CN107921172A - 止血组合物及装置 - Google Patents
止血组合物及装置 Download PDFInfo
- Publication number
- CN107921172A CN107921172A CN201680029721.2A CN201680029721A CN107921172A CN 107921172 A CN107921172 A CN 107921172A CN 201680029721 A CN201680029721 A CN 201680029721A CN 107921172 A CN107921172 A CN 107921172A
- Authority
- CN
- China
- Prior art keywords
- acid
- weight
- hemostatic composition
- accounts
- composition
- 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.)
- Withdrawn
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 105
- 230000002439 hemostatic effect Effects 0.000 title claims abstract description 46
- 229920001864 tannin Polymers 0.000 claims abstract description 31
- 239000001648 tannin Substances 0.000 claims abstract description 31
- 235000018553 tannin Nutrition 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 24
- 102000009123 Fibrin Human genes 0.000 claims abstract description 19
- 108010073385 Fibrin Proteins 0.000 claims abstract description 19
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229950003499 fibrin Drugs 0.000 claims abstract description 19
- 229920001661 Chitosan Polymers 0.000 claims abstract description 16
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 16
- 239000005017 polysaccharide Substances 0.000 claims abstract description 16
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229960002684 aminocaproic acid Drugs 0.000 claims abstract description 12
- 239000000648 calcium alginate Substances 0.000 claims abstract description 12
- 235000010410 calcium alginate Nutrition 0.000 claims abstract description 12
- 229960002681 calcium alginate Drugs 0.000 claims abstract description 12
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=O)[C@H]1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 claims abstract description 12
- 239000003112 inhibitor Substances 0.000 claims abstract description 11
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 claims abstract description 11
- 229960000401 tranexamic acid Drugs 0.000 claims abstract description 11
- 229960003375 aminomethylbenzoic acid Drugs 0.000 claims abstract description 9
- QCTBMLYLENLHLA-UHFFFAOYSA-N aminomethylbenzoic acid Chemical compound NCC1=CC=C(C(O)=O)C=C1 QCTBMLYLENLHLA-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000002253 acid Substances 0.000 claims abstract description 8
- 239000000084 colloidal system Substances 0.000 claims abstract description 8
- 229910052709 silver Inorganic materials 0.000 claims abstract description 7
- 239000004332 silver Substances 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 150000004676 glycans Chemical class 0.000 claims abstract 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 9
- 239000011159 matrix material Substances 0.000 claims description 9
- -1 anion polysaccharide Chemical class 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 238000000227 grinding Methods 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 230000000844 anti-bacterial effect Effects 0.000 claims description 4
- 239000000284 extract Substances 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 230000005855 radiation Effects 0.000 claims description 4
- 230000001954 sterilising effect Effects 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 4
