JP2004154558A - Multi-chamber container for storing fluid replacement for filtration type artificial kidney - Google Patents
Multi-chamber container for storing fluid replacement for filtration type artificial kidney Download PDFInfo
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- JP2004154558A JP2004154558A JP2003309227A JP2003309227A JP2004154558A JP 2004154558 A JP2004154558 A JP 2004154558A JP 2003309227 A JP2003309227 A JP 2003309227A JP 2003309227 A JP2003309227 A JP 2003309227A JP 2004154558 A JP2004154558 A JP 2004154558A
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- 210000003734 kidney Anatomy 0.000 title claims abstract description 25
- 238000001914 filtration Methods 0.000 title abstract description 7
- 238000002637 fluid replacement therapy Methods 0.000 title abstract description 4
- 239000003814 drug Substances 0.000 claims abstract description 55
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 54
- 229940079593 drug Drugs 0.000 claims abstract description 51
- 239000012530 fluid Substances 0.000 claims abstract description 36
- 230000003204 osmotic effect Effects 0.000 claims abstract description 32
- 235000017557 sodium bicarbonate Nutrition 0.000 claims abstract description 27
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims abstract description 27
- 239000000243 solution Substances 0.000 claims description 115
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 72
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 66
- 239000000126 substance Substances 0.000 claims description 62
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 52
- 239000011780 sodium chloride Substances 0.000 claims description 36
- 239000007864 aqueous solution Substances 0.000 claims description 35
- 235000002639 sodium chloride Nutrition 0.000 claims description 34
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 32
- 239000001103 potassium chloride Substances 0.000 claims description 26
- 235000011164 potassium chloride Nutrition 0.000 claims description 26
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 21
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 20
- 239000008103 glucose Substances 0.000 claims description 20
- 239000001632 sodium acetate Substances 0.000 claims description 18
- 235000017281 sodium acetate Nutrition 0.000 claims description 18
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 17
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 16
- 239000001110 calcium chloride Substances 0.000 claims description 16
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 16
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 16
- 235000011054 acetic acid Nutrition 0.000 claims description 15
- 239000007788 liquid Substances 0.000 claims description 14
- 235000011148 calcium chloride Nutrition 0.000 claims description 10
- 238000002955 isolation Methods 0.000 claims description 8
- 150000001720 carbohydrates Chemical class 0.000 claims description 7
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 5
- 239000003002 pH adjusting agent Substances 0.000 claims description 4
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 claims description 3
- 229910001424 calcium ion Inorganic materials 0.000 claims description 3
- 239000011777 magnesium Substances 0.000 claims description 3
- 229910052749 magnesium Inorganic materials 0.000 claims description 3
- 229910001425 magnesium ion Inorganic materials 0.000 claims description 3
- 238000003860 storage Methods 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 235000001055 magnesium Nutrition 0.000 claims 1
- 230000035515 penetration Effects 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 9
- 230000002411 adverse Effects 0.000 abstract description 8
- 238000004891 communication Methods 0.000 abstract description 6
- 239000007789 gas Substances 0.000 description 15
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 14
- 239000005022 packaging material Substances 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 10
- 235000011147 magnesium chloride Nutrition 0.000 description 10
- 239000001301 oxygen Substances 0.000 description 10
- 229910052760 oxygen Inorganic materials 0.000 description 10
- 238000002156 mixing Methods 0.000 description 9
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 8
- 239000003792 electrolyte Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 239000001569 carbon dioxide Substances 0.000 description 7
- 229910002092 carbon dioxide Inorganic materials 0.000 description 7
- 239000004033 plastic Substances 0.000 description 7
- 229920003023 plastic Polymers 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- -1 glucose Chemical class 0.000 description 6
- 239000008155 medical solution Substances 0.000 description 6
- 230000001954 sterilising effect Effects 0.000 description 5
- 238000004659 sterilization and disinfection Methods 0.000 description 5
- 238000001802 infusion Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 229920000139 polyethylene terephthalate Polymers 0.000 description 3
- 239000005020 polyethylene terephthalate Substances 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 229920000219 Ethylene vinyl alcohol Polymers 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
- 239000004677 Nylon Substances 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 2
- 229960005069 calcium Drugs 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000002615 hemofiltration Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 238000005192 partition Methods 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- 208000010444 Acidosis Diseases 0.000 description 1
- 239000001736 Calcium glycerylphosphate Substances 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-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
- 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
- 206010027417 Metabolic acidosis Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 239000004227 calcium gluconate Substances 0.000 description 1
- 235000013927 calcium gluconate Nutrition 0.000 description 1
- 229960004494 calcium gluconate Drugs 0.000 description 1
- UHHRFSOMMCWGSO-UHFFFAOYSA-L calcium glycerophosphate Chemical compound [Ca+2].OCC(CO)OP([O-])([O-])=O UHHRFSOMMCWGSO-UHFFFAOYSA-L 0.000 description 1
- 229940095618 calcium glycerophosphate Drugs 0.000 description 1
- 235000019299 calcium glycerylphosphate Nutrition 0.000 description 1
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 1
- 229940026110 carbon dioxide / nitrogen Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000000385 dialysis solution Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 239000004715 ethylene vinyl alcohol Substances 0.000 description 1
- 229920002457 flexible plastic Polymers 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000012812 general test Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000005001 laminate film Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229960002337 magnesium chloride Drugs 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 229960003390 magnesium sulfate Drugs 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920005672 polyolefin resin Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000005033 polyvinylidene chloride Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 235000007715 potassium iodide Nutrition 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 229920005992 thermoplastic resin Polymers 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
Landscapes
- Package Specialized In Special Use (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- External Artificial Organs (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
本発明は、ダブルバッグ型キット製剤などの用時液体連通することにより患者に投与するろ過型人工腎臓用補液収容複室容器に関する。さらに詳細には、薬液ポートが設けられた室のｐＨ値あるいは浸透圧比が生理的許容範囲内の輸液製剤であり、液体連通することなく患者に投与されても、患者への悪影響を及ぼす恐れのない、ろ過型人工腎臓用補液収容複室容器に関する。 TECHNICAL FIELD The present invention relates to a double-chamber container for storing a replacement fluid for a filtration-type artificial kidney, which is administered to a patient by liquid communication at the time of use, such as a double bag-type kit preparation. More specifically, it is an infusion preparation in which the pH value or the osmotic pressure ratio of the room provided with the drug solution port is within a physiologically acceptable range, and even if administered to a patient without fluid communication, there is a risk of adversely affecting the patient. The present invention relates to a multi-compartment container containing a replacement fluid for a filtered artificial kidney.
