1277651 A7 B7 五、發明説明) 發明領域 本發明主要係關於某些乳酸样菌株在治療過敏上之新用 途。 發明背景 過敏係指一種對正常無害之物質發展出免疫媒介不良反 應之後天潛在能力。過敏反應會誇發產生如搔疼、咳喷：、 缘喘、打喷f、流眼淚、發炎及疲勞等症狀。一般相信， 過敏反應包括早期的專一性免疫反應及晚期的發炎反應。 有報告指出，過敏原（例如花粉及塵蟎）會刺激高親合力免疫 球蛋白（IgE)受體以引起過敏之早期階段。例如，肥大細胞 及嗜鹼白血球經過敏原刺激後，會釋放出組織胺及細胞激 素，而後，肥大細胞及續驗白血球所釋放的細胞激素會藉 由增加發炎細胞而引發過敏的後期階段。亦有報告指出， 嗜伊紅血球、巨噬細胞、淋巴細胞、嗜中性白血球及血小 板的匯集會啟動劇烈的發炎循環。過敏的晚期階段會擴大 初期的免疫反應，並依序謗發釋放出更多的發炎細胞 (Blease 等人，Chemokines and their role in airway hyper-reactivity，穴es 2000 ; 1 : 54-6 1)。 為了治療過敏症狀，業已研究各式的治療法，其中已有 使用抗過敏藥劑及組織胺Η受體拮抗劑（抗組織胺）的治療。 组織胺拮抗劑的使用可拮抗對過敏原反應而由肥大細胞釋 放出之組織胺。組織胺拮抗劑可減少組織胺在標的組織所 造成之泛紅、搔癢及腫脹現象，並可預防或減緩肥大細胞 因去顆粒化後所產生的許多症狀。然而，抗組織胺亦會造 ____-4-_ 本紙張尺度適用中國國家標準(CNS) Α4規格(210 X 297公釐） 1277651 A7 B7 五、發明説明（2 ) 成某些不良反應，諸如注意力降低、反應遲鈍及嗜睡（美國 專利第0，225,3 32號）。 亦有某些報告指出，可藉由調節細胞激素來治療過敏。 在這些報告中發現干擾素T (IN F - r )會抑制T h 2淋巴細胞 中細胞激素的過度表現（特別是IL-4的分泌），進而降低B細 胞增生。除此之外，IN F - T可刺激T h 1的免疫反應，及抑 制 IgE 的合成（Sareneva T 等人，Influenza A virus-induced INF-α/β and IL-18 synergistically enhance IFN- y gene expression in human T cells ’ J Immunol 1998 ; 160 : 6032-603 8 ; Shida K 等人，case/· inhibits antigen-induced IgE secretion through regulation of cytokine production in murine splenocyte culture， Int drc/z /mmzzwo/ 1 998 ; 115 : 278-287)。因為INF- r 可 抑制B細胞的增生及IgE分泌，因此，吾等相信INF - 7可有 效治療過敏。 乳酸菌是革蘭氏陽性細菌，常作為食品工業醱酵之用。 近來的研究證明，乳酸菌可刺激細胞的INF- T分泌 (Contractor NV 等人，Lymphoid hyperplasia, autoimmunity and compromised intestinal intraepithelial lymphocyte development in colitis-free gno to biotic IL-2-deficient mice，J /mmwm/ 1998 ; 1 60 : 385-3 9 4)。某些特定的乳酸 菌（諸如雙叉桿菌乳酸菌/acn\y)及短乳酸样 菌（Ζα〇ω6α(：/7/Μ 亞種可以刺激源自小氣及人類血液 之淋巴細胞中INF- r的分泌（美國專利公開案第 ______^_ 本紙張尺度適用中國國家標準(CNS) A4規格(210X 297公釐） 1277651 A7 B7 五、發明説明（3 2002/0031503 A1號；美國專利第5,556, 785號）。另外亦有報 告指出，乳酸菌可刺激源自人顧或老鼠之淋巴細胞分泌介 白素1 2 (IL -1 2 )，IL · 1 2為一種T細胞刺激細胞激素，其可 活化T細胞及N K細胞分泌INF· τ* (Hessle等人，Lactobacilli from human gastrointestinal mucosa are strong stimulators of IL-12 production ^ Clin Exp Immunol 1999 ; 116 ·· 276-282)。 發明概述 本發明提供某些乳酸样菌株在治療過敏上之新用途。 一方面，本發明提供用以治療過敏之組合物，該組合物 包含可刺激含量達到可有效治療過敏之INF - r分泌之乳酸 菌株，該菌株係選自由以下所組成之群：植物乳酸桿菌 CCRC 12944、嗜酸性乳酸桿菌CCRC 14079、鼠李糖乳酸捍 菌CCRC 10940、副乾酪乳酸样菌副乾酪亞種CCRC 14023、 德氏乳酸样菌保加利亞亞種CCRC 12297、德氏乳酸桿菌保 加利亞亞種CCRC 1 40 0 7、及德氏乳酸桿菌保加利亞亞種 CCRC 14069。 另一方面，本發明提供一種可刺激INF- r分泌之乳酸菌株 之用途，其係用於製造治療過敏之醫藥配方，該菌株係選 自由以下所組成之群：植物乳酸桿菌CCRC 12944、嗜酸性 乳酸桿菌CCRC 14079、鼠李糖乳酸样菌CCRC 10940、副乾 酪乳酸桿菌副乾酪亞種CCRC 14023、德氏乳酸桿菌保知利 亞亞種CCRC 12297、德氏乳酸桿菌保加利亞亞種CCHe 14007、及德氏乳酸样菌保加利亞亞種CCRC 14069。 圖式簡要說明 _____-6- 本紙張尺度適用中國國家標準(CNS) A4規格(210X 297公釐） 1277651 A7 __ B7 五、發明説明（4 ) — "~ 圖1所示為乳酸桿菌菌株與淋巴細胞共同培養後，INF - r 之分泌量。乳酸菌與淋巴細胞分別共同培養1 2及3 6小時 後，以ELISA偵測INF - r之分泌量。INF - r含量以吸收值 (0.D·數值）表示。圖中，「PC」代表作為陽性控制組之乾 酪乳酸桿菌CCRC 10697; 「NC」代表作為陰性控制組之德 氏乳酸桿菌保加利亞亞種CCRC 1407 1 ; 1代表植物乳酸捍 菌CCRC 12944 ; 2代表嗜酸性乳酸样菌CCRC 14079 ; 3代表 鼠李糖乳酸样菌CCRC 10940 ; 4代表副乾酪乳酸桿菌副乾酪 亞種CCRC 14023 ; 5代表德氏乳酸样菌保加利亞亞種CCRC 12297 ; 6代表德氏乳酸捍菌保加利亞亞種CCRC 14007，及 7代表德氏乳酸样菌保加利亞亞種CCRC 14069。 圖2所示為乳酸桿菌菌株與周邊血液單核細胞（pbmc)共 同培養後，INF- r之分泌量。乳酸菌與PBMC分別共同培養 12、48及72小時後，以ELISA偵測INF- r的分泌量。INF-T含量以吸收值（O.D.數值）表示。試驗中，乾酪乳酸样菌 CCRC 10697為陽性控制組；德氏乳酸桿菌保加利克亞種 CCRC 14071為陰性控制組；副乾酪乳酸桿菌副乾酪亞種 CCRC 14023為試驗菌株。 發明詳細說明 根據本發明，意外地發現某些刺激inf- r分泌之乳酸样 菌菌株可用以治療過敏。 一方面’本發明提供一種治療一個體過敏之組合物，其 包含可刺激inf-r分泌之乳酸菌株，該菌株係選自由以下 所組成之群：植物乳酸桿菌CCRC 12944、嗜酸性乳酸桿菌 _____士_ 本紙張尺度適用中國國家標準(CNS) A4規格(210X297公釐) - 1277651 A7 B7 五、發明説明（5 CCRC 14079、鼠李糖乳酸桿菌CCRC 10940、副乾酪乳酸样 菌副乾酪亞種CCRC 14023、德氏乳酸桿菌保加利亞亞種 CCRC 12297、德氏乳酸样菌保加利亞亞種CCRC 14007、及 德氏乳酸桿菌保加利亞亞種CCRC 14069。這些菌株均寄存 於台灣新竹食品工業發展研究所（FIRDI)内，因此，公眾可 自FIRDI取得前述的菌株。這些菌株是安全、天然、無毒 性，且符合G.R.A.S( Generally Regarded as Safe，普遍認為 安全）標準，這些菌株常用於食品中，且對人體無害。 根據本發明，已證明當這些菌株與淋巴細胞共同培養 時，具有刺激INF- r分泌的能力。其中之一株已證明可刺激 周邊血液單核細胞（PBMC)分泌INF-T。在本發明最佳的具 體實例中，發現副乾酪乳酸捍菌副乾酪亞種CCRC14023刺激 INF - r分泌的能力優於（四倍）陽性控制組之乾酪乳酸桿菌 CCRC 10697。 根據本發明，治療過敏時所用的乳酸菌可為活的菌株或 去活性（inactive)菌株，例如，活的菌株經加熱步驟或此技 術中其他常用以殺死乳酸菌的處理方式處理後，可得去活 性菌株。 本專利說明書中，「過敏」乙詞係指由inf- r調節的過 敏。過敏疾病包括鼻炎、鼻竇炎、氣喘、過敏性肺炎、外 部過敏齒槽炎、結膜炎、蓴麻疹、溼疹、皮膚炎、過敏反 應、血管水腫、過敏性頭痛及偏頭痛、及某些腸胃疾病。 現已證明，能刺激inf - r分泌之益生菌可治療異位性溼疹 (Isolauri E 等人，Probiotics in the management of atopic ______-8- 本紙張尺度適用中國國家標準(CNS) A4規格(210x 297公釐） 1277651 A7 B7 五、發明説明（6 ) eczema， Clinical and experimental Allergy 2000 » 30 * 1604-1610 ; Sutas Y等人，Suppression of lymphocyte proliferation in vitro by bovine caseins hydrolyzed with Lactobacillus casei GG-derived enzyme j J Allergy Clin Immunol 1996 ； 98 ♦ 216-224 ； Kalliomaki M等人，Probiotics in primary prevention of atopic disease: a randomized placebo-controlled trial，Lancet 2001 ； 357 : 1076-79)。 根據本發明，乳酸菌株可包含於人類正常攝取之醫藥組 合物、膳食補充劑、食品、或其組分中。在本發明之一較 佳具體實施例中，乳酸菌株係以食品的方式給予，諸如牛 乳醱酵後所產製之凝結乳製品。根據本發明所製備之食品 可以很方便地投與嬰兒或小孩。 另一方面，本發明提供一種可刺激inf - r分泌之乳酸菌 株之用途，其係用於製造治療過敏之醫藥配方，該菌株係 選自由以下所組成的群：植物乳酸样菌CCRC 12944、嗜酸 性乳酸捍菌CCRC 14 079、鼠李糖乳酸捍菌CCRC 10940、副 乾赂乳酸桿菌副乾酪亞種CCRC 14023、德氏乳酸样菌保加 利亞亞種CCRC 12297、德氏乳酸样菌保加利亞亞種CCRC 14007、及德氏乳酸样菌保加利亞亞種ccrc 14069。 兹以下列實例予以詳細說明本發明，惟並不意味本發明 僅侷限於此等實例所揭示之内容。 