CN103974701A - 慢性肾脏病的改善、预防剂 - Google Patents
慢性肾脏病的改善、预防剂 Download PDFInfo
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- CN103974701A CN103974701A CN201280060370.3A CN201280060370A CN103974701A CN 103974701 A CN103974701 A CN 103974701A CN 201280060370 A CN201280060370 A CN 201280060370A CN 103974701 A CN103974701 A CN 103974701A
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- kidney disease
- chronic kidney
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Abstract
本发明目的在于提供一种不像既有的对症疗法药剂，而是可增加eGFR值，并可改善肾功能本身的慢性肾脏病改善剂。制备了含有5-氨基乙酰丙酸(ALA)或者其衍生物或其盐作为有效成分的慢性肾脏病改善和/或预防剂。优选的是，所述ALA类中含有柠檬酸亚铁钠等含金属的化合物。作为上述ALA类，可优选例示ALA及其甲基酯、乙基酯、丙基酯、丁基酯、戊基酯等各种酯类，以及它们的盐酸盐、磷酸盐、硫酸盐等。
Description
技术领域
本发明涉及一种慢性肾脏病的改善和/或预防剂，更具体地说，本发明涉及一种包含5-氨基乙酰丙酸(ALA)或者其衍生物或其盐的慢性肾脏病的改善和/或预防剂。
背景技术
所谓“慢性肾脏病”，是指肾脏功能慢性下降的疾病，即便同为肾脏疾患，仍可与急性的肾炎等区分。由于肾脏可发挥通过过滤来除去血液中的代谢废物的作用，若肾脏功能下降则代谢废物会累积于体内，而呈现所谓尿毒症的症状。此外，有时因过滤功能下降导致有用的营养成分、离子排出至尿中，而发生营养失调、电解质的丧失，或因造血因子红细胞生成素的生产量在肾脏中降低，而引起肾性贫血。日语里将非常重要的事，以用于毒物代谢的两个器官——肝脏、肾脏的首字并列地称为「肝肾」，由此可知，肾脏确实是一种重要的器官。
若肾功能下降持续恶化，则会引起尿毒症、引起恶心、焦躁、倦怠感、水肿、晕眩、高血压、呼吸困难等症状，若置之不理，有时还会引起肾衰竭而死亡。
关于慢性肾脏病，尽管有因受伤、休克等引起的急性肾衰竭未能复原而转变至慢性肾脏病的实例，但它通常因肾脏功能长期缓慢下降而发病。此外，在很多情况下，慢性肾脏病伴有肾脏的萎缩，肾脏一旦萎缩便无法复原。
为减缓疾病的恶化，主要进行食物疗法或生活的控制；为减轻压力而限制工作量，以及为减轻肾脏的负担而限制蛋白质和盐分量，然而长期的饮食限制对患者造成了极大的负担。
已知还不知道有直接治疗慢性肾脏病的药剂，以下列举为了改善慢性肾脏病目前所使用的主要药物：
1)肾上腺皮质激素、免疫抑制剂
作为针对肾炎、肾病综合征等的对症疗法使用。
2)抗血小板药
以使血流顺畅来减轻肾脏负担为目的而使用，但有出血不止的风险。
3)降血压剂(钙拮抗剂、ACE抑制剂、ARB药、α阻断剂)
以降低血压来减轻肾脏负担为目的而使用。
4)钙剂、活性型维生素D制剂
作为肾功能下降时应对钙缺乏的对策使用。
5)铁剂、红细胞生成素
作为肾功能下降时应对贫血的对策使用。
6)高尿酸治疗药
作为肾功能下降时应对高尿酸的对策使用。
7)高脂血症治疗药
降低血清胆固醇以减轻肾脏负担。
8)糖尿病治疗药(磺酰基系、那格列奈(nateglinide)系、双胍系、胰岛素等)
用于糖尿病性肾病变中的糖尿病的治疗。
这些均未能直接改善肾功能，通过对症疗法或辅助疗法()以减缓疾病恶化为目的，因此目前并不存在针对慢性肾脏病的治本性医药品。