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- 239000001263 FEMA 3042 Substances 0.000 claims description 3
- 235000015523 tannic acid Nutrition 0.000 claims description 3
- 229920002258 tannic acid Polymers 0.000 claims description 3
- 229940033123 tannic acid Drugs 0.000 claims description 3
- 241000196324 Embryophyta Species 0.000 claims description 2
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 claims description 2
- 229910001863 barium hydroxide Inorganic materials 0.000 claims description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 2
- 239000000920 calcium hydroxide Substances 0.000 claims description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 2
- 238000011049 filling Methods 0.000 claims description 2
- 239000004310 lactic acid Substances 0.000 claims description 2
- 235000014655 lactic acid Nutrition 0.000 claims description 2
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 2
- 239000000347 magnesium hydroxide Substances 0.000 claims description 2
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 2
- 229960005137 succinic acid Drugs 0.000 claims description 2
- KCEGAEHLRAFSLL-UHFFFAOYSA-N benzoic acid carbamic acid Chemical compound NC(O)=O.OC(=O)c1ccccc1 KCEGAEHLRAFSLL-UHFFFAOYSA-N 0.000 claims 3
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims 2
- 244000248349 Citrus limon Species 0.000 claims 1
- 235000005979 Citrus limon Nutrition 0.000 claims 1
- 150000001768 cations Chemical class 0.000 claims 1
- 238000005660 chlorination reaction Methods 0.000 claims 1
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 claims 1
- 238000002156 mixing Methods 0.000 abstract description 6
- 229940045110 chitosan Drugs 0.000 abstract 1
- 206010052428 Wound Diseases 0.000 description 18
- 208000032843 Hemorrhage Diseases 0.000 description 17
- 208000027418 Wounds and injury Diseases 0.000 description 16
- 208000034158 bleeding Diseases 0.000 description 16
- 230000000740 bleeding effect Effects 0.000 description 16
- 239000000243 solution Substances 0.000 description 15
- 239000002245 particle Substances 0.000 description 14
- 230000023597 hemostasis Effects 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 235000013339 cereals Nutrition 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 7
- 238000004132 cross linking Methods 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 150000004804 polysaccharides Chemical class 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 108010088842 Fibrinolysin Proteins 0.000 description 5
- 210000004204 blood vessel Anatomy 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000006399 behavior Effects 0.000 description 4
- 210000001124 body fluid Anatomy 0.000 description 4
- 239000010839 body fluid Substances 0.000 description 4
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 4
- 238000004806 packaging method and process Methods 0.000 description 4
- 239000000419 plant extract Substances 0.000 description 4
- 229940012957 plasmin Drugs 0.000 description 4
