JPH09328401A - Organ preservation liquid - Google Patents
Organ preservation liquidInfo
- Publication number
- JPH09328401A JPH09328401A JP14465296A JP14465296A JPH09328401A JP H09328401 A JPH09328401 A JP H09328401A JP 14465296 A JP14465296 A JP 14465296A JP 14465296 A JP14465296 A JP 14465296A JP H09328401 A JPH09328401 A JP H09328401A
- Authority
- JP
- Japan
- Prior art keywords
- organ preservation
- preservation solution
- solution
- molecular weight
- mmol
- 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
- 239000007788 liquid Substances 0.000 title abstract description 7
- 239000000082 organ preservation Substances 0.000 title abstract 3
- 229920001612 Hydroxyethyl starch Polymers 0.000 claims abstract description 12
- 229940050526 hydroxyethylstarch Drugs 0.000 claims abstract description 12
- 230000003204 osmotic effect Effects 0.000 claims abstract description 9
- 229910001414 potassium ion Inorganic materials 0.000 claims abstract description 8
- 229910001415 sodium ion Inorganic materials 0.000 claims abstract description 8
- 239000003792 electrolyte Substances 0.000 claims abstract description 7
- 239000000126 substance Substances 0.000 claims abstract description 7
- 239000000084 colloidal system Substances 0.000 claims abstract 3
- 239000000162 organ preservation solution Substances 0.000 claims description 22
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 claims description 6
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 claims description 6
- 239000001569 carbon dioxide Substances 0.000 claims description 5
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 5
- 210000000056 organ Anatomy 0.000 abstract description 8
- 230000010410 reperfusion Effects 0.000 abstract description 8
- 230000010412 perfusion Effects 0.000 abstract description 4
- 238000005406 washing Methods 0.000 abstract 1
- 210000004185 liver Anatomy 0.000 description 14
- 239000003761 preservation solution Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 108700042768 University of Wisconsin-lactobionate solution Proteins 0.000 description 9
- 238000002054 transplantation Methods 0.000 description 9
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 5
- 235000019796 monopotassium phosphate Nutrition 0.000 description 5
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 5
- 210000003240 portal vein Anatomy 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- AEQDJSLRWYMAQI-UHFFFAOYSA-N 2,3,9,10-tetramethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline Chemical compound C1CN2CC(C(=C(OC)C=C3)OC)=C3CC2C2=C1C=C(OC)C(OC)=C2 AEQDJSLRWYMAQI-UHFFFAOYSA-N 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- 210000003494 hepatocyte Anatomy 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 239000000176 sodium gluconate Substances 0.000 description 4
- 235000012207 sodium gluconate Nutrition 0.000 description 4
- 229940005574 sodium gluconate Drugs 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 3
- 229960003459 allopurinol Drugs 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 3
- 229960003957 dexamethasone Drugs 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000017074 necrotic cell death Effects 0.000 description 3
- 210000000496 pancreas Anatomy 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 2
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 206010019663 Hepatic failure Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 2
- 210000000013 bile duct Anatomy 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- -1 halogen ion Chemical class 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 208000007903 liver failure Diseases 0.000 description 2
- 231100000835 liver failure Toxicity 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 210000005164 penile vein Anatomy 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DSCUFZSWIGAJKM-UHFFFAOYSA-N 2-chloro-2-hydroxypropanoic acid Chemical compound CC(O)(Cl)C(O)=O DSCUFZSWIGAJKM-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
- 206010002091 Anaesthesia Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000725101 Clea Species 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-N Gluconic acid Natural products OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical group OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 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
- 238000011887 Necropsy Methods 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- HLCFGWHYROZGBI-JJKGCWMISA-M Potassium gluconate Chemical compound [K+].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O HLCFGWHYROZGBI-JJKGCWMISA-M 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000011685 brown norway rat Methods 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 1
- ZEWYCNBZMPELPF-UHFFFAOYSA-J calcium;potassium;sodium;2-hydroxypropanoic acid;sodium;tetrachloride Chemical compound [Na].[Na+].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[Ca+2].CC(O)C(O)=O ZEWYCNBZMPELPF-UHFFFAOYSA-J 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 210000002767 hepatic artery Anatomy 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229940085991 phosphate ion Drugs 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000004224 potassium gluconate Substances 0.000 description 1
- 235000013926 potassium gluconate Nutrition 0.000 description 1
- 229960003189 potassium gluconate Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Landscapes
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、臓器移植に際して
用いられる臓器保存液に関するものである。TECHNICAL FIELD The present invention relates to an organ preservation solution used for organ transplantation.
