TW201904596A - 含有葉黃素類或其鹽及菱屬植物加工物之腦功能障礙之預防及/或改善用組成物 - Google Patents
含有葉黃素類或其鹽及菱屬植物加工物之腦功能障礙之預防及/或改善用組成物Info
- Publication number
- TW201904596A TW201904596A TW107118656A TW107118656A TW201904596A TW 201904596 A TW201904596 A TW 201904596A TW 107118656 A TW107118656 A TW 107118656A TW 107118656 A TW107118656 A TW 107118656A TW 201904596 A TW201904596 A TW 201904596A
- Authority
- TW
- Taiwan
- Prior art keywords
- brain
- composition
- lutein
- acid
- processed product
- Prior art date
Links
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Abstract
本發明提供一種含有葉黃素類或其鹽及菱屬植物之加工物作為有效成分的新穎腦功能障礙之預防及/或改善用組成物,尤其可利用作為醫藥及飲食品的組成物。
Description
本發明係關於含有葉黃素類或其鹽及菱屬(Trapa)植物之加工物作為有效成分的腦功能障礙之預防及/或改善用組成物。
近年,受到高齡化社會之影響,起因於老化所伴隨之腦功能降低的腦疾病,例如,記憶障礙、失智症、阿茲海默症等之患者逐日增加,成為很大社會問題。又,老化以外,亦已知因β類澱粉蛋白質蓄積於腦內,而腦神經細胞死滅,引起失智症或阿茲海默症等腦功能障礙。
失智症等腦功能障礙之治療劑,受限於會通過腦屏障之物質,有效治療劑幾乎不存在。再者,腦功能障礙之治療劑必須長期間服用,副作用大,且有藉由組合所造成之弊害。因此,無法說是已確立了對腦功能降低、腦疾病等之有效預防及/或治療方法。於是,腦功能障礙之預防‧治療用之醫藥以外,亦期望無副作用或毒性且 可長期攝取之飲食品形式,例如,可作為補充品攝取的腦功能障礙之預防‧改善用飲食品的開發。
為類胡蘿蔔素之一種的葉黃素,已知有維持眼睛健康,對白內障或老年黃斑症之治療或預防的效果,係在眼科領域中作為醫藥品或補充品被廣泛使用。葉黃素由於具有抗氧化作用,在眼科疾病以外,亦可使用於因活性氧之氧化而發生的老化所伴隨之現象。例如,在非專利文獻1中,暗示著葉黃素對老化所伴隨之失智症或阿茲海默症可能有效。
菱屬(Trapa)植物由於果實具有滋養強壯、促進消化之效能,藉由將全草煎煮飲用,而可達到防止宿醉及視力之改善效果,被使用作為醫藥品或食品。
在專利文獻1中記載:加齡相關疾病中,由美拉德反應所生成之終末糖化產物(advanced glycation end products:AGEs)的蓄積會有意義地增加;菱屬植物之萃取物具有美拉德反應抑制作用,且有對於白內障、軟骨彈力降低、皮膚老化(皮膚彈力降低、為皺紋或鬆弛之原因的膠原交聯形成、為肌膚暗沉之原因的色素沉著等)所伴隨之現象的抑制為有用的可能性;然後亦有對於已知為美拉德反應參與之糖尿病合併症的預防‧治療為有用的可能性。在專利文獻2中記載:菱科植物對於不孕症之改善為有用;對於不孕症之改善,作為一個關連因子而列舉AGEs之生成抑制;然後亦暗示AGEs參與阿茲海默症、巴金森氏病等神經退行性疾病、由酒精成癮所造成之腦障礙、老化現象等之可能性。
然而,尚未有具體地報告菱屬植物,例如菱萃取物等菱屬植物加工品,係對於阿茲海默症或失智症等腦功能障礙之預防及改善為有用。又,並未知悉菱屬植物可改善由腦內β類澱粉蛋白蓄積所造成之腦功能降低。
再者,未有報導於腦功能障礙之預防及改善使用了葉黃素類與菱萃取物等菱屬植物之加工品之組合的實例。
專利文獻1 日本特開2010-077123號公報
專利文獻2 日本特開2016-145182號公報
非專利文獻1 James M. Stringham et al., "Nitric Oxide and Lutein: Function, Performance, and Protection of Neural Tissue", Foods 2015, 4, 678-389; doi: 10.3390/foods4040678
本發明之目的,為提供含有葉黃素類或其鹽及菱屬植物之加工物作為有效成分的腦功能障礙之預防及/或改善用組成物,尤其可利用作為醫藥及飲食品之組成物。
本發明人等為了解決上述課題,著眼於腦功能障礙,尤其是與腦內β類澱粉蛋白蓄積相關之腦功能障礙,尋求藉由將複數種來自天然物之成分加以組合之有效治療法而試行各種研究,專心檢討之結果,發現在將葉黃素類或其鹽與菱屬植物之加工物併用或形成合劑而進行了投與的情況,於被單次投與β類澱粉蛋白之小鼠中,顯著地改善腦功能障礙,而完成了本發明。尤其,本發明人等發現了藉由將此等有效成分組合,而預防‧改善效果會比先前之葉黃素投與更顯著地增強。
亦即,本發明提供以下態樣之發明。
[1]一種腦功能障礙之預防及/或改善用組成物,其含有葉黃素類或其鹽及菱屬植物之加工物作為有效成分。
[2]如[1]記載之組成物,其中葉黃素類為葉黃素、玉米黃質或內消旋玉米黃質。
[3]如[1]或[2]記載之組成物,其中菱屬植物為選自包含無角菱(Trapa acornis Nakano)、小果菱(Trapa incisa Sieb.et Zuc.,或稱姬菱)、日本菱(Trapa japonica Flerov)、二角菱(Trapa bispinosa Roxb.,或稱唐菱)、歐菱(Trapa natans L.)及鬼菱(Trapa natans L.var.japonica Nakai)之群組的至少一種。
[4]如[1]至[3]中任一項記載之組成物,其中菱屬植物之加工物為菱屬植物之果皮的粉碎物及/或萃取物。
