WO2018103729A1 - 绿原酸在制备增强食欲的药物或保健品中的用途 - Google Patents

绿原酸在制备增强食欲的药物或保健品中的用途 Download PDF

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WO2018103729A1
WO2018103729A1 PCT/CN2017/115150 CN2017115150W WO2018103729A1 WO 2018103729 A1 WO2018103729 A1 WO 2018103729A1 CN 2017115150 W CN2017115150 W CN 2017115150W WO 2018103729 A1 WO2018103729 A1 WO 2018103729A1
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chlorogenic acid
health care
care product
preparation
use according
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PCT/CN2017/115150
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English (en)
French (fr)
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张洁
黄望
宁玲
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四川九章生物科技有限公司
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Publication of WO2018103729A1 publication Critical patent/WO2018103729A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention relates to the use of chlorogenic acid in preparing an appetite-enhancing drug or health care product, and belongs to the field of medicine.
  • Anorexia is a common disease in children and occurs mostly in children aged 1 to 6 years. Patients with anorexia have a loss of appetite or loss of appetite for a long time. Seeing food is not greedy or even refusing to eat can lead to malnutrition, anemia, rickets and low immunity. Repeated respiratory infections may occur in children's growth and development, nutritional status and intellectual development. The extent of the impact.
  • the present invention provides the use of chlorogenic acid for the preparation of an appetite-enhancing drug or health care product.
  • the medicament or health care product has the efficacy of treating and/or preventing anorexia.
  • the medicament or health care product has the efficacy of treating and/or preventing anorexia in children.
  • the medicament or health care product has the effect of regulating the brain gut peptide-appetite center.
  • the medicament or the health care product has the effects of increasing the concentration of ⁇ -EP, decreasing the concentration of CCK-8, increasing the expression level of VIP, or decreasing the expression level of SS.
  • the medicine or health care product has the effects of increasing the concentration of ⁇ -EP in the hypothalamus, gastric antrum, and plasma, decreasing the concentration of CCK-8 in the hypothalamus and plasma, and increasing the expression of VIP in the fundus tissue and the jejunum segment. Reduce the role of SS expression in the fundus and jejunal segments.
  • the medicament or health care product has an effect of improving immunity.
  • the medicament or health care product has an effect of increasing the spleen index, the thymus index, serum IL-2 or IL-6.
  • the medicament or the health care product is prepared by adding an effective amount of chlorogenic acid as an active ingredient to an acceptable auxiliary or auxiliary component in a pharmaceutically or health care product.
  • auxiliary component is other ingredients having an appetite enhancing effect, and may include, for example, a traditional Chinese medicine ingredient such as licorice, dried tangerine peel, hawthorn, ebony, digestive enzyme component and/or probiotic component.
  • a traditional Chinese medicine ingredient such as licorice, dried tangerine peel, hawthorn, ebony, digestive enzyme component and/or probiotic component.
  • the above-mentioned single chlorogenic acid form or a combination of chlorogenic acid and a pharmaceutical ingredient having the same efficacy is an effective pharmaceutical ingredient, and an acceptable auxiliary agent in a pharmaceutically or health care product is subjected to a corresponding preparation method or process.
  • the corresponding oral preparation can be obtained.
  • excipients may include excipients acceptable and used, for example, in tablets, granules, powders, capsules, suspensions, solutions, buccal, dandruffs, granules or pills. Or auxiliary ingredients.
  • the preparation is an oral preparation.
  • the preparation is a tablet, a granule, a powder, a capsule, a suspension, a solution, a pill, a buccal, a dan or a granule.
  • the pharmaceutical or health care product contains 30 to 500 mg of chlorogenic acid per preparation unit.
  • the present invention also provides a method of enhancing appetite which is administered to a subject with chlorogenic acid.
  • the present invention provides the use of chlorogenic acid for the preparation of an appetite-enhancing drug or health care product.