【０００２】[0002]
【従来の技術】肝臓、腎臓、膵臓、心臓、肺臓等の臓器
の移植に際して、摘出された臓器は、移植するまでの
間、新鮮な状態に維持する必要があり、臓器保存液が重
要な役割を果たしている。初期の移植に際しては、ユー
ロコリンズ液が用いられていたが、その場合における臓
器の保存可能な時間は、肝臓の場合でも２４時間未満で
あり、より長時間保存可能な保存液が求められていた。2. Description of the Related Art When transplanting an organ such as liver, kidney, pancreas, heart or lung, the excised organ must be kept in a fresh state until transplantation, and organ preservation solution plays an important role. Plays. At the time of the initial transplantation, Euro-Collins solution was used, but in that case, the preservation time of the organ was less than 24 hours even in the case of the liver, and a preservation solution that can be preserved for a longer time was demanded. .
【０００３】最近、ウイスコンシン大学のグループが膵
臓移植時の保存液としてＵＷ液を開発した（特公平７−
６８０８２号、特公平８−２２８０１号）。このＵＷ液
は、膵臓の保存のみならず肝臓や腎臓の保存液としても
有用であり、肝臓の２４時間保存が可能となった。Recently, a group at the University of Wisconsin has developed UW solution as a preservation solution for pancreas transplantation (Japanese Patent Publication No. 7-
68082, Japanese Examined Patent Publication No. 8-22801). This UW solution is useful not only as a preservation solution for the pancreas but also as a preservation solution for the liver and kidneys, and the liver can be preserved for 24 hours.
【０００４】しかしながら、ＵＷ液は溶液状態では室温
で不安定であり、用時溶解を余儀なくされており、か
つ、高価につく等の問題点がある。又、ＵＷ液は、粘稠
性が高いため、急速な注入が困難であり、電解質組成が
細胞内液組成に基づいているので、再灌流直前にグラフ
トからの溶液の十分なリンスが必要で、そのため臓器の
活きの良さが損なわれる原因ともなっている。又、高浸
透圧により、グラフト周辺の急激な変化のために再灌流
障害の起こる可能性がある。However, the UW liquid is unstable at room temperature in a solution state, and is required to be dissolved at the time of use, and it is expensive. In addition, since the UW solution is highly viscous, rapid injection is difficult, and since the electrolyte composition is based on the intracellular solution composition, sufficient rinsing of the solution from the graft immediately before reperfusion is necessary. Therefore, it is also a cause of impairing the vitality of the organ. Also, hyperosmotic pressure can cause reperfusion injury due to abrupt changes around the graft.
【０００５】[0005]
【発明が解決しようとする課題】本発明者らは、このよ
うな従来品の問題点に鑑み、溶液状態において長期間安
定であり、臓器を長期間保存可能、再環流直前のリンス
が不要、移植後の機能不全が少ない、安価な臓器保存液
の開発を検討した。In view of such problems of conventional products, the inventors of the present invention are stable for a long period of time in a solution state, can store organs for a long period of time, and need no rinse immediately before reperfusion. We investigated the development of an inexpensive organ preservation solution with little dysfunction after transplantation.
【０００６】[0006]
【課題を解決するための手段】その結果、電解質及び合
成コロイド物質からなる臓器保存液において、実質的に
分子量３５万以下のものを含まない平均分子量５０万−
６５万のヒドロキシエチル澱粉を２−３．５％含有する
臓器保存液を開発したところ、所期の性質を有する臓器
保存液が得られた。As a result, in an organ preservation solution comprising an electrolyte and a synthetic colloidal substance, an average molecular weight of 500,000-containing substantially no molecular weight of 350,000 or less.
When an organ preservation solution containing 2-50,000% of 650,000 hydroxyethyl starch was developed, an organ preservation solution having desired properties was obtained.
