久散热凉席面料及其制备方法 |
CN111714689B (zh) * | 2020-07-09 | 2022-04-22 | 石家庄亿生堂医用品有限公司 | 一种壳聚糖止血粉及其制备方法 |
CN114813270B (zh) * | 2022-04-08 | 2024-04-19 | 南雄阳普医疗科技有限公司 | 一种血液促凝剂及其制备方法和应用 |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090156711A1 (en) * | 2007-12-18 | 2009-06-18 | Van Holten Robert W | Hemostatic device |
WO2010145817A2 (en) * | 2009-06-16 | 2010-12-23 | Baxter International Inc. | Hemostatic sponge |
WO2012091636A2 (ru) * | 2010-12-30 | 2012-07-05 | Федеральное Государственное Бюджетное Образовательное Учреждение Высшего Профессионального Образования "Саратовский Государственный Университет Имени Н.Г. Чернышевского" | Биополимерное волокно, состав формовочного раствора для его получения, способ приготовления формовочного раствора, полотно биомедицинского назначения, способ его модификации, биологическая повязка и способ лечения ран |
WO2012123728A2 (en) * | 2011-03-11 | 2012-09-20 | Medtrade Products Limited | Haemostatic material |
CN104114198A (zh) * | 2012-02-01 | 2014-10-22 | 哈莫斯塔蒂斯有限公司 | 止血伤口敷料 |
CN104159527A (zh) * | 2012-03-06 | 2014-11-19 | 弗罗桑医疗设备公司 | 包含止血糊剂的压力容器 |
CN104888265A (zh) * | 2015-05-08 | 2015-09-09 | 四川大学 | 温敏型胶原基复合止血凝胶及其制备方法 |
CN105358182A (zh) * | 2013-07-09 | 2016-02-24 | 伊西康公司 | 止血垫组件药盒和方法 |
US20160206773A1 (en) * | 2015-01-20 | 2016-07-21 | Shaker A. Mousa | Composition and method for stopping hemorrhage, infection, and accelerating healing in various types of wound or burns |
WO2016176186A1 (en) * | 2015-04-27 | 2016-11-03 | KOSTRUBA, Pavel | Hemostatic composition and device |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2716872C (en) | 2008-02-29 | 2015-02-10 | Ferrosan Medical Devices A/S | Device for promotion of hemostasis and/or wound healing |
CN101804218A (zh) * | 2010-04-13 | 2010-08-18 | 王艳 | 含有云南白药或者云南白药提取物的人体可吸收外伤敷料 |
EA026104B1 (ru) * | 2015-04-02 | 2017-03-31 | Общество С Ограниченной Ответственностью "Тектум" | Кровоостанавливающее и ранозаживляющее средство |
WO2018119320A1 (en) * | 2016-12-21 | 2018-06-28 | Cresilon, Inc. | Hemostatic compositions with antifibrinolytic agents |
JP2020534267A (ja) * | 2017-09-12 | 2020-11-26 | シルパ メディケア リミテッドShilpa Medicare Limited | 膝関節形成のためのトラネキサム酸噴霧 |
-
2018
- 2018-02-14 GB GB1802380.4A patent/GB2571080A/en not_active Withdrawn
-
2019
- 2019-02-14 JP JP2020566335A patent/JP2021514394A/ja active Pending
- 2019-02-14 CN CN201980013232.1A patent/CN112384255A/zh active Pending
- 2019-02-14 EP EP19710468.0A patent/EP3752210A1/en active Pending
- 2019-02-14 WO PCT/GB2019/050396 patent/WO2019158926A1/en unknown
- 2019-02-14 RU RU2020127558A patent/RU2020127558A/ru unknown
- 2019-02-14 US US16/968,710 patent/US20200376157A1/en active Pending
- 2019-02-14 CA CA3090350A patent/CA3090350A1/en active Pending
- 2019-02-14 MX MX2020008368A patent/MX2020008368A/es unknown
- 2019-02-14 AU AU2019220619A patent/AU2019220619A1/en active Pending
- 2019-02-14 BR BR112020016382-1A patent/BR112020016382A2/pt not_active Application Discontinuation
