TWI807545B - 製造囊化益生菌的方法、囊化益生菌、包含其之食品或功能性健康食品、醫藥組合物或藥劑及化妝品組合物 - Google Patents
製造囊化益生菌的方法、囊化益生菌、包含其之食品或功能性健康食品、醫藥組合物或藥劑及化妝品組合物 Download PDFInfo
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- TWI807545B TWI807545B TW110147538A TW110147538A TWI807545B TW I807545 B TWI807545 B TW I807545B TW 110147538 A TW110147538 A TW 110147538A TW 110147538 A TW110147538 A TW 110147538A TW I807545 B TWI807545 B TW I807545B
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- Prior art keywords
- alginate
- probiotics
- encapsulated
- hydrogel
- present
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- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims abstract description 63
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Abstract
揭露一種不中斷製造囊化益生菌的方法,其中藉由在含有藻酸鹽、會透過結合藻酸形成水凝膠之鹽類(較佳為不溶性碳酸鹽)及可選之包封增強劑的培養基中培養益生菌之簡單方法來自發形成藻酸鹽水凝膠,益生菌會被藻酸鹽水凝膠包封,從而不僅大幅改善益生菌的包封過程,還顯著改善益生菌的冷凍乾燥生存力、耐熱性、儲存穩定性及體內穩定性(耐酸性及耐膽汁性)。
Description
本發明係關於透過自發形成骨架型膠囊保護膜的技術不中斷地製造囊化益生菌(encapsulated probiotics)的方法,尤其係關於益生菌被包埋(entrapped)於藻酸鹽水凝膠內之製造囊化益生菌的方法,其中藻酸鹽水凝膠藉由在含有藻酸鹽、會透過結合藻酸形成水凝膠之鹽類及可選之包封增強劑的培養基中培養益生菌來自發形成。
益生菌(probiotics)係對體內健康有益的活微生物。至今已知大部分的益生菌為乳酸菌(lactic acid bacteria),一些包含桿菌(Bacillus)。自從俄羅斯科學家Elie Metchnikoff因發
現保加利亞人之所以長壽的原因是因為食用了以乳酸桿菌(Lactobacillus)發酵的牛奶而獲得諾貝爾獎(Mercenier A.et al.,Curr.Pharm.Des.9(2):175-191,2003)後,乳酸菌和益生菌的功能就為人所研究。
益生菌的代表性作用包含抗菌活性、緩解抗生素相關之腹瀉、降低乳糖不耐症、抗癌活性、降低血液膽固醇、抑制胃中的幽門螺旋桿菌(Helicobacter pylori)、舒緩易激結腸炎(irritable colitis)、舒緩克隆氏症(Crohn’s disease)、舒緩潰傷性結腸炎、調節免疫功能等。益生菌可分為腸道藥物或乳酸菌製劑(人類藥物)、作為食品添加劑的益生菌及乳酸菌食品(某種健康食品)。乳酸菌食品係藉由培養諸如乳酸桿菌、乳酸球菌(Lactococcus)、雙岐桿菌(Bifidobacterium)等活細菌再將其與食品混合並為了穩定及易於攝取而做成粉末、顆粒、錠劑及膠囊的產品,並且包含乳酸菌發酵食品、乳酸菌發酵牛奶及乳酸菌飲料以外的產品。
在藉由發酵生長的細菌之中,乳酸菌係主要由發酵產生乳酸的細菌。乳酸菌係微生物工業中最重要的微生物群之一,主要用於生產發酵食品,例如泡菜、優酪乳、起司、乳酪及酸菜,亦廣泛用作促進健康的功能性益生菌。
目前,乳酸菌分為12個屬(乳酸桿菌屬(Lactobacillus)、肉桿菌屬(Carnobacterium)、奇異菌屬
(Atopobium)、乳酸球菌屬(Lactococcus)、片球菌屬(Pediococcus)、四聯球菌屬(Tetragenococcus)、明串珠菌屬(Leuconostoc)、魏斯氏菌屬(Weissella)、酒球菌屬(Oenococcus)、腸球菌屬(Enterococcus)、鏈球菌屬(Streptococcus)及漫遊菌屬(Vagococcus)),通常使用之乳酸菌的示例包含桿菌(例如乳酸桿菌屬(Lactobacillus spp.))及球菌(例如乳酸球菌屬(Lactococcus spp.)、鏈球菌屬(Streptococcus spp.)、明串珠菌屬(Leuconostoc spp.)及片球菌屬(Pediococcus spp.))(Taejin Kang,BioWave,2009,Vol 11,No 7,pp 1-20)。
將乳酸菌製造成食品的過程大致上包含培養乳酸菌、回收細胞、冷凍乾燥、粉碎(pulverization)、商品化等。在此程序中,乳酸菌會受到各種物理及化學壓力。具體而言,在回收細胞的過程中,乳酸菌在濃縮過程中會受到滲透壓的影響,在冷凍乾燥的過程中,乳酸菌因劇烈的溫度變化而脫水及在細胞質中或細胞外形成冰晶,因而會受到溫度及滲透壓的影響。此外,在粉碎及商品化的過程中,當暴露於高溫及高壓或被空氣中的水分水合時,乳酸菌會變得不穩定。當暴露於氧氣中時,不僅諸如乳酸菌發酵食品、乳酸菌發酵牛奶及乳酸菌飲料之短期保存的液態產品,還有長期保存之粉末形式的產品,已注意到構成細胞膜的脂肪酸會氧化且生存力(viability)會降低之問題(韓國專利第10-1605516號)。
同時,為了使包含乳酸菌之細菌被視為益生菌,它們必須在胃酸及膽酸中存活、抵達小腸並在腸中增殖並定居,並且必須在腸道中發揮有用的作用,並且為無毒且無致病性。然而,包含乳酸菌之多種有益細菌在胃中會暴露於pH降至3以下的酸性環境,並且在小腸中會受膽酸的影響,故其生存力會大幅降低。
因此,開發了多種將細菌包封(encapsulating)的方法,以在冷凍乾燥這些有益細菌的過程中提升穩定性並在體內抵達腸道的過程中提升有益細菌的生存力。舉例而言,韓國專利申請案第2003-0009268號揭露一種製造微膠囊的方法,其中培養乳酸菌並與藻酸及CaCO3攪拌以獲得微膠囊形成組合物及乳酸菌的混合物,以含有少量乙酸(CH3COOH)及CaCl2的凝聚溶液(coagulation solution)噴灑微膠囊形成組合物及乳酸菌的混合物並固化,接著以CaCl2二次固化。