ろ過型人工腎臓用補液において、必要な成分である炭酸水素ナトリウムとマグネシウムイオン、カルシウムイオンは、同一液中に存在した場合、不溶性の塩である炭酸マグネシウム、炭酸カルシウムの沈殿を生じる。このため、使用時までこれらの成分は別々に保存する必要がある。また、他の成分であるブドウ糖などの糖類は、アルカリ性溶液中で保存すると分解・変性が生じやすく、特に熱滅菌等により加熱されると、着色が生じる。このため、ブドウ糖を含有する薬液は、使用時までは酸性であるように調整されることが好ましい。したがって、薬液充填容器として複室容器を用いることにより、重炭酸塩および還元糖の安定性が高まり、ろ過型人工腎臓用補液の安全性及び安定性を高めることができる（例えば、特許文献１、特許文献２参照。）。
現在、ろ過型人工腎臓用補液は、可撓性のプラスチック容器（バッグ）に収容するのが一般的であり、用時液体連通できるような隔離手段によって複室に区画されている。当該容器の１室には、塩基性で高浸透圧の薬液が封入され、他の１室には、酸性で低浸透圧の薬液が封入される。当該容器の各々の室に封入された薬液は、用時液体連通する事により生理的なｐＨ値および浸透圧比に調整された後に、患者に投与される。
現在市販されている、複室に区画され、ろ過型人工腎臓用補液が収容された容器製剤においては、薬液が封入された１室に薬液ポートが設けられており、該薬液ポートから輸液チューブを通して、患者への投与が行われている。
In the filtration-type artificial kidney replacement fluid, necessary components, sodium hydrogen carbonate, magnesium ion, and calcium ion, when present in the same liquid, cause precipitation of insoluble salts, magnesium carbonate and calcium carbonate. For this reason, these components need to be stored separately until use. In addition, saccharides such as glucose, which are other components, are liable to be decomposed and denatured when stored in an alkaline solution, and are colored especially when heated by heat sterilization or the like. For this reason, it is preferable that the drug solution containing glucose is adjusted to be acidic until use. Therefore, by using a multi-chamber container as the drug solution filling container, the stability of bicarbonate and reducing sugar is increased, and the safety and stability of the replacement fluid for the filtration type artificial kidney can be improved (for example, Patent Document 1, See Patent Document 2.).
At present, the replacement fluid for the filtration-type artificial kidney is generally housed in a flexible plastic container (bag), and is divided into multiple chambers by an isolation means that allows liquid communication at the time of use. One chamber of the container is filled with a basic, high osmotic pressure chemical, and the other chamber is filled with an acidic, low osmotic pressure chemical. The medicinal solution sealed in each chamber of the container is adjusted to a physiological pH value and an osmotic pressure ratio by communicating the liquid at the time of use, and is then administered to a patient.
In currently marketed container preparations which are divided into multiple chambers and contain a replacement fluid for a filtration-type artificial kidney, a medicine port is provided in one chamber in which the medicine is sealed, and the medicine port is passed through the infusion tube from the medicine port. , Has been administered to patients.
複室に区画されたろ過型人工腎臓用補液が収容された容器において、用時混合後の浸透圧比およびｐＨ値が生理的範囲であり、なおかつ、用時混合前の各室に収容された薬液も浸透圧比およびｐＨ値が生理的範囲内である製剤が、安全で人体に優しい製剤として望まれている。 In the container containing the replacement fluid for the filtration type artificial kidney partitioned into multiple chambers, the osmotic pressure ratio and pH value after mixing at the time of use are within the physiological range, and the drug solution stored at each room before mixing at the time of use Also, a preparation having an osmotic pressure ratio and a pH value within a physiological range is desired as a safe and human-friendly preparation.
本発明者らは、上記課題を解決するために、鋭意検討した結果、用時液体連通するダブルバッグ型キットのろ過型人工腎臓用補液収容複室容器において、薬液ポートが設けられた室の液性を、生理的なｐＨ値および／または浸透圧比となるように調整することにより、単剤投与しても人体に悪影響を与えない製剤を見出し、本発明に到達した。 Means for Solving the Problems The present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, in a double-chamber kit for a filtration-type artificial kidney replacement fluid accommodating double-chamber that is in liquid communication when used, a liquid in a chamber provided with a drug port is provided. By adjusting the sex to a physiological pH value and / or osmotic pressure ratio, a formulation that does not adversely affect the human body even when administered as a single agent was found, and the present invention has been achieved.
