CN1713926A - 腹膜透析法 - Google Patents

腹膜透析法 Download PDF

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CN1713926A
CN1713926A CNA2003801036528A CN200380103652A CN1713926A CN 1713926 A CN1713926 A CN 1713926A CN A2003801036528 A CNA2003801036528 A CN A2003801036528A CN 200380103652 A CN200380103652 A CN 200380103652A CN 1713926 A CN1713926 A CN 1713926A
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桐林慶
頼岡徳在
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Abstract

提供了含有三磷酸腺苷或其盐的腹膜透析液及采用该腹膜透析液的腹膜透析法。它是即使长期实施透析也不会产生腹膜损伤的安全的腹膜透析液。

Description

腹膜透析法
技术领域
本发明涉及腹膜透析时的腹膜损伤的预防治疗剂、不产生腹膜损伤等的安全的腹膜透析液及使用了该透析液的腹膜透析法。
背景技术
如果发生肾衰竭，则体内的废弃物无法充分排泄，尿氮(BUN)、肌酸内酰胺(Cr)、磷(P)、钾(K)等尿毒症性物质在血中的浓度升高，导致各种症状。该症状包括易疲劳、气短、尿量减少、浮肿、食欲下降等，还包括高血压、高钾血症、贫血等。如果置之不理会导致死亡，因此对于尿毒症的治疗需进行血液透析、腹膜透析或肾移植。
其中，腹膜透析与血液透析相比，具有如下优点，即，无需机器和人手，不去医院也可进行，由于腹膜透析是一个缓慢的过程，所以可保持病人身体状况的稳定，不会导致低血压和透析后的疲劳感，而且无血液透析那样的时间限制，因此近年来被广泛采用。
但是，腹膜透析是利用了作为半透膜的腹膜的透析，它是在腹腔内植入导管、在其中注入含高浓度的葡萄糖的透析液、在存储5～6小时后排液的手段，所以如果长期进行，则出现因高浓度的葡萄糖导致的腹膜硬化、腹膜炎等引发腹膜功能损伤等问题。
发明的揭示
因此，本发明提供了不会产生腹膜损伤、可长期连续使用的腹膜透析液及使用了该透析液的腹膜透析法。
本发明者着眼于覆盖腹膜表皮的腹膜间皮细胞，找寻可防止高浓度的糖存在下产生的腹膜间皮细胞的损伤的成分，发现三磷酸腺苷(ATP)或其盐具有防止腹膜间皮细胞受损的作用，所以ATP或其盐作为腹膜损伤预防治疗剂有用，还发现如果掺入ATP或其盐，则可获得能够长期实施腹膜透析的透析液，从而完成了本发明。
即，本发明提供了含有ATP或其盐的腹膜透析液。
此外，本发明提供了以ATP或其盐为有效成分的腹膜损伤预防治疗剂。
本发明还提供了以ATP或其盐为有效成分的糖引起的细胞损伤的治疗剂。
本发明还提供了ATP或其盐在腹膜透析液的制备中的应用。
本发明还提供了ATP或其盐在腹膜损伤预防治疗剂的制备中的应用。
本发明还提供了ATP或其盐在糖引起的细胞损伤的治疗剂的制备中的应用。
本发明还提供了以采用含有效量的ATP或其盐的透析液为特征的腹膜透析法。
本发明还提供了以给予有效量的ATP或其盐为特征的腹膜损伤的处置方法。
本发明还提供了以给予有效量的ATP或其盐为特征的糖引起的细胞损伤的处置方法。
利用本发明获得即使长期进行透析也不会产生腹膜损伤的安全的腹膜透析液。
附图的简单说明
图1表示ATP对葡萄糖(5.8mM、75mM、140mM)引起的HPMC的细胞生存率(吸光度)的下降的效果。
图2表示腺苷对葡萄糖(5.8mM、75mM、140mM)引起的HPMC的细胞生存率(吸光度)的下降的效果。
图3表示ATP受体拮抗剂(舒拉明，Suramin，10μM)影响ATP对葡萄糖(5.8mM、75mM、140mM)引起的HPMC的细胞生存率(吸光度)的下降的效果的结果。
图4为表示ATP受体拮抗剂(活性蓝，Reactive Blue，2，30μM)影响ATP对葡萄糖(5.8mM、75mM、140mM)引起的HPMC的细胞生存率(吸光度)的下降的效果的结果。
图5表示ATP受体拮抗剂(PPADS，10μM)影响ATP对葡萄糖(5.8mM、75mM、140mM)引起的HPMC的细胞生存率(吸光度)的下降的效果的结果。
实施发明的最佳方式
本发明所用的三磷酸腺苷(ATP)作为细胞功能的能量源而众所周知，但完全未知其对细胞、特别是腹膜间皮细胞因高浓度的糖、特别是葡萄糖造成的损伤有防止作用。此外，如下面的实施例所示，如果在ATP受体拮抗体对腹膜间皮细胞进行前处理后使ATP发挥作用，则未见对腹膜间皮细胞损伤的改善作用。由此可知，ATP的细胞损伤治疗作用并不是将ATP引入细胞内部作为能量源使其发挥作用，而是通过ATP受体使其发挥作用。
作为ATP的盐，较好为钠盐等碱金属盐，镁盐和钙盐等碱土类金属盐等。
本发明的腹膜透析液含有有效量的ATP或其盐。腹膜透析液中的ATP或其盐的浓度为10～5000μM，较好为50～3000μM，更好为50～2000μM。
本发明的腹膜透析液中除了ATP或其盐以外，最好还含有葡萄糖及电解质。葡萄糖浓度为1000～4000mg/dl，特别好为1200～3600mg/dl。此外，电解质可采用Na+、Ca2+、Mg2+及Cl-。Na+较好为100～200mEq/l，Ca2+较好为4～5mEq/l，Mg2+较好为1～2mEq/l，Cl-较好为80～120mEq/l。此外，最好还掺入乳酸等有机酸30～50mEq/l。腹膜透析液的渗透压最好调整至300～700m0sm/l。余量为水。