目前，肾功能下降的根本性治疗仅限于肾移植或透析。然而，肾移植不仅造成患者的负担，还有肾脏提供者的问题。而且，由于透析也使患者长时间受到定期制约，以致生活方式极为受限，且据估计的每人每年一千万日元的治疗费已造成直接涉及国民医疗费高涨的社会问题。
就肾功能来说，尽管辅助性地采用检测血尿或蛋白质量的尿液检查，但主要是利用血清肌酸酐值、和由血清肌酸酐值与年龄依下式所计算的肾小球滤过率(eGFR)来判定。
[数1]
GFR(肾小球滤过率)的推算式
单位：mL/min/1.73m2
男性：eGFR＝194×Cr-1.094×年龄-0.287
女性：eGFR＝0.739×男性的eGFR计算式
当上述eGFR低于90时则判定为肾脏病，低于60时会呈现水肿等自觉症状，低于30时需有透析的准备，而低于15时，如未进行肾移植或透析则因尿毒症致命的可能性增高。一旦罹患慢性肾脏病，通常eGFR值并无法改善，只能由节制和对症疗法来延缓疾病的恶化。在日本，每8人中即有1人为慢性肾脏病患者，据估计患者数为1330万人。接受透析的患者亦有26万人存在，且每年增加1万人。慢性肾脏病的治疗药的开发可拯救患者自不用说，在解救拮据的医疗经济方面也成为国家的课题。
此外，已知的是慢性肾病是因作为造血因子的红细胞生成素的产量下降而引起贫血。关于贫血与ALA的关系，已经报道了ALA对于仔猪的贫血防止是有效的(例如参照专利文献1)。
【现有技术文献】
【专利文献】
【专利文献1】日本专利第4754731号公报
发明内容
发明所要解决的问题
本发明的目的在于提供一种并不是现有的慢性肾脏病的对症疗法药剂，而是可增加eGFR值，并可改善肾功能本身的慢性肾脏病改善剂。
用于解决问题的手段
本发明的发明人等在持续进行各种关于ALA的医疗的应用的探讨当中，当为了研究ALA的药物动力学而进行放射性标记的ALA(14C-ALA)的施用实验时，结果确认不仅在所预期的肝脏或肌肉中，在肾脏中也可发现来自ALA的放射线的累积。由于ALA水溶性高，来自ALA的放射线量在肾脏即使较高，一般来说也无特别的疑问。然而，意外的是，当过量施用ALA时，可看出即使进行排尿，经过一段时间后放射线仍会存留于肾脏。由此可得这样的想法：由体外施用的ALA存留于肾脏，这意味着其在肾脏中发挥某种作用。
基于上述想法，本发明的发明人等彻底地分析研究ALA、ALA的代谢物与肾功能的关系，并反复进行探讨，结果完全意外的是，得出所谓“不得不认为ALA或ALA的代谢物与肾脏原本的过滤毒物的功能息息相关”的结论。
如上所述，关于贫血与ALA的关系，已报道ALA对于防止仔猪的贫血是有效的，但伴随个体急速成长而引起的贫血与伴随慢性肾脏病而引起的贫血，即便为相同症状但原因相异。此外，本发明的发明人等还发现ALA有改善癌性贫血(cancerous anemia)的效果，但认为此为癌特异性溶血反应的抑制所致。而且，本发明的发明人等已发现ALA有助于糖尿病的改善。通过ALA所达到的糖尿病的改善，可认为主要是肌肉或肝脏内的线粒体的电子传递系统改善所致，其机制与通过ALA所达到的慢性肾脏病的改善相异。慢性肾脏病由糖尿病恶化的实例确实有很多，但ALA可改善非由糖尿病所致的慢性肾脏病的eGFR值，因此可知通过ALA所达到的糖尿病的改善与慢性肾脏病的改善，其技术思想是完全不同的。
关于在慢性肾脏病的改善中ALA的作用，可推定不是已经明了的ALA的各种效果、卟啉或血红素前体所产生的效果、提升电子传递系统的效果、癌患者的防止溶血效果、免疫赋活效果、抗氧化效果的任一种。虽然ALA所达到的慢性肾脏病的改善的作用机制的阐明需要进一步的研究，但由“eGFR值直接改善”、“来自标记化ALA的放射线长期存留于肾脏”，可推论“认为ALA直接涉及、或是ALA代谢物涉及肾脏的肾小球中用于过滤的基底膜的修复或主动过滤系统(active filtration system)的强化是合理的”。以慢性肾脏病而言，若肾功能开始下降、过滤能力降低的过滤体形成，则会对剩余的正常的过滤体造成负担，因而造成了在正常的过滤体的功能下降的情况下的恶性循环。