TW201141499A - Immunoglobulin a secretion promoter - Google Patents
Immunoglobulin a secretion promoter Download PDFInfo
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- TW201141499A TW201141499A TW100107324A TW100107324A TW201141499A TW 201141499 A TW201141499 A TW 201141499A TW 100107324 A TW100107324 A TW 100107324A TW 100107324 A TW100107324 A TW 100107324A TW 201141499 A TW201141499 A TW 201141499A
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- Prior art keywords
- iga
- extract
- iga antibody
- group
- secretion
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Description
201141499 六、發明說明: 【發明所屬之技術領域】 本發明係可期待細菌及病毒等預防感染效果及預防過 敏效果之IgA分泌促進劑,特別係有關可期待上呼吸道的 IgA分泌促進效果之組成物。 【先前技術】 於口腔、氣管、消化道等生體內與外界接觸的面,爲 了預防外界之病毒及細菌入侵,構築了稱爲黏膜免疫強大 的防禦系統。在黏膜表面上,自唾液腺及黏液腺等分泌源 源不絕的黏液,物理性的防止病毒及細菌入侵,同時藉由 黏液中存在的抗體、抗菌胜肽、酵素等的作用來防禦生體 的外敵。於該防禦系統中擔任最重要的角色是免疫球蛋白 A(IgA)抗體,具有去除病毒及細菌等以及防止附著於黏膜 面等作用(非專利文件1 )。 有關IgA抗體與感染症的關係,已報告在動物實驗中 ,使對於中耳炎的原因菌具特異性的IgA抗體增加時,原 因菌的感染被抑制(非專利文件2 )。另外,將對某種引 起感冒的病毒具特異性的IgA抗體投藥予人體的鼻腔內時 ,該病毒的感染被抑制(非專利文件3 )。
IgA抗體除具有防禦生體來自細菌及病毒等感染的作 用之外,亦被認爲可阻止引起過敏反應的外來抗原自黏膜 入侵生體(非專利文件4 )。 由上述背景認爲若可促進IgA抗體的分泌,對於細菌 201141499 及病毒等的感染症預防及預防過敏有效。 至今已揭示具有IgA抗體分泌促進作用之各種乳酸菌 及擔子菌(專利文件1〜4)、多糖類及寡糖類(專利文件 5〜9、非專利文件5 ),係多與於腸內產生IgA抗體有關者 ,與口腔、鼻腔及氣管等呼吸系的器官內具有IgA分泌促 進作用及感染抑制作用有關者僅爲少數(專利文件2、專 利文件1 〇 )。 先前技術文件 專利文件 專利文件1 :專利第296 8 3 74號公報 專利文件2 :專利第3 8 1 8 3 1 9號公報 專利文件3 :特開平1 1 -92 3 8 9號公報 專利文件4:特開2005-97 1 33號公報 專利文件5:專利第4162147號公報 專利文件6:特開2001 -641 8 1號公報 專利文件7 :特開2003-2 1 0239號公報 專利文件8 :特開2006-702 1 7號公報 專利文件9 :特開2 0 0 6 - 2 1 3 6 7 1號公報 專利文件10:特開2009- 1 6 1 447號公報 專利文件11 :特開2002-370993號公報 非專利文件 非專利文件 1 : Brandtzaeg P.,International Journal of
Medical Microbiology,2003 年,293 卷,1 號,3 〜15 頁,Role of secretory antibodies in the defence against infections. 201141499 非專利文件2: Hotomi M. et al·,Vaccine, 1998 年,16 卷,20 號,1 950 〜1 956 頁,Specific mucosal immunity and enhanced nasopharyngeal clearance of nontypeable Haemophilus influenzae after intranasal immunization with outer membrane protein P 6 and cholera toxin. 非專利文件 3 ·· Heikkinen T. et al·, Pediatric
