TW200902033A - Neuroblast proliferate accelerant and nerve protuberance extend accelerant - Google Patents

Neuroblast proliferate accelerant and nerve protuberance extend accelerant Download PDF

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TW200902033A
TW200902033A TW097110697A TW97110697A TW200902033A TW 200902033 A TW200902033 A TW 200902033A TW 097110697 A TW097110697 A TW 097110697A TW 97110697 A TW97110697 A TW 97110697A TW 200902033 A TW200902033 A TW 200902033A
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neuroblast
acid
agent
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TWI465237B (en
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Junji Tanaka
Hiroshi Shi-Moda
Hiromichi Murai
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Sinphar Pharmaceutical Co Ltd
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Abstract

This invention provides a Neuroblast proliferate accelerant, the Neuroblast proliferate accelerant can activate the Neuroblast to proliferate and activate wherein a nerve protuberance to extend, even the Neuroblast is in healthy stage, the Neuroblast proliferate accelerant can still activate the Neuroblast to differentiate to a neuron, so as to prevent from the brain degeneration, and even to improve the function of the brain, the characteristic of the Neuroblast proliferate accelerant is to extract a phenylethanoid glycosides of Cistanche as a active principle, the phenylethanoid glycosides includes at least a echinacoside and an acteoside. The Neuroblast proliferate accelerant can apply to the drug, external use ointment, beverage and feed of the human kind and mammiferous animal.

Description

200902033 九、發明說明: 【發明所屬之技術領域】 本發明係一種神經芽細胞(Neuroblast,又稱神經 母細胞、成神經細胞)增殖促進劑及神經突起伸展劑, 本發明可廣泛應用於包括人類在内之哺乳類動物藥 品、皮膚外用劑及食品中。 【先前技術】 按’自古以來在醫學上已確效,列當科 草本植物的新鮮莖對於不孕症、陽痿、便秘等疾病有相 當療效(請參考專利文獻1),另外,列當科草本植物的 新鮮莖對於血液及腎臟相當有益。這些多年生寄生草本 植物廣泛栽種於中國西北地方,有些地方稱它們為“沙 漠人參”,而列當科草本植物中,又以全寄生植物管花 肉夜蓉 Cistanche tubulosa (Schrenk.) ¥igh%氣後最 大宗。 而曰本子者針對列當科(以对如植物之化學 分及藥理活性進行—系統研究,研究結果發現,列當科 ^中的苯乙醇_化合物為—主要活性成分(例如, j考非糊讀卜3),岭乙醇脑化合物可作為有 =的麻劑、代謝促進劑、記憶改善劑及性慾促進劑 ^引起1學界針料縣乙醇脑化合㈣醫學特性 發生= 卜之1,其結果顯示,給予大腦 之大腦恢復其1另r類化合物後,可使原本病變 力月b,另外,請參見非專利文獻4,將一 200902033 神經芽細胞加入一 TNFa使該神經芽細胞發生病變,再加 入5亥笨乙醇苷類化合物後,該神經芽細胞之神經突起的 伸展可恢復至原本正常狀態。 專利文獻1 :日本特開2004-250449號公報 非專利文獻 1 : Sato T, et al. Yakugaku Zasshi, 1985, 105(12): 1131 非專利文獻 2 : Jimenez C.,et al. Nat. Prod· Rep., 1994, 11 (6): 591 非專利文獻 3 : Cometa F.,et al. Fitoterapia, 1993, 64 (3): 195 非專利文獻 4 : Deng Min, et al. Pharmacoe Sin, 2004, 25 (10): 1276-1284 惟’上述專利文獻1雖然發現在大腦功能發生病變 情況下,透過給予一苯乙醇苷類化合物可以使大腦功能 得以恢復,但是在專利文獻1中完全沒有記載在大腦發 生病變前苯乙醇苷類化合物可以提高大腦功能之作用, 另外’上述非專利文獻4中雖然記載有在使該神經芽細 胞發生病變之後,透過給予苯乙醇苷類化合物可使其神 經突起伸展從進而使大腦恢復功能,但是在非專利文獻 4中對下列情況則一無所知:在該神經芽細胞沒有發生 病變情況下’透過加入苯乙醇皆類化合物,可以使該神 經芽細胞增殖,並且可使該神經芽細胞之神經突起伸展。 由此可見,上述習用方式仍有諸多缺失,實非一良 善之方法,亟待加以改良。 【發明内容】 200902033 有馨於上述習用之缺點,因此,發明人依據多年來 從事此課題之相關經驗,乃經過長久努力研究與實驗, 並配合相關學理,終於開發設計出本發明之一種「神經 芽細胞增殖促進劑及神經突起伸展劑」。 在前述之資料背景下,發明人發現了下列事實:在 沒有發生病變之神經芽細胞(SK-N-SH)中加入笨乙醇 苷類化合物或者含有苯乙醇苷類化合物的列當科植物 萃取物後,可促進神經芽細胞之增殖,同時可以促進神 經芽細胞之神經突起伸展,進而完成了本發明,換言 之’本發明目的在於提供一種神經芽細胞增殖促進劑和 神經突起伸展劑,即使在神經芽細胞沒有發生病變情況 下,該神經芽細胞增殖促進劑和神經突起伸展劑仍可促 進該神經芽細胞之增殖,並可以促進神經芽細胞的神經 突起的伸展,由此促使該神經芽細胞分化為神經細胞, 即使在神經細胞發生變性之情況下,申經芽細胞增殖 促進劑和神經突起伸展劑也可以有效地防止神經細胞 之減少,從而可以有效地預防由大腦引起之衰老,同時 進一步提高大腦功能。 為了解决上述問題,作為第一發明之神經芽細胞增 進別#特徵在於該神經芽細胞增殖促進劑以苯乙 醇苦類化^物為有效成分。另外’該神經芽細胞增瘦促 進劑含有松果’和類葉升麻芽中的至少—種作為所 化合物’更重要的是,該苯乙醇確化合 物係含有松果料及類葉升歸兩者。 卜作為第一發明之神經芽細胞增殖促進劑,其 200902033 特徵在於該神經芽細胞增殖促進劑係以一列當科植物 之萃取物為有效成分,該萃取物中含有苯乙醇^類化合 物作為有效成分’該苯乙醇翻貞化合物係含有松果菊^ 及類葉升料其巾至少-種,並且更重要的是,該萃取 物中含有松果料及類葉升㈣兩者作為所述笨 苷類化合物。 — 而,作為第三發明之神經突起伸展劑,其特徵在於 該神經突起伸展劑係以一苯乙醇芽類化合物為有效成 分,該苯乙醇·貞化合物係含有松果菊瓶類葉升麻苦 其*中至少-種’並且更重要的是,該萃取物中含有松果 菊苷及類葉升麻苷兩者作為所述苯乙醇苷類化合物。 該神經突起伸展劑係含有松果菊普及類葉升麻苦 中至少-種作為所述苯乙醇普類化合物,其中,該神經 =起伸展劑含有松果㈣及賴升麻料者作為所述 苯乙醇苦類化合物,而作為第四發明的神經突起伸展 劑’其特徵在於鱗經突起伸展船謂t科植物之萃^ 物為有效成分,另外,該萃取物中係含有苯乙醇苦類化 合物作為有效成分’又,重要的是,該萃取物中含有松 果菊苦及類葉升麻皆中的至少一種作為所述苯乙醇苷 類化物’並且更重要的是,該萃取物巾含有松果菊普 及類葉升歸兩者作為該苯乙_類化合物。 上述第一發明及第二發明之神經芽細胞增殖促進 劑即使在神經芽細胞沒有發生病變情況下,該神經芽 細胞增殖促進劑亦可促進神經芽細胞之增殖,進而促進 神經芽細胞轉分化為神經細胞,藉此可進—步提高記憶 200902033 力、计异力及纖力等功能,另外,即使在由於衰老等 而引起神經細胞發生變性之情況下,透過使神經芽細胞 分化為神經細胞,可維持大腦功能’因此,可以有效地 預防大腦的衰老或認知症等腦障礙之發生。 而第三發明及第四發明之神經突起伸展劑,即使在 神經芽細胞沒有發生_情況下,該神經突起伸展劑仍 可促進神經突起之伸展’因此,對於正常的大腦,由於 該神經突起伸展劑還能夠建構很多突觸,所以可進一步 提高大腦功能’另-方面’即使由於衰料使神經細胞 發生變性’因該神經突起伸展劑可以快速建構用於彌補 該神經細胞功能之細,所以可轉持大腦功能,可有 效地預防大腦衰老或認知症等腦病變發生。 以下針對本發明進行詳細說明:本發明中之“神經 芽細胞增殖促進劑及神經突起伸展劑(以下也 “神經芽細胞增殖促進_,,),,,其特徵 产 醇·化合物為有效成分。另外,在本說明金中, 經芽細胞增殖促進鮮,’意指“神經芽細胞增殖促進 劑”和“神經突起伸展劑”這兩者。 此處,所述“苯乙醇苦類化合物,,是指下面的化學 式(1)所表示之化合物:200902033 IX. Description of the Invention: [Technical Field] The present invention is a neuroblast (Neuroblast, neuroblast) proliferation promoter and a neurite stretcher, and the present invention can be widely applied to humans. In mammalian medicines, skin external preparations and foods. [Prior Art] According to the 'medical effect since ancient times, the fresh stems of the herbaceous plants are quite effective for diseases such as infertility, impotence, constipation (please refer to Patent Document 1), and in addition, the herb The fresh stems of plants are quite beneficial for the blood and kidneys. These perennial parasitic herbaceous plants are widely cultivated in northwestern China. In some places, they are called “desert ginseng”, while in the herb family, the parasitic plant is Cistanche tubulosa (Schrenk.). After the biggest. However, the author of this book is directed to the group (for the chemical and pharmacological activities such as plants - systematic research, the results found that the phenylethyl alcohol in the group is the main active ingredient (for example, j test non-paste) Read Bu 3), Ling ethanol brain compound can be used as an anesthetic agent, a metabolic enhancer, a memory improver and a libido promoter ^ caused by a school of acupuncture county ethanol brain (4) medical characteristics occur = Bu 1, the results show After the brain of the brain is restored to its other r-type compound, the original lesion may be b. In addition, please refer to Non-Patent Document 4, adding a 200902033 nerve bud cell to a TNFa to cause the neuroblast cell to undergo lesions, and then adding After the chlorophyll-like compound, the neurite of the neuroblastic cell can be restored to the original normal state. Patent Document 1: Japanese Patent Laid-Open Publication No. 2004-250449 Non-Patent Document 1: Sato T, et al. Yakugaku Zasshi , 1985, 105(12): 1131 Non-Patent Document 2: Jimenez C., et al. Nat. Prod· Rep., 1994, 11 (6): 591 Non-Patent Document 3: Cometa F., et al. Fitoterapia, 1993, 64 (3): 195 Non-Patent Document 4: Deng Min, et al. Pharmacoe Sin, 2004, 25 (10): 1276-1284 However, the above Patent Document 1 found that in the case of a brain function lesion, administration of a phenylethanoid glycoside compound can be made. Although the function of the brain is restored, there is no description in Patent Document 1 that the phenylethanoid compound can enhance the function of the brain before the lesion occurs in the brain. In addition, the above-mentioned Non-Patent Document 4 describes that the nerve bud cells are caused to have lesions. Thereafter, by giving the phenylethanoid compound, the neurites can be stretched to restore the function of the brain, but in Non-Patent Document 4, the following cases are not known: in the case where the nerve bud has no lesion, 'through Adding a phenylethyl alcohol compound can proliferate the nerve bud cells and stretch the neurites of the nerve bud cells. Thus, there are still many defects in the above-mentioned conventional methods, which is not a good method and needs to be improved. [Summary of the Invention] 200902033 has the disadvantages of the above-mentioned conventional use, therefore, the inventor has relied on The related experience of this subject has been developed and designed with the long-term efforts and research, and finally developed a "nerve cell proliferation promoter and neurite outgrowth agent" according to the present invention. People have discovered the fact that the addition of a stupid glucoside compound or a lindenyl plant extract containing phenylethanoid glycosides to neuroblasts (SK-N-SH) without lesions can promote neuroblasts. Proliferation, at the same time, can promote the neurite outgrowth of nerve bud cells, thereby completing the present invention, in other words, the present invention aims to provide a neuroblast cell proliferation promoting agent and a neurite outgrowth agent, even in the case where the neuroblast cells are not diseased, The neuroblast cell proliferation promoting agent and the neurite outgrowth agent can still promote the proliferation of the nerve bud cells, and can promote the stretching of the neurites of the nerve bud cells, thereby promoting the differentiation of the nerve bud cells into nerve cells, even in the nerve cells. In the case of degeneration, the bud cell proliferation promoter and nerve Since extension agent may effectively prevent reduction of the nerve cell, thereby effectively preventing the aging caused by the brain, while further improving brain function. In order to solve the above problems, the neuroblast cell growth factor of the first invention is characterized in that the neuroblast cell proliferation promoting agent has a phenethyl alcohol compound as an active ingredient. In addition, the nerve bud cell thinning promoting agent contains at least one of pinecone and chlorophyll bud as the compound. More importantly, the phenylethylidene compound contains pinecone and leaf-like stalks. . As a neuroblast growth promoting agent of the first invention, the 200902033 is characterized in that the neuroblast cell proliferation promoting agent is an extract of a group of Denko plants, and the extract contains a phenylethyl alcohol compound as an active ingredient. 'The phenylethanol turning compound contains at least one species of echinacea^ and a leaf-like extract, and more importantly, the extract contains both pinecone and eugenoid (4) as the aglycon Compound. Further, the neurite outgrowth agent of the third invention is characterized in that the neurite outstretching agent is an phenanthrene bud compound which contains an echinacea bottle and leaves At least one of its * and more importantly, the extract contains both echinacoside and flavonoids as the phenylethanoid glycoside compound. The neurite outgrowth agent contains at least one species of the genus Echinacea in the genus Echinacea, wherein the nerve = the stretching agent contains pine nuts (4) and the lycopene as the a phenylethyl alcohol compound, and the neurite stretcher as the fourth invention is characterized in that the scallops are extended as an active ingredient of the t plant, and the extract contains a phenylalanine compound. As an active ingredient, it is important that the extract contains at least one of Echinacea and C. sinensis as the phenylethanide, and more importantly, the extract towel contains pine. Both of them are popular as the phenethyl compound. The neuroblast growth promoting agent according to the first invention and the second invention of the above invention can promote the proliferation of the neuroblast cells and promote the transdifferentiation of the neuroblast cells even if the neuroblast cells do not have a lesion. The nerve cells can further improve the functions of the memory 200902033, the calculation of the force, and the fiber strength. In addition, even if the nerve cells are degenerated due to aging, the nerve cells are differentiated into nerve cells. It can maintain brain function's. Therefore, it can effectively prevent brain disorders such as aging or cognitive diseases. The neurite outgrowth of the third invention and the fourth invention, even in the case where the nerve bud cells do not occur, the neurite stretcher can promote the stretching of the neurites. Therefore, for the normal brain, since the nerve protrusions are stretched The agent can also construct a lot of synapses, so it can further improve the brain's function 'other-side' even if the nerve cells are degenerated due to the failure of the nerves, because the neurite outgrowth can be quickly constructed to compensate for the fineness of the nerve cells, so Switching to brain function can effectively prevent brain lesions such as brain aging or cognitive symptoms. Hereinafter, the present invention will be described in detail. In the present invention, a "nerve cell proliferation promoting agent and a neurite outgrowth agent (hereinafter also referred to as "nerve cell proliferation promoting") are characterized in that an alcohol-producing compound is an active ingredient. Further, in the present specification, bud cell proliferation promotes freshness, which means both "neuroblast cell proliferation promoting agent" and "neurite stretcher". Here, the "benzyl alcohol compound" refers to a compound represented by the following chemical formula (1):