[5]一種腦功能障礙之預防及/或改善用組成物,其含有葉黃素或其鹽及二角菱之加工物作為有效成分。
[6]如[5]記載之組成物,其中二角菱之加工物為二角菱之果皮之粉碎物及/或萃取物。
[7]如[5]記載之組成物,其中二角菱之加工物為菱萃取物。
[8]如[1]至[7]中任一項記載之組成物,其為經口或非經口投與用。
[9]如[1]至[8]中任一項記載之組成物,其為醫藥組成物。
[10]如[1]至[8]中任一項記載之組成物,其為食品組成物。
[11]如[10]記載之組成物,其為健康食品、功能性食品、營養輔助食品、補充品、保健功能食品、特定保健用食品、營養功能性食品或功能性標示食品。
[12]如[1]至[11]中任一項記載之組成物,其為軟膠囊、硬膠囊、液劑、果凍、軟糖、錠劑或散劑。
[13]如[1]至[12]中任一項記載之組成物,其中腦功能障礙為腦功能降低及伴隨其之自覺症狀。
[14]如[13]記載之組成物,其中腦功能降低及伴隨其之自覺症狀為認知、學習及記憶功能之降低。
[15]如[1]至[9]及[12]中任一項記載之醫藥組成物,其中腦功能障礙為與腦內β類澱粉蛋白蓄積相關之疾病。
[16]如[1]至[9]及[12]中任一項記載之醫藥組成物,其中腦功能障礙為與腦之錐體細胞減少相關的疾病。
[17]如[15]或[16]記載之醫藥組成物,其中前述疾病為阿茲海默症或失智症。
[18]一種腦功能障礙之治療方法,其特徵為將治療上有效量之葉黃素類或其鹽與菱屬植物之加工物組合,而對患者進行投與。
[19]如[18]記載之治療方法,其中將葉黃素類或其鹽與菱屬植物之加工物併用。
[20]如[19]記載之治療方法,其中將葉黃素類或其鹽與菱屬植物之加工物同時或於不同時間分別投與。
[21]一種葉黃素類或其鹽與菱屬植物之加工物的組合,其係用以使用於腦功能障礙之預防及/或改善。
[22]一種葉黃素類或其鹽與菱屬植物之加工物的組合之用途,其係用於預防及/或治療腦功能障礙用之醫藥的製造。
[23]一種含葉黃素類或其鹽的腦功能障礙之預防及/或改善用組成物,其特徵為與菱屬植物之加工物併用。
[24]一種含菱屬植物之加工物的腦功能障礙之預防及/或改善用組成物,其特徵為與葉黃素類或其鹽併用。
[25]一種增強含葉黃素類或其鹽之組成物的腦內β類澱粉蛋白蓄積之抑制作用的方法,其係藉由摻合菱屬植物之加工物。
[26]一種腦之錐體細胞的減少抑制劑,其含有葉黃素類或其鹽及菱屬植物之加工物作為有效成分。
[27]一種組成物,其係含有菱屬植物之加工物作為有效成分的腦功能障礙之預防及/或改善用組成物,其中腦功能障礙為與腦內β類澱粉蛋白蓄積相關之疾病。
[28]一種治療方法,其係特徵為將治療上有效量之菱屬植物的加工物對患者進行投與的腦功能障礙之治療方法,其中腦功能障礙為與腦內β類澱粉蛋白蓄積相關的疾病。
[29]一種菱屬植物之加工物,其係用以使用於腦功能障礙之預防及/或改善之菱屬植物之加工物,其中腦功能障礙為與腦內β類澱粉蛋白蓄積相關的疾病。
[30]一種用途,其係製造用以預防及/或治療腦功能障礙用之醫藥的菱屬植物之加工物之用途,其中腦功能障礙為與腦內β類澱粉蛋白蓄積相關的疾病。
[31]一種組成物,其係含有菱屬植物之加工物作為有效成分的腦功能障礙之預防及/或改善用組成物,其中腦功能障礙為與腦之錐體細胞之減少相關的疾病。
[32]一種治療方法,其係特徵為將治療上有效量之菱屬植物之加工物對患者進行投與的腦功能障礙之治療方法,其中腦功能障礙為與腦之錐體細胞之減少相關的疾病。
[33]一種菱屬植物之加工物,其係用以使用於腦功能障礙之預防及/或改善的菱屬植物之加工物,其中腦功能障礙為與腦之錐體細胞之減少相關的疾病。
[34]一種用途,其係製造用以預防及/或治療腦功能障礙之醫藥的菱屬植物之加工物之用途,其中腦功能障礙為與腦之錐體細胞減少相關的疾病。
[35]一種組成物,其係含有葉黃素類或其鹽作為有效成分的腦功能障礙之預防及/或改善用組成物,其中腦功能障礙為與腦內β類澱粉蛋白蓄積相關的疾病。
[36]一種治療方法,其係特徵為將治療上有效量之葉黃素類或其鹽對患者進行投與的腦功能障礙之治療方法,其中腦功能障礙為與腦內β類澱粉蛋白蓄積相關的疾病。
[37]一種菱屬植物之加工物,其係用以使用於腦功能障礙之預防及/或改善之葉黃素類或其鹽,其中腦功能障礙為與腦內β類澱粉蛋白蓄積相關的疾病。
[38]一種用途,其係製造用以預防及/或治療腦功能障礙之醫藥的葉黃素類或其鹽之用途,其中腦功能障礙為與腦內β類澱粉蛋白蓄積相關的疾病。
[39]一種組成物,其係含有葉黃素類或其鹽作為有效成分的腦功能障礙之預防及/或改善用組成物,其中腦功能障礙為與腦之錐體細胞減少相關的疾病。
[40]一種治療方法,其係特徵為將治療上有效量之葉黃素類或其鹽對患者進行投與的腦功能障礙之治療方法,其中腦功能障礙為與腦之錐體細胞減少相關的疾病。
[41]一種菱屬植物之加工物,其係用以使用於腦功能障礙之預防及/或改善之葉黃素類或其鹽,其中腦功能障礙為與腦之錐體細胞減少相關的疾病。
[42]一種用途,其係製造用以預防及/或治療腦功能障礙之醫藥的葉黃素類或其鹽之用途,其中腦功能障礙為與腦之錐體細胞減少相關的疾病。
若依照本發明,則可期待藉由將葉黃素類或其鹽與菱屬植物之加工物併用或形成合劑投與而將腦 功能改善至正常狀態。又,葉黃素類或其鹽及菱屬植物之加工物,可期待被利用作為醫藥組成物及食品組成物。
圖1係呈示各群(偽手術、對照、菱萃取物、葉黃素、菱萃取物+葉黃素)之Y迷路試驗的結果。再者,圖中條形圖表示各群之自發性交替行動率(%)。
圖2係呈示各群(偽手術、對照、菱萃取物、葉黃素、菱萃取物+葉黃素)之克魯弗巴雷拉(KB)染色組織標本之海馬CA1區域之錐體細胞層的面積(μm2)。
以下,詳細說明本發明。
在本發明中,「葉黃素類」意指來自植物、動物、微生物等天然物者,例如,從萬壽菊、菠菜、羽衣甘藍等植物;蛋黃;眼睛之網膜、黃斑等所萃取‧精製的葉黃素或其代謝物或以化學方法所合成之葉黃素或代謝物(以一般合成方法製造者)。又,來自天然物者,其原料種類、產地、製造方法無特別限定。