Infectious Disease Journal,1 998 年,17卷,5號,3 67 〜372 頁, Intranasally administered immunoglobulin for the prevention of rhinitis in children. 非專利文件4:池澤善郎,低過敏食品的開發,CMC出 版,41_49頁 非專利文件 5 : Scholtens P.A. et al.,Journal of Nutrition, 2008 年,138 卷,6 號,1141 〜1147 頁,Fecal secretory immunoglobulin A is increased in healthy infants who receive a formula with short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides. 【發明內容】 [發明欲解決之課題] 有鑑於上述課題,本發明係以提供不僅於腸道內,於 口腔及呼吸道亦具有IgA分泌促進作用之醫藥組成物爲目 的0 [解決課題之手段] 201141499 本發明團隊專心硏究後發現虞美人萃取物具有IgA分 泌促進作用,遂完成以其爲基礎的本發明。 [發明的效果] 本發明之虞美人萃取物,不僅於腸道內具有IgA分泌 促進作用,於口腔及呼吸道亦具有IgA分泌促進作用,因 此,藉由攝取該萃取物抑制病毒及細菌的感染,另外亦可 預防過敏發生。 本發明中發現具有IgA分泌促進作用的虞美人(學名 :Papaver rhoeas L.)係嬰粟花科的植物,別名爲虞美人 草。一般認爲具有鎭靜、催眠、止痛作用等,使用爲鎭咳 藥及鎭靜劑。 雖然與含香草植物的免疫賦活劑有關之專利(專利文 件1〇中記載有作爲香草植物一例之嬰粟花,但欠缺發明 的具體性,亦無有關IgA的記載。 本發明中使用的虞美人萃取物,可使用虞美人的花、 葉及莖,較佳係使用虞美人的花、水、或與水具親水性有 機溶媒之混合物,進行萃取。 並未限定萃取方法及溶劑種類。溶劑可使用水以外, 尙可使用乙醇、甲醇、丙醇、甘油、丙二醇等醇類,及醚 、酮、醋酸乙酯、氯仿、己烷等有機溶劑或與該等溶劑組 合者。然而自安全性的觀點而言,以使用乙醇或與其之混 合溶液進行萃取爲佳。 爲獲得萃取物的萃取條件係可於高溫、室溫、低溫任 -8 - 201141499 —種溫度下進行萃取,但以40〜90°C下0.5〜5小時爲佳 萃取物可直接使用溶液狀,亦可使用進而經過濾卷 除萃取溶劑之後,再進行減壓乾燥或冷凍乾燥而成爲米 狀者,或可使用經濃縮者。另外亦可使用將該等萃取半 有機溶劑分畫,或藉由管柱層析儀等分畫純化者。進A 可再加上脫臭、脫色等純化處理》 並未特別限定虞美人萃取物的含量,相對於飲食物 製劑,換算爲乾燥重量以0.01重量%以上爲佳,含0.1〜 重量%更佳。 並未特別限定虞美人萃取物的攝取方法,可藉由經 攝取、舌下投藥等攝取、經鼻投藥攝取、對皮下及血管 局部的直接投藥等各種周知之方法。 含本發明之虞美人萃取物的醫藥組成物,可利用爲 藥品、准藥品、或飮食品等。 使用於醫藥品時可作爲經口劑投藥。經口劑的劑型 舉出錠劑、膠囊劑、散劑、糖漿劑、液劑等。使用於飲 品時可舉出飲料等飲料品、糖果、仙貝、餅乾等食品以 ,尙可舉出香煙、口香糖等嗜好品、飼料及飼料類、漱 藥水、牙膏等化妝品類,無法全數列舉,本發明可使用 各式各樣的物品》 使用於醫藥品及准醫藥品時,可含藥理學上容許的 種或二種以上的載體,及進而因應需要含有爲了進行治 的有效成分。此外,亦可含有賦形劑、結合劑、崩解劑 滑澤劑、分散劑、界面活性劑、可塑劑、懸濁劑、乳化 去 末 經 亦 或 90 □ 內 醫 可 食 外 喉 於 療 % 劑 -9- 201141499 、稀釋劑、緩衝劑、抗氧化劑、制細菌劑等。 使用於食品時可含有食品製造所容許的食材、載體、 賦形劑、添加劑、增量劑、著色劑、香料等·» 另外有關虞美人萃取物以外的成份,並未限定於上述 ,本發明亦可任意含有周知的各種成分。 本發明之含虞美人萃取物的醫藥品、准藥品或飲食品 等,可根據各自的技術領域中周知的任一種方法進行製造 。於其製造過程中,可以周知的任一種方法添加虞美人萃 取物。 本發明之含虞美人萃取物的醫藥組成物不僅可使用於 人類,亦可使用於人類以外的動物(以下略稱作非人類動 物)。非人類動物可舉出哺乳類、昆蟲類、兩棲類、魚類 等人類以外的動物。 【實施方式】 [實施例] 以下以實施例說明本發明,但本發明之範圍並未限定 於該等實施例。 [實施例1] 調製熱水萃取物 粉碎100 g的虞美人花後,加入相對於試料重量10倍 的水,於70 °C下萃取2小時。過濾不溶物後,將萃取液冷 凍乾燥得熱水萃取物3 7.5 g。 -10- 201141499 [實施例2] 使用來自培氏斑(Peyer's patch)的淋巴球細胞進行 IgA抗體產生促進作用之in vitro評價 摘出小鼠(BALB/c系,雌性,6周齡)的小腸,取下 培氏斑並浸入含2%牛胎兒血清(FCS)之RPMI1 620培養基 。以剪刀裁斷培氏斑,再以細胞過濾器(BD Biosciences 製,孔徑爲7〇μη〇回收淋巴球細胞》離心回收的細胞懸濁 液,並吸去上清液後,加入complete medium調整淋巴球 細胞懸濁液的細胞濃度爲4xl06 cells/ml。