化学式(1 ) 200902033 對S亥苯乙醇苦類化合物不特別限定,例如,可以列 舉松果菊苷、類葉升麻苷、2,-乙醯基類葉升麻苷 (2'-acetylacteoside) 、 campneoside I 、 campneoside Π、管花肉蓰蓉苷A(cistantubuloside A)、管花肉蓰 蓉苷B1、管花肉蓰蓉苷B2、管花肉蓰蓉苷α、管花肉 蓰蓉苷C2、crenatoside、去咖啡醯基類葉升麻苷 (decaffeoylacteoside)、異類葉升麻苷 (isoacteoside)、紅景天苷(rhodioloside)、 syringalide A 3’-ot-L-rhamnopyranoside 和管花普 a (tubuloside A)等成分’另外,這些化合物可以只使用 其中一種,亦可合用二種以上。 另外,所述神經芽細胞增殖促進劑含有松果菊苷及 和類葉升麻苷中至少一種作為苯乙醇苷類化合物,這是 因為該等可以具有更顯著之神經芽細胞增殖作用及神經 犬起伸展作用,另外更重要的是,該神經突起伸展劑中 至少含有松果菊苷作為有效成分,這是因為其可以具有 更優異之神經突起伸展作用。 對獲彳于笨乙醇苷類化合物的方法沒有特別限定,可 以透過合成得到,也可以通過從植物中萃取,另外,在 從植物中萃取之情況下,對作為原料之植物沒有特別的 限定,例如:可以列舉生藥地黃、唇形科植物水蘇、胡 椒科胡椒屬撖欖枝果實及列當科草本植物等,又,可以 單獨使用一種所述植物來萃取苯乙醇苷類化合物,亦可 合用二種以上植物來萃取苯乙醇苷類化合物,而在這些 植物中,最佳選擇為列當科植物,係因為在列當科植物 200902033 中’作為苯乙醇轴化合物’除了松果菊苷和類葉升麻 苷之外’還含有2,_乙醯基類葉升麻苷 (2f-acetylacteoside) ' campneoside I > campneoside Π、管花肉楗蓉苷A(cistantubui〇side a)、管花肉蓰 蓉苷B1、管花肉蓰蓉苷B2、管花肉蓰蓉苷π、管花肉 蓰容苷C2 、去咖啡醯基類葉升麻苷 (decaffeoylacteoside)、異類葉升麻苷 (isoacteoside)、紅景天苷(rhodioloside)、The chemical formula (1) 200902033 is not particularly limited, and examples thereof include echinacoside, flavonoids, and 2'-acetylacteoside. Campneoside I, campneoside Π, Cistantubuloside A, Cistanche B., Cistanche B2, Cistanche, C. C. C. Crenatoside, decaffeeoylacteoside, isoacteoside, rhodiolaside, syringalide A 3'-ot-L-rhamnopyranoside and tubuloside A (Equivalent component) In addition, these compounds may be used alone or in combination of two or more. In addition, the nerve bud cell proliferation promoting agent contains at least one of echinacoside and cyanidin as a phenylethanoid glycoside, because these may have more significant neuroblast proliferation and nerve dogs. The stretching action and, more importantly, the neurite stretching agent contains at least echinacoside as an active ingredient because it can have a more excellent neurite stretching effect. The method for obtaining the stupid ethanol glycoside compound is not particularly limited, and it can be obtained by synthesis, or can be extracted from plants, and when extracted from plants, the plant as a raw material is not particularly limited, for example, : Listed as raw medicine Rehmannia glutinosa, Labiatae sylvestris, Piper pepper, Phyllostachys pubescens, and genus Herbaceous plants, etc., and one of the plants may be used alone to extract phenylethanoid glycosides, or may be used in combination Two or more plants are used to extract phenylethanoid glycosides, and among these plants, the best selection is from the genus Lepaceae, because in the genus 200902033, 'as a phenylethanol axis compound' except for echinacoside and In addition to the leaf asparagine, it also contains 2,2-ethyl ketones (2f-acetylacteoside) 'campneoside I > campneoside Π, cicadaubui 〇side a, tube flower meat Cistyl B1, Cistanche B. tubercosis, Cistanche tubulosa π, tube flower carmine glycoside C2, decaffeoyl acteoside (decaffeoylacteoside), heterologous leaf asparagine (isoacteoside) Salidroside (rhodioloside),

syringalide A SH-rhamnopyranoside 和管花皆 A (tubuloside A)等,具有更顯著之神經芽細胞增殖作用 及神經突起伸展作用,而此處,對用作原料之列當科植 物沒有特別限定,例如:可以列舉全寄生植物管花肉蓰 篆(Cistanche tubulosa)、m氣蓉 iCistanche salsa) > mUAeginetia indica) > % (i ^{Boschniakia ros57ca)等’但並不僅限於這些植物,另一方面,這些 植物可以只使用一種,也可以二種以上合用,在這些植 物中,最佳選擇為使用全寄生植物管花肉蓰蓉 {Cistanche tubulosa) ° 以下列出該苯乙醇苷類化合物中之成分與所述化學 式⑴之間關係。但是,crenMoside的結構式如下面 的化學式(2)所示。在所述製備物中基本上只含有少量 或微量的除了上述成分中的松果菊苷和類葉升麻苷之外 的其他成分。Syringalide A SH-rhamnopyranoside and tubeuloside A, etc., have more prominent neuroblast cell proliferation and neurite extension, and here, there is no particular limitation on the plant used as a raw material, for example: The whole parasitic plant Cistanche tubulosa, mConganche salsa) > mUAeginetia indica) > % (i ^{Boschniakia ros57ca), etc. 'but not limited to these plants, on the other hand, these Plants may be used alone or in combination of two or more. Among these plants, the best choice is to use the whole parasitic plant Cistanche tubulosa (Cistanche tubulosa). The components and contents of the phenylethanoid glycosides are listed below. The relationship between the chemical formulas (1). However, the structural formula of crenMoside is shown in the following chemical formula (2). The preparation contains substantially only a small amount or a small amount of other components than the echinacoside and the flavonoid in the above components.

化學式(2) Crenatoside 200902033 表1神經芽細胞增殖促進劑和神經突起伸展劑中 之主要成分: 成分 R1 R2 R3 R4 R5 R6 R7 2-Acety1acteos i de Ac Rha Cf H H OH OH Acteoside H Rha Cf H H OH OH Campneoside I H Rha Cf H 0Me(S/R) OH OH Campneoside II H Rha Cf H 0H(S/R) OH OH Cistantubuloside A H Rha Cf Glc H H OH 氺C i stantubu1os i des H Rha Cm/ Glc H OH OH B1/B2 c-Cm *C i stantubu1os i des H Rha Cf Glc 0H(S/R) OH OH C1/C2 Decaff eoy1ac teos i de H Rha H H H OH OH Echinacoside H Rha Cf Glc H OH OH Isoacteoside H Rha H Cf H OH OH Rhodioloside H H H H H H OH (Salidroside) Syringalide A 3-αΊ H Rha Cf H H H OH -rhamnopyranos i de Tubuloside A Ac Rha Cf Glc H OH OH Crenatoside 參見上述結構式 上述表1中所示化合物均可以通過高效液相色譜法 200902033 (HPLC)確認,此時,高效液相色譜法之條件如下所 示,其固定相為C18烷基矽烷鍵合矽膠,流動相為乙 腈-0.05 Μ磷酸水溶液(洗脫梯度為4: 96〇 15:85), 流速為1毫升/分鐘,檢測波長為330 nm。 本發明之第二種神經芽細胞增殖促進劑之特徵在於 以從列當科植物中所萃取的萃取物作為有效成分。 此處,對用作原料之列當科植物沒有特別限定,例 如’可以列舉全寄生植物管花肉蓰蓉 tubuJosa)、鹽^ t 肉薇蓉(Cistanche saJsa)、野氣 \ {Aeginetia indict)、奮{Boschniakia rossica) 等,但並不只限於這些植物。另外,這些植物可以只使 用一種’也可以二種以上合用,另外,在這些列當科植 物中’最佳選擇係使用全寄生植物管花肉蓰蓉 (Cistanche tubulosa) ° 更進一步來說,所述“萃取物”中較佳選擇含有苯 乙醇苷類化合物’此處,對該“苯乙醇苷類化合物,’沒 f 有特別限定’可以列舉松果菊苷、類葉升麻苷、2,-乙醯 、 甘、… 基類葉升麻苦(2’-acetylacteoside)、campneoside I、 campneoside II、管花肉链蓉苷 A(cistantubuloside A)、管花肉蓰蓉苷B1、管花肉蓰蓉苷B2、管花肉蓰蓉苷 C1、管花肉蓰蓉苷C2、crenatoside、去咖啡醯基類葉 升麻苷(decaffeoylacteoside)、異類葉升麻苦 (isoacteoside)、紅景天苷(rhodioloside)、Chemical formula (2) Crenatoside 200902033 Table 1 Main components of neuroblast cell proliferation promoter and neurite extensor: Component R1 R2 R3 R4 R5 R6 R7 2-Acety1acteos i de Ac Rha Cf HH OH OH Acteoside H Rha Cf HH OH OH Campneoside IH Rha Cf H 0Me(S/R) OH OH Campneoside II H Rha Cf H 0H(S/R) OH OH Cistantubuloside AH Rha Cf Glc HH OH 氺C i stantubu1os i des H Rha Cm/ Glc H OH OH B1/ B2 c-Cm *C i stantubu1os i des H Rha Cf Glc 0H(S/R) OH OH C1/C2 Decaff eoy1ac teos i de H Rha HHH OH OH Echinacoside H Rha Cf Glc H OH OH Isoacteoside H Rha H Cf H OH OH Rhodioloside HHHHHH OH (Salidroside) Syringalide A 3-αΊ H Rha Cf HHH OH -rhamnopyranos i de Tubuloside A Ac Rha Cf Glc H OH OH Crenatoside See above structural formula The compounds shown in Table 1 above can be passed by high performance liquid chromatography 200902033 (HPLC) confirmed that the conditions of high performance liquid chromatography were as follows, the stationary phase was C18 alkyl decane bonded tannin, and the mobile phase was acetonitrile-0.05 Μphosphoric acid. (Gradient elution 4: 96〇 15:85), flow rate of 1 ml / min, detection wavelength was 330 nm. The second neuroblast growth promoting agent of the present invention is characterized in that an extract extracted from a plant of the genus Leycote is used as an active ingredient. Here, the plant used as a raw material is not particularly limited, and for example, 'may be enumerated as the parasitic plant TubuJosa, salt C t (Cistanche saJsa), wild gas \ {Aeginetia indict), {Boschniakia rossica), etc., but not limited to these plants. In addition, these plants may be used alone or in combination of two or more. In addition, in these plants, 'the best choice is to use the full parasitic plant Cistanche tubulosa. Further, In the "extract", it is preferred to include a phenylethanoid glycoside compound. Here, the "phenylethanoid glycoside compound, 'f is not particularly limited'" may be exemplified by echinacoside or phylloside. - 醯, 甘, ... base class 2'-acetylacteoside, campneoside I, campneoside II, cistantubuloside A, tuberculosis B1, tube flower 蓰Rhizoma B, C. tuberculosis C1, Cistanche C. sinensis C2, crenatoside, decaffeoylacteoside, isoacteoside, rhodiolaside ),

syringalide A 3'-a-L-rhamnopyrano side 和管花苦 A (tubuloside A)等成分。此時’所述萃取物中可以只含 14 200902033 有-種上述成分,也可以含有二種以上成分之混合物, 其中,較佳選擇係含有松果菊苷及類葉升麻苷中至少一 種0 疋牡您早取物用作神經突起伸展劑之 情況下’解取物中較㈣擇為至少含有松果菊苦,係 因其可以具有更優異之神經突起伸展作用。 此時’對松果料之含量沒有_限定,以列當科 植物(例如’全寄生植物管花肉㈣(仏⑽也 ⑽))之萃取物之總品質作為1〇〇品質%時,松果 菊皆之含量為ίο品質%〜70品質%、較佳選擇為15品質 %〜50品質%、更佳選擇為2〇品質%〜4〇品 步 =,《〜38_。另外,對類_^; =又口有=·定’叫#科働萃㈣之總品質作為 輪,類葉升麻普之含量為1品質%〜40品質%、 =^為5品骸,品質%、更佳選擇為7品質%〜 貝心進一步選擇為8品«〜1〇品質%。 可以^葦對植物之被萃取部位沒有特別限定, _ ’、 、里等,只要可以達到所期望之效果即 ^德選擇係從列當科植物的莖、特別是新鮮的莖中 沒有原=之列當科植物中獲得萃取物之方法並 取法等 ,可以列舉溶劑萃取法、超臨界萃 田·?Λ 方面採用¥劑萃取法來進行萃取時,斟新伯 用的溶劑沒㈣概定,轉 200902033 刮另外’對所述極十生溶劑沒有特別限定,例如,可以 列舉水、曱醇、乙醇、異丙醇、丙酮、1,3-丁二醇、乙 一-、丙二醇、甘油、醋酸、醋酸乙酯、醚等。這些溶 劑I僅使用—種,亦可合用2種以上;較佳的是,隨後 進行稀釋、丨農縮、乾燥及純化等處理,因為透過處理可 獲仔含有高濃度之笨乙醇苷類化合物萃取物,另外,作 為純化方法’例如,可以列舉活性炭處理、樹脂吸附處 理、離子交換樹脂、液-液逆流分配等方法。 下面詳述該萃取物之具體製備之實施例,但萃取物 之製備方法並不限於以下實施例。 該萃取物之製造方法由萃取及純化二個階段所構 成;在第一階段中,將列當科植物(例如,全寄生植物 & ^匕肉e加加仏幼))的莖(較佳選擇為 4植物之新鮮莖)切成薄片、或粉碎成微粒或粉末狀, 接下來’將該薄片、或微粒或粉末浸潰在水或甲醇、乙 醇等低級脂肪醇等溶劑或混合溶液中,此時,在室溫下 進行萃取。接著,過濾該混合溶液,並在減壓條件下或 真空條件下濃縮該濾液,得到萃取物’而在第二階段中, 將該萃取物於水中加熱後,透過將該萃取物轉移至填充 有D-101型或AB—8型大孔吸附樹脂之吸附柱中進行純 化,此時,使用水、甲醇、乙醇、水與甲醇之混合液、 或者水與乙醇之混合液等作為沖洗溶劑,對來對該吸附 柱進行沖洗。沖洗時,可以將上述沖洗溶劑以一定濃度 之〉谷液形式來沖洗,亦可以將上述沖洗溶劑按照一濃度 梯度來沖洗,再收集沖洗液,經濃縮後,採用公知乾燥 16 200902033 ^法來,行絲,躲歧錢完錢, 取 物’该萃取物中含有笨乙醇鶴化合物。 j明之神經芽細胞增殖促進劑等亦可以用作各種 =“之原料,以作為飲时品,例如,可以列舉以 :用油(沙拉油)、點心類(口香糖 餅乾、零食,,片、小甜點等類(籌 c拉麵等)、乳製品(牛奶、雪糕二 等)、调味品(味增、大馨等)、湯類、飲料(果汁、咖Syringalide A 3'-a-L-rhamnopyrano side and tubeuloside A and other ingredients. At this time, the extract may contain only 14 of the above-mentioned components, and may also contain a mixture of two or more components. Among them, it is preferred to contain at least one of echinacoside and flavonoids. In the case where the oysters are used as a neurite outgrowth agent, the extract is more likely to contain at least the pineal chrysanthemum because it can have a superior neurite outgrowth. At this time, there is no limit to the content of the pine nut material, and the total quality of the extract of the plant (for example, 'whole parasitic plant tube flower (4) (仏(10) also (10))) is 1% by mass. The content of the fruit is ίο quality%~70% by mass, preferably 15% by mass to 50% by mass, more preferably 2% by mass%~4〇品步=, "~38_. In addition, the total quality of the class _^; = 口 有 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 % of quality, better choice is 7% by mass ~ Behind is further selected as 8 products «~1〇 quality%. There is no particular limitation on the extracted parts of the plant, _ ', 里, etc., as long as the desired effect can be achieved, that is, the selection of the genus from the stems of the plants, especially the fresh stems, is not The method for obtaining an extract from a plant of the genus Lepaceae, and the method of taking the method, etc., may be exemplified by a solvent extraction method, a supercritical extraction field, and a supercritical extraction method. When the extraction is carried out by using a solvent extraction method, the solvent used by the new agent is not (four) 200902033 There is no particular limitation on the above-mentioned polar solvent, and examples thereof include water, decyl alcohol, ethanol, isopropanol, acetone, 1,3-butylene glycol, ethyl-, propylene glycol, glycerin, acetic acid, and acetic acid. Ethyl ester, ether, etc. These solvents I may be used alone or in combination of two or more; preferably, they are subsequently subjected to dilution, agrotrophy, drying, and purification, because the treatment can be carried out by extracting a high concentration of stupid ethanol glycosides. Further, examples of the purification method include, for example, an activated carbon treatment, a resin adsorption treatment, an ion exchange resin, and a liquid-liquid countercurrent distribution. Specific examples of the preparation of the extract are detailed below, but the preparation method of the extract is not limited to the following examples. The method for producing the extract is composed of two stages of extraction and purification; in the first stage, the stem of the plant (for example, a parasitic plant & The fresh stems of 4 plants are selected to be sliced or pulverized into fine particles or powders, and then the sheet, or fine particles or powder is impregnated in water or a solvent or a mixed solution of a lower aliphatic alcohol such as methanol or ethanol. At this time, extraction was carried out at room temperature. Next, the mixed solution is filtered, and the filtrate is concentrated under reduced pressure or under vacuum to obtain an extract. In the second stage, after the extract is heated in water, the extract is transferred to the filled portion. Purification in the adsorption column of D-101 or AB-8 macroporous adsorption resin. At this time, use water, methanol, ethanol, a mixture of water and methanol, or a mixture of water and ethanol as a washing solvent. To flush the column. When rinsing, the rinsing solvent may be washed in a certain concentration of gluten solution, or the rinsing solvent may be washed according to a concentration gradient, and then the rinsing liquid is collected, and after concentration, the well-known drying method is used. Going through the line, hiding the money, taking the item 'The extract contains a stupid ethanol crane compound. The neuroblastic cell proliferation promoting agent and the like can also be used as various raw materials for drinking, for example, oil (salad oil), snacks (chewing gum biscuits, snacks, tablets, small). Desserts (such as c ramen, etc.), dairy products (milk, ice cream, etc.), condiments (weizeng, Daxin, etc.), soups, drinks (juice, coffee)