  • the pharmacodynamic experiments showed that chlorogenic acid can significantly increase the food intake of rats with anorexia and increase their body weight, and the effect is comparable to that of the commercially available drug Jiangzhong Jianweixiaoshi, indicating that chlorogenic acid has a significant appetite-enhancing effect and can be used.
  • the treatment of anorexia has broad clinical application prospects.
  • the raw materials and equipment used in the specific embodiments of the present invention are known products and are obtained by purchasing commercially available products.
  • the special feed for modeling has high crude protein and crude fat content, low content of various minerals and multivitamins, especially calcium, iron and riboflavin.
  • the main cause of the model is the same as the main cause of anorexia in children. .
  • the animals were allowed to eat freely in the experiment, which is also very close to the clinical situation.
  • Group A blank control group.
  • Group B model control group.
  • Group C chlorogenic acid high dose group, referred to as high dose group.
  • Group D small dose group of chlorogenic acid, referred to as low dose group.
  • E Positive control group.
  • Group A was fed with conventional feed (ie, large, mouse common feed M02), and the other 4 groups were fed with special feed.
  • the special feed is prepared by mixing fish pine, milk powder, corn flour, soybean powder, white sugar, fresh eggs and fresh fat meat in a ratio of 1:1:1:2:1:1.8:2, kneading into biscuits, drying, 4 °C Refrigerated for use. All animals were kept in single cages and fed freely for 4 weeks. The food intake and body mass were recorded daily, and the average food intake of the model rats decreased by 20% to 30% or the body mass was lower than the control group by 10% to 15%. After 4 days, the model was successfully established. Start gavage.
  • Group A and group B were given equal volume of distilled water daily, group C and group D were given the corresponding dose of 2 mL of chlorogenic acid aqueous solution, and group E was given 2 mL of Jiangzhong Jianweixiaoshi suspension. Rats in each group were intragastrically administered once a day for 16 days. 2, the collection of specimens
  • Determination of spleen index and thymus index The weight of the spleen and thymus was weighed by an electronic balance and calculated in mg/g body weight.
  • Determination of serum IL-2 and IL-6 they were separately detected by radioimmunoassay (the specific method was operated according to the kit instructions).
  • Determination of CCK-8 and ⁇ -EP determined by radioimmunoassay technique (specific method is applied according to the radioimmunoassay kit, and the US standard 16 probe r counter is used to automatically reduce the standard curve and print the result).
  • the unit of food intake is g; * compared with the model control group, P is less than 0.05, # compared with the blank control group, P is less than 0.05
  • the weight unit is g; * compared with the model control group P is less than 0.05, # compared with the blank control group P is less than 0.05
  • chlorogenic acid can significantly increase the food intake and increase the body weight of rats with anorexia, and the effect is similar to that of the commercially available drug Jiangzhong Jianweixiaoshi, indicating that chlorogenic acid has a significant appetite-enhancing effect and can be used for anorexia. Treatment of the disease.
  • the hypothalamus is the center of regulation of diet and energy balance. There are multiple key areas that regulate feeding behavior, such as the lateral thalamic area (LH), the hypothalamic ventral medial (VMH), the arcuate nucleus (ARC), and the paraventricular nucleus. (PVN), etc., various neuronal nuclei in the hypothalamus can produce a series of appetite regulating factors that promote or suppress appetite. They cooperate and interact to form a complex appetite regulating network.
  • One of the main causes of anorexia is that due to the unreasonable intake of food ingredients, the secretion of brain-gut peptides is disordered, which in turn affects the appetite center and affects the feeding behavior. That is, the "brain-gut peptide-appetite center" disorder is the development of anorexia. Important link. The purpose of this experiment was to investigate the effect of chlorogenic acid on brain gut peptide levels in anorexia model rats.
  • --endorphin is an endogenous opioid peptide that can be synthesized and secreted in both brain tissue and gastrointestinal tract, and has an appetite-promoting effect; while octapeptide cholecystokinin (CCK-8) has inhibition.
