CN112972540A - 一种防醉解酒保肝组合物及制备方法以及应用 - Google Patents
一种防醉解酒保肝组合物及制备方法以及应用 Download PDFInfo
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- CN112972540A CN112972540A CN202110279750.7A CN202110279750A CN112972540A CN 112972540 A CN112972540 A CN 112972540A CN 202110279750 A CN202110279750 A CN 202110279750A CN 112972540 A CN112972540 A CN 112972540A
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Abstract
本发明提供了一种防醉解酒保肝组合物,包括:2wt%~8wt%的果胶;0.5wt%~2wt%的葛根提取物;0.3wt%~0.9wt%的姜黄素;0.1wt%~1wt%的柑橘黄酮;0.1wt%~1wt%的枳椇子总黄酮;余量为水。本发明提供的配方各组分配伍搭配合理,协同起效,即可以延缓乙醇吸收入血速度起到防醉的作用,又可以加速乙醇分解起到解酒保肝作用,同时还具有保肝护肝作用,因此以此配方开发防醉解酒保肝产品可以得到良好的防醉解酒保肝效果。
Description
技术领域
本发明属于生物制药技术领域,具体涉及一种防醉解酒保肝组合物及制备方法以及应用。
背景技术
我国是酒类消费大国,2016年酒类消费规模近万亿元,其中白酒消费约6000亿元,并以约10%的速度增长,啤酒消费1800亿元,近些年每年消费基本持平,葡萄酒消费约500亿元,每年增长约10%。酒文化渗透于整个中华文明史中,适当饮酒可以促进血液循环、通络散寒、散湿止痛、调节心情、消除疲劳、缓解紧张等,但是急性大量饮酒可引起恶心、呕吐、记忆力减退、注意力不集中、精细运动能力受损和情绪不稳定,严重时甚至可因呼吸肌麻痹而导致死亡。长期饮酒更是能引起精神障碍、胃溃疡以及脂肪肝、酒精性肝炎、肝硬化等疾病,有研究表明食道癌、肝癌发病率的升高似乎也与饮酒有关。因此开发有效的解酒保肝药物受到大众的普遍关注。
解酒保肝药物的作用核心是降低患者血中乙醇及其代谢产物的浓度,减轻其对各器官的损伤。根据乙醇在体内的代谢特点,当前的药物主要从两方面发挥作用:(1)抑制酒精的胃肠吸收,加强乙醇在胃肠道的首过效应,降低血中的乙醇浓度;(2)药物直接作用于肝代谢酶系,加速乙醇及其代谢产物的消除速率,减轻其对组织和细胞的损害。目前通过合成方法研制解酒保肝药物并未取得实质性的进展,在继承传统医药的基础上大力开发天然产物防醉解酒保肝产品已成为当前研究重点。
发明内容
有鉴于此,本发明要解决的技术问题在于提供一种防醉解酒保肝组合物及制备方法以及应用,本发明提供的防醉解酒保肝组合物均为天然产物,并且具有显著的防醉解酒保肝效果。
本发明提供了一种防醉解酒保肝组合物,包括:
2wt%~8wt%的果胶;
0.5wt%~2wt%的葛根提取物;
0.3wt%~0.9wt%的姜黄素;
0.1wt%~1wt%的柑橘黄酮;
0.1wt%~1wt%的枳椇子总黄酮;
余量为水。
优选的,所述果胶选自柑橘果胶或苹果果胶,所述果胶的分子量为150~350kD,酯化度10%~50%。
本发明还提供了一种上述防醉解酒保肝组合物的制备方法,包括以下步骤:
A)将果胶和葛根提取物溶于去离子水中,得到混合水溶液;
B)将姜黄素、柑橘黄酮、枳椇子总黄酮分散到海藻酸钠溶液中后制备海藻酸钙凝胶微球;
C)将混合水溶液与海藻酸钙凝胶微球混合,得到防醉解酒保肝组合物。
优选的,所述制备海藻酸钙凝胶微球的方法为:
姜黄素、柑橘黄酮、枳椇子总黄酮分散到海藻酸钠溶液中,然后将混合液滴入氯化钙溶液中形成海藻酸钙凝胶微球。
