本發明提供一種益生菌組合物,其包含乾酪乳酸桿菌培養物、胚芽乳酸桿菌培養物、副乾酪乳酸桿菌培養物及醫藥上可接受之外用賦形劑。 參考以下對本發明之各態樣、實例、及伴隨相關描述之化學圖式及表格的詳細描述,可更容易地瞭解本發明。在揭示及描述本發明之組合物之前,應瞭解,除非由申請專利範圍另外特別地指出,否則本發明不受限於特定製備方法、載劑或調配物、或將本發明益生菌調配成用於局部或非經腸投予之產物或組合物的特定模式,此係由於熟習相關技術之通常知識者非常清楚此等事情是可以加以變化的。亦應瞭解,本文所用之術語僅用於描述特定態樣之目的而不意欲用於限制性本發明之範疇。 除非另外指出,否則如本發明所用之以下術語應解釋為具有以下含義。 範圍在本文中通常表述為「約」一個特定值及/或至「約」另一個特定值。當表述此類範圍時,一態樣為包括一個特定值及/或至另一個特定值之範圍。類似地,當值藉由使用字「約」表述為近似值時,應瞭解特定值可形成另一態樣。另外應瞭解,每一範圍之各端點皆有顯著性,一端點與另一端點既有相關性,亦彼此獨立。 「視情況」或「視情況地」意謂隨後所述之事件或狀況可能發生或可能不發生,且該描述包括該事件或狀況發生之情況及其未發生之情況。舉例而言,「視情況包含藥劑」意謂該藥劑可能存在或可能不存在。 必須指出,除非上下文另外清楚規定,否則如本說明書及隨附申請專利範圍中所用之單數形式「一」及「該」包括複數個所指標的物。因此,除非上下文另外需要,否則單數術語應包括複數且複數術語應包括單數。 如本文所用之術語「個體」表示任何動物,較佳為哺乳動物,且更佳為人類。個體之實例包括人類、非人類靈長類動物、齧齒動物、天竺鼠、兔、綿羊、豬、山羊、乳牛、牛、馬、狗、貓及其轉殖基因物種。 術語如本文所提供之化合物的「有效量」意謂該益生菌之量足以提供對所需功能之所需調節。如下文所指出,確實的需要量將在個體之間有變化,此視個體之疾病病況、身體狀況、年齡、性別、物種及體重、組合物之特性及配方等而定。給藥方案可經調整以誘導最佳治療反應。舉例而言,可每日投予若干分次劑量,或可依治療情形之緊急程度按比例減少劑量。因此,很難指定確實的「有效量」。然而,本發明領域中具有通常知識者使用常規實驗即可確定適當的有效量。 如本文所用之術語「治療」表示逆轉、減輕或改善此術語所適用之病症或病狀、或該病症或病狀之一或多種症狀,或抑制其進展。 如本文所用之術語「載劑」或「賦形劑」係指自身並不為治療劑,而是用作用於將治療劑傳遞至個體之載劑及/或稀釋劑及/或佐劑或媒劑,或添加至調配物中以改善調配物之處理或儲存性質或允許或有助於組合物之劑量單位形成適於投予之劑量單位的任何物質。適合之載劑或賦形劑為一般熟習製造醫藥調配物或食品之通常知識者所熟知。載劑或賦形劑可包括(舉例而言但不限於)緩衝劑、稀釋劑、崩解劑、黏著劑、濕潤劑、聚合物、潤滑劑、滑動劑、為遮蔽或抵消不良味道或氣味而添加之物質、調味劑、染料、芳香劑、如親水性或親脂性膠化劑、防腐劑、抗氧化劑、溶劑、香料、填料、顏料、臭味吸收劑、等滲透劑、錠劑佐劑、保濕劑、螯合劑、結合劑及為改善組合物之外觀而添加之物質。可接受之載劑或賦形劑包括但不限於檸檬酸鹽緩衝劑、磷酸鹽緩衝劑、乙酸鹽緩衝劑、碳酸氫鹽緩衝劑、硬脂酸、硬脂酸鎂、氧化鎂、磷酸及硫酸之鈉鹽及鈣鹽、碳酸鎂、滑石、明膠、阿拉伯膠、海藻酸鈉、果膠、糊精、甘露糖醇、山梨糖醇、乳糖、蔗糖、澱粉、明膠、纖維素物質(諸如烷酸之纖維素酯及纖維素烷基酯)、低熔點蠟、可可脂、胺基酸、尿素、醇類、抗壞血酸、磷脂、蛋白質(例如血清白蛋白)、乙二胺四乙酸(EDTA)、二甲亞碸(DMSO)、氯化鈉或其他鹽、脂質體、甘露糖醇、山梨糖醇、甘油或粉末、聚合物(諸如聚乙烯吡咯啶酮、聚乙烯醇及聚乙二醇)、及其他醫藥學上可接受之物質。載劑不應破壞治療劑之藥理學活性,且在以足以傳遞治療量之藥劑的劑量投予時應無毒性。 單獨的益生菌其作用能力有限,根據本發明之組合物包含多種益生菌之組合,具有治療各種皮膚病症之療效。 於本發明之一具體實施例中,乾酪乳酸桿菌係為IBS041(購自創百股份有限公司)、Lc6(購自元弘草本科研有限公司)或LCC138(購自麗豐實業股份有限公司)菌株;胚芽乳酸桿菌係為BH02(購自創百股份有限公司)、Lp01(購自康普森貿易有限公司)、Lp28(購自生合生物科技股份有限公司)、Lp168(購自麗豐實業股份有限公司)或SL89(購自元弘草本科研有限公司)菌株;副乾酪乳酸桿菌係為BH08(購自創百股份有限公司)、Lp33(購自生合生物科技股份有限公司)、Lpc39(購自元弘草本科研有限公司)或Lpc178(購自麗豐實業股份有限公司)菌株。 根據本發明之益生菌組合物中益生菌之菌數係具有治療有效量,本發明領域中具有通常知識者使用常規實驗即可確定適當的有效量,於本發明之一較佳具體實施例中,菌數範圍為約106
cfu/g (mL)至約1014
cfu/g (mL);更佳係為約108
cfu/g (mL)至約1012
cfu/g (mL);尤佳係為約109
cfu/g (mL)至約1011
cfu/g (mL)。 另一方面,為取得傑出之療效,各益生菌培養物於益生菌組合物中之比例為基於組合物之總重量為100%,乾酪乳酸桿菌培養物之重量含量為約0.01%至約20%,較佳為約1%至約10%;胚芽乳酸桿菌培養物之重量含量為約0.001%至約15%,較佳為約0.01%至約10%;副乾酪乳酸桿菌之重量含量為約0.001%至約15%,較佳為約0.01%至約10%。 於本發明之一較佳具體實施例中,針對不同之皮膚病症,根據本發明之益生菌組合物可另包含其他益生菌培養物,較佳地,根據本發明之益生菌組合物可另包含乳酸桿菌屬培養物、鏈球菌屬培養物、雙叉桿菌屬培養物或酵母菌培養物。 於本發明之一較佳具體實施例中,乳酸桿菌屬培養物包含但不限於保加利亞乳桿菌(Lactobacillus bulgaricus
),例如LDB198(購自麗豐實業股份有限公司);鼠李糖乳桿菌(Lactobacillus rhamnosus
),例如LCR103(購自麗豐實業股份有限公司)、BH09(購自創百股份有限公司)、LR04(購自康普森貿易有限公司)、LGG176(購自麗豐實業股份有限公司);羅氏乳桿菌(Lactobacillus reuteri
),例如購自康普森貿易有限公司;唾液乳酸桿菌(Lactobacillus salivarius
),例如CRL 1328(購自康普森貿易有限公司);短乳桿菌(L. brevis
),例如購自創百股份有限公司;短雙歧桿菌(Bifidobacterium breve
),例如BR03(購自康普森貿易有限公司);乾酪乳桿菌(L. casei
),例如IBS041(購自創百股份有限公司);發酵乳桿菌(L. fermentum
),例如BH03(購自創百股份有限公司);嗜酸乳酸桿菌(Lactobacillus acidophilus
),例如DDS-1(購自創百股份有限公司)、LA107(購自麗豐實業股份有限公司)、LA05(購自元弘草本科研有限公司);芽孢乳酸菌(Bacillus coagulans
),例如Unique IS-2(購自創百股份有限公司)、BC208(購自麗豐實業股份有限公司);納豆芽孢桿菌(Bacillus subitils
natto),例如BSN287(購自麗豐實業股份有限公司);乳酸球菌(Enterococcus faecalis
),例如EC-12(購自康普森貿易有限公司)。 於本發明之一較佳具體實施例中,鏈球菌屬培養物培養物包含但不限於嗜熱鏈球菌(Streptococcus thermoplilus
),例如ST138(購自麗豐實業股份有限公司)。 於本發明之一較佳具體實施例中,雙叉桿菌屬培養物包含但不限於比菲德氏菌(Bifidobacterium bifidum
),例如BB223(購自麗豐實業股份有限公司)、BGN4®(購自創百股份有限公司);雷特氏菌(Bifidobacterium lactis
),例如BLA281(購自麗豐實業股份有限公司);龍根菌(Bifidobacterium longum
),例如BL268(購自麗豐實業股份有限公司)、BORI®(購自創百股份有限公司)、BL03(購自康普森貿易有限公司)、BL08(購自元弘草本科研有限公司)。根據本發明之培養物係指使益生菌增殖過程中之產物,其包含但不限於活化菌體、不活化菌體、或其蛋白質、胜肽、分泌物或代謝產物。該培養物可進一步經純化或濃縮,以獲得治療有效劑量。該等純化或濃縮之方法為本發明所屬技術領域中具通常知識者可進行者。 根據本發明之益生菌組合物較佳為醫藥組合物或化妝品組合物。 依據不同之投予方式,根據本發明之益生菌組合物可為不同之形式,例如氣溶膠、乳液、奈米乳液、液體、溶液、凝膠、微囊體、乳劑、粉末、顆粒、乳膏、膏糊、油膏、軟膏、糊狀物、懸浮液、分散液、發泡體、軟膏劑或噴劑。 本發明之醫藥組合物可藉由本發明領域中已知之任何方法局部或全身投予,包括但不限於藉由肌肉內、皮內、靜脈內、皮下、腹膜內、鼻內、經口、黏膜或外部途徑投予。適當的投藥途徑、調配方法及投藥時程可由本發明領域中具有通常知識者來決定。在本發明中,醫藥組合物可根據相應投藥途徑以多種方式調配,諸如液體溶液、懸浮液、乳液、糖漿、錠劑、丸劑、膠囊、持續釋放調配物、散劑、顆粒、安瓿、注射液、輸注液、套組、軟膏、洗劑、擦劑、乳膏或其組合。視情況,其可經滅菌或與任何醫藥學上可接受之載劑或賦形劑混合,其中有許多醫藥學上可接受之載劑或賦形劑已為一般技術者所知。 本發明所言之外部途徑亦可稱為局部投藥,包含但不限於以吹氣或吸入投藥。局部投藥之各類製劑實例包含軟膏、乳液、乳霜、凝膠、發泡體,以經皮貼片輸送之製劑,吸入或吹氣用之粉末、噴霧劑、氣溶膠、膠囊或藥匣,或滴劑(例如眼睛用或鼻子用滴劑),供霧化用溶液/懸浮液、栓劑、陰道藥栓、駐留灌腸劑及咀嚼劑或可吸入之錠劑或藥片或脂質或為膠囊製劑。 軟膏、乳霜及凝膠可例如配合水性或油性基質,且添加適用增稠劑及/或膠凝劑及/或溶劑調配。該基質因此可包含例如水及/或油,如液態鏈烷或植物油,如花生油或蓖麻油,或溶劑如聚乙二醇。可依據基質性質使用之增稠劑及膠凝劑包含軟質鏈烷、硬脂酸鋁、鯨醯硬脂基醇、聚乙二醇、毛脂肪、蜜蠟、羧基聚亞甲基及纖維素衍生物,及/或單硬脂酸甘油酯,及/或非離子性乳化劑。 乳液可配合水性或油性基質調配,且通常亦含有一或多種乳化劑、安定劑、分散劑、懸浮劑或增稠劑。 外塗用粉末可配合任何適用之粉末狀基質形成,例如滑石、乳糖或澱粉。滴劑可配合水性或非水性基質調配,且亦包括一或多種分散劑、溶解劑、懸浮劑或保存劑。 噴霧組合物可例如調配成水溶液或懸浮液,或調配成自預加壓袋輸送之氣溶膠,如劑量吸入器,且配合使用適用之液化推進劑。適用於吸入用之氣溶膠組合物可為懸浮液或溶液,該氣溶膠組合物可視情況含有額外之技藝中習知之調配佐藥,如介面活性劑例如油酸或卵磷脂及共溶劑例如乙醇。 局部用製劑可藉由每天對欲作用之區域施用一或多次投藥;且在皮膚區域上較佳使用覆蓋貼片。可藉由黏著劑儲存系統持續或延長輸送。 根據本發明之化妝品組合物可為水相調配物,其本質上包括水;其亦可包含水及與水互溶溶劑之混合物(在25℃為大於50重量%之水互溶力),例如含1至5個碳原子之低碳單醇,如乙醇或異丙醇,含2至8個碳原子之二醇,如丙二醇、乙二醇、1,3-丁二醇、或二丙二醇,C 3 -C 4 酮與C 2 -C 4 醛,及甘油。該水相調配物較佳為水性凝膠或水凝膠調配物之形式。水凝膠調配物包含增稠劑以將液態溶液增稠。增稠劑之實例包括但不限於碳合物、纖維素為主材料、膠、海藻素、瓜爾膠、果膠、鹿角菜苷、明膠、礦物性或經改質礦物性增稠劑、聚乙二醇與多醇、聚丙烯醯胺、及其他之聚合增稠劑。較佳為使用對組合物賦與安定性及最適流動特性之增稠劑。 根據本發明之化妝品組合物可為乳液或乳霜調配物之形式。其可含乳化界面活性劑,這些界面活性劑可選自陰離子及非離子界面活性劑。對於界面活性劑之性質及功能(乳化),可參考文件"Encyclopedia of Chemical Technology,Kirk-Othmer",第22卷,第333-432頁,第3版,1979,Wiley,對於陰離子及非離子界面活性劑,特別是該參考資料之第347-377頁。 較佳地,用於本發明組合物之界面活性劑係選自:非離子界面活性劑:脂肪酸,脂肪醇,聚乙氧化或聚乙二醇化脂肪醇,如聚乙氧化硬脂醇或鯨蠟基硬脂醇,蔗糖之脂肪酸酯,烷基葡萄糖酯,特別是C1
-C6
烷基葡萄糖之聚氧伸乙基化脂肪酸酯,及其混合物;陰離子界面活性劑:經胺、氨水或鹼鹽中和之C16
-C30
