CN100357312C - 赖氨酸七叶皂苷及其制备方法和其用途 - Google Patents
赖氨酸七叶皂苷及其制备方法和其用途 Download PDFInfo
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- CN100357312C CN100357312C CNB2005101055854A CN200510105585A CN100357312C CN 100357312 C CN100357312 C CN 100357312C CN B2005101055854 A CNB2005101055854 A CN B2005101055854A CN 200510105585 A CN200510105585 A CN 200510105585A CN 100357312 C CN100357312 C CN 100357312C
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- methionin
- aescin
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- lysine
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Abstract
Description
剂量(escin计)(mg·kg-1) | 动物数(n) | 肿胀值[X±S(mg)] | 抑制率(%) | ED50(p=0.95)(mg·kg-1) |
1.000.500.250.1250.4ml NS. | 1010101010 | 8.2±3.6210.31±4.5412.24±4.6714.94±4.2318.16±4.82 | 54.8***43.2**32.6*17.7△/ | 0.74(0.88~0.62) |
剂量(escin计)(mg·kg-1) | 动物数(n) | 肿胀值[X±S(mg)] | 抑制率(%) | ED50(p=0.95)(mg·kg-1) |
1.000.500.250.1250.4ml NS. | 1212121212 | 8.14±3.2511.82±2.9514.29±2.6916.20±1.9221.21±2.49 | 61.6***44.3***32.6***23.6***/ | 0.54(0.82~0.44) |
剂量(β-七叶皂苷计)(mg·kg-1) | 动物数(n) | 肿胀值(X±S,mg) | 抑制率(%) | ED50(p=0.95)(mg·kg-1) |
0.600.300.150.0750.4ml NS | 1010101010 | 9.25±3.0112.78±2.8315.75±2.5917.18±1.8820.91±2.31 | 55.8**38.8**24.7**17.8*/ | 0.497(0.69~0.36) |
剂量(β-七叶皂苷计)(mg·kg-1) | 动物数(n) | 肿胀值(X±S,mg) | 抑制率(%) | ED50(p=0.95)(mg·kg-1) |
0.600.300.150.0750.4ml NS | 1010101010 | 8.02±2.2511.71±2.3114.14±2.3916.12±2.0121.12±1.96 | 62.0***44.6***33.0**23.7**/ | 0.35(0.56~0.21) |
剂量(mg·kg-1) | 动物数(n) | 肿胀值(X±S,mg) | 抑制率(%) | ED50(mg·kg-1) |
248160.4ml NS | 1010101010 | 16.02±2.12*14.13±1.91**10.21±1.87***8.16±2.01***20.86±1.85 | 23.2032.2651.0560.88/ | 8.70 |
剂量(mg·kg-1) | 动物数(n) | 肿胀值(X±S,mg) | 抑制率(%) | ED50(mg·kg-1) |
1.53.06.01200.4ml NS | 1010101010 | 15.28±2.21*12.62±2.31**10.02±1.98***7.59±2.33***19.92±1.93 | 23.3236.6449.7061.89/ | 6.18 |
剂量(七叶皂苷计)(mg·kg-1) | 动物数(n) | 肿胀值(X±S,mg) | 抑制率(%) | ED50(p=0.95)(mg·kg-1) |