すなわち、本発明は、
（１）用時連通可能な隔離手段を有する複数の室に区画され、薬液ポートを有する容器において、薬液ポートが設けられた１室に炭酸水素ナトリウムを含有する薬液（Ａ）を収容した、ろ過型人工腎臓用補液収容複室容器、
（２）薬液（Ａ）の浸透圧比が約０．８〜２．０である、請求項１記載の補液収容複室容器、
（３）薬液（Ａ）のｐＨ値が約６．５〜８．５である、上記（１）記載の補液収容複室容器、
（４）薬液（Ａ）の浸透圧比が約１である、上記（１）記載の補液収容複室容器、
（５）２室からなる上記（１）記載の補液収容複室容器、
（６）薬液（Ａ）のｐＨ値が約６．５〜８．５、浸透圧比が約０．８〜２．０であり、薬液ポートが設けられていない１室に収容される薬液（Ｂ）の浸透圧比が約０．８〜２．０である、上記（１）記載の補液収容複室容器、
（７）薬液（Ａ）のｐＨ値が約６．８〜７．８、浸透圧比が約０．８〜１．２である、上記（１）記載の補液収容複室容器、
（８）薬液（Ｂ）がカルシウムイオン、マグネシウムイオンおよび糖類を含有する、上記（６）記載の補液収容複室容器、
（９）薬液（Ａ）が炭酸水素ナトリウム、塩化ナトリウムおよび塩化カリウムを含む水溶液であり、薬液（Ｂ）が塩化カルシウム、塩化マグネシウム、ブドウ糖およびｐＨ調整剤を含む水溶液である、請求項６記載の補液収容複室容器、
（１０）薬液（Ａ）が、（１）塩化ナトリウム、炭酸水素ナトリウム、酢酸ナトリウムおよび酢酸の水溶液、（２）塩化ナトリウム、塩化カリウムおよび炭酸水素ナトリウムの水溶液、（３）塩化ナトリウム、炭酸水素ナトリウムおよび酢酸ナトリウムの水溶液、（４）塩化ナトリウム、塩化カリウム、炭酸水素ナトリウムおよび酢酸ナトリウムの水溶液、（５）塩化ナトリウム、塩化カリウム、炭酸水素ナトリウムおよび酢酸の水溶液のいずれかであり、薬液（Ｂ）が、（１）塩化ナトリウム、塩化カリウム、塩化カルシウム、塩化マグネシウム、ブドウ糖および酢酸の水溶液、（２）塩化ナトリウム、塩化カルシウム、塩化マグネシウム、酢酸ナトリウム、ブドウ糖および酢酸の水溶液、（３）塩化ナトリウム、塩化カリウム、塩化カルシウム、塩化マグネシウム、酢酸ナトリウム、ブドウ糖および酢酸の水溶液のいずれかである、請求項６記載の補液収容複室容器、
（１１）薬液（Ａ）が、塩化ナトリウム、炭酸水素ナトリウム、酢酸ナトリウムおよび酢酸の水溶液であり、薬液（Ｂ）が、塩化ナトリウム、塩化カリウム、塩化カルシウム、塩化マグネシウム、ブドウ糖および酢酸の水溶液である、請求項６記載の補液収容複室容器、
（１２）用時連通可能な隔離手段を有する複数の室に区画され、薬液ポートを有する容器において、収容される全ての薬液の浸透圧比が約１であることを特徴とする、ろ過型人工腎臓用補液収容複室容器、
（１３）薬液（Ａ）が、塩化ナトリウム、塩化カリウム、炭酸水素ナトリウムおよび酢酸の水溶液であり、薬液（Ｂ）が、塩化ナトリウム、塩化カリウム、塩化カルシウム、塩化マグネシウム、酢酸ナトリウム、ブドウ糖および酢酸の水溶液である、請求項６記載の補液収容複室容器、
（１４）薬液（Ａ）が、塩化ナトリウム、塩化カリウム、炭酸水素ナトリウムの水溶液であり、薬液（Ｂ）が、塩化ナトリウム、塩化カリウム、塩化カルシウム、塩化マグネシウム、酢酸ナトリウム、ブドウ糖および酢酸の水溶液である、請求項６記載の補液収容複室容器
に関する。
That is, the present invention
(1) Filtration in which a container having a chemical liquid port is partitioned into a plurality of chambers having isolation means capable of communicating at the time of use and containing a chemical liquid (A) containing sodium hydrogen carbonate in one chamber provided with the chemical liquid port Multi-chamber container for rehydration fluid for type artificial kidney,
(2) The replenisher-containing dual-chamber container according to claim 1, wherein the osmotic pressure ratio of the drug solution (A) is about 0.8 to 2.0.
(3) The multi-chamber container for accommodating replacement fluid according to (1), wherein the pH value of the drug solution (A) is about 6.5 to 8.5.
(4) The replenisher containing double-chamber container according to (1), wherein the osmotic pressure ratio of the drug solution (A) is about 1.
(5) The two-chamber replacement fluid storage container according to (1) above,
(6) The chemical solution (B) which has a pH value of approximately 6.5 to 8.5 and an osmotic pressure ratio of approximately 0.8 to 2.0, and is housed in one room not provided with a chemical port. ) Wherein the osmotic pressure ratio is about 0.8 to 2.0;
(7) The replenisher containing double-chamber container according to the above (1), wherein the pH value of the drug solution (A) is about 6.8 to 7.8 and the osmotic pressure ratio is about 0.8 to 1.2.
(8) The replenisher-containing double-chamber container according to (6), wherein the drug solution (B) contains calcium ions, magnesium ions, and saccharides.
(9) The chemical solution according to claim 6, wherein the chemical solution (A) is an aqueous solution containing sodium hydrogen carbonate, sodium chloride and potassium chloride, and the chemical solution (B) is an aqueous solution containing calcium chloride, magnesium chloride, glucose and a pH adjuster. Double chamber container for fluid replacement,
(10) The chemical solution (A) is (1) an aqueous solution of sodium chloride, sodium hydrogen carbonate, sodium acetate and acetic acid, (2) an aqueous solution of sodium chloride, potassium chloride and sodium hydrogen carbonate, (3) sodium chloride, sodium hydrogen carbonate And (4) an aqueous solution of sodium chloride, potassium chloride, sodium bicarbonate and sodium acetate, (5) an aqueous solution of sodium chloride, potassium chloride, sodium bicarbonate and acetic acid, and a chemical solution (B) (1) an aqueous solution of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glucose and acetic acid, (2) an aqueous solution of sodium chloride, calcium chloride, magnesium chloride, sodium acetate, glucose and acetic acid, (3) sodium chloride, Potassium chloride, calcium chloride Um, magnesium chloride, sodium acetate, either an aqueous solution of glucose and acetate, replacement fluid accommodating multi-chamber container according to claim 6, wherein,
(11) The drug solution (A) is an aqueous solution of sodium chloride, sodium hydrogen carbonate, sodium acetate and acetic acid, and the drug solution (B) is an aqueous solution of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glucose and acetic acid. A multi-chamber container for accommodating replacement fluid according to claim 6,
(12) A filtration type artificial kidney, which is divided into a plurality of chambers having isolation means capable of communicating with each other and has a chemical liquid port, wherein the osmotic pressure ratio of all the chemical liquids contained is about 1. Multi-chamber container for liquid replacement,
(13) The drug solution (A) is an aqueous solution of sodium chloride, potassium chloride, sodium hydrogen carbonate and acetic acid, and the drug solution (B) is a solution of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium acetate, glucose and acetic acid. The replenisher containing double-chamber container according to claim 6, which is an aqueous solution,
(14) The drug solution (A) is an aqueous solution of sodium chloride, potassium chloride, and sodium hydrogen carbonate, and the drug solution (B) is an aqueous solution of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium acetate, glucose, and acetic acid. The present invention relates to a multi-chamber container for accommodating replacement fluid according to claim 6.
