JP4178563B2 - Two-chamber Vitamin B1 combination nutritional infusion - Google Patents
Two-chamber Vitamin B1 combination nutritional infusion Download PDFInfo
- Publication number
- JP4178563B2 JP4178563B2 JP20970197A JP20970197A JP4178563B2 JP 4178563 B2 JP4178563 B2 JP 4178563B2 JP 20970197 A JP20970197 A JP 20970197A JP 20970197 A JP20970197 A JP 20970197A JP 4178563 B2 JP4178563 B2 JP 4178563B2
- Authority
- JP
- Japan
- Prior art keywords
- chamber
- infusion
- vitamin
- infusion solution
- electrolyte
- 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.)
- Expired - Lifetime
Links
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- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 title claims description 92
- 229930003451 Vitamin B1 Natural products 0.000 title claims description 47
- 229960003495 thiamine Drugs 0.000 title claims description 47
- 235000010374 vitamin B1 Nutrition 0.000 title claims description 47
- 239000011691 vitamin B1 Substances 0.000 title claims description 47
- 235000016709 nutrition Nutrition 0.000 title claims description 33
- 239000003978 infusion fluid Substances 0.000 claims description 89
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- 239000008103 glucose Substances 0.000 claims description 48
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- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
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- 229940095618 calcium glycerophosphate Drugs 0.000 description 1
- 235000019299 calcium glycerylphosphate Nutrition 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 229960002401 calcium lactate Drugs 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
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- 229960000355 copper sulfate Drugs 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003635 deoxygenating effect Effects 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- CHFUHGDBYUITQJ-UHFFFAOYSA-L dipotassium;2,3-dihydroxypropyl phosphate Chemical compound [K+].[K+].OCC(O)COP([O-])([O-])=O CHFUHGDBYUITQJ-UHFFFAOYSA-L 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960002089 ferrous chloride Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 1
- 229910000358 iron sulfate Inorganic materials 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- VRIVJOXICYMTAG-IYEMJOQQSA-L iron(ii) gluconate Chemical compound [Fe+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O VRIVJOXICYMTAG-IYEMJOQQSA-L 0.000 description 1
- 239000005001 laminate film Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
- 239000011654 magnesium acetate Substances 0.000 description 1
- 235000011285 magnesium acetate Nutrition 0.000 description 1
- 229940069446 magnesium acetate Drugs 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229960002337 magnesium chloride Drugs 0.000 description 1
- 235000011147 magnesium chloride Nutrition 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
- 229940091250 magnesium supplement Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940099596 manganese sulfate Drugs 0.000 description 1
- 239000011702 manganese sulphate Substances 0.000 description 1
- 235000007079 manganese sulphate Nutrition 0.000 description 1
- SQQMAOCOWKFBNP-UHFFFAOYSA-L manganese(II) sulfate Chemical compound [Mn+2].[O-]S([O-])(=O)=O SQQMAOCOWKFBNP-UHFFFAOYSA-L 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 235000016236 parenteral nutrition Nutrition 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 229920005606 polypropylene copolymer Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 239000005033 polyvinylidene chloride Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 229960004109 potassium acetate Drugs 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 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
- 239000011600 potassium glycerophosphate Substances 0.000 description 1
- 235000000491 potassium glycerophosphate Nutrition 0.000 description 1
- 235000007715 potassium iodide Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- IFGCUJZIWBUILZ-UHFFFAOYSA-N sodium 2-[[2-[[hydroxy-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyphosphoryl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid Chemical compound [Na+].C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O IFGCUJZIWBUILZ-UHFFFAOYSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 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