選可刺激淋巴細胞分泌INF· r之乳酸菌枝 產雙事先選定表1中所列的六十七株乳酸菌株，同 時’亦註明作為陽性控制組（PC)及陰性控制組（NC)之菌 ----------9- _— 本紙張尺度適用中S s家標準(CNS) A4規格(·χ 297公爱） 1277651 A7 B7 五、發明説明（7 ) 株。所有的菌株均購自FIRDI。 表1 編號 乳酸菌株 CCRC編號 PC 乾酶乳桿菌（LacMMc/Z/w 如） 10697 NC 德氏乳故样菌保加利亞亞種⑽ delbrueckii subsp. Bulgaricus) 14071 1 植物乳毁群蔑（Lactobacillus plantarum) 10069 2 植物乳酸桿菌 10357 3 植物乳酸样菌 11697 4 植物乳酸桿菌 12250 5 植物乳酸桿菌 12251 6 植物乳酸捍菌 12327 7 植物乳酸桿菌 12944 8 植物乳酸桿菌 14059 9 植物乳酸桿菌 15478 10 約氏乳故择隹（Lactobacillus johnsonii) 14004 11 嗜酸性乳酸桿菌似） 14026 12 言、李條 1 後择菌（Lactobacillus rhamnosus) 14029 13 嗜酸性乳酸桿菌 14064 14 嗜酸性乳酸捍菌 14065 15 嗜酸性乳酸样菌 14079 16 乳故桿囷種 16000 17 嗜酸性乳酸桿菌 16092 18 嗜酸性乳酸桿菌 16099 19 嗜酸性乳酸桿菌 17009 20 嗜酸性乳酸桿菌 17064 2 1 嚐酸性乳酸桿菌 10695 22 乾酪乳酸桿菌乾酪亞種 {Lactobacillus casei subsp. Casei) 10358 23 鼠李糖乳酸桿菌 10940 24 乾酪乳酸桿菌乾酪亞種 11197 25 鼠李糖乳酸样菌 11673 26 副乾酪乳酸桿菌副乾酪亞種 (Lactobacillus paracasei subsp. Paracasei) 12193 27 副乾酪乳酸桿菌副乾酪亞種 12248 _____-10- 本紙張尺度適用中國國家標準(CNS) A4規格(210X 297公釐） 1277651 A7 B7 五、發明説明（8 28 乾酪乳酸桿菌乾酪亞種 12249 29 乾酪乳酸桿菌乾酪亞種 12272 30 副乾酶乳酸样囷副乾酶亞種 14001 3 1 副乾酪乳酸样菌副乾酪亞種 14023 32 乾酪乳酸桿菌乾酪亞種 14025 33 乾酪乳酸桿菌乾酪亞種 14073 34 乾酪乳酸样菌乾酪亞種 14074 35 乾酶乳酸样菌乾酷亞種 14080 36 乾酪乳酸捍菌乾酪亞種 14082 37 乾酪乳酸桿菌乾酪亞種 14083 38 乾酪乳酸样菌乾酪亞種 14084 39 乾酪乳酸样菌乾酪亞種 14705 40 乾酪乳酸样菌乾酪亞種 16093 4 1 乾酪乳酸桿菌乾酪亞種 16094 42 副乾酪乳酸桿菌副乾酪亞種 16100 43 乾酶乳酸样菌乾酶亞種 17001 44 乾酪乳酸样菌乾酪聂瑕 17002 45 乾酶乳酸样菌乾酶亞種 17004 46 乾酪乳酸桿菌乾酪亞種 17005 47 德氏乳酸样菌保加利亞亞種 10696 48 瑞士乳酸捍菌（Z/acic^ac/7/似 /2e/vei/c⑽） 11052 49 德氏乳酸桿菌保加利亞亞種 12255 50 德氏乳酸样菌保加利亞亞種 12297 5 1 德氏乳酸桿菌保加利亞亞種 14007 52 德氏乳酸样菌保加利亞亞種 14008 53 德氏乳酸样菌保加利亞亞種 14009 54 德氏乳酸样菌保加利亞亞種 14010 55 德氏乳酸桿菌保加利亞亞種 14069 56 德氏乳酸桿菌保加利亞亞種 14075 57 德氏乳酸样菌保加利亞亞種 14077 58 德氏乳酸桿菌保加利亞亞種 14090 59 德氏乳酸样菌保加利亞亞種 14091 60 德氏乳酸样菌保加利亞亞種 14098 6 1 德氏乳酸样菌保加利亞亞種 16050 6 2 德氏乳酸样菌保加利亞亞種 16051 _____- 11 - 本紙張尺度適用中國國家標準(CNS) A4規格(210 X 297公釐）1277651 A7 B7 V. INSTRUCTIONS OF THE INVENTION Field of the Invention The present invention is primarily directed to new uses of certain lactic acid-like strains in the treatment of allergies. BACKGROUND OF THE INVENTION Allergy refers to a potential ability to develop an adverse immune response to a normally harmless substance. Allergic reactions can be exaggerated to produce symptoms such as pain, coughing, sputum, sneezing, tearing, inflammation and fatigue. It is generally believed that allergic reactions include early specific immune responses and advanced inflammatory responses. It has been reported that allergens (such as pollen and dust mites) stimulate high-affinity immunoglobulin (IgE) receptors to cause early stages of allergies. For example, mast cells and basophils can release histamine and cytokines when stimulated by a sensitive source, and then the mast cells and the cytokines released by the white blood cells will trigger the late stages of allergies by increasing the inflammatory cells. It has also been reported that the collection of eosinophils, macrophages, lymphocytes, neutrophils and platelets initiates a vigorous cycle of inflammation. The late stages of allergies expand the initial immune response and release more inflammatory cells in sequence (Blease et al, Chemokines and their role in airway hyper-reactivity, es 2000; 1 : 54-6 1). In order to treat allergy symptoms, various treatments have been studied, among which anti-allergic agents and histamine receptor antagonists (antihistamines) have been used. The use of histamine antagonists antagonizes histamine released by mast cells in response to allergens. Histamine antagonists reduce the redness, itching and swelling of histamine in the target tissue and prevent or slow down many of the symptoms of mast cells after degranulation. However, antihistamines can also be made ____-4-_ This paper scale applies to Chinese National Standard (CNS) Α4 specifications (210 X 297 mm) 1277651 A7 B7 V. Invention Description (2) In some adverse reactions, such as Reduced attention, unresponsiveness, and lethargy (US Patent No. 0,225,3 32). There are also reports that can treat allergies by regulating cytokines. In these reports, it was found that interferon T (IN F - r ) inhibits the excessive expression of cytokines in T h 2 lymphocytes (especially the secretion of IL-4), thereby reducing B cell proliferation. In addition, IN F - T stimulates the immune response of Thr 1 and inhibits the synthesis of IgE (Sareneva T et al, Influenza A virus-induced INF-α/β and IL-18 synergistically enhanced IFN- y gene expression In human T cells ' J Immunol 1998 ; 160 : 6032-603 8 ; Shida K et al , case / · inhibits antigen-induced IgE secretion through regulation of cytokine production in murine splenocyte culture, Int drc/z /mmzzwo/ 1 998 ; 115: 278-287). Because INF-r inhibits B cell proliferation and IgE secretion, we believe that INF-7 is effective in treating allergies. Lactic acid bacteria are Gram-positive bacteria and are often used as a fermentation industry for the food industry. Recent studies have shown that