EP3780954A1 - Procédé de suivi de la viabilité d'un greffon - Google Patents
Procédé de suivi de la viabilité d'un greffonInfo
- Publication number
- EP3780954A1 EP3780954A1 EP19717903.9A EP19717903A EP3780954A1 EP 3780954 A1 EP3780954 A1 EP 3780954A1 EP 19717903 A EP19717903 A EP 19717903A EP 3780954 A1 EP3780954 A1 EP 3780954A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- graft
- composition
- oxygen
- sealed container
- extracellular
- 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
- 238000000034 method Methods 0.000 title claims abstract description 42
- 238000012544 monitoring process Methods 0.000 title claims abstract description 12
- 230000035899 viability Effects 0.000 title claims description 8
- 239000000203 mixture Substances 0.000 claims abstract description 73
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 67
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 64
- 239000001301 oxygen Substances 0.000 claims abstract description 64
- 102000018146 globin Human genes 0.000 claims abstract description 35
- 108060003196 globin Proteins 0.000 claims abstract description 35
- 239000000523 sample Substances 0.000 claims abstract description 30
- 241000243818 Annelida Species 0.000 claims abstract description 28
- 239000000162 organ preservation solution Substances 0.000 claims abstract description 25
- 102000002067 Protein Subunits Human genes 0.000 claims abstract description 21
- 108010001267 Protein Subunits Proteins 0.000 claims abstract description 21
- 238000006213 oxygenation reaction Methods 0.000 claims abstract description 9
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 102000001554 Hemoglobins Human genes 0.000 claims description 50
- 108010054147 Hemoglobins Proteins 0.000 claims description 50
- 239000000243 solution Substances 0.000 claims description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims description 12
- 241000243812 Arenicola marina Species 0.000 claims description 8
- 238000011088 calibration curve Methods 0.000 claims description 8
- INGWEZCOABYORO-UHFFFAOYSA-N 2-(furan-2-yl)-7-methyl-1h-1,8-naphthyridin-4-one Chemical compound N=1C2=NC(C)=CC=C2C(O)=CC=1C1=CC=CO1 INGWEZCOABYORO-UHFFFAOYSA-N 0.000 claims description 7
- 239000003792 electrolyte Substances 0.000 claims description 7
- 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 claims description 6
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 claims description 6
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 claims description 6
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 claims description 6
- 229960003459 allopurinol Drugs 0.000 claims description 6
- 239000008103 glucose Substances 0.000 claims description 6
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 claims description 6
- 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 claims description 5
- 229920001612 Hydroxyethyl starch Polymers 0.000 claims description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 5
- 229930195725 Mannitol Natural products 0.000 claims description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 5
- 229940050526 hydroxyethylstarch Drugs 0.000 claims description 5
- 239000000594 mannitol Substances 0.000 claims description 5
- 235000010355 mannitol Nutrition 0.000 claims description 5
- 238000005259 measurement Methods 0.000 claims description 5
- 239000012528 membrane Substances 0.000 claims description 5
- 229920001223 polyethylene glycol Polymers 0.000 claims description 5
- 239000011591 potassium Substances 0.000 claims description 5
- 229910052700 potassium Inorganic materials 0.000 claims description 5
- 238000002054 transplantation Methods 0.000 claims description 5
- 239000003963 antioxidant agent Substances 0.000 claims description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
- 241000142415 Arenicolidae Species 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- 229920002307 Dextran Polymers 0.000 claims description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- 241000243820 Polychaeta Species 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 3
- 229910001882 dioxygen Inorganic materials 0.000 claims description 3
- 235000013922 glutamic acid Nutrition 0.000 claims description 3
- 239000004220 glutamic acid Substances 0.000 claims description 3
- 150000003893 lactate salts Chemical class 0.000 claims description 3
- 229940099584 lactobionate Drugs 0.000 claims description 3
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 claims description 3
- 239000011777 magnesium Substances 0.000 claims description 3
- 235000000346 sugar Nutrition 0.000 claims description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 claims description 2
- 229930091371 Fructose Natural products 0.000 claims description 2
- 239000005715 Fructose Substances 0.000 claims description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 2
- 241001534230 Nereididae Species 0.000 claims description 2
- 241000243827 Nereis Species 0.000 claims description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- 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 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 235000001014 amino acid Nutrition 0.000 claims description 2
- 150000001413 amino acids Chemical class 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 239000000084 colloidal system Substances 0.000 claims description 2
- 229940050410 gluconate Drugs 0.000 claims description 2
- 229930195712 glutamate Natural products 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- 238000004020 luminiscence type Methods 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000000565 sealant Substances 0.000 claims description 2
- 229910052709 silver Inorganic materials 0.000 claims description 2
- 239000004332 silver Substances 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 150000008163 sugars Chemical class 0.000 claims description 2