优选的,所述海藻酸钠溶液的浓度为0.5wt%~2wt%,所述氯化钙溶液的浓度为0.5wt%~5wt%。
本发明还提供了一种上述防醉解酒保肝组合物在制备防醉解酒保肝的药物或保健食品中的应用。
与现有技术相比,本发明提供了一种防醉解酒保肝组合物,包括:2wt%~8wt%的果胶;0.5wt%~2wt%的葛根提取物;0.3wt%~0.9wt%的姜黄素;0.1wt%~1wt%的柑橘黄酮;0.1wt%~1wt%的枳椇子总黄酮;余量为水。本发明以果胶为基本原料开发防醉解酒保肝配方,果胶进入胃后遇到胃酸会形成保护膜可以延缓酒精吸收速度,葛根提取物可以促进血液中的酒精代谢分解,快速降低血液中乙醇浓度,姜黄素能够提高肝组织中的谷胱甘肽含量,加速乙醇分解,降低体内乙醇的含量,柑橘黄酮具有抗氧化作用可以清除乙醇代谢生成的自由基,保护肝脏免受自由基的损伤,枳椇子总黄酮可有效减轻酒精引起的炎症反应,抗纤维化的形成,对酒精性肝损伤有良好的防治作用。该配方各组分配伍搭配合理,协同起效,即可以延缓乙醇吸收入血速度起到防醉的作用,又可以加速乙醇分解起到解酒保肝作用,同时还具有保肝护肝作用,因此以此配方开发防醉解酒保肝产品可以得到良好的防醉解酒保肝效果。
具体实施方式
本发明提供了一种防醉解酒保肝组合物,包括:
2wt%~8wt%的果胶;
0.5wt%~2wt%的葛根提取物;
0.3wt%~0.9wt%的姜黄素;
0.1wt%~1wt%的柑橘黄酮;
0.1wt%~1wt%的枳椇子总黄酮;
余量为水。
本发明提供了的防醉解酒保肝组合物包括2wt%~8wt%的果胶,优选为2wt%、4wt%、6wt%、8wt%,或2wt%~8wt%之间的任意值。在本发明中,所述果胶选自柑橘果胶或苹果果胶,所述果胶的分子量为150~350kD,优选为200~300kD,酯化度10%~50%,优选为20%~40%。果胶溶液在胃内可以形成凝胶,保护胃黏膜不与酒精直接接触,具有延缓酒精吸收的作用。
本发明提供的防醉解酒保肝组合物还包括0.5wt%~2wt%的葛根提取物,优选为0.5wt%、1.0wt%、1.5wt%、2.0wt%,或0.5wt%~2wt%之间的任意值。葛根提取物主要成分为异黄酮类物质,如葛根素、葛根素-7-木糖甙、大豆黄酮、大豆黄酮甙、β-谷甾醇、花生酸等,具有促进乙醇分解的作用,同时还具有清除自由基和抗氧化作用,保护肝脏免受自由基的损伤。本发明对所述葛根提取物的来源并没有特殊限制,一般市售或自行制备。
本发明提供的防醉解酒保肝组合物还包括0.3wt%~0.9wt%的姜黄素,优选为0.3wt%、0.5wt%、0.7wt%、0.9wt%,或0.3wt%~0.9wt%之间的任意值。姜黄素是姜黄中分离出来多酚类化合物,能够提高肝组织中的谷胱甘肽含量,而谷胱甘肽可以分解乙醇从而降低体内乙醇的含量,同时还具有抗氧化作用,具有保肝护肝作用。本发明对所述姜黄素的来源并没有特殊限制,一般市售或自行制备。
本发明提供的防醉解酒保肝组合物还包括0.1wt%~1wt%的柑橘黄酮,优选为0.1wt%、0.3wt%、0.5wt%、0.7wt%、0.9wt%、1.0wt%,或0.1wt%~1wt%之间的任意值。柑橘黄酮主要成分有柚皮素、橙皮素、芹菜黄素、木犀草素、槲皮素、柚皮苷、橙皮苷、柚皮芸香苷等,具有超强抗氧化的作用,可以清除乙醇代谢生成的自由基,保护肝脏免受自由基的损伤。本发明对所述柑橘黄酮的来源并没有特殊限制,一般市售或自行制备。
本发明提供的防醉解酒保肝组合物还包括0.1wt%~1wt%的枳椇子总黄酮,优选为0.1wt%、0.3wt%、0.5wt%、0.7wt%、0.9wt%、1.0wt%,或0.1wt%~1wt%之间的任意值。枳椇子总黄酮主要成分有山奈酚、洋芹素、杨梅素、槲皮素、双氢杨梅素等,可有效减轻酒精引起的炎症反应,抗纤维化的形成,对酒精性肝损伤有良好的防治作用。