lactic acid bacteria can stimulate INF-T secretion of cells (Contractor NV et al, Lymphoid hyperplasia, autoimmunity and compromised intestinal intraepithelial lymphocyte development in colitis-free gno to biotic IL-2-deficient mice, J /mmwm/1998; 1 60 : 385-3 9 4). Certain specific lactic acid bacteria (such as Bifidobacterium lactic acid bacteria / acn \ y) and short lactic acid-like bacteria ( Ζ α 〇 ω6α (: / 7 / Μ subspecies can stimulate the secretion of INF-r from lymphocytes derived from small gas and human blood) (US Patent Publication No. ______^_ This paper scale applies to China National Standard (CNS) A4 specification (210X 297 mm) 1277651 A7 B7 V. Invention Description (3 2002/0031503 A1; US Patent No. 5,556, 785 In addition, it has been reported that lactic acid bacteria can stimulate the secretion of interleukin 1 2 (IL -1 2 ) from lymphocytes derived from human or mouse, and IL · 12 is a T cell stimulating cytokine that activates T cells. And NK cells secrete INF·τ* (Hessle et al, Lactobacilli from human gastrointestinal mucosa are strong stimulators of IL-12 production ^ Clin Exp Immunol 1999; 116 · 276-282). SUMMARY OF THE INVENTION The present invention provides certain lactic acid-like strains. A novel use in the treatment of allergies. In one aspect, the present invention provides a composition for treating allergy, the composition comprising a lactic acid strain capable of stimulating an INF-r secretion effective for treating allergy, the strain The following groups are selected: Lactobacillus plantarum CCRC 12944, Lactobacillus acidophilus CCRC 14079, Lactobacillus rhamnosus CCRC 10940, Lactobacillus paracasei subfamily CCRC 14023, Lactobacillus-like bacteria Bulgarian subspecies CCRC 12297, Lactobacillus delbrueckii subsp. bulgaricus CCRC 1 40 0 7 , and Lactobacillus delbrueckii subsp. bulgaricus CCRC 14069. In another aspect, the present invention provides a use of a lactic acid strain capable of stimulating INF-r secretion, which is used For the manufacture of a pharmaceutical formula for treating allergy, the strain is selected from the group consisting of Lactobacillus plantarum CCRC 12944, Lactobacillus acidophilus CCRC 14079, rhamnosyl lactate CCRC 10940, Lactobacillus paracasei subfamily CCRC 14023, Lactobacillus delbrueckii L. subspecies CCRC 12297, Lactobacillus delbrueckii subsp. bulgaricus CCHe 14007, and Lactobacillus bulgaricus subspecies Bulgarian subspecies CCRC 14069. Schematic description _____-6- This paper scale applies China National Standard (CNS) A4 Specification (210X 297 mm) 1277651 A7 __ B7 V. Invention Description (4) — "~ Figure 1 shows Lactobacillus The amount of INF-r secreted after the strain was co-cultured with lymphocytes. Lactic acid bacteria and lymphocytes were co-cultured for 12 and 36 hours, respectively, and the secretion of INF-r was detected by ELISA. The INF-r content is expressed as an absorption value (0.D·value). In the figure, "PC" represents Lactobacillus casei CCRC 10697 as a positive control group; "NC" represents Lactobacillus delbrueckii subsp. bulgaricus CCRC 1407 1 as a negative control group; 1 represents plant lactic acid bacteria CCRC 12944; Acidic lactic acid-like bacteria CCRC 14079; 3 stands for rhamnosyl-like bacteria CCRC 10940; 4 stands for Lactobacillus paracasei sub-chicken subspecies CCRC 14023; 5 stands for lactic acid-like bacteria Bulgarian subspecies CCRC 12297; 6 stands for lactic acid 德The Bulgarian subspecies CCRC 14007, and 7 represent the lactic acid-like bacteria Bulgarian subspecies CCRC 14069. Figure 2 shows the secretion of INF-r after the Lactobacillus strain was co-cultured with peripheral blood mononuclear cells (pbmc). Lactic acid bacteria and PBMC were co-cultured for 12, 48 and 72 hours, respectively, and the secretion of INF-r was detected by ELISA. The INF-T content is expressed as an absorption value (O.D. value). In the experiment, the cheese lactate-like bacteria CCRC 10697 was a positive control group; the Lactobacillus delbrueckii BCG 14071 was a negative control group; the Lactobacillus paracasei sub-flower subspecies CCRC 14023 was a test strain. DETAILED DESCRIPTION OF THE INVENTION In accordance with the present invention, it has been unexpectedly discovered that certain strains of lactic acid-like bacteria that stimulate the secretion of inf-r can be used to treat allergies. In one aspect, the invention provides a composition for treating a body allergy comprising a lactic acid strain capable of stimulating inf-r secretion, the strain being selected from the group consisting of Lactobacillus plantarum CCRC 12944, Lactobacillus acidophilus ____ _士_ This paper scale applies to China National Standard (CNS) A4 specification (210X297 mm) - 1277651 A7 B7 V. Description of invention (5 CCRC 14079, Lactobacillus rhamnosus CCRC 