TW201311158A - 壽命延長劑 - Google Patents
壽命延長劑 Download PDFInfo
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- TW201311158A TW201311158A TW101122394A TW101122394A TW201311158A TW 201311158 A TW201311158 A TW 201311158A TW 101122394 A TW101122394 A TW 101122394A TW 101122394 A TW101122394 A TW 101122394A TW 201311158 A TW201311158 A TW 201311158A
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- sugar
- psicose
- glucose
- allose
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Abstract
本發明係提供一種能簡便攝取且安全、並能依接近通常食物形式攝取的壽命延長劑、及壽命延長方法。本發明的壽命延長劑的特徵在於:含有以能作為甘味料使用的稀有醣類作為有效成分。
Description
本發明係關於由可作為甘味料使用的糖組成物所構成之壽命延長劑。更具體而言,係關於由含有可作為甘味料使用之D-阿洛酮糖及/或D-阿洛糖的糖組成物所構成之壽命延長劑。
不僅是日本國內,於先進國家各國,高齡化已構成嚴重的社會問題。與壽命及老化之控制有關的因子中,最確實能延長壽命者係熱卡限制(Caloric restriction:CR),目前在線蟲至哺乳類等廣範圍生物種均已確認到效果(例如非專利文獻1)。然而,熱卡限制係減少每日的飲食,並非實際的方法。
關於壽命延長雖已有多數研究,但難以稱得上已完全明朗。老化現象延遲效果說不上與壽命延長效果同義,例如關於利用動物實驗,發現具有延遲老化現象之效果的維生素E,雖可期待對小鼠與大鼠之壽命延長效果並正在研究中,惟目前認為維生素E尚未發現明確的壽命延長效果(專利文獻1)。
關於壽命延長已有數種報告,例如報告有源自水果(蘋果)的多酚係作為預防心衰竭或鬱血性心衰竭,能延長鬱血性心衰竭的模型小鼠的壽命(專利文獻2)。又,報告有含有α-次亞麻酸與亞麻油酸的特定物性油脂組成物,可延長易發生腦
中風大鼠的壽命(專利文獻3)。該等壽命延長效果係針對特定疾病的模型小鼠、經攝取高熱卡食物的小鼠等,利用預防或治療特定疾病或病理狀態,而使壽命延長。
能使正常個體的壽命延長之組成物,報告有以特定的幾丁聚醣(專利文獻4)、過氧化酶(專利文獻5)、及活性碳(專利文獻6)為有效成分者。活性碳並非能被活體內吸收的化合物,根據專利文獻6,該幾丁聚醣、過氧化酶的壽命延長效果並不明顯。
[專利文獻1]日本專利特開平8-176006
[專利文獻2]日本專利特開2007-197374號公報
[專利文獻3]日本專利特開2005-210978號公報
[專利文獻4]日本專利特開2005-289839號公報
[專利文獻5]日本專利特開平5-124980號公報
[專利文獻6]日本專利特開2010-208969號公報
[專利文獻7]日本專利特開2002-17392號公報
[專利文獻8]WO2008/142860號公報
[專利文獻9]日本專利第3333969號公報
[專利文獻10]WO2010/113785號公報
[專利文獻11]日本專利特開2007-91696號公報
[非專利文獻1]鍋島陽一、「老化生物學」、Medical Sciences International(股)(2000)p287
[非專利文獻2]The 3rd Symposium of International Society of Rare Sugars.
