201141495 六、發明說明： 【發明所屬之技術領域】 本發明係關於一種具有褥瘡改善作用之組合物。更詳細 而言，本發明係關於一種含有乳酸菌作為有效成分之具有 褥瘡改善作用之組合物、以及作為其醫藥、試劑及飲食品 之用途。 【先前技術】 褥瘡係由於持續之壓迫而使流向皮膚、皮下脂肪組織、 肌肉之血流中斷，從而導致該等組織死絕之狀態。於搏瘡 之預防或治療中，為確保局部之血流，而實施以體壓分散 為目的之包括看護、預防、營養管理、皮膚保養在内之局 部療法。於褥瘡之局部療法中，必需正確判斷褥瘡之狀 態，選擇適合該狀態之處理、外用藥及創傷包覆材料，而 應用於患者。於先前之褥，瘡之局部療&中n必需高度 專業之知識，因此要求開發一種更簡便之新的治療法。 且說’近年來’正進行以下嘗試，即關於乳㈣等腸内 細菌，對疾病之預防效果及疾病症狀之改善效果等進行驗 證’欲將其用作可簡便地攝取且安全性較高之醫藥或飲食 品。 例如，關於自人腸管單離之乳酸菌即糞腸球菌£(：_12株 (以下」有時簡稱為「EC_12」），本案申請人報告有抑制 絨毛萎縮之效果及腸管上皮細胞增殖抑制效果（專利文獻 1、非專利文獻υ、腸内菌群之改善效果、通便促進效果 及通便改善㈣之機制（專利文獻2、非專利文獻2〜句、對 I53738.doc 201141495 李斯特菌感染之生物體防禦效果（非專利文獻5)、耐藥菌之 排除效果（專利文獻3)、自然免疫及獲得性免疫之活化效果 (非專利文獻6)、對接觸性皮炎之炎症抑制效果（專利文獻 4)、I型過敏反應（哮喘、花粉病、異位性皮炎）之減輕效果 (專利文獻5、非專利文獻7)、類風濕性關節炎之改善效果 (專利文獻6)、漢生病（麻風病）之預防效果（專利文獻7)、抗 腫瘤效果（非專利文獻8)及燒傷之治癒促進效果（非專利文 獻9)等。 亦包括上述報告在内，迄今為止關於乳酸菌等腸内細菌 已報告有對各種疾病之症狀改善效果，但仍未報告有應用 於褥瘡改善之例。 先前技術文獻 專利文獻 專利文獻1 :曰本專利特開2008-255080號公報 專利文獻2:曰本專利特開2004-5 1530號公報 專利文獻3:曰本專利特開2006-89421號公報 專利文獻4:日本專利特開2006-28050號公報 專利文獻5:曰本專利特開2007-91694號公報 專利文獻6:曰本專利特開2007-254333號公報 專利文獻7 :曰本專利特開2007-290992號公報 非專利文獻 非專利文獻1 :吉田容子等人，第62次曰本營養.食品學會 大會講演要旨集p247(2008) 非專利文獻 2: Microb. Ecol. Health Dis.，17(2), 107-113 153738.doc 201141495 (2005) 非專利文獻3 : Microb. Ecol· Health Dis.，16(4)，188-194 (2004) 非專利文獻 4 : Biosci. Biotechnol. Biochem.，71，60589-1-4 (2007) 非專利文獻 5 : J· New Rem. & Clin.，53(3)，78-88 (2004) 非專利文獻 6 : Animal Sci. J·，78, 92-97 (2007) 非專利文獻 7 : Skin Research, Suppl. 10, 38-44 (2008) 非專利文獻8 :大塚昌孝等人，第15次日本生物治療學會 抄錄集 pll0(2002) 非專利文獻9:山田薰等人’第147次曰本獸醫學會學術集 會講演要旨集p295(2009) 【發明内容】 發明所欲解決之問題 本發明係鑒於上述狀況而成者’其目的在於提供一種具 有褥瘡改善作用’可簡便地投予或攝取，且具有較高之安 全性之組合物》 解決問題之技術手段 本發明者等人為解決上述課題，對褥瘡之小鼠模型中之 乳酸菌之效果進行了研究。具體而言，使料鼠模型攝取 作為乳酸菌之一例之糞腸球菌⑺匕^株），評價其褥瘡改 善作用。其結果’於該小鼠模型中，自褥瘡形成後早期開 始便確認到褥瘡面積之減少，又，於褥瘡形成後之初期， 確認到各種炎症性細胞激素或生長因子 丁〈阿度表現，因此 153738.doc 201141495 判定可促進創傷治癒。進而可判定，於褥瘡形成後之後 期，炎症性細胞激素或生長因子之表現減少，與對照相比 可更快地恢復正常狀態。如此般，糞腸球菌(㈣株)自 褥瘡形成後之早期階段開始便表現出其改善作用。進而， 根據陰性對照群與同日投予糞腸球g(Ec_i2株）之群之比 較，亦可判定，該效果於自褥瘡形成前開始預防性地投予 糞腸球菌（EC-12株）之情形時尤為顯著。 根據以上’本發明者等人發現’翼腸球菌（ec i2株）作 為用於褥瘡之預防或早期階段之治癒的醫藥或飲食品而極 其有用，從而完成本發明。 更詳細而言，本發明係提供如下發明者。 ⑴種用於褥瘡之改善之組合物，其係、含有乳酸菌作為 有效成分而成。 ⑺如（1)之組合物，其中乳酸菌係屬於腸球菌屬者。 (3) 如（1)之組合物，其中乳酸菌為糞腸球菌。 (4) 如⑴至（3)中任—項之組合物，其係醫藥組合物。 (5) 如（4)之組合物，其係經口投予者。 (6) 如（4)或（5)之組合物，其係於褥瘡形成前預防性地投 予。 ()如（1)至（3)巾任—項之纟且合物其係飲食品。 (8) 如（7)之組合物，其係經口攝取者。 (9) 如(7)或(8)之組合物，其係於褥瘡形成前攝取。 (〇)如(4)至(9)中任一項之組合物，丨附加有主旨用於改 善褥瘡之標示。 153738.doc201141495 VI. Description of the Invention: TECHNICAL FIELD OF THE INVENTION The present invention relates to a composition having an acne-improving effect. More specifically, the present invention relates to a composition having an acne-improving action containing lactic acid bacteria as an active ingredient, and use as a medicine, a reagent, and a food or drink thereof. [Prior Art] Acne is a state in which the flow of blood to the skin, subcutaneous fat tissue, and muscle is interrupted due to continued compression, resulting in the death of the tissues. In the prevention or treatment of psoriasis, in order to ensure local blood flow, local treatments including care, prevention, nutrition management, and skin care for the purpose of dispersing body pressure are implemented. In the local treatment of acne, it is necessary to correctly determine the state of acne, and select a treatment, a topical drug, and a wound covering material suitable for the state, and apply it to a patient. Previously, the topical treatment of the sore and the high level of professional knowledge required a new and simpler treatment. In addition, it is said that 'in recent years' is an attempt to verify the preventive effect of the disease and the improvement of the disease symptoms in the intestinal bacteria such as milk (4), and to use it as a medicine that can be easily ingested and has high safety. Or food or drink. For example, regarding the lactic acid bacteria isolated from human intestinal tract, namely Enterococcus faecalis £ (: _12 strain (hereinafter sometimes referred to as "EC_12"), the applicant reported that it has the effect of inhibiting villus atrophy and the inhibitory effect of intestinal epithelial cell proliferation (patent Literature 1, non-patent literature, improvement of intestinal flora, laxative effect, and improvement of laxative (IV) (Patent Document 2, Non-Patent Document 2 to sentence, to I53738.doc 201141495 Listeria infection Body-defending effect (Non-Patent Document 5), elimination effect of drug-resistant bacteria (Patent Document 3), activation effect of natural immunity and acquired immunity (Non-Patent Document 6), and inflammation-inhibiting effect on contact dermatitis (Patent Document 4) ) The alleviation effect of type I allergic reaction (asthma, pollinosis, atopic dermatitis) (Patent Document 5, Non-Patent Document 7), Rheumatoid Arthritis Improvement Effect (Patent Document 6), Han Sin (Leprosy) The preventive effect (Patent Document 7), the antitumor effect (Non-Patent Document 8), and the healing effect of burns (Non-Patent Document 9), etc. In the case of intestinal bacteria such as