脂肪酸,及其混合物。較佳為使用可得到水包油或水包蠟乳液之界面活性劑。 根據本發明之化妝品組合物可進一步包含有效量之生理上可接受抗氧化劑,其選自由丁基化對甲酚、丁基化氫醌一甲醚與生育酚組成之群組。 本發明之組合物可進一步包含天然或改質胺基酸、天然或改質固醇化合物、天然或改質膠蛋白、絲蛋白或大豆蛋白。 本發明之組合物較佳為調配成局部應用於角蛋白材料,如皮膚、毛髮、睫毛、或指甲。其可為正常用於此型應用之任何表現形式,特別是水性或油性溶液、水包油或油包水乳液、聚矽氧乳液、微乳液或奈米乳液、水性或油性凝膠或液體、漿狀或固態水合產物之形式。 本發明通常可為流體且可具有白色或有色乳霜、軟膏、乳汁、洗劑、漿液、漿料、慕斯、或凝膠之外觀。其可視需要以氣溶膠、貼片或粉末之形式局部地應用於皮膚上。其亦可為固態形式,例如棒形式。其可作為皮膚用保養產品及/或化妝產品使用。或者,其可調配成洗髮精或潤絲精。 本發明另提供一種如前述益生菌組合物之用途,其係用以製備治療皮膚病症之藥物。 本發明又提供一種於一個體中治療皮膚病症之方法,其包含給予該個體治療有效量之如前述益生菌組合物及視需要之醫藥上可接受之載劑或賦形劑。 根據本發明,該皮膚病症係選自由物理性高溫造成之傷口、糖尿病患之傷口、異位性皮膚炎、過敏、淡化疤痕、皮膚粗糙、脫皮、抑制黑色素生成、蚊蟲叮咬、發炎性病狀、扭傷、切割傷、裂傷、擦傷、刺傷、曬傷、燒傷、水泡、單純皰疹、粉刺、膿皰、痤瘡、青春痘擠壓後造成的傷口、皮膚撕裂、供體和接受移植部位、血腫、壓傷、潰瘍、破皮、皮膚受損後的脫皮、抓後的破皮、雷射修復引起的損傷、挫傷、皮疹、擴張紋痕、瘢痕、妊娠紋、結疤或老化或環境暴露之效應所致。 於本發明之一較佳具體實施例中,該益生菌組合物包含乾酪乳酸桿菌Lc6培養物、胚芽乳酸桿菌SL89培養物、副乾酪乳酸桿菌Lpc39培養物,其於傷口癒合之動物模型中,老鼠皮膚傷口實驗第7天傷口癒合即達到95%以上,顯著優於單一益生菌之作用。 以下之非限制性之實例有助於本發明所屬技術領域中具通常知識者實施本發明。該等實例不應視為過度地限制本發明。本發明所屬技術領域中具有通常知識者可在不背離本發明之精神或範疇的情況下對本文所討論之實施例進行修改及變化,而仍屬於本發明之範圍。實例 1 :益生菌組合物對傷口癒合之效果
益生菌組合物:乾酪乳酸桿菌Lc6菌粉(購自元弘草本科研有限公司)、胚芽乳酸桿菌SL89菌粉(購自元弘草本科研有限公司)、副乾酪乳酸桿菌Lpc39菌粉(購自元弘草本科研有限公司),將菌粉依Lc6:SL89:Lpc39為30%: 35%: 35%之比例溶於蒸餾水後,使用離心方式取其沉澱物,將前述所得之沈澱物以10%之比例,與凝膠形成劑(Acrylates/C10-30 alkyl acrylate crosspolymer)調配成凝膠。 動物模型:為模擬傷口癒合情況,將小鼠背部皮層打洞(5 mm)後,使用益生菌組合物處理,觀察傷口癒合情形。實驗小鼠5隻,左邊為益生菌組合物處理組及右邊為未使用益生菌組合物對照組。將上述調配之益生菌組合物每天塗抹一次於傷口部位,對照組則使用無添加益生菌組合物之凝膠。 結果:如圖1(A)及(C)所示,統計益生菌組合物使用後對傷口癒合面積的影響,第一天結果顯示未處理益生菌組相較於打洞後,傷口面積約縮小20%,而處理益生菌組傷口面積縮小約40%。於給藥7天後發現,使用益生菌組合物後對傷口面積縮小約95%,而未處理組縮小約80%。此結果顯示,益生菌組合物對於傷口癒合具有顯著的促進作用。實例 2 :益生菌組合物對糖尿病傷口癒合之效果
益生菌組合物:乾酪乳酸桿菌LCC138菌粉(購自麗豐實業股份有限公司)、胚芽乳酸桿菌LP01菌粉(購自康普森貿易有限公司)、副乾酪乳酸桿菌BH08菌粉(購自創百股份有限公司),將菌粉依LCC138:LP01:BH08為30%: 35%: 35%之比例溶於蒸餾水後,使用離心方式取其沉澱物,將前述所得之沈澱物以10%之比例,與凝膠形成劑(Acrylates/C10-30 alkyl acrylate crosspolymer)調配成凝膠。 動物模型:為模擬糖尿病傷口癒合情況,使用鏈脲佐菌素(Streptozotocin,STZ)誘發糖尿病小鼠,將背部皮層打洞(5 mm)後,使用益生菌組合物處理,觀察傷口癒合情形。實驗為益生菌組合物處理組及未使用益生菌組合物對照組,兩組小鼠各5隻,將上述調配之益生菌組合物每天塗抹一次於傷口部位,對照組則使用無添加益生菌組合物之凝膠。 結果:如圖1(B)及(C)所示,統計益生菌組合物使用後對傷口癒合面積的影響,第五天結果顯示,未處理益生菌組相較於打洞後,傷口面積約縮小18%,而處理益生菌組傷口面積縮小約55%。於給藥7天後發現,使用益生菌組合物後對傷口面積縮小約71%,而未處理組縮小約25%。此結果顯示,益生菌組合物對於糖尿病傷口癒合具有顯著的促進作用。實例 3 : 益生菌組合物對燙傷傷口癒合之效果
益生菌組合物:乾酪乳酸桿菌IBS041菌粉(購自創百股份有限公司)、胚芽乳酸桿菌LP168菌粉(購自麗豐實業股份有限公司)、副乾酪乳酸桿菌Lpc39菌粉(購自元弘草本科研有限公司),將菌粉依IBS041:LP168:Lpc39為30%: 35%: 35%之比例溶於蒸餾水後,使用離心方式取其沉澱物,將前述所得之沈澱物以10%之比例,與凝膠形成劑(Acrylates/C10-30 alkyl acrylate crosspolymer)調配成凝膠。 動物模型:為模擬燙傷傷口癒合情況,將小鼠背部皮層燙熨(5 mm)後,使用益生菌組合物處理,觀察傷口癒合情形。實驗為益生菌組合物處理組及未使用益生菌組合物對照組,兩組小鼠各5隻,將上述調配之益生菌組合物每天塗抹一次於傷口部位,對照組則使用無添加益生菌組合物之凝膠。 結果:如圖2(A)及(B)所示,統計益生菌組合物使用後對燙傷傷口癒合面積的影響,第7天結果顯示,未處理益生菌組相較於燙傷後,傷口面積約縮小5%,而處理益生菌組傷口面積縮小約18%。於給藥14天後發現,使用益生菌組合物後對傷口面積縮小約46%,而未處理組縮小約11%。此結果顯示,益生菌組合物對於燙傷傷口癒合具有顯著的促進作用。實例 4 : 益生菌組合物對痤瘡之效果
益生菌組合物:乾酪乳酸桿菌Lc6菌粉(購自元弘草本科研有限公司)、胚芽乳酸桿菌BH02菌粉(購自創百股份有限公司)、副乾酪乳酸桿菌Lpc39菌粉(購自元弘草本科研有限公司),將菌粉依Lc6:BH02:Lpc39為30%: 35%: 35%之比例溶於蒸餾水後,使用離心方式取其沉澱物,將前述所得之沈澱物以10%之比例,與凝膠形成劑(Acrylates/C10-30 alkyl acrylate crosspolymer)調配成凝膠。 實驗模型:臉上長有痤瘡之自願受試者,使用益生菌組合物處理後,觀察痤瘡情形。將上述調配之益生菌組合物每天塗抹一次於痤瘡部位,對照組則使用無添加益生菌組合物之凝膠。 結果:如圖3(A)~(F)所示,統計益生菌組合物使用後對痤瘡回復的影響,結果顯示膿皰型痤瘡一般時程約為3~4天(A)。結節型痤瘡一般時程約為6~7天(C)。使用益生菌組合物後膿皰型痤瘡約12~24小時回復(B)、結節型痤瘡約48小時回復(D)。(E)以痤瘡面積統計益生菌組合物對痤瘡回復的影響。結果顯示,使用益生菌組合物後對痤瘡回復約24~48小時相較於未使用的痤瘡回復約96小時以後,具有顯著的促進作用。(F)群聚型痤瘡為程度較嚴重之痤瘡,一般時程約為數星期至一個月,在使用益生菌組合物後約14天回復,具有顯著的促進作用。實例 5 : 益生菌組合物對蚊蟲叮咬之效果
益生菌組合物:乾酪乳酸桿菌LCC138菌粉(購自麗豐實業股份有限公司)、胚芽乳酸桿菌SL89菌粉(購自元弘草本科研有限公司)、副乾酪乳酸桿菌Lpc39菌粉(購自元弘草本科研有限公司),將菌粉依LCC138:SL89:Lpc39為30%: 35%: 35%之比例溶於蒸餾水後,使用離心方式取其沉澱物,將前述所得之沈澱物以10%之比例,與凝膠形成劑(Acrylates/C10-30 alkyl acrylate crosspolymer)調配成凝膠。 實驗模型:被蚊蟲叮咬之自願受試者,使用益生菌組合物處理後,觀察回復情形。將上述調配之益生菌組合物每天塗抹一次於叮咬部位。 結果:如圖4(A)~(C)所示,益生菌組合物使用後對蚊蟲叮咬的影響,結果顯示,使用益生菌組合物後0.5-3小時對蚊蟲叮咬之腫包有止癢及消除作用(A)和(B)。(C)為益生菌組合物對台灣鋏蠓(小黑蚊)叮咬作用。一般台灣鋏蠓叮咬之癢性丘疹約7~10天。使用益生菌組合物後3小時對台灣鋏蠓叮咬之癢性丘疹有止癢及消除作用。實例 6 :益生菌組合物對曬傷之效果
益生菌組合物:乾酪乳酸桿菌IBS041菌粉(購自創百股份有限公司)、胚芽乳酸桿菌LP28菌粉(購自生合生物科技股份有限公司)、副乾酪乳酸桿菌LP178菌粉(購自麗豐實業股份有限公司),將菌粉依IBS041:LP28:LP178為30%: 35%: 35%之比例溶於蒸餾水後,使用離心方式取其沉澱物,將前述所得之沈澱物以10%之比例,與凝膠形成劑(Acrylates/C10-30 alkyl acrylate crosspolymer)調配成凝膠。 實驗模型:曬傷之自願受試者,使用益生菌組合物處理後,觀察回復情形。將上述調配之益生菌組合物每天塗抹一次於曬傷部位。 結果:如圖5(A),曬傷皮膚泛紅一般為時程為1週,使用益生菌組合物後24小時皮膚沒有曬傷之疼痛、乾燥粗糙及皮屑剝落之脫皮現象。實例 7 :益生菌組合物對蕁麻疹之效果
益生菌組合物:乾酪乳酸桿菌Lc6菌粉(購自元弘草本科研有限公司)、胚芽乳酸桿菌LP01菌粉(購自康普森貿易有限公司)、副乾酪乳酸桿菌LP33菌粉(購自生合生物科技股份有限公司),將菌粉依Lc6:LP01:LP33為30%: 35%: 35%之比例溶於蒸餾水後,使用離心方式取其沉澱物,將前述所得之沈澱物以10%之比例,與凝膠形成劑(Acrylates/C10-30 alkyl acrylate crosspolymer)調配成凝膠。 實驗模型:蕁麻疹之自願受試者,使用益生菌組合物處理後,觀察回復情形。將上述調配之益生菌組合物每天塗抹一次於蕁麻疹部位。 結果:如圖5(B),使用益生菌組合物後24小時對蕁麻疹部位有止癢及消除作用。實例 8 :益生菌組合物對濕疹之效果
益生菌組合物:乾酪乳酸桿菌LCC138菌粉(購自麗豐實業股份有限公司)、胚芽乳酸桿菌SL89菌粉(購自元弘草本科研有限公司)、副乾酪乳酸桿菌LP178菌粉(購自麗豐實業股份有限公司),將菌粉依LCC138:SL89:LP178為30%: 35%: 35%之比例溶於蒸餾水後,使用離心方式取其沉澱物,將前述所得之沈澱物以10%之比例,與凝膠形成劑(Acrylates/C10-30 alkyl acrylate crosspolymer)調配成凝膠。 實驗模型:濕疹之自願受試者,使用益生菌組合物處理後,觀察回復情形。將上述調配之益生菌組合物每天塗抹一次於濕疹部位。 結果:如圖5(C),濕疹一般為時程為3-7天,使用益生菌組合物後0.5~1小時對濕疹部位有止癢及消除作用。實例 9 :益生菌組合物對接觸性皮膚炎之效果
益生菌組合物:乾酪乳酸桿菌IBS041菌粉(購自創百股份有限公司)、胚芽乳酸桿菌LP01菌粉(購自康普森貿易有限公司)、副乾酪乳酸桿菌LP39菌粉(購自元弘草本科研有限公司),將菌粉依IBS041:LP01:LP39為30%: 35%: 35%之比例溶於蒸餾水後,使用離心方式取其沉澱物,將前述所得之沈澱物以10%之比例,與凝膠形成劑(Acrylates/C10-30 alkyl acrylate crosspolymer)調配成凝膠。 實驗模型:接觸性皮膚炎之自願受試者,使用益生菌組合物處理後,觀察回復情形。將上述調配之益生菌組合物每天塗抹一次於接觸性皮膚炎部位。 結果:如圖5(D),接觸性皮膚炎一般為時程為1~2週,使用益生菌組合物後24~48小時對接觸性皮膚炎部位有止癢及消除作用。實例 10 :益生菌組合物對傷疤淡化之效果
益生菌組合物:乾酪乳酸桿菌Lc6菌粉(購自元弘草本科研有限公司)、胚芽乳酸桿菌SL89菌粉(購自元弘草本科研有限公司)、副乾酪乳酸桿菌BH08菌粉(購自創百股份有限公司),將菌粉依Lc6:SL89:BH08為30%: 35%: 35%之比例溶於蒸餾水後,使用離心方式取其沉澱物,將前述所得之沈澱物以10%之比例,與凝膠形成劑(Acrylates/C10-30 alkyl acrylate crosspolymer)調配成凝膠。 實驗模型:臉部車禍受傷之傷疤之自願受試者,使用益生菌組合物處理後,觀察回復情形。將上述調配之益生菌組合物每天塗抹早晚各一次於傷疤部位。 結果:如圖6,使用益生菌組合物處理20天後傷疤部位有逐漸淡化的現象,處理40天後更具其顯著淡化及美白效果。 上述實施例僅為說明本發明之原理及其功效,而非限制本發明。習於此技術之人士對上述實施例所做之修改及變化仍不違背本發明之精神。本發明之權利範圍應如後述之申請專利範圍所列。