[非專利文獻3]Sulston, J. E. and Brenner, S. (1974) Genetics 77, 95-104
[非專利文獻4]Piper、M. D. W. and Bartke, A., Cell Metab 8, 99-104(2008)
[非專利文獻5]Colman, R. J. etal., Science 325, 201-204(2009)
[非專利文獻6]Heilboronn, L. K. and Ravussin E., Am J Clin Nutr 78, 361-369(2003)
[非專利文獻7]Ingram, D. K. et al., Aging Cell 5, 97-108(2006)
[非專利文獻8]Braeckman, B. P. and Vanfletren J. R., Exp Gerontol 42, 90-98(2007)
本發明目的在於提供:即便依接近食物的形式持續使用,能可安全且有效地延長壽命的壽命延長劑,藉由使動物攝取D-阿洛酮糖、D-阿洛糖等作為甘味料使用的稀有醣類,可壽命延長。
已知有利用攝取熱卡限制進行節食,而延長線蟲類、蒼蠅、老鼠、猴子等動物的壽命。又,已知利用攝取熱卡限制進行之節食係使與老化有關的疾病、例如糖尿病、癌症、阿滋海默症等之發病延緩,而使人類壽命延長。然而,現實上,因為難以長期間持續利用攝取熱卡限制進行節食,因而要求模擬攝取熱卡限制節食以達同樣效果的手段。本發明目的在於提供藉由與此種習知壽命延長手段同樣的機制,而有效解決課題的手法。
本發明者發現,以能作為甘味料使用的稀有醣類(rare sugar)作為有效成分之組成物,對壽命延長具有貢獻,遂完成本發明。
即,本發明主旨係如下述(1)至(6)的壽命延長劑。
(1)一種壽命延長劑,係以能作為甘味料使用的稀有醣類作為有效成分。
(2)如上述(1)所記載的壽命延長劑,其中,稀有醣類係D-阿洛酮糖及/或D-阿洛糖。
(3)如上述(1)所記載的壽命延長劑,其中,稀有醣類係含有D-阿洛酮糖及/或D-阿洛糖的糖組成物。
(4)如上述(3)所記載的壽命延長劑,其中,相對於糖質含量,含有D-阿洛酮糖0.5~17.0%及D-阿洛糖0.2~10.0%的糖組成物。
(5)如上述(4)所記載的壽命延長劑,其中,以D-葡萄糖及/或D-果糖作為原料糖,相對於總糖質含量,轉換成D-阿洛酮糖為0.5~17.0%及D-阿洛糖為0.2~10.0%的混合糖。
(6)如上述(4)或(5)所記載的壽命延長劑,其中,含有能作為甘味料使用之稀有醣類的異構化糖。
(7)如上述(1)至(6)中任一項所記載的壽命延長劑,其中,藉由增強超氧化物歧化酶(SOD)、以及過氧化氫酶(catalase)的生成或其活性,而達成壽命延長。
(8)如上述(1)至(7)中任一項所記載的壽命延長劑,其中,利用與攝取熱卡限制狀態的壽命延長同樣之機制達成壽命延長。
根據本發明,可提供以能作為甘味料使用的稀有醣類、較佳D-阿洛酮糖及/或D-阿洛糖作為有效成分,即便依接近食物的形式持續使用,仍可安全且有效果地延長壽命的壽命延長劑。
更具體而言,可提供一種壽命延長劑,係由能作為甘味料使用的糖組成物所構成,該糖組成物係以D-葡萄糖及/或D-果糖作為原料糖,相對於總糖質含量,轉換成D-阿洛酮糖0.5~17.0%、及D-阿洛糖0.2~10.0%的混合糖,含有該D-阿洛酮糖及/或D-阿洛糖作為有效成分的壽命延長劑。
可提供一種壽命延長劑,係藉由增強超氧化物歧化酶
(SOD)、以及過氧化氫酶的生成或其活性,而達成壽命延長的壽命延長劑。
再者,可提供一種藉由與依攝取熱卡限制節食進行的同樣機制,達成壽命延長的壽命延長劑。
本發明係關於以能作為甘味料使用之稀有醣類,作為有效成分之壽命延長劑,稀有醣類可舉例如D-阿洛酮糖及/或D-阿洛糖。