complete medium係使用含 10% FCS、50μΜ 之 2-mercaptoethanol、1 mM之丙酮酸鈉、100 U/ml之盤尼西林、lOOpg/ml之鏈黴素 之RPMI 1 620培養基。於96孔盤中分別加入0.05 ml之淋巴 球細胞懸濁液與溶解的試料之培養培養基(試料係調整至 最終濃度爲lOOppm),於37°C,5% C02下培養一星期。 回收培養液並進行離心後,以三明治ELIS A法測定上清液 中總IgA抗體量。將未添加試料進行培養作爲對照之總IgA 抗體量設定爲1,計算添加試料進行培養時之總IgA抗體量 的相對値。 以三明治ELISA法測定總IgA抗體量 上述之以三明治ELISA法之測定係以下述步驟進行。 於96孔ELISA盤中分別加入100μ1之Ιμ/ml抗小鼠免疫 球蛋白抗體溶液,於4°C下反應一夜使抗體吸附於盤上。 -11 - 201141499 倒掉盤中溶液,分別加入180μ1之含1%牛胎兒血清(BSA )之PBS,並於室溫下孵育1小時,屏蔽目標以外的蛋白質 之非特異性的吸附•以含0.05% Tween 20之PBS ( PBST ) 洗淨各微孔後,加入試料溶液並於室溫下孵育2小時。再 以PBST洗淨各微孔後,各加入25ng的結合過氧化酶之抗小 鼠IgA抗體並於室溫下孵育1小時後,加入過氧化酶基質使 其反應2分鐘。其後加入0.5N鹽酸使反應停止,測定450nm 之吸光度。使用作爲標準物質之小鼠IgA抗體製作檢量線 ,並測定IgA抗體量。 結果如表1所示,將虞美人(花)的熱水萃取物以濃 度爲lOOppm添加於培養基時,培養基中IgA抗體量爲未添 加時之2.6倍。 [表1] 試料 IgA抗體量 湘對値) 植物名 部位 虞美人 花 2.6 [實施例3] 對小鼠投以反覆混餌之IgA分泌促進作用之評價-1 調製於普通飼料(MF,Oriental Yeast )中混合5% ( w/w)虞美人(花)的熱水萃取物之試驗試料。將6隻7周 齡小鼠(BALB/c系)分作對照群與試驗群(每群3隻), 對照群爲普通飼料,試驗群爲試驗飼料,自由攝食並飼育 6星期》自飼育開始回收每一星期的糞便,分別將其懸濁 於磷酸緩衝溶液中使濃度成爲1〇〇 mg/ml,進行離心後, -12- 201141499 以與實施例2相同之三明治ELISA法測定上清液中總IgA抗 體量。 結果係以各個體於〇週時總IgA抗體量設定爲1時之相 對値示於表2。比較平均値時,糞便中總IgA抗體量之相對 値與對照群相比,以投予群爲較高値。 [表2]
IgA量測定結果 群 個體 編號 總IgA抗體量(與各個體0週時之相對値) 0週 1週 2週 3週 4週 5週 6週 對 照 群 1 1.00 0.42 0.47 0.35 0.23 0.17 0.38 2 1.00 1.27 1.58 0.42 0.58 0.37 1.03 3 1.00 0.86 0.53 0.26 0.23 0.25 0.53 平均 1.00 0.85 0.86 0.34 0.34 0.26 0.64 投 予 群 4 1.00 2.42 2.54 1.78 0.63 1.25 2.21 5 1.00 2.46 0.94 1.68 1.31 1.28 2.79 6 1.00 0.95 0.13 0.48 0.18 0.38 1.05 平均 1.00 1.94 1.20 1.31 0.71 0.97 2.02 [實施例4] 對小鼠投以反覆混餌之IgA分泌促進作用之評價-2 調製於普通飼料(MF,Oriental Yeast )中混合5% ( w/w )虞美人(花)的熱水萃取物之試驗試料。將12隻7周 齡小鼠(BALB/c系)分作對照群與試驗群(每群6隻), 對照群爲普通飼料,試驗群爲試驗飼料,飼育並使其自由 攝食。於第 4 週以 5 0pg 的 Phosphorylcholine-Keyhole Limpet Hemocyanin ( PC-KLH,細菌共通的抗原)經鼻投 予使其致敏。其後亦每星期經鼻致敏,自第3次經鼻致敏 1星期後收集鼻腔黏液(100〜2〇〇μ1/隻)及鼻腔黏膜固有 -13- 201141499 層淋巴球細胞(lxl〇5〜5 xio5 cells/隻),測定總IgA抗體 量及總IgA抗體產生細胞數、具PC特異的IgA抗體價及具 PC特異的IgA抗體產生細胞數。另外,回收糞便,將其懸 濁於磷酸緩衝溶液中使濃度成爲100 mg/ml,進行離心後 ,測定上清液中總IgA抗體量。總IgA抗體量及具PC特異的 IgA抗體價之測定係使用三明治ELISA法,具PC特異的IgA 抗體產生細胞數之測定係以enzyme-linked immunospot ( ELISPOT)法進行。另外,由於可自各動物採集之鼻腔黏 膜固有層淋巴球細胞數目稀少,故以3隻小鼠份量的細胞 爲一單位,以2個檢體進行IgA抗體產生細胞數之測定。 使用三明治ELISA法之IgA抗體量之測定 上述總IgA抗體量之測定係以與實施例2相同之三明治 ELISA法進行。另外上述之具PC特異的IgA抗體量之測定 ,除了將最初之使其吸附於ELIS A盤之抗小鼠免疫球蛋白 抗體,以PC-BSA取代之外,以與實施例2相同之三明治 ELISA法進行測定。 