TWI241893B - A composition including isoflavones refined from plant - Google Patents

A composition including isoflavones refined from plant Download PDF

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TWI241893B
TWI241893B TW087116374A TW87116374A TWI241893B TW I241893 B TWI241893 B TW I241893B TW 087116374 A TW087116374 A TW 087116374A TW 87116374 A TW87116374 A TW 87116374A TW I241893 B TWI241893 B TW I241893B
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composition
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item
plant
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Mark Empie
Eric Gugger
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Archer Daniels Midland Co
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/34—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only
    • C07D311/36—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only not hydrogenated in the hetero ring, e.g. isoflavones
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    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A23L33/11—Plant sterols or derivatives thereof, e.g. phytosterols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/488—Pueraria (kudzu)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/55—Linaceae (Flax family), e.g. Linum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/68—Plantaginaceae (Plantain Family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/82—Theaceae (Tea family), e.g. camellia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
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    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/326—Foods, ingredients or supplements having a functional effect on health having effect on cardiovascular health
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/3262—Foods, ingredients or supplements having a functional effect on health having an effect on blood cholesterol
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/21—Plant extracts
    • A23V2250/2116—Flavonoids, isoflavones
    • A23V2250/21172—Soy Isoflavones, daidzein, genistein

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  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Gynecology & Obstetrics (AREA)
  • Agronomy & Crop Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
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Description

1241893 九、發明說明： 式中Λ乃取代1997年(民國八十六年)十月二曰第 ου/υ60,549號之臨時性申請。 a 【發明所屬之技術領域】 ㈣ίΠ’韻於植物萃取物，尤其_植物化學㈣，包括： 質：植物皂素、兒茶酸、木素糖、酚酸與異黃酮；尤 二、亞麻、茶、可可等類植物；以及顧此類組合 物作為營養補充品或食物添加濟之方法。 【先前技術】 皆知植物物質含有數類4分子量之有機化合物，其在各 生物活性。傳統上，此類化合物被認為不具養分，但 爾顯示這些物質在鋪維護上，在化學猶上及在減 Γ"'貝"爾豕循裱有關之一些情狀或疾病包括睡眠失調及陰道乾 _症上可扮演重要之角色。 一般飲食中之食用植物或作為草藥療法/補充的物質品皆可 =、^構相_化合物。與其他植物相比較，這些相關物質往往 龙里質與分布上均較特殊。此類具生物活性之化合物最有名為類 只_、異κ _、植物皂素、木素糖、生物驗、兒茶酸與紛酸。 、流行病學研究與疾病有關之飲食發現若干飲食中所含之成 伤田了，降低人類感染某些疾病之風險。東方人食用大豆可以降 ，罹患乳癌、舰癌、結職及冠狀^臟病；而芬蘭人罹患列腺 癌比例也已下降。研究者目前正針對飲食中特定組合物進行研 究，以了解上述流行病學觀察結果。 在飲食中食用之各種植物，有數種是含有豐富之植物化學 物。大旦製品含有高量之異黃酮及植物皂素。非精製之食用穀物， 1241893 如 :大麥，psyllium、稻米、亞麻、燕麥則含 某些非食用植物亦為此類化學分子::源了:? =激，質。茶類植物亦含有豐富的植物fb;=i 兒余酸及酚酸。 異it可治療或獅憾、列腺癌、讀癌與結腸 3及期間有關齡類徵候群，包括陣發性發熱二p=e:^ 鬆症。異黃料獨也見效於包括喊狀特定心臟病 官應用上，降低膽固醇—脂肪量，調整血管生成，及1他血管 =效果。甚至於，異黃酮單獨使用連帶能減少頭痛呆症、 毛乂及酸酒症，同時也能增強免疫性。 單獨個木素糖也能預防絲療乳癌、列腺癌及結腸癌，同 =也能減少陣發性麵’髓骨f職症及顯示#抗猶性病毒 此力，木素糖也能抵抗細胞有絲分裂及具殺菌功效，一種植物木 素糖叫鄰苯二酚•二氫癒創木酸曾被食品工業當作抗氧化劑使用。 單獨使用植物皂素能預防或治療皮膚癌，結腸癌，減少血中 ^固醇’及能增強免疫性及魏絲活性。植物皂侧時顯示具 抗氧化劑效果及可當作自由基清道夫。 酚酸已顯示具抗氧化活性。 食用高大豆含量之人，可減少許多上述各類徵候群。此顯示 ，用如發現於大豆中含一定比例之植物化學物質組合物之飲食可 月b導致附加的或協力效用。然而，高大豆含量飲食對西方消費者 有些不良作用，如·胃腸氣脹、不良味覺及遲疑，而改變其生活 型態將大豆納入飲食中，即使為了這些益處。 目前所知，屬異環狀酚類異黃酮包括：大豆類化合物5,7,4_ 二羥基異黃酮（genistin)、黃豆呋（daidzin)、甘氨酸素（giycitein)、 1241893 雞豆黃素A (biochanin A)、牛尿酚（equol)、芒柄花黃素 (formononetin)、去曱安哥拉紫檀素（〇-desmethylangolensin)與 自然衍生物。當這些化合物被食用時，這些化合物以及糖肽其配 基或去曱基糖肽配基化合物，如5,7,4-三羥基異黃酮（或染料木配 質），與黃豆呋原，皆具類似活性。而其有時被稱為植物雌激素。 木素糖定義為含2,3-二基丁烷構造之化合物。其包括··羅 漢松脂素（matairesinol)、閉異落葉松脂素（sec〇is〇iariciresinol)、 落葉松脂素（lariciresinol)、異落葉松脂素（is〇iariciresinol)、去 曱二氫愈創木酸(nordihydroguaiaretic acid)、松脂醇(pinoresinol)、 橄欖樹脂素（olivil)與其他可能是腸内醋及腸二醇之前趨物與變 異物，其中包括雙糖肽。 