CN101588807B - D-核糖在制备治疗心律失常的药物中的应用 - Google Patents

D-核糖在制备治疗心律失常的药物中的应用 Download PDF

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CN101588807B
CN101588807B CN2008800029553A CN200880002955A CN101588807B CN 101588807 B CN101588807 B CN 101588807B CN 2008800029553 A CN2008800029553 A CN 2008800029553A CN 200880002955 A CN200880002955 A CN 200880002955A CN 101588807 B CN101588807 B CN 101588807B
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J·D·赫里克
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Abstract

以5-15克日剂量给予的D-核糖减少或者预防患有心房纤维性颤动的人的心房纤维性颤动的发生。

Description

D-核糖在制备治疗心律失常的药物中的应用
相关申请 
本申请要求2007年1月23日提交的美国临时申请60/881,940的优先权。 
发明背景 
心脏，与其它肌肉一样，是过神经纤维的电刺激引起收缩的。正常的电传导系统允许由心脏的窦房结产生的神经脉冲传播至心肌并且刺激心肌有规则地进行收缩，产生有效的心脏搏动。在神经脉冲以正常的功能性方式行进时，认为心脏是搏动正常。在神经脉冲减小或者不均匀时，认为心脏是心律失常。心律失常可能是突发性的(即，急性的并且持续时间短)、或者是慢性的。 
期外收缩(或者漏搏)通常是急性的、复发性的事件，其可能是由于潜在的心脏病、瓣膜缺陷引起的，或者可能由触发因素(例如，咖啡因、烟碱或酒精)诱导的。期外收缩可能被感觉是“心悸”，并且尽管使人不安，但是在本质上没有危险。治疗方案包括对潜在的心脏病况的治疗和避免触发因素。 
心动过速是指心率增加，并且可能是由使肾上腺素水平升高的任何触发因素引起的，所述因素例如应激、锻炼、高涨的情绪、咖啡因或安非他明。随着情况的平息，心率恢复正常。心率不齐的严重形式是阵发性心动过速，其中在没有触发因素的情况下或者在触发因素平息之后心室迅速地并且长时间收缩。这种病况难以治疗并且可能是致 命的，因为心室可以进入纤维性颤动，其中血压下降到零并且循环停止。要保持生命，必须立即用去纤颤机器干预。 
心房纤维性颤动是不那么严重的情况。在纤维性颤动中发生心房颤动时，血液没有有效地通过心室。在纤维性颤动的持续时间短的情况下，循环通常没有减少；然而停滞的血液汇集可能凝结，并且凝块可能通往肺循环床、冠状动脉、脑或其它器官。据估计，大约220万美国人患有心房纤维性颤动并且大约15％的中风与这种病况有关。阵发性心房纤维颤动在发病过程中产生不舒适的模糊症状，或者受试者可能完全不知道所述病况。通过EKG上不存在P波来进行诊断，P波不存在表明心房去极化。 
心房纤维性颤动可以用延缓心率的药物、用阿司匹林或华法林稀释血液以保护患者免于凝血、用β阻断剂控制心率、钙通道阻断剂或强心苷进行治疗。心电图(Electrocardioversion)可以持续的正常化结果。 
仍需要没有副作用的简单的治疗来帮助控制心律失常。 
发明内容
本申请人发现，低剂量的D-核糖治疗心房纤维性颤动并且部分或完全地预防其发生。每天给予5克D-核糖，将其作为单剂量服用或者分为两个剂量服用，对于预防心房纤维性颤动是有效的。更优选地，分为2-4个剂量的每天10克D-核糖对于预防心房纤维性颤动是有效的。最优选地，受试者每天摄取被分为至少3个剂量的15克D-核糖。在一个剂量中至多摄取5克的D-核糖。 
所述D-核糖可以以少量水服用、散置在食物上、或者作为粉末摄取。 
发明详述 
D-核糖用于改善骨骼肌和心肌的用途已有文献报导。美国专利6,159943教导，D-核糖可以减轻锻炼引起的骨骼肌痛性痉挛和疼痛。待决的美国专利申请10/692,388教导，低剂量的D-核糖可以改善充血性心力衰竭患者的心脏功能。尽管D-核糖用于改善骨骼肌和心肌功能的用途现在是公知的，但是在本发明之前关于D-核糖对神经功能的影响一无所知。不希望束缚于理论，申请人推测在以下研究中发现的D-核糖的有益作用可能是由于改善了神经脉冲的传输。 
对确诊心房纤维性颤动的8名患者给予D-核糖。结果概述如下。 
  患者  编号   AT的持续时  间   每天的D-核糖  量   其它药物   是否缓解
  1   最近   N/R*   CoQ   完全的、立即的缓解
  2   N/R   N/R   N/R   完全的、立即的缓解
  3   N/R   5克   N/R   有帮助
  4   N/R   5克     在两周内完全缓解
  5   20年   10克   CoQ、L-卡尼汀、Mg   完全的、立即的缓解
  6   N/R   10-15克   N/R   几乎不存在
  7   N/R   5克   N/R   完全的、立即的缓解
*N/R＝未报告 
从上述数据可见，不是所有的患者都发生心房纤维性颤动的完全和立即的缓解。摄取更优选和最优选剂量D-核糖的5号和6号患者都产生完全和立即的缓解。3号和4号患者只产生部分的缓解(3)或延迟的缓解(4)。因此，推荐患者每天摄取10-15克的D-核糖。 
所述的缓解保持一年以上。因此，因为给予低剂量的D-核糖没有 副作用，建议这种使用应该是长持续时间的或者长期的。尽管15克日剂量已经证明是最有效的，但是可以摄取更大量的D-核糖，最高为一天30克，条件是单个剂量不超过8克，优选不超过5克。在其它研究中已经看到，在超过大约8克的剂量时，许多人经历胀气和腹泻，如待决的美国专利申请10/692,388中更充分地讨论的。大多数人耐受对于本文中教导的用途是有效的5克的剂量，而不发生这些消化系统症状。 

Claims (4)

1.D-核糖制备用于长期治疗患有心房纤维性颤动的人的心房纤维性颤动的药物的用途。
2.权利要求1的用途，其中所述药物提供日剂量为5-30克的D-核糖。
3.权利要求1的用途，其中所述药物提供日剂量为10-15克的D-核糖。
4.权利要求1的用途，其中所述药物提供单个剂量为不超过8克的D-核糖。
CN2008800029553A 2007-01-23 2008-01-23 D-核糖在制备治疗心律失常的药物中的应用 Active CN101588807B (zh)

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US88194007P 2007-01-23 2007-01-23
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PCT/US2008/000845 WO2008091618A1 (en) 2007-01-23 2008-01-23 Use of d-ribose to treat cardiac arrhythmias

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JP7082258B2 (ja) 2016-02-01 2022-06-08 バイオエナジー ライフ サイエンス，インコーポレイティド うっ血性心不全に罹っている対象を治療するためのリボースの使用

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US8101581B2 (en) 2012-01-24
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CA2674717A1 (en) 2008-07-31
WO2008091618A1 (en) 2008-07-31
BRPI0806231A2 (pt) 2011-09-06
WO2008091618A8 (en) 2010-04-01
US20080176809A1 (en) 2008-07-24
ATE487485T1 (de) 2010-11-15
ES2352154T3 (es) 2011-02-16
CN101588807A (zh) 2009-11-25
JP2010526884A (ja) 2010-08-05
CA2674717C (en) 2015-10-13
DE602008003411D1 (de) 2010-12-23

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