- 239000003064 xanthine oxidase inhibitor Substances 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims 1
- 229910001415 sodium ion Inorganic materials 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000009472 formulation Methods 0.000 description 10
- 239000003761 preservation solution Substances 0.000 description 10
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 8
- 210000000056 organ Anatomy 0.000 description 7
- 238000004321 preservation Methods 0.000 description 7
- 238000007789 sealing Methods 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 108010024636 Glutathione Proteins 0.000 description 5
- 229960003180 glutathione Drugs 0.000 description 5
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 4
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
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- 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 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 3
- 235000019796 monopotassium phosphate Nutrition 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
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- 229920001184 polypeptide Polymers 0.000 description 3
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 238000012883 sequential measurement Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000003068 static effect Effects 0.000 description 3
- 101100283604 Caenorhabditis elegans pigk-1 gene Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 102000019197 Superoxide Dismutase Human genes 0.000 description 2
- 108010012715 Superoxide dismutase Proteins 0.000 description 2
- 108700042768 University of Wisconsin-lactobionate solution Proteins 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- LLSDKQJKOVVTOJ-UHFFFAOYSA-L calcium chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Ca+2] LLSDKQJKOVVTOJ-UHFFFAOYSA-L 0.000 description 2
- 229940052299 calcium chloride dihydrate Drugs 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000005496 eutectics Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002262 irrigation Effects 0.000 description 2
- 238000003973 irrigation Methods 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 229940050906 magnesium chloride hexahydrate Drugs 0.000 description 2
- DHRRIBDTHFBPNG-UHFFFAOYSA-L magnesium dichloride hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[Cl-].[Cl-] DHRRIBDTHFBPNG-UHFFFAOYSA-L 0.000 description 2
- 229940091250 magnesium supplement Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- BIRNWOIQDVFTSP-WWNCWODVSA-M potassium (2R,3R,4R,5R)-2,3,5,6-tetrahydroxy-4-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhexanoate Chemical compound [K+].OC[C@@H](O)[C@@H](O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O)[C@H](O)[C@@H](O)C([O-])=O BIRNWOIQDVFTSP-WWNCWODVSA-M 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- JKHVDAUOODACDU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(2,5-dioxopyrrol-1-yl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCN1C(=O)C=CC1=O JKHVDAUOODACDU-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 101100421200 Caenorhabditis elegans sep-1 gene Proteins 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 108700027941 Celsior Proteins 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
- 241001573881 Corolla Species 0.000 description 1
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- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108010064719 Oxyhemoglobins Proteins 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
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- 238000009582 blood typing Methods 0.000 description 1
- 229960005069 calcium Drugs 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
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- VTYGSWGUBDXCRA-UHFFFAOYSA-L dipotassium;2-oxopentanedioate Chemical class [K+].[K+].[O-]C(=O)CCC(=O)C([O-])=O VTYGSWGUBDXCRA-UHFFFAOYSA-L 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
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- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
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- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0236—Mechanical aspects
- A01N1/0263—Non-refrigerated containers specially adapted for transporting or storing living parts whilst preserving, e.g. cool boxes, blood bags or "straws" for cryopreservation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/403—Cells and electrode assemblies
- G01N27/406—Cells and probes with solid electrolytes
- G01N27/407—Cells and probes with solid electrolytes for investigating or analysing gases
- G01N27/409—Oxygen concentration cells
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0205—Chemical aspects
- A01N1/021—Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
- A01N1/0226—Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0236—Mechanical aspects
- A01N1/0263—Non-refrigerated containers specially adapted for transporting or storing living parts whilst preserving, e.g. cool boxes, blood bags or "straws" for cryopreservation
- A01N1/0273—Transport containers
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0278—Physical preservation processes
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0236—Mechanical aspects
- A01N1/0242—Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components
- A01N1/0247—Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components for perfusion, i.e. for circulating fluid through organs, blood vessels or other living parts
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2496/00—Reference solutions for assays of biological material
- G01N2496/70—Blood gas control solutios containing dissolved oxygen, bicarbonate and the like
Definitions
- the present invention relates to a method of monitoring (monitoring) the oxygenation of a graft, waiting for its transplantation.
