WO2022021779A1 - 用于高脂血和脂肪肝的药膳食疗产品组合物及其制备方法 - Google Patents
用于高脂血和脂肪肝的药膳食疗产品组合物及其制备方法 Download PDFInfo
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Definitions
- the invention belongs to the technical field of health care products, and in particular relates to a medicated dietary therapy product composition for hyperlipidemia and fatty liver and a preparation method thereof.
- Fatty liver is a disease caused by excessive accumulation of fat in liver cells due to various reasons.
- Survey data show that the incidence of fatty liver in adults in my country is 20%-30%, which has replaced chronic hepatitis B as the most common chronic liver disease in my country.
- Fatty liver and hyperlipidemia are twin brothers. According to sampling survey data in recent years, the prevalence of hyperlipidemia in the healthy population is as high as 46.8%.
- Modern medicine still lacks an ideal treatment method for fatty liver and hyperlipidemia.
- the main chemical drugs are statins, fibrates, and cholesterol absorption inhibitors. Single drugs often have limited efficacy, and there are different degrees of liver and kidney toxicity, muscle Side effects like soreness and even rhabdomyolysis.
- the technical problem to be solved by the present invention is to overcome the defects of the prior art, and to provide a medicated dietary therapy product composition for hyperlipidemia and fatty liver and a preparation method thereof.
- the invention provides a medicated dietary therapy product composition for hyperlipidemia and fatty liver, which is prepared from the following raw materials by weight:
- a kind of preparation method of medicated dietary therapy product composition for hyperlipidemia and fatty liver it comprises the steps:
- the raw materials were weighed according to the weight parts of the above-mentioned medicated dietary therapeutic product composition for hyperlipidemia and fatty liver, and the sea buckthorn leaves, moringa leaves, chicory, amla, purslane, cassia seeds, pueraria lobata, perilla seeds, firewood Hemp seed, kelp and lotus leaf are mixed, add 8 to 15 times the mass of water to soak for 15 to 60 minutes, heat and reflux for extraction for 0.5 to 2 hours, and filter with 80 to 200 meshes to obtain the first extract;
- the first extraction solution and the second extraction solution are mixed, concentrated, and added with chitosan oligosaccharide and xylo-oligosaccharide to obtain the medicinal and dietary therapeutic product composition for hyperlipidemia and fatty liver.
- the medicated dietary therapy product composition for hyperlipidemia and fatty liver of the present invention can remove turbidity and dampness, reduce lipid and protect liver, and prevent and treat hyperlipidemia and fatty liver. It has significant hypolipidemic activity, reducing total cholesterol, triglycerides and low density lipoprotein; anti-inflammatory, antioxidant, liver protection; increasing total lipase activity, accelerating fat degradation; improving insulin resistance, reducing lipogenesis; improving intestinal Micro-ecology, reduce fat absorption. Network pharmacology analysis found that many components in this product can effectively prevent and treat hyperlipidemia and relieve related symptoms caused by it. It is a precise medicated dietary product with clear main components and clear targets. Further, the preparation method of the medicated dietary therapy product composition for hyperlipidemia and fatty liver is prepared by a specific process, with good effect and low cost, and meets the needs of industrialized production.
- FIG. 1 is a network diagram of a traditional Chinese medicine raw material-active ingredient-action target association network of a medicinal-dietary-therapeutic product composition for hyperlipidemia and fatty liver provided by an embodiment of the present invention.
- the embodiment of the present invention provides a medicated dietary therapy product composition for hyperlipidemia and fatty liver, which is prepared from the following raw materials by weight:
- emodin methyl ether, chrysophanol, leucanthin, chicory lactone A, chicoryside C, etc. in the above-mentioned raw materials have obvious anti-inflammatory activity.
- Chicory reduces the levels of TC, TG, LDL, AST, ALT in serum, inhibits the expression of IL-6, TNF- ⁇ , FFA, IKK ⁇ , NF- ⁇ B p65, improves hepatocyte swelling and necrosis in diabetic-fatty liver rats, and inhibits liver Fat accumulation in cells.
- Lactucin reduces adipogenesis-related gene expression by inhibiting JAK2/STAT3 phosphorylation, reduces obesity, and protects the liver.
- the flavonoids in chicory have antioxidant, anti-inflammatory, and liver-protective properties.
- Anthraquinones in cassia seeds can inhibit fat peroxidation in rats with fatty liver, reduce serum TC, TG, LDL, AST, ALT levels, protect liver, and improve glucose and lipid metabolism.
- emodin reduces serum TC, TG, LDL, AST, ALT levels, down-regulates CYP2E1, increases the expression of genes such as PPAR ⁇ , and improves alcoholic liver injury and hyperlipidemia.
- Chrysophanol reduces blood sugar levels, reduces blood TC, TG and increases HDL-C levels, inhibits obesity, reduces IL1 ⁇ , IL6, increases IL10, and inhibits inflammation, which are related to activating the AMPK/SIRT1 pathway.
- Chrysophanol and Emodin reduce gamma-glutamyl Transpeptidase (GGT) activity, increased GSH level, increased CYP2E1 expression, inhibited alcoholic liver injury, and had a certain preventive effect on fatty liver and hyperlipidemia.
- GTT gamma-glutamyl Transpeptidase
- Cassiaside B2 inhibits protein tyrosine phosphatase 1B (PTP1B), improves insulin resistance and lowers blood sugar; it can also reduce dietary intake by inhibiting 5-HT2C and exert an anti-obesity effect.
- Laminaria can enhance LCAT, PL, LPL activities, reduce serum TC, TG, LDL levels, reduce body weight and improve hyperlipidemia.
- Fucoidan reduced the levels of FBG, TC, TG, AST, ALT, and MDA in the liver tissue of diabetic mice and increased the levels of SOD, CAT, and insulin in the serum, and improved the liver damage caused by diabetes.
- Emblica has good anti-hyperlipidemia, anti-arteriosclerosis, anti-diabetic effects, and kaempferol and luteolin can inhibit the activity of DPP4 to exert anti-diabetic effects.
- Gallic acid reduces lipid peroxidation, reduces AST and ALT levels, inhibits TNF ⁇ and IL8, and exerts hepatoprotective effects through antioxidants.