然而,此包封過程並未完全包覆細胞的表面,菌株的耐酸性及耐膽汁性仍未充分改善,此外,存在有益生菌的無菌處理困難之問題,因其通常需要進行將所培養的細菌回收並接著與包覆組合物攪拌之多個步驟。尤其,在工業大量生產中經濟效益差,這是不期望的。
因此,本發明人致力開發一種新的包封過程,其展現出改善的益生菌的體內穩定性並相較於習知的包封過程更簡化,並且確定當在含有預定濃度之藻酸鹽及碳酸鹽的培養基中培養益
生菌時,益生菌的冷凍乾燥生存力、耐熱性及體內穩定性(耐酸性及耐膽汁性)可顯著改善,其短期及長期儲存穩定性亦可大幅改善,進而相關技術方案匯結成本發明。
(專利文件1)韓國專利第10-1605516號
(專利文件2)韓國專利申請案第10-2003-0009268號
(非專利文件1)Taejin Kang, BioWave, 2009, Vol. 11, No. 7, pp 1-20
(非專利文件2)Mercenier A. et al., Curr. Pharm. Des. 9(2):175-191, 2003
本發明之一目的在於提供透過相較於習知製造囊化益生菌技術為簡單之自發形成骨架型膠囊保護膜的技術來製造展現出改善之乳酸菌的冷凍乾燥生存力、耐熱性、儲存穩定性及體內穩定性之囊化益生菌的方法,以及提供透過上述方法製造之囊化益生菌的用途。
為了達成上述目的,本發明提供製造囊化益生菌的方法,其中益生菌被包埋於藻酸鹽水凝膠內,包含:(a)藉由在含有藻酸鹽及會透過結合藻酸形成水凝膠之鹽類的培養基中培養益生菌來自發形成一藻酸鹽水凝膠;以及
(b)回收被自發形成的藻酸鹽水凝膠包封的益生菌。
此外,本發明提供透過上述方法製造之囊化益生菌,以及包含其之組合物、食品、功能性健康食品、化妝品及藥劑。
此外,本發明提供本發明之囊化益生菌在製造組合物、食品、功能性健康食品、化妝品及/或藥劑的用途。
此外,本發明提供本發明之囊化益生菌在預防或治療疾病的用途。
此外,本發明提供緩解、預防或治療疾病的方法,包含給予本發明之囊化益生菌。
本發明之上述及其他目的、特徵及其他優點將由以下詳細說明並結合附圖更清楚地被理解,其中:圖1揭示根據本發明較佳實施例之製造囊化益生菌的方法;圖2揭示透過習知之藻酸鹽包封方法及本發明之包封方法所製造之益生菌膠囊的粒徑;以及圖3A至圖3C分別揭示沒有進行包封之乾燥細胞(圖3A)、僅施以包封劑(藻酸鹽)之乾燥細胞(圖3B)以及同時施以包封劑(藻酸鹽)及包封增強劑(澱粉)之乾燥細胞(圖3C)的SEM影像(刻度增量為1微米(μm))。
除非另有定義,否則於此使用之所有技術及科學術
語具有與本發明所屬領域中具有通常知識者所通常理解之意義相同的意義。一般而言,於此使用之命名法在本領域中為眾所周知且典型。
在本發明中,已證實當在同時含有藻酸鹽及會透過結合藻酸形成水凝膠之鹽類的培養基中培養益生菌時,二價陽離子會因隨益生菌增殖而產生之酸的作用從而會透過結合藻酸形成水凝膠之鹽類釋放,並結合培養基中的藻酸,因此自發形成藻酸/二價陽離子水凝膠,隨後自發形成之藻酸/二價陽離子水凝膠與細胞一起回收,從而製造膠囊,其中益生菌透過相較於習知方法為極其簡單的方法被包封。
舉例而言,當會透過結合藻酸形成水凝膠之鹽類為碳酸鈣時,鈣會因在益生菌培養的過程中產生之酸而從碳酸鈣釋放,所釋放之鈣會結合藻酸鹽,因此自發形成藻酸鈣水凝膠。
因此,本發明係關於一種製造囊化益生菌的方法,包含:(a)藉由在含有藻酸鹽及會透過結合藻酸形成水凝膠之鹽類的培養基中培養益生菌來自發形成一藻酸鹽水凝膠;以及(b)回收被自發形成的藻酸鹽水凝膠包封的益生菌。
於此使用之用語「包封(encapsulation)」係指以包封劑包覆原料或將原料包埋於包封劑內。舉例而言,可進行益生菌存在於由包封劑組成之膠囊殼內部之儲藥型(reservoir type)
或是益生菌被包埋於由包封劑組成之基質中之骨架型(matrix type)的包封(Zuidam and Nedovic,(2010)Encapsulation Technologies for Active Food Ingredients and Food Processing,Springer),但本發明不限於此。在本發明中,包封能夠穩定益生菌或保護益生菌免於外部環境及體內環境的影響。
於此使用之用語「囊化益生菌」係指被多種包封劑(例如碳水化合物、糖漿、膠(gums)、水凝膠等)包覆的形式或是被包埋於基質內的形式之益生菌。在本發明中,用語「囊化益生菌」可與「益生菌膠囊(probiotic capsules)互換使用並可具有相同意義。
在本發明中,囊化益生菌可為益生菌存在於由包封劑組成之膠囊殼內部的儲藥型或是益生菌被包埋於由包封劑組成之基質中的骨架型,但本發明不限於此。
在本發明中,囊化益生菌的益生菌被包埋於藻酸鹽水凝膠內。
於此使用之用語「包埋」或「被包埋」表示益生菌被包封於本發明之藻酸鹽水凝膠的結構內所包含之空間或孔隙內。除了益生菌以外,如培養基、水、營養物等之培養組合物亦可包封於空間或孔隙內。
在本發明中,藻酸鹽在水中的溶解度較佳為0.1克/升(g/L)以上,更佳為0.1g/L至10g/L,藻酸鹽較佳為選自由藻酸鈉、藻酸鉀、藻酸鎂、藻酸鈣、藻酸鋰及藻酸銨組成之群組,
但不限於此,可使用任何符合本發明之目的之藻酸鹽而不受限制。
在本發明中,培養基中所包含之藻酸鹽的量為0.1至40g/L,較佳為0.2至15g/L,更佳為0.5至2g/L,最佳為0.8至1.2g/L,但不限於此。
此外,根據本發明之會透過結合藻酸形成水凝膠之鹽類可為在水中的溶解度為0.1g/L以下之二價陽離子鹽,較佳為0.00001g/L至0.1g/L,較佳為含有二價陽離子的鹼性鹽。舉例而言,會透過結合藻酸形成水凝膠之鹽類可為含有二價陽離子的碳酸鹽或硝酸鹽。
舉例而言,含有二價陽離子的碳酸鹽可為選自由碳酸鈣、碳酸鋇、碳酸錳、碳酸銅、碳酸鋅、碳酸鉛、碳酸鎘、碳酸鈷、碳酸鎳及碳酸鍶組成之群組之至少一者,但不限於此。
在另一示例中,含有二價陽離子的硝酸鹽可為選自由硝酸鈣、硝酸鋇、硝酸錳、硝酸銅、硝酸鋅、硝酸鉛、硝酸鎘、硝酸鈷、硝酸鎳及硝酸鍶組成之群組之至少一者,但不限於此。
在本發明中,會透過結合藻酸形成水凝膠之鹽類的量為0.5至10g/L,較佳為1至9g/L,更佳為1.5至8g/L,最佳為2至7g/L,但不限於此。
在本發明中,會透過結合藻酸形成水凝膠之鹽類可用以使陽離子被由培養益生菌所產生之酸解離。
在本發明中,由培養益生菌所產生之酸為在益生菌
的代謝過程中產生之有機酸。由培養益生菌所產生之酸的示例可包含但不限於乳酸、醋酸、檸檬酸、蘋果酸、琥珀酸等。
在本發明中,在步驟(a)中,由培養益生菌所產生之酸可導致陽離子從會透過結合藻酸形成水凝膠之鹽類解離。
在本發明中,在步驟(a)中,藉由使藻酸與從會透過結合藻酸形成水凝膠之鹽類解離的陽離子耦合可形成藻酸鹽水凝膠。
在本發明中,在步驟(a)中,益生菌可藉由培養來增殖。
