CN1195269A - 脂质代谢改善剂 - Google Patents
脂质代谢改善剂 Download PDFInfo
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- CN1195269A CN1195269A CN97190700A CN97190700A CN1195269A CN 1195269 A CN1195269 A CN 1195269A CN 97190700 A CN97190700 A CN 97190700A CN 97190700 A CN97190700 A CN 97190700A CN 1195269 A CN1195269 A CN 1195269A
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Abstract
本发明公开了一种具有改善脂质代谢作用或抗肥胖作用的食品、饲料或人或动物的脂质代谢改善剂或抗肥胖剂,是含有通式(Ⅰ)所示的化合物或其盐(以下总称为吴茱萸碱类)作为有效成分制成的,上式中,>A-B-表示>CR1-NR2-(其中R1表示氢或羟基、R2表示氢或低级烷基、或R1与R2共同表示价键)或>C=N+(R3)-(其中R3表示低纸烷基);当>A-B-表示>CR1-NR2-时,n表示0;当>A-B-表示>C=N+(R3)-时,n表示1,X-表示阴离子。
Description
技术领域
本发明涉及具有改善脂质代谢作用或抗肥胖作用的食品、医药品或饲料。
背景技术
脂质代谢是指以来源于食品的甘油三酯为主体的脂肪在机体内的异化(分解)、同化(蓄积)过程,广义来说包括脂质的产能反应、脂肪酸的生物合成、酰基甘油的生物合成、磷脂的代谢、胆固醇的代谢等。
肥胖是指身体各部位的脂肪组织蓄积了过量的脂肪的状态,已知它与高血压、高脂血症、糖尿病、脑卒中、动脉硬化、心肌梗塞等有很深的关系。
抗肥胖,即作为肥胖的治疗或预防方法,可大致分为抑制能量摄取与促进能量消费两类方法。作为前者的方法,可有摄取或服用糖或脂肪的替代物如魔芋等食物纤维或匙羹藤Gymnema sylvestre(特开平6-343421)等抑制吸收物质或抑制食欲物质。作为后者的方法,有运动或者摄取或服用脂质代谢改善剂如辣椒辣素(特公平4-058303)或大豆多肽〔大豆蛋白质荣养研究会会志13,58-58(1992)〕等方法。然而,持续进行运动有困难,而辣椒辣素因为辣,有摄取量有限的问题。因此期待开发出有效的脂质代谢改善剂。
现在,对于家畜、家禽或养殖鱼来说,为促进其生长而给予浓厚的饲料,结果,这些家畜、家禽或养殖鱼发生脂质代谢异常。另外,宠物也有由于饲料过量摄取以及运动不足而产生的肥胖问题。
吴茱萸碱是从生药芸香科植物吴茱萸中提取的化合物[Journal ofPharmaceutical Sciences,7S,612-613(1986)]。
作为吴茱萸碱的药理作用,除利尿作用、发汗作用之外,已知还可作为寒症改善剂(特开平4-305527)、脑机能改善剂(特开昭63-287724)、抗炎症性外用剂(特开平6-312932)、强心剂(特开昭60-224622),还有血管舒张作用[European Journl of Pharmacology,215,277-283(1992)]、镇痛作用[Biol.Pharm.Bull,20(3),243-248(1997)]等,但它的改善脂质代谢作用或抗肥胖作用却并非已知。
吴茱萸次碱、脱氢吴茱萸碱、羟基吴茱萸碱与吴茱萸碱相同,都是从吴茱萸中得到的结构相似的化合物。而且,其中前2种化合物的生物活性也有与吴茱萸碱相同的血管舒张作用[European Journal ofPharmacology,257,59-66(1994)]。另外,吴茱萸次碱还具有与吴茱萸碱相同的镇痛作用[Biol.Chem.Bull,20(3),243-248(1997)]。然而,上述3种化合物中的任何一个,其改善脂质代谢作用或抗肥胖作用均非已知。
吴茱萸(Evodia rutaecarpa)为吴茱萸属植物,除一般作为健胃剂、利尿剂、镇痛剂使用之外,已知还可作为养发生发食品(特开昭61-1619)、含吴茱萸提取液的化妆品(特开昭59-122414)、酒精吸收抑制剂(特开平3-264534)、牙周病治疗剂发挥作用。然而,其改善脂质代谢作用或抗肥胖作用却非已知。
崖椒属(
Fagara)植物F.rhetza为印度尼西亚的传统药用植物,已知有治疗疟疾、痢疾、呕吐的效果[Chem.Pharm.Bull,40(9),2325-2330(1992)]。不过,其改善脂质代谢作用或抗肥胖作用也非已知。
