CN113384635A - 一种降低机体肝损伤的混合物及其制备方法 - Google Patents
一种降低机体肝损伤的混合物及其制备方法 Download PDFInfo
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Abstract
本发明公开了一种降低机体肝损伤的混合物及其制备方法,该混合物及雾化给药是由以下重量计的原料制成:乙醇0g~15g、丙二醇20g~70g、丙三醇20g~70g、甜味剂0.001g~0.1g和植物提取物5㎎~20㎎。相比现有技术,本发明的有益效果在于:本发明通过试验研究发现,由人参、枸杞、白芷和银杏叶按照重量比为1:1:2:5~5:6:6:10进行恒温变压超临界二氧化碳萃取得到的植物提取物,而后该植物提取物、乙醇、丙三醇和丙二醇以及甜味剂进行充分混合,所得到的混合物经雾化给药能够降低烟碱对于人体肝脏的损坏,提高机体免疫力,并且对烟碱成瘾大鼠具有良好的烟碱替代性,恢复了烟碱对肝脏产生的炎症反应。
Description
技术领域
本发明涉及一种降低机体肝损伤的混合物及其制备方法。
背景技术
烟碱(尼古丁)是烟草中含量最高的生物碱,是烟草烟气中主要致瘾物质。烟碱和乙酰胆碱结构相似,是烟碱乙酰胆碱受体的激动剂,通过对细胞体上胆碱受体的作用,可以调节部分神经递质如乙酰胆碱、多巴胺、去甲肾上腺素的释放,并参与神经细胞的可塑性调节过程。烟碱通过介导神经细胞中多巴胺的释放,可以使人产生愉悦感并可能形成嗜好,这是行程烟碱依赖的原因之一。然而,烟碱对外周器官还有一定的毒性。有研究表明,短期内过量摄入烟碱会导致动物死亡,例如大鼠的烟碱急性毒性LD50分别为1mg/kg(静脉注射)及50mg/kg(经口)。此外,长期烟碱暴露还会对肾脏、肺部和支气管、肝脏等造成毒性损伤,机体免疫力的下降,造成肝脏产生的坏死、中毒等损伤炎症反应的问题,从而影响人的身体健康。
发明内容
针对上述问题,本发明提供了一种降低机体肝损伤的混合物及其制备方法。
为解决上述技术问题,本发明所采用的技术方案是:一种降低机体肝损伤的混合物,该混合物及雾化给药是由以下重量计的原料制成:乙醇0g~15g、丙二醇20g~70g、丙三醇20g~70g、甜味剂0.001g~0.1g和植物提取物5㎎~20㎎。
优选的,所述植物提取物为人参、枸杞、白芷和银杏叶的混合提取物,其中人参、枸杞、白芷和银杏叶粉末按照重量比为1:1:2:5~5:6:6:10进行混合提取。
优选的,所述人参提取物包括人参皂甙C-K、人参皂甙Rg、人参皂甙Rg5、人参皂甙aPPD、人参皂甙Rc。
还提供了一种降低机体肝损伤的混合物的制备方法,包括以下步骤:(一)、先将人参、枸杞、白芷和银杏叶按照重量比为1:1:2:5~5:6:6:10装入萃取釜中进行萃取,在萃取过程需要加入混合物粉末重量的5%乙醇和10%丙二醇,并且在萃取全程需要加入超临界CO2恒温变压萃取,即得植物提取物;
(二)、将该植物提取物、乙醇、丙三醇和丙二醇以及甜味剂进行充分混合,即可得本发明的混合物及雾化给药。
优选的,将步骤(一)中的所有药材按“一锅法”总共进行了三次萃取,第一次萃取的温度为50℃,萃取压力为10MPa,萃取时间为50min;第二次萃取的温度为50℃,萃取压力为15MPa,萃取时间120min;第三次萃取的温度为50℃,萃取压力为35MPa,萃取时间100min。
优选的,所述乙醇为95%(v/v)乙醇。
