FR2956330A1 - Dissolving a gas or gas mixture in a liquid solution comprises cooling the solution at a specified temperature, contacting the obtained solution with a gas or gas mixture and dissolving a part of gas in the solution and recovering - Google Patents
Dissolving a gas or gas mixture in a liquid solution comprises cooling the solution at a specified temperature, contacting the obtained solution with a gas or gas mixture and dissolving a part of gas in the solution and recovering Download PDFInfo
- Publication number
- FR2956330A1 FR2956330A1 FR1051148A FR1051148A FR2956330A1 FR 2956330 A1 FR2956330 A1 FR 2956330A1 FR 1051148 A FR1051148 A FR 1051148A FR 1051148 A FR1051148 A FR 1051148A FR 2956330 A1 FR2956330 A1 FR 2956330A1
- Authority
- FR
- France
- Prior art keywords
- gas
- liquid solution
- solution
- gases
- dissolved
- 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- Withdrawn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
- 239000006193 liquid solution Substances 0.000 title claims abstract description 41
- 239000000203 mixture Substances 0.000 title claims abstract description 26
- 238000001816 cooling Methods 0.000 title claims abstract description 19
- 239000007789 gas Substances 0.000 claims abstract description 85
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims abstract description 28
- 238000000034 method Methods 0.000 claims abstract description 22
- 229910052786 argon Inorganic materials 0.000 claims abstract description 14
- 210000000056 organ Anatomy 0.000 claims description 23
- 239000012620 biological material Substances 0.000 claims description 18
- 239000007788 liquid Substances 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 11
- 210000004185 liver Anatomy 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- 238000004321 preservation Methods 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 210000003734 kidney Anatomy 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 229910052724 xenon Inorganic materials 0.000 claims description 5
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 claims description 5
- 206010030113 Oedema Diseases 0.000 claims description 4
- 210000002216 heart Anatomy 0.000 claims description 4
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 3
- 239000001307 helium Substances 0.000 claims description 3
- 229910052734 helium Inorganic materials 0.000 claims description 3
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 229910000037 hydrogen sulfide Inorganic materials 0.000 claims description 3
- 210000000936 intestine Anatomy 0.000 claims description 3
- 229910052743 krypton Inorganic materials 0.000 claims description 3
- DNNSSWSSYDEUBZ-UHFFFAOYSA-N krypton atom Chemical compound [Kr] DNNSSWSSYDEUBZ-UHFFFAOYSA-N 0.000 claims description 3
- 150000002632 lipids Chemical class 0.000 claims description 3
- 229910052754 neon Inorganic materials 0.000 claims description 3
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 claims description 3
- 230000003204 osmotic effect Effects 0.000 claims description 3
- 210000000496 pancreas Anatomy 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 229910052704 radon Inorganic materials 0.000 claims description 3
- SYUHGPGVQRZVTB-UHFFFAOYSA-N radon atom Chemical compound [Rn] SYUHGPGVQRZVTB-UHFFFAOYSA-N 0.000 claims description 3
- 239000011555 saturated liquid Substances 0.000 claims description 3
- 239000000463 material Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 description 25
- 238000002054 transplantation Methods 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 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 description 6
- 239000000082 organ preservation Substances 0.000 description 6
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- 239000003642 reactive oxygen metabolite Substances 0.000 description 5
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 4
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- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
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- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 2
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 2
- 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 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
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- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
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- SOHWLKBJOBHROR-MCDZGGTQSA-N (2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol;phosphoric acid Chemical compound OP(O)(O)=O.C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O SOHWLKBJOBHROR-MCDZGGTQSA-N 0.000 description 1
- KPGXRSRHYNQIFN-UHFFFAOYSA-L 2-oxoglutarate(2-) Chemical compound [O-]C(=O)CCC(=O)C([O-])=O KPGXRSRHYNQIFN-UHFFFAOYSA-L 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
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- 108090000695 Cytokines Proteins 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
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 208000034706 Graft dysfunction Diseases 0.000 description 1
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 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 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- DVKFVGVMPLXLKC-PUGXJXRHSA-N [(2s,3r,4s,5s,6r)-2-[(2s,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] dihydrogen phosphate Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@]1(CO)[C@@]1(OP(O)(O)=O)[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DVKFVGVMPLXLKC-PUGXJXRHSA-N 0.000 description 1
- 230000007950 acidosis Effects 0.000 description 1
- 208000026545 acidosis disease Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 1
- 229960003459 allopurinol Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
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- 239000011575 calcium Substances 0.000 description 1
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- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 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
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- MWEQTWJABOLLOS-UHFFFAOYSA-L disodium;[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-oxidophosphoryl] hydrogen phosphate;trihydrate Chemical compound O.O.O.[Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP([O-])(=O)OP(O)([O-])=O)C(O)C1O MWEQTWJABOLLOS-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