花椒属(Zanthoxylum)植物Z.rhetsa、Z.budrunga,有报告其具有细胞毒性〔J.Nat.Prod.,42(6),697(1979)〕。不过,其改善脂质代谢作用或抗肥胖作用却非已知。
Araliopsis属植物A.tabouensis、A.soyauxii已知对淋病有效〔Planta medica,29,310-317(1976)〕。不过,其改善脂质代谢作用或抗肥胖作用并非已知。
发明的公开
本发明涉及具有改善脂质代谢作用或抗肥胖作用的食品,其中含有作为有效成分的通式(I)表示的化合物或其盐(以下总称为吴茱萸碱类):
上式中,>A-B-表示>CR1-NR2-(其中R1表示氢或羟基,R2表示氢或低级烷基,或R1与R2共同表示价键)或>C=N+(R3)-(其中R3表示低级烷基);当>A-B-为>CR1-NR2-时,n表示0;当>A-B-为>C=N+(R3)-时,n表示1,X-表示阴离子。
另外,本发明涉及以含有吴茱萸碱类作为有效成分制成的脂质代谢改善剂或抗肥胖剂,通过给与有效量的吴茱萸碱类而改善脂质代谢或抗肥胖的方法,吴茱萸碱类在制备用于改善脂质代谢或抗肥胖的药物组合物中的应用,以及由含有有效量的吴茱萸碱类与药理学容许载体组成、具有药理学容许给药形态的用于改善脂质代谢或抗肥胖的组合物。
另外,本发明涉及含有吴茱萸碱类作为有效成分组成的具有改善脂质代谢作用或抗肥胖作用的饲料。
此外,本发明涉及含有吴茱萸碱类作为有效成分组成的具有改善脂质代谢作用或抗肥胖作用的饲料添加剂,通过给以有效量的吴茱萸碱类而改善动物脂质代谢的方法或抗肥胖的方法,吴茱萸碱在制造用于改善脂质代谢或抗肥胖的饲料添加剂中的应用,吴茱萸碱在改善动物脂质代谢或抗肥胖方面的应用,或由含有有效量的吴茱萸碱与药理学容许的载体组成的具有药理学容许的给药形态的用于动物的改善脂质代谢或抗肥胖的组合物。
在通式(I)中各基团的定义方面,作为R2或R3的低级烷基,可以相同或不同、可以是直链或支链、碳原子数为1-6,例如可举出甲基、乙基、丙基、异丙基、丁基、仲丁基、叔丁基、戊基、新戊基、己基等,优选甲基。
作为阴离子,可举出氢离子、卤素离子、源于无机酸的阴离子、源于有机酸的阴离子等。作为卤素离子,可举出氟离子、氯离子、溴离子、碘离子等。作为源于无机酸的阴离子,可举出例如硝酸根离子、硫酸根离子、磷酸根离子、碳酸根离子等。作为源于有机酸的阴离子,可举出例如甲酸离子、醋酸离子、乳酸离子、柠檬酸离子、磷酸离子、谷氨酸离子等源于羧酸的阴离子。
作为盐,可举出酸加成盐,例如可举出盐酸盐、马来酸盐、酒石酸盐、柠檬酸盐等有机酸盐。
作为通式(I)表示的具体的吴茱萸碱类,可举出吴茱萸碱、吴茱萸次碱、去氢吴茱萸碱、羟基吴茱萸碱等。
吴茱萸碱可使用市售品(Kishida化学株式会社生产),也可以按例如特开昭52-77098号、特公昭58-434号公报[(R,S)-吴茱萸碱]或J.Chem.Soc.Chem.Commun,10,1092-1093(1982)(S)-吴茱萸碱]中记载的化学合成方法或从芸香科吴茱萸属的植物[吴茱萸(Evodia rutaecarpa)、石虎(E.officinalis)、臭檀(E.danielli)、楝叶吴茱萸(E.meliaefolia等)],崖椒属的植物(Fagara rhetza等)、花椒属植物(Zanthoxylum rhetsa、Z.budrunga、黄心花椒Z.flavum等)、Araliopsis属植物(Araliopsis tabouensis,A.soyauxii等)等含有吴茱萸碱的植物的植物体,按照例如Journal of Pharmaceutical Sciences.75,612-613(1986)中记载的方法提取并应用。
吴茱萸碱存在光学异构体,用化学合成法得到的是S构型、R构型两种异构体,自植物得到的是S构型体。本发明中可任意采用S构型异构体、R构型异构体以及它们的混合物,优选采用S构型异构体。
吴茱萸次碱可选用市售品(Kishida化学株式会社生产),也可选用例如特开昭53-77100、J.Org.Chem.,
50,1246-1255(1985)中记载的化学合成方法或芸香科的吴茱萸属植物(吴茱萸,楝叶吴茱萸等)、崖椒属植物(Fagara rhetza等)、花椒属(Zanthoxylum rhetsa、Z.limonella、全缘叶花椒Z.integrifoliolum)等含吴茱萸次碱的植物按例如Chem.Pharm.Bull.,
37,1820-1822(1989)记载的方法提取并应用。
上式中,X-表示阴离子,阴离子的含义与前面相同。
脱氢吴茱萸碱可按照例如J.Org.Chem.,
