TW201127389A - Prophylactic composition for influenza infection - Google Patents

Prophylactic composition for influenza infection Download PDF

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TW201127389A
TW201127389A TW099143199A TW99143199A TW201127389A TW 201127389 A TW201127389 A TW 201127389A TW 099143199 A TW099143199 A TW 099143199A TW 99143199 A TW99143199 A TW 99143199A TW 201127389 A TW201127389 A TW 201127389A
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composition
culture
milk
influenza
propionic acid
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TW099143199A
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TWI476000B (en
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Masao Takami
Shinya Nagafuchi
Satoshi Takasugi
Hiroyasu Akatsu
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Meiji Dairies Corp
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    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/20—Milk; Whey; Colostrum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/145—Orthomyxoviridae, e.g. influenza virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55588—Adjuvants of undefined constitution
    • A61K2039/55594—Adjuvants of undefined constitution from bacteria
    • C—CHEMISTRY; METALLURGY
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    • C12N2760/00011—Details
    • C12N2760/16011—Orthomyxoviridae
    • C12N2760/16111—Influenzavirus A, i.e. influenza A virus
    • C12N2760/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

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  • Immunology (AREA)
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Abstract

It was clarified that a culture of a propionic acid bacterium exhibited a prophylactic effect on influenza infection. Disclosed is a composition comprising a culture of a propionic acid bacterium which is capable of potentiating the induction of a neutralizing antibody in an animal that has been inoculated with an influenza vaccine. The fact that the component constituting the aforesaid composition has been eaten by humans over a long time assures