The present invention provides a probiotic composition comprising a Lactobacillus casei culture, a Lactobacillus embryonica culture, a Lactobacillus paracasei culture and a pharmaceutically acceptable external excipient. With reference to the following detailed descriptions of various aspects, examples, and chemical schemes and tables accompanying related descriptions of the present invention, the present invention can be understood more easily. Before disclosing and describing the composition of the present invention, it should be understood that, unless otherwise specifically indicated by the scope of the patent application, the present invention is not limited to specific preparation methods, carriers or formulations, or the probiotics of the present invention are formulated for use The specific mode of the product or composition for topical or parenteral administration is due to those who are familiar with the relevant technology knowing that these things can be changed. It should also be understood that the terms used herein are only used for the purpose of describing specific aspects and are not intended to be used to limit the scope of the present invention. Unless otherwise indicated, the following terms as used in the present invention should be interpreted as having the following meanings. Ranges are generally expressed herein as "about" one specific value and/or to "about" another specific value. When expressing such a range, one aspect is a range that includes one specific value and/or to another specific value. Similarly, when a value is expressed as an approximation by using the word "about", it should be understood that a particular value can form another aspect. In addition, it should be understood that each end point of each range is significant, and one end point and the other end point are both related and independent of each other. "Depending on the situation" or "depending on the situation" means that the event or situation described later may or may not occur, and the description includes the occurrence and non-occurrence of the event or situation. For example, "including a drug as appropriate" means that the drug may or may not be present. It must be pointed out that unless the context clearly dictates otherwise, the singular forms "one" and "the" used in the scope of this specification and the appended application include plural of the indicated objects. Therefore, unless the context requires otherwise, singular terms shall include pluralities and plural terms shall include the singular. The term "individual" as used herein means any animal, preferably a mammal, and more preferably a human. Examples of individuals include humans, non-human primates, rodents, guinea pigs, rabbits, sheep, pigs, goats, cows, cows, horses, dogs, cats, and transgenic species thereof. The term "effective amount" of a compound as provided herein means that the amount of the probiotic is sufficient to provide the desired adjustment to the desired function. As pointed out below, the actual required amount will vary from individual to individual, depending on the individual's disease condition, physical condition, age, sex, species and weight, composition characteristics and formula, etc. The dosage regimen can be adjusted to induce the best therapeutic response. For example, several divided doses can be administered daily, or the dose can be reduced in proportion to the urgency of the treatment situation. Therefore, it is difficult to specify an exact "effective amount". However, a person with ordinary knowledge in the field of the present invention can use routine experiments to determine the appropriate effective amount. The term "treatment" as used herein means reversing, alleviating or ameliorating the condition or condition to which this term applies, or one or more symptoms of the condition or condition, or inhibiting its progression. The term "carrier" or "excipient" as used herein means that it is not a therapeutic agent itself, but is used as a carrier and/or diluent and/or adjuvant or vehicle for delivering the therapeutic agent to an individual Or any substance that is added to the formulation to improve the handling or storage properties of the formulation or to allow or facilitate the formation of a dosage unit of the composition into a dosage unit suitable for administration. Suitable carriers or excipients are well known to those skilled in the production of pharmaceutical formulations or foods. Carriers or excipients may include (for example, but not limited to) buffers, diluents, disintegrants, adhesives, wetting agents, polymers, lubricants, slip agents, for masking or counteracting unpleasant tastes or odors. Added substances, flavoring agents, dyes, fragrances, such as hydrophilic or lipophilic gelling agents, preservatives, antioxidants, solvents, fragrances, fillers, pigments, odor absorbents, iso-osmotic agents, lozenge adjuvants, Moisturizers, chelating agents, binding agents and substances added to improve the appearance of the composition. Acceptable carriers or excipients include but are not limited to citrate buffer, phosphate buffer, acetate buffer, bicarbonate buffer, stearic acid, magnesium stearate, magnesium oxide, phosphoric acid and sulfuric acid Sodium and calcium salts, magnesium carbonate, talc, gelatin, gum arabic, sodium alginate, pectin, dextrin, mannitol, sorbitol, lactose, sucrose, starch, gelatin, cellulose substances (such as alkanoic acid) Cellulose esters and cellulose alkyl esters), low melting waxes, cocoa butter, amino acids, urea, alcohols, ascorbic acid, phospholipids, proteins (e.g. serum albumin), ethylenediaminetetraacetic acid (EDTA), two Methanesulfide (DMSO), sodium chloride or other salts, liposomes, mannitol, sorbitol, glycerol or powder, polymers (such as polyvinylpyrrolidone, polyvinyl alcohol and polyethylene glycol), and Other pharmaceutically acceptable substances. The carrier should not destroy the pharmacological activity of the therapeutic agent, and should be non-toxic when administered in a dose sufficient to deliver a therapeutic amount of the agent. A single probiotic has a limited effect. The composition according to the present invention contains a combination of multiple probiotics, which has the effect of treating various skin diseases. In a specific embodiment of the present invention, the Lactobacillus casei strains are strains of IBS041 (purchased from Chuanglibai Co., Ltd.), Lc6 (purchased from Yuanhong Herbal Research Co., Ltd.), or LCC138 (purchased from Laifeng Industrial Co., Ltd.); The Lactobacillus germ strains are BH02 (purchased from Chuangxinbai Co., Ltd.), Lp01 (purchased from Compson Trading Co., Ltd.), Lp28 (purchased from Shenghe Biotechnology Co., Ltd.), and Lp168 (purchased from Laifeng Industrial Co., Ltd.) ) Or SL89 (purchased from Yuanhong Herbal Scientific Research Co., Ltd.); Lactobacillus paracasei is BH08 (purchased from Chuanglibai Co., Ltd.), Lp33 (purchased from Shenghe Biotechnology Co., Ltd.), Lpc39 (purchased from Yuanhong Herbal Research Co., Ltd.) Co., Ltd.) or Lpc178 (purchased from Lai Fung Industrial Co., Ltd.) strain. The number of probiotic bacteria in the probiotic composition according to the present invention has a therapeutically effective amount. Those with ordinary knowledge in the field of the present invention can use routine experiments to determine the appropriate effective amount. In a preferred embodiment of the present invention , The bacterial count ranges from about 10 6 cfu/g (mL) to about 10 14 cfu/g (mL); more preferably, it is about 10 8 cfu/g (mL) to about 10 12 cfu/g (mL); especially The preferred range is about 10 9 cfu/g (mL) to about 10 11 cfu/g (mL). On the other hand, in order to achieve outstanding efficacy, the proportion of each probiotic culture in the probiotic composition is 100% based on the total weight of the composition, and the weight content of the Lactobacillus casei culture is about 0.01% to about 20% , Preferably about 1% to about 10%; the weight content of Lactobacillus embryonicum culture is about 0.001% to about 15%, preferably about 0.01% to about 10%; the weight content of Lactobacillus paracasei is about 0.001 % To about 15%, preferably about 0.01% to about 10%. In a preferred embodiment of the present invention, for different skin conditions, the probiotic composition according to the present invention may additionally include other probiotic cultures, preferably, the probiotic composition according to the present invention may additionally include Lactobacillus culture, Streptococcus culture, Bifidobacterium culture, or yeast culture. In a preferred embodiment of the present invention, the Lactobacillus culture includes but is not limited to Lactobacillus bulgaricus , such as LDB198 (purchased from Laifeng Industrial Co., Ltd.); Lactobacillus rhamnosus ), such as LCR103 (purchased from Lai Fung Industrial Co., Ltd.), BH09 (purchased from Chuang Chuan Bai Co., Ltd.), LR04 (purchased from Compson Trading Co., Ltd.), LGG176 (purchased from Lai Fung Industrial Co., Ltd.); Lactobacillus reuteri , for example, purchased from Compson Trading Co., Ltd.; Lactobacillus salivarius , such as CRL 1328 (purchased from Compson Trading Co., Ltd.); Lactobacillus brevis , for example Purchase of Bifidobacterium Co., Ltd.; Bifidobacterium breve , such as BR03 (purchased from Compson Trading Co., Ltd.); Lactobacillus casei ( L. casei ), such as IBS041 (purchase of Bifidobacterium breve) ; Lactobacillus fermentum ( L. fermentum ), such as BH03 (purchased from Chuangxinbai Co., Ltd.); Lactobacillus acidophilus (Lactobacillus acidophilus), such as DDS-1 (purchased from Chuangxinbai Co., Ltd.), LA107 (purchased from Lactobacillus Fung Industrial Co., Ltd.), LA05 (purchased from Yuanhong Herbal Scientific Research Co., Ltd.); Bacillus coagulans , such as Unique IS-2 (purchased from Chin Fung Co., Ltd.), BC208 (purchased from Lai Fung Industrial Co., Ltd.) ); Bacillus subitils natto, such as BSN287 (purchased from Lai Fung Industrial Co., Ltd.); Lactococcus ( Enterococcus faecalis ), such as EC-12 (purchased from Compson Trading Co., Ltd.). In a preferred embodiment of the present invention, the Streptococcus culture culture includes but is not limited to Streptococcus thermoplilus , such as ST138 (purchased from Lai Fung Industrial Co., Ltd.). In a preferred embodiment of the present invention, the Bifidobacterium culture includes but is not limited to Bifidobacterium bifidum , such as BB223 (purchased from Laifeng Industrial Co., Ltd.), BGN4® (purchased from Chuangbai Co., Ltd.); Bifidobacterium lactis , such as BLA281 (purchased from Lai Fung Industrial Co., Ltd.); Bifidobacterium longum (Bifidobacterium longum), such as BL268 (purchased from Lai Fung Industrial Co., Ltd.), BORI® (purchased from Chuangjibai Co., Ltd.), BL03 (purchased from Compson Trading Co., Ltd.), BL08 (purchased from Yuanhong Herbal Research Co., Ltd.). The culture according to the present invention refers to the product in the process of proliferating probiotics, which includes but is not limited to activated bacteria, inactivated bacteria, or proteins, peptides, secretions or metabolites thereof. The culture can be further purified or concentrated to obtain a therapeutically effective dose. Such purification or concentration methods can be carried out by those with ordinary knowledge in the technical field to which the present invention pertains. The probiotic composition according to the present invention is preferably a pharmaceutical composition or a cosmetic composition. According to different administration methods, the probiotic composition according to the present invention can be in different forms, such as aerosol, emulsion, nanoemulsion, liquid, solution, gel, microcapsule, emulsion, powder, granule, cream , Paste, ointment, ointment, paste, suspension, dispersion, foam, ointment or spray. The pharmaceutical composition of the present invention can be administered locally or systemically by any method known in the art, including but not limited to intramuscular, intradermal, intravenous, subcutaneous, intraperitoneal, intranasal, oral, mucosal or Vote from external channels. Appropriate route of administration, formulation method, and schedule of administration can