JPS6125001B2 - - Google Patents
Info
- Publication number
- JPS6125001B2 JPS6125001B2 JP15001378A JP15001378A JPS6125001B2 JP S6125001 B2 JPS6125001 B2 JP S6125001B2 JP 15001378 A JP15001378 A JP 15001378A JP 15001378 A JP15001378 A JP 15001378A JP S6125001 B2 JPS6125001 B2 JP S6125001B2
- Authority
- JP
- Japan
- Prior art keywords
- solution
- liquid
- glucose
- preservation
- mcs
- 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
Links
- 239000000203 mixture Substances 0.000 claims description 15
- 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 10
- 239000008103 glucose Substances 0.000 claims description 10
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 2
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019797 dipotassium phosphate Nutrition 0.000 claims description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims 1
- 235000019341 magnesium sulphate Nutrition 0.000 claims 1
- 239000000162 organ preservation solution Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 description 29
- 239000007788 liquid Substances 0.000 description 24
- 210000000056 organ Anatomy 0.000 description 10
- 238000004321 preservation Methods 0.000 description 8
- 238000003860 storage Methods 0.000 description 8
- 210000003734 kidney Anatomy 0.000 description 7
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 229960001231 choline Drugs 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 3
- 238000007654 immersion Methods 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 150000003248 quinolines Chemical class 0.000 description 3
- 239000012488 sample solution Substances 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 210000002977 intracellular fluid Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 239000003761 preservation solution Substances 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- QZVCTJOXCFMACW-UHFFFAOYSA-N Phenoxybenzamine Chemical compound C=1C=CC=CC=1CN(CCCl)C(C)COC1=CC=CC=C1 QZVCTJOXCFMACW-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- ZEWYCNBZMPELPF-UHFFFAOYSA-J calcium;potassium;sodium;2-hydroxypropanoic acid;sodium;tetrachloride Chemical compound [Na].[Na+].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[Ca+2].CC(O)C(O)=O ZEWYCNBZMPELPF-UHFFFAOYSA-J 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- WRUGWIBCXHJTDG-UHFFFAOYSA-L magnesium sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Mg+2].[O-]S([O-])(=O)=O WRUGWIBCXHJTDG-UHFFFAOYSA-L 0.000 description 1
- 229940061634 magnesium sulfate heptahydrate Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 239000000082 organ preservation Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 229960003418 phenoxybenzamine Drugs 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Agricultural Chemicals And Associated Chemicals (AREA)
Description
本発明は、移植器官の洗浄、保存のための塩溶
液に関するものであり、さらに詳しくは、細胞内
液に類似した電解質組成を有するコリンの溶液
（Collins’solution）の改良、すなわち修正コリ
ン溶液（以下M.C.Sと記す）を提供するものであ
る。
近年において器官の移植に際しての器管の保存
技術の進展はめざましく特に腎保存技術の進歩は
死体腎移植の普及を益々促進している。この進歩
は、主としてその保存液の改良によるところが多