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229910021645 metal ion Inorganic materials 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- RNKMOGIPOMVCHO-SJMVAQJGSA-N 1,3,6-trigalloyl glucose Chemical compound C([C@@H]1[C@H]([C@@H]([C@@H](O)[C@H](OC(=O)C=2C=C(O)C(O)=C(O)C=2)O1)OC(=O)C=1C=C(O)C(O)=C(O)C=1)O)OC(=O)C1=CC(O)=C(O)C(O)=C1 RNKMOGIPOMVCHO-SJMVAQJGSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- 241000065610 Cotinus Species 0.000 description 2
- 108010074864 Factor XI Proteins 0.000 description 2
- JPYHHZQJCSQRJY-UHFFFAOYSA-N Phloroglucinol Natural products CCC=CCC=CCC=CCC=CCCCCC(=O)C1=C(O)C=C(O)C=C1O JPYHHZQJCSQRJY-UHFFFAOYSA-N 0.000 description 2
- 244000264648 Rhus coriaria Species 0.000 description 2
- 235000013178 Rhus coriaria Nutrition 0.000 description 2
- 239000002250 absorbent Substances 0.000 description 2
- 230000002745 absorbent Effects 0.000 description 2
- 230000009102 absorption Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 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 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 229940127554 medical product Drugs 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- QCDYQQDYXPDABM-UHFFFAOYSA-N phloroglucinol Chemical compound OC1=CC(O)=CC(O)=C1 QCDYQQDYXPDABM-UHFFFAOYSA-N 0.000 description 2
- 229960001553 phloroglucinol Drugs 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 229940079877 pyrogallol Drugs 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 108010039627 Aprotinin Proteins 0.000 description 1
- 241001092371 Bergenia Species 0.000 description 1
- 240000004972 Bergenia crassifolia Species 0.000 description 1
- 235000014785 Bergenia crassifolia Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 241001474374 Blennius Species 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102000016362 Catenins Human genes 0.000 description 1
- 108010067316 Catenins Proteins 0.000 description 1
- 239000005714 Chitosan hydrochloride Substances 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 102100030563 Coagulation factor XI Human genes 0.000 description 1
- 241000134400 Cotinus coggygria Species 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 206010063560 Excessive granulation tissue Diseases 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- 108010014172 Factor V Proteins 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 241000007067 Lagochilus Species 0.000 description 1
- 241000353560 Lagochilus inebrians Species 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102100038124 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 241000612118 Samolus valerandi Species 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 244000044283 Toxicodendron succedaneum Species 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000002316 cosmetic surgery Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 208000001780 epistaxis Diseases 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 229960004222 factor ix Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 229940074391 gallic acid Drugs 0.000 description 1
- 235000004515 gallic acid Nutrition 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 210000001126 granulation tissue Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000000893 inhibin Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 108010076401 isopeptidase Proteins 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 230000003961 neuronal insult Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000035699 permeability Effects 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
