TWI386485B - 瓦茸菌株(Tramete Versicolor)及其萃取物,以及其用途 - Google Patents
瓦茸菌株(Tramete Versicolor)及其萃取物,以及其用途 Download PDFInfo
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- Heart & Thoracic Surgery (AREA)
Description
本發明係關於,瓦茸菌株,其萃取物,以及其用途,特別是有關具有優越之血小板凝集抑制作用,化學增活素基因表現抑制作用,抗突變性(antimutagenecity)作用,抗腫瘤作用,抗高血壓作用等生物學活性的瓦茸菌株。
向來蕈類並非僅用於食品亦可用於藥品,已知各種具有藥效的蕈類。其中,瓦茸菌係漢方藥中稱為「雲芝」者,具有抗腫瘤活性。再者,臨床上亦使用由瓦茸菌來源的蛋白多糖體所開發之抗腫瘤劑(一般名:PSK,商品名:Krestin)。
又,近年來,有報告揭示對TGF-β或PDGF的選擇性結合作用(專利文獻1),依據對免疫系統未成熟動物投予而得之癌或感染病症的預防效果(專利文獻2),前驅脂肪細胞分化抑制效果(專利文獻3)等。
然而,對於瓦茸菌的藥效並非完全明瞭,且欲尋求較已知效果更具優越效果的菌株。
(專利文獻1)特開平8-113540號公報(專利文獻2)特開平11-60495號公報(專利文獻3)特開平2004-75640號公報
本發明鑒於上述以往技術的課題,其目的係提供有用的活性非常優越的新穎瓦茸菌及其用途。
為了達到前述目的,本發明人等對市販或野生的瓦茸菌重覆進行深入雜交育種研究的結果,成功獲得對於血小板凝集抑制作用,化學增活素基因表現抑制作用,抗突變性作用,抗腫瘤作用,抗高血壓作用,免疫調節作用等特別優越的瓦茸菌株。此外,本發明人發現將該瓦茸菌與微細藻類或其他擔子菌類等加以組合,則其作用係協同地上升,遂完成本發明。
亦即,本發明之瓦茸菌株係寄存號碼FERM BP-10633之瓦茸菌株。
本發明之血小板凝集抑制劑,化學增活素基因表現抑制劑,抗突變性劑,抗腫瘤劑,抗高血壓劑,或者免疫調節劑係包含上述瓦茸菌及/或其萃取物為有效成分。
再者,上述瓦茸菌及/或其萃取物可配合於飲食品或醫藥組成物等口服用組成物中。
再者,上述瓦茸菌及/或其萃取物可配合於化妝料,醫藥用外用劑等皮膚外用組成物中。
再者,於本發明中,上述瓦茸菌及/或其萃取物可一同再併用一種以上選自微細藻類及其他擔子菌及該等之萃取物所組成之組群者更佳。
本發明特定之瓦茸菌及/或其萃取物具有優越之血小板凝集抑制作用,化學增活素基因表現抑制作用及抗突變性作用,抗腫瘤作用,抗高血壓作用,免疫調節作用。且與微細藻類及其他擔子菌類組合時,其作用係協同地上升。本發明的瓦茸菌安全性高,即使長期連續使用,產生副作用的可能性亦非常的低,而可用於作為以預防/改善發炎,過敏,腫瘤或其他疾病為目的之飲食品,化妝品,醫藥品等。再者,本發明的瓦茸菌與以往之品種相較,其菌絲的成長性或生理機能均非常高,因而能安定的使用。
於本發明使用之瓦茸菌株屬於多孔菌科(Polyporaceae)革蓋菌屬(Coriolus)的雲芝(Trametes versicolor)(L.:Fr.),Pilat,國際寄存於獨立行政法人產業技術總合研究所專利生物寄存中心,於2006年6月28日寄存之寄存號碼FERM BP-10633之瓦茸菌株(商標名:Tanakayosiho株)。此係,自同一中心國內寄存之寄存號碼FERM P-20377(2005年1月26日寄存)移交管理之物品。本發明人之一的江口文陽所寄存。
該瓦茸菌株係由熊本縣天然產生之野生瓦茸菌株,藉由利用原生質體(protoplast)化技術雜交育種而得之新穎瓦茸菌株,與以往之品種或親株比較,係在菌絲的成長或生理機能,血小板凝集抑制作用,化學增活素基因表現抑制作用,抗突變性作用,抗腫瘤作用等方面均具有最高活性者。對於抗高血壓作用,免疫抑制作用亦具有高度活性。有關該菌株的製作方法或篩選方法及效果,於實施例中詳細記載。
本發明的寄存號碼FERM BP-10633的瓦茸菌株的科學性質如以下所示。
1.科學的性質…菌的特徵:於含有碳源及氮源的營養培養基,形成白色菌落。此外,於光學顯微鏡下觀察到扣子體(clamp connection)。
2.分類學上的位置…擔子菌。