  • the appetite effect which is a pair of antagonistic substances in the regulation of hypothalamic feeding, plays an important role in physiological regulation and pathological food intake reduction.
  • the physiological function of VIP is to stimulate the secretion of pancreatic juice and intestinal juice, protect the intestinal mucosa, and regulate gastrointestinal absorption.
  • SS can widely inhibit gastrointestinal motility, including gastric emptying, gastric segmentation, and the like.
  • the expression levels of VIP and SS in the experimental groups were shown in Tables 5 and 6.
  • Table 5 Optical and SS optical density values of chlorogenic acid in gastric fundus of rats in each group
  • the VIP in the gastric fundus tissue and the jejunum segment of the model group was significantly decreased, and SS was significantly increased.
  • the VIP in the gastric fundus tissue of the chlorogenic acid administration group of the present invention was compared.
  • the expression level increased significantly and the expression of SS decreased significantly. There were significant differences.
  • the expression of VIP in the jejunum segment of rats was also significantly increased, even higher than that of the blank control group.
  • the SS in the jejunal segment of the rat was significantly decreased, which was comparable to that of the blank control group.
  • chlorogenic acid has a significant regulatory effect on CCK-8, ⁇ -EP, VIP and SS, and can exert a good therapeutic effect on anorexia.
  • Anorexia patients have anorexia for a long time, because the intake of protein-heat energy is insufficient, which often leads to decreased immune function and increased prevalence.
  • the purpose of this experiment was to investigate the regulation of chlorogenic acid on the immune function of anorexia model rats.