根據ELIS POT法測定IgA抗體產生細胞數 上述之根據ELISPOT法測定具PC特異的IgA抗體產生 細胞數之測定係以下述步驟進行。 於市售之96孔ELISPOT用硝化纖維素膜之盤中,分別 加入ΙΟΟμΙ之抗小鼠免疫球蛋白抗體(5Pg/ml PBS ),或 PC- BSA ( 5pg/ml PBS)並於4°C下反應一夜使其吸附於盤 14 - 201141499 上。倒掉盤中溶液’以comPlete medium進行屏蔽後,加 入經適當稀釋之來自鼻腔黏膜固有層淋巴球細胞懸濁液, 於37°C,5% C02下毈育4小時。以PBS洗淨後,加入i〇〇ng 的結合過氧化酶之抗小鼠IgA抗體並於4°C下使其反應一夜 。以PBS洗淨後,加入發色基質 (3-amino-9-ethylcarbazole)液,並於室溫且避光條件下,使其發色30 分鐘。以水洗淨並使其乾燥後,以實體顯微鏡計測spot做 爲產生抗體細胞。 測定糞便中總IgA量 回收糞便,將其懸濁於PBS中使濃度成爲100 mg/ml並 進行離心後,以與實施例2相同之三明治ELISA法測定上清 液中總IgA量。 結果如表3及表4所示。鼻腔黏液及糞便的總IgA量以 投予群較高,鼻腔黏膜固有層的總產生IgA細胞數亦以投 予ϋ較高。認爲係藉由虞美人萃取物的混餌投予,可促進 腸道及呼吸道系分泌IgA。 15- 201141499 [表3]
IgA量測定結果 鼻腔黏液 糞便 總 IgAS 具PC特異的IgA抗體價 總IgA量 (ng/ml) (Reciprocal log2 titer) (μ g/ml) 對照群 投予群 對照群 投予群 對照群 投予群 210 289 0 1 8.5 21.9 231 734 4 2 5.4 8.0 各個體之 260 297 5 5 3.7 8.8 測定値 300 358 4 4 2.3 13.1 263 299 4 3 2.0 4.2 211 454 3 4 2.1 5.2 平均値 246 405 3.3 3.2 4.0 10.2 標準誤差 14.2 70.5 0.7 0.6 1.0 2.7 [表4] 產生IgA細胞數測定結果 總IgA產生細胞數 (cells/10ecells) 具PC特異的產生IgA抗體細胞數 (cells/IO'celIs) 對照群 投予群 對照群 j 投予群 測定値 83 126 26 | 29 100 140 20 1 j 37 平均値 92 133 23 ί 33 [實施例5] 對小鼠投以反覆混餌之IgA分泌促進作用之評價-3 調製於普通飼料(MF,Oriental Yeast )中混合5% ( w/w)虞美人(花)的熱水萃取物之試驗試料。將20隻7周 齡小鼠(BALB/c系)分作對照群與試驗群(每群10隻), 以與實施例4相同方法,測定鼻腔黏液的總Iga抗體量及具 PC特異的IgA抗體價、糞便的總IgA抗體量。 -16- 201141499 結果如表5所示。鼻腔黏液的總IgA量以投予群較高, 認爲係藉由虞美人萃取物的混餌投予,可促進呼吸道系分 泌 IgA。 [表5] I g A量測定結果 「鼻腔獅 糞便 總IgA量 具PC特異的IgA抗體價 MlgA 量 (ηκ/mO (Reciproca log2 titer) (Mg/ml〉 對照群 投予群 對照群 投予群 對照群 投予群 424 553 6 7 2.0 8.3 574 435 6 6 2.2 0.9 422 254 8 6 2.9 3.9 277 525 5 6 3.7 2.8 名個體之: 683 779 6 7 1.9 8.1 測定値_ 175 672 6 7 4.4 1.3 272 176 6 6 3.3 1.4 191 254 8 6 2.7 1.7 231 289 5 6 2.2 2.1 303 287 6 7 2.1 2*2 平均値 355 422 6.2 6.4 2.7 3.3 標準誤差 50.5 60.9 0.31 0.15 0.25 0.82 [實施例6 ] 對小鼠反覆舌下投予之IgA分泌促進作用之評價-1 使7周齡小鼠(BALB/c系)4隻爲1群並分作對照群與 投予群,以普通飼料(MF,Oriental Yeast )飼育。投予 群自飼育開始時以用量爲4mg/日的虞美人(花)熱水萃取 物之水溶液進行每日舌下投予,對照群則僅以等量的水進 行舌下投予。於第4週以50μ8的PC-KLH經鼻投予使其致敏 ,其後亦每星期經鼻致敏,自第3次經鼻致敏之1星期後收 集鼻腔黏液及鼻腔黏膜固有層淋巴球細胞,測定總IgA抗 -17- 201141499 體量及總IgA抗體產生細胞數。總igA抗體量之測定係使用 與實施例2相同之三明治ELISA法,IgA抗體產生細胞數之 測定係使用與實施例4相同之 enzyme-linked immuno spot (ELI SPOT)法進行。另外,由於可自各動物採集之鼻腔黏 膜固有層淋巴球細胞數目稀少,故以4隻小鼠份量的細胞 爲一單位’以2個檢體進行Iga抗體產生細胞數之測定。 結果如表6及表7所示》鼻腔黏液的總IgA量及總IgA抗 體產生細胞數以投予群較高,認爲係藉由虞美人萃取物的 舌下投予,可促進呼吸道系分泌IgA,增加產生IgA細胞。 [表6] 總IgA量 (ng/ml) 對照群 投予群 各個體之 測定値 247 265 262 222 155 165 240 619 平均 226 318 [表7] 總IgA產生細胞數 (cells/106cells) 對照群 投予群 各測定値 500 790 320 900 平均値 410 845 [實施例7] 對小鼠反覆舌下投予之IgA分泌促進作用之評價-2 使7周齡小鼠(BALB/c系)15隻爲1群並分作對照群與 -18- 201141499 投予群,以普通飼料(MF,Oriental Yeast )飼育。投予 群自飼育開始時以用量爲4mg/日的虞美人(花)熱水萃取 物之水溶液進行每日舌下投予,對照群則僅以等量的水進 行舌下投予。於第4週以50μ8的PC-KLii經鼻投予使其致敏 ,其後亦每星期經鼻致敏,自第3次經鼻致敏之1星期後收 集鼻腔黏液及鼻腔黏膜固有層淋巴球細胞,測定總IgA抗 體量及總IgA抗體產生細胞數,以及具PC特異的IgA抗體價 及具PC特異的IgA抗體產生細胞數。另外,回收糞便並將 其懸濁於磷酸緩衝溶液中,進行離心後,測定上清液中總 IgA抗體量。總IgA抗體量及具PC特異的IgA抗體價之測定 係使用與實施例2相同之三明治ELISA法,IgA抗體產生細 胞數之測定係使用與實施例4相同之enzyme-linked immunospot(ELISPOT)法進行。另外,由於可自各動物採 集之鼻腔黏膜固有層淋巴球細胞數目稀少,故以3隻小鼠 份量的細胞爲一單位,以2個檢體進行IgA抗體產生細胞數 之測定。 結果如表8及表9所示。任一項目均以投予群較對照群 爲高,認爲係藉由虞美人萃取物的舌下投予,增加了腸道 及呼吸道系的產生IgA細胞數與IgA分泌量。 -19- 201141499 [表8] I g A量測定結果 鼻腔黏液 糞便 總 IgAfl: 具PC特異的IgA抗體價 總IgA量 (ng/ml) (Reciprocal og2 titer) (β g/ml) 對照群 投予群 對照群 投予群 對照群 投予群 168 271 6 7 8.1 15.6 178 308 6 7 11.4 12.8 207 397 6 8 5.1 2.8 372 382 5 7 2.1 5.7 194 415 6 7 1.2 10.1 288 291 6 6 3.0 4.0 299 700 7 8 4.2 10.1 各個體之 測定値 601 588 7 7 1.6 13.3 245 260 6 6 4.1 6.9 342 293 8 8 4.1 1.1 359 215 8 6 7.1 3.7 381 500 7 8 4.4 2.5 178 391 7 8 0.6 2.1 298 370 7 7 4.8 1.7 357 364 7 7 4.5 2.6 平均値 298 383 6.6 7.1 4.4 6.3 標準誤差 29 34 0.2 0.2 0.7 1.2 -20- 201141499 [表9] 產生IgA細胞數測定結果 總IgA產生細胞數 (cells/10'cells) 具PC特異的產生IgA抗體細胞數 (cells/tOecells) 對照群 投予群 對照群 投予群 各組的測定値 27S 467 83 300 267 433 175 308 321 548 155 222 417 571 166 238 764 921 240 213 4S5 837 223 201 680 771 359 500 555 802 398 458 516 703 375 4S0 547 813 419 513 平均値 480 686 259 340 標準誤差 S3 54 38 40 [實施例8] 對小鼠反覆經鼻投予之IgA分泌促進作用之評價_ 1 使7周齡小鼠(BALB/c系)6隻爲1群並分作對照群與 投予群,以普通飼料(MF,Oriental Yeast)飼育。投予 群自飼育開始時以用量爲2mg/日的虞美人(花)熱水萃取 物之水溶液進行每日經鼻投予,對照群則僅以等量的水進 行經鼻投予。於第4週以5(^g的PC-KLH經鼻投予使其致敏 ,其後亦每星期經鼻致敏,自第3次經鼻致敏之1星期後收 集鼻腔黏液及鼻腔黏膜固有層淋巴球細胞,測定總IgA抗 體量及總IgA抗體產生細胞數。總IgA抗體量之測定係使用 與實施例2相同之三明治ELISA法,IgA抗體產生細胞數之 -21 - 201141499 測定係使用與實施例4相同之enzyme-linked immuno spot (ELISPOT)法進行。另外,由於可自各動物採集之鼻腔黏 膜固有層淋巴球細胞數目稀少,故以3隻小鼠份量的細胞 爲一單位’以2個檢體進行IgA抗體產生細胞數之測定》 結果如表10及表1 1所示。鼻腔黏液的總IgA抗體量及 總IgA抗體產生細胞數以投予群較高,認爲係藉由虞美人 萃取物的經鼻投予,促進呼吸道系分泌IgA,及增加產生 IgA細胞。 [表 10] 顧gA量 (ng/ml) 對照群 投予群 各個體之 測定値 327 402 211 569 229 210 392 293 432 487 497 402 ' 平均 348 394 [表 11] 麒gA產生細胞數 (cells/106cells) 對照群 投予群 各測定値 400 462 369 523 400 483 300 442 平均値 367 477 [實施例9] 對小鼠反覆經鼻投予之IgA分泌促進作用之評價-2 •22- 201141499 使5〜6個月大之小鼠(BALB/c系)5隻爲1群並分作對 照群與投予群,以普通飼料(MF,Oriental Yeast )飼育 。投予群自飼育開始時以用量爲2mg/日的虞美人(花)熱 水萃取物之水溶液進行每日經鼻投予,對照群則僅以等量 的水進行經鼻投予。於第4週以50μβ的PC-KLH經鼻投予使 其致敏,其後亦每星期經鼻致敏,自第3次經鼻致敏之1星 期後收集鼻腔黏液及鼻腔黏膜固有層淋巴球細胞,測定總 IgA抗體量及總IgA抗體產生細胞數。總IgA抗體量之測定 係使用與實施例2相同之三明治ELISA法,IgA抗體產生細 胞數之測定係使用與實施例4相同之enzyme-linked immunospot(ELISPOT)法進行。另外,由於可自各動物採 集之鼻腔黏膜固有層淋巴球細胞數目稀少,故以2〜3隻小 鼠份量的細胞爲一單位,以2個檢體進行IgA抗體產生細胞 數之測定。 結果如表12及表13所示。鼻腔黏液的總IgA抗體量及 總IgA抗體產生細胞數以投予群較高,認爲係藉由虞美人 萃取物的經鼻投予,促進呼吸道系分泌IgA,及增加產生 IgA細胞。 [表 12] 總IgA量 (ng/ml) 對照群 投予群 各個體之 測定値 220 349 531 1020 688 538 499 618 424 734 平均 472 652 -23- 201141499 [表 13] 總IgA產生細胞數 (cells/10ecells) 對照群 投予群 各測定値 769 1077 692 1000 1091 1227 773 1227 平均値 831 1133 進而使用實施例1所調製之虞美人萃取物,遵循常用 方法調製錠劑、散劑、吸入劑、點鼻藥、口香糖、糖果、 巧克力、餅乾、果凍、錠果、冰淇淋'冰凍水果汁、飲料 。以下揭示其配方。另外,未因該等調製物而限制本發明 品之範圍。 [實施例10] 遵循下述配方調製錠劑。 D-甘露糖醇 35.0% 乳糖 27-5 結晶纖維素 12·5 羥丙基纖維素 5·0 實施例1之虞美人萃取物 20.0 10 0.0% [實施例11] 遵循下述配方調製錠劑。 乳糖 5 4.5% -24 201141499 玉米澱粉 38.5 硬酯酸鎂 2.0 實施例1之虞美人萃取物 5.0 10 0.0% [實施例12] 遵循下述配方調製膠囊劑。 乳糖 8.0% 硬酯酸鎂 2.0 實施例1之虞美人萃取物 90.0 10 0.0% [實施例13] 遵循下述配方調製散劑。 乳糖 4 0.0% 馬鈴薯澱粉 15.0 實施例1之虞美人萃取物 45.0 10 0.0% [實施例14] 遵循下述配方調製吸入劑。 乙醇 5.0% 實施例1之虞美人萃取物 0.5 L-薄荷醇 1.0 -25- 201141499 水 9 3.5 10 0.0% [實施例l5] 遵循下述配方調製點鼻藥。 甲基水楊酸 0.03g 馬來酸氯苯吡胺 0.3 dl-鹽酸麻黃素 0.3
Tween 8 0 0.2 氯化卡基二甲羥銨 0.01 氯化鈉 0.6 1 N氫氧化鈉 適量 實施例1之虞美人萃取物 0.01 水 適量 100.0ml (ρΗ6·8) [實施例16] 以下述配方調製口香糖。 橡膠基底 20.0% 砂糖 52.0 葡萄糖 14.0 水飴 13.0 香料 0.5 -26- 201141499 實施例1之虞美人萃取物 0.5 10 0.0% [實施例17] 以下述配方調製口香糖。 橡膠基底 20.0% 砂糖 5 3.0 葡萄糖 15.0 水飴 10.5 香料 0.5 實施例1之虞美人萃取物 1.0 10 0.0% [實施例1 8 ] 以下述配方調製口香糖。 橡膠基底 20.0% 砂糖 54.0 葡萄糖 14.0 水飴 9.3 香料 0.7 實施例1之虞美人萃取物 2.0 10 0.0% [實施例19] -27 201141499 以下述配方調製糖果。 砂糖 4 5.0% 水飴 40.0 香料 0.5 L-薄荷醇 0.3 實施例1之虞美人萃取物 0.2 水 14.0 10 0.0% [實施例20] 以下述配方調製糖果。 砂糖 5 0.0% 水飴 33.0 檸檬酸 1.0 香料 0.6 實施例1之虞美人萃取物 1.0 水 14.4 10 0.0% 施例2 1 ] 以下述配方調製巧克力。 可可粉 2 0.0% 全脂奶粉 20.0 可可脂 17.0 -28 201141499 粉糖 41.7 卵磷脂 0.5 香料 0.2 實施例1之虞美人萃取物 0.6 10 0.0% [實施例22] 以下述配方調製餅乾。 砂糖 3 1.0% 小麥粉 26.5 片栗粉 26.5 奶油 4.0 蛋 10.5 小蘇打粉 0.3 實施例1之虞美人萃取物 1.2 10 0.0% 施例23] 以下述配方調製果凍。 