本發明的壽命延長劑係藉由增強例如超氧化物歧化酶(SOD)以及過氧化氫酶的生成,而延長動物的壽命。SOD係屬於將超氧陰離子(‧O2-)不均化為氧與過氧化氫的氧化還原酵素。在活性中心具有銅(II)離子與鋅(II)離子(Cu,ZnSOD)、或者錳(III)離子(MnSOD)或鐵(III)離子(FeSOD)般之二價或三價金屬離子的酵素,大多局部存在於細胞質(Cu,ZnSOD)與粒線體(MnSOD)中。具有減少氧化應力(oxidative stress)的作用。SOD係於人類(亦涵蓋所有的哺乳動物與大部分的脊椎動物)中有3種,SOD1存在於細胞質,SOD2存在於粒線體,SOD3存在於細胞外空間。SOD1與SOD3含有銅與鋅,相對地SOD2係在活性中心具有錳。線蟲中則有5種SOD,SOD-1、-5存在於細胞質,SOD-2、-3存在於粒線體,SOD-4存在於細胞外空間。
過氧化氫酶屬於將過氧化氫不均化為氧與水的氧化還原
酵素。在活性中心具有鐵(III)離子。廣泛分佈於微生物、動植物等嗜氧性生物中,於動物則大多存在於肝、腎細胞中通稱過氧化體(peroxisome)的細胞小器官中、或紅血球中。線蟲中有2種過氧化氫酶,CTL-1存在於細胞質,CTL-2存在於過氧化體。
依此,因為SOD及過氧化氫酶屬於動物的共通物,因而認為本發明對廣範圍的動物能發揮作為壽命延長劑的作用效果。
本發明中,經利用野生型C.clegans N2、與氧感受性突變種的mev-1進行測定壽命的試驗,結果N2因0.5%(w/v)的D-阿洛酮糖而延長17%壽命,mev-1則經即時定量RT-PCR施行測定,結果粒線體局部Mn-SOD(sod-3)基因的表現量成為1.7倍。關於SOD酵素的活性度,N2及mev-1分別成為1.5倍、1.3倍。又,N2中利用0.5%(w/v)的D-阿洛酮糖,使細胞質局部性及過氧化體過氧化氫酶(分別為ctl-1、ctl-2)的基因表現量均成為1.5倍。
依此,D-阿洛酮糖係利用氧化應力耐性增強而發揮壽命的延長作用。已有報告指出攝取熱卡限制狀態的線蟲壽命延長,係利用胰島素/IGF訊息路徑所調節的抗氧化蛋白質(SOD、過氧化氫酶等)之衍生而造成(非專利文獻8)。利用稀有醣類造成的SOD與過氧化氫酶之行為,係與利用攝取熱卡限制進行節食同樣的過程所造成,二者呈現同樣的結
果。利用D-阿洛酮糖攝取所造成的壽命延長,可認為係由圖9所記載的機制所造成。
具有類似攝取熱卡限制劑之作用效果的化合物,例如有:2-去氧-D-葡萄糖係抑制醣解系;屬於葡萄酒之多酚的白藜蘆醇(resveratrol)係活化去乙醯化酶;屬於免疫抑制劑的雷帕黴素(rapamycin)係抑制TOR;屬於抗糖尿病劑的二甲雙胍係活化AMPK(AMP-activated protein kinase,腺苷酸活化蛋白激酶)。該等化合物因為毒性大、效果低而仍不足等理由,尚未被實用化。
另一方面,亦可作為可食性甘味料使用的本發明之稀有醣類,係具有對人體不致構成影響且作用效果亦大的特性,因而容易實用化。
以下,針對本發明由稀有醣類所構成的壽命延長劑進行詳細說明。
屬於糖之基本單位的單醣中,相對於大量存在於自然界中之以D-葡萄糖(glucose)為代表的「天然型單醣」,將在自然界中僅微量存在的單醣定義為「稀有醣類」。單醣全部共59種,其中確認天然型單醣為7種、稀有醣類52種。稀有醣類的存在量非常少,例如相較於D-葡萄糖(glucose),D-阿洛糖存在量非常少。
目前可大量生產的稀有醣類已有D-阿洛酮糖與D-阿洛
糖。D-阿洛酮糖被分類為屬於稀有醣類之酮己醣的阿洛酮糖之D體,並為六碳糖(C6H12O6)。此種D-阿洛酮糖包括從自然界中萃取者,利用化學式或生化式合成法所合成者等,可依任何手段取得。D-阿洛糖(D-Allohexose)係分類為醛醣(醛已醣)的阿洛糖之D體,為熔點178℃的六碳糖(C6H12O6)。近年來,已有如專利文獻7所記載,在含有D-阿洛酮糖的溶液中,使D-木糖‧異構酶(isomerase)產生作用,而從D-阿洛酮糖生成D-阿洛糖的製法。如上述,D-阿洛酮糖、D-阿洛糖屬於天然微量存在的單醣,該等稀有醣類並無對人類具毒性的報告,可認為對動物的毒性較低。
而且,D-阿洛酮糖甘味優質且清爽,不致有如糖精般之伴隨苦味與澀味所造成的不適感,反而類似於果糖的甘味。甘味度係蔗糖的約70%。且,D-阿洛酮糖及/或D-阿洛糖屬於無熱卡,由健康而言亦屬於適合作為甘味料使用的稀有醣類。
作為壽命延長劑的含有稀有醣類作為有效成分且能作為甘味料使用的糖組成物之具體態樣,係果糖比例為20~80重量份,葡萄糖與阿洛酮糖的合計比例為80~20重量份左右,在將葡萄糖與阿洛酮糖的合計設為100重量份時,阿洛酮糖為5重量份以上、較佳10重量份以上的比率,接近砂
