TWI813993B - 一種靈芝液態發酵液用於製備預防、改善或治療阿茲海默症或阿茲海默症引起的相關病症的組合物之用途 - Google Patents
一種靈芝液態發酵液用於製備預防、改善或治療阿茲海默症或阿茲海默症引起的相關病症的組合物之用途 Download PDFInfo
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- TWI813993B TWI813993B TW110117083A TW110117083A TWI813993B TW I813993 B TWI813993 B TW I813993B TW 110117083 A TW110117083 A TW 110117083A TW 110117083 A TW110117083 A TW 110117083A TW I813993 B TWI813993 B TW I813993B
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- ganoderma lucidum
- disease
- alzheimer
- liquid fermentation
- fermentation broth
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- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
本發明提供一種靈芝液態發酵液用於製備預防、改善或治療阿茲海默症或阿茲海默症引起的相關病症的組合物之用途,其中該靈芝液態發酵液的製備方法,包括:將該靈芝菌種在液態培養基中培養,得到一種靈芝液態發酵產物,將該靈芝液態發酵產物固液分離,移除菌絲體,得到該靈芝液態發酵液。其中該預防及改善阿茲海默症是改善記憶損傷、改善焦慮狀態改變、降低腦中GFAP(Glial fibrillary acidic protein)活化、β型澱粉樣蛋白累積或降低腦組織中氧化傷害的發生。
Description
本發明是關於靈芝液態發酵產物對預防及治療阿茲海默症或阿茲海默症引起的相關病症的功效。
依據國際失智症協會(Alzheimer's Disease International;ADI)2019年全球失智症報告,估計全球有超過5千萬名失智者,到2050年預計將成長至1億5千2百萬人,每三秒就有一人罹患失智症;目前失智症相關成本為每年一兆美元,且至2030年預計將增加一倍。由於阿茲海默症(Alzheimer's disease;AD)相關的醫療及社會成本相當高,且會影響患者家人的生活品質,因此預防阿茲罕默症是近年相當重視的議題。
阿茲海默症是一種不可逆、進行性,造成腦神經細胞死亡的神經退化性疾病,症狀來自於腦部控制思考,記憶及語言區域的神經元,產生退化性的影響,進而造成語言能力及空間記憶辨識能力的喪失。
病理學上顯示出腦組織萎縮、皮質出現老年斑(Senile plaques)和神經纖維糾結(Neurofibrillary tangles)等現象,有關阿茲海默症的病理機制尚未明確,然而目前研究指出β型澱粉樣蛋白(β-amyloid peptide;Aβ)的形成與前驅物(Amyloid precursor protein;APP),經過蛋白水解過程參與酵素β-分泌酶(BACE1)和γ-分泌酶(γ-secretase)有關(參照非專利文獻 1、2)。
App
NL -G-F/NL-G-F Mice為近年較新的AD 基因型小鼠,於2014年後陸續有研究發表相關研究(參照非專利文獻 3),App
NL -G-F/NL-G-F Mice為Swedish、Iberian及Arctic突變基因,Swedish突變基因會增加Aβ的累積、Iberian突變基因會增加Aβ42/Aβ40的比率、Arctic突變基因則促進寡聚化(Oligomerization)及減少蛋白質水解以促進Aβ的累積。
如何找出治療阿茲海默症的保健食品、藥物或中草藥為本發明欲解決之課題。
靈芝(
Ganoderma lucidum)主要為中國傳統上使用的中藥,在靈芝的相關研究中指出靈芝具有多重功效,包括提升免疫力、改善心血管疾病、減少肝臟中的毒素、抗腫瘤、改善認知障礙等作用(參照非專利文獻 4、5、6、7、8、9)。
利用深層液態發酵技術所得之靈芝液態發酵產物相較於傳統中藥的靈芝子實體,在部位、型態、化學活性成分與藥理作用均不相同。目前以靈芝改善或預防阿茲海默症的相關研究中,尚未有利用不含有靈芝菌絲體的靈芝液態發酵產物用於改善或預防阿茲海默症。
Rahman 等人管餵大鼠靈芝子實體的熱水萃取物(200 mg/kg bw)持續8周,可改善AD大鼠的記憶力及學習能力,但未證實可以改善腦組織中Aβ及GFAP(glial fibrillary acidic protein)表現量(參照非專利文獻 10)。Yu等人管餵小鼠靈芝三萜類(低劑量0.35 g/ kg、高劑量1.4 g/ kg)持續60天,行為實驗中可改善AD小鼠的記憶,且可以減緩神經細胞的凋亡以及氧化傷害,但未證實可以改善腦組織中Aβ及GFAP表現量(參照非專利文獻 11)。Lai 等人管餵小鼠靈芝子實體的石油醚與乙醇萃取物(100 mg/kg/d)持續6個月,可減少AD小鼠腦中Aβ及Tau蛋白的累積,但未證實可以改善腦組織中GFAP表現量(參照非專利文獻 12)。Huang等人管餵小鼠靈芝水萃物(WGL,200 mg/kg)及其中的靈芝多醣類(GLP,30 mg/kg) 持續90天,可減少AD小鼠腦中Aβ累積以及促進神經細胞增生,但未證實可以改善腦組織中GFAP表現量(參照非專利文獻 13)。
雖然目前已有利用靈芝子實體或孢子的萃取物改善阿茲海默症,但尚未有以靈芝液態發酵產物運用於改善或預防阿茲海默症及阿茲海默症引起的相關病症的研究。
〔先前技術文獻〕
〔非專利文獻〕
〔非專利文獻 1〕Spies, P. E., Verbeek, M. M., van Groen, T., & Claassen, J. A. (2012). Reviewing reasons for the decreased CSF Abeta42 concentration in Alzheimer disease. Front Biosci (Landmark Ed), 17, 2024-2034.