聚糊精水溶液 3 1.0% 山梨糖醇水溶液 8.0 巴拉金糖水溶液 9.0 麥芽糖水溶液 20.0 海藻糖水溶液 11.0 -29 201141499 明膠 10.0 酒石酸 1.0 實施例1之虞美人萃取物 3.0 1 ο ο. ο % [實施例24] 以下述配方調製錠菓。 砂糖 7 6.0% 葡萄糖 20.0 蔗糖脂肪酸酯 0.2 香料 0.1 實施例1之虞美人萃取物 0.5 水 3.2 10 0.0% 施例2 5 ] 以下述配方調製錠菓。 砂糖 7 2.0% 乳糖 19.8 蔗糖脂肪酸酯 0.2 實施例1之虞美人萃取物 5.0 水 3.0 10 0.0% -30 201141499 [實施例26] 以下述配方調製錠劑。 砂糖 2 8.8% 蔗糖脂肪酸酯 0.2 實施例1之虞美人萃取物 70.0 水 1.0 10 0.0% 施例27] 以下述配方調製冰淇淋。 蛋黃 11.0% 砂糖 13.5 牛奶 37.0 鮮奶油 37.0 香草豆莢 0.5 實施例1之虞美人萃取物 1.0 10 0.0% [實施例28] 以下述配方調製冰凍果汁水。 橘子果汁 2 0.0% 砂糖 29.5 實施例1之虞美人萃取物 0.5 水 50.0 -31 201141499 10 0.0% [實施例29] 以下述配方調製飮料。 橘子果汁 40.0% 異性化糖 15.3 檸檬酸 0.1 維他命C 0.05 香料 〇.1 實施例1之虞美人萃取物 〇.〇5 水 4 4.4 10 0.0% [實施例30] 以下述配方調製飲料。 葡萄柚果汁 70.0% 異性化糖 12.0 檸檬酸 0.1 維他命C 0.05 香料 0.1 實施例1之虞美人萃取物 0.1 水 適量 10 0.0% -32
Claims (1)
- 201141499 七、申請專利範圍: 1. 一種IgA分泌促進劑,其特徵係含有虞美人萃取物 〇 2. 一種醫藥組成物,其特徵係含有如申請專利範圍 第1項之IgA分泌促進劑換算爲乾燥重量爲〇.〇1 %〜90% » 3. 如申請專利範圍第2項之醫藥組成物,其係經口攝 取。 4. 如申請專利範圍第2項之醫藥組成物’其係經舌下 投藥而攝取。 5. 如申請專利範圍第2項之醫藥組成物’其係經鼻投 藥而攝取。 6. 一種食品,其特徵係含有如申請專利範圍第1項之 IgA分泌促進劑。 7. —種醫藥組成物,其特徵係含有如申請專利範圍 第1項之IgA分泌促進劑。 -33- 201141499 四 指定代表囷: (一) 本案指定代表圖為:無 (二) 本代表圖之元件代表符號簡單說明:無 201141499 五 本案若有化學式時,請揭示最能顯示發明特徵的化學 式:無
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| CN103764157A (zh) * | 2011-08-24 | 2014-04-30 | 罗蒂株式会社 | 流感病毒感染抑制剂 |
| JP6653564B2 (ja) * | 2015-12-18 | 2020-02-26 | アサヒ飲料株式会社 | 赤ぶどう果汁入り飲料の澱の発生を抑制する方法 |
| JP7313519B1 (ja) * | 2022-07-08 | 2023-07-24 | 日本甜菜製糖株式会社 | IgA産生促進剤及びIgA産生促進用の飼料組成物 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPS60262859A (ja) * | 1984-06-08 | 1985-12-26 | Shuzo Nakazono | 食品用天然赤色素の製造法 |
| JP2968374B2 (ja) | 1991-05-16 | 1999-10-25 | 株式会社ヤクルト本社 | IgA産生促進剤 |
| JP3563089B2 (ja) * | 1993-07-14 | 2004-09-08 | 三省製薬株式会社 | 皮膚外用剤 |
| JPH1192389A (ja) | 1997-09-17 | 1999-04-06 | Nichinichi Seiyaku Kk | 免疫賦活剤 |
| JP2001064181A (ja) | 1999-08-27 | 2001-03-13 | Otsuka Pharmaceut Co Ltd | 免疫賦活組成物 |
| JP2002370993A (ja) * | 2001-06-13 | 2002-12-24 | Bussan Biotech Kk | ハーブを含む免疫賦活剤 |
| JP2003201239A (ja) | 2001-11-05 | 2003-07-18 | Meiji Milk Prod Co Ltd | 免疫賦活食品組成物 |
| KR101095712B1 (ko) | 2003-08-21 | 2011-12-20 | 오츠카 세이야쿠 가부시키가이샤 | 점막 면역 부활 작용을 갖는 유산균 |
| JP2005097133A (ja) | 2003-09-22 | 2005-04-14 | Unitika Ltd | ハナビラタケ由来IgA産生促進剤 |