bacteria, an effect of improving the symptoms of various diseases has been reported, but an example of application to the improvement of acne has not been reported. PRIOR ART DOCUMENT Patent Document Patent Document 1: Patent Publication No. 2008-255080 Patent Document 2 Patent Document 3: Japanese Laid-Open Patent Publication No. 2006-89421, Patent Document 4: Japanese Patent Laid-Open No. 2006-28050, Patent Document 5: Japanese Patent Laid-Open No. 2007- Japanese Patent Laid-Open No. 2007-254333 Patent Document 7: Japanese Patent Laid-Open No. 2007-290992 Non-Patent Document Non-Patent Document 1: Yoshida Yoshiko, etc., 62nd Nutrition .Food Society Conference Lecture Highlights p247 (2008) Non-Patent Document 2: Microb. Ecol. Health Dis., 17(2), 107-113 153738.doc 201141495 (2005) Non-Patent Document 3: Microb. Ecol· Health Dis .16(4), 188-194 (2004) Non-Patent Document 4: Biosci. Biotechnol. Biochem., 71, 60589-1-4 (2007) Non-Patent Document 5: J· New Rem. & Clin., 53(3), 78-88 (2004) Non-Patent Document 6: Animal Sci. J., 78, 92-97 (2007) Non-Patent Document 7: Skin Research, Suppl. 10, 38-44 (2008) Non-Patent Document 8: Ogata Masahiro et al., 15th Japanese Society for Biotherapeutics, Transcripts pll0 (2002) Non-Patent Document 9: Yamada Kaoru et al. 'The 147th 曰 曰 兽医 兽医 兽医 学术 295 295 295 p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p In the present invention, the inventors of the present invention have studied the effects of lactic acid bacteria in a mouse model of acne in order to solve the above problems. Specifically, the mouse model was taken as an Enterococcus faecalis (7) strain, which is an example of a lactic acid bacterium, and its acne-improving effect was evaluated. As a result, in the mouse model, the reduction of the area of the acne was confirmed from the early stage after the formation of the acne, and in the early stage after the formation of the acne, various inflammatory cytokines or growth factors were confirmed, so 153738.doc 201141495 The judgment can promote wound healing. Further, it can be judged that the expression of inflammatory cytokines or growth factors is reduced in the later stage after the formation of acne, and the normal state can be restored more quickly than the control. In this way, Enterococcus faecalis (S4 strain) showed an improvement from the early stage after the formation of acne. Further, according to the comparison between the negative control group and the group of the fecal gut g (Ec_i2 strain) administered on the same day, it is also determined that the effect is to prevent the administration of Enterococcus faecalis (EC-12 strain) before the formation of hemorrhoids. The situation is particularly significant. The present inventors have found that 'Enterococcus faecium (ec i2 strain) is extremely useful as a medicine or a food or drink for the prevention of acne or the healing of an early stage, and the present invention has been completed. In more detail, the present invention provides the following inventors. (1) A composition for improving acne, which comprises lactic acid bacteria as an active ingredient. (7) The composition according to (1), wherein the lactic acid bacteria belong to the genus Enterococcus. (3) The composition of (1), wherein the lactic acid bacterium is Enterococcus faecalis. (4) A composition according to any one of (1) to (3), which is a pharmaceutical composition. (5) A composition according to (4) which is administered orally. (6) A composition according to (4) or (5) which is administered prophylactically prior to the formation of acne. () The foods of (1) to (3) are the ingredients of the food. (8) A composition according to (7) which is an oral ingestor. (9) A composition according to (7) or (8) which is taken before acne formation. (〇) The composition according to any one of (4) to (9), to which a label for the purpose of improving acne is attached. 153738.doc
S •6 201141495 發明之效果 藉由將本發明之組合物以醫藥品之形式進行投予或以飲 食品之形式進行攝取，可實現生物體中之褥瘡之改善。尤 其疋，藉由在褥瘡形成前預防性地投予本發明之組合物， 可獲得顯著之效果。本發明之組合物於褥瘡之預防或褥瘡 之早期階段之治癒中有用。λ，本發明之組合物之有效成 刀為乳自文菌，女全性較尚。因此，用作醫藥之情形時可經 口投予，與先前之褥瘡之局部療法不同，其簡便並且對褥 瘡患者之負擔亦較小。X，本發明之組合物作為健康食品 等飲食品，健康者可於日常中容易地攝取，而實現褥瘡之 預防。 【實施方式】 本發明提供一種含有乳酸菌作為有效成分而成之用於褥 瘡之改善之組合物。 於本發明中，所謂「褥瘡」，係指由於持續之壓迫而使 流向皮膚、皮下脂肪組織、肌肉之血流中冑，從而導致該 等組織死絕之狀態'。於本發明中，所謂「褥瘡之改善作 用」，係指包括藉由乳酸菌之投予或攝取，而使褥瘡難以 產生' 所產生之褥瘡成為輕&、抑制搏瘡之惡化、加快轉 瘡之治癒。又，係指於所形成之褥瘡到治癒為止之過程 中’不僅包括改善整體之情形’ #包括改善特定階段之情 形。如本實施例所示般’褥瘡之改善作用例如可藉由搏瘡 面積之測定、或炎症性細胞激素或生長因子之表現之測定 而評價。 153738.doc 201141495 作為本發明之組合物之有效成分即「乳酸菌」，可例示 屬於腸球菌屬、雙叉桿菌屬、乳酸桿菌屬、鏈^菌屬及I 球菌屬者，但只要具有褥瘡改善作肖，則並無特別限制。 作為屬於腸球菌屬之乳酸菌，例如可列舉：糞腸球菌、 原腸球菌’作為屬於雙叉桿菌屬之細菌，例如可列舉·龍 根雙又桿菌、短型雙叉桿菌、雙岐雙又桿菌，作為^於乳 酸桿菌屬之細菌，可列舉：嗜酸乳酸桿菌、乾酪乳酸桿 菌、唾液乳酸桿菌，作為屬於鏈球菌屬之細菌，例如可列 舉嗜熱鏈球菌等，作為屬於乳球菌屬之細菌，例如可列 舉：乳脂乳球菌、乳酸乳球菌等。本發明之組合物中所使 用之乳酸菌較佳為屬於腸球菌屬者，尤佳為糞腸球菌。 再者，本實施例中所使用之糞腸球菌£0：_12株（£(：_12)於 2005年2月25曰（原寄存曰）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（〒305_5466，日本茨城縣築波 市東1丁目1番地1中央第6)(受託編號為FERM BP 1028句。 作為糞腸球菌’除EC-12株以外亦可，利用ATCC19433、 ATCC14508、ATCC23655、IFO16803、IFO16804 等菌 株。 