〔非專利文獻 2〕Zhao, H. B., Lin, S. Q., Liu, J. H., & Lin, Z. B. (2004). Polysaccharide extract isolated from ganoderma lucidum protects rat cerebral cortical neurons from hypoxia/reoxygenation injury. J Pharmacol Sci, 95(2), 294-298.
〔非專利文獻 3〕Saito, T., Matsuba, Y., Mihira, N., Takano, J., Nilsson, P., Itohara, S., Iwata, N., Saido, T.C., (2014). Single App knock-in mouse models of Alzheimer’s disease. Nat. Neurosci. 17(5):661-3.
〔非專利文獻 4〕Gao, Y., Zhou, S., Jiang, W., Huang, M., & Dai, X. (2003). Effects of Ganopoly® (A Ganoderma lucidum Polysaccharide Extract) on the Immune Functions in Advanced‐Stage Cancer Patients. Immunological Investigations, 32(3), 201-215.
〔非專利文獻 5〕Gokce, E. C., Kahveci, R., Atanur, O. M., Gurer, B., Aksoy, N., Gokce, A., Kahveci, O. (2015). Neuroprotective effects of Ganoderma lucidum polysaccharides against traumatic spinal cord injury in rats. Injury, 46(11), 2146-2155.
〔非專利文獻 6〕Jiang, J., Slivova, V., Harvey, K., Valachovicova, T., & Sliva, D. (2004). Ganoderma lucidum suppresses growth of breast cancer cells through the inhibition of Akt/NF-kappaB signaling. Nutr Cancer, 49(2), 209-216.
〔非專利文獻 7〕Kanmatsuse, K., Kajiwara, N., Hayashi, K., Shimogaichi, S., Fukinbara, I., Ishikawa, H., & Tamura, T. (1985). [Studies on Ganoderma lucidum. I. Efficacy against hypertension and side effects]. Yakugaku Zasshi, 105(10), 942-947.
〔非專利文獻 8〕Lin, Z., & Sun, L. (2019). Antitumor Effect of Ganoderma (Lingzhi) Mediated by Immunological Mechanism and Its Clinical Application. Adv Exp Med Biol, 1182, 39-77.
〔非專利文獻 9〕Sun, X. Z., Liao, Y., Li, W., & Guo, L. M. (2017). Neuroprotective effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis. Neural Regen Res, 12(6), 953-958.
〔非專利文獻 10〕Rahman, M. A., Hossain, S., Abdullah, N., & Aminudin, N. (2020). Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), Ameliorates Nonspatial Learning and Memory Deficits in Rats with Hypercholesterolemia and Alzheimer's Disease. Int J Med Mushrooms, 22(11), 1067-1078.
〔非專利文獻 11〕Yu, N., Huang, Y., Jiang, Y., Zou, L., Liu, X., Liu, S., Zhu, Y. (2020). Ganoderma lucidum Triterpenoids (GLTs) Reduce Neuronal Apoptosis via Inhibition of ROCK Signal Pathway in APP/PS1 Transgenic Alzheimer's Disease Mice. Oxid Med Cell Longev, 2020, 9894037.