10940, sub-chees lactis-like sub-cheese subspecies CCRC 14023, Lactobacillus delbrueckii subsp. bulgaricus CCRC 12297, lactic acid-like bacteria Bulgarian subspecies CCRC 14007, and Lactobacillus delbrueckii subsp. bulgaricus CCRC 14069. These strains are deposited in the Hsinchu Food Industry Development Research Institute (FIRDI), Taiwan. Therefore, the public can obtain the aforementioned strains from FIRDI. These strains are safe, natural, non-toxic, and comply with GRAS (General Regarded as Safe) standards, which are commonly used in foods and are harmless to humans. According to the present invention, it has been demonstrated that when these strains are co-cultured with lymphocytes, they have the ability to stimulate INF-r secretion. One of these strains has been shown to stimulate peripheral blood mononuclear cells (PBMC) to secrete INF-T. In a preferred embodiment of the invention, the ability of the genus C. lactis subsp. A Lactobacillus casei CCRC 10697 superior to the (quadruple) positive control group. According to the present invention, the lactic acid bacteria used in the treatment of allergy may be a live strain or an inactive strain, for example, a live strain subjected to a heating step or this technique Other commonly used treatments to kill lactic acid bacteria can be used to obtain active strains. In this patent specification, the term "allergy" refers to allergies regulated by inf-r. Allergic diseases include rhinitis, sinusitis, asthma, allergies. Pneumonia, external allergic alveolitis, conjunctivitis, urticaria, eczema, dermatitis, allergic reactions, angioedema, allergic headaches and migraine, and certain gastrointestinal diseases. It has been proven to stimulate the secretion of inf - r Probiotics can treat atopic eczema (Isolauri E et al., Probiotics in the management of atopic ______-8- This paper scale applies to the Chinese National Standard (CNS) A4 Specifications (210x 297 mm) 1277651 A7 B7 V. Description of invention (6) eczema, Clinical and experimental Allergy 2000 » 30 * 1604-1610 ; Sutas Y et al., Suppression of lymphocyte proliferation in vitro by bovine caseins hydrolyzed with Lactobacillus casei GG -derived enzyme j J Allergy Clin Immunol 1996; 98 ♦ 216-224; Kalliomaki M et al, Probiotics in primary prevention of atopic disease: a randomized placebo-controlled trial, Lancet 2001; 357: 1076-79). According to the present invention, the lactic acid strain can be contained in a pharmaceutical composition, a dietary supplement, a food, or a component thereof which is normally ingested by a human. In a preferred embodiment of the invention, the lactic acid strain is administered in the form of a food product, such as a coagulated dairy product produced after calf fermentation. The food prepared according to the present invention can be conveniently administered to an infant or a child. In another aspect, the present invention provides a use of a lactic acid strain capable of stimulating inf-r secretion, which is for use in the manufacture of a pharmaceutical formulation for treating allergy, the strain being selected from the group consisting of: lactic acid-like bacteria CCRC 12944, hobby Acidic lactic acid bacteria CCRC 14 079, rhamnosus lactobacillus CCRC 10940, Lactobacillus subsp. paraphylla CCRC 14023, lactic acid-like bacteria Bulgarian subspecies CCRC 12297, lactic acid-like bacteria Bulgarian subspecies CCRC 14007 And the lactic acid-like bacteria Bulgarian subspecies ccrc 14069. The present invention is illustrated by the following examples, which are not intended to be construed as limiting the invention. Select the lactic acid bacteria strain that can stimulate the lymphocyte secretion of INF·r. The sixty-seven strains of lactic acid listed in Table 1 are selected in advance, and 'the bacteria that are also indicated as the positive control group (PC) and the negative control group (NC) are also indicated. ---------9- _- This paper scale applies to the S s family standard (CNS) A4 specification (·χ 297 public) 1277651 A7 B7 V. Invention description (7) strain. All strains were purchased from FIRDI. Table 1 No. Lactic acid strain CCRC No. PC Lactobacillus dry bacterium (LacMMc/Z/w) 10697 NC Deer's milk-like bacteria Bulgarian subspecies (10) delbrueckii subsp. Bulgaricus) 14071 1 Lactobacillus plantarum 10069 2 Lactobacillus plantarum 10357 3 Lactic acid-like bacteria 11697 4 Lactobacillus plantarum 12250 5 Lactobacillus plantarum 12251 6 Lactobacillus plantarum 12327 7 Lactobacillus plantarum 12944 8 Lactobacillus plantarum 14059 9 Lactobacillus plantarum 15478 10 Lactobacillus Johnsonii) 14004 11 Lactobacillus acidophilus) 14026 12 words, Lactobacillus rhamnosus 14029 13 Lactobacillus acidophilus 14064 14 Eosinophilic lactobacillus 14065 15 Eosinophilic lactobacillus 14079 16 16000 17 Lactobacillus acidophilus 16092 18 Lactobacillus acidophilus 16099 19 Lactobacillus acidophilus 17009 20 Lactobacillus acidophilus 17064 2 1 Acidic Lactobacillus 10695 22 Lactobacillus casei subsp. Casei 10358 23 Rat Lactobacillus citrate 10940 24 cheese Acid bacillus subspecies 11197 25 rhamnosyl lactic acid bacteria 11673 26 Lactobacillus paracasei subsp. Paracasei 12193 27 Lactobacillus paracasei sub-species 12248 _____-10- This paper scale applies to China National Standard (CNS) A4 Specification (210X 297 mm) 1277651 A7 B7 V. Description of Invention (8 28 Lactobacillus subtilis subsp. 