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229960002901 sodium glycerophosphate Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- REULQIKBNNDNDX-UHFFFAOYSA-M sodium;2,3-dihydroxypropyl hydrogen phosphate Chemical compound [Na+].OCC(O)COP(O)([O-])=O REULQIKBNNDNDX-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- UIERGBJEBXXIGO-UHFFFAOYSA-N thiamine mononitrate Chemical compound [O-][N+]([O-])=O.CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N UIERGBJEBXXIGO-UHFFFAOYSA-N 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000003466 welding Methods 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
【０００１】
【産業上の利用分野】
本発明は高カロリー輸液療法に用いられる２室容器入りビタミンＢ１配合栄養輸液剤、より詳しくは隔離手段により２室に区画された可撓性容器の第１室にブドウ糖及びビタミンＢ１を含み、電解質を含まない輸液を収容し、且つ第２室にアミノ酸、電解質及び安定化剤を含む輸液を収容した２室容器入りビタミンＢ１配合栄養輸液剤に関する。
【０００２】
【従来の技術】
近年、高カロリー輸液療法は著しい進歩を遂げ、経口若しくは経腸栄養補給が不能又は不十分で、経中心静脈栄養に頼らざるを得ない患者に対し、水分、電解質、アミノ酸及び糖質等の補給のために使用されている。しかし、高カロリー輸液療法施行中に、ビタミンＢ１欠乏により、重篤なアシドーシスが起こることがある。
【０００３】
そこで、臨床においては高カロリー基本液に注射器を用いてビタミン注射液を混注する操作が行われている。しかしこれらの混注操作は、▲１▼薬剤の移し替えに時間がかかる、▲２▼操作が繁雑である、▲３▼誤操作の可能性がある、▲４▼ガラス製アンプルの場合、ガラス粉末の混入のおそれがある、▲５▼雑菌汚染の可能性がある等の問題もあった。
【０００４】
このような問題を解決するために近年、アシドーシスに対して予防効果があるビタミンＢ１を予め配合した栄養輸液剤の検討がなされている。しかし、ビタミンＢ１は非常に不安定であり、安定性に優れたビタミンＢ１配合栄養輸液剤は、なお充分満足すべきものは得られていなかった。
【０００５】
そこで最近、予め水溶性ビタミンＢ類を配合した高カロリー輸液基本液とアミノ酸輸液の用時混合型輸液剤として、▲１▼ビタミンＢ類の保存安定性を維持するために高カロリー輸液基本液のｐＨを４以下にし、▲２▼ビタミンＢ類の混合後の安定性を維持するために通常アミノ酸輸液に安定剤として使用されている亜硫酸塩を含ませない輸液剤が開示されている（特開平８−１４３４５９号公報）。
この輸液剤において、ビタミンＢ１を含む輸液は加熱滅菌時及び保存中の安定性を保つために通常低ｐＨ（ｐＨ４以下）に調整されていることから、多量のｐＨ調整剤を必要とし、輸液成分のバランスを崩すことにもなる。
一方、アミノ酸輸液においては亜硫酸塩が添加されていないため保存中にアミノ酸の含量低下や輸液剤が着色するという問題が生じてくる。
【０００６】
【発明が解決しようとする課題】
本発明の課題は、ビタミンＢ１の安定性のみならず、アミノ酸の含量低下や着色の問題をも解決した高カロリー輸液用２室容器入りビタミンＢ１配合栄養輸液剤を提供することにある。
【０００７】
【課題を解決するための手段】
本発明者は、第１室にブドウ糖とビタミンＢ１を含み、電解質を含まない輸液を収容し、第２室にアミノ酸、電解質及び安定化剤を含む輸液を収容した輸液剤において、第１室に収容した輸液のｐＨ範囲及びｐＨ調整剤、更に第２室に収容した輸液に添加する安定化剤の量を詳細に検討した結果、上記目的を達成できることを見出し、本発明を完成するに至った。
【０００８】
すなわち、本発明は連通可能な隔離手段により２室に区画された可撓性容器の第１室にブドウ糖及びビタミンＢ１を含み、電解質を含まない輸液を収容し、第２室にアミノ酸、電解質及び安定化剤を含む輸液を収容した２室容器入りビタミンＢ１配合栄養輸液剤であって、第１室及び第２室に収容されている輸液が下記成分を下記組成範囲で含有し、第１室に収容されている輸液のｐＨが３．５〜５．０に調整されていることを特徴とする２室容器入りビタミンＢ１配合栄養輸液剤を提供するものである。
【０００９】
【００１０】
【発明の実施の形態】
本発明の２室容器入りビタミンＢ１配合栄養輸液剤の第１室にはブドウ糖及びビタミンＢ１を含み、電解質を含まない輸液剤が収容される。ビタミンＢ１としては、例えば塩酸チアミン、硝酸チアミン等が挙げられ、好ましくは塩酸チアミンが用いられる。
【００１１】
上記第１室に収容される輸液のｐＨは、生体に対する安全性の面からｐＨ３．５〜５．０に調整されるのが好ましい。更に好ましくはより生理的ｐＨに近いｐＨ４．５の近傍、すなわち４．０〜５．０に調整するのがよい。
本発明者は、ｐＨ調整剤として特定の酸、すなわち酢酸又はマレイン酸を用いることによって、生理的ｐＨにおいてもビタミンＢ１の分解を抑制することができることを見出した。これが本発明の重要な要点の一つである。
【００１２】
本発明の２室容器入りビタミンＢ１配合栄養輸液剤の第２室には、アミノ酸、電解質及び安定化剤を含む輸液が収容される。アミノ酸としては、従来より栄養補給を目的として利用されている各種のアミノ酸が挙げられ、例えばＬ−イソロイシン、Ｌ−ロイシン、Ｌ−バリン、Ｌ−リジン、Ｌ−メチオニン、Ｌ−フェニルアラニン、Ｌ−スレオニン、Ｌ−トリプトファン、Ｌ−アルギニン、Ｌ−ヒスチジン、グリシン、Ｌ−アラニン、Ｌ−プロリン、Ｌ−アスパラギン酸、Ｌ−セリン、Ｌ−チロシン、Ｌ−グルタミン酸、Ｌ−システイン等が例示される。前記アミノ酸は、通常遊離アミノ酸の形態で用いられるが、薬理学的に許容される塩、例えばナトリウム、カリウムとの金属塩、酢酸、リンゴ酸との有機酸塩、塩酸、硫酸との鉱酸塩等の形態でもよい。
【００１３】
また、本発明における電解質とは輸液分野で用いられる意味における電解質であって、ナトリウム、カリウム、カルシウム、マグネシウム、リン、塩素等が挙げられる。電解質の供給源としては、従来より輸液に用いられている各種水溶性塩が使用できる。例えば、炭酸水素ナトリウム、炭酸ナトリウム、リン酸二水素ナトリウム、リン酸水素二ナトリウム、酢酸ナトリウム、乳酸ナトリウム、クエン酸ナトリウム、塩化ナトリウム、硫酸ナトリウム、塩化カリウム、ヨウ化カリウム、リン酸二水素カリウム、リン酸水素二カリウム、乳酸カリウム、クエン酸カリウム、酢酸カリウム、乳酸カリウム、乳酸カルシウム、グリセロリン酸ナトリウム、グリセロリン酸カリウム、グリセロリン酸カルシウム、グルコン酸カルシウム、塩化カルシウム、塩化マグネシウム、硫酸マグネシウム、酢酸マグネシウム、塩化亜鉛、硫酸亜鉛、硫酸鉄、塩化第一鉄、塩化第二鉄、グルコン酸鉄、硫酸銅、硫酸マンガン等を挙げることができる。
【００１４】
更に、第２室の輸液剤には、亜硫酸水素ナトリウム、亜硫酸ナトリウム、ピロ亜硫酸ナトリウム、チオ硫酸ナトリウム、ロンガリット等の亜硫酸塩が安定化剤として添加される。本発明者は、この安定化剤としての亜硫酸塩の量を０．０２ｇ／Ｌ〜０．２ｇ／Ｌとすることによって、アミノ酸の安定性を維持できるだけでなく、第１室の輸液剤と第２室の輸液剤とを混合した際、ビタミンＢ１の分解を抑制することができたという、これまで両立し難いと思われた２つの効果を見出した。これが本発明の重要な要件の一つである。
【００１５】
上記第２室に収容される輸液剤は、ｐＨ調整剤として塩酸、酢酸又は水酸化ナトリウム等を用いてｐＨ６．０〜８．０に調整される。
【００１６】
本発明の２室容器入りビタミンＢ１配合栄養輸液剤は、上述した組成物の他に必要に応じ、本発明の目的である輸液の安定性を損なわない範囲において、微量元素、他のビタミン類等の栄養素、その他の成分を第１室及び／又は第２室に一日摂取量を考慮して配合することができる。
【００１７】
本発明の２室容器入りビタミンＢ１配合栄養輸液剤は、通常用いられている公知の方法に準拠して製造できる。例えば各室にそれぞれの輸液を窒素等の不活性ガス雰囲気下で充填後、加熱滅菌するのが好ましい。加熱滅菌として高圧蒸気滅菌を行う場合は、１００〜１３０℃、５〜４０分間行われる。
【００１８】
本発明に用いられる隔離手段によって２室が形成された可撓性容器としては、中央部が帯状に剥離可能に熱疑似溶着法により溶着され、厳密に隔離された個室のそれぞれに輸液注入口又は排出口が設けられたものが挙げられる。その材質としてはプラスチック製の柔軟なものであればよく、例えば、ポリ塩化ビニル、ポリプロピレン、ポリエチレン、エチレン酢酸ビニル共重合体等が挙げられる。
更に、安定性を確保するために、上記プラスチック容器をガスバリアー性の高い包材を用いて包装し、包材とプラスチック容器の空間部を不活性ガス置換後、同時に脱酸素剤（商品名：エージレス、三菱瓦斯化学社製）を封入するのが好ましい。その包材としては、ポリエステル、エチレンビニルアルコール共重合体、ポリエチレンテレフタレート、ポリ塩化ビニリデン、ナイロン等の材質やこれらのラミネートフィルムからなるものが挙げられる。
【００１９】
本発明の２室容器入りビタミンＢ１配合栄養輸液剤の投与量は、症状、年齢、体重に応じて適宜増減できるが、通常成人１日あたり５００〜３０００ｍｌ、好ましくは１０００ｍｌ〜２０００ｍｌとするのがよい。
【００２０】
【実施例】