【０００７】この臓器保存液においては、カリウムイオ
ンとナトリウムイオンのモル比が０．４−０．８であ
り、ｐＨ値が７．１−７．５であり、浸透圧が２８０−
３３０ｍＯｓｍ／Ｌであり、粘度が１．８−２．５ｃｐ
（センチポイズ）である。また、炭酸ガスを２０−４０
％含有する混合ガスでガス置換することにより、保存性
の良い、より好ましい臓器保存液が得られた。In this organ preservation solution, the molar ratio of potassium ion to sodium ion is 0.4-0.8, the pH value is 7.1-7.5, and the osmotic pressure is 280-.
330 mOsm / L and viscosity is 1.8-2.5 cp
(Centipoise). In addition, carbon dioxide gas 20-40
%, A more preferable organ preservation solution having a good preservation property was obtained by gas substitution with the mixed gas containing the same.
【０００８】[0008]
【発明の実施の形態】本発明の臓器保存液においては、
平均分子量５０万−６５万のヒドロキシエチル澱粉を使
用する。ここで使用するヒドロキシエチル澱粉は、低分
子量のものを含まないものが好ましく、例えば、分子量
２０万以下のものを含まないヒドロキシエチル澱粉や、
実質的に３５万以下の低分子量のものを含まないヒドロ
キシエチル澱粉を含まないものを使用する。また使用す
るヒドロキシエチル澱粉の分子量が例えば、５０万−６
５万や５５万−６０万のように分子量分布の狭いものを
選択すれば更に良い製品が得られる。ヒドロキシエチル
澱粉は、通常、２−３．５％の濃度で用い、望ましくは
３％前後が良い結果をもたらす。BEST MODE FOR CARRYING OUT THE INVENTION In the organ preservation solution of the present invention,
Hydroxyethyl starch having an average molecular weight of 500,000 to 650,000 is used. The hydroxyethyl starch used here is preferably one that does not contain low molecular weight ones, such as hydroxyethyl starch that does not contain one with a molecular weight of 200,000 or less,
A hydroxyethyl starch-free substance that does not substantially contain a low molecular weight substance of 350,000 or less is used. The hydroxyethyl starch used has a molecular weight of, for example, 500,000-6.
Even better products can be obtained by selecting those having a narrow molecular weight distribution such as 50,000 or 550,000-600,000. Hydroxyethyl starch is usually used at a concentration of 2-3.5%, preferably around 3% gives good results.
【０００９】含有する電解質イオン濃度としては、カリ
ウムイオンに対するナトリウムイオンのモル比が０．４
−０．８の範囲にあることが好ましく、０．４−０．５
の範囲にあることが特に好ましい。The concentration of electrolyte ions contained is such that the molar ratio of sodium ions to potassium ions is 0.4.
It is preferably in the range of -0.8, 0.4-0.5
It is particularly preferable that it is in the range.
【００１０】陰イオン源としては、リン酸２水素イオ
ン、リン酸１水素イオン、炭酸イオン、炭酸水素イオ
ン、クロル等のハロゲンイオンの他、乳酸、酢酸、プロ
ピオン酸、β−ヒドロキシ酪酸、クエン酸、グルコン酸
等の酸類を用いることも出来る。また、マンニトール、
トレハロース、キシロース、グルコース、ラクトース等
の比較的小分子量の糖類を適当量添加することが出来
る。Examples of the anion source include dihydrogen phosphate ion, monohydrogen phosphate ion, carbonate ion, hydrogen carbonate ion, halogen ion such as chloro, lactic acid, acetic acid, propionic acid, β-hydroxybutyric acid, and citric acid. Acids such as gluconic acid and the like can also be used. Also, mannitol,
An appropriate amount of saccharides having a relatively small molecular weight such as trehalose, xylose, glucose and lactose can be added.
【００１１】これらを溶解する臓器保存剤は、上述した
如き酸源或いはアルカリ金属及び／又はアルカリ土類金
属イオン源を用いてｐＨ値を所望のｐＨ値に調節するこ
とができるが、７．１−７．５の範囲であることが好ま
しい。又、浸透圧も所望の浸透圧とすることが出来る
が、２８０−３３０ｍＯｓｍ／Ｌの範囲であることが好
ましく、２８０−３１０ｍＯｓｍ／Ｌ、２９０−３００
ｍＯｓｍ／Ｌの範囲であることが特に好ましい。粘度も
所望の粘度に調製することが出来るが、１．８−２．５
ｃｐの範囲とすることが好ましく、２．１−２．４ｃｐ
の範囲とすることが更に好ましい。The organ preservative which dissolves these can adjust the pH value to a desired pH value by using the above-mentioned acid source or alkali metal and / or alkaline earth metal ion source. It is preferably in the range of -7.5. The osmotic pressure can also be a desired osmotic pressure, but it is preferably in the range of 280-330 mOsm / L, and 280-310 mOsm / L, 290-300.