只要处于正常状态下，即使摘出一个肾脏仍可过着一般的生活，如此在正常情况下肾功能虽有余力(available power)，但在慢性肾脏病发病前此余力会缓缓减少，终至进入前述的不良循环中。于慢性肾脏病发病前只要摄取含有ALA的制剂，此余力部分便得以改善，或可通过减缓此功能下降，可预防或延缓慢性肾脏病的发病。此外，亦发现铁化合物等含金属的化合物若与ALA相结合则可增强本发明的效果。在矿物质充足的情况下、或在另外摄取的情况下，单独施用ALA时毫无任何问题。矿物质当中，与其它国家相比，对红肉的摄取量较少的日本人有缺乏铁的倾向。因此，尽管在针对红肉的摄取量较少的日本人的实施例中亦同时添加了铁，但若以具有充足的储存铁的人为对象时则无此必要。此外，尽管众所周知的是ALA会代谢成卟啉，光照射时会显示出PDT(光动力学治疗)、PDD(光动力学诊断)活性，但对于本发明的慢性肾脏病改善剂，“光”并非是必要的。
本发明的发明人等经过进一步对于施用方法、与其他成分及其他药剂的组合、施用量等深入反复研究，而确立包含ALA的慢性肾脏病的改善和/或预防剂，从而完成了本发明。
即，本发明是有关：
(1)慢性肾脏病的改善和/或预防剂，其特征在于含有以下式(I)表示的化合物或其盐，
(式中，R1表示氢原子或酰基，R2表示氢原子、直链或支化烷基、环烷基、芳基或芳烷基)；
(2)如上述(1)所述的慢性肾脏病的改善和/或预防剂，其中，R1及R2为氢原子；
(3)如上述(1)或(2)所述的慢性肾脏病的改善和/或预防剂，其进一步含有一种或二种以上的含金属的化合物；
(4)如上述(3)所述的慢性肾脏病的改善和/或预防剂，其中，所示含金属的化合物为含有铁、镁、锌、镍、钒、铜、铬、钼或钴的化合物；
(5)如上述(3)所述的慢性肾脏病的改善和/或预防剂，其中，所述含金属的化合物为含有铁、镁或锌的化合物；
(6)如上述(3)所述之慢性肾脏病的改善和/或预防剂，其中，所述含金属的化合物为含有铁的化合物。
此外，本发明亦有关：
(7)慢性肾脏病的改善和/或预防方法，其特征在于施用以式(I)表示的化合物或其盐、或者施用以式(I)表示的化合物或其盐及含金属的化合物。作为其他形态，本发明系有关一种供使用于慢性肾脏病的改善方法和/或预防方法之以式(I)表示之化合物或其盐、或者以式(I)表示之化合物或其盐及含金属的化合物。
【发明之效果】
根据本发明的慢性肾脏病的改善和/或预防剂，可获得所谓能直接改善肾脏的过滤能力、和/或预防肾脏的过滤能力下降的迄今的药剂所没有的优良慢性肾脏病改善情形，可大幅改善慢性肾脏病患者的生活品质(QOL)。
附图说明
图1表示摄取本发明的慢性肾脏病的改善和/或预防剂前与摄取后血清肌酸酐值及eGFR值的图表。
具体实施方式
本发明中“慢性肾脏病”是指一般在医疗领域中被称为CKD的慢性肾功能下降的症状，并指从以下:
(1)伴有构造或功能异常的肾损害或
(2)肾小球滤过率下降的状态
两种症状中的任一种或两种所看出的，除短暂出现病症即消失以外的肾功能下降，且不用管达到发病的原因。
此外，ALA用量一旦降低，效果便会减弱，若恢复至原用量则可得到原来的效果，由此来确认本发明的慢性肾脏病的预防效果。
可用作本发明的慢性肾脏病的改善和/或预防剂的有效成分的化合物可例示为以式(I)表示的化合物或其盐(以下将这些总称为“ALA类”)。亦称为δ-氨基乙酰丙酸的ALA是式(I)的R1及R2皆为氢原子的情况，是氨基酸的1种。作为ALA衍生物，可例举式(I)的R1为氢原子或酰基、式(I)的R2为氢原子、直链或支化烷基、环烷基、芳基或芳烷基的ALA以外的化合物。
作为式(I)中的酰基，可例举甲酰基、乙酰基、丙酰基、丁酰基、异丁酰基、戊酰基、异戊酰基、三甲基乙酰基、己酰基、辛酰基、苄基羰基(benzylcarbonyl)等直链或支化的碳数1-8的烷酰基、或苯甲酰基、1-萘甲酰基、2-萘甲酰基等碳数7-14的芳酰基。
作为式(I)中的烷基，可例举甲基、乙基、丙基、异丙基、丁基、异丁基、仲丁基、叔丁基、戊基、异戊基、新戊基、己基、庚基、辛基等直链或支化的碳数1-8的烷基。
