CN1255183C - 心肌肽素及其用途 - Google Patents
心肌肽素及其用途 Download PDFInfo
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- CN1255183C CN1255183C CNB031413528A CN03141352A CN1255183C CN 1255183 C CN1255183 C CN 1255183C CN B031413528 A CNB031413528 A CN B031413528A CN 03141352 A CN03141352 A CN 03141352A CN 1255183 C CN1255183 C CN 1255183C
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- Prior art keywords
- copeptin
- myocardium
- cardiac muscle
- ischemia
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Images
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
心肌肽素活性 OD值(x±s) | ||
分组 | 30μg/ml | 5μg/ml |
正常对照组阿霉素损伤组 | 0.691±0.032**0.274±0.011 | |
不同pH处理组3.0 30min60min4.0 30min60min5.0 30min60min6.0 30min60min7.0 30min60min8.0 30min60min9.0 30min60min | 0.331±0.014**0.314±0.007**0.315±0.008**0.004±0.015**0.364±0.022**0.064±0.017**0.041±0.023**0.332±0.015**0.320±0.018**0.327±0.010**0.339±0.008**0.308±0.01**50.313±0.006**0.279±0.017 | 0.320±0.015**0.309±0.010**0.307±0.015**0.311±0.007**0.379±0.019**0.353±0.023**0.344±0.011**0.327±0.016**0.358±0.023**0.328±0.012**0.332±0.022**0.309±0.010**0.289±0.0200.274±0.013 |
OD值( x±s) | ||
分组 | 5μg/ml | t值 |
正常对照组阿霉素损伤组 | 0.344±0.014**0.272±0.015 | 9.93 |
P1P2P3P4P5心肌肽素组 | 0.318±0.004**0.295±0.012**0.309±0.012**0.317±0.017**0.303±0.014**0.298±0.005** | 6.3443.395.455.614.273.47 |
心肌肽素溶液(mg氮/ml) | 注射用心肌肽素(mg氮/瓶) | |||||
批号 | 960419 | 960422 | 960423 | 960501 | 960502 | 960503 |
总氮 | 1.788 | 1.926 | 1.628 | 3.816 | 4.250 | 4.100 |
有机氮 | 1.589 | 1.743 | 1.460 | 3.612 | 3.919 | 3.722 |
无机氮 | 0.199 | 0.183 | 0.168 | 0.204 | 0.331 | 0.378 |
测定方法 | ||
双缩脲法 | 福林-酚法 | 定氮法(多肽有机氮) |
溶液(mg/ml)960419 1.65960422 1.85960423 2.00制剂(mg/瓶)960501 3.26960502 3.63960503 3.73 | 2.72.82.69.99.29.2 | 1.581.741.463.613.923.72 |
注射用心肌肽素 | |||
批号 | 960501 | 960502 | 960503 |
游离氨基酸总氮量g/L | 0.257 | 0.285 | 0.286 |
注射用心肌肽素 | |||
批号 | 960501 | 960502 | 960503 |
多肽有机氮g/L | 3.612 | 3.919 | 3.722 |
游离氨基酸氮g/L | 0.257 | 0.285 | 0.286 |
游离氨基酸含氮量占总有机氮量百分比(%) | 6.643 | 6.823 | 7.135 |
批号 | 吸收波长(nm) |
溶液(mg/m1)960422960423960419制剂(mg/瓶)960501960502960503 | 200.4199.8201.2200.4201.8201.6 |
批号 | 色谱峰保留时间(min) | ||||
P1 | P2 | P3 | P4 | P5 | |
960501 | 30.5 | 31.8 | 32.8 | 35.0 | 38.7 |
960502 | 30.5 | 31.2 | 32.8 | 35.0 | 38.7 |
960503 | 31.2 | 32.7 | 35.0 | 38.7 | |
X | 30.7 | 31.5 | 32.7 | 35.0 | 38.7 |
批号 | 分子量(道尔顿) | ||||
P1 | P2 | P3 | P4 | P5 | |
960501 | 6023 | 4588 | 3665 | 2233 | 969 |
960502 | 6027 | 5261 | 3688 | 2234 | 971 |
960503 | 5165 | 3709 | 2236 | 875 | |
X | 5736 | 4519 | 3676 | 2234 | 971 |
加入量ml | ||||||
加入物 | 0 | 1 | 2 | 3 | 4 | 5 |
RNA标准液 | 0 | 0.2 | 0.4 | 0.6 | 0.8 | 1.0 |
蒸馏水 | 1.0 | 0.8 | 0.6 | 0.4 | 0.2 | 0 |
地衣酚试剂 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 |