采用本发明的含有ATP或其盐的腹膜透析液可防止腹膜损伤，可防止因高浓度的糖引起的细胞损伤，特别是腹膜间皮细胞损伤。这里，作为腹膜损伤可例举腹膜炎、硬化性被囊性腹膜炎、顽固性延迟性腹膜炎、弥漫性腹膜炎等。但是，本发明的腹膜损伤预防治疗剂及细胞损伤治疗剂不论腹膜透析液的形态如何，可以口服、静脉内给药、肌内给药、局部给药等方式被使用。这些给药剂型可通过掺入制药学所允许的载体、利用对本领域普通技术人员来说公知惯用的制剂方法制得。
调制口服用固形制剂时，可在ATP或其盐中加入赋形剂，并根据需要加入粘合剂、崩解剂、润滑剂、着色剂、矫味剂和脱臭剂后，通过常规方法制得片剂、包衣片剂、颗粒剂、散剂和胶囊剂等。上述添加剂可采用该领域常用的添加剂，例如，作为赋形剂可例举乳糖、白糖、氯化钠、葡萄糖、淀粉、碳酸钙、白陶土、微晶纤维素、硅酸等，作为粘合剂可例举水、乙醇、丙醇、单糖、葡萄糖液、淀粉液、明胶液、羧甲基纤维素、羟丙基纤维素、羟丙基淀粉、甲基纤维素、乙基纤维素、虫胶、磷酸钙、聚乙烯吡咯烷酮等，作为崩解剂可例举干燥淀粉、褐藻酸钠、琼脂粉末、碳酸氢钠、碳酸钙、月桂基硫酸钠、单甘油硬脂酸酯、乳糖等，作为润滑剂可例举精制滑石粉、硬脂酸盐、硼砂、聚乙二醇等，作为矫味剂可例举白糖、橙皮、柠檬酸和酒石酸等。
调制口服用液体制剂时，可在ATP或其盐中加入矫味剂、缓冲剂、稳定剂和脱臭剂，通过常法制得内服溶液剂、糖浆剂、酏剂等。这种情况下，作为矫味剂可例举香草醛等，作为缓冲剂可例举柠檬酸钠等，作为稳定剂可例举西黄蓍胶、阿拉伯树胶和明胶等。
调制注射剂时，可在ATP或其盐中加入pH调整剂、缓冲剂、稳定剂、等渗剂和居麻剂等，通过常法制得皮下、肌内及静脉内注射剂。这种情况下的pH调整剂及缓冲剂可例举柠檬酸钠、乙酸钠、磷酸钠等。作为稳定剂可例举焦亚硫酸钠、EDTA、巯基乙酸、硫代乳酸等。作为居麻剂可例举盐酸普鲁卡因、盐酸利多卡因等。作为等渗剂可例举氯化钠和葡萄糖等。
本发明的前述医药品(腹膜透析液除外)的给药量因年龄、体重、症状、给药方式及给药次数等而有所不同，通常成人最好1天1次或分数次口服或静脉内给药1～1000mg的ATP。
采用腹膜透析液进行透析时，可按照一般的腹膜透析法实施。即，利用在腹腔内植入了导管的肾病患者的腹膜中、通过该导管在其中注入含ATP的透析液(通常1.5～2.0L)的方法，或者是利用注入含ATP的生理葡萄糖浓度液后再注入以往的透析液(例如，上述高浓度的葡萄糖液)的方法实施透析，在存储约5～6小时后排液。通常该操作1天进行3～5次。这里，葡萄糖的生理浓度为0.08～0.16％(w/v)。
实施例
以下例举实施例对本发明进行更详细的说明，但本发明并不仅限于此。
实施例1
将腹膜间皮细胞(HPMC)在含ATP(0、10、100及1000μM)的培养液(M199)中预培养3小时。用HPMC培养液(生理盐水缓冲剂)洗涤后，将其在含有3种浓度(5.8mM、75mM、140mM)的葡萄糖的培养液(M199)中培养8小时，用细胞计数法(WST-1)测定HPMC的细胞生存率。
其结果如图1所示，在不含ATP的培养液中对HPMC进行预培养的情况下，随着葡萄糖浓度的提高细胞生存率下降，与此相反，如果在含ATP的培养液中对HPMC进行预培养，则由高浓度的葡萄糖引起的细胞生存率的下降得到了实质性的改善。
实施例2
用作为ATP代谢物的腺苷替代ATP，探讨其对高浓度葡萄糖中的HPMC的细胞生存率的下降的作用。
其结果如图2所示，未确认腺苷对HPMC的细胞生存率的下降具有ATP那样的改善作用。
实施例3
在实施例1的于含ATP的培养液中进行预培养之前，采用作为选择性的ATP受体拮抗剂的(1)舒拉明(P2X、P2Y受体拮抗剂，10μM)、(2)活性蓝2(P2Y受体拮抗剂，30μM)或(3)PPADS(P2X受体拮抗剂，10μM)，对HPMC进行30分钟的预培养，然后与实施例1同样进行实验。
其结果如图3、4、5所示，如果使ATP受体拮抗剂发挥作用，则未确认ATP对HPMC的细胞生存率下降的改善作用。
从实施例1的结果可知，ATP具有实质性地防止由高浓度葡萄糖引起的腹膜间皮细胞的损伤的作用。从实施例2及3的结果可知，ATP的这种作用并不是将ATP引入细胞内作为能量源使其发挥作用而产生的效果，而是通过P2受体直接发挥作用。
实施例4
腹膜透析液的配方
(1)含ATP的透析液
在3种含葡萄糖的透析液(1.36、2.27、3.86％)中添加氯化钠、乳酸钠、氯化钙、氯化镁等，使它们的浓度与以往相同，并添加ATP使其浓度达到50～2000μM。
(2)含ATP的生理葡萄糖浓度液
在生理葡萄糖浓度液(0.1％)中添加氯化钠、乳酸钠、氯化钙、氯化镁等，使它们的浓度与以往相同，并添加ATP使其浓度达到50～2000μM。

Claims (20)

1.腹膜透析液，其特征在于，含有三磷酸腺苷或其盐。
2.如权利要求1所述的腹膜透析液，其特征还在于，还含有葡萄糖及电解质。
3.腹膜损伤预防治疗剂，其特征在于，以三磷酸腺苷或其盐为有效成分。
4.糖引起的细胞损伤的治疗剂，其特征在于，以三磷酸腺苷或其盐为有效成分。
5.如权利要求4所述的治疗剂，其特征还在于，糖引起的细胞损伤为葡萄糖引起的腹膜间皮细胞的损伤。
6.三磷酸腺苷或其盐在腹膜透析液的制备中的应用。
7.如权利要求6所述的应用，其特征还在于，所述透析液还含有葡萄糖及电解质。
8.三磷酸腺苷或其盐在腹膜损伤预防治疗剂的制备中的应用。
9.三磷酸腺苷或其盐在糖引起的细胞损伤的治疗剂的制备中的应用。
10.如权利要求9所述的应用，其特征还在于，糖引起的细胞损伤为葡萄糖引起的腹膜间皮细胞的损伤。
11.腹膜透析法，其特征在于，采用含有效量的三磷酸腺苷或其盐的透析液。
12.如权利要求11所述的腹膜透析法，其特征还在于，在腹腔内植入了导管的肾病患者的腹膜中，利用该导管注入含有效量的三磷酸腺苷或其盐的透析液。