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 230000002522 swelling effect Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 108010080213 vascular factor Proteins 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- 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
- A61K31/185—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
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
-
- 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
- A61K31/7024—Esters of saccharides
-
- 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
- A61K31/70—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
- A61K31/734—Alginic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/38—Silver; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61L24/043—Mixtures of 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/08—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—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
- A61L2300/104—Silver, e.g. silver sulfadiazine
-
- 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
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/418—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
- 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
- A61L2300/432—Inhibitors, antagonists
-
- 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)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Surgery (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Materials Engineering (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Materials For Medical Uses (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
止血组合物包含藻酸钙、壳聚糖、ε‑氨基己酸、选自氨基甲基苯甲酸和凝血酸的酸、以及单宁。制备该止血组合物的方法包括混合一种或多种多糖基体、单宁、溶解纤维蛋白抑制剂、胶质银和溶剂以形成混合物,以及在25‑80℃的温度下干燥所述混合物,直至残留含水量为约15‑20%。
Description
发明领域和背景
本发明涉及包含生物可吸收成分的止血组合物。在一方面,本发明用于局部止血装置,例如用于抑制血液流动,并且其可以应用于在出血伤口和受损血管上的或对出血伤口和受损血管的现场救护和急救护理中,从而阻止各种强度的毛细血管或混合型出血。其还可以用于外科手术实践中。在一方面,本发明的止血组合物和装置可以通过将本发明的粉末组合物直接地覆盖或倾倒或迁移到血流向伤口的源头而使用。
如果血管被物理创伤损坏(包括外科手术的后果),发生出血。根据损坏的效果,出血可以导致血液损失,这可能影响个体的正常功能。在出血起源于骨的不可延伸的腔体的情况下,溢出的血液的积聚可以导致软组织由于升高的压力而受损。如果出血被放任不管且没有得到处理,其将最终被正常发生的生理学过程(其特征为涉及血管因素、血小板因子和血浆因子的组合活性的一系列事件)抑制。
发明概述
根据本发明的一方面,提供了止血组合物,包含:藻酸钙;壳聚糖;ε-氨基己酸;选自氨基甲基苯甲酸和凝血酸的酸;以及单宁。
根据本发明的其他方面,提供了止血组合物,包含多糖基体;溶解纤维蛋白抑制剂;以及单宁。
根据本发明的又一方面,提供了制备止血组合物的方法,所述方法包括:混合一种或多种多糖基体、单宁、溶解纤维蛋白抑制剂、胶质银和溶剂以形成混合物;以及在25-80℃的温度下干燥该混合物,直至残留的含水量为约15-20%。
本发明的组合物和装置在本发明的一个实施方案中是软的,并且具有粉状或颗粒状外观。粒径可以宽泛地变化,从肉眼可见至微观尺寸。
优选地,本发明的组合物和装置二者不会引发对周围组织的任何损坏或显著损坏作用,在应用期间没有热影响(其实际上不变热),并且是无毒的。该组合物的粉末易于复制(repeat)伤口轮廓并且将其紧密覆盖。
本发明的组合物可以用于增强在外科手术介入或其他损伤的众多实例中对出血的抑制。这包括大的腹部器官(肝、脾或肠)的外科手术;用于防止脑组织或神经组织的压迫损坏的神经外科手术;在其间频繁发生广泛性出血(其难以由其他手段抑制)的整形外科手术;在用于抑制从缝合位置渗出性出血的血管外科手术;口腔或牙医外科手术,例如拔牙;以及鼻出血。
体外实验揭示组合物的止血性质,其通过基于抑制来自肝脏和脾脏的伤口以及各种病原学的伤口的薄壁组织出血而未引发周围组织的任何反应的实验而得以证实。
此外,发现该组合物对伤口的再生过程产生刺激作用,其在加速肉芽组织生长、提高边缘和岛屿上皮形成以及促进用于上皮细胞迁移、血管侵入和无疤伤口愈合的有利条件中得以反映。
本发明的基于吸收剂的组合物和装置的止血作用(或作用类型)之一可以与吸收血液的多孔性和能力有关。例如,典型的明胶海绵吸收比其自身重量高约40-50倍的血液量。然而,海绵膨胀可能导致不良事件。在它们已经吸收液体之后膨胀,海绵可以挤压周围组织,并且存在发生神经损坏的可能性。因此,亟需解决限制包含吸收剂(其在与体液接触之后膨胀)的止血装置的膨胀的问题。当构建或使用本发明的止血组合物时,优选显著解决这种问题。
本发明的一个优势是提供确保明显的止血性质且膨胀趋势降低(使其更安全地使用)以及具有修缮和杀菌作用的装置。
这可以凭借组合物来实现,该组合物在本发明的一方面中包括:多糖基体,其包括藻酸钙和壳聚糖;单宁(单宁酸(tannic acid))或其他有机单宁、或含单宁的植物提取物;溶解纤维蛋白抑制剂(例如ε-氨基己酸、氨甲环酸和氨基甲基苯甲酸);以及胶质银。