〔非專利文獻 12〕Lai, G., Guo, Y., Chen, D., Tang, X., Shuai, O., Yong, T., Wu, Q. (2019). Alcohol Extracts From Ganoderma lucidum Delay the Progress of Alzheimer's Disease by Regulating DNA Methylation in Rodents. Front Pharmacol, 10, 272.
〔非專利文獻 13〕Huang, S., Mao, J., Ding, K., Zhou, Y., Zeng, X., Yang, W., Pei, G. (2017). Polysaccharides from Ganoderma lucidum Promote Cognitive Function and Neural Progenitor Proliferation in Mouse Model of Alzheimer's Disease. Stem Cell Reports, 8(1), 84-94.
有鑑於先前技術之不足,本案發明人希望提供一種可以改善及預防阿茲海默症的保健食品,並為將來發展改善、治療及預防失智症提供一重要研發方向,即成為本發明在此欲解決的重要課題。
本發明之目的為提供一種靈芝液態發酵液用於製備預防、改善或治療阿茲海默症或阿茲海默症引起的相關病症的組合物之用途,其中該靈芝液態發酵液的製備方法,包括:將該靈芝菌種在液態培養基中培養,得到一種靈芝液態發酵產物,將該靈芝液態發酵產物固液分離,移除菌絲體,得到該靈芝液態發酵液。
為達前述發明目的,其中該靈芝菌種的寄存編號為BCRC930215。
為達前述發明目的,其中該阿茲海默症引起的相關病症是阿茲海默症引起的記憶損傷。
為達前述發明目的,其中該阿茲海默症引起的相關病症是阿茲海默症引起的焦慮狀態改變。
為達前述發明目的,其中該預防、改善或治療阿茲海默症是降低腦中GFAP活化。
為達前述發明目的,其中該預防、改善或治療阿茲海默症是降低β型澱粉樣蛋白累積。
為達前述發明目的,其中該預防、改善或治療阿茲海默症是降低腦組織中氧化傷害的發生。
為達前述發明目的,其中該靈芝液態發酵液可以經由凍乾,得到一種靈芝液態發酵液凍乾粉。
為達前述發明目的,其中該靈芝液態發酵液或該靈芝液態發酵液凍乾粉的人體有效劑量為每公斤體重服用8至200毫克。
為達前述發明目的,其中該靈芝液態發酵液或該靈芝液態發酵液凍乾粉的人體最佳劑量為每公斤體重服用15至100毫克。
綜上所述,靈芝液態發酵液可以改善記憶損傷及焦慮狀態改變、降低腦中GFAP活化與β型澱粉樣蛋白累積、降低腦組織中氧化傷害的發生,可以有效預防及改善阿茲海默症及阿茲海默症引起的相關病症。
本發明之新穎技術特徵,包含特定特徵,係揭示於申請專利範圍,針對本發明之技術特徵,較佳之理解茲配合說明書、依據本發明原理之實施例、和圖式將本發明較佳之實施例詳細說明。
本說明書中所述之所有技術性及科學術語,除非另外有所定義,皆為該所屬領域具通常知識者可共同瞭解的意義;本發明所使用之材料,除有特別指明者,皆為市售易於取得之材料。
本說明書用語「有效量(Effective amount)」或「治療(Therapeutically)有效量」,係指涉化合物或藥物之一足夠量,可於服用者服藥後減輕一或多項疾病症狀或生理狀況;其結果為降低和/或緩和徵象(Sign)、症狀(Symptom)、或病因,或為其他生理系統之有意圖之改變。舉例而言,治療之「有效量」係包含一本發明提供化合物之可於臨床上顯著降低疾病症狀之劑量。一適當之有效量,其有效值取決於通常藥學技術,如藥物增量方法(Dose escalation methods)。
本說明書用語「提高」、「提升」、「增強」或近似用語,係指涉增加或延長藥物之意圖之效力或持續期間。因此,提升治療藥物之療效,其中「提升」係指涉其餘治療系統中增加或延長之能力,該能力係藥效或持續期間。本說明書用語「提高有效量」係指涉一用以增加另一於治療系統中之治療藥物效果之適當量。