The range of mOsm / L is particularly preferable. Although the viscosity can be adjusted to a desired viscosity, 1.8-2.5
The range of cp is preferably 2.1-2.4 cp
It is more preferable to set the range to.
【００１２】このようにして得られた臓器保存液は、活
性炭添加ないし活性炭フィルター等を用いて処理するの
が良い。また、必要に応じて保存液を炭酸ガスでバブリ
ングすることにより長期に亘って安定性を保つことが出
来る。更に、炭酸ガス濃度２０−４０％好ましくは２０
−３０％の不活性ガスを充填することにより、組成の変
化を防止することができる。このようにして得られる本
発明の臓器保存液は、ガラス瓶やバッグ等に収納して滅
菌することにより更に安定に長期間保存することが出来
る。The organ preservation solution thus obtained is preferably treated with activated carbon added or an activated carbon filter. If necessary, bubbling the storage solution with carbon dioxide can maintain stability for a long period of time. Further, the carbon dioxide concentration is 20-40%, preferably 20.
By filling with -30% of an inert gas, it is possible to prevent the composition from changing. The organ preservation solution of the present invention thus obtained can be stored more stably for a long period of time by storing it in a glass bottle, a bag or the like and sterilizing it.
【００１３】[0013]
［実施例１］グルコン酸カリウム４３．５ミリモル、グ
ルコン酸ナトリウム４６．５ミリモル、炭酸水素ナトリ
ウム１０ミリモル、リン酸２水素ナトリウム６．５ミリ
モル、リン酸１水素ナトリウム１８．５ミリモル、マン
ニトール４０ミリモル及び平均分子量６０万のヒドロキ
シエチル澱粉３０グラムを溶解し、ｐＨを７．４に調整
して１リットルの水溶液とした。カリウムイオンとナト
リウムイオンのモル比が０．４３５、浸透圧が３２５ｍ
Ｏｓｍ／Ｌ、粘度が２．３０ｃｐである臓器保存液を得
た。[Example 1] Potassium gluconate 43.5 mmol, sodium gluconate 46.5 mmol, sodium hydrogen carbonate 10 mmol, sodium dihydrogen phosphate 6.5 mmol, sodium monohydrogen phosphate 18.5 mmol, mannitol 40 mmol. And 30 g of hydroxyethyl starch having an average molecular weight of 600,000 were dissolved and the pH was adjusted to 7.4 to obtain 1 liter of an aqueous solution. The molar ratio of potassium ion to sodium ion is 0.435, the osmotic pressure is 325m.
An organ preservation solution having an Osm / L and a viscosity of 2.30 cp was obtained.
【００１４】［実施例２］１リットル中に、グルコン酸
ナトリウムを９０ミリモル、炭酸水素ナトリウムを１０
ミリモル、リン酸２水素カリウムを６．５ミリモル、リ
ン酸１水素カリウムを３０ミリモル、マンニトールを４
０ミリモル、平均分子量６０万のヒドロキシエチル澱粉
を３％濃度で含有し、カリウムイオンとナトリウムイオ
ンの比を０．６６５、ｐＨ値を７．４、浸透圧を３２５
ｍＯｓｍ／Ｌ、粘度を２．３０ｃｐに調節した臓器保存
液。[Example 2] 90 mmol of sodium gluconate and 10 mmol of sodium hydrogen carbonate were added to 1 liter.
Mmol, potassium dihydrogen phosphate 6.5 mmol, potassium dihydrogen phosphate 30 mmol, mannitol 4
It contains 0 mmol of hydroxyethyl starch having an average molecular weight of 600,000 at a concentration of 3%, a potassium ion to sodium ion ratio of 0.665, a pH value of 7.4 and an osmotic pressure of 325
Organ preservation solution with mOsm / L and viscosity adjusted to 2.30 cp.