糖的甘味度與味質,屬於能預防肥胖等生活習慣病的甘味料(專利文獻8)。
該甘味料係其成分的果糖、葡萄糖、阿洛酮糖之混合物,將各成分進行混合便可獲得。果糖、葡萄糖屬於天然界中一般存在的單醣,除了從天然界中施行離析而可獲得之外,果糖亦可從對葡萄糖施行葡萄糖異構酶處理而獲得的果糖葡萄糖液糖等施行分離而獲得。又,葡萄糖係將澱粉施行水解而進行製造。又,阿洛酮糖係在天然界中僅些微存在的稀有醣類之一種,可藉由對果糖施行酮己醣3-表異構酶處理而獲得。該製造方法係藉由各構成成分的混合即可獲得;但在以葡萄糖作為原料,使葡萄糖異構酶作用而製造的果糖葡萄糖液糖中,添加D-阿洛酮糖亦可獲得;藉由對上述所獲得果糖葡萄糖液糖更進一步使D-酮醣-3-表異構酶作用,而將果糖其中一部分轉換為D-阿洛酮糖亦可獲得。又,在葡萄糖溶液中,使葡萄糖異構酶與D-酮醣-3-表異構酶同時作用,可將葡萄糖、果糖、D-阿洛酮糖依單一步驟製造成上述特定範圍的新甘味料。就成本面而言,直接連結葡萄糖的葡萄糖異構酶處理(異構化)步驟與D-酮醣-3-表異構酶處理步驟的製造法,以及利用葡萄糖異構酶與D-酮醣-3-表異構酶的混合酵素系,從葡萄糖一次地製造目標糖組成物的方法,係由成本面而言較有利。
D-阿洛酮糖的調配比例係果糖與(葡萄糖與阿洛酮糖的合
計)之比,較佳為80~20重量份:20~80重量份。若果糖達80份以上,雖然甘度增加,但另一方面將導致體感(body feeling)降低。反之,若果糖在20份以下,則有甘度感不足的傾向。又,將葡萄糖與阿洛酮糖的合計設為100重量份時,若阿洛酮糖達5重量份以上的比率,則成為具有砂糖之甘味度與味質的甘味料,而達10重量份以上的比率時,則顯示預防肥胖的效果。
製造方法係在以果糖葡萄糖液糖、葡萄糖、或澱粉作為起始原料時,有各種方法。
例如:(1)從澱粉或葡萄糖製作果糖葡萄糖液糖,再使酮醣-3表異構酶產生作用而製作阿洛酮糖。(2)在將澱粉經分解的分解葡萄糖液糖中,使葡萄糖異構酶與酮醣-3表異構酶依混合酵素狀態作用。
(1)分解果糖葡萄糖液糖液之製成
分解果糖葡萄糖液糖係依照常法,以馬鈴薯或甘藷等澱粉為原料,使用經固定化或依批式製成的α澱粉酶、葡萄糖澱粉酶、葡萄糖異構酶等酵素進行製造。澱粉原料及所使用之酵素的種類並不僅侷限於上述。又,視需要亦可施行利用酸分解進行的葡萄糖液製造、使用鹼進行異構化。
(2)從果糖葡萄糖液糖液糖液製造D-阿洛酮糖
對所生成的分解異構化糖液連續地使表異構酶作用,生成葡萄糖與果糖及阿洛酮糖的混合糖液。
將含有異構酶與表異構酶的固定化酵素填充於適當管柱中,並連續流入分解葡萄糖液糖,再分取反應液。又,此情況,亦可起始物質並非葡萄糖而是澱粉,使用α澱粉酶與葡萄糖澱粉酶更進一步組合的混合酵素系。
製造本發明糖組成物時,葡萄糖異構酶係作用於葡萄糖,將其中一部分轉換為果糖的酵素,亦可使用精製酵素,該酵素亦可為生產微生物。又,酮己醣3-表異構酶係將果糖等酮己醣的3位OH施行異構化之酵素,已知有D-塔格糖-3-表異構酶、D-阿洛酮糖3-表異構酶(專利文獻9:可從屬於假單孢菌屬的細菌獲得的D-酮己醣-3-表異構酶、及非專利文獻2)。又,亦可為精製酵素、或將該酵素生產微生物施行固定化的固定化酵素、固定化微生物。
再者,若在通常所使用之以果糖42重量份及葡萄糖58重量份為構成糖的異構化糖中,使作為酮己醣3-表異構酶的塔格糖-3-表異構酶作用,則生成葡萄糖58重量份、果糖34重量份、阿洛酮糖8重量份。然而,若使葡萄糖異構酶與塔格糖-3-表異構酶的混合酵素作用於葡萄糖,則意外地獲得葡萄糖41重量份、果糖48重量份、阿洛酮糖11重量
份的混合物。得知相較於習知果糖葡萄糖液糖,任一混合物之甘味度、甘味質均較接近砂糖。又,藉由在該等混合物中進一步添加果糖、葡萄糖,可調整甘味度、味質。
含有D-阿洛酮糖與D-阿洛糖的糖組成物,可例示含有稀有醣類的異構化糖。
目前,已實用化的糖之混合物中,由通稱「異構化糖」的D-葡萄糖與D-果糖所構成的液糖,係在飲食品等的製造中,屬於利用頻率最高的液糖。異構化糖有如葡萄糖果糖液糖、果糖葡萄糖液糖、高果糖液糖等,但該等目前係利用葡萄糖異構酶將D-葡萄糖(glucose)轉換為D-果糖(果糖)的異構化反應,僅能工業性實用化,因而統稱為「異構化糖」。著眼於特定的六碳醣(hexose)所具有之生理性作用,在獲得含有特定六碳醣之糖組成物目的下所製造的混合糖係屬於新穎之糖組成物。