3.培養條件(1)培養基名…SMYA培養基(S:蔗糖,M;麥芽萃取物(malto extract),Y:酵母萃取物,A:洋菜)S,A→市販品M,Y→Difco公司製(2)培養基的組成…培養基每1000ml 1% 蔗糖 (相當於10g)1% 麥芽萃取物 (相當於10g)0.4% 酵母萃取物 (相當於4g)2% 洋菜 (相當於20g)(3)培養基的pH…5.0至7.0(最適合pH5.5)(4)培養基的殺菌條件…121℃ 20分(5)培養溫度…28℃(6)培養期間…10天(7)氧氣要求性…好氧性
4.保管條件可以凍結法保存。(1)凍結條件…-80℃(2)保護劑…10至20%甘油水溶液(最適當為20%)(3)凍結後之復原率…1年內100%,3年內99%
5.生存試驗的條件(1)微生物的復原…40℃(2)接種,培養,確認法…與培養條件相同。
於本發明,瓦茸菌株可使用子實體、其子實體的萃取物,或者亦可使用該萃取物的乾燥物,又,子實體可為生鮮者或經乾燥者均可,惟就操作性,保存性,萃取效率等點而言,以使用乾燥子實體為佳。為了有效率地攝取有效量,以使用子實體的乾燥粉末或者其萃取物為適當,特別以利用萃取物為佳。
再者,本發明係適宜地使用子實體,惟亦可期待其菌絲體之效果。菌絲體可利用於含有碳源及氮源的培養基中培養種菌所得之生鮮或乾燥之菌絲體,以乾燥物為簡便。
為得到瓦茸菌萃取物,首先以對瓦茸菌之組織進行破壞處理為宜。藉此而能高效率地進行萃取。破壞瓦茸菌組織之手段,有藉由珠磨器,漩渦摻合器,均勻化器等各種粉碎混合機之粉碎處理;藉由爆碎機等之衝擊破碎處理;凍結處理,超音波處理等物理處理,以氫氧化鈉等之水溶液之鹼處理,以纖維素酶(Cellulase)或果膠酶(Pectinase)等具有細胞壁分解作用的酶處理進行之;浸透壓處理等化學處理;該等可單獨或適當地組合而進行。此等組織破壞處理中,瓦茸菌之子實體作為原料時以粉碎處理或酶處理為宜,菌絲體作為原料時以酶處理為宜。
酶處理可利用習知的細胞壁分解酶或者多糖分解酶,可使用一種或二種以上的纖維素酶,半纖維素酶、殼糖酶,α-及β-葡萄醣醛酸酶(glucuronidase),果膠酶,聚木糖酶(xylanase),α-及β-聚葡萄糖酶等。以酶處理瓦茸菌時,以於施行適當細微斷裂或粉碎處理之瓦茸菌中之加入上述酶的水溶液,並加以震動或者攪拌為宜。
為得到本發明的瓦茸菌萃取物,於如上述將組織經破壞處理之瓦茸菌中,加入萃取溶劑適當攪拌,即可進行萃取處理。
萃取溶劑並無特別限定,例如可列舉水,甲醇,乙醇等一級醇;1,3-丁二醇,丙二醇等多元醇;乙酸乙酯等低級烷酯;苯,己烷等烴類;乙醚,丙酮等;可使用該等兩種以上之組合。適合的萃取溶劑可列舉水,甲醇,乙醇,1,3-丁二醇或該等之混合溶劑。特別以熱水萃取瓦茸菌子實體乾燥粉末者為佳。
再者,萃取操作亦可於常溫常壓下進行,於1至5氣壓,60至150℃的加壓及加熱下進行亦可。具體而言,例如,以熱水等萃取後,以離心分離或減壓過濾使萃取液與殘渣分離為佳。
對萃取後之殘渣以與上述相同之條件進行再萃取處理,亦可重覆進行此萃取操作。
又,萃取物可為萃取液或其乾燥物。若作成乾燥物時,可藉由減壓濃縮,殺菌冷凍乾燥,噴霧乾燥等處理,去除萃取液中之萃取溶劑。
瓦茸菌的菌絲體之延伸係以27℃附近最佳,子實體的生長係以10至12℃的低溫處理為宜。栽培期間係菌絲蔓延係於20至25日之間,接著,子實體生長需要20天左右。以2.5公斤容量之袋栽培可期待約200克之收穫。培養基材之碎屑以大部份的闊葉樹即合適,亦能使用經加水堆積的衫木。
本發明的瓦茸菌株由於血小板凝集抑制作用,化學增活素基因表現抑制作用優越,而可用於血栓形成之預防及改善,血流改善,發炎性或過敏性疾病的預防及改善等。此外,若作為皮膚外用劑經皮的投予,對於發炎性或過敏性皮膚疾病亦能期待預防及改善的效果。
再者,本發明的瓦茸菌株其於抗突變性作用,抗腫瘤作用亦優越。於環境中存在種種突變性物質,咸認此為生物體內傷害DNA,且為癌或其他疾病的原因之一。因此,能抑制突變之活性的本發明的瓦茸菌株可用於此種疾病的預防。再者,亦可用於腫瘤細胞的增殖抑制。
再者,本發明的瓦茸菌株具有抗高血壓作用而可改善高血壓症。
再者,本發明的瓦茸菌株由於具有免疫調節作用,而可望調整生物體內免疫系統的平衡而能預防疾病及維持身體健康。
口服攝取本發明的瓦茸菌株時,係依據各別狀態而不同,並無特別限定,瓦茸菌萃取物(乾燥質量),可為成人(60kg體重),每天0.001至1克,且可為0.01至0.5克。
此外,已明瞭藉由於本發明之瓦茸菌及/或其萃取物中併用選自微細藻類及其他擔子菌類及其萃取物之至少一種,則其活性為協同性的向上。
微細藻類可適合地使用綠藻類,特別更適合使用蛋白核小球藻(chlorella pyrenoidosa),但非限定於此。
再者,可適合地使用選自其他擔子菌,如姬松茸(巴西蘑菇)(Agaricus blazei),桑黃(phllinus linteus),香菇(lentinus edodes)及冬蟲夏草(Cordyces sinesis)之至少一種。