- the delivery of grafts requires particularly strict hygiene and temperature conditions in order to keep the graft in a state of being implanted.
- the conventional graft delivery procedure comprises a first explantation step in which the graft is taken from a donor under aseptic conditions, usually in the operating room. The graft is then placed in a sealed pot which is placed in a first sealed plastic bag by a clip closure. This set is then placed in a second plastic bag of the same type and closed in the same way. The whole is arranged in an insulating transport cooler filled with a refrigerant substance (for example ice and / or eutectic gels) which makes it possible to maintain the graft at a temperature slightly above 0 ° C.
- a refrigerant substance for example ice and / or eutectic gels
- the bags covering the sealed pot preserve the graft from contact with the refrigerant and the ambient air potentially carrying germs. Arrived at destination, the set consisting of the two bags and the jar containing the graft is removed from the insulating transport cooler and introduced into the implantation room, which is also aseptic.
- the graft has a limited life span, which varies by organ (for example 4 hours for a heart, 10 hours for a liver and lungs, 36 hours for a kidney).
- the Applicant has now found a method answering this problem.
- This method is simple to perform, and can extend the life of the graft.
- the method according to the invention makes it possible to evaluate the oxygenation of the graft.
- the subject of the invention is therefore a method for monitoring (or monitoring) the oxygenation of a graft, comprising:
- the organ preservation solution is mixed with at least one oxygen carrier, to obtain a composition.
- the organ preservation solution is mixed with at least one oxygen carrier selected from Annelides extracellular hemoglobin, its globins and globin protomers, to obtain a composition in the sealed container;
- steps c) and d) being performed simultaneously or in any order.
- the method according to the invention is thus concerned with a physiological parameter, i.e. the amount of dissolved oxygen present in the medium surrounding the graft. It thus accurately reflects the viability of the graft.
- the method according to the invention may comprise a step e) of transporting the sealed container, in particular to the place of transplantation of the graft to a recipient.
- the recipient is preferably a mammal.
- the recipient is a human, in particular waiting for a transplant, or a non-human mammal, for example a pig.
- the method according to the invention comprises a step a) of supplying an organ preservation solution in a sealed container.
- an organ preservation solution is in particular as described below.
- the organ preservation solution is mixed with at least one oxygen carrier.
- the organ preservation solution comprises at least one oxygen carrier.
- Such an oxygen carrier is advantageously selected from reversibly oxygen-binding molecules.
- a transporter is chosen from Annelides extracellular hemoglobin, globins and globin protomers.
- the method according to the invention thus comprises a step a) of mixing an organ preservation solution with at least one oxygen carrier, preferably at least one molecule chosen from Annelides extracellular hemoglobin. , globins and protomers of globin, to obtain a composition, in a sealed container.
- step a) thus comprises:
- At least one oxygen carrier preferably at least one globin, a globin protomer or an extracellular Annelides hemoglobin, and
- the oxygen carrier according to the invention is preferably at least one molecule chosen from Annelides extracellular hemoglobin, globins and globin protomers.
- the extracellular hemoglobin of Annelids is present in the three classes of Annelids: Polychaetes, Oligochaetes and Achetes. We speak of extracellular hemoglobin because it is naturally not contained in a cell, and can therefore circulate freely in the blood system without chemical modification to stabilize or make it functional.
- Annelides extracellular hemoglobin is a giant biopolymer of molecular weight between 2000 and 4000 kDa, consisting of about 200 polypeptide chains between 4 and 12 different types that are generally grouped into two categories.
- the first category comprising 144 to 192 elements, groups together so-called "functional" polypeptide chains which carry an active heme-type site and are capable of reversibly binding oxygen; they are globin-like chains with masses between 15 and 18 kDa and are very similar to vertebrate type a and b chains.