再者,葉黃素類能夠以生理學上或醫藥上容許之各種鹽形式來使用。就鹽形式而言,亦包含酯體。就鹽而言,可列舉例如與鹽酸、氫溴酸、氫碘酸、硝酸、硫酸、磷酸等無機酸所形成之鹽;與乙酸、富馬酸、馬來酸、琥珀酸、檸檬酸、酒石酸、己二酸、葡萄糖酸、葡庚糖酸、葡糖醛酸、對苯二甲酸、甲磺酸、乳酸、馬尿酸、 1,2-乙二磺酸、依沙酸、乳糖酸、油酸、雙羥萘酸、多聚半乳醣醛酸、硬脂酸、單寧酸、三氟甲磺酸、苯磺酸、對甲苯磺酸、硫酸月桂酯、硫酸甲酯、萘磺酸、磺基水楊酸等有機酸所形成之鹽;與溴離子、氯離子、碘離子等鹵素離子所形成之鹽;與鋰、鈉、鉀等鹼金屬所形成之鹽;與鈣、鎂等鹼土金屬所形成之鹽;與鐵、鋅等所形成之金屬鹽;與氨之鹽;與三乙二胺、2-胺基乙醇、2,2-亞胺基雙(乙醇)、1-去氧-1-(甲基胺基)-2-D-山梨醇、2-胺基-2-(羥基甲基)-1,3-丙二醇、普魯卡因、N,N-雙(苯基甲基)-1,2-乙二胺等有機胺所形成之鹽等。又,酯體可為單酯體,亦可為二酯體,可列舉例如與乙酸、月桂酸、肉荳蔻酸、辛酸、十五烷酸、棕櫚酸、棕櫚油酸,十七烷酸、反油酸、蓖麻油酸、芹子酸、異油酸、桐酸、石榴酸、酮基十八碳三烯酸、十八碳四烯酸、反鱈油酸、5-二十碳烯酸、5-二十二碳烯酸、鲸蠟烯酸、芥酸、5,13-二十二碳二烯酸、鯊油酸、癸酸、蘋婆酸、十二碳烯酸、油酸、硬脂酸、二十碳五烯酸、二十二碳六烯酸、亞油酸、亞麻酸、花生四烯酸等所形成之酯體。
就葉黃素類之例而言,無特別限定,然而可列舉葉黃素、玉米黃質、內消旋玉米黃質。本發明中之葉黃素類或其鹽,較佳為葉黃素或其鹽。本發明中之葉黃素類或其鹽,可包含2種以上。
在本發明中,「葉黃素」意指化學名為(3R,3’R,6’R)-β,ε-胡蘿蔔素-3,3’-二醇,以下述式:
所表示的化合物。葉黃素為綠黃色蔬菜富含的類胡蘿蔔素之一種,是體內所存在的主要類胡蘿蔔素之一。
在本發明中,「玉米黃質」意指化學名為(3R,3’R)-β,β-胡蘿蔔素-3,3’-二醇,以下述式:
所表示的化合物。玉米黃質為類似β胡蘿蔔素之脂溶性物質,是葉黃素之構造異構物(葉黃素之代謝物)。玉米黃質在黃斑部大量存在,具有保護黃斑部之作用。
在本發明中,「內消旋玉米黃質」意指化學名為(3R,3’S)-β,β-胡蘿蔔素-3,3’-二醇,以下述式:
所表示之化合物。內消旋玉米黃質為玉米黃質之立體異構物(葉黃素之代謝物)。內消旋玉米黃質具有與玉米黃質同樣之作用。
葉黃素類或其鹽可相對於本發明之組成物之總重量,例如以0.1~90重量%,較佳以0.5~80重量%,更佳以1~70重量%,進一步更佳以1.5~60重量%,特佳以2~50重量%之量來摻合。
葉黃素類或其鹽可對於成人,每1日以例如0.1~500mg,較佳以0.5~250mg,更佳以1~100mg,進一步更佳以3~75mg,特佳以5~50mg之量來進行投與。
在本發明中,「菱屬植物」意指菱科之一年生水草。就菱屬(Trapa)植物之具體例而言,雖無特別限定,然而可列舉無角菱(Trapa acornis Nakano)、小果菱(Trapa incisa Sieb.et Zuc.)、日本菱(Trapa japonica Flerov)、二角菱(Trapa bispinosa Roxb.)、歐菱(Trapa natans L.)、鬼菱(Trapa natans L.var.japonica Nakai)。本發明中之菱屬植物,較佳為日本菱、二角菱及鬼菱,特佳為二角菱。
在本發明中,「菱屬植物之加工物」意指從從前述菱屬植物之全體或各部位調製‧製造的粉碎物、萃取物及彼等之乾燥物。就菱屬植物之部位而言,可列舉例如花、花穗、果皮、果實、果肉、莖、葉、枝、枝葉、幹、樹皮、根莖、根皮、根、種子、癭、心材、地上部及地下部,特佳為果皮。菱屬植物之加工物,例如,可藉由將各部位原樣,或切斷成適當大小、粉碎、榨汁、溶劑萃取,又,視需要使其乾燥而調製‧製造。再者,亦可將2種以上之菱屬植物的各部位適宜混合而調製‧製造。
菱屬植物之萃取物之萃取方法,雖無限定為此等者,然而可列舉批次萃取、使用了管柱萃取之連續萃取等。就萃取溶劑而言,例如,可使用水、有機溶劑或彼等之混合溶劑。就有機溶劑而言,可列舉例如甲醇、乙醇等低級醇;氯仿、乙酸乙酯、正己烷。較佳為水、甲醇或乙醇。又,亦可將此等溶劑2種以上混合而使用。
萃取溶劑之使用量可依據菱屬植物之種類或部位、萃取溶劑之種類等而適宜決定。菱屬植物與萃取溶劑之重量比,例如為1:2~1:30,較佳為1:3~1:20,特佳為1:5~1:10。
又,萃取時間為例如數分鐘~30日,較佳為1小時~15日,萃取溫度為例如5~100℃。
菱屬植物之萃取物可原樣使用萃取之溶液,亦可視需要進一步施加精製處理。該精製處理依照通常之方法進行即可,例如,可藉由將菱屬植物之萃取物依照常法過濾而精製。然後,亦可將所得到之濾液進行減壓濃縮、凍結乾燥等,形成菱屬植物之乾燥物。
就菱屬植物之加工物而言,例如,可使用菱屬植物之果皮萃取物或其乾燥物。菱屬植物之果皮萃取物或其乾燥物,例如,可藉由將菱屬植物之果皮用水或甲醇、乙醇等低級醇萃取,過濾,濃縮,視情況加入賦形劑等添加劑,再乾燥而調製‧製造。
就菱屬植物之加工物而言,以二角菱之加工物的菱萃取物為特佳。菱萃取物為以二角菱果皮為原料之熱水萃取物,大量地含有為抗糖化活性成分的多酚類。
菱屬植物之加工物,可相對於本發明之組成物之總重量,而例如以0.1~99重量%,較佳以1~95重量%,更佳以10~90重量%,進一步更佳以25~85重量%,特佳以60~80重量%之量來摻合。
菱屬植物之加工物可對於成人,每1日例如以0.1~2000mg,較佳以1~1500mg,更佳以10~1000mg,進一步更佳以25~500mg,特佳以50~300mg之量投與。
菱屬植物之加工物中含有多酚。在本發明中,相對於菱屬植物之加工物之總重量的多酚之含量的下限,係例如為0.1重量%,較佳為5重量%,特佳為10重量%。又,其上限為例如80重量%,較佳為70重量%,特佳為60重量%。再者,彼等之上限及下限可適宜組合而使用。更具體而言,相對於菱屬植物之加工物之總重量的多酚之含量,係例如為0.1~80重量%,較佳為5~70重量%,特佳為10~60重量%。又,多酚含量可依照例如福林-橋卡替奧(Folin-Ciocalteu)法等測定。