be determined by a person with ordinary knowledge in the field of the present invention. In the present invention, the pharmaceutical composition can be formulated in a variety of ways according to the corresponding route of administration, such as liquid solutions, suspensions, emulsions, syrups, lozenges, pills, capsules, sustained release formulations, powders, granules, ampoules, injections, Infusion, kit, ointment, lotion, liniment, cream or a combination thereof. Depending on the circumstances, it can be sterilized or mixed with any pharmaceutically acceptable carrier or excipient, among which many pharmaceutically acceptable carriers or excipients are known to those skilled in the art. The external route mentioned in the present invention can also be called local administration, including but not limited to inhalation or inhalation administration. Examples of various preparations for topical administration include ointments, emulsions, creams, gels, foams, preparations delivered by transdermal patches, powders for inhalation or insufflation, sprays, aerosols, capsules or cartridges, Or drops (for example, drops for eyes or nose), solutions/suspensions for atomization, suppositories, vaginal suppositories, retention enemas and chewables or inhalable lozenges or tablets or lipids or capsule preparations. Ointments, creams, and gels can be formulated, for example, with an aqueous or oily base, and an appropriate thickener and/or gelling agent and/or solvent are added. The matrix may therefore comprise, for example, water and/or oils, such as liquid paraffins or vegetable oils, such as peanut oil or castor oil, or solvents such as polyethylene glycol. Thickeners and gelling agents that can be used according to the nature of the matrix include soft alkanes, aluminum stearate, cetostearyl alcohol, polyethylene glycol, hair fat, beeswax, carboxypolymethylene and cellulose derivatives Substance, and/or glycerol monostearate, and/or nonionic emulsifier. The emulsion can be formulated with an aqueous or oily base, and usually also contains one or more emulsifiers, stabilizers, dispersants, suspending agents or thickeners. The powder for external coating can be formed with any suitable powdery base, such as talc, lactose or starch. The drops can be formulated with an aqueous or non-aqueous base, and also include one or more dispersing agents, dissolving agents, suspending agents or preservatives. The spray composition can be formulated, for example, as an aqueous solution or suspension, or as an aerosol delivered from a pre-pressurized bag, such as a dose inhaler, together with a suitable liquefied propellant. The aerosol composition suitable for inhalation may be a suspension or a solution. The aerosol composition may optionally contain additional formulation adjuvants known in the art, such as surfactants such as oleic acid or lecithin and co-solvents such as ethanol. Topical preparations can be administered one or more times per day to the area to be affected; and it is preferable to use a covering patch on the skin area. The adhesive storage system can be used for continuous or extended delivery. The cosmetic composition according to the present invention may be an aqueous phase formulation, which essentially includes water; it may also include a mixture of water and a water-miscible solvent (more than 50% by weight of water-miscibility at 25° C.), for example, containing 1 Low-carbon monoalcohols with to 5 carbon atoms, such as ethanol or isopropanol, glycols with 2 to 8 carbon atoms, such as propylene glycol, ethylene glycol, 1,3-butanediol, or dipropylene glycol, C 3 -C 4 ketones and C 2 -C 4 aldehydes, and glycerol. The aqueous phase formulation is preferably in the form of an aqueous gel or a hydrogel formulation. The hydrogel formulation contains a thickener to thicken the liquid solution. Examples of thickeners include, but are not limited to, carbon compounds, cellulose-based materials, gums, seaweeds, guar gum, pectin, carrageenin, gelatin, mineral or modified mineral thickeners, poly Ethylene glycol and polyol, polyacrylamide, and other polymeric thickeners. It is preferable to use a thickener that imparts stability and optimal flow characteristics to the composition. The cosmetic composition according to the present invention may be in the form of an emulsion or cream formulation. It may contain emulsifying surfactants, and these surfactants may be selected from anionic and nonionic surfactants. For the properties and functions (emulsification) of surfactants, please refer to the document "Encyclopedia of Chemical Technology, Kirk-Othmer", Volume 22, Pages 333-432, 3rd Edition, 1979, Wiley, for anionic and non-ionic interfaces Active agents, especially pages 347-377 of this reference. Preferably, the surfactant used in the composition of the present invention is selected from: nonionic surfactants: fatty acids, fatty alcohols, polyethoxylated or pegylated fatty alcohols, such as polyethoxylated stearyl alcohol or cetyl alcohol Stearyl alcohol, fatty acid esters of sucrose, alkyl glucose esters, especially polyoxyethylated fatty acid esters of C 1 -C 6 alkyl glucose, and mixtures thereof; anionic surfactants: amine, ammonia Or C 16 -C 30 fatty acids neutralized by alkali salts, and mixtures thereof. It is preferable to use a surfactant that can obtain an oil-in-water or wax-in-water emulsion. The cosmetic composition according to the present invention may further comprise an effective amount of a physiologically acceptable antioxidant, which is selected from the group consisting of butylated p-cresol, butylated hydroquinone monomethyl ether and tocopherol. The composition of the present invention may further comprise natural or modified amino acids, natural or