い。例えば、臨床的に用いられている腎移植のた
めの腎の保存法は、供与者（donor）の腎を受領
者（recipient）に移植する前にまず内部の血液
を完全に洗い流し、その後低温浸漬〔Lancet2
1219〜1222（1969）〕、又は、低温潅流保存
〔Lancet2 536（1967）〕する方法である。前者は
短時間の保存法として、後者は長時間保存法とし
て実用化されている。
浸漬保存法のうちでは、現在細胞外液に近いリ
ンゲルラクテートよりも、むしろ細胞内液に近い
コリン（Collins′solution）液を用いた方がすぐ
れた保存結果が得られることから腎の洗浄保存液
としてはCollins′液が有効であることがしだいに
明らかとなりつつある（Lancet 前上同）。又、
近年わが国においても死体腎移植が臨床的にもし
だいに普及しはじめCollins′液の有用性がたかま
りつつある。しかし、もともとコリン溶液はPHが
7.0と低いうえ、沈澱物を生じやすく、塩溶液の
安定性が悪く、製剤としても規格化されたものを
調製しえず、腎等の移植器官の浸漬液としては、
均一な製剤として実用化しえないものであつた。
そこで、本発明者らは移植器官特に腎を保存する
ための浸漬又は洗浄液について、至適電解質組成
の検討をなし、移植器官の浸漬、洗浄液として安
定性の高いしかも移植器官保存効果のすぐれた
MCSを見い出し本発明を完成させた。
すなわち本発明は、コリン溶液の組成において
MgSO4・7H2Oの濃度を0.60〜0.90ｇ／とした
ことを特徴とする修正コリン溶液（MCS）から
なり、その基本組成はglucose22〜28ｇ／、
KH2PO41.8〜2.3ｇ／、MgSO4・7H2O0.6〜0.9
ｇ／、KCl0・97〜1.27ｇ／、K2HPO47.2〜
11.2ｇ／、NaHCO30.67〜0.97ｇ／である。
本発明で提供したMCSは、glucose22〜28ｇ／
、KH2PO41.8〜2.3ｇ／、MgSO4・7.H2O0.6
〜0.9ｇ／、KCl0.97〜1.27ｇ／、K2HPO47.2
〜11.2ｇ／、NaHCO30.67〜0.97ｇ／である
が、これはCollins′溶液のKH2PO42.05ｇ／、
K2HPO49.7ｇ／、KCl1.12ｇ／、
NaHCO30.84ｇ／、glucose25.0ｇ／、
MgSO4・7H2O7.38ｇ／において、Mg++濃度を
通常の約1/10含有するものである。この溶液の組
成の選択の結果、この溶液はPH7.3〜7.4を示す。
又、このMCSは製剤化にあたつては、Ａ液、
Ｂ液という選択をなし、それぞれを別個に作成
し、使用時に両者を混ぜあわせるという方法がそ
の安定性のためにより好ましく推奨される。Ａ液
としては、glucose、KH2PO4、MgSO4・7H2O、
Ｂ液としては、KCl、K2HPO4、NaHCO3を含有
し、各々等量混合時の終濃度が前記濃度になるよ
うに調整する。これらは用時、等量を混合して、
浸漬、洗浄液として利用される。
Ａ液のPHは、4.0以下であり、Ｂ液のPHは、8.5
〜9.0である。Ａ液の保存は、酸性であるため容
器およびゴム栓の選定に問題はないが、Ｂ液は弱
アルカリ性のため硬質ガラスの容器および耐アル
カリ性の栓の選定が必要である。これらは、各液
の調整後、分注、施栓、滅菌を経て商品として提
供される。なお又、このMCSは、Ａ，Ｂ液に分
けず調整される場合には、低温での保存が必須で
あり、より好ましくは24時間以内の使用が望まれ
る。
MCSへの追加添加薬剤としては、必要に応じ
次のものが混合可能である。
プロカイン塩酸塩（procaine HCl）、ヘパリン
（Heperin）、フエノキシベンズアミン（phenoxy
−bezamine）、インシユリン（Insulin）、デキサ
メサザン（Dexamethasone）、メチルプレドニソ
ローン（Methylprednisolone）、抗生物質
（Antibiotics）例えばペニシリン。
本発明からなる保存液の使用方法は以下に説明
される。前記Ａ液、Ｂ液を混合した溶液でもつ
て、移植用官管を洗浄し、器官内部の血液を完全
に洗い流し、その後器官貯蔵器でＡ，Ｂ混合液中
約４℃に冷却保存し、約30時間以内の間での器官
の移植に供するのである。
以下に実施例を示す。
実施例 １
Ａ液の調製
15のガラスビンに7.6の蒸留水（70〜85
℃）をいれ、ブドウ糖400ｇ、リン酸−１−カリ
ウム28.4ｇ、硫酸マグネシウム・７水和塩12ｇ、
重亜硫酸水素ナトリウム3.2ｇを投入し、撹拌下
濃縮し、全量を８とする。
活性炭８ｇを投入し、70〜80℃15分間撹拌後、
過によつて活性炭を除去し、口経0.65μのミリ
ポアフイルターで、清澄用過をしついで分注、
施栓、捲締めをなし、121℃、20のオートクレー
ブ滅菌をなし調製した。
Ｂ液の調製
Ａ液の調製も同じ条件下で、投入原料として塩
化カリウム17.92ｇ、リン酸−２−カリウム113.9
ｇ、重炭酸ナトリウム13.12ｇとする以外はＡ液
調製における処理をくり返し調製した。
Ａ液とＢ液の混合
前記調製したＡ液とＢ液を同量ずつ混合し、
KH2PO41.89ｇ／、MgSO4・7H2O0.75ｇ／、
glucose25ｇ／、KCl1.12ｇ／、K2HPO47.60
ｇ／、NaHCO30.82ｇ／を含有する溶液をえ
た。
試験例
上記実施例で調製した各試験試料液を冷室、室
温37℃の３つの温度条件下に保存した後、以下の
各項目について経時的な変化を観察した。
(1) PH
各種条件下で保存したサンプル液についてＡ液
単独、Ｂ液単独Ａ液とＢ液の等量混合液のそれぞ
れについて表示の各温度におけるPHの経時的な変
化を測定した。結果は、表１に示す通りである。
The present invention relates to saline solutions for cleaning and preserving transplanted organs, and more particularly to an improved choline solution having an electrolyte composition similar to intracellular fluid, i.e., a modified choline solution. (hereinafter referred to as MCS). In recent years, there have been remarkable advances in organ preservation techniques for organ transplants, and in particular advances in kidney preservation techniques are increasingly promoting the spread of cadaveric kidney transplants. This progress is largely due to improvements in the preservation solution. For example, the method of kidney preservation used clinically for kidney transplantation is to first completely flush out the blood inside the donor's kidney before transplanting it to the recipient, and then cold-immerse it. [Lancet2