13.如权利要求11或12所述的腹膜透析法，其特征还在于，透析液中的三磷酸腺苷或其盐的浓度为10～5000μM。
14.如权利要求11或12所述的腹膜透析法，其特征还在于，透析液中还含有葡萄糖及电解质。
15.如权利要求14所述的腹膜透析法，其特征还在于，葡萄糖浓度为1000～4000mg/dl。
16.如权利要求11所述的腹膜透析法，其特征还在于，在腹腔内植入了导管的肾病患者的腹膜中，利用该导管注入含有效量的三磷酸腺苷或其盐及生理浓度的葡萄糖的透析液，然后注入含高浓度葡萄糖的透析液。
17.如权利要求16所述的腹膜透析法，其特征还在于，葡萄糖的生理浓度为0.08～0.16％(w/v)，葡萄糖浓度为1000～4000mg/dl。
18.腹膜损伤的处置方法，其特征在于，给予有效量的三磷酸腺苷或其盐。
19.糖引起的细胞损伤的处置方法，其特征在于，给予有效量的三磷酸腺苷或其盐。
20.如权利要求19所述的处置方法，其特征还在于，糖引起的细胞损伤为葡萄糖引起的腹膜间皮细胞的损伤。
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Families Citing this family (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7235589B2 (en) * 2004-09-21 2007-06-26 Bio Numerik Pharmaceuticals, Inc. Method of treating patients undergoing kidney dialysis
ES2400001T3 (es) 2007-03-02 2013-04-04 Zytoprotec Gmbh Fluido de diálisis peritoneal basado en carbohidratos que comprende residuo de glutamina
TW200936619A (en) 2007-11-15 2009-09-01 Univation Tech Llc Polymerization catalysts, methods of making, methods of using, and polyolefin products made therefrom
US8992517B2 (en) 2008-04-29 2015-03-31 Virginia Tech Intellectual Properties Inc. Irreversible electroporation to treat aberrant cell masses
US9867652B2 (en) 2008-04-29 2018-01-16 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation using tissue vasculature to treat aberrant cell masses or create tissue scaffolds
US10245098B2 (en) 2008-04-29 2019-04-02 Virginia Tech Intellectual Properties, Inc. Acute blood-brain barrier disruption using electrical energy based therapy
CA2722296A1 (en) 2008-04-29 2009-11-05 Virginia Tech Intellectual Properties, Inc. Irreversible electroporation to create tissue scaffolds
US9198733B2 (en) 2008-04-29 2015-12-01 Virginia Tech Intellectual Properties, Inc. Treatment planning for electroporation-based therapies
US10702326B2 (en) 2011-07-15 2020-07-07 Virginia Tech Intellectual Properties, Inc. Device and method for electroporation based treatment of stenosis of a tubular body part
US11272979B2 (en) 2008-04-29 2022-03-15 Virginia Tech Intellectual Properties, Inc. System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies
US11254926B2 (en) 2008-04-29 2022-02-22 Virginia Tech Intellectual Properties, Inc. Devices and methods for high frequency electroporation
US10117707B2 (en) 2008-04-29 2018-11-06 Virginia Tech Intellectual Properties, Inc. System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies
US10448989B2 (en) 2009-04-09 2019-10-22 Virginia Tech Intellectual Properties, Inc. High-frequency electroporation for cancer therapy