薬液ポートが設けられた１室に収容された薬液が、ほぼ生理的ｐＨ値および浸透圧比であり、薬液を調剤する医療従事者が、複室容器の各室に収容された薬液を混合せずに、誤って患者への投与を行っても、患者への生理的悪影響はほとんどない。また、薬液を混合した後のｐＨ値が約７．０〜７．６、浸透圧比が１付近であり、投与時の痛みが全くない。
さらに、補液収容複室容器に収容される全ての薬液の浸透圧比を約１とした場合、いずれの室にポートを設けたとしても、薬液を混合せずに誤って患者への投与を行い、投与時の痛み等の患者への生理的悪影響を与える恐れがない。
薬液ポートが設けられた１室に収容された薬液が、ほぼ生理的ｐＨ値および浸透圧比であり、薬液を調剤する医療従事者が、複室容器の各室に収容された薬液を混合せずに、誤って患者への投与を行っても、患者への生理的悪影響はほとんどない。また、薬液を混合した後のｐＨ値が約７．０〜７．６、浸透圧比が１付近であり、投与時の痛みが全くない。
さらに、補液収容複室容器に収容される全ての薬液の浸透圧比を約１とした場合、いずれの室にポートを設けたとしても、薬液を混合せずに誤って患者への投与を行い、投与時の痛み等の患者への生理的悪影響を与える恐れがない。
The medical solution contained in one room provided with the medical solution port has almost a physiological pH value and an osmotic pressure ratio, and a medical worker dispensing the chemical solution does not mix the medical solutions contained in each room of the multi-chamber container. In addition, there is almost no physiological adverse effect on the patient even if the administration is performed by mistake. Further, the pH value after mixing the drug solution is about 7.0 to 7.6, and the osmotic pressure ratio is around 1, and there is no pain at the time of administration.
Furthermore, when the osmotic pressure ratio of all the drug solutions contained in the replacement fluid containing multi-chamber container is set to about 1, even if a port is provided in any of the chambers, the drug solution is erroneously administered to the patient without mixing, There is no risk of having a physiological adverse effect on the patient such as pain during administration.
The medical solution contained in one room provided with the medical solution port has almost a physiological pH value and an osmotic pressure ratio, and a medical worker dispensing the chemical solution does not mix the medical solutions contained in each room of the multi-chamber container. In addition, there is almost no physiological adverse effect on the patient even if the administration is performed by mistake. Further, the pH value after mixing the drug solution is about 7.0 to 7.6, and the osmotic pressure ratio is around 1, and there is no pain at the time of administration.
Furthermore, when the osmotic pressure ratio of all the drug solutions contained in the replacement fluid containing multi-chamber container is set to about 1, even if a port is provided in any of the chambers, the drug solution is erroneously administered to the patient without mixing, There is no risk of having a physiological adverse effect on the patient such as pain during administration.
本発明のろ過型人工腎臓用補液とは、血液浄化法の一種である血液ろ過に用いられる体液の補充液である。血液ろ過とは、体外循環により血流をフィルターで膜ろ過分離する治療法であり、フィルターには透析液は流さず、大量の限外ろ過を行い体内不要物質の除去を行う。この際、体重増加分以上に除去した水分は置換液によって補充する。この置換液がろ過型人工腎臓用補液である。 The replacement fluid for a filtered artificial kidney of the present invention is a replenisher for bodily fluids used for hemofiltration, which is a type of blood purification method. Hemofiltration is a treatment method in which a blood flow is separated by membrane filtration through a filter by extracorporeal circulation. A large amount of ultrafiltration is performed by removing a dialysate through the filter to remove unnecessary substances in the body. At this time, the water removed more than the weight gain is replenished with the replacement liquid. This replacement solution is a replacement fluid for a filtered artificial kidney.
本発明において、薬液ポートが設けられた１室に収容される薬液（Ａ）としては、炭酸水素ナトリウムを含有する水溶液が好ましい。炭酸水素ナトリウムの代わりに炭酸水素カリウムを用いてもよい。炭酸水素ナトリウムを含有する水溶液としては、従来から各種透析液、人工腎臓用補液に使用されるものであればよく、炭酸水素ナトリウムの単独水溶液、炭酸水素カリウム等との混合液あるいはさらに種々の電解質成分を加えた混合液が挙げられる。
該薬液における炭酸水素イオン濃度は、特に限定されるものではないが、通常約０．０１〜１Ｍの範囲である。
本発明において使用する薬液（Ａ）は、炭酸水素ナトリウムの他に必要により電解質成分を含有してもよい。電解質成分の陽イオンとしては、重炭酸と反応して不溶性塩を生じないナトリウムイオン、カリウムイオンなどが挙げられる。
薬液（Ａ）のｐＨ値は、通常、約６．５〜８．５であり、好ましくは約６．８〜８．５、最も好ましくは約６．８〜７．８である。
従って、薬液（Ａ）には、安定性の面から糖類を含んでいないことが好ましい。
薬液（Ａ）の浸透圧比は、通常、約０．８〜２．０が用いられる。好ましくは約１であり、さらに好ましくは約０．８〜１．２である。浸透圧比約１とは、浸透圧比約０．８〜１．４である。本発明において、浸透圧比は、生理食塩液の与えるオスモル濃度に対する薬液のオスモル濃度の比を意味する（第十四改正日本薬局方解説書 一般試験法 Ｂ−３１０頁）。薬液（Ａ）の電解質濃度は、このような条件を満たすように調製される。
In the present invention, an aqueous solution containing sodium bicarbonate is preferable as the chemical solution (A) contained in one chamber provided with the chemical solution port. Potassium hydrogen carbonate may be used instead of sodium hydrogen carbonate. The aqueous solution containing sodium bicarbonate may be any of those conventionally used in various dialysates and replacement fluids for artificial kidneys, such as a single aqueous solution of sodium bicarbonate, a mixed solution with potassium bicarbonate, or various other electrolytes. A mixed solution to which the components are added can be given.