以下、実験例、実施例及び試験例を挙げ、本発明をより詳細に説明するが、本発明はこれらに限定されるものではない。
【００２１】
〔実施例１〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
表１に示した第１室成分を注射用蒸留水８００ｍｌに加温溶解し、微量の酢酸を用いてｐＨを３．５に調整した後、更に注射用蒸留水を加えて全量を１０００ｍｌとした溶液を０．２μｍのメンブランフィルターで濾過し、ブドウ糖及び塩酸チアミンを含有する輸液を得た。
２）アミノ酸、電解質及び安定化剤を含有する輸液の調製
表１に示した第２室成分を注射用蒸留水８００ｍｌに加温溶解し、更に注射用蒸留水を加えて全量を１０００ｍｌとした溶液を０．２μｍのメンブランフィルターで濾過し、アミノ酸、電解質及び安定化剤を含有する輸液を得た。
【００２２】
【表１】
３）輸液バッグへの充填
２室に区画された輸液バッグの第１室に、上記１）で調製したブドウ糖及びビタミンＢ１を含有する輸液８００ｍｌを、窒素雰囲気下で充填し、密封した。次いで、容器を反転させ、第２室に、上記２）で調製したアミノ酸及び電解質を含有する輸液２００ｍｌを、窒素雰囲気下で充填し、密封した。この輸液バッグを、高圧蒸気滅菌（１０５℃、３０分）した後、窒素雰囲気下、脱酸素剤と共にガスバリアー性包材（エバールフィルム）で包装し、密封し、本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００２４】
〔実施例２〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
酢酸を用いてｐＨを４．０に調整した以外は、実施例１と同様にしてブドウ糖及び塩酸チアミンを含有する輸液を得た。
２）アミノ酸、電解質及び安定化剤を含有する輸液の調製
実施例１と同様にしてアミノ酸、電解質及び安定化剤を含有する輸液を得た。
３）輸液バッグへの充填
実施例１と同様にして本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００２５】
〔実施例３〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
酢酸を用いてｐＨを４．５に調整した以外は、実施例１と同様にしてブドウ糖及び塩酸チアミンを含有する輸液を得た。
２）アミノ酸、電解質及安定化剤を含有する輸液の調製
実施例１と同様にしてアミノ酸及び電解質を含有する輸液を得た。
３）輸液バッグへの充填
実施例１と同様にして本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００２６】
〔実施例４〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
ｐＨ調整剤を用いなかった以外は、実施例１と同様にしてブドウ糖及び塩酸チアミンを含有するの輸液を得た（ｐＨは５．０）。
２）アミノ酸、電解質及び安定化剤を含有する輸液の調製
実施例１と同様にしてアミノ酸、電解質及び安定化剤を含有する輸液を得た。
３）輸液バッグへの充填
実施例１と同様にして本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００２７】
〔実施例５〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
マレイン酸を用いてｐＨを４．０に調整した以外は、実施例１と同様にしてブドウ糖及び塩酸チアミンを含有する輸液を得た。
２）アミノ酸、電解質及び安定化剤を含有する輸液の調製
実施例１と同様にしてアミノ酸、電解質及び安定化剤を含有する輸液を得た。
３）輸液バッグへの充填
実施例１と同様にして本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００２８】
〔実施例６〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
マレイン酸を用いてｐＨを４．５に調整した以外は、実施例１と同様にしてブドウ糖及び塩酸チアミンを含有する輸液を得た。
２）アミノ酸、電解質及び安定化剤を含有する輸液の調製
実施例１と同様にしてアミノ酸、電解質及び安定化剤を含有する輸液を得た。
３）輸液バッグへの充填
実施例１と同様にして本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００２９】
〔実施例７〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
表１に示した第１室成分を注射用蒸留水８００ｍｌに加温溶解し、微量の酢酸を用いてｐＨを４．５に調整した後、更に注射用蒸留水を加えて全量を１０００ｍｌとした溶液を０．２μｍのメンブランフィルターで濾過し、ブドウ糖及びビタミンＢ１を含有する輸液を得た。
２）アミノ酸、電解質及び安定化剤を含有する輸液の調製
実施例１と同様にしてアミノ酸、電解質及び安定化剤を含有する輸液を得た。
３）輸液バッグへの充填
２室に区画された輸液バッグの第１室に、上記１）で調製したブドウ糖及び塩酸チアミンを含有する輸液７００ｍｌを、窒素雰囲気下で充填し、密封した。次いで、容器を反転させ、第２室に、上記２）で調製したアミノ酸及び電解質を含有する輸液３００ｍｌを、窒素雰囲気下で充填し、密封した。この輸液バッグを高圧蒸気滅菌（１０５℃、３０分）した後、窒素雰囲気下、脱酸素剤と共にガスバリアー性包材（エバールフィルム）で包装し、密封し、本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００３０】
〔実施例８〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
表１に示した第１室成分を注射用蒸留水８００ｍｌに加温溶解し、微量の酢酸を用いてｐＨを４．５に調整した後、更に注射用蒸留水を加えて全量を１０００ｍｌとした溶液を０．２μｍのメンブランフィルターで濾過し、ブドウ糖及び塩酸チアミンを含有する輸液を得た。
２）アミノ酸、電解質及び安定化剤を含有する輸液の調製
実施例１と同様にしてアミノ酸、電解質及び安定化剤を含有する輸液を得た。
３）輸液バッグへの充填
２室に区画された輸液バッグの第１室に、上記１）で調製したブドウ糖及び塩酸チアミンを含有する輸液６００ｍｌを、窒素雰囲気下で充填し、密封した。次いで、容器を反転させ、第２室に、上記２）で調製したアミノ酸及び電解質を含有する輸液４００ｍｌを、窒素雰囲気下で充填し、密封した。この輸液バッグを、高圧蒸気滅菌（１０５℃、３０分）した後、窒素雰囲気下、脱酸素剤と共にガスバリアー性包材（エバールフィルム）で包装し、密封し、本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００３１】
〔実施例９〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
表２に示した第１室成分を注射用蒸留水８００ｍｌに加温溶解し、微量の酢酸を用いてｐＨを４．０に調整した後、更に注射用蒸留水を加えて全量を１０００ｍｌとした液を０．２μｍのメンブランフィルターで濾過し、ブドウ糖及び塩酸チアミンを含有する輸液を得た。
２）アミノ酸、電解質及び安定化剤を含有する輸液の調製
下記表２に示した第２室成分を、注射用蒸留水８００ｍｌに加温溶解し、微量の酢酸でｐＨを７．４に調整した後、更に注射用蒸留水を加えて全量を１０００ｍｌとした液を０．２μｍのメンブランフィルターで濾過し、アミノ酸、電解質及び安定化剤を含有する輸液を得た。
【００３２】
【表２】
３）輸液バッグへの充填
２室に区画された輸液バッグの第１室に、上記１）で調製したブドウ糖及び塩酸チアミンを含有する輸液８００ｍｌを、窒素雰囲気下で充填し、密封した。次いで、容器を反転させ、第２室に、上記２）で調製したアミノ酸及び電解質を含有する輸液２００ｍｌを、窒素雰囲気下で充填し、密封した。この輸液バッグをを、高圧蒸気滅菌（１０５℃、３０分）した後、窒素雰囲気下、脱酸素剤と共にガスバリアー性包材（エバールフィルム）で包装し、密封し、本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００３４】
〔実施例１０〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
表２に示した第１室成分を注射用蒸留水７００ｍｌに加温溶解し、微量の酢酸を用いてｐＨを４．０に調整した後、更に注射用蒸留水を加えて全量を１０００ｍｌとした液を０．２μｍのメンブランフィルターで濾過し、ブドウ糖及び塩酸チアミンを含有する輸液を得た。
２）アミノ酸、電解質及び安定化剤を含有する輸液の調製
実施例９と同様にしてアミノ酸、電解質及び安定化剤を含有する輸液を得た。
３）輸液バッグへの充填
２室に区画された輸液バッグの第１室に、上記１）で調製したブドウ糖及び塩酸チアミンを含有する輸液７００ｍｌを、窒素雰囲気下で充填し、密封した。次いで、容器を反転させ、第２室に、上記２）で調製したアミノ酸及び電解質を含有する輸液３００ｍｌを、窒素雰囲気下で充填し、密封した。各液を収容した容器を、高圧蒸気滅菌（１０５℃、３０分）した後、窒素雰囲気下、脱酸素剤と共にガスバリアー性包材（エバールフィルム）で包装し、密封し、本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００３５】
〔実施例１１〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
表２に示した第１室成分を注射用蒸留水８００ｍｌに加温溶解し、微量の酢酸を用いてｐＨを４．０に調整した後、更に注射用蒸留水を加えて全量を１０００ｍｌとした液を０．２μｍのメンブランフィルターで濾過し、ブドウ糖及び塩酸チアミンを含有する輸液を得た。
２）アミノ酸、電解質及び安定化剤を含有する輸液の調製
実施例９と同様にしてアミノ酸、電解質及び安定化剤を含有する輸液を得た。３）輸液バッグへの充填
