CN105169277A - 一种保肝利胆的栀子口服液及其制备方法 - Google Patents
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Abstract
一种保肝利胆的栀子口服液,其所述口服液包括以下重量份数的原料药:栀子10~50份,茵陈10~20份,茯苓10~20份,金钱草10~20份,香附10~20份,赤芍10~20份,益母草10~20份,玉米须10~20份,天花粉10~20份,生地10~20份,虎杖10~20份,知母10~20份,败酱草10~20份,连翘10~20份,三棱10~20份,黄芩10~20份,黄精10~20份,莪术10~20份,墨旱莲10~20份,车前草10~20份。栀子清热,泻火,凉血。治热病虚烦不眠,黄疸,淋病,消渴,目赤,咽痛,吐血,衄血,血痢,尿血,热毒疮疡,扭伤肿痛。
Description
技术领域
本发明涉及含有来源于植物、动物或矿物原料的医用保健品,特别涉及一种保肝利胆的栀子口服液及其制备方法。
背景技术
肝胆疾病是严重危害人类健康的常见病多发病,目前无特效药物促进肝细胞再生和防止肝细胞坏死。栀子GardeniajasminoidesEllis为茜草科植物栀子的干燥成熟果实,属于卫生部公布的药食两用物品。栀子味苦、性寒,有泻火除烦、清热利湿、凉血解毒的功效,是临床常用的保肝利胆药。很多经典名方中都有栀子的配伍使用,如《伤寒论》中的茵陈蒿汤、《金匮要略》中的栀子大黄汤等。同时,栀子也是现代临床治疗急、慢性肝炎常用药味。栀子肝毒性逐渐被报道后,临床用药开始”忌讳”使用栀子,从而影响了处方的疗效。故有必要对栀子的保肝利胆作用及其肝毒性进行深入探讨。
栀子具有抗氧化、抗炎、抗自由基损伤、促进胆汁分泌、抗病毒、保护神经细胞等药理作用,其化学成分主要包括环烯醚萜苷类、二萜类、有机酸酯类以及其他化合物。栀子及其主要有效成分具有保肝利胆的作用,对四氯化碳、异硫氰酸一1一萘酯J、黄曲霉素B等诱导的肝损伤具有良好的保护作用。
栀子有利尿作用,有抗血小板聚集作用,有促进小鼠网状内皮系统吞噬功能作用,有抗小鼠耳廓二甲苯致炎作用。栀子对大鼠有显著利胆作用,并使给药后胆汁中的胆固醇、胆红素排出总量增加,有利于防治胆结石栀子性苦、寒、无毒;气微,味微酸而苦;入心、肝、肺、胃经。栀子花含黄酮类栀子素、果胶、鞣质、藏红花素等,根、叶、花皆可入药,有镇静、降压,抑菌、致泻、镇痛、抗炎,调节平滑肌,加速软组织的愈合等作用,有泻火除烦,消炎祛热,清热利尿,外用解毒之功效。
栀子清热,泻火,凉血。治热病虚烦不眠,黄疸,淋病,消渴,目赤,咽痛,吐血,衄血,血痢,尿血,热毒疮疡,扭伤肿痛。
是药三分毒,栀子对肝脏的作用具有两面性,临床使用栀子时应尤为注意。其解决办法如下:通过中药配伍,既发挥栀子的临床疗效,又消除或减弱其损伤肝脏的毒副作用;控制剂量;加强“量效关系”和“量毒关系”研究;运用现代技术,体内外方法结合评价。虽然国内外对栀子保肝利胆的作用的研究报道颇多,但对其体外评价的实验报道很少,有必要进行更全面的研究以探明其作用机制。目前对栀子肝毒性的研究偏少,其作用机制尚不明确,还需进行更深的研究。
发明内容
本发明所要解决的技术问题在于,是药三分毒,栀子对肝脏的作用具有两面性,临床使用栀子时应尤为注意。其解决办法如下:通过中药配伍,既发挥栀子的临床疗效,又消除或减弱其损伤肝脏的毒副作用;控制剂量;加强“量效关系”和“量毒关系”研究;运用现代技术,体内外方法结合评价。虽然国内外对栀子保肝利胆的作用的研究报道颇多,但对其体外评价的实验报道很少,有必要进行更全面的研究以探明其作用机制。
为解决上述技术问题,本发明提供一种保肝利胆的栀子口服液,其所述口服液包括以下重量份数的原料药:栀子10~50份,茵陈10~20份,茯苓10~20份,金钱草10~20份,香附10~20份,赤芍10~20份,益母草10~20份,玉米须10~20份,天花粉10~20份,生地10~20份,虎杖10~20份,知母10~20份,败酱草10~20份,连翘10~20份,三棱10~20份,黄芩10~20份,黄精10~20份,莪术10~20份,墨旱莲10~20份,车前草10~20份。
所述保肝利胆的栀子口服液,其所述口服液中各种原料药的重量份数可以为:栀子10~30份,茵陈10~20份,茯苓10~20份,金钱草10~20份,香附10~20份,赤芍10~20份,益母草10~20份,玉米须10~20份,天花粉10~20份,生地10~20份,虎杖10~20份,知母10~20份,败酱草10~20份,连翘10~20份,三棱10~20份,黄芩10~20份,黄精10~20份,莪术10~20份,墨旱莲10~20份,车前草10~20份。
所述保肝利胆的栀子口服液,其所述口服液中各种原料药的重量份数还可以为:栀子10~50份,茵陈10~20份,茯苓10~20份,金钱草10~20份,香附10~20份,赤芍10~20份,益母草10~20份,玉米须10~20份,天花粉10~20份,生地10~20份,虎杖10~20份,知母10~20份,败酱草10~20份,连翘10~20份,三棱10~20份,黄芩10~20份,黄精10~20份,莪术10~20份,墨旱莲10~20份,车前草10~20份。
为解决上述技术问题,本发明还提供一种保肝利胆的栀子口服液的制备方法,其所述口服液的制备步骤包括:
a.栀子的制备,作为组分1;
b.将所述其余原料药放入乙醇中加热回流提取2次,作为组分2;
c.将上述两种提取液组分1和组分2合并,浓缩后加蜂蜜或糊精调和,消毒杀菌后制备成口服液装瓶。