加入量ml | ||||||
加入物 | 0 | 1 | 2 | 3 | 4 | 5 |
RNA标准液 | 0 | 0.2 | 0.4 | 0.6 | 0.8 | 1.0 |
DH2O | 1.0 | 0.8 | 0.6 | 0.4 | 0.2 | 0 |
二苯胺试剂 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 |
批号 | t值 |
960501960502960503960101 | 5.83.27.97.8 |
保留时间(min) | |||||||||
主峰 | 101 | 501 | 502 | 503 | 1101 | 1102 | 1103 | 201 | 301 |
P1P2P3P4P5 | 1.9222.5062.6543.1564.240 | 1.9012.5042.6513.1444.203 | 1.9202.5002.6463.1344.181 | 1.9152.5022.6453.1284.159 | 1.9252.6433.1244.148 | 1.9242.6393.1144.128 | 1.9492.6403.1174.133 | 1.9542.6383.1154.129 | 1.9902.6383.1154.107 |
百分面积% | |||||||||
主峰 | 101 | 501 | 502 | 503 | 1101 | 1102 | 1103 | 201 | 301 |
P1P2P3P4P5 | 18.310.610.437.413.2 | 12.311.713.345.48.8 | 13.49.211.147.89.6 | 15.712.48.838.615.9 | 13.45.243.822.8 | 13.55.243.422.6 | 11.45.147.322.9 | 14.45.846.818.5 | 16.14.742.223.6 |
组别 | 剂量(mg/Kg) | 病变值±SD |
假手术缺血—再灌注缺血—再灌注+生理盐水缺血—再灌注+心肌肽素缺血—再灌注+心得安 | ---1.05.010.02.0 | 0.36±0.461.97±1.4ΔΔΔ2.68±1.3*1.85±1.6*0.73±0.96***0.33±0.42***0.71±0.84*** |
组别 | 剂量(mg/Kg) | n | ∑ΔST(mV) | ∑NST(个) |
缺血—再灌注组血—再灌注+生理盐水组缺血—再灌注+心肌肽素组 | --2.05.0 | 101066 | 109±32115±24*70.8±16***37.8±12*** | 28.9±5.231.1±5.1*19.5±4.8***9.33±3.9*** |
组别 | 剂量(mg/Kg) | n | ∑ΔST(mV) | ∑NST(个) |
缺血组缺血+生理盐水组缺血+心肌肽素组缺血+心得安组 | --2.05.010.02.0 | 12126666 | 40.5±1040.0±12*29.9±2.9***25.6±5.7***19.7±4.0***22.8±6.4*** | 11.1±2.111.2±1.5*8.67±2.2**7.33±1.5***6.17±1.2***6.17±1.5*** |
组别 | 剂量(mg/Kg) | n | 心肌CPK(u/100mg pro) | 血浆CPK(u/100ml) |
假手术缺血—再灌注缺血—再灌注+生理盐水缺血—再灌注+心肌肽素缺血—再灌注+维拉帕米缺血—再灌注+心肌细胞生长刺激肽 | 0.52.010.01.05.0 | 1010888888 | 980±63522±65ΔΔΔ501±59*732±98***904±95***976±95***886±115***890±97*** | 164±64374±54ΔΔΔ337±48*210±50***157±31***134±24***192±60***199±35*** |
组别 | 剂量(mg/kg) | n | 心肌LDH(u/mg pro) | 血浆LDH(u/ml) |
假手术缺血—再灌注缺血—再灌注+生理盐水缺血—再灌注+心肌肽素缺血—再灌注+维拉帕米缺血—再灌注+心肌细胞生长刺激肽 | ---0.52.010.01.05.0 | 1010888888 | 76.7±19110±27ΔΔΔ112±19*97.1±12*763±22***64.8±17***75.1±23***83.0±17*** | 40.9±9.5120±20ΔΔΔ1162±12*93.9±17***59.7±12***52.6±13***46.7±8.8***60.9±15*** |
组别 | 剂量(mg/kg) | n | 心肌MDA(nmol/100mg pro) | 血浆MDA(nmol/ml) |
假手术缺血—再灌注缺血—再灌注+生理盐水缺血—再灌注+心肌肽素缺血—再灌注+维拉帕米缺血—再灌注+心肌细胞生长刺激肽 | 0.52.010.01.05.0 | 1010888888 | 68.3±8.4135±10ΔΔΔ127±15*73.1±13***60.5±10.4***49.8±9.4***66.6±19.8***75.2±9.7*** | 22.3±1.863.6±11ΔΔΔ58.4±11*38.1±6.2***27.7±5.5***25.5±5.1***24.9±6.6***39.2±5.3*** |
组别 | 剂量(mg/Kg) | FFA(μmol/100ml) |
假手术缺血—再灌注缺血—再灌注+生理盐水缺血—再灌注+心肌肽素缺血—再灌注+心得安缺血—再灌注+心肌细胞生长刺激肽 | ---1.05.010.02.05.0 | 60.6±7.8129±26ΔΔΔ121±10*85.4±5.0***77.7±7.1***71.4±11***77.1±6.4***89.2±6.7*** |
组别 | 剂量(μg/ml) | 冠脉流出液CPK(J/L) | ||
缺血前 | 缺血期 | 再灌期 | ||
假手术缺血—再灌流 | -- | 15.3±1.516.3±2.3Δ | 16.5±1.824.8±2.7ΔΔΔ | 17.1±2.035.4±4.3ΔΔΔ |