盼酸包括對-虱苯酸（p_hydrobenzoic acid )、原兒茶酸 (protocatechuic acid )及香草酸（vanillic acid )。其他酚酸尚有綠 原酸（chlorogenic acid )、咖啡酸（caffeic acid )、阿魏酸（feruiic acid)、沒食子酸（gallicacid)、芥子酸（Sinapicacid)、丁香酸 (syringicacid)、香豆酸（coumaric acid)、肉桂酸（dnnamicacid)、 龍膽酸（gentisic acid)、水楊酸（salicylic acid)、羥苯曱酸（hydr〇Xy benzoic acid )、羥苯乙酸（hydroxy phenyl acetic acids )及其衍生 物。酚酸類物質尚應涵蓋來自天然蔬果中之各種同分異構物及衍 生物。 兒茶酸或黃烷醇包括：表沒食子兒茶酸（epigallocatechin)、 兒茶酸（catechin)、表兒茶酸（epicatechin)與沒食子兒茶酸 (gallocatechin) 〇 、 皂化物為含27個碳（C-27)之類固醇，其支鏈經代謝產生螺 方疋細酮。自然生成之皂化物為植物皂素，其為類固醇或三音主 體之3_0葡萄糖肽。毛地黃中之毛地黃息甘為植物息素。植物息 素包括·皂甘配基之糖肽如三類苷或類固醇；及醣類如 阿拉伯糖、半乳糖、葡萄醛酸。典型之豆科植物皂素為：異白芷 1241893 菌（Glycy—zaglabra)之干草皂甘（甘草次酸（glycyrrhetinic add) +葡萄醛酸（glucuronic add))，大豆中之大豆皂素以及苜蓿 (Medicagosativa)中之苜蓿植物皂素（alfalfasap〇nin)。植物皂 素，含已被認定三苷類酚之化學實體，如：蕃茄素（t〇matine)、 大豆皂甘配基盼 A，B，C，D，E 及 F (s0yasap0gen0is a，b，c，d，E and F) ’ 人蔘皂甘部分 3 與 4 (ginsengoside fraction 3 and 4)，苜稽 内酸（medicagenic acid)、常春配基、干草皂甘 (glycyrrhizin digitonin)、毛地黃皂甘（qUmaja sap〇nin)、皂樹 酸（lucemicacid)、紫苜蓿酸（zahnicacid)。植物中所含之上述 各種化合物之自然改變物亦包括於此認定。 所需之改良組合物，其成分大體包括異黃酮、木素糖、皂化 物、植物皂素、及/或酚酸，其將產生較服用單一物質更佳之效果。 此外’品要車父天然成分》辰度萄含更南之有效植物化學物質之組合 物。此允許個人方便食用這類植物化學物作為營養補充劑或食物 添加劑。 【發明内容】 本發明之目的在於提供一般大眾一個方便方式異黃酮、木素 糖、植物皂素、兒茶酸、及/或紛酸，作為營養補充攝取劑或傳統 食物成分。 本發明之另一目的為提供最佳之植物化學物萃取組合物予消 費者，遞送足夠的濃度以易於服用如··丸狀、片狀、膠囊狀、液 體或為食物之成分。 本發明之再另一目的為將植物化學萃取物製備成可局部使用 之乳霜或乳液。在此形式，異黃酮、木素糖、植物皂素、兒茶酸 及/或酚酸懸浮於一適當液體或凝膠體中以提供一安定之乳霜或乳 液以供使用。 1241893 处明之又另—目的為提供—萃取物濃度，盆化學組成盥自 然植物所發現之化學物質極為相近。 ，、匕子、，、成，、自 秉持上述發明構想，異黃酮、木素糖、植物 或=均自適當植物中萃取出，以提供一較天然丄匕高之 組成物’且其中-種或多種生物活性物質較天然物質高出五倍。 用以獨S或與r種或多種其他植物萃取物合併使 h 、、且口。此外，本萃取組合物可與一種或多種營養劑 ::可:成::=r 液體、乳霜、粉末或食物成分。 襄樂九 ⑽^些物可糊充航食物m之職知方法包 裝供給。廷些物質主要在提供健康及福祉。 【實施方式】 良組Γ7㈣含高量異伽、木素糖及其他植物化學 物如去，大旦片、大豆糖蜜、大豆乳漿、紅苜蓿、苜蓿、亞麻、 可可、茶或葛根分娜得。這些均可單獨分_與其他已知 量異黃酮、木素糖、植物皂素、兒茶酸無酸之植物—起分館: 分館結果從來源物質中移除大量之水、碳水化合物、蛋白質盘月匕 肪。此分餾方法較佳為揭露在同時審理中之美國專 ^ 號或美_帆_6號，或乙酸w 國專利第5,702,752號讓渡於本發明之受讓人。 、 、可單獨或合併細之其他萃取方法包括溶解度差異法、 法、溶劑萃取法、韻法、分子量差異碱法及沉澱法。