12249 29 Lactobacillus subfamily 12272 30 Paralyzed enzyme Lactic acid-like deuterium sub-lyase subspecies 14001 3 1 Pair of cheese Lactobacillus subsp. paraphylla 14023 32 Lactobacillus casei cheese subsp. 14025 33 Lactobacillus cheese subsp. 14073 34 Lactic acid bacteria subspecies 14074 35 Dry enzyme Lactic acid bacteria dry subspecies 14080 36 Cheese Lactobacillus subtilis 14082 37 Lactobacillus cheese subspecies 14083 38 Lactic acid-like mushroom subspecies 14084 39 Lactic acid-like mushroom subspecies 14705 40 Lactic acid-like mushroom sub-species 16093 4 1 Lactobacillus cheese Species 16094 42 Lactobacillus paracasei subsp. paraphylla 16100 43 dry enzyme lactate-like bacterial subspecies 17001 44 dry Casein-like bacteria cheese Nie 瑕 17002 45 dry enzyme lactic acid-like bacteria dry enzyme subspecies 17004 46 Lactobacillus casei sub-species 17005 47 De lactic acid-like bacteria Bulgarian subspecies 10696 48 Swiss lactic acid bacteria (Z/acic^ac/7 /like/2e/vei/c(10)) 11052 49 Lactobacillus delbrueckii subsp. bulgaricus 12255 50 Lactobacillus bulgaricus bacterium Bulgarian subspecies 12297 5 1 Lactobacillus delbrueckii subsp. bulgaricus 14007 52 DeLalactic bacteria bacterium Bulgarian subspecies 14008 53 DeLalactic bacteria Bulgarian subspecies 14009 54 DeLalactic bacteria Bulgarian subspecies 14010 55 Lactobacillus delbrueckii subsp. Bulgaria 14069 56 Lactobacillus delbrueckii subsp. bulgaricus 14075 57 DeLalactic bacteria Bulgarian subspecies 14077 58 Dessert Lactobacillus Bulgarian subspecies 14090 59 DeLalactic bacteria Bulgarian subspecies 14091 60 DeLalactic bacteria Bulgarian subspecies 14098 6 1 DeLalactic bacteria Bulgarian subspecies 16050 6 2 DeLalactic bacteria Bulgarian subspecies 16051 _____- 11 - This paper size applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm)
1277651 A7 B7 五、發明説明（9 ) 63 德氏乳酸桿菌保加利亞亞種 16052 64 德氏乳酸捍菌保加利亞亞種 16053 65 副乾酪乳酸桿菌副乾酪亞種 12188 66 短乳酸桿菌 12247 67 短乳酸桿菌 14060 在這些菌株中，有三十八株是安全、天然、無毒性，且 符合G.R.A.S(普遍視為安全）的標準。所有的菌株均以乳酸 菌MRS培養液（DIFCO 0881)在3 7°C下培養至停滯期，以 3000g離心15分鐘收集菌株，並以2毫升及1毫升PBS(磷酸 緩衝鹽水，pH 7.2)清洗。將所培養的菌株再懸浮於1毫升 PBS中，而後在95 °C加熱30分鐘，經高溫高壓滅菌處理 後，將之置於PBS中，於_20QC下保存。 淋巴細胞培養：版氣菲司可夫（Fischloff)( Fischkoff S. A· Graded increase in probability of eosinophilic differentiation of HL-60 promyelocytic leukemia cells induced by culture under alkaline condition ^ Leukemia Research 1988 ； 12(8) * 679-686) 所述之方法處理HL-60CCRC 60273(選殖體15HL-60)細胞 (購自 FIRDI)。將 HL-60 細胞置於 RPME 1640(pH7.2)中進 行繼代培養（subcultured)，將之謗導分化成嗜伊紅細胞，而 後再以RPMI 1640(pH7.7)進行數代的繼代培養，以獲得淋 巴細胞樣品。在每個淋巴細胞樣品中，將細胞密度調整成 每個樣品含5 χΙΟ6個細胞。將淋巴細胞樣品以2毫升RPMI 1640(卩117.7)培養6小時。 刺激顶F- τ分泌：將淋巴細胞樣品與一定量的前述菌株共 同培養，並以乾酪乳酸桿菌CCRC 10697作為陽性控制組， _________-12-_ — 本紙張尺度適用中國國家標準(CNS) Α4規格(210 X 297公釐） 1277651 A7 B7 —- — ------- ----------- ----------. … "一Μ — - 五、發明説明（1Q ) 而德氏乳酸桿菌保加利亞亞種CCRC 14071作為陰性控制 組。共同培養1 2、3 6及6 0小時後，分別收集每個樣品細 胞。再懸浮所收集的細胞，並以2000rpm離心5分鐘’測定 每個樣品中上清液中IN F - τ含量。 涿启/細-r # f，根據西達（Shida)等人（Shida K.等人， Lactobacillus casei inhibits antigen induced IgE secretion through regulation of cytokine production in murine splenoeyte cultures， Int Arch Allergy Immunol 199S ·， 115 ·· 27S-2S1)所 述之ELISA方法測定INF - τ含量，該方法步騾包括： - 在ELISA培養盤的每個槽孔内加入150微升溶於塗覆缓 衝液（每公升含有8.00克NaCl、0·20克KC1、1.44克 Na2HP04、〇·24克ΚΗ2Ρ〇4、30.0克牛血清白蛋白、及 〇·5〇克NaN3，ρΗ7·4)中之2.5微克/毫升純化小鼠抗人 類INF - r抗體； - 於室溫下以40 rpm轉速震盪培養盤； • 將培養盤在4°C下靜置一夜； - 倒去槽孔中的塗覆緩衝液； - 以洗滌緩衝液（每公升含有8.00克NaCU、0.20克KC1、 1.44 克 Na2HPO4、0.24 克 ΚΗ2Ρ〇4、〇·5 毫升 Tween 20、及0.50克NaN3 ’ pH7.4)清洗培養盤的每個槽孔3 分鐘，共清洗二次； - 以蒸餾水清洗培養盤每個槽孔； - 在培養盤的每個槽孔中加入200微升阻斷緩衝液； - 將培養盤置於室溫下至少靜置2小時； — ------ -13-___ 本紙浪尺度適用中國國家標準(CNS) A4規格(210 X 297公釐） 1277651 A7 B7 五、發明説明（u ) - 倒去槽孔中的阻斷緩衝液； - 以洗滌缓衝液清洗培養盤的每個槽孔3分鐘，共清洗三 次； - 以蒸餾水清洗培養盤每個槽孔； • 將淋巴細胞樣品上清液加至培養盤的每個槽孔中； - 於4 °C下以4 0 rpm轉速隔夜震盪培養盤； - 倒去槽孔中的樣品， - 以洗滌緩衝液清洗培養盤的每個槽孔3分鐘，共清洗三 次，接著再以蒸館水清洗； - 將經稀釋緩衝液稀釋之150微升生物素小鼠抗人類INF-r抗體加至培養盤的每個槽孔中； - 將培養盤在室溫下靜置2小時； - 以洗滌緩衝液清洗培養盤的每個槽孔3分鐘，共清洗三 次，接著再以蒸餾水清洗； - 在培養盤的每個槽孔中加入經稀釋缓衝液稀釋之150微 升抗生物素蛋白鏈菌素-驗性磷酸酶（抗生蛋白鏈菌素-AKP)； - 將培養盤在室溫下靜置1小時； - 以洗務緩衝液清洗培養盤的每個槽孔3分鐘，共清洗四 次，接著再以蒸館水清洗； - 在培養盤的每個槽孔中加入150微升對-硝基苯基磷酸 (pNpp)受質； - 將培養盤在室溫下靜置，直至完成受質反應； - 測定培養盤每個槽孔在405毫微米（換言之OD405)之 ____-14-_ 本紙張尺度適用中國國家標準(CNS) A4規格(210 X 297公釐） 1277651 A7 B7 五、發明説明（12 ) 吸收值。 結果：株乳酸菌刺激INF - τ含量的結果列於表2中。 