该组合物的多糖基体可以是交联的。使用药学可接受的化学试剂以及使用辐射的交联是可能的;最优选的交联方法经由脱氢热处理法来进行。
该组合物的聚合物基体的交联度对其功能性具有影响,包括附着于伤口组织的能力、吸收周围生物学体液,等。可以控制聚合物基体的交联度。最优选的膨胀程度(在与体液接触后组合物的体积增加)为1.5-5倍。
组合物的膨胀性质可以通过在填充有蒸馏水的量筒中组合物体积的增加来测量。测量放置在该量筒中的装置的量,然后添加过量的水。然后,测量在膨胀结束之后装置的增加的体积。也可以在生理盐水中测量膨胀,其给出对体液中的膨胀的更精确的评估。
本发明的止血组合物可以包含一定量的残留水,例如至多约8重量%。然而,残留水并未计算成海绵总重量的一部分。这意味着,当其成为包含某一重量%的某一组分(例如藻酸钙)的海绵时,基于组合物总重量的无水基础(即,基于排除可能结合的任何水的总重量)来计算重量%。
发明详述
下文将描述包括实施方案及变体的本发明的进一步细节。
止血组合物的可能的含量
组合物的活性基体由天然多糖组成。这些包括藻酸钙(为阴离子多糖)和壳聚糖(为阳离子多糖)。它们确保或促进血液吸收以及在装置颗粒表面上的止血所涉及的血液组分的浓缩;此外,它们的比例优化组合物的止血性质。
可以在止血组合物中使用其他海藻盐。优选地选择多价金属离子,以使它们与海藻根形成微溶的化合物,即,用作交联金属离子。例如,多价金属离子包括,例如,与藻酸根形成微溶化合物的碱土金属和过渡金属的离子。碱土金属离子,例如镁或钙,是优选的。钙是特别优选的。因此,根据本发明,钙盐是最优选的,因为它们是生理学相容的,并且具有与藻酸根相关的交联或凝胶形成的高能力。此外,藻酸钙将钙离子(Ca2+)递送至伤口区域,由此活化止血过程并促进在后续过程中的伤口区域中的愈合。除了壳聚糖之外,该组合物可以包括其衍生物,例如,盐,例如氯化壳聚糖、乙酸壳聚糖、柠檬酸壳聚糖,以及其药学可接受的修饰物。这些衍生物的使用不限制在本发明的组合物中使用其他衍生物。
包含在该组合物中的溶解纤维蛋白抑制剂改善组合物的止血性质。哺乳动物身体具有固有的溶解纤维蛋白系统,其可以由纤维蛋白沉积而活化。通过溶解纤维蛋白,该系统有助于维持受损血管的内腔是开放的。然而,在其中目标是迅速止血的情形下,溶解纤维蛋白活性可以抵消另外止血装置(例如本发明的组合物)的止血作用。溶解纤维蛋白抑制的药理学途径可以包括抑制血纤维蛋白溶酶或血纤维蛋白溶酶原向血纤维蛋白溶酶的转变。溶解纤维蛋白抑制剂的应用降低了蛋白水解酶血纤维蛋白溶酶对来自纤维蛋白的可溶性肽的裂解(水解)的影响,所述可溶性肽随后被肽酶裂解。已知血纤维蛋白溶酶还作用于其他凝结因子:纤维蛋白原(因子I)、因子V、因子VIII、因子XII和凝血素,其不仅具有溶解血栓作用,还具有抗凝作用。因此,由于溶解纤维蛋白抑制剂,血纤维蛋白溶酶活性或其血浆水平下降,导致凝血增加。因此,在本发明的止血组合物中包含的具有抗-溶解纤维蛋白性质的试剂可以是有利的。该组合物可以主要包含选自氨基己酸、氨甲环酸和氨基甲基苯甲酸的抗-溶解纤维蛋白试剂。最优选的是抗-溶解纤维蛋白试剂的组合,即,氨基己酸和凝血酸,或氨基己酸和氨基甲基苯甲酸。当局部应用时,这些试剂的组合在比这些试剂单独各自使用的情况显著更长的时段内显著地降低再出血的风险。这些溶解纤维蛋白抑制剂的应用不限制在本发明的止血组合物中应用具有类似作用的其他类似试剂的可能性。当确定在组合物中的重量百分比时,可以应用以下试剂:抑肽酶、胃酶抑制素、亮抑酶肽、抗蛋白酶、胰凝乳蛋白酶抑制素、纤链蛋白和其他手段。
单宁或其他有机单宁增强组合物的止血活性并且确保组织通透性降低,由此降低再出血的风险。单宁使细胞蛋白质变性,形成白蛋白盐(albuminate)保护膜,并且还对一些微生物具有杀菌或抑菌作用。单宁是具有带负电荷的粒子和脱水性质的胶质物质。已知在单宁中大量羟基的存在提高止血过程的活性。本发明在一方面可以利用有机单宁作为分子量为500-20,000的主要由焦棓酚、儿茶酚、藤黄酚衍生的多酚化合物,其能够与蛋白质和生物碱形成强键,并且具有单宁(tanning)性质。它们的非限制性实例包括:没食子酸、鞣花酸、儿茶酚、焦棓酚和藤黄酚。本发明的止血组合物还可以使用含单宁的植物提取物,例如,以下的提取物:栎属、岩白菜属(厚叶岩白菜(Bergenia crassifolia))、兔唇花属(Lagochilus inebrians Bunge)、黄栌(黄栌(Cotinus coggygria))和漆树(西西里漆树(Rhus coriaria))。所述提取物的应用不限制使用其他含单宁的提取物。优选地在本发明的组合物中使用植物单宁或合成单宁,因为在化学方面,它们是非常纯的并且易于标准化,这对于装置的大规模生产是重要的。
出血的结果之一是皮肤和其他创伤病损的微生物感染机会可能是非常高的。因此,可以有利地向该组合物引入杀菌组分。胶质银颗粒可以被引入该组合物中。银纳米颗粒是尺寸为1-100nm的银原子聚集体,其表面被一层稳定剂分子包围,这确保水/稳定剂/银纳米颗粒体系的长使用寿命。优选地,粒径应为3-30nm之内。如果其是药学可接受的,则制备重构的银颗粒的方法不是重要的。用于本发明的优选方法是在基于单宁的单宁水溶液或水-乙醇溶液中重新获得硝酸盐的方法。
在赋形剂中,调节和维持某一酸度水平的各种物质可以在工艺过程中使用,以及在决定应用该装置期间的pH值时使用。例如,可以采用以下酸:盐酸、乙酸、柠檬酸、琥珀酸和乳酸。氢氧化物是:氢氧化钠、氢氧化钾、氢氧化钙、氢氧化钡和氢氧化镁。
此外,本发明的止血装置可以包含缓冲剂。缓冲剂的实例包括碱金属盐,例如,氯化物、乙酸盐、柠檬酸盐、磷酸盐、磷酸一氢盐、碳酸盐、碳酸氢盐和琥珀酸盐。显然,可以使用上述缓冲剂的混合物。这些物质的使用不限制使用其他类似物质。
优选组合物的实例:
为了确保本发明的组合物的止血性质,重要的成分为:
(1)藻酸钙;
(2)壳聚糖;
(3)ε-氨基己酸;
(4)氨基甲基苯甲酸或凝血酸(作为替代物,但不是完全起作用的选项);
(5)单宁(单宁酸)或其他有机单宁酸或含单宁酸-植物提取物。
胶质银颗粒是向组合物提供杀菌活性的额外成分,其扩展了组合物应用的范围。
赋形剂可以包括在工艺过程中以及在决定应用该装置期间的pH值时调节和维持某一酸度水平的各种试剂。
下表列出根据本发明的止血组合物的一方面的各种成分或组分,包括一系列其中此类组分可以存在的范围,该范围在组分的有效功能性与其优选功能性之间变化。
以重量%(基于干重)计的组合物成分比如下所示,作为本发明的实例:
制备方法的实例
可以以多种不同方式制备根据本发明的止血组合物,并且在优选的实施方案中,制备可以包含以下步骤:
(I)混合组合物的多糖基体、单宁(或其他有机单宁,包括含单宁的植物提取物)、溶解纤维蛋白抑制剂(ε-氨基己酸、氨甲环酸和氨基甲基苯甲酸)、胶态银和溶剂。
为了避免在混合期间获得不均匀的混合物(这是潜在可能的),并且为了确保组合物成分的活化,在高温下进行根据本发明的一个方面的混合,所述高温例如25-80℃、如25-40℃、或35-80℃的温度。
混合组合物成分和溶剂通常在机械影响下进行。因此,在混合物期间和/或在混合物之后即刻,所得的混合物应优选地经历离心分离、高速涡旋、敲打或本领域专业人员已知的其他类型的机械影响。
(II)在步骤(I)获得的混合物的干燥。
在混合之后,可以将所得的混合物倾倒入合适的托盘或放置在特氟龙板或硅板上,并且在不搅拌的情况下干燥。干燥过程可以在25-80℃的温度下进行,直至残留含水量为15-20%。在这样的条件下,干燥是耗时的。持续时间取决于在混合物中存在的溶剂的量以及蒸发面积,并且可以特别地从约12小时至约48小时变化。将产物干燥至小于8%的残留湿度可以在高达105-115℃的温度下进行,但不超过1-2小时。