s亥等乳酸菌可於本發明之組合物中僅使用1種，亦可調 配2種以上之菌種而用於本發明之組合物中。又，於本發 明之組合物中’乳酸菌可以活菌之形式及死菌體之形式而 使用。就耐熱性優異、品質穩定、無味無臭之方面而言， 死菌體作為本發明之組合物之有效成分而較佳。作為本發 明之組合物中之死菌體’可使用經加熱殺菌之菌體。經加 153738.doc 201141495 熱殺菌之菌體可藉由以下方式而製備，即例如利用過慮、 離•”離等方法’自依照常法培養乳酸菌而得之培養物回 收菌體，水洗後使其料於水等中，並於丨贼以下（較佳 為8〇〜12代）加熱處理3G分鐘以内⑽〜3〇分鐘）後，視需 要進行濃縮、乾燥。再者，糞腸球菌eci2株之經加熱殺 菌之菌體之微細粉末係作為商品名「ec_i2(ef p。體）」 (Combi股份有限公司製造）而市售。 本發明之組合物可為具有褥瘡改善作用之醫藥組合物、 飲食品（包括動物用飼料）、或動物模型實驗等中所使用之 試劑之形態。 於本實施例巾#使褥瘡之小鼠模型攝取翼腸球菌 12株），則自褥瘡形成後早期開始便確認到褥瘡面積之明 顯減少…該效果尤其是於自褥瘡形成前開始預防性地 投予糞腸球_CM2株）之情形時較大。因此，本發明之 組合物尤其是可較佳地用作預防性地投予之醫藥組合物或 預防性地（日常地）攝取之飲食品，藉此可進行褥瘡之預防 或早期階段之治癒。 又若使本貫施例中之小鼠模型攝取糞腸球菌（EC_【2 株），則可確認，於褥瘡形成後之初期，與對照相比，炎 症性細胞激素或生長因子進行高度表現，而促進創傷治 瘡；進而可確認’於褥瘡形成後之後期，與對照相比，炎 症性細胞激素或生長因子之表現減少，相比對照可更快地 恢復正㊉狀態。因此，本發明之組合物亦可用作用以促進 褥瘡形成後之初期之炎症性細胞激素或生長因子（例如江_ 153738.doc 201141495 Ια基因、TNF-α基因、TGF-β基因、FGF-7基因、FGF-IO基 因）之表現抑制的組合物、及用以促進褥瘡形成後之後期 之k症性細胞激素或生長因子（例如JL-1 a基因、IL-8基 因、TNF-α基因、TGF-β基因、FGF-10基因）之表現抑制的 組合物。 本發明之組合物可利用公知之製藥學方法進行製劑化。 例如可以膠囊劑、錠劑、丸劑、液劑、散劑、顆粒劑、細 粒劑、膜衣劑（film coating agent)、圓粒劑、口含劑、舌 下劑、咀嚼劑、口腔劑、膏劑（paste agent)、糖漿劑、懸 浮劑、酏劑、乳劑、塗佈劑、軟膏劑、硬膏劑、糊劑、經 皮吸收型製劑、洗劑、吸引劑 '霧劑、注射劑、栓劑等之 形式經口或非經口地使用e本發明係將腸内細菌即乳酸菌 作為有效成分之組合物，可藉由經口而簡便地投予或攝 取。即，本發明之組合物之較佳之投予或攝取方法為利用 經口之投予或攝取。 於該等製劑化中，可與藥理學上或作為飲食品所容許之 載體、具體而言為滅菌水或生理鹽水、植物油、溶劑、主 料、乳化劑、懸浮劑、界面活性劑、穩定劑、香味劑、芳 香劑、賦形劑、媒劑、防腐劑、結合劑、稀釋劑、等張 劑、鎮痛劑、增量劑、崩解劑、緩衝劑、塗佈劑、潤滑 劑、著色劑、甜味劑、黏稠劑、矯味矯臭劑、溶解助劑或 其他添加劑等進行適當組合。 於將本發明之組合物用作醫藥組合物之情形時，亦可與 用於褥瘡之預防或治療之公知之醫藥組合物併用。 153738.docS • 6 201141495 Effects of the Invention The composition of the present invention can be improved in the body by administering the composition in the form of a pharmaceutical or in the form of a food. In particular, significant effects can be obtained by prophylactically administering the composition of the present invention prior to the formation of acne. The compositions of the present invention are useful in the prevention of acne or in the early stages of acne. λ, the effective forming of the composition of the present invention is self-bacterial, and female is more complete. Therefore, it can be administered orally when used as a medicine, and unlike the previous topical treatment of acne, it is simple and has a small burden on patients with acne. X. The composition of the present invention is a food or drink such as a health food, and a healthy person can easily ingest it on a daily basis to prevent acne. [Embodiment] The present invention provides a composition for improving acne comprising lactic acid bacteria as an active ingredient. In the present invention, "acne" refers to a state in which blood flow to the skin, subcutaneous fat tissue, and muscles due to continuous compression causes the tissues to die. In the present invention, the "improving effect of acne" means that it is difficult to produce acne by the administration or ingestion of lactic acid bacteria, and it is light & cure. Also, in the process of forming the acne to cure, it includes not only the improvement of the overall situation, but also the improvement of the specific stage. The improvement effect of the acne as shown in the present embodiment can be evaluated, for example, by measurement of the area of the pock, or measurement of the expression of an inflammatory cytokine or a growth factor. 153738.doc 201141495 The "lactic acid bacteria" which is an active ingredient of the composition of the present invention can be exemplified by Enterococcus, Bifidobacterium, Lactobacillus, Streptococcus, and I cocci, but as long as it has acne improvement Xiao, there is no special limit. Examples of the lactic acid bacteria belonging to the genus Enterococcus include, for example, Enterococcus faecalis and Enterococcus faecalis as bacteria belonging to the genus Bifidobacterium, and examples thereof include B. rhizogenes, Bifidobacterium breve, Bifidobacterium breve Examples of the bacterium belonging to the genus Lactobacillus include Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus saliva. As a bacterium belonging to the genus Streptococcus, for example, Streptococcus thermophilus can be cited as a bacterium belonging to the genus Lactococcus. For example, Lactococcus lactis, Lactococcus lactis, etc. are mentioned. The lactic acid bacteria used in the composition of the present invention are preferably those belonging to the genus Enterococcus, and particularly preferably Enterococcus faecalis. Furthermore, the Enterococcus faecalis £0: _12 strain (£(: _12) used in the present embodiment was deposited at the Patent Bio-Reservation Center of the Industrial Technology Research Institute of the Independent Administrative Corporation in February 25, 2005 (original deposit). (〒305_5466, the sixth in the center of the 1st, 1st, 1st, Tsukuba, Ibaraki, Ibaraki, Japan) (The number is FERM BP 1028. The Enterococcus faecalis can be used in addition to the EC-12 strain, using ATCC19433, ATCC14508, ATCC23655, IFO16803. And strains such as IFO16804. The lactic acid bacteria such as shai may be used alone or in combination