啡、紅茶、茶、碳較料、運統料等)為代表之一般 it或者健康食品(片劑、膠囊等)、營養補品(營養 飲料朴在㈣飲用食品中均可適當配有本發明之神經 芽細胞增殖劑等。 可根據這錄时品麵,在其巾加人各種成分, 例如可以使用葡萄糖、果糖、蔗糖、麥芽糖、山梨糖 醇、甜葉菊武(Stevioside)、玉米糖製、乳糖、檸檬酸、 酒石酸、蘋果酸、琥賴、乳酸、L-抗壞血酸、dh— =生素E、異抗壞血酸納、甘油、丙二醇、甘油脂肪酸 1、聚甘油脂肪酸I旨、雜脂職m雜脂肪酸 酉曰、丙二醇脂肪酸酯、阿拉伯膠、角叉菜聚糖 (carrageenan)、酪蛋白、明膠、果膠、瓊脂、維生素 B類、煙醯胺、泛酸鈣、氨基酸類、鈣鹽類'色素、香 料、保存鮮食品原材料,另外,在具有轉健康功能 之本發明,即神經芽細胞增殖促進劑中,也可以加入其 他如抗氧化物質或健康食品原材料等輔劑,該輔劑例如 有抗氧化物質、還原型抗壞血酸(維生素C)、維生素E、 17 200902033 還原型谷胱甘肽、生育三烯酚、維生素A衍生物、番茄 紅素、β-玉米黃質、蝦青素、玉米黃質、岩藻黃、尿酸、 泛醌、輔酶Q10、葉酸、大蒜萃取物、大蒜素、芝麻素、 木質素類、兒茶素、異黃酮、查爾酮、縣質類、黃酮類、 香显素、異香豆素類、越橘萃取物、熊果苦、丹寧、花 ,苷、蘋果多酚、葡萄籽萃取物、鞣花酸、曲酸、沙棘 萃取物保健食品原材料、ν.(維生素)A、VM、VB2、VB6、 VB12、VC、VD、VE、VP、膽鹼、煙醯胺、泛酸、葉酸鈣、 EPA、低聚糖、食物纖維、角_、大豆_脂、牛績酸、 ^氏藻(DunalieUa)、蛋白質、二十八烷醇、臟、蛋 黃印磷脂、亞油酸、乳鐵蛋白、鎮、辞、鉻、砸、卸、 亞鐵血紅素、牡蠣肉萃取物、脫乙醯殼多糖、幾丁質低 聚糖,原蛋白、軟骨素、郁金、甘草、构把子、桂皮: 山楂、生薑、靈芝、蜆貝萃取物、甲魚、甘草、构把子、 桂皮、山楂、生薑、靈芝、車前草、黃花菊、洋甘菊、 蒲公英、扶桑花、蜂蜜、求—k >、蜂王衆、萊檬、薰 衣草、野玫瑰果、迷迭香、鼠尾草、雙歧桿菌、桿菌 ^aecalis)、有胞子性乳酸g、小麥胚芽油、_油、 紫穌=、大豆油、中鏈脂肪酸、姬松茸(Amicus)、銀 杏,萃取物、郁金、軟骨素、鮮胚芽萃取物、靈芝、 洋蔥、DHA、EPA、DPA、甜茶、冬蟲夏草、大蒜、蜜蜂軒、 番木瓜、普洱茶、蜂膠、千里眼樹、十、蜂王 漿、鑛葉棕萃取物、透明質酸、夥原蛋白、㈣、海豹 油、震魚軟骨、葡萄糖胺、㈣脂、磷脂酿 七、桑葉、大豆萃取物、紫錐關植物、西伯利亞4 200902033 (工、/々口年)、大麥萃取物、橄欖葉、撖欖果實、匙囊 藤(Gymnema)、大花紫薇、五層龍屬植物(Salacia)、 藤黃屬植物(Garcinia)、脫乙酿殼多糖、貫葉連翹^、大 棗、人參、西番蓮、青菜花、胎盤、薏苡、葡萄種子、 花生皮、越橘、黑升麻、水飛薊、月桂、鼠尾草、迷迭 香、羅布麻、黑醋、口'一亇一茶、瑪劲n、紅花、亞麻、 烏龍茶、花棘豆、咖σ非因、辣椒域(capsaicin)、木寡 糖、葡萄糖胺、騫麥、柑橘屬植物、食物纖維、蛋白質、 梅幹、螺旋藻、大麥嫩葉、核酸、酵母、香菇、梅肉、 氨基酸、深海鯊魚萃取物、諾麗(noni)、牡礪肉、甲魚、 蘑菇(シ十y (£二才y )'車前草、櫻桃(7七口今)、 鳳梨、香蕉、桃、杏、哈密瓜、草莓、樹莓、橘子、岩 藻依聚糖、桑黃、鹤莓、硫酸軟骨素、鋅、鐵、神經醯 胺、si lk peptide、甘氨酸、煙酸、蔓荊子、神經醯胺、 L-半胱氨酸、L-肉域、紅葡萄葉、黍、問荊、生物素、 積雪草、藍靛果忍冬、碧蘿芷(PYCN〇GEIyj〇L)、蜂鬥菜、 大黃、丁香、迷迭香、兒茶素、普洱茶、檸檬酸、啤酒 酵母、^ 口—卜、黑大豆、生薑、莪術、納豆菌、紅 麴、生育二烯酚、乳鐵蛋白、肉桂、韃靼蕎麥、可哥粉、 柚子籽萃取物、紫蘇籽萃取物、紐籽萃取物、月見草 萃取物、辦萃取物、α—硫辛酸、GAM、生咖啡豆萃取 物、蜂鬥菜萃取物、_桃籽萃取物、溫州桔萃取物、 生薑萃取物及蝦青素等。 β作為具體之製造方法,躲用噴霧傾或者冷康乾 燥之方法,可直接將本發日狀神料細胞增殖促進劑等 19 200902033 (如果是萃取物,則將該萃取物與糊精—起)製成粉末、 ::品ί=外從而容ί地將它們包含彬 根據只際需要’亦可將本發明之 胞輕促進鮮鱗㈣與阿拉鱗料合劑 〜’衣成粉末狀或者顆粒狀,然後添加到固型食 ▲在萃取物情況下’可直接將該萃取物添加到 飲枓中’也可以將該萃取物分散溶解於(例如)水、乙 醇、甘油姐合物巾,再添㈣飲料中。 本發明之神經芽細朗雜補也可以 包括醫藥品及«料品)之树,可品 加入本發明之神經芽細胞增= =卜所述樂品,另外,所述藥品可以用於人類, 類:物:作為可以與本發明之神經芽細胞 (曰葡萄糖':丨:σ之製劑原料,例如’可以列舉賦形劑 =纖氣::::,、高嶺 粉等)、枯合劑(蒸餾水、生理鹽水、乙醇:嶺石 粉液、明膠溶液,甲基纖維素,酸鉀、 Γ等)、崩解劑(藻酸納、_、碳酸氫納、 二’’、月桂基硫酸鈉、單硬脂酸甘油醋、殿粉、乳糖、 ==、明膠、乙醇等)、崩解抑制劑(白糖、硬 美石n由等)、吸收促進劑(季錢域、月桂 ^酉夂㈣)、吸附劑(甘油、殿粉、乳糖、高嶺土、皂 二醇=3)及潤滑劑(精製滑石粉、硬脂酸鹽、聚乙 20 200902033 作為本發明之神、經芽細胞增殖促進劑的給藥方法, /-般來說,可以採用片劑、丸劑、軟膠囊劑、硬夥囊 微粒劑、散劑、顆粒劑等形式經口給藥,另外,作^ 體製劑,水溶性製劑可以經口給藥,也可以非經口給藥’ 作為非口服制而給藥時,可以將本發明之神經芽細於 增殖促進劑等分散於乙醇或水等合適之可溶試劑中、、,^ 後以巴布劑、洗劑、軟膏劑、釘劑、乳劑等劑型來使用, 又,本發明之神經芽細胞增殖促進解之水溶性製劑可 直接使用’亦可向該水溶性製射加人分散劑、懸濁'劑、 穩定劑等,織以巴布劑、洗劑、軟f劑、賴、乳 等劑型來使用。 給藥劑量可以根據給藥方法、病情、患者的年齡等 而變化,但是一般來說,成年人可以按照i天給予的有 效成分為5 mg〜400 mg、兒童按照i天給予的有效成分 為0.5 mg〜200 mg左右的劑量來給藥。 本發明之神經芽細胞增殖促進劑等作為藥品使用 時’其加入之比例可以根據劑型來適當改變,一般來說, 口服給藥或者通過枯膜吸收而給藥時,神經芽細胞增殖 促進劑等之加入比例可以為大約〇. 〇1重量%〜1〇重量%, 而非口服給藥時,神經芽細胞增殖促進劑等之加入比例 可以為0.01重量%〜20重量%左右。另外,由於給藥劑量 根據各種條件的不同而調整,所以有時即使給予之劑量 小於上述給藥劑量範圍時仍足夠,而有時給藥劑量則需 要超過上述劑量範圍,醫藥組合物中除了含有上述神經 芽細胞增殖促進劑等外,也可以含有醫藥領域中常用之 21 200902033 已^其他化合物、以及可以含有在適合於經口給藥的开) 式τ成i所需要之化合物,該化合物,例如可以列舉乳 糖贏軼、羥丙基纖維素、高嶺土、滑石粉及碳酸鈣等。 另外,在哺乳類動物飼料中亦可含有本發明之神經 芽細胞增贿進解,可以_與上述飲时品相同之 方法,將本發明之神經芽_增殖促進解包含在動物 飼料中另外’對可使用之動物飼料的動物沒有特別限 定,例如,該飼料可用於牛、豬等家畜動物、狗、猶、 倉鼠等寵物等,可以使_粉、伽轉,此時,作為 ::麵:子Γ有小麥粉、米粉、黑麥粉、燕麥粉、稗 以:八Γ ί玉米粉及大丑粉等’這些麵粉亦可二種 物去用之麵粉,可以給寵物提供碳水化合 物;f、呂養素,在所述麵粉中,最佳選擇係用小麥粉,該 镇2可以單獨或者適當組合制強力粉、中力粉°、 =^’另外所述小麥粉也可以與其它的麵粉合用,另 :二=經熱處理後之動物飼料彈性,也可以將小 ^二小4、大豆蛋白質等組合使用,而且,小麥 中所3有轉皮之網狀結構在加熱處理後會形成一〔 組織結構,有助於改善口感。 / 對本發明切使_食_ 用雞肉、豬肉、牛肉、单内…繼疋可以使 馬肉等,從口味:考廣最:二:肉、兔肉、火雞肉及 用的古、土令古考心取佳使用雞肉’可以通過採用當 且,、中間水ί家畜類動物並解剖後得到該食用肉,而 且中間水刀產品或低水分狀態之產 要是由於脂肪氧化而引起的,所以食用= 22 200902033 量少或是已除去脂肪之痩肉’另外,在飼料中含有食用 肉,不僅可以給錢提供優良之動物性蛋白質,而且還 可以改善寵物之嗜好。Ordinary it or healthy foods (tablets, capsules, etc.), nutritional supplements (nutritional beverages, etc.) can be appropriately equipped with the present invention, such as brown, black tea, tea, carbon, materials, etc. A neuroblastic cell proliferation agent, etc. According to this recording, various ingredients can be added to the towel, for example, glucose, fructose, sucrose, maltose, sorbitol, Stevioside, corn sugar, lactose can be used. , citric acid, tartaric acid, malic acid, amber, lactic acid, L-ascorbic acid, dh- = biotin E, sodium erythorbate, glycerol, propylene glycol, glycerol fatty acid 1, polyglycerol fatty acid I, miscellaneous fatty acid 酉Anthraquinone, propylene glycol fatty acid ester, gum arabic, carrageenan, casein, gelatin, pectin, agar, vitamin B, nicotinamide, calcium pantothenate, amino acids, calcium salts, pigments, spices In addition, in the present invention having the function of transferring health, that is, the nerve cell proliferation promoting agent, other substances such as antioxidant substances or health food raw materials may be added. An adjuvant, such as an antioxidant, reduced ascorbic acid (vitamin C), vitamin E, 17 200902033 reduced glutathione, tocotrienol, vitamin A derivative, lycopene, beta-corn yellow Quality, astaxanthin, zeaxanthin, fucoidan, uric acid, ubiquinone, coenzyme Q10, folic acid, garlic extract, allicin, sesamin, lignin, catechin, isoflavones, chalcone, county Quality, flavonoids, aroma, isocoumarin, bilberry extract, bearberry bitter, tannin, flower, glycosides, apple polyphenols, grape seed extract, ellagic acid, kojic acid, sea buckthorn extract Health food raw materials, ν. (vitamin) A, VM, VB2, VB6, VB12, VC, VD, VE, VP, choline, nicotinamide, pantothenic acid, calcium folate, EPA, oligosaccharides, dietary fiber, horn _ , soybean _ fat, bovine acid, Dunali Ua, protein, octacosanol, dirty, egg yolk, phospholipid, linoleic acid, lactoferrin, town, remarks, chromium, strontium, unloading, ferrous Heme, oyster meat extract, acetaminophen, chitin oligosaccharide, proprotein, chondroitin, Yujin, licorice, stalk, cinnamon: hawthorn, ginger, ganoderma, mussel extract, turtle, licorice, stalk, cinnamon, hawthorn, ginger, ganoderma, plantain, gerbera, chamomile, dandelion, hibiscus Flowers, honey, seeking -k >, bee king, lime, lavender, rose hip, rosemary, sage, bifidobacteria, bacillus ^aecalis), cytosolic lactic acid g, wheat germ oil, _ Oil, purple sugar, soybean oil, medium chain fatty acid, Amicus, Ginkgo biloba, extract, turmeric, chondroitin, fresh germ extract, ganoderma lucidum, onion, DHA, EPA, DPA, sweet tea, Cordyceps sinensis, garlic , Bee Xuan, Papaya, Pu'er Tea, Propolis, Clairvoyance Tree, Ten, Royal Jelly, Mineral Leaf Palm Extract, Hyaluronic Acid, Collagen Protein, (D), Seal Oil, Shock Fish Cartilage, Glucosamine, (D) Lipid, Phospholipid 7. Mulberry leaves, soybean extract, Echinacea plant, Siberia 4 200902033 (work, / 々口年), barley extract, olive leaf, 撖 果实 fruit, Gymnema, big flower Ziwei, five layers Salacia, Garcinia, Garcinia, St. John's wort, jujube, ginseng, passionflower, green cabbage, placenta, alfalfa, grape seed, peanut skin, bilberry, black cohosh, water fly Quail, bay laurel, sage, rosemary, apocynum, balsamic vinegar, mouth 'one tea, Ma Jinn, safflower, flax, oolong tea, Oxytropis chinensis, ginseng, capsaicin, capsaicin Xylo-oligosaccharides, glucosamine, buckwheat, citrus, dietary fiber, protein, prunes, spirulina, barley green leaves, nucleic acids, yeast, shiitake mushrooms, plum meat, amino acids, deep sea shark extract, noni, Oyster meat, soft-shelled turtle, mushroom (シ10y (£二才y)' plantain, cherry (7 seven mouths today), pineapple, banana, peach, apricot, cantaloupe, strawberry, raspberry, orange, fucoidan , mulberry yellow, crane, chondroitin sulfate, zinc, iron, ceramide, si lk peptide, glycine, niacin, vine, ceramide, L-cysteine, L-meat, red grapes Leaves, cockroaches, quails, biotin, Centella asiatica, Lonicera japonica L., Pycnogenol® (PYCN〇GEIyj〇L ), butterbur, rhubarb, clove, rosemary, catechin, Pu'er tea, citric acid, brewer's yeast, ^ mouth - Bu, black soybean, ginger, medlar, natto, red peony, fertility Phenol, lactoferrin, cinnamon, buckwheat, cocoa powder, grapefruit seed extract, perilla seed extract, New Zealand seed extract, evening primrose extract, extract, α-lipoic acid, GAM, green coffee bean extract , butterbur extract, _ peach seed extract, Wenzhou orange extract, ginger extract and astaxanthin. As a specific manufacturing method, β can be used as a method of spray or cold drying, and can directly use the present invention as a cell proliferation promoter. 19 200902033 (If it is an extract, the extract and the dextrin ) made into powder, :: product ί = externally and thus contain them according to the needs of the 'only need to light the cells of the invention to promote the fresh scales (four) and the arsenic mixture ~ 'clothed into powder or granular And then added to the solid food ▲ In the case of the extract, 'the extract can be directly added to the drink '', the extract can also be dispersed and dissolved in, for example, water, ethanol, glycerin sister towel, and then added (4) In the beverage. The neuronal fine hybrid supplement of the present invention may also include a medicinal product and a "item" tree, and may be added to the nerve bud cells of the present invention to increase the quality of the product, and the drug may be used for humans. Class: substance: as a nerve bud cell which can be combined with the present invention (曰 glucose ': 丨: σ preparation raw materials, for example, 'except excipients = fiber::::, kaolin powder, etc.), dry agent (distilled water , physiological saline, ethanol: lings powder solution, gelatin solution, methyl cellulose, potassium acid, cesium, etc.), disintegrating agent (sodium alginate, _, sodium bicarbonate, two '', sodium lauryl sulfate, single hard Fatty acid glycerin vinegar, house powder, lactose, ==, gelatin, ethanol, etc.), disintegration inhibitor (white sugar, hard stone n, etc.), absorption enhancer (season money domain, laurel ^ 酉夂 (4)), adsorption Agent (glycerin, house powder, lactose, kaolin, soap diol = 3) and lubricant (refined talcum powder, stearate, polyethyl 20 200902033 as a method for administering the god, bud cell proliferation promoting agent of the present invention , / - In general, tablets, pills, soft capsules, hard capsule microgranules, powders can be used Oral administration in the form of granules or the like, and in addition, as a preparation, the water-soluble preparation may be administered orally or may be administered orally. When administered as a non-oral preparation, the nerve bud of the present invention may be finely divided. The proliferative enhancer or the like is dispersed in a suitable soluble reagent such as ethanol or water, and then used in a dosage form such as a cataplasm, a lotion, an ointment, a nail, or an emulsion, and the neuroblastic cell of the present invention. The water-soluble preparation for promoting proliferation can be directly used, or the water-soluble injection can be added to a dispersing agent, a suspension agent, a stabilizer, etc., and woven with a cloth, a lotion, a soft agent, a lyrium, a milk, etc. The dosage form can be used according to the administration method, the condition, the age of the patient, etc., but generally, the active ingredient which can be administered by an adult in an i day is 5 mg to 400 mg, and the child is administered according to i day. The active ingredient is administered in a dose of about 0.5 mg to 200 mg. When the neuroblastic cell proliferation promoting agent or the like of the present invention is used as a medicine, the ratio of the addition can be appropriately changed depending on the dosage form, and generally, it is administered orally. Dry film suction When administered, the addition ratio of the neuroblast growth promoter or the like may be about 〇1 % 1% by weight to 1% by weight, and when not administered orally, the addition ratio of the nerve bud cell proliferation promoting agent or the like may be 0.01. The weight is about -20% by weight. In addition, since the dose is adjusted according to various conditions, sometimes even if the dose is less than the above-mentioned dose range, sometimes the dose needs to exceed the above dose range. The pharmaceutical composition may contain, in addition to the above-mentioned neuroblast cell proliferation promoting agent, the other compounds which are commonly used in the field of medicine, and may be contained in a compound suitable for oral administration. A compound which is required, and examples of the compound include lactose-winning, hydroxypropylcellulose, kaolin, talc, and calcium carbonate. In addition, the mammalian animal feed may also contain the neuroblast-promoting solution of the present invention, and the nerve bud-proliferation promoting solution of the present invention may be included in the animal feed in the same manner as the above-mentioned drinking time product. The animal of the animal feed that can be used is not particularly limited. For example, the feed can be used for livestock animals such as cattle and pigs, dogs, babies, hamsters, and the like, and can be used to make _ powder and gamma, at this time, as: face: There are wheat flour, rice flour, rye flour, oat flour, glutinous rice: gossip gluten corn flour and large ugly powder, etc. 'These flours can also be used in two kinds of flour to provide pets with carbohydrates; f, Lu Yangsu In the flour, the best choice is to use wheat flour, the town 2 can be used alone or in combination to make a strong powder, medium strength powder °, = ^ 'the other wheat flour can also be combined with other flour, another: two = animal feed elasticity after heat treatment, can also be used in combination with small 2, small 4, soy protein, etc., and the reticular structure of the skin in 3 of wheat will form a [structural structure after heating treatment. For improvement Taste. / For the present invention, cut _ _ _ with chicken, pork, beef, single inside... followed by 疋 can make horse meat, etc., from the taste: Kao Guang most: two: meat, rabbit meat, turkey and used ancient, earthen ancient test The use of chicken meat can be obtained by using the animal meat and dissecting the animal meat, and the production of the intermediate water knife product or the low water state is caused by fat oxidation, so the consumption = 22 200902033 A small amount of fat or fat that has been removed. In addition, the consumption of meat in the feed not only provides excellent animal protein, but also improves the pet's taste.