  • the spleen index and thymus index of the model control group were significantly lower than those of the blank control group.
  • the large and small doses of chlorogenic acid significantly increased the spleen index and thymus index in rats, and were significantly higher than the model control group.
  • the spleen index and thymus index of the chlorogenic acid high-dose group and the low-dose group were also Significantly increased, indicating that chlorogenic acid can increase the weight of immune organs under pathological conditions and under normal conditions.
  • the present invention provides the use of chlorogenic acid in the preparation of an appetite-enhancing drug or health care product.
  • the pharmacodynamic experiments showed that chlorogenic acid can significantly increase the food intake of rats with anorexia and increase their body weight, and the effect is comparable to that of the commercially available drug Jiangzhong Jianweixiaoshi, indicating that chlorogenic acid has a significant appetite-enhancing effect and can be used.
  • the treatment of anorexia has broad clinical application prospects.

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Abstract

绿原酸在制备增强食欲的药物或保健品中的用途。药效实验表明，绿原酸可大幅提高厌食症大鼠的摄食量，并使其体重增加，且效果与市售药物江中健胃消食片相当，说明绿原酸具有显著的增强食欲效果，可用于厌食症的治疗，具有广阔的临床应用前景。

Description

绿原酸在制备增强食欲的药物或保健品中的用途 技术领域
本发明涉及绿原酸在制备增强食欲的药物或保健品中的用途，属于医药领域。
背景技术
正常人一般都有良好的食欲，这是判断人体健康的重要标志之一。因此，食欲异常往往表示人体处于病理状态。食欲减退是临床上最为常见的食欲异常症状，通常是由于疾病影响、喂养不当或情绪因素等引起的不想进食或进食量显著减少，对人体健康具有明显危害：轻者摄食量降低、体重减轻、面色萎黄，严重的患者则会出现营养不良、免疫力低下、代谢和内分泌紊乱等问题，甚至可能因极度缺乏营养而出现恶病质状态、机体衰竭从而危及生命。
厌食症是儿童常见的疾病,多发于1～6岁儿童。厌食症患者较长时间食欲缺乏或食欲减退，见食不贪，甚至拒食，可导致营养不良、贫血、佝偻病及免疫力低下，出现反复呼吸道感染，对儿童生长发育、营养状态和智力发展也有不同程度的影响。
因此，开发具有增强食欲功效的药物或保健品，尤其是对厌食症具有治疗作用的药物或保健品，显得尤为重要。
发明内容
本发明的目的在于提供绿原酸在制备增强食欲的药物或保健品中的用途。
本发明提供了绿原酸在制备增强食欲的药物或保健品中的用途。
进一步地，所述的药物或保健品具有治疗和/或预防厌食症的功效。
进一步地，所述的药物或保健品具有治疗和/或预防小儿厌食症的功效。
进一步地，所述的药物或保健品具有调节脑肠肽-食欲中枢的作用。