1219-1222 (1969)] or low-temperature perfusion preservation [Lancet2 536 (1967)]. The former has been put into practical use as a short-term preservation method, and the latter as a long-term preservation method. Among the immersion preservation methods, better preservation results can be obtained by using Collins' solution, which is closer to intracellular fluid than Ringer's lactate, which is closer to extracellular fluid. It is becoming increasingly clear that Collins' solution is effective for this purpose (Lancet, supra). or,
In recent years, cadaveric kidney transplantation has become increasingly common clinically in Japan, and the usefulness of Collins' solution is increasing. However, choline solution originally has a pH of
7.0, it is easy to form precipitates, the stability of the salt solution is poor, and standardized formulations cannot be prepared.
It could not be put to practical use as a uniform preparation.
Therefore, the present inventors investigated the optimal electrolyte composition of a immersion or washing solution for preserving transplanted organs, especially kidneys, and found that it is highly stable as a immersion or washing solution for transplanted organs, and has an excellent effect of preserving transplanted organs.
Discovered MCS and completed the present invention. That is, the present invention provides that in the composition of the choline solution,
It consists of a modified choline solution (MCS) characterized by a concentration of MgSO 4 7H 2 O of 0.60 to 0.90 g/, and its basic composition is glucose 22 to 28 g/,
KH 2 PO 4 1.8~2.3g/, MgSO 4・7H 2 O0.6~0.9
g/, KCl0・97~1.27g/, K 2 HPO 4 7.2~
11.2 g/, NaHCO 3 0.67-0.97 g/. The MCS provided in the present invention is glucose 22-28g/
, KH 2 PO 4 1.8-2.3g/, MgSO 4・7.H 2 O0.6
~0.9g/, KCl0.97~1.27g/, K 2 HPO 4 7.2
~11.2 g/, NaHCO 3 0.67-0.97 g/, which is higher than the Collins' solution of KH 2 PO 4 2.05 g/,
K2HPO4 9.7g /, KCl1.12g/,
NaHCO 3 0.84g/, glucose 25.0g/,
At 7.38 g/MgSO 4 7H 2 O, the Mg ++ concentration is about 1/10 of the normal concentration. As a result of the choice of the composition of this solution, it exhibits a pH of 7.3-7.4. In addition, when formulating this MCS, liquid A,
It is more preferable and recommended for stability to select Solution B, prepare each separately, and mix the two at the time of use. As liquid A, glucose, KH 2 PO 4 , MgSO 4・7H 2 O,
The B solution contains KCl, K 2 HPO 4 , and NaHCO 3 and is adjusted so that the final concentration of each when mixed in equal amounts becomes the above concentration. Before use, mix equal amounts of
Used as a dipping and cleaning solution. The pH of liquid A is 4.0 or less, and the pH of liquid B is 8.5.