0.9000.4500.2250.1120.4ml NS | 1010101010 | ***6.20±1.89**9.01±1.42**9.52±2.12*12.01±3.7215.42±2.96 | 59.841.638.322.1/ | 0.5(0.89~0.41) |
组别 | 剂量(mg·kg-1) | 动物数(n) | 吸光度 | 抑制率(%) |
总七叶皂苷钠赖氨酸总七叶皂苷 | 1.51.2 | 1010 | 0.2057±0.055**0.1995±0.038** | 40.342.1 |
谷胱苷肽∶赖氨酸总七叶皂苷(3∶1)赖氨酸β-七叶皂苷谷胱苷肽∶赖氨酸β-七叶皂苷(3∶1)空白对照 | 1.01.00.8同体积生理盐水 | 10101010 | 0.1938±0.042**0.1765±0.052**0.1674±0.046**0.3446±0.086 | 43.848.751.4/ |
组别 | 剂量 | 动物数(n) | 脑含水量(%) | 脑指数 |
假手术对照脑缺血模型组总七叶皂苷钠组Esc-Lys∶Lys.HCl(3∶1) | N.SN.S1 mg·kg-11mg·kg-1 | 10101010 | 74.0±1.680.1±2.2△△77.5±2.2*75.10±1.9** | 0.801±0.0310.890±0.034△△0.855±0.036*0.820±0.040** |
剂量(mg·kg-1) | 对数剂量(X) | 动物数(n) | 死亡数(r) | 死亡率(%) | 概率单位(Y) |
2.052.563.204.005.006.25 | 0.3120.4080.5050.6020.6990.796 | 151515151515 | 1236914 | 61320406093 | 3.453.874.164.755.256.48 |
剂量(mg·kg-1) | 对数剂量 | 动物数(n) | 死亡数(r) | 死亡率(%) | 概率单位(Y) |
10.007.004.903.432.40 | 1.0000.8450.6900.5350.380 | 1818181818 | 139631 | 725033175.5 | 5.585.004.564.053.45 |
剂量(mg·kg-1) | 对数剂量(x) | 动物数(n) | 死亡数(r) | 死亡率(%) | 概率单位(Y) |
10.007.004.903.432.40 | 1.0000.8450.6900.5350.380 | 1616161616 | 129631 | 755638196 | 5.675.154.694.123.45 |
剂 量(mg·kg-1) | 对数剂量(x) | 动物数(n) | 死亡数(r) | 死亡率(%) | 概率单位(Y) |
5.003.502.451.72 | 0.6990.5440.3890.234 | 16161616 | 12975 | 75564431 | 5.675.154.854.50 |
剂量(mg·kg-1) | 对数剂量(x) | 动物数(n) | 死亡数(r) | 死亡率(%) | 概率单位(Y) |
45.0036.0028.8023.0418.43 | 1.6531.5561.4591.3621.266 | 1818181818 | 1713831 | 947244165 | 6.555.584.854.013.36 |
剂量(mg·kg-1) | 对数剂量(x) | 动物数(n) | 死亡数(r) | 死亡率(%) | 概率单位(Y) |
45.0036.0028.8023.0418.43 | 1.6531.5561.4591.3621.266 | 1818181818 | 139531 | 725027175 | 5.585.004.394.053.36 |
组别 | 剂量(mg·kg-1) | 对数剂量 | 动物数(n) | 死亡数(r) | 死亡率(%) | LD50(mg·kg-1)P=0.95 |
谷胱苷肽∶赖氨酸总七叶皂苷(10∶1) | 42.0029.4020.5814.4110.08 | 1.6231.4681.3131.1591.003 | 1010101010 | 107763 | 10070706030 | 14.22(15.36~12.88mg·kg-1) |
谷胱苷肽∶赖氨酸总七叶皂苷(3∶1) | 10.008.006.405.124.10 | 1.0000.9030.8060.7090.613 | 1212121212 | 107531 | 835842258 | 7.00mg·kg-1(8.21~6.01mg·kg-1) |
剂量(mg·kg-1) | 对数剂量(X) | 动物数(n) | 动物死亡数(r) | 死亡率(%)(p) | 概率(Y) |