进一步地，所述的药物或保健品具有提高β-EP浓度、降低CCK-8浓度、提高VIP表达量或降低SS表达量的作用。
进一步地，所述的药物或保健品具有提高下丘脑、胃窦部、血浆中β-EP浓度，降低下丘脑、血浆中CCK-8浓度，提高胃底组织、空肠段组织中VIP表达量，降低胃底组织、空肠段组织中SS表达量的作用。
进一步地，所述的药物或保健品具有提高免疫力的功效。
进一步地，所述的药物或保健品具有提高脾指数、胸腺指数、血清IL-2或IL-6的功效。
进一步地，所述的药物或保健品是以有效量的绿原酸为活性成分，加入药学上或保健品中可接受的辅料或者辅助性成分制备而成的制剂。
进一步地，所述的辅助性成分为其他具有增强食欲功效的成分，可包括如中药成分甘草、陈皮、山楂、乌梅，消化酶成分和/或益生菌成分等。
进一步的，将上述的单一绿原酸形式或是绿原酸与具有同类功效的药物成分组成的复方形式有效药物成分，加上药学上或保健品中可以接受的辅料经相应的制剂方法或过程，即可得到相应的口服制剂形式的药物。
进一步地，上述的可接受的辅料，可包括例如在片剂、颗粒剂、散剂、胶囊剂、混悬剂、溶液剂、口含剂、丹剂、冲剂或丸剂中可接受的和使用的辅料或辅助性成分。
进一步地，所述的制剂为口服制剂。
进一步地，所述的制剂为片剂、颗粒剂、散剂、胶囊剂、混悬剂、溶液剂、丸剂、口含剂、丹剂或冲剂。
进一步地，所述的药物或保健品中每制剂单位含有绿原酸30～500mg。
本发明还提供了一种增强食欲的方法，它是给予受试者绿原酸。
本发明提供了绿原酸在制备增强食欲的药物或保健品中的用途。药效实验表明，绿原酸可大幅提高厌食症大鼠的摄食量，并使其体重增加，且效果与市售药物江中健胃消食片相当，说明绿原酸具有显著的增强食欲效果，可用于厌食症的治疗，具有广阔的临床应用前景。
显然，根据本发明的上述内容，按照本领域的普通技术知识和惯用手段，在不脱离本发明上述基本技术思想前提下，还可以做出其它多种形式的修改、替换或变更。
以下通过实施例形式的具体实施方式，对本发明的上述内容再作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基于本发明上述内容所实现的技术均属于本发明的范围。
具体实施方式
本发明具体实施方式中使用的原料、设备均为已知产品，通过购买市售产品获得。
实施例1绿原酸增强食欲的动物实验
1、动物模型的建立
本实施例根据中美长期合作课题--中国健康与营养调查资料中提到的我国2-6岁儿童膳食中脂肪、蛋白质达到较高水平，而钙、铁、核黄素等摄入量较低的情况，建模用的特制饲料中，粗蛋白、粗脂肪含量高，多种矿物质及多种维生素含量低下，尤其是钙、铁、核黄素低下，模型病因与小儿厌食主要病因相同。且实验中使动物自由进食，也与临床情况十分接近。
选断乳后1周龄的健康SD大鼠50只，质量(60±10)g，雌雄各半。将50只大鼠适应性喂养1周后，依据数字随机表法分为5组，每组10只。A组：空白对照组。B组：模型对照组。C组：绿原酸大剂量组，简称大剂量组。D组：绿原酸小剂量组，简称小剂量组。E:阳性对照组。
所有动物在同一条件下喂养(室温20～24℃，相对湿度50％)。A组以常规饲料(即大、小鼠普通育成饲料M02)喂养，其余4组用特制饲料喂养。特制饲料采用鱼肉松、奶粉、玉米粉、黄豆粉、白糖、鲜鸡蛋、鲜肥肉按照1∶1∶1∶2∶1∶1.8∶2比例混匀，捏成饼干状，晾干，4℃冷藏备用。所有动物均单笼饲养，自由进食饮水，共饲养4周。每日记录进食量及身体质量，以造模大鼠摄食量平均下降20％～30％或身体质量低于对照组10％～15％且维持4d后为造模成功，造模成功后各组开始灌胃。A组和B组每日灌服等体积蒸馏水，C组和D组灌服相应剂量的绿原酸水溶液2mL，E组每日灌服江中健胃消食片混悬液2mL。各组大鼠均每日灌胃1次，连续灌胃16d。2、标本的采集
每天观察动物进食量及体重，在试验结束后，所有动物在同一时间段眼球采血，分两组保存，一组采血前每管加抑肽酶20ul/ml，眼眶取血后注入肝素管内充分摇匀，静置，然后以4000r/min低温离心10min分离血浆，于-70摄氏度保存待测。另一组眼眶取血注入肝素管内摇匀，静置，然后以4000r/min低温离心10min分离得到血清保存于-70摄氏度待测；取血后迅速将大鼠断头，取出全脑和胃，入沸生理盐水中煮5min，分离下丘脑，刮取胃窦部粘膜，分别用分析天平称重后置玻璃匀浆管内加入1mol/L冰醋酸1ml，充分匀浆后倒入塑料试管内，于室温下放置100min，加NaOH 1ml，4000r/min低温离心10min，取上清液于-70摄氏度保存待测。同时解刨取脾、胸腺，取空肠段组织。