- EGCG not only significantly reduced body weight, mesenteric fat mass, fasting blood glucose, insulin resistance, serum cholesterol and the severity of fatty liver; EGCG increased cholesterol 7 ⁇ -hydroxylase, HMG-CoA reductase, LDL levels, and decreased intestinal bile acid content It can also exert antioxidant and anti-inflammatory effects through TGF/SMAD, PI3 K/Akt/FoxO1, NF ⁇ B and other signaling pathways, thereby reducing fatty liver.
- Myricetin reduces blood sugar, serum cholesterol, triglyceride levels, and lowers blood pressure; it also has anti-arrhythmic and myocardial ischemia protection effects, it can slow down isoproterenol-induced cardiac rhythm acceleration, reduce serum LDH, CK, AST, ALT levels, Elevated SOD and CAT levels.
- Nuciferine reduces dietary intake and body weight, reduces serum levels of TC, TG, LDL-C, and FFA, inhibits the release of inflammatory factors such as TNF ⁇ and IL6, increases antioxidant enzymes such as SOD, CAT, and GPx, improves insulin resistance, and regulates adipogenesis. Gene expression, ultimately ameliorating high-fat-induced liver damage degeneration and metabolic syndrome.
- Perilla seeds contain unsaturated fatty acids such as linoleic acid and ⁇ -linolenic acid. Linoleic acid and ⁇ -linolenic acid can reduce the levels of TC and TG in plasma, increase serum adiponectin, improve insulin resistance, reduce liver enlargement, and inhibit TNF ⁇ . Express. Puerarin protects the liver through antioxidant effects, inhibits lipid peroxidation, reduces serum TC, TG, LDL-C, and increases HDL-C. Its blood lipid-lowering effect is related to the regulation of CYP7A1, HMG-CoA-R, and LDLR.
- Daidzein increases the expression of GLUT4 and IRS-1 by promoting adipocyte differentiation and activating PPAR ⁇ , thereby increasing glucose uptake in insulin-stimulated adipocytes and exerting an anti-glycemic effect.
- Purslane is rich in omega-3 fatty acids, kaempferol, luteolin, quercetin, apigenin and other components, which can significantly improve dexamethasone-induced hyperlipidemia, including reducing serum total TC, TG, fatty acids, LDL-C, increase HDL-C, inhibit liver damage.
- Apigenin-induced AMPK activation reduces the expression of PPAR ⁇ , SCD-1 and other adipogenesis-related genes, thereby inhibiting adipogenesis.
- Apigenin not only reduces serum TC, TG, LDL-C, increases HDL-C, and regulates cholesterol metabolism, thereby exerting anti-hyperlipidemia effects; it can also inhibit H2O2-induced vascular endothelial cell damage and protect blood vessels.
- Chitosan reduces high-fat diet-induced rat body weight, liver and heart index, fat/body weight ratio, maintains liver and serum SOD, ALT, AST activities, reduces serum TC, TG, LDL-C levels, and increases PPAR ⁇ and hepatic lipase (HL) expression, thereby improving the metabolism of liver lipids, protecting the liver from oxidative damage, and can be used for the treatment of hyperlipidemia.
- the network pharmacology study (Fig.
- the medicated dietary therapy product composition for hyperlipidemia and fatty liver is prepared from the following raw materials by weight: 8-10 parts of sea buckthorn leaves, 5-7 parts of moringa leaves, 8-10 parts of chicory, 8 ⁇ 10 parts of Empress, 5-7 parts of Purslane, 8-10 parts of Cassia, 8-10 parts of Pueraria, 8-10 parts of Perilla, 8-10 parts of Hemp Seed, 5-7 parts of Kombu, 5 ⁇ 7 copies of lotus leaf, 0.4 ⁇ 0.6 copies of chitosan oligosaccharides, 0.8 ⁇ 1.2 copies of xylo-oligosaccharides.
- the medicated dietary therapy product composition for hyperlipidemia and fatty liver is prepared from the following raw materials by weight: 9 parts of sea buckthorn leaves, 6 parts of moringa leaves, 9 parts of chicory, 9 parts of amla japonica, 6 parts of purslane, 9 parts of cassia seeds, 9 parts of pueraria, 9 parts of perilla seeds, 6 parts of hemp seed, 6 parts of kelp, 6 parts of lotus leaf, 0.5 parts of chitosan oligosaccharide, and 1 part of xylo-oligosaccharide.
- the prescription all adopts food-grade raw materials, is safe and effective, has low production cost and reliable preventive effect.
- Lactucin reduces adipogenesis-related gene expression by inhibiting JAK2/STAT3 phosphorylation, reduces obesity, and protects the liver.
- Luteolin has antioxidant, anti-inflammatory properties and can protect the liver.
- Cassia Cassiaside B2 (Cassiaside B2) Emodin-3-methyl ether ether) Chrysophanol Emodin (Emodin) Rhein 1
- the anthraquinone compounds in cassia seeds can inhibit the fat peroxidation in rats with fatty liver, reduce the levels of serum TC, TG, LDL, AST and ALT, and protect the liver.
- Cisaside B2 inhibits protein tyrosine phosphatase 1B (PTP1B), improves insulin resistance and lowers blood sugar; it can also reduce dietary intake by inhibiting 5-HT2C and exert an anti-obesity effect.
- Chrysophanol and Emodin inhibit alcoholic liver injury by reducing GGT activity, increasing GSH, and increasing CYP2E1 expression, and have a certain preventive effect on fatty liver and hyperlipidemia.
- Emodin reduces serum TC, TG, LDL, AST, and ALT levels, down-regulates CYP2E1, increases the expression of genes such as PPAR ⁇ , and improves alcoholic liver injury and hyperlipidemia.
- Kumbu polysaccharide Fucoidan 1 Laminaria can enhance LCAT, PL and LPL activities, reduce serum TC, TG, LDL levels, reduce body weight and improve hyperlipidemia.
- Fucoidan reduced the levels of FBG, TC, TG, AST, ALT, and MDA in the liver tissue of diabetic mice and increased the levels of SOD, CAT, and insulin in the serum, and improved the liver damage caused by diabetes.