50,1246-1255(1985)中记载的化学合成方法,或按例如American Journal of Chinese Medicine10,75-85(1982)中记载的方法从芸香科吴茱萸属植物(吴茱萸、楝叶吴茱萸等)等含脱氢吴茱萸碱的植物的植物体提取并应用。
羟基吴茱萸碱是如式(V)所示的化合物。
羟基吴茱萸碱可按例如(日本)药学杂志(J.of the PharmaceuticalSociety of Japan),
82,619-626(1962)记载的方法从例如芸香科吴茱萸属的植物(吴茱萸等)、花椒属植物(Zanthoxylum rhetsa等)、Araliopsis属植物(A.tabouensis等)等含羟基吴茱萸碱的植物的植物体提取并应用。
本发明中,吴茱萸碱类可使用纯化品或纯品,不过作为食品、医药品、饲料、只要不含有不适当的杂质,也可以采用粗品或粗纯化的吴茱萸碱类。
作为粗品或粗纯化的吴茱萸碱类,可举出例如含有吴茱萸碱类的植物的叶、干、茎皮、根、果实等植物体,或自该植物体得到的含有吴茱萸碱类的粉碎物、浸膏、粗制物或纯化物,上述植物优选芸香科植物,更优选吴茱萸属植物(Evodia)、崖椒属植物(Fagara)、花椒属植物(Zanthoxylum)或Araliopsis属植物。
作为含有吴茱萸碱的植物的植物体,优选采用吴茱萸、Fagararhetza、Zanthoxylum rhetsa、Araliopsis tabouensis或楝叶吴茱萸等的果实或茎皮或根皮。
含有吴茱萸碱类的粉碎物,可通过将含有吴茱萸碱类的植物的植物体干燥后粉碎的方法得到。
含有吴茱萸碱类的浸膏,可通过将该粉碎物单独或组合使用水、甲醇、丙醇、丁醇等醇类,丙酮等亲水性溶剂或二乙醚、乙酸乙酯、氯仿、苯等有机溶剂提取。
吴茱萸碱类的粗纯化品或纯化品是将该粉碎物或该浸膏上样至以Diaion HP-20(注册商标;三菱化学公司生产)等多孔聚合物、SephadexLH-20(注册商标Pharmacia LKB生物技术公司生产)等葡聚糖凝胶(Sephadex)、正相硅胶、反相硅胶、聚酰胺、活性炭或纤维素等作为担体的柱层析或制备高效液相色谱,用薄层层析(展开剂:95%甲醇、显色剂:5%硫酸乙醇)确定目标成分,同时按其所在级分加以纯化,从而使吴茱萸碱类得以纯化。为得到吴茱萸碱类的纯化品或纯品,期望将上述操作进行适当组合并重复进行,必要时也可进行重结晶操作。
本发明的食品可通过向食品原料、特别是原来基本上不含吴茱萸碱类的食品原料中以纯品、纯化品、粗纯化品等形态或以脂质代谢改善剂或抗肥胖剂的形态加入吴茱萸碱类,吴茱萸碱类应加入0.001%以上,优选0.01-20%,更优选0.05%-1%,可按照一般的食品制造方法加工制造。
作为食品的种类,可举出果汁、清凉饮料、茶类、乳酸菌饮料、发酵乳、冷食品、乳制品(黄油、乳酪、酸奶、加工乳、脱脂乳等)、畜肉制品(火腿、香肠、汉堡包等)、鱼肉制品(鱼糕、鱼卷、油炸鱼丸子等)、蛋制品(蛋卷、蛋豆腐等)、点心类(蛋糕、果冻、快餐点心)、面包类、面类、咸菜类、熏制品、干菜、甜烹海味(佃煮)、腌制品、汤类、调制品等。
作为本发明食品的形态,只要含有吴茱萸碱类,除可以为冷冻食品、粉末食品、薄片状食品、瓶装食品、罐装食品、蒸馏罐食品(retort food)、胶囊状食品、药片状食品等形态之外,还可有例如蛋白质、糖类、脂肪、微量元素、维生素类、乳化剂、香料等配合成的自然流食、半消化营养食品以及成分营养食品、液剂等加工形态等,可以是任意形态。
本发明的食品作为健康食品、功能性食品,除可作为减肥食品外,还可用于脂肪肝、高血压、高脂血症、动脉硬化症、糖尿病、心肌梗塞等疾病的治疗、预防或改善。在这些情况下,优选按每日经口摄取吴茱萸碱类0.1-2000毫克的量来加工的食品。
本发明的脂质代谢改善剂或抗肥胖剂可以是片剂、散剂、细粒剂、颗粒剂、胶囊剂、糖浆剂、肠溶剂、锭剂、注射剂、输液等任意剂形。制剂的给药形态没有特别的限制,作为给药途径,可举出经口给药、静脉内给药、腹腔内给药、皮下给药、肌肉内给药等方式。其中优选经口给药。经口给药时,可将吴茱萸碱类纯品、纯化物、粗纯化物等直接给予,也可以与医药学容许的赋形剂共同制成片剂、散剂、细粒剂、颗粒剂、胶囊剂、糖浆剂等形态给予。作为赋形剂,可以使用山梨醇、乳糖、葡萄糖、乳糖、糊精、淀粉、结晶纤维素等糖类,碳酸钙、硫酸钙等无机物,蒸馏水、芝麻油、玉米油、橄榄油、棉子油等常用的任意赋形剂。制剂化的时候,可以使用粘合剂、润滑剂、分散剂、混悬剂、乳化剂、稀释剂、缓冲剂、抗氧化剂、细菌抑制剂等添加剂。用作为注射剂时,可以加入适当的缓冲剂、等张剂,或采用以植物油等油溶解之后的溶液。