4、检测方法
脾指数与胸腺指数的测定：用电子天平称脾、胸腺的重量，以mg/g体重分别计算。血清IL-2,IL-6的测定：采用放免法分别对其进行检测(具体方 法按照试剂盒说明书操作)。CCK-8、β-EP的测定：用放射免疫检测技术测定(具体方法按放射免疫药盒说明加样，用美国产16探头r计数仪自动少秒标准曲线并打印结果)。胃底组织、空肠段VIP、SS的测定：面积为1.5cm×1cm，固定、包埋、切片，覆多聚赖氨酸，HE染色后待测；用免疫组化法将胃组织切片分别用VIP、SS一抗染色后分析结果，由于VIP、SS表达含量用平均光密度值来比较各组中该物质表达含量的多少。
5、统计学处理
所有数据均采用均数±标准差表示，采用SPSS13.0统计软件处理，各指标组间根据方差齐性采用多因素方差分析。
6、试验结果及统计分析
6.1对厌食大鼠一般情况的影响
6.1.1各组试验动物摄食量的变化比较
表1 各组试验动物摄食量的变化比较结果
Figure PCTCN2017115150-appb-000001
注：摄食量单位为g；*与模型对照组比较P小于0.05，#与空白对照组比较P小于0.05
试验第1天各组动物摄食量无显著性差异，至第8天，相较于空白对照组(A组)，四个造模组动物摄食量减少了平均下降了20％-30％，并持续4天，提示造模成功；从第16天开始，相较于模型对照(B组)，大、小剂量绿原酸灌胃C、D组大鼠摄食量显著上升，至第24天后与空白对照组(A)相比无显著差异；另外，绿原酸灌胃大、小剂量组(C、D组)大鼠摄食量的变化幅度与阳性药物对照E组相比无显著性差异。
6.1.2各组动物体重的变化比较
表2 各组动物体重的变化比较结果
Figure PCTCN2017115150-appb-000002
注：体重单位为g；*与模型对照组比较P小于0.05，#与空白对照组比较P小于0.05
试验第1天各组动物体重无显著性差异，至第8天，与空白对照组对比，四个造模组动物体重均低于对照组10％～15％并持续4天，提示造模成功；从第12天开始灌胃，第16天开始，相较于模型对照B组，绿原酸灌胃C、D组大鼠体重显著上升，至第24天后与空白对照组相比无显著差异，与阳性药物对照E组相比，体重提升效果相当。
以上结果表明，绿原酸可大幅提高厌食症大鼠的摄食量，并使其体重增加，且效果与市售药物江中健胃消食片相当，说明绿原酸具有显著的增强食欲效果，可用于厌食症的治疗。
6.2对脑肠肽-食欲中枢的调节作用
下丘脑是调节饮食和能量平衡的中枢，其中散在分布着多个调节摄食行为的关键区，如下丘脑外侧区(LH)、下丘脑腹内侧(VMH)、弓状核(ARC)、室旁核(PVN)等，下丘脑中的各种神经核团可产生一系列食欲调节因子，促进或抑制食欲，它们协同合作、相互影响，形成了一个复杂的“食欲调节网”。厌食症产生的主要原因之一是由于摄入食物成分不合理，导致脑肠肽分泌紊乱，进而作用于食欲中枢，影响摄食行为，即“脑肠肽-食欲中枢”紊乱是厌食症发生发展的重要环节。本实验的目的是考察绿原酸对厌食模型大鼠脑肠肽水平的影响。
6.2.1绿原酸对β-内啡肽(β-EP)、八肽胆囊收缩素(CCK-8)水平的影响
β-内啡肽(β-EP)为一种内源性阿片肽，在脑组织和胃肠道均能合成、分泌，具有促进食欲作用；而八肽胆囊收缩素(CCK-8)具有抑制食欲作用，此 两者在下丘脑摄食调控中是一对相互拮抗的物质，在生理性调控和病理学摄食量减少中起着重要作用。
表3 绿原酸对CCK-8浓度的影响
Figure PCTCN2017115150-appb-000003
注：*与模型对照组比较P小于0.05，#与空白对照组比较P小于0.05
各实验组大鼠下丘脑、血浆中CCK-8水平测定结果见表3。试验结果显示，造模成功后，动物下丘脑及血浆CCK-8浓度较空白对照组升高，绿原酸大剂量组、小剂量组大鼠下丘脑、血浆CCK-8浓度均较模型对照组降低，与空白对照组水平相当。
表4 绿原酸对β-EP浓度的影响
Figure PCTCN2017115150-appb-000004
注：*与模型对照组比较P小于0.05，#与空白对照组比较P小于0.05
各组大鼠β-EP水平测定结果见表4。试验结果显示，模型对照组大鼠下丘脑β-EP浓度与空白对照组比较无显著性差异，胃窦、血浆中β-EP浓度显著减少。绿原酸大剂量组、小剂量组下丘脑、胃窦部和血浆中的β-EP浓度均较模型组升高。且下丘脑、胃窦中的β-EP浓度显著高于空白对照组。6.2.2绿原酸对血管活性肠肽(VIP)、生长抑素(SS)水平的影响