雖然可以採用各種方絲配製所述寵物飼料,但是 較佳方法例為:配製含有麵粉(優選為小麥粉)和食用 肉所攪拌之原料混合物(下文中稱為“生麵團,,),待成 形後寻進行加熱處理。對所述生_巾之麵粉及食用肉 組成沒有_蚊,—絲說,崎成由5㈣%左右、 較佳選擇為10%〜50%左右之麵粉,5%〜_左右、較佳選 擇為2G%~5⑽左右之食用肉以及必需量水分所組成之生 麵團,而且’在額Aw調節狀情況下,該Aw調節劑 之添加量為5%〜30%左右、較佳選擇為1〇%〜2〇%左右,又, 水的用量可以根據所述生麵團之混合櫈拌、成形程度以 及麵粉、食用肉、Aw調節劑等用量來適當調節。對該生 麵團之配製方法並沒有特別的限定,較佳選擇是,首先 用斬拌機、切碎機等將所述仙肉製成肉銘,此時,為 了在製成肉餡的食用肉中充分含有氣泡,最好將該食用 肉細切,再向製成肉餡之食用肉中加入麵粉、水以及根 據而要還可以加入Aw調節劑等,充分授拌使其中含有氣 泡,從而配製成含有氣泡之生麵團,其中在配製生麵團 叶,也可以加入發泡劑,特別是在除了小麥粉以外的其 他麵粕用作所述麵粉的情況下,較佳選擇係使用發泡 劑’透過加入發泡劑’可以使生麵團中均勻地含有微小 氣泡,以作為發泡劑使用,可以使用各種發泡劑,但是 從氣泡之穩定性等方面考慮,較佳選擇係使用大豆蛋白 23 200902033 類發泡劑或經酶分解之大豆蛋白類發泡劑。 將製備之生細赫並經過加熱處賴,即得 物用飼料’其中在生麵_成型時,係根據寵物在 時之容易程度及飼養人操作之容易程度等,將該飼激 成合適形狀,例如片狀、棒狀、圓片狀、環狀、心型等, 另外,可以將由姻魏合組分所製備之生麵團用各 不同色素染色、或者加人蔬菜或水果等,以製成具 同外觀之多種生_,再將·生細組合成多層 狀或者同心_狀,進喊型,對成通的生麵團之力: 熱手段沒有特別的限定,例如,所述加熱手段可夹 烘箱加熱及微波加鮮,這些加財_是普^ 的,可以按照常用方法進行加熱處理,而經過加 後之飼料,其水分含量—般為勝概左右,經過 力口熱處理後,由於水分蒸發以及氣鱗脹,即生麵圏膨 化,另外由於是在短時間内使水分蒸發,所以a 從而提高了保存性。另外,在小麥粉用作所述麵粉的 ::二過加熱處理’小麥粉中所含有的麵皮的網狀結 二從而改善口感。而且’在採祕箱加熱的情 ,下、有在所述飼料中產生獨特的色調(狐色)或香 氣的優點’而在制微波加熱的情況下,由於 團的内部開始加熱,所以可以使生麵團均勻膨化,具 到含有均勻氣泡的飼料這樣的優點。在進行_ n里時,優選的是,使所得到的飼料中Aw調節在 二〇. 9的1圍内。如上所述,通過將Aw調節在此範圍 内’可以顯著提高飼料的保存性。 24 200902033 經由上述綠所製備之聽的娜,其為具有麵包 的形狀之飼料’由於該飼料具有錄的Π感以及合適的 柔軟性和· ’所以適麵伽犬、老齡犬餘等牙齒 能力弱的陪伴動物的飼料、點心等。將上述動物用飼料 以合適的量容納在包裝容器内,密封後製成產品。作為 所述包裝容器,優選使用不透氧氣的包材。作為包裳的 形狀’可以列舉真空包裝、填充有活性炭的包裝等,但Although the pet food can be formulated using various square yarns, a preferred method is as follows: preparing a raw material mixture (hereinafter referred to as "dough,") which is mixed with flour (preferably wheat flour) and edible meat, to be formed. After looking for heat treatment, there is no _ mosquito to the flour and meat composition of the raw _ towel, and the silk is about 5 (four)%, preferably about 10% to 50%, 5%~_ The left and right, preferably selected from 2G% to 5 (10) of the edible meat and the necessary amount of moisture, and the amount of the Aw modifier added is about 5% to 30% in the case of the Aw adjustment. The preferred choice is about 1% to about 2%, and the amount of water can be appropriately adjusted according to the mixing stool of the dough, the degree of forming, and the amount of flour, meat, Aw conditioner, etc. The preparation method is not particularly limited. Preferably, the meat is first made into a meat by a chopper, a chopper, etc., in order to sufficiently contain bubbles in the meat to be made into meat. It is best to cut the meat carefully and then make it Add the flour, water and the Aw conditioner according to the edible meat, and mix it to make it contain bubbles, so as to prepare the dough containing the bubbles, in which the dough leaves can be added. In the case where a foaming agent is used as the flour in particular, other than wheat flour, it is preferred to use a foaming agent 'by adding a foaming agent' to uniformly contain fine bubbles in the dough. As the foaming agent, various foaming agents can be used, but from the viewpoint of stability of the bubble, etc., it is preferred to use a soy protein 23 200902033 type foaming agent or an enzymatically decomposed soy protein type foaming agent. The heat is applied to the appropriate shape, for example, when the dough is formed, according to the easiness of the pet at the time and the ease of operation of the breeder, etc. a sheet, a rod, a disc, a ring, a heart, etc., in addition, the dough prepared from the sage component can be dyed with different pigments, or added with vegetables or fruits, etc. In order to produce a variety of raw materials with the same appearance, and then combine the raw and thin into a multi-layered or concentric _ shape, into the shouting type, the force of the dough into the pass: there is no special limitation on the thermal means, for example, The heating means can be combined with oven heating and microwave freshening. These riches are common to the heat treatment, and after the added feed, the moisture content is generally about the victory, after the heat treatment. After that, since the water evaporates and the gas swells, that is, the dough is puffed, and since the water is evaporated in a short time, a improves the preservability. In addition, the wheat flour is used as the flour: Heat treatment of the reticular knot of the dough contained in the wheat flour to improve the taste. And 'in the case of heating the secret box, there is the advantage of producing a unique color (fox color) or aroma in the feed' On the other hand, in the case of microwave heating, since the inside of the pellet starts to be heated, the dough can be uniformly expanded and the feed containing uniform bubbles can be obtained. In the case of _ n, it is preferred that the Aw in the obtained feed is adjusted within a range of two 〇. As described above, the preservation of the feed can be remarkably improved by adjusting Aw within this range. 24 200902033 The scent of Na, which is prepared by the above-mentioned green, is a kind of bread-shaped feed. 'Because the feed has a sense of sensation and appropriate softness, it is suitable for the fangs, old dogs and other teeth. Feeds, snacks, etc. of accompanying animals. The animal feed described above is contained in a packaging container in an appropriate amount and sealed to form a product. As the packaging container, it is preferred to use an oxygen-impermeable packaging material. The shape of the baggage may be a vacuum package or a package filled with activated carbon, but