例如,作為當以生理性效果優異的D-阿洛酮糖及D-阿洛糖為目的之六碳醣,在從以D-葡萄糖與D-果糖為主組成的混合糖而廣泛取得之「異構化糖」,製造含有D-阿洛酮糖與D-阿洛糖的轉換型異構化糖之情況,與含有所製造目標之既定量六碳醣的原料糖為不同糖組成之混合糖,係屬於新穎的糖組成物。
配合目標之機能的種類、程度、使用態樣、使用量等,相對於糖質含量,決定目標之六碳醣含有量,再於獲得其之目的下依最佳製造條件進行處理,可製造目標組成的混合糖。即,藉由將作為原料糖之以D-葡萄糖與D-果糖為主組成之屬於混合糖的異構化糖、或由D-葡萄糖及/或D-果糖所構成的原料糖液,藉由在從鹼性離子交換樹脂、鹼、及鈣鹽所構成群組中選擇一種以上存在的系統中施行處理,則使將作為原料糖的D-葡萄糖與D-果糖轉換為目標之D-阿洛酮糖與D-阿洛糖之屬於平衡反應的異構化反應產生,而可製得含有與原料的異構化糖為不同糖組成的D-阿洛酮糖及D-阿洛糖之糖組成物,其組成係相對於糖質含量,含有0.5~17.0%D-阿洛酮糖及0.2~10.0%D-阿洛糖的糖組成物(參照專利文獻10)。該六碳醣組成物的特徵係同時含有D-阿洛酮糖與D-阿洛糖,可例示較佳係由相對於糖質含量,含有1.0~15.0%D-阿洛酮糖與0.4~8.0%D-阿洛糖的組成所構成者,更佳係由含有2.5~8.0%左右D-阿洛酮糖與1.5~5.0%D-阿洛糖的組成所構成者。D-阿洛酮糖與D-阿洛糖共存的六碳醣組成物可發揮明顯效果,相較於D-阿洛酮糖或D-阿洛糖的單獨效果,可達到無法預期的相乘效果。例如在生理效果方面可發揮優異的效果。此種相乘效果特別係於體重減少率、體脂肪減少率、攝餌量減少率均能顯示特別的效果。又,當攝取含有D-阿洛酮糖與D-阿洛糖的糖組成物時,亦可發
現血糖值降低、胰島素值降低。關於糖組成物所造成的胰島素值降低,係目前為止在單獨攝取D-阿洛酮糖或D-阿洛糖的試驗中尚未獲知的效果。
糖組成物在發揮上述優異的效果時,關於相對於D-阿洛酮糖與D-阿洛糖總糖質的比例,D-阿洛酮糖較佳係0.5~15.0%、更佳1.0~15.0%、特佳2.5~8%範圍。又,D-阿洛糖較佳係0.2~10.0%、更佳0.4~8.0%、特佳1.5~5.0%範圍。
D-阿洛酮糖與D-阿洛糖的總量較佳係0.7~25.0%、更佳1.4~23.0%、特佳4.0~13.0%範圍。
該糖組成物係依照喜好亦可併用蔗糖、糖醇阿斯巴甜、甜菊等甘味料。又,為了賦予體感等,亦可併用甘味度較低的水溶性食物纖維(多醣類、菊糖、難消化性糊精等),且依照目的、喜好,亦可併用混合其他的生理活性成分使用。
本發明的壽命延長劑可使用於例如:醫藥品或醫藥外用藥、口腔用組成物、化妝品、食品、保健用食品、患者用食品、食品素材、保健用食品素材、患者用食品素材、食品添加物、保健用食品添加物、患者用食品添加物、飲料、保健用飲料、患者用飲料、飲料水、保健用飲料水、患者用飲料水、藥劑、製劑原料、飼料、病畜及/或病獸用飼料。
將本發明壽命延長劑使用於食品的情況,可調製為:保持原本形態、經水等稀釋的形態、懸浮於油等的形態、乳液狀
形態食物、或者添加了食品業界一般使用之載體的形態等。飲料的形態有如非酒精飲料或酒精飲料。非酒精飲料可舉例如:碳酸系飲料、果汁飲料、花蜜飲料(nectar drink)等非碳酸系飲料、清涼飲料、運動飲料、茶、咖啡、可可等;又,酒精飲料的形態可舉例如:啤酒、發泡酒、第三類啤酒、清酒、梅酒、葡萄酒、香檳、甜酒、燒酒、藥酒等形態。
本發明壽命延長劑之作為食品素材或食品添加物的使用形態,可舉例如:錠劑、膠囊劑、使其溶解於飲料等之中的粉末或顆粒等固態劑、凝膠等半固態體、飲料水等液體、經稀釋後才使用的高濃度溶液等。任意的成分係可適當調配通常食品中所添加的維生素類、碳水化合物、色素、香料等。食品可依液狀或固態等任意形態食用。亦可利用明膠等施行外包而作成膠囊化的軟膠囊劑後供食用。膠囊係藉由例如在原料明膠中添加水而溶解,再於其中添加可塑劑(甘油、D-山梨糖醇等)而調製得的明膠皮膜所製作。