- the second category counting from 36 to 42 elements, groups polypeptide chains called "structure” or “linkers” having little or no active site but allowing the assembly of subunits called twelfths or protomers.
- Each molecule of hemoglobin consists of two superimposed hexagons which are called hexagonal bilayer and each hexagon is itself formed by the assembly of six subunits (or “twelfths” or “protomers”). ) in the form of a drop of water.
- the native molecule consists of twelve of these subunits (dodecamer or protomer). Each subunit has a molecular weight between 200 and 250 kDa, and is the functional unit of the native molecule.
- the extracellular hemoglobin of Annelids is selected from the extracellular hemoglobins of Polychaete Annelids, preferably from the extracellular hemoglobins of the family Arenicolidae and the extracellular hemoglobins of the family Nereididae. Even more preferentially, the extracellular hemoglobin of Annelides is chosen from the extracellular hemoglobin of Arenicola marina and the extracellular hemoglobin of Nereis, more preferably the extracellular hemoglobin of Arenicola marina.
- the composition may also comprise at least one globin protomer of Annelides extracellular hemoglobin. Said protomer constitutes the functional unit of native hemoglobin, as indicated above.
- composition may also comprise at least one globin chain of Annelides extracellular hemoglobin.
- a globin chain may in particular be chosen from the Ax and / or Bx type globin chains of Annelides extracellular hemoglobin.
- Annelides extracellular hemoglobin and its globin protomers have intrinsic superoxide dismutase (SOD) activity, and therefore require no antioxidants to function, in contrast to the use of mammalian hemoglobin, for which the molecules Antioxidants are contained inside the red blood cell and are not related to hemoglobin.
- SOD superoxide dismutase
- Annelides extracellular hemoglobin, its globin protomers and / or globins do not require a cofactor to function, unlike mammalian hemoglobin, especially human hemoglobin.
- the extracellular hemoglobin of Annelides, its protomers of globin and / or its globins not having a blood typing, they make it possible to avoid any problem of immunological reaction.
- the extracellular hemoglobin of Annelids in particular the extracellular hemoglobin of Arenicola marina, makes it possible to transfer oxygen to the graft for several hours, for example at least 10 hours, preferably at least 15 hours. hours, preferably at least 20 hours, preferably at least 21, 22, 23, 25 or 28 hours, especially compared to the preservation solution alone.
- the extracellular hemoglobin of Annelides makes it possible to maintain the pO 2 of the solution or composition in which the graft is immersed at a constant level for several hours, for example at least 10 hours, preferably at least 15 hours, preferably at least 20 hours, preferably at least 21, 22, 23, 25, 28 or 30 hours.
- the organ preservation solution makes it possible to maintain the basic metabolism of the constituent cells of the graft. It serves a triple purpose: to wash the arterial blood of the graft, to bring the graft homogeneously to the desired temperature of preservation, and to protect and prevent lesions caused by ischemia and reperfusion and to optimize the recovery of function.
- the organ preservation solution is therefore clinically acceptable.
- the organ preservation solution is an aqueous solution having a pH of between 6.5 and 7.5, comprising salts, preferably chloride, sulfate, sodium, calcium, magnesium and potassium ions; sugars, preferably mannitol, raffinose, sucrose, glucose, fructose, lactobionate (which is a sealant), or gluconate; antioxidants, preferably glutathione; active agents, preferably xanthine oxidase inhibitors such as allopurinol, lactates, amino acids such as histidine, glutamic acid (or glutamate), tryptophan; and optionally colloids such as hydroxyethyl starch, polyethylene glycol or dextran.