是優選的是同時填充有去氧劑(例如,工一2 Μ TM 等)和活性炭的包裝。採__包裝形式,在保存期 間可以防止由魏氣㈣起的品質惡似及微生物的繁 殖0 ” 本發明之神經芽細胞增殖促進鮮也可以用作皮膚 夕=劑(包括化妝品、醫藥品以及㈣料品),期待該 皮膚外關具有神經突起伸展作用。另外,所述皮膚外 麟人類、,也可㈣於除了人_外的其他哺 、隹丄物作為可以配伍有本發明的神經芽細胞增殖促 1的皮膚外用劑的形式,例如,可以列舉乳液、肥 ί、洗面劑、洗澡劑、護膚霜、乳液、化妝水、花露水、 2須用乳膏、賴収液、條油、防_b妝水、粉 =、粉底、香水、面膜(pack)、指甲膏、指曱油(_朴 =甲油洗液、眉黛、胭脂、眼霜、眼影、染睫毛油、眼 紅、唇f、洗頭液、護髮素、染發劑、分散液、 二、”另外作為可以配伍有本發明的神經芽細胞增 卷進劑等的醫藥品或醫藥部外品的形式,可以列舉軟 网劑、乳劑、外用液等。 25 200902033 在上述形式的皮膚外㈣中,除了含有本發明的神 經芽ί胞增殖促進鮮之外,在不㈣神經突起伸展作 用的範圍内’也可以加人下述物質,所述物質為可以加 入到化妝扣、^•藥部外品等皮膚外用劑巾的成分,包括 油類成分、高級醇、脂肪酸、紫外線吸收劑、粉末、顏 料、表面活性劑、多辑、糖類、高分子、生理活性物 質」合劑、k氧化劑、香料、_劑等。以下雖然羅列 出攻些物質的鮮,但是本發麵不只限於這些例子。 U)油類成分的例子酯類的油類成分舉例有:三 2-乙基己酸甘油酯、2-乙基己酸十六醇酯、肉豆謹酸異 丙醋、肉豆蔻酸丁g旨、棕櫚酸異丙酉旨、硬脂酸乙酿、棕 槪辛S旨、異硬鑛異十六_旨、硬麟獨、肉豆謹 ,丁酯、亞油酸乙g旨、亞油酸異丙酯、油酸乙酿、肉豆 蔻酸異十六_旨、岐級異十八_旨、棕櫚酸異十八 醇醋、肉豆蔻酸辛基十二_旨、異硬麟異十六醇醋、 夭一g文一乙g曰、己一酸二異丙酯、新戊酸異廿十醇酯、 三(辛基癸酸)甘油酯、三2_乙基己酸三羥甲基丙酯、三 異硬脂酸二&甲基丙g旨、四2_乙基己酸季細醇醋、辛 酸十六醇i旨、月桂酸钱、月桂酸己g旨、肉豆蔻酸癸龜、 肉丑謹酸岐«_旨、肉域針六_旨、硬脂酸十八 醇酯、油酸癸酯、蓖麻醇酸十六醇酯、月桂酸異十八醇 酯、肉立蔻酸異三癸酯、肉豆蔻酸異十六醇酯、肉豆蔻 酸異十八醇酯、棕櫚酸異十六醇酯、棕櫚酸異十八醇酯、 硬脂酸辛酯、硬脂酸異十六醇酯、油酸異癸酯、油酸9辛 基十二醇酯、亞油酸辛基十二醇酯、異硬脂酸異丙酯、 26 200902033 2-乙基己酸十八醇十六醇酯、乙基己酸十八醇酯、異 硬脂酸己酯、二辛酸乙二醇酯、二油酸乙二醇酯、二癸 酸丙二醇醋、二(辛基癸酸)丙二醇酯、二辛酸丙二醇酷、 二癸酸新戊二醇酯、二辛酸新戊二醇酯、三辛酸甘油酯、 三(十一酸)甘油酯、三異棕櫚酸甘油酯、三異硬脂酸甘 油酯、新戊酸辛基十二醇酯、辛酸異十八醇酯、異壬酸 辛酯、新癸二酸己基十二醇酯、新癸二酸辛基十二醇酯、 異硬脂酸異十六醇酯、異硬脂酸異十八醇酯、異硬脂酸 辛基十一醇酯、聚甘油油酸酯、聚甘油異硬脂酸醋、石炭 酸二丙酯、碳酸二烷基(C12-C18)酯、檸檬酸三異十六醇 酯、榉檬酸三異廿十醇酯、檸檬酸三異辛酯、乳酸月桂 酉旨、乳酸肉豆蔻酯、乳酸十六醇酯、乳酸辛基十二醇酯、 檸檬酸三乙酯、檸檬酸乙醯基三乙酯、檸檬酸乙醯基三 丁S曰、檸檬酸三辛酯、蘋果酸二異十八醇酯、羥基硬脂 酸2-乙基己酯、琥珀酸二2-乙基己酯、己二酸二異丁 酯、癸一酸二異丙酯、癸二酸二辛酯、硬脂酸膽崔醇酯、 異硬月曰酸膽g醇自旨、經基硬脂酸膽轉自旨、油酸膽留醇 醋、油酸二氫膽留醇酯、異硬脂酸植物轉酯、油酸植 物留醇酉旨、12-硬脂醯基經基硬脂酸異十六醇酉旨、12_硬 脂醯基絲硬脂酸十八醇醋、12_硬脂醯基經基硬脂酸異 十八醇自日等。㈣的油類成分舉例m稀、液態石 磁、α—稀烴低聚物、異錢、白地犧 '石蠛、液態異石 蠘、聚丁埽、微晶壞、凡士林等。動植物油及其硬化油、 以及天然的蟻舉例有:牛脂、硬化牛脂、豬脂、硬化猪 脂、馬油、硬化馬油、紹油、才—(棘鯛 27 200902033 其硬化油;鱷梨油、杏仁油、心等動物油及 種子油、杏仁油、木立廣蒼油撤可哥脂、«桃 米胚芽油、玄米油、紅花油、牛 油,油'茶籽油、山茶油、玉=::月:草 采軒油、掠櫚核油、硬化棕櫚核油、花歸 油、蓖麻油、硬化蓖麻油、向日葵葙 化生 巴油、硬化霍霍巴油、_堅果二=軒:、霍霍 籽油、蝴_、㈣、硬化椰=及= 硬化油;蜂躐、高酸價蜂€、羊毛脂、還原羊=2 =毛脂、液狀羊毛脂、巴西棕侧、褐煤蝶等壞。矽 乳烷類的油類成分舉例有:二甲基聚 ,、甲基環聚魏貌、八甲基聚嫩甲= %夕碰m切纽、甲 ς 改性有機聚魏f·甲基十六 =壯物、—甲基魏燒.甲基权域祕 =、絲祕械財纽、料雜械砂氧燒: 風基改性石夕剩油、氨基改性有機聚石夕氧炫、二f基石夕氧 烷醇(Dimethlconol )、石夕酮膠、丙婦基補、三甲 矽燒氧基石夕酸、石夕_RTV膠等。氟類的油類成分舉例^. ί氣聚I氟改財機聚魏炫、氟化射、氟化碳、 ^代醇、鼠代院基·聚經基亞貌基共改性有機聚石夕氧烷 等。 ^高級醇的例子有:月桂基醇、肉豆謹醇、録蠟 醇、十八炫醇、異十八貌醇、油醇、二十二醇、2_乙基 28 200902033 己醇、十六烧醇、辛基十二烧醇等。 ⑶脂肪酸的例子有:辛酸、癸酸、十-碳烯酸、 月桂酸、肉豆謹酸、棕櫊酸、棕櫚油酸、硬脂酸、異硬 脂酸、油酸、亞油酸、亞麻酸、花生酸、花生四稀酸、 二十二酸、芥子酸、2-乙基己酸等。 ⑷紫外線吸收劑的例子有··對氨基安息香酸、對 氨基安息魏触、職基安息魏乙基二雜丙酿、 對氣基安息魏甘触、對氨基安息雜乙自旨、對氨基 安息香酸辛s旨、龍基安息魏辛基二〇旨、水揚酸2 二醇醋、水揚酸辛g旨、水揚酸三乙醇胺、水揚酸苯醋、 水揚酸丁絲S旨、水揚酸㈣旨、水騎同孟§旨、桂皮酸 节醋、對甲氧基桂皮酸辛醋、對甲氧基桂皮酸2_乙基己 酯、二對甲氧基桂皮酸單2-乙基己酸甘油酯、對甲氧基 桂皮酸異丙酯、對甲氧基桂皮酸二乙醇胺、二異丙基. 二異丙基桂皮酸酯混合物、尿刊酸、尿刊酸乙酯、羥基 甲氧基苯甲_、經基甲氧基苯甲咐酸及其鹽、二經基 甲氧基苯甲_、二絲甲氧基苯甲酮磺酸納、二經基苯 甲酮、二羥基二甲氧基苯甲酮、羥基辛氧基苯甲酮、四 羥基苯甲酮、丁基甲氧基二苯甲醯基甲烷、2,4,6_三苯 胺基對-(2-乙基己基—1-羧基)_ι,3, 5-三嗪、2-(2-羥基 5甲基笨基)苯並三唑、鄰_氨基苯子酸甲酯、2_氨基 -3’3-二苯基丙稀酸2_乙基己酯、苯基苯並咪唑硫酸、 3- (4-曱基苯亞甲基)樟腦、異丙基二苯曱醯基甲烷、 4- (3’ 4-二甲氧基苯基亞甲基)_2, 5—二氧代咪唑烷基 丙馱2-乙基己酯等,以及這些物質的高分子衍生物或石夕 29 200902033 院衍生物等。 (5)粉末、顏料的例子有··紅色1〇4號、红色2〇ι 號、黃色4號、藍色!號、黑色4〇1號等色素;黃色4 號AL沉;殿色料、黃色2_ βΑ沉;殿色料等沉殿色素; 尼龍粉、絲粉、氨基曱酸乙g旨粉、特氟隆(注冊商 粉、石夕_粉、聚甲基丙烯酸甲_粉、纖維素粉、澱:、 =球狀彈性體粉末、聚乙烯粉等高分子;黃色氧化鐵、 ,色乳化鐵、黑色氧化鐵、氧化鉻、炭黑、群青、深藍 等有色顏料;氧化鋅、氧化鈦、氧化 _ 石粉、雲母、自舞、純土自色顏料;滑 带母㈣读出…, 板狀鋇等體質顏料; Γ酸鋇、糊、碳酸鎂,_、 夕酉义鎮等金屬鹽;石夕、氧化銘等無機粉末 硬脂酸鎂、棕槪鋅、岐驗鋅 日1呂 酸鋅、十-稀酸辞等金屬肥阜;膨潤== 鱗。對這些粉末的形狀(球形、棒狀、針狀、板^化 :Γ也紡錘狀等)和粒徑沒有特別的限定。 ί 、頻脂處理法、懸垂處理法、 理法、_合劑處理法、油劑處理法、Ν- 處理法、金屬肥钱理法、 ’ i旨處理法、無機化合物處理法、等 行表面處理。 切里法荨)對這些粉末預先進It is preferred to package with both an oxygen scavenger (e.g., a 2 Μ TM, etc.) and activated carbon. In the form of packaging, it can prevent the deterioration of quality and microbial growth from Wei (4) during storage. ” The proliferation of nerve cells in the present invention can also be used as a skin agent (including cosmetics, pharmaceuticals, and (4) Items), it is expected that the external skin of the skin has a neurite outgrowth effect. In addition, the skin may be externally human, or (4) other than the human beings, other feedings and scorpions as the nerve buds of the present invention can be compatible. The form of the skin external preparation for promoting cell proliferation 1 may, for example, be an emulsion, a fat, a facial cleanser, a bathing agent, a skin cream, a lotion, a lotion, a toilet water, a cream, a lotion, a strip of oil, and an anti-aging agent. _b makeup water, powder =, foundation, perfume, mask, nail paste, finger oil (_Pak = nail polish, eyebrow, rouge, eye cream, eye shadow, mascara, eye red, lip f, A shampoo, a conditioner, a hair dye, a dispersion, and a second, and a form of a pharmaceutical product or a pharmaceutical product which can be used together with the nerve bud cell entrainment agent of the present invention, etc. , emulsion, external liquid, etc. 25 200902033 In addition to the above-mentioned form of skin (4), in addition to the proliferation of the nerve cells of the present invention, in the range of not (four) neurite outgrowth, the following substances may be added, and the substance may be added. Ingredients for skin external preparations such as makeup buttons, medicines, etc., including oil components, higher alcohols, fatty acids, ultraviolet absorbers, powders, pigments, surfactants, multi-parts, sugars, polymers, physiological activities "Material" mixture, k oxidizing agent, perfume, _agent, etc. Although the following is a list of some of the fresh substances, the present invention is not limited to these examples. U) Examples of oil components The oil components of esters are exemplified by: -ethylhexanoate, hexadecyl 2-ethylhexanoate, isopropyl vinegar, diced acid, isopropyl citrate, stearic acid, brown eucalyptus S, different hard ore, different 16 _, hard lindane, peas, butyl ester, linoleic acid, isopropyl linoleate, oleic acid, and myristic acid , 岐 grade different eighteen _ purpose, palmitic acid isostearyl vinegar, myristate octyl ten _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ethylhexanoic acid trimethylol propyl ester, triisostearic acid di & methyl propyl glycerol, tetra-2-ethylhexanoic acid sterol vinegar, caprylic acid cetyl alcohol, lauric acid money, laurel酸 己 、, myristic acid 癸 turtle, meat ugly acid 岐 «_ purpose, meat domain needle six _ purpose, stearic acid stearyl ester, oleic acid decyl ester, ricinoleic acid cetyl ester, laurel Acid isostearyl alcohol ester, isotridecyl myristate, isohexadecanol myristate, isostearyl myristate, isohexadecanol palmitate, isostearyl palmitate, Octyl stearate, isohexadecanol stearate, isodecyl oleate, 9 octyldodecanol oleate, octyldodecanol linoleate, isopropyl isostearate, 26 200902033 2 - Ethyl hexadecanol hexadecanol ester, octadecyl ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol diacetate, Di(octyl decanoic acid) propylene glycol ester, dioctanoic acid propylene glycol cool, two Neopentyl glycolate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl tris(undecanoate), glyceryl triisopalmitate, glyceryl triisostearate, octyl 12 pivalate Alcohol ester, isostearyl octanoate, octyl isophthalate, hexyl dodecyl neodecanoate, octyl dodecyl neodecanoate, isohexadecyl isostearate, isostearic acid Octadecanol ester, octyl undecyl isostearate, polyglycerol oleate, polyglyceryl isostearic acid vinegar, dipropyl carbamate, dialkyl (C12-C18) carbonate, citric acid Hexaol ester, triisodecyl citrate, triisooctyl citrate, lactic acid lauryl, crotonyl lactate, cetyl lactate, octyl lauryl lactate, triethyl citrate , Ethyl citrate triethyl citrate, Ethyl citrate tributyl sulfonate, Trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, succinic acid 2 -ethylhexyl ester, diisobutyl adipate, diisopropyl phthalate, dioctyl sebacate, cholesteryl stearate, isostearyl cholesteryl hard Acid bile to the purpose, oleic acid bile glycol vinegar, dihydrocholesterol oleate, isostearic acid plant transesterification, oleic acid plant sterol, 12-stearyl sulfhydryl sulphate Hexaol, 12-stearyl sulphate, stearic acid, stearyl sulphate, 12-stearyl sulphate, succinic acid, stearic acid, etc. (4) Examples of oil components are m-thin, liquid-stone, alpha-dilute hydrocarbon oligomers, iso-money, Baidi-san, stone sputum, liquid stellite, polybutylene, microcrystalline, and petrolatum. Examples of animal and vegetable oils and their hardened oils, as well as natural ants are: tallow, hardened tallow, lard, hardened lard, horse oil, hardened horse oil, simmered oil, and only - (thorny 27 200902033 hardened oil; avocado oil , almond oil, heart and other animal oils and seed oil, almond oil, Mu Liguang scented oil can be removed, "peach rice germ oil, black rice oil, safflower oil, butter, oil 'tea seed oil, camellia oil, jade =: : Month: Cao Cai Xuan oil, palm kernel oil, hardened palm kernel oil, flower oil, castor oil, hardened castor oil, sunflower glutinous oil, hardened jojoba oil, _ nut two = Xuan:, Hoho seeds Oil, butterfly _, (four), hardened coconut = and = hardened oil; bee sting, high acid price bee, lanolin, reduced sheep = 2 = hair fat, liquid lanolin, Brazilian brown side, brown coal butterfly and so on. Examples of the oil components of the lactane include: dimethyl poly, methylcyclo-poly-form, octamethyl-poly-n-== 夕 m m-cut, formazan modified organic poly-f-methyl = Zhuang, - Wei Weizhuo. Methyl rights domain secret =, silk secret machinery and wealth, material miscellaneous sand oxy-combustion: wind-based modified stone night oil, amino modified organic polymerization Dioxilconol, Dimethlconol, Lixi Kejiao, Bingfuji, Trimethylhydrazine, Oxygen, and Shixi_RTV, etc. Examples of fluorine-based oils ^. Gas-polymerized I-fluorine-changing machine, Wei Weixuan, fluorinated shot, fluorinated carbon, ^-alcohol, rat-derived base, poly-based mesomorphic group, modified organopolyoxane, etc. ^Example of higher alcohol There are: lauryl alcohol, myristyl alcohol, wax alcohol, octadecyl alcohol, isooctadecanol, oleyl alcohol, behenyl alcohol, 2_ethyl 28 200902033 hexanol, hexadecanol, octyl Twelve alcohols, etc. (3) Examples of fatty acids are: caprylic acid, capric acid, decenoic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid , linoleic acid, linolenic acid, arachidic acid, peanut tetrazoic acid, dodecanoic acid, sinapic acid, 2-ethylhexanoic acid, etc. (4) Examples of ultraviolet absorbers include · amino benzoic acid, amino-amino benzoin Touch, occupational rest, Weiethyl dihydrogen, brewing, gas-based rest, Wei Gan, p-amino, benzoic acid, cis-amino benzoic acid, sylvestris Salicylic acid 2 diol vinegar, salicylic acid sulphate, salicylic acid triethanolamine, salicylic acid benzene vinegar, salicylic acid butyl sulphate, salicylic acid (four) purpose, water riding with Meng § purpose, cinnamic acid festival Vinegar, p-methoxycinnamic acid vinegar, p-methoxycinnamic acid 2-ethylhexyl ester, di-p-methoxycinnamic acid mono-2-ethylhexanoate, isopropyl p-methoxycinnamate, P-methoxycinnamic acid diethanolamine, diisopropyl. Diisopropyl cinnamic acid ester mixture, urinary acid, ethyl urate, hydroxymethoxybenzyl, methoxymethoxybenzoic acid And its salt, dimethoxymethyl benzoyl, sodium dimethyl benzophenone sulfonate, dibenzobenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctyloxybenzophenone , tetrahydroxybenzophenone, butyl methoxy dibenzoylmethane, 2,4,6-triphenylamine p-(2-ethylhexyl-1-carboxy)_ι, 3, 5-triazine, 2- (2-hydroxy-5methylphenyl)benzotriazole, o-aminobenzoic acid methyl ester, 2-amino-3'3-diphenylacrylic acid 2-ethylhexyl ester, phenyl benzimidazole Sulfuric acid, 3-(4-mercaptobenzylidene) camphor, isopropyldiphenylmethylmethane, 4-(3'4-dimethoxyphenylmethylene)_2, 5-dioxoimidazolidinylpropan-2-ethylhexyl ester, and the like, or a polymer derivative of these materials or Shi Xi 29 200902033 Derivatives, etc. (5) Examples of powders and pigments include red 1〇4, red 2〇ι, yellow 4, and blue! No., black 4〇1 and other pigments; yellow No. 4 AL sink; temple color, yellow 2_β Α sink; temple color and other sinking pigment; nylon powder, silk powder, amino bismuth citrate powder, Teflon (Registrar powder, Shi Xi _ powder, polymethyl methacrylate powder _ powder, cellulose powder, lake:, = spherical elastomer powder, polyethylene powder and other polymers; yellow iron oxide, color emulsified iron, black oxidation Iron, chrome oxide, carbon black, ultramarine blue, dark blue and other colored pigments; zinc oxide, titanium oxide, oxidation _ stone powder, mica, self-dance, pure earth pigment; slip tape mother (four) read..., slab-like enamel and other body pigments ; metal salts such as bismuth citrate, paste, magnesium carbonate, _, 夕酉义镇; Shi Xi, Oxidation and other inorganic powders such as magnesium stearate, palm strontium zinc, zinc sulphate day zinc sulphate, ten-dilute acid Words such as metal fertilizers; swelling == scales. The shape of these powders (spherical, rod-shaped, needle-like, plate-like: Γ and spindle-like) and particle size are not particularly limited. ί, frequency grease treatment, Draping treatment method, rational method, _ mixture treatment method, oil treatment method, Ν-treatment method, metal fertilizer method, 'i treatment method, no Compound processing method, a surface treatment and the like. Cherry method nettle) of these powders advanced pre