with two or more species in the composition of the present invention. Further, in the composition of the present invention The lactic acid bacteria can be used in the form of live bacteria and in the form of dead cells. The dead cells are preferably used as an active ingredient of the composition of the present invention in terms of excellent heat resistance, stable quality, and tasteless and odorless. The dead cells in the composition can be sterilized by heat sterilization. The cells which are heat-sterilized by adding 153738.doc 201141495 can be prepared by the following methods, for example, using the method of excessive care, separation, and the like. according to The culture body obtained by culturing the lactic acid bacteria by the normal method recovers the cells, and after washing with water, it is made into water or the like, and is heated under the thief (preferably 8 〇 to 12 generations) for 3 G minutes (10) to 3 〇 minutes) In addition, the fine powder of the heat-sterilized cells of the Enterococcus faecalis eci2 strain is commercially available as the trade name "ec_i2 (ef p body)" (manufactured by Combi Co., Ltd.). The composition of the present invention may be in the form of a pharmaceutical composition having a acne-improving effect, a food product (including an animal feed), or an agent used in an animal model test or the like. In the present embodiment, the mouse model of acne is made. When 12 strains of Enterococcus faecalis were taken, the significant reduction in the area of the acne was confirmed from the early stage after the formation of acne... This effect is especially the case when the faecal intestine _CM2 strain is administered prophylactically before the formation of acne. Big. Therefore, the composition of the present invention can be preferably used as a prophylactically administered pharmaceutical composition or a preventive (daily) ingested food or drink, whereby the prevention of acne or the healing of an early stage can be carried out. Further, when the mouse model in the present example was ingested with Enterococcus faecalis (EC_[2 strains), it was confirmed that inflammatory cytokines or growth factors were highly expressed in the early stage after the formation of acne, compared with the control. The wound is treated to promote the wound; further, it can be confirmed that the performance of the inflammatory cytokine or the growth factor is reduced compared with the control in the later stage after the formation of the acne, and the positive ten state can be restored more quickly than the control. Therefore, the composition of the present invention can also be used as an inflammatory cytokine or growth factor for promoting the initial stage of acne formation (for example, _ 153738.doc 201141495 Ια gene, TNF-α gene, TGF-β gene, FGF-7 gene a composition inhibiting the expression of the FGF-IO gene), and a k-like cytokine or growth factor (for example, JL-1 a gene, IL-8 gene, TNF-α gene, TGF) for promoting post-acne formation. A composition for inhibiting the expression of the -β gene, FGF-10 gene). The composition of the present invention can be formulated by a known pharmaceutical method. For example, capsules, troches, pills, liquids, powders, granules, fine granules, film coating agents, round granules, buccal agents, sublingual agents, chewables, buccal agents, ointments (paste agent), syrup, suspending agent, expectorant, emulsion, coating agent, ointment, plaster, paste, percutaneous absorption preparation, lotion, attractant 'fog, injection, suppository, etc. Oral or non-oral use e The present invention is a composition in which an enteric bacterium, that is, a lactic acid bacterium, is used as an active ingredient, and can be easily administered or ingested by oral administration. That is, a preferred method of administration or ingestion of the composition of the present invention is by oral administration or ingestion. In the formulation, it can be used as a carrier for pharmacological or food or beverage, specifically sterilized water or physiological saline, vegetable oil, solvent, main ingredient, emulsifier, suspending agent, surfactant, stabilizer. , flavoring agents, fragrances, excipients, vehicles, preservatives, binding agents, diluents, isotonic agents, analgesics, extenders, disintegrating agents, buffers, coating agents, lubricants, colorants Suitable combinations of sweeteners, thickeners, flavoring agents, dissolution aids or other additives. When the composition of the present invention is used as a pharmaceutical composition, it may be used in combination with a known pharmaceutical composition for the prevention or treatment of acne. 153738.doc