２室に区画された輸液バッグの第１室に、上記１）で調製したブドウ糖及び塩酸チアミンを含有する輸液６００ｍｌを、窒素雰囲気下で充填し、密封した。次いで、容器を反転させ、第２室に、上記２）で調製したアミノ酸及び電解質を含有する輸液４００ｍｌを、窒素雰囲気下で充填し、密封した。この輸液バッグを、高圧蒸気滅菌（１０５℃、３０分）した後、窒素雰囲気下、脱酸素剤と共にガスバリアー性包材（エバールフィルム）で包装し、密封し、本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００３６】
〔比較例１〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
酢酸を用いてｐＨを３．０に調整した以外は、実施例１と同様にしてブドウ糖及び塩酸チアミンを含有する輸液を得た。
２）アミノ酸、電解質及び安定化剤を含有する輸液の調製
実施例１と同様にしてアミノ酸、電解質及び安定化剤を含有する輸液を得た。
３）輸液バッグへの充填
実施例１と同様にして本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００３７】
〔比較例２〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
クエン酸を用いてｐＨを４．０に調整した以外は、実施例１と同様にしてブドウ糖及び塩酸チアミンを含有する輸液を得た。
２）アミノ酸、電解質及び安定化剤を含有する輸液の調製
実施例１と同様にしてアミノ酸、電解質及び安定化剤を含有する輸液を得た。
３）輸液バッグへの充填
実施例１と同様にして本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００３８】
〔比較例３〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
クエン酸を用いてｐＨを４．５に調整した以外は、実施例１と同様にしてブドウ糖及び塩酸チアミンを含有する輸液を得た。
２）アミノ酸、電解質及び安定化剤を含有する輸液の調製
実施例１と同様にしてアミノ酸、電解質及び安定化剤を含有する輸液を得た。
３）輸液バッグへの充填
実施例１と同様にして本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００３９】
〔比較例４〕
１）ブドウ糖及び塩酸チアミンを含有する輸液の調製
水酸化ナトリウムを用いてｐＨを６．０に調整した以外は、実施例１と同様にしてブドウ糖及び塩酸チアミンを含有する輸液を得た。
２）アミノ酸、電解質及び安定化剤を含有する輸液の調製
実施例１と同様にしてアミノ酸、電解質及び安定化剤を含有する輸液を得た。
３）輸液バッグへの充填
実施例１と同様にして本発明の２室容器入りビタミンＢ１配合栄養輸液剤を得た。
【００４０】
〔比較例５〜８〕
１）第１室用輸液の調製
表３に示した第１室成分を注射用蒸留水８００ｍｌに加温溶解し、各ｐＨ調整剤を用いてｐＨを３．５に調整した後、更に注射用蒸留水を加えて全量を１０００ｍｌとした溶液を０．２μｍのメンブランフィルターで濾過し、第１室用の輸液を得た。
２）第２室用輸液の調製
次に、表３に示した第２室成分を、注射用蒸留水８００ｍｌに加温溶解し、更に注射用蒸留水を加えて全量を１０００ｍｌとした溶液を０．２μｍのメンブランフィルターで濾過し、第２室用の輸液を得た。
【００４１】
３）輸液バッグへの充填
２室に区画された輸液バッグの第１室に、上記で調製した第１室用の輸液８００ｍｌを、窒素雰囲気下で充填し、密封した。次いで、容器を反転させ、第２室に、上記で調製した第２室用の輸液２００ｍｌを、窒素雰囲気下で充填し、密封した。この輸液バッグを、高圧蒸気滅菌（１０５℃、３０分）した後、窒素雰囲気下脱酸素剤と共にガスバリアー性包材（エバールフィルム）で包装し、密封し、比較例５〜８の輸液剤を得た。
【００４２】
【表３】
〔比較例９〜１０〕
１）第１室用輸液の調製
表４に示した第１室成分を注射用蒸留水８００ｍｌに加温溶解し、酢酸を用いてｐＨを３．５に調整した後、更に注射用蒸留水を加えて全量を１０００ｍｌとした溶液を０．２μｍのメンブランフィルターで濾過し、第１室用の輸液を得た。
２）第２室用輸液の調製
次に、表４に示した第２室成分を、注射用蒸留水８００ｍｌに加温溶解し、更に注射用蒸留水を加えて全量を１０００ｍｌとした溶液を０．２μｍのメンブランフィルターで濾過し、第２室用の輸液を得た。
【００４４】
３）輸液バッグへの充填
２室に区画された輸液バッグの第１室に、上記で調製した第１室用の輸液８００ｍｌを、窒素雰囲気下で充填し、密封した。次いで、容器を反転させ、第２室に、上記で調製した第２室用の輸液２００ｍｌを、窒素雰囲気下で充填し、密封した。この輸液バッグを、高圧蒸気滅菌（１０５℃、３０分）した後、窒素雰囲気下脱酸素剤と共にガスバリアー性包材（エバールフィルム）で包装し、密封し、比較例９〜１０の輸液剤を得た。
【００４５】
【表４】
〔試験例１〕安定性試験
上記で製造した各輸液バッグを、４０℃（７５％）で３カ月間保存し、経時的に第１室の塩酸チアミンの残存率（％）を測定した。その結果を下記表５に示す。
【００４７】
【表５】
〔結果〕
その結果、クエン酸でｐＨ調整した輸液は１ヵ月後からビタミンＢ１の著しい残存率の低下を示した。一方、酢酸又はマレイン酸を用いてｐＨを３．５〜５．０に調整した輸液のみが良好な安定性を維持できることがわかった。
【００４９】
〔試験例２〕安定性試験
上記で製造した各輸液バッグを、４０℃（７５％）で３カ月間保存し、経時的に第１室の塩酸チアミンの残存率（％）を測定した。その結果を下記表６に示す。
【００５０】
【表６】
〔結果〕
その結果、実施例１では３カ月後も塩酸チアミンの残存率は９０％以上であったが、比較例５〜８は塩酸チアミンの残存率が低下し、安定性を維持できないことがわかった。従って、第１室にブドウ糖及びビタミンＢ１を含み、電解質を含まない輸液を収容し、第２室にアミノ酸、電解質及び安定化剤を収容した輸液が最も安定性に優れていることがわかった。
【００５２】
〔試験例３〕安定性試験
実施例１、７、８及び比較例９について、４０℃（７５％）３カ月間保存後の第１室の塩酸チアミン残存率、ブドウ糖残存率、ブドウ糖の分解指標となる２８４ｎｍにおける吸光度、着色の指標となる４３０ｎｍにおける透過率及び外観を測定した。一方、第２室はアミノ酸の中で最も不安定なＬ−システインの残存率、着色の指標となる４３０ｎｍにおける透過率及び外観を測定した。その結果を、表７及び８示す。
【００５３】
【表７】
【表８】
〔結果〕
１）第１室の塩酸チアミンの３カ月後の残存率は、いずれの例も９０％以上であった。更に、ブドウ糖の残存率も、９９％以上であり、吸光度、透過率、外観にもほとんど変化は認められなかった。
２）第２室のＬ−システインの３カ月後の残存率は９５％以上であった。更に他のアミノ酸についても９５〜１０５％とほとんど変化は認められなかった。また、透過率及び外観についても変化は認められなかった。しかし、比較例９では安定化剤が少ないためＬ−システインの残存率の低下と、着色が認められた。
以上の結果から、本発明の２室容器入りビタミンＢ１配合栄養輸液剤は、滅菌時の安定性及び長期間の保存安定性に優れていることが明らかとなった。
【００５６】
〔試験例４〕混合後の安定性試験
実施例１、７、８及び比較例１０について、第１室と第２室間の隔壁を開通し混合した後、４８時間後の塩酸チアミンの残存率と外観を測定した。その結果を下記表９に示す。
【００５７】
【表９】
〔結果〕
その結果、塩酸チアミンの残存率はいずれも９０％以上であり、外観においても着色や沈殿は認められず、２液を混合した後の安定性も良好であった。しかし、比較例１０では安定化剤が多すぎるため塩酸チアミンの残存率は、８０％以下となり混合後の安定性を維持できないことがわかった。
【００５９】
【発明の効果】
以上のように、本発明は連通可能な隔離手段により２室に区画された可撓性容器の第１室にブドウ糖及びビタミンＢ１を含み、電解質を含まない輸液を収容し、第２室にアミノ酸、電解質及び安定化剤を含む輸液を収容し、且つ第１室に収容されている輸液が酢酸又はマレイン酸を用いてｐＨ３．５〜５．０に調整されているているので、長期間の保存安定性に優れた２室容器入りビタミンＢ１配合栄養輸液剤を提供できる。更に、臨床使用時において混合後の安定性に優れ、かつ容易に混合することができるので誤操作、ガラス粉末の混入、雑菌汚染、異物混入等を起こさずに投与できるという利点を有する。[0001]
[Industrial application fields]
The present invention relates to a vitamin B1-containing nutritional infusion solution containing a two-chamber container used for high-calorie infusion therapy, and more specifically, glucose and vitamin B1 are contained in the first chamber of a flexible container partitioned into two chambers by an isolation means, and an electrolyte The present invention relates to a vitamin B1-containing nutritional infusion solution containing a two-chamber container that contains an infusion solution containing no amino acids and contains an infusion solution containing an amino acid, an electrolyte, and a stabilizer in a second chamber.