- salts preferably chloride, sulfate, sodium, calcium, magnesium and potassium ions
- sugars preferably mannitol, raffinose, sucrose, glucose, fructose, lactobionate (which is a sealant), or glucon
- the organ preservation solution is chosen from:
- Hydroxyethyl starch 50 g / L
- IGL-1 ® having an osmolality of 320 mOsm / kg and a pH of 7.4, of the following formulation, for one liter in water:
- Polyethylene glycol (molecular weight: 35 kDa): 1 g / L,
- Lactobionic acid 80 mM
- Multi Organs Abs ® 30 and SCOT Vascular Grafts ® Macopharma comprising in particular both the high molecular weight polyethylene glycol (20 kDa),
- BMPS Belzer ® or Belzer solution infusion machine or KPS1, especially comprising 100 mEq / L of sodium, 25 mEq / L potassium, pH 7.4 at ambient temperature, and having an osmolarity of 300 mOsm / L,
- Soltran ® having an osmolality of 486 mOsm / kg and a pH of 7.1, and of the following formulation for one liter in water:
- Glucose 5 mM Ringer lactate ® , of the following formulation, in water, the pH being between 6.0 and 7.5 at room temperature, and having an osmolarity of 276.8 mOsmol / L:
- Lactates 27.7 mM
- Steen® solution comprising human serum albumin, dextran and extracellular electrolytes with a low concentration of potassium.
- the composition of step a) has a pH of between 6.5 and 7.6, and comprises: at least one globin, a globin protomer or an extracellular hemoglobin of Annelides, preferably of Arenicolidae,
- NaOH preferably in an amount of between 20 and 125 mM
- KH 2 PO 4 preferably in an amount of between 20 and 25 mM
- MgCl 2 preferably in an amount of between 3 and 5 mM
- adenosine preferably in an amount of between 3 and 5 mM
- glutathione preferably in an amount of between 2 and 4 mM
- allopurinol preferably in an amount of between 0 and 1 mM
- the extracellular hemoglobin of Annelides, its protomers of globin and / or its globins is present at a concentration, relative to the final volume of composition, of between 0.001 mg / ml and 100 mg / ml, preferably between 0.005 mg and 20 mg / ml, more preferably between 0.5 mg / ml and 5 mg / ml, in particular 1 mg / ml.
- the composition of step a) has an osmolarity of between 250 and 350 mOsm / L, preferably between 275 and 310 mOsm / L, preferably about 302 mOsm / L.
- the sealed container used in the process according to the invention, especially in step a), is any container suitable for the transport of graft.
- Such containers are known from the prior art.
- the container is as described in application FR2994163.
- the sealed container corresponds to the Biotainer 2.8L kit. It can be included in a carrying case, such as the one marketed under the name Vitalpack® EVO TM by E3 Cortex.
- the sealed container is a pot (or rigid primary packaging) - of sufficient size to contain the graft and the composition of step a) - closed by a lid provided with a handle.
- the cover comprises an opening, preferably circular, allowing the passage of the oxygen probe. This opening is waterproof: the edges of the opening are preferably coated with a seal and allow the attachment of the oxygen sensor.
- the sealed container is placed in a flexible plastic container as defined below, defining a first sealed internal volume called useful volume and a second sealed volume called reserve volume adjacent to the first volume, a sealing member extending between the two volumes to define a hermetic border between the two volumes.
- the sealed container is placed in the useful volume.
- the sealed container, placed in the useful volume of the container can be placed in a carrying case.
- a refrigerant, especially used during transport, can be placed in the container.
- the flexible plastic container defines a first hermetic interior volume (useful volume) and a second hermetic volume (reserve volume) adjacent to the first volume, a sealing member extending between the two volumes to define a boundary hermetic between the two volumes.
- the first volume has at its end opposite the second volume a device for opening and sealing a first access to the first volume, the second volume being shaped so that a cut through the second volume, releases two prehensile portions of the container whose spacing removes the hermetic boundary between the two volumes to form a second access to the first volume distinct from the first access.
- the cutting of the reserve volume protects the sealing element of any retention of liquid especially from the refrigerant substance used during transport.
- any traces of liquid remain on the outer wall of the container, the inside of the prehensile portions (and therefore the sealing element) being preserved from any pollution.
- the spacing of the prehensile portions ensures that no pollution can migrate to the sealing member.
- the introduction of the sealed container by a first access and its extraction by a second access preserves the sealed container, preventing it from being exposed to possible contamination of the first access that would have occurred during packaging operations.
- such a container is made by superposition of two sheets of flexible plastic material having free edges secured together.
- the container can be easily made to the dimensions of the contents (sealed container).
- the secured edges of the plastic sheets can be secured with peelable bonds. This then allows, by simple pulling, a corolla opening of the bag over its entire length and releases the contents without it being necessary to roll up the package around the sealed container.
- the sealing element comprises a peelable connection between two plastic surfaces.