【００１５】［実施例３］リン酸２水素カリウム６．５
ミリモル、リン酸１水素カリウム１８．５ミリモル、グ
ルコン酸ナトリウム９０ミリモル、炭酸水素ナトリウム
１０ミリモル、マンニトール４０ミリモル及び平均分子
量６０万のヒドロキシエチル澱粉３０グラムを溶解し、
ｐＨを７．３２に調整して１リットルの水溶液とした。
この水溶液は、カリウムイオンとナトリウムイオンのモ
ル比が０．４３５、浸透圧が２９１ｍＯｓｍ／Ｌ、粘度
が２．３０ｃｐの臓器保存液である。[Example 3] Potassium dihydrogen phosphate 6.5
Mmol, potassium monohydrogen phosphate 18.5 mmol, sodium gluconate 90 mmol, sodium bicarbonate 10 mmol, mannitol 40 mmol and 30 g of hydroxyethyl starch having an average molecular weight of 600,000 are dissolved,
The pH was adjusted to 7.32 to give 1 liter of aqueous solution.
This aqueous solution is an organ preservation solution having a molar ratio of potassium ion to sodium ion of 0.435, an osmotic pressure of 291 mOsm / L, and a viscosity of 2.30 cp.
【００１６】［実験例］室温で一年間保存した実施例３
の臓器保存液を用い、これに使用直前に１リットル当た
りアロプリノール０．７２ミリモル、デキサメタゾン４
ミリグラムを溶解して、次の実験に供した。また、対照
として、４℃に三ヶ月保存したＵＷ液にデキサメタゾ
ン、アロプリノールを使用直前に溶解して使用した。[Experimental Example] Example 3 stored for one year at room temperature
Immediately before use, allopurinol 0.72 mmol, dexamethasone 4 was used.
The milligram was melt | dissolved and it used for the following experiment. As a control, dexamethasone and allopurinol were dissolved in a UW solution stored at 4 ° C. for 3 months just before use.
【００１７】手術は単独の外科医により、鎌田の方法に
従ってエーテル麻酔下に行った。動物は、２３０−３０
０ｇの雄ブラウン−ノルウェイラット（ＣＬＥＡ Ｊａ
ｐａｎ，Ｉｎｃ．）をドナー及びレシピエントとして使
用した。実験に先立って、１２時間の明暗サイクル下２
５℃で飼育し、通常のラット用食餌と水を与えた。ラッ
トは２群に分け、一方を保存液としてＵＷ液を用いるＵ
Ｗ群、もう一方を本発明の保存液群とした。Surgery was performed by a single surgeon under ether anesthesia according to Kamata's method. The animals are 230-30
0 g of male Brown-Norway rat (CLEA Ja
pan, Inc. ) Was used as donor and recipient. 2 hours under a 12-hour light-dark cycle prior to the experiment
The animals were raised at 5 ° C. and fed a normal rat diet and water. Rats are divided into two groups, one of which uses UW solution as a preservative solution U
The W group and the other group were the preservative solutions of the present invention.
【００１８】ドナーの肝を摘出する前に、２５０ユニッ
トのヘパリンを陰茎静脈に注射し、各保存液１０ｍｌを
用いて肝を門脈内より灌流した。摘出直後、門脈と肝下
大静脈を冷却した各保存液中でカフ処理した。次に、肝
を各保存液５０ｍｌ中で３０時間４℃で保存した。グラ
フト肝の重量を、保存前後に測定した。ＵＷ液での保存
終了後に、冷却した乳酸リンゲル液４ｍｌを用いて、門
脈より注入してリンスしたが、本発明の保存液ではこの
ようなリンスを行わなかった。肝上大静脈の縫合、門脈
及び肝上大静脈縫合のカフ法によって肝移植を行った。
肝動脈は再形成しなかった。胆管は、２本の胆管中にポ
リエチレンチューブを挿入して縫合した。手術後、乳酸
リンゲル１ｍｌ及び７％重炭酸ナトリウム０．５ｍｌを
陰茎静脈より注入した。Before removing the donor liver, 250 units of heparin was injected into the penile vein, and 10 ml of each preservation solution was used to perfuse the liver from the portal vein. Immediately after the extraction, the portal vein and the subhepatic vena cava were cuff-treated in each cooled preservation solution. Next, the liver was stored in 50 ml of each preservation solution for 30 hours at 4 ° C. The weight of the grafted liver was measured before and after storage. After the end of the storage with the UW solution, 4 ml of the cooled lactated Ringer's solution was used to inject and rinse from the portal vein, but the storage solution of the present invention did not perform such a rinse. Liver transplantation was performed by the suture of the suprahepatic vena cava, the portal vein and the cuff method of suture of the suprahepatic vena cava.