- Gallic acid reduces lipid peroxidation, reduces AST and ALT levels, inhibits TNF ⁇ and IL8, and exerts hepatoprotective effects through antioxidants.
- EGCG can not only significantly reduce body weight, mesenteric fat mass, fasting blood glucose, insulin resistance, serum cholesterol and the severity of fatty liver; it can also exert antioxidant and anti-inflammatory effects through TGF/SMAD, PI3 K/Akt/FoxO1, NF ⁇ B and other signaling pathways , thereby reducing fatty liver.
- Kaempferol and luteolin can inhibit DPP4 activity to exert antidiabetic effect.
- Nuciferine reduces dietary intake and body weight, lowers serum levels of TC, TG, LDL-C, and FFA, inhibits the release of inflammatory factors such as TNF ⁇ and IL6, increases antioxidant enzymes such as SOD, CAT, and GPx, improves insulin resistance, and regulates adipogenesis. Gene expression, ultimately ameliorating high-fat-induced liver damage degeneration and metabolic syndrome.
- Alpha-linolenic acid Luteolin 1 Linoleic acid and ⁇ -linolenic acid can reduce the levels of TC and TG in plasma, increase serum adiponectin, improve insulin resistance, reduce liver enlargement, and inhibit the expression of TNF ⁇ .
- Pueraria Puerarin Daidzin Daidzein Formononetin 1, Puerarin protects the liver through antioxidant effects, inhibits lipid peroxidation, reduces serum TC, TG, LDL-C, increases HDL-C, regulates CYP7A1, HMG-CoA-R, LDLR, thereby reducing blood lipids.
- Daidzein increases GLUT4 and IRS-1 expression by activating PPAR ⁇ , thereby increasing glucose uptake in insulin-stimulated adipocytes and exerting anti-diabetic effects.
- purslane Kaempferol Luteolin Quercetin Apigenin 1, Kaempferol, luteolin, quercetin, apigenin and other components can significantly improve dexamethasone-induced hyperlipidemia, including reducing serum total TC, TG, fatty acid, LDL-C, increasing HDL-C, inhibiting Liver damage.
- Apigenin not only reduces serum TC, TG, LDL-C, but also increases HDL-C and regulates cholesterol metabolism, thereby exerting anti-hyperlipidemia effect.
- Chitosan Chitosan reduces high-fat diet-induced rat body weight, liver and cardiac indices, maintains liver and serum SOD, ALT, AST activities, reduces serum TC, TG, LDL-C levels, and increases PPAR ⁇ and hepatic lipase (HL) expression , thereby improving the metabolism of liver lipids and protecting the liver from oxidative damage.
- HL hepatic lipase
- the embodiment of the present invention also provides the above-mentioned preparation method of the medicated dietary therapy product composition for hyperlipidemia and fatty liver, which comprises the following steps:
- the raw materials were weighed according to the weight portion of the above-mentioned medicated dietary therapy product composition for hyperlipidemia and fatty liver, and the sea buckthorn leaves, moringa leaves, chicory, amla, purslane, cassia seeds, pueraria lobata, perilla seeds, firewood Hemp seed, kelp and lotus leaf are mixed, add 8 to 15 times the mass of water to soak for 15 to 60 minutes, heat and reflux for extraction for 0.5 to 2 hours, and filter with 80 to 200 meshes to obtain the first extract;
- the first extraction solution and the second extraction solution are mixed, concentrated, and added with chitosan oligosaccharide and xylo-oligosaccharide to obtain the medicinal and dietary therapeutic product composition for hyperlipidemia and fatty liver.
- the raw materials are weighed according to the weight portion of the above-mentioned medicated dietary therapy product composition for hyperlipidemia and fatty liver, cassia seeds and hemp seeds are broken, packaged with gauze bags, and then mixed with sea buckthorn leaves, moringa leaves, chicory, Mix Emblica, purslane, pueraria, perilla, kelp, and lotus leaf, add 8 to 15 times the mass of water to soak for 20 to 40 minutes, heat and reflux for 0.5 to 2 hours, and filter with 100 to 200 meshes to obtain the first extract;
- the filtrate is concentrated under reduced pressure to a density of about 1.08 to obtain a concentrated solution for later use; the concentrated solution is added with maltodextrin, stirred evenly, and spray-dried (nozzle).
- the air inlet temperature is set to 150 degrees, and the air outlet temperature is 80 degrees), and the extract powder is obtained, which is ready for use.
- chitosan oligosaccharide and xylo-oligosaccharide with the above spray-dried powder, granulate, dry, divide into 10 g/bags, and prepare granules.
- the final form of the product can be various, including powder, granule, tablet, honey pill, cream, oral liquid, syrup, etc.
- the drying method can be spray drying, vacuum drying, freeze drying, etc.; the granulation method can be dry granulation, wet granulation, one-step granulation and the like.
- the above-mentioned medicinal and dietary therapeutic product compositions for hyperlipidemia and fatty liver can be extracted, concentrated, dried or pulverized by methods acceptable to relevant laws and regulations on pharmacy, food, health care products, etc., and further processed into products.
- Active ingredients can be made into suitable administration forms (including granules, powders, oral liquids, tablets, etc.) or food forms such as tablet candies, meal powders, solid beverages, etc., to meet the market demand for related products. belong to the protection scope of the present invention.