[0002]
[Prior art]
In recent years, high-calorie infusion therapy has made significant progress, and supplementation with water, electrolytes, amino acids, carbohydrates, etc. for patients who have been unable to orally lack oral or enteral nutrition and have to rely on central parenteral nutrition Has been used for. However, severe acidosis may occur due to vitamin B1 deficiency during high calorie infusion therapy.
[0003]
Therefore, in clinical practice, an operation of injecting a vitamin injection solution into a high-calorie basic solution using a syringe is performed. However, in these mixed injection operations, (1) it takes time to transfer the drug, (2) the operation is complicated, (3) there is a possibility of erroneous operation, (4) in the case of a glass ampule, There were also problems such as the possibility of contamination and (5) possible contamination with germs.
[0004]
In recent years, in order to solve such problems, studies have been made on nutritional infusions containing vitamin B1 that has a preventive effect on acidosis. However, vitamin B1 is very unstable, and a vitamin B1-containing nutritional infusion solution excellent in stability has not been sufficiently satisfactory.
[0005]
Therefore, recently, as a mixed-type infusion solution for high calorie infusions and amino acid infusions pre-mixed with water-soluble vitamin Bs, (1) in order to maintain the storage stability of vitamin Bs, An infusion solution containing no sulfite, which is usually used as a stabilizer in amino acid infusion solutions in order to maintain pH after mixing of (2) vitamin Bs with a pH of 4 or less is disclosed (Japanese Patent Laid-Open No. Hei. 8-143459).
In this infusion, since the infusion containing vitamin B1 is usually adjusted to a low pH (pH 4 or less) in order to maintain stability during heat sterilization and storage, a large amount of pH adjuster is required. It will also break the balance.
On the other hand, since no sulfite is added to amino acid infusion solutions, problems such as a decrease in amino acid content and coloring of infusion agents occur during storage.
[0006]
[Problems to be solved by the invention]
An object of the present invention is to provide a vitamin B1-containing nutritional infusion solution containing a two-chamber container for high-calorie infusion that solves not only the stability of vitamin B1 but also the problems of amino acid content reduction and coloring.
[0007]
[Means for Solving the Problems]
The inventor contains glucose and vitamin B1 in the first chamber, contains an infusion solution that does not contain an electrolyte, and contains an infusion solution that contains an amino acid, an electrolyte, and a stabilizer in the second chamber. As a result of detailed examination of the pH range and pH adjuster of the contained infusion solution and the amount of stabilizer added to the infusion solution contained in the second chamber, it was found that the above object can be achieved, and the present invention has been completed. .
[0008]
That is, the present invention contains glucose and vitamin B1 in a first chamber of a flexible container partitioned into two chambers by a separating means that can communicate with each other, and contains an infusion solution that does not include an electrolyte, and an amino acid, an electrolyte, and an electrolyte in the second chamber A vitamin B1-containing nutritional infusion solution containing a two-chamber container containing an infusion solution containing a stabilizer, wherein the infusion solution contained in the first chamber and the second chamber contains the following components in the following composition range, The vitamin B1-containing nutritional infusion solution in a two-chamber container is provided, wherein the pH of the infusion solution contained in the container is adjusted to 3.5 to 5.0.
[0009]
[0010]
DETAILED DESCRIPTION OF THE INVENTION
In the first chamber of the two-chamber mixed vitamin B1 nutritional infusion solution of the present invention, an infusion solution containing glucose and vitamin B1 and not containing electrolyte is accommodated. Examples of vitamin B1 include thiamine hydrochloride and thiamine nitrate, and preferably thiamine hydrochloride is used.
[0011]
The pH of the infusion contained in the first chamber is preferably adjusted to pH 3.5 to 5.0 from the viewpoint of safety to the living body. More preferably, the pH should be adjusted to a value close to physiological pH 4.5, that is, 4.0 to 5.0.
The present inventor has found that the use of a specific acid, that is, acetic acid or maleic acid as a pH adjusting agent can suppress the degradation of vitamin B1 even at physiological pH. This is one of the important points of the present invention.
[0012]
In the second chamber of the two-chamber container-containing vitamin B1 mixed nutrient infusion solution of the present invention, an infusion solution containing an amino acid, an electrolyte, and a stabilizer is accommodated. Examples of amino acids include various amino acids conventionally used for the purpose of nutritional supplementation, such as L-isoleucine, L-leucine, L-valine, L-lysine, L-methionine, L-phenylalanine, and L-threonine. , L-tryptophan, L-arginine, L-histidine, glycine, L-alanine, L-proline, L-aspartic acid, L-serine, L-tyrosine, L-glutamic acid, L-cysteine and the like. The amino acids are usually used in the form of free amino acids, but pharmacologically acceptable salts such as metal salts with sodium and potassium, organic acid salts with acetic acid and malic acid, mineral acid salts with hydrochloric acid and sulfuric acid. Etc. may be used.
[0013]
The electrolyte in the present invention is an electrolyte in the meaning used in the field of infusion, and includes sodium, potassium, calcium, magnesium, phosphorus, chlorine and the like. As a supply source of the electrolyte, various water-soluble salts conventionally used for infusion can be used. For example, sodium bicarbonate, sodium carbonate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium acetate, sodium lactate, sodium citrate, sodium chloride, sodium sulfate, potassium chloride, potassium iodide, potassium dihydrogen phosphate, Dipotassium hydrogen phosphate, potassium lactate, potassium citrate, potassium acetate, potassium lactate, calcium lactate, sodium glycerophosphate, potassium glycerophosphate, calcium glycerophosphate, calcium gluconate, calcium chloride, magnesium chloride, magnesium sulfate, magnesium acetate, chloride Examples include zinc, zinc sulfate, iron sulfate, ferrous chloride, ferric chloride, iron gluconate, copper sulfate, and manganese sulfate.
[0014]
Furthermore, sulfites such as sodium bisulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, Rongalite and the like are added to the infusion agent in the second chamber as a stabilizer. The inventor can not only maintain the stability of the amino acid by adjusting the amount of sulfite as the stabilizer to 0.02 g / L to 0.2 g / L, but also the infusion agent in the first chamber and the first solution. When mixing with the infusion agent in two chambers, the present inventors found two effects that have been thought to be difficult to achieve at the same time, in which the degradation of vitamin B1 could be suppressed. This is one of the important requirements of the present invention.
[0015]
The infusion agent accommodated in the second chamber is adjusted to pH 6.0 to 8.0 using hydrochloric acid, acetic acid, sodium hydroxide or the like as a pH adjuster.
[0016]
In addition to the above-described composition, the two-chamber containered vitamin B1 nutritional infusion solution of the present invention is a trace element, other vitamins, etc. as long as it does not impair the stability of the infusion solution that is the object of the present invention. The other nutrients and other components can be added to the first chamber and / or the second chamber in consideration of the daily intake.
[0017]
The vitamin B1-containing nutritional infusion solution containing a two-chamber container of the present invention can be produced according to a commonly used known method. For example, it is preferable to heat sterilize after filling each chamber with an infusion solution under an inert gas atmosphere such as nitrogen. When performing high-pressure steam sterilization as heat sterilization, it is performed at 100 to 130 ° C. for 5 to 40 minutes.
[0018]
As a flexible container in which two chambers are formed by the separating means used in the present invention, the central portion is welded by a thermal pseudo-welding method so that the strip can be peeled off, and an infusion port or The thing provided with the discharge port is mentioned. The material may be any plastic material, and examples thereof include polyvinyl chloride, polypropylene, polyethylene, and ethylene vinyl acetate copolymer.
Furthermore, in order to ensure stability, the plastic container is packaged with a packaging material having a high gas barrier property, and after replacing the space between the packaging material and the plastic container with an inert gas, an oxygen scavenger (trade name: It is preferable to enclose AGELESS (Mitsubishi Gas Chemical Co., Ltd.). Examples of the packaging material include materials such as polyester, ethylene vinyl alcohol copolymer, polyethylene terephthalate, polyvinylidene chloride, nylon, and laminate films thereof.