S • 10- 201141495 於將本發明之組合物用作飲食品之情形時，該飲食品例 如可為健康食品、功能性食品、特定保健用食品、營養輔 助食品、病者用食品或動物用飼料。本發明之飲食品除了 可以如上所述之組合物之形式攝取以外，亦可以各種飲食 品之形式攝取。作為飲食品之具體例，可列舉：果蔬汁、 清涼飲料水、茶飲料、飲料劑、果凍狀飲料、功能性飲料 等各種飲料；啤酒等酒精飲料；飯類、面類、麵包類及麵 團類等含有碳水化合物之食品；魚肉火腿、香腸、水產練 製品等練製品；咖喱、澆汁菜、中式湯等蒸煮製品；湯 類，牛奶、乳飲料、冰淇淋、乳酪、酸乳酪等乳製品；豆 醬'酸乳酪、乳酸菌、醱酵飲料、醃潰品等醱酵物；豆製 品；餅乾、曲奇等西式點心類；饅頭或羊羹等曰式點心 類；糖果類、口香糖類、軟糖、果凍、布丁等冷凍甜點或 冰凍甜點等各種點心類；速食湯、速食醬湯等速食食品、 微波爐應對食品等。進而，亦可列舉製備成粉末、顆粒、 銳劑、膠囊劑、液狀、膏狀或果〉東狀之健康飲食品。 本發明之組合物可以包括人在内之動物作為對象而使 用，作為人以外之動物’並無特別限制，可以各種家畜、 家禽、寵物、實驗用動物等作為對象。具體而言，可列 舉：猪、牛、馬、羊、山羊、雞、野鴨、駝鳥、鴨、狗、 描、兔、倉鼠、小鼠、大鼠、猴等，但並不受該等之限 制。 用該技術領域中公知之製 可添加對褥瘡之改善有效 本發明中之飲食品之製造可利 造技術而實施。於該飲食品中， 153738.doc -11· 201141495 之1種或2種以上之成分（例如營養素等）。又亦可藉由與 發揮褥瘡之改善以外之魏的其他成分或其他魏性食品 組合而製成多功能性之飲食品。 於投予或攝取本發明之組合物之情形時，其投予量或攝 取量可根據對象之年齡、體重、褥瘡之症狀、健康狀態、 組合物之種類（醫藥品、飲食品等）等而適當選擇。例如， 乳酸菌每次之投予量或攝取量通常為〇 〇1 mg/kg體重〜1〇〇 mg/kg體重，較佳為〗mg/kg體重〜1〇呵心體重。如此 般’本發明亦提供一種對象之褥瘡之改善方法’其特徵在 於對對象投予乳酸菌或使對象攝取乳酸菌。 本發明之組合物之製品（醫藥品、飲食品、試劑）或其說 明書可為附加主旨為有用於改善褥瘡之標示者。此處所謂 「於製品或說明書中附加標示」，係指於製品之本體、容 器、包裝等中附加標示，或於揭示製品資訊之說明書、隨 附文件、宣傳物、其他印刷物等中附加標示。於主旨為用 於改善#瘡之標示中’可包括藉由投予或攝取乳酸菌而使 褥瘡得到改善之機理㈣之資訊。作為機理，例如可列舉 有關如下之資m，即與褥瘡關連之炎症性細胞激素或生長 因子（例如IL-ct基因、IL_8基因、TNF a基因、丁即邛基 因、FGF-7基因、FGIM〇基因）之作用或表現。 實施例 以下，基於實施例及比較例對本發明進行更加具體之說 明，但本發明並非限定於以下實施例者。 [實施例1]小鼠模型中之仏12之褥瘡改善效果之研究 153738.docS • 10-201141495 When the composition of the present invention is used as a food or beverage, the food or drink may be, for example, a health food, a functional food, a specific health food, a nutritional supplement, a patient food or an animal feed. . The food or drink of the present invention can be ingested in the form of a composition as described above, and can also be ingested in the form of various foods and drinks. Specific examples of foods and drinks include various beverages such as fruit and vegetable juices, refreshing beverage water, tea beverages, beverages, jelly-like beverages, and functional beverages; alcoholic beverages such as beer; rice, noodles, breads, and doughs. Foods containing carbohydrates; ham, sausages, aquatic products, etc.; curry products, curry, Chinese soup, etc.; soups, milk, milk drinks, ice cream, cheese, yogurt, etc.; Sauces, such as yoghurt, lactic acid bacteria, lyophilized beverages, salted products, etc.; soy products; western-style snacks such as biscuits and cookies; simmered snacks such as taro or mutton; confectionery, chewing gum, jelly, jelly, Various kinds of snacks such as puddings such as frozen desserts and frozen desserts; fast-food soups such as instant soups and instant soups, and microwave ovens for foods. Further, healthy foods and drinks prepared into powders, granules, sharpeners, capsules, liquids, pastes or fruits can also be mentioned. The composition of the present invention can be used as an object for animals including humans, and is not particularly limited as long as it is a human, a poultry, a pet, an experimental animal or the like. Specific examples include pigs, cows, horses, sheep, goats, chickens, wild ducks, ostriches, ducks, dogs, rabbits, hamsters, mice, rats, monkeys, etc., but are not subject to such restrictions. . The improvement of acne can be added by a system known in the art. The manufacture of the food or drink of the present invention can be carried out by a technique. In the food or drink, one or two or more components (for example, nutrients, etc.) of 153738.doc -11· 201141495. It is also possible to make a multifunctional food or drink by combining with other ingredients of Wei other than the improvement of acne or other Wei foods. In the case of administering or ingesting the composition of the present invention, the dose or intake may be based on the age, body weight, symptoms of acne, state of health, type of composition (medicine, food, etc.), etc. Appropriate choice. For example, the dosage or intake of the lactic acid bacteria is usually 〇1 mg/kg body weight to 1 〇〇 mg/kg body weight, preferably 〗 〖mg/kg body weight~1 〇 heart weight. Thus, the present invention also provides a method for improving acne of a subject, which is characterized in that a lactic acid bacterium is administered to a subject or a lactic acid bacterium is ingested by a subject. The articles (pharmaceuticals, foods and drinks, reagents) of the composition of the present invention or instructions therefor may be an additional subject matter for the purpose of improving acne. The term "additional labeling in the product or in the specification" as used herein refers to the labeling of the body, container, packaging, etc. of the product, or the labeling of the product information, accompanying documents, promotional materials, other printed materials, etc. The subject matter is intended to improve the indication of # sores' may include information on the mechanism (4) for improving acne by administering or ingesting lactic acid bacteria. As the mechanism, for example, an inflammatory cytokine or a growth factor (for example, an IL-ct gene, an IL_8 gene, a TNF a gene, a guanine gene, a FGF-7 gene, a FGIM〇) associated with acne may be cited. The role or performance of a gene). EXAMPLES Hereinafter, the present invention will be specifically described based on examples and comparative examples, but the present invention is not limited to the following examples. [Example 1] Study on the improvement effect of acne 12 in a mouse model 153738.doc