在菱屬植物之加工物為菱屬植物之果皮萃取物的情況,相對於菱屬植物之果皮萃取物之總重量的多酚之含量的下限,係例如為0.1重量%,較佳為1重量%,更佳為5重量%,進一步更佳為10重量%,特佳為20重量%。又,其上限為例如90重量%,較佳為80重量%,更佳為70重量%,進一步更佳為65重量%,特佳為60重量%。再者,彼等之上限及下限可適宜組合而使用。更具體而言,相對於菱屬植物之果皮萃取物之總重量的多酚之含量,係例如為0.1~90重量%,較佳為1~80重量%,更佳為5~70重量%,進一步更佳為10~65重量%,特佳為20~60重量%。
在本發明中,「腦功能障礙」意指引起腦本身及神經系統相關之腦功能降低的障礙,例如,複合有1個以上下列病症之症狀的障礙:失語症、注意力障礙、記憶障礙、行動及感情之障礙、半側空間忽視、履行功能障礙、失用症(apraxia)、半側身體失認、區域記憶障礙、失認症等。
在本發明中,「腦功能降低」意指因加齡或疾病而造成之腦功能降低,亦包含腦功能之維持。又,亦包含因腦內之β類澱粉蛋白蓄積所造成的腦功能降低及因腦之錐體細胞減少所造成的腦功能降低。就誘發腦功能降低之疾病而言,可列舉加齡所伴隨之老化、阿茲海默症、失智症。又,在本發明中,「伴隨其之自覺症狀」只要為因腦功能降低所造成之自覺症狀即可,可列舉例如認知、學習、記憶、智能及動機之降低。
在本發明中,「腦功能障礙之預防及/或改善用組成物」意指用於預防、改善及/或治療引起腦功能降低之疾病及伴隨其之自覺症狀的組成物。其中,在本發明中,「改善」意指疾病之症狀‧狀態之好轉、疾病之症狀‧狀態之惡化的防止或延遲、疾病之症狀進行的逆轉、防止或延遲或疾病之治療,「預防」意指使適用對象之疾病之發病防止或發病延遲或使適用對象之疾病之發病的危險性降低。
在本發明中,「治療」意指疾病之所有治療(例如,改善、減輕、進行之抑制等)。又,亦可包含疾病之發病及/或進行之阻止。
在本發明中,「患者」意指人類及其他動物,例如,狗、貓、馬等。患者較佳為哺乳動物,更佳為人類。
在本發明中,「治療上之有效量」意指在組織、系統、動物或人類中,會誘發研究者或醫師所要求的生物學或醫藥回應之有效成分的量。又,「治療上之有效量」包含下述意義:在為了治療疾病而對哺乳動物進行投與之情況,能使該疾病之治療為充分的有效成分(葉黃素類或其鹽、菱屬植物之加工物等)之量。「治療上之有效量」依存於有效成分、疾病及其嚴重度、以及隨著被治療之哺乳動物的年齡、體重等而改變。
再者,「有效量」包含下述意義:於以適當之用量投與之際,會產生急性或慢性之治療效果的有效成分(葉黃素類、菱屬植物之加工物等)之量。就此治療效果而言,可列舉疾病/狀態及相關合併症之症狀、徵兆及達基礎病理可檢測程度的預防、矯正、抑制、或逆轉。
作為該有效量,可列舉本發明之葉黃素類或菱屬植物之加工物單獨的量、本發明之葉黃素類與菱屬植物之加工物之組合的量及/或與其他有效成分組合之本發明之有效成分的量。
在本發明中,「錐體細胞」意指主要存在於大腦皮質的投射性之興奮性神經細胞。擔任大腦皮質之區域內‧區域間及從皮質至皮質下之訊息傳達的重要角色。若錐體細胞萎縮、損傷、細胞數減少,則會引起失智症、阿茲海默症等腦功能障礙。
葉黃素類或其鹽與菱屬植物之加工物的組合,係因會預防及/或改善失智症、阿茲海默症等之腦功能障礙,而被期待抑制腦之錐體細胞的減少。
在本發明中,葉黃素類或其鹽與菱屬植物之加工物的組合比率,無特別限定,可適宜選擇以達成腦功能障礙之預防及/或改善效果。該組合比率無特別限定,可例如在1:100~100:1,較佳在1:50~5:1,更佳為在1:20~2:1之範圍適宜選擇。
在本發明之葉黃素類或其鹽與菱屬植物之加工物的組合中,兩種有效成分可分別投與,又亦可形成單一製劑一起投與。又,可將本發明之組合之一種成分,相對於其他成分,於預先、於同時、或於之後投與。此等成分亦可調製成單一製劑型或分離之製劑型的醫藥製劑。
就本發明之葉黃素類或其鹽與菱屬植物之加工物的組合形式之例而言,無特別限定,可列舉以下之(I)及(II)之形式:(I)同時含有葉黃素類或其鹽、及菱屬植物之加工物兩成分的單一製劑(1個組成物、摻合劑)形式;及(II)以個別製劑的形式具有含葉黃素類或其鹽之製劑(組成物)及含菱屬植物之加工物之製劑(組成物)。
在該(II)相關之形式的情況中,可將各製劑同時投與,或安排適宜之時間間隔而個別投與;為了達成期望之腦功能障礙的預防及/或改善效果,可採用適當之投與計畫。
在此等有效成分係被調製成單一製劑之情況,無特別限定,不過對於每1重量份之葉黃素類或其鹽,可將菱屬植物之加工物以0.01~100重量份,較佳0.2~50重量份,更佳0.5~20重量份之比率混合。又,在單一製劑中,雖無特別限定,但例如相對於該製劑之組成物而含有其活性成分之和為0.1~99重量%。
本發明之組成物,若在不妨礙腦功能障礙之預防及/或改善效果的範圍,則亦可依照本身為習知之方法適宜摻合其他有效成分(例如,具有輔助效果之物質)及添加劑。