- step a an organ preservation solution contained in a sealed container is thus obtained.
- a hemoglobin, globin, or Annelid globin protomer composition and an organ preservation solution, contained in a sealed container are preferably obtained.
- Step b) then comprises immersing the graft in this composition.
- the graft can be any organ that can be transplanted.
- the graft is a kidney, a heart, a pancreas, a lung, a liver or a whole heart-lungs.
- a graft immersed in the solution obtained in step a) or in the composition obtained in step a) is then obtained.
- the graft is fully immersed in the solution or composition.
- the amount of solution or composition used varies according to the volume of the graft.
- the weight ratio composition in milliliter: graft (in grams) is between 2: 1 and 4: 1.
- the method according to the invention comprises introducing an oxygen probe into the solution or composition obtained in a), or into the composition of step b): this is step c).
- the oxygen probe is directly introduced into the composition, and not on the graft.
- the conventional graft oxygenation monitoring typically comprises the evaluation of the total organ oxygen consumption rate (WOOCR), and uses an oxygen probe which is placed directly on the irrigation systems of the graft, for example on the artery and the vein (thus upstream and downstream) of the graft.
- WOOCR total organ oxygen consumption rate
- Such manipulation is not necessarily easy to implement, takes a certain time (at least a few minutes), and can be harmful for the graft.
- the oxygen sensor is directly introduced into the composition or the solution in which the graft bathes. This avoids any invasive step in the graft.
- step c) of the process according to the invention preferably comprises the introduction of a single oxygen probe into the solution or composition obtained in a), or into the composition of step b).
- the oxygen sensor is preferably unique.
- the process according to the invention does not use two oxygen probes.
- the oxygen probe introduced is not particularly brought into contact with the graft, in particular is not placed directly on a graft irrigation system (i.e. artery or vein).
- the oxygen probe is introduced into the organ preservation solution comprising at least one oxygen carrier, in which the graft is immersed.
- the oxygen probe, or oximeter, used makes it possible to measure the concentration of molecular oxygen in the liquid mixture obtained in a) or b), thus to measure the quantity of dissolved oxygen present in the solution or composition of step a) or in the composition of step b). This measure avoids any invasive step in the graft.
- the oxygen probe is a Clark electrode. It comprises a probe head coated with a membrane, the probe head consisting of an electrode composed of a platinum cathode and a silver anode immersed in an electrolyte (in particular an alkaline solution of sodium phosphate Na 3 PO 4, for example at 50 g / L).
- an electrolyte in particular an alkaline solution of sodium phosphate Na 3 PO 4, for example at 50 g / L.
- the electrolyte - electrolyte assembly is separated from the liquid medium by the membrane, which is permeable to oxygen but impermeable to water and ions.
- the operating principle is as follows: a potential difference (for example 800 mV) is established between anode and cathode, the oxygen present between the electrodes is reduced. The intensity of the resulting current is proportional to the oxygen concentration in the electrolyte.
- a potential difference for example 800 mV
- the oxygen sensor is a sensor for measuring dissolved oxygen by optical measurement, in particular by luminescence.
- it does not include a membrane or electrolyte.
- Such a probe is commercially available, especially under the reference Optod (Digisens range) by Ponsel.
- the oxygen probe is a portable model, preferably a pocket model.
- it is the ProfiLine Oxi 3205 model of WTW.
- the probe is sealed. Preferably, it is fixed on the lid of the sealed container.
- step c) the oxygen probe is placed directly in the composition, therefore in the medium in which the graft is immersed. This is much simpler and convenient, and faster. In addition, this step is not harmful for the graft because strictly non-invasive.
- the oxygen probe may be directly introduced into the solution or composition obtained in step a), and then the graft is added to said composition.
- the graft is first added to the solution or composition of step a), and then the oxygen probe is introduced into the resulting mixture.
- the probe since the probe is in particular fixed on the lid of the sealed container, it can be introduced into the mixture at the same time as the step of fixing the lid on the sealed container, thus at the same time as step d).
- the method according to the invention comprises a step d) of closing the sealed container.
- steps c) and d) can be performed simultaneously or in any order.
- the probe in the case where the probe is fixed on the lid of the sealed container, it can be introduced into the mixture at the same time as the step of fixing the lid on the sealed container; in this case steps c) and d) are simultaneous.