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- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 230000010247 heart contraction Effects 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 229940050526 hydroxyethylstarch Drugs 0.000 description 1
- 239000000819 hypertonic solution Substances 0.000 description 1
- 229940021223 hypertonic solution Drugs 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- 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 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 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 description 1
- 238000011084 recovery Methods 0.000 description 1
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- 238000005057 refrigeration Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
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
- A01N1/10—Preservation of living parts
- A01N1/12—Chemical aspects of preservation
- A01N1/122—Preservation or perfusion media
- A01N1/125—Freeze protecting agents, e.g. cryoprotectants or osmolarity regulators
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/20—Mixing gases with liquids
- B01F23/23—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids
- B01F23/231—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids by bubbling
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/20—Mixing gases with liquids
- B01F23/23—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids
- B01F23/2319—Methods of introducing gases into liquid media
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/70—Pre-treatment of the materials to be mixed
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/70—Pre-treatment of the materials to be mixed
- B01F23/702—Cooling materials
Landscapes
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
L'invention concerne un procédé de dissolution d'un gaz ou d'un mélange de gaz dans une solution liquide comprenant les étapes de refroidissement de la solution liquide à une température de refroidissement inférieure à 10 °C de façon à obtenir une solution liquide froide ; de mise en contact de la solution liquide froide obtenue à l'étape a) avec un gaz ou un mélange de gaz et de dissolution d'au moins une partie dudit ou desdits gaz dans ladite solution liquide froide ; et de récupération d'une solution liquide contenant le ou les gaz dissous. Avantageusement, le gaz est de l'argon.The invention relates to a method for dissolving a gas or a mixture of gases in a liquid solution comprising the steps of cooling the liquid solution to a cooling temperature of less than 10 ° C. so as to obtain a cold liquid solution ; contacting the cold liquid solution obtained in step a) with a gas or a mixture of gases and dissolving at least a portion of said one or more gases in said cold liquid solution; and recovering a liquid solution containing the dissolved gas or gases. Advantageously, the gas is argon.
Description
La présente invention concerne un procédé pour augmenter la solubilité d'un gaz ou d'un mélange de gaz dans une solution liquide utilisée pour la conservation de matières biologiques, comme des organes, des tissus ou des cellules, en particulier des matières biologiques à des fins de transplantation. The present invention relates to a method for increasing the solubility of a gas or a mixture of gases in a liquid solution used for the preservation of biological materials, such as organs, tissues or cells, in particular biological materials at biological levels. transplantation purposes.
La conservation et la transplantation d'un organe sont associées aux lésions causées par une reperfusion ischémique dans lesdits organes. Dans des conditions ischémiques, l'adénosine triphosphate (ATP) est épuisée et l'absence d'oxygène résultant convertit le métabolisme aérobie en un métabolisme anaérobie. Les conséquences peuvent en être une acidose intracellulaire, un oedème cellulaire, la mise en jeu de cascades enzymatiques de l'inflammation et l'apoptose (ou mort) cellulaire. Lors de la reperfusion d'un organe, d'un tissu ou d'une cellule ischémique, c.-à-d. après une greffe, des espèces réactives de l'oxygène, de l'oxyde nitrique (NO) et des cytokines pro-inflammatoires sont libérés de façon concomitante à l'expression des molécules d'adhérence. Ceci amène à la mobilisation et à l'emprisonnement des leucocytes au sein du tissu ou organe greffé et, ultérieurement, à certaines dysfonctions des greffes comme l'enseigne S. Reddy et al., « Liver transplantation from non-heart-beating donors: current status and future prospects. Liver Transpl. 2004 ; 10 (10):1223-32. Une conservation à froid à environ 4 °C des organes ou des tissus ralentit le métabolisme et limite les effets d'une ischémie, même si une activité métabolique considérable existe tout de même à seulement environ 1 °C tel que l'enseigne P. A. Clavien et al., «Preservation and reperfusion injuries in liver allografts. An overview and synthesis of current studies. » Transplantation 1992 ; 53 (5):957-78. L'ajout de solutions de conservation telles que la solution de l'Université du Wisconsin empêche les cellules de gonfler pendant un stockage ischémique à froid. Ces solutions augmentent la capacité antioxydante des organes (glutathion) et stimulent la génération de phosphate à haute énergie (adénosine) lors de la reperfusion. Bien que ce procédé de conservation d'organe soit efficace, certains organes, par ex., 5 à 15 % des foies et 20 à 30 % des reins, ne fonctionnent pas normalement lors de la transplantation comme le décrit J. H. Southard et al., « Organ preservation. » Ann. Rev. Med., 1995 ; 46:235-47. Ainsi, un stockage statique à froid dans des solutions existantes est inadéquat pour assurer le fonctionnement d'un organe après une transplantation, en particulier à partir de donneurs dont le coeur ne bat pas. En outre, dans des systèmes de perfusion par machine, l'organe est relié à une pompe par l'artère, ce qui pompe continuellement une solution de conservation à froid à travers l'organe. La solution procure des nutriments et parfois de l'oxygène, enlève les métabolites toxiques et réduit l'accumulation d'acide lactique. Ces systèmes peuvent également avoir la capacité de surveiller le débit, la pression et la résistance interne de l'organe, et d'évaluer sa viabilité comme l'explique M. L. Henry, «Pulsatile preservation in renal transplantation» ; Transplant. Proc 1997 ; 29 (8):3575-6. Une question cruciale relativement à l'application d'une perfusion hypothermique par machine pour la conservation du foie est l'équilibre essentiel entre la pression de perfusion et l'apparition d'une lésion endothéliale comme l'enseigne N. A. van der PA 't Hart et al.; « Hypothermic machine perfusion of the liver and the critical balance between perfusion pressures and endothelial injury. » Transplant Proc 2005 ; 37 (1):332-4. En outre, une perfusion hypothermique par machine nécessite une surveillance et une correction continues des compositions chimiques ainsi que de la pression et du débit afin d'être optimale. Ainsi, le procédé requiert beaucoup de temps et de main-d'oeuvre et, par conséquent, est coûteux. En règle générale, une perfusion d'organe nécessite une expertise considérable et les résultats peuvent être très différents d'un praticien à l'autre. Un autre problème avec la conservation d'organes que l'on observe avec les solutions actuelles de perfusion du rein est l'oxydation rapide du glutathion qui est un composant clé des solutions actuelles de perfusion du rein qui sert d'antioxydant, ce qui se traduit par une réduction de l'élimination par oxydation des radicaux libres. Ceci nuira à la qualité de la conservation de l'organe et mènera à de faibles résultats après la transplantation. Il a déjà été proposé d'utiliser des atmosphères hyperbares pour la conservation des organes. Plus précisément, des gaz à pression élevée ont été appliqués pour augmenter la concentration de saturation de l'oxygène en solution. Toutefois, en raison de la complexité de l'appareillage requis et du potentiel de dommage à l'organe pendant la compression ou l'expansion des gaz comme la chambre hyperbare est remplie et rouverte plus tard, cette solution n'est pas considérée comme satisfaisante. The preservation and transplantation of an organ is associated with lesions caused by ischemic reperfusion in these organs. In ischemic conditions, adenosine triphosphate (ATP) is depleted and the resulting lack of oxygen converts aerobic metabolism into anaerobic metabolism. The consequences may be intracellular acidosis, cellular edema, the enzymatic cascades involved in inflammation, and cell apoptosis (or death). During reperfusion of an organ, tissue or ischemic cell, ie after a graft, reactive oxygen species, nitric oxide (NO) and pro-inflammatory cytokines are released concomitantly with the expression of the adhesion molecules. This leads to the mobilization and imprisonment of leukocytes within the grafted tissue or organ and, subsequently, to certain graft dysfunctions as taught by S. Reddy et al., "Liver transplantation from non-heart-beating donors: current status and future prospects. Liver Transpl. 2004 ; 10 (10): 1223-32. A cold storage at about 4 ° C of organs or tissues slows the metabolism and limits the effects of ischemia, even if a considerable metabolic activity still exists at only about 1 ° C as PA Clavien and al., "Preservation and reperfusion injuries in liver allografts. An overview and synthesis of current studies. Transplantation 1992; 53 (5): 957-78. The addition of preservation solutions such as the University of Wisconsin solution prevents cells from swelling during cold ischemic storage. These solutions increase the antioxidant capacity of organs (glutathione) and stimulate the generation of high energy phosphate (adenosine) during reperfusion. Although this method of organ preservation is effective, some organs, e.g., 5 to 15% of the livers and 20 to 30% of the kidneys, do not function normally during transplantation as described by JH Southard et al. "Organ preservation. Ann. Rev. Med., 1995; 46: 235-47. Thus, static cold storage in existing solutions is inadequate to ensure the functioning of an organ after transplantation, especially from donors whose heart does not beat. In addition, in machine perfusion systems, the organ is connected to a pump by the artery, which continuously pumps a cold preservation solution through the organ. The solution provides nutrients and sometimes oxygen, removes toxic metabolites and reduces lactic acid build-up. These systems may also have the ability to monitor the flow, pressure and internal resistance of the organ, and to evaluate its viability as explained by L. Henry, "Pulsatile preservation in renal transplantation"; Transplant. Proc 1997; 29 (8): 3575-6. A crucial question regarding the application of hypothermic machine perfusion for liver preservation is the essential balance between perfusion pressure and the onset of endothelial injury as taught by NA van der PA 't Hart et al.; "Hypothermic machine infusion of the liver and the balance between infusion and endothelial injury. Transplant Proc 2005; 37 (1): 332-4. In addition, machine hypothermic infusion requires continuous monitoring and correction of chemical compositions as well as pressure and flow to be optimal. Thus, the process requires a lot of time and labor and, therefore, is expensive. In general, an organ perfusion requires considerable expertise and the results can be very different from one practitioner to another. Another problem with organ preservation that is observed with current kidney perfusion solutions is the rapid oxidation of glutathione which is a key component of current kidney perfusion solutions that serve as an antioxidant, which is translated by a reduction of the elimination by oxidation of the free radicals. This will affect the quality of organ preservation and lead to poor results after transplantation. It has already been proposed to use hyperbaric atmospheres for the preservation of organs. Specifically, high pressure gases have been applied to increase the saturation concentration of oxygen in solution. However, because of the complexity of the required equipment and the potential for damage to the organ during compression or expansion of gases as the hyperbaric chamber is filled and reopened later, this solution is not considered satisfactory. .
Par conséquent, le problème à résoudre est de proposer un procédé pour l'obtention d'une dissolution efficace des gaz ou des mélanges de gaz protecteurs dans une solution de conservation d'organes pour améliorer la survie des organes, des tissus ou des cellules entreposés dans ladite solution de conservation d'organes, pendant la conservation, c'est-à-dire le stockage, et après la transplantation. Therefore, the problem to be solved is to provide a method for obtaining effective dissolution of gases or protective gas mixtures in an organ preservation solution to improve the survival of stored organs, tissues or cells. in said organ preservation solution, during storage, i.e., storage, and after transplantation.
La solution de la présente invention est un procédé de dissolution d'un gaz ou d'un mélange de gaz dans une solution liquide comprenant les étapes : a) de refroidissement de la solution liquide à une température de refroidissement inférieure à 10 °C de façon à obtenir une solution liquide froide, b) de mise en contact de la solution liquide froide obtenue à l'étape a) avec un gaz ou un mélange de gaz et de dissolution d'au moins une partie dudit ou desdits gaz dans ladite solution liquide froide, c) de récupération d'une solution liquide contenant le ou les gaz dissous. Selon le cas, le procédé de l'invention peut comprendre l'une ou plusieurs des caractéristiques suivantes : - il comprend au moins une autre étape : d) de maintien de la solution liquide contenant le ou les gaz dissous à la température de refroidissement inférieure à 10 °C, ou e) de refroidissement de la solution liquide contenant le ou les gaz dissous à une température de refroidissement inférieure à 10 °C, avant son utilisation. - la température de refroidissement est inférieure à 7 °C, de préférence entre 1 et 6 °C, 10 plus préférablement entre 2 et 4 °C. - la solution liquide contenant le ou les gaz dissous est gardée dans une enceinte hermétiquement fermée. - à l'étape b), la solution liquide froide est saturée d'un gaz ou d'un mélange de gaz choisis parmi le xénon, l'argon, l'hydrogène, le H2S, l'hélium, le krypton, le néon, le radon ou le 15 CO et des mélanges de ceux-ci. - à l'étape b), la solution liquide froide est saturée d'argon. - il comprend en outre l'étape d'entreposage de la solution liquide contenant le ou les gaz dissous à une température de refroidissement inférieure à 10 °C, de préférence entre 1 et 6 °C. - l'on fait barboter le gaz ou le mélange de gaz dans la solution liquide jusqu'à l'obtention 20 d'une solution liquide saturée. - la solution comprend de l'eau et/ou des substances dissoutes destinées à maintenir une concentration osmotique souhaitée et/ou des substances dissoutes destinées à prolonger la conservation de la matière biologique. - la solution contient des substances dissoutes destinées à prévenir un oedème et/ou des 25 substances dissoutes destinées à éliminer des radicaux libres. - le liquide est une solution ou une émulsion contenant un ou plusieurs excipients, comme un lipide, destinés à améliorer la solubilité d'un gaz dans le liquide. L'invention porte aussi sur l'utilisation d'une solution liquide contenant un ou des gaz dissous obtenue par un procédé selon l'invention pour conserver une matière biologique choisie 30 parmi des cellules, des tissus et des organes biologiques, ladite solution liquide étant mise en contact avec ou au moins partiellement immergée dans ladite matière biologique, la matière biologique étant de préférence un organe humain à transplanter. De préférence, ladite matière biologique est choisie parmi le coeur, le rein, le foie, le pancréas et l'intestin. 35 Selon la présente invention, le refroidissement de la solution de conservation à une température de refroidissement inférieure à 10 °C, par ex., d'environ 2 à environ 4 °C, avant saturation par un gaz ou un mélange de gaz augmente la solubilité dudit gaz ou desdits mélanges. En d'autres termes, la présente invention propose de dissoudre des gaz ou des mélanges de gaz protecteurs dans une solution de conservation d'organes pour obtenir une formulation liquide saturée en gaz qui peut être utilisée pour améliorer la survie des matières biologiques, comme des organes, des tissus et des cellules, pendant la conservation et après la transplantation desdites matières biologiques. Selon l'invention, les gaz qui peuvent être utilisés sont choisis parmi le xénon, l'argon, l'hydrogène, le H2S, l'hélium, le krypton, le néon, le radon et le CO puisque ces gaz ont des effets cytoprotecteurs. The solution of the present invention is a method for dissolving a gas or a mixture of gases in a liquid solution comprising the steps of: a) cooling the liquid solution to a cooling temperature below 10 ° C. obtaining a cold liquid solution, b) contacting the cold liquid solution obtained in step a) with a gas or a mixture of gases and dissolving at least a portion of said gas in said liquid solution cold, c) recovery of a liquid solution containing the dissolved gas or gases. Depending on the case, the process of the invention may comprise one or more of the following characteristics: it comprises at least one other step: d) maintaining the liquid solution containing the dissolved gas (s) at the lower cooling temperature; at 10 ° C, or e) cooling the liquid solution containing the dissolved gas (s) to a cooling temperature below 10 ° C, before use. the cooling temperature is below 7 ° C, preferably between 1 and 6 ° C, more preferably between 2 and 4 ° C. the liquid solution containing the dissolved gas (s) is kept in a hermetically sealed enclosure. in step b), the cold liquid solution is saturated with a gas or a mixture of gases chosen from xenon, argon, hydrogen, H2S, helium, krypton, neon , radon or CO and mixtures thereof. in step b), the cold liquid solution is saturated with argon. it furthermore comprises the step of storing the liquid solution containing the dissolved gas (s) at a cooling temperature below 10 ° C., preferably between 1 and 6 ° C. the gas or gas mixture is bubbled into the liquid solution until a saturated liquid solution is obtained. the solution comprises water and / or dissolved substances intended to maintain a desired osmotic concentration and / or dissolved substances intended to prolong the conservation of the biological material. the solution contains dissolved substances intended to prevent edema and / or dissolved substances intended to eliminate free radicals. the liquid is a solution or an emulsion containing one or more excipients, such as a lipid, intended to improve the solubility of a gas in the liquid. The invention also relates to the use of a liquid solution containing one or more dissolved gases obtained by a process according to the invention for preserving a biological material chosen from cells, tissues and biological organs, said liquid solution being contacted with or at least partially immersed in said biological material, the biological material preferably being a human organ to be transplanted. Preferably, said biological material is selected from the heart, the kidney, the liver, the pancreas and the intestine. According to the present invention, cooling the preservation solution to a cooling temperature below 10 ° C, e.g. from about 2 to about 4 ° C, before saturation with a gas or a mixture of gases increases the solubility of said gas or said mixtures. In other words, the present invention provides for dissolving gases or mixtures of protective gases in an organ preservation solution to obtain a gas-saturated liquid formulation that can be used to enhance the survival of biological materials, such as organs, tissues and cells, during storage and after transplantation of said biological materials. According to the invention, the gases that can be used are selected from xenon, argon, hydrogen, H2S, helium, krypton, neon, radon and CO since these gases have cytoprotective effects .
De préférence, le gaz à dissoudre dans la formulation liquide est l'argon. Lorsqu'il est mis en contact avec la solution, le gaz a de préférence une température inférieure à 50 °C, il est de préférence à la température ambiante (c.-à-d. d'environ 20 à 25 °C) ou moins, plus préférablement inférieure à 15 °C. En outre, on utilise le gaz à une pression qui est de préférence égale ou supérieure à 1 atm. Preferably, the gas to be dissolved in the liquid formulation is argon. When contacted with the solution, the gas preferably has a temperature below 50 ° C, preferably at room temperature (i.e., about 20 to 25 ° C) or less, more preferably below 15 ° C. In addition, the gas is used at a pressure which is preferably equal to or greater than 1 atm.
En fait, une augmentation de la pression augmenterait la concentration du gaz dans la solution. Néanmoins, l'effet de la température conformément à la présente invention persiste indépendamment de la pression, c.-à-d., jusqu'à plusieurs atmosphères. Lors de l'utilisation d'une formulation liquide selon la présente invention pour conserver des matières biologiques, leur survie et leur viabilité après transplantation sont accrues grâce à une réduction des espèces réactives de l'oxygène (ROS) qui endommagent l'organe (coeur, rein, foie, pancréas et intestin), les tissus (os, moelle osseuse, tendons, cornée, valvules cardiaques, veines, bras, cellules souches et peau) ou les cellules individuelles prélevés. De plus, les gaz améliorent également la tolérance à l'hypoxie des matières biologiques pendant la période ischémique. In fact, an increase in pressure would increase the concentration of the gas in the solution. Nevertheless, the effect of the temperature in accordance with the present invention persists independently of the pressure, i.e., up to several atmospheres. When using a liquid formulation according to the present invention to conserve biological materials, their survival and viability after transplantation are increased by a reduction of reactive oxygen species (ROS) which damage the organ (heart kidney, liver, pancreas and intestine), tissues (bone, bone marrow, tendons, cornea, heart valves, veins, arms, stem cells and skin) or individual cells removed. In addition, the gases also improve hypoxia tolerance of biological materials during the ischemic period.