The bicarbonate ion concentration in the chemical solution is not particularly limited, but is usually in the range of about 0.01 to 1M.
The chemical solution (A) used in the present invention may contain an electrolyte component as necessary in addition to sodium hydrogen carbonate. Examples of the cation of the electrolyte component include a sodium ion and a potassium ion that do not generate an insoluble salt by reacting with bicarbonate.
The pH value of the drug solution (A) is generally about 6.5 to 8.5, preferably about 6.8 to 8.5, and most preferably about 6.8 to 7.8.
Therefore, it is preferable that the drug solution (A) does not contain a saccharide from the viewpoint of stability.
The osmotic pressure ratio of the chemical solution (A) is usually about 0.8 to 2.0. Preferably it is about 1, more preferably about 0.8 to 1.2. The osmotic pressure ratio of about 1 is an osmotic pressure ratio of about 0.8 to 1.4. In the present invention, the osmotic pressure ratio means the ratio of the osmolarity of a drug solution to the osmolarity given by a physiological saline solution (14th revised edition of the Japanese Pharmacopoeia, General Test Methods, page B-310). The electrolyte concentration of the drug solution (A) is adjusted to satisfy such a condition.
本発明において、薬液ポートが設けられた１室以外の他の１室に収容される薬液（Ｂ）は、少なくとも重炭酸と不溶性の塩を生じる陽イオン（カルシウムおよびマグネシウムなど）を含む溶液であり、通常、他の電解質成分のイオンおよび糖類を含んでいる。
電解質成分としては、従来から使用されているものは何れも使用可能であり、例えば、塩化ナトリウム、酢酸ナトリウム、クエン酸ナトリウム、塩化カリウム、ヨウ化カリウム、クエン酸カリウム、酢酸カリウム、クエン酸カルシウム、グリセロリン酸カルシウム、グルコン酸カルシウム、硫酸マグネシウム、塩化マグネシウム等をあげることができる。
糖類としては、グルコース、キシリトール、ソルビトールなどが挙げられ、還元糖であるグルコースが特に好ましい。さらにグリセロールなどの多価アルコールも使用できる。
本発明において使用する薬液（Ｂ）は、通常、そのｐＨ値が約２．５〜５．５であり、好ましくは約３．０〜５．０、最も好ましくは約３．０〜４．５である。薬液（Ａ）と使用時の浸透圧比を考慮して、薬液（Ｂ）の浸透圧比は、通常、約０．８〜１．２に調整され、好ましくは約１．０に調整される。
また、溶液（Ａ）および溶液（Ｂ）を混合した溶液のｐＨ値は、通常、約６．８〜７．８であり、好ましくは約７．０〜７．６である。また混合後の浸透圧比は、通常、約０．８〜１．２であり、好ましくは、約１．０である。
In the present invention, the chemical solution (B) accommodated in one chamber other than the one provided with the chemical solution port is a solution containing at least cations (such as calcium and magnesium) that form bicarbonate and an insoluble salt. , Usually containing ions and saccharides of other electrolyte components.
As the electrolyte component, any of those conventionally used can be used, for example, sodium chloride, sodium acetate, sodium citrate, potassium chloride, potassium iodide, potassium citrate, potassium acetate, calcium citrate, Examples thereof include calcium glycerophosphate, calcium gluconate, magnesium sulfate, magnesium chloride and the like.
Examples of the saccharide include glucose, xylitol, and sorbitol, and glucose, which is a reducing sugar, is particularly preferable. Further, polyhydric alcohols such as glycerol can be used.
The chemical solution (B) used in the present invention generally has a pH value of about 2.5 to 5.5, preferably about 3.0 to 5.0, and most preferably about 3.0 to 4.5. It is. The osmotic pressure ratio of the chemical solution (B) is generally adjusted to about 0.8 to 1.2, preferably about 1.0, in consideration of the osmotic pressure ratio between the chemical solution (A) and the time of use.
The pH value of the solution obtained by mixing the solution (A) and the solution (B) is usually about 6.8 to 7.8, and preferably about 7.0 to 7.6. The osmotic pressure ratio after mixing is generally about 0.8 to 1.2, and preferably about 1.0.
具体的な薬液（Ａ）および薬液（Ｂ）の組み合わせとしては、薬液（Ａ）が炭酸水素ナトリウム、塩化ナトリウムを含有し、さらに必要に応じて、ナトリウム以外の炭酸イオンと沈殿を生じない電解質（カリウムなど）や、ｐＨ調整剤（無水酢酸ナトリウムや氷酢酸など）を含有しており、薬液（Ｂ）が炭酸塩と沈殿を生じるカルシウム、マグネシウム等、他の電解質、糖類、およびｐＨ調整剤を含有するものが挙げられる。一例としては、薬液（Ａ）が塩化ナトリウム、塩化カリウム、炭酸水素ナトリウム、酢酸ナトリウム、酢酸を含有し、薬液（Ｂ）が塩化ナトリウム、塩化カリウム、塩化カルシウム、塩化マグネシウム、酢酸ナトリウム、ブドウ糖、酢酸を含有するものが挙げられる。
前記薬液（Ａ）および薬液（Ｂ）は、自体公知の方法に従って製造することができる。
As a specific combination of the drug solution (A) and the drug solution (B), the solution (A) contains sodium bicarbonate and sodium chloride, and if necessary, an electrolyte which does not precipitate with carbonate ions other than sodium ( Potassium salt) and a pH adjuster (such as anhydrous sodium acetate and glacial acetic acid). The chemical solution (B) contains other electrolytes, saccharides, and a pH adjuster, such as calcium and magnesium, which precipitate with carbonate. Containing. As an example, the drug solution (A) contains sodium chloride, potassium chloride, sodium bicarbonate, sodium acetate, and acetic acid, and the drug solution (B) contains sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium acetate, glucose, acetic acid. And the like.