作為營養輔助食品或機能性食品的例子,可舉例如經調配入醣類、脂肪、微量元素、維生素類、化劑、香料等的流動食物、半消化營養食物、成分營養食物、飲料劑、膠囊劑、經腸營養劑等加工形態。在上述各種食品中,例如運動飲料、營養飲料等飲食物,為了營養均衡、使風味變佳,亦可更進一步調配入胺基酸、維生素類、礦物類等營養性添加物或組成物、香辛料、香料、色素等。
本發明的壽命延長劑可應用於家畜、家禽、寵物類的飼料用。可調配於例如乾狗糧、乾貓糧、濕式狗糧、濕式貓糧、半濕性狗糧、養雞用飼料、牛、豬等家畜用飼料中。飼料本身可依照常法進行調製。
依此,本發明的壽命延長劑亦可使用於除了人類以外的動物,例如:牛、馬、豬、羊等家畜用哺乳類;雞、鵪鶉、鴕鳥等家禽類;蟲類、鳥類或小型哺乳類等寵物類;養殖魚類等。
活用本發明壽命延長劑之壽命延長效果的藥劑,係除了單獨使用該等之外,亦可調配入一般的賦形劑、安定劑、保存劑、結合劑、崩解劑等適當添加劑,選擇液劑、顆粒劑、細粒劑、散劑、錠劑、膠囊劑、丸劑、軟膏劑、貼劑、撒粉、噴霧劑或注射劑等適當的劑型進行製劑,再經口式、經鼻式、經皮式或經靜脈式進行投藥。
適用於經口投藥、經鼻投藥、經皮投藥或經靜脈投藥的醫藥用之有機或無機固態、半固態或液態載體、溶解劑或稀釋劑,可使用於將本發明組成物調製作為藥劑。水、明膠、乳糖、澱粉、硬脂酸鎂、滑石、動‧植物油、苄醇、膠質、聚伸烷二醇、石油樹脂、椰子油、羊毛脂、或醫藥所使用的其他載體,全部均可使用作為含有本發明組成物的藥劑之載體。又,亦可適當將安定劑、濕潤劑、乳化劑、或者用於改變滲透壓或維持調配劑適當pH的鹽類,使用作為輔助藥劑。
再者,本發明的壽命延長劑亦可使用於化妝品。近年來,化妝品等的製劑化亦有使用可溶性薄膜的趨勢。例如作為使香料等保持的芳香膜等,在心情轉換、預防口臭等目的下,使用有可食性之可溶性薄膜。又,亦有將保持著保濕劑等的化妝品用薄膜使用作為面膜,或溶解於水中當作乳液使用的構想,因而均可利用該等。
再者,作為食品、醫藥品等的包裝材、或作為保持食品、醫藥品等有效成分的載體,已提案有顯示優異的溶解性與薄膜特性,亦可適合使用於該等用途的可溶性薄膜(專利文獻11),因而亦可利用該等。
依此,可將本發明的壽命延長劑應用於:飲食品、食品添加劑、醫藥品、醫藥外用藥、口腔用組成物、化妝品、飼料等各種用途。
針對本發明利用實施例進行更詳細說明,惟本發明並不因實施例而受任何限定。
(A)試驗方法
(1)實驗動物
使用線蟲Caenorhabditis elegans之屬於野生型的N2株。
(2)培養基
線蟲的培養係使用完全S液體培養基(非專利文獻3)。在
培養基中依D-阿洛酮糖或D-阿洛糖成為0.25%(14mM)、0.5%(28mM)的方式添加。餌係添加大腸桿菌E.coil OP50株成為30mg濕重/mL。為排除生殖細胞對壽命的影響,添加屬於細胞分裂抑制物質的2'-去氧-5-氟尿苷成為40μM。
(3)線蟲之生存率與平均壽命的測定
將4日齡的年輕成蟲使用於生存率與平均壽命的測定。所調製的液體培養基係於直徑3.5cm的塑膠培養皿10片中分別分注2mL。每1片培養皿各移入10隻線蟲(計100隻),並於20℃中進行培養。至第3日為止前係每天、其後則每隔2~3日便持續植入新的培養基。觀察係在更新植入時實施,記錄生存數。
(B)試驗結果
(1)隨天數經過的線蟲生存率
添加0.25%、0.5%D-阿洛酮糖、0.5%D-阿洛糖添加時,隨天數經過的線蟲生存率變化,係如圖1與圖2所示。又,對照組的線蟲生存率變化亦示於圖1及2中。
(2)壽命延長效果
由天數經過與線蟲生存率所計算之平均壽命的比較結果,係如下。
1)0.25%D-阿洛酮糖處理時的平均壽命係18.9日(對照15.8日),平均壽命延長20%。
2)0.5%D-阿洛糖處理時的平均壽命係15.8日(對照12.5
日),平均壽命延長26%。
(C)結果
由以上的結果可確認利用以稀有醣類為有效成分的組成物所進行之處理,平均壽命最大可延長26%。
除了使用線蟲Caenorhabditis elegans之屬於野生種的N2,並將D-阿洛酮糖濃度設為0.5%(w/v)之外,其餘均與實施例1同樣地施行培養並測定壽命。含D-阿洛酮糖之組成物處理時,線蟲N2的生存率係如圖3所示,D-阿洛酮糖濃度設為0.5%時的平均壽命係27日,相較於無D-阿洛酮糖的對照之23日,得知壽命獲得延長。