有關此種微細藻類或擔子菌類之萃取方法,可依據前期瓦茸菌的萃取法或者其他習知方法進行。
已有關於上述微細藻類或擔子菌類具有抗腫瘤活性的報告,惟藉由與本發明的瓦茸菌併用,比該等單獨使用時,其活性為協同的提昇。又,確認於血小板凝集抑制作用,化學增活素基因表現抑制作用,抗突變性作用均有協同提昇之效果。
兩者的混合比例並無特別限定,瓦茸菌及/或其萃取物,與微細藻類,其他擔子菌及該等之萃取物的合計量之比率係以質量比1:1至25:1之範圍為宜,5:3至15:1的範圍更佳。
使用本發明的瓦茸菌或其萃取物調製口服用組成物時,依常用法可作成散劑,錠劑,膠囊劑,顆粒劑,茶劑,懸浮化劑,流體萃取劑,液劑,糖漿劑等。又,製劑化時,視需要可使用通常的製劑化載體,例如,賦形劑,結合劑,崩解劑,滑澤劑,著色劑,矯味矯臭劑,賦香劑等。再者,視需要亦可以適合之被覆劑等施予膜衣(劑皮)。
又,該等並不限於醫藥用途,亦可做為機能性食物,健康食品,輔助營養劑等使用。該等例如可以果凍,糖果,軟糖(gummi),餅乾,果汁,以及其他種種不同形態攝取。
此外,作為皮膚外用劑使用時,亦可於通常習知的皮膚外用劑基劑中配合瓦茸菌萃取物。本發明的皮膚外用劑係除上述必需成分之外,適需要亦可適當配合通常於化粧品或醫藥品等皮膚外用劑所使用之成分,例如,美白劑,保濕劑,抗氧化劑,防腐劑,油性成分,紫外線吸收劑,界面活性劑,增黏劑,醇類,粉末成分,色材,香料,水性成分,水,高分子化合物,螯合劑,pH調整劑,維他命類,胺基酸,各種皮膚營養劑.藥劑等。
皮膚外用劑可使用作為醫藥品,醫藥部外用品,化粧品,其劑型為軟膏,乳膏,乳液,化粧水,美容敷料,浴用劑,片狀製劑,泡沫劑、噴劑,條劑等以往皮膚外用劑所用者均可,並無特別限定。
此等口服用組成物中或皮膚外用組成物中的瓦茸菌添加量(係視目的或用途等即可適當地決定,通常瓦茸菌萃取物(乾燥質量)為組成物之0.0001質量%以上。較佳係0.001至20質量%,以0.01至10質量%更佳。
以下,以具體例說明本發明,惟本發明並不為其所限定。
本發明的瓦茸菌株FERMBP-10633係如下述,以利用原生質體(protoplast)化技術之雜交育種法而得之試驗菌株中,於生理生化學試驗及藥理活性試驗中,與以往品種或親株比較,選擇採用最優越之菌株(試驗株1)者。
使用下述源自孢子之單核菌絲之親株A1,及源自原生質體之單核菌絲之親株B1,將依據菇類的一般雜交育種法而得之二核化菌絲體以顯微鏡觀察,係獲得複數的試驗株。
(1)源自孢子之單核菌絲(親株A1)的調製由產自日本熊本縣菊池市之野生瓦茸菌子實體A,無菌地採取孢子(一核),以多層洋菜培養基進行培養。培養再生之單核菌絲的菌落,作為雜交用菌絲(親株A1)。培養條件係26±2℃,以相對濕度80%以上進行。
(2)源自原生質體的單核菌絲(親株B1)的調製由產自熊本縣菊池市之野生瓦茸菌子實體B,無菌地分離二核菌絲體。
此菌絲體以SMY洋菜培養基(含有1%蔗糖,1%麥芽萃取物,0.4%酵母萃取物,2%洋菜),培養7天,將得到的菌絲體以內徑5mm的鑽孔器(cork borer)打穿。將該菌株接種於裝有SMY液體培養基(含有1%蔗糖,1%麥芽萃取物,0.4%酵母萃取物)40mL之100mL容量三角燒瓶中。靜置培養7天後,以磁性攪拌器及攪拌子磨碎菌絲體,調製菌絲體懸浮液。
將此懸浮液2 mL接種於另外之SMY液體培養基中,3天內每天進行繼代培養,而得原生質體調製用菌絲體。此外,培養條件係26±2℃,於相對濕度80%以上進行。
以尼龍篩網(孔徑10×10 μ m)過濾原生質體調製用菌絲體,收集菌體。將所得之菌絲體200mg(生重量)加至溶解有(2%Novzyme-234(Novo Industry A/S),0.5%Zymolyase-20T(生化學工業公司),0.2%幾丁質酶(Sigma Chemical Co.,)及0.5mol/L甘露糖醇之0.05mol/L順丁烯二酸緩衝溶液(pH6.0)2mL中,以震幅40mm,震動次數70/min,震動溫度28℃下,震動1小時,進行酶處理(原生質體化處理)。
以自動過濾器(MIRACULOUS)(Calbiochem Corporation製)過濾此處理液,以1100g×10分鐘離心分離該過濾液。使用0.05mol/L順丁烯二酸緩衝溶液(pH6.0,含有滲透壓調節劑),將所得之沉澱物(原生質體),重覆離心分離之操作3次以清洗之獲得純化的原生質體。
此純化的原生質體以多層洋菜培養基進行培養,由再生之菌落篩選單核菌絲,作為雜交用菌株(親株B1).