作为式(I)中的环烷基，可例举环丙基、环丁基、环戊基、环己基、环庚基、环辛基、环十二烷基、1-环己烯基等可存在饱和、或一部分不饱和键的碳数3-8的环烷基。
作为式(I)中的芳基，可例举苯基、萘基、蒽基、菲基等碳数6-14的芳基。
作为式(I)中的芳烷基，芳基部分可例示与上述芳基相同的基团，烷基部分亦可例示与上述烷基相同的基团，具体可例举苄基、苯乙基、苯丙基、苯丁基、二苯甲基、三苯甲基、萘甲基、萘乙基等碳数7-15的芳烷基。
作为上述ALA衍生物，优选为其中R1为甲酰基、乙酰基、丙酰基、丁酰基等的化合物、或其中上述R2为甲基、乙基、丙基、丁基、戊基等的化合物，优选可例举上述R1与R2的组合为甲酰基与甲基、乙酰基与甲基、丙酰基与甲基、丁酰基与甲基、甲酰基与乙基、乙酰基与乙基、丙酰基与乙基、丁酰基与乙基的组合等。
ALA类只要在活体内以由式(I)表示的ALA或其衍生物的状态作为有效成分而发挥作用即可，依据施用形式，只要以用于提升溶解性的各种盐、酯或者可由活体内的酶分解的前体药物(前体)的形式施用即可。举例而言，作为ALA或其衍生物的盐，可例举药理学上可接受的酸加成盐、金属盐、铵盐、有机胺加成盐等。作为酸加成盐，可例示如盐酸盐、氢溴酸盐、氢碘酸盐、磷酸盐、硝酸盐、硫酸盐等各无机酸盐、甲酸盐、乙酸盐、丙酸盐、甲苯磺酸盐、琥珀酸盐、草酸盐、乳酸盐、酒石酸盐、乙醇酸盐、甲磺酸盐、丁酸盐、戊酸盐、柠檬酸盐、延胡索酸盐、马来酸盐、苹果酸盐等各有机酸加成盐。作为金属盐，可例示锂盐、钠盐、钾盐等各碱金属盐、镁盐、钙盐等各碱土金属盐、铝、锌等各金属盐。作为铵盐，可例示铵盐、四甲基铵盐等烷基铵盐等。作为有机胺盐，则可例示三乙胺盐、哌啶盐、吗啉盐、甲苯胺盐等各盐。此外，此等盐在使用时亦能以溶液形式使用。
以上的ALA类当中，优选为ALA、及ALA甲基酯、ALA乙基酯、ALA丙基酯、ALA丁基酯、ALA戊基酯等各种酯类、以及它们的盐酸盐、磷酸盐、硫酸盐，作为特别优选的，可例示ALA盐酸盐、ALA磷酸盐。
上述ALA类可通过化学合成、利用微生物生产、利用酶生产等任意的公知方法来制造。此外，上述ALA类可形成水合物(hydrate)或溶剂合物，亦可单独或适当组合2种以上来使用ALA类。
本发明的慢性肾脏病的改善和/或预防剂优选以在不发生过多症的范围，进一步含有含金属的化合物；作为所述含金属的化合物的金属部分，可例举铁、镁、锌、镍、钒、钴、铜、铬、钼，但优选为铁、镁、锌，其中作为更优选的可例示铁。
以上述铁化合物而言，可为有机盐或无机盐，作为无机盐可例举氯化铁、三氧化二铁、硫酸铁、焦磷酸亚铁，作为有机盐则可例举属羧酸盐，例如作为羟基羧酸盐的柠檬酸亚铁、柠檬酸铁钠、柠檬酸亚铁钠、柠檬酸铁铵等柠檬酸盐、焦磷酸铁、乳酸铁、葡萄糖酸亚铁、二乙三胺五乙酸铁钠、二乙三胺五乙酸铁铵、乙二胺四乙酸铁钠、乙二胺五乙酸铁铵、二羧甲基谷氨酸铁钠、二羧甲基谷氨酸铁铵、富马酸亚铁、乙酸铁、草酸铁、琥珀酸亚铁、琥珀酸柠檬酸铁钠等有机酸盐、或血红素铁(heme iron)、右旋糖酐铁、三亚乙基四胺铁、乳铁蛋白铁、转铁蛋白铁、铁叶绿酸钠(sodium iron chlorophyllin)、铁蛋白铁(ferritin iron)、含糖氧化铁(saccharated iron oxide)、硫酸甘氨酸亚铁(ferrous glycine sulphate)。
作为上述镁化合物，可例举柠檬酸镁、苯甲酸镁、乙酸镁、氧化镁、氯化镁、氢氧化镁、碳酸镁、硫酸镁、硅酸镁、硝酸镁、二乙三胺五乙酸镁二铵、乙二胺四乙酸镁二钠、镁原卟啉。
作为上述锌化合物，可例举氯化锌、氧化锌、硝酸锌、碳酸锌、硫酸锌、二乙三胺五乙酸锌二铵、乙二胺四乙酸锌二钠、锌原卟啉、含锌的酵母。
上述含金属的化合物可分别使用1种或2种以上，作为含金属的化合物的施用量，以摩尔比计，可以为ALA类的施用量的0-100倍，优选为0.01倍-10倍，更优选为0.1倍-8倍。