…、 較佳之組合物為已知之商業化產品之改良品，主要是其每克 1241893 所s植物化學物之量與影響生理魏之不職物化學物質的量。 取物期被食用，且尤其有關於對健康助益之攝 其&供了傳染病學上的證據。此外，其它 = 進之相關植物化學物，而此類植物化學物乃源自其原 扯/斤得之組合物較佳者為包括5_95%之異黃酮、〇_7G%太音 .之間，其中異黃酮主要5,7,4-三經基里黃酮之夭 前缝魅黃素A及黃豆甘原與/^前趨物芒 ί =二:丨？5,7,4 物。 到1 ·100之間。較佳地，異黃酮主要為糖基衍生 此組合物之比率可很容易的經由改變植物來源或結合萃取 物來源而有所㈣。故進—步研究顯示不同植物化學之結合 些健康狀況更為有效，而此特定之組合物亦將有所改變。’、 ，前已知異黃酮、木素糖與植物4素對治療或預防各類癌症 〇有助盈，其中包括乳癌、列腺癌、皮膚癌與結腸癌。 :一般確信此改良組合物可以化學預防之方式提供極大助益。 而最近之實驗亦證實此一信念。 範例一 進行一系列之初步動物實驗以了解食用大豆製品對皮下植入 LNCaP之SCiD雄鼠生長之影響。高異黃酮含量之大豆蛋白分離 物（SPI) (2耄克異黃酮/公克spi)由美國密蘇里州之國際蛋白 技術公司（pr〇tein Technology International)提供。一種大豆植物 化予％取物為含有28.5%之大豆異黃酮及不同量之其它大豆植物 1241893 化合物之大豆植物化學濃縮物(spc)，由美國伊利諾 ===娜。满f賴備_驗食物。表 r 、、且貫驗g物，測疋食物攝取量、體重與腫瘤體 束 ，分_清進行PSA分析。腫^:= 福===石壌包埋並切成4_對‘二ap= ce )作原位减化學測定朗行血管钱 =基=瓣飾聽編咖雕 ，表 餵艮之控制組相比，給予處理SPI (20%)、SPC (i〇% spi 和SPC (1.0% )之雄鼠腫瘤量分別減少12%、28% 及 析ί果顯示蛋白質來源對軸生長無顯著影 析顯不腫瘤量與飲食中異黃_量成反比（膜瘤量 (立方υ=·α_8+2.121Χ異黃_ (毫克），❿㈣㈣⑹。 缺表三則顯示SPC㈣丨J在1.0%飲食對細胞洞亡程序、、 ，官新生之鱗。其顯示大豆植物化學物之食品添加劑可以促進 癌細胞壯和抑繼瘤細胞之增絲抑制在 瘤姆新生之抑做果並不觀，可 試管實驗顯示5,7,4-三經基異黃_大豆植物化學濃 抑制LNCaP細胞分泌PSA至介f中。以％及5()職；；=^ 經基異黃酮處理時，PSA之濃度可分顺少_與74%，·而以^ 及50mm之大豆植物化學濃縮物處理時，pgjA可分別降低31%及 42% 〇 1241893 表一實驗食物成份（公克) 配方1 酪蛋白質 配方2 SPI 配方3 酪蛋白質 /LSPC 配方4 SPI/LSPC 配方5 酪蛋白質 /HSPC 配方6 SPI/HSP C SPI 0 200 0 200 0 200 酪蛋白質 200 0 200 0 200 0 DL-甲硫胺酸 3 3 3 3 3 3 玉米澱粉 150 150 150 150 150 150 蔗糖 500 500 500 500 500 500 纖維素，BW200 50 50 50 50 50 50 玉米油 50 50 50 50 50 50 礦物質混合物， S10001 35 35 35 35 35 35 維他命混合物， V10001 10 10 10 10 10 10 二酒石酸膽鹼 2 2 2 2 2 2 大豆植物化合物 0 0 2 2 10 10 總計（公克） 1000 1000 1002 1002 1010 1010 (異黃酮，毫克/公斤 食物） 0 245 341 586 705 950
1 : Dr.E.A.Ulman Research Diets，Inc·自 AIN 公式微幅修改 表二最終體重、總食物攝取量、總異黃酮攝取量及腫瘤體積 處理 體重 食物攝取量 總異黃酮量 腫瘤體積 公克/公尺 (立方公分） 酪蛋白質 22.^0.51 46^3.1 0.00 土 0·00 2.32 土 0·312 SPI 23·1±0·7 46.2±2.8 17·00±6·37 2.06 士 0.32 酪蛋白質 21.4 士 0.7 41.2±3.4 14.03 士 14 1.88 士 0.35 /LSPC SPI/LSPC 22.6±0.6 50.1 士 4.7 29.36土 2·76 1.66 士 0.29" 酪蛋白質 22.2 士 0.7 44.8±6.1 76.38土10.40 1.64 土 0.22# /HSPC SPI/HSPC 22.0 土 0.6 47.5 土 1.7 92.53士 3.22 1.39±0.30"