對於為安定地利用菌株,重要的是菌株需要有高度的成長性及生理機能。於此首先,進行以菌絲成長及以漆酶(laccase)活性作為指標的篩選。試驗方法,如下述。
(1)於固體培養基的菌絲成長菌絲體分別以SMY洋菜培養基培養7天,所得之菌絲體以內徑5mm之鑽孔器打穿。將此菌絲體接種於裝有新的SMY洋菜培養基25mL之內徑90mm的培養皿上,以培養溫度26±2℃,相對濕度80%以上,進行8天培養後,以肉眼測定菌絲體成長量(mm)及菌絲密度(n=10)。菌絲密度係以[高:++++][普通:+++][低:++][非常低:+]評估之。
(2)於液體培養基的菌絲成長將菌絲體分別以SMY洋菜培養基培養7天,所得之菌絲體以內徑5mm之鑽孔器打穿。接種於裝有SMY液體培養基40mL的100mL容量的三角燒瓶中。以培養溫度26±2℃,相對濕度80%以上,進行21天靜置培養後,以預先計量至恆重的濾紙過濾收集菌絲體。於乾燥機內乾燥後,計量含有菌絲體的濾紙的恆重,依減法算出菌絲體增殖量(mg)(n=10)。
(3)漆酶活性將菌絲體接種於含有1mM藜蘆酸(veratric acid)之SMY液體培養基,於培養溫度26±2℃,相對濕度80%以上,培養13天。使用分光光度計依常法測定(參照木材學會誌,40(1),107-110頁(1994年)等)。
(4)結果試驗結果示於表1。
親株A1及親株B1係如上述操作所得之單核菌絲。
親株A2及親株B2係二核菌絲,分別於製作出親株A1及親株B1之前,將由瓦茸菌子實體A及瓦茸菌子實體B分離之原種菌進行繼代培養而得者。
瓦茸菌I,瓦茸菌II係分別由日本群馬縣高崎市,東京奧多摩町採取之野生瓦茸菌所得之分離株(二核菌絲)。
試驗之結果,於所得之多數試驗株(僅試驗株1至4示於表1)中,特別是試驗株1具有高度菌絲成長性及生理的機能,與親株及以往品種比較亦非常優越。
再者,進行血小板凝集試驗,化學增活素基因表現抑制試驗,抗突變性試驗。
(1)瓦茸菌熱水萃取之萃取物粉末的調製瓦茸菌乾燥子實體微粉末40g與750mL蒸餾水混合,90℃攪拌1至2小時進行萃取。其後,離心分離(3000rpm,15分鐘),回收之上清液以蒸餾器濃縮(約10倍)。-80℃下,凍結該濃縮液,凍結乾燥而回收瓦茸菌熱水萃取之萃取物粉末3.5g,以此作為樣品供試驗。
試驗株1至4之外,對親株的瓦茸菌子實體A及瓦茸菌子實體B,及瓦茸菌I(群馬縣高崎市產),瓦茸菌II(東京奧多摩町產)之子實體以相同的處理調製熱水萃取之萃取物粉末,供試驗。
(2)血小板凝集抑制試驗人類血液於室溫以1100rpm離心20分鐘,製備富含血小板血漿(PRP(platet-rich plasma)後,進一步以3000rpm離心5分鐘,製備缺血小板血漿(PPP,platetet-poor plasma)。將PRP 223 μ l於37℃預備加溫後,分別添加瓦茸菌熱水萃取之萃取物粉末(溶解於DMSO成為濃度2%者)2 μ l或DMSO 2 μ l作為對照,進一步,於37℃培養3分鐘後,加入25 μ l的凝集誘發物質二十碳四烯酸鈉水溶液(500nM)。
產生的凝集係使用凝集計(MCM血球示蹤器,MCM醫學公司製)測定。受驗樣品的最大凝集率(以PPP之值為100,由受驗樣品的凝集曲線求得之最大值)與控制組的最大凝集率相比較,以評估對受驗樣品二十碳四烯酸鈉水溶液所引起的血小板凝集的抑制作用。
(3)化學增活素基因表現抑制試驗人類皮膚纖維芽細胞於直徑6cm的培養皿中,以含有10%牛胎兒血清的DMEM培養基(Dulbecco’s Modified Eagle Medium)培養至群集狀態,作為受驗培養基供試驗。
於受驗培養基中添加瓦茸菌熱水萃取之萃取物粉末(溶解於適量DMSO者),DMSO(陰性對照),氫皮質酮(陽性對照)。瓦茸菌熱水萃取之萃取物粉末及DMSO的最終濃度係分別為0.01%(乾燥質量),氫皮質酮的最終濃度係10- 7
M。
再者,添加已知會促進化學增活素基因表現之腫瘤壞死因子TNF-α(1ng/ml),於37℃培養6小時。
接著,以一般方法,由細胞分離RNA,合成CDNA後,以定量的PCR法(TaqMan PCR法),測定IL-8基因的表現量。又,使用作為內部標準基因的GAPDH(甘油醛3磷酸脫氫酶)基因,修正所得的數據。
再者,人類皮膚纖維芽細胞可由市販得到。例如,由倉敷紡績公司購得。此外,人類纖維芽細胞的培養可依培養動物細胞用的一般方法進行,惟以含有10%牛胎兒血清之DMEM培養基特佳。
(4)抗突變性試驗於試驗管中加入突變劑(含有0.2M之2-胺基-3-甲基咪唑(4,5-f)喹喏啉的DMSO溶液)0.1mL及瓦茸菌熱水萃取之萃取物粉末(以DMSO溶解成為0.25至1%濃度者,於下述圖表中係1%)1.9mL並加以混合,37℃下靜置6小時。
其後,於此試管中添加沙門氏菌(Salmonella)TA98株液(His+回復突變,以DMSO溶解成為5至7%濃度者,於下述圖表中係7%)0.1mL,S9mix0.5mL,及軟洋菜2mL並加以混合。
將該混合液0.05mL接種於最少葡萄糖洋菜培養基,37℃下培養48小時。計算增殖的組胺酸非要求性菌落數,依下式算出抗突變性(%)。抗突變性(%)=[(NC-NB)-(NS-NB)]/(NC-NB)X100NS:加入樣品液時的菌落數NC:取代樣品液而添加DMSO時的菌落數(控制組)NB:取代樣品液及突變劑而添加DMSO的菌落數(空白組)
(5)結果結果如第1圖所示。由第1圖得知,試驗株1對血小板凝集抑制作用,化學增活素(IL-8)基因表現量之抑制作用,抗突變性作用之任一者均具有非常高的活性,比起以往品種,其他試驗株或親株均非常優越。