The hepatic artery did not remodel. The bile duct was sutured by inserting a polyethylene tube into the two bile ducts. After the surgery, 1 ml of Ringer's lactate and 0.5 ml of 7% sodium bicarbonate were infused through the penile vein.
【００１９】１０匹のレシピエントについて、生存検査
を行った。レシピエントは、個々にゲージに入れ、自由
に食餌と水を与え、毎日観察した。移植後、１日、３
日、７日に体重を測定し、採血を行い、血清ＡＳＴ，Ａ
ＬＴ，ＬＤＨ値を測定した。１日目の採血は、手術後約
２４時間に行った。レシピエントが７日以内に死亡した
場合は、剖検して死因を調査した。A survival test was performed on 10 recipients. Recipients were individually gaged, allowed food and water ad libitum and observed daily. 1 day after transplantation, 3
On 7th and 7th, weigh yourself and collect blood to collect serum AST, A
The LT and LDH values were measured. Blood collection on the first day was performed about 24 hours after the surgery. If the recipient died within 7 days, necropsy was performed to investigate the cause of death.
【００２０】また、個々のレシピエントの肝は組織学的
に検査した。生存とは別に、それぞれ３サンプルを３０
時間保存後、及び門脈の再還流５時間に肝組織サンプル
を採取し、直ちに１０％ホルマリンで固定し、パラフィ
ンで処理した。切片はヘマトキシリン，エオシンで染色
し、光学顕微鏡で観察した。The liver of each recipient was examined histologically. Apart from survival, 30 samples of each 3
After storage for a period of time and 5 hours after reperfusion of the portal vein, a liver tissue sample was collected, immediately fixed with 10% formalin, and treated with paraffin. The sections were stained with hematoxylin and eosin and observed with a light microscope.
【００２１】［生存率］生存率はウイルコキソン・テス
トで比較した。グラフトの重量はペアード・テストで比
較した。その他の値は、マン−ホイットニー・テストで
比較した。有意差はｐ＜０．０５とした。[Survival Rate] The survival rate was compared by the Wilcoxon test. Graft weights were compared in a paired test. Other values were compared by the Mann-Whitney test. The significant difference was p <0.05.
【００２２】本発明保存液群では、１０例中８例が７日
間生存した。１例は肝不全のため３日で死亡し、もう１
例は胆嚢合併症で７日間で死亡した。一方、ＵＷ液群に
おいては、６例が７日間生存し、肝不全３例及び腹腔内
出血４例が３日以内に死亡した。生存したレシピエント
の移植直後、１日、３日、７日後における体重は両群間
に有意差はなかった。グラフトの重量は、本発明保存液
群では３０時間後に有意に増加し、一方、ＵＷ液群にお
いては有意に低下した。In the preservation solution group of the present invention, 8 out of 10 cases survived for 7 days. One died of liver failure in 3 days and another 1
The example died of gallbladder complications in 7 days. On the other hand, in the UW liquid group, 6 cases survived for 7 days, and 3 cases of liver failure and 4 cases of intraperitoneal hemorrhage died within 3 days. Immediately after transplantation, 1 day, 3 days, and 7 days after transplantation, there was no significant difference in body weight between the surviving recipients. The weight of the graft was significantly increased after 30 hours in the preservation solution group of the present invention, while it was significantly decreased in the UW solution group.
【００２３】［組織学的検査］両保存液を用いて３０時
間保存した標本は、肝細胞の変成及び壊死は観察され
ず、肝構築もほぼ維持されていた。本発明保存液群にお
いて、僅かに肝細胞の浮腫及び洞様毛細血管隙の拡張が
観察されたが、ＵＷ液群においては観察されなかった。
再灌流後５時間で、洞様毛細血管隙への赤血球及び好中
球浸潤が両群の肝において観察された。しかし、本発明
保存液群では、肝細胞の壊死及び変性は観察されず、肝
構築も維持されていたが、ＵＷ液群の全ての肝におい
て、肝細胞の一部壊死が観察された。[Histological Examination] Deterioration and necrosis of hepatocytes were not observed in the specimens preserved for 30 hours using both preservation solutions, and liver architecture was almost maintained. In the preservation solution group of the present invention, edema of hepatocytes and expansion of sinusoidal capillary spaces were slightly observed, but not in the UW solution group.