在真空下干燥是更优选的,在此情形下,使用至少约300毫米汞柱(mm Hg)的真空水平是可行的。下限由所用的设备的类型来决定。然而,应当避免正在干燥的混合物的强烈发泡和沸腾,尤其在其中存在过量的溶剂的情况下。干燥温度可以与不使用真空的干燥中的干燥温度相同。
混合冻干是甚至更优选的。此处,冷冻步骤应当在不高于-25℃的温度下进行。在冻干期间,应当进行该过程直至残留含水量不高于5%。
(III)在步骤(II)获得的混合物的任选的热处理。
在以上的步骤(II)之后,产物可以任选地通过在高温(例如约110-180℃的范围内)下的处理来稳定化。稳定化时间取决于温度,但其通常为约15分钟至2小时。如果在步骤(II)未使用高温方法,则有利地进行该步骤。优选地在真空下进行稳定化。
(IV)研磨在步骤(II)和(III)获得的产物。
如果根据上文所述的这些步骤获得的产物不是本发明的期望部分(fractional)的组合物的粉末或颗粒,则其可以经历研磨。因此,在托盘或板上干燥期间,可以形成产物的海绵状形式。在干燥期间还可以形成团块和聚集体(颗粒结块成为团块)。可以将产物研磨成粉末,例如,使用旋转床、挤出、破碎机或离心式研磨机。优选地在具有碾磨设置调节的磨碎机上研磨产物。如果在产生期望尺寸级别的粉末或颗粒形式的产物的设备上进行干燥,则研磨可以不是必须的。本发明的平均粒径小于250μm。更优选的平均粒径为70-100μm。
应考虑到粉末颗粒的部分(fractional)组合物应当是平均尺寸的颗粒、大颗粒(250-500μm)和至少10μm的较小颗粒之间的折中方案。在一方面,在粉末中的大量精细部分的存在显著地增加了其活性表面积、向伤口表面的颗粒附着,并且降低了该组合物的生物拆分(bioresolution)(生物吸收)的时间。另一方面,较小的颗粒更容易被渗出的血液冲洗,并且在粉末的部分组成中不足量的大颗粒可能导致不足的伤口引流。由此,当应用的层厚度是相当大时,组合物可能较差地被血液浸泡;因此,在伤口区域形成薄且催的血凝块。
(V)止血组合物的填充和包装。
单独的包装可以具有各种形式。一种优选的包装形式是药囊或药棒(stick)。对于药店而言,装置在包装中的优选重量为2.5g和5g;对于单独现场救护药箱和外科手术用途而言,为5g和10g。
(VI)最终灭菌。
止血装置在包装中由辐射来灭菌。灭菌可以通过施用辐射(例如β-或γ-辐射)来进行。辐射剂量通常为10-60kGy,例如20-60kGy、或25-50kGy、或15-25kGy、或15-20kGy,即,约15kGy、20kGy或25kGy。这样的处理降低了装置的生物负载,并且还可以增强在医疗产品中分子链的交联。优选地施用电子加速器来灭菌。
本发明的止血组合物和装置可以具有在开放性伤口上的单独使用、或在现场应用中的单独使用,以及在创伤性损伤中的单独使用。
对于单独使用,装置不需要任何专门的专业技能或专门的储存条件(-5℃至40℃),使其易于用在与血液损失有关的各种病原学的伤口上。
该装置在撕裂或刺穿伤口或各种类型的出血损伤的开放性伤口表面上的应用可以提供对出血的快速且可靠的抑制。可以应用该组合物以完全覆盖靶标位点(例如伤口)。
对于剧烈的出血,该装置可以由绷带固定并以厚层(过量)形式应用,这促进固定绷带(retentive bandage)的移除,而不损坏血凝块,因此医疗产品的与绷带接触的上层保持干燥。
在介入期间的外科手术实践中:在对内脏器官的外科手术介入期间额外的或完全的抑制出血;处理渗出性缝合。
该止血装置可以主要地用作粉末或以颗粒形式使用;然而,在本发明的其他实施方案中,以膏剂形式使用也是可行的。在给出的语境中,术语“膏剂”是指其中装置粉末的颗粒分散在液体介质中的固体或半固体分散体系。装置的粉末还可以称为凝胶-或膏剂-形成剂。膏剂的特征在于比水高的动态黏度。
膏剂可以通过将止血装置的颗粒悬浮在液体介质(即,含水介质)中而制备。通常,每1g的装置使用约1-5ml的液体介质。液体介质优选地为含水介质,但可以使用其他可接受的药学介质。含水介质可以包含溶解于其中的浓度接近于盐水溶液的诸如氯化钠的盐。
该装置可以用于单独现场救护药箱,以及由药店销售。
在本说明书中,所示的实施方案和实例应被认为是示例性的,然不是对所公开或要求保护的设备和步骤的限制。尽管本文提供的许多实例涉及方法行为或系统元件的特定组合,但是应理解那些行为和那些元件可以以其它方式组合以实现相同的目的。不意欲将仅关于一个实施方案而讨论的行为、元件和特征从其他实施方案中的类似作用中排除。
如本文所用,“多个”意指两个以上。如本文所述,一“组”物件可以包括一个或多个此类物件。如本文所用,无论在说明书或权利要求中,术语“包括”、“包含”、“携带”、“具有”、“含有”、“涵括”等应被理解成开放式的,即,意指包括但不限于。对于权利要求,仅有连接语“由...组成”和“基本由...组成”分别为封闭式或半封闭式措词。在权利要求中使用顺序术语、例如“第一”、“第二”等来修饰权利要求的要素,自身并非意味着一个权利要求的要素相对于另一要素的任何优先性、在先性或顺序性,或者其中进行该方法的行为的临时顺序,而是仅用作标签以将具有某一名称的一个权利要求的要素与具有相同名称(除了使用顺序术语)的另一要素相区分,从而区分权利要求的要素。如本文所用,“和/或”意指列出的物件是供选择的方案,但该供选择的方案还包括所列出的物件的任何组合。
Claims (27)
1.止血组合物,包含:
藻酸钙;
壳聚糖;
ε-氨基己酸;
选自氨基甲基苯甲酸和凝血酸的酸;以及
单宁。
2.如权利要求1所述的止血组合物,其中
所述藻酸钙占20-75重量%;
所述壳聚糖占1-7.5重量%;
所述ε-氨基己酸占2.5-10重量%;
所述氨基甲酸苯甲酸占0.5-3重量%且所述凝血酸占0.5-2.5重量%;以及
所述单宁占1-30重量%。
3.如权利要求2所述的止血组合物,其中
所述藻酸钙占35-72重量%;
所述壳聚糖占1.5-7重量%;
所述ε-氨基己酸占3-9重量%;
所述氨基甲酸苯甲酸占1-2.5重量%且所述凝血酸占0.75-2重量%;以及
所述单宁占2.5-27重量%。
4.如权利要求3所述的止血组合物,其中
所述藻酸钙占45-70重量%;
所述壳聚糖占1.5-6重量%;
所述ε-氨基己酸占4-7重量%;
所述氨基甲酸苯甲酸占1-2重量%且所述凝血酸占1-1.5重量%;以及
所述单宁占4-25重量%。
5.如权利要求1所述的止血组合物,还包含胶质银。
6.如权利要求1所述的止血组合物,其中所述单宁选自单宁酸、有机单宁和含单宁的植物提取物中的一种或多种。
7.如权利要求1所述的止血组合物,还包含残留的水。
8.如权利要求7所述的止血组合物,其中水以至多约8重量%存在。
9.如权利要求1所述的止血组合物,还包含杀菌组分。
10.如权利要求1所述的止血组合物,还包含用于调节和维持所选酸度水平以建立所述组合物的pH值的至少一种物质。
11.如权利要求10所述的止血组合物,其中所述用于调节的物质选自盐酸、乙酸、柠檬酸、琥珀酸、乳酸、氢氧化钠、氢氧化钾、氢氧化钙、氢氧化钡和氢氧化镁中的一种或多种。
12.如权利要求1所述的止血组合物,还包含缓冲剂。
13.止血组合物,包含:
多糖基体;
溶解纤维蛋白抑制剂;以及
单宁。
14.如权利要求13所述的止血组合物,其中所述多糖基体包括阴离子多糖和阳离子多糖。
15.如权利要求14所述的止血组合物,其中所述阴离子多糖基体包括藻酸钙,并且所述阳离子多糖包括壳聚糖。
16.如权利要求15所述的止血组合物,其中所述壳聚糖选自柠檬酸壳聚糖、氯化壳聚糖、乙酸壳聚糖中的一种或多种。