the high safety and good taste thereof and, therefore, said composition can be taken over a long period of time. In addition, the aforesaid composition can contain, as optional components, a milk fermentation product and an oligosaccharide. It can be also expected that another effect of controlling the functions of the intestines is achieved by administering the aforesaid composition.

Description

201127389 四、 指定代表圖： (一） 本案指定代表圖為：第（2A)圖。 (二） 本代表圖之元件符號簡單說明：無。 五、 本案若有化學式時，請揭示最能顯示發明特徵的化學式： 六、 發明說明： 【發明所屬之技術領域】 本發明係關於含有丙酸菌的培養物的組成物。或者， 本發明係關於用於預防流行性感冒感染症的組成物或預防 【先前技術】 流行性感冒係以流行性感冒病毒為病原體的感染力強 的感染症。流行性感冒病毒(Influenzavirus)係屬於正黏 病毒科（知紿⑽的負股單鏈RNA病毒。正黏病 毒科由流行性感冒病毒i個屬構成(…科)。由於核蛋 白質的抗原性的不同，流行性感冒病毒存在有^的3種 次相對於專門以人類為寄主並感染的B型及c型，A 型流行性感冒病毒可感染哺乳動物或鳥類等廣泛的生物。 因此’會在鳥類或哺乳動物的體内發生基因的雜交， 產生病原性或抗原性不同的變異病毒。 ” 例如，近年來在全世界流行的豬流行性感冒，係由於 201127389 A型HIN1亞型流行性硌罝 主 这目病毋的感染而發病的流行性感 冒。豬的流行性感冒病毒，櫨切 〜 H會類且與造成大 ㈣有關。且據預測會大流行(pandemlc)的鳥的強毒性流 订性感目’據認為是鳥類的強毒性流行性感冒病毒獲得對 於人類的感染力而可能造成大流行(管原民枝等人，觸)。 目前已有阻礙流行性感冒病毒增殖的治療藥市隹。目 前市售的流行性感冒的治療藥，當於感染後的早期階段適 當投藥時，可期待有充分的治療效果。但是，尤其是對於 老年人、孩童、患病者等高危險群，流行性感冒仍然是危 險的感染症。X ’也有人報告出現對於治療藥有抗藥性的 病毒。 即使是已開發治療藥的現在，為了防止流行性感冒的 重症化，接種流行性感冒疫苗仍有意義。若接種流行性感 S疫田，則會誘導對抗流行性感冒病毒的中和抗體，可防 止感染後的病毒的增殖或感染擴大（C. Avendan〇 et ai，201127389 IV. Designated representative map: (1) The representative representative of the case is: (2A). (2) A brief description of the symbol of the representative figure: None. 5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to a composition of a culture containing propionic acid bacteria. Alternatively, the present invention relates to a composition for preventing influenza infection or prevention. [Prior Art] Infectious influenza is an infectious disease with an infectious virus as a pathogen. The influenza virus (Influenzavirus) belongs to the Orthomyxoviridae (10) negative-stranded single-stranded RNA virus. The Orthomyxoviridae is composed of influenza genus i (genus). Due to the antigenicity of nuclear proteins In contrast, there are three types of influenza viruses in comparison with type B and type C, which are mainly hosted and infected by humans. Type A influenza virus can