表2 CCRC編號 12小時(OD) 36小時(OD) 60小時(OD) 陽性控制組 0.156 0.295 0.106 陰性控制組 0.117 0.241 0.103 10069 0.117 0.304 0.107 10357 0.129 0.267 0.104 11697 0.112 0.397 0.104 12250 0.122 0.335 0.156 12251 0.177 0.293 0.110 12327 0.131 0.289 0.111 12944 0.152 0.427 0.092 14059 0.111 0.363 0.102 15478 0.157 0.385 0.109 14004 0.162 0.399 0.106 14026 0.115 0.405 0.103 14029 0.131 0.272 0.110 14064 0.114 0.337 0.164 14065 0.159 0.244 0.110 14079 0.142 0.342 0.099 16000 0.123 0.255 0.105 16092 0.127 0.254 0.114 16099 0.114 0.262 0.114 17009 0.111 0.276 0.117 17064 0.147 0.272 0.114 10695 0.131 0.274 0.118 10358 0.148 0.271 0.119 10697 0.160 0.340 0.098 10940 0.336 0.335 0.109 11197 0.150 0.293 0.104 11673 0.109 0.298 0.106 12193 0.116 0.305 0.111 12248 0.160 0.284 0.112 12249 0.142 0.267 0.112 12272 0.120 0.276 0.112 14001 0.173 0.410 0.108 ____· 15- 本紙張尺度適用中國國家標準(CNS) A4規格(210X297公釐） 1277651 A7 B7 五、發明説明（13 ) 14023 0.120 0.538 0.125 14025 0.142 0.339 0.110 14073 0.157 0.398 0.104 14074 0.125 0.455 0.117 14080 0.124 0.308 0.116 14082 0.148 0.248 0.113 14083 0.129 0.203 0.116 14084 0.153 0.335 0.121 14705 0.159 0.277 0.122 16093 0.131 0.328 0.127 16094 0.160 0.309 0.114 16100 0.158 0.316 0.121 17001 0.219 0.252 0.123 17002 0.155 0.207 0.120 17004 0.236 0.112 0.119 17005 0.125 0.320 0.104 10696 0.122 0.373 0.122 11052 0.142 0.316 0.107 12255 0.118 0.325 0.116 12297 0.121 0.418 0.105 14007 0.122 0.502 0.110 14008 - 0.359 0.100 14009 0.224 0.293 0.103 14010 0.150 0.312 0.100 14069 0.146 0.440 0.161 14071 0.144 0.270 0.099 14075 0.152 0.319 0.100 14077 0.163 0.342 0.102 14090 0.203 0.302 0.106 14091 0.184 0.288 0.097 14098 0.147 0.242 0.101 16050 0.136 0.264 0.098 16051 0.135 0.250 0.103 16052 0.132 0.386 0.104 16053 0.132 0.314 0.113 12188 0.150 0.263 0.101 12247 0.137 0.246 0.103 14060 0.167 0.328 0.103 _____- 16- 本紙張尺度適用中國國家標準(CNS) A4規格(.210X297公釐） 1277651 A7 B7 五、發明説明（14 ) 在此6 7株菌株中，發現下列七株可以刺激淋巴細胞中 INF- r的分泌：植物乳酸桿菌CCRC 12944、嗜酸性乳酸样 菌CCRC 14079、鼠李糖乳酸样菌CCRC 10940、副乾酪乳酸 桿菌副乾酪亞種CCRC 14023、德氏乳酸桿菌保加利亞亞種 CCRC 12297、14007及14069，這些結果示於圖1中。副乾酪 乳酸桿菌副乾酪亞種CCRC 14023及德氏乳酸样菌保加利亞 亞種CCRC 12297、14007及14069所得之OD405數值高於陽 性控制組，甚至比陰性控制組高4倍，除此之外，除了鼠李 糖乳酸样菌CCRC 10940外，其他菌株在36小時後所收集的 共同培養液之OD405數值是12小時後共同培養液數值的3 倍。 實例2 :經乳酸菌刺激之周邊血液單核細胞後之inf- r分 法分離周邊血液箪核細胞：给5毫升費寇-海沛吉（Ficoll-Hypaque)(l7- 1400-02，法瑪西亞（Pharmacia))加至 5 毫升源 自自願者之血液樣品中，而後以500g速度離心30分鐘。從 界面中取出周邊單核細胞（PBMC)，並以PBS清洗兩次。將 PBMC(105個細胞/毫升）轉種至6槽孔培養盤的槽孔内，其 中每個槽孔含有2毫升pH 7.7的RPMI 1640培養液。 W滄r分泌··利用實例1所述的類似方法，將PBMC 與植物乳酸桿菌CCRC 12944、嗜酸性乳酸桿菌CCRC 14079、鼠李糖乳酸样菌CCRC 10940、副乾酪乳酸桿菌副乾 酪亞種CCRC 14023、德氏乳酸桿菌保加利亞亞種CCRC 12297、14007及14069 (107個細胞/毫升）共同培養，並以 乾酪乳酸桿菌CCRC 10697作為陽性控制組，而德氏乳酸桿 _____-17-____ 本紙張尺度適用中國國家標準(CNS) A4規格(210 X 297公釐） 1277651 A7 B7 五、發明説明（15 ) 菌保加利亞亞種CCRC 14071作為陰性控制組。在共同培養 2 4、4 8及7 2小時後，收集細胞，再懸浮，並以2000 rpm 速度離心5分鐘，以實例1所述的相同方法測定上清液中 INF- 7* 含量。 ,#耒：七株菌株刺激PBMC後所得INF- 7的結果列於表3 中，而副乾酪乳酸样菌副乾酪亞種CCRC 14023的結果特別 列於圖2中。 表3 時間 CCRC編號 OD INFi濃度 (毫微iy毫升） 24小時 陽性控制組 0.1945 861.5 12944 0.1685 731.5 14079 0.1892 836.5 10940 0.223 1004 14023 0.23 1039 12297 0.195 864 14007 0.165 714 14069 0.2015 896.5 48小時 陽性控制組 0.2095 936.5 12944 0.1605 691.5 14079 0.244 1109 10940 0.305 1414 14023 0.267 1224 12297 0.1555 666.5 14007 0.141 594 14069 0.165 714 72小時 陽性控制組 0.2575 1176.5 12944 0.159 684 14079 0.17 739 10940 0,193 854 14023 0.1895 836.5 12297 0.147 624 14007 0.133 554 14069 0.17 739 __-18- 本紙張尺度適用中國國家標準(CNS) A4規格(210 X 297公釐） 1277651 A7 B7 五、發明説明（ ） v16 在共同培養24小時後，所收集樣品之00405數值是陰性 控制組的1 · 2倍；在共同培養4 8小時後，所收集樣品之數值 疋陰性控制組的1 . 8倍，且是陽性控制組的1 · 3倍；而共同 培養7 2小時後的數值是陰性控制組的i 3倍。 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。因此，習於此技術之人士對上述實施例所做之修 改及變化仍不達背本發明之精神。本發明之權利範圍應如 後述之申請專利範圍所列。1277651 A7 B7 V. Description of invention (9) 63 Lactobacillus delbrueckii subsp. bulgaricus 16052 64 Lactobacillus delbrueckii subsp. bulgaricus 16453 65 Lactobacillus paracasei sub-species 12188 66 Lactobacillus brevis 12247 67 Lactobacillus brevis 14060 Thirty-eight of these strains are safe, natural, non-toxic, and meet GRAS (Generally Recognized as Safe) standards. All the strains were cultured in lactic acid bacteria MRS medium (DIFCO 0881) at 37 ° C until the stagnation period, and the strain was collected by centrifugation at 3000 g for 15 minutes, and washed with 2 ml and 1 ml of PBS (phosphoric acid buffered saline, pH 7.2). The cultured strain was resuspended in 1 ml of PBS, and then heated at 95 ° C for 30 minutes, and after autoclaving, it was placed in PBS and stored at -20C. Lymphocyte culture: Fischkoff S. A· Graded increase in probability of eosinophilic differentiation of HL-60 promyelocytic leukemia cells induced by culture under alkaline condition ^ Leukemia Research 1988 ; 12(8) * 679 -686) The method described treats HL-60CCRC 60273 (selection 15HL-60) cells (purchased from FIRDI). HL-60 cells were subcultured in RPME 1640 (pH 7.2), differentiated into eosinophils, and then subcultured for several generations with RPMI 