17.如权利要求13所述的止血组合物,其中所述溶解纤维蛋白抑制剂包括选自ε-氨基己酸、氨基甲基苯甲酸和凝血酸中的一种或多种。
18.如权利要求13所述的止血组合物,还包含胶质银。
19.如权利要求13所述的止血组合物,其中所述多糖基体是交联的。
20.用于制备止血组合物的方法,所述方法包括:
混合一种或多种多糖基体、单宁、溶解纤维蛋白抑制剂、胶质银和溶剂以形成混合物;以及
在25-80℃的温度下干燥所述混合物,直至残留含水量为约15-20%。
21.如权利要求20所述的方法,还包括在已经干燥所述混合物之后对其热处理以使所述混合物稳定化。
22.如权利要求20所述的方法,其中所述混合在25-80℃的高温下进行。
23.如权利要求20所述的方法,其中所述混合物通过离心分离、高速涡旋或敲打来进行。
24.如权利要求20所述的方法,其中所述干燥步骤在真空中进行。
25.如权利要求20所述的方法,还包括研磨步骤。
26.如权利要求20所述的方法,还包括填充和包装所述止血组合物的步骤。
27.如权利要求20所述的方法,还包括通过辐射对所述组合物灭菌的步骤。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562153442P | 2015-04-27 | 2015-04-27 | |
US62/153,442 | 2015-04-27 | ||
PCT/US2016/029323 WO2016176186A1 (en) | 2015-04-27 | 2016-04-26 | Hemostatic composition and device |
Publications (1)
Publication Number | Publication Date |
---|---|
CN107921172A true CN107921172A (zh) | 2018-04-17 |
Family
ID=57199548
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201680029721.2A Withdrawn CN107921172A (zh) | 2015-04-27 | 2016-04-26 | 止血组合物及装置 |
Country Status (4)
Country | Link |
---|---|
US (1) | US20160346239A1 (zh) |
EP (1) | EP3288601A1 (zh) |
CN (1) | CN107921172A (zh) |
WO (1) | WO2016176186A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113425889A (zh) * | 2021-06-25 | 2021-09-24 | 延安大学 | 一种抗菌止血海绵及其制备方法和应用 |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11504341B2 (en) * | 2016-10-27 | 2022-11-22 | Egy-Nano Pharma, Lp | Nanotechnology-based hemostatic dressings |
WO2018119320A1 (en) * | 2016-12-21 | 2018-06-28 | Cresilon, Inc. | Hemostatic compositions with antifibrinolytic agents |
WO2019232135A1 (en) * | 2018-05-31 | 2019-12-05 | Hcs Innovation Llc | Natural polymer-based tissue adhesive with healing-promoting properties |
US11571492B2 (en) | 2017-08-04 | 2023-02-07 | Hcs Innovation, Llc | Natural polymer-based tissue adhesive with healing-promoting properties |
MX2020002697A (es) * | 2017-09-12 | 2020-09-09 | Shilpa Medicare Ltd | Pulverizador de acido tranexamico para la artroplastia de rodilla. |
TR201713929A2 (tr) | 2017-09-20 | 2019-04-22 | Montero Gida Sanayi Ve Ticaret Anonim Sirketi | Ki̇tosan ve alji̇natin hemostati̇k kompozi̇syonlari |
GB2571080A (en) * | 2018-02-14 | 2019-08-21 | Medtrade Products Ltd | Haemostatic material |
CN108721686A (zh) * | 2018-04-20 | 2018-11-02 | 朱清 | 一种低毒复合止血粉的制备方法 |
US11654057B2 (en) | 2020-04-09 | 2023-05-23 | Bio 54, Llc | Devices for bleeding reduction and methods of making and using the same |
KR102564911B1 (ko) * | 2020-12-29 | 2023-08-10 | 울산과학기술원 | 개질된 하이드로겔 |
US11642324B1 (en) | 2022-03-01 | 2023-05-09 | Bio 54, Llc | Topical tranexamic acid compositions and methods of use thereof |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003035115A2 (en) * | 2001-10-26 | 2003-05-01 | Baxter International Inc. | Fibrin membrane and methods for its preparation- application to artificial skin |
WO2004060172A1 (en) * | 2002-12-31 | 2004-07-22 | Marine Polymer Technologies, Inc. | Hemostatic compositions and uses therefor |
RU2005110226A (ru) * | 2005-04-08 | 2006-10-20 | Сергей Александрович Киселев (RU) | Гемостатическое средство и способ его получения |
CN101001649A (zh) * | 2004-07-09 | 2007-07-18 | 弗罗桑公司 | 包括透明质酸的止血组合物 |
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 |