US9283051B2 (en) 2008-04-29 2016-03-15 Virginia Tech Intellectual Properties, Inc. System and method for estimating a treatment volume for administering electrical-energy based therapies
US10272178B2 (en) 2008-04-29 2019-04-30 Virginia Tech Intellectual Properties Inc. Methods for blood-brain barrier disruption using electrical energy
US10238447B2 (en) 2008-04-29 2019-03-26 Virginia Tech Intellectual Properties, Inc. System and method for ablating a tissue site by electroporation with real-time monitoring of treatment progress
US11638603B2 (en) 2009-04-09 2023-05-02 Virginia Tech Intellectual Properties, Inc. Selective modulation of intracellular effects of cells using pulsed electric fields
US11382681B2 (en) 2009-04-09 2022-07-12 Virginia Tech Intellectual Properties, Inc. Device and methods for delivery of high frequency electrical pulses for non-thermal ablation
WO2010138919A2 (en) 2009-05-28 2010-12-02 Angiodynamics, Inc. System and method for synchronizing energy delivery to the cardiac rhythm
US9895189B2 (en) 2009-06-19 2018-02-20 Angiodynamics, Inc. Methods of sterilization and treating infection using irreversible electroporation
ES2365429B1 (es) * 2010-03-05 2012-09-06 Universidad De Castilla De La Mancha Solucion para dialisis peritoneal
US8425455B2 (en) 2010-03-30 2013-04-23 Angiodynamics, Inc. Bronchial catheter and method of use
WO2012025602A1 (en) 2010-08-26 2012-03-01 Vib Vzw Insect binding antibodies
EP2627274B1 (en) 2010-10-13 2022-12-14 AngioDynamics, Inc. System for electrically ablating tissue of a patient
CN103228682B (zh) 2010-11-30 2015-07-22 尤尼威蒂恩技术有限责任公司 用经萃取的金属羧酸盐聚合烯烃的方法
WO2012074710A1 (en) 2010-11-30 2012-06-07 Univation Technologies, Llc. Catalyst composition having improved flow characteristics and methods of making and using the same
BR112013016116B1 (pt) 2010-12-22 2020-04-28 Univation Tech Llc processo de polimerização e sistema catalisador
US9861733B2 (en) 2012-03-23 2018-01-09 Nxstage Medical Inc. Peritoneal dialysis systems, devices, and methods
CA2830085A1 (en) 2011-03-23 2012-09-27 Nxstage Medical, Inc. Peritoneal dialysis systems, devices, and methods
BR112013029135B1 (pt) 2011-05-13 2020-12-15 Univation Technologies, Llc Composição e processo de polimerização
US9078665B2 (en) 2011-09-28 2015-07-14 Angiodynamics, Inc. Multiple treatment zone ablation probe
EP2750797B1 (en) 2011-11-08 2020-04-01 Univation Technologies, LLC Methods of preparing a catalyst system