Abstract
一种用于高脂血和脂肪肝的药膳食疗产品组合物,由以下重量份的原料制备而成:沙棘叶1~15份,辣木叶1~20份,菊苣1~15份,余甘子1~20份,马齿苋1~20份,决明子1~20份,野葛根1~15份,紫苏子1~15份,火麻仁1~20份,昆布1~16份,荷叶1~15份,壳寡糖0.1~3份,低聚木糖0.5~5份。以及,提供上述用于高脂血和脂肪肝的药膳食疗产品组合物的制备方法。所述用于高脂血和脂肪肝的药膳食疗产品组合物疗效明确、作用靶点和药理效应清晰、原料来源广、成本低、制备方法简单,患者依从性高等特点,可以有效防治高血脂和缓解其引起的相关症状。
Description
本发明属于保健品技术领域,具体涉及一种用于高脂血和脂肪肝的药膳食疗产品组合物及其制备方法。
脂肪肝(fatty liver)是指由于各种原因引起的肝细胞内脂肪堆积过多的病变。调查数据显示我国成年人脂肪肝的发病率在20%-30%,已取代慢性乙型肝炎成为我国最常见慢性肝病。脂肪肝与高脂血症是一对孪生兄弟。据近年抽样调查数据,高脂血症在健康体检人群中的患病率更是高达46.8%。
现代医学对脂肪肝和高脂血症现在尚缺乏理想的治疗方法,主要的化学药物有他汀类、贝特类、胆固醇吸收抑制类,单一药物常常疗效有限,而且存在不同程度肝肾毒性、肌肉酸痛、甚至横纹肌溶解等副作用。
中医药被认为对高血脂、脂肪肝的疗效明确,而且安全低毒。中成药主要有:丹田降脂丸、血脂康胶囊、香丹清脂颗粒,降脂灵片等等,但是这些都属于药物类产品,这些药品需要在临床医生或者药师的指导下用药,不宜用于预防,不属于食同源类健康产品,且目前相关产品的成分不清楚、作用靶点不清楚。现代药理研究显示有大量药食同源的中药也具有良好降脂作用。为了充分发挥传统中医药的防治优势,开发系列早期预防、中期治疗、后期康复的安全有效的、质量可靠、有效成分清晰、作用靶点清楚的精准药膳,具有非常重要的意义和较大市场需求。
发明内容
本发明所要解决的技术问题在于克服现有技术之缺陷,提供一种用于高脂血和脂肪肝的药膳食疗产品组合物及其制备方法。
本发明提供一种用于高脂血和脂肪肝的药膳食疗产品组合物,由以下重量份的原料制备而成:
沙棘叶1~15份,
辣木叶1~20份,
菊苣1~15份,
余甘子1~20份,
马齿苋1~20份,
决明子1~20份,
野葛根1~15份,
紫苏子1~15份,
火麻仁1~20份,
昆布1~16份,
荷叶1~15份,
壳寡糖0.1~3份,
低聚木糖0.5~5份。
以及,一种用于高脂血和脂肪肝的药膳食疗产品组合物的制备方法,其包括如下步骤:
按照上述用于高脂血和脂肪肝的药膳食疗产品组合物的重量份称取原料,将沙棘叶,辣木叶,菊苣,余甘子,马齿苋,决明子,野葛根,紫苏子,火麻仁,昆布和荷叶混合,加8~15倍质量份的水浸泡15~60分钟,加热回流提取0.5~2小时,80~200目过滤,得第一提取液;
向药渣中加8~15倍质量份的水回流提取0.5~2小时,80~200目过滤,得第二提取液;
将第一提取液和第二提取液混合,浓缩,加入壳寡糖和低聚木糖,获得所述用于高脂血和脂肪肝的药膳食疗产品组合物。
本发明的用于高脂血和脂肪肝的药膳食疗产品组合物,蠲浊化湿、降脂护肝,防治高脂血症和脂肪肝。其具有显著的降血脂活性,降低总胆固醇、甘油三酯和低密度脂蛋白;抗炎、抗氧化、保护肝脏;提高总脂酶活性,加速脂肪降解;改善胰岛素抵抗,减少脂肪生成;改善肠道微生态,减少脂肪吸收。网络药理分析发现本品中很多成分可以有效的防治高血脂和缓解其引起的相关症状,是一款主成分清晰,靶点明确的精准药膳产品。进一步,所述用于高脂血和脂肪肝的药膳食疗产品组合物的制备方法采用特定的工艺制备,效果好,成本低,符合产业化生产需要。
图1是本发明实施例提供的用于高脂血和脂肪肝的药膳食疗产品组合物的中药原料-活性成分-作用靶点关联网络图。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白,以下结合附图及实施例,对本发明进行进一步详细说明。应当理解,此处所描述的具体实施例仅仅用以解释本发明,并不用于限定本发明。
本发明实施例提供一种用于高脂血和脂肪肝的药膳食疗产品组合物,由以下重量份的原料制备而成:
沙棘叶1~15份,
辣木叶1~20份,
菊苣1~15份,
余甘子1~20份,
马齿苋1~20份,
决明子1~20份,
野葛根1~15份,
紫苏子1~15份,
火麻仁1~20份,
昆布1~16份,
荷叶1~15份,
壳寡糖0.1~3份,
低聚木糖0.5~5份。
其中,上述原料中的大黄素甲醚、大黄酚、山莴苣苦素、菊苣内酯 A 、苦苣菜苷 C等具有明显的抗炎活性。菊苣减少血清中TC、TG、LDL、AST、ALT水平,抑制IL-6、TNF-α、FFA、IKKβ、NF-κB p65表达,改善糖尿病-脂肪肝大鼠的肝细胞肿胀、坏死,抑制肝细胞中脂肪聚集。Lactucin通过抑制JAK2/STAT3磷酸化减少脂肪生成相关的基因表达,减少肥胖,保护肝脏。菊苣中的黄酮类化合物,比如Kaempferol、Luteolin具有抗氧化、抗炎作用,能保护肝脏。决明子中的蒽醌类化合物能抑制脂肪肝大鼠的脂肪过氧化,降低血清TC、TG、LDL、AST、ALT水平,保护肝脏,也能改善糖脂代谢。其中大黄素emodin减少血清TC、TG、LDL、AST、ALT水平,下调CYP2E1,增加PPARγ等基因表达,改善酒精性肝损伤和高脂血症。Chrysophanol降低血糖水平,减少血中TC、TG并增加HDL-C水平,抑制肥胖,同时减少IL1β、IL6,增加IL10,抑制炎症,这些作用于激活AMPK/SIRT1通路有关。Chrysophanol和Emodin通过降低gamma-glutamyl