12 1241893 J；數值為平均值1鮮差代表對於食物攝取或體重並無顯著影 3 ··與控制組比較，SPI/LSPC、酪 具有較小腫瘤體積(*··Ρ<〇·〇4，·**·· p<〇 〇〇5)及SPI/HSPC顯著 處理 控制組〇ν=2Ϊ ϊ~~^ /HSPC(n=2) ΑΙ (% TUNEL) 6·07土 0.88 Ίθ.75 土 0.54 ^1(%PCNA) "5U±lT 微血管密度 "ul±3.8 9.7i〇.7
數值以平均值±標準差
，_A 制血管新生與增Ϊ _丨_壯程序，同時抑 或木雜可減輕雜期有__群，如_性_ 是由於雌性激素的活性。故此文中所描述之 症狀之減輕更為有效。 艮、、且。物應對廷些 又，異黃酮對心臟血管相關症狀亦有正面 膽固醇（植物息素亦對膽固醇有正面影燮）、’丙 疾病但花費卻較低。 银减乂匕贓血吕 異黃酮」木雜與祕皂素__經及免 .症 rr迄 ί=應 用改良之組合物，例如皮下注射、靜脈内注射、肌 内注射，或以鼻_人如儒方式喷至黏敝織，或以軟膏或 13 !241893 乳霜方式塗抹於皮膚。 可以固態或液態方式之任何適合媒介服用改良之組合物，如 :劑、膠气、粉末、軟膠、液體、懸浮液、乳化劑、軟膏或乳液 式攝取。該改良組合物亦可以食物添加濟或補充劑方式服用之。 改良組合物之服用量隨個體、服用方式及欲得成效而定。一 般有效劑量為1〇_2〇〇〇毫克/劑。 範例二藥片製造 ，專利所提供之組合物可用於製備成藥片狀或其他服用变 士二，例二提供—膠囊製備之實例。具活性之成分濃度愈高則其 易^成片狀或乳膠狀。此一性質可將其他營養劑加入其中。 二實例是製備-植物化學物片㈣含摘與維他命E，作為維護 月，健康並/或減少停經後之症狀如陣發性發熱。在此實施例之實 f U備了含*125毫克異黃酮濃縮物(50 ·克異黃酮化合物) 之600毫克乾狀壓縮片劑。而在此片劑中即含鈣與鎂。 乾狀壓縮片劑之生產首趣下列成分置於12()夸脫之哈伯 HobartM合器中擾拌：四公斤之改良組合物（39·83%異黃晒）、 二梨醇、嶋公斤之硬醋酸鎮、1111公斤磷酸二辦。 以史脫克ΒΒ2㈣壓賴在丨键力下將之壓縮成 片^ ’母片重量為_毫克並含125 53毫克之改良組合物 5〇笔克之總異黃酮。 Y或者，一種植物化學濃縮物可以單一服用方式提供之， 5膚乳液或添加於傳統條之條齡，継為i。到細。二 i暂於促進健康與福祉。益處包括癌症預防、雌激素與 L if=病，ί,:下严甲狀腺-生殖腺軸、減低酒精依 U即痛血f、免疫與神經系統、抗_性病源體效用及止 !241893 兩片式動物性膠囊之製備方法為將0106公克之改良組合物 ^44.35%異黃_)灌入〇狀空膠囊之一半，並以另一半之 緊，其可提供47.2毫克之總異黃酮。 、 範例四 廿表四列出植物化學物製品之不同來源之比較。其顯示本發明 ，黃酮濃縮物之組合物之植物化學較一般自然蔬果中含量高^甚 多。明顯地，糖肽類異黃酮葡萄糖與植物皂素含量較食物來源高 出一百倍以上，而較可自然濃縮此類植物化學物質之植物幼芽^ 出二十倍以上。本發明之異黃酮濃縮物，與其他濃縮物相比較，^ 示異黃酮為後者產物之優勢成分，其會減少其他有益於健康之^ ，化學物。此外，其他產品之萃取技術利用改變其成份(尤其是異 _ 貝酮)之技術’故其並非與自然蔬果中物質完全相同（美 號 3,637,562) 種改良組合物與其他先前敘述之組合物相比較，結果顯示 於表四 表四本發明之比較產品 產品樣本 異黃酮糖 類產品(毫 克/克） 異黃酮配 基產品(毫 克/克） 改良組合物 401.1 3.37 大豆 1.748-2.77 6a 2.776a-0.07 5 大豆麵粉(去脂） 1.969a 0.045a 大豆芽 24.32d 0,85 d 專利產物\?丁1：) ΝΑ 2,5-6.5e 專利產物\?丁1：> ΝΑ 5.1-14.7f 專利產物叭？丁1) ΝΑ 1.7-3.5g 5,7,4-三羥 基異黃_/ 黃豆甘原 it_ T〇6il 木素糖(毫 克/克） 植物皂素 (亳克/克） 酚酸(亳克 /克）