相比现有技术,本发明的有益效果在于:本发明通过试验研究发现,由人参、枸杞、白芷和银杏叶按照重量比为1:1:2:5~5:6:6:10进行萃取得到的植物提取物,而后该植物提取物、乙醇、丙三醇和丙二醇以及甜味剂进行充分混合,所得到的混合物经雾化给药能够降低烟碱对于人体肝脏的损坏,不会引起机体免疫力的下降并且对烟碱成瘾大鼠是有良好的烟碱替代性,恢复了烟碱会对肝脏产生的坏死、中毒等损伤炎症反应。
具体实施方式
以下结合实施例对本发明的具体实施方式作进一步详细说明。
实施例1
本发明在具体实施时,可由以下重量计的原料制成:乙醇1g、丙二醇20g、丙三醇20g、甜味剂0.001g和植物提取物5㎎,其中植物提取物为人参、枸杞、白芷和银杏叶的混合提取物;由下列方法制备得到:
(一)、先将人参、枸杞、白芷提和银杏叶的粉末按照重量比为1:1:2:5装入超临界萃取釜中,往超临界萃取釜内通入超临界CO2,并加入混合物粉末重量的5%的95%(v/v)乙醇作为夹带剂,而后调节萃取釜的温度50℃、萃取压力为10MPa、萃取时间50min;紧接着,再次调节萃取釜的萃取压力到15MPa、萃取时间为120min;最后,再调节萃取釜的萃取压力到35MPa、萃取时间为100min,加入混合物粉末重量的10%丙二醇作为接收剂,即得植物提取物;
(二)、将该植物提取物、乙醇、丙三醇和甜味剂以及剩下的丙二醇进行充分混合,即可得本发明的混合物,该混合物经雾化给药,即可代替烟碱,降低机体肝损伤。
实施例2
本发明在具体实施时,可由以下由以下重量计的原料制成:乙醇15g、丙二醇70g、丙三醇70g、甜味剂0.1g和植物提取物20㎎,其中植物提取物为人参、枸杞、白芷和银杏叶粉末的混合提取物;由下列方法制备得到:(一)、先将人参、枸杞、白芷和银杏叶的粉末按照重量比为5:6:6:10装入超临界萃取釜中,往超临界萃取釜内通入超临界CO2,并加入混合物粉末重量的5%的95%(v/v)乙醇作为夹带剂,而后调节萃取釜的温度50℃、萃取压力为10MPa、萃取时间50min;紧接着,再次调节萃取釜的萃取压力到15MPa、萃取时间为120min;最后,再调节萃取釜的萃取压力到35MPa、萃取时间为100min,加入混合物粉末重量的10%丙二醇作为接收剂,即得植物提取物;
(二)、将该植物提取物、乙醇、丙三醇和甜味剂以及剩下的丙二醇进行充分混合,即可得本发明的混合物,该混合物经雾化给药,即可代替烟碱,降低机体肝损伤。
实施例3
本发明在具体实施时,可由以下由以下重量计的原料制成:乙醇7g、丙二醇40g、丙三醇40g、甜味剂0.05g和植物提取物12㎎,其中植物提取物为人参皂甙、枸杞、白芷和银杏叶粉末的混合提取物;由下列方法制备得到:
(一)、先将人参、枸杞、白芷和银杏叶的粉末按照重量比为3:4:4:7装入超临界萃取釜中,往超临界萃取釜内通入超临界CO2,并加入混合物粉末重量的5%的95%(v/v)乙醇作为夹带剂,而后调节萃取釜的温度50℃、萃取压力为10MPa、萃取时间50min;紧接着,再次调节萃取釜的萃取压力到15MPa、萃取时间为120min;最后,再调节萃取釜的萃取压力到35MPa、萃取时间为100min,加入混合物粉末重量的10%丙二醇作为接收剂,即得植物提取物;
(二)、将该植物提取物、乙醇、丙三醇和甜味剂以及剩下的丙二醇进行充分混合,即可得本发明的混合物,该混合物经雾化给药,即可代替烟碱,降低机体肝损伤。