[0019]
The dosage of the vitamin B1 mixed nutritional infusion solution in the two-chamber container of the present invention can be appropriately increased or decreased depending on the symptoms, age, and body weight, but is usually 500 to 3000 ml, preferably 1000 to 2000 ml per day for an adult. .
[0020]
【Example】
EXAMPLES Hereinafter, although an experiment example, an Example, and a test example are given and this invention is demonstrated in detail, this invention is not limited to these.
[0021]
[Example 1]
1) Preparation of an infusion containing glucose and thiamine hydrochloride
The components in the first chamber shown in Table 1 were dissolved in 800 ml of distilled water for injection by heating and the pH was adjusted to 3.5 using a small amount of acetic acid, and further distilled water for injection was added to make the total volume 1000 ml. The solution was filtered through a 0.2 μm membrane filter to obtain an infusion containing glucose and thiamine hydrochloride.
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
The solution in the second chamber shown in Table 1 was dissolved by heating in 800 ml of distilled water for injection, and the solution made up to 1000 ml with the addition of distilled water for injection was filtered through a 0.2 μm membrane filter to obtain amino acids, electrolytes and An infusion containing a stabilizer was obtained.
[0022]
[Table 1]
3) Filling the infusion bag
The first chamber of the infusion bag divided into two chambers was filled with 800 ml of the infusion solution containing glucose and vitamin B1 prepared in 1) above under a nitrogen atmosphere and sealed. Next, the container was inverted, and 200 ml of the infusion solution containing the amino acid and electrolyte prepared in 2) above was filled in the second chamber under a nitrogen atmosphere and sealed. This infusion bag is sterilized by high-pressure steam (105 ° C, 30 minutes), then wrapped with a gas barrier wrapping material (eval film) together with an oxygen scavenger in a nitrogen atmosphere, sealed, and filled with the two-chamber vitamin of the present invention B1 nutritional infusion solution was obtained.
[0024]
[Example 2]
1) Preparation of an infusion containing glucose and thiamine hydrochloride
An infusion containing glucose and thiamine hydrochloride was obtained in the same manner as in Example 1 except that the pH was adjusted to 4.0 using acetic acid.
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
In the same manner as in Example 1, an infusion solution containing an amino acid, an electrolyte, and a stabilizer was obtained.
3) Filling the infusion bag
In the same manner as in Example 1, a vitamin B1-containing nutritional infusion solution containing a two-chamber container of the present invention was obtained.
[0025]
Example 3
1) Preparation of an infusion containing glucose and thiamine hydrochloride
An infusion solution containing glucose and thiamine hydrochloride was obtained in the same manner as in Example 1 except that the pH was adjusted to 4.5 using acetic acid.
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
In the same manner as in Example 1, an infusion containing an amino acid and an electrolyte was obtained.
3) Filling the infusion bag
In the same manner as in Example 1, a vitamin B1-containing nutritional infusion solution containing a two-chamber container of the present invention was obtained.
[0026]
Example 4
1) Preparation of an infusion containing glucose and thiamine hydrochloride
An infusion solution containing glucose and thiamine hydrochloride was obtained in the same manner as in Example 1 except that no pH adjuster was used (pH is 5.0).
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
In the same manner as in Example 1, an infusion solution containing an amino acid, an electrolyte, and a stabilizer was obtained.
3) Filling the infusion bag
In the same manner as in Example 1, a vitamin B1-containing nutritional infusion solution containing a two-chamber container of the present invention was obtained.
[0027]
Example 5
1) Preparation of an infusion containing glucose and thiamine hydrochloride
An infusion containing glucose and thiamine hydrochloride was obtained in the same manner as in Example 1 except that the pH was adjusted to 4.0 using maleic acid.
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
In the same manner as in Example 1, an infusion solution containing an amino acid, an electrolyte, and a stabilizer was obtained.
3) Filling the infusion bag
In the same manner as in Example 1, a vitamin B1-containing nutritional infusion solution containing a two-chamber container of the present invention was obtained.
[0028]
Example 6
1) Preparation of an infusion containing glucose and thiamine hydrochloride
An infusion containing glucose and thiamine hydrochloride was obtained in the same manner as in Example 1 except that the pH was adjusted to 4.5 using maleic acid.
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
In the same manner as in Example 1, an infusion solution containing an amino acid, an electrolyte, and a stabilizer was obtained.
3) Filling the infusion bag
In the same manner as in Example 1, a vitamin B1-containing nutritional infusion solution containing a two-chamber container of the present invention was obtained.
[0029]
Example 7
1) Preparation of an infusion containing glucose and thiamine hydrochloride
The components in the first chamber shown in Table 1 were dissolved in 800 ml of distilled water for injection by heating and the pH was adjusted to 4.5 using a small amount of acetic acid. Then, distilled water for injection was further added to make the total volume 1000 ml. The solution was filtered through a 0.2 μm membrane filter to obtain an infusion containing glucose and vitamin B1.
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
In the same manner as in Example 1, an infusion solution containing an amino acid, an electrolyte, and a stabilizer was obtained.
3) Filling the infusion bag
The first chamber of the infusion bag divided into two chambers was filled with 700 ml of the infusion solution containing glucose and thiamine hydrochloride prepared in 1) above under a nitrogen atmosphere and sealed. Subsequently, the container was inverted, and the second chamber was filled with 300 ml of an infusion solution containing the amino acid and electrolyte prepared in 2) above under a nitrogen atmosphere and sealed. This infusion bag was autoclaved (105 ° C., 30 minutes), then wrapped with a gas barrier wrapping material (eval film) together with an oxygen scavenger in a nitrogen atmosphere, sealed, and vitamin B1 in a two-chamber container of the present invention. A formulated nutritional infusion was obtained.
[0030]
Example 8
1) Preparation of an infusion containing glucose and thiamine hydrochloride
The components in the first chamber shown in Table 1 were dissolved in 800 ml of distilled water for injection by heating and the pH was adjusted to 4.5 using a small amount of acetic acid. Then, distilled water for injection was further added to make the total volume 1000 ml. The solution was filtered through a 0.2 μm membrane filter to obtain an infusion containing glucose and thiamine hydrochloride.
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
In the same manner as in Example 1, an infusion solution containing an amino acid, an electrolyte, and a stabilizer was obtained.
3) Filling the infusion bag
The first chamber of the infusion bag divided into two chambers was filled with 600 ml of the infusion solution containing glucose and thiamine hydrochloride prepared in 1) above under a nitrogen atmosphere and sealed. Then, the container was inverted, and the second chamber was filled with 400 ml of an infusion solution containing the amino acid and electrolyte prepared in 2) above under a nitrogen atmosphere and sealed. This infusion bag is sterilized by high-pressure steam (105 ° C, 30 minutes), then wrapped with a gas barrier wrapping material (eval film) together with an oxygen scavenger in a nitrogen atmosphere, sealed, and filled with the two-chamber vitamin of the present invention B1 nutritional infusion solution was obtained.
[0031]
Example 9
1) Preparation of an infusion containing glucose and thiamine hydrochloride
The components in the first chamber shown in Table 2 were dissolved by heating in 800 ml of distilled water for injection, the pH was adjusted to 4.0 with a small amount of acetic acid, and distilled water for injection was further added to make the total volume 1000 ml. The solution was filtered through a 0.2 μm membrane filter to obtain an infusion containing glucose and thiamine hydrochloride.
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
The ingredients in the second chamber shown in Table 2 below were dissolved by heating in 800 ml of distilled water for injection, and the pH was adjusted to 7.4 with a small amount of acetic acid, and then distilled water for injection was further added to make the total volume 1000 ml. The solution was filtered through a 0.2 μm membrane filter to obtain an infusion solution containing an amino acid, an electrolyte, and a stabilizer.
[0032]
[Table 2]
3) Filling the infusion bag
The first chamber of the infusion bag divided into two chambers was filled with 800 ml of the infusion solution containing glucose and thiamine hydrochloride prepared in 1) above under a nitrogen atmosphere and sealed. Next, the container was inverted, and 200 ml of the infusion solution containing the amino acid and electrolyte prepared in 2) above was filled in the second chamber under a nitrogen atmosphere and sealed. This infusion bag is sterilized under high pressure steam (105 ° C, 30 minutes), then wrapped with a gas barrier packaging material (eval film) together with an oxygen scavenger in a nitrogen atmosphere, sealed, and contained in the two-chamber container of the present invention A vitamin B1-containing nutrient infusion was obtained.