已知種種發炎性,過敏性皮膚疾病或肌膚乾裂之發病,與二十碳四烯酸或其代謝物白三烯,凝血脂素(thromboxane,亦稱為血栓素),前列腺素有關聯。例如,以發炎性異常角化性疾病之乾癬,於其患部表皮確認有高濃度之二十碳四烯酸代謝物的存在,於過敏性皮膚疾病之異位性皮膚炎或接觸性皮膚炎,濕疹亦顯示與二十碳四烯酸代謝物有關聯。此外,由於前列腺素類或凝血脂素類具有使血小板凝集的作用,因而咸認抑制由二十碳四烯酸合成前列腺素類或凝血脂素類的化合物具有抗血栓效果,亦即,血流改善效果再者,近年來已知對於種種發炎性,過敏性皮膚疾病的發病,支配炎症性細胞的游走及活性化之化學增活素(Chemotactic Cytokine,Chemokine)有很強的關聯性。化學增活素係分子量8至10kDa之具有肝素結合性的鹼性蛋白之總稱,咸認於活體中,作用於與發炎相關的種種細胞的發炎部位游走;活性化的中心,對於發炎的引發扮演重要的角色。
於皮膚疾病中咸認,接觸性皮膚炎、異位性皮膚炎等發炎部位中嗜中球,嗜酸球等之發炎細胞游走.活性化而與發炎的發生.增幅有關。因此,此種情況,已知由皮膚的角化細胞,纖維芽細胞等細胞產生介白素-8(IL-8,interleukin-8)等化學增活素。再者,已知發炎性異常角化性疾病之乾癬係於其皮膚患部有大量IL-8存在。
因此,抑制IL-8等化學增活素的表現,咸認對於此種發炎性或過敏性疾病症狀的改善及預防有效。
此外,環境中,有種種突變性物質存在,此於活體內傷害DNA,咸認成為癌或其他疾病的原因之一。所以,能夠抑制突變原的活性之抗突變性物質可用於預防此種疾病。
為調查於以上試驗中,成長性,生理的機能性以及活性最優越的試驗株1的安全性,而進行急性毒性試驗,亞急性毒性試驗。
(1)試驗方法(a)急性毒性遵循OECD化學毒性試驗指南(1987年),以小鼠進行急性口服毒性試驗(n=10)。樣品係使用上述瓦茸菌熱水萃取之萃取物粉末。投予量係200,400,600,800以及2000mg/kg.單次投藥。投藥後,至24天進行個體觀察。
(b)亞急性毒性遵循OECD化學毒性試驗指南(1987年),以小鼠進行亞急性毒性試驗(口服投藥)(n=10)。樣品係使用上述瓦茸菌熱水萃取之萃取物粉末。投予量係以200,400,600,800以及2000mg/kg.每日進行一次投藥。每日投藥共28天。
(2)結果(a)急性毒性試驗株1係於急性毒性試驗中,即使為2000mg/kg之口服投予量,亦未見到死亡個體及臟器.血液之變性,確認其安全性非常高。
例如,已知作為化學增活素表現抑制劑之氫皮質酮具有強烈的作用。上述化學增活素表現抑制試驗中,氫皮質酮基因表現量為0.13時即顯示高度抑制作用。但是,類固醇賀爾蒙長期使用時,會引起發炎,組織障礙,潰瘍形成等副作用。對於此,試驗株1之抑制效果雖不及氫皮質酮的程度,但無副作用的疑慮,因安全性高而可長期連續使用。
再者,對試驗株1,分別以親株A,親株B,及以往品種進行對歭培養培養。此試驗係觀察對歭之兩菌種(菌落)之接觸面是否形成帶線(zone line),而能簡便地判定兩者的相同性。試驗如以下進行。
將通過口徑0.8mm(20mesh)篩孔的山毛櫸科(Fagus crenata Blume)的木粉與米糠以5:1(質量比)之比例混合,加水至含水率成為75%。塞入長250mm,口徑30mm的玻璃管的中央,以120℃,1.2氣壓的條件,高壓高溫滅菌30分鐘。由此木粉培養基的兩端各別接種菌株,以溫度26℃,相對濕度75%以上的條件培養。以肉眼觀察帶線形成之有無。
此結果,試驗株1對於任一親株及以往品種均形成帶線,因此,咸認與此等之相同性低,而視為相異之品種。
由以上之結果,本發明者選擇此試驗株1,國內寄存於獨立行政法人產業技術綜合研究所專利生物寄存中心(寄存號碼FERMP-20377),更進一步,將其移管於國際寄存(寄存號碼FERMBP-10633),作為本發明採用之瓦茸菌。
第2圖係以含水乙醇作為萃取溶劑,萃取溫度係室溫(25℃),其餘均與上述相同的方法調製瓦茸菌萃取粉末,並進行藥理活性試驗的結果。由第2圖得知,熱水萃取時,活性為最高,以含水乙醇萃取亦可確認其活性。此外,以萃取粉末回收率的觀點而言,確認以熱水萃取有較佳之傾向。
再者,關於瓦茸菌株FERM BP-10633之抗腫瘤作用,使用肉腫瘤(sarcoma)180培養細胞進行試驗。
(1)受驗培養基的調配以MEM α液體培養基87%(不含麩醯胺,重層含:INC Biomedicals Inc.),10%牛胎兒血清(以56℃不活化處理30至60分鐘:GIBCO),2%的200mM麩醯胺液(29.23mg/mL:INC Biomedicals Inc.),1%的青黴素.鏈黴素(10,000單位/mL:GIBCO)的比例添加並混合作為受驗培養基使用。
(2)樣品液的調製以PBS將瓦茸菌(FERM BP-10633)熱水萃取粉末稀釋1000倍,以於高壓高溫下經滅菌處理之溶液作為樣品液使用。控制組係使用僅以PBS同樣滅菌處理之溶液。
(3)試驗方法將受驗培養基各180 μ L,分別注入96孔盤,再添加肉腫瘤180癌細胞株10 μ L,及樣品液10 μ L。肉腫瘤180癌細胞數為5×103
細胞/孔(200 μ L)。以37℃,5%CO2
靜置48小時後,計算細胞數。
(4)結果結果如表2所示。樣品液對於肉腫瘤180癌細胞發揮顯著的增殖抑制效果。因此,咸認本發明之瓦茸菌FERM BP-10633具有抗腫瘤作用。