所述步骤a中,可以将收获的栀子洗净,将其浸泡水中1-2小时,然后放入提取罐加热提取2次,每次1-2小时,去上清液,合并提取液,100-120目滤过,再经截流分子量为5000-10000的超滤柱超滤,超滤液减压浓缩相对密度为80℃时1.06的浸膏,加热浓缩至膏状,静置备用,成组分1备用。
所述步骤b中,可以将所述其余原料泡入10倍量乙醇中,加热提取2次,每次1-2小时,去上清液,合并提取液,100-120目滤过,再经截流分子量为5000-10000的超滤柱超滤,超滤液减压浓缩相对密度为80℃时1.06的浸膏,加热浓缩至膏状,静置备用,成组分2。
所述步骤c中,可以将组分1和组分2合并后,置入双效真空浓缩器中,浓缩至90℃时相对密度为1.36的浓缩液,置0~5℃低温冷藏24小时;将冷藏液加0.3%的助滤剂硅藻土,过滤,滤液再置入双效真空浓缩器中,浓缩至每1ml含0.1g生药量;浓缩后的膏剂加蜂蜜或糊精调和,紫外线消毒杀菌后装瓶。
为解决上述技术问题,本发明再提供一种保肝利胆的栀子口服液的制备方法,其制备步骤还可以为:
a.栀子的制备,作为组分1;
b.将所述其余原料药加水浸泡、提取3次作为组分2;
c.将组分1和组分2混合,浓缩后加蜂蜜调和,紫外线消毒杀菌后装瓶。
所述步骤a中,可以将洗净栀子放于10倍量乙醇中,加热提取2次,每次1-2小时,去上清液,合并提取液,100-120目滤过,再经截流分子量为5000-10000的超滤柱超滤,超滤液减压浓缩相对密度为80℃时1.06的浸膏,加热浓缩至膏状,静置备用,成组分1;所述步骤b中,可以将所述其余原料放入占其质量5-10倍量水中,浸泡1-2小时,加热提取2次,每次1-2小时,去上清液,合并提取液,100-120目滤过,将2次提取液合并静置,减压并浓缩至药液浓度为0.6g生药/mL,抽滤后,滤液的相对密度约为20℃时1.08;减压至0.03-0.08MPa,温度保持在60-80℃,浓缩至相对密度为1.20,温度至60℃-70℃的浸膏,作为组分2。
所述步骤c中,可以将组分1和组分2的合并,然后放入减压浓缩罐内,减压回收乙醇,浓缩至药液浓度为0.1g生药/mL,抽滤至滤液的相对密度为20℃时1.06;上述滤液经体积为10L的大孔吸附树脂柱吸附后,用10倍树脂柱体积的去离子水或蒸馏水洗脱,再用5倍树脂柱体积的95%乙醇洗脱,收集乙醇洗脱液,去除溶剂,调和蜂蜜,紫外线消毒杀菌后装瓶。
栀子清热,泻火,凉血。治热病虚烦不眠,黄疸,淋病,消渴,目赤,咽痛,吐血,衄血,血痢,尿血,热毒疮疡,扭伤肿痛。是药三分毒,栀子对肝脏的作用具有两面性,临床使用栀子时应尤为注意。其解决办法如下:通过中药配伍,既发挥栀子的临床疗效,又消除或减弱其损伤肝脏的毒副作用;控制剂量;加强“量效关系”和“量毒关系”研究;运用现代技术,体内外方法结合评价。虽然国内外对栀子保肝利胆的作用的研究报道颇多,但对其体外评价的实验报道很少,有必要进行更全面的研究以探明其作用机制。本发明对CCL4引起的急性肝损伤有明显的保护作用,有使SGOT显著降低作用。血清转氨酶升高主要反映肝细胞变性、坏死,细胞膜通透性升高,使肝细胞内GPT、GOT释放入血所致。有文献报道由CCL4中毒引起的动物SGPT、SGOT升高与肝细胞损伤程度呈粗略平行关系。本发明有选择性地降低SGOT作用,大剂量使肝脏指数减少,也说明本发明有较好的保肝作用。本发明大大改进中药提取技术,使得中药的有毒成分降到最低,可以使人体吸收,大大提高其利用率。
具体实施方式
栀子GardeniajasminoidesEllis为茜草科植物栀子的干燥成熟果实,属于卫生部公布的药食两用物品。栀子味苦、性寒,有泻火除烦、清热利湿、凉血解毒的功效,是临床常用的保肝利胆药。很多经典名方中都有栀子的配伍使用,如《伤寒论》中的茵陈蒿汤、《金匮要略》中的栀子大黄汤等。同时,栀子也是现代临床治疗急、慢性肝炎常用药味。栀子肝毒性逐渐被报道后,临床用药开始”忌讳”使用栀子,从而影响了处方的疗效。故有必要对栀子的保肝利胆作用及其肝毒性进行深入探讨。
1栀子保肝利胆作用
栀子具有抗氧化、抗炎、抗自由基损伤、促进胆汁分泌、抗病毒、保护神经细胞等药理作用,其化学成分主要包括环烯醚萜苷类、二萜类、有机酸酯类以及其他化合物。栀子及其主要有效成分具有保肝利胆的作用,对四氯化碳、异硫氰酸一1一萘酯J、黄曲霉素B等诱导的肝损伤具有良好的保护作用。
1.1栀子保肝利胆的物质基础研究
栀子中化学成分比较复杂,人们对其药理作用进行了深入的研究,关于栀子苷、京尼平、西红花苷(crocin,藏红花素)和西红花酸(crocetin,藏红花酸)的研究最多。栀子苷是栀子中的主要有效成分,被现行药典列为栀子含量检测指标。
京尼平在栀子中含量较少,是栀子苷在肠道中的水解产物。西红花苷类是一种水溶性的类胡萝卜素,是一种天然的色素,常作为食品添加剂使用。有学者认为,栀子发挥保肝利胆作用的物质是西红花苷和西红花酸。但业内对于西红花苷类保肝利胆作用观点不一,有研究认为,西红花苷类有保肝利胆作用,亦有持不同意见者。其原因可能为西红花苷类的纯度不同或是来源的植物不同,实验方法及条件的不
而导致实验结果的差异。
1.1.1栀子苷有报道用示踪剂观察栀子苷的分布,发现栀子苷具有一定的肝靶向性。京尼平苷经大鼠十二指肠给药,可显著增加大鼠的胆汁流量、增加胆汁内HCO3一浓度、降低胆汁内胆固醇含量的作用,而西红花苷无相关作用。