- step c) takes place before step d); either after closing the container: in this case, step d) takes place before step c).
- the graft can be transported in good conditions to its destination.
- the monitoring of the oxygenation of the graft is performed in real time.
- the transport can be carried out by any means (land or air transport), and requires no special condition. This is advantageous compared to the use of oxygen gas, which is present in specific containers (bottles in general) maintained at a given pressure, so less easy to transport (especially by air).
- Step e) of transport can be carried out by placing the sealed container in a suitable container.
- a suitable container is known from the prior art, and is suitable for graft transport.
- this container is a carrying case, for example as described in application EP1688124. It is more particularly a bag for the transport of a graft for a transplant involving at least one inner wall delimiting at least two compartments each having a working part, a first compartment being intended to receive one or more bottles and / or pots of biological samples from the donor (for example blood) protected by a block of flexible and elastic material while a second compartment contains an isothermal tank for receiving the sealed container according to the invention.
- the isothermal tank may comprise crushed ice or blocks of eutectic material.
- the transport is carried out by placing the sealed container in a bag marketed under the name Vitalpack® EVO TM by E3 Cortex.
- the graft can be preserved in dynamic perfusion.
- the process according to the invention may also comprise, after step d) and / or e), a step e ') of establishing a calibration curve representing the pO 2 of the composition obtained in a) in which the graft is immersed, optionally normalized with respect to graft weight, as a function of time.
- the pO 2 is in particular expressed in mmHg or in bar or in%.
- this calibration curve makes it possible to deduce, for a given graft, the optimal duration of oxygenation. For example, for a kidney, obtaining a calibration curve makes it possible to deduce the maximum duration of oxygenation, if a pO 2 of at least 50% is desired.
- the present invention also relates to a method for determining the viability of a graft, including the use of the calibration curve described above. This curve is obtained in particular according to the method described above.
- Such a method for determining the viability of a graft comprises in particular the following steps:
- step (i) providing an organ preservation solution in a sealed container.
- step (i) comprises mixing an organ preservation solution with at least one oxygen carrier selected from Annelides extracellular hemoglobin, its globins and globin protomers, in order to obtain a composition, in a sealed container;
- step (ii) the maximum time elapsing between step (ii) and the end of step (v) is determined according to the calibration curve described above, keeping said pO2 at a physiologically acceptable value.
- physiologically acceptable pO 2 value is meant a value that allows viability of the graft.
- the purpose of this study is to establish a link between the effects of extracellular hemoglobin Arenicola marina (M101) on the reduction of ischemia / reperfusion injury in static cold preservation and the mechanism of action of the molecule.
- M101 extracellular hemoglobin Arenicola marina
- sequential measurements are performed both at the functional level and at the cellular level.
- HEM02life® Hemarina SA
- HEM02life® Hemarina SA
- the kidneys were washed with 200 ml of UW (Bridge to Life) organ preservation solution or 200 ml of UW + 1 g / L HEM02life®. The kidneys were weighed after tightening. The kidneys were immersed immediately in an organ reservoir hermetically sealed and filled with 800 ml of their respective solutions (standard solution: UW and UW + HEM02life® 1 g / L) at 6 ° C.
- Oxygen binding the functionality of M101 is followed by spectrophotometry allowing the characterization of oxyhemoglobin (Hb02) and deoxyhemoglobin (deoxy-Hb).
- the absorption spectra are recorded over the range 370-640 nm (UVmc2, SAFAS, Monaco) according to the method described by Thuiller et al. 201 1, Supplementation With a New Therapeutic Oxygen Carrier Reduces Chronic Fibrosis and Organ Dysfunction in Kidney Static Preservation: A New 02 Therapeutic Molecule Improves Static Kidney Preservation. Am J Transplant. 201 Sep 1; 1 (9): 1845-60.
- Dissolved 02 (d02) and pH are measured using a 02 sensor (WTW Oxi 3205) and a pH sensor (WTW pH31 10) directly in the closed (hermetic) tank.
- the spectral signature of M101 from 52h to 55h is characteristic of deoxyHb and shows that the molecule has transferred all its oxygen to the solution.