此外,測試瓦茸菌FERM BP-10633於活體內對於肉腫瘤180癌細胞之增殖抑制效果。
(1)試驗方法以BALB/c-nu/nu(無毛小鼠)4週齡的小鼠24隻為供試驗動物。由5週齡開始,移植肉腫瘤180癌細胞1X106
細胞/0.05mL於小鼠之左腹部,分成以下的3組進行投藥。
(i)控制組:強制口服投予水(不投予瓦茸菌子實體熱水萃取之萃取物粉末)。
(ii)50mg/kg投予組:由5週齡開始,投予瓦茸菌子實體熱水萃取之萃取物粉末,每天50mg/kg(小鼠每40g相當於2mg/0.2ml)強制口服投予。
(iii)500mg/kg投予組:由5週齡開始,投予瓦茸菌子實體熱水萃取粉末,每天500mg/kg(小鼠每40g相當於20mg/0.2ml)強制口服投予。
肉腫瘤180癌細胞移植後,每週進行腫瘤的體積測定。
(2)結果如表3所示,試驗組(投予組)與控制組(非投予組)比較,顯著地抑制腫瘤的成長。
如上述,本發明的瓦茸菌株FERM BP-10633具有非常高的活性,惟更進一步以增進活性為目的,對與微細藻類或其他擔子菌類之併用,亦進行檢討。
(1)試驗1首先,使用上述瓦茸菌(FERM BP-10633)熱水萃取物粉末,及下列(i)至(iii)之綠藻萃取物粉末,香菇萃取物粉末,以及綠藻香菇萃取物粉末作為受驗樣品,依據上述相同的方法,進行血小板凝集抑制試驗,化學增活素基因表現抑制試驗,及抗突變性試驗。
其結果,如第3圖所示,瓦茸菌(FERM BP-10633)熱水萃取物粉末與綠藻萃取物粉末或者香菇萃取物粉末或者綠藻香菇萃取物粉末併用時,與各別單獨使用時進行比較,確認對血小板凝集抑制作用,化學增活素基因表現抑制作用,抗突變性作用係協同性增強。特別是,混合綠藻香菇萃取物粉末時,其效果顯著。
(i)綠藻萃取物粉末的調製於綠藻萃取槽中,加入綠藻(Chlorella pyrenoidosa)40kg及蒸餾水750L,升溫至90℃後,進行萃取30分鐘。其後,離心分離回收上清液,而得綠藻萃取液。
此萃取液以蒸餾器濃縮至約45L(約18倍),於其中加入β-環糊精40kg,以混練機攪拌同時以滾筒乾燥(滾筒乾燥機表面溫度約150℃,反應溫度約90℃)乾燥至含水量為5%以下。以粉碎機粉碎乾燥物中產生的片狀乾燥物,而得約50kg之綠藻萃取物粉末。
(ii)香菇萃取物粉末的調製於香菇萃取槽中,加入香菇(Lentinus edodes)的片狀乾燥子實體40kg及蒸餾水750L,升溫至85℃後,進行萃取60分鐘。其後,於香菇擠壓機擠壓同時回收萃取物部分,離心分離回收上清液,而得香菇萃取液。
此萃取液於蒸餾器濃縮至約45L(約18倍),於其中加入β-環糊精40kg,以混練機攪拌同時以滾筒乾燥(滾筒乾燥機表面溫度約150℃,反應溫度約90℃)乾燥至含水量為5%以下。以粉碎機粉碎乾燥物中產生的片狀乾燥物,而得約50kg之香菇萃取粉末。
(iii)綠藻香菇萃取物粉末的調製將上述綠藻萃取液650L與上述香菇萃取液620L混合,以蒸餾器濃縮至約70L,於其中,加入β-環糊精27.5kg,以混練機攪拌同時以滾筒乾燥(滾筒乾燥機表面溫度約150℃,反應溫度約90℃)乾燥至含水量為5%以下。以粉碎機粉碎乾燥物中產生的片狀乾燥物,而得約40kg之綠藻香菇萃取物粉末。
(2)試驗2此外,亦依照下列處方例1至2調製飲料劑,與上述同樣的方法進行試驗。其結果,如表4所示,任何飲料劑對於血小板凝集抑制作用,化學增活素基因表現抑制作用,抗突變性作用均顯示很高的活性。
處方例1 機能性飲料(精製水50mL中含有下列成分)
處方例2 機能性飲料(精製水50mL中含有下列成分)
使用高血壓自然發症大鼠(spontaneous hypertension rat:SHR(4週齡),由日本Charles River公司購入),進行活體內試驗。SHR係7至15週齡,100%自然發症高血壓之個體。其血壓為10週齡平均約171mmHg,最高血壓達到約200 mmHg以上。SHR小鼠亦顯示膽固醇代謝異常及胰島素抗性。
(1)單次投藥試驗對SHR(10週齡,雄),使用鼻胃管將瓦茸菌(FERM BP-10633)熱水萃取之萃取物粉末,綠藻萃取物粉末,或其1:1之混合物(質量比)以萃取物粉末3.3mg/kg之用量口服投予,觀察血壓(n=6)。控制組係投予水。投藥8小時的平均收縮壓如以下表5所示。
如表5,於各個投予組,可確認血壓下降作用,混合物投予組之血壓最低。
再者,對SHR(10週齡,雄),使用鼻胃管投予上述處方例2之飲料劑,以瓦茸菌熱水萃取之萃取物粉末3.3mg/kg用量口服投予,投藥開始之前及至投予後48小時,經時地測定血壓(n=5)。
第4圖,以控制組(非投予組)的平均收縮壓為0,對試驗組(投予組)的平均收縮壓作圖。由此結果得知,試驗組於投藥30分鐘後,比起控制組血壓開始降低,投藥4至10小時,血壓最低。其後,血壓慢慢上升,惟上升緩慢,達到與控制組相同程度的血壓,需要約48小時。
(2)慢性投予試驗:再者,於SHR(5週齡,雄),使用鼻胃管將上述處方例2之飲料劑以瓦茸菌熱水萃取之萃取物粉末3.3mg/kg用量投藥11週,至16週齡,其間每日一次每日口服投予,投藥開始之前及各口服投予之前,測定血壓(n=5)。
第5圖表示控制組(非投予組)及試驗組(投予組)每1週之平均收縮壓的變化。控制組係隨著週齡增加血壓同時漸漸上升,16週齡(投藥11週)時,血壓超過220mmHg。相對於此,試驗組係至8週齡(投藥3週)血壓逐漸上升,其後,於170至180mmHg的範圍內穩定地變化。