本发明还提供了一种上述防醉解酒保肝组合物的制备方法,包括以下步骤:
A)将果胶和葛根提取物溶于去离子水中,得到混合水溶液;
B)将姜黄素、柑橘黄酮、枳椇子总黄酮分散到海藻酸钠溶液中后制备海藻酸钙凝胶微球;
C)将混合水溶液与海藻酸钙凝胶微球混合,得到防醉解酒保肝组合物。
本发明将果胶和葛根提取物溶于去离子水中,得到混合水溶液。具体的,将果胶和葛根提取物溶于去离子水中,微滤去除不溶性杂质。
本发明将姜黄素、柑橘黄酮、枳椇子总黄酮分散到海藻酸钠溶液中后制备海藻酸钙凝胶微球。其中,所述制备海藻酸钙凝胶微球的具体方法为:
姜黄素、柑橘黄酮、枳椇子总黄酮分散到海藻酸钠溶液中,然后将混合液滴入氯化钙溶液中形成海藻酸钙凝胶微球。
所述海藻酸钠溶液的浓度为0.5wt%~2wt%,优选为1.0wt%~1.5wt%;所述氯化钙溶液的浓度为0.5wt%~5wt%,优选为1.0wt%~4wt%。
本发明还提供了一种上述防醉解酒保肝组合物在制备防醉解酒保肝的药物或保健食品中的应用。
本发明提供的技术方案具有如下的技术优点:
(1)本发明提供的技术方案开发了一种新的防醉解酒保肝配方,果胶可以延缓乙醇吸收入血速度起到防醉的作用;葛根提取物和姜黄素具有加速乙醇分解的作用,可以起到解酒保肝的效果;柑橘黄酮具有抗氧化的作用,可以清除乙醇代谢生成的自由基,保护肝脏免受自由基的损伤,枳椇子总黄酮可有效减轻酒精引起的炎症反应,抗纤维化的形成,对酒精性肝损伤有良好的防治作用,柑橘黄酮和枳椇子总黄酮具有保肝护肝作用。
(2)本发明提供的技术方案中各组分配伍具有多重防醉解酒及保肝护肝作用,能产生良好的解酒防醉保肝效果。
(3)本发明提供的技术方案中生产工艺流程操作简单,易于工艺放大和工业化生产。
为了进一步理解本发明,下面结合实施例对本发明提供的防醉解酒保肝组合物及制备方法以及应用进行说明,本发明的保护范围不受以下实施例的限制。
实施例1
1、本实施例提供的一种解酒防醉保肝新配方,包含如下几种组分:
(1)柑橘果胶含量3%(w/w),分子量为240kD,酯化度为20%;
(2)葛根提取物1.0%(w/w);
(3)姜黄素0.5%(w/w);
(4)柑橘黄酮0.4%(w/w);
(5)枳椇子总黄酮0.35%(w/w);
余量为水。
2、制备方法:
(1)果胶和葛根提取物溶于去离子水中,微滤去除不溶性杂质;
(2)姜黄素、柑橘黄酮、枳椇子总黄酮分散到质量浓度为1.5wt%的海藻酸钠溶液中,然后将混合液滴入质量浓度为1.1wt%的氯化钙溶液中形成海藻酸钙凝胶微球;
(3)将海藻酸钙凝胶微球清洗干净后加入到果胶、葛根提取物溶液中,得到最终产品。
对比例1
1、本对比例提供的一种解酒防醉保肝新配方,包含如下几种组分:
(1)葛根提取物1.0%(w/w);
(2)姜黄素0.5%(w/w);
(3)柑橘黄酮0.4%(w/w);
(4)枳椇子总黄酮0.35%(w/w);
余量为水。
2、制备方法同实施例1,仅是步骤(1)中不加入果胶。
对比例2
本对比例提供的一种解酒保肝防醉新配方,包含柑橘果胶含量3%(w/w),分子量为240kD,酯化度为20%;余量为水。
对比例3
本对比例提供的一种解酒防醉保肝新配方,包含葛根提取物1.0%(w/w);余量为水。
对比例4
本对比例提供的一种解酒保肝防醉新配方,包含姜黄素0.5%(w/w)。
具体制备方法如下:姜黄素分散到质量浓度为1.5wt%的海藻酸钠溶液中,然后将混合液滴入质量浓度为1.1wt%的氯化钙溶液中形成海藻酸钙凝胶微球。
对比例5
本对比例提供的一种解酒防醉保肝新配方,包含柑橘黄酮0.4%(w/w)。
具体制备方法如下:柑橘黄酮分散到质量浓度为1.5wt%的海藻酸钠溶液中,然后将混合液滴入质量浓度为1.1wt%的氯化钙溶液中形成海藻酸钙凝胶微球。
对比例6
本对比例提供的一种解酒防醉保肝新配方,包含枳椇子总黄酮0.35%(w/w)。