~9.0. When storing Solution A, since it is acidic, there is no problem in selecting a container and a rubber stopper; however, since Solution B is slightly alkaline, it is necessary to select a hard glass container and an alkali-resistant stopper. After each liquid is prepared, it is dispensed, capped, and sterilized before being provided as a commercial product. Furthermore, when this MCS is prepared without being divided into liquids A and B, it is essential to store it at a low temperature, and it is more preferable to use it within 24 hours. As additional additives to MCS, the following can be mixed as necessary. Procaine HCl, Heparin, Phenoxybenzamine
-bezamine), Insulin, Dexamethasone, Methylprednisolone, Antibiotics such as penicillin. The method of using the preservation solution according to the invention is explained below. The organ for transplantation is washed with a mixture of the liquids A and B, and the blood inside the organ is completely washed away.Then, the organ is stored cooled at about 4°C in the mixed liquid A and B in an organ storage container. Organs can be transplanted within 30 hours. Examples are shown below. Example 1 Preparation of Solution A 7.6 volumes of distilled water (70-85%) in 15 glass bottles
℃), 400 g of glucose, 28.4 g of 1-potassium phosphate, 12 g of magnesium sulfate heptahydrate,
Add 3.2 g of sodium bisulfite and concentrate with stirring to bring the total volume to 8. After adding 8g of activated carbon and stirring for 15 minutes at 70-80℃,
Activated carbon was removed by filtration, and then filtered for clarification and dispensed using a Millipore filter with a diameter of 0.65μ.
The container was capped, rolled, and sterilized in an autoclave at 121°C for 20 hours. Preparation of Solution B: Preparation of Solution A was conducted under the same conditions, using 17.92 g of potassium chloride and 113.9 g of potassium 2-phosphate as input materials.
The procedure for preparing Solution A was repeated except that the amount of sodium bicarbonate was 13.12 g. Mixing of liquid A and liquid B Mix equal amounts of liquid A and liquid B prepared above,
KH 2 PO 4 1.89g/, MgSO 4・7H 2 O 0.75g/,
glucose25g/, KCl1.12g/, K 2 HPO 4 7.60
A solution containing 0.82 g/g of NaHCO 3 was obtained. Test Example After storing each of the test sample solutions prepared in the above examples under three temperature conditions: a cold room and a room temperature of 37°C, changes over time were observed for each of the following items. (1) PH Regarding the sample solutions stored under various conditions, changes in PH over time at each indicated temperature were measured for each of Solution A alone, Solution B alone, and a mixture of equal volumes of Solutions A and B. The results are shown in Table 1.