实施例4
本发明在具体实施时,可由以下由以下重量计的原料制成:乙醇5g、丙二醇30g、丙三醇30g、甜味剂0.01g和植物提取物10㎎,其中植物提取物为人参、枸杞、白芷和银杏叶粉末的混合提取物;由下列方法制备得到:
(一)、先将人参、枸杞、白芷和银杏叶的粉末按照重量比为2:3:3:4装入超临界萃取釜中,往超临界萃取釜内通入超临界CO2,并加入混合物粉末重量的5%的95%(v/v)乙醇作为夹带剂,而后调节萃取釜的温度50℃、萃取压力为10MPa、萃取时间50min;紧接着,再次调节萃取釜的萃取压力到15MPa、萃取时间为120min;最后,再调节萃取釜的萃取压力到35MPa、萃取时间为100min,加入混合物粉末重量的10%丙二醇作为接收剂,即得植物提取物;
(二)、将该植物提取物、乙醇、丙三醇和甜味剂以及剩下的丙二醇进行充分混合,即可得本发明的混合物,该混合物经雾化给药,即可代替烟碱,降低机体肝损伤。
实施例5
本发明在具体实施时,可由以下由以下重量计的原料制成:乙醇10g、丙二醇60g、丙三醇60g、甜味剂0.06g和植物提取物15㎎,其中植物提取物为人参、枸杞、白芷和银杏叶粉末的混合提取物;由下列方法制备得到:
(一)、先将人参、枸杞、白芷和银杏叶的粉末按照重量比为4:5:5:8装入超临界萃取釜中,往超临界萃取釜内通入超临界CO2,并加入混合物粉末重量的5%的95%(v/v)乙醇作为夹带剂,而后调节萃取釜的温度50℃、萃取压力为10MPa、萃取时间50min;紧接着,再次调节萃取釜的萃取压力到15MPa、萃取时间为120min;最后,再调节萃取釜的萃取压力到35MPa、萃取时间为100min,加入混合物粉末重量的10%丙二醇作为接收剂,即得植物提取物;
(二)、将该植物提取物、乙醇、丙三醇和甜味剂以及剩下的丙二醇进行充分混合,即可得本发明的混合物,该混合物经雾化给药,即可代替烟碱,降低机体肝损伤。
大鼠烟碱成瘾模型实验及烟碱替代研究
将待测的30只大鼠依次单独装入68cm×29cm×39cm(长×宽×高)的CPP装置中,打开拱形门挡板,并让其各自适应内部环境2d,每日1次,每次单独适应40min,然后放回笼内饲养。第3天开始对所有大鼠的CPP基准值进行持续10min的测试(0d),并剔除在白箱停留时间不足5%及超过50%的大鼠,挑选出24只大鼠并随机分成对照组和实验组(0.2mg/kg烟碱),每组12只。实验开始后(1d)在奇数日对实验组大鼠注射烟碱溶液,对照组注射PBS缓冲液,并放入CPP装置的白箱中让其自由活动40min;在偶数日对实验组和对照组大鼠均注射PBS缓冲液,并放入CPP装置的黑箱中让其自由活动40min。于第7、11及15天分别测试大鼠的CPP数值及穿梭次数,测试时间点设定在当日注射烟碱/PBS缓冲液之前,分别得到3、5及7次给药周期后大鼠的成瘾状态。然后将实验组的12只小鼠分成两组,每组6只,一组维持原来的奇数日注射烟碱溶液为实验组1,另一组把烟碱溶液改为本发明的混合物为实验组2,对照组随机选取6只记为对照组1,分别于第17、21及25天测试两组实验组和对照组的大鼠的CPP数值及穿梭次数,测试时间点设定在当日注射烟碱/PBS缓冲液之前,分别得到8、10及12次给药周期后大鼠的成瘾状态。
*表示在P<0.05水平上显著相关。
*表示在P<0.05水平上显著相关。