具体制备方法如下:枳椇子总黄酮分散到质量浓度为1.5wt%的海藻酸钠溶液中,然后将混合液滴入质量浓度为1.1wt%的氯化钙溶液中形成海藻酸钙凝胶微球。
实施例2解酒保肝产品动物实验:
1、实验方法:
(1)实验动物及分组
C57BL/6小鼠100只,雄性,体重15~30g,适应性饲养7天,随机分为空白组(10只)、模型组(10只)、海王金樽组(市场上销售的解酒药、10只)、实施例1组合配方组(10只)、对比例1无果胶组合配方组(10只),对比例2果胶组(10只)、对比例3葛根提取物组(10只)、对比例4姜黄素组:(10只)、对比例5柑橘黄酮组(10只)、对比例6枳椇子总黄酮组(10只)。
(2)造模及给药
1)造模方式:除空白组外全部组,共90只,实验前禁食12h,用38°富裕老窖以0.15mL/10g体重灌服。
2)给药时间:造模后30min,全部醉倒,灌胃给药1次。
3)给药剂量:模型组:0.25mL/10g生理盐水;海王金樽组:阳性对照600mg/kg;组合配方组:600mg/kg;无果胶配方组:600mg/kg;果胶组:600mg/kg;葛根提取物组:600mg/kg;姜黄素组:600mg/kg;柑橘黄酮组:600mg/kg;枳椇子总黄酮组:600mg/kg。
上述的给药剂量均为产品的使用量。
(3)观察
1)观察并记录小鼠的活动情况:造模给药后观察。
具体指标:醉酒指标:以小鼠爬行不稳、后腹拖地、毛松散、闭眼不懂;醒酒指标:以活动自如、灵活、精神、毛顺滑。
2)观察小鼠醒酒时间和醒酒率:90min、120min、180min和240min。醒酒时间测定方法如下:给酒后测定小鼠醉倒时间,然后测定小鼠恢复意识的时间,醒酒时间=恢复意识的时间-醉倒时间,然后取10只小鼠醒酒时间平均值。
3)观察并记录24h内小鼠的死亡只数。
4)24h后采血测血液中乙醇浓度。
5)24h后取小鼠肝脏测测丙二醛含量。(丙二醛含量代表肝脏内的脂质氧化物浓度,也代表肝脏受损伤程度,含量越高肝脏受损伤程度越大)
试验方法:
①用预冷的PBS(0.01M,pH=7.4)冲洗肝脏组织,取出残留液;
②将剪碎的组织与对应体积的PBS(组织样本:PBS=1:9),具体体积可根据实验需要调整,记录称重的组织;
③加入玻璃匀浆器中,于冰上充分研磨;
④最后将匀浆液于5000g离心5-10min,取上清检测浓度备用。
⑤丙二醛检测试剂盒ELISA法测丙二醛浓度。
2、实验结果见表1
表1
由表1可知,组合配方具有较好的解酒防醉保肝效果,并且解酒防醉保肝效果高于单一组分,并且解酒防醉保肝效果也高于作为对照的市场上销售的解酒药海王金樽。
实施例3
1、本发明提供的一种解酒防醉保肝新配方,包含如下几种组分:
(1)柑橘果胶3%(w/w),分子量为110kD,酯化度为30%;
(2)葛根提取物1.0%(w/w);
(3)姜黄素0.3%(w/w);
(4)柑橘黄酮0.4%;
(5)枳椇子总黄酮0.35%。
2、制备方法同实施例1
对比例7
1、本对比例提供的一种解酒防醉保肝新配方,包含如下几种组分:
(1)葛根提取物1.0%(w/w);
(2)姜黄素0.3%(w/w);
(3)柑橘黄酮0.4%(w/w);
(4)枳椇子总黄酮0.35%(w/w);
余量为水。
2、制备方法同实施例1,仅是步骤(1)中不加入果胶。
对比例8
本对比例提供的一种解酒防醉保肝新配方,包含柑橘果胶3%(w/w),分子量为110kD,酯化度为30%;余量为水。
实施例4
1、实验方法同实施例2
每组小鼠10只。
2、动物实验结果见表2
表2:
由表2可知,组合配方具有较好的解酒防醉效果,并且由于所用的果胶分子量低于150kD,所以解酒防醉效果较实施例1差,由于组合配方含有柑橘黄酮和枳椇子总黄酮,因此保肝效果与实施例1相比没有差别。
实施例5
1、本发明提供的一种解酒防醉保肝新配方,包含如下几种组分:
(1)柑橘果胶3%(w/w),分子量为7kD,酯化度为10%;