另有类似研究发现,西红花酸可抑制胆汁分泌,而京尼平苷和京尼平可显著增加大鼠胆汁流量。京尼平苷叫可预防肝细胞损伤,但西红花苷无此作用。研究表明,栀子苷在肠道内细菌一葡萄糖苷酶的作用下水解成京尼平,提示栀子苷的作用物质基础与水解产物有关。京尼平在栀子苷肝保护中的意义,值得进一步研究。此外,洪敏等建立了肝细胞萃取一HPLC分析法,并应用其分析栀子中保肝作用的活性成分。初步检测到栀子水提液主要的2个保肝效应成分,1个为栀子苷,另1个有待进一步鉴定。由此观之,该法基本可以反映化合物与细胞生物靶点(受体、通道、酶等)的相互作用;该体系中的保留成分和其药理作用有显著的相关性,可用于中药复杂体系物质基础的分析,或是一种很有应用前景的方法。综上,栀子苷确有保肝利胆的作用,这为其治疗肝脏疾病相关的新药开发提供了依据。
1.1.2栀子黄色素类栀子黄色素(gardeniayellow)是从栀子中提取的一类天然色素,藏红花素、藏红花酸是其主要有效成分”。,二者主要作用部位可能是肝脏和肾脏,这对其肝保护研究有一定的指导意义。栀子黄色素可有效调节cck~T损伤小鼠血清相关检测指标,具肝保护作用。西红花酸通过提高谷胱甘肽的浓度和增强谷胱甘肽s一转肽酶和谷胱甘肽氧化酶的活性;改善微循环,促进胆汁的分泌和排泄,从而降低异常增高的球蛋白和总胆红素,对慢性病毒性肝炎、肝炎后肝硬化有防治作用。藏红花可降低胆固醇和增加脂肪代埘,常配伍山楂、草决明、泽泻等,用于脂肪肝的治疗;或伍用郁金、茵陈、栀子等,发挥清热利肝退黄的作用,用治慢性肝炎。西红花苷可在小鼠肠道内被水解成西红花酸,然后吸收人,在体内又被转化成西红花酸的葡萄糖醛酸代谢物;推测该代谢物可能是西红花酸和西红花苷在体内发挥作用的活性分子形式。但使用相同剂量的西红花酸和西红花苷后,体内药浓度曲线明显不同,推测二者存体内的代谢是不同的。
栀子及其有效成分栀子苷、西红花苷等存一定剂量范围内都有保肝利胆的作用。药典要求栀子中栀子苷的含量≥1.8%,而两红花苷的含量较低,故栀子保肝利胆的成分可能主要为栀子苷。
1.2栀子保肝利胆作用及其机制研究
1.2.1基础动物研究Kang等发现栀子提取物和京尼平苷可降低肝微粒体中P4503A免疫相关蛋白密度。以小鼠四氯化碳急性肝损伤为模型研究发现其不影响细胞色素P4503A的活性,但能显著抑制正常小鼠肝微粒体细胞色素P4502El的活性,降低自由基生成速率;增加谷胱甘肽含量及GST活性,增强清除自由基的能力,降低自由基对肝细胞的损伤,以起到保肝作用。二者在对P4503A的不同作用,可能与其模型不同而导致动物体内生化的改变有关。对大鼠静脉注射京尼平苷与京尼平后发现在相同剂量下,后者短时间内有显著的利胆作用,提示京尼平苷可能被口一糖苷酶水解生成苷元京尼平而发挥作用。
栀子苷对大鼠肌注黄曲霉素B。(AFB,2mg·kg)诱导的肝损伤具有一定的保护作用,可能是由二栀子苷参与了肝脏组织的防御机制,包括增加GST活性对AFB的解毒作用和介导一谷酰胺半胱氨酸合成酶对GSH的合成。另有报道,栀子苷能增加AFB诱导的肝损伤的GST和GSH-Px的活性,通过增加AFB的新陈代谢来减少AFB诱导的非程序DNA合成,这可能是京尼平苷发挥对肝保护的化学预防效应的机制之一。茵陈蒿汤预给药可抑制肝细胞的凋亡和损伤。方中主要成分京尼平苷经肠道代谢后产生的京尼平是茵陈蒿汤的药效物质。在体外京尼平也能抑制Fas诱导的肝细胞凋亡。京尼平能抑制Jo2诱导的小鼠的肝脏凋亡蛋白一3和8的活性并降低线粒体膜电位。提示京尼平通过干扰MPT来抑制肝细胞凋亡可能是茵陈蒿汤发挥治疗作用的机制。
综上,栀子提取物、栀子苷和京尼平保肝利胆作用的机制可能为:①减少自由基生成和增强清除自由基的能力;②调节脂肪细胞因子释放和PPARct表达;③通过其抗炎作用用丁预防和治疗肝炎;④促进胆汁的分泌和排泄。
1.3含栀子复方的保肝利胆作用
茵陈蒿汤存亚洲国家被广泛用于治疗各种肝脏疾病,京尼平是其中的一种代谢产物,可防治GalN/LPS介导的大鼠肝损伤。京尼平可能通过抑制TNF-a的生成而改善急性肝损伤的肝功能指标。京尼平在急性肝炎模型中能抑制肝细胞的凋亡和损伤,通过抑制TNF-的过度表达来改善肝脏功能紊乱。茵陈蒿汤可能是通过相关蛋白介导和谷胱甘肽系统调节胆汁酸形成而发挥利胆作用的。
不明原因的严重肝炎难以治疗,经常发展为亚急性肝炎或肝衰竭。一名不明原因的胆汁淤积肝炎患者,其慢性肝炎导致肝纤维化变化,后来给予7.5g·d的茵陈蒿汤,发现通过治疗有改善肝脏功能和利胆作用。茵陈蒿汤中的有效成分京尼平苷通过抑制肠道细菌的增殖表现。对严重肝炎有的良好治疗效果。茵陈蒿汤和栀子均能降低血清转氨酶和1FN一-y的浓度。在体外实验研究中,京尼平和茵陈色原酮能显著抑制刀豆蛋白A刺激脾细胞产生的IFN一-y的生成。
茵陈蒿汤可能通过抑制刀豆蛋白A介导的IFN-和IL一12的生成而对肝脏起保护作用。黄连解毒汤能减弱大鼠由D-GlaN介导肝的抗氧化防御系统的紊乱,从而起到肝保护作用。栀子大黄汤对酒精性肝炎大鼠有保护作用,黄酮类、蒽醌类和环烯醚帖类可能是其有效的化学成分。综上,研究者对含栀子复方治疗肝脏疾病方面进行了深人的研究,其可能是通过主要有效成分的抗氧化、抗炎、促进胆汁分泌等作用,而发挥保肝作用。
2栀子肝毒性研究
肝脏是药物代谢的主要器官,大多数药物进入体循环后,都将被肝脏摄取、代谢。故肝脏是药源性组织损伤的主要靶器官之一。通常,中药被认为是无”毒性”的,但不正确使用也会导致肝损伤。肝损伤的发生机制较复杂,通常可分为免疫机制和化学机制。免疫机制主要通过一氧化氮、细胞因子、补体及免疫变态反应等产生损伤;化学机制主要通过细胞色素P450及结合反应产生的中间代谢产物产生损伤。
