CN1293868C - α－环丙氨酸在制备治疗心脑血管疾病药物中的应用 - Google Patents
α－环丙氨酸在制备治疗心脑血管疾病药物中的应用 Download PDFInfo
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Abstract
本发明涉及α-环丙氨酸(1-aminocyclopropanecarboxylicacid，ACPC)在制备治疗心脑血管疾病药物中的应用，尤其是在制备治疗高血压症、心脑血管血栓症、脑卒中症药物中的应用。本发明所述的α-环丙氨酸(ACPC)可有效防治高血压症、心脑血管血栓症、脑卒中症等心脑血管疾病，对脑血管、心脏、肾脏进行有效保护，无毒副作用，药理作用明确，为新药筛选提供了基础。
Description
(一)技术领域
本发明涉及α-环丙氨酸(ACPC)在制备治疗心脑血管疾病药物中的新用途，尤其是在制备预防治疗高血压症、心脑血管血栓症、脑卒中症药物及保护脑血管、心脏、肾脏药物中的应用。
(二)背景技术
α-环丙氨酸(1-aminocyclopropanecarboxylic acid，ACPC)为天然非蛋白特种氨基酸，目前主要用于制备禽类饲料添加剂，已有报道α-环丙氨酸(ACPC)可用于制备治疗精神类疾病药物，如焦虑症、抑郁症等，还未有α-环丙氨酸应用于治疗制备心脑血管疾病药物的相关报道。
(三)发明内容
本发明即是为了提供α-环丙氨酸(ACPC)在制药领域的新用途，即α-环丙氨酸(ACPC)在制备心脑血管疾病药物中的应用，尤其是在制备治疗高血压症、心脑血管血栓症、脑卒中症药物中的应用。
本发明采用的技术方案是：
α-环丙氨酸(ACPC)应用于制备治疗心脑血管疾病药物。
尤其是，所述的α-环丙氨酸应用于制备治疗高血压症药物、治疗心脑血管血栓症药物或防治脑卒中症药物。实验证明，α-环丙氨酸(ACPC)可抑制血压上升，改善增加脑血流量，防止脑出血，防止血管梗塞，预防脑卒中发生、降低脑卒中死亡率，并可有效保护保护脑神经细胞，保护心脏和肾脏，避免心脏肥大和肾脏硬化萎缩。
所述的药物还可含有药物赋型剂或载体。
α-环丙氨酸也与其他药物共同使用。
本发明所述的α-环丙氨酸在制备心脑血管疾病药物中的应用的有益效果主要体现在：(1)α-环丙氨酸可有效治疗高血压症、心脑血管血栓症、脑卒中症等心脑血管疾病，对脑血管、心脏、肾脏进行有效保护，无毒副作用；(2)药理作用明确，为新药筛选提供了基础。
(四)附图说明
图1为给药1个月后SHR-SP大鼠Laser-Doppler血流图像，左为α-环丙氨酸(ACPC)治疗群，右为对照群；
图2为脑卒中死亡大鼠和ACPC治疗存活大鼠脑像，A为脑出血，B为脑软化(脑梗塞)，C为脑软化(出血合并)，D为轻度脑血栓，E为给ACPC、治疗基本正常大鼠；
图3为SHR-SP大鼠心脏比较，右为对照，左为给ACPC大鼠；
图4为SHR-SP大鼠肾脏比较，左为对照，右为给ACPC大鼠。
(五)具体实施方式
下面结合具体实施例对本发明进行进一步描述：
实施例1：SHR-SP大鼠药理实验
(1)模型与方法：
SHR-SP大鼠20只分成ACPC治疗组和对照组、每组10只。α-环丙氨酸(ACPC)治疗组按50mg/kg(50mgACPC/ml蒸馏水)剂量腹腔注射(iP)，对照组注射同比量的蒸馏水。每日一次、每周五日注射。对自然发生高血压、脑卒中大鼠的降血压、预防脑卒中的效果进行观察。
(2)测定指标：
实验前、开始后每周一次测定收缩压(SBP)、舒张压(DBP)、心率(HR)。
给药第四周收集24小时尿、进行NO等排泄量的测定。
给药四周后，レ一ザ一·ドツプラ一(Laser-Doppler)血流图像化测定血流量，见图1。
观察脑卒中的发症率、脑卒中的死亡率。
大鼠解剖，摘出心、脑、肾脏进行病理学分析。
(3)结果：
①收缩压(SBP)，α-环丙氨酸(ACPC)治疗组给药后二周比对照组下降24mg汞柱(P＜0.001)；舒张压(DBP)，α-环丙氨酸(ACPC)治疗组比对照组下降16mg汞柱(P＜0.01)；心率(HR)没有显著差异。
②给药第四周收集24小时尿、进行NO等排泄量的测定，α-环丙氨酸(ACPC)治疗组0.76μmol，对照组1.36μmol，下降约50％(P＜0.05)。
③脑血流测定值，α-环丙氨酸(ACPC)治疗组1.5，对照组1.2，增加25％(P＜0.05)。
④脑卒中的发症率，根据大鼠的神经行动症状(痛觉敏感、肢体麻痹等)判定大鼠是否发症，观察实验开始后100天内大鼠的脑卒中发症状况：对照组10只全部发症(100％)，α-环丙氨酸(ACPC)治疗组2只发症(20％)。
⑤脑卒中的死亡率，对照组10只70-82天内全部发症死亡(100％)，α-环丙氨酸(ACPC)治疗组1只于80天发症死亡(10％)，其余9只100天后仍存活。
⑥心、脑、肾脏进行病理学分析，见图2、图3、图4：图2显示α-环丙氨酸(ACPC)有效防治脑卒中；图3显示α-环丙氨酸(ACPC)有效保护心脏，心脏正常，对照心脏肥大；图4显示α-环丙氨酸(ACPC)有效保护肾脏，肾脏正常，对照肾脏硬化萎缩。
Claims (5)
1.α-环丙氨酸在制备治疗心脑血管疾病药物中的应用。
2.如权利要求1所述的α-环丙氨酸在制备治疗心脑血管疾病药物中的应用，其特征在于所述的α-环丙氨酸应用于制备治疗高血压症药物。
3.如权利要求1所述的α-环丙氨酸在制备治疗心脑血管疾病药物中的应用，其特征在于所述的α-环丙氨酸应用于制备治疗心脑血管血栓症药物。