给药量可因年龄、性别、疾病的程度,给药形态、给药次数、剂型等而各不同,但以成人为对象经口给药时,按0.1-2000mg/日,分1-4次给予有效成分吴茱萸碱类是适当的。另外,如果有必要,也可以采用上述范围以外的给药量。
本发明的脂质代谢改善剂或抗肥胖剂可用于脂肪肝、高血压、高脂血症、动脉硬化症、糖尿病、心肌梗塞等疾病以及肥胖的治疗以及预防。
作为本发明中的饲料,只要是对哺乳类、鸟类、爬行类、两栖类、鱼类等动物有改善脂质代谢作用或抗肥胖作用的饲料均可,例如可举出犬、猫、鼠等宠物用饲料,牛、猪等家畜用饲料,鸡、火鸡等家禽用饲料,真鲷、黄尾笛鲷等养殖鱼用饲料。
本发明的饲料添加剂可以将吴茱萸碱类以纯品、纯化品、粗纯化品等形态使用,也可以使用含有吴茱萸碱类的植物的植物体本身或从该植物体得到的含有吴茱萸碱的粉碎物、浸膏、粗纯化物或纯化物。如果有必要,也可以将该饲料添加剂按常法混合或溶解,加工制造成例如粉末、颗粒、丸剂、片剂、各种液剂的形态并使用。
本发明的饲料是将上述饲料配加剂配合入饲料而得到的。本发明饲料添加剂在饲料中的配合量可根据饲料种类、通过摄取该饲料期待获得的效果等进行适当选择。一般来说,可以向饲料原料,特别是原来基本上不含有吴茱萸碱类的饲料原料中加入本发明的饲料添加剂,使吴茱萸碱类含量在0.001%以上,优选0.01-20%,更优选0.05%-1%,并按照一般的饲料制造方法制造加工得到本发明的饲料。试验例1对小鼠内脏脂肪的效果
采用含有吴茱萸碱的饲料进行以下实验。
9周龄的C3H系雄性小鼠,用按表1组成配制的未加入吴茱萸的饲料A预饲8日。预饲结束之后,每组4只,分为2组。一组(饲料A摄取组)小鼠给与饲料A,另一组(饲料B摄取组)给与按表1组成配制的加入吴茱萸碱的饲料B,分别给与12日,禁食1日后,第13日处死。处死后,迅速摘出肾脏周围以及睾丸周围的脂肪,测定其重量。另外,每日测定试验期内的饲料摄取量。
表1
结果如表2所示。
饲料A%(w/w) | 饲料B%(w/w) | |
吴茱萸碱 | - | 0.03 |
酪蛋白 | 20 | 20 |
豚脂 | 10 | 10 |
蔗糖 | 10 | 10 |
复合矿物质 | 4 | 4 |
复合维生素 | 1 | 1 |
纤维素粉末 | 2 | 2 |
胆酸钠 | 0.125 | 0.125 |
氯化胆碱 | 0.2 | 0.2 |
玉米淀粉 | 52.675 | 52.645 |
表2
饲料A摄取组 | 饲料B摄取组 | |
平均饲料摄取量(g/日) | 3.30±0.08* | 3.21±0.09 |
睾丸周围脂肪(g) | 0.246±0.019 | 0.219±0.010 |
肾周围脂肪(g) | 0.116±0.01a | 0.083±0.08 |
*:平均值的标准差
a:相对于饲料B摄取组,p<0.05,为有显著差异
从脂肪量上来看,饲料B摄取组与饲料A摄取组相比,肾周围脂肪明显减少。另外,睾丸周围的脂肪量,饲料B摄取组也表现出减少的倾向。饲料摄取量两组间没有明显差异,没有饲料嗜好上的问题。由此可见,吴茱萸碱有改善脂质代谢作用或抗肥胖作用。试验例2对大鼠体重、内脏脂肪、脂肪分解的效果
采用含有按参考例1制得的吴茱萸浸膏进行以下实验。
4周龄的SD系雄性大鼠,以按表3组成配制的未加入吴茱萸浸膏的低脂肪饲料C预饲7日。预饲结束之后,按体重,将无显著差异的3只为1组,共分9组。各组中有1只禁食1日后饲以加入吴茱萸浸膏的饲料E,各组另2只分别按组内属于进食饲料E组的鼠的进食量饲以低脂肪饲料C以及高脂肪饲料D,进行成对饲养。由于饲料C与饲料E中脂肪含量不同,在等量摄取时,从饲料C中摄取的热量为从饲料E摄取热量的78%。上述饲养进行21日,禁食1日之后,处死。处死后迅速摘出肾脏周围以及睾丸周围的脂肪,并测定其重量。另外,通过以下方法测定脂肪分解活性。此外,试验期内每天测定体重。脂肪分解活性的测定:
各大鼠肾周围脂脏以剪刀剪50次剪碎,称取100-300毫克后,加入含有2%白蛋白的Krebs-Ringer碳酸氢盐缓冲液(以下简称为KRB缓冲液1.9mL,将试样调制成为2份检品,上述试样在37℃反应5分钟。向1个检品中加入含有0.2毫克/毫升去甲肾上腺素-2%白蛋白的KRB缓冲液0.1毫升,37℃反应1小时,为反应样。另1检品中加入含2%白蛋白的KRB缓冲液0.1毫升,冰冷却5分钟,为反应前对照样。各样品分别以0.45微米的膜状滤器(Millipore公司出品)过滤,用市售的测定试剂盒(Determiner NEFA,协和Medex公司出品)测定滤液中游离脂肪酸量,计算分解的甘油三酯量。从反应样值减去反应前对照样值即为活性值。
表3
结果如表4所示。