栀子水提取物和京尼平苷叫大剂量使用可致肝损伤。有关,如现行药典规定的栀子用量为3~9g,倘若服用30g甚至更高的剂量,可能会导致肝脏的损伤。栀子具有保肝利胆作用,但剂量过大或疗程偏长时可现肝毒性,所以在临床运用栀子治疗疾病时,应在中医药理论的指导下,控制使用剂量并制定合理的疗程。利用中药配伍,或通过炮制及制剂工艺的优化来增强其疗效,降低其毒性。运用栀子和健脾保肝方配伍使用,可以增效和减毒,对治疗急性肝损伤的作用最佳。随着中医药的发展与使用的规范化,以及对中药肝毒性相关因素的研究,临床医师在用药时应更加注重从整体观出发辩证用药,一因制宜,尽可能地降低和消除中药不良反应的发生。
是药三分毒,栀子对肝脏的作用具有两面性,临床使用栀子时应尤为注意。其解决办法如下:通过中药配伍,既发挥栀子的临床疗效,又消除或减弱其损伤肝脏的毒副作用;控制剂量;加强“量效关系”和“量毒关系”研究;运用现代技术,体内外方法结合评价。虽然国内外对栀子保肝利胆的作用的研究报道颇多,但对其体外评价的实验报道很少,有必要进行更全面的研究以探明其作用机制。目前对栀子肝毒性的研究偏少,其作用机制尚不明确,还需进行更深的研究。
黄精以根茎入药。具有补气养阴,健脾,润肺,益肾功能。用于治疗脾胃虚弱,体倦乏力,口干食少,肺虚燥咳,精血不足,内热消渴等症。对于糖尿病很有疗效。酒黄精又称炙黄精。为净黄精加酒和黑豆等辅料蒸后切片晒干入药者。兼有遁经络之功。黄精具有降血压,降血糖,降血脂,防止动脉粥样硬化,延缓衰老和抗菌等作用,黄精多糖具有免疫激活作用。用于阴虚肺燥,干咳少痰,及肺肾阴虚的劳嗽久咳等。用于脾胃虚弱。既补脾阴,又益脾气,用于肾虚精亏得头晕,腰膝酸软,须发早白及消渴等。黄精壮筋骨,益精髓,变白发;适宜用于肺阴不足所致的咳嗽痰少,干咳无痰,咳血等症。
茯苓味甘、淡、性平,入药具有利水渗湿、益脾和胃、宁心安神之功用。现代医学研究:茯苓能增强机体免疫功能,茯苓多糖有明显的抗肿瘤及保肝脏作用。茯苓性味甘淡平,入心、肺、脾经。具有渗湿利水,健脾和胃,宁心安神的功效。可治小便不利,水肿胀满,痰饮咳逆,呕逆,恶阻,泄泻,遗精,淋浊,惊悸,健忘等症。茯苓之利水,是通过健运脾肺功能而达到的,与其它直接利水的中药不同。用于脾虚泄泻,带下茯苓既能健脾,又能渗湿,对于脾虚运化失常所致泄泻、带下,应用茯苓有标本兼顾之效,常与党参、白术、山药等配伍。有可用为补肺脾,治气虚之辅佐药。
香附辛微苦甘,平功能主治:理气解郁,调经止痛。用于肝郁气滞,胸、胁、脘腹胀痛,消化不良,月经不调,经闭痛经,寒疝腹痛,乳房胀痛。《纲目》载其:散时气寒疫,利三焦,解六郁,消饮食积聚,痰饮痞满,跗肿,腹胀,脚气,止心腹、肢体、头、目、齿、耳诸痛,痈疽疮疡,吐血,下血,尿血,妇人崩漏带下,月候不调,胎前产后百病。
益母草味辛苦、凉。活血、祛淤、调经、消水。治疗妇女月经不调,胎漏难产,胞衣不下,产后血晕,瘀血腹痛,崩中漏下,尿血、泻血,痈肿疮疡。益母草含益母草碱、延胡索酸等物质,有活血调经、降血压、利尿消肿等作用。
知母为著名中药,性苦寒,有滋阴降火、润燥滑肠、利大小便之效。属清热下火药,主治:温热病、高热烦渴、咳嗽气喘、燥咳、便秘、骨蒸潮热、虚烦不眠、消渴淋浊。用于阴虚火旺,肺肾亏所致的骨节蒸潮热、盗汗、心烦等症。知母有滋阴降火的作用。常同黄柏相须为用,配入养阴药中,如知柏地黄丸。可用于阴虚消渴,症见口渴、饮多、尿多者。本品有滋阴润澡、生津止渴功效。同天花粉、五味子等配合使用可增强疗效,如玉液汤。清热泻火:用于高热烦渴,常配生石膏;用于肺热咳嗽,常配贝母。滋阴降火:用于阴虚之发热、盗汗,常配黄柏、地黄。《本经》:主消渴热中,除邪气肢体浮肿,下水,补不足,益气。《别录》:疗伤寒久疟烦热,胁下邪气,膈中恶及风汗内疸。
生地:生地也叫生地黄,玄参科多年生草本植物地黄RehmanniaglutinosaLibosch.的新鲜或干燥的块根。清热、生津、润燥、滑肠、破瘀、生新、止痛、调经、金疮瘀、凉血、止血;鲜地黄和生地黄的作用是有所不同的。鲜地黄清热生津,可以止血和凉血,经常是用于热病伤阴,吐血、咽喉肿痛、舌绛烦渴、发斑发疹以及衄热等病症。相对于鲜地黄,生地黄是凉血清热,也可以生津,还可以养阴,多用于治疗阴虚内热、骨蒸劳热、舌绛烦渴、发斑发疹等问题。生地性寒,功能为滋阴补肾。不只生津止渴和凉血清热,还对血崩、月经不调、胎动不安、便秘等有作用,凡是血分有热伤阴的人,都可以经常服用。如果想要治疗温热病,可以用生地做清营汤;如果是治疗温病的后期,由于余热还没消尽,应该把生地用来煮青蒿鳖甲汤。
黄芩其以根入药,味苦、性寒,有清热燥湿、泻火解毒、止血、安胎等功效。主治温热病、上呼吸道感染、肺热咳嗽、湿热黄胆、肺炎、痢疾、咳血、目赤、胎动不安、高血压、痈肿疖疮等症。黄芩的临床抗菌性比黄连好,而且不产生抗药性。《本草纲目》:治风热湿热头疼,奔豚热痛,火咳肺痿喉腥,诸失血。《别录》:疗痰热胃中热,小腹绞痛,消谷,利小肠,女子血闭,淋露下血,小儿腹痛。
茵陈清热利湿;退黄。主治:黄疸、小便不利、湿疮瘙痒、传染性黄疸型肝炎。有利胆,保护肝功能,解热,抗炎,降血脂,降压,扩冠等作用.茵陈有显著的保肝作用,对甲,乙型肝炎,黄疸型肝炎,有显著的疗效。有利胆,促进胆汁分泌,增加胆汁中胆酸和胆红素排出的作用.能增加心脏冠脉血流量,改善微循环,并有降血压,降血脂,抗凝血,利尿解热平喘,驱除蛔虫及抑制多种致病性皮肤真菌与细菌的作用。
金钱草是一种常见植物,而且是一种中药材,他主要功效就是可以预防结石和利胆排石可以说对结石有非常好治疗和预防作用,利水通淋;清热解毒;散瘀消肿,清利湿热,沙淋,尿涩作痛,黄疸尿赤,痈肿疔疮,主治肝胆及泌尿系结石;热淋;肾炎水肿;湿热黄疸;疮毒痈肿;毒蛇咬伤;跌打损伤。
赤芍苦,微寒。归肝经。主治功效:清热凉血;活血祛瘀。主温毒发斑;吐血衄血;肠风下血;目赤肿痛;痈肿疮疡;闭经;痛经;崩带淋浊;瘀滞胁痛;疝瘕积聚;跌扑损伤。用于温毒发斑,吐血衄血,目赤肿痛,肝郁胁痛,经闭痛经,症瘕腹痛,跌扑损伤,痈肿疮疡。《本经》:主邪气腹痛,除血痹,破坚积,寒热疝瘕,止痛,利小便,益气。《别录》:通顺血脉,缓中,散恶血,逐贼血,去水气,利膀胱大小肠,消痈肿,时行寒热,中恶腹痛,腰痛。《药性论》:治肺邪气,腹中疞痛,血气积聚,通宣脏腑拥气,治邪痛败血,主时疾骨热,强五脏,补肾气,治心腹坚胀,妇人血闭不通,消瘀血,能蚀脓。
玉米须味甘、淡,性平。有利尿消肿;清肝利胆的功效。主水肿,小便淋沥,黄疸,胆囊炎,胆结石,高血压,糖尿病,乳汁不通。《滇南本草》:宽肠下气。治妇人乳结,乳汁不通,红肿疼痛,怕冷发热,头痛体困。《岭南采药录》:和猪肉煎汤治糖尿病。又治小便淋沥砂石,苦痛不可忍,煎汤频服。
天花粉天花粉为葫芦科植物栝蒌的根,是一种中药,为清热泻火类药物,其具体功效是清热泻火,生津止渴,排脓消肿。主治:治热病口渴、消渴、黄疸、肺燥咳血、痈肿、痔痿。对于治疗糖尿病,常用它与滋阴药配合使用,以达到标本兼治的作用。《本草汇言》:天花粉,退五脏郁热,如心火盛而舌干口燥,肺火盛而咽肿喉痹,脾火盛而口舌齿肿,痰火盛而咳嗽不宁。若肝火之胁胀走注,肾火之骨蒸烦热,或痈疽已溃未溃,而热毒不散,或五疸身目俱黄,而小水若淋若涩,是皆火热郁结所致,惟此剂能开郁结,降痰火,并能治之。又其性甘寒,善能治渴,从补药而治虚渴,从凉药而治火渴,从气药而治郁渴,从血药而治烦渴,乃治渴之要药也。
虎杖微苦,微寒。归肝、胆、肺经。功能与主治清热解毒,利胆退黄,祛风利湿,散瘀定痛,止咳化痰。用于关节痹痛,湿热黄疸,经闭,产后瘀血不下,癓瘕,咳嗽痰多,水火烫伤,跌打损伤,痈肿疮毒。虎杖煎剂作用,对外伤出血有明显止血作用,内服对上消化道出血也有止血作用。《日华子本草》:治产后恶血不下,心腹胀满。排脓,主疮疖痈毒,妇人血晕,扑损瘀血,破风毒结气。《滇南本草》:攻诸肿毒,止咽喉疼痛,利小便,走经络。治五淋白浊,痔漏,疮痈,妇人赤白带下。
败酱草,败酱草为败酱科草本植物黄花和白花败酱的带根全草。《神农本草经》列为上品,为常用的清热解毒药。其性味辛、苦、微寒,有清热解毒、消痈排脓、祛瘀止痛之功。地方上称苦益菜,草本植物,多生长于山坡草地等地方,味辛、苦,用于中药熬煮时有浓烈的脚臭味,有清热解毒,祛瘀排脓等功效。性凉,味辛、苦。功能主治:清热解毒,祛瘀排脓。用于阑尾炎、痢疾、肠炎、肝炎、眼结膜炎、产后瘀血腹痛、痈肿疔疮。
连翘清热,解毒,散结,消肿。治温热,丹毒,斑疹,痈疡肿毒,瘰疬,小便淋闭。《本经》:主寒热,鼠痿,瘰疬,痈肿恶疮,瘿瘤,结热。《别录》:去白虫。
三棱归肝、脾经。有破血行气,消积止痛的功效。用于症瘕痞块,痛经,瘀血经闭,胸痹心痛,食积胀痛。《本草纲目》:通肝经积血,女人月水,产后恶血。《开宝》:老癖症瘕,积聚结块,产后恶血血结,通月水,堕胎,止痛利气。
墨旱莲菊科,一年生草本植物。直立,具匍匐茎;叶对生,披针形;头状花序,腋生或顶生,花白色;瘦果黑色。全国广布种。常见于田梗,沟溪边湿地。全草药用,能收敛、止血、补肝肾之功效。滋补肝肾、凉血止血,可治各种吐血,肠出血等症。捣汁涂眉发,能促进毛发生长,内服有乌发、黑发功效。《唐本草》说,墨旱莲“主血痢,针灸疮发,洪血不可止者敬之”《日华子本草》中也说,墨旱莲可以“排脓,止血,通小肠,敷一切疮并蚕瘑”。
车前草,中药名。为车前科植物车前PlantagoasiaticaL.或平车前PlantagodepressaWilld.的干燥或新鲜全草。归肝、肾、膀胱经。清热,利尿,祛痰,凉血,解毒。用于水肿尿少,热淋涩痛,暑湿泻痢,痰热咳嗽,吐血衄血,痈肿疮毒。《别录》:金疮,止血衄鼻,瘀血血瘕,下血,小便赤,止烦下气,除小虫。
莪术根茎称“莪术”,供药用,主治“气血凝滞,心腹胀痛,症瘕,积聚,宿食不消,妇女血瘀经闭,跌打损伤作痛。”块根称“绿丝郁金”,有行气解郁,破瘀,止痛的功用。辛、苦,温。归肝、脾经。破血行气,消积止痛。用于血瘀腹痛、肝脾肿大、心腹胀痛,积聚,妇女血瘀经闭,跌打损伤作痛饮食积滞。行气止痛,破血消积:用于气滞血瘀之经闭、胸胁痛、腹痛及症瘕肿块等。常配三棱。
本发明具体实施方式
具体实施例1:
将晾晒好的栀子泡入10倍量乙醇中,加热提取2次,每次1-2小时,去上清液,合并提取液,100-120目滤过,再经截流分子量为5000-10000的超滤柱超滤,超滤液减压浓缩相对密度为80℃时1.06的浸膏,加热浓缩至膏状,静置备用,成组分1。
将其余原料药茵陈,茯苓,金钱草,香附,赤芍,益母草,玉米须,天花粉,生地,虎杖,知母,败酱草,连翘,三棱,黄芩,黄精,莪术,墨旱莲,车前草,放入10倍量乙醇中,浸泡1-2小时,加热提取2次,每次1-2小时,合并提取液,静置后去上清液,然后放入减压浓缩罐内,减压回收乙醇,浓缩至药液浓度为0.6g生药/mL,抽滤至滤液的相对密度为80℃时1.06的浸膏,成为组分2。
将组分1和组分2合并后置入双效真空浓缩器中,浓缩至90℃时相对密度为1.36的浓缩液,置0~5℃低温冷藏24小时;将冷藏液加0.3%的助滤剂硅藻土,过滤,滤液再置入双效真空浓缩器中,浓缩至每1ml含0.1g生药量;浓缩后的膏剂加糊精调和,紫外线消毒杀菌后装瓶。
具体实施例2:
将晾晒好的栀子5000g泡入10倍量乙醇中,加热提取2次,每次1-2小时,去上清液,合并提取液,100-120目滤过,再经截流分子量为5000-10000的超滤柱超滤,超滤液减压浓缩相对密度为80℃时1.06的浸膏,加热浓缩至膏状,静置备用,成组分1。
将茵陈1500g,茯苓1500g,金钱草1500g,香附1500g,赤芍1500g,益母草1500g,玉米须1500g,天花粉1500g,生地1500g,虎杖1500g,知母1500g,败酱草1500g,连翘1500g,三棱1500g,黄芩1500g,黄精1500g,莪术1500g,墨旱莲1500g,车前草1500g,将其余原料药的药放入10倍量乙醇中,浸泡1-2小时,加热提取2次,每次1-2小时,合并提取液,静置后去上清液,然后放入减压浓缩罐内,减压回收乙醇,浓缩至药液浓度为0.6g生药/mL,抽滤至滤液的相对密度为20℃时1.06的浸膏,成为组分2。将组分1和组分2合并后置入双效真空浓缩器中,浓缩至90℃时相对密度为1.35的浓缩液,置0~5℃低温冷藏24小时;将冷藏液加0.3%的助滤剂硅藻土,过滤,滤液再置入双效真空浓缩器中,浓缩至每1ml含0.1g生药量;浓缩后的膏剂加糊精调和,紫外线消毒杀菌后装瓶。
具体实施例3:将晾晒好的栀子4000g浸泡水中1小时,然后放入提取罐加热煮沸1小时,过滤,滤液备用;滤渣加水,第二次加热,煮沸45分钟,过滤,滤液备用;滤渣再加水,第三次加热煮沸半小时,过滤;将三次滤液合在一起,用纱布过滤,残渣中加入50-60%乙醇,60℃-70℃继续浸提2h,每10min搅拌一次,纱布过滤,合并浸提液,成组分1,将所述其余原料茵陈1200g,茯苓1100g,金钱草1100g,香附1200g,赤芍1200g,益母草1200g,玉米须1200g,天花粉12500g,生地1200g,虎杖1200g,知母1200g,败酱草1200g,连翘1100g,三棱1100g,黄芩1100g,黄精1200g,莪术1200g,墨旱莲1200g,车前草1100g放入5-10倍量乙醇中,浸泡1-2小时,加热提取2次,每次1-2小时,去上清液,合并提取液,100-120目滤过,将2次提取液合并静置,减压回收乙醇,并浓缩至药液浓度为0.6g生药/mL,抽滤后,滤液的相对密度约为20℃时1.08;减压至0.03-0.08MPa,温度保持在60-80℃,浓缩至相对密度为1.20,温度至60℃-70℃的浸膏,作为组分2。将组分1和组分2合并后置入双效真空浓缩器中,浓缩至90℃时相对密度为1.05的浓缩液,置0~5℃低温冷藏24小时;将冷藏液加0.3%的助滤剂硅藻土,过滤,滤液再置入双效真空浓缩器中,浓缩至每1ml含0.1g生药量;浓缩后的膏剂加糊精调和,紫外线消毒杀菌后装瓶。
具体实施例4:将晾晒好的栀子3500g泡入10倍量乙醇中,加热提取2次,每次1-2小时,去上清液,合并提取液,100-120目滤过,再经截流分子量为5000-10000的超滤柱超滤,超滤液减压浓缩相对密度为80℃时1.06的浸膏,加热浓缩至膏状,静置备用,成组分1。将茵陈1100g,茯苓1100g,金钱草1100g,香附1100g,赤芍1100g,益母草1100g,玉米须1100g,天花粉1100g,生地1100g,虎杖1200g,知母1200g,败酱草1100g,连翘1200g,三棱1200g,黄芩1200g,黄精1200g,莪术1200g,墨旱莲1200g,车前草1200g,将所述原料药放入粉碎机粉碎后,将颗粒物放入乙醇中加热回流提取2次,每次1~2小时,将2次提取液合并静置;将上述乙醇提取过的药渣加10倍量水加热回流提取2次,每次1~2小时,将2次提取液合并静置,将上述两种提取液合并,作为组分2;合并组分1组分2减压浓缩相对密度为80℃时1.36的滤液,回收乙醇,调入蜂胶,紫外线杀菌后装瓶。
试验例1:本发明急性毒性试验
一、试验材料:
动物:昆明种小鼠,体重21-24g,雌雄各半,山东大学生物试验室育种。药物:本发明口服液(按实施方法2制备)。
二、方法:
1、LD50计算:采用改良寇氏法,将小鼠随机分成5组,每组10只,雌雄各半,将栓剂溶解,配成最大浓度,按小鼠最大允许容量给药,所给剂量按生药量依次为18,14.4,11.5,9.2,7.4(g.kg-1),在动物禁食(不禁水)18小时后,一日内分两次给药(间隔半小时),每次0.5ml,观察动物死亡情况。
2、最大耐受剂量测定(MTD值):取小鼠20只,雌雄各10只。将栓剂加蒸馏水溶解,配成最高浓度,按动物的最大耐受量,以注射灌喂器能抽动为准。在动物禁食(不禁水)18小时后,一日内分两次给药(间隔半小时),每次0.5ml(每ml含生药0.36g),总药量为18g生药/kg.d,相当临床成人50Kg体重用量的300倍。给药后连续观察7天。
三、试验结果:
在LD50计算中当用最大允许浓度和最大允许容量给予小鼠时(18g/Kg.d),未见小鼠死亡,即未测出LD50,只可求最大耐受剂量,在7天观察期中,动物其食欲、活动、毛色、精神状态等皆正常,发育正常,未见有死亡。即选用相当于临床剂量的300倍药量,并无不良反应发生,表明急性毒性极小,MTD>18g/Kg.d。
试验例2:本发明急性皮肤刺激试验报告
1、实验目的:检测本发明对实验动物皮肤的刺激/腐蚀作用和强度
2、材料和方法:
2.1.受试物:本发明口服液(按实施例方法2制得)
2.2.实验动物:壹级大耳白种家兔,10只,雌性,体重2.1-2.3kg;由青岛大学医学院生物系实验动物中心提供;
2.3.试验方法:
选用皮肤完好的健康家兔10只,于试验前24小时将其背部脊柱两侧被毛剪掉,去毛面积左、右各约4cm×4cm。试验时取受试物0.2ml涂于2.5cm×2.5cm的二层纱布上,敷贴于一侧去毛皮肤表面,油纸覆盖,胶布固定。另一侧皮肤作为空白对照。封闭4小时后,去除覆盖物,并用温水清洗去残留受试物,于去除受试物后的1、24和48小时观察涂抹部位皮肤反应,并评分。
3、实验结果:实验动物皮肤未出现任何红斑,红肿,发炎现象。
4、小结:根据《消毒技术规范》(1999)中皮肤刺激反应评分标准判定,本发明对动物皮肤刺激强度属无刺激性。
实施例3:长期毒性实验资料
1、实验方法
将豚鼠随机份成4组,每组15只。在豚鼠背部脊柱两侧将脱毛剂均匀涂上,使其脱毛范围约40平方厘米。洗净脱毛剂,观察24小时后每组豚鼠分别涂本发明口服液溶液0.2、0.4和0.8ml,分别含生药92、184和368mg,另一组涂溶媒0.8ml每日二次,连续30天,观察豚鼠的一般情况,实验结束后处死动物进行血液学、血液生化及病理学检查。
2、结果
上述三组用药豚鼠躯干去毛区,未见局部皮肤有水肿、充血、红斑、出血点及溃疡。用药组与对照组动物毛发色泽、摄食、四肢活动等对照组无明显差异,血液生化检查,用药组与对照组均在正常范围。病理组织学检查,实验各组心、肝、肾及局部皮肤均未见明显病变。提示,本发明中药口服液长期用药对局部皮肤及全身重要脏器均未见明显的毒性作用。
试验结果表明:本发明口服液实验安全。该药对乙型链球菌、金黄色葡萄球菌、大肠杆菌的最小抑制浓度为1∶150,淋球菌为1∶150,白色念珠菌为1∶300,对1∶20稀释度时的杀灭时间为5分钟,1∶50时为10分钟,1∶100时为20分钟,1∶200时为40分钟,1∶400时为8小时。
药理学实验:
栀子对正常小鼠由四氯化碳引起的肝损伤有明显保护作用,表现为SGOT显著降低,使肝体比降低(大剂量)。对正常大鼠有显著的利胆作用,胆汁流量增加持续2h。熊去氧胆酸流量增加持续1小时。胆汁中胆固醇、胆红素给药前和给药后组间比较未见显著差异性。为此我们进行了实验研究。
1材料与方法药物:本发明提醇沉液的制备:取一定量本发明原料药,水煎两次,水浴上浓缩至一定体积后加95乙醇沉淀杂质,过液,滤液回收乙醇。配成100浓度。
云芝肝泰系吉林省集安制药厂生产,批号为吉卫药准字~831430011。熊去氧胆酸为日本三菱化成生产。动物ICR小鼠,SD大鼠均由本院动物研究室提供。
1.1对四氯化碳引起的小鼠肝损伤的保护作用:雄性小鼠78只,体重18-23g,按体重随机分层分成六组,每组13只。本发明3个剂量组2.5g/kg、5.0g/kg、10.0g/kg,阳性对照药云芝肝泰10g/kg,模型组,水对照组每天灌胃给药一次,连续6d,于第六天给药后1h除水对照组外其余各组均皮下注射0.15的四氯化碳菜油5ml/kg。16h后摘眼球取血用北京化工厂产的试剂盒测定血清SGPT、SGOT。解剖出肝脏称重,根据处死时体重计算每只小鼠的肝体比、数据以均值士标准差表示,组间进行t检验。
1.2对正常大鼠胆汁流量的影响1.2.1
胆汁流量的测定:取大鼠60只,雄性,体重250~350g,称重随机分成五组,每组12只,实验前禁食12h,不禁水。实验以10%乌拉坦1.0g/kg腹腔注射麻醉,仰位固定于手术台,沿腹正中线切开腹壁,找出十二指肠,在降部肠系膜中找到白色有韧性的胆管,在其下穿二根丝线,结扎乳头部,向肝脏方向作“V”形切口,插入硬质塑料管,结扎固定,即可见有淡黄绿色胆汗流出,试管收集胆汁,术后以盐水纱布覆盖腹腔,待稳定1h后,先收集30min的胆汁,作为给药前的基础值,然后分组给药(经十二指肠)。本发明3个剂量组2.5g/kg、5.0g/kg、10.0g/kg,水对照组,阳性药熊去氧胆酸0.5g/kg。给药后每隔30min收集测量1次胆汁。共4h。
1.2.2胆汁成分的测定:将给药前,给药后4h收集的胆汁测定胆红素(伊利康生物技术有限公司生产,咖啡因法)。胆固醇含量测定用东欧生物工程公司生产的试剂盒,酶法测定。
2实验结果
2.1对四氯化碳引起的小鼠肝损伤的保护作用:四氯化碳引起的SGPT、SGOT显著升高P<0.01,说明造型成功。本发明使SGOT显著降低三个剂量组均P<O.05,本发明对SGPT无明显影响。云芝肝泰使SGPT、SGOT显著降低(P-~O.05)。泽兰10g/kg组使肝体比显著低于四氯化碳模型组。详见表1。
表1本发明对四氯化碳中毒小鼠血清转氨酶的影响(X±S)
注:组间进行t检验,与四氯化碳组比*P<0.05,**P<0.01
2.2对正常大鼠胆汁流量的影响:本发明2.5g/kg组使正常大鼠胆汁流量增加,持续2h,以给药后的30min增加最显著<0.05)。5.0g/kg组给药2h各时相都显著增加<0.05.10.0g/kg组给药后90min内各时相都比对照组显著升高(P<0.01,P<0.05)。阳性药熊去氧胆酸也使流量增加,持续1h。P<0.05详见表2。
表2泽兰对麻醉大鼠胆汁流量的影响(X±S)
注t以给药前流量为100%,组问进行t检验,与对照组比*P<0.05,**P<0.01.本发明给药前、给药后涓定胆汁中胆红素和胆同醇含量与对照组相比未见显著差异。详见表3。
表3本发明对大鼠胆汁中胆固醇、胆红素排出量的影响(X±S)
讨论:
肝胆疾病是严重危害人类健康的常见病多发病,目前无特效药物促进肝细胞再生和防止肝细胞坏死。我们的实验已经证明本发明有良好抗实验性肝硬变作用。本实验表明本发明对CCL4引起的急性肝损伤有明显的保护作用,有使SGOT显著降低作用。血清转氨酶升高主要反映肝细胞变性、坏死,细胞膜通透性升高,使肝细胞内GPT、GOT释放入血所致。有文献报道由CCL4中毒引起的动物SGPT、SGOT升高与肝细胞损伤程度呈粗略平行关系。本发明有选择性地降低SGOT作用,大剂量使肝脏指数减少,也说明本药有较好的保肝作用。
栀子有利尿作用,有抗血小板聚集作用,有促进小鼠网状内皮系统吞噬功能作用,有抗小鼠耳廓二甲苯致炎作用。栀子对大鼠有显著利胆作用,并使给药后胆汁中的胆固醇、胆红素排出总量增加,有利于防治胆结石。本发明大大改进中药提取技术,使得中药的有毒成分降到最低,可以使人体吸收,大大提高其利用率。
Claims (10)
1.一种保肝利胆的栀子口服液,其特征在于,所述口服液包括以下重量份数的原料药:栀子10~50份,茵陈10~20份,茯苓10~20份,金钱草10~20份,香附10~20份,赤芍10~20份,益母草10~20份,玉米须10~20份,天花粉10~20份,生地10~20份,虎杖10~20份,知母10~20份,败酱草10~20份,连翘10~20份,三棱10~20份,黄芩10~20份,黄精10~20份,莪术10~20份,墨旱莲10~20份,车前草10~20份。
2.根据权利要求1所述保肝利胆的栀子口服液,其特征在于,所述口服液中各种原料药的重量份数为:栀子10~30份,茵陈10~20份,茯苓10~20份,金钱草10~20份,香附10~20份,赤芍10~20份,益母草10~20份,玉米须10~20份,天花粉10~20份,生地10~20份,虎杖10~20份,知母10~20份,败酱草10~20份,连翘10~20份,三棱10~20份,黄芩10~20份,黄精10~20份,莪术10~20份,墨旱莲10~20份,车前草10~20份。
3.根据权利要求1所述保肝利胆的栀子口服液,其特征在于,所述口服液中各种原料药的重量份数为:栀子10~50份,茵陈10~20份,茯苓10~20份,金钱草10~20份,香附10~20份,赤芍10~20份,益母草10~20份,玉米须10~20份,天花粉10~20份,生地10~20份,虎杖10~20份,知母10~20份,败酱草10~20份,连翘10~20份,三棱10~20份,黄芩10~20份,黄精10~20份,莪术10~20份,墨旱莲10~20份,车前草10~20份。
4.一种如权利要求1~3中任一项所述保肝利胆的栀子口服液的制备方法,其特征在于,所述口服液的制备步骤包括:
a.栀子的制备,作为组分1;
b.将所述其余原料药放入乙醇中加热回流提取2次,作为组分2;
c.将上述两种提取液组分1和组分2合并,浓缩后加蜂蜜或糊精调和,消毒杀菌后制备成口服液装瓶。
5.根据权利要求4所述保肝利胆的栀子口服液的制备方法,其特征在于,所述步骤a中,将收获的栀子洗净,将其浸泡水中1-2小时,然后放入提取罐加热提取2次,每次1-2小时,去上清液,合并提取液,100-120目滤过,再经截流分子量为5000-10000的超滤柱超滤,超滤液减压浓缩相对密度为80℃时1.06的浸膏,加热浓缩至膏状,静置备用,成组分1备用。
6.根据权利要求4所述保肝利胆的栀子口服液的制备方法,其特征在于,所述步骤b中,将所述其余原料泡入10倍量乙醇中,加热提取2次,每次1-2小时,去上清液,合并提取液,100-120目滤过,再经截流分子量为5000-10000的超滤柱超滤,超滤液减压浓缩相对密度为80℃时1.06的浸膏,加热浓缩至膏状,静置备用,成组分2。
7.根据权利要求4所述保肝利胆的栀子口服液的制备方法,其特征在于,所述步骤c中,将组分1和组分2合并后,置入双效真空浓缩器中,浓缩至90℃时相对密度为1.36的浓缩液,置0~5℃低温冷藏24小时;将冷藏液加0.3%的助滤剂硅藻土,过滤,滤液再置入双效真空浓缩器中,浓缩至每1ml含0.1g生药量;浓缩后的膏剂加蜂蜜或糊精调和,紫外线消毒杀菌后装瓶。
8.一种如权利要求1~3中任一项所述保肝利胆的栀子口服液的制备方法,其特征在于,制备步骤还可以为:
a.栀子的制备,作为组分1;
b.将所述其余原料药加水浸泡、提取3次作为组分2;
c.将组分1和组分2混合,浓缩后加蜂蜜调和,紫外线消毒杀菌后装瓶。
9.根据权利要求8所述保肝利胆的栀子口服液的制备方法,其特征在于,所述步骤a中,将洗净栀子放于10倍量乙醇中,加热提取2次,每次1-2小时,去上清液,合并提取液,100-120目滤过,再经截流分子量为5000-10000的超滤柱超滤,超滤液减压浓缩相对密度为80℃时1.06的浸膏,加热浓缩至膏状,静置备用,成组分1;所述步骤b中,将所述其余原料放入占其质量5-10倍量水中,浸泡1-2小时,加热提取2次,每次1-2小时,去上清液,合并提取液,100-120目滤过,将2次提取液合并静置,减压并浓缩至药液浓度为0.6g生药/mL,抽滤后,滤液的相对密度约为20℃时1.08;减压至0.03-0.08MPa,温度保持在60-80℃,浓缩至相对密度为1.20,温度至60℃-70℃的浸膏,作为组分2。
10.根据权利要求8所述保肝利胆的栀子口服液的制备方法,其特征在于,所述步骤c中,将组分1和组分2的合并,然后放入减压浓缩罐内,减压回收乙醇,浓缩至药液浓度为0.1g生药/mL,抽滤至滤液的相对密度为20℃时1.06;上述滤液经体积为10L的大孔吸附树脂柱吸附后,用10倍树脂柱体积的去离子水或蒸馏水洗脱,再用5倍树脂柱体积的95%乙醇洗脱,收集乙醇洗脱液,去除溶剂,调和蜂蜜,紫外线消毒杀菌后装瓶。
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