10.007.505.364.223.17 | 1.0000.8750.7500.6260.500 | 1212121212 | 97421 | 755833178 | 5.675.204.564.053.59 |
盐类名 | 成分名称 | 最小有效量(mg·kg-1) | ED50(mg·kg-1) | LD50(mg·kg-1) | 治疗指数Ti(LD50/ED50) |
钠盐赖氨酸盐 | 总七叶皂苷B-七叶皂苷异七叶皂苷总七叶皂苷B-七叶皂苷 | 0.125~0.25≤0.25-≤0.125≤0.075 | 0.740.58.70.540.35 | 4.22.8130.046.766.27 | 5.75.63.4513.517.9 |
异七叶皂苷 | -- | 6.18 | 35.75 | 5.78 |
反应级 | 刺激反应 |
012345 | 无明显变化轻度充血,其范围在0.5×1.0厘米以下中度充血,其范围在0.5×1.0厘米以上重度充血,伴有肌肉变性出现坏死,有褐色变性出现广泛坏死 |
品名(注射部位总固体) | 股四头肌刺激反应(测量单位cm) | 反应级数 | 股四头肌刺激反应(测量单位:cm) | 反应级数 | 反应级数和 |
总七叶皂苷钠(5mg) | ①重度充血4.7×4.8②重度充血4.0×4.7 | 33 | ③重度充血4.4×4.9④重度充血4.4×4.7 | 33 | 12 |
赖氨酸总七叶皂苷(5.5mg) | ①轻度充血0.56×0.9②轻度充血2.0×0.15 | 11 | ③中度充血1.8×0.44④轻度充血1.46×0.3 | 21 | 5 |
赖氨酸七叶皂苷∶盐酸赖氨酸(1∶3)(20mg) | ①轻度充血0.3×0.4②轻度充血1.0×0.5 | 11 | ③中度充血0.5×1.2④无充血 | 20 | 4 |
B-七叶皂苷钠(5mg) | ①有褐色变性②出现坏死 | 44 | 出现坏死有褐色变性 | 44 | 16 |
赖氨酸七叶皂苷(5.5mg) | ①轻度充血0.5×1.0②轻度充血0.6×1.2 | 22 | ③轻度充血0.5×1.0④轻度充血0.6×0.9 | 12 | 6 |
赖氨酸总七叶皂苷∶谷胱甘肽(1∶3)(20mg) | ①中度充血4.4×0.52②中度充血2.6×0.95 | 22 | ③中度充血3.2×0.49④中度充血3.11×1.06 | 22 | 8 |
剂量10-5g/ml | 例数 | 犬大隐静脉条张力增加(%) | |
总七叶皂苷钠 | 赖氨酸总七叶皂苷 | ||
5.09.016.229.252.5 | 55555 | 8.315±9.30513.016±8.67820.913±6.95634.889±9.00342.158±7.681 | 7.9987±8.36412.8865±7.41219.8983±7.03135.023±10.62543.012±6.983 |
谷胱甘肽∶赖氨酸七叶皂苷 | 剂量(以Escin计) | 动物数(n) | 肿胀值(X±S,mg) | 抑制率(%) |
10∶16∶13∶10.4ml NS. | 0.45mg·kg-1 | 10101010 | **12.31±1.92**12.19±1.83**12.89±2.0520.56±1.88 | 40.140.737.3/ |
谷胱甘肽∶赖氨酸总七叶皂苷(总固体物) | 剂量(Escin计)mg·kg-1 | 股四头肌刺激反应(测量单位:cm) | 反应级数 | 股四头肌刺激反应(测量单位:cm) | 反应级数 | 总反应级数 |
10∶1(55mg) | 5 | ①重度充血4.5×4.2②重度充血3.4×1.49 | 33 | ①中度充血2.4×0.96②中度充血2.9×0.56 | 22 | 10 |
6∶1(35mg) | 5 | ①中度充血1.85×0.5②中度充血2.78×0.48 | 22 | ①中度充血1.1×0.52②中度充血3.2×1.12 | 22 | 8 |
3∶1(20mg) | 5 | ①中度充血4.4×0.52②中度充血2.6×0.95 | 22 | ①中度充血2.4×0.96②中度充血2.9×0.56 | 22 | 8 |
组别 | 剂量(以escin计,iv) | 动物数(n) | 脑含水量(%) | 抑制率(%) |
假手术对照组脑缺血模型1∶31∶61∶10 | NS.同体积NS.同体积0.5mg.kg-10.5mg.kg-10.5mg.kg-1 | 1010101010 | 74.00±1.6080.10±2.2077.81±1.9076.96±1.8077.00±2.00 | //37.551.450.8 |