1640 (pH 7.7). To obtain a lymphocyte sample. In each lymphocyte sample, the cell density was adjusted to contain 5 χΙΟ 6 cells per sample. Lymphocyte samples were incubated for 6 hours in 2 ml RPMI 1640 (卩 117.7). Stimulation of top F-τ secretion: Co-culture of lymphocyte samples with a certain amount of the aforementioned strain, and using Lactobacillus casei CCRC 10697 as a positive control group, _________-12-_ — This paper scale applies to Chinese National Standard (CNS) Α4 specifications (210 X 297 mm) 1277651 A7 B7 —- — —------ ----------- ----------. ... "一Μ — - V Invention Description (1Q) Lactobacillus delbrueckii subsp. bulgaricus CCRC 14071 was used as a negative control group. After co-cultivation for 1, 2, 6 and 60 hours, each sample cell was collected separately. The collected cells were resuspended and centrifuged at 2000 rpm for 5 minutes to determine the amount of IN F - τ in the supernatant of each sample.涿启/细-r # f, according to Shida K. et al. (Shida K. et al., Lactobacillus casei inhibits antigen induced IgE secretion through regulation of cytokine production in murine splenoeyte cultures, Int Arch Allergy Immunol 199S ·, 115 · The ELISA method described in 27S-2S1) measures the INF-τ content. The method steps include: - Adding 150 μl of each of the wells of the ELISA plate to the coating buffer (8.00 g NaCl per liter) , 0. 20g KC1, 1.44g Na2HP04, 〇·24g ΚΗ2Ρ〇4, 30.0g bovine serum albumin, and 〇·5〇g NaN3, ρΗ7·4) 2.5 μg/ml purified mouse anti-human INF - r antibody; - shake the plate at 40 rpm at room temperature; • leave the plate at 4 ° C overnight; - pour off the coating buffer in the well; - wash buffer (per liter Containing 8.00 g NaCU, 0.20 g KC1, 1.44 g Na2HPO4, 0.24 g ΚΗ2Ρ〇4, 〇·5 ml Tween 20, and 0.50 g NaN3 'pH7.4), each well of the culture dish was washed for 3 minutes, and washed twice. ; - Wash each slot of the culture tray with distilled water; - Add 200 μl of blocking buffer to each well of the plate; - Allow the plate to stand at room temperature for at least 2 hours; — ------ -13-___ This paper wave scale applies to China Standard (CNS) A4 size (210 X 297 mm) 1277651 A7 B7 V. Description of invention (u) - Pour off the blocking buffer in the well; - Wash each well of the plate with wash buffer for 3 minutes Wash a total of three times; - Wash each well of the plate with distilled water; • Add the supernatant of the lymphocyte sample to each well of the plate; - Shake the plate overnight at 4 °C at 4 °C - Pour off the sample in the slot, - Wash each well of the plate with wash buffer for 3 minutes, wash a total of three times, then rinse with steaming water; - 150 μL of diluted dilution buffer Mouse anti-human INF-r antibody was added to each well of the culture plate; - The plate was allowed to stand at room temperature for 2 hours; - Each well of the plate was washed with washing buffer for 3 minutes. Wash three times, then rinse with distilled water; - Add dilution buffer to each well of the plate Release 150 μl of streptavidin-test phosphatase (streptavidin-AKP); - leave the plate at room temperature for 1 hour; - wash the plate with wash buffer Each well was cleaned four times for 3 minutes, then washed with steaming water; - 150 μl of p-nitrophenyl phosphate (pNpp) was added to each well of the plate; - will be cultured The plate is allowed to stand at room temperature until the endurance reaction is completed. - The cell size of each plate is 405 nm (in other words, OD405). ____-14-_ This paper size is applicable to the Chinese National Standard (CNS) A4 specification ( 210 X 297 mm) 1277651 A7 B7 V. Description of invention (12) Absorbance value. Results: The results of stimulation of INF-τ content by strains of lactic acid bacteria are shown in Table 2. Table 2 CCRC number 12 hours (OD) 36 hours (OD) 60 hours (OD) Positive control group 0.156 0.295 0.106 Negative control group 0.117 0.241 0.103 10069 0.117 0.304 0.107 10357 0.129 0.267 0.104 11697 0.112 0.397 0.104 12250 0.122 0.335 0.156 12251 0.177 0.293 0.110 12327 0.131 0.289 0.111 12944 0.152 0.427 0.092 14059 0.111 0.363 0.102 15478 0.157 0.385 0.109 14004 0.162 0.399 0.106 14026 0.115 0.405 0.103 14029 0.131 0.272 0.110 14064 0.114 0.337 0.164 14065 0.159 0.244 0.110 14079 0.142 0.342 0.099 16000 0.123 0.255 0.105 16092 0.127 0.254 0.114 16099 0.114 0.262 0.114 17009 0.111 0.276 0.117 17064 0.147 0.272 0.114 10695 0.131 0.274 0.118 10358 0.148 0.271 0.119 10697 0.160 0.340 0.098 10940 0.336 0.335 0.109 11197 0.150 0.293 0.104 11673 0.109 0.298 0.106 12193 0.116 0.305 0.111 12248 0.160 0.284 0.112 12249 0.142 0.267 0.112 12272 0.120 0.276 0.112 14001 0.173 0.410 0.108 ____· 15- This paper scale applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 1277651 A7 B7 Five (13) 14023 0.120 0.538 0.125 14025 0.142 0.339 0.110 14073 0.157 0.398 0.104 