-
2020
- 2020-08-03 ZA ZA2020/04802A patent/ZA202004802B/en unknown
Patent Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090156711A1 (en) * | 2007-12-18 | 2009-06-18 | Van Holten Robert W | Hemostatic device |
WO2010145817A2 (en) * | 2009-06-16 | 2010-12-23 | Baxter International Inc. | Hemostatic sponge |
CN102802683A (zh) * | 2009-06-16 | 2012-11-28 | 巴克斯特国际公司 | 止血海绵 |
WO2012091636A2 (ru) * | 2010-12-30 | 2012-07-05 | Федеральное Государственное Бюджетное Образовательное Учреждение Высшего Профессионального Образования "Саратовский Государственный Университет Имени Н.Г. Чернышевского" | Биополимерное волокно, состав формовочного раствора для его получения, способ приготовления формовочного раствора, полотно биомедицинского назначения, способ его модификации, биологическая повязка и способ лечения ран |
WO2012123728A2 (en) * | 2011-03-11 | 2012-09-20 | Medtrade Products Limited | Haemostatic material |
CN104114198A (zh) * | 2012-02-01 | 2014-10-22 | 哈莫斯塔蒂斯有限公司 | 止血伤口敷料 |
CN104159527A (zh) * | 2012-03-06 | 2014-11-19 | 弗罗桑医疗设备公司 | 包含止血糊剂的压力容器 |
CN105358182A (zh) * | 2013-07-09 | 2016-02-24 | 伊西康公司 | 止血垫组件药盒和方法 |
US20160206773A1 (en) * | 2015-01-20 | 2016-07-21 | Shaker A. Mousa | Composition and method for stopping hemorrhage, infection, and accelerating healing in various types of wound or burns |
WO2016176186A1 (en) * | 2015-04-27 | 2016-11-03 | KOSTRUBA, Pavel | Hemostatic composition and device |
CN104888265A (zh) * | 2015-05-08 | 2015-09-09 | 四川大学 | 温敏型胶原基复合止血凝胶及其制备方法 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115814149A (zh) * | 2022-12-30 | 2023-03-21 | 东华大学 | 一种改性羧甲基壳聚糖止血材料及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
US20200376157A1 (en) | 2020-12-03 |
RU2020127558A (ru) | 2022-03-15 |
BR112020016382A2 (pt) | 2020-12-15 |
MX2020008368A (es) | 2020-09-25 |
WO2019158926A1 (en) | 2019-08-22 |
AU2019220619A1 (en) | 2020-08-27 |
CA3090350A1 (en) | 2019-08-22 |
KR20210018183A (ko) | 2021-02-17 |
GB2571080A (en) | 2019-08-21 |
JP2021514394A (ja) | 2021-06-10 |
ZA202004802B (en) | 2022-12-21 |
GB201802380D0 (en) | 2018-03-28 |
EP3752210A1 (en) | 2020-12-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20230270914A1 (en) | Haemostatic material | |
CN112384255A (zh) | 止血材料 | |
US10973946B1 (en) | Haemostatic material | |
US9950091B2 (en) | Composition and method for stopping hemorrhage, infection, and accelerating healing in various types of wound or burns | |
EP3003411B1 (en) | Degradable haemostat composition | |
EP2233157A1 (en) | A biocompatible denatured starch sponge material | |
KR20120125465A (ko) | 건조 분말 피브린 실란트 | |
WO2010002435A2 (en) | Hemostatic pouch and method to stabilize hemostatic components | |
WO2021128050A1 (en) | Hemostatic paste and uses thereof | |
US10583216B2 (en) | Scaffold compositions for tissue repair | |
KR102683263B1 (ko) | 지혈재 | |
AU2015202402B2 (en) | Haemostatic material |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |