JP2003171288A - Leucocyte-removed blood product, method for producing the same and formulation set for the same - Google Patents
Leucocyte-removed blood product, method for producing the same and formulation set for the sameInfo
- Publication number
- JP2003171288A JP2003171288A JP2001374410A JP2001374410A JP2003171288A JP 2003171288 A JP2003171288 A JP 2003171288A JP 2001374410 A JP2001374410 A JP 2001374410A JP 2001374410 A JP2001374410 A JP 2001374410A JP 2003171288 A JP2003171288 A JP 2003171288A
- Authority
- JP
- Japan
- Prior art keywords
- blood
- bag
- leukocyte
- plasticizer
- citrate
- 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
- 239000010836 blood and blood product Substances 0.000 title claims abstract description 41
- 229940125691 blood product Drugs 0.000 title claims abstract description 41
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 12
- 239000000203 mixture Substances 0.000 title description 5
- 238000009472 formulation Methods 0.000 title description 4
- 210000004369 blood Anatomy 0.000 claims abstract description 85
- 239000008280 blood Substances 0.000 claims abstract description 85
- 239000004014 plasticizer Substances 0.000 claims abstract description 76
- 239000012503 blood component Substances 0.000 claims abstract description 56
- -1 citric acid ester Chemical class 0.000 claims abstract description 39
- BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical compound ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 claims abstract description 38
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229920005989 resin Polymers 0.000 claims abstract description 22
- 239000011347 resin Substances 0.000 claims abstract description 22
- 210000003743 erythrocyte Anatomy 0.000 claims description 65
- 210000000265 leukocyte Anatomy 0.000 claims description 39
- 238000002360 preparation method Methods 0.000 claims description 20
- 150000002148 esters Chemical class 0.000 claims description 12
- ARCGXLSVLAOJQL-UHFFFAOYSA-N anhydrous trimellitic acid Natural products OC(=O)C1=CC=C(C(O)=O)C(C(O)=O)=C1 ARCGXLSVLAOJQL-UHFFFAOYSA-N 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 8
- 239000003761 preservation solution Substances 0.000 claims description 8
- WWXUGNUFCNYMFK-UHFFFAOYSA-N Acetyl citrate Chemical compound CC(=O)OC(=O)CC(O)(C(O)=O)CC(O)=O WWXUGNUFCNYMFK-UHFFFAOYSA-N 0.000 claims description 7
- 229920000098 polyolefin Polymers 0.000 claims description 7
- DHCXHCJAJQCYKX-UHFFFAOYSA-N 2-(2-butanoyloxy-2-oxoethyl)-2-hydroxybutanedioic acid Chemical compound CCCC(=O)OC(=O)CC(O)(C(O)=O)CC(O)=O DHCXHCJAJQCYKX-UHFFFAOYSA-N 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
- VXRUADVCBZMFSV-UHFFFAOYSA-N 2-acetyloxypropane-1,2,3-tricarboxylic acid Chemical group CC(=O)OC(CC(O)=O)(CC(O)=O)C(O)=O VXRUADVCBZMFSV-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- WUPLWFRHWSPKJA-UHFFFAOYSA-N 2-hydroxy-4-oxoheptane-1,2,3-tricarboxylic acid Chemical compound CCCC(=O)C(C(O)=O)C(O)(C(O)=O)CC(O)=O WUPLWFRHWSPKJA-UHFFFAOYSA-N 0.000 claims description 2
- 239000000306 component Substances 0.000 abstract description 8
- 210000002381 plasma Anatomy 0.000 description 22
- 238000012360 testing method Methods 0.000 description 15
- 238000003860 storage Methods 0.000 description 13
- 206010018910 Haemolysis Diseases 0.000 description 10
- 230000008588 hemolysis Effects 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 9
- JNXDCMUUZNIWPQ-UHFFFAOYSA-N trioctyl benzene-1,2,4-tricarboxylate Chemical compound CCCCCCCCOC(=O)C1=CC=C(C(=O)OCCCCCCCC)C(C(=O)OCCCCCCCC)=C1 JNXDCMUUZNIWPQ-UHFFFAOYSA-N 0.000 description 8
- 238000011156 evaluation Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 239000004803 Di-2ethylhexylphthalate Substances 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 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 6
- BJQHLKABXJIVAM-UHFFFAOYSA-N bis(2-ethylhexyl) phthalate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1C(=O)OCC(CC)CCCC BJQHLKABXJIVAM-UHFFFAOYSA-N 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000008103 glucose Substances 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 102000001554 Hemoglobins Human genes 0.000 description 4
- 108010054147 Hemoglobins Proteins 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- IJRKANNOPXMZSG-SSPAHAAFSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC(=O)CC(O)(C(O)=O)CC(O)=O IJRKANNOPXMZSG-SSPAHAAFSA-N 0.000 description 3
- QZCLKYGREBVARF-UHFFFAOYSA-N Acetyl tributyl citrate Chemical compound CCCCOC(=O)CC(C(=O)OCCCC)(OC(C)=O)CC(=O)OCCCC QZCLKYGREBVARF-UHFFFAOYSA-N 0.000 description 3
- PGIBJVOPLXHHGS-UHFFFAOYSA-N Di-n-decyl phthalate Chemical compound CCCCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCCCCC PGIBJVOPLXHHGS-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 229940127219 anticoagulant drug Drugs 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
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- 235000005911 diet Nutrition 0.000 description 3
- 229940011871 estrogen Drugs 0.000 description 3
- 239000000262 estrogen Substances 0.000 description 3
- 239000004310 lactic acid Substances 0.000 description 3
- 235000014655 lactic acid Nutrition 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000011056 performance test Methods 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- TUUQISRYLMFKOG-UHFFFAOYSA-N trihexyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCCCCCOC(=O)CC(C(=O)OCCCCCC)(OC(C)=O)CC(=O)OCCCCCC TUUQISRYLMFKOG-UHFFFAOYSA-N 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- OAZWDJGLIYNYMU-UHFFFAOYSA-N Leucocrystal Violet Chemical compound C1=CC(N(C)C)=CC=C1C(C=1C=CC(=CC=1)N(C)C)C1=CC=C(N(C)C)C=C1 OAZWDJGLIYNYMU-UHFFFAOYSA-N 0.000 description 2
- 206010058667 Oral toxicity Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 238000004555 blood preservation Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 238000001784 detoxification Methods 0.000 description 2
- QQVHEQUEHCEAKS-UHFFFAOYSA-N diundecyl benzene-1,2-dicarboxylate Chemical compound CCCCCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCCCCCC QQVHEQUEHCEAKS-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 230000004660 morphological change Effects 0.000 description 2
- 231100000418 oral toxicity Toxicity 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920002635 polyurethane Polymers 0.000 description 2
- 239000004814 polyurethane Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- MCYOMTIRKWLYBQ-UHFFFAOYSA-N 2-[1-(6,6-diethyloctoxy)-1,3-dioxobutan-2-yl]-2-hydroxybutanedioic acid Chemical compound CCC(CC)(CC)CCCCCOC(=O)C(C(=O)C)C(CC(=O)O)(C(=O)O)O MCYOMTIRKWLYBQ-UHFFFAOYSA-N 0.000 description 1
- GHCZTIFQWKKGSB-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phosphoric acid Chemical compound OP(O)(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O GHCZTIFQWKKGSB-UHFFFAOYSA-N 0.000 description 1
- 238000009636 ATP test Methods 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 239000004804 Butyryltrihexylcitrate Substances 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 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 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 101150000715 DA18 gene Proteins 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical group [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000007978 cacodylate buffer Substances 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 230000005757 colony formation Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
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- 238000012258 culturing Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
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- 229940079593 drug Drugs 0.000 description 1
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- 239000003480 eluent Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000002657 fibrous material Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 238000005534 hematocrit Methods 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-N o-dicarboxybenzene Natural products OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000003617 peroxidasic effect Effects 0.000 description 1
- 125000005498 phthalate group Chemical class 0.000 description 1
- 239000008029 phthalate plasticizer Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
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- 102000004169 proteins and genes Human genes 0.000 description 1
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- 230000002441 reversible effect Effects 0.000 description 1
- 102220240796 rs553605556 Human genes 0.000 description 1
- 238000011076 safety test Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
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- 238000010561 standard procedure Methods 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 229920005992 thermoplastic resin Polymers 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- GWVUTNGDMGTPFE-UHFFFAOYSA-N trihexyl 2-butanoyloxypropane-1,2,3-tricarboxylate Chemical compound CCCCCCOC(=O)CC(C(=O)OCCCCCC)(OC(=O)CCC)CC(=O)OCCCCCC GWVUTNGDMGTPFE-UHFFFAOYSA-N 0.000 description 1
- AMMPRZCMKXDUNE-UHFFFAOYSA-N trihexyl 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CCCCCCOC(=O)CC(O)(C(=O)OCCCCCC)CC(=O)OCCCCCC AMMPRZCMKXDUNE-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- External Artificial Organs (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
【0001】[0001]
【発明の属する技術分野】本発明は、白血球除去血液製
剤とその製造方法およびそのための製剤セットに関する
ものである。TECHNICAL FIELD The present invention relates to a leukocyte-removed blood preparation, a method for producing the same, and a set of preparations therefor.
【0002】[0002]
【従来の技術】現在輸血用血液は、血液の有効利用及び
輸血者負担軽減の目的から、供血者から得た血液を遠心
力により各成分へと分離し、別々の容器中で保存する方
法が取られている。従来こうして分離された血液成分、
特に赤血球製剤の保存にはフタル酸エステル系可塑剤、
特にフタル酸ジ−2−エチルヘキシル(DEHP)で可
塑化した塩化ビニル樹脂(以後、塩ビと表記することが
ある)製容器が使用されている。2. Description of the Related Art Currently, for blood transfusion, there is a method of separating blood obtained from a donor into respective components by centrifugal force and storing them in separate containers for the purpose of effectively using the blood and reducing the burden on the transfused person. Has been taken. Blood components conventionally separated in this way,
Especially for storing red blood cell preparations, phthalate plasticizers,
Particularly, a container made of vinyl chloride resin (hereinafter sometimes referred to as vinyl chloride) plasticized with di-2-ethylhexyl phthalate (DEHP) is used.
【0003】フタル酸エステルのある種のものは優れた
可塑剤であるとともに、赤血球製剤の保存においては赤
血球膜の安定化をもたらし、保存中の赤血球劣化、とり
わけ溶血、細胞の形態変化を抑制する作用を有すること
が知られている。(文献:Blood、1984、pp1270)[0003] Certain phthalates are excellent plasticizers and also stabilize red blood cell membranes during storage of red blood cell preparations, and suppress red blood cell deterioration during storage, especially hemolysis and cell morphological changes. It is known to have an action. (Reference: Blood, 1984, pp1270)
【0004】一方、近年、赤血球中に溶出した可塑剤の
毒性が主な関心事となっている。とりわけ従来から塩ビ
用可塑剤として使用されてきたDEHPがげっ歯類の肝
臓発癌物質であることが確認され、さらには近年、経
口、経静脈を介して生体中に移行したDEHPが精子数
減少を誘導する危険性があることが報告された。On the other hand, in recent years, the toxicity of plasticizers eluted in red blood cells has become a major concern. In particular, it has been confirmed that DEHP, which has been used as a plasticizer for PVC from the past, is a liver carcinogen in rodents, and in recent years, DEHP, which has been transferred into the living body through oral or intravenous administration, reduces sperm count. It was reported that there was a risk of induction.
【0005】こうした問題を解決するため、DEHPに
変え、例えばトリメリット酸エステル、特にトリメリッ
ト酸トリオクチル(TOTM)といった非溶出性可塑剤
を用いた塩ビ製血液バッグや、ポリオレフィン製血液バ
ッグが検討されたが、分離された血液成分、とりわけ赤
血球製剤中に著しい溶血が起こるため、長期間にわたっ
て赤血球製剤を保存することはできなかった。In order to solve these problems, a vinyl chloride blood bag and a polyolefin blood bag using a non-eluting plasticizer such as trimellitic acid ester, especially trioctyl trimellitate (TOTM), instead of DEHP, have been studied. However, it was not possible to store the red blood cell product for a long period of time because of significant hemolysis in the separated blood components, especially the red blood cell product.
【0006】また、可塑剤としてアセチルクエン酸トリ
−n−ブチル(ATBC)のようなクエン酸エステルを
含有する塩ビ製血液保存バッグも検討されたが、これら
のバッグ中で赤血球を長期間保存した場合、1%を超え
る著しい溶血を起こした。またある種のクエン酸エステ
ルを可塑剤として含有する塩ビ製血液保存バッグでは、
保存赤血球が形態的な変化を起こした。[0006] Further, vinyl chloride blood storage bags containing a citrate ester such as acetyl tri-n-butyl citrate (ATBC) as a plasticizer were also examined, but red blood cells were stored for a long time in these bags. In some cases, more than 1% significant hemolysis occurred. Also, in a PVC blood storage bag containing a certain type of citrate ester as a plasticizer,
The stored red blood cells undergo morphological changes.
【0007】血液バッグとは別に、赤血球製剤中の赤血
球の劣化を抑制するために、赤血球の保存液に、カルチ
ニン、ビタミンEのようなある種のビタミン類(Transfu
sion、1997、pp166)や高分子の糖類を添加することが
考えられるが、この種の薬剤は高温での滅菌処理におい
て分解や失活を受けやすいことが予想される。このよう
に、安全な状態で長期間保存が可能な赤血球製剤が特に
望まれている。Apart from the blood bag, in order to suppress the deterioration of red blood cells in the red blood cell preparation, certain vitamins such as cartinin and vitamin E (Transfu
sion, 1997, pp166) and the addition of high molecular weight saccharides are considered, but it is expected that this kind of drug is susceptible to decomposition and inactivation during sterilization at high temperature. Thus, a red blood cell preparation that can be stored safely for a long period of time is particularly desired.
【0008】[0008]
【発明が解決しようとする課題】本発明の目的は、より
安全な状態で長期間保存することができる輸血用血液製
剤、その製造方法、およびそのための製剤セットを提供
することにある。An object of the present invention is to provide a blood transfusion product which can be stored in a safer state for a long period of time, a method for producing the same, and a set of preparations therefor.
【0009】[0009]
【課題を解決するための手段】例えば、輸血用赤血球製
剤を長期間保存すると、赤血球の溶血が生じるが、その
原因としては、温度変化、バッグ表面との接触といった
物理的な要因、および保存血液中に共存する成分による
化学的な要因が考えられる。中でも共存する白血球が放
出する過酸化物質等の影響が大きいものと考えられる。For example, when a red blood cell preparation for blood transfusion is stored for a long period of time, hemolysis of red blood cells occurs. Physical causes such as temperature change, contact with the bag surface, and stored blood are the causes. Chemical factors due to coexisting components are considered. Above all, it is considered that the influence of peroxidative substances released by coexisting leukocytes is great.
【0010】本発明者は、血液成分中の白血球を収容前
に取り除いた後に血液成分を分離し、分離された血液成
分を、生体に対する安全性の高い容器に収容すれば、赤
血球の溶血がなく、輸血用血液製剤の安全性を著しく向
上させることが可能になることを見出し、本発明に到達
した。The inventor of the present invention eliminates hemolysis of erythrocytes by removing the white blood cells from the blood components before containing them and then separating the blood components and storing the separated blood components in a container with high safety for the living body. The inventors have found that it is possible to significantly improve the safety of blood products for blood transfusion, and have reached the present invention.
【0011】すなわち、長期間保存可能な輸血用赤血球
製剤は、収容前に血液中に存在する白血球を、血液製剤
セットに組み込まれたフィルターで取り除いた後に遠心
分離し、分離された血液成分、特に赤血球成分を、生体
に対する影響が懸念されるDEHPを含有しない塩ビ製
バッグに収容することにより入手可能になったのであ
る。That is, the erythrocyte preparation for transfusion that can be stored for a long period of time is a blood component separated from the leukocyte existing in the blood before being stored by a filter incorporated in the blood preparation set and then centrifuged to separate the separated blood component, particularly It became possible to store the red blood cell component in a vinyl chloride bag that does not contain DEHP, which is likely to affect the living body.
【0012】第一の本発明は、採血バッグに白血球除去
フィルターが連結し、該白血球除去フィルターに複数の
血液成分バッグが連結してなり、該血液成分バッグの少
なくとも1つがクエン酸エステル系可塑剤を含有する塩
化ビニル樹脂製である血液製剤セットを用いて、実質的
に白血球が除去された血液を、前記クエン酸エステル系
可塑剤を含有する塩化ビニル樹脂製血液成分バッグに収
容してなることを特徴とする白血球除去血液製剤であ
る。In the first aspect of the present invention, a leukocyte removal filter is connected to a blood collection bag, and a plurality of blood component bags are connected to the leukocyte removal filter, and at least one of the blood component bags is a citrate ester plasticizer. Using a blood product set made of a vinyl chloride resin containing, the blood from which white blood cells have been substantially removed is stored in a blood component bag made of a vinyl chloride resin containing the citrate plasticizer. Is a leukocyte-removed blood product.
【0013】好ましい第一の本発明は、前記実質的に白
血球が除去された血液を遠心力により分離し、得られた
血液成分のうち赤血球を、前記クエン酸エステル系可塑
剤を含有する塩化ビニル樹脂製血液成分バッグに収容し
てなる白血球除去血液製剤である。In a preferred first aspect of the present invention, the blood substantially free of leukocytes is separated by centrifugal force, and red blood cells among the blood components obtained are vinyl chloride containing the citrate plasticizer. This is a leukocyte-removed blood product contained in a resin blood component bag.
【0014】前記血液成分バッグの少なくとも1つを除
く他のバッグが、クエン酸エステル系可塑剤またはトリ
メリット酸エステル系可塑剤を含有する塩化ビニル樹脂
製バッグであるのが好ましい。It is preferable that the other bag except at least one of the blood component bags is a vinyl chloride resin bag containing a citrate ester plasticizer or a trimellitic acid ester plasticizer.
【0015】前記クエン酸エステル系可塑剤が、一般式
1(式中R1 はアセチル基またはブチリル基、R2 は炭
素数3〜8のアルキル基を表す)で示されるものである
ことが好ましい。It is preferable that the citric acid ester plasticizer is represented by the general formula 1 (wherein R 1 represents an acetyl group or a butyryl group, and R 2 represents an alkyl group having 3 to 8 carbon atoms). .
【式2】 [Formula 2]
【0016】前記クエン酸エステル系可塑剤が、アセチ
ルクエン酸トリアルキルエステルまたはブチリルクエン
酸トリアルキルエステルであることが好ましい。The citric acid ester plasticizer is preferably acetyl citric acid trialkyl ester or butyryl citric acid trialkyl ester.
【0017】前記アセチルクエン酸トリアルキルエステ
ルが、アセチルクエン酸トリ−n−ブチル(ATB
C)、アセチルクエン酸トリ−n−ヘキシル(ATH
C)およびアセチルクエン酸トリエチルヘキシル(AT
EHC)からなる群より選ばれる少なくとも1つである
ことが好ましい。The acetyl citrate trialkyl ester is acetyl citrate tri-n-butyl (ATB
C), tri-n-hexyl acetyl citrate (ATH
C) and triethylhexyl acetylcitrate (AT
It is preferably at least one selected from the group consisting of EHC).
【0018】前記ブチリルクエン酸トリアルキルエステ
ルが、ブチリルクエン酸トリ−n−ヘキシル(BTH
C)であることが好ましい。The butyryl citrate trialkyl ester is butyryl citrate tri-n-hexyl (BTH
C) is preferred.
【0019】前記血液成分バッグの少なくとも1つが、
赤血球保存液を封入しているものであるのが好ましい。At least one of the blood component bags is
It is preferable that the red blood cell preservation solution is enclosed.
【0020】第二の本発明は、予め採血バッグに採取さ
れた血液を、白血球除去フィルターに通して白血球を除
去し、得られた実質的に白血球を含有しない血液を、ク
エン酸エステル系可塑剤を含有する塩化ビニル樹脂製血
液成分バッグに封入することを特徴とする白血球除去血
液製剤の製造方法である。In a second aspect of the present invention, the blood collected in advance in a blood collection bag is passed through a leukocyte removal filter to remove leukocytes, and the obtained blood containing substantially no leukocytes is citrate ester plasticizer. A method for producing a leukocyte-removed blood product, which comprises encapsulating in a vinyl chloride resin blood component bag containing
【0021】前記実質的に白血球を含有しない血液を遠
心力により分離し、分離された血液成分のうち、赤血球
を前記クエン酸エステル系可塑剤を含有する塩化ビニル
樹脂製血液成分バッグに分別封入することが好ましい。The blood containing substantially no white blood cells is separated by centrifugal force, and among the separated blood components, red blood cells are separately sealed in a vinyl chloride resin blood component bag containing the citrate plasticizer. It is preferable.
【0022】第三の本発明は、採血バッグと、該採血バ
ッグと連結された白血球除去フィルターと、該白血球除
去フィルターに連結された複数の血液成分バッグを備え
る血液製剤セットであって、該血液成分バッグの少なく
とも1つが、クエン酸エステル系可塑剤を含有する塩化
ビニル樹脂製バッグであることを特徴とする白血球除去
血液製剤セットである。A third aspect of the present invention is a blood product set comprising a blood collection bag, a leukocyte removal filter connected to the blood collection bag, and a plurality of blood component bags connected to the leukocyte removal filter, At least one of the component bags is a vinyl chloride resin bag containing a citric acid ester plasticizer, which is a leukocyte-removing blood product set.
【0023】前記採血バッグが、血液成分バッグに含有
される可塑剤と異なる可塑剤を含有する塩化ビニル樹脂
製バッグまたはポリオレフィン製バッグであるのが好ま
しい。The blood collection bag is preferably a vinyl chloride resin bag or a polyolefin bag containing a plasticizer different from the plasticizer contained in the blood component bag.
【0024】[0024]
【発明の実施の形態】本発明の白血球除去血液製剤は、
血液中の白血球を取り除くことを目的とするフィルター
の上流側に、採血バッグが接続され、該白血球除去フィ
ルターの下流側に少なくとも3種の血液成分バッグが、
チューブによって無菌的に連結されてなる白血球除去血
液製剤セットにおいて、該成分バッグがクエン酸エステ
ル系可塑剤を含有する塩ビ製バッグを用いることにより
製剤される。すなわち、本発明の血液製剤は、該セット
の採血バッグに採取された血液を、該フィルターを通し
て白血球を除去し、その後、遠心分離を行い、比重差に
より分離された血液成分を前記血液成分バッグに分別封
入することにより製造される。ここで、白血球除去フィ
ルターは、白血球と同時に血小板を捕捉するものであっ
てもよい。BEST MODE FOR CARRYING OUT THE INVENTION The leukocyte-removed blood product of the present invention comprises:
A blood collection bag is connected to the upstream side of the filter intended to remove leukocytes in the blood, and at least three types of blood component bags are connected to the downstream side of the leukocyte removal filter.
In a leukocyte-removing blood product set which is aseptically connected by a tube, the component bag is prepared by using a vinyl chloride bag containing a citrate ester plasticizer. That is, the blood product of the present invention removes leukocytes from the blood collected in the blood collection bag of the set through the filter and then performs centrifugation to separate the blood component separated by the difference in specific gravity into the blood component bag. It is manufactured by separately packaging. Here, the leukocyte removal filter may be one that captures platelets at the same time as leukocytes.
【0025】本発明の採血バッグは、塩ビ100質量部
に対して60〜80質量部のTOTM、フタル酸ジ−n
−デシル(DnDP)といった非溶出性可塑剤、もしく
は45〜65質量部のクエン酸エステル系可塑剤を添加
した塩化ビニル樹脂、もしくはポリオレフィン、ポリウ
レタンといった非塩ビ製軟質高分子ポリマーからなる。
該バッグ内部にはACD(アシッドサイトレートデキス
トロース)、CPD(サイトレート・フォスフェイト・
デキストロース)等の抗凝固剤が封入されている。The blood collecting bag of the present invention comprises 60 to 80 parts by mass of TOTM and di-n phthalate per 100 parts by mass of vinyl chloride.
A non-eluting plasticizer such as decyl (DnDP), a vinyl chloride resin added with 45 to 65 parts by mass of a citrate ester plasticizer, or a non-vinyl chloride soft polymer such as polyolefin or polyurethane.
Inside the bag, ACD (acid citrate dextrose), CPD (citrate phosphate,
An anticoagulant such as dextrose) is encapsulated.
【0026】前記バッグには、採血針を備える採血チュ
ーブが連結されている。採血チューブは、採血バッグと
同様に、非溶出性可塑剤もしくはクエン酸エステル系可
塑剤で可塑化した塩化ビニル樹脂、もしくはポリオレフ
ィン、ウレタンといった非塩ビ製軟質高分子ポリマーか
らなる。A blood collection tube having a blood collection needle is connected to the bag. Similar to the blood collection bag, the blood collection tube is made of a vinyl chloride resin plasticized with a non-eluting plasticizer or a citrate ester plasticizer, or a non-vinyl chloride soft polymer such as polyolefin or urethane.
【0027】本発明の白血球除去フィルターは、血液中
の白血球を捕捉することを目的とするフィルターであ
り、血液中に含有する大多数の白血球および血小板を除
去するものである。この目的を達成するため、繊維状
物、織布、不織布、多孔質体、粒子状物質等を充填した
フィルターのいずれをも使用することができる。フィル
ターの素材は、親水性材料、疎水性材料のいずれであっ
てもよい。The leukocyte-removing filter of the present invention is a filter whose purpose is to capture leukocytes in blood, and removes most leukocytes and platelets contained in blood. In order to achieve this object, any of a fibrous material, a woven cloth, a non-woven cloth, a porous material, a filter filled with a particulate matter and the like can be used. The material of the filter may be either a hydrophilic material or a hydrophobic material.
【0028】本発明の血液成分バッグは、全血を濃厚赤
血球および血漿へと分離、保存するために用いられる液
密性のバッグであって、その材質は前記採血バッグと同
様可塑剤で可塑化した塩化ビニル樹脂または非溶出性可
塑剤で可塑化した塩化ビニル樹脂である。クエン酸エス
テル系可塑剤としては、一般式1で示されるものが使用
される。The blood component bag of the present invention is a liquid-tight bag used for separating and storing whole blood into concentrated red blood cells and plasma, and its material is plasticized with a plasticizer as in the blood collection bag. Vinyl chloride resin or a vinyl chloride resin plasticized with a non-eluting plasticizer. As the citric acid ester plasticizer, the one represented by the general formula 1 is used.
【式3】
(式中R1 はアセチル基またはブチリル基、R2 は炭素
数3〜8のアルキル基を表す)[Formula 3] (In the formula, R 1 represents an acetyl group or a butyryl group, and R 2 represents an alkyl group having 3 to 8 carbon atoms.)
【0029】具体的には、アセチルクエン酸トリ−n−
ブチル(ATBC)、アセチルクエン酸トリ−n−ヘキ
シル(ATHC)、アセチルクエン酸トリエチルヘキシ
ル(ATEHC)などのアセチルクエン酸トリアルキル
エステルや、ブチリルクエン酸トリ−n−ヘキシル(B
THC)、ブチリルクエン酸トリエチルヘキシル(BT
EHC)などのブチリルクエン酸トリアルキルエステル
が好ましい。また、非溶血性可塑剤としては、トリメリ
ット酸トリオクチル(TOTM)、フタル酸ジ−n−デ
シル(DnDP)、フタル酸ジウンデシル(DUP)が
好適例として挙げられる。Specifically, acetylcitrate tri-n-
Butyl (ATBC), acetyl citrate tri-n-hexyl (ATHC), acetyl citrate triethylhexyl (ATEHC) and other acetyl citrate trialkyl esters, and butyryl citrate tri-n-hexyl (B
THC), butyryl citrate triethylhexyl (BT
Butyryl citrate trialkyl esters such as EHC) are preferred. Further, examples of the non-hemolytic plasticizer include trioctyl trimellitate (TOTM), di-n-decyl phthalate (DnDP) and diundecyl phthalate (DUP).
【0030】以下、図面を用いて、本発明の白血球除去
血液製剤セットと血液製剤の製造方法の代表例をさらに
詳細に説明する。Representative examples of the leukocyte-removed blood product set and the method for producing a blood product of the present invention will be described in more detail below with reference to the drawings.
【0031】供血者から採血された血液は採血バッグ1
に導入され、採血バッグ内に存在する抗凝固剤と混合さ
れる。これにより、血液の凝固が防止される。抗凝固処
理された血液は、重力により、または採血バッグを押圧
する等の方法により、連結チューブを通って白血球除去
フィルター2に送られる。白血球除去フィルターにより
大多数の白血球および血小板が除去される。該フィルタ
ーを通過した血液は、連結チューブを通って第1血液成
分バッグ3に送られるが、該血液は赤血球および血漿か
らなる。Blood collected from the donor is the blood collection bag 1
And is mixed with the anticoagulant present in the blood collection bag. This prevents blood coagulation. The anticoagulated blood is sent to the leukocyte removal filter 2 through the connecting tube by gravity or by a method such as pressing a blood collection bag. The leukocyte depletion filter removes the majority of leukocytes and platelets. The blood passing through the filter is sent to the first blood component bag 3 through the connecting tube, and the blood consists of red blood cells and plasma.
【0032】その後、白血球除去フィルター2と第1血
液成分バッグ3との間の連結チューブをアルミリングで
圧着、もしくはヒートシーラーで熱融着した後、血液成
分バッグ3〜5を該フィルターから切り離し、血液成分
バッグ3〜5だけを束ねて遠心分離機にかけ、血液成分
バッグ3内の血液を分離する。これにより第1血液成分
バッグ3中の血液は層分離し、上清に血漿、下層に濃厚
赤血球が蓄積する。Thereafter, the connecting tube between the leukocyte removal filter 2 and the first blood component bag 3 is pressure-bonded with an aluminum ring or heat-sealed with a heat sealer, and then the blood component bags 3 to 5 are separated from the filter. Only the blood component bags 3 to 5 are bundled and subjected to a centrifugal separator to separate the blood in the blood component bag 3. Thereby, the blood in the first blood component bag 3 is separated into layers, and plasma is accumulated in the supernatant and concentrated red blood cells are accumulated in the lower layer.
【0033】それから、第1血液成分バッグ3中の上清
を第2血液成分バッグ4に移し、第1血液成分バッグ3
に残留した濃厚赤血球に、血液成分バッグ5に予め封入
していた赤血球保存液を加えた。赤血球保存液として
は、アデニン、マンニトール、ソルビトール、グアノシ
ン等を1種類以上含む生理溶液が好ましく用いられる。
赤血球保存液を濃厚赤血球へ加えることにより赤血球の
保存日数がさらに長くなり、輸血に用いることが可能に
なる。Then, the supernatant in the first blood component bag 3 is transferred to the second blood component bag 4, and the first blood component bag 3
The red blood cell preservation solution that had been pre-sealed in the blood component bag 5 was added to the concentrated red blood cells remaining in the above. As the red blood cell preservation solution, a physiological solution containing one or more kinds of adenine, mannitol, sorbitol, guanosine and the like is preferably used.
By adding the erythrocyte preservation solution to the concentrated erythrocytes, the erythrocytes can be stored for a longer period of time and can be used for blood transfusion.
【0034】以上のようにして、血漿が封入された第2
血液成分バッグ4と、赤血球保存液加濃厚赤血球が封入
された第1血液成分バッグ3が、輸血用保存血液製剤と
して製品化される。As described above, the second plasma-enclosed second
The blood component bag 4 and the first blood component bag 3 in which the concentrated red blood cells containing red blood cell preservation solution are sealed are commercialized as a preserved blood product for transfusion.
【0035】[0035]
【実施例】以下、実施例により本発明をさらに具体的に
説明するが、本発明はこれら実施例によって何ら限定さ
れるものではない。The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.
【0036】(実施例1〜6、比較例1〜5)
(バッグの製造と製剤セットの組立て)表1に示す可塑
剤を表1に示す組成で含有する熱可塑性樹脂製シート
(厚さ390μm)を、重ね合わせ、裁断し、周辺部を
熱シールすることにより採血バッグ(容量200mL)を
作製した。また、同様にして血液成分バッグを作製し
た。(Examples 1 to 6 and Comparative Examples 1 to 5) (Manufacture of Bag and Assembly of Preparation Set) A thermoplastic resin sheet (thickness: 390 μm) containing the plasticizer shown in Table 1 in the composition shown in Table 1. ) Were piled up and cut, and the peripheral portion was heat-sealed to prepare a blood collection bag (volume: 200 mL). Also, a blood component bag was produced in the same manner.
【0037】[0037]
【表1】 [Table 1]
【0038】血液成分バッグ内にチューブを通して赤血
球保存液(MAP液)50mLを分注し、各成分バッグ間
を可逆性のチューブで連結するとともに、採血バッグと
分離バッグ間に白血球除去フィルターを連結した。該フ
ィルターはポリウレタン製の多孔質体で構成されてい
る。50 mL of a red blood cell preservation solution (MAP solution) was dispensed through a tube in the blood component bag, and each component bag was connected with a reversible tube, and a leukocyte removal filter was connected between the blood collection bag and the separation bag. . The filter is composed of a porous body made of polyurethane.
【0039】採血バッグに採血チューブを接続し、該チ
ューブを通して抗凝固剤(ACD液)30mLを分注し、
製剤セットを組立てた。次に、製剤セットに高圧蒸気滅
菌(121℃、30min)を施した。なお、製剤セットにおけ
る各バッグの構成材料を表2に示す。A blood collection tube was connected to the blood collection bag, 30 mL of the anticoagulant (ACD solution) was dispensed through the tube,
The formulation set was assembled. Next, the formulation set was subjected to high-pressure steam sterilization (121 ° C., 30 min). The constituent materials of each bag in the formulation set are shown in Table 2.
【0040】[0040]
【表2】 [Table 2]
【0041】(血液成分の分離)
(実施例検体の調製)採血した全血(200mL)を、白
血球除去フィルターを通過させ、白血球除去全血を得
た。定法(輸血学会誌、1991、pp404)に従い、白除し
た全血を遠心分離し、赤血球濃厚液および血漿へと分層
した。分層した血漿を血漿バッグ(図1のバッグ4)に
分離し、残留した赤血球濃厚液に赤血球保存液を加えM
AP加濃厚赤血球を調製した。(Separation of Blood Components) (Preparation of Specimen of Example) Blood sampled (200 mL) was passed through a leukocyte depletion filter to obtain leukocyte depleted whole blood. According to the standard method (Journal of the Transfusion Society, 1991, pp404), white blood that had been whitened was centrifuged and separated into red blood cell concentrate and plasma. The separated plasma is separated into a plasma bag (bag 4 in Fig. 1), and a red blood cell preservation solution is added to the remaining red blood cell concentrate to add M
AP enriched red blood cells were prepared.
【0042】(比較例検体の調製)採血した全血を、前
記同様に遠心分離し、血漿およびバッフイーコート層を
分層した。分層した血漿およびバッフイーコート層をそ
れぞれ血液成分バッグに移し、残留した赤血球濃厚液に
MAP液を加えMAP加濃厚赤血球を調製した。得られ
たMAP加濃厚赤血球は、4〜6℃の低温冷蔵庫中で6
週間静置保存した。また分離した血漿は、−20℃の冷
凍庫中で凍結保存した。(Preparation of Sample of Comparative Example) The collected whole blood was centrifuged in the same manner as above to separate the plasma and the buffer coat layer. The separated plasma and buffy coat layer were respectively transferred to blood component bags, and MAP solution was added to the remaining concentrated red blood cell concentrate to prepare MAP-enriched red blood cells. The MAP-enriched red blood cells obtained were placed in a low-temperature refrigerator at 4 to 6 ° C for 6 minutes.
It was stored statically for a week. The separated plasma was frozen and stored in a freezer at -20 ° C.
【0043】(血液保存性能評価試験)
(溶血レベルの確認)MAP加濃厚赤血球封入バッグ
を、21日、42日間保存し、実施例検体および比較例
検体から検体血液1mLを無菌的に取り、取り出したサン
プル中のヘモグロビン濃度およびヘマトクリット値を自
動血球数測定装置(SE-9000、Sysmex社)で測定した。(Blood Preservation Performance Evaluation Test) (Confirmation of Hemolysis Level) The MAP-concentrated erythrocyte-enclosed bag was stored for 21 days and 42 days, and 1 mL of sample blood was aseptically taken from the sample of the example and the sample of the comparative example and taken out The hemoglobin concentration and hematocrit value in each sample were measured with an automatic blood cell counter (SE-9000, Sysmex).
【0044】該サンプルを遠心分離機(RL-100、TOMY精
工社)にて、1500G、10分間遠心し上清の血漿を採取
し、ロイコクリスタルバイオレット法(LCV法)により、
該血漿中のヘモグロビン濃度を測定した。以上により得
られた測定値を次式に代入し、溶血率を算出した。The sample was centrifuged at 1500 G for 10 minutes with a centrifuge (RL-100, TOMY Seiko Co., Ltd.) to collect the plasma of the supernatant, and the leuco crystal violet method (LCV method) was used.
The hemoglobin concentration in the plasma was measured. The measured value obtained as described above was substituted into the following equation to calculate the hemolysis rate.
【0045】[0045]
【数1】 [Equation 1]
【0046】(赤血球細胞形態)MAP加濃厚赤血球封
入バッグを、21日、42日間保存し、実施例および比
較例から無菌的に取り分けた血液から、10μLの血液
を取り、1質量%のグルタルアルデヒドの入った0.1
Mカコジル酸緩衝液(pH7.4)中に入れ、4℃の恒
温槽中で一昼夜静置し、赤血球細胞を固定した。(Red blood cell morphology) The MAP-enriched red blood cell-sealed bag was stored for 21 days and 42 days, and 10 μL of blood was taken from the blood aseptically separated from Examples and Comparative Examples, and 1% by mass of glutaraldehyde. With 0.1
The cells were placed in an M cacodylate buffer (pH 7.4) and allowed to stand overnight in a constant temperature bath at 4 ° C. to fix red blood cells.
【0047】ガラス板に、グルタルアルデヒド固定した
赤血球細胞を付着させ、白金蒸着処理を行い、走査型電
子顕微鏡(JSM-840、日本電子)で赤血球細胞300個を
観察した。Longster等の方法(Vox sang、1972、pp16
1)に従い赤血球細胞の形態を分類し、それぞれの形態
に従って各係数をかけ、その総和を3で割り、細胞10
0個あたりの点数を赤血球細胞形態値(Morphological S
core)とした。Erythrocyte cells fixed with glutaraldehyde were attached to a glass plate, platinum vapor deposition treatment was performed, and 300 red blood cells were observed with a scanning electron microscope (JSM-840, JEOL). Longster et al. Method (Vox sang, 1972, pp16
Classify the morphology of red blood cells according to 1), multiply each coefficient according to each morphology, divide the sum by 3, and divide by 10 cells.
Red blood cell morphology value (Morphological S
core).
【0048】(ATP濃度)0日目およびMAP加濃厚
赤血球封入バッグを、21日、42日間保存し、実施例
の検体および比較例の検体から検体血液1mLを無菌的に
取り、取り出したサンプル液中のATP濃度を市販の測
定キット(ATPテスト、Sigma)を用いて酵素法にて測定
した。保存21、42日目のATP濃度を、0日目のA
TP濃度を100%とする相対量で表した。(ATP concentration) The day 0 and MAP-enriched erythrocyte-enclosed bags were stored for 21 days and 42 days, and 1 mL of sample blood was aseptically taken from the sample of the example and the sample of the comparative example and taken out. The ATP concentration therein was measured by an enzymatic method using a commercially available measurement kit (ATP test, Sigma). The ATP concentration on the 21st and 42nd days of storage is
The TP concentration was expressed as a relative amount with 100%.
【0049】(グルコース消費量)0日目およびMAP
加濃厚赤血球封入バッグを、21日、42日間保存し、
実施例の検体および比較例の検体から検体血液を無菌的
に取り、取り出したサンプル中のグルコース濃度を市販
のキット(グルコーステストワコー、和光純薬)で測定
した。得られたグルコース濃度を、サンプル中のヘモグ
ロビン濃度で除し、0日目からの変化量をグルコース消
費量とした。(Glucose consumption) Day 0 and MAP
Store the concentrated red blood cell enclosed bag for 21 days, 42 days,
Blood samples were taken aseptically from the samples of Examples and Comparative Examples, and the glucose concentration in the taken samples was measured with a commercially available kit (Glucose Test Wako, Wako Pure Chemical Industries, Ltd.). The obtained glucose concentration was divided by the hemoglobin concentration in the sample, and the amount of change from day 0 was taken as the glucose consumption amount.
【0050】(乳酸濃度)0日目およびMAP加濃厚赤
血球封入バッグを、21日、42日間保存し、実施例の
検体および比較例の検体から検体血液を無菌的に取り、
取り出したサンプル中の乳酸濃度を市販のキット(F−
テスト乳酸、ベーリンガー・マンハイム)で測定した。
得られた乳酸濃度を、サンプル中のヘモグロビン濃度で
除し、0日目からの変化量を乳酸産生量とした。(Lactate concentration) Day 0 and the MAP-enriched red blood cell-encapsulated bag were stored for 21 days and 42 days, and sample blood was aseptically taken from the sample of the example and the sample of the comparative example.
Use the commercially available kit (F-
Test lactic acid, Boehringer Mannheim).
The obtained lactic acid concentration was divided by the hemoglobin concentration in the sample, and the amount of change from day 0 was defined as the lactic acid production amount.
【0051】(可塑剤溶出量)
<赤血球製剤>MAP加濃厚赤血球封入りバッグを42
日間保存し、実施例の検体および比較例の検体から血液
1mLを無菌的に取り分けた。これにイソプロピルアルコ
ールを加えて、血液中のタンパクを沈殿させた後、クロ
ロホルムを加えて可塑剤を抽出し、ガスクロマトグラフ
ィ−法により各可塑剤濃度を定量した。(Elution amount of plasticizer) <Red blood cell preparation> 42
After being stored for 1 day, 1 mL of blood was aseptically separated from the sample of the example and the sample of the comparative example. Isopropyl alcohol was added to this to precipitate the protein in blood, chloroform was added to extract the plasticizer, and the concentration of each plasticizer was quantified by gas chromatography.
【0052】<血漿製剤>分離後室温で12時間保存し
た血漿、および30日間凍結保存後、37℃で1時間加
温し、溶解した後の血漿からサンプルを取り分け、赤血
球製剤同様血漿中に溶出した可塑剤量を定量した。<Plasma preparation> After separation, plasma was stored at room temperature for 12 hours, and after cryopreservation for 30 days, it was heated at 37 ° C for 1 hour, and a sample was taken from the plasma after dissolution and eluted into plasma like the red blood cell preparation. The amount of plasticizer added was quantified.
【0053】(安全性試験)
<経口毒性>5重量%濃度のTween80(ポリオキシエチ
レンソルビタンモノオレエート)で可塑剤を懸濁後、2
%(w/w)の比率で粉餌と混合し、7週齢のラットに4日
間食餌させた。なお、対照としてTween80のみを混合し
た粉餌を与えたラットを用いた。断頭後、肝臓を摘出
し、重量を測定後、3倍容量の緩衝液を用いてホモゲネ
イトを作製し、これを2500rpm、5分の条件で遠心分離
した後の上清を測定検体とした。(Safety test) <Oral toxicity> After suspending a plasticizer with Tween 80 (polyoxyethylene sorbitan monooleate) at a concentration of 5% by weight, 2
% (W / w) was mixed with the powdered diet, and 7-week-old rats were fed for 4 days. As a control, a rat fed with a diet containing only Tween 80 was used. After decapitation, the liver was removed, the weight was measured, homogenate was prepared using 3 times the volume of buffer solution, and the homogenate was centrifuged at 2500 rpm for 5 minutes, and the supernatant was used as the measurement sample.
【0054】ポリアクリルアミドゲルを用いて電気泳動
を行い、分子量77kDaに相当する解毒関連酵素タンパ
ク質に相当するバンドの濃さをデンシトメーターで測定
し、Tween80のみを懸濁させた粉餌を与えた対照例を1
00%とする比率にて表した。また、体重100gに対
する肝臓重量を肝臓質量比とした。Electrophoresis was carried out using a polyacrylamide gel, and the density of a band corresponding to a detoxification-related enzyme protein corresponding to a molecular weight of 77 kDa was measured with a densitometer to give a powdered diet in which only Tween 80 was suspended. Control example 1
It was expressed as a ratio of 00%. Moreover, the liver weight to 100 g of body weight was defined as the liver mass ratio.
【0055】<細胞毒性>可塑剤添加シート3.0gを
牛血清加MEM培地30mLで37℃、24時間抽出した
ものを検体とし、培養後約50コロニーとなるようにL
929細胞を播種したウェル内に、検液1mLを入れ、炭
酸ガス培養器内で37℃、7日間培養し、出現コロニー
数をカウントした。空試験(培地のみ)、陽性、陰性対
照を同時に行い、試験の正当性を確認した。空試験のコ
ロニー数に対する検体のコロニー数の比からコロニー形
成率(%)を求めた。<Cytotoxicity> A plasticizer-added sheet (3.0 g) extracted with 30 mL of MEM medium supplemented with bovine serum at 37 ° C. for 24 hours was used as a sample, and L was collected so as to give about 50 colonies after culturing.
1 mL of the test solution was placed in the well in which 929 cells were seeded, and the cells were cultured in a carbon dioxide incubator at 37 ° C. for 7 days, and the number of appearing colonies was counted. The validity of the test was confirmed by simultaneously performing a blank test (medium only) and positive and negative controls. The colony formation rate (%) was calculated from the ratio of the number of sample colonies to the number of blank test colonies.
【0056】<エストロゲン結合性>各可塑剤をジメチ
ルスルホキシド(DMSO)に懸濁後、DMSOを用い
て希釈系列を作製し、市販の測定キットを用いてエスト
ロゲン結合性を評価した。<Estrogen-binding property> Each plasticizer was suspended in dimethylsulfoxide (DMSO), DMSO was used to prepare a dilution series, and the estrogen-binding property was evaluated using a commercially available measurement kit.
【0057】(物性評価)
<柔軟性>溶融プレスシートを成形し、JIS K72
15に準拠して表面硬度(A硬度)を測定した。(Evaluation of Physical Properties) <Flexibility> A melt-pressed sheet is molded, and JIS K72 is used.
The surface hardness (A hardness) was measured according to 15.
【0058】<強度>溶融プレスシートを成形し、JI
S K7113に準拠して引張強さを測定した。試験片
は2号型試験片、試験速度は200mm/min、試験機はオ
ートグラフAGS-110A((株)島津製作所製)で試験を行
った。<Strength> A melt press sheet is molded and
Tensile strength was measured according to SK7113. The test piece was a No. 2 type test piece, the test speed was 200 mm / min, and the tester was Autograph AGS-110A (manufactured by Shimadzu Corporation).
【0059】<評価結果>表3〜4に示すMAP加濃厚
赤血球保存性能評価試験、表5に示す血漿中への可塑剤
溶出量および表6に示す各可塑剤の安全性、物性試験の
結果から、本発明の血液製剤およびその製造方法は次の
ように総括される。表3〜4に示す血液保存性能試験の
結果、実施例1〜4および比較例3〜5との比較から、
クエン酸エステル系可塑剤で可塑化した塩ビ製バッグに
保存した赤血球中の溶血率は、保存前に白血球除去を行
うことにより、いずれのクエン酸エステル系可塑剤につ
いても低くなった。<Evaluation Results> MAP-enriched red blood cell preservation performance evaluation tests shown in Tables 3 to 4, plasticizer elution amount in plasma shown in Table 5, and safety and physical property test results of each plasticizer shown in Table 6. Therefore, the blood product of the present invention and the method for producing the same are summarized as follows. As a result of the blood preservation performance test shown in Tables 3 to 4 and comparison with Examples 1 to 4 and Comparative Examples 3 to 5,
The hemolysis rate in red blood cells stored in a vinyl chloride bag plasticized with a citric acid ester plasticizer was low for all citric acid ester plasticizers by removing leukocytes before storage.
【0060】表6に示す安全性評価試験の結果、フタル
酸エステル系可塑剤の経口毒性の肝臓質量比、解毒酵素
発現量は、他のクエン酸エステル系可塑剤、トリメリッ
ト酸エステル系可塑剤より高かった。また、エストロゲ
ン結合能に関しては、フタル酸エステル系可塑剤、トリ
メリット酸エステル系可塑剤では、結合能が認められた
のに対し、クエン酸エステル系可塑剤では、結合能が認
められなかった。以上より、クエン酸エステル系可塑剤
の安全性が、フタル酸エステル系可塑剤、トリメリット
酸エステル系可塑剤より高いことが明らかになった。表
5に示す物性評価の結果、A硬度は全て78〜83で同
程度であり、血液バッグの材料として十分な柔軟性を有
することが分かった。また、引張強さは全て20MPa 以
上であり、血液バッグとして遠心分離の使用などにも十
分に耐えることが分かった。As a result of the safety evaluation test shown in Table 6, the ratio of the oral toxicity of the phthalate ester plasticizer to the liver mass ratio and the amount of detoxification enzyme expression were found to be other citrate ester plasticizers and trimellitic acid ester plasticizers. It was higher. Regarding the estrogen-binding ability, the phthalate ester-based plasticizer and the trimellitic acid ester-based plasticizer showed the binding ability, whereas the citrate ester-based plasticizer did not show the binding ability. From the above, it became clear that the safety of the citric acid ester plasticizer is higher than that of the phthalic acid ester plasticizer and the trimellitic acid ester plasticizer. As a result of the evaluation of physical properties shown in Table 5, all the A hardness values were 78 to 83, which were about the same, and it was found that the material has sufficient flexibility as a material for the blood bag. Further, it was found that the tensile strengths were all 20 MPa or more, and that they could sufficiently withstand the use of centrifugation as a blood bag.
【0061】また採血バッグとして非溶出性の可塑剤で
あるトリメリット酸トリオクチル(TOTM)を用いた
塩ビ製バッグ(実施例5)とポリオレフィンバッグ(実
施例6)の結果から、前記評価結果は、採血バッグとし
て溶出性の可塑剤を含まない塩ビ製もしくは非塩ビ製ポ
リマー材料を用いても同様の効果が得られた。From the results of the vinyl chloride bag (Example 5) and the polyolefin bag (Example 6) using non-eluting plasticizer trioctyl trimellitate (TOTM) as the blood collection bag, the above evaluation results are as follows: Similar effects were obtained when a vinyl chloride or non-vinyl chloride polymer material containing no eluent plasticizer was used as the blood collection bag.
【0062】さらに血漿中に溶出した可塑剤量を定量し
た表5の結果から、血漿保存用バッグの可塑剤としてト
リメリット酸エステル系可塑剤を用いた実施例5と実施
例1との比較から、血漿保存用バッグに添加した可塑剤
としてトリメリット酸エステル系可塑剤を用いること
で、さらに血漿成分中への不要な可塑剤の溶出を抑制で
き、血液製剤の安全性を向上させることができた。Further, from the results of Table 5 in which the amount of the plasticizer eluted in the plasma was quantified, comparison was made between Example 5 and Example 1 in which the trimellitic acid ester plasticizer was used as the plasticizer of the plasma storage bag. By using a trimellitic acid ester plasticizer as a plasticizer added to the blood plasma storage bag, it is possible to further suppress the elution of unnecessary plasticizer into plasma components and improve the safety of blood products. It was
【0063】表3に示すMAP加濃厚赤血球保存性試験
の結果、実施例1〜3と実施例4との比較から、クエン
酸エステル系可塑剤としてアセチルクエン酸トリアルキ
ルを用いることにより、保存赤血球細胞の形態をより良
好な状態で維持できることが明らかである。As a result of the MAP concentrated erythrocyte preservative test shown in Table 3, comparison between Examples 1 to 3 and 4 shows that trialkyl acetyl citrate was used as the citrate ester plasticizer to preserve the stored erythrocytes. It is clear that the cell morphology can be better maintained.
【0064】表3に示すMAP加濃厚赤血球保存性試験
の結果、実施例1、2および実施例3との比較から、ア
セチルトリクエン酸エステルの内、特にn−アルキルエ
ステルを用いることにより保存中の溶血をより低い条件
で保存できた。As a result of the MAP concentrated erythrocyte preservative test shown in Table 3, comparison with Examples 1 and 2 and Example 3 revealed that among the acetyl tricitrate esters, particularly n-alkyl esters were used for storage. Hemolyzed was preserved under lower conditions.
【0065】表3に示すMAP加濃厚赤血球保存性試験
の結果、実施例1、2および実施例3との比較から、ア
セチルトリクエン酸エステルの内、特にn−アルキルエ
ステルを用いることにより、保存赤血球中への可塑剤の
溶出が少ない条件で赤血球を保存することができた。As a result of the MAP concentrated erythrocyte preservative test shown in Table 3, comparison with Examples 1 and 2 and Example 3 revealed that among acetyl tricitric acid esters, particularly n-alkyl ester was used for preservation. The red blood cells could be stored under the condition that the elution of the plasticizer into the red blood cells was small.
【0066】表3に示すMAP加濃厚赤血球保存性能試
験の結果、実施例1および実施例2との比較から、n−
アルキルエステルの内、アセチルトリ−n−ヘキシルシ
トレート(ATHC)を用いることにより、保存赤血球
製剤の溶血を抑制することができた。As a result of the MAP concentrated erythrocyte storage performance test shown in Table 3, comparison with Example 1 and Example 2 revealed that n-
By using acetyltri-n-hexyl citrate (ATHC) among the alkyl esters, it was possible to suppress hemolysis of the stored red blood cell preparation.
【0067】表3に示すMAP加濃厚赤血球保存性能試
験の結果、トリヘキシルクエン酸エステルの内、特にブ
チリルクエン酸トリ−n−ヘキシル(BTHC)を用い
ることにより保存赤血球の溶血率を抑制できた。As a result of the MAP concentrated erythrocyte storage performance test shown in Table 3, the hemolysis rate of stored erythrocytes could be suppressed by using trihexyl citrate, especially tri-n-hexyl butyryl citrate (BTHC).
【表3】 [Table 3]
【表4】 [Table 4]
【表5】 [Table 5]
【表6】 [Table 6]
【0068】[0068]
【発明の効果】以上から明らかなように、保存前に白血
球を除去して得た血液製剤、特に赤血球製剤を、クエン
酸エステル系可塑剤を含有する塩ビ製バッグに封入して
保存する本発明の場合には、フタル酸エステル系可塑剤
を含有する塩ビ製バッグを用いた場合、または白血球除
去することなく調製した血液製剤をクエン酸エステル系
可塑剤を含有する塩ビ製バッグに封入して保存する場合
に比べ、生体に対する安全性が高く、保存中の血液製剤
に対する障害の少ない輸血用血液製剤の保存方法であ
る。As is apparent from the above, the present invention in which a blood product obtained by removing leukocytes prior to storage, particularly an erythrocyte product, is enclosed and stored in a vinyl chloride bag containing a citrate plasticizer In the case of using, a vinyl chloride bag containing a phthalate plasticizer is used, or a blood product prepared without leukocyte removal is enclosed in a vinyl chloride bag containing a citrate plasticizer and stored. It is a method of preserving a blood product for transfusion that has higher safety to the living body and less damage to the blood product during storage as compared with the case of
【0069】こうした効果は採血バッグとして、トリメ
リット酸トリオクチルのような非溶出性可塑剤で可塑化
された塩ビもしくはポリオレフィンのような非塩ビポリ
マーを用いることによっても同様に観察され、さらに、
血漿保存用バッグとしてトリメリット酸エステルのよう
な非溶出性可塑剤を併用することにより、赤血球製剤の
保存性を何ら損なうことなく、また血漿製剤中への可塑
剤混入量をさらに減少することができるため、輸血用血
液製剤の安全性の向上に寄与する方法と考えられる。These effects are similarly observed by using, as a blood collection bag, a vinyl chloride plasticized with a non-eluting plasticizer such as trioctyl trimellitate or a non-vinyl chloride polymer such as a polyolefin.