15 1241893 PTI 產物h ΝΑ 970 12.8 ΝΑ ΝΑ ΝΑ PTI 產物h ΝΑ 640 2.0 ΝΑ ΝΑ ΝΑ 大豆蜜糖（乾式） 27.6 o.i 1 1.37^ ΝΑ ΝΑ 5.788 Novogen1 0.0 550 1-1.7 ιοί ΝΑ ΝΑ ΝΑ a:WangH.和MurphyP.A·，農業食物化學期刊， 1994,42,1666-1673. b:AndersonR.L·和 WolfW.J·，營養期刊，125:581S-588S，1995 c:SeoA.和 MorrC.V·，農業食物化學期刊，1984, 32, 530-533· d:SoyLifeTM宣傳文獻 e: WO 95/10530, PCT/US94/10697 e: WO 95/10512, PCT/US94/10699 e: WO 95/10529, PCT/US94/10696 h: NCI文獻 i:Novogen宣傳文獻 範例五 該改良組合物包含糖肽形式之異黃酮，較先前描述之含糖肽 配基類之組合物在體溫下之溶解度為高。 用量瓶製備5,7,4-三羥基異黃酮(genistein)、染料木咲 (genistin)、黃豆呋原(daidzein)、黃豆呋(diadzin)與異黃酮濃縮物。 將樣品置於37°C之水浴中17小時，既而以〇·2微米針筒式過濾器 快速過濾以去除粒狀物。濾液則以高效能液相層析法（HpLC)^ 析異黃酮濃度。結果列於表五。 表五：異黃酮糖肽類與糖肽配基類溶解度之比較 1241893 異黃酮樣品 5,7,4-三經 基異黃_ (ppm) 染料木甘 (ppm) 黃豆甘原 (ppm) 黃豆甘 (PPm) 5,7,4_三羥基異黃酮 7.42 染料木甘 33.89 黃豆甘原 3.64 黃豆甘 48.51 — 異黃酮濃縮物 0.492 30.075 0.672 T7.69 糖肽類形式之黃豆呋與染料木呋，在37°C下之濃度較相對之 糖肽配基類形式至少分別高出4.57與13·32倍。 對異黃酮之改變為去除異黃酮週邊之碳水化合物。此一改變 使異黃酮較不易溶於水。維護自然改變，糖基作用，可促進溶解 度。此一事實顯現於表五中溶解度之比較。與相對之非糖肽類形 式比較，染料木呋異黃酮之溶解度高出4·6倍，而黃豆呋異黃酮高 出13.3倍。高溶解度使腸道生物有較佳生物利用性。糖基作用並 不會抑制其在腸道之吸收，因為腸中細菌可在吸收前將糖肽形式 轉變為糖肽配基類形式。 範例六 木素糖可以下列方法自亞麻中萃取。 —978克之脫脂亞麻肉（F1)以2000克85%之乙醇在40°C下 萃取10分鐘，形成泥狀物。泥狀物經過濾後，以6000克酒精重 複萃取兩次。 酒精部分在70°C真空狀態下揮發，形成1186克之液態物。 此-液態倾_克之水減合。 17 1241893
上述混合物錢oo分子量分_超 液以及1283克之濾渣。 賴 H 濾渣部分經冷凍乾燥後，形成27.84克之樣品（F2)。 767克之部分則在贼下以每分鐘1()^狀速度注入至 35宅升 =XAD-4樹脂管柱中。出流液收集並乾燥，形成14 8克 樣品（F3 )。屢-4為-種吸收性樹醋商標名，講自R〇hm &細。 管柱以四倍的體積U40毫升）之7〇%乙醇在赃下沖洗。 洗出液在7G°C真錄態下揮發乾燥，形成U9克樣品（F4) 對四個部分進行木素糖含量分析並以閉異落葉松脂素 (secoisolariciresinol)重量計算濃度。如表六所示，此一萃取方法可 提高木素糖之濃度。 表六·木素糖濃度（以閉異落葉松脂素計算） 部分 F1 F2 F3 F4 閉異落葉松脂素 濃度（毫克/克） 2.3 1.9 4.8 13.4 酚酸 除此之外，將本發明之改良組合物運用於治療或預防各類癌 症，結果如下列文獻所示，其中包括：（1) Lunyin Yu等人，American Society for Nutritional Sciences, 2003, 389-392.(2)Michael J. Plewa 等人，Mutation Research，402, 211-218(1998).(3)Michael J· Plewa 等 人 ’ Teratogenesis，Carcinogenesis，and Mutagenesis ， 19, 121-135(1999).(4)Zeming Jin 等人，American Society for Nutritional Sciences，2002，3186-3187.(5)Mark A· Berhow 等人，Mutation Research, 448,1 l-22(2000).(6)Mohammed Hosny 等人，J· Nat· Prod·， 65, 805-812(2002).(7)Novasoy search abstract/09/19/03(8)2003 AUA Abstract Submitter(9)Zeming Jin 等人，American Society for 1241893
Nutritional Sciences，2002, 3186-3190.(10)Jin-Rong Zhou 等人 ’ The