本发明的慢性肾脏病改善和/或预防剂所含有的ALA类与含金属的化合物，可作成包含ALA类及含金属的化合物的组合物来施用、或各自单独施用，但在各自单独施用时，优选的是同时施用它们；于此，“同时”不仅指“于同时刻进行”，亦指“即便为非同时，为使ALA类及含金属的化合物的施用能够发挥相加效果，优选为相乘效果，亦于两者间未隔开相当间隔之下进行”的意思。
作为本发明的慢性肾脏病改善和/或预防剂的施用路径，可例举亦包舌下施用的经口施用、或者利用导管的肾脏直接施用、吸入施用、包括静脉滴注的静脉内施用、使用泥罨剂(cataplasm)等的经皮施用、坐药、或利用鼻胃管、鼻肠管、胃造口管(gastrostomy tube)或是肠造口管的强制性肠道营养法(enteral nutrition)所进行的施用等非经口施用等。
作为本发明的慢性肾脏病改善和/或预防剂的剂型，可根据上述施用路径来适当决定，可例举注射剂、点滴剂(drops)、片剂、胶囊剂、细粒剂、散剂、液剂、溶于糖浆等的水剂(liquid agents)、泥罨剂、坐药剂等。
为制备本发明的慢性肾脏病改善和/或预防剂，可视需求添加药理学上可接受的载体、赋形剂、稀释剂、添加剂、崩解剂、结合剂(binder)、被覆剂、润滑剂、助流剂(glidant)、滑剂(lubricating agent)、增味剂(flavoring agent)、甜味剂、增溶剂、溶剂、凝胶剂、营养剂等，具体可例示水、生理食盐水、动物性脂肪及油、植物油、乳糖、淀粉、明胶、结晶性纤维素、树胶(gum)、滑石、硬脂酸镁、羟丙基纤维素、聚烷撑二醇(polyalkylene glycol)、聚乙烯醇、甘油。此外，以水溶液形式制备本发明的慢性肾脏病改善和/或预防剂时，为防止ALA类的分解，需留意勿使水溶液呈碱性，若其呈碱性时，亦可通过去除氧气来防止分解。
作为本发明的慢性肾脏病改善剂的施用量、频率、时间，尽管将因慢性肾脏病患者的年龄、体重、症状等而异，但作为ALA类的施用量，以ALA的摩尔换算计，可例举成人每人0.01mmol-25mmol/日，优选为0.025mmol-7.5mmol/日，更优选为0.075mmol-5.5mmol/日，进一步优选为0.2mmol-2mmol/日，作为施用频率，则可例示一日一次至多次的施用或静脉滴注等所进行的连续施用。施用时间可基于肌酸酐、尿素氮、eGFR等表示肾脏功能的指标，利用该技术领域的药理学家或临床医师已知的方法来确定。此外，作为本发明的慢性肾脏病预防剂的施用量、频率、时间，尽管因对象的年龄、体重、症状等而异，但作为ALA类的施用量，以ALA摩尔换算计，可例举成人每人0.004mmol-6.5mmol/日，优选为0.008mmol-2mmol/日，更优选为0.15mmol-1.5mmol/日，进一步优选为0.17mmol-0.45mmol/日，作为施用频率，则可例示一日一次至多次的施用。施用时间可基于肌酸酐、尿素氮、eGFR等表示肾脏功能的指标，在观察勿使肾功能恶化发生的同时，利用该技术领域的药理学家或临床医师已知的方法来确定。
以下根据实施例对本发明更具体进行说明，但本发明的技术范围并不限定于这些例示。
【实施例1】
针对长期罹患慢性肾脏病的72岁女性进行调查。该女性经诊断为非糖尿病。(1)2010年12月22日、及(2)2011年1月4日起约7周，按每日摄取50mg氨基乙酰丙酸磷酸盐与57.4mg柠檬酸亚铁钠后的2011年2月24日的尿素氮、血清肌酸酐、eGFR与慢性肾脏病的诊断结果示于以下表1。
【表1】
由上述表1可知慢性肾脏病已改善。曾经被诊断为肾衰竭的人复原的实例极为少有，可知本发明的肾脏病改善剂的效果是与众不同的。
【实施例2】
对经诊断为慢性肾脏病的68岁男性，针对氨基乙酰丙酸磷酸盐与柠檬酸亚铁钠的摄取效果进行调查。该男性自48岁时起血清肌酸酐值即上升至1.3左右，尽管已对其开了Uralyt(日本Chemiphar公司制)的处方，但未被诊断为糖尿病。
针对以下的：
(a)开始服用氨基乙酰丙酸磷酸盐与柠檬酸亚铁钠前；
(b)摄取50mg氨基乙酰丙酸磷酸盐与57.4mg柠檬酸亚铁钠1个月后；
(c)其后，转换为5mg氨基乙酰丙酸磷酸盐与5.74mg柠檬酸亚铁钠并摄取1个月后；