就可摻合於本發明之組成物的其他有效成分而言,可列舉例如維生素A群;類胡蘿蔔素類(排除葉黃素);維生素B群;維生素C群;維生素D群;維生素E群;生育三烯酚類;麩胱甘肽及此等之衍生物或此等之鹽;兒茶素、花青素、單寧、蘆丁、異黃酮、綠原酸、鞣花酸、薑黃素、香豆素等多酚類;亞麻油酸、α-或γ-次亞麻油酸、花生四烯酸、二十碳五烯酸、沙丁魚酸、二十二碳六烯酸及其衍生物或彼等之鹽;選自膠原、彈性蛋白、纖連蛋白、角蛋白之蛋白質及彼等之衍生物以及水解物;甘醇酸、乳酸、蘋果酸、檸檬酸、水楊酸等α-羥基酸及彼等之衍生物或彼等之鹽;血清除蛋白、脾臟、胎盤、雞冠、蜂王漿、酵母、乳酸菌、雙歧桿菌、靈芝、胡蘿蔔、日本當藥、迷迭香、黃柏、大蒜、扁柏酚、千金藤素、蘆薈、丹參、山金車、洋甘菊、白樺、弟切草、桉樹、無患子、旋覆花、雞血藤、山扁豆、桑 白皮、當歸、拳參、苦參、山楂、白百合、啤酒花、野薔薇、薏苡仁、魚腥草、海藻、納豆、檸檬草、木槿、銀杏葉萃取物、磷脂絲胺酸等天然物及彼等之萃取物;腺苷三磷酸、腺苷二磷酸、腺苷一磷酸等腺苷酸衍生物;鐵、釩、鉬、錳、銅、鉀、鎂、鈣、鋅、硒、碘等礦物質類;甘露醇、木糖醇、葡萄糖胺等單糖類;透明質酸、硫酸軟骨素、硫酸皮膚素、硫酸乙醯肝素、肝素、硫酸角質素、糖原、幾丁質、殼聚糖等多醣類;去氧核糖核酸、核糖核酸等核酸類;其他甘草酸、鳥嘌呤、黏蛋白、泛醌、α-硫辛酸、二十八烷醇,大蒜素、蒜胺酸、以及彼等之混合物。較佳為維生素A群;類胡蘿蔔素類(排除葉黃素);維生素B群;維生素C群;維生素D群;維生素E群;生育三烯酚類;麩胱甘肽及此等之衍生物或此等之鹽;兒茶素、花青素、鞣花酸等之多酚類;亞麻油酸、α-或γ-次亞麻油酸、花生四烯酸、二十碳五烯酸、沙丁魚酸、二十二碳六烯酸及其衍生物或彼等之鹽;選自膠原、彈性蛋白、纖連蛋白、角蛋白之蛋白質及彼等之衍生物以及水解物;銅、鋅等礦物質類;黏蛋白、泛醌、α-硫辛酸、以及彼等之混合物。更佳為維生素A群;類胡蘿蔔素類(排除葉黃素);維生素C群;維生素E群;生育三烯酚類;麩胱甘肽及此等之衍生物或此等之鹽;兒茶素、花青素、鞣花酸等多酚類;二十碳五烯酸、二十二碳六烯酸及其衍生物或彼等之鹽;銅、鋅等礦物質類;黏蛋白、泛醌、α-硫辛酸、以及彼等之混合物。
其他有效成分可相對於組成物之總重量,而例如以0.1~99重量%,較佳以1~90重量%,更佳以5~80重量%,進一步更佳以10~70重量%,特佳以20~60重量%之量來摻合。又,亦可將2種以上組合使用。
就可摻合於本發明之組成物的添加劑而言,可列舉賦形劑、增黏劑、乳化劑(例如,蜜蠟、甘油脂肪酸酯)。
本發明之組成物可進行經口或非經口(例如,皮下、肌肉內或靜脈內)投與。本發明之組成物可與賦形劑、增黏劑、乳化劑等添加劑混合,而調製成期望之劑型。就本發明之組成物的劑型而言,無特別限定,然而可列舉軟膠囊、硬膠囊、液劑、果凍、軟糖、錠劑、散劑及凝膠狀劑等補充品的形式。
本發明之組成物可使用作為飲食品及醫藥(包含人類以外之哺乳類用醫藥品)。在本發明中,本發明之組成物對飲食品及醫藥之摻合量無特別限定,然而可依據適用之目的(對象疾病、症狀之種類等)、適用對象(人類、人類以外之動物(較佳為哺乳類,特佳為狗、貓等))、適用對象部位、適用對象之性別或年齡、飲食品及醫藥之形式、此等投與或攝取方法或其次數、嗜好等而適宜設定。
在本發明中,在將本發明之組成物調製作為醫藥(醫藥品、醫藥部外品等)的情況,可摻合葉黃素類或其鹽及菱屬植物之加工物與其他藥效成分、藥學上可容許之載劑及添加劑。例如,可作為藥學上可容許之 載劑及添加劑而混合黏合劑、崩散劑、潤滑劑、濕潤化劑、緩衝劑、防腐劑、香料等,調製成期望之劑型。就醫藥之劑型而言,並無特別限定,但可列舉注射劑、外用劑、吸入劑、栓劑、薄膜劑、片劑、液劑、散劑、錠劑、顆粒劑、膠囊劑、糖漿劑、點眼劑、洗眼劑、點鼻劑。此等劑型中,又較佳為適合經口投與之劑型(亦即,內服用醫藥品),特佳為例如片劑、液劑、散劑、錠劑、顆粒劑、膠囊劑、軟膠囊劑、糖漿劑。此等劑型可使用作為例如,腦功能降低之預防及/或治療用的醫藥品。
在本發明中,在將本發明之組成物調製作為食品組成物(健康食品、功能性食品、營養輔助食品、補充品、保健功能食品、特定保健用食品、營養功能性食品、功能性標示食品等)的情況,係可將葉黃素類或其鹽及菱屬植物之加工物,與甜味料、著色料、防腐料、增黏劑、安定劑、凝膠化劑、糊劑、抗氧化劑、發色劑、漂白劑、防黴菌劑(防黴劑)、東方食品、口香糖基料、香料、酸味料、調味料、乳化劑、pH調整劑、鹽水、膨脹劑、營養強化劑或其他飲食品材料混合,而調製成期望之形式。就本發明之組成物的形式而言,並無特別限定,但可列舉凝膠狀劑、顆粒、細粒、膠囊、軟膠囊、錠劑、粉末、液劑、半固體劑等補充品類型之食品;碳酸飲料、清涼飲料、乳飲料、酒精飲料、果汁飲料、茶類、營養飲料等飲料;粉末果汁、粉末湯等粉末飲料;口香糖、糖果錠、糖果、小餅、軟糖、米餅、餅乾、果凍等糖果類;麵包、麵類、穀類食品、果醬、調味料等 形式。此等之形式可使用作為例如腦功能降低之預防及/或改善用飲食品,例如,一般飲食品之外,亦可使用作為營養輔助食品、功能性標示食品、特定保健用食品、病人用食品等保健品。
在本發明之組成物為食品組成物之情況,該組成物可標示為「腦功能降低之預防(或抑止)及/或改善(或治療)」。又,「腦功能降低之預防及/或改善」亦可標示為例如,「改善健康年長者因加齡而降低的腦活動性,使為認知功能之一部分的記憶(察覺、想出語言、數字或圖形等)之精確度或判斷之正確度提高」、「提高為認知功能之一部分的記憶(知覺‧認識之事物的想起)之精確度」、「維持為認知功能之一部分的記憶力(想出語言‧物之印象‧位置訊息的能力)之功能」、「支援為認知功能之一部分的計算‧語言‧圖形‧狀況等訊息之記憶的功能」、「維持為認知功能之一部分的記憶力(記憶、想出日常生活中發生之行動或判斷的能力)之功能」、「使為認知功能之一部分的記憶(察覺、想出語言、數字或圖形等)之精確度或判斷之正確度提高」、「提高為認知功能之一部分的記憶(知覺‧認識的事物之想起)之精確度」、「為認知功能之一部分的記憶(想出認知之語言‧物之印象‧體驗)之精確度或判斷之正確度提高」、「維持為認知功能之一部分的記憶(語言、人臉)」、「維持為認知功能之一部分的記憶力(察覺、想起語言或圖形等之能力)」、「維持為認知功能之一部分的記憶力(想起不久前見聞之事 