By using a non-eluting plasticizer such as trimellitic acid ester as a bag for storing plasma, it is possible to further reduce the amount of plasticizer mixed in the plasma product without impairing the preservability of the red blood cell product. Therefore, it is considered to be a method that contributes to improving the safety of blood products for transfusion.
【図1】 本発明の白血球除去血液製剤の製剤セットの
概念図である。FIG. 1 is a conceptual diagram of a preparation set of the leukocyte-removed blood preparation of the present invention.
1: 採血バッグ 2: 白血球除去フィルター 3〜5: 血液成分バッグ 1: Blood collection bag 2: Leukocyte removal filter 3-5: Blood component bag
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 FI テーマコート゛(参考) A61P 7/00 A61J 1/00 331B 331A Fターム(参考) 4C077 AA12 BB02 BB03 BB04 CC04 DD13 KK01 NN02 PP08 PP21 4C087 AA01 AA05 DA04 DA18 MA16 MA66 NA03 ZA51 ─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. 7 Identification code FI theme code (reference) A61P 7/00 A61J 1/00 331B 331A F term (reference) 4C077 AA12 BB02 BB03 BB04 CC04 DD13 KK01 NN02 PP08 PP21 4C087 AA01 AA05 DA04 DA18 MA16 MA66 NA03 ZA51
Claims (12)
し、該白血球除去フィルターに複数の血液成分バッグが
連結してなり、該血液成分バッグの少なくとも1つがク
エン酸エステル系可塑剤を含有する塩化ビニル樹脂製で
ある血液製剤セットを用いて、実質的に白血球が除去さ
れた血液を、前記クエン酸エステル系可塑剤を含有する
塩化ビニル樹脂製血液成分バッグに収容してなることを
特徴とする白血球除去血液製剤。1. A blood-collecting bag connected to a leukocyte-removing filter, and a plurality of blood-component bags connected to the leukocyte-removing filter, wherein at least one of the blood-component bags contains a citrate ester plasticizer. Using a blood product set made of a resin, the blood from which white blood cells have been substantially removed is stored in a vinyl chloride resin blood component bag containing the citrate plasticizer, Removed blood products.
心力により分離し、得られた血液成分のうち赤血球を、
前記クエン酸エステル系可塑剤を含有する塩化ビニル樹
脂製血液成分バッグに収容してなる請求項1に記載の白
血球除去血液製剤。2. The blood from which the white blood cells have been substantially removed is separated by centrifugal force, and red blood cells among the blood components obtained are
The leukocyte-removed blood product according to claim 1, which is housed in a vinyl chloride resin blood component bag containing the citrate plasticizer.
く他のバッグが、クエン酸エステル系可塑剤またはトリ
メリット酸エステル系可塑剤を含有する塩化ビニル樹脂
製バッグである請求項1または2に記載の白血球除去血
液製剤。3. The bag other than at least one of the blood component bags is a vinyl chloride resin bag containing a citric acid ester plasticizer or a trimellitic acid ester plasticizer. The leukocyte-removed blood product described.
1(式中R1 はアセチル基またはブチリル基、R2 は炭
素数3〜8のアルキル基を表す)で示されるものである
請求項1ないし3のいずれかに記載の白血球除去血液製
剤。 【式1】 4. The citric acid ester plasticizer is represented by the general formula 1 (wherein R 1 represents an acetyl group or a butyryl group, and R 2 represents an alkyl group having 3 to 8 carbon atoms). Item 4. The leukocyte-removed blood product according to any one of Items 1 to 3. [Formula 1]
ルクエン酸トリアルキルエステルまたはブチリルクエン
酸トリアルキルエステルである請求項1ないし4のいず
れかに記載の白血球除去血液製剤。5. The leukocyte-removing blood product according to claim 1, wherein the citric acid ester plasticizer is acetyl citric acid trialkyl ester or butyryl citric acid trialkyl ester.
ルが、アセチルクエン酸トリ−n−ブチル、アセチルク
エン酸トリ−n−ヘキシルおよびアセチルクエン酸トリ
エチルヘキシルからなる群より選ばれる少なくとも一つ
である請求項5に記載の白血球除去血液製剤。6. The acetyl citric acid trialkyl ester is at least one selected from the group consisting of acetyl citrate tri-n-butyl, acetyl citrate tri-n-hexyl and acetyl citrate triethylhexyl. The leukocyte-removed blood preparation according to 5.
ルが、ブチリルクエン酸トリ−n−ヘキシルである請求
項5に記載の白血球除去血液製剤。7. The leukocyte-removed blood product according to claim 5, wherein the butyryl citrate trialkyl ester is butyryl citrate tri-n-hexyl.
赤血球保存液を封入している請求項1ないし7のいずれ
かに記載の白血球除去血液製剤。8. At least one of the blood component bags comprises:
The leukocyte-removed blood product according to any one of claims 1 to 7, wherein a red blood cell preservation solution is enclosed.
球除去フィルターに通して白血球を除去し、得られた実
質的に白血球を含有しない血液を、クエン酸エステル系
可塑剤を含有する塩化ビニル樹脂製血液成分バッグに封
入することを特徴とする白血球除去血液製剤の製造方
法。9. Blood collected in advance in a blood collection bag is passed through a leukocyte removal filter to remove leukocytes, and the obtained blood containing substantially no leukocytes is vinyl chloride containing a citrate plasticizer. A method for producing a leukocyte-removed blood product, characterized by encapsulating in a resin blood component bag.
遠心力により分離し、分離された血液成分のうち、赤血
球を前記クエン酸エステル系可塑剤を含有する塩化ビニ
ル樹脂製血液成分バッグに分別封入する請求項9に記載
の白血球除去血液製剤の製造方法。10. The blood containing substantially no white blood cells is separated by centrifugal force, and among the separated blood components, red blood cells are separated into a vinyl chloride resin blood component bag containing the citrate ester plasticizer. The method for producing a leukocyte-removed blood product according to claim 9, which is encapsulated.
た白血球除去フィルターと、該白血球除去フィルターに
連結された複数の血液成分バッグを備える血液製剤セッ
トであって、該血液成分バッグの少なくとも1つが、ク
エン酸エステル系可塑剤を含有する塩化ビニル樹脂製バ
ッグであることを特徴とする白血球除去血液製剤セッ
ト。11. A blood product set comprising a blood collection bag, a leukocyte removal filter connected to the blood collection bag, and a plurality of blood component bags connected to the leukocyte removal filter, wherein at least one of the blood component bags is provided. Is a bag made of vinyl chloride resin containing a citric acid ester plasticizer, and a leukocyte-removing blood product set.
有される可塑剤と異なる可塑剤を含有する塩化ビニル樹
脂製バッグまたはポリオレフィン製バッグである請求項
11に記載の白血球除去血液製剤セット。12. The leukocyte-removing blood product set according to claim 11, wherein the blood collecting bag is a vinyl chloride resin bag or a polyolefin bag containing a plasticizer different from the plasticizer contained in the blood component bag.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001374410A JP2003171288A (en) | 2001-12-07 | 2001-12-07 | Leucocyte-removed blood product, method for producing the same and formulation set for the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001374410A JP2003171288A (en) | 2001-12-07 | 2001-12-07 | Leucocyte-removed blood product, method for producing the same and formulation set for the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2003171288A true JP2003171288A (en) | 2003-06-17 |
Family
ID=19182972
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|---|---|---|---|
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