4.如权利要求1所述的α-环丙氨酸在制备治疗心脑血管疾病药物中的应用，其特征在于所述的α-环丙氨酸应用于制备防治脑卒中症药物。
5.如权利要求1～4之一所述的α-环丙氨酸在制备治疗心脑血管疾病药物中的应用，其特征在于所述的药物还含有药物赋型剂或载体。
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7606308B2 (en) | 2003-09-07 | 2009-10-20 | Microsoft Corporation | Signaling macroblock mode information for macroblocks of interlaced forward-predicted fields |
| US7924920B2 (en) | 2003-09-07 | 2011-04-12 | Microsoft Corporation | Motion vector coding and decoding in interlaced frame coded pictures |
| US9088785B2 (en) | 2001-12-17 | 2015-07-21 | Microsoft Technology Licensing, Llc | Skip macroblock coding |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2006213611A (ja) * | 2005-02-02 | 2006-08-17 | Suzuka Univ Of Medical Science | １‐アミノシクロプロパンカルボン酸等を主成分とする脳卒中又は脳卒中後遺症の予防用又は治療用薬剤 |
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| JPS50142572A (zh) * | 1974-04-25 | 1975-11-17 | ||
| WO1991001724A1 (en) * | 1989-07-27 | 1991-02-21 | G.D. Searle & Co. | Renal-selective prodrugs for the treatment of hypertension |
| US6017957A (en) * | 1989-08-08 | 2000-01-25 | The United States Of America As Represented By The Department Of Health And Human Services | Partial agonists of the strychnine insensitive glycine modulatory site of the N-methyl-D-aspartate receptor complex as neuropsychopharmacological agents |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPS50142572A (zh) * | 1974-04-25 | 1975-11-17 | ||
| WO1991001724A1 (en) * | 1989-07-27 | 1991-02-21 | G.D. Searle & Co. | Renal-selective prodrugs for the treatment of hypertension |
| US6017957A (en) * | 1989-08-08 | 2000-01-25 | The United States Of America As Represented By The Department Of Health And Human Services | Partial agonists of the strychnine insensitive glycine modulatory site of the N-methyl-D-aspartate receptor complex as neuropsychopharmacological agents |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9088785B2 (en) | 2001-12-17 | 2015-07-21 | Microsoft Technology Licensing, Llc | Skip macroblock coding |
| US7606308B2 (en) | 2003-09-07 | 2009-10-20 | Microsoft Corporation | Signaling macroblock mode information for macroblocks of interlaced forward-predicted fields |
| US7924920B2 (en) | 2003-09-07 | 2011-04-12 | Microsoft Corporation | Motion vector coding and decoding in interlaced frame coded pictures |
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