物的能力)」、「維持為認知功能之一部分的記憶力(察覺、想起日常生活中所見聞之訊息的能力)之功能」、「維持為認知功能之一部分的記憶力(記憶、想起計算‧言語‧狀況等訊息的能力)之功能」、「維持為認知功能之一部分的記憶力(記憶、想起見到或聽到之內容的能力)之功能」、「支援為認知功能之一部分的記憶力(察覺、想起日常生活中見聞之訊息、語言‧事物之印象、位置訊息的能力)之功能」、「維持為認知功能之一部分的記憶力(記憶想出日常生活中見到或聽到之訊息的能力)之功能」、「支援為認知功能之一部分的計算‧言語‧圖形‧故事‧顏色‧狀況等訊息之記憶的功能(察覺事物並保持記憶之能力)」、「在日常生活中感到疲勞之疲勞感的減輕、伴隨頭腦不清楚‧注意力降低之疲勞感的緩和、必須單純記憶或判斷之作業效率的提高上具有用的功能」、「維持中老年者伴隨加齡而降低之為認知功能之一部分的記憶力、注意力、判斷力、空間認識力」、「維持中老年者之為認知功能之一部分的記憶力(察覺、想起語言或圖形等之能力)」、「維持中老年者之伴隨加齡而降低的認知功能之一部分(記憶力、注意力、判斷力、空間認識力)的作用」、「支援中老年者之為認知功能之一部分的計算‧言語‧圖形‧狀況等訊息之記憶的功能」、「支援中老年者之為認知功能之一部分的計算‧言語‧圖形‧狀況等訊息之記憶的功能」、「維持健康中老年者伴隨加齡而降低的為認知功能之一部分的記憶力(察覺、想出語言或圖形等之 能力)」、「支援中老年者伴隨加齡而降低的為認知功能之一部分的數字‧文字‧圖形‧空間等訊息之記憶的功能」、「適用於關心伴隨加齡之記憶力降低者的功能(對記憶之保持‧檢索‧再生有用)」、「緩和由於加齡而為認知功能之一部分之記憶功能(記憶訊息,順利想起訊息並判斷之功能)降低的作用」、「維持腦之為認知功能之一部分的記憶力(想起不久前所見聞之事物的能力)」、「維持為認知功能之一部分的運動功能之功能」、「改善伴隨腦功能降低之視覺功能(視力‧眼球運動‧兩眼協作‧調節功能等之從眼之輸入功能及藉由腦認知視覺訊息‧記憶‧印象之處理功能的協作‧調節)降低」、「緩和因加齡而導致為認知功能之一部分的視覺功能降低之作用」、「維持腦之為認知功能之一部分的視覺功能」、「維持為認知功能之一部分的視覺功能之功能」,再者亦可可標示為類似彼等。標示可直接地或間接地進行,就直接標示之例而言,可列舉記載於商品本身,包裝盒、容器、標籤、標牌等包裝上;就間接標示之例而言,可列舉藉由交易文件、操作說明書、附件、型錄、網站、門市、展示會、看板、公告欄、報紙、雜誌、電視、廣播、電子郵件等進行的廣告‧宣傳活動。
以下,呈示製劑例及試驗例之結果,然而此等僅用於使本發明能更充分被理解,而非用於限定本發明之範圍。
以下呈示本發明之代表性製劑例。再者,在下述製劑例中,各成分之摻合量為作成軟膠囊之情況之每1膠囊的含量。
對Slc:ddY(SPF:Specific-Pathogen-Free)小鼠(供給源:日本SLC股份有限公司)投與試料(媒體對照、菱萃取物、葉黃素、菱萃取物+葉黃素),然後,注入β類澱粉蛋白溶液,進行Y迷路試驗,評價了菱萃取物、葉黃素及其併用投與對學習障礙之改善作用。實施了該試驗2次。再者,關於Y迷路試驗,係依據Takayoshi MAMIYA et al.,"Effects of Pre-Germinated Brown Rice on β-Amyloid Protein-Induced Learning and Memory Deficits in Mice",Biol.Pharm.Bull.,July 2004,27(7),1041-1045進行,並進行了評價。
雄性、5週齡、Slc:ddY(SPF)小鼠(體重:23~28g:n=32)
使用上述小鼠,依照以下之順序製作了模型小鼠:將戊巴比妥鈉(東京化成工業股份有限公司)以40mg/kg經腹腔內對小鼠進行投與(投與液量:10mL/kg)以進行麻醉。麻醉後,以勒沃布比卡因(levo bupivacaine)鹽酸鹽(Popscaine(註冊商標)0.25%注射液,丸石製藥股份有限公司)經皮下投與至頭皮(0.1mL)。剪除小鼠頭頂部分之毛,將頭部固定於腦定位固定裝置。將頭皮以碘酊消毒後切開,使頭蓋骨露出,將頭蓋骨上之結合組織以棉棒去除後,用吹風機乾燥,使前囟(bretgma)之位置容易看見。使用牙科用鑽器,在前囟側方1mm(右側)、後方0.2mm之頭蓋骨,開鑿不鏽鋼製管刺入用之穴。從骨表面至2.5mm之深度,將外徑0.5mm之矽膠管及連接微型注射器之不鏽鋼製管垂直刺入。將3μL(6μmol/3μL)之β類澱粉蛋白溶液(偽手術群為3μL之注射用水)用微型注射器泵經3分鐘注入腦室內。注入後,插入不鏽鋼製管,原樣靜置3分鐘,將不鏽鋼製管慢慢移開。然後,去除不鏽鋼製管,將頭蓋穴以非吸收性骨髓止血劑(NESTOP(註冊商標)、Alfresa Pharma股份有限公司)填塞,將頭皮縫合。將小鼠從腦定位固定裝置移開,送回飼養籠中。
β類澱粉蛋白溶液係將β類澱粉蛋白(Amyloid-β Protein(25-35);Polypeptide Laboratories)以注射用水溶 解成2mM,並於37℃之定溫保管庫中培育4日而調製。就偽手術用媒體而言,係使用了注射用水。
‧媒體對照(注射用水+紅花油)
‧菱萃取物
在菱萃取物原材料(林兼產業股份有限公司)中加入注射用水(大塚製藥工場股份有限公司),調製成0.2mg/mL。
‧葉黃素
在葉黃素(Katra Phytochem[India]Private Limited)中加入紅花油(和光純藥興業股份有限公司),調製成0.04mg/mL。
將Slc:ddY小鼠以各群之平均體重約略相等之方式,隨機地分為5群(偽手術、媒體對照、菱萃取物、葉黃素、菱萃取物+葉黃素)(每個實驗群n=10)。對於各群,於同時期開始了試料之投與。接著,從投與開始日算起第8日,進行了β類澱粉蛋白溶液之投與及偽手術用媒體(注射用水)之投與。對於各群,投與之試料種類及投與量,如下表所示。各試料係以10mL/kg,1日1次,進行了14日的強制經口投與。關於試料,係於投與注射用水或菱萃取物後10分鐘以後,投與了紅花油或葉黃素。又,在全部群中,係使試驗用小鼠於各試料之外,自由攝取了MF飼料(東方酵母股份有限公司製)。
Y迷路試驗係使用了塑膠製之Y字型迷路(Unicom有限公司)作為實驗裝置,其中1條窄道之長度為39.5cm、底寬為4.5cm、壁之高度為12cm,3條窄道分別呈120度分歧。
在第14日投與約1小時後,將小鼠置於Y字型迷路之任一窄道,記錄8分鐘於迷路內自由探索時所移動之窄道的序號。將在窄道移動之次數當作總進行數,並將其中連續地選擇互異之3條窄道的組合數,當作自發性交替行動數,使用下述之式子算出自發性交替行動率(%)。