饲料C%(w/w) | 饲料D%(w/w) | 饲料E%(w/w) | |
吴茱萸提取液(参考例1) | - | - | 1.35 |
酪蛋白 | 20 | 20 | 20 |
豚脂 | 5 | 15 | 15 |
玉米油 | 5 | 15 | 15 |
蔗糖 | 30 | 30 | 30 |
复合矿物质 | 4 | 4 | 4 |
复合维生素 | 1 | 1 | 1 |
纤维素粉 | 2 | 2 | 2 |
氯化胆碱 | 0.2 | 0.2 | 0.2 |
玉米淀粉 | 32.80 | 12.80 | 11.45 |
吴茱萸碱浓度(%w/w) | 0 | 0 | 0.02 |
表4
摄取饲料C组 | 摄取饲料D组 | 摄取饲料E组 | |
热量摄取量 | 1101.8±16.0* | 1421.6±21.7 | 1410.9±21.4 |
(Cal/21日) | |||
结束时体重(g) | 215.2±3.6 | 252.7±3.5c | 226.8±4.3 |
体重增加量(g) | 101.3±2.6a | 138.2±2.9 | 112.3±3.8 |
体重增加量/热量摄取量g/Cal | 0.0920±0.0020b | 0.0972±0.0011c | 0.0797±0.0029 |
睾丸周围脂肪(g) | 31.9±0.25b | 4.06±0.24c | 2.28±0.14 |
肾周围脂肪(g) | 3.70±0.30 | 5.68±0.39c | 3.06±0.29 |
脂肪分解活性(μmol/g/hr) | 2.75±0.81b | 3.19±0.34b | 6.35±0.93 |
*平均值的标准差
相对于摄取饲料E组,a:P<0.05,b:P<0.01,C:P<0.001,为有显著
差异
从体重来说,摄取饲料E组与摄取饲料D组相比,摄取热量几乎相同,而体重增加得到显著抑制。另外,相对于热量摄取量的体重增加量不仅明显比摄取饲料D组要少,而且也明显比总摄取热量少的摄取饲料C组少。
从脂肪量来说,摄取饲料E组与摄取饲料D组相比,肾周围和睾丸周围脂肪量显著减少。另外,与总摄取热量少的摄取饲料C组相比,睾丸周围脂肪量显著减少,肾周围也显示了减少倾向。
从脂肪分解活性来说,摄取饲料E组与摄取饲料C和D的组相比,有显著增加,脂质代谢得到改善。由此可见,含有吴茱萸碱的吴茱萸浸膏具有改善脂质代谢作用或抗肥胖作用。
实施发明的最佳方式实施例1
按以下配料比制作蛋糕(30个份)。
低筋面粉 100g
淀粉 74g
水 14g
吴茱萸碱 0.6g
发酵粉 2小匙
盐 1/2小匙
蛋 1个
黄油 80g
牛乳 2大匙
蜂蜜 少量实施例2
按以下配料比制做清凉饮料(10瓶份)。
吴茱萸碱 1g
维生素C 1g
维生素B1 5mg
维生素B2 10mg
维生素B6 25mg
糖浆 150g
柠檬酸 3g
香料 1g
水加至1000mL。实施例3
按以下配料比制作面包(4斤份)。
吴茱萸碱 2.4g
强力面粉 1kg
砂糖 50g
食盐 20g
脱脂乳粉 20g
油脂(Shortening) 60g
酵母(鲜) 30g
酵母养料(Yeast food) 1g
水 650g实施例4
按以下配比按常法制备片剂(每片300mg)
吴茱萸碱 10mg
乳糖 230mg
玉米淀粉 30mg
合成硅酸铝 12mg
羧甲基纤维素钙 15mg
硬脂酸镁 3mg实施例5
按以下配比按常法制备散剂(每包1000mg)。
吴茱萸碱 10mg
乳糖 800mg
玉米淀粉 190mg实施例6
按以下配比制备硬胶囊剂(每胶囊360mg)
吴茱萸碱 10mg
乳糖 230mg
玉米淀粉 100mg
羟丙基纤维素 20mg
向10mg吴茱萸碱内加入230mg乳糖和100mg玉米淀粉混合,向其中加入20mg羟丙基纤维素的水溶液并捏和。然后用挤出制粒机以常法制成颗粒。将上述颗粒填充于明胶硬胶囊内制成硬胶囊剂。实施例7
按以下配比制备软胶囊剂(每胶囊170mg)
吴茱萸碱 10mg
大豆油 160mg
将10mg吴茱萸碱加入160mg大豆油内,混合。然后采用转模(Rotary dies)式自动成形机以常法填充于软胶囊内制成软胶囊剂。实施例8
按以下配料比制成小鼠(小白鼠)用饲料(1个月份)。
吴茱萸碱 0.03g
酪蛋白 20g
豚脂 10g
蔗糖 10g
复合矿物质 4g
复合维生素 1g
纤维素粉 2g
胆酸钠 0.125g
氯化胆碱 0.2g
玉米淀粉 52.645g实施例9
按以下配比以常法制备散剂(每包1000mg)
吴茱萸次碱 10mg
乳糖 800mg
玉米淀粉 190mg实施例10
按以下配比制备软胶囊剂(每胶囊170mg)。
脱氢吴茱萸碱 10mg