14074 0.125 0.455 0.117 14080 0.124 0.308 0.116 14082 0.148 0.248 0.113 14083 0.129 0.203 0.116 14084 0.153 0.335 0.121 14705 0.159 0.277 0.122 16093 0.131 0.328 0.127 16094 0.160 0.309 0.114 16100 0.158 0.316 0.121 17001 0.219 0.252 0.123 17002 0.155 0.207 0.120 17004 0.236 0.112 0.119 17005 0.125 0.320 0.104 10696 0.122 0.373 0.122 11052 0.142 0.316 0.107 12255 0.118 0.325 0.116 12297 0.121 0.418 0.105 14007 0.122 0.502 0.110 14008 - 0.359 0.100 14009 0.224 0.293 0.103 14010 0.150 0.312 0.100 14069 0.146 0.440 0.161 14071 0.144 0.270 0.099 14075 0.152 0.319 0.100 14077 0.163 0.342 0.102 14090 0.203 0.302 0.106 14091 0.184 0.288 0.097 14098 0.147 0.242 0.101 16050 0.136 0.264 0.098 16051 0.135 0.250 0.103 16052 0.132 0.386 0.104 16053 0.132 0.314 0.113 12188 0.150 0.263 0.101 12247 0.137 0.246 0.103 14060 0.167 0.328 0.103 _____- 16- This paper size applies National Standard (CNS) A4 Specification (.210X297 mm) 1277651 A7 B7 V. Description of Invention (14) Among the 67 strains, the following seven strains were found to stimulate the secretion of INF-r in lymphocytes: Lactobacillus plantarum CCRC 12944, eosinophilic lactic acid-like bacteria CCRC 14079, rhamnosyl-lactic acid CCRC 10940, Lactobacillus paracasei sub-chicken CCRC 14023, Lactobacillus delbrueckii subsp. bulgaricus CCRC 12297, 14007 and 14069, these results are shown in the figure 1 in. The OD405 value of Lactobacillus paracasei subfamily CCRC 14023 and the lactic acid-like bacteria Bulgarian subspecies CCRC 12297, 14007 and 14069 were higher than the positive control group, even 4 times higher than the negative control group, except Except for the rhamnosyl-like bacterium CCRC 10940, the OD405 value of the co-culture solution collected by other strains after 36 hours was 3 times the value of the co-culture solution after 12 hours. Example 2: Inf-r fractionation of peripheral blood mononuclear cells stimulated by lactic acid bacteria to separate peripheral blood nucleus cells: 5 ml of Ficoll-Hypaque (l7-1400-02, Pharmacia) (Pharmacia)) was added to 5 ml of blood samples from volunteers and then centrifuged at 500 g for 30 minutes. Peripheral monocytes (PBMC) were removed from the interface and washed twice with PBS. PBMC (105 cells/ml) was transferred to wells of a 6-well culture dish, each of which contained 2 ml of RPMI 1640 medium at pH 7.7. W沧r secretion·· Using a similar method as described in Example 1, PBMC and Lactobacillus plantarum CCRC 12944, Lactobacillus acidophilus CCRC 14079, rhamnosyl lactate CCRC 10940, Lactobacillus paracasei subfamily CCRC 14023 Lactobacillus delbrueckii subsp. bulgaricus CCRC 12297, 14007 and 14069 (107 cells/ml) were co-cultured with Lactobacillus casei CCRC 10697 as a positive control group, while Dessert lactic acid rod _____-17-____ paper scale Applicable to China National Standard (CNS) A4 specification (210 X 297 mm) 1277651 A7 B7 V. Description of invention (15) Bacterial subspecies CCRC 14071 is used as a negative control group. After co-cultivation for 24, 48 and 72 hours, the cells were collected, resuspended, and centrifuged at 2000 rpm for 5 minutes, and the INF-7* content in the supernatant was determined in the same manner as described in Example 1. #耒: The results of INF-7 obtained after stimulation of PBMC by the seven strains are shown in Table 3, and the results of the sub-cheese-like sub-chicken subspecies CCRC 14023 are specifically shown in Fig. 2. Table 3 Time CCRC number OD INFi concentration (nano iy ml) 24 hours positive control group 0.1945 861.5 12944 0.1685 731.5 14079 0.1892 836.5 10940 0.223 1004 14023 0.23 1039 12297 0.195 864 14007 0.165 714 14069 0.2015 896.5 48 hours positive control group 0.2095 936.5 12944 0.1605 691.5 14079 0.244 1109 10940 0.305 1414 14023 0.267 1224 12297 0.1555 666.5 14007 0.141 594 14069 0.165 714 72 hours positive control group 0.2575 1176.5 12944 0.159 684 14079 0.17 739 10940 0,193 854 14023 0.1895 836.5 12297 0.147 624 14007 0.133 554 14069 0.17 739 __- 18- This paper scale applies to Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1277651 A7 B7 V. Invention description ( ) v16 After 24 hours of co-cultivation, the value of 00405 of the collected sample is 1 of the negative control group. · 2 times; after 48 hours of co-cultivation, the value of the collected samples was 1.8 times that of the negative control group and 1.3 times that of the positive control group; and the value after 72 hours of co-culture was negative control. Group i 3 times. The above-described embodiments are merely illustrative of the principles and effects of the invention and are not intended to limit the invention. Therefore, modifications and variations of the embodiments described above will be apparent to those skilled in the art. The scope of the invention should be as set forth in the appended claims.