W與(”舌性劑的例子•離子型表面活性劑可以 列舉有.脂肪酸肥東、苴A A ot-fe基磺酸鹽、烷基磺酸鹽、烷 30 200902033 基稀丙基績酸鹽、院基萘續酸鹽、烧基硫酸鹽、p〇E烧 基醚硫酸鹽、烷基氨基硫酸鹽、烷基磷酸鹽、p〇E烷基 磷酸鹽、烷基氨基磷酸鹽、烷醯基烷基牛磺酸鹽、N-醯 基氣基酸鹽、Ρ0Ε烧基醚羧酸鹽、烧基續基琥珀酸鹽、 烷基磺基醋酸鈉、醯基化水解膠原蛋白肽鹽、全氟烷基 磷酸酯等。陽離子型表面活性劑可以列舉有:烷基三曱 基氯化錄、硬脂醯基三甲基氯化錄、硬脂醯基三甲基溴 化銨、十八碳醯基十六碳醯基三甲基氣化銨、二硬脂醯 基二甲基氯化銨、硬脂醯基二甲基苄基氯化銨、二十二 碳醯基三甲基溴化銨、氣化新潔爾滅、二十二酸氨基丙 基二曱基羥基丙酯氣化敍、硬脂酸二乙基氨基乙醯胺、 硬脂酸二曱基氨基丙醯胺、羊毛脂衍生物季銨鹽等。兩 性表面活性劑可以列舉有··羧基甜菜域型、醯胺基甜菜 域型、%基甜菜域型、羥基續基甜菜域型、酿胺基續基 甜菜域型、磷酸甜菜域型、氨基羧酸鹽型、咪唑啉衍生 物型、醯胺基胺型等。非離子型表面活性劑可以列舉有·· 丙二醇脂肪酸酯、甘油脂肪酸酯、聚甘油脂肪酸酯、山 梨糖醇脂肪酸酯、Ρ0Ε脫水山梨醇脂肪酸酯、p〇E山梨糖 醇脂肪酸酯、Ρ0Ε甘油脂肪酸酯、P0E烷基醚、p〇E脂肪 酸醋、Ρ0Ε硬化萬麻油、Ρ0Ε.Ρ0Ρ共聚物、p〇Ep〇p =基 醚、聚醚改性矽氧烷月桂酸烷基醇醯胺、烷基氧化胺二 氫化大豆卵磷脂等。天然表面活性劑可以列舉有:卵磷 脂、皂苷、糖類表面活性劑等。 (Ό多元醇、糖的例子可以列舉有:乙二醇、一 乙二醇、聚乙二醇、丙二醇、二丙二醇、聚丙二醇、甘 31 200902033 油、二甘油、聚甘油、3-曱基-1,3-丁二醇、1,3-丁二醇、 山梨醇、甘露醇、蜜三糖、赤蘚糖醇、葡萄糖、蔗糖、 果糖、木糖、乳糖、麥芽糖、麥芽糖醇、海藻糖、烧基 化海藻糖、混合異性糖、硫酸化海藻糖、支鏈澱粉等。 另外也可以使用它們的化學修飾物等。 (8)高分子的例子有:丙烯酸酯/曱基丙烯酸酯共聚 物。今只兮< 久'、互應化學株式會社製造)、醋酸乙烯 酯/巴豆酸共聚物(b夕> 28-1310、NSC株式會社製造)、 醋酸乙烯醋/巴豆酸/新癸酸乙烯酯共聚物(28-2930、NSC 株式會社製造)、甲基乙烯基喊馬來酸半酯(力、y卜k 7 7 ES、ISP株式會社製造)、丙烯酸叔丁酯/丙烯酸乙酯 /曱基丙烯酸共聚物(儿匕7—、BASF株式會社製造)、 乙烯基吡咯烷酮/乙酸乙烯酯/丙酸乙烯酯共聚物(儿匕 只:^一瓜VAP、BASF株式會社製造)、乙酸乙烯基酯/ 巴豆酸共聚物(小匕七7卜CA、BASF株式會社製造)、 乙酸乙烯基酯/巴豆酸/乙烯基吡咯烷酮共聚物(小匕七 v卜CAP、BASF株式會社製造)、乙烯基吡咯烷_/丙 烯酸酯共聚物(小匕、7 k 7夕只、BASF株式會社製造)、 丙稀酸酯/丙稀醢胺共聚物(々儿卜今示一小卜,、8八別 株式會社製造)、乙酸乙烯基酯/馬來酸丁酯/丙烯酸異冰 片酯共聚物卜、八、/于一、ISP株式會社製造)、鲮 基乙烯基聚合物(力一水求一小、BFGoodri ch公司製造)、 丙烯酸.曱基丙烯酸烷基共聚物(弋S a k >、即 Goodrich公司製造)等陰離子型高分子化合物;或者甲 基丙稀酸二烧基氨基乙®旨聚合物的乙酸兩性化合物(a 32 200902033 力7才一7—、三菱化學株式會社製造)、丙烯酸辛基丙 烯醯胺/丙烯酸羥基丙S旨/曱基丙烯酸丁基氨基乙酯共聚 物(AMPHOMER、NSC株式會社製造)等兩性高分子化合 物;乙烯基。比洛烧酮/曱基丙烯酸二甲基氨基乙酯的季碳 化物(GAFQUAT、ISP公司製造)、甲基乙烯基氣化咪唑 鏽/乙烯基吡洛烷酮共聚物(儿匕一卜、BASF株式會 社製造)等陽離子型高分子化合物;聚乙烯吼洛烧酮(小 匕只17—小K 'BASF株式會社製造)、乙烯〇比嘻烧酮/W and ("Examples of lingual agents" ionic surfactants may be exemplified by fatty acid fertilizers, 苴AA ot-fe sulfonates, alkyl sulfonates, alkane 30 200902033 propyl propyl acid salts, Alkyl naphthate, alkyl sulfate, p〇E alkyl ether sulfate, alkyl amino sulfate, alkyl phosphate, p〇E alkyl phosphate, alkyl amino phosphate, alkyl alkane Taurate, N-mercaptoyl acid salt, oxime alkyl ether carboxylate, alkyl succinate, sodium alkyl sulfoacetate, thiolated hydrolyzed collagen peptide salt, perfluoroalkane Phosphate esters, etc. The cationic surfactants may be exemplified by alkyl tridecyl chloride, stearyl trimethyl chloride, stearyl trimethyl ammonium bromide, and octadecyl fluorenyl. Hexadecamethyltrimethylammonium hydride, distearyl dimethylammonium chloride, stearyl dimethyl benzyl ammonium chloride, docosalyltrimethylammonium bromide, Gasification of neostigmine, behenic acid aminopropyl decyl hydroxypropyl ester gasification, stearic acid diethylaminoacetamide, stearic acid dinonylaminopropionamide, lanolin derivative Quaternary ammonium salts, etc. The amphoteric surfactants may be exemplified by a carboxyl beet domain type, a guanyl beet domain type, a % based beet domain type, a hydroxy contiguous beet domain type, a stilbene contiguous beet domain type, and a phosphoric acid. Examples of the sugar beet type, the aminocarboxylate type, the imidazoline derivative type, the guanamine type, etc. Examples of the nonionic surfactant include propylene glycol fatty acid ester, glycerin fatty acid ester, and polyglycerin fatty acid ester. Sorbitol fatty acid ester, Ρ0Ε sorbitan fatty acid ester, p〇E sorbitol fatty acid ester, Ε0Ε glycerin fatty acid ester, P0E alkyl ether, p〇E fatty acid vinegar, Ρ0Ε hardened kenaf oil, Ρ0Ε.Ρ0Ρ Copolymer, p〇Ep〇p=yl ether, polyether modified decane decanoic acid alkyl decylamine, alkyl amine oxide dihydrogenated soybean lecithin, etc. Natural surfactants may be exemplified by lecithin and saponin. , saccharide surfactants, etc. (Examples of hydrazine polyols, sugars include: ethylene glycol, monoethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, gan 31 200902033 oil, diglycerin, poly Glycerol, 3-mercapto-1,3-butanediol 1,3-butanediol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylose, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed heterosexuality Sugar, sulfated trehalose, amylopectin, etc. It is also possible to use chemical modifications thereof, etc. (8) Examples of the polymer are: acrylate/mercapto acrylate copolymer. Today only 兮<久', Vinyl acetate/crotonic acid copolymer (bashi > 28-1310, manufactured by NSC Co., Ltd.), vinyl acetate vinegar/crotonic acid/vinyl neodecanoate copolymer (28-2930, NSC Co., Ltd.), methyl vinyl shoddenic acid half ester (force, y b k 7 7 ES, manufactured by ISP), t-butyl acrylate / ethyl acrylate / methacrylic acid copolymer -, manufactured by BASF Co., Ltd.), vinylpyrrolidone / vinyl acetate / vinyl propionate copolymer (children only: ^ one melon VAP, manufactured by BASF Co., Ltd.), vinyl acetate / crotonic acid copolymer (small Seven 7 Bu CA, manufactured by BASF Co., Ltd.), acetic acid Vinyl ester/crotonic acid/vinylpyrrolidone copolymer (small 匕7v CAP, manufactured by BASF Corporation), vinylpyrrolidine _/acrylate copolymer (small 匕, 7k 7 夕, manufactured by BASF Corporation) ), acrylate/acrylamide copolymer (a small cloth, as shown in 8), vinyl acetate/butyl maleate/isobornyl acrylate copolymer, eight , / Yu Yi, ISP Co., Ltd.), fluorenyl vinyl polymer (manufactured by BF Goodri ch), acrylic acid alkyl methacrylate (弋S ak >, Goodrich Anionic polymer compound such as Manufactured; or an acetic acid amphoteric compound of methacrylic acid dialkylaminoethane® polymer (a 32 200902033, 7 7-7, manufactured by Mitsubishi Chemical Corporation), octyl propylene acrylate An amphoteric polymer compound such as decylamine/acrylic acid hydroxypropyl S/butyl cyanoacrylate copolymer (manufactured by AMPHOMER, NSC Co., Ltd.); vinyl group. Quaternary carbide of pirone ketone/dimethylaminoethyl methacrylate (GAFQUAT, manufactured by ISP), methyl vinyl vaporized imidazole rust/vinyl pyridoxone copolymer (baby 匕, BUSF) A cationic polymer compound such as manufactured by Co., Ltd.; polyvinylpyrrolidone (small smear only 17-small K 'BASF Co., Ltd.), vinyl hydrazine ketone ketone /

醋酸乙稀基酯共聚物(儿匕义:7—^VA、BASF株式會 社製造)、.乙烯吡咯烷酮/曱基丙烯酸二甲基氨基乙酯共 聚物(:7水”7—937、ISP公司製造)、乙烯基己内醯 胺/乙烯吡咯烷酮/曱基丙烯酸二甲基氨基乙酯共聚物 (:7水17—VC713、ISP公司製造)等非離子型高分 子化合物等。另外,下列來源於天然的高分子化合物也 疋適用的.纖維素及其衍生物、角蛋白及膠原蛋白或它 們的衍生物、海藻酸鈣、普魯蘭多糖、瓊脂、明膠、羅 望子種子多糖、黃原膠、角叉菜聚糖、高甲氧基果膠、 低甲氧基果膠、瓜爾膠、阿拉轉、結晶纖維素、阿拉 伯半乳聚糖、刺梧桐樹膠、黃挪、海驗、白蛋白、 酪蛋白、凝膠多糖、結冷膠、葡聚糖等。 (9)生理活性成分的例?作為生理活性成分,在 塗敷於皮膚上的情況中,可以列舉那些可以給皮膚帶來 某種生理活性的物質。例如,可以列舉美白成分、免疫 賦活劑、抗老化劑、防紫外線劑、痩身劑、拉伸劑、抗 氧化知&毛肖彳、月毛劑、保濕劑、促進血液迴圈劑、 33 200902033 抗菌劑、殺菌劑、乾燥劑、冷感劑、溫感劑、維生素類、 氣基酸、創傷治癒促進劑、刺激緩和劑、鎮痛劑、細胞 賦活劑、酶成分等。作為與這些生理活性成分配伍的合 適的成分的例子,例如有:返陽草萃取物、鱷梨萃取物、 土常山萃取物、蜀葵萃取物、山金車萃取物、蘆薈萃取 物、杏萃取物、杏核萃取物、銀杏萃取物、菌香萃取物、 郁金萃取物、烏龍茶萃取物、營實萃取物、松果菊葉萃 取物、黃芩萃取物、黃檗萃取物、黃連萃取物、大麥萃 取物、小連翹萃取物、野芝麻萃取物、豆掰菜萃取物、 橘子萃取物、海水乾燥物、海藻萃取物、水解彈性蛋白、 水解麥子粉末、水解絲、洋甘菊萃取物、胡蘿萄萃取物、 茵陳蒿萃取物、甘草萃取物、扶桑萃取物、火棘萃取物、 金雞納萃取物、黃瓜萃取物、鳥苷、梔子萃取物、山白 竹萃取物、苦參萃取物、胡桃萃取物、葡萄柚萃取物、 繡球藤萃取物、螺旋藻萃取物、桑萃取物、龍膽草萃取 物、紅茶萃取物、酵母萃取物、牛蒡萃取物、玄米發酵 萃取物、米胚芽油、聚合草萃取物、骨膠原、越橘萃取 物、細辛萃取物、柴胡萃取物、臍帶萃取液、鼠尾草萃 取物、肥皂草萃取物、小竹萃取物、山楂萃取物、花椒 萃取物、香益萃取物、地黃萃取物、紫根萃取物、紫蘇 萃取物、椴樹萃取物、繡線菊萃取物、芍藥萃取物、菖 蒲根萃取物、白樺萃取物、問荊萃取物、常春藤萃取物、 西洋山楂萃取物、接骨木萃取物、西洋蓍草萃取物、西 洋薄荷萃取物、鼠尾草萃取物、錦葵萃取物、川芎萃取 物、獐牙菜萃取物、大豆萃取物、大棗萃取物、百里香 34 200902033 萃取物、茶萃取物、丁香萃取物、茅草萃取物、陳皮萃 取物、當歸萃取物、金盞菊萃取物、桃仁萃取物、檜樹 萃取物、魚腥草萃取物、番茄萃取物、納豆萃取物、人 參萃取物、蒜萃取物、野薔薇萃取物、扶桑萃取物、麥 門冬萃取物、歐芹萃取物、蜂蜜、金縷梅萃取物、夏白 菊萃取物、香茶菜萃取物、紅沒藥醇、枇杷萃取物、蒲 公英萃取物、蜂鬥菜萃取物、茯苓萃取物、假葉樹萃取 物、葡萄萃取物、蜂膠、絲瓜萃取物、紅花萃取物、胡 椒薄荷萃取物、菩提樹萃取物、牡丹萃取物、啤酒花萃 取物、松萃取物、歐洲七葉樹萃取物、水芭焦萃取物、 無患子萃取物、香蜂花萃取物、桃萃取物、矢車菊萃取 物、桉樹萃取物、虎耳草萃取物、薏苡仁萃取物、艾蒿 萃取物、薰衣草萃取物、蘋果萃取物、萵苣萃取物、擰 杈萃取物、紫雲英萃取物、薔薇萃取物、迷迭香萃取物、 羅馬甘菊萃取物、蜂王漿萃取物等。另外、還可以列舉: 去氧核糖核酸、粘多糖類、透明質酸鈉、硫酸軟骨素鈉、 骨膠原、彈性蛋白、幾丁質、脫乙醯殼多糖、水解印殼 膜等生物高分子;氨基酸、搞肽、乳_、尿素、吼 祕峨_、甜菜域、乳清、三甲基甘氨酸等保渴成 分;神經脂質、神經酿胺、植物鞘氨醇、膽固醇、膽固Ethyl acetate copolymer (Kaiyiyi: 7-^VA, manufactured by BASF Co., Ltd.), vinylpyrrolidone/dimethylaminoethyl methacrylate copolymer (: 7 water) 7-937, manufactured by ISP ), non-ionic polymer compounds such as vinyl caprolactam/vinylpyrrolidone/dimethylaminoethyl methacrylate copolymer (: 7 water 17-VC713, manufactured by ISP), etc. The polymer compound is also suitable for use. Cellulose and its derivatives, keratin and collagen or their derivatives, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharide, xanthan gum, horn Cucurbita, high methoxyl pectin, low methoxyl pectin, guar gum, ala conversion, crystalline cellulose, arabinogalactan, karaya gum, yellow nautical, sea test, albumin, cheese Protein, curdlan, gellan gum, dextran, etc. (9) Examples of physiologically active ingredients? As a physiologically active ingredient, in the case of application to the skin, those which can bring some kind of physiology to the skin can be cited. Active substance. For example, List whitening ingredients, immunostimulating agents, anti-aging agents, anti-UV agents, body lotions, stretching agents, anti-oxidation know & Mao Xiaoying, moon hair, moisturizer, blood circulation promoting agent, 33 200902033 antibacterial agent, A bactericide, a desiccant, a cold sensitizer, a warming agent, a vitamin, a gas-based acid, a wound healing promoter, a stimulating emollient, an analgesic, a cell activating agent, an enzyme component, etc. as a suitable distribution for these physiological activities Examples of ingredients include, for example, backgrass extract, avocado extract, earthen mountain extract, hollyhock extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, ginkgo extract , bactericidal extract, turmeric extract, oolong tea extract, turmeric extract, echinacea extract, scutellaria extract, scutellaria extract, berberine extract, barley extract, small forsythia extract, wild sesame Extract, cardamom extract, orange extract, seawater dry matter, seaweed extract, hydrolyzed elastin, hydrolyzed wheat powder, hydrolyzed silk, chamomile extract, coriander extract , Artemisia annua L. extract, licorice extract, hibiscus extract, Pyracantha extract, cinchona extract, cucumber extract, guanosine, hazelnut extract, mountain white bamboo extract, Sophora flavescens extract, walnut extract , grapefruit extract, hydrangea extract, spirulina extract, mulberry extract, gentian extract, black tea extract, yeast extract, burdock extract, black rice fermentation extract, rice germ oil, polymer grass Extract, Collagen, Bilberry Extract, Asarum Extract, Bupleurum Extract, Umbilical Cord Extract, Sage Extract, Soap Extract, Bamboo Extract, Hawthorn Extract, Pepper Extract, Xiangyi Extract, Rehmannia Extract, Purple Root Extract, Perilla Extract, Eucalyptus Extract, Spiraea Extract, Peony Extract, Caladium Root Extract, White Birch Extract, Euphorbia Extract, Ivy Extract, Western hawthorn extract, elderberry extract, yarrow extract, western mint extract, sage extract, mallow extract, Chuanxiong extract, sauerkraut extract, soy extract , jujube extract, thyme 34 200902033 extract, tea extract, clove extract, thatch extract, dried tangerine peel extract, angelica extract, calendula extract, peach extract, eucalyptus extract, surimi Grass extract, tomato extract, natto extract, ginseng extract, garlic extract, wild rose extract, hibiscus extract, wheat meringue extract, parsley extract, honey, witch hazel extract, daisy extract , fragrant tea extract, bisabolol, alfalfa extract, dandelion extract, butterbur extract, alfalfa extract, fake leaf extract, grape extract, propolis, loofah extract, safflower extract , Peppermint Extract, Linden Extract, Peony Extract, Hop Extract, Pine Extract, Horse Chestnut Extract, Water Barley Extract, Sapindus Extract, Fragrant Bee Flower Extract, Peach Extract, Cornflower Extract, Eucalyptus Extract, Saxifrage Extract, Coix Seed Extract, Artemisia Extract, Lavender Extract, Apple Extract, Lettuce Extract, Screw Extract, milk vetch extract, rose extract, rosemary extract, Roman chamomile extract, royal jelly extract and the like. In addition, there may be mentioned: biopolymers such as deoxyribonucleic acid, mucopolysaccharide, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, hydrolyzed shell film; Amino acid, peptide, milk _, urea, 吼 secret 峨, sugar beet, whey, trimethylglycine and other thirst-quenching ingredients; neurolipids, spirulina, sphingosine, cholesterol, cholesterol