除了使用線蟲Caenorhabditis elegans之屬於氧感受性突變種的mev-1,並將D-阿洛酮糖濃度設為0.25%之外,其餘均與實施例1同樣地施行培養並測定壽命。含D-阿洛酮糖之組成物處理時,線蟲mev-1的生存率係如圖4所示,D-阿洛酮糖濃度設為0.25%時的平均壽命係16日,相較於無D-阿洛酮糖的對照之12日,得知壽命獲得延長。
使用線蟲Caenorhabditis elegans之屬於野生種的N2、及屬於氧感受性突變種的mev-1,在D-阿洛酮糖濃度設為0.5%(w/v)的液體培養基10mL中施行培養。培養基係分注
於直徑10cm的塑膠培養皿中,對每1片培養皿放入約1000隻線蟲。除了上述之外,其餘均與實施例1同樣地進行培養,在培養第6日採取試料,並比較SOD的mRNA基因表現,如圖5所示。測定粒線體的Mn-SOD、胞質凝膠的Cu/Zn-SOD之RNA基因層面(gene level)。二線蟲均呈現SOD基因表現增加。
使用線蟲Caenorhabditis elegans之屬於野生種的N2、及屬於氧感受性突變種的mev-1,並與實施例4同樣地施行飼養。飼養第7日採取試料,測定溶菌液中的SOD活性,如圖6所示。得知二線蟲均因D-阿洛酮糖而增加SOD活性。
使用線蟲Caenorhabditis elegans之屬於野生種的N2、及屬於氧感受性突變種的mev-1,並與實施例4同樣地施行培養,在培養第6日便採取試料,比較過氧化氫酶的mRNA基因表現,如圖7所示。測定胞質凝膠的ctl-1、過氧化體的CTL-2之RNA基因層面。二線蟲均呈現SOD基因表現增加。
使用線蟲Caenorhabditis elegans之屬於野生種的N2,並與實施例4同樣地進行飼養。在飼養第7日採取試料,測定溶菌液中的過氧化氫酶活性,如圖8所示。得知二線蟲均因
D-阿洛酮糖而增加過氧化氫酶活性。
將D-阿洛酮糖餵飼大鼠並檢討其生育狀態。
將3周齡的公韋斯系大鼠24隻分為4組(各組6隻),使其自由攝取:(1)在CE-2(CLEA Japan股份有限公司製)中添加2.5%果糖的飼料(CE-2-F)、(2)在CE-2中添加2.5%D-阿洛酮糖的飼料(CE-2-P)、(3)含有異構化糖的飼料(源自異構化糖的糖質28.5%+澱粉28.5%(w/w):HFCS)、(4)含有「含稀有醣類之糖漿」(RareSugar股份有限公司製)的飼料(源自「含稀有醣類之糖漿」的糖質28.5%+澱粉28.5%:RSS)等各飼料、與水,飼養10個月。待飼養結束後,測定各大鼠的體重並解剖,施行腦等各器官的重量測定。測定值係依、平均值±標準偏差表示,施行t檢定。
飼養結束時的大鼠體重(g)係CE-2-F組:452±11、CE-2-P組:436±12、HFSC組:417±12、RSS組:391±17,CE-2-F組與CE-2-P組之間、HFSC組與RSS組之間的各組間出現有效的體重減少。另一方面,關於各器官重量,亦就CE-2-F組與CE-2-P組之間、HFSC組與RSS組之間分別進行比較,在腦重量及肌肉重量並未發現有效差。
由以上得知,即便經10個月的長期飼養時,含有D-阿洛
酮糖、D-阿洛酮糖、或D-阿洛糖等稀有醣類的「含稀有醣類之糖漿」,可抑制肥胖,另一方面,並未發現老齡期常出現的腦重量及肌肉量減少,因而教示可抑制隨老化衍生的腦萎縮與肌肉量降低之可能性。
利用本發明,發現天然界微量存在的單醣(稀有醣類)之新穎特性,並開發新用途。
根據本發明可提供一種含有能作為甘味料使用的稀有醣類(較佳係D-阿洛酮糖及/或D-阿洛糖),可簡便攝取且安全、並可依接近通常食物的形式攝取之壽命延長劑。
近年所開發之依照從自然界大量存在的單醣生產稀有醣類之方法所獲得的稀有醣類,係可利用本發明而提供其新的用途,因而產業上的可利用性大。
圖1係表示利用線蟲N2進行之含有0.25%D-阿洛酮糖之組成物處理時的生存率的圖表。
圖2係表示利用線蟲N2進行之含有0.5%D-阿洛糖之組成物處理時的線蟲生存率的圖表。
圖3係表示利用線蟲N2進行之含有0.5%(w/v)D-阿洛酮糖之組成物處理時的生存率的圖表。
圖4係表示利用線蟲mev-1進行之含有0.25%(w/v)D-阿洛酮糖之組成物處理時的生存率的圖表。