大豆油 160mg
将10mg脱氢吴茱萸碱加入160mg大豆油中混和。然后以转模式自动成型机按常法填充于软胶囊内,制成软胶囊剂。实施例11
按以下配比制成小鼠(小白鼠)用饲料(1个月份)。
羟基吴茱萸碱 0.03g
酪蛋白 20g
豚脂 10g
蔗糖 10g
复合矿物质 4g
复合维生素 1g
纤维素粉末 2g
胆酸钠 0.125g
氯化胆碱 0.2g
玉米淀粉 52.645g实施例12
按以下配比制造1000mL茶饮料。
吴茱萸浸膏(参考例1) 5g
茶叶 15g
以热水1000mL溶出。实施例13
按以下配比以常法制备片剂(每片300mg)。
吴茱萸浸膏(参考例1) 50mg
乳糖 190mg
玉米淀粉 30mg
合成硅酸铝 12mg
羧甲基纤维素钙 15mg
硬脂酸镁 3mg实施例14
按以下配比制造口香糖(30个份)。
吴茱萸浸膏(参考例1) 1g
口香糖基料 25g
砂糖 63g
淀粉浆 10g
香料 1g实施例15
按以下配比制造糖果(20个份)。
吴茱萸浸膏(参考例1) 1g
砂糖 80g
淀粉浆 20g
香料 1g实施例16
按以下配比制备软胶囊剂(每胶囊170mg)
Fagara rhetza浸膏(参考例2) 50mg
大豆油 120mg
向120mg大豆油内添加Fagara rhetza浸膏,混合。以转模式自动成型机以常法充填软胶囊,制得软胶囊剂。实施例17
按以下配比制造桔子酱。
Zanthoxylum rhetsa浸膏(参考例3) 7g
酸橙皮 500g
砂糖 200g
酸橙果汁 1个量实施例18
按以下配比制造真鲷鱼用饲料。
Araliopsis tabouensis浸膏(参考例4) 10g
鱼粉 25g
鸡肉粉 100g
肉骨粉 150g
浓缩鱼汁 25g
大豆粕 260g
小麦粉 125g
玉米 250g
小麦胚芽 40g
紫花苜蓿粉 40g
食盐 5g
抗氧化剂 20g参考例1吴茱萸浸膏的制备方法
向吴茱萸果实2.5kg中加入10L乙醇,冷浸2日。回收提取液后,重复2次同样操作,得到30L乙醇提取液。将其以滤布(Hoechst公司制造,Miracloth)过滤,滤液在减压下浓缩至干,得100g浸膏。参考例2 Fagara rhetza浸膏的制备方法
向Fagara rhetza茎皮200g中加入1L甲醇,冷浸2日。回收提取液后,继续继续2次同样操作,得到3L甲醇提取液。将其以滤布(Hoechst公司制造,Miracloth)过滤,滤液在减压下浓缩至干,得19.6g浸膏。参考例3 Zanthoxylum rhetsa浸膏的制备方法
向Zanthoxylum rhetsa根皮200g中加入1L乙醇,冷浸2日。回收提取液后,重复2次同样操作,得到3L乙醇提取液。将其以滤布(Hoechst公司制造,Miracloth)过滤,滤液在减压下浓缩至干,得7.1g浸膏。参考例4 Araliopsis tabouensis浸膏的制备方法
向Araliopsis tabouensis茎皮250g中加入1L氯仿,冷浸2日。回收提取液后,重复2次同样操作,得到3L氯仿提取液。将其以滤布(Hoechst公司制造,Miracloth)过滤,滤液在减压下浓缩至干,得9.6g浸膏。参考例5吴茱萸碱的定量
将参考例1~4得到的浸膏用乙醇溶解,浓度为0.01%(w/v),将此溶液10μL以高效液相色谱仪(岛津公司制,ODS柱:4.6mm I.D.25cm,流动相:50%乙腈水溶液,检出波长254nm)定量。
结果如表5所示。
表5
植物名 | 干浸膏中吴茱萸碱的含量%(w/w) |
吴茱萸(参考例1) | 1.13 |
Fagara rhetza(参考例2) | 2.94 |
Zanthoxylum rhetsa(参考例3) | 0.014 |
Araliopsis tabouensis(参考例4) | 0.018 |
工业上的实用性
根据本发明,可以提供具有改善脂质代谢作用或抗肥胖作用的食品、医药品或饲料。
Claims (20)
2.根据权利要求1记载的食品,是在基本上不含有吴茱萸碱类的食品原料中添加吴茱萸碱类制成的。
3.根据权利要求1记载的食品,是在基本上不含有吴茱萸碱类的食品原料中添加含有吴茱萸碱类的植物的植物体或自该植物体得到的含有吴茱萸碱的粉碎物、浸膏、粗纯化物或纯化物制成的。
4.根据权利要求3记载的食品,其中所说的含有吴茱萸碱类的植物是芸香科植物。
5.根据权利要求3记载的食品,其中所说的含有吴茱萸碱类的植物,是选自吴茱萸属、Fagara属、花椒属、以及Araliopsis属的植物。
6.脂质代谢改善剂或抗肥胖剂,含有吴茱萸碱类作为有效成分。
7.改善脂质代谢的方法或抗肥胖方法,是通过给与有效量的吴茱萸碱类而实现的。