缺血—再灌流+心肌肽素缺血—再灌流+维拉帕米 | 10501001 | 16.1±2.6*15.6±1.7*15.5±2.7*16.3±2.0* | 20.7±1.7***17.9±2.7***15.3±2.1***16.2±2.8*** | 22.7±2.3***19.0±2.3***16.5±2.4***16.0±1.8*** |
组别 | 剂量(μg/ml) | 冠脉流出液LDH(U/L) | ||
缺血前 | 缺血期 | 再灌期 | ||
假手术缺血—再灌流缺血—再灌流+心肌肽素缺血—再灌流+维拉帕米 | -10501001 | 11.8±0.7911.7±0.83Δ12.0±0.58*11.8±0.53*11.2±0.55*11.4±0.78* | 12.6±1.117.3±1.9ΔΔΔ13.4±1.1***12.9±1.1***12.2±0.79***13.0±0.62*** | 11.8±0.6924.7±1.7ΔΔΔ15.3±1.4***13.4±0.76***12.9±0.93***14.3±0.95*** |
时间(min) | 心肌耗氧量(MYO2) | 心肌氧利用率(O2ext) |
心肌肽素2 mg/kg(N=8) | ||
251020 | -23.0±26-21.0±13***-18.0±14-9.00±12 | -4.00±130±8.0-2.00±6.0-2.00±12 |
心肌肽素5 mg/kg(N=7) | ||
251020 | -36.0±24**-26.0±21**-19.0±15**-8.00±10 | -5.00±136.00±8.06.00±6.0*-14.0±35 |
心肌肽素10 mg/kg(N=6) | ||
5102030 | -22.0±25-21.0±14**-8.00±4.0*-10.0±7.0* | 9.00±5***2.00±5.03.00±4.0-6.00±15 |
普萘洛尔2 mg/kg(N=6) | ||
251030 | -31.0±13*-30.0±13***-33.0±10***-32.0±14*** | -3.00±1.03.00±7.03.00±8.03.00±9.0 |
组别 | 药物 | 输注剂量(mg/kg) | 输注速度(ml/min) |
溶剂对照组受试物低剂量组受试物高剂量组阳性药物对照组 | 甘露醇心肌肽素+甘露醇心肌肽素+甘露醇维拉帕米 | 1205+12010+1200.25 | 2222 |
药物 | 剂量(mg/kg) | 动物数(n) | 梗塞范围(%) |
溶剂对照心肌肽素心肌肽素维拉帕米 | -5100.25 | 5555 | 19.4±3.0211.8±3.13*10.2±3.2**12.5±3.4* |
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CNB031413528A CN1255183C (zh) | 2003-06-04 | 2003-06-04 | 心肌肽素及其用途 |
PCT/CN2004/000138 WO2004108751A1 (fr) | 2003-06-04 | 2004-02-23 | Cardiomyopeptidine, son procede de production et son utilisation |
EP04713508A EP1661907B1 (en) | 2003-06-04 | 2004-02-23 | Method of preparing cardio myopeptidin |
DK04713508.2T DK1661907T3 (da) | 2003-06-04 | 2004-02-23 | Fremgangsmåde til fremstilling af cardiomyopeptidin |
US10/567,286 US7427663B2 (en) | 2003-06-04 | 2004-02-23 | Cardio myopeptidin, the production and the use thereof |
AT04713508T ATE545653T1 (de) | 2003-06-04 | 2004-02-23 | Verfahren zur herstellungs von cardio myopeptidin |
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CN101012455B (zh) * | 2005-11-14 | 2011-05-18 | 大连珍奥药业有限公司 | 一种生化物质的灭活方法、一种心肌肽素的制备方法及其用途 |
CN101265292B (zh) * | 2007-03-16 | 2011-09-14 | 大连珍奥药业有限公司 | 多肽类物质、其制备方法及其用途 |
US8940865B2 (en) * | 2008-07-15 | 2015-01-27 | Dalian Zhen-Ao Pharmaceutical Co, Ltd. | Myocardial peptide, preparation method and uses thereof |
CN101612384B (zh) * | 2009-07-23 | 2012-06-20 | 中国人民解放军第二军医大学 | 多肽小分子mlif在制备防治心肌缺血药物中的应用 |
CN106668069A (zh) * | 2015-11-04 | 2017-05-17 | 张志强 | 胆提取物、其提取方法及其应用 |
CN106546694A (zh) * | 2016-11-01 | 2017-03-29 | 青海盐湖工业股份有限公司 | 一种测定有机胺含量的方法 |
CN108478781B (zh) * | 2018-05-08 | 2020-11-13 | 大连理工大学 | 注射用心肌肽的冻干工艺 |
CN114982962A (zh) * | 2022-05-31 | 2022-09-02 | 中科康盛(河北)生物科技有限公司 | 一种提高心脏缺氧耐受力功能的配方及原料制备方法 |
CN115684608B (zh) * | 2022-11-03 | 2024-01-09 | 大连珍奥药业股份有限公司 | 一种靶向心肌肽治疗心肌缺血再灌注损伤的代谢标志物及其应用 |
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