由此,顯示藉由持續攝取含有本發明的瓦茸菌萃取物之組成物,可改善高血壓,且可將血壓控制於一定範圍內。
再者,臨床地調查對於高血壓患者之抗高血壓作用。
(1)試驗方法:受驗患者係收縮壓經常性為150至170mm/Hg前後的高血壓患者10人(男7名,女3名)。受驗者的平均收縮壓係162mmHg,平均舒張壓係96mmHg,此為,投藥開始前10天大致相同。
由投藥開始日(第0天)至70天內,每日,1天1次,使受驗患者口服攝取上述處方例2的飲料劑。攝取量係1日50mL(瓦茸菌熱水萃取之萃取物粉末200mg)。投藥期間中,在投藥之前測定血壓。
此外,以含凝固抑制劑的採血管採取患者的血液,一般而言,基於臨床檢查測定法測定血中腎素濃度,及血中升壓素I濃度。
(2)結果第6圖係以投藥開始日之血壓為0,對(a)舒張壓及(b)收縮壓的變化每5日作圖。收縮壓係投藥開始第5天開始下降,至70天均有緩慢降低的傾向。舒張壓係投藥開始之第10天開始下降,至約第30天則幾乎不再降低,而於一定範圍內穩定地變化。
由此結果顯示本發明含有瓦茸菌萃取物之組成物可降低高血壓患者的血壓,推測即使慢性地攝取,亦無過度降低血壓的疑慮。
此外,於第7圖中顯示受驗者的血中腎素濃度,血中生壓素I濃度之變化。伴隨著投予日數的增加,腎素濃度上升,而升壓素I減少。由此,推測於活體並內對內分泌的腎素,升壓素及其他賀爾蒙並未過度促進分泌或過度抑制,而能控制血壓。
對於免疫調節作用亦進行調查。
(1)試驗方法受驗患者係健康的成人30名。受驗患者於1個月間,每天,1天1次,口服攝取上述處方例2之飲料劑。攝取量係1天50mL(瓦茸菌熱水萃取之萃取物粉末200mg)。其後,停止攝取2個月。
於攝取開始前,攝取開始後10天及1個月,攝取停止後2個月,將受驗患者的血液以裝有血液凝固抑制劑之採血管採血,基於一般的臨床檢查測定法,各別測定T細胞及NK細胞的免疫細胞百分率。
(2)結果第8圖表示投予期間(1個月)以及其後的投予停止期間(2個月)之T細胞數(%)及NK細胞數(%)。慢性投予期間中,隨著投予日數的增加,T細胞數及NK細胞數同時增加。而投予停止後,NK細胞及T細胞同時開始降低,其為緩慢降低,而回到投予開始前的程度需要2個月。
由此顯示本發明之含有瓦茸菌萃取物的組成物具有免疫賦活化效果,藉由繼續地攝取而有相當高的持續性效果。
下文,進一步例示本發明之含有瓦茸菌(FERM BP-10633)萃取物的組成物之例。
處方例3 乳霜
處方例4 乳液
處方例5 膠劑
處方例6 洗劑
第1圖示本發明的瓦茸菌株(試驗株1,FERM BP-10633),其他的製成的雜種株(試驗株2至4),對有關製成試驗株使用之親株A及親株B,以往品種的瓦茸菌I及瓦茸菌II,其子實體熱水萃取物之血小板凝集抑制劑作用,化學增活素基因表現抑制作用,抗突變性作用的比較圖(控制組為DMSO)。
第2圖示本發明瓦茸菌株(試驗株1,FERM BP-10633),的子實體熱水萃取物及含水乙醇萃取物之血小板凝集抑制作用,化學增活素基因表現抑制作用,抗突變性作用的比較圖(控制組為DMSO)。
第3圖示本發明瓦茸菌株(試驗株1,FERM BP-10633)的子實體熱水萃取物與綠藻(chlorella)及/或香菇子實體的熱水萃取物混合時,表示血小板凝集抑制作用,化學增活素基因表現抑制作用,抗突變性作用之協同效果的圖(控制組為DMSO)。
第4圖示將含有本發明瓦茸菌株(試驗株1,FERM BP-10633)的子實體熱水萃取物之組成物對SHR一次投予後,表示相對於控制組(非投予)收縮壓的經時變化圖。
第5圖示將含有本發明瓦茸菌株(試驗株1,FERM BP-10633)的子實體熱水萃取物之組成物對SHR慢性投予時,及非投予(控制組)時,收縮壓的經時變化圖。
第6圖示將含有本發明瓦茸菌株(試驗株1,FERM BP-10633)的子實體熱水萃取物之組成物對高血壓患者慢性投予時,(a)舒張壓,及(b)收縮壓的經時變化圖。
第7圖示將含有本發明瓦茸菌株(試驗株1,FERM BP-10633)的子實體熱水萃取物之組成物對高血壓患者慢性投予時,(a)血中腎素濃度,及(b)升壓素I濃度的經時變化圖。
第8圖示將含有本發明瓦茸菌株(試驗株1,FERM BP-10633)的子實體熱水萃取物之組成物對30名健康人士於1個月慢性投予,接著,於2個月間停止投藥時,T細胞數及NK細胞數的經時變化圖。
Claims (13)
- 一種瓦茸菌株,其國際寄存號碼為FERM BP-10633,台灣寄存號碼為BCRC930087。
- .一種血小板凝集抑制劑,係包含申請專利範圍第1項的瓦茸菌株及/或其子實體於1至5氣壓、60至150℃之加壓、加熱下萃取而得之熱水萃取物為有效成分。
- 一種化學增活素基因表現抑制劑,係包含申請專利範圍第1項的瓦茸菌株及/或其萃取物為有效成分。
- 一種抗突變性劑,係包含申請專利範圍第1項的瓦茸菌株及/或其萃取物為有效成分。
- 一種抗腫瘤劑,係包含申請專利範圍第1項的瓦茸菌株及/或其子實體於1至5氣壓、60至150℃之加壓、加熱下萃取而得之熱水萃取物為有效成分。
- 一種抗高血壓劑,係包含申請專利範圍第1項的瓦茸菌株及/或其子實體於1至5氣壓、60至150℃之加壓、加熱下萃取而得之熱水萃取物為有效成分。
- 一種免疫調節劑,係包含申請專利範圍第1項的瓦茸菌株及/或其子實體於1至5氣壓、60至150℃之加壓、加熱下萃取而得之熱水萃取物為有效成分。
- 一種口服用組成物,係包含申請專利範圍第1項的瓦茸菌株及/或其子實體於1至5氣壓、60至150℃之加壓、加熱下萃取而得之熱水萃取物者。