在本發明中,在步驟(a)中,所培養之益生菌的全部或一部分可被包埋於自發形成之藻酸鹽水凝膠內。
再者,在本發明中,步驟(a)中的培養基可更含有包封增強劑。
包封增強劑用以提升藻酸鹽水凝膠膠囊的堅固性,包封增強劑不可溶。舉例而言,包封增強劑可為選自由澱粉、結晶纖維素、幾丁聚醣、羧甲基纖維素(CMC)及脫脂奶粉組成之群組之至少一者,但不限於此。以澱粉作為包封增強劑的一例,當培養基額外含有澱粉時,由會透過結合藻酸形成水凝膠之鹽類的結合而形成之水凝膠與澱粉會與益生菌混合,從而製造具有更堅固的結構的益生菌膠囊。
在本發明中,在培養基中所包含之包封增強劑的量
為1至20g/L,較佳為2至10g/L,更佳為3至5g/L,最佳為5g/L。
在本發明一實施例中,已證實相較於使用碳酸鈣及冷凍保護劑(cryoprotectant)所製造之製劑,透過本發明之包封方法而不使用冷凍保護劑製造之益生菌膠囊展現出非常優異的冷凍乾燥生存力、耐熱性、在模擬胃腸溶液中的存活率及長期/短期之儲存穩定性。
在本發明中,培養基可如習知的培養基般含有冷凍保護劑,但即使不使用冷凍保護劑,亦可展現出優異的冷凍乾燥生存力、耐熱性、在模擬胃腸溶液中的存活率及長期/短期之儲存穩定性。較佳為培養基不含冷凍保護劑。
再者,在本發明中,已證實在二價陽離子鹽被培養益生菌的過程中益生菌所分泌之酸解離的過程(例如碳酸鈣解離成鈣離子)中會防止培養液(culture broth)的pH過度降低,故可有效率培養益生菌而不需在培養步驟中額外調整pH。
因此,在本發明中,在含有藻酸鹽及會透過結合藻酸形成水凝膠之鹽類的培養基中培養益生菌的過程中,不進行額外pH調整步驟或過程,或是相較於習知的培養過程,進行最小限度的pH調整步驟或過程。
在相應的過程中,益生菌菌株的接種濃度及培養時間可依據菌株類型而適當改變,這對本領域通常知識者為顯而易
見。於此,在接種後的最初濃度可為1×104至5×109菌落形成單位/毫升(CFU/mL),較佳為5×105至4×108CFU/mL,但不限於此。並且,益生菌菌株的培養時間較佳為4小時以上,更佳為6小時以上,使得會透過結合藻酸形成水凝膠之鹽類(例如碳酸鹽)可充分解離,但本發明不限於此。
在本發明中,可藉由回收在步驟(a)中所培養之益生菌的全部或一部分以及自發形成的藻酸鹽水凝膠來進行步驟(b)。
在本發明中,在步驟(b)回收之囊化益生菌可被自然包埋於在步驟(a)自發形成的藻酸鹽水凝膠內。
在本發明中,在步驟(b)之回收的過程中,在步驟(a)未被包埋於自發形成的藻酸鹽水凝膠內的一些益生菌可另外被包埋於藻酸鹽水凝膠內。
在本發明中,在步驟(b)中,當步驟(a)之培養基額外含有包封增強劑時,可回收藻酸鹽水凝膠、包封增強劑及益生菌。
在本發明中,步驟(b)可包含冷卻步驟(a)的培養產物。在本發明中,可在等於或低於培養溫度之溫度下進行冷卻,較佳為37℃以下,更佳為約20℃以下,在本發明一實施例中,培養產物冷卻至約20℃,但本發明不限於此。
在本發明中,步驟(b)可包含進行離心。
在本發明中,步驟(b)可藉由同時回收藻酸鹽水凝膠及益生菌來進行。
在本發明中,在步驟(b)中,在回收的同時或之前攪拌或混合步驟(a)的培養液。舉例而言,藻酸鹽水凝膠及益生菌,或是藻酸鹽水凝膠、包封增強劑及益生菌,可在回收細胞並提供有攪拌件的槽中同時回收並混合。
在本發明中,未被自然包埋於步驟(a)中形成之藻酸鹽水凝膠的一些益生菌可透過混合來另外被包埋。
在本發明中,可進一步進行步驟(c)冷凍乾燥所回收之囊化益生菌。
在本發明中,當進一步進行步驟(c)冷凍乾燥所回收之囊化益生菌時,在將所回收之材料在步驟(c)之冷凍乾燥機分散的過程中可進行攪拌,可進行自然混合。
在本發明中,在步驟(b)之後及步驟(c)之前可額外進行攪拌或混合。具體而言,藻酸鹽水凝膠及益生菌可在回收同時混合,或是可在回收後另外混合。
在本發明中,益生菌可選自由乳酸桿菌屬(Lactobacillus sp.)、雙岐桿菌屬(Bifidobacterium sp.)、鏈球菌屬(Streptococcus sp.)、乳酸球菌屬(Lactococcus sp.)、腸球菌屬(Enterococcus sp.)、明串珠菌屬(Leuconostoc sp.)、片球菌屬(Pediococcus sp.)及魏斯氏菌屬(Weissella sp.)組成之群
組。由於本發明之技術特徵在於證實在菌株培養的過程中優越的藻酸鹽水凝膠包覆可作為改善有益細菌在被包含人類之動物攝取時之生產性、分布及體內穩定性的方法,故對於本領域具有通常知識者顯而易見的是本發明可應用於除了上述細菌以外的有益細菌。
在本發明中,益生菌可為例如選自以下表1所示之菌株中之至少一者,但不限於此。
本發明說明書中使用之菌株的屬名或種名可能不同
於由Zheng等人(Int.J.Syst.Evol.Microbiol.2020;70)重新建立的種名,本領域具有通常知識者可參考相應文件的描述而輕易理解菌株的屬/種。
同時,相較於在益生菌包封方法中在益生菌的培養完成之後引入分開的包封步驟之習知技術,如上所述本發明之方法經簡化,這有利於生產經濟以及減少可能由引入分開的包封步驟所造成之汙染的擔憂,或有利於改善品質控制的方便性,再者,相較於透過習知技術製造之益生菌膠囊,所製造之益生菌的冷凍乾燥生存力、耐熱性、儲存穩定性及體內穩定性受到顯著改善。
因此,本發明另一態樣係關於透過根據本發明之製造囊化益生菌的方法所製造之囊化益生菌。
於此使用之用語「包封」及「囊化益生菌」可理解為與在上述製造囊化益生菌的方法中所描述者具有相同的意義。
在本發明中,囊化益生菌可為益生菌存在於由包封劑組成之膠囊殼內部的儲藥型或是益生菌被包埋於由包封劑組成之基質中的骨架型,較佳為骨架型(Zuidam and Nedovic,(2010)Encapsulation Technologies for Active Food Ingredients and Food Processing,Springer),但本發明不限於此。
在本發明中,囊化益生菌可使益生菌被包埋於藻酸鹽水凝膠內。
在本發明中,囊化益生菌可用作為原料,較佳為功能性原料,其包含於發酵牛奶、加工牛奶、發酵醬油、發酵泡菜、
功能性飲料、功能性食品、一般食品、藥劑、化妝品等,並較佳使用作為口服給藥之功能性健康食品的有效成分。
因此,本發明又另一態樣係關於含有根據本發明之囊化益生菌的組合物以及包含其之食品、功能性健康食品及藥劑。
本發明在另一態樣係關於本發明之囊化益生菌或包含其之組合物在製造食品及/或功能性健康食品的用途。
於此使用之用語「食品」係指肉、香腸、麵包、巧克力、糖果、零食、甜點、披薩、拉麵、其他麵條、口香糖、包含冰淇淋之乳製品、多種湯、飲料、茶、飲品、酒精飲料、維生素複合物、功能性健康食品及健康食品,並包含一般意義上的所有食品。