La formulation liquide saturée en gaz, comme l'argon, peut être placée dans un contenant et la matière biologique à conserver est immergée dans ladite formulation liquide de façon à ce qu'elle soit protégée par l'action du fluide et des molécules de gaz contenues dans celui-ci. De préférence, la température de la formulation est maintenue entre 1 et 10 °C, de préférence d'environ 2 à 5 °C. Le contenant qui contient la solution saturée de gaz et la matière biologique à conserver peut être entreposé dans une unité de réfrigération ou un endroit similaire. La solution liquide dans laquelle le gaz est dissous comprend de l'eau et d'autres substances destinées à maintenir une concentration osmotique souhaitée et/ou à prolonger la conservation de la matière biologique et/ou à prévenir un oedème et/ou à éliminer des radicaux libres. The liquid saturated gas formulation, such as argon, may be placed in a container and the biological material to be preserved is immersed in said liquid formulation so that it is protected by the action of the fluid and gas molecules. contained in this one. Preferably, the temperature of the formulation is maintained at 1 to 10 ° C, preferably at about 2 to 5 ° C. The container that contains the saturated gas solution and the biological material to be stored may be stored in a refrigeration unit or similar location. The liquid solution in which the gas is dissolved comprises water and other substances intended to maintain a desired osmotic concentration and / or to prolong the conservation of biological material and / or to prevent edema and / or to eliminate free radicals.
Ladite solution liquide peut être une solution ou une émulsion contenant un ou plusieurs excipients, comme un lipide, destinés à améliorer la solubilité du gaz dans le liquide. Said liquid solution may be a solution or an emulsion containing one or more excipients, such as a lipid, for improving the solubility of the gas in the liquid.
En fait, beaucoup de solutions liquides appropriées pour conserver les organes sont disponibles sur le marché. Par exemple, certains exemples de solutions de conservation d'organes dans lesquelles un gaz peut être dissous conformément à la présente invention, et leurs compositions, sont donnés dans le tableau 1 (Maathuis et al. «Perspectives in organ preservation. » Transplantation 2007 ; 83: 1289-1298). In fact, many liquid solutions suitable for preserving organs are available on the market. For example, some examples of organ preservation solutions in which a gas can be dissolved in accordance with the present invention, and their compositions, are given in Table 1 (Maathuis et al., "Perspectives in Organ Preservation." Transplantation 2007; 83: 1289-1298).
TABLEAU 1 EC HOC PBS UW HTK CEL IGL-1 Colloïdes (g/1) HES 50 PEG -35 1 Agents d'imperméabilité (mM) Citrate 80 Glucose 195 Histidine 198 30 Lactobionate 100 80 100 Mannitol 185 38 60 Raffinose 30 30 Saccharose 140 Tampons (mM) Citrate 80 Histidine 198 30 K2HPO4 15 KH2PO4 43 25 25 NaHCO3 10 NaH2PO4 13 Na2HPO4 56 Électrolytes (mM) Calcium 0,0015 0,25 0,5 Chlorure 15 20 32 42 Magnésium 4 13 Sulfate de magnésium 40 5 5 Potassium 115 79 120 9 15 25 Sodium 10 84 125 25 15 100 120 Éliminateurs de ROS (mM) Allopurinol 1 1 Glutathion 3 3 3 Mannitol 185 38 60 Tryptophane 2 Additifs (mM) Adénosine 5 5 Acide glutamique 20 Cétoglutarate 1 Légende : EC : EuroCollins ; HOC : solution hypertonique de citrate /Marshalls ; PBS : saccharose tamponné au phosphate ; UW : solution d'entreposage à froid de l'Université du Wisconsin ; CEL : Celsior ; HTK : histidine-tryptophane-cétoglutarate ; IGL-1 : Institut George Lopez ; HES : amidon d'hydroxyéthyle ; PEG-35 : polyéthylèneglycol avec un poids moléculaire moyen de 35 kDa ; ROS : espèces réactives de l'oxygène. Comme exemple de l'efficacité du procédé conformément à la présente invention, la solubilité du xénon, de l'argon, de l'azote et de l'oxygène dans l'eau à une atmosphère et à diverses températures, compilée par E. Wilhelm, «Low pressure solubility of gases in liquid water. » Chemical Reviews. 