本說明書用語「治療」、「治療中」、「療法」,係包含以治療或預防之方式緩和、減輕、或改善至少一項疾病症狀或生理狀況、預防新增之症狀、抑制疾病或生理狀況、阻止或減緩疾病發展、造成疾病或生理狀況之復原、減緩因疾病造成的生理狀況、停止疾病症狀或生理狀況。
本發明提供一種包含靈芝液態發酵液的組合物,該靈芝液態發酵液係將靈芝菌種進行液態發酵培養,發酵培養的產物固液分離,移除子實體,保留發酵液而得,其中,該組合物係為醫藥組合物、膳食增補劑組合物、食品組合物或保健食品組合物。
實施例 1
靈芝液態發酵液之製備
如圖1所示靈芝液態發酵液之製備流程如下,S01:靈芝菌種在液態培養基中培養,得到靈芝液態發酵產物;S02:固液分離,移除菌絲體,得到靈芝液態發酵液;S03:將靈芝液態發酵液凍乾,得到靈芝發酵液凍乾粉,以方便使用及延長保存期限。
於一較佳實施例中,靈芝液態發酵液之製備流程如圖2所示,取一定量之靈芝菌種(
Ganoderma lucidum,GANO99),以寄存編號BCRC 930215被寄存於台灣的食品工業發展研究所的生物資源保存及研究中心,並以寄存編號DSM 33211被寄存於德國微生物以及細胞培養物收集中心有限公司(Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH),先接種於固態培養基以平板培養,接種液態培養基進行菌種培養,再以發酵槽於攪拌、通氣之條件下培養3~15天,得到靈芝液態發酵產物,其中液態培養基含有綜合性碳源1~10%、綜合性氮源0.1~2%、無機鹽類0.01~0.3%、微量礦物質0.01~0.3%、並經過滅菌,靈芝液態發酵產物包含靈芝菌絲體及靈芝液態發酵液。液態發酵產物進行固液分離,固液分離程序係以3-15%矽藻土加入發酵產物中,經壓榨過濾得到液狀的靈芝發酵液;其中綜合性碳源包括但不限於葡萄糖、蔗糖、果糖、麥芽糖、麥芽糊精、澱粉等;其中綜合性氮源包括但不限於酪蛋白、乳清蛋白、奶粉,植物性蛋白、酵母及大豆蛋白;其中固液分離程序包括但不限於加入矽藻土壓榨過濾、離心等。
AD動物模式
本案AD實驗動物為C57BL/B6-App
NL-G-F/NL-G-F 小鼠。小鼠飼養在恒溫(21℃-22℃)房間,每隔12小時光暗迴圈調節。實驗的時段為9: 00-13: 00,非實驗期間小鼠自由進食鼠糧及飲水。
動物實驗設計
實驗組別:年齡5個月小鼠於馴養後,隨機分成4組:
(1) WT組:Wild type小鼠 (N=9),給予正常飲用水,作為正常對照組。
(2) AD組:C57BL/B6-App
NL-G-F/NL-G-F 小鼠 (N=6),給予正常飲用水。
(3) GL1_L組:C57BL/B6-App
NL-G-F/NL-G-F 小鼠 (N=8),餵食低劑量靈芝(1X; 205 mg/kg靈芝發酵液凍乾粉)。
(4) GL1_H組:C57BL/B6-App
NL-G-F/NL-G-F 小鼠 (N=9),餵食高劑量靈芝(5X; 1025 mg/kg靈芝發酵液凍乾粉)。
小鼠於年齡達5個月時開始管餵靈芝(
Ganoderma lucidum,GANO99)樣品,將靈芝發酵液凍乾粉與正常飲用水混和,每週管餵5天,每天管餵1次,持續餵至小鼠年齡達9個月後犧牲。動物行為實驗於犧牲前一個月進行,期間仍持續管餵樣品至小鼠年齡9個月時犧牲。將小鼠以安樂死方式犧牲,收集腦組織、心臟採血及收集糞便樣本,樣本進行組織病理學分析。
依據美國食品藥物管理局在2005年提出的「Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers」規範,人體與小鼠之換算系數為12.3倍,故本次實驗依照小鼠每公斤體重給予205 mg(低劑量)、1025 mg(高劑量)之靈芝發酵液凍乾粉,經係數換算後人體使用量為每公斤體重給予16.6 mg、83.3mg之靈芝發酵液凍乾粉。
實驗指標