transpeptidase (GGT)活性,升高GSH水平,增加CYP2E1表达抑制酒精性肝损伤,对脂肪肝和高脂血症有一定预防作用。Cassiaside B2抑制蛋白酪氨酸磷酸酶1B(PTP1B),改善胰岛素抵抗,降低血糖;也能通过抑制5-HT2C减少饮食摄入,发挥抗肥胖作用。昆布多糖能增强LCAT、PL、LPL活性,降低血清TC、TG、LDL水平,减轻体重并改善高脂血症。Fucoidan减少糖尿病小鼠肝组织中FBG、TC、TG、AST、ALT、MDA水平以及增加血清中SOD、CAT、胰岛素水平,改善糖尿病引起的肝损伤。余甘子具有很好的抗高脂血症、抗动脉硬化、抗糖尿作用,其中的山奈酚和木犀草素可抑制DPP4活性发挥抗糖尿病作用。没食子酸减少脂质过氧化,降低AST、ALT水平,抑制TNFα和IL8,通过抗氧化发挥肝保护作用。EGCG不仅能明显降低体重,肠系膜脂肪量,空腹血糖,胰岛素抵抗,血清胆固醇和脂肪肝的严重程度;EGCG 增加胆固醇7α-羟化酶,HMG-CoA还原酶,LDL水平,降低肠道胆汁酸含量;还能通过TGF/SMAD, PI3 K/Akt/FoxO1,NFκB等信号通路发挥抗氧化抗炎作用,从而减轻脂肪肝。Myricetin减少血糖、血清胆固醇、甘油三酯水平,降低血压;也有抗心律失常、保护心肌缺血作用,它能减慢异丙肾上腺素诱导的心律加快、减少血清LDH、CK、AST、ALT水平、升高SOD、CAT水平。Nuciferine减少饮食摄入、体重,降低血清TC、TG、LDL-C、FFA 水平,抑制TNFα、IL6等炎症因子释放,增加SOD、CAT、GPx等抗氧化酶,改善胰岛素抵抗,调节脂肪生成的相关基因表达,最终改善高脂诱导的肝脏损伤变性和代谢综合征。紫苏子中含有亚油酸、α-亚麻酸等不饱和脂肪酸,亚油酸、α-亚麻酸能降低血浆中TC、TG水平,增加血清脂联素,改善胰岛素抵抗,减轻肝脏肿大,抑制TNFα表达。葛根素通过抗氧化作用保护肝脏,抑制脂质过氧化,减少血清中TC、TG、LDL-C,增加HDL-C,其降血脂作用与调节CYP7A1、HMG-CoA-R、LDLR有关。大豆苷元通过促进脂肪细胞分化,激活PPARγ来增加GLUT4和IRS-1表达,从而提高胰岛素刺激的脂肪细胞中葡萄糖摄取,发挥抗糖尿作用。马齿苋中富含ω-3脂肪酸、山奈酚、木樨草素、槲皮素、芹菜素等成分,能显著改善地塞米松诱导的高脂血症,包括降低血清总TC、TG、脂肪酸、LDL-C,升高HDL-C,抑制肝脏损伤。芹菜素诱导AMPK激活使PPARγ、SCD-1等与脂肪形成相关的基因表达降低,从而抑制脂肪形成。芹菜素不仅降低血清TC、TG、LDL-C,升高HDL-C,调节胆固醇代谢,从而发挥抗高脂血症的作用;也能抑制H2O2诱导的血管内皮细胞损伤,保护血管。壳聚糖(Chitosan)减轻高脂饮食诱导的大鼠体重、肝脏和心脏指数、脂肪/体重比,维持肝脏和血清SOD、ALT、AST活性,降低血清TC、TG、LDL-C水平,增加PPARα和肝脂肪酶(HL)表达,从而改善肝脏脂质的代谢,保护肝脏免受氧化损伤,可用于高脂血症治疗。网络药理学研究(图1)明确了所述用于高脂血和脂肪肝的药膳食疗产品组合物主治病症的相关靶点、有效成分、作用靶点,明确了主治病症-靶点-药效成分作用关系网络,明确了参与作用的生理/病理通路过程,同时,配方的成分-靶点-药理作用机制网络研究结果与主治病症衔接一致,符合现代精准医学原则。同时本品成本低,符合产业化生产需要。
优选地,所述用于高脂血和脂肪肝的药膳食疗产品组合物由以下重量份的原料制备而成:沙棘叶8~10份,辣木叶5~7份,菊苣8~10份,余甘子8~10份,马齿苋5~7份,决明子8~10份,野葛根8~10份,紫苏子8~10份,火麻仁8~10份,昆布5~7份,荷叶5~7份,壳寡糖0.4~0.6份,低聚木糖0.8~1.2份。更具体地,所述用于高脂血和脂肪肝的药膳食疗产品组合物由以下重量份的原料制备而成:沙棘叶9份,辣木叶6份,菊苣9份,余甘子9份,马齿苋6份,决明子9份,野葛根9份,紫苏子9份,火麻仁6份,昆布6份,荷叶6份,壳寡糖0.5份,低聚木糖1份。该处方全部采用食品级原料,安全有效,生产成本底,预防效果可靠。如图1所示,本品中很多成分可以有效的防治高血脂和缓解其引起的相关症状。是一款主成分清晰,靶点明确的精准药膳产品。由于网络药理学关系图1空间布局限制,用英文名称或缩写代替,具体中英文对应如表1所示。
表1
英文名 | 中文名 | 英文名 | 中文名 |
Kaempferol | 山奈酚 | GLUT4 | 促葡萄糖转运蛋白成员4 |
Luteolin | 毛地黄黄酮 | GSH | 谷胱甘肽 |
Lactucin | 莴苣苦素 | GSK3B | 糖原合酶激酶3β |
Chicory lactone A | 菊苣内酯A | HDL-C | 高密度脂蛋白胆固醇 |
Chicory Glycosides C | 菊苣糖苷C | HIF-1α | 低氧诱导因子1α |
Cichoric acid | 菊苣酸 | HMG-CoA-R | 3-羟基-3-甲基戊二酸单酰辅酶A还原酶 |
Cassiaside B2 | 决明子苷B2 | HO1 | 血红素加氧酶1 |
Emodin-3-methyl ether | 大黄素甲醚 | HTR3A | 5-羟色胺受体3A |
Chrysophanol | 大黄酚 | ICAM1 | 细胞间粘附分子1 |