[0034]
Example 10
1) Preparation of an infusion containing glucose and thiamine hydrochloride
The ingredients in the first chamber shown in Table 2 were dissolved by heating in 700 ml of distilled water for injection, the pH was adjusted to 4.0 with a small amount of acetic acid, and distilled water for injection was further added to make the total volume 1000 ml. The solution was filtered through a 0.2 μm membrane filter to obtain an infusion containing glucose and thiamine hydrochloride.
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
In the same manner as in Example 9, an infusion solution containing an amino acid, an electrolyte, and a stabilizer was obtained.
3) Filling the infusion bag
The first chamber of the infusion bag divided into two chambers was filled with 700 ml of the infusion solution containing glucose and thiamine hydrochloride prepared in 1) above under a nitrogen atmosphere and sealed. Subsequently, the container was inverted, and the second chamber was filled with 300 ml of an infusion solution containing the amino acid and electrolyte prepared in 2) above under a nitrogen atmosphere and sealed. The container containing each solution is sterilized under high pressure steam (105 ° C., 30 minutes), then wrapped with a gas barrier wrapping material (eval film) together with an oxygen scavenger in a nitrogen atmosphere, and sealed. A vitamin B1-containing nutritional infusion solution in a container was obtained.
[0035]
Example 11
1) Preparation of an infusion containing glucose and thiamine hydrochloride
The components in the first chamber shown in Table 2 were dissolved by heating in 800 ml of distilled water for injection, the pH was adjusted to 4.0 with a small amount of acetic acid, and distilled water for injection was further added to make the total volume 1000 ml. The solution was filtered through a 0.2 μm membrane filter to obtain an infusion containing glucose and thiamine hydrochloride.
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
In the same manner as in Example 9, an infusion solution containing an amino acid, an electrolyte, and a stabilizer was obtained. 3) Filling the infusion bag
The first chamber of the infusion bag divided into two chambers was filled with 600 ml of the infusion solution containing glucose and thiamine hydrochloride prepared in 1) above under a nitrogen atmosphere and sealed. Then, the container was inverted, and the second chamber was filled with 400 ml of an infusion solution containing the amino acid and electrolyte prepared in 2) above under a nitrogen atmosphere and sealed. This infusion bag is sterilized by high-pressure steam (105 ° C, 30 minutes), then wrapped with a gas barrier wrapping material (eval film) together with an oxygen scavenger in a nitrogen atmosphere, sealed, and filled with the two-chamber vitamin of the present invention B1 nutritional infusion solution was obtained.
[0036]
[Comparative Example 1]
1) Preparation of an infusion containing glucose and thiamine hydrochloride
An infusion containing glucose and thiamine hydrochloride was obtained in the same manner as in Example 1 except that the pH was adjusted to 3.0 using acetic acid.
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
In the same manner as in Example 1, an infusion solution containing an amino acid, an electrolyte, and a stabilizer was obtained.
3) Filling the infusion bag
In the same manner as in Example 1, a vitamin B1-containing nutritional infusion solution containing a two-chamber container of the present invention was obtained.
[0037]
[Comparative Example 2]
1) Preparation of an infusion containing glucose and thiamine hydrochloride
An infusion containing glucose and thiamine hydrochloride was obtained in the same manner as in Example 1 except that the pH was adjusted to 4.0 using citric acid.
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
In the same manner as in Example 1, an infusion solution containing an amino acid, an electrolyte, and a stabilizer was obtained.
3) Filling the infusion bag
In the same manner as in Example 1, a vitamin B1-containing nutritional infusion solution containing a two-chamber container of the present invention was obtained.
[0038]
[Comparative Example 3]
1) Preparation of an infusion containing glucose and thiamine hydrochloride
An infusion containing glucose and thiamine hydrochloride was obtained in the same manner as in Example 1 except that the pH was adjusted to 4.5 using citric acid.
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
In the same manner as in Example 1, an infusion solution containing an amino acid, an electrolyte, and a stabilizer was obtained.
3) Filling the infusion bag
In the same manner as in Example 1, a vitamin B1-containing nutritional infusion solution containing a two-chamber container of the present invention was obtained.
[0039]
[Comparative Example 4]
1) Preparation of an infusion containing glucose and thiamine hydrochloride
An infusion solution containing glucose and thiamine hydrochloride was obtained in the same manner as in Example 1 except that the pH was adjusted to 6.0 using sodium hydroxide.
2) Preparation of infusion containing amino acids, electrolytes and stabilizers
In the same manner as in Example 1, an infusion solution containing an amino acid, an electrolyte, and a stabilizer was obtained.
3) Filling the infusion bag
In the same manner as in Example 1, a vitamin B1-containing nutritional infusion solution containing a two-chamber container of the present invention was obtained.
[0040]
[Comparative Examples 5 to 8]
1) Preparation of infusion for the first chamber
The components in the first chamber shown in Table 3 were dissolved by heating in 800 ml of distilled water for injection, and the pH was adjusted to 3.5 using each pH adjuster. Then, distilled water for injection was further added to bring the total amount to 1000 ml. The solution was filtered through a 0.2 μm membrane filter to obtain an infusion solution for the first chamber.
2) Preparation of second room infusion
Next, the components in the second chamber shown in Table 3 were dissolved by heating in 800 ml of distilled water for injection, and a solution made up to 1000 ml by adding distilled water for injection was further filtered through a 0.2 μm membrane filter. An infusion for the second chamber was obtained.
[0041]
3) Filling the infusion bag
The first chamber of the infusion bag partitioned into two chambers was filled with 800 ml of the infusion solution for the first chamber prepared above in a nitrogen atmosphere and sealed. Next, the container was inverted, and the second chamber was filled with 200 ml of the infusion solution for the second chamber prepared above in a nitrogen atmosphere and sealed. This infusion bag was sterilized by high-pressure steam (105 ° C., 30 minutes), then wrapped with a gas barrier packaging material (eval film) together with an oxygen scavenger in a nitrogen atmosphere, sealed, and the infusion agents of Comparative Examples 5-8 were used. Obtained.
[0042]
[Table 3]
[Comparative Examples 9 to 10]
1) Preparation of infusion for the first chamber
The components in the first chamber shown in Table 4 were dissolved by heating in 800 ml of distilled water for injection, the pH was adjusted to 3.5 using acetic acid, and then the distilled water for injection was further added to make a total volume of 1000 ml. Filtration through a 0.2 μm membrane filter gave an infusion solution for the first chamber.
2) Preparation of second room infusion
Next, the components in the second chamber shown in Table 4 were dissolved by heating in 800 ml of distilled water for injection, and the solution made up to 1000 ml by adding distilled water for injection was filtered through a 0.2 μm membrane filter, An infusion for the second chamber was obtained.
[0044]
3) Filling the infusion bag
The first chamber of the infusion bag partitioned into two chambers was filled with 800 ml of the infusion solution for the first chamber prepared above in a nitrogen atmosphere and sealed. Next, the container was inverted, and the second chamber was filled with 200 ml of the infusion solution for the second chamber prepared above in a nitrogen atmosphere and sealed. This infusion bag was autoclaved (105 ° C., 30 minutes), then wrapped with a gas barrier wrapping material (eval film) together with a deoxygenating agent in a nitrogen atmosphere, sealed, and the infusion agents of Comparative Examples 9-10 were used. Obtained.
[0045]
[Table 4]
[Test Example 1] Stability test
Each infusion bag produced above was stored at 40 ° C. (75%) for 3 months, and the residual rate (%) of thiamine hydrochloride in the first chamber was measured over time. The results are shown in Table 5 below.
[0047]
[Table 5]
〔result〕
As a result, the infusion solution adjusted to pH with citric acid showed a significant decrease in the residual rate of vitamin B1 after one month. On the other hand, it was found that only the infusion solution adjusted to pH 3.5 to 5.0 using acetic acid or maleic acid can maintain good stability.