記憶損傷:以動物行為實驗水迷津實驗(Morris water maze test;MWM)、Y 型迷宮(Y maze)評估AD小鼠記憶損傷狀況。MWM實驗是將小鼠游泳的水池中分為四個象限: TQ=目標象限;OQ=目標象限對面的象限;LQ=目標象限左邊的象限; RQ=目標象限右邊的象限,觀察小鼠在TQ象限游泳的時間和距離,時間和距離越長表示記憶力愈好。Y maze實驗是在Novel zone中放食物,讓小鼠在Novel zone探索,之後再將食物移開,讓小鼠在Y maze中自由探索,若小鼠在Novel zone待得時間長表示記憶力較好。
焦慮狀態:以動物行為實驗十字迷宮(Elevated plus maze test;EPMT)評估AD小鼠焦慮狀態。十字迷宮由開放臂(open arm)和封閉臂(close arm)各兩條組成,呈十字形交叉,交叉部分為中央區域,整個十字形迷宮距地面有一定的高度,小鼠面對開放臂產生好奇心而想要探索,同時又有著趨暗避明的天性,兩者之間發生探究與回避的衝突行為,產生焦慮心理。可以通過比較小鼠在開放臂和封閉臂內的滯留時間和路程來評估小鼠的焦慮行為。一般認為,小鼠在開放臂中滯留的時間和路程越多,小鼠的焦慮水準越低。
腦組織病理學:進行免疫組織化學染色,腦組織之病理切片根據染色呈度、分佈範圍及佔組織的百分比。
統計方法
本實驗結果以平均值±標準差(Mean±SD)方式表示。利用SPSS軟體進行統計分析,以One-way ANOVA進行檢定,再利用Duncan’s Multiple Range test檢定各組樣本間之組間差異。當p-value<0.05時,代表具有顯著差異,結果呈現中使用不同英文字母(a、b 或 c)標記。
實施例 1
靈芝液態發酵液改善記憶損傷
圖3A、圖3B是MWM實驗的Probe test結果,觀察靈芝液態發酵產物對AD造成之記憶損傷的影響,結果顯示,AD組在目標象限(TQ)的時間和距離顯著低於WT組;然而靈芝高、低劑量組在TQ的時間及距離有顯著高於AD組的現象,且與WT組未達顯著差異。顯示補充靈芝高、低劑量對AD小鼠記憶損傷有顯著改善的效果,MWM實驗結果證實靈芝液態發酵產物可以使AD小鼠的記憶損傷回復至接近正常。
圖4是Y maze結果,觀察靈芝液態發酵產物對AD造成之記憶損傷的影響,結果顯示,AD組待在Novel arm的時間顯著低於WT組,而靈芝高、低劑量組均有顯著高於AD組的現象。顯示補充靈芝高、低劑量對AD小鼠記憶損傷有顯著改善的效果,Y maze結果也證實靈芝液態發酵產物可以使AD小鼠的記憶損傷回復至正常。
實施例 2
靈芝液態發酵液改善焦慮狀態
圖5是EPMT結果,觀察靈芝液態發酵產物對AD造成之焦慮狀態的影響,結果顯示,AD組相較於WT組待在close arm的時間顯著性較短;而待在open arm的時間顯著性較長,而靈芝高、低劑量組待在close arm的時間顯著高於AD組的現象;然而待在open arm的時間,靈芝高、低劑量組均顯著低於AD組的現象,顯示AD小鼠焦慮狀態較不顯著,而靈芝高、低劑量組的焦慮狀態均與WT鼠相似,EPMT結果顯示靈芝液態發酵產物可以使AD小鼠的焦慮狀態回復至正常。
實施例 3
靈芝液態發酵液降低腦中GFAP活化與Aβ累積
GFAP是一種通常在大腦中發現的蛋白質,GFAP過度活化被認為與阿茲海默症相關。圖6為AD 小鼠腦檢體之GFAP免疫組織化學染色結果,結果定量如圖7A(海馬迴)、圖7B(皮質層)所示,結果顯示,AD組海馬迴和皮質層的GFAP表現量顯著高於WT組;長期補充高或低劑量靈芝對AD鼠可以減少GFAP的活化,顯示長期補充靈芝對AD鼠腦中GFAP的活化有抑制的效果,其中以高劑量組於皮質層的效果較佳。
圖8為AD 小鼠腦檢體之Aβ免疫組織化學染色結果,結果定量如圖9A(海馬迴)、圖9B(皮質層)所示,結果顯示,AD組海馬迴和皮質層的Aβ表現量顯著高於WT組,顯示長期補充靈芝對AD鼠的Aβ累積有抑制的效果,長期補充高或低劑量靈芝對AD鼠可以減少GFAP的活化而造成Aβ的累積,其中以高劑量組於皮質層的效果較佳。
實施例 4
靈芝液態發酵液降低腦組織中氧化傷害的發生