modified sterol compounds, natural or modified glial protein, silk protein or soy protein. The composition of the present invention is preferably formulated for topical application to keratin materials such as skin, hair, eyelashes, or nails. It can be in any form normally used for this type of application, especially aqueous or oily solutions, oil-in-water or water-in-oil emulsions, silicone emulsions, microemulsions or nanoemulsions, aqueous or oily gels or liquids, In the form of a slurry or solid hydration product. The present invention can generally be fluid and can have the appearance of a white or colored cream, ointment, milk, lotion, serum, slurry, mousse, or gel. It can be topically applied to the skin in the form of aerosol, patch or powder as needed. It can also be in solid form, for example in stick form. It can be used as skin care products and/or makeup products. Or, it can be formulated into shampoo or conditioner. The present invention also provides a use of the aforementioned probiotic composition, which is used to prepare a medicament for the treatment of skin disorders. The present invention also provides a method for treating skin disorders in an individual, which comprises administering to the individual a therapeutically effective amount of the aforementioned probiotic composition and optionally a pharmaceutically acceptable carrier or excipient. According to the present invention, the skin condition is selected from wounds caused by physical high temperature, diabetic wounds, atopic dermatitis, allergies, scar reduction, rough skin, peeling, inhibition of melanin production, mosquito bites, inflammatory conditions, sprains , Cuts, lacerations, scrapes, stab wounds, sunburns, burns, blisters, herpes simplex, acne, pustules, acne, wounds caused by acne, skin tears, donor and transplant sites, hematomas, Crush, ulcer, broken skin, peeling after skin damage, broken skin after scratching, damage caused by laser repair, contusion, rash, expansion scars, scars, stretch marks, scars or effects of aging or environmental exposure Caused by. In a preferred embodiment of the present invention, the probiotic composition comprises a Lactobacillus casei Lc6 culture, a Lactobacillus embryonica SL89 culture, a Lactobacillus paracasei Lpc39 culture, which is used in an animal model of wound healing. On the 7th day of the skin wound experiment, wound healing reached more than 95%, which was significantly better than a single probiotic. The following non-limiting examples are helpful for those skilled in the art to which the invention belongs to implement the invention. These examples should not be viewed as unduly limiting the invention. Those with ordinary knowledge in the technical field to which the present invention pertains can modify and change the embodiments discussed herein without departing from the spirit or scope of the present invention, and still fall within the scope of the present invention. Example 1 : The effect of probiotic composition on wound healing Probiotic composition: Lactobacillus casei Lc6 powder (purchased from Yuanhong Herbal Research Co., Ltd.), Lactobacillus embryonicum SL89 (purchased from Yuanhong Herbal Research Co., Ltd.), vice Lactobacillus casei Lpc39 bacterial powder (purchased from Yuanhong Herbal Scientific Research Co., Ltd.), dissolve the bacterial powder in distilled water according to the ratio of Lc6: SL89: Lpc39 to 30%: 35%: 35%, and use the centrifugal method to take the sediment, and The precipitate obtained above is formulated into a gel with a gel forming agent (Acrylates/C10-30 alkyl acrylate crosspolymer) at a ratio of 10%. Animal model: In order to simulate wound healing, a hole (5 mm) was drilled into the back cortex of the mouse and treated with a probiotic composition to observe the wound healing. There are 5 experimental mice, the left side is the probiotic composition treatment group and the right side is the control group without the probiotic composition. The probiotic composition formulated above was applied to the wound once a day, and the control group used a gel without the probiotic composition. Result: As shown in Figure 1 (A) and (C), the effect of probiotic composition on wound healing area after use was calculated. The results on the first day showed that the wound area of the untreated probiotic group was approximately reduced compared with that after the hole was punched. 20%, while the wound area of the probiotic group was reduced by about 40%. After 7 days of administration, it was found that the wound area was reduced by about 95% after using the probiotic composition, while the untreated group was reduced by about 80%. This result shows that the probiotic composition has a significant promoting effect on wound healing. Example 2 : Effect of probiotic composition on diabetic wound healing Probiotic composition: Lactobacillus casei LCC138 powder (purchased from Lai Fung Industrial Co., Ltd.), Lactobacillus embryonicum LP01 powder (purchased from Compson Trading Co., Ltd.) ), Lactobacillus paracasei BH08 bacterial powder (purchased from Chuangli Bai Co., Ltd.), dissolve the bacterial powder in distilled water at the ratio of LCC138: LP01: BH08 to 30%: 35%: 35%, and then use centrifugation to collect the precipitate The resulting precipitate is mixed with a gel forming agent (Acrylates/C10-30 alkyl acrylate crosspolymer) at a ratio of 10% to form a gel. Animal model: In order to simulate diabetic wound healing, use streptozotocin (STZ) to induce diabetic mice, punch a hole (5 mm) in the back cortex, and treat it with a probiotic composition to observe the wound healing. The experiment is the probiotic composition treatment group and the control group without probiotic composition. There are 5 mice in