=./等油性成分;咖酸、甘L P 甘卓:欠酸、氣化溶_、愈創藍油烴、口: P y/等免疫賦活劑;維生素 J 維生素c、維生素D、維E、$、維生素即、 煙酸醯胺、維生素c醋等音、,:弓、生物素、 曰等維生素類,尿囊素、二氣乙酸 200902033 二異丙胺、4-躲甲基環己酸料軸分;生育盼 胡蘿自素、黃酮、鞣質、木質素、皂普等抗氧化劑;α_ 經酸、β-鐵等細胞賦活劑;γ_穀維素、維生素ε衍生 物等血液迴圈促視黃醇、視黃醇魅物等創傷治 癒劑;白蛋白、曲酸、胎盤萃取物、硫續、縣花酸、二 油酸、凝錢、魏甘轉美白劑;風箱射、甘草萃 取$、辣椒素、檜醇、峨化蒜萃取物、鹽酸呢咳醇、DLt 生月驗、醋酸DL-oc-生育酚、煙酸、煙酸衍生物、泛酸 鈣、D-泛醇、乙醯基泛醯乙基醚、生物素、尿囊素、異 丙基曱基苯紛、雌二醇、乙块基雌二醇、卡普氣録、苯 紫氯錢、鹽酸苯海拉明、夕力十一》、掉腦、水揚酸、 壬酸香子_胺、壬燒酸香子蘭醯胺、口夕卜y才今 、'十五烷酸甘油酯、L-薄荷醇、單硝基愈創木酚、 間苯二酚、7_氨基丁酸、苄索氣銨、鹽酸美西律、植物 生長素、雌激素、斑蝥酊、環孢菌素、吡啶硫酮鋅、t 卜口 17小千^ ^、米諾地爾、單硬脂酸聚氧乙烯山梨 聚糖、薄荷油、寸甘4丰米萃取物等育毛劑等。 (10)抗氧化劑的例子可以列舉··亞硫酸氫鈉、亞硫 酸納、異抗壞血酸、異抗壞血軸、硫代二丙酸二月桂 酉曰、生育酚、f苯基雙胍、去甲二氫愈創木酸、對羥基 苯甲醚、丁基羥基笨甲醚、二丁基羥基甲苯、硬脂酸抗 壞血酸酯、棕櫚酸抗壞血酸酯、沒食子酸辛酯、沒食子 酸丙酯、類胡蘿蔔素、黃酮、鞣質、木質素、皂苷、蘋 果萃取物和丁香萃取物等具有抗氧化效果的植物萃取物 等。 36 200902033 (11)溶劑的例子可以列舉:純化水、乙醇、低級醇、 醚類、LPG、碳氣化合物、N-曱基κ烧酮、氟取代醇、 具有揮發性的直鏈石夕氧烧、次生氟利昂等。 【實施方式】 為便於貴審查委員能對本發明之技術手段及運 作過程有更進-步之認識與瞭解實施例配合圖 式,詳細說明如下。 本發明係一種「神經芽細胞增殖促進劑及神經突起 伸展劑」’本發明之神經芽細胞增殖促進劑之製備實施例 一 ’係製備一列當科全寄生植物管花肉蓰蓉(&对如 如/%//)(下文中簡稱為“管花肉蓰蓉”)之萃取物, 該製備係包括以下步驟: 步驟一:萃取;取一管花肉蓰蓉新鮮莖之薄片l〇kg 浸潰於該薄片8倍量之水中,將該薄片在浸潰1小時 後,用水煎煮2小時成為一混合物,同時將煎煮後之該 混合物過濾,即得一第一濾液,另外,將過濾後之一該 混合物殘渣與該殘渣之4倍量40%乙醇混合後,再煎煮 4小時,再次進行過濾, 得到一第二濾液’再將該第二濾液過濾後之殘渣依上述 同樣步驟’將殘渣與該殘渣之4倍量40%乙醇混合後, 再煎煮4小時並進行過濾,重複操作2次,得到一第三 濾液及一第四濾液,再合併該第一、第二、第三及第四 濾液’進行一真空濃縮,使其比重濃縮至1.05,即得 一最終萃取物(該最終萃取物之重量為6.2kg)。 步驟二:純化;將上述該最終萃取物置於其一半重 37 200902033 量之水中加熱(5〇。〇,使其溶解於水中,即得 物溶液,再將該萃取物溶液置於—填充預先處= D-101型大孔吸附樹脂的吸附柱中, 柱^以得該新鮮莖2倍量之水溶液,再以— 洗該吸附柱’得到-該新鮮莖2倍量之施乙醇L 水溶液’將該第-水減再切行前狀刻 驟’得到H醇之第二水溶液,合併該第―、第二 水溶液,經過-濃縮及乾燥程序,即得—含有苯 ^=./Equivalent oily ingredients; coffee acid, Gan LP Ganzhuo: anodic acid, gasification solution _, guaiac blue oil hydrocarbon, mouth: P y / and other immune activators; vitamin J vitamin c, vitamin D, vitamin E, $, vitamins, niacinamide, vitamin c vinegar, etc.,: bow, biotin, bismuth and other vitamins, allantoin, di-acetic acid 200902033 diisopropylamine, 4-isomethylcyclohexanoate Fermentation expectant carotene, flavonoids, tannins, lignin, soap and other antioxidants; α_ acid, β-iron and other cell activators; γ_ oryzanol, vitamin ε derivatives and other blood circulation Retinol, retinol charm and other wound healing agents; albumin, kojic acid, placenta extract, sulphur, county flower acid, dioleic acid, condensed money, Weigan to whitening agent; bellows, licorice extract $, capsaicin, sterol, simmered garlic extract, cough HCl, DLt, monthly test, DL-oc-tocopherol acetate, niacin, nicotinic acid derivative, calcium pantothenate, D-panthenol, acetamidine Base ubiquinone ethyl ether, biotin, allantoin, isopropyl decyl benzene, estradiol, ethyl estradiol, Kapp gas recording, phenyl violet money, phenyl sea HCl Ming, Xi Li eleven, off brain, salicylic acid, citric acid fragrant _ amine, simmered acid vanillyl amide, mouth y y y, today, 'pentadecanoic acid glyceride, L-menthol, single Nitroguaiacol, resorcinol, 7-aminobutyric acid, benzethonium hydrochloride, mexiletine hydrochloride, auxin, estrogen, canthaxanthin, cyclosporin, zinc pyrithione, t Oral hair dyes such as 17 small thousand ^ ^, minoxidil, polyoxyethylene sorbitan monostearate, peppermint oil, and indigo 4 extracts. (10) Examples of antioxidants include sodium hydrogen sulfite, sodium sulfite, erythorbic acid, diarrhea, thiodipropionate, lauric acid, tocopherol, f-phenyl guanidine, and guanidine Hydrogen guaiac acid, p-hydroxyanisole, butyl hydroxymethyl ether, dibutyl hydroxy toluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, Plant extracts having antioxidant effects such as carotene, flavonoids, tannins, lignin, saponins, apple extracts, and clove extracts. 36 200902033 (11) Examples of the solvent include purified water, ethanol, lower alcohol, ether, LPG, carbon gas compound, N-fluorenyl ketone ketone, fluorine-substituted alcohol, and volatile linear smoldering , secondary Freon and so on. [Embodiment] In order to facilitate the review committee to have a more advanced understanding of the technical means and operation process of the present invention and to understand the embodiment with the drawings, the details are as follows. The present invention relates to a "brain cell proliferation promoting agent and a neurite outgrowth agent", "Preparation Example 1 of the neuroblast cell proliferation promoting agent of the present invention", and prepares a column of the whole parasitic plant Cistanche tubulosa (& For example, if the extract is in the form of /%// (hereinafter referred to as "Cistanche tubulosa"), the preparation includes the following steps: Step 1: Extraction; take a tube of fresh stem of Cistanche tubulosa l〇kg Dip into the water of 8 times the amount of the sheet, and after immersing the sheet for 1 hour, it is decocted with water for 2 hours to form a mixture, and the mixture after decoction is filtered to obtain a first filtrate, and, in addition, After the filtration, the residue of the mixture is mixed with 4 times of 40% ethanol of the residue, and then boiled for 4 hours, and filtered again to obtain a second filtrate. The residue after filtering the second filtrate is subjected to the same steps as above. 'The residue was mixed with 4 times the amount of 40% ethanol of the residue, and then boiled for 4 hours and filtered. The operation was repeated twice to obtain a third filtrate and a fourth filtrate, and the first and second were combined. The third and fourth filtrates Concentrated, it is concentrated to a specific gravity of 1.05, yielding a final extract (by weight of the final extract was 6.2kg). Step 2: Purification; the above final extract is placed in water with a half weight of 37 200902033 (5 〇. 〇, so that it is dissolved in water, that is, the solution is obtained, and then the extract solution is placed - pre-filled = D-101 type macroporous adsorption resin in the adsorption column, the column is obtained with 2 times the amount of the fresh stem aqueous solution, and then - washing the adsorption column 'to obtain - the fresh stem 2 times the amount of ethanol solution L ' The first water-reducing and then cutting is performed to obtain a second aqueous solution of H alcohol, and the first and second aqueous solutions are combined, and after -concentration and drying procedures, the benzene is contained.

類化合物之萃取物(該萃取物之重量為Q 865⑷。 以高效液相法(HPLC)來測定其中松果菊普及類 升麻芽之含量,該,之條件如下:固定相為—⑽ 絲魏鍵合梦膠,流動相為m 15%醋酸水溶液 (30:70),其流速為1毫升/分鐘,其檢職長為咖舰。 各秤取於60 X真空中乾燥24㈣之—松果菊苦及 一類葉升麻苷,並溶解於一 50%曱醇中,配製成一對照 办液(該對照溶液濃度為lmL溶液中含有〇· lmg溶質)。 一邊以超音波處理,一邊將含有該苯乙醇苷類化合 物之該萃取物50mg溶解於一裝有適量5〇%甲醇之邠mL 容量瓶中 ,向上述溶液中再加入50%甲醇,並調節至25虬刻度 處,精密量取該溶液約lniL,置於一 10mL之容量瓶中, 加入5(U甲醇直至刻度,最後再以一 〇· 膜過濾後, 即製備完成一樣品溶液。 w 分別量取5μ1該對照溶液及該樣品溶液,並分別注 入一高效液相色譜儀中,分別測定其中之松果菊苷及類 38 200902033 葉升麻苷之峰面積,最後根據其峰面積計算含量,其結 果顯示,該松果菊苷在該萃取物中之含量為37. 5%、類 葉升麻苷在該萃取物中之含量為9.0%。 貫施例二及實施例三,係分別為一松果菊苷(在本 實施例中該松果菊苷為杏輝藥品工業股份有限公司所製 造)及一類葉升麻苷純品(在本實施例中該一類葉升麻 苷純為杏輝藥品工業股份有限公司所製造)對神經芽 細胞增殖作用之實驗(請參閱第二圖所示)。 實驗一:神經芽細胞增殖作用之評價試驗方法,將 一人類神經牙細胞(該神經芽細胞為一 )混懸 在一 MEM培養基(該MEM培養基内含有一 1〇%FCS、一 lOOimits/mL青黴素及一議^虬鏈黴素)中,在一 6刪之シ十一 k中各加入5ml之上述混懸液,然後加入 配製成各種濃度之實施例—中該管花肉祕萃取物,培 養5天’然後採用MTT測定法來評價培養第5天之該細 胞增殖度’其結果如第-騎示’並按朗樣步驟對實 施例二和實關三之該萃取物進行試驗,絲如第二圖 所示。 如第-圖所示,當採用Μττ測定法測定細胞之增殖 度日寸’發㈣官化岐料取物表現出濃度依賴性之神 經芽細胞增殖作用’當該管花肉薇蓉萃取物濃度為1〇 /zg/mL時,該神經芽細胞增殖度為7%,當該管花肉蓰 蓉萃取物濃度為3G#g/mL時,該神㈣細胞增殖度為 通,由此絲可t㈣:即使在轉經芽細胞沒有發生病 變狀態下’該管制_萃取物仍财使人類神經芽細 39 200902033 胞(SK-N-SH)增殖之作用,另外,如第二圖所示 用MTT測以測定該神經芽細胞之增殖度時,發現該松 果菊普及该賴升料表·濃度依賴性之神經芽細 胞增瘦作用,尤其是松果菊苦在1//g/mL和1〇㈣此 的濃度下表現出—_差異,藉此亦可確認··即使在該 神經芽細胞沒有發生病變狀態下,該苯乙料類化^ 物’尤其是該松果菊肢該㈣升麻苦亦具有使人 經芽細胞(SK-N-SH)增殖之作用。 實驗二:神經突起伸展作用之評價 將人類之神經芽細胞(SK_N_SH)混懸在—MEM培 養基(含有- 10%FCS、- 1〇〇 units/mL青黴素及⑽ #gAnL鏈黴素)中,在一 6刪シ十一卜中各加入鼬丄 士述混懸液’再加入配製成各種濃度之實施例一中該管 才匕肉蓰容萃取物,用顯微鏡來觀察神經突起隨時間之變 化同相紀錄,結果如第三圖所示,另外,按照同 樣步驟對實施例二和實施例三之萃取物也進行試驗,其 結果分別如第四圖和第五圖所示。 如第三圖所示,該對照組雖然表現出一細胞增殖現 象,但是基本上並觀察不到其神經突起伸展的樣子,與 此形成對照的是’該管花肉蓰蓉萃取物組可觀察到較多 之神經突起伸展(參考第三圖實線圈内之情況),尤其 當該管花肉蓰蓉萃取物濃度為30//g/mL時,可以發現 §亥神餐突起與相鄰的細胞形成一網路,由此可以確認: 即使在該神經芽細胞沒有發生病變之狀態下,該管花肉 萃心i萃取物同樣具有濃度依賴性之神經突起伸展作用。 40 200902033 一細圖中,該對照組雖然表現出 樣子,盘絲本上觀察不顺經突起伸展的 該類_2=’^果菊倾(第四圖)及 起伸# U圖)則可以贿到較多之神經突 外考第四圖及第五圖之虛線圈内情況),另 如-二A、果料組中,於低濃度時刊顯地觀察到該 二起與相鄰的細胞形成一網路(參考 圈/ 二的情況),*此可確認:即使在該神經芽細胞沒有發= ^早礙的狀態下,鮮乙_類化合物,尤其是該 皆及鋼葉升麻朗樣具有濃度依雛地促進神參: 起伸展之作用。 〜犬 下面列舉本發明中神經芽細胞增殖促進劑之一配 方例,但該配方例並不用於限定本發明。 _ 53.0重量% 20.0 10.0 16.0 0.5 0.5 配方例一:口香糖 砂糖 膠基 葡萄糖 水飴 香料 神經芽細胞增殖促進劑 等The extract of the compound (the weight of the extract is Q 865 (4). The content of the ascending buds of the echinacea is determined by high performance liquid chromatography (HPLC), and the conditions are as follows: the stationary phase is - (10) silk Wei bonding Dream gel, mobile phase is m 15% aqueous acetic acid solution (30:70), its flow rate is 1 ml / min, its inspection is long for the coffee ship. Each scale is taken in 60 X vacuum to dry 24 (four) - pine cone chrysanthemum and a class Leaf asparagine, dissolved in a 50% sterol, formulated into a control solution (the concentration of the control solution is 1 mL of solution containing 〇·lmg solute). While ultrasonically treated, it will contain the phenylethyl alcohol. 50 mg of the extract of the glycoside compound was dissolved in a 邠mL volumetric flask containing an appropriate amount of 5% methanol, and 50% methanol was further added to the above solution, and adjusted to a 25-inch scale, and the solution was accurately weighed to about 1 niL. Put in a 10mL volumetric flask, add 5 (U methanol to the mark, and finally filter with a membrane), then prepare a sample solution. w separately measure 5μ1 of the control solution and the sample solution, respectively Inject into a high performance liquid chromatograph and measure separately The 5%, the class of the content of the echinacoside in the extract is 37.5%, the class of the content of the echinacoside and the genus 38. The content of scutellarin in the extract is 9.0%. According to the second embodiment and the third embodiment, each is an echinacoside (in the present embodiment, the echinacoside is limited to the nectar pharmaceutical industry. The company's manufacture) and a class of pure lutein (in this example, the class of leaf asparagine purely manufactured by Xinghui Pharmaceutical Industry Co., Ltd.) on the proliferation of neuroblasts (see the second figure) Experiment 1: Evaluation method for evaluating the proliferation of nerve bud cells, a human neurotooth cell (the nerve bud cells are one) was suspended in an MEM medium (the MEM medium contained 1% FCS, one In the case of lOOimits/mL penicillin and a streptomycin, 5 ml of the above suspension is added to each of the 6 删11k, and then added to the various examples of the composition - the tube meat Secret extract, cultured for 5 days' then determined by MTT To evaluate the cell proliferation degree on the 5th day of culture, the result is as shown in the first step, and the extract of Example 2 and the actual Guan 3 was tested according to the sample step, as shown in the second figure. - As shown in the figure, when the Μττ assay is used to determine the proliferative degree of the cells, the 官 发 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 当 当 当 当 当 当 当 当 当 当 当 当 当 当When 〇/zg/mL, the proliferation rate of the nerve bud cells is 7%. When the concentration of the extract of Cistanche tubulosa is 3G#g/mL, the cell proliferation degree of the god (four) is pass, and thus the silk can be t (four): Even if the transfusion of bud cells does not occur in the lesion state, the extract is still responsible for the proliferation of human neuroblasts 39 200902033 cells (SK-N-SH), in addition, as measured by MTT as shown in the second figure When the proliferation degree of the nerve bud cells was measured, it was found that the echinacea popularizes the concentration-dependent neuroblast cell thinning effect, especially the pineal chrysanthemum bitterness at 1//g/mL and 1〇(4). This concentration shows a difference of -, which can also be confirmed. Even if the neuroblast has no lesions The state of the styrene-based material was ^ 'In particular, the Echinacea limb pain cohosh also has the effect (iv) proliferation of people over bud cells (SK-N-SH). Experiment 2: Evaluation of neurite outgrowth The human neuroblasts (SK_N_SH) were suspended in -MEM medium (containing -10% FCS, -1〇〇units/mL penicillin, and (10) #gAnL streptomycin). Add a 鼬丄 述 混 ' ' ' シ シ シ シ シ シ シ ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' The results were recorded in the same phase, and the results were as shown in the third figure. Further, the extracts of Example 2 and Example 3 were also tested in the same manner, and the results are shown in Fig. 4 and Fig. 5, respectively. As shown in the third figure, although the control group showed a cell proliferation phenomenon, the neurite outgrowth was not observed at all, and in contrast, the tuberculosis extract group was observed. More neurite outgrowth (refer to the case of the solid coil in the third figure), especially when the concentration of the Cistanche tubulosa extract is 30//g/mL, you can find the sacred food prominence and adjacent The cells form a network, and it can be confirmed that the tube extract is also in a concentration-dependent neurite outgrowth even in the state where the neuroblasts do not have lesions. 40 200902033 In a fine picture, although the control group showed its appearance, the _2='^果菊(4th) and the extension #U figure which can not be observed by the protrusions on the silk screen can be Bribe to more neurite out of the fourth and fifth pictures of the virtual coil), as in the -two A, fruit group, at low concentrations, the two observations and adjacent The cells form a network (in the case of reference circle/two), * this confirms that even in the state where the nerve bud cells are not issued, the fresh B-type compound, especially the steel and the leaf The Lang sample has a concentration to promote the Ginseng: the role of stretching. ~ Dogs The following is an example of a formulation of a neuroblast growth promoter in the present invention, but the formulation is not intended to limit the present invention. _ 53.0% by weight 20.0 10.0 16.0 0.5 0.5 Formulation Example 1: Chewing gum, sugar, gum base, glucose, water, spices, nerve bud cell proliferation promoter, etc.