Rhein | 大黄酸 | IFN | 干扰素 |
Emodin | 大黄素 | IFNγ | 干扰素γ |
Polysaccharides | 多糖 | IGF2 | 胰岛素样生长因子2 |
Fucoidan | 岩藻多糖 | IKBA | 核因子κB抑制剂α |
(-)-epigallocatechin 3-O-gallate | 表没食子儿茶素没食子酸酯 | IKBKB | 核因子κB激酶β亚基抑制剂 |
Gallic acid | 没食子酸 | IL10 | 白介素10 |
Quercetin | 槲皮素 | IL1β | 白介素1β |
Isorhamnetin | 异鼠李素 | IL2 | 白介素2 |
Nuciferine | 荷叶碱 | IL4 | 白介素4 |
Roemerine | 莲碱 | IL6 | 白介素6 |
Linoleic acid | 亚油酸 | IL8 | 白介素8 |
α-linolenic acid | α-亚麻酸 | INSR | 胰岛素受体 |
Puerarin | 葛根素 | JAK2 | 非受体型酪氨酸蛋白激酶2 |
Daidzin | 大豆苷 | JNK | 应激活化蛋白激酶 |
Daidzein | 大豆苷元 | LC3 | LC3 |
Formononetin | 刺芒柄花素 | LDH | 乳酸脱氢酶 |
Apigenin | 芹菜素 | LDL | 低密度脂蛋白 |
Chitosan | 壳聚糖 | LDL-C | 低密度脂蛋白-C |
5-HT2C | 5-羟色胺 | LPL | 脂蛋白酯酶 |
ACACA | 乙酰辅酶A羧化酶1 | LXR-α | 肝X受体α |
ACC | 乙酰辅酶A羧化酶 | MAOA | 单胺氧化酶A |
ACE2 | 血管紧张素转化酶2 | MAOB | 单胺氧化酶B |
ACHE | 乙酰胆碱酯酶 | MAPK8 | 丝裂原活化蛋白激酶8 |
adiponectin | 脂联素 | MDA | 丙二醛 |
ADRA1B | α1B肾上腺素受体 | MMP2 | 基质金属蛋白酶2 |
ADRA1D | α1D肾上腺素受体 | MMP9 | 基质金属蛋白酶9 |
ADRB2 | β2肾上腺素受体 | mTOR | 哺乳动物雷帕霉素靶蛋白 |
AKR1B1 | 醛糖还原酶 | NCOA2 | 核受体共激活剂2 |
AKT | 丝氨酸/苏氨酸蛋白激酶 | NFκB | 核因子κB |
ALDH2 | 醛脱氢酶2 | NLRP3 | NLR家族含Pyrin结构域3 |
ALOX5 | 花生四烯酸5-脂氧合酶 | NO | 一氧化氮 |
ALT | 谷丙转氨酶 | NOS2 | 一氧化氮合成酶2 |
AMPK | AMP依赖的蛋白激酶 | NOX4 | 还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶4 |
AST | 谷草转氨酶 | OLR1 | 氧化型低密度脂蛋白受体1 |
AT1 | 血管紧张素 | p53 | 细胞肿瘤抗原p53 |
BAX | 凋亡调节因子BAX | PGC1α | 过氧化物酶体增殖物激活受体γ共激活因子1α |
BCL2 | 凋亡调节因子BCL2 | PGR | 孕激素受体 |
BDNF | 脑源性神经生长因子 | PGS2 | 微管蛋白聚谷氨酰胺酶复合物亚基2 |
C/EBPα | 重组人CCAAT增强子结合蛋白α | PI3K | 磷脂酰肌醇-4,5-双磷酸3-激酶 |
C/EBPβ | 重组人CCAAT增强子结合蛋白β | PIK3CG | 磷脂酰肌醇-4,5-双磷酸3-激酶催化亚基γ |
CASP1 | 半胱天冬酶1 | PPARα | 过氧化物酶体增殖物激活受体α |
CASP3 | 半胱天冬酶3 | PPARγ | 过氧化物酶体增殖物激活受体γ |
CASP7 | 半胱天冬酶7 | PTEN | 磷脂酰肌醇-3,4,5-三磷酸3-磷酸酶PTEN |
CASP9 | 半胱天冬酶9 | PTGS1 | 前列腺素合成酶1 |
CAT | 过氧化氢酶 | PTGS2 | 前列腺素合成酶2 |
CDK1 | 细胞周期蛋白依赖性激酶1 | PTP1B | 蛋白酪氨酸磷酸酶1B |
CHRM1 | 毒蕈碱型乙酰胆碱受体M1 | SCD-1 | 硬脂酰辅酶A去饱和酶1 |
CHRM2 | 毒蕈碱型乙酰胆碱受体M2 | SIRT1 | 沉默信息调节因子1 |
COX2 | 环氧合成酶2 | Smad3 | 信号转导分子 Smad3 |
CYP2E1 | 细胞色素P450同工酶2E1 | SOD | 超氧化物歧化酶 |
DPP4 | 二肽基肽酶IV | SREBP-1c | 固醇调节元件结合蛋白1c |
EGFR | 表皮生长因子受体 | STAT1 | 信号转导和转录激活子1 |
ELK1 | ETS结构域蛋白Elk-1 | STAT3 | 信号转导和转录激活子3 |
ERK | 细胞外调节蛋白激酶 | TC | 总胆固醇 |
FABP4 | 脂肪酸结合蛋白4 | TG | 甘油三酯 |
FAS | 脂肪酸合成酶 | TGFβ | 转化生长因子β |
FFA | 游离脂肪酸 | TIMP1 | 金属蛋白酶组织抑制因子1 |
FoxO1 | 叉形头转录因子1 | TNF | 肿瘤坏死因子 |
GABRA1 | γ-氨基丁酸受体α1亚基 | TNFα | 肿瘤坏死因子α |
GABRA2 | γ-氨基丁酸受体α2亚基 | ULK1 | unc-51 样自噬激活激酶1 |