Prstate，53，143-153(2002).(1 l)J〇anne N· Davis 等人，Free Radical Biology & Medicine，30，1293-1302(2001).(12)Jin-Rong Zhou 等 人 ’ American Society for Nutritional Sciences， 1999, 1628-1632.(13)Zora Djuric 等人，Cancer Letters，172, l-6(2001).(14)Amy L· Hewitt 等人，Cancer Letters，192, 133-143(2003)·。由文獻中之實驗數據可知，當本發明之含有植物 化學餾分物之改良組合物用以治療或預防各類癌症時，的_極有 助益。 雖然本發明已發表較佳實施例以便於協助對本發明之了解， 但本發明亦可在不背離發明原則下，有各種不同實^例 發 明在不背離所附申請專利範圍之發明原則下，應涵蓋 ^ 實施例、改良及與實施例相當之範例。 此 【圖式簡單說明】 【主要元件符號說明】

Claims (1)

  1. Ί241893 94.8, 十、申請專利範圍： ：:卜 1·二種營養或食品補充組合物，其為至少兩種以上由植物提煉所 得之植物，學齡物所組成，其中該至少兩種植物化學鶴分物 至少包含第一植物化學餾分物及第二植物化學餾分物，而並中 該第、一植物化學餾分物及第二植物化學餾分物兩者互不相^， 且係選2由異黃酮、木素糖、植物皂素及酚酸所構成之族群， 其中異黃酮佔該組合物重量百分比5%-90%、木素糖佔 物重里百分比1%-70%、植物皂素佔該組合物重量百分比 5%_70%以及酚酸佔該組合物重量百分比1%_7〇%，且其中至少 種遥疋的植物化學館分物包含至少佔組合物的重量比。 2·t請專利範圍第！項之組合物，其中基本上含至少占观重 =自由異黃酮、木素糖、植物4素、兒茶酸及㈣ 之 族中的植物化學物質。 X 利1t圍第1項之組合物，其中基本上含至少占_重 異调、木素糖、植物皂素、絲酸及_所構成之 知的植物化學物質。 人 5 4·如申請專娜圍第1項之組合物，其巾基本上含 •如自申==齡物，㈣黃崎木雜之比例選 7.=ί= 圍以 ㈣素_錄椒比例 1241893 酸之比例選自 9·如申請專利範圍第1項之組合物，其中木素糖對盼 100··ι至1:100之範圍。 刀 酸之比例 1〇·如申請專利範圍第1項之組合物，其中植物皂 選自100:1至1:100之範圍。 合物，射兒魏騎酸之比例選 12·如申請專利範圍第1項之組合物，其中異黃酮選擇自基本上由 5,7,4-二經基異黃酮、黃豆甘原、甘氨酸素、雞豆黃素a、芒柄 花黃素及其他天然化合物。 、 亡 13·如申請專利範圍第丨項之組合物，其中木素糖選擇自基本上由 羅漢松脂素、閉異落葉松脂素、落葉松脂素、異落葉松脂素、 去曱二氫愈創木酸、松脂醇、橄欖樹脂素及腸内脂及腸二醇之 前驅物及其他天然化合物所構成之族中。 14·如申請專利範圍第！項之組合物，其中植物皂素選自基本上由 蕃茄素(tomatine)、大豆皂甘配基盼A，B，C，D，E及 F(soyasapogenols A，B，C，D，E and F)、胰植物皂素(SOySapnin)、 苜蓿植物皂素(alfalfasaponin)、人蔘皂甘部分3、4(ginsengoside fraction)、苜蓿内酸(medicagenic acid)、常春配基(hederagenin)、 干草皂甘（glycyrrhizin digitoning)、毛地黃皂甘（qUiiiaja saponin)、皂樹酸(lucemic acid)、紫苜蓿酸(zahnic acid)及其他天 然所構成之族中。 15·如申請專利範圍第1項之組合物，其中酚酸選擇自基本上由綠 原酸(chlorogenic acid)、咖徘酸(caffeic acid)、阿魏酸(fernlic acid)、沒食子酸(gallic acid)、芥子酸(sinapic acid)、丁香酸 (syringic acid)、香草酸(vanillic acid)、香豆酸(coumeric acid)、肉 桂酸(cinnamic acid)、龍膽酸(gentisic acid)、水楊酸(salicylic acid)、經苯曱酸(hydroxy benzoic acid)、經苯乙酸(hydroxy phenyl 1241893 acetic acids)及其他衍生物所構成之族中。 16.=，利範圍第i項之組合物，其中兒茶酸選擇自基本上由 族fr、表兒命酸、沒食子兒茶酸及表沒食子兒茶酸所構成之 17·如申請專利範圍第1項之組合物，其中該植物為大豆。 