each group. The probiotic composition formulated above is applied to the wound once a day, and the control group uses the probiotic composition without addition. The gel of the thing. Results: As shown in Figure 1 (B) and (C), the effect of the probiotic composition on the wound healing area after the use of the probiotic composition was calculated. The results on the fifth day showed that the wound area of the untreated probiotic group was about Reduced by 18%, while the wound area of the probiotic group was reduced by about 55%. After 7 days of administration, it was found that the wound area was reduced by about 71% after using the probiotic composition, while the untreated group was reduced by about 25%. This result shows that the probiotic composition has a significant promoting effect on diabetic wound healing. Example 3 : The effect of probiotic composition on scald wound healing Probiotic composition: Lactobacillus casei IBS041 powder (purchased from Chuanglibai Co., Ltd.), Lactobacillus embryonicum LP168 powder (purchased from Laifeng Industrial Co., Ltd.) , Lactobacillus paracasei Lpc39 bacterial powder (purchased from Yuanhong Herbal Scientific Research Co., Ltd.), the bacterial powder is dissolved in distilled water according to the ratio of IBS041: LP168: Lpc39 to 30%: 35%: 35%, and the sediment is collected by centrifugation , The precipitate obtained above is formulated into a gel with a gel forming agent (Acrylates/C10-30 alkyl acrylate crosspolymer) at a ratio of 10%. Animal model: In order to simulate the healing of scalded wounds, the mouse back cortex was ironed (5 mm) and treated with a probiotic composition to observe the wound healing. The experiment is the probiotic composition treatment group and the control group without probiotic composition. There are 5 mice in each group. The probiotic composition formulated above is applied to the wound once a day, and the control group uses the probiotic composition without addition. The gel of the thing. Results: As shown in Figure 2 (A) and (B), the effect of probiotic composition on the healing area of scalded wounds after use was calculated. The results on the 7th day showed that the wound area of the untreated probiotic group was about Reduced by 5%, while the wound area of the probiotic group was reduced by about 18%. After 14 days of administration, it was found that the wound area was reduced by about 46% after using the probiotic composition, while the untreated group was reduced by about 11%. This result shows that the probiotic composition has a significant promoting effect on the healing of scalded wounds. Example 4 : The effect of probiotic composition on acne Probiotic composition: Lactobacillus casei Lc6 powder (purchased from Yuanhong Herbal Research Co., Ltd.), Lactobacillus embryonicum BH02 powder (purchased from Chuangxinbai Co., Ltd.), side cheese Lactobacillus Lpc39 bacterial powder (purchased from Yuanhong Herbal Scientific Research Co., Ltd.), dissolve the bacterial powder in distilled water according to the ratio of Lc6: BH02: Lpc39 to 30%: 35%: 35%. The obtained precipitate is mixed with a gel forming agent (Acrylates/C10-30 alkyl acrylate crosspolymer) at a ratio of 10% to form a gel. Experimental model: Voluntary subjects with acne on their faces were treated with a probiotic composition to observe the acne situation. The probiotic composition formulated above was applied to the acne area once a day, and the control group used a gel without the probiotic composition. Results: As shown in Figure 3(A)~(F), the effect of the probiotic composition on the recovery of acne after use was calculated. The results showed that the general duration of pustular acne was about 3 to 4 days (A). The general duration of nodular acne is about 6 to 7 days (C). After using the probiotic composition, pustular acne recovers in about 12-24 hours (B), and nodular acne recovers in about 48 hours (D). (E) Calculate the effect of probiotic composition on acne recovery based on the area of acne. The results show that the recovery of acne after use of the probiotic composition is about 24 to 48 hours, compared with the recovery of unused acne after about 96 hours, it has a significant promoting effect. (F) Cluster acne is a more serious type of acne. The general duration is about a few weeks to one month, and it recovers in about 14 days after using the probiotic composition, which has a significant promoting effect. Example 5 : Effect of probiotic composition on mosquito bites Probiotic composition: Lactobacillus casei LCC138 powder (purchased from Lai Fung Industrial Co., Ltd.), Lactobacillus embryonicum SL89 (purchased from Yuanhong Herbal Research Co., Ltd.), Lactobacillus paracasei Lpc39 bacterial powder (purchased from Yuanhong Herbal Scientific Research Co., Ltd.), dissolve the bacterial powder in distilled water according to the ratio of LCC138: SL89: Lpc39 to 30%: 35%: 35%, and use the centrifugal method to take the sediment. The precipitate obtained above is formulated into a gel with a gel forming agent (Acrylates/C10-30 alkyl acrylate crosspolymer) at a ratio of 10%. Experimental model: Voluntary subjects bitten by mosquitoes were treated with the probiotic composition, and the recovery was observed. The probiotic composition formulated above is applied to the bite site once a day. Results: As shown in Figure 4(A)~(C), the probiotic composition has an effect on mosquito bites after use. The results show that 0.5-3 hours after using the probiotic composition, the mosquito bite swelling can relieve itching and Elimination effects (A) and (B). (C) is the effect of the probiotic composition on the bite of Taiwan midges (small black mosquitoes). Generally, itchy papules from bites of Taiwan midges are about 