1977 ; 77(2): 219-262, est illustrée à la figure 1. Faire barboter un gaz à travers un liquide augmente la vitesse à laquelle le gaz se dissout dans le liquide mais ni la concentration de saturation finale, ni la solubilité du gaz dans le liquide ne seront modifiées. La figure 1 montre le coefficient de solubilité d'Ostwald, qui est défini comme le volume d'un gaz pur qui se dissout dans un volume unitaire de solvant pur par atmosphère à une température et à une pression données, pour le xénon, l'argon, l'azote et l'oxygène dans l'eau. En prenant l'argon comme exemple, le coefficient de solubilité augmente d'environ 0,035 à la température ambiante (c.-à-d., à 22 °C) à 0,050 à 2 °C. Par conséquent, pour augmenter la concentration de saturation de l'argon dans une solution aqueuse de conservation d'organes, la solution doit être maintenue à une température froide non seulement pendant la période de conservation, mais également pendant l'étape de préparation, c.-à-d., lorsque le gaz se dissout dans la solution. De préférence, la solution est refroidie à une température inférieure à 10 °C et plus préférablement inférieure à 5 °C (mais supérieure à 0 °C). TABLE 1 EC HOC PBS UW HTK CEL IGL-1 Colloids (g / 1) HES 50 PEG -35 1 Impermeability agents (mM) Citrate 80 Glucose 195 Histidine 198 30 Lactobionate 100 80 100 Mannitol 185 38 60 Raffinose 30 30 Sucrose 140 Buffers (mM) Citrate 80 Histidine 198 30 K2HPO4 15 KH2PO4 43 25 25 NaHCO3 10 NaH2PO4 13 Na2HPO4 56 Electrolytes (mM) Calcium 0.0015 0.25 0.5 Chloride 15 20 32 42 Magnesium 4 13 Magnesium sulfate 40 5 5 Potassium 115 79 120 9 15 25 Sodium 10 84 125 25 15 100 120 ROS Eliminators (mM) Allopurinol 1 1 Glutathione 3 3 3 Mannitol 185 38 60 Tryptophan 2 Additives (mM) Adenosine 5 5 Glutamic acid 20 Ketoglutarate 1 Legend: EC: EuroCollins ; HOC: hypertonic solution of citrate / Marshalls; PBS: phosphate buffered sucrose; UW: cold storage solution from the University of Wisconsin; CEL: Celsior; HTK: histidine-tryptophan-ketoglutarate; IGL-1: George Lopez Institute; HES: hydroxyethyl starch; PEG-35: polyethylene glycol with an average molecular weight of 35 kDa; ROS: reactive species of oxygen. As an example of the efficiency of the process according to the present invention, the solubility of xenon, argon, nitrogen and oxygen in water at an atmosphere and at various temperatures, compiled by E. Wilhelm Low pressure solubility of gases in liquid water. Chemical Reviews. 1977; 77 (2): 219-262, is illustrated in FIG. 1. Sparging a gas through a liquid increases the rate at which the gas dissolves in the liquid but neither the final saturation concentration nor the solubility of the gas in the liquid. the liquid will not be changed. Figure 1 shows the Ostwald solubility coefficient, which is defined as the volume of a pure gas that dissolves in a unit volume of pure solvent per atmosphere at a given temperature and pressure, for xenon, argon, nitrogen and oxygen in water. Using argon as an example, the solubility coefficient increases from about 0.035 at room temperature (i.e., at 22 ° C) to 0.050 at 2 ° C. Therefore, to increase the saturation concentration of argon in an aqueous organ preservation solution, the solution must be maintained at a cold temperature not only during the storage period, but also during the preparation step, c i.e., when the gas dissolves in the solution. Preferably, the solution is cooled to a temperature below 10 ° C and more preferably below 5 ° C (but above 0 ° C).
Une concentration accrue de l'argon dissous dans la solution pendant la conservation des organes, c.-à-d., le stockage et le transport, peut mener à un effet thérapeutique amélioré pendant le stockage à froid et le transport. La figure 2 montre schématiquement un mode de réalisation d'un appareil qui peut être utilisé pour la préparation d'une solution de conservation d'organes en utilisant des gaz cytoprotecteurs ou des mélanges conformément à la présente invention. An increased concentration of dissolved argon in the solution during organ preservation, ie, storage and transport, can lead to an improved therapeutic effect during cold storage and transport. Figure 2 schematically shows an embodiment of an apparatus that can be used for the preparation of an organ preservation solution using cytoprotective gases or mixtures according to the present invention.