用語「功能性健康食品」與用語「特定保健用食品(food for special health use,FoSHU)」具有相同意義,係指除了營養供給之外為了有效率展現生物調節功能而加工之具有高醫藥及藥學效果的食品。於此,「功能性」表示為健康之目的而獲得有益功效,例如對於人體的結構及功能的營養調節或生理作用。本發明之食品可使用本領域常用的方法來製造,在製造時,可添加本領域常用的原料及成分。此外,食品的形態只要是被認為食品的製品即不受限,根據本發明之功能性健康食品可為粉末、顆粒、錠劑、膠囊或飲料的形態。
健康食品係具有超過一般食品之健康維持或促進之
活性作用的食品,健康補充食品係用於健康補充目的之食品。在某些情況下,用語「功能性健康食品」、「健康食品」及「健康補充食品」可互換使用。
食品組合物可更包含生理上可接受的載體,載體的類型並不特別受,可使用本領域常用之任何載體。
並且,組合物可包含常用於食品組合物中之額外的成分,以改善氣味、味道、外觀等。舉例而言,可包含維生素A、C、D、E、B1、B2、B6、B12、菸鹼酸、生物素、葉酸、泛酸等。此外,可包含礦物質,例如鋅(Zn)、鐵(Fe)、鈣(Ca)、鉻(Cr)、鎂(Mg)、錳(Mn)、銅(Cu)等。此外,可包含胺基酸,例如離胺酸、色胺酸、半胱胺酸、纈胺酸等。
此外,組合物可包含食品添加劑,例如防腐劑(山梨酸鉀、苯甲酸鈉、水楊酸、去氫乙酸鈉等)、消毒劑(漂白粉、高漂白粉、次氯酸鈉等)、抗氧化劑(丁羥甲氧苯(BHA)、丁基羥基甲苯(BHT)等)、色料(焦油色素等)、顯色劑(亞硝酸鈉等)、飄白劑(亞硫酸鈉)、調味劑(MSG等)、甜味劑(甘味精、環己胺磺酸鹽(cyclamate)、糖精、鈉等)、風味劑(香草精、內酯等)、膨脹劑(明礬、D-酒石酸氫鉀等)、強化劑、乳化劑、增稠劑(增稠物)、薄膜形成劑、膠基劑(gum base agents)、泡沫抑制劑、溶劑、改善劑等。添加劑可依據食品的類型而選擇,並可以適當量使用。
在本發明中,除了透過本發明之方法製造之囊化益生菌以外,食品可更包含人類食用可接受的食品補充添加劑,並可與其他食品或食品成分一起使用,並可根據通常方法適當使用。所包含之有效成分之量可依據使用目的(預防、保健或治療)而適當決定。
含有根據本發明之囊化益生菌的食品可以發酵牛奶、加工牛奶、發酵醬油、發酵泡菜及一般食品的形式使用,但不限於此。
並且,含有根據本發明之囊化益生菌的功能性健康食品較佳可為選自由粉末、顆粒、錠劑、膠囊、飲料、茶、發酵牛奶、加工牛奶、發酵醬油、發酵泡菜及維生素複合物組成之群組之形式,但本發明不限於此。
此外,本發明係關於包含根據本發明之囊化益生菌的醫藥組合物及藥劑。
本發明又另一態樣係關於本發明之囊化益生菌或包含其之組合物在製造醫藥組合物及/或藥劑的用途。
本發明使用之用語「預防」及「治療」應被解釋為最廣泛的意義。於此,「預防」表示預防患者之疾病的一或多種臨床症狀的進展,該患者可能接觸或易罹患該疾病但尚未經歷或顯現出該疾病的症狀,「治療」表示阻止或減少疾病的進展或是一或多種臨床症狀的任何動作。
除了含有本發明之囊化益生菌作為有效成分以外,醫藥組合物可更包含常用於醫藥組合物中之適合的載體、賦形劑及稀釋劑。
可包含於組合物中之載體、賦形劑及稀釋劑包含但不限於乳糖、葡萄糖(dextrose)、蔗糖、山梨醇、甘露醇、木醣醇、丁四醇(erythritol)、氫化麥芽糖(maltitol)、澱粉、阿拉伯膠、藻酸鹽、明膠、磷酸鈣、矽酸鈣、纖維素、甲基纖維素、微晶纖維素、聚乙烯氫吡咯酮(polyvinyl pyrrolidone)、水、羥苯甲酸甲酯、羥苯甲酸丙酯、滑石、硬脂酸鎂及礦物油。在配製組合物時,可使用常用的稀釋劑或賦形劑來製備,例如填充劑、增量劑、黏結劑、濕潤劑、崩散劑、界面活性劑等。
根據本發明之醫藥組合物可根據通常的方法以各種劑型配製並使用。適合的劑型較佳包含口服製劑,例如錠劑、丸劑、粉末、顆粒、糖衣錠劑、硬或軟膠囊、溶液、懸浮液、乳液、注射劑、噴霧劑(aerosols)等。在這些製劑之中,最佳為顆粒及粉末丸劑。含有桔梗(Platycodon grandiflorum)萃取物的口服藥劑可以Yonggaksan為例。其他製劑包含但不限於外用製劑、栓劑及無菌注射溶液。
根據本發明之醫藥組合物可使用醫藥上惰性有機或無機載體來配製成適合的劑型。具體而言,當製劑為錠劑、包衣錠劑、糖衣錠劑或硬膠囊時,其可包含乳糖、蔗糖、澱粉或其衍
生物、滑石、碳酸鈣、明膠、硬脂酸或其鹽。此外,當製劑為軟膠囊時,其可包含植物油、蠟、脂肪以及半固態及液態多元醇。此外,當製劑為溶液或糖漿形式時,可包含水、多元醇、甘油及植物油。
除了上述載體以外,根據本發明之醫藥組合物可更包含防腐劑、穩定劑、濕潤劑、乳化劑、增溶劑、甜味劑、色料、滲透壓控制劑、抗氧化劑等。
根據本發明之醫藥組合物以醫藥有效量給藥。在本發明中,「醫藥有效量」係足以以適用於藥學治療之合理的利益/風險比例治療疾病之量,有效劑量程度可依據包含患者的疾病類型、嚴重程度、藥物活性、藥物敏感性、給藥時間、給藥途徑、排泄率、治療期間及服用藥物之因素以及藥學領域中眾所周知之其他因素來決定。根據本發明之醫藥組合物可作為單獨治療劑或結合其他治療劑給藥,可與習知治療劑依序或同時給藥,並可給藥一次或多次。考量所有上述因素,重要的是以能夠使用最小量來獲得最大效果且無副作用之量給予組合物,這可由本領域具有通常知識者輕易決定。
本發明之醫藥組合物可透過各種途徑給予受試者。給藥模式可為例如口服給藥。給藥可透過皮下注射、靜脈注射、肌內注射、子宮內硬膜注射(intrauterine dural injection)或腦血管內注射(intracerebrovascular injection)來進行。本發明之醫藥
組合物的給藥模式取決於作為有效成分之藥物的類型以及多種相關因素,例如所治療之疾病、給藥途徑、患者的年齡、性別及體重以及疾病的嚴重程度。含有根據本發明之囊化益生菌的醫藥組合物及藥劑可用於治療或預防消化性疾病,尤其可展現出改善胃、結腸及小腸的功能之功效。
具體而言,其可用於(i)改善、預防或治療選自由消化不良、缺乏食慾、厭食、過食、不消化、由消化不良所致之胃脹氣、便祕、稀糞、腹瀉及腹脹氣組成之群組之任何症狀,(ii)抑制異常腸發酵,及/或(iii)促進消化或提升腸功能,但本發明不限於此。
本發明之進一步態樣係關於本發明之囊化益生菌在預防或治療疾病的用途。
本發明之進一步態樣係關於治療疾病之方法,包含將本發明之囊化益生菌給予受試者。
在本發明中,疾病可為消化性疾病,方法可用於(i)改善、預防或治療選自由消化不良、缺乏食慾、厭食、過食、不消化、由消化不良所致之胃脹氣、便祕、稀糞、腹瀉及腹脹氣組成之群組之任何症狀,(ii)抑制異常腸發酵及/或(iii)促進消化或提升腸功能,但本發明不限於此。
本發明之進一步態樣係關於包含根據本發明之囊化益生菌的化妝品組合物。