infect a wide range of organisms such as mammals or birds. Genes hybridize in birds or mammals to produce pathogenic or antigenic variant viruses." For example, swine influenza, which is popular worldwide in recent years, is due to the 201127389 type A HIN1 subtype epidemic. Influenza caused by the infection of the disease, the influenza virus of the pig, the sputum ~ H will be related to the cause of the big (four), and it is predicted that the pandemic (pandemlc) of the bird's strong toxicity flow The sexy eye 'is considered to be a bird's virulent influenza virus that can cause a pandemic for human infections (in the case of the original people, etc.). A therapeutic drug for proliferation. Currently, a commercially available influenza drug can be expected to have sufficient therapeutic effects when it is appropriately administered at an early stage after infection. However, especially for the elderly, children, and the sick. In the case of a high-risk group, influenza is still a dangerous infection. X's also reported a virus that is resistant to a therapeutic drug. Even if it is a drug that has been developed, in order to prevent the seriousness of influenza, the vaccination is popular. The vaccine is still meaningful. If it is vaccinated with the epidemic, it will induce neutralizing antibodies against the influenza virus, which will prevent the proliferation of the virus or the infection from spreading (C. Avendan〇et ai,

Zhu Q et al.)。對於與作為疫苗接種的病毒的抗原性類似 的病毒，防止重症化的效果高。已有報告指出，與疫苗接 種的健康正常的成人中的中和抗體的誘導率（7〇_9〇%)相 比，老年人的誘導率較低（l7_53%)(G(3Qdwin K，et 老年人由於免疫力降低’因此，若感染會重症化，有時會 造成死亡’因此，提高於老年人的中和抗體誘導率尤其重 要。 [先前技術文獻] 專利文獻 1 ..W0 2001/028547 g 201127389 專利文獻 2:W0 2004/085364 專利文獻 3:W0 2007/023935 專利文獻 4:WO 2005/094850 非專利文獻1 :菅原民枝等人，感染症誌，2008, 82:427-433 非專利文獻 2 : World Heal th Organization : Department of Communicable Disease Surveillance and Response Global Influenza Programmed, 2005. 非專利文獻 3:C，Avendano et al.，J Parenter Enteral Nutr. 2004;28:348-54. 非專利文獻 4:ZhuQ，etal.，BiochemBiophysRes Commun. 2005;329:87-94. 非專利文獻 5:Goodwin K, et al.，Vaccine. 2006 Feb 20:24(8):1159-69. 