自發性交替行動率(%)=[自發性交替行動數/(總進行數-2)]×100
將對於模型小鼠,各群之Y迷路試驗的結果示於圖1及表2。總進行數、自發性交替行動數及自發性交替行動率,係以全部群中n=10之平均值表示。
在自發性交替行動率方面,媒體對照群與偽手術群比較時,可見自發性交替行動率之有意義降低(在t檢定中,p<0.05)。亦即,在媒體對照群中,與偽手術群相比,記憶Y迷路中曾進入之窄道臂的能力有意義地降低了,因此暗示因類澱粉蛋白β之投與而記憶障礙發生。
另一方面,菱萃取物群、菱萃取物+葉黃素群則相對於媒體對照群,而自發性交替行動率增加了。
因此,證明了菱萃取物群、及菱萃取物+葉黃素群之小鼠,記憶Y迷路中曾進入之窄道的能力比媒體對照群提升。在葉黃素群中,在自發性交替行動率並未見到有改善作用,然而藉由比較菱萃取物之投與、和菱萃取物+葉黃素之併用,可見到其在記憶障礙之改善作用上有效果。
由以上之試驗結果,證實了藉由菱萃取物或菱萃取物+葉黃素之投與,而改善記憶Y迷路中曾進入之窄道的能力之降低,自發性交替行動率會大幅度增加。由此,認定菱萃取物或菱萃取物+葉黃素之投與係對於起因於β類澱粉蛋白蛋白質之腦功能障礙或阿茲海默型失智症具有改善效果,尤其菱萃取物+葉黃素之投與,對於起因於β類澱粉蛋白蛋白質之腦功能障礙或阿茲海默型失智症具有顯著的改善效果。
從試驗例1之各實驗群之小鼠摘出腦,製作病理組織標本,並進行了病理組織評價。將相關試驗實施了2次。
將試驗例1之各實驗群之小鼠,於使用異氟醚溶液麻醉下,開胸使心臟露出,於心房置入切口。使用裝上注射針之聚丙烯製拋棄式注射筒,從左心室將針插入,注入約30mL之冰冷生理食鹽液後,以約30mL之10體積%中性緩衝福馬林溶液灌流。確認灌流後死亡,將全腦摘出,浸漬於10體積%中性緩衝福馬林溶液中。
摘出之腦依照常法進行石蠟包埋後,於前囟-1.70mm附近製作1片病理切片,並於前囟-2.80mm附近製作1片病理切片(不連續),使用各部位製作了克魯弗巴 雷拉染色(KB染色)組織標本。再者,切出後之腦保存於10體積%中性緩衝福馬林中。
1)對於各標本,由光學顯微鏡像確認最靠近前囟-1.70mm及前囟-2.80mm的海馬CA1區域之錐體細胞層(George Paxinos and Keith B.J.Franklin.(2013).The Mouse Brain in stereotaxic coordinates.Elsevier),選擇左右腦之任一者作為評價對象。
2)使用顯微鏡用數位相機,以物鏡10倍攝影。
3)合成所攝影之數位圖像,將評價對象製成1個圖像。
4)使用二次元圖像解析軟體WinROOF2015系統Version 3.6(三谷商事股份有限公司),測定海馬CA1區域之錐體細胞層的面積。
將海馬CA1區域之錐體細胞層之面積的測定結果示於圖2及表3。在全部群中,係以n=2之平均值表示。
在海馬CA1區域之錐體細胞層的面積方面,在媒體對照群,與偽手術群比較而可見錐體細胞層之面積的減少。因此,顯示了因類澱粉蛋白β之投與,而腦之錐體細胞減少。
另一方面,在菱萃取物群、葉黃素群、菱萃取物+葉黃素群,相對於媒體對照群而可見海馬CA1區域之錐體細胞層之面積的增加。
從以上之試驗結果,證實了藉由菱萃取物、葉黃素或菱萃取物+葉黃素之投與,而腦之錐體細胞的減少被抑制。由此,可見菱萃取物、葉黃素或菱萃取物+葉黃素之投與,對於腦之錐體細胞之減少所伴隨的腦功能障礙或阿茲海默型失智症具有預防或改善效果,尤其菱萃取物+葉黃素之投與,係對於腦之錐體細胞之減少所伴隨的腦功能障礙或阿茲海默型失智症具有顯著之改善效果。
本發明由於使用葉黃素類或其鹽及菱屬植物之加工物作為有效成分,而不僅是作為醫藥組成物,作為飲食品或補充品等食品組成物亦為有用,可在寬廣的領域中,提供安全性高之腦功能障礙的預防及/或改善用組成物。
Claims (18)
- 一種腦功能障礙之預防及/或改善用組成物,其含有葉黃素類或其鹽及菱屬植物之加工物作為有效成分。
- 如請求項1之組成物,其中葉黃素類為葉黃素、玉米黃質或內消旋玉米黃質。
- 如請求項1或2之組成物,其中菱屬植物為選自包含無角菱(Trapa acornis Nakano)、小果菱(Trapa incisa Sieb.et Zuc.)、日本菱(Trapa japonica Flerov)、二角菱(Trapa bispinosa Roxb.)、歐菱(Trapa natans L.)及鬼菱(Trapa natans L.var.japonica Nakai)之群組中的至少一種。
- 如請求項1至3中任一項之組成物,其中菱屬植物之加工物為菱屬植物之果皮的粉碎物及/或萃取物。
- 一種腦功能障礙之預防及/或改善用組成物,其含有葉黃素或其鹽及二角菱之加工物作為有效成分。
- 如請求項5之組成物,其中二角菱之加工物為二角菱之果皮的粉碎物及/或萃取物。
- 如請求項5之組成物,其中二角菱之加工物為菱萃取物。
- 如請求項1至7中任一項之組成物,其係用於經口或非經口投與。
- 如請求項1至8中任一項之組成物,其為醫藥組成物。
- 如請求項1至8中任一項之組成物,其為食品組成物。
- 如請求項10之組成物,其為健康食品、功能性食品、營養輔助食品、補充品、保健功能食品、特定保健用食品、營養功能性食品或功能性標示食品。
- 如請求項1至11中任一項之組成物,其為軟膠囊、硬膠囊、液劑、果凍、軟糖、錠劑或散劑之形式。
- 如請求項1至12中任一項之組成物,其中腦功能障礙為腦功能降低及伴隨其之自覺症狀。
- 如請求項13之組成物,其中腦功能降低及伴隨其之自覺症狀為認知、學習及記憶功能之降低。
- 如請求項1至9及12中任一項之醫藥組成物,其中腦功能障礙為與腦內β類澱粉蛋白蓄積相關聯之疾病。
- 如請求項1至9及12中任一項之醫藥組成物,其中腦功能障礙為與腦之錐體細胞之減少相關連的疾病。
- 如請求項15或16之醫藥組成物,其中該疾病為阿茲海默症或失智症。