8.吴茱萸碱类在制备用于改善脂质代谢或抗肥胖的药物组合物中的应用。
9.吴茱萸碱类在改善脂质代谢或抗肥胖中的应用。
10.用于改善脂质代谢或抗肥胖的组合物,是由有效量的吴茱萸碱类与药理学容许的载体以药理学容许的给与形式制成的。
11.具有改善脂质代谢作用或抗肥胖作用的饲料,含有吴茱萸碱类作为有效成分。
12.根据权利要求11记载的饲料,是在基本上不含有吴茱萸碱类的饲料原料中添加吴茱萸碱类制成的。
13.根据权利要求11记载的饲料,是在基本上不含有吴茱萸碱类的饲料原料中添加含有吴茱萸碱类的植物的植物体或自该植物体得到的含有吴茱萸碱的粉碎物、浸膏、粗纯化物或纯化物制成的。
14.根据权利要求13记载的饲料,其中所说的含有吴茱萸碱类的植物是芸香科植物。
15.根据权利要求13记载的饲料,其中所说的含有吴茱萸碱类的植物,是选自吴茱萸属、Fagara属、花椒属、以及Araliopsis属的植物。
16.具有改善脂质代谢作用或抗肥胖作用的饲料添加剂,含有吴茱萸碱类作为有效成分。
17.改善动物的脂质代谢的方法或抗肥胖方法,是通过给与有效量的吴茱萸碱类而实现的。
18.吴茱萸碱类在制备用于改善脂质代谢或抗肥胖的饲料添加剂中的应用。
19.吴茱萸碱类在改善动物的脂质代谢或抗肥胖中的应用。
20.用于动物的改善脂质代谢或抗肥胖的组合物,是由有效量的吴茱萸碱类与药理学容许的载体以药理学容许的给与形式制成的。
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CN107375281A (zh) * | 2017-08-04 | 2017-11-24 | 上海华堇生物技术有限责任公司 | 羟基吴茱萸碱的药物用途 |
JP2019034926A (ja) * | 2017-08-10 | 2019-03-07 | 小林製薬株式会社 | 加齢性肥満改善剤及び脂肪分解力改善剤 |
CN109288843A (zh) * | 2018-11-19 | 2019-02-01 | 青岛大学 | 吴茱萸碱的降血脂作用 |
KR102294072B1 (ko) * | 2020-11-19 | 2021-08-26 | (주)알피바이오 | 식물성 츄어블 연질캡슐용 조성물 및 이를 통해 형성된 식물성 츄어블 연질캡슐 |
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JPS6046086B2 (ja) * | 1982-12-28 | 1985-10-14 | 一丸ファルコス株式会社 | ゴシユユ抽出液含有化粧料 |
JPS60224622A (ja) * | 1984-04-23 | 1985-11-09 | Mitsubishi Chem Ind Ltd | 強心剤 |
DE3520761A1 (de) * | 1984-06-11 | 1985-12-12 | Ajinomoto Co., Inc., Tokio/Tokyo | Verwendung von vanillylamin oder vanillylamiden zur foerderung des fettstoffwechsels |
JPS611619A (ja) * | 1984-06-14 | 1986-01-07 | Osaka Chem Lab | 育毛養毛食品 |
JPS62148426A (ja) * | 1985-12-23 | 1987-07-02 | Rooto Seiyaku Kk | 歯周病治療剤 |
JPS63287724A (ja) * | 1987-05-20 | 1988-11-24 | Tsumura & Co | 脳機能改善剤 |
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JPH0458303A (ja) * | 1990-06-28 | 1992-02-25 | Toshiba Corp | プログラマブルコントローラ |
EP0498890B1 (en) * | 1990-08-16 | 1996-12-11 | Iatron Laboratories, Inc. | Central nervous system activator |
JPH04305527A (ja) * | 1991-03-29 | 1992-10-28 | Kanebo Ltd | 冷え症改善剤 |