(d)转换为摄取5mg氨基乙酰丙酸磷酸盐与5.74mg柠檬酸亚铁钠2个月后；
(e)其后，改回摄取50mg氨基乙酰丙酸磷酸盐与57.4mg柠檬酸亚铁钠1个月后；
的各个检查值以时间顺序排列的结果示于以下表2。
【表2】
由上述表2可明了，当摄取50mg氨基乙酰丙酸磷酸盐时eGFR值显著改善(增加)，若将氨基乙酰丙酸磷酸盐减量至5mg及柠檬酸亚铁钠减量至5.74mg，eGFR值的改善速度下降，但再次改回50mg的氨基乙酰丙酸磷酸盐时则可看出明显的改善。摄取的男性从慢性肾脏病特有的倦怠感中解脱，得到改善而可享受每周2、3次30分钟左右的散步乐趣，可知采用本发明的肾脏病改善剂得以明显提升生活品质。
【实施例3】
对约5年前因癌症摘出一个肾，其后形成慢性肾脏病的74岁男性针对氨基乙酰丙酸磷酸盐与柠檬酸亚铁钠的摄取效果进行调查。该男性的HbA1c为6.6而被诊断为非糖尿病。图1显示了每日摄取150mg氨基乙酰丙酸磷酸盐与172mg柠檬酸亚铁钠前与摄取后的血清肌酸酐值及eGFR值
由图1可明了，其显示明显的血清肌酸酐下降，明确表示ALA对于慢性肾脏病是有效的。以该患者的病情而言，虽因“摘出一个肾”的物理性问题而造成慢性肾脏病，但对此类患者亦有效果，这意味着每单位面积的肾脏的过滤膜的能力提高，因此在研究本药剂的作用机制方面将备受瞩目
【产业上可利用性】
可于医疗领域中有利地利用本发明的慢性肾脏病改善和/或预防剂。
Claims (7)
1.慢性肾脏病的改善和/或预防剂，其特征在于含有以下式(I)表示的化合物或其盐，
[化学式1]
式中，R1表示氢原子或酰基；R2表示氢原子、直链或支化烷基、环烷基、芳基或芳烷基。
2.如权利要求1所述的慢性肾脏病的改善和/或预防剂，其中，R1及R2为氢原子。
3.如权利要求1或2所述的慢性肾脏病的改善和/或预防剂，其进一步含有一种或二种以上的含金属的化合物。
4.如权利要求3所述的慢性肾脏病的改善和/或预防剂，其中，所述含金属的化合物为含有铁、镁、锌、镍、钒、铜、铬、钼或钴的化合物。
5.如权利要求3所述的慢性肾脏病的改善和/或预防剂，其中，所述含金属的化合物为含有铁、镁或锌的化合物。
6.如权利要求3所述的慢性肾脏病的改善和/或预防剂，其中，所述含金属的化合物为含有铁的化合物。
7.慢性肾脏病的改善和/或预防方法，其特征在于施用以下式(I)表示的化合物或其盐、或者以下式(I)表示的化合物或其盐及含金属的化合物，
[化学式2]
式中，R1表示氢原子或酰基，R2表示氢原子、直链或支化烷基、环烷基、芳基或芳烷基。
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| CN201280060370.3A Pending CN103974701A (zh) | 2011-10-12 | 2012-10-05 | 慢性肾脏病的改善、预防剂 |
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| US9707196B2 (en) | 2011-10-12 | 2017-07-18 | Sbi Pharmaceuticals Co., Ltd. | Treatment agent and/or prophylactic agent for side effects of cancer drugs |
| JP5881722B2 (ja) * | 2011-10-12 | 2016-03-09 | Ｓｂｉファーマ株式会社 | がん性貧血改善・予防剤 |
| CN104105482B (zh) * | 2011-10-12 | 2017-10-24 | 思佰益药业股份有限公司 | 红细胞生成素产生促进剂 |
| US10286036B2 (en) * | 2017-05-12 | 2019-05-14 | Aurinia Pharmaceuticals Inc. | Protocol for treatment of lupus nephritis |