GFAP | 胶质纤维酸性蛋白 | VCAM1 | 血管细胞粘附蛋白1 |
GGT | γ-谷氨酰转肽酶 | VEGFA | 血管内皮生长因子A |
部分组分具体作用如表2所示:
表2
中药 | 特征性成分 | 活性 |
菊苣 | 山莴苣素(Lactucin) 菊苣内酯 A (Chicory lactone A) 苦苣菜苷 C(Chicory Glycosides C) 菊苣酸(Cichoric acid) 木犀草素(Luteolin) | 1、 菊苣减少血清中TC、TG、LDL、AST、ALT水平,抑制IL-6、TNF-α、FFA、IKKβ、NF-κB表达,改善糖尿病-脂肪肝大鼠的肝细胞肿胀、坏死,抑制肝细胞中脂肪聚集;其中大黄素甲醚、大黄酚、山莴苣素、菊苣内酯 A 、苦苣菜苷 C等具有明显的抗炎活性。 2、 Lactucin通过抑制JAK2/STAT3磷酸化减少脂肪生成相关的基因表达,减少肥胖,保护肝脏。 3、 Luteolin具有抗氧化、抗炎作用,能保护肝脏。 |
决明子 | 决明子苷B2(Cassiaside B2) 大黄素甲醚(Emodin-3-methyl ether) 大黄酚(Chrysophanol) 大黄素(Emodin) 大黄酸(Rhein) | 1、 决明子中的蒽醌类化合物能抑制脂肪肝大鼠的脂肪过氧化,降低血清TC、TG、LDL、AST、ALT水平,保护肝脏。 2、 Cassiaside B2抑制蛋白酪氨酸磷酸酶1B(PTP1B),改善胰岛素抵抗,降低血糖;也能通过抑制5-HT2C减少饮食摄入,发挥抗肥胖作用。 3、 Chrysophanol和Emodin通过降低GGT活性,升高GSH,增加CYP2E1表达抑制酒精性肝损伤,对脂肪肝和高脂血症有一定预防作用。 4、 Emodin减少血清TC、TG、LDL、AST、ALT水平,下调CYP2E1,增加PPARγ等基因表达,改善酒精性肝损伤和高脂血症。 |
昆布 | 多糖 Fucoidan | 1、 昆布多糖能增强LCAT, PL and LPL活性,降低血清TC、TG、LDL水平,减轻体重并改善高脂血症。 2、 Fucoidan减少糖尿病小鼠肝组织中FBG、TC、TG、AST、ALT、MDA水平以及增加血清中SOD、CAT、胰岛素水平,改善糖尿病引起的肝损伤。 |
余甘子 | 没食子酸(Gallic acid) (-)-表没食子儿茶素没食子酸酯(EGCG) 木犀草素(Luteolin) 山奈酚(Kaempferol) | 1、 没食子酸减少脂质过氧化,降低AST、ALT水平,抑制TNFα和IL8,通过抗氧化发挥肝保护作用。 2、 EGCG不仅能明显降低体重,肠系膜脂肪量,空腹血糖,胰岛素抵抗,血清胆固醇和脂肪肝的严重程度;还能通过TGF/SMAD, PI3 K/Akt/FoxO1,NFκB等信号通路发挥抗氧化抗炎作用,从而减轻脂肪肝。 3、 山奈酚和木犀草素可抑制DPP4活性发挥抗糖尿病作用。 |
沙棘 | 槲皮素(Quercetin) 异鼠李素(Isorhamnetin) 山奈酚(Kaempferol) 杨梅素(Myricetin) | 1、 Myricetin减少血糖、血清胆固醇、甘油三酯水平,降低血压;也能减慢异丙肾上腺素诱导的心律加快、减少血清LDH、CK、AST、ALT水平、升高SOD、CAT水平。 2、 槲皮素、山奈酚通过激活PPARγ发挥降糖作用,改善代谢综合征。 |
荷叶 | 荷叶碱(Nuciferine) 莲碱(Roemerine) 槲皮素(Quercetin) 异鼠李素(Isorhamnetin) | 1、 Nuciferine减少饮食摄入、体重,降低血清TC、TG、LDL-C、FFA 水平,抑制TNFα、IL6等炎症因子释放,增加SOD、CAT、GPx等抗氧化酶,改善胰岛素抵抗,调节脂肪生成的相关基因表达,最终改善高脂诱导的肝脏损伤变性和代谢综合征。 |
紫苏子 | 亚油酸(Linoleic acid) α-亚麻酸(α-linolenic acid) 木犀草素(Luteolin) | 1、 亚油酸、α-亚麻酸能降低血浆中TC、TG水平,增加血清脂联素,改善胰岛素抵抗,减轻肝脏肿大,抑制TNFα表达。 |
野葛根 | 葛根素(Puerarin) 大豆苷(Daidzin) 大豆苷元(Daidzein) 刺芒柄花素(Formononetin) | 1、 葛根素通过抗氧化作用保护肝脏,抑制脂质过氧化,减少血清中TC、TG、LDL-C,增加HDL-C,调节CYP7A1、HMG-CoA-R、LDLR,从而降低血脂。 2、 大豆苷元通过激活PPARγ来增加GLUT4和IRS-1表达,从而提高胰岛素刺激的脂肪细胞中葡萄糖摄取,发挥抗糖尿作用。 |
马齿苋 | 山奈酚(Kaempferol) 木犀草素(Luteolin) 槲皮素(Quercetin) 芹菜素(Apigenin) | 1、 山奈酚、木樨草素、槲皮素、芹菜素等成分,能显著改善地塞米松诱导的高脂血症,包括降低血清总TC、TG、脂肪酸、LDL-C,升高HDL-C,抑制肝脏损伤。 2、 芹菜素不仅降低血清TC、TG、LDL-C,升高HDL-C,调节胆固醇代谢,从而发挥抗高脂血症的作用。 |
壳聚糖 | Chitosan | 1、 壳聚糖减轻高脂饮食诱导的大鼠体重、肝脏和心脏指数,维持肝脏和血清SOD、ALT、AST活性,降低血清TC、TG、LDL-C水平,增加PPARα和肝脂肪酶(HL)表达,从而改善肝脏脂质的代谢,保护肝脏免受氧化损伤。 |