The drug solution (A) and the drug solution (B) can be produced according to a method known per se.
本発明において、複数の室に区画された容器とは、複数の室とそれらの室のうち少なくとも１室に薬液ポートを有する容器であり、その形状、厚さは特に限定されないが、例えばバッグの形状などが挙げられる。
本発明に使用する複室容器の材質は、通常の医療用輸液容器等に用いられる材料であれば特に限定されないが、通常、透明性および可塑性を有するプラスチック材料が用いられる。プラスチック材料としては、従来から使用されているポリプロピレン、ポリエチレンなどのポリオレフィン系樹脂、ポリ塩化ビニル系樹脂を含む一般的な熱可塑性樹脂が挙げられる。本発明では容器のガス透過性は特に制限されない。製造工程において、高圧蒸気滅菌を行う場合には少なくとも１０５℃の温度に耐える材質が望まれる。
In the present invention, a container partitioned into a plurality of chambers is a container having a plurality of chambers and a drug solution port in at least one of the chambers, and the shape and thickness thereof are not particularly limited. Shape and the like.
The material of the multi-chamber container used in the present invention is not particularly limited as long as it is a material used for an ordinary medical infusion container and the like, and usually, a plastic material having transparency and plasticity is used. Examples of the plastic material include conventionally used polyolefin resins such as polypropylene and polyethylene, and general thermoplastic resins including polyvinyl chloride resins. In the present invention, the gas permeability of the container is not particularly limited. When high-pressure steam sterilization is performed in the manufacturing process, a material that can withstand a temperature of at least 105 ° C. is desired.
さらに本発明において、容器の複室間は、用時連通可能な隔離手段で隔離されている。用時連通可能な隔離手段とは、使用時に容器外部からの操作により該隔離手段を破壊または開口させて各室を連通させることができ、これによって内容物を外気にさらすことなく容易に混合できるものである。
該隔離手段としては、特に限定されるものではなく、種々公知の隔離手段をいずれも採用することができる。例えば、易剥離性を有するシール、仕切り部に溶着された中空栓又は外側から挟み込んだクリップなどを挙げることができる。易剥離性を有するシールとしては、剥離強度が容器の外周部を溶着させた部分よりも接着強度の小さなシール、あるいは接着部において、接着強度を低下させるための部材が挿入されたシールなどが挙げられる。
Further, in the present invention, the multiple chambers of the container are isolated by an isolation means capable of communicating at the time of use. The isolation means that can be communicated at the time of use can break or open the isolation means by operation from the outside of the container at the time of use to allow each chamber to communicate, thereby easily mixing the contents without exposing the contents to the outside air. Things.
The isolating means is not particularly limited, and any of various known isolating means can be employed. For example, a seal having an easy peeling property, a hollow plug welded to a partition, or a clip sandwiched from the outside can be used. Examples of the seal having easy peelability include a seal having a peel strength smaller than that of a portion where the outer peripheral portion of the container is welded, or a seal in which a member for lowering the bond strength is inserted in the bonded portion. Can be
本発明の複室に区画され、ろ過型人工腎臓用補液が収容された容器において、薬液が封入された室のうち少なくとも１室に薬液ポートが設けられており、該薬液ポートから輸液チューブ等を通して、患者への投与が行われる。 In the container partitioned into multiple chambers of the present invention and containing the replacement fluid for the filtration-type artificial kidney, at least one of the chambers in which the drug solution is sealed is provided with a drug port, and the drug port is passed through the infusion tube or the like from the drug port. Is administered to the patient.
本発明において薬液（Ａ）のような重炭酸塩を含有する薬液は、一般に重炭酸ナトリウムが分解して炭酸ナトリウムと炭酸ガスとなる。この分解反応が進むに従って、充填された薬液中の炭酸ガスが放出され、薬液のｐＨ値が上昇する。
このようにｐＨ値が上昇した重炭酸塩含有薬液を患者に投与すると、本来の機能である代謝性アシドーシスの矯正が行われず、むしろ、副作用の危険性があり、所期の目的が達成されない。
ろ過型人工腎臓用補液が収容された複室容器として、近年、プラスチック製容器が主流として用いられているが、プラスチック容器としては、通常、高いガス透過性を有する材質のものが使用される。こような容器に重炭酸塩含有薬液を充填すると、加熱滅菌時や長期保存時に発生した炭酸ガスを薬液に再吸収することなく、容器壁から外部へ放出され、薬液のｐＨ値に変化が生じる。
In the present invention, in a chemical solution containing a bicarbonate such as the chemical solution (A), sodium bicarbonate is generally decomposed into sodium carbonate and carbon dioxide gas. As the decomposition reaction proceeds, carbon dioxide in the filled chemical solution is released, and the pH value of the chemical solution increases.
When a bicarbonate-containing drug solution having an increased pH value is administered to a patient, the metabolic acidosis, which is an essential function, is not corrected, but rather there is a risk of side effects, and the intended purpose is not achieved.
In recent years, plastic containers have been mainly used as a multi-chamber container containing a replacement fluid for a filtration-type artificial kidney. In recent years, plastic containers made of a material having high gas permeability have been used. When such a container is filled with a bicarbonate-containing chemical solution, the carbon dioxide gas generated during heat sterilization or long-term storage is released from the container wall without being reabsorbed into the chemical solution, causing a change in the pH value of the chemical solution. .