| US20190224275A1 (en) | 2017-05-12 | 2019-07-25 | Aurinia Pharmaceuticals Inc. | Protocol for treatment of lupus nephritis |
| US11255838B2 (en) | 2017-11-03 | 2022-02-22 | Lysulin, Inc. | Levels, functions, and resistances related to chronic conditions by using lysine-based supplements |
| US10653720B2 (en) | 2017-11-03 | 2020-05-19 | Lysulin, Inc. | Prevention of protein glycation using lysine/zinc supplements |
| US10610544B2 (en) | 2017-11-03 | 2020-04-07 | Lysulin, Inc. | Insulin resistance and beta cell function using lysine-based supplements |
| US10656166B2 (en) | 2017-11-03 | 2020-05-19 | Lysulin, Inc. | Inhibiting chronic blood and nephrological disorders using lysine-based supplements |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1538839A (zh) * | 2001-07-31 | 2004-10-20 | ��ī�����˹��ʽ���� | 猪生长促进剂和猪生长促进方法 |
| JP2011016753A (ja) * | 2009-07-08 | 2011-01-27 | Sbi Alapromo Co Ltd | ５−アミノレブリン酸若しくはその誘導体、又はそれらの塩を有効成分とするがんの予防・改善剤 |
| CN102164596A (zh) * | 2008-10-27 | 2011-08-24 | Sbi5-Ala生物技术股份有限公司 | 以5-氨基乙酰丙酸或其衍生物、或它们的盐作为有效成分的成人病的预防、改善剂 |
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| US8614204B2 (en) * | 2003-06-06 | 2013-12-24 | Fibrogen, Inc. | Enhanced erythropoiesis and iron metabolism |
| CA2579032C (en) | 2004-09-02 | 2011-11-29 | Cosmo Oil Co., Ltd. | Use of an .delta.-amino acid as thymocyte growth agent |
| JP4814501B2 (ja) * | 2004-09-02 | 2011-11-16 | コスモ石油株式会社 | 抗酸化機能向上剤 |
| RU2376035C2 (ru) * | 2005-04-19 | 2009-12-20 | Хилл`С Пет Ньютришн, Инк. | Способы и композиции для предотвращения и лечения болезни почек у кошек |
| JP2006008720A (ja) * | 2005-07-06 | 2006-01-12 | Yamaha Motor Co Ltd | 腎臓機能改善剤 |