La solution de conservation (2) est gardée dans un récipient (1) à une température régulée (3), par exemple, par l'intermédiaire d'un bain de glace ou d'eau froide. Selon l'invention, la température de la solution contenant un gaz est maintenue de préférence entre 1 et 10 °C, plus préférablement d'environ 2 à 5 °C. En fait, le gaz ou le mélange de gaz (6), comme de l'argon, est d'abord alimenté à partir d'une source (10) de gaz, comme une bouteille de gaz, est ensuite transporté par une conduite de gaz à un débit prescrit qui est régulé par un régulateur de débit (11) et il barbotte ensuite à travers la solution par un diffuseur de bulles (4). Un manomètre (9) peut être utilisé pour surveiller la pression à l'intérieur du récipient (1) ou de la chambre, qui, si souhaité, peut être réglée en ouvrant ou en fermant partiellement une soupape (5) à la sortie de l'écoulement gazeux. The preservation solution (2) is kept in a container (1) at a controlled temperature (3), for example, through an ice bath or cold water. According to the invention, the temperature of the gas-containing solution is preferably maintained at 1 to 10 ° C, more preferably at about 2 to 5 ° C. In fact, the gas or mixture of gases (6), such as argon, is first fed from a source (10) of gas, such as a gas cylinder, is then transported by a gas line. gas at a prescribed rate which is regulated by a flow regulator (11) and then bullets through the solution by a bubble diffuser (4). A pressure gauge (9) can be used to monitor the pressure inside the vessel (1) or the chamber, which, if desired, can be adjusted by partially opening or closing a valve (5) at the outlet of the vessel. gaseous flow.
Un analyseur de gaz (7) peut être utilisé pour surveiller la concentration des gaz dans la chambre (1), de façon à s'assurer de l'élimination complète de l'air résiduel de la chambre (1), ainsi que de l'élimination de l'oxygène et/ou de l'azote précédemment dissous de la solution si nécessaire et si souhaitée. Éventuellement, le gaz qui sort de la chambre (1) peut être récupéré dans le circuit (12) et 20 recyclé par l'unité de recyclage (8), pour minimiser la consommation de gaz coûteux. A gas analyzer (7) can be used to monitor the concentration of gases in the chamber (1), so as to ensure the complete removal of residual air from the chamber (1), as well as the removal of previously dissolved oxygen and / or nitrogen from the solution if necessary and if desired. Optionally, the gas leaving the chamber (1) can be recovered in the circuit (12) and recycled by the recycling unit (8) to minimize the costly gas consumption.
Claims (13)
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| FR1051148A FR2956330A1 (en) | 2010-02-18 | 2010-02-18 | Dissolving a gas or gas mixture in a liquid solution comprises cooling the solution at a specified temperature, contacting the obtained solution with a gas or gas mixture and dissolving a part of gas in the solution and recovering |
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| FR1051148A Withdrawn FR2956330A1 (en) | 2010-02-18 | 2010-02-18 | Dissolving a gas or gas mixture in a liquid solution comprises cooling the solution at a specified temperature, contacting the obtained solution with a gas or gas mixture and dissolving a part of gas in the solution and recovering |
Country Status (1)
| Country | Link |
|---|---|
| FR (1) | FR2956330A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2789234A1 (en) * | 2013-04-10 | 2014-10-15 | Showa Freezing Plant Co., Ltd. | Solution utilizing nitrogen contained water for preserving or flushing organs for transplantation, method for preparing the solution and method for preserving or flushing organs for transplantation utilizing the solution |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1149900A1 (en) * | 2000-04-26 | 2001-10-31 | Wolfgang Dr. Thasler | Solution for preserving human liver cells, preserved cells, and their use |
-
2010
- 2010-02-18 FR FR1051148A patent/FR2956330A1/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1149900A1 (en) * | 2000-04-26 | 2001-10-31 | Wolfgang Dr. Thasler | Solution for preserving human liver cells, preserved cells, and their use |
Non-Patent Citations (3)
| Title |
|---|
| E. WILHELM: "Low-pressure solubility of gases in liquid water", CHEMICAL REVIEWS, vol. 77, no. 2, 1977, pages 219 - 262, XP002592790 * |
| PAGEL ET AL: "Cardioprotection by Noble Gases", JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA, SAUNDERS, PHILADELPHIA, PA, US, vol. 24, no. 1, 1 February 2010 (2010-02-01), pages 143 - 163, XP026869285, ISSN: 1053-0770, [retrieved on 20090520] * |
| WAN CHIDAN ET AL: "Experimental study on the cryopreservation of LLC-PK1 epithelial cells with hypoxic UW solution", HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY. JOURNAL (MEDICALSCIENCES) = HUAZHONG KEJI DAXUE XUEBAO (YIXUE YINGDEWEN BAN), HUAZHONG KEJI DAXUE, TONGJI YIXUEYUAN, CN LNKD- DOI:10.1007/S11596-007-0419-0, vol. 27, no. 4, 1 August 2007 (2007-08-01), pages 426 - 428, XP002584625, ISSN: 1672-0733 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2789234A1 (en) * | 2013-04-10 | 2014-10-15 | Showa Freezing Plant Co., Ltd. | Solution utilizing nitrogen contained water for preserving or flushing organs for transplantation, method for preparing the solution and method for preserving or flushing organs for transplantation utilizing the solution |
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