EP2951211B1 (en) 2013-01-30 2019-11-13 Univation Technologies, LLC Processes for making catalyst compositions having improved flow
CA2943378C (en) 2014-04-02 2023-09-12 Univation Technologies, Llc Continuity compositions and methods of making and using the same
CN112807074A (zh) 2014-05-12 2021-05-18 弗吉尼亚暨州立大学知识产权公司 电穿孔系统
US10694972B2 (en) 2014-12-15 2020-06-30 Virginia Tech Intellectual Properties, Inc. Devices, systems, and methods for real-time monitoring of electrophysical effects during tissue treatment
WO2016118566A1 (en) 2015-01-21 2016-07-28 Univation Technologies, Llc Methods for gel reduction in polyolefins
EP3247548B1 (en) 2015-01-21 2021-09-01 Univation Technologies, LLC Methods for controlling polymer chain scission
ES2852023T3 (es) 2015-03-10 2021-09-10 Univation Tech Llc Composiciones de catalizador secadas por pulverización, métodos para su preparación y uso en procedimientos de polimerización de olefinas
US10533063B2 (en) 2015-04-20 2020-01-14 Exxonmobil Chemical Patents Inc. Supported catalyst systems and processes for use thereof
US10519256B2 (en) 2015-04-27 2019-12-31 Univation Technologies, Llc Supported catalyst compositions having improved flow properties and preparation thereof
DE102015007842A1 (de) * 2015-06-18 2016-12-22 Fresenius Medical Care Deutschland Gmbh Dialyselösung
US10905492B2 (en) 2016-11-17 2021-02-02 Angiodynamics, Inc. Techniques for irreversible electroporation using a single-pole tine-style internal device communicating with an external surface electrode
WO2018151903A1 (en) 2017-02-20 2018-08-23 Exxonmobil Chemical Patents Inc. Supported catalyst systems and processes for use thereof
EP3641850A4 (en) 2017-06-24 2021-03-17 NxStage Medical Inc. METHODS AND SYSTEMS FOR THE MANUFACTURE AND / OR TREATMENT OF PERITONEAL DIALYSIS FLUID
EP3661981A1 (en) 2017-08-04 2020-06-10 ExxonMobil Chemical Patents Inc. Polyethylene compositions and films prepared therefrom
US11607537B2 (en) 2017-12-05 2023-03-21 Virginia Tech Intellectual Properties, Inc. Method for treating neurological disorders, including tumors, with electroporation
WO2019169081A2 (en) 2018-02-28 2019-09-06 Nxstage Medical, Inc. Fluid preparation and treatment devices, methods, and systems
US11925405B2 (en) 2018-03-13 2024-03-12 Virginia Tech Intellectual Properties, Inc. Treatment planning system for immunotherapy enhancement via non-thermal ablation
US11311329B2 (en) 2018-03-13 2022-04-26 Virginia Tech Intellectual Properties, Inc. Treatment planning for immunotherapy based treatments using non-thermal ablation techniques