本发明实施例还提供上述用于高脂血和脂肪肝的药膳食疗产品组合物的制备方法,其包括如下步骤:
按照上述用于高脂血和脂肪肝的药膳食疗产品组合物的重量份称取原料,将沙棘叶,辣木叶,菊苣,余甘子,马齿苋,决明子,野葛根,紫苏子,火麻仁,昆布和荷叶混合,加8~15倍质量份的水浸泡15~60分钟,加热回流提取0.5~2小时,80~200目过滤,得第一提取液;
向药渣中加8~15倍质量份的水回流提取0.5~2小时,80~200目过滤,得第二提取液;
将第一提取液和第二提取液混合,浓缩,加入壳寡糖和低聚木糖,获得所述用于高脂血和脂肪肝的药膳食疗产品组合物。
优选地,按照上述用于高脂血和脂肪肝的药膳食疗产品组合物的重量份称取原料,将决明子、火麻仁破碎,用纱布袋封装,再与沙棘叶,辣木叶,菊苣,余甘子,马齿苋,野葛根,紫苏子,昆布,荷叶混合,加8~15倍质量份的水浸泡20~40分钟,加热回流提取0.5~2小时,100~200目过滤,得第一提取液;
向药渣中加8~15倍质量份的水,加热回流提取0.5~2小时,100~200目过滤,得第二提取液。
更具体地,所述用于高脂血和脂肪肝的药膳食疗产品组合物,滤液减压浓缩至密度约为1.08,得浓缩液备用;浓缩液加入麦芽糊精,搅拌均匀,喷雾干燥(喷嘴进风温度设为150度,出风口温度80度),即得提取物粉末,备用。
取上述喷干粉加入壳寡糖和低聚木糖,混合均匀;分装,10 g/袋,即得固体饮料。
或者,以上述喷雾干燥的粉末加入壳寡糖和低聚木糖,进行制粒,干燥,分装、10 g/袋,制备成颗粒剂。
采用喷干粉,加入壳寡糖和低聚木糖等适宜的食品原料,进行制粒,干燥,压片;做成适宜的片剂形式即可。
产品的最终形式可以是多种,包括粉剂、颗粒、片剂、蜜丸、膏滋、口服液、糖浆剂等。制备工艺中,干燥方式可以是喷雾干燥、真空干燥、冷冻干燥等;制粒方法可以是干法制粒、湿法制粒、一步制粒等。
采用药学、食品、保健品等相关法规可以接受的方法,均可以对上述用于高脂血和脂肪肝的药膳食疗产品组合物进行提取、浓缩、干燥或粉碎,进一步加工为产品,保留复方的有效成分,制成适宜的给药形式(包括颗粒剂、粉剂、口服液、片剂等剂型)或者食品形式如压片糖果、餐粉、固体饮料等形式,满足市场对相关产品的需求,均属于本发明保护的范围。
以下通过具体配方和制备工艺的实施例来说明上述用于高脂血和脂肪肝的药膳食疗产品组合物及其制备方法。
实施例1:
称取沙棘叶9 kg,辣木叶6 kg,菊苣9 kg,余甘子9 kg,马齿苋6 kg,野葛根9 kg,紫苏子9 kg,昆布6 kg和荷叶6 kg混合,将决明子9 kg和火麻仁6 kg破碎装袋,与上述组分混合,加水15倍浸泡30分钟,加热回流提取1小时,200目过滤,药渣加12倍水回流提取1小时;合并两次提取液,减压浓缩密度约为1.08,加入麦芽糊精适量,喷雾干燥,即得提取物;加入0.5 kg 寡聚糖和1 kg低聚木糖,混合均匀,上粉末包装机,分装,制成固体饮料,10 g/袋。
实施例2:
选择100位血脂高患者作为保健品每日服用上述用于高脂血和脂肪肝的药膳食疗产品组合物制备的固体饮料,每天2~3次;每次取本品一袋,加入100~200毫升热水冲调搅至溶解后,食用。连服两周,有80%以上患者的血脂有不同程度的降低。
Claims (6)
- 一种用于高脂血和脂肪肝的药膳食疗产品组合物,其特征在于,所述药膳食疗组合物由以下重量份的原料制备而成:沙棘叶1~15份,辣木叶1~20份,菊苣1~15份,余甘子1~20份,马齿苋1~20份,决明子1~20份,野葛根1~15份,紫苏子1~15份,火麻仁1~20份,昆布1~16份,荷叶1~15份,壳寡糖0.1~3份,低聚木糖0.5~5份。
- 如权利要求1所述的用于高脂血和脂肪肝的药膳食疗产品组合物,其特征在于,所述药膳食疗组合物由以下重量份的原料制备而成:沙棘叶8~10份,辣木叶5~7份,菊苣8~10份,余甘子8~10份,马齿苋5~7份,决明子8~10份,野葛根8~10份,紫苏子8~10份,火麻仁8~10份,昆布5~7份,荷叶5~7份,壳寡糖0.4~0.6份,低聚木糖0.8~1.2份。
- 如权利要求2所述的用于高脂血和脂肪肝的药膳食疗产品组合物,其特征在于,所述药膳食疗组合物由以下重量份的原料制备而成:沙棘叶9份,辣木叶6份,菊苣9份,余甘子9份,马齿苋6份,决明子9份,野葛根9份,紫苏子9份,火麻仁6份,昆布6份,荷叶6份,壳寡糖0.5份,低聚木糖1份。
- 一种用于高脂血和脂肪肝的药膳食疗产品组合物的制备方法,其特征在于,包括如下步骤:按照权利要求1~3任一所述的用于高脂血和脂肪肝的药膳食疗产品组合物的重量份称取原料,将沙棘叶,辣木叶,菊苣,余甘子,马齿苋,决明子,野葛根,紫苏子,火麻仁,昆布和荷叶混合,加8~15倍质量份的水浸泡15~60分钟,加热回流提取0.5~2小时,80~200目过滤,得第一提取液;向药渣中加8~15倍质量份的水回流提取0.5~2小时,80~200目过滤,得第二提取液;将第一提取液和第二提取液混合,浓缩,加入壳寡糖和低聚木糖,获得所述用于高脂血和脂肪肝的药膳食疗产品组合物。
- 如权利要求4所述的用于高脂血和脂肪肝的药膳食疗产品组合物的制备方法,其特征在于,将决明子、火麻仁破碎,用纱布袋封装,再与沙棘叶,辣木叶,菊苣,余甘子,马齿苋,野葛根,紫苏子,昆布,荷叶混合。
- 如权利要求4所述的用于高脂血和脂肪肝的药膳食疗产品组合物的制备方法,其特征在于,向药渣中加10~15倍质量份的水。
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