VIP的生理功能为刺激胰液和肠液分泌，保护肠黏膜，调节胃肠吸收。SS可广泛抑制胃肠运动，包括胃排空、胃分节运动等。各实验组大鼠VIP、SS的表达水平见表5、6。
表5 绿原酸对各组大鼠胃底组织中VIP、SS光密度值
Figure PCTCN2017115150-appb-000005
注：*与模型对照组比较P小于0.05，#与空白对照组比较P小于0.05
表6 绿原酸对各组大鼠空肠段组织中VIP、SS光密度值
Figure PCTCN2017115150-appb-000006
注：*与模型对照组比较P小于0.05，#与空白对照组比较P小于0.05
与空白对照组相比，模型组大鼠胃底组织和空肠段组织中VIP显著降低，SS显著升高，与模型对照对照组比较，本发明绿原酸给药组大鼠胃底组织中VIP表达量明显上升、SS表达量大幅下降，均有显著性差异；大鼠空肠段组织中VIP表达量也显著提高，甚至显著高于空白对照组的表达水平。大鼠空肠段组织中SS显著降低，与空白对照组表达水平相当。
以上结果表明，绿原酸对CCK-8、β-EP、VIP、SS均具有显著的调控作用，对厌食症可发挥较好的治疗效果。
6.3对厌食症大鼠免疫功能的调节作用
厌食症患者厌食日久，因摄入的蛋白-热能均不足，往往会导致免疫功能减低，患病率增高。本实验的目的是考察绿原酸对厌食模型大鼠免疫功能的调节作用。
表7 各组动物脾指数、胸腺指数的比较结果
Figure PCTCN2017115150-appb-000007
注：*与模型对照组比较P小于0.05，#与空白对照组比较P小于0.05
从表7可以看出，与空白对照组比较，模型对照组脾指数、胸腺指数显著降低。给药绿原酸大、小剂量能显著提高大鼠脾指数及胸腺指数，且明显高于模型对照组，与空白对照组比较，绿原酸大剂量组、小剂量组脾指数及胸腺指数也显著增加，说明绿原酸可以增加病理条件下及正常情况下免疫器官的重量。
表8 各组动物血清IL-2、IL-6水平的比较结果
Figure PCTCN2017115150-appb-000008
注：*与模型对照组比较P小于0.05，#与空白对照组比较P小于0.05
从表8可以看出，绿原酸大、小剂量组均能显著增高模型大鼠血清IL-2、IL-6含量，且显著高于模型对照组。与空白对照组比较，无显著性差异。
综上所述，本发明提供了绿原酸在制备增强食欲的药物或保健品中的用途。药效实验表明，绿原酸可大幅提高厌食症大鼠的摄食量，并使其体重增加，且效果与市售药物江中健胃消食片相当，说明绿原酸具有显著的增强食欲效果，可用于厌食症的治疗，具有广阔的临床应用前景。
以上所述仅为本发明的较佳实施例，并不用以限制本发明，凡在本发明的思路技术和原则之内，所做的任何修改，等同替换、改进等，均应包含在本发明的保护范围内。

Claims (11)

  1. 绿原酸在制备增强食欲的药物或保健品中的用途。
  2. 如权利要求1所述的用途，其特征是：所述的药物或保健品具有治疗和/或预防厌食症的功效。
  3. 如权利要求1或2所述的用途，其特征是：所述的药物或保健品具有调节脑肠肽-食欲中枢的作用。
  4. 如权利要求1～3任意一项所述的用途，其特征是：所述的药物或保健品具有提高β-EP浓度、降低CCK-8浓度、提高VIP表达量或降低SS表达量的作用。
  5. 如权利要求1或2所述的用途，其特征是：所述的药物或保健品具有提高免疫力的功效。
  6. 如权利要求5所述的用途，其特征是：所述的药物或保健品具有提高脾指数、胸腺指数、血清IL-2或IL-6的功效。
  7. 如权利要求1～6任意一项所述的用途，其特征是：所述的药物或保健品是以有效量的绿原酸为活性成分，加入药学上或保健品中可接受的辅料或者辅助性成分制备而成的制剂。
  8. 如权利要求7所述的用途，其特征是：所述的制剂为口服制剂。
  9. 如权利要求8所述的用途，其特征是：所述的制剂为片剂、颗粒剂、散剂、胶囊剂、混悬剂、溶液剂、口含剂、丹剂、冲剂或丸剂。
  10. 如权利要求1所述的用途，其特征是：所述的药物或保健品中每制剂单位含有绿原酸30～500mg。
  11. 一种增强食欲的方法，其特征是：给予受试者绿原酸。
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