このため、本発明において、複数の室に区画された容器として、ガス透過性のプラスチック材料を使用する場合、該容器は、さらにガス非透過性包装材で包装して、炭酸ガス放出による薬液の変化を防止してもよい。
ガス非透過性包装材としては、例えばエチレンビニルアルコール共重合体（ＥＶＯＨ）、ポリエチレンテレフタレート（ＰＥＴ）ポリ塩化ビニリデン（ＰＶＤＣ）、ナイロンなどから構成された包装材、そしてこれらの素材にシリカやアルミナなどのガスバリア性物質の蒸着処理を行った包装材、また、これらの素材を組み合わせた多層フィルムから作製された包装材が使用できる。ここでいうガス非透過性とは、通常、酸素透過率が１０ｍｌ／ｍ２／２４時間／１気圧以下、好ましくは１ｍｌ／ｍ２／２４時間/１気圧以下のもであればよい。
また、該包装材は酸素検知剤の変色を確認できる透明性を有し、かつ、液体非透過性の包装材を使用することが望ましい。
For this reason, in the present invention, when a gas-permeable plastic material is used as a container partitioned into a plurality of chambers, the container is further packaged with a gas-impermeable packaging material, and the chemical solution is released by releasing carbon dioxide gas. Changes may be prevented.
Examples of the gas impermeable packaging material include a packaging material composed of ethylene vinyl alcohol copolymer (EVOH), polyethylene terephthalate (PET), polyvinylidene chloride (PVDC), nylon, and the like. And a packaging material produced from a multilayer film in which these materials are combined can be used. The gas impermeable here, usually oxygen permeability 10 ml / m 2/24 hours / 1 atmosphere or less, preferably as long as also the following 1 ml / m 2/24 hours / 1 atm.
Further, it is desirable to use a packaging material that has transparency so that the discoloration of the oxygen detector can be confirmed and is liquid-impermeable.
また、ガス非透過性包装材にピンホールが生じた場合、容器壁から放出された炭酸ガスがさらに包装材の外部へ放出され、容器に充填された薬液のｐＨ値がやはり上昇し、また、炭酸ガスの放出により重炭酸塩の含量が低下するなどの変化が生じる。このような薬液を過誤に投与すると、副作用の危険性が懸念される。
このため、上記薬液を充填したプラスチック製容器をガス非透過性包装材に収容する際、包装材とプラスチック製容器の空間部に酸素検知剤を封入してもよい。酸素検知剤としては、酸素の存在により、その物性を変化させるものであれば、特に制限されないが、好ましくは酸素の存在により、変色をともなうもの、例えば、三菱瓦斯化学（株）製エージレスアイなどが例示される。
また、該空間部のガス状態については、酸素検知剤の変色を迅速に生じさせるために、空間部の空気を窒素あるいは二酸化炭素／窒素混合ガスで置換したり、種々公知の脱酸素剤を併用してもよい。
Further, when a pinhole occurs in the gas impermeable packaging material, carbon dioxide gas released from the container wall is further released to the outside of the packaging material, and the pH value of the chemical solution filled in the container also increases, Changes such as a decrease in bicarbonate content are caused by the release of carbon dioxide gas. If such a drug solution is incorrectly administered, there is a concern about the risk of side effects.
For this reason, when the plastic container filled with the chemical solution is accommodated in the gas impermeable packaging material, an oxygen detector may be sealed in the space between the packaging material and the plastic container. The oxygen detector is not particularly limited, as long as it changes its physical properties in the presence of oxygen. Preferably, the oxygen detector has a color change due to the presence of oxygen, such as Ageless Eye manufactured by Mitsubishi Gas Chemical Co., Ltd. Is exemplified.
Regarding the gas state in the space, the air in the space is replaced with nitrogen or a carbon dioxide / nitrogen mixed gas, or various known oxygen absorbers are used in combination in order to promptly change the color of the oxygen detector. May be.
本発明において、薬液の容器への充填、滅菌、包装材による包装、空間部を炭酸ガス雰囲気とする手段等は、通常の注射液の製造等に慣用される各種手段に従うことができる。 In the present invention, the filling of the drug solution into the container, the sterilization, the packaging with the packaging material, the means for setting the space to a carbon dioxide atmosphere, and the like can be in accordance with various means commonly used in the production of ordinary injection solutions.
以下に、実施例に基づいて、本発明をより詳細に説明するが、本発明はこれらの実施例に限定されるものではない。 Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.
下記表１の組成（実施例１）の薬液（A）の各成分を注射用水に溶解させた後、孔径０．２２μｍのメンブレンフィルターで濾過し、塩化ナトリウム４．６４ｇ、無水酢酸ナトリウム、８２．８ｍｇ炭酸水素ナトリウム５．９４ｇ及び氷酢酸３００ｍｇからなる組成の水溶液１０００ｍLを製造した。この溶液を、連通可能な隔壁を有する２室からなる透明性ポリプロピレン製複室バッグ（平均厚み約０．５ｍｍ）の１室に１０００ｍL充填した。
一方、下記表２の組成（実施例１）の薬液（Ｂ）の各成分を注射用水に溶解させ、塩化ナトリウム７．７ｇ、塩化カリウム０．３ｇ、塩化カルシウム５１９．８ｍｇ、塩化マグネシウム２０５．４ｍｇ、ブドウ糖２．０２ｇおよび氷酢酸６０．０ｍｇからなる組成の水溶液１０２０ｍＬを製造した。この溶液を薬液（Ａ）と同様の方法で濾過し、透明性ポリプロピレン製複室バッグの他室に１０２０ｍＬ充填した後、常法に従って、１２１℃、２０分間にて高圧蒸気滅菌を行った。
このようにして得られた該薬液入り複室バッグを室温に冷却後、脱酸素剤（大江化学(株)製タモツＤ）および酸素検知剤（三菱瓦斯化学(株)製エージレスアイ）を複室バッグと外包装材（シリカ蒸着ＰＥＴ／ナイロン／ＣＰＰのラミネートフィルム）の間に収容し、さらに複室バッグと外包装材との空間部を高純度窒素ガスを用いて置換し、密封して、ろ過型人工腎臓用補液収容複室容器を製造した。
After dissolving each component of the drug solution (A) having the composition shown in Table 1 (Example 1) in water for injection, the solution was filtered through a membrane filter having a pore size of 0.22 μm, and 4.64 g of sodium chloride, anhydrous sodium acetate, 82. 1000 mL of an aqueous solution having a composition comprising 8 mg of sodium hydrogencarbonate 5.94 g and glacial acetic acid 300 mg was produced. This solution was filled in a chamber of a transparent polypropylene double-chamber bag (average thickness: about 0.5 mm) comprising two chambers each having a partition wall capable of communicating with the solution in an amount of 1000 mL.