剂量(mg.kg-1)(以总七叶皂苷计) | 动物数(n) | 肿胀值X±S(mg) | 抑制率(%) | ED50(p=0.95)mg.kg-1 |
0.8700.4350.2180.109空白对照组(NS.) | 1212121212 | 8.26±3.7611.30±2.9912.42±3.0416.22±3.0118.39±2.34 | 55***38.6***32.5***11.8*/ | 0.68(1.08~0.56) |
剂量(mg.kg-1,以皂苷计) | 动物数(n) | 肿胀值X±S(mg) | 抑制率(%) | ED50(p=0.95)mg.kg-1 |
0.8700.4350.2180.109空白对照组NS、0.5ml | 1212121212 | 8.06±3.6911.18±2.8912.29±3.0215.06±3.0419.19±2.16 | 57.99**41.70**35.90**21.50**/ | 0.59(0.99~0.46) |
剂量(mg.kg-1,以皂苷计) | 动物数(n) | 肿胀值(X±S,mg) | 抑制率(%) | ED50(p=0.95)(mg.kg-1) |
0.8700.4350.2180.109空白对照组NS、0.5ml | 1212121212 | 7.46±3.019.05±2.7212.98±2.5614.61 ±2.8319.76±2.23 | 62.2**54.2**34.3**26.0**/ | 6.73(10.2~5.5) |
剂量(mg.kg-1)(以总七叶皂苷计) | 对数剂量(x) | 动物数(n) | 死亡数(r) | 死亡率(%) | 概率单位(y) |
15.0010.507.355.143.60 | 1.1761.0210.8660.7110.556 | 1010101010 | 87642 | 8070604020 | 5.845.525.254.754.16 |
剂量(mg.kg-1)(以β-七叶皂苷计) | 对数剂量(x) | 动物数(n) | 死亡数(r) | 死亡率(%) | 概率单位(y) |
15.0010.507.355.143.60 | 1.1761.0210.8660.7110.556 | 1010101010 | 98742 | 9080704020 | 6.285.845.524.754.16 |
剂量mg.kg-1(以异七叶皂苷计) | 对数剂量(x) | 动物数(n) | 死亡数(r) | 死亡率(%) | 概率单位(y) |
45.0036.0028.8023.0418.43 | 1.6531.5561.4591.3621.266 | 1010101010 | 97531 | 9070503010 | 6.285.525.004.483.72 |
皂苷及其盐名称 | 剂量计算方法 | 抗炎活性(ED50mg.kg-1) | LD50mg.kg-1 | 相对治疗指数(Ti) | 对静脉血管刺激作用(注射1ml含5mg) | |
皂苷名称 | 盐的名称 | |||||
总七叶皂苷 | 赖氨酸盐 | 以总七叶皂苷计 | 0.54 | 6.76 | 13.50 | 几乎无刺激作用 |
精氨酸盐 | 0.68 | 6.68 | 9.82 | 有严重刺激反应 | ||
B-七叶皂苷 | 赖氨酸盐 | 以β-七叶皂苷计 | 0.35 | 6.27 | 17.90 | 几乎无刺激作用 |
精氨酸盐 | 0.59 | 6.11 | 10.36 | |||
异七叶皂苷 | 赖氨酸盐 | 以异七叶皂苷计 | 6.18 | 35.75 | 5.78 | |
精氨酸盐 | 6.73 | 28.37 | 4.21 |
Claims (49)
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CN104147055A (zh) * | 2014-07-08 | 2014-11-19 | 武汉爱民制药有限公司 | 赖氨酸七叶皂苷及其盐在制备治疗i型超敏反应药物中的用途 |
CN104288167B (zh) * | 2014-10-29 | 2017-08-25 | 马应龙药业集团股份有限公司 | 一种治疗痔疮的七叶皂苷钠制剂及其制备方法 |
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CN1687103A (zh) * | 2005-03-24 | 2005-10-26 | 成都圣诺科技发展有限公司 | 水溶性七叶皂苷盐化合物及其制备方法 |
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