| AU2006279429B2 (en) * | 2005-08-17 | 2010-02-25 | Hill's Pet Nutrition, Inc. | Methods and compositions for the prevention and treatment of kidney disease |
| JP2009542653A (ja) * | 2006-07-05 | 2009-12-03 | ジェンザイム コーポレーション | リン酸塩過剰血症のための鉄（ｉｉ）含有治療剤 |
| US9018257B2 (en) * | 2011-03-24 | 2015-04-28 | Bar Ilan University | 5-aminolevulinic acid derivatives, methods for their preparation and uses thereof |
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- 2012-10-05 JP JP2013538531A patent/JP5881721B2/ja active Active
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- 2012-10-05 US US14/350,526 patent/US9475755B2/en active Active
- 2012-10-05 CN CN201810181324.8A patent/CN108403678A/zh active Pending
- 2012-10-05 CN CN201280060370.3A patent/CN103974701A/zh active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1538839A (zh) * | 2001-07-31 | 2004-10-20 | ��ī�����˹��ʽ���� | 猪生长促进剂和猪生长促进方法 |
| CN102164596A (zh) * | 2008-10-27 | 2011-08-24 | Sbi5-Ala生物技术股份有限公司 | 以5-氨基乙酰丙酸或其衍生物、或它们的盐作为有效成分的成人病的预防、改善剂 |
| JP2011016753A (ja) * | 2009-07-08 | 2011-01-27 | Sbi Alapromo Co Ltd | ５−アミノレブリン酸若しくはその誘導体、又はそれらの塩を有効成分とするがんの予防・改善剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108403678A (zh) | 2018-08-17 |
| JP5881721B2 (ja) | 2016-03-09 |
| TWI583377B (zh) | 2017-05-21 |
| JPWO2013054765A1 (ja) | 2015-03-30 |
| EP2767276A1 (en) | 2014-08-20 |
| HK1252824A1 (zh) | 2019-06-06 |
| TW201318623A (zh) | 2013-05-16 |
| EP2767276A4 (en) | 2015-05-06 |
| US9475755B2 (en) | 2016-10-25 |
| JP2016033159A (ja) | 2016-03-10 |
| WO2013054765A1 (ja) | 2013-04-18 |
| HK1200324A1 (zh) | 2015-08-07 |
| US20140256806A1 (en) | 2014-09-11 |
| EP2767276B1 (en) | 2018-10-03 |
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