- the pO 2 was measured at 100% O 2 dissolved in both tanks at t0 and did not decrease for 55 h at 6 ° C.
- the pO 2 is indexed to 100% O 2 dissolved at 6 ° C at the beginning of the experiment. The first hour, the pO 2 decreases rapidly to 50% in both solutions.
- the results on the pO 2 are in FIG. 1.
- the pO 2 continues to decrease sharply in the solution which does not contain HEM02life® to reach 0% after 24 h.
- HEM02life® is a good oxygen transporter and is able to distribute it as it is stored, up to 52 hours.
- the parallel measurements of pO 2 and the functional analysis show that at that time, dissolved G0 2 is at 0% in the preservation solution, which means that HEM02life® delivered all its transported oxygen.
- HEM02life® is a very good oxygen donor to a fluid. The molecule distributes oxygen to maintain 50% O 2 dissolved from 1 h to 30 h, then until the depletion of oxygen transported from 30h to 52h. A decline is observable at 30h and G02 dissolved slowly decreases to 0% at 52h. Without HEM02life®, 50% of the pO 2 is reached after 1 h, and the pO 2 is already 0% after 24 h.
- the pH results are in FIG. 2.
- the pH was measured. It is very stable in both tanks containing UW (pH 7.4), and UW + HEM02life® 1 g / L (pH 7.5).
- the pH is very stable in the HEM02life® solution 1 g / L, around 7.4, from the beginning to 55 hours.
- the pH in the UW preservation solution without HEM02life® 1 g / L decreases from 7.4 to 7.1 in 55 hours. The difference is probably explained by the acidosis of the reservoir containing the kidney without HEM02life® 1 g / L.
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Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR1853340A FR3080002B1 (fr) | 2018-04-17 | 2018-04-17 | Procede de suivi de la viabilite d'un greffon |
PCT/EP2019/059685 WO2019201863A1 (fr) | 2018-04-17 | 2019-04-15 | Procédé de suivi de la viabilité d'un greffon |
Publications (1)
Publication Number | Publication Date |
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EP3780954A1 true EP3780954A1 (fr) | 2021-02-24 |
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Application Number | Title | Priority Date | Filing Date |
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EP19717903.9A Pending EP3780954A1 (fr) | 2018-04-17 | 2019-04-15 | Procédé de suivi de la viabilité d'un greffon |
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Country | Link |
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US (1) | US20210172900A1 (fr) |
EP (1) | EP3780954A1 (fr) |
FR (1) | FR3080002B1 (fr) |
WO (1) | WO2019201863A1 (fr) |
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WO2024023068A1 (fr) * | 2022-07-26 | 2024-02-01 | Hemarina | Utilisation d'une molécule d'annélide pour le traitement et/ou la prévention d'au moins une maladie associée à l'activation du complément |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
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FR2881723B1 (fr) | 2005-02-08 | 2007-04-27 | E3 Cortex Sa | Sacoche pour le transport de greffons en vue de transplantation |
WO2010128159A1 (fr) * | 2009-05-07 | 2010-11-11 | Hemarina | Nouvelle hémoglobine et ses utilisations |
FR2975869B1 (fr) * | 2011-05-31 | 2017-03-03 | Hemarina | Composition de preservation d'organe et utilisations |
FR2994163B1 (fr) | 2012-07-31 | 2014-08-22 | E3 Cortex | Conteneur hermetique et procede d'emballage mettant en oeuvre un tel conteneur |
US8785116B2 (en) * | 2012-08-10 | 2014-07-22 | Paragonix Technologies, Inc. | Methods for evaluating the suitability of an organ for transplant |
-
2018
- 2018-04-17 FR FR1853340A patent/FR3080002B1/fr active Active
-
2019
- 2019-04-15 WO PCT/EP2019/059685 patent/WO2019201863A1/fr unknown
- 2019-04-15 EP EP19717903.9A patent/EP3780954A1/fr active Pending
- 2019-04-15 US US17/047,945 patent/US20210172900A1/en active Pending
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US20210172900A1 (en) | 2021-06-10 |
FR3080002B1 (fr) | 2020-11-20 |
FR3080002A1 (fr) | 2019-10-18 |
WO2019201863A1 (fr) | 2019-10-24 |
BR112020021030A2 (pt) | 2021-01-19 |
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