【表】【table】
【表】
まずＡ液については、いづれの条件下で保存し
た場合とも保存期間の経過につれ、しだいに酸性
側にかたむく傾向がみとめられたが、その程度は
わずかであつた。この傾向は保存温度条件が高い
ほど著明であつた。又、Ｂ液についてはいずれの
条件下で保存した場合もほぼ同じような傾向を示
し、12ケ月の保存期間中多少のPHの変化は認めら
れたがいずれも規格内であり、問題はないものと
思われる。さらにＡ液とＢ液の等量混合液につい
てはいづれの群とを著明な差はなく安定であつ
た。これとのことからＡ液にわずかながら経時的
に酸性側にPHがかたむく傾向がうかがえたが、実
際使用時のPH、即ちＡ液とＢ液の等量混合液のPH
がほとんど変化しないことから考え保存12ケ月ま
でPHに関して問題はない。
(2) 沈澱物の生成
Ａ液単独、Ｂ液単独、Ａ液とＢ液の等量混合液
のいづれも肉眼的観察の結果、異物は調製後及び
４℃、又は室温での１ケ月保存の結果いづれも認
められなかつた。しかし、対照としておこなつた
コリン溶液（Collins′soiution）（組成前出）で
は、混合直後から白色の沈澱物が観察された。
(3) 着色度
グルコース2.5W／Ｖ％を含むＡ液を37℃の保
存条件下で保存した場合でも保存12ケ月まで肉眼
的には全く着色はなく事実O.D.420mmにおける吸
光度も最も高いもので0.004とほとんど着色によ
ると思われる吸光度の変化は認められなかつた。
又、他のサンプル液についても同様で肉眼的なら
びにO.D.420mmにおける吸光度から全く着色はな
いものと判断された。
(4) ブドウ糖含量
Ａ液について、旋光度計により25℃下でセル層
長50mmのセルを用い、各サンプル液の偏光角度を
求め計算によりブドウ糖含量を経時的に測定した
結果、表２に示すごとき温度におけるいづれの条
件下で保存した場合とも各サンプル液中のブドウ
糖含量は規格内でほとんど問題はないものと思わ
れる。しかしながら、いづれの群とも時間の経過
にともないその含有率がわずかに低下する傾向が
みとめられた。[Table] First, with regard to Solution A, it was observed that under any conditions it was stored, it tended to gradually become more acidic as the storage period progressed, but the extent of this was slight. This tendency was more pronounced as the storage temperature conditions were higher. In addition, liquid B shows almost the same trends when stored under any conditions, and although some changes in PH were observed during the 12-month storage period, all were within the specifications and there were no problems. I think that the. Furthermore, the mixture of equal amounts of liquids A and B was stable with no significant difference between the groups. From this, it seems that the PH of liquid A tends to shift slightly towards the acidic side over time, but the PH at the time of actual use, that is, the PH of a mixture of equal amounts of liquid A and B.
Considering that there is almost no change in pH, there is no problem with pH until storage for 12 months. (2) Formation of precipitates As a result of visual observation of liquid A alone, liquid B alone, and a mixture of equal amounts of liquid A and B, foreign substances were found after preparation and after storage for one month at 4°C or room temperature. None of the results were acceptable. However, in the choline solution (composition listed above) used as a control, a white precipitate was observed immediately after mixing. (3) Degree of coloration Even when solution A containing glucose 2.5W/V% is stored at 37℃, there is no visible coloration at all until 12 months of storage, and in fact, the absorbance at OD420mm is the highest at 0.004. Almost no change in absorbance was observed, which was considered to be due to coloring.
The same was true for the other sample solutions, and it was determined that there was no coloration at all from the naked eye and the absorbance at OD420 mm. (4) Glucose content For liquid A, the glucose content was measured over time using a polarimeter at 25°C using a cell with a cell layer length of 50 mm, calculating the polarization angle of each sample liquid, and the results are shown in Table 2. Regardless of the conditions at which the samples were stored, the glucose content in each sample liquid was within the specifications and there would be almost no problems. However, a tendency was observed for the content to decrease slightly over time in all groups.