- 一種腦之錐體細胞的減少抑制劑,其含有葉黃素類或其鹽及菱屬植物之加工物作為有效成分。
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JP2017-109046 | 2017-06-01 | ||
JP2017109046 | 2017-06-01 |
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TW201904596A true TW201904596A (zh) | 2019-02-01 |
TWI790238B TWI790238B (zh) | 2023-01-21 |
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TW111149672A TW202317072A (zh) | 2017-06-01 | 2018-05-31 | 腦功能障礙之預防及/或改善用組成物 |
TW107118656A TWI790238B (zh) | 2017-06-01 | 2018-05-31 | 含有葉黃素類或其鹽及菱屬植物加工物之腦之錐體細胞的減少抑制劑 |
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EP (1) | EP3632418A4 (zh) |
JP (2) | JP7130635B2 (zh) |
KR (1) | KR20200011442A (zh) |
CN (1) | CN110691590A (zh) |
TW (2) | TW202317072A (zh) |
WO (1) | WO2018221650A1 (zh) |
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JP2020150848A (ja) * | 2019-03-20 | 2020-09-24 | 小林製薬株式会社 | 経口組成物 |
JP2020158476A (ja) * | 2019-03-28 | 2020-10-01 | 御木本製薬株式会社 | アミロイド線維形成阻害剤 |
WO2024143060A1 (ja) * | 2022-12-26 | 2024-07-04 | サントリーホールディングス株式会社 | 脳神経細胞保護用組成物 |
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JP2010077123A (ja) | 2008-08-29 | 2010-04-08 | Hayashikane Sangyo Kk | メイラード反応阻害剤 |
KR101116757B1 (ko) | 2009-01-23 | 2012-03-13 | 한국과학기술연구원 | 능실로부터 분리된 신규 화합물 및 이를 함유하는 항산화 조성물 |
MX353505B (es) * | 2009-11-09 | 2018-01-17 | Dsm Ip Assets B V Star | Uso de composiciones que contienen luteina para mejorar ciertos aspectos de la memoria. |
CN102762616B (zh) * | 2010-02-24 | 2014-07-16 | 巴斯夫欧洲公司 | 制备吸水性聚合物颗粒的方法 |
EP2978418A1 (en) * | 2013-03-28 | 2016-02-03 | OmniActive Health Technologies Limited | Neuroprotective effect of carotenoids in brain |
JP6077045B2 (ja) | 2015-01-29 | 2017-02-08 | 正雄 神野 | 不妊の改善剤組成物 |
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- 2018-05-31 US US16/617,323 patent/US20210128492A1/en not_active Abandoned
- 2018-05-31 KR KR1020197036354A patent/KR20200011442A/ko not_active Application Discontinuation
- 2018-05-31 WO PCT/JP2018/020944 patent/WO2018221650A1/ja active Application Filing
- 2018-05-31 TW TW111149672A patent/TW202317072A/zh unknown
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CN110691590A (zh) | 2020-01-14 |
EP3632418A4 (en) | 2021-02-24 |
TWI790238B (zh) | 2023-01-21 |
TW202317072A (zh) | 2023-05-01 |
WO2018221650A1 (ja) | 2018-12-06 |
KR20200011442A (ko) | 2020-02-03 |
EP3632418A1 (en) | 2020-04-08 |
US20210128492A1 (en) | 2021-05-06 |
JP2022169695A (ja) | 2022-11-09 |
JPWO2018221650A1 (ja) | 2020-04-02 |
JP7130635B2 (ja) | 2022-09-05 |
JP7429739B2 (ja) | 2024-02-08 |
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