本發明之進一步態樣係關於根據本發明之囊化益生菌在製造化妝品組合物的用途。
在本發明中,化妝品組合物依據囊化益生菌的功效可應用於多種功能及用途,可用於例如保濕皮膚、強化皮膚屏障(skin barrier)、安撫皮膚、預防或改善皮膚損傷或改善皮膚屏障、預防或改善老化或是改善皮膚狀況,但本發明不限於此。
在本發明中,改善皮膚狀況使用於一般意義,不僅包含改善可見的皮膚狀況,還有直接或間接影響皮膚健康的因素。
在本發明中,化妝品組合物可更包含美容上可接受的賦形劑或載體,例如取決於劑型可更包含多種已知的添加劑。舉例而言,可更包含選自由載體、乳化劑、濕潤劑、界面活性劑、螯合劑、抗氧化劑、消毒劑、穩定劑及其組合組成之群組之任何添加劑。
在本發明中,載體的示例可包含但不限於動物油、植物油、蠟、石蠟、澱粉、黃蓍膠(tragacanth)、纖維素衍生物、聚乙二醇、聚矽氧、膨土(bentonite)、矽石、滑石、氧化鋅、乳糖、氫氧化鋁、矽酸鈣、聚醯胺粉末、水、乙醇、異丙醇、碳酸乙酯、乙酸乙酯、苄醇、苯甲酸苄酯、丙二醇、1,3-丁二醇油、甘油脂族酯、聚乙二醇、液態稀釋劑、諸如乙氧基化異硬脂醇、聚氧乙烯山梨醇酯(polyoxyethylene sorbitol ester)及聚氧乙烯山梨糖醇酯(polyoxyethylene sorbitan ester)之懸浮劑、微晶纖維素、
偏氫氧化鋁、洋菜膠(agar)、硫酸脂族醇酯、硫酸脂族醇醚酯、磺酸基琥珀酸單酯、羥乙磺酸鹽(isethionate)、咪唑啉衍生物、牛磺酸甲酯、肌胺酸鹽、硫酸脂肪酸醯胺醚酯、烷基醯胺基甜菜鹼、脂族醇、脂肪酸甘油酯、脂肪酸二乙醇醯胺、羊毛脂衍生物、乙氧基化甘油脂肪酸酯及其組合。
在本發明中,乳化劑之示例可包含但不限於液態石蠟、辛酸十六酯、硬脂酸等。
在本發明中,濕潤劑的示例可包含但不限於甘油、丁二醇、丙二醇、二丙二醇、戊二醇、己二醇、聚乙二醇、山梨醇等。
在本發明中,螯合劑的示例可包含但不限於以二胺四乙酸鈉(EDTA)、α-羥基脂肪酸、乳鐵蛋白、α-羥基酸、檸檬酸、乳酸、蘋果酸、膽綠素等。
在本發明中,抗氧化劑的示例可包含但不限於丁羥甲氧苯、二丁羥甲氧苯、五倍子酸丙酯等。
此外,除了本發明之囊化益生菌以外,本發明之化妝品組合物可更包含至少一有效成分。
在本發明中,化妝品組合物可根據預期用途及方法以多種已知的製劑製備並使用。舉例而言,根據本發明之化妝品組合物可為例如以下形式:乳液、面霜、潤膚乳、滋養霜、保濕霜、眼霜、精華液、化妝軟膏、噴霧、凝膠、面膜、防曬乳、底
妝、粉底、粉末、卸妝霜、卸妝乳、卸妝油、卸妝泡沫、肥皂或沐浴乳,但不限於此。
在根據本發明之用於皮膚改善之化妝品組合物中,當皮膚為頭皮或頭髮時,化妝品組合物可為例如以下形式:養髮液、潤髮劑、護髮油、護髮液、毛髮營養液、洗髮乳、護髮乳、毛髮護理、髮霜、毛髮營養霜、毛髮保濕霜、毛髮按摩霜、髮蠟、髮用霧劑、髮膜、營養髮膜、洗髮皂、髮用清潔泡沫、髮油、乾髮劑、護髮劑、染髮劑、燙髮劑、髮用漂白劑、髮膠、髮釉、理髮、定型液、髮用保濕劑、髮用慕斯或髮用噴霧,但不限於此。
在本發明中,可以美容上可接受之量包含作為化妝品組合物之有效成分的囊化益生菌以及添加劑,較佳為在各國規定之範圍內,例如在不超過由中國政府制定之「化妝品安全評估技術導則」所記載之最大量的範圍。
在本發明中,化妝品組合物可包含於功能性化妝品中。功能性化妝品的標準可依據韓國食品藥品安全部所規定之「功能性化妝品標準和測試方法」,例如化妝品組合物可具有美白、除皺、染髮、抗UV、緩解粉刺、減少掉髮等功能,但本發明不限於此。
在本發明中,化妝品組合物可包含於台灣政府所規定之「化妝品含有醫療或毒劇藥物基準」所記載之含藥化妝品或一般化妝品中。
透過以下示例可獲得對本發明之更好的理解。這些示例僅用以說明本發明,不應被解釋為限制本發明的範圍,這對本領域具有通常知識者為顯而易見。
示例
實驗例1.確認透過根據本發明之製造囊化益生菌的方法獲得之益生菌膠囊的性質
在實驗例1中使用之控制組及示例揭示於以下表2。
控制組1
於7.5升(L)之小型發酵槽(jar fermentor)中製備補充有3g/L碳酸鈣的4L之益生菌培養基(含有30g/L葡萄糖(Daesang)、10g/L酵母萃取物(Biospringer)、15g/L水解大豆蛋白(Tatua)及0.1g/L硫酸鎂(Kali)),並在121℃滅菌25分鐘。將胚芽乳酸桿菌(Lactobacillus plantarum IDCC 3501)(KCTC登入號:13586BP)、洛德乳酸桿菌(Lactobacillus reuteri IDCC 3701)或糞腸球菌(Enterococcus faecium IDCC 2102)接種
至所製備的培養基中,使菌株的初始活細胞數為約1×108CFU/mL,接著在37℃、150rpm培養16小時。在培養終止後,將培養液冷卻至20℃,然後離心收集細胞,接著將細胞冷凍乾燥。
控制組2
於7.5L之小型發酵槽中製備補充有3g/L碳酸鈣的4L之益生菌培養基(含有30g/L葡萄糖(Daesang)、10g/L酵母萃取物(Biospringer)、15g/L水解大豆蛋白(Tatua)及0.1g/L硫酸鎂(Kali)),並在121℃滅菌25分鐘。將胚芽乳酸桿菌IDCC 3501(KCTC登入號:13586BP)、洛德乳酸桿菌IDCC 3701或糞腸球菌IDCC 2102接種至所製備的培養基中,使菌株的初始活細胞數為約1×108CFU/mL,接著在37℃、150rpm培養16小時。在培養終止後,將培養液冷卻至20℃,然後離心收集細胞,接著將細胞與冷凍保護劑(100g/L麥芽糊精+50g/L果寡醣(fructooligosaccharide))以與細胞溶液相同之量(v/w)混合並冷凍乾燥。
示例1
於7.5L之小型發酵槽中製備補充有3g/L碳酸鈣及1g/L藻酸鈉的4L之益生菌培養基(含有30g/L葡萄糖(Daesang)、10g/L酵母萃取物(Biospringer)、15g/L水解大豆蛋白(Tatua)及0.1g/L硫酸鎂(Kali)),並在121℃滅菌25分鐘。將胚芽乳酸桿菌IDCC 3501(KCTC登入號:13586BP)、
洛德乳酸桿菌IDCC 3701或糞腸球菌IDCC 2102接種至所製備的培養基中,使菌株的初始活細胞數為約1×108CFU/mL,接著在37℃、150rpm培養16小時。在培養終止後,將培養液冷卻至20℃,然後在20℃以6,700g離心20分鐘收集細胞,接著將細胞冷凍乾燥。
示例2
於7.5L之小型發酵槽中製備補充有3g/L碳酸鈣、1g/L藻酸鈉及5g/L玉米澱粉的4L之益生菌培養基(含有30g/L葡萄糖(Daesang)、10g/L酵母萃取物(Biospringer)、15g/L水解大豆蛋白(Tatua)及0.1g/L硫酸鎂(Kali)),並在121℃滅菌25分鐘。將胚芽乳酸桿菌IDCC 3501(KCTC登入號:13586BP)、洛德乳酸桿菌IDCC 3701或糞腸球菌IDCC 2102接種至所製備的培養基中,使菌株的初始活細胞數為約1×108CFU/mL,接著在37℃、150rpm培養16小時。在培養終止後,將培養液冷卻至20℃,然後離心收集細胞,接著將細胞冷凍乾燥(圖1)。