S •12· 201141495 將「生 使用BALB/e系1G週大雄性小鼠作為供試動物 理鹽水投予群（對照群）」、r 預防性EC-12投予群 「同日ECM2投予群」設定為試驗群，各群使用υ 隻）小鼠。 將小鼠馴化後，於麻醉下使用市f之理髮推子對背部正 中進行剃毛後，利用除毛霜進行除毛。以蒸館水仔細_ 除毛部。於制毛之次曰，提起背部正中皮膚，以兩個磁鐵 板（magnet plate)(直徑12 mmx厚度5麵，ιΐ8〇⑺夾持並 保持12小時後，將磁體卸除12小時（9點安裝，加卸除卜 連續3曰重複該循環’製作褥瘡。再者，僅於製作褥瘡時 進行個別飼養。製作褥瘡時，皮下投予丁基原啡因P mg/kg)作為鎮痛劑。關於搏瘡製作方法，依據^〜^ al.(J. Invest. Surg. 2004. 17:221·227)而進行。 於「預防性似2投予群」及「同日Ε(Μ2投予群」中， 駐⑶懸浮於生理鹽水中，且咖2成為10 mg/kg(體重） 之方式每日對小鼠強制進行經口投予。對「生理鹽水投予 群」’係經口投予滅菌生理鹽水。對「預防性咖2投予 群」投予ECM2、及對「生理鹽水投予群」投予生理鹽水 係自褥瘡開始之7日前開始，每日i次早上9點進行直至進 行剖檢為止。對「同日EC·12投予群」投予ECM2係自褥瘡 製作日開始，每日i次早上9點進行，直至進行剖檢為止。 對於創傷部之狀態，每曰觀察並拍攝成照片，藉由照片 之圖像分析而測定創傷部面積。製作褥瘡後，於第3日、 第6日帛11日對各群中各5隻進行剖檢。腹腔投予戊巴比 153738.doc 201141495 妥（Schering-Plough) ’深麻醉後，藉由放血進行屠殺。將 創傷面積縮小率作為將「預防性EC-12投予群」之最大褥 瘡面積設為100時之值而算出》 f 其結果，關於創傷面積縮小率，自褥瘡形成後第4曰開 始’與「同日EC-12投予群」及「生理鹽水投予群」相 比，「預防性EC-12投予群」表現出更低之值（圖i )。 關於創傷部樣品，本發明者等人進而確認到細胞激素及 生長因子之mRNA表現。 於公知之細胞激素中’ IL-8為藉由il-1或tnF等炎症性 細胞激素之刺激，而由以白血球為代表、及纖維母細胞或 内皮細胞等各種細胞所產生之白血球趨化因子（Leuk〇cyte Chem〇tactic Factor)。又’ IL_la於各種免疫活性細胞 (immUnocompetent ceU)中具有多種生理活性，但作為其最 重要之作用，已知有可誘導輔助τ細胞之IL_2產生，且經 由IL-2促進T細胞之分化、增殖。又，TNFa經由几丨或 PGE2、膠原酶等之產生而引起發熱或各種炎症反應，因 此可認為其係炎症反應中之媒介物之一。 已头a知之生長因子中，TGF_p於組織受到傷害 時’促m細胞向傷害部位之趨化。由於巨t細胞自身 亦分泌TGF-β，因此藉由該分泌可增加纖維母細胞，而協 同地促進創傷治癒過程。又’ FGF_7為不僅對纖維母細 胞’而且對各種細胞表現出增瘦、分化等活性之多功能性 訊號分子’別名稱作KGF(Keminc)eyte a—―加，角 質細胞增殖因子）。又，FGJM()屬於纖維母細胞增殖因子 153738.doc 9 -14 * 201141495 家族中之FGF-7之亞家族。 於本實施例中，關於作為細胞激素之上述IL-la、IL-8及 TNF-a、及作為生長因子之上述TGF-β、FGF-7及FGF-10， 對其表現進行了研究。 具體而言，自創傷部樣品萃取RNA後，藉由反轉錄合成 cDNA，以該cDNA為模板，使用表1中記載之引子進行即 時PCR(Polymerase Chain Reaction，聚合酶鏈反應）(Rotor-Gene 6200(凯傑（Qiagen)公司））。 再者，於RNA之萃取中使用QuickGene 810系統及 QuickGene RNA tissue套組 SII(Fuji Film公司），於反轉錄 中使用 PrimeScript RT reagent 套組（Perfect Real Time ; Takara Bio)。作業係依據操作說明書而實施。測定值係以 GAPDH(glyceraldehyde-3-phosphate dehydrogenase，甘油 醛-3-磷酸脫氫酶）進行修正。 [表1] 前置引子 反置引子 GAPDH GGTGTCTTCACCACCATGGA CAGAAGGGGCGGAGATGAT (序列編號：1) (序列編號：2) IL-la TTGGTTAAATGACCTGCAACA GAGCGCTCACGAACAGTTG · (序列編號：3) (序列編號：4) IL-8 TGAAGCTCCCTTGGTTCAGAA TGCCATCAGAGCAGTCTGTCTT (序列編號：5) (序列編號：6) TNF-a TGTCTACTGAACTTCGGGGTGA GAAGATGATCTGAGTGTGAGGTCT (序列編號：7) (序列編號：8) TGF-β TGGAGTTCAGACACTCAACACA AAGCTTCGGGATTTATGGTGT (序列編號：9) (序列編號：10) FGF-10 CGGGACCAAGAATGAAGACT GCAACAACTCCGATTTCCAC (序列編號：Π) (序列編號：12) 其結果，關於「預防性EC-12投予群」之皮膚褥瘡組織 中之mRNA表現量，於褥瘡製作後第3曰’於IL-8以外之炎 153738.doc •15- 201141495 症性細胞激素及所有生長因子中，相比「同日EC-12投予 群」及「生理鹽水投予群」而提高（表2、表3)。另一方 面’於褥瘡製作後第6日，於r預防性ec-1 2投予群」中， 所有炎症性細胞激素及FGF-7以外之生長因子之表現相比 「同日EC-12投予群」及「生理鹽水投予群」而降低（表 2 、表3)。 [表2] 3曰後 IL_la IL-8 TNF-a 對照群 3.20 1.09 0.95 預防性EC-12投予群 4.60 1.04 1.13 同日EC-12投予群 2.64 1.73 0.42 6曰後 IL-la IL-8 TNF-a 對照群 1.60 1.26 1.13 預防性EC-12投予群 0.89 0.62 0.48 同曰EC-12投予群 1.30 0.74 0.64 [表3] 3曰後 TG^~ FGF-7 FGF-10 對照組 1.03 1.04 0.41 預防性EC-12投予群 1.15 1.25 0.58 同曰EC-12投予群 0.42 1.45 0.14 6曰後 FGF-7 FGF-10 對照群 1.17 1.04 5.28 預防性EC-12投予群 0.37 1.19 0.00 同曰EC-12投予群 0.64 0.98 1.52 自褥瘡之產生至治癒為止之過程通常分為（1)出血凝固 期、（2)炎症期、（3)增殖期、（4)成熟期之4個階段，相比 「同日EC-12投予群」及「生理鹽水投予群」，於「預防 性EC-12投予群」中，於褥瘡產生第4日確認到褥瘡面積之 -16· 153738.docS •12· 201141495 “The use of BALB/e 1G large male mice as a test physical saline administration group (control group)”, r Preventive EC-12 administration group “on the same day ECM2 administration group” It was set as a test group, and each group used only mice. After the mice were acclimated, the hair was removed under the anesthesia using a hair clipper of the city f, and the hair removal cream was used for hair removal. Take steaming water carefully _ hair removal. After the hair is made, lift the back center skin and remove the magnet for 12 hours (9 points installation) after holding and holding the magnet plate (diameter 12 mmx thickness 5 faces, ιΐ8〇 (7) for 12 hours) Adding and removing the sputum and repeating the cycle for 3 consecutive times to make acne. In addition, it is only for individual feeding when making acne. When making acne, subcutaneous administration of butyl morphine (P mg/kg) is used as an analgesic. The method is carried out according to ^~^ al. (J. Invest. Surg. 2004. 17:221·227). In the "preventive like 2 vote group" and "the same day Μ (Μ2 voted for group), resident (3) The mice were orally administered by intrauterine administration in a manner of 10 mg/kg (body weight) suspended in physiological saline. The "salt-administered group" was orally administered with sterile saline. "Preventive coffee 2 is administered to the group" and ECM2 is administered to the "salt-administered group". The physiological saline solution is administered from the 7th day before the start of the acne, and it is performed at 9:00 am every day until the necropsy is performed. "European day EC.12 is given to the group" and the ECM2 system is started from the hemorrhoids production day. Until the necropsy is performed, the state of the wound is observed and photographed, and the area of the wound is measured by image analysis of the photograph. After the acne is produced, on the 3rd, 6th, and 