| JP2006070217A (ja) | 2004-09-03 | 2006-03-16 | Kitasato Inst:The | オウギ属植物地上部由来の多糖および生体防御機能賦活化剤 |
| JP2006213671A (ja) | 2005-02-04 | 2006-08-17 | Taiyo Kagaku Co Ltd | 粘膜免疫賦活組成物 |
| JP4162147B2 (ja) | 2005-04-21 | 2008-10-08 | ホクレン農業協同組合連合会 | アレルギー抑制剤 |
| JP2008208100A (ja) * | 2007-02-28 | 2008-09-11 | Nisshin Seifun Group Inc | 免疫賦活剤及び免疫賦活食品 |
| JP5196997B2 (ja) | 2007-12-28 | 2013-05-15 | 花王株式会社 | 口腔用組成物 |
| JP2010057395A (ja) * | 2008-09-02 | 2010-03-18 | Kizakura Co Ltd | 腸管免疫調節作用を有する乳酸菌 |
| JP2010150206A (ja) * | 2008-12-26 | 2010-07-08 | Kaneka Corp | 粘膜免疫賦活作用および免疫バランス調整作用を有する経腸栄養剤 |
| JP5372547B2 (ja) * | 2009-02-17 | 2013-12-18 | マイクロアルジェコーポレーション株式会社 | 免疫グロブリンa産生促進剤 |
| JP5585769B2 (ja) * | 2009-05-15 | 2014-09-10 | ダイソー株式会社 | 腸管免疫賦活能を有する乳酸菌に対する効果促進剤 |
| US9101566B2 (en) * | 2009-06-25 | 2015-08-11 | Kirin Holdings Kabushiki Kaisha | Fermentation product of cereal plant-derived material and immunomodulator |
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2011
- 2011-03-03 WO PCT/JP2011/001261 patent/WO2011108275A1/ja not_active Ceased
- 2011-03-03 BR BR112012022203A patent/BR112012022203A2/pt not_active IP Right Cessation
- 2011-03-03 CN CN201180012014.XA patent/CN102781457B/zh not_active Expired - Fee Related
- 2011-03-03 EP EP11750388.8A patent/EP2543381A4/en not_active Withdrawn
- 2011-03-03 KR KR1020127025829A patent/KR101896123B1/ko not_active Expired - Fee Related
- 2011-03-03 PH PH1/2012/501715A patent/PH12012501715A1/en unknown
- 2011-03-03 JP JP2012503020A patent/JP5879254B2/ja not_active Expired - Fee Related
- 2011-03-04 TW TW100107324A patent/TW201141499A/zh unknown
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| EP2543381A4 (en) | 2013-09-18 |
| BR112012022203A2 (pt) | 2016-07-05 |
| HK1176546A1 (zh) | 2013-08-02 |
| CN102781457B (zh) | 2015-01-14 |
| EP2543381A1 (en) | 2013-01-09 |
| JPWO2011108275A1 (ja) | 2013-06-20 |
| KR20130037672A (ko) | 2013-04-16 |
| JP5879254B2 (ja) | 2016-03-08 |
| KR101896123B1 (ko) | 2018-09-07 |
| WO2011108275A1 (ja) | 2011-09-09 |
| CN102781457A (zh) | 2012-11-14 |
| PH12012501715A1 (en) | 2012-11-12 |
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