實驗例1-1.評估冷凍乾燥生存力
使用篩孔尺寸為425μm的篩網將各示例及控制組之冷凍乾燥的益生菌粉碎、秤重並與麥芽糊精以對應整體粉末的一半重量之量混合。為了量測所製備之冷凍乾燥的益生菌及培養液中的活細胞數,以緩衝溶液(磷酸鹽-檸檬酸鹽緩衝液,Sigma-
Aldrich,P4809)進行連續稀釋,散布於MRS洋菜培養基上,接著在37℃培養24小時,然後對產生之菌落進行計數。冷凍乾燥生存力以冷凍乾燥的益生菌中的活細胞總數相對於培養液中的活細胞總數之比例的百分比來表示。
分析各菌株之冷凍乾燥粉末中的活細胞數之結果揭示於以下表3。IDCC 3501菌株之相對於培養液中之活細胞數的生存力,在控制組1及控制組2分別為23.5%及48.8%,但在示例1及示例2分別為60.6%及83.8%,表示經進行包封之冷凍乾燥的益生菌中的冷凍乾燥生存力高。尤其,同時使用包封劑及包封增強劑的示例2展現出的生存力相較於未經額外處理之控制組1高3.7倍,相較於控制組2高1.8倍。
基於分析IDCC 3701及IDCC 2102菌株之冷凍乾燥粉末中的活細胞數之結果,證實相對於培養液之冷凍乾燥後的生存力顯著提升,如IDCC 3501菌株。這表示自發形成之包封劑及包封增強劑可有效作為冷凍保護劑發揮功能而不需使用額外的冷凍保護劑。
實驗例1-2.評估耐熱性
益生菌膠囊在加工成攝取形式時會經歷各種致命的條件,尤其在加壓成錠劑時,其會瞬間暴露於高溫及高壓。為了確認可透過包封而在菌株生長範圍外的高溫下保護活細胞,將各冷凍乾燥之菌株的活細胞粉末0.1g懸浮於10mL之緩衝溶液,並在水浴中於60℃加熱1小時,然後量測其生存力。將經熱處理的益生菌連續稀釋,散布於MRS洋菜培養基上,接著在37℃培養24小時,然後對產生之菌落進行計數。耐熱性結果以D值表示,其為使活細胞數降低至原本數量的1/10所需的時間(分鐘)。於此,D值係由使活細胞數降低至原本數量的1/10所需的時間來獲得,故數值愈高,則在60℃的耐熱性愈高。基於D值的比較結果,證實所有菌株在示例1及示例2相較於在控制組1及控制組2,展現出較高的耐熱性(以下表4)。
實驗例1-3.在模擬胃腸溶液中的存活率
被攝入人體的益生菌會暴露在難以存活的環境中,直到其以存活狀態抵達腸。十二指腸分泌之胃酸及膽酸為典型之例。因此,為了確認活益生菌的攝取穩定性,量測在食品被攝取時在模擬胃腸道條件的溶液中的存活率。
為了製備模擬胃溶液,將55g/L MRS培養基溶解於蒸餾水,調整成pH為3.0,並接著在121℃滅菌15分鐘以製備酸性MRS培養基。將各冷凍乾燥之菌株的活細胞粉末0.1g懸浮於10mL之MRS培養基,並以100rpm攪拌在37℃培養1小時。將1mL之懸浮液連續稀釋,散布於MRS洋菜培養基上,接著在37℃培養24小時,然後對產生之菌落進行計數。
為了製備模擬腸溶液,將膽汁(Oxgall,Sigma-Aldrich)以4g/L之濃度溶解於蒸餾水,並調整成pH為7.4。將90mL之模擬腸溶液添加至模擬胃溶液的懸浮液中,以100rpm攪拌在37℃培養2小時,間隔1小時取樣,隨後進行連續稀釋,散布於MRS洋菜培養基上,並在37℃培養24小時,然後對產生之菌落進行計數。
當在模擬胃腸溶液中處理益生菌粉末時,IDCC 3501菌株分別在控制組1及控制組2展現出0.3%及15.0%之存活率,分別在示例1及示例2中展現出24.9%及59.8%之存活率。尤其,
示例2在模擬胃溶液中展現出90%以上之耐酸性,最終在3小時之處理後,其存活率較控制組1高721倍,較控制組2高7.2倍(以下表5)。
相較於控制組1及控制組2,IDCC 3701及IDCC 2102菌株在示例1及示例2中亦展現出存活率增加至少1.6倍至最多60倍(以下表6)。
這表示在本發明之冷凍乾燥益生菌製劑中自發形成之包封劑及包封增強劑能在實際的胃腸道中有效保護細胞。
實驗例1-4.儲存穩定性
在分配及儲存乾燥的益生菌原料的過程中,活細胞活性會因溫度、氧氣、水分等因素而逐漸降低。諸如包封之物理屏障能夠藉由保護益生菌細胞免於受此種致命因素的影響而有助於改善儲存穩定性。儘管可由在原料混合及包裝步驟中使用抗氧化劑及脫氧劑或是透過防潮處理來提供針對氧氣及水分的保護,但原料本身仍需要有承受其將暴露之溫度的能力。因此,為了抑制原料的吸濕性,將冷凍乾燥益生菌粉末與作為賦形劑之乾燥玉米澱粉以對應益生菌粉末之量的1至10倍的量混合,接著分開包裝於鋁袋中以防止接觸氧氣及水分。將包裝好的原料在40℃及50℃之嚴苛條件下儲存7天,接著量測短期生存力,在25℃及30℃儲存90天後量測長期生存力。將所儲存之原料以緩衝溶液連續稀釋,散布於MRS洋菜培養基上,接著在37℃培養24小時,然後對產生之菌落進行計數。
基於在嚴苛溫度條件下將益生菌粉末儲存7天後生存力的量測結果,IDCC 3501菌株於40℃的生存力在控制組1及控制組2中分別為1.1%及14.7%,在示例1及示例2中分別為
40.1%及87.2%。並且,其於50℃的生存力在控制組1及控制組2中分別為0.03%及0.2%,在示例1及示例2中分別為5.4%及14.3%。因此,相較於細胞僅經簡單乾燥而無任何後處理之控制組1以及使用冷凍保護劑乾燥之控制組2,經進行包封處理之冷凍乾燥的益生菌表現出較高的短期儲存穩定性。此外,在同時培養包封劑及包封增強劑之示例2的嚴苛條件下的穩定性較僅單獨培養包封劑之示例1高至少兩倍(以下表7及表8)。
相較於控制組,IDCC 3701及IDCC 2102菌株在嚴苛條件下亦表現出相當優異的穩定性,表示透過自發形成根據本發明之骨架型膠囊保護膜的技術製造之乳酸菌的冷凍乾燥製劑,具有非常高的儲存穩定性。
基於將益生菌粉末於25℃及30℃下儲存90天後的生存力的量測結果,IDCC 3501菌株於25℃的生存力在控制組1及控制組2中分別為1.9%及17.8%,在示例1及示例2中分別為56.0%及95.7%,此外,其於30℃的生存力在控制組1及控制組2中分別為0.09%及8.3%,在示例1及示例2中分別為35.0%及86.5%。與上述嚴苛條件的結果相似,示例2的儲存穩定性最高,其次為示例1、控制組2及控制組1,尤其,作為本發明之較佳實施例之示例2於25℃下表現出之90%以上的高穩定性。
相較於控制組,IDCC 3701及IDCC 2102菌株在嚴苛條件下亦展現出相當優異的穩定性,表示透過自發形成根據本發明之骨架型膠囊保護膜的技術製造之乳酸菌的冷凍乾燥製劑,不僅在短期儲存還有在90天以上之長期儲存上具有非常高的儲存穩定性(表7及表8)。