【發明内容】 (發明欲解決之課題） 本發明之課題在於提供一種含有丙酸菌的培養物的組 成物°尤其本發明之課題在於提供一種具有流行性感冒病 毒感染症的預防效果的組成物。或者，本發明之課題在於 提供一種具有整腸作用的組成物。 (解決課題的方式） 抓灯性感冒疫苗的病毒感染預防作用，主要依存於病 毋中和抗體的誘導。因，疫苗接種後刺激中和抗體的誘 導據吻為對於增強疫苗的預防作用有效。或者，病毒感 201127389 染時，在患者體内形成—般的免疫反應所誘導的病毒中和 抗體，為患者的重要生體防禦機能之一。本案發明人等， 對於能夠增強因流行性感冒疫苗或病毒感染所產生的病毒 中和抗體的誘導之成分反覆研究。結果發現，在投予特定 的微生物培養物的動物中，流行性感冒疫苗接種時的病毒 中和抗體的誘導被增強，乃完成本發明。亦即，本發明係 關於以下組成物及其用途。 [1 ]種流行性感冒感染症的預防組成物，包含丙酸菌的 培養物。 [2 ]如[1 ]之流行性感冒感染症的預防組成物，其中丙酸菌 馬夤 K 丙敗★于魯{Prop ion 1 bacterium freudenrei chi 。 [3 ]如[1 ]之流行性感冒感染症的預防組成物，更額外地包 含乳發酵成分及寡糖任一者或兩者。 [4 ]如[3 ]之流行性感冒感染症的預防組成物，其中乳發酵 成分係以乳酸桿菌屬的乳酸菌及鏈球菌 屬的乳酸菌之任一者或兩者使乳發酵的 乳、或其混合物。 [5 ]如[3 ]或[4 ]之流行性感冒感染症的預防組成物，其中 乳發酵成分為非熟成乳酪。 [6 ]如[3 ]之流行性感冒感染症的預防組成物，其中構成敢 述寡糖的糖之至少一種為半乳糖。 [7 ]如[3 ]或[4 ]之流行性感冒感染症的預防組成物，其中 該組成物包含丙酸菌的培養物及乳發酵成分，且兩者經過 殺菌。 *=： 5 201127389 [8] 如[1]至[5]中任一項之流行性感冒感染症的預防組成 物’係用於對接種流行性感冒疫苗的動物經腸投予。 [9] 如[3]之流行性感冒感染症的預防組成物，包含以下營 養素： 丙酸菌的培養物； 乳發酵成分； 寡糖； 蛋白質； 糖； 脂質；及 食物纖維。 [10]如[9]之流行性感冒感染症的預防組成物，更額外地 包含選自由維生素類、礦物質類、有機酸及有機鹼所構成 的群組中之至少1種營養素。 [11 ] 一種於已接種流行性感冒疫苗的動物中之流行性感 冒病毒的中和抗體的誘導促進劑，包含丙酸菌的培養物。 [12 ] —種流行性感冒感染症的預防方法，包含以下步驟. (1) 對於動物投予丙酸菌的培養物之步驟；及 (2) 對於動物接種流行性感冒疫苗之步驟。 [13]如[12]之流行性感冒感染症的預防方法，其中在步驟 (2)之别、後或同時，至少進行1次步驟（1)。 Π4]如[12]或[13]之流行性感冒感染症的預防方法，其中 在步驟（1)中，丙酸菌的培養物與乳發酵成分及寡糖任2者 或兩者一起投予。 201127389 Π5] —種組成物，含有以下成分（a)〜（c): (a) 寡糖、 (b) 乳發酵成分，及 (c) 丙酸菌的培養物。 [16]如[15]之組成物，其中，構成前述寡糖的糖之至少 種為半乳糖。 [17 ]如[15 ]或[16 ]之組成物，係整腸用組成物。 (發明效果） 本發明之組成物’增強流行性感冒疫苗的中和抗體誘 導作用。本發明的組成物可調製為既為流質食物等而投; 人的成分來製造。因此’本發明的組成物已有高度安全性 的保障。θ而’不僅可與疫苗接種同時投予本發明之組成 物’也可在其前後持續投予本發明之組成物。藉由持續的 投予’可以持續期待因本發明之組成物所形成的中和 的誘導促進作用。 為了增強對始自於流行性感冒病毒的病毒疫苗的免疫 反應，在疫苗中常會調配佐劑。調配疫苗的佐齊丨，當然要 求南度安全性。因&，開發新穎的佐劑時，需要謹慎的安 全性試驗。對此，構成本發明組成物的各成分，由於均已 為食品被食用I ’雖持續經腸投予人，也已證明沒有危險 ,。再者’本發明的組成物’可以組合公知的佐劑而經腸 投予。亦即’不僅是安全性，從提供新的選項作為對疫苗 的免疫反應的增強方法之觀點，本發明的意義重大。 本發明的組成物，其較佳態樣中，藉由既為流質食物 7 201127389 或食品而廣泛攝取的成分之組合而提供。因&，藉由將本 發明的組成物作成流質食物持續攝取，可造成對流行性感 冒病毒的中和抗體的誘導能力常在增高的狀態。對於如老 年人或住院患者具有流行性感冒重症化風險的人群流行 性感冒病毒的感染是嚴峻的問題。但是，若將本發明的組 成物作成流質食物而預防性投予，則可提高族群全體對於 感染的預防能力》 【實施方式】 (實施發明的形態） 本發明&供包含丙酸菌的培養物之流行性感冒感染症 的預防組成物，或流行性感冒感染症的預防劑。 本發明的預防劑或組成物，包含丙酸菌的培養物。丙 酸卤’係指丙酸桿菌屬（/Vopj 的革蘭氏陽性 的厭氧菌’無氧地從糖類形成丙酸的微生物。具體而言， 可將如下的微生物培養物添加到本發明組成物中。 