18. 如申請專利範圍第17項之組合物，其中該大豆選自由大豆、豆 類食物、糖蜜、豆類乳漿、豆類蛋白f及豆類麵粉。 19. 如申請專利翻第1項之組合物，其巾該兩種以上齡物之選 擇係以該混合之顧分物可針對並預防某一疾病為一輪廊基礎。、 20. 如^請專利範圍第19項之組合物，其中該組合物係為一產品， 且該產品係選自由藥片、膠囊、藥丸、濃縮物、藥粉、藥液及 添加食物成份所構成之族中。 21. 以如申請專利範圍第2〇項之組合物，其中該藥片包括： a.該植物之組合物；及 b· —填充物選自由山梨醇、乳糖、纖維素及磷酸氫鈣所構成之 族中。 22·以如申睛專利範圍第21項之組合物，其中該產品另外增加一種 補品選自由磷酸氫鈣、硬脂酸鎂、檸檬酸鈣、蘋果酸j弓、其他 鈣來源、維他命、及礦物質所構成之族中。 23.如申請專利範圍第22項之組合物，其中該組合物係為一 口服膠 囊產品，而在該口服膠囊產品中組合物所占之重量百分比是在 15%至25%之間；以及該填充物所占之重量百分比是在65%至 85%之間。 24·如申請專利範圍第22項之組合物，其中該產品包括： a·組合物所占重量百分比是在15%至25%之間； 1241893 b.該填充物所占重量百分比是在65%至85%之間；及 c•補品所占重量百分比是在1%至25%之間。 25.如申請專利範圍第23項之組合物，其中該口服膠囊產品包括一 膠囊，該膠囊包括： a·—種植物組合物之預設處理劑量；及 b· —種精製膠囊。 26·，申請專利範圍第25項之組合物，其中該植物組合物係由一種 選自大豆、紅苜蓿、葛、亞麻、苜蓿、茶及可可之組群之植物 所萃取而得。 27·如申請專利範圍第25項之組合物，其產品所包括之植物組合物 約在10毫克至2〇〇〇毫克之間。 28·如申請專利範圍第1項之組合物，其中該植物為亞麻。 29·如申請專利範圍第28項之組合物，其成份係由百分比至少在1 %以上之木素糖所構成。 30·如申請專利範圍第28項之組合物，其成份係由重量百分比至少 在50%以上之木素糖所構成。 31·如申請專利範圍第1項之组合物，其中該選定之植物化學物質 以本質原始型態存在。 32·如申睛專利範圍第1項之組合物，其中異黃酮以本質葡萄糖化 合物型態存在。 、 33·如申睛專利範圍第1項之組合物，其被當成食品添加劑。 34·如申請專利範圍第1項之組合物，其被當成日常補品。 35·如申凊專利範圍第1項之組合物，其中該植物為茶。 36·如申請專利範圍第1項之組合物，其中該植物為可可。 1241893 37·—種組合物，係以下列步驟製成： a·^—種包括有酒精溶劑之溶液自選自由蛋白、玉米、乳漿、 糖案、溶解物及幼芽所構成的植物之族中萃取脫脂物質以 一泥狀物； 、 b·過濾步驟(a)之泥狀物以產生一酒精分離物； e•蒸發步驟(b)之酒精分離物以產生一液態物； d·超過濾步驟(c)之液態物； e•將步驟(d)之濾液注入樹脂槽； f·收集經該樹脂槽洗過之流出流液； 植物—混合物，其包含至少兩種以上提煉自 仆ίίί干鶴7刀物及第二植物化學餾分物，而其中該第-植物 匕物及第二植物化學齡物兩者互不相同，f 2 以二素杨、兒茶酸及_構成= 佔該組合物重量百且量4= 化學翁物包含至少伯組合請的重= 藥丸及藥月所構成之族中。< 心&自由漢縮物、藥粉、膠囊、 〖積，並 且可進嫩量體— ，請= 4!如申揭叙族中。 申遍爾37狀嶋，軸物為大豆。 1241893 42·如申請專利範圍第38項之組合物，其中步驟（c)包括一稀釋 液態物之步驟。 43·如申請專利範圍第37項之組合物，該步驟更進一步包含及所增 加分餾該出流液之步驟，用以選擇至少一種由異黃酮、木素糖、 植物息素、兒茶酸與酚酸所構成之族。 44·如申晴專利範圍第37項之組合物，該步驟更進一步包含增加分 顧該出流液之步驟，用以選擇異黃酮。 45·如申請專利範圍第37項之組合物，其中步驟（a)之溶液約 70%為乙醇及萃取製程在40°C情況下進行。 46·如申晴專利範圍第38項之組合物，其中步驟（c)之蒸發 在真空且約70°C情況下進行。
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ATE270894T1 (de) 2004-07-15
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US6261565B1 (en) 2001-07-17
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