100.0 重量°/〇 配方例二:咀嚼片 逛原水餘 砂糖 40. 0重量% 20.0 41 200902033 葡萄糖 20.0 明膠 4.7 水 9.68 葡萄汁 4.0 葡萄風味 0.6 色素 0.02 神經芽細胞增殖促進劑 1.0 等 100.0重量% 配方例三:糖果 砂糖 50. 0重量% 水飴 33.0 水 14.4 有機酸 2.0 香料 0.2 神經芽細胞增殖促進劑 0.4 等 100. 0重量% 配方例四:酸乳酪(硬式.軟式) 牛奶 41.5重量% 脫脂粉乳 5.8 砂糖 8.0 瓊脂 0.15 明膠 0.1 乳酸菌 0.005 42 200902033 神經芽細胞增殖促進劑 等 0.4 香料 微量 水 補足 配方例五:清涼飲料 100. 0重量% 果糖葡萄糖的糖液 30. 0重量% 乳化劑 0.5 神經芽細胞增殖促進劑 等 0.05 香料 適量 純化水 補足 配方例六:小甜點 100. 0重量% 砂糖 76.4重量% 葡萄糖 19.0 蔗糖脂肪酸酯 0.050.2 神經芽細胞增殖促進劑 等 0.5 純化水 3.9 配方例七:軟膠囊 100. 0重量% 葡萄籽油 87. 0重量% 乳化劑 12.0 神經芽細胞增瘦促進劑 1.0 43 200902033 等 配方例八:片劑 乳糖 結晶纖維素 澱粉分解物 甘油脂肪酸酯 神經芽細胞增殖促進劑 等 100. 0重量% 54. 0重量% 30.0 10.0 5.0 1.0 100. 0重量% 配方例九:顆粒内服劑(醫藥品) 神經芽細胞增殖促進劑 1.0重量% 等 乳糖 30.0 玉米澱粉 60.0 結晶纖維素 8.0 聚乙烯吡咯烷酮 1.0 100. 0重量% 配方例十:化妝f 角鯊烷 20. 0重量% 蜂纖 5.0 精製荷荷芭油 5.0 甘油 5.0 甘油單硬脂酸酯 2.0 聚氧乙烯(20)山梨聚糖單硬脂 2.0 44 200902033 酸酯 神經芽細胞增殖促進劑等 2.0 防腐劑 適量 香料 適量 純化水 補足 100.0 重量°/〇 配方例Ί:化妝水 乙醇 5.0重量% 甘油 2.0 1,3-丁二醇 2.0 聚乙烯油醚 0.5 擰檬酸鈉 0.1 檸檬酸 0· 1 神經芽細胞增殖促進劑 0.1 等 純化水 補足 100. 0重量% 配方例十二:潤體乳 澳洲堅果油 2.0重量% 肉豆蔻酸辛基十二烷基 10.0 酯 甲基苯基聚矽氧烷 5.0 二十二烷醇 3.0 硬脂酸 3.0 鯊肝醇 1.0 45 200902033 單硬脂酸甘油酉旨 1.0 四油酸聚氧乙烯山梨糖 2.0 醇 氫添加大豆填脂 1.0 神經醯胺 0.1 棕櫚酸視黃醇酯 0.1 防腐劑 適量 積雪草萃取物 1.0 神經芽細胞增殖促進劑 1.0 等 1,3-丁二醇 5.0 純化水 補足 100. 0重量% 配方例十三:乳液 角鯊烷 4.0重量% 凡士林 2.5 錄蠛醇 2.0 甘油 2.0 親油型單硬脂酸甘油酯 1.0 硬脂酸 1.0 L-精氨酸 1.0 神經芽細胞增殖促進劑 0.5 等 氳氧化鉀 0.1 香料 微量 46 200902033 純化水 補足 100. 0重量% 配方例十四··洗浴用劑(液狀) 丙二醇 50. 0重量% 乙醇 20.0 硫酸鈉 5.0 神經芽細胞增殖促進劑 0.5 等 羊毛脂 0.5 牛油果油 0.5 色素 1.5 香料 22.0 100. 0重量% 配方例十五:貓食 玉米粉 34. 0重量% 小麥粉 35.0 肉粉 15.0 牛脂 8.9 食鹽 1.0 鳒魚萃取物 4.0 神經芽細胞增殖促進劑 1.0 等 牛磺酸 0· 1 維生素類 0.5 礦物質類 0.5 47 200902033 loo. 〇重量% 30.0重量% 15.0 10.0 25.0 5. 0 5. 0 8.9 0.1 0.5 0.5 配方例十六:狗食 玉米粉 肉類(雞肉) 脫脂大豆 小麥粉 麵糠類 神經芽細胞增殖促進劑 等 動物性油脂 辱·糖 維生素 礦物質 如 4- 100.0 重量%100.0 Weight ° / 〇 Formulation Example 2: Chewable tablets around raw water granulated sugar 40. 0% by weight 20.0 41 200902033 Glucose 20.0 Gelatin 4.7 Water 9.68 Grape juice 4.0 Grape flavor 0.6 Pigment 0.02 Neuroblast cell proliferation promoter 1.0, etc. 100.0% by weight Formulation example 3: candy granules 50. 0% by weight leeches 33.0 water 14.4 organic acids 2.0 spices 0.2 nerve bud cell proliferation promoter 0.4, etc. 100. 0% by weight Formulation Example 4: yoghurt (hard. soft) Milk 41.5% by weight Skim milk 5.8 Sugar 8.0 agar 0.15 gelatin 0.1 lactic acid bacteria 0.005 42 200902033 nerve bud cell proliferation promoter, etc. 0.4 fragrance trace water tonic formula 5: refreshing beverage 100. 0% by weight fructose glucose sugar solution 30. 0% by weight emulsifier 0.5 nerve bud cell proliferation promotion Agent, etc. 0.05 Proper amount of purified water to make up the formula Example 6: Small dessert 100. 0% by weight Sugar 76.4% by weight Glucose 19.0 Sucrose fatty acid ester 0.050.2 Neuroblast proliferation promoter 0.5 etc. Purified water 3.9 Formulation Example 7: Soft capsule 100 0% by weight Grape seed 8重量% 54. 0重量% 54. 0重量% 54. 0重量% 54. 0重量% 54. 0重量% emulsifier 12.0 neuroblast cell thinning accelerator 1.0 43 200902033 and other formula 8: tablets lactose crystal cellulose starch decomposition products glycerol fatty acid ester neuroblast cell proliferation promoter, etc. 100. 0% by weight 54. 0% by weight 30.0 10.0 5.0 1.0 100. 0% by weight Formulation Example 9: granules for internal use (pharmaceuticals) Neuroblast cell proliferation promoter 1.0% by weight Lactose 30.0 Corn starch 60.0 Crystalline cellulose 8.0 Polyvinylpyrrolidone 1.0 100. 0 weight % Formulation Example 10: Makeup f Squalane 20. 0% by weight Bee fiber 5.0 Refined jojoba oil 5.0 Glycerin 5.0 Glycerol monostearate 2.0 Polyoxyethylene (20) sorbitan monostearate 2.0 44 200902033 Ester Neuroblast cell proliferation promoter, etc. 2.0 Preservatives Proper amount of flavored purified water to make up 100.0 Weight ° / 〇 Formulation example: lotion ethanol 5.0% by weight Glycerin 2.0 1,3-butanediol 2.0 Polyethylene ether ether 0.5 Sodium citrate 0.1 citric acid 0·1 neuroblast cell proliferation promoter 0.1 and other purified water to make up 100. 0% by weight Formulation Example 12 Body Lotion Macadamia Nut Oil 2.0% by Weight Myristate Octadecyl 10.0 Ester Methyl Phenyl Polyoxane 5.0 Dodecanol 3.0 Stearic Acid 3.0 Shark Liver Alcohol 1.0 45 200902033 Monostearate Monostearate 1.0 1.0 Oleic acid polyoxyethylene sorbose 2.0 Alcohol hydrogen added soybean fat filling 1.0 Neural decylamine 0.1 palmitol acid retinol ester 0.1 Preservative amount of Centella asiatica extract 1.0 Neuroblast cell proliferation promoter 1.0 and other 1,3-butyl Glycol 5.0 purified water to make up 100. 0% by weight Formulation Example 13: Emulsion squalane 4.0% by weight Vaseline 2.5 Recording sterol 2.0 Glycerin 2.0 Lipophilic glyceryl monostearate 1.0 Stearic acid 1.0 L-arginine 1.0 芽 增殖 增殖 增殖 神经 神经 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 2009 Bud Cell Proliferation Promoter 0.5, etc. Lanolin 0.5 Avocado Oil 0.5 Pigment 1.5 Spice 22.0 100. 0% by weight Formulation Example 15: Cat Food Corn Flour 34 0% by weight Wheat flour 35.0 Meat meal 15.0 Beef fat 8.9 Salt 1.0 Carp extract 4.0 Neuroblast cell proliferation promoter 1.0 Etc. Taurine 0·1 Vitamins 0.5 Minerals 0.5 47 200902033 loo. 〇 Weight % 30.0% by weight 15.0 10.0 25.0 5. 0 5. 0 8.9 0.1 0.5 0.5 Formulation Example 16: Dog food cornmeal meat (chicken) Defatted soybean wheat flour facial paralysis neuroblast cell proliferation promoter and other animal oils and oils, sugar, vitamins and minerals such as 4 - 100.0% by weight

Mm ㈣可吨供—增殖促 即使在神經芽上= 亦可促進細胞增殖促進劑及神經突起伸展劑 足進神、.、工牙細胞之增殖,並可以促進神經芽細胞的 神經突起之伸展,促使神經芽細胞分化為神經細胞,即 使在神經細胞發生變性的情況下,該神經芽細胞增瘦促 進劑及神經突起伸展劑也可以有效地防止神經細胞減 少’藉以有效地預防由大腦引起之衰老,同時提高大腦 功能。 按,上述詳細說明為針對本發明之一種較佳之可 行實施例說明而已,惟該實施例並非用以限定本發明之 48 200902033 申睛專利範圍,舉凡其他未脫離本發明所揭示之技藝精 神下所完成之均等變化與修飾變更,均應包含於本發明 所涵蓋之專利範圍中。 【圖式簡單說明】 第一圖係為管花肉蓰蓉萃取物對人類神經芽細胞之 增殖作用圖。 第一圖係為松果菊苷及類葉升麻苷對人類神經芽細 胞之增殖作用圖。 第三圖係為管花肉蓰蓉萃取物引起神經突起之伸展 狀態照片。 ^四圖係'為松果菊普引起神經突起之伸展狀態昭片。 弟五圖係為類葉升《狀神經突起之伸展狀t >7 ° …、、、 【主要元件符號說明】 49Mm (4) can provide tons of proliferation - even on the nerve buds = can also promote cell proliferation promoters and neurite outstretchers to advance into the gods, and the growth of dental cells, and can promote the expansion of nerve cells neurites, Promote the differentiation of nerve bud cells into nerve cells, even in the case of degeneration of nerve cells, the nerve bud cell thinning promoter and neurite outgrowth can effectively prevent the reduction of nerve cells 'by taking effective prevention of aging caused by the brain While improving brain function. The above detailed description is intended to be illustrative of a preferred embodiment of the present invention, and is not intended to limit the scope of the invention, which is not limited by the spirit of the invention disclosed herein. Equivalent changes and modifications of the modifications are intended to be included in the scope of the patents covered by the present invention. [Simple description of the diagram] The first figure is the proliferation effect of Cistanche tubulosa extract on human neuroblasts. The first panel is a graph showing the proliferative effect of echinacoside and flavonoids on human neuroblasts. The third picture is a photograph of the stretched state of the neurites caused by the extract of Cistanche tubulosa. ^The four-picture system is the extension of the neurite outgrowth caused by the pineal chrysanthemum. The fifth figure of the younger brother is the type of leaf swelling. The extension of the sinusoidal protrusion t > 7 ° ..., ,, [Description of the main components] 49

Claims (1)

200902033 十、申請專利範圍: 1. 一種以一苯乙醇苷類化合物為有效成份之神經芽細胞 增殖促進劑。 2·如申請專利範圍第1項所敘述之一種神經芽細胞增殖 促進劑,其中δ亥苯乙醇苦類化合物係至少包含一松果 菊苷及一類葉升麻苷其中之一。 3. —種以一列當科植物萃取物為一有效成份之神經芽細 胞增殖促進劑。 4. 如申請專利範圍第3項所敘述之一種神經芽細胞增殖 促進劑’其中該有效成份為該萃取物中一笨乙醇苷類 化合物。 5. 如申請專利範圍第4項所敘述之一種神經芽細胞增殖 促進劑,其中該笨乙醇苷類化合物係至少為一松果菊苷 及一類葉升麻苷其中之一。 6. —種以一苯乙醇苷類化合物為一有效成份之神經突起 伸展劑。 7·如申請專利範圍第6項所敘述之一種神經突起伸展 劑’其中s亥笨乙醇苦類化合物係至少為一松果菊苦及 一類葉升麻苷其中之一。 8· —種以一列當科植物萃取物為一有效成份之神經突起 伸展劑。 9. 如申請專利範圍第8項所敘述之一種神經突起伸展 劑’其中該有效成份為一苯乙醇苷類化合物。 10. 如申請專利範圍第9項所敘述之一種神經突起伸展 劑’該笨乙醇苷類化合物係至少為一松果菊苷及一類 50 200902033 葉升麻苷其中之一。 11· -種可包括人仙之哺乳__品,該藥品係 以申請專利範圍第丨至5項中任何—項所敘述之神經 芽細胞增殖促進劑或以申請專利範圍第6至10項中任 何-項所敘述之神經突起伸展劑作為—有效成分。 比-種可驗包括人仙之哺摘祕皮料用劑,該 皮膚外用劑係以申請專利範圍第1至5項令任何一項 所 =神經芽細胞增殖促進劑或以申請專利範圍第 有效成^中任何一項所敎述之神經突起伸展劑作為一 13·至mu品,該制食品係对請專利範圍第1 以申項所敘述之神經芽細胞增殖促進劑或 圍第6至1G項中任何—項所_之神 、、-工犬起伸展劑作為一有效成分。 類動物飼料’該哺乳類動物飼料係以申請 、klUl至5項中任何—項所敘述之 增殖促進劑或以申請專利範圍第6至 、、、^ 所敘述之神_繼_為,:任何一項 51200902033 X. Patent application scope: 1. A neuroblast cell proliferation promoter with monophenyleglucoside as an active ingredient. A neuroblast growth promoter according to the first aspect of the invention, wherein the δ-Hexylethanol compound comprises at least one of pineconate and one type of lutein. 3. A neuroblast proliferation promoter which is an active ingredient of a family of plant extracts. 4. A neuroblast cell proliferation promoting agent as described in claim 3, wherein the active ingredient is a stupid alcohol glycoside compound in the extract. 5. A neuroblast proliferation promoter as described in claim 4, wherein the stearyl glycoside compound is at least one of echinacoside and one type of lutein. 6. A neurite outgrowth agent having a phenylethanoid glycoside compound as an active ingredient. 7. A neurite outgrowth agent as described in claim 6 wherein the sulphuric ethanolaceous compound is at least one of a cupola chrysanthemum and a class of flavonoids. 8. A neurite outstretcher with an extract of the plant extract as an active ingredient. 9. A neurite outgrowth agent as described in claim 8 wherein the active ingredient is a phenylethanoid glycoside compound. 10. A neurite outgrowth agent as described in claim 9 wherein the stupid glucoside compound is at least one of echinacoside and one of the classes 50 200902033. 11· - The species may include the breastfeeding __ product of the human genus, the drug is a neuroblast cell proliferation promoter described in any of the scopes of the patent application range 5-1 to 5 or 10 in the scope of the patent application Any of the neurite outstretchers described as an active ingredient. The specific type of the skin may include a human skin extracting agent, which is effective in any one of the claims 1 to 5 of the patent application, or a patent application scope. The neurite outgrowth agent described in any one of the above is a 13· to mu product, and the food system is the first to be patented. The neuroblast cell proliferation promoter or the surrounding 6th to 1G described in the application. Any of the items in the item, the god, and the dog, act as an active ingredient. Animal-like feed 'The mammalian feed is the proliferation promoter described in the application, any of the items klUl to 5, or the _ _ _ _ _ _ _ _ _ _ _ _ _ Item 51
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