On the other hand, each component of the drug solution (B) having the composition shown in Table 2 (Example 1) was dissolved in water for injection, and 7.7 g of sodium chloride, 0.3 g of potassium chloride, 519.8 mg of calcium chloride, and 205.4 mg of magnesium chloride were dissolved. Then, 1020 mL of an aqueous solution having a composition consisting of 2.02 g of glucose and 60.0 mg of glacial acetic acid was produced. This solution was filtered in the same manner as for the drug solution (A), and the other compartment of the transparent polypropylene double-chamber bag was filled with 1020 mL, and then subjected to high-pressure steam sterilization at 121 ° C. for 20 minutes according to a conventional method.
After cooling the thus-obtained multi-chamber bag containing a chemical solution to room temperature, a deoxidizer (Tamotsu D manufactured by Oe Chemical Co., Ltd.) and an oxygen detector (Ageless Eye manufactured by Mitsubishi Gas Chemical Co., Ltd.) were used. It is housed between the bag and the outer packaging material (laminate film of silica-deposited PET / nylon / CPP), and the space between the multi-chamber bag and the outer packaging material is replaced with high-purity nitrogen gas and sealed. A multi-compartment container containing a replacement fluid for a filtration-type artificial kidney was manufactured.
実施例１と同様にして、表１および表２の組成（実施例２）の薬液（Ａ）および薬液（Ｂ）を製造し、ろ過型人工腎臓用補液収容複室容器を製造した。 In the same manner as in Example 1, a chemical solution (A) and a chemical solution (B) having the compositions shown in Tables 1 and 2 (Example 2) were produced, and a multi-compartment container containing a replacement fluid for a filtered artificial kidney was produced.
実施例１と同様にして、表１および表２の組成（実施例３）の薬液（Ａ）および薬液（Ｂ）を製造し、ろ過型人工腎臓用補液収容複室容器を製造した。 In the same manner as in Example 1, a chemical solution (A) and a chemical solution (B) having the compositions shown in Tables 1 and 2 (Example 3) were produced, and a multi-compartment container for replacement fluid for a filtration-type artificial kidney was produced.
実施例１と同様にして、表１および表２の組成（実施例４）の薬液（Ａ）および薬液（Ｂ）を製造し、ろ過型人工腎臓用補液収容複室容器を製造した。 In the same manner as in Example 1, a chemical solution (A) and a chemical solution (B) having the compositions shown in Tables 1 and 2 (Example 4) were produced, and a multi-compartment container for replacement fluid for a filtration-type artificial kidney was produced.
実施例１と同様にして、表１および表２の組成（実施例５）の薬液（Ａ）および薬液（Ｂ）を製造し、ろ過型人工腎臓用補液収容複室容器を製造した。
In the same manner as in Example 1, a chemical solution (A) and a chemical solution (B) having the compositions shown in Tables 1 and 2 (Example 5) were produced, and a multi-compartment container containing a replacement fluid for a filtered artificial kidney was produced.
Claims (14)
The chemical solution (A) is an aqueous solution of sodium chloride, potassium chloride, and sodium hydrogen carbonate, and the chemical solution (B) is an aqueous solution of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium acetate, glucose, and acetic acid. Item 7. A multi-chamber container for accommodating replacement fluid according to Item 6.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004108059A1 (en) * | 2003-06-06 | 2004-12-16 | Otsuka Pharmaceutical Factory, Inc. | Aseptic combination preparation |
| JP2006341113A (en) * | 2003-06-16 | 2006-12-21 | Fuso Pharmaceutical Industries Ltd | Medical fluid used by being mixed and having improved safety |
| WO2007063638A1 (en) * | 2005-11-29 | 2007-06-07 | Otsuka Pharmaceutical Factory, Inc. | Multichamber bag and gas barrier film |
| JP2018079320A (en) * | 2016-11-09 | 2018-05-24 | ニプロ株式会社 | Replenishment liquid for blood filtration |
| JP2018079319A (en) * | 2016-11-09 | 2018-05-24 | ニプロ株式会社 | Replenishment liquid for blood filtration |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP7246203B2 (en) * | 2018-02-23 | 2023-03-27 | ニプロ株式会社 | hemofiltration replenisher |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004108059A1 (en) * | 2003-06-06 | 2004-12-16 | Otsuka Pharmaceutical Factory, Inc. | Aseptic combination preparation |
| JPWO2004108059A1 (en) * | 2003-06-06 | 2006-07-20 | 株式会社大塚製薬工場 | Aseptic formulation |
| US8404274B2 (en) | 2003-06-06 | 2013-03-26 | Otsuka Pharmaceutical Factory, Inc. | Aseptic combination preparation |
| JP2006341113A (en) * | 2003-06-16 | 2006-12-21 | Fuso Pharmaceutical Industries Ltd | Medical fluid used by being mixed and having improved safety |
| JP4533351B2 (en) * | 2003-06-16 | 2010-09-01 | 扶桑薬品工業株式会社 | In-use mixed chemicals with improved safety |
| WO2007063638A1 (en) * | 2005-11-29 | 2007-06-07 | Otsuka Pharmaceutical Factory, Inc. | Multichamber bag and gas barrier film |
| JP2018079320A (en) * | 2016-11-09 | 2018-05-24 | ニプロ株式会社 | Replenishment liquid for blood filtration |
| JP2018079319A (en) * | 2016-11-09 | 2018-05-24 | ニプロ株式会社 | Replenishment liquid for blood filtration |
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