實驗例2.比較透過本發明之包封方法與習知的藻酸鹽包封方法製造之益生菌膠囊的性質
在實驗例2中使用之控制組(製造藻酸鈣原料的一
般方法)及示例如下所示。
控制組1
於7.5L之小型發酵槽中製備補充有3g/L碳酸鈣的4L之益生菌培養基(含有30g/L葡萄糖(Daesang)、10g/L酵母萃取物(Biospringer)、15g/L水解大豆蛋白(Tatua)及0.1g/L硫酸鎂(Kali)),並在121℃滅菌25分鐘。將胚芽乳酸桿菌IDCC 3501(KCTC登入號:13586BP)接種至所製備的培養基中,使其初始活細胞數為約1×108CFU/mL,接著在37℃、150rpm培養16小時。在培養終止後,將培養液冷卻至20℃,然後離心收集400mL之細胞溶液。將如此離心之細胞溶液與藉由添加10mL之蒸餾水與0.4g之藻酸鈉及2g之玉米澱粉而獲得之懸浮液混合、均質化,然後逐滴添加1%氯化鈣水溶液,從而將其製備成珠型(bead form),然後進行冷凍乾燥並收集乾燥的粉末。
控制組2
將以與控制組1相同方式製備之經離心的細胞溶液添加水凝膠、均質化然後冷凍乾燥,其中水凝膠係藉由添加0.4g之藻酸鈉、2g之玉米澱粉及1.2g之碳酸鈣至100mL之蒸餾水以及在以200rpm攪拌下以0.1毫升/秒(mL/sec)之速率添加10%乳酸溶液直至pH為4.00來獲得。使用篩孔尺寸為425μm的篩網將冷凍乾燥細胞粉碎、秤重並與麥芽糊精以對應整體粉末的一半重量之量混合。
示例1
於7.5L之小型發酵槽中製備補充有3g/L碳酸鈣、1g/L藻酸鈉及5g/L玉米澱粉的4L之益生菌培養基(含有30g/L葡萄糖(Daesang)、10g/L酵母萃取物(Biospringer)、15g/L水解大豆蛋白(Tatua)及0.1g/L硫酸鎂(Kali)),並在121℃滅菌25分鐘。將胚芽乳酸桿菌IDCC 3501(KCTC登入號:13586BP)接種至所製備的培養基中,使其初始活細胞數為約1×108CFU/mL,接著在37℃、150rpm培養16小時。在培養終止後,將培養液冷卻至20℃,然後離心收集細胞,接著將細胞冷凍乾燥(圖1)。
實驗例2-1.評估冷凍乾燥生存力
為了量測在控制組及示例中所製備之冷凍乾燥的益生菌及培養液中的活細胞數,以與實驗例1-1相同的方式評估冷凍乾燥生存力。
基於分析在冷凍乾燥粉末中的活細胞數以及證實相對於在培養液中的活細胞數的生存力之結果,冷凍乾燥生存力在控制組1及控制組2中分別為68.7%及43.1%,但在示例1中為84.1%,其被視為相對高。這表示相較於對細胞進行後處理,在培養步驟中形成包封劑能更有效作為冷凍保護劑(以下表9)。
實驗例2-2.評估耐熱性
基於以與實驗例1-2相同的方式評估控制組與示例之活細胞粉末的耐熱性之結果,控制組1及控制組2的D值分別為14.8分鐘及14.2分鐘,但示例1的D值為15.7分鐘,這被視為相對高。因此,證實透過本發明之包封培養過程製造之原料展現出顯著高的耐熱性(以下表10)。
實驗例2-3:在模擬胃腸溶液中的存活率
量測所製備之益生菌(控制組1、控制組2及示例1)各自在模擬胃腸溶液中的存活率及崩解率(disintegration rate)。以與實驗例1-3相同的方式評估在模擬胃腸溶液中的存活率,並在模擬腸溶液中處理所製備之各益生菌2小時後,進一步使用鹽水(0.9%氯化鈉)作為稀釋溶液分析經處理之各益生菌,
並以鹽水分析結果相較於使用緩衝溶液(磷酸鹽-檸檬酸鹽緩衝液)完全溶解經處理之益生菌的水凝膠而獲得之分析結果的比例來決定在模擬胃腸溶液中的崩解率。(崩解率=以模擬胃腸溶液及鹽水稀釋處理2小時後的分析結果/以模擬胃腸溶液及磷酸鹽-檸檬酸鹽緩衝液稀釋處理2小時後的分析結果)
在示例1及控制組1之間最終存活率的差異為約2.1%,這表示其之間的相似性,但示例1的崩解率高至少四倍。這些結果表明,當如控制組1所示包封成珠型時,保護益生菌免受模擬胃腸溶液之影響的能力優異,但益生菌難以如示例1所示在胃腸道中有效崩解及增殖。控制組2表現出與示例1相似的崩解率,但存活率低於示例1,故提供針對模擬胃腸溶液之保護的能力不足(以下表11及表12)。因此,證實相較於習知的藻酸鹽包封方法,本發明之包封方法在實際的胃腸道中展現出優異的崩解性及穩定性。
實驗例2-4.儲存穩定性
以與實驗例1-4相同之方式包裝所製造之各原料,將包裝好的原料在40℃及50℃之嚴苛條件下儲存7天,接著量測短期生存力,在25℃及30℃儲存90天後量測長期生存力。將所儲存之原料以緩衝溶液連續稀釋,散布於MRS洋菜培養基上,接著在37℃培養24小時,然後對產生之菌落進行計數。
基於在嚴苛溫度條件下將益生菌粉末儲存7天後生存力的量測結果,其於40℃的生存力在控制組1及控制組2中分別為72.5%及36.1%,但在示例1中為88.1%,其被視為相對高。並且,其於50℃的生存力在控制組1及控制組2中分別為10.2%及4.3%,但在示例1中為15.4%,其相較於控制組為高。因此,相較於將藻酸鹽應用於後處理步驟中之控制組的原料,在培養步驟中經進行包封處理之示例1的原料表現出高的短期儲存穩定性(以下表13)。
基於取決於溫度之將益生菌粉末儲存90天後的生存力的量測結果,其於25℃的生存力在控制組1及控制組2中分別為76.3%及49.1%,但在示例1中為97.2%,其於30℃的生存力在控制組1及控制組2中分別為58.2%及31.0%,但在示例1中為86.5%,其亦相對高。與短期儲存穩定性之結果相似,相較於控制組1及控制組2,示例1展現出高的長期儲存穩定性,尤其於25℃表現出95%以上之非常高的生存力(以下表14)。
實驗例2-5.分析包封劑的粒徑
比較在培養步驟中自發形成包封劑之示例1與在體外人工形成包封劑之控制組2之間的粒徑。將在示例1中於離心步驟中獲得之細胞溶液以鹽水稀釋,然後以纖維素濾紙(1004047,Whatman)過濾三次收集沉澱物,接著將沉澱物冷凍乾燥。藉由將示例1及控制組2之各乾燥包封劑溶解於鹽水使用粒徑分析儀(LS-I3-320,Beckman Coulter)分析粒徑。
基於乾燥包封劑之粒徑的分析結果,包封劑的平均粒徑在示例1中為82.45μm,在控制組2為146.09μm,表示示例1的包封劑展現出細微的粒徑(圖2)。因此,證實在培養步驟中自發形成包封劑之示例1中,在包封細胞的過程中能夠填充較小的細胞間隙,從而有助於改善穩定性。
基於上述實驗例的結果,相較於使用藻酸鹽包封成珠型之控制組1的過程,以及分開製備藻酸鹽然後使用與示例相同的原理與細胞溶液混合之控制組2的過程,自發形成藻酸鹽包封劑並與細胞溶液混合之根據本發明之製備包封劑的方法,展現出相當優異的冷凍乾燥生存力、耐熱性、在模擬胃腸溶液中的存活率及短期/長期儲存穩定性。尤其,證實透過本發明製備之包封劑為非常細微的顆粒,因此能透過填充細胞之間的間隙發揮保護作用以防止對會不利影響益生菌的存活的各種因素。因此,證