11th, Five out of the group were examined by necropsy. The intraperitoneal administration of pentobarbital 153738.doc 201141495 (Schering-Plough) 'After deep anesthesia, the blood was used for slaughter. The wound area reduction rate was taken as the "preventive EC-12 "The maximum acne area of the group" is calculated as the value of 100". The result is that the wound area reduction rate starts from the fourth 后 after the formation of acne and the same day EC-12 is administered to the group and the saline injection "Preventive EC-12 administration group" showed a lower value (Fig. i). The inventors of the present invention confirmed the mRNA expression of cytokines and growth factors. In the well-known cytokine, 'IL-8 is a white blood cell chemokine produced by various cells such as leukocytes or fibroblasts or endothelial cells stimulated by inflammatory cytokines such as il-1 or tnF. Leuk〇cyte Chem〇tactic Fac Further, IL_la has various physiological activities in various immunocompetent cells (immUnocompetent ceU), but as its most important role, it is known to induce IL_2 production of helper tau cells and promote T cells via IL-2. Differentiation and proliferation. In addition, TNFa causes fever or various inflammatory reactions through the production of several sputum or PGE2, collagenase, etc., so it can be considered as one of the vectors in the inflammatory reaction. Among the growth factors known as TGF_p When the tissue is injured, it promotes the chemotaxis of m cells to the injury site. Since the giant t cells themselves secrete TGF-β, the secretion can increase the fibroblasts, and synergistically promote the wound healing process. Further, FGF_7 is a versatile signal molecule which exhibits activity such as thinning and differentiation for various cells, and is called KGF (Keminc) eyte a--, keratinocyte proliferation factor. Further, FGJM() belongs to the subfamily of FGF-7 in the fibroblast growth factor 153738.doc 9 -14 * 201141495 family. In the present example, the above-described effects of IL-la, IL-8 and TNF-a as cytokines, and TGF-β, FGF-7 and FGF-10 as growth factors were examined. Specifically, after extracting RNA from the wound sample, cDNA was synthesized by reverse transcription, and the primer was used as a template, and the primer described in Table 1 was used for real-time PCR (Polymerase Chain Reaction) (Rotor-Gene 6200). (Qiagen))). Further, a QuickGene 810 system and a QuickGene RNA tissue kit SII (Fuji Film) were used for RNA extraction, and a PrimeScript RT reagent kit (Perfect Real Time; Takara Bio) was used for reverse transcription. The operation is carried out in accordance with the operating instructions. The measured value was corrected by GAPDH (glyceraldehyde-3-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase). [Table 1] Pre-introduction primer GAPDH GGTGTCTTCACCACCATGGA CAGAAGGGGCGGAGATGAT (SEQ ID NO: 1) (SEQ ID NO: 2) IL-la TTGGTTAAATGACCTGCAACA GAGCGCTCACGAACAGTTG · (SEQ ID NO: 3) (SEQ ID NO: 4) IL-8 TGAAGCTCCCTTGGTTCAAAA TGCCATCAGAGCAGTCTGTCTT (sequence No.: 5) (SEQ ID NO: 6) TNF-a TGTCTACTGAACTTCGGGGTGA GAAGATGATCTGAGTGTGAGGTCT (SEQ ID NO: 7) (SEQ ID NO: 8) TGF-β TGGAGTTCAGACACTCAACACA AAGCTTCGGGATTTATGGTGT (SEQ ID NO: 9) (SEQ ID NO: 10) FGF-10 CGGGACCAAGAATGAAGACT GCAACAACTCCGATTTCCAC ( SEQ ID NO: Π) (SEQ ID NO: 12) As a result, the amount of mRNA expression in the skin acne tissue of the "prophylactic EC-12 administration group" was 3rd after the production of acne, and inflammation other than IL-8. 153738.doc •15- 201141495 Among the cytokines and all growth factors, it was improved compared with the “EC-12 group administered on the same day” and the “salt group” (Table 2, Table 3). On the other hand, on the 6th day after the production of acne, in the r prophylactic ec-1 2 administration group, all inflammatory cytokines and growth factors other than FGF-7 were compared with the "on the same day EC-12 administration. Groups and "saline group were reduced" (Table 2, Table 3). [Table 2] 3曰 IL_la IL-8 TNF-a Control group 3.20 1.09 0.95 Prophylactic EC-12 administration group 4.60 1.04 1.13 Same day EC-12 administration group 2.64 1.73 0.42 6曰 IL-la IL-8 TNF -a Control group 1.60 1.26 1.13 Prophylactic EC-12 administration group 0.89 0.62 0.48 Peer EC-12 administration group 1.30 0.74 0.64 [Table 3] 3曰 TG^~ FGF-7 FGF-10 Control group 1.03 1.04 0.41 Prophylactic EC-12 administration group 1.15 1.25 0.58 Peer EC-12 administration group 0.42 1.45 0.14 6曰 FGF-7 FGF-10 Control group 1.17 1.04 5.28 Prophylactic EC-12 administration group 0.37 1.19 0.00 Peer EC -12 dose group 0.64 0.98 1.52 The process from hemorrhoids to cure is usually divided into (1) bleeding clotting period, (2) inflammatory phase, (3) proliferative phase, and (4) mature phase. In the "preventive EC-12 group", the "preventive EC-12 group" was confirmed in the "preventive EC-12 group" on the 4th day of acne generation -16 153738.doc