[0049]
[Test Example 2] Stability test
Each infusion bag produced above was stored at 40 ° C. (75%) for 3 months, and the residual rate (%) of thiamine hydrochloride in the first chamber was measured over time. The results are shown in Table 6 below.
[0050]
[Table 6]
〔result〕
As a result, in Example 1, the residual ratio of thiamine hydrochloride was 90% or more even after 3 months, but in Comparative Examples 5 to 8, it was found that the residual ratio of thiamine hydrochloride was lowered and the stability could not be maintained. Therefore, it was found that an infusion solution containing glucose and vitamin B1 in the first chamber and containing no electrolyte and containing an amino acid, an electrolyte and a stabilizer in the second chamber had the best stability.
[0052]
[Test Example 3] Stability test
For Examples 1, 7, 8 and Comparative Example 9, the remaining rate of thiamine hydrochloride, glucose remaining rate, glucose remaining rate, absorbance at 284 nm, which is a degradation index of glucose, after storage at 40 ° C. (75%) for 3 months, The transmittance and appearance at 430 nm as an index were measured. On the other hand, in the second chamber, the residual rate of the most unstable L-cysteine among amino acids, the transmittance at 430 nm, which is an index of coloring, and the appearance were measured. The results are shown in Tables 7 and 8.
[0053]
[Table 7]
[Table 8]
〔result〕
1) The residual rate of thiamine hydrochloride in the first chamber after 3 months was 90% or more in all examples. Furthermore, the residual ratio of glucose was 99% or more, and almost no change was observed in absorbance, transmittance, and appearance.
2) The residual rate of L-cysteine in the second chamber after 3 months was 95% or more. Further, other amino acids were hardly changed to 95 to 105%. Also, no changes were observed in the transmittance and appearance. However, in Comparative Example 9, since there were few stabilizers, a decrease in the residual rate of L-cysteine and coloring were observed.
From the above results, it was clarified that the vitamin B1-containing nutrient infusion solution containing a two-chamber container of the present invention is excellent in sterilization stability and long-term storage stability.
[0056]
[Test Example 4] Stability test after mixing
In Examples 1, 7, 8 and Comparative Example 10, the partition wall between the first chamber and the second chamber was opened and mixed, and then the residual ratio and appearance of thiamine hydrochloride after 48 hours were measured. The results are shown in Table 9 below.
[0057]
[Table 9]
〔result〕
As a result, the residual ratio of thiamine hydrochloride was 90% or more, and no coloration or precipitation was observed in the appearance, and the stability after mixing the two liquids was good. However, in Comparative Example 10, since there were too many stabilizers, the residual ratio of thiamine hydrochloride was 80% or less, indicating that stability after mixing could not be maintained.
[0059]
【The invention's effect】
As described above, the present invention contains glucose and vitamin B1 in the first chamber of the flexible container partitioned into two chambers by the separating means capable of communicating, and contains an infusion without electrolyte, and the second chamber contains amino acids. Since the infusion solution containing the electrolyte and the stabilizer is contained, and the infusion solution contained in the first chamber is adjusted to pH 3.5 to 5.0 using acetic acid or maleic acid, It is possible to provide a vitamin B1-containing nutritional infusion solution containing a two-chamber container with excellent storage stability. Furthermore, it has the advantage that it can be administered without causing erroneous operations, contamination of glass powder, contamination with bacteria, contamination with foreign substances, etc. because it is excellent in stability after mixing during clinical use and can be easily mixed.
Claims (2)
第１室
成 分 配合量（１Ｌ中）
ブドウ糖 １００〜５００ｇ
ビタミンＢ １１.２５〜１２.５ｍｇ
第２室
成 分 配合量（１Ｌ中）
アミノ酸として
Ｌ−イソロイシン ３.８〜１２.３ｇ
Ｌ−ロイシン ９.１〜１６.８ｇ
Ｌ−リジン ３.９ 〜１５.６ｇ
Ｌ−メチオニン １.０〜１５.２ｇ
Ｌ−フェニルアラニン ０.３〜１５.４ｇ
Ｌ−スレオニン ２.５〜９.７ｇ
Ｌ−トリプトファン ０.７〜４.１ｇ
Ｌ−バリン ３.３〜１７.１ｇ
Ｌ−アルギニン ０〜２０.５ｇ
Ｌ−ヒスチジン ０〜７.５ｇ
グリシン ０〜２１.９ｇ
Ｌ−アラニン ０〜１１.５ｇ
Ｌ−システイン ０〜１.４ｇ
Ｌ−アスパラギン酸 ０〜７.２ｇ
Ｌ−グルタミン酸 ０〜８.４ｇ
Ｌ−プロリン ０〜１２.８ｇ
Ｌ−セリン ０〜５.６ｇ
Ｌ−チロシン ０〜０.８ｇ
電解質として
ナトリウム １５〜６０ｍＭ
カリウム ０〜４０ｍＭ
カルシウム ０〜１５ｍＭ
マグネシウム ０〜１２ｍＭ
リン ０〜１５ｍＭ
塩素 １５〜６０ｍＭ
亜鉛 ０〜３０μｍｏｌ
安定化剤として
亜硫酸塩よりなる安定化剤 ０.０２〜０.２ｇThe first chamber of the flexible container partitioned into two chambers by the isolation means capable of communication contains glucose and vitamin B1, contains an infusion without electrolyte, and the second chamber contains amino acids, electrolytes and stabilizers. A vitamin B1-containing nutritional infusion solution containing a two-chamber container containing an infusion solution, wherein the infusion solution contained in the first chamber and the second chamber contains the following components within the following composition range, and the first chamber The pH of the infusion contained in the first chamber is adjusted to 3.5 to 5.0, and the pH of the infusion contained in the first chamber is adjusted using acetic acid or maleic acid. A nutritional infusion solution containing vitamin B1 in a two-chamber container.
Room 1 Component Blending amount (1L)
Glucose 100-500g
Vitamin B 11.25 to 12.5mg
2nd chamber component Blending amount (1L)
L-isoleucine 3.8 to 12.3 g as an amino acid
L-leucine 9.1 to 16.8 g
L-lysine 3.9 to 15.6 g
L-methionine 1.0 to 15.2 g
L-Phenylalanine 0.3-15.4g
L-threonine 2.5-9.7g
L-tryptophan 0.7-4.1g
L-valine 3.3 to 17.1 g
L-Arginine 0-20.5g
L-Histidine 0-7.5g
Glycine 0-21.9g
L-alanine 0 to 11.5 g
L-cysteine 0 to 1.4 g
L-aspartic acid 0-7.2 g
L-glutamic acid 0-8.4g
L-proline 0-12.8g
L-serine 0-5.6 g
L-tyrosine 0-0.8g
Sodium as electrolyte 15-60mM
Potassium 0-40mM
Calcium 0-15mM
Magnesium 0-12mM
Phosphorus 0-15mM
Chlorine 15-60 mM
Zinc 0-30 μmol
Stabilizer consisting of sulfite as stabilizer Stabilizer 0.02-0.2g
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20970197A JP4178563B2 (en) | 1997-07-18 | 1997-07-18 | Two-chamber Vitamin B1 combination nutritional infusion |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20970197A JP4178563B2 (en) | 1997-07-18 | 1997-07-18 | Two-chamber Vitamin B1 combination nutritional infusion |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH1135471A JPH1135471A (en) | 1999-02-09 |
| JP4178563B2 true JP4178563B2 (en) | 2008-11-12 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP20970197A Expired - Lifetime JP4178563B2 (en) | 1997-07-18 | 1997-07-18 | Two-chamber Vitamin B1 combination nutritional infusion |
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| Country | Link |
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| JP (1) | JP4178563B2 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101039224B1 (en) * | 2003-05-22 | 2011-06-03 | 가부시키 가이샤 오오쯔카 세이야쿠 고우죠우 | Peripheral IV Solution and Stabilization Method of Vitamin B1 |
| JP2006001945A (en) * | 2005-09-01 | 2006-01-05 | Terumo Corp | Vitamin b1-formulated comprehensive transfusion for peripheral intravenous administration |
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|---|---|
| JPH1135471A (en) | 1999-02-09 |
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