7 to 10 days. 3 hours after using the probiotic composition, it can relieve itching and eliminate the itchy papules caused by biting midges in Taiwan. Example 6 : The effect of probiotic composition on sunburn Probiotic composition: Lactobacillus casei IBS041 powder (purchased from Chuanglibai Co., Ltd.), Lactobacillus embryonicum LP28 powder (purchased from Shenghe Biotechnology Co., Ltd.), Lactobacillus paracasei LP178 powder (purchased from Lai Fung Industrial Co., Ltd.), the powder is dissolved in distilled water at the ratio of IBS041: LP28: LP178 to 30%: 35%: 35%, and the sediment is collected by centrifugation , The precipitate obtained above is formulated into a gel with a gel forming agent (Acrylates/C10-30 alkyl acrylate crosspolymer) at a ratio of 10%. Experimental model: Voluntary subjects with sunburn, after treatment with the probiotic composition, observe the recovery. The probiotic composition formulated above is applied to the sunburned area once a day. Result: As shown in Figure 5(A), the sunburned skin usually has a time course of 1 week. After 24 hours of using the probiotic composition, there is no sunburn pain, dryness and roughness, and peeling of scaly. Example 7 : Effect of probiotic composition on urticaria Probiotic composition: Lactobacillus casei Lc6 powder (purchased from Yuanhong Herbal Research Co., Ltd.), Lactobacillus embryonicum LP01 (purchased from Compson Trading Co., Ltd.), Lactobacillus paracasei LP33 bacterial powder (purchased from Shenghe Biotechnology Co., Ltd.), the bacterial powder is dissolved in distilled water at the ratio of Lc6: LP01: LP33 to 30%: 35%: 35%, and the sediment is collected by centrifugation , The precipitate obtained above is formulated into a gel with a gel forming agent (Acrylates/C10-30 alkyl acrylate crosspolymer) at a ratio of 10%. Experimental model: Voluntary subjects with urticaria, after treatment with the probiotic composition, observe the recovery. The probiotic composition formulated above is applied to the urticaria area once a day. Result: As shown in Figure 5(B), the probiotic composition has antipruritic and elimination effects on the urticaria part 24 hours after the use of the probiotic composition. Example 8 : Effect of probiotic composition on eczema Probiotic composition: Lactobacillus casei LCC138 powder (purchased from Laifeng Industrial Co., Ltd.), Lactobacillus embryonicum SL89 (purchased from Yuanhong Herbal Scientific Research Co., Ltd.), Lactobacillus paracasei LP178 powder (purchased from Lai Fung Industrial Co., Ltd.), the powder is dissolved in distilled water at the ratio of LCC138: SL89: LP178 to 30%: 35%: 35%, and the sediment is collected by centrifugation , The precipitate obtained above is formulated into a gel with a gel forming agent (Acrylates/C10-30 alkyl acrylate crosspolymer) at a ratio of 10%. Experimental model: Voluntary subjects with eczema, after treatment with the probiotic composition, observe the recovery. The probiotic composition formulated above is applied to the eczema area once a day. Result: As shown in Figure 5(C), eczema generally lasts for 3-7 days, 0.5 to 1 hour after using the probiotic composition, it can relieve itching and eliminate the eczema. Example 9 : The effect of probiotic composition on contact dermatitis. Probiotic composition: Lactobacillus casei IBS041 powder (purchased from Chuangbai Co., Ltd.), Lactobacillus embryonicum LP01 powder (purchased from Compson Trading Co., Ltd.) ), Lactobacillus paracasei LP39 bacterial powder (purchased from Yuanhong Herbal Scientific Research Co., Ltd.), the bacterial powder is dissolved in distilled water according to the ratio of IBS041: LP01: LP39 to 30%: 35%: 35%, and the precipitate is collected by centrifugation The resulting precipitate is mixed with a gel forming agent (Acrylates/C10-30 alkyl acrylate crosspolymer) at a ratio of 10% to form a gel. Experimental model: Voluntary subjects with contact dermatitis, after treatment with the probiotic composition, observe the recovery. The probiotic composition formulated above is applied to the contact dermatitis area once a day. Results: As shown in Figure 5(D), contact dermatitis generally lasts for 1 to 2 weeks, and the probiotic composition can relieve itching and eliminate the contact dermatitis within 24 to 48 hours. Example 10 : Effect of probiotic composition on scar reduction Probiotic composition: Lactobacillus casei Lc6 powder (purchased from Yuanhong Herbal Research Co., Ltd.), Lactobacillus embryonicum SL89 (purchased from Yuanhong Herbal Research Co., Ltd.), vice Lactobacillus casei BH08 bacterial powder (purchased from Chuanglibai Co., Ltd.), dissolve the bacterial powder in distilled water according to the ratio of Lc6: SL89: BH08 to 30%: 35%: 35%. The precipitate obtained above is formulated into a gel with a gel forming agent (Acrylates/C10-30 alkyl acrylate crosspolymer) at a ratio of 10%. Experimental model: Voluntary subjects with facial scars injured in a car accident, treated with a probiotic composition, and observed the recovery. The probiotic composition formulated above is applied to the scars once a day in the morning and evening. Result: As shown in Fig. 6, the scars gradually faded after 20 days of treatment with the probiotic composition, and the obvious fade and whitening effects were observed after 40 days of treatment. The above-mentioned embodiments only illustrate the principles and effects of the present invention, but do not limit the present invention. Modifications and changes made by those skilled in the art to the above-mentioned embodiments still do not violate the spirit of the present invention. The scope of rights of the present invention should be listed in the scope of patent application described later.