【表】
(5) 重炭酸塩含量
同様な炭酸においてＢ液中の炭酸ガス量をガス
クロマトグラフ法により求め炭酸ガスのモル数よ
り重炭酸塩含量に換算しなおして求めた重炭酸塩
含量の経時的変化の結果を第３に示した。
表より明らかなように12ケ月の保存期間中いづ
れのサンプルともその含量はわずかに低下する傾
向が認められた。しかもこの傾向は、冷室よりも
室温あるいは37℃で保存した場合の方が著明であ
つた。おそらくこの重炭酸塩含量の低下はゴム栓
からのCO2ガスとしての緩徐な逃散によるものと
思われる。
しかし、Ｂ液のPHであるPH8.6〜8.8程度では重
炭酸塩は96％程度がHCO3 -の形で存在しており
CO2ガスとして存在する量はわずか１％程度で、
たとえCO2ガスとしてゴム栓よりぬけでるとして
もその量はわずかなものと思われる。又、ある程
度のCO2ガスとしてのゴム栓からのもれがさけら
れないことから重炭酸塩含量の若干の低下はやむ
をえないものと思われる。[Table] (5) Bicarbonate content Bicarbonate content determined over time by calculating the amount of carbon dioxide in liquid B using a similar carbonic acid using gas chromatography and converting the number of moles of carbon dioxide into bicarbonate content. The results of this change are shown in the third section. As is clear from the table, the content tended to decrease slightly in all samples during the 12-month storage period. Moreover, this tendency was more pronounced when stored at room temperature or 37°C than when stored in a cold room. This decrease in bicarbonate content is probably due to slow escape as CO 2 gas from the rubber stopper. However, at pH 8.6 to 8.8, which is the pH of liquid B, about 96% of bicarbonate exists in the form of HCO 3 - .
The amount that exists as CO 2 gas is only about 1%.
Even if CO 2 gas escapes from the rubber stopper, the amount is thought to be small. Also, since some amount of CO 2 gas leaks from the rubber stopper, a slight decrease in the bicarbonate content seems unavoidable.
【表】【table】
Claims (1)
2.3ｇ／、MgSO4・7H2O0.60〜0.90ｇ／、
KCl0.97〜127ｇ／、K2HPO47.20〜11.20ｇ／
、NaHCO30.67〜0.97ｇ／を基本組成とする
移植器官保存液。1 Glucose 22.0-28.0g/, KH 2 PO 4 1.8-
2.3g/, MgSO4・7H2O0.60 ~ 0.90g/,
KCl0.97~127g/, K2HPO4 7.20 ~11.20g/
, a transplant organ preservation solution having a basic composition of 0.67 to 0.97 g/NaHCO 3 .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15001378A JPS5576814A (en) | 1978-12-06 | 1978-12-06 | Preservative solution for organ transplant |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15001378A JPS5576814A (en) | 1978-12-06 | 1978-12-06 | Preservative solution for organ transplant |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5576814A JPS5576814A (en) | 1980-06-10 |
| JPS6125001B2 true JPS6125001B2 (en) | 1986-06-13 |
Family
ID=15487561
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15001378A Granted JPS5576814A (en) | 1978-12-06 | 1978-12-06 | Preservative solution for organ transplant |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5576814A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0541310U (en) * | 1991-11-06 | 1993-06-01 | 株式会社ダイヘン | Combined electrical equipment for power distribution and telephone communication |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0688881B2 (en) * | 1985-09-17 | 1994-11-09 | 久則 内田 | How to store transplanted organs |
| EP0697169B1 (en) * | 1993-05-07 | 2000-11-15 | Chugai Seiyaku Kabushiki Kaisha | Organ preservative |
| CN1057192C (en) * | 1997-09-10 | 2000-10-11 | 上海长征医院 | Method for preparing preservation liquid for various kinds of living organs and the prepns. thereof |
| WO2001045678A2 (en) * | 1999-12-21 | 2001-06-28 | Id Pharma Gmbh | Medicament, a method for its production and the use thereof |
| JP4774837B2 (en) * | 2005-07-07 | 2011-09-14 | パナソニック株式会社 | Refrigerant compressor |
-
1978
- 1978-12-06 JP JP15001378A patent/JPS5576814A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0541310U (en) * | 1991-11-06 | 1993-06-01 | 株式会社ダイヘン | Combined electrical equipment for power distribution and telephone communication |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5576814A (en) | 1980-06-10 |
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