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JPH06343421A (ja) * | 1993-06-08 | 1994-12-20 | Yasutake Hichi | 肥満防止能を有する高脂質食品 |
JP3452986B2 (ja) | 1994-09-13 | 2003-10-06 | 花王株式会社 | 脂肪分解促進剤 |
KR100203456B1 (ko) * | 1995-06-20 | 1999-06-15 | 한승수 | 디하이드로에보디아민-에이치씨1를 유효성분으로 함유하는 알츠하이머병에 의한 치매 치료제 |
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1997
- 1997-06-12 KR KR1019980700875A patent/KR19990036207A/ko not_active Application Discontinuation
- 1997-06-12 US US09/011,016 patent/US5998421A/en not_active Expired - Lifetime
- 1997-06-12 CN CN97190700A patent/CN1195269A/zh active Pending
- 1997-06-12 WO PCT/JP1997/002034 patent/WO1997047209A1/ja not_active Application Discontinuation
- 1997-06-12 TW TW086108110A patent/TW464495B/zh not_active IP Right Cessation
- 1997-06-12 JP JP50144998A patent/JP3938942B2/ja not_active Expired - Lifetime
- 1997-06-12 EP EP97926235A patent/EP0852117A4/en not_active Withdrawn
- 1997-06-12 CA CA002229077A patent/CA2229077C/en not_active Expired - Lifetime
- 1997-06-12 AU AU31067/97A patent/AU724098B2/en not_active Ceased
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1999
- 1999-09-15 US US09/395,992 patent/US6214831B1/en not_active Expired - Lifetime
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2000
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105873564A (zh) * | 2013-10-30 | 2016-08-17 | 尤尼根公司 | 皮肤护理组合物及其使用方法 |
CN105873564B (zh) * | 2013-10-30 | 2021-01-19 | 尤尼根公司 | 皮肤护理组合物及其使用方法 |
Also Published As
Publication number | Publication date |
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EP0852117A4 (en) | 1999-02-03 |
CA2229077A1 (en) | 1997-12-18 |
CA2229077C (en) | 2007-09-25 |
WO1997047209A1 (fr) | 1997-12-18 |
TW464495B (en) | 2001-11-21 |
US5998421A (en) | 1999-12-07 |
US6214831B1 (en) | 2001-04-10 |
KR19990036207A (ko) | 1999-05-25 |
JP3938942B2 (ja) | 2007-06-27 |
AU724098B2 (en) | 2000-09-14 |
CN1312075A (zh) | 2001-09-12 |
EP0852117A1 (en) | 1998-07-08 |
AU3106797A (en) | 1998-01-07 |
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