S 201141495 明顯減少。又，於褥瘡產生第3日可見到炎症性細胞激素 及生長因子之高度表現，其後，於褥瘡產生第6日，該等 之表現戲劇地降低。根據該等事實，揭示了尤其是藉由自 褥瘡形成前開始投予EC-12，可對褥瘡產生初期之褥瘡之 化癒產生效果。又，根據該等事實，暗示了 EC_12亦可用 於褥瘡之預防。 產業上之可利用性 如乂上所說明般，藉由將本發明之組合物以醫藥品之形 式進仃技予或以飲食品之形式進行攝取，可實現生物體中 褥瘡之改善。作為本發明之組合物之有效成分的乳酸菌 為腸内細® ’可藉由經口進行投予或攝取。本發明之組合 物由於*全性較高、可簡便地投予或攝取，因此可期待作 為”有褥瘡之改善作用之新的醫藥或健康食品等之用途。 【圖式簡單說明】 群系表不「預防性£匸-12投予群」、「同日EC_12投予 日.&理鹽水投予群」之自褥瘡形成後第3日至第11 轉瘡面積縮小率的圖。將「預防性£〇_12投予群」之 敢大褥瘡面積設為⑽，算出創傷面積縮小率。 153738.doc 201141495 序列表 <110>日商康貝股份有限公司 <120>具有褥瘡改善作用之組合物 <130> P09-020 <140> 100106584 <141> 2011-02-25 <150> 2010-042303 <151> 2010-02-26 <160> 12 <170〉Patentln第 3.1 版 <210〉 1 <211〉 20 <212〉 DNA <213〉人工 <220〉 <223〉一種人工合成之引子序列 <400〉 1 ggtgtcttca ccaccatgga 20 <210> 2 <211〉 19 <212> DNA <213〉人工 <220> <223〉一種人工合成之引子序列 <400> 2 cagaaggggc ggagatgat 19 <210> 3 〈211> 21 <212〉 DNA <213〉人工 <220〉 <223〉一種人工合成之引子序列 <400〉 3 ttggttaaat gacctgcaac a 21 <210〉 4 <211> 19 <212> DNA <213〉X工 <220> <223〉一種人工合成之引子序列 <400> 4 gagcgctcac gaacagttg <210〉 5 <211〉 21 153738-序列表.doc 19 201141495 <212> DNA <213〉人工 <220〉 <223〉一種人工合成之引子序列 <400> 5 tgaagctccc ttggttcaga a <210〉 6 <211> 22 <212〉 DNA <213〉人工 <220> <223〉一種人工合成之引子序列 <400> 6 tgccatcaga gcagtctgtc tt <210〉 7 <211> 22 <212〉 DNA <213〉人工 <220〉 <223〉一種人工合成之引子序列 <400〉 7 tgtctactga acttcggggt ga <210> 8 <211〉 24 <212〉 DNA <213〉人工 <220〉 <223〉一種人工合成之引子序列 <400〉 8 gaagatgatc tgagtgtgag gtct <210〉 9 <211〉 22 <212〉 DNA 〈213>人工 <220〉 <223〉一種人工合成之引子序列 <400〉 9 tggagttcag acactcaaca ca <210〉 10 <211〉 21 <212> DNA <213〉人工 <220〉 153738-序列表.doc 21 201141495 〈223> —種人工合成之引子序列 <400〉 10 aagcttcggg atttatggtg t <210〉 11 <211〉 20 <212〉 DNA <213〉人工 <220〉 <223〉一種人工合成之引子序列 <400> 11 20 cgggaccaag aatgaagact <210〉 12 <211> 20 <212> DNA 〈213>人工 <220〉 〈223> —種人工合成之引子序列 <400> 12 20 gcaacaactc cgatttccac 153738-序列表.docS 201141495 is significantly reduced. Further, on the third day after the occurrence of acne, high expression of inflammatory cytokines and growth factors was observed, and thereafter, on the sixth day of acne production, the performance was drastically lowered. Based on these facts, it has been revealed that the administration of EC-12, especially since the formation of acne, can have an effect on the healing of acne at the beginning of acne. Also, based on these facts, it is suggested that EC_12 can also be used for the prevention of acne. Industrial Applicability As described above, the composition of the present invention can be improved in the body by ingesting the composition in the form of a pharmaceutical or in the form of a food or drink. The lactic acid bacterium which is an active ingredient of the composition of the present invention is an enteric fine ‘ can be administered or ingested orally. Since the composition of the present invention has a high degree of completeness and can be easily administered or ingested, it can be expected to be used as a new medicine or health food having an effect of improving acne. [Simplified illustration] Group table A graph showing the reduction rate of the area of the wound from the third day to the eleventh day after the formation of hemorrhoids in the "preventive 匸-12 投 群 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 The area of the acne acne that "preventive 〇 12 _ _ 12 is administered to the group" is set to (10), and the wound area reduction rate is calculated. 153738.doc 201141495 Sequence Listing <110> Japanese Business Co., Ltd. <120> Composition with acne-promoting effect <130> P09-020 <140> 100106584 <141> 2011-02-25 <;150> 2010-042303 <151> 2010-02-26 <160> 12 <170>Patentln version 3.1 <210> 1 <211> 20 <212> DNA <213>manual< 220> <223> A synthetic primer sequence <400> 1 ggtgtcttca ccaccatgga 20 <210> 2 <211> 19 <212> DNA <213>manual <220><223> Synthetic primer sequence <400> 2 cagaaggggc ggagatgat 19 <210> 3 <211> 21 <212> DNA < 213 > 213 > 220 < 223 > 223 > A synthetic primer sequence <400 > 3 Ttggttaaat gacctgcaac a 21 <210> 4 <211> 19 <212> DNA <213>X<220><223>a synthetic primer sequence <400> 4 gagcgctcac gaacagttg <210> 5 <211> 21 153738 - Sequence Listing.doc 19 201141495 <212> DNA <213>Artificial<220><2 23> A synthetic primer sequence <400> 5 tgaagctccc ttggttcaga a <210> 6 <211> 22 <212> DNA <213>manual<220><223> A synthetic primer sequence <400> 6 tgccatcaga gcagtctgtc tt <210> 7 <211> 22 <212> DNA < 213 > 213 > 220 < 223 > 223 > A synthetic primer sequence <400 > 7 tgtctactga acttcggggt ga <210> 8 <211> 24 <212> DNA <213>Artifical<220><223> A synthetic primer sequence <400> 8 gaagatgatc tgagtgtgag gtct <210> 9 <211 〉 22 <212> DNA <213> 人工<220> <223> A synthetic primer sequence <400> 9 tggagttcag acactcaaca ca <210> 10 <211> 21 <212> DNA <213>Artifical<220> 153738-Sequence List.doc 21 201141495 <223> - a synthetic primer sequence <400> 10 aagcttcggg atttatggtg t <210> 11 <211> 20 <212> DNA <213>Artifical<220><223> A synthetic primer sequence<400> 11 20 cgggaccaag aatgaagact <210> 12 <211> 20 <212> DNA <213>manual<220> <223>-a synthetic primer sequence <400> 12 20 gcaacaactc cgatttccac 153738- List.doc