圖10為AD 小鼠腦檢體之SOD免疫組織化學染色結果,結果定量如圖11A(海馬迴)、圖11B(皮質層)所示,結果顯示,海馬迴及皮質層中的SOD表現量中,以AD組在SOD表現量顯著低於WT組;靈芝低劑量組海馬迴中的SOD表現量顯著高於AD組,而靈芝高劑量組有高於AD組的趨勢;皮質層的SOD表現量,靈芝高、低劑量組均顯著高於AD組,顯示靈芝的抗氧化效果在皮質層較為顯著。
綜上所述,本發明是第一個以不含菌絲體的靈芝液態發酵液用於治療阿茲海默症,靈芝液態發酵液可以改善記憶損傷及焦慮狀態改變、降低腦中GFAP活化與Aβ累積、降低腦組織中氧化傷害的發生,可以有效預防及改善阿茲海默症。
上列詳細說明係針對本發明之可行實施例之具體說明,惟該實施例並非用以限制本發明之專利範圍,凡未脫離本發明技藝精神所為之等效實施或變更,均應包含於本案之專利範圍中。
圖1是靈芝液態發酵液的製備流程。
圖2是靈芝液態發酵流程與試驗樣品製備示意圖。
圖3A是MWM的Probe test中的距離結果,觀察靈芝對AD小鼠記憶損傷的影響。
圖3B是MWM的Probe test中的時間結果,觀察靈芝對AD小鼠記憶損傷的影響。
圖4是Y maze結果,觀察靈芝對AD小鼠記憶損傷的影響。
圖5A是EPMT中在close arm的時間,觀察靈芝對AD小鼠焦慮狀態的影響。
圖5B是EPMT中在open arm的時間,觀察靈芝對AD小鼠焦慮狀態的影響。
圖6是AD小鼠腦組織GFAP免疫組織染色結果。
圖7A是AD小鼠腦組織(海馬迴)GFAP免疫組織染色的量化結果。
圖7B是AD小鼠腦組織(皮質層)GFAP免疫組織染色的量化結果。
圖8是AD小鼠腦組織Aβ免疫組織染色結果。
圖9A是AD小鼠腦組織(海馬迴) Aβ免疫組織染色的量化結果。
圖9B是AD小鼠腦組織(皮質層) Aβ免疫組織染色的量化結果。
圖10是AD小鼠腦組織SOD免疫組織染色結果。
圖11A是AD小鼠腦組織(海馬迴)SOD免疫組織染色的量化結果。
圖11B是AD小鼠腦組織(皮質層)SOD免疫組織染色的量化結果。
靈芝(
Ganoderma lucidum)菌株 GANO99係於2019年11月22日寄存於台灣的食品工業發展研究所的生物資源保存及研究中心,寄存編號為BCRC 930215。
靈芝(
Ganoderma lucidum)菌株 GANO99係於2019年7月10日寄存於德國微生物以及細胞培養物收集中心有限公司(Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH),寄存編號為DSM 33211。
Claims (7)
- 一種靈芝液態發酵液用於製備預防、改善或治療阿茲海默症或阿茲海默症引起的相關病症的組合物之用途,其中該靈芝液態發酵液的製備方法,包括:將該靈芝菌種在液態培養基中於攪拌、通氣之條件下培養,得到一種靈芝液態發酵產物,將該靈芝液態發酵產物固液分離,移除菌絲體,得到該靈芝液態發酵液;其中該阿茲海默症是因為促進寡聚化(Oligomerization)及減少蛋白質水解造成β型澱粉樣蛋白的累積;其中該靈芝菌種的寄存編號為BCRC 930215,該靈芝液態發酵液或靈芝液態發酵液凍乾粉的人體有效劑量為每公斤體重服用8至200毫克。
- 如申請專利範圍第1項所述之用途,其中該阿茲海默症引起的相關病症是阿茲海默症引起的記憶損傷。
- 如申請專利範圍第1項所述之用途,其中該阿茲海默症引起的相關病症是阿茲海默症引起的焦慮狀態改變。
- 如申請專利範圍第1項所述之用途,其中該預防、改善或治療阿茲海默症是降低腦中GFAP活化。
- 如申請專利範圍第1項所述之用途,其中該預防、改善或治療阿茲海默症是降低腦組織中氧化傷害的發生。
- 如申請專利範圍第1項所述之用途,其中該靈芝液態發酵液可以經由凍乾,得到一種靈芝液態發酵液凍乾粉。
- 如申請專利範圍第1或6項所述之用途,其中該靈芝液態發酵液或靈芝液態發酵液凍乾粉的人體最佳劑量為每公斤體重服用15至100毫克。
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