EP3784677A4 (en) 2018-04-26 2022-03-09 ExxonMobil Chemical Patents Inc. NON-COORDINATING ANION ACTIVATORS CONTAINING A CATION WITH LARGE ALKYL GROUPS
EP3810666B1 (en) 2018-06-19 2024-07-31 ExxonMobil Chemical Patents Inc. Polyethylene compositions and films prepared therefrom
US11950835B2 (en) 2019-06-28 2024-04-09 Virginia Tech Intellectual Properties, Inc. Cycled pulsing to mitigate thermal damage for multi-electrode irreversible electroporation therapy
WO2021119089A1 (en) 2019-12-11 2021-06-17 Exxonmobil Chemical Patents Inc. Processes for introduction of liquid activators in olefin polymerization reactions
US20230141606A1 (en) 2020-03-25 2023-05-11 Exxonmobil Chemical Patents Inc. Alkylation of Transition Metal Coordination Catalyst Complexes
WO2021262842A1 (en) 2020-06-26 2021-12-30 Exxonmobil Chemical Patents Inc. COPOLYMERS OF ETHYLENE, α-OLEFIN, NON-CONJUGATED DIENE, AND ARYL-SUBSTITUTED CYCLOALKENE, METHODS TO PRODUCE, BLENDS, AND ARTICLES THEREFROM
WO2021262838A1 (en) 2020-06-26 2021-12-30 Exxonmobil Chemical Patents Inc. Copolymers composed of ethylene, a-olefin, non-conjugated diene, and substituted styrene and articles therefrom
WO2022035484A1 (en) 2020-08-10 2022-02-17 Exxonmobil Chemical Patents Inc. Methods for delivery of non-aromatic solutions to polymerization reactors

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5677290A (en) * 1990-05-10 1997-10-14 Fukunaga; Atsuo F. Therapeutic use of adenosine compounds as surgical anesthetics
US5679650A (en) * 1993-11-24 1997-10-21 Fukunaga; Atsuo F. Pharmaceutical compositions including mixtures of an adenosine compound and a catecholamine
DE69406649T2 (de) * 1993-02-10 1998-03-05 Astra Pharmaceuticals Ltd., Kings Langley, Hertfordshire N-alkyl-2-substituierte atp-analoge
US5547942A (en) * 1994-01-04 1996-08-20 Rapaport; Eliezer Method of treatment of diabetes mellitus by administration of adenosine 5'-t
JPH09143063A (ja) 1995-11-22 1997-06-03 Kose Corp 外用に適する組成物
JP3623294B2 (ja) * 1995-11-28 2005-02-23 株式会社新素材総合研究所 電解質液が収容された医療用容器及びその製造方法
KR100384188B1 (ko) * 1997-08-22 2003-06-18 시미즈 세이야꾸 가부시키가이샤 글루코스 함유 제제
EP2070535B1 (en) * 1998-08-24 2015-07-08 Kurokawa, Kiyoshi Drugs for relieving carbonyl stress and peritoneal dialysates
US6309673B1 (en) * 1999-09-10 2001-10-30 Baxter International Inc. Bicarbonate-based solution in two parts for peritoneal dialysis or substitution in continuous renal replacement therapy

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