实验组与对照组相比,在第3、5及7次给药周期后的测试中实验组大鼠的穿梭次数均高于对照组,结果均有显著性差异,表明烟碱暴露引起大鼠自发活动程度上升。实验组1、实验组2与对照组1比较,在第8、10及12次给药周期后的测试中,实验组1与实验组2的大鼠的穿梭次数均高于对照组,结果均有显著性差异,表明本发明的混合物及雾化给药能在很大程度上起到替代烟碱的效果。
大鼠血常规测试结果显示,实验组1与对照组1相比,实验组大鼠血液中EOS值降低(P=0.039),差异具有统计学意义。嗜酸性粒细胞是白细胞的一种,EOS值降低可能意味着机体的应激反应及免疫水平下降。实验组2与对照组1比较EOS值变化不大,说明实验组2不会引起机体的应激反应及免疫水平的下降。及本发明的混合物及雾化给药相对于烟碱来说,克服了烟碱存在的炎症反应。
血生化检测结果显示,实验组1与对照组1相比,实验组大鼠GGT和TBIL值升高,差异具有统计学意义(P值分别为0.023和0.010)。血液中GGT含量可以作为一种检测肝脏损伤的血清酶,该指标的升高代表肝细胞膜渗漏(肝细胞坏死的显著特征之一)。同样,TBIL含量的升高也意味着肝脏可能出现了炎症、坏死及中毒等损伤。实验组1大鼠血液中GGT及TBIL的含量均略高于对照组,实验组2大鼠血液中GGT及TBIL的含量与对照组相差不大,表面本发明的混合物及雾化给药不会对肝脏产生炎症等不良反应。
以上所述仅为本发明的较佳实施例而已,并不用以限制本发明,凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等,均应包含在本发明的保护范围之内。
Claims (6)
1.一种降低机体肝损伤的混合物,其特征在于,该混合物及雾化给药是由以下重量计的原料制成:乙醇0g~15g、丙二醇20g~70g、丙三醇20g~70g、甜味剂0.001g~0.1g和植物提取物5㎎~20㎎。
2.根据权利要求1所述的一种降低机体肝损伤的混合物,其特征在于:所述植物提取物为人参、枸杞、白芷和银杏叶的混合提取物,其中人参、枸杞、白芷和银杏叶粉末按照重量比为1:1:2:5~5:6:6:10进行恒温变压超临界CO2混合提取。
3.根据权利要求2所述的一种降低机体肝损伤的混合物,其特征在于:所述人参提取物包括人参皂甙C-K、人参皂甙Rg、人参皂甙Rg5、人参皂甙aPPD、人参皂甙Rc。
4.根据权利要求1至3任一所述的一种降低机体肝损伤的混合物的制备方法,其特征在于,包括以下步骤:
(一)、先将人参、枸杞、白芷提和银杏叶的粉末按照重量比为1:1:2:5~5:6:6:10装入萃取釜中进行萃取,在萃取过程需要加入混合物粉末重量的5%乙醇和10%丙二醇,并且在萃取全程需要加入超临界CO2提取,即得植物提取物;
(二)、将该植物提取物、乙醇、丙三醇和丙二醇以及甜味剂进行充分混合,即可得本发明的混合物及雾化给药。
5.根据权利要求4所述的一种降低机体肝损伤的混合物的制备方法,其特征在于:将步骤(一)中的所有药材按“一锅法”总共进行了三次萃取,第一次萃取的温度为50℃,萃取压力为10MPa,萃取时间为50min;第二次萃取的温度为50℃,萃取压力为15MPa,萃取时间120min;第三次萃取的温度为50℃,萃取压力为35MPa,萃取时间100min。
6.根据权利要求4所述的一种降低机体肝损伤的混合物的制备方法,其特征在于:所述乙醇为95%(v/v)乙醇。
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