費氏丙酸桿菌ionibacterium freudenreichii') > 特氏丙酸桿菌（/>. t力刀//)、 丙數丙後椁菌（p. acid j prop ionic j) 詹氏丙酸桿菌（户./e/75^/7//)等。 這些丙酸菌為用於製造乳酪（cheese)的微生物》除此 之外，以下的微生物也可作為丙酸菌。 貪婪丙酸桿菌（八shi/⑽）、 座瘡丙酸桿菌（尺、 201127389 嗜' 淋巴丙酸桿菌（/>· 历力//⑽）、 顆粒丙酸桿菌（八wa/7i//0lsa历）。 這些微生物從自然界或發酵乳中單離的方法為公知。 丙酸菌也可利用在瑞士乳酪（Swi ss cheese)製造時使用的 微生物。本發明中的丙酸菌培養物，係指將如上述的丙酸 菌於適當的培養條件培養後的培養物。丙酸菌的培養方法 為公知。丙酸菌在培養時，可應用W003/016544A1等記载 的條件。例如，培養丙酸菌的培養基，已知有在脫脂奶粉 或脫脂奶粉的蛋白分解處理物中添加啤酒酵母萃取物等的 組成。若在適當培養基中接種費氏丙酸桿菌 (Propionibacterjum fjreudenreichi i)而可増殖丙敗菌的 條件下培養’可獲得丙酸菌的培養物。 或者，以高濃度培養丙酸菌的方法，有以在乳清蛋白 /辰縮物（Whey Protein Concentrate: WPC)或其酵素分解物 中添加礦物質及單糖的培養基培養丙 開特許平™號公報)。例如，以含有 物的培養基培養費氏丙酸桿菌（汾—❿ /—m.⑽）而獲得的培養物，作為本發明的丙酸菌的 培養物為較佳。或者，％丙酸菌的效率培養法而言，有將 與丙酸菌以不同的培#槽_面使培養液循環一面 的方法(曰本公開特許平號公報)。藉由這此 培養方法而獲得的丙酸菌培養物， 成物中。 也了調配於本發明的組 例如 添加乳清加工品作為培養基 的主成分，可高密 9 201127389 度地培養丙酸菌。乳清的加工品，例如以下成分。 乳清粉末， 乳清或乳清粉末的蛋白酶處理物。 培養基中除了添加乳清蛋白以外，也可添加礦物質、 單糖的混合物。為了降低培養基中的糖濃度，可添加乳清 蛋白濃縮物（以下也稱為WPC)作為乳清蛋白質源。wpc可藉 由將乳清進行透析處理而減少乳糖含量來獲得。乳清蛋= 濃縮物，可進-步將蛋白質成分以高純度分離，而成為乳 清蛋白分離物（以下也稱為WPI:^除了在培養基添加這些 成分以外，也可分別添加適量的糖及不足的礦物質，將培 養基的組成用於培養丙酸菌。 乳清係例如將脂肪、酪蛋白、脂溶性維生素等從牛乳 除去時所殘留的水溶性成分。乳清一般而言，係在天然乳 路、粗凝乳酶酪蛋白製造時，為副產物而獲得的乳酪乳清 或粗凝乳酶乳清（或也稱為甜乳清）、從脫脂乳製造酸酪蛋 白或夸克乳酷（Quark Cheese)時獲得的路蛋白乳清、夸克 乳清（或也稱為酸乳清）。乳清的主成分為蛋白質（沒-乳球 蛋白、α -乳白蛋白等）、乳糖、水溶性維生素、鹽類（礦物 貝成分），各別的特徵’在作為牛乳成分的研究較作為乳清 成分的研究清楚。 「乳清相關製品」，例如：將乳清濃縮處理後的濃縮乳 清、將乳清乾燥處理後的乳清粉末末、將乳清的主要蛋白 貝等以超過濃（U1 traf i 1 trat i on : UF )法等進行濃縮處理後 乾燥處理的乳清蛋白濃縮物（Whey Protein Concentrate: 10 201127389 以下也稱為WPC)、將乳清利用微過濾（Micr〇filtrati〇n:MF) 法或離心分離.法等除去脂肪後以UF法濃縮處理後進行乾 燥處理的脫脂WPC(低脂肪、高蛋白質）、將乳清的主要蛋 白質利用離子交換樹脂法或凝膠過濾法等選擇性地分層處 理後進行乾燥處理的乳清蛋白分離物（Whey Pr〇tein Isolate’以下也稱為wpi)、利用奈米過濾（Nan〇filtrati〇n: NF )法或電透析法等進行脫鹽處理後乾燥處理的脫鹽乳 /月將來自於乳清的礦物質成分進行沉澱處理後利用離心 分離法等濃縮處理的礦物質濃縮乳清等。這些之中，含有 乳蛋白質乾重（固體成分的）15%〜8〇%的wpc，作為蛋白質濃 縮乳清粉末的形式，根據平成1()年3月㈣日乳等政府法 令的部分修正’定義為乳製品(關於濃縮乳清、乳清粉末、 WPC、孔清蛋白濃縮粉末，只要是經過乳等政府法令規定的 製k步驟者即為乳製品，無論是否有經過脫鹽步驟）。 乳π蛋白濃縮物（WPC)，係將乳清的主要蛋白質等利用 超過遽（Ultrafiltrati〇n:UF)法等濃縮處理後乾燥處理而 獲得者。-般而言，為固體成分約25%以上為乳清（whey) 蛋白者的總稱。可藉由從乳清使乳糖或鹽類等減少，使乳 /月蛋白貝相對增加’使成為固體成分約約8⑽而獲 得。尤其，以含有乳蛋白質乾重15%，%的卯c，依照乳等 政府法令定義為蛋白質濃縮乳清粉末。 乳&蛋白濃縮物（WPC)的標 干衣运乃法， ⑴將乳清進行膜分離後，進行濃縮的階段。或 ⑺將乳清進行膜分離後，進行i缩、乾燥的階段。 11 201127389 —又，濃縮處理可使用一般的裝置或方法，例如使用真 空蒸發罐（蒸發器）、真空荃、薄膜垂直上升管狀型濃縮機、 薄膜垂直下降管狀型濃