圖5係表示線蟲N2及mev-1中的SOD基因表現因D-阿洛酮糖所造成的影響的圖表。
圖6係表示線蟲N2及mev-1中的SOD活性因D-阿洛酮糖所造成的影響的圖表。
圖7係表示線蟲N2及mev-1中的過氧化氫酶基因表現因D-阿洛酮糖所造成的影響的圖表。
圖8係表示線蟲N2的過氧化氫酶活性因D-阿洛酮糖所造成的影響的圖表。
圖9係表示由D-阿洛酮糖進行的壽命延長機制的圖。
Claims (6)
- 一種壽命延長劑,係以能作為甘味料使用的稀有醣類作為有效成分。
- 如申請專利範圍第1項之壽命延長劑,其中,稀有醣類係D-阿洛酮糖及/或D-阿洛糖。
- 如申請專利範圍第1項之壽命延長劑,其中,稀有醣類係含有D-阿洛酮糖及/或D-阿洛糖的糖組成物。
- 如申請專利範圍第1項之壽命延長劑,其中,稀有醣類係含有D-阿洛酮糖及/或D-阿洛糖的糖組成物,相對於糖質含量,含有D-阿洛酮糖0.5~17.0%及D-阿洛糖0.2~10.0%的糖組成物。
- 如申請專利範圍第1項之壽命延長劑,其中,稀有醣類係含有D-阿洛酮糖及/或D-阿洛糖的糖組成物;以D-葡萄糖及/或D-果糖作為原料糖,相對於總糖質含量,轉換成D-阿洛酮糖為0.5~17.0%及D-阿洛糖為0.2~10.0%的混合糖。
- 如申請專利範圍第1項之壽命延長劑,其中,稀有醣類係含有D-阿洛酮糖及/或D-阿洛糖的糖組成物;以D-葡萄糖及/或D-果糖作為原料糖,相對於總糖質含量,轉換成D-阿洛酮糖為0.5~17.0%及D-阿洛糖為0.2~10.0%,而作為甘味料使用之稀有醣類的異構化糖。
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GB201309076D0 (en) | 2013-03-15 | 2013-07-03 | Tate & Lyle Ingredients | Improved sweetener |
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GB201309077D0 (en) | 2013-03-15 | 2013-07-03 | Tate & Lyle Ingredients | Improved sweetener |
CN103789377A (zh) * | 2013-12-24 | 2014-05-14 | 山西天骄食业有限公司 | 一种生物转化红枣单糖开发含阿洛酮糖功能性枣汁的技术 |
CN103710329A (zh) * | 2013-12-24 | 2014-04-09 | 山西天骄食业有限公司 | 一种基因工程技术制备共表达重组酶的方法 |
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EP3560348B1 (en) * | 2016-12-21 | 2023-12-06 | Cj Cheiljedang Corporation | Amino acid beverage containing allulose |
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JP7449511B2 (ja) | 2020-05-22 | 2024-03-14 | 松谷化学工業株式会社 | 加齢に伴う認知機能の低下予防又は改善用の組成物 |
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KR20130001163A (ko) | 2013-01-03 |
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CN102836166B (zh) | 2017-06-13 |
ES2555134T3 (es) | 2015-12-29 |
JP6216493B2 (ja) | 2017-10-18 |
CN102836166A (zh) | 2012-12-26 |
EP2537422A1 (en) | 2012-12-26 |
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