實當透過本發明之方法囊化益生菌菌株時,相較於一般的藻酸鹽包封過程,會展現出高的細胞保護能力。
實驗例3.益生菌膠囊的結構性質
使用SEM觀察胚芽乳酸桿菌IDCC 3501(KCTC登入號:13586BP)的囊化原料。使用FE-SEM(S-4700,Hitachi)以25,000X放大倍率觀察未進行本發明之包封過程的乾燥細胞、僅施以包封劑之乾燥細胞(與實驗例1之示例1相同)以及同時施以包封劑及包封增強劑的乾燥細胞(與實驗例1之示例2相同)。
在未進行包封之乾燥細胞(圖3A)中,細胞之間有明顯間隙,但在僅施以包封劑之乾燥細胞(圖3B)中以及在同時施以包封劑及包封增強劑之乾燥細胞(圖3C)中,細胞被包封劑包圍且其之間的間隙被填補。並且,當觀察細胞菌落的三維結構時,相較於僅施以包封劑之乾燥細胞,施以包封增強劑的乾燥細胞具有相對小的表面積,這表示形成相對少暴露於威脅益生菌之生存的環境的結構(圖3A至圖3C)。
因此,證實透過根據本發明之包封方法製造之益生菌膠囊在結構上非常穩定。
儘管以上詳細揭示本發明之具體實施例,但對於本領域具有通常知識者而言顯而易見的是上述描述僅為較佳示例性實施例且不會被解使為限制本發明的範圍。因此,本發明之實質
範圍由申請專利範圍及其均等範圍所定義。
Claims (20)
- 一種以藻酸鹽水凝膠製造一囊化益生菌(encapsulated probiotics)的方法,包含:(a)藉由在含有一藻酸鹽及會透過結合藻酸形成水凝膠之一鹽類的一培養基中培養一益生菌,隨著該益生菌的增殖而同時自發形成一藻酸鹽水凝膠;以及(b)回收被自發形成的該藻酸鹽水凝膠包封的該益生菌,其中在步驟(a)中,因培養該益生菌而產生之酸使陽離子從會透過結合藻酸形成水凝膠之該鹽類解離,所解離之陽離子及藻酸彼此耦合,從而自發形成該藻酸鹽水凝膠。
- 如請求項1所述之方法,其中該囊化益生菌的該益生菌被包埋(entrapped)於該藻酸鹽水凝膠內。
- 如請求項1所述之方法,其中該囊化益生菌為骨架型(matrix type)。
- 如請求項1所述之方法,其中該藻酸鹽在水中的溶解度為0.1克/升以上。
- 如請求項4所述之方法,其中該藻酸鹽選自由藻酸鈉、藻酸鉀、藻酸鎂、藻酸鈣、藻酸鋰及藻酸銨組成之群組。
- 如請求項1所述之方法,其中會透過結合藻酸形成水凝膠之該鹽類在水中的溶解度為0.1克/升以下。
- 如請求項6所述之方法,其中會透過結合藻酸形成水凝膠之該鹽類為二價陽離子的一碳酸鹽或一硝酸鹽。
- 如請求項7所述之方法,其中該碳酸鹽選自由碳酸鈣、碳酸鋇、碳酸錳、碳酸銅、碳酸鋅、碳酸鉛、碳酸鎘、碳酸鈷、碳酸鎳及碳酸鍶組成之群組。
- 如請求項7所述之方法,其中該硝酸鹽選自由硝酸鈣、硝酸鋇、硝酸錳、硝酸銅、硝酸鋅、硝酸鉛、硝酸鎘、硝酸鈷、硝酸鎳及硝酸鍶組成之群組。
- 如請求項1所述之方法,其中該藻酸鹽在該培養基中的含量為0.1克/升至40克/升,會透過結合藻酸形成水凝膠之該鹽類在該培養基中的含量為0.5克/升至10克/升。
- 如請求項1所述之方法,其中在步驟(a)的該培養基更含有一包封增強劑。
- 如請求項11所述之方法,其中該包封增強劑選自由澱粉、結晶纖維素、幾丁聚醣、羧甲基纖維素及脫脂奶粉組成之群組。
- 如請求項12所述之方法,其中該包封增強劑在該培養基中的含量為1克/升至20克/升。
- 如請求項1所述之方法,其中該益生菌選自由乳酸桿菌屬(Lactobacillus sp.)、雙岐桿菌屬(Bifidobacterium sp.)、鏈球菌屬(Streptococcus sp.)、乳酸球菌屬(Lactococcus sp.)、腸球菌屬(Enterococcus sp.)、明串珠菌屬(Leuconostoc sp.)、片球菌屬(Pediococcus sp.)及魏斯氏菌屬(Weissella sp.)組成之群組。
- 如請求項1所述之方法,更包含(c)冷凍乾燥所回收之被該藻酸鹽水凝膠包封的該益生菌。
- 一種囊化益生菌,透過如請求項1至15之任一項所述之方法製造。
- 如請求項16所述之囊化益生菌,其中該益生菌被包埋於藻酸鹽水凝膠內。
- 一種食品或功能性健康食品,包含如請求項16所述之囊化益生菌。
- 一種醫藥組合物或藥劑,包含如請求項16所述之囊化益生菌。
- 一種化妝品組合物,包含如請求項16所述之囊化益生菌。
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CN105567669A (zh) * | 2016-01-08 | 2016-05-11 | 魏永刚 | 益生菌微胶囊制剂及其制备方法 |
CN109700781A (zh) * | 2019-02-25 | 2019-05-03 | 绍兴同创生物科技有限公司 | 一种靶向肠道的益生菌微胶囊及其制备方法 |
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KR101605516B1 (ko) | 2015-06-11 | 2016-03-23 | 주식회사 종근당바이오 | 유산균의 생존율, 저장안정성, 내산성 또는 내담즙성을 증가시키는 방법 |
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CN109700781A (zh) * | 2019-02-25 | 2019-05-03 | 绍兴同创生物科技有限公司 | 一种靶向肠道的益生菌微胶囊及其制备方法 |
Non-Patent Citations (2)
Title |
---|
期刊 Nicole Morin et al., "Production of Lactococcus lactis biomass by immobilized cell", Journal of Industrial Microbiology, 9 (1992) 131-135.;期刊 Gauri Aeron, Shiwangi M (2017) Immobilization and microencapsulation. J Adv Res Biotech 2(3): 1-4.;期刊 刘瑛华、赵进宝、吕秀芳,微胶囊包埋技术在益生菌制品中的应用,2004 * |
期刊 刘瑛华、赵进宝、吕秀芳,微胶囊包埋技术在益生菌制品中的应用,2004。 |
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KR20220088367A (ko) | 2022-06-27 |
AU2021400709A1 (en) | 2023-07-13 |
JP2023554512A (ja) | 2023-12-27 |
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