Five hours after reperfusion, red blood cell and neutrophil infiltration into the sinusoidal space was observed in the livers of both groups. However, in the preservation solution group of the present invention, necrosis and degeneration of hepatocytes were not observed, and liver construction was maintained, but partial necrosis of hepatocytes was observed in all the livers of the UW solution group.
【００２４】［実施例４］リン酸２水素カリウム１０ミ
リモル、リン酸１水素カリウム３５ミリモル、グルコン
酸ナトリウム９０ミリモル、炭酸水素ナトリウム１０ミ
リモル、トレハロース５０ミリモル、平均分子量６０万
のヒドロキシエチル澱粉３０グラム、アロプリノール
０．７２ミリモル、デキサメタゾン４ミリグラムを１リ
ットル当たり配合し、ｐＨ値を７．３２に調整した。こ
の配合剤は、カリウムイオンとナトリウムイオンのモル
比が０．８０、浸透圧が３００ｍＯｓｍ／Ｌ、粘度が
２．３０ｃｐである臓器保存液である。Example 4 10 mmol of potassium dihydrogen phosphate, 35 mmol of potassium dihydrogen phosphate, 90 mmol of sodium gluconate, 10 mmol of sodium hydrogen carbonate, 50 mmol of trehalose, 30 g of hydroxyethyl starch having an average molecular weight of 600,000. , 0.72 mmol of allopurinol and 4 mg of dexamethasone were added per liter to adjust the pH value to 7.32. This compounding agent is an organ preservation solution having a molar ratio of potassium ion and sodium ion of 0.80, an osmotic pressure of 300 mOsm / L, and a viscosity of 2.30 cp.
【００２５】[0025]
【発明の効果】本発明により得られる臓器保存液は、長
期間安定であるばかりでなく、初期灌流液として安全に
使用できる。また、再灌流前のリンスは不必要であり、
摘出中の灌流及び再灌流後に速やかなウォッシュアウト
が可能である。INDUSTRIAL APPLICABILITY The organ preservation solution obtained by the present invention is not only stable for a long period of time, but can be safely used as an initial perfusion solution. Also, rinsing before reperfusion is unnecessary,
Rapid washout is possible after perfusion during resection and reperfusion.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 河原崎 秀雄 東京都世田谷区三宿２−28−36−101 (72)発明者 杉山 隆之 静岡県清水市美濃輪町３番12号 (72)発明者 加藤 桂子 静岡県清水市緑が丘12番８号 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Hideo Kawarazaki 2-28-36-101 Sanjuku Setagaya-ku, Tokyo (72) Inventor Takayuki Sugiyama 3-12 Minowacho, Shimizu-shi, Shizuoka (72) Inventor Keiko Kato 12-8 Midorigaoka, Shimizu City, Shizuoka Prefecture
Claims (3)
保存液において、平均分子量５０万−６５万で分子量３
５万以下のものを実質的に含まないヒドロキシエチル澱
粉を２−３．５％含有し、カリウムイオンとナトリウム
イオンのモル比が０．４−０．８であり、ｐＨ値が７．
１−７．５であり、浸透圧が２８０−３３０ｍＯｓｍ／
Ｌであり、粘度が１．８−２．５ｃｐであることを特徴
とする臓器保存液。1. An organ preservation solution comprising an electrolyte and a synthetic colloidal substance, having an average molecular weight of 500,000-650,000 and a molecular weight of 3
It contains 2-3.5% of hydroxyethyl starch which does not substantially contain 50,000 or less, the molar ratio of potassium ion to sodium ion is 0.4 to 0.8, and the pH value is 7.
1-7.5 and osmotic pressure of 280-330 mOsm /
An organ preservation solution, which is L and has a viscosity of 1.8-2.5 cp.
保存液において、炭酸ガス２０−４０％を含有する混合
ガスでガス置換したことを特徴とする請求項１記載の臓
器保存液。2. The organ preservation solution according to claim 1, wherein the organ preservation solution composed of an electrolyte and a synthetic colloid substance is gas-substituted with a mixed gas containing 20 to 40% of carbon dioxide gas.