CN101837143A (zh) * | 2010-04-22 | 2010-09-22 | 胡堃 | 一种药物缓释止血组合物及制备方法 |
CN102596164A (zh) * | 2009-10-26 | 2012-07-18 | 日产化学工业株式会社 | 化妆料、皮肤外用剂、以及医疗用仪器 |
WO2014039891A2 (en) * | 2012-09-07 | 2014-03-13 | C. R. Bard, Inc. | Medical article securement systems |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7276235B2 (en) * | 1998-11-18 | 2007-10-02 | Zlb Behring Gmbh | Tissue glue with improved antiadhesive properties |
GB2393120A (en) * | 2002-09-18 | 2004-03-24 | Johnson & Johnson Medical Ltd | Compositions for wound treatment |
IL178867A (en) * | 2006-10-26 | 2010-05-31 | Vladimir N Filatov | Hemostatic textile material |
GB2461019B (en) * | 2008-04-25 | 2013-06-05 | Medtrade Products Ltd | Haemostatic material |
US9114188B2 (en) * | 2010-01-13 | 2015-08-25 | Allergan, Industrie, S.A.S. | Stable hydrogel compositions including additives |
-
2016
- 2016-04-26 EP EP16786988.2A patent/EP3288601A1/en not_active Withdrawn
- 2016-04-26 CN CN201680029721.2A patent/CN107921172A/zh not_active Withdrawn
- 2016-04-26 WO PCT/US2016/029323 patent/WO2016176186A1/en unknown
- 2016-04-26 US US15/138,562 patent/US20160346239A1/en not_active Abandoned
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003035115A2 (en) * | 2001-10-26 | 2003-05-01 | Baxter International Inc. | Fibrin membrane and methods for its preparation- application to artificial skin |
WO2004060172A1 (en) * | 2002-12-31 | 2004-07-22 | Marine Polymer Technologies, Inc. | Hemostatic compositions and uses therefor |
CN101001649A (zh) * | 2004-07-09 | 2007-07-18 | 弗罗桑公司 | 包括透明质酸的止血组合物 |
RU2005110226A (ru) * | 2005-04-08 | 2006-10-20 | Сергей Александрович Киселев (RU) | Гемостатическое средство и способ его получения |
CN102596164A (zh) * | 2009-10-26 | 2012-07-18 | 日产化学工业株式会社 | 化妆料、皮肤外用剂、以及医疗用仪器 |
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 |
CN101837143A (zh) * | 2010-04-22 | 2010-09-22 | 胡堃 | 一种药物缓释止血组合物及制备方法 |
WO2014039891A2 (en) * | 2012-09-07 | 2014-03-13 | C. R. Bard, Inc. | Medical article securement systems |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113425889A (zh) * | 2021-06-25 | 2021-09-24 | 延安大学 | 一种抗菌止血海绵及其制备方法和应用 |
Also Published As
Publication number | Publication date |
---|---|
EP3288601A1 (en) | 2018-03-07 |
WO2016176186A1 (en) | 2016-11-03 |
US20160346239A1 (en) | 2016-12-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107921172A (zh) | 止血组合物及装置 | |
US10195312B2 (en) | Modified starch material of biocompatible hemostasis | |
EP1981511B1 (en) | Hemostatic material | |
EP2203053B1 (en) | Modified starch material of biocompatible hemostasis | |
EP1976537B1 (en) | Hemostatic material | |
US20140086898A1 (en) | Fragmented polymeric compositions and methods for their use | |
KR20170093243A (ko) | 유동성 지혈 조성물 | |
WO2012123728A2 (en) | Haemostatic material | |
JP2011509932A5 (zh) | ||
Zhao et al. | Preparation and characterization of tranexamic acid modified porous starch and its application as a hemostatic agent | |
CN116209482B (zh) | 具有富含止血促进剂的表面的止血复合聚集体材料 | |
CN109125795A (zh) | 一种多糖止血组合物及其制备方法与应用 |
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 | ||
WW01 | Invention patent application withdrawn after publication |
Application publication date: 20180417 |
|
WW01 | Invention patent application withdrawn after publication |