- 一種口服用組成物,係包含申請專利範圍第1項的瓦茸菌及/或其萃取物,以及一種以上選自微細藻類及其 他擔子菌類及該等的萃取物所成組群之物。
- 一種飲食品,係由申請專利範圍第8項或第9項的組成物所組成者。
- 一種醫藥組成物,係由申請專利範圍第8項或第9項的組成物所組成者。
- 一種皮膚外用組成物,係包含申請專利範圍第1項的瓦茸菌株及/或其子實體於1至5氣壓、60至150℃之加壓、加熱下萃取而得之熱水萃取物者。
- 一種皮膚外用組成物,係包含申請專利範圍第1項的瓦茸菌株及/或其萃取物,以及一種以上選自微細藻類及其他擔子菌類及該等的萃取物所成組群之物。
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US7829098B2 (en) | 2005-11-08 | 2010-11-09 | Vita Green Health Products Co., Ltd | Herbal powder extracts and methods of preparing and using the same |
US8956624B2 (en) | 2007-12-19 | 2015-02-17 | Elc Management, Llc | Compositions and methods for treating skin with extract from Trametes |
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5008243A (en) * | 1983-08-11 | 1991-04-16 | Kureha Kagaku Kogyo Kabushiki Kaisha | Pharmaceutical composition containing a glycoprotein |
CN1364572A (zh) * | 2001-01-16 | 2002-08-21 | 杨孟君 | 纳米云芝菌制剂药物及其制备方法 |
CN1634121A (zh) * | 2004-10-15 | 2005-07-06 | 北京正大绿洲医药科技有限公司 | 灵芝多糖、云芝多糖滴丸 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6045531A (ja) * | 1983-08-11 | 1985-03-12 | Kureha Chem Ind Co Ltd | 抗高脂血症剤 |
JP2711201B2 (ja) * | 1992-10-06 | 1998-02-10 | 東洋製薬株式会社 | 連鎖球菌抗菌剤 |
JPH1160495A (ja) * | 1997-08-20 | 1999-03-02 | Kureha Chem Ind Co Ltd | 免疫系未成熟動物用の疾病予防剤 |
US20020176796A1 (en) * | 2000-06-20 | 2002-11-28 | Purepulse Technologies, Inc. | Inactivation of microbes in biological fluids |
CN100363384C (zh) * | 2001-12-29 | 2008-01-23 | 福州绿谷生物药业技术研究所 | 草栽灵芝多糖肽及其提取方法 |
WO2005021703A1 (ja) * | 2003-08-29 | 2005-03-10 | Yamaha Hatsudoki Kabushiki Kaisha | 微生物の培養装置、培養装置への袋の挿入方法 |
JP4618770B2 (ja) * | 2004-02-12 | 2011-01-26 | 株式会社クレハ | 新規な血圧降下剤および食品 |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5008243A (en) * | 1983-08-11 | 1991-04-16 | Kureha Kagaku Kogyo Kabushiki Kaisha | Pharmaceutical composition containing a glycoprotein |
CN1364572A (zh) * | 2001-01-16 | 2002-08-21 | 杨孟君 | 纳米云芝菌制剂药物及其制备方法 |
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AU2006273203A1 (en) | 2007-02-01 |
EP1918363A1 (en) | 2008-05-07 |
EP1918363B1 (en) | 2016-09-28 |
IL189030A (en) | 2011-12-29 |
EP1918363A4 (en) | 2011-02-02 |
CN101233225A (zh) | 2008-07-30 |
CN101233225B (zh) | 2012-03-14 |
WO2007013588A1 (ja) | 2007-02-01 |
TW200736389A (en) | 2007-10-01 |
AU2006273203B2 (en) | 2011-07-28 |
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