保存液において、活性炭処理し、かつ炭酸ガスでバブリ
ング処理したことを特徴とする請求項１又は２記載の臓
器保存液。3. The organ preservation solution according to claim 1 or 2, wherein the organ preservation solution comprising an electrolyte and a synthetic colloid substance is treated with activated carbon and bubbled with carbon dioxide gas.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14465296A JPH09328401A (en) | 1996-06-06 | 1996-06-06 | Organ preservation liquid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14465296A JPH09328401A (en) | 1996-06-06 | 1996-06-06 | Organ preservation liquid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH09328401A true JPH09328401A (en) | 1997-12-22 |
Family
ID=15367073
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14465296A Pending JPH09328401A (en) | 1996-06-06 | 1996-06-06 | Organ preservation liquid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH09328401A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000072601A (en) * | 1998-08-31 | 2000-03-07 | Univ Kanagawa | Preservation method for isolated mammalian organs |
| CN109221084A (en) * | 2018-09-20 | 2019-01-18 | 中国人民解放军第二军医大学第二附属医院 | A kind of dedicated preservation liquid of pancreas and preparation method thereof |
-
1996
- 1996-06-06 JP JP14465296A patent/JPH09328401A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000072601A (en) * | 1998-08-31 | 2000-03-07 | Univ Kanagawa | Preservation method for isolated mammalian organs |
| CN109221084A (en) * | 2018-09-20 | 2019-01-18 | 中国人民解放军第二军医大学第二附属医院 | A kind of dedicated preservation liquid of pancreas and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5306711A (en) | Organ preservative solution | |
| US5145771A (en) | Rinse solution for organs and tissues | |
| SUMIMOTO et al. | 24-hour rat liver preservation using UW solution and some simplified variants | |
| CA2427765C (en) | Evaluation and preservation solution | |
| KR950015064B1 (en) | Compositions suitable for organ preservation and storage | |
| Jacobsen et al. | Effect of cooling and warming rate on glycerolized rabbit kidneys | |
| US20130171613A1 (en) | Flush preservation solution | |
| WO1981002103A1 (en) | Solution for perfusion-preserving organ to be transplanted,and preserving method | |
| JPH0640801A (en) | Solution for transplanted organs | |
| AU762062B2 (en) | Aqueous solution for preserving tissues and organs | |
| Aeba et al. | University of Wisconsin solution for pulmonary preservation in a rat transplant model | |
| CN103025155B (en) | Organ cold storage composition | |
| JPH0656601A (en) | Electrolyte solution for organ for transplantation | |
| HUP9900112A2 (en) | Preservation solution | |
| Yoshida et al. | Comparison of the effectiveness of ET-Kyoto with Euro-Collins and University of Wisconsin solutions in cold renal storage | |
| US8512940B2 (en) | Method for preserving liver in a solution comprising dibutyryl cAMP | |
| JP2009067811A (en) | Flash storage solution for donor organs | |
| JPH09328401A (en) | Organ preservation liquid | |
| Cheng et al. | Verapamil improves rat hepatic preservation with UW solution | |
| Ohwada et al. | Advantages of Celsior solution in graft preservation from non-heart-beating donors in a canine liver transplantation model | |
| CN105407716A (en) | Formulations containing poly (0-2-hydroxyethyl) starch for increasing the oxygen-content, stability and shelf life of an organ and tissue preservation solution | |
| WO2014176224A1 (en) | Organ and tissue preservation solutions having increased oxygen-content, stability and shelf life | |
| Lahnborg et al. | Disturbances of reticulo-endothelial function following experimental liver transplantation | |
| KR20010002227A (en) | Composition for the Preservation of Organs and Blood Cells | |
| Lambert et al. | Glomerular damage after kidney preservation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A711 | Notification of change in applicant |
Effective date: 20050628 Free format text: JAPANESE INTERMEDIATE CODE: A712 |
|
| A521 | Written amendment |
Effective date: 20050630 Free format text: JAPANESE INTERMEDIATE CODE: A821 |
|
| A977 | Report on retrieval |
Effective date: 20060511 Free format text: JAPANESE INTERMEDIATE CODE: A971007 |
|
| A131 | Notification of reasons for refusal |
Effective date: 20060523 Free format text: JAPANESE INTERMEDIATE CODE: A131 |
|
| A02 | Decision of refusal |
Effective date: 20060926 Free format text: JAPANESE INTERMEDIATE CODE: A02 |