(2)葛根提取物1.0%;
(3)姜黄素0.3%(w/w);
(4)柑橘黄酮0.4%(w/w);
(5)枳椇子总黄酮0.35%(w/w);
余量为水。
2、制备方法同实施例1。
对比例9
1、本对比例提供的一种解酒防醉保肝新配方,包含:
(1)葛根提取物1.0%;
(2)姜黄素0.3%(w/w);
(3)柑橘黄酮0.4%(w/w);
(4)枳椇子总黄酮0.35%(w/w);
余量为水。
2、制备方法同实施例1,仅是步骤(1)中不加入果胶
对比例10
本对比例提供的一种解酒防醉保肝新配方,包含:柑橘果胶3%(w/w),分子量为7kD,酯化度为10%;余量为水。
实施例6
1、实验方法同实施例2
每组小鼠10只。
2、动物实验结果见表3
表3
由表3可知,组合配方解酒防醉保肝效果与市场上销售的解酒药海王金樽相比没有显著差异,主要原因是所用的果胶分子量只有7kD,没有解酒防醉效果,所以组合配方解酒防醉效果较差,由于组合配方含有柑橘黄酮和枳椇子总黄酮,因此保肝效果与实施例1相比没有差别。
实施例7
1、本发明提供的一种解酒防醉保肝新配方,包含如下几种组分:
(1)柑橘果胶含量3%(w/w),分子量为240kD,酯化度为20%;
(2)葛根提取物1.4%(w/w);
(3)姜黄素0.6%(w/w);
(4)柑橘黄酮0.5%(w/w);
(5)枳椇子总黄酮0.5%(w/w);
余量为水。
2、制备方法同实施例1
对比例11
1、本对比例提供的一种解酒防醉保肝新配方,包含:
(1)葛根提取物1.4%(w/w);
(2)姜黄素0.6%(w/w);
(3)柑橘黄酮0.5%(w/w);
(4)枳椇子总黄酮0.5%(w/w);
余量为水。
2、制备方法同实施例1,仅是步骤(1)中不加入果胶
对比例12
本对比例提供的一种解酒防醉保肝新配方,包含:柑橘果胶含量3%(w/w),分子量为240kD,酯化度为20%,余量为水。
实施例8
1、实验方法同实施例2
每组小鼠10只。
2、动物实验结果见表4
表4
由表4可知,解酒防醉保肝产品动物实验显示喂食组合配方醒酒时间较模型组(未给药)降低46.9%;90min醒酒率较模型组提高20%,120min醒酒率提高40%,180min醒酒率提高60%,240min醒酒率提高40%;24h后血液中乙醇浓度低于模型组53.4%,肝脏内丙二醇含量也显著下降。
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (6)
1.一种防醉解酒保肝组合物,其特征在于,包括:
2wt%~8wt%的果胶;
0.5wt%~2wt%的葛根提取物;
0.3wt%~0.9wt%的姜黄素;
0.1wt%~1wt%的柑橘黄酮;
0.1wt%~1wt%的枳椇子总黄酮;
余量为水。
2.根据权利要求1所述的组合物,其特征在于,所述果胶选自柑橘果胶或苹果果胶,所述果胶的分子量为150~350kD,酯化度10%~50%。
3.一种如权利要求1或2所述的防醉解酒保肝组合物的制备方法,其特征在于,包括以下步骤:
A)将果胶和葛根提取物溶于去离子水中,得到混合水溶液;
B)将姜黄素、柑橘黄酮、枳椇子总黄酮分散到海藻酸钠溶液中后制备海藻酸钙凝胶微球;
C)将混合水溶液与海藻酸钙凝胶微球混合,得到防醉解酒保肝组合物。
4.根据权利要求3所述的制备方法,其特征在于,所述制备海藻酸钙凝胶微球的方法为:
姜黄素、柑橘黄酮、枳椇子总黄酮分散到海藻酸钠溶液中,然后将混合液滴入氯化钙溶液中形成海藻酸钙凝胶微球。
5.根据权利要求4所述的制备方法,其特征在于,所述海藻酸钠溶液的浓度为0.5wt%~2wt%,所述氯化钙溶液的浓度为0.5wt%~5wt%。
6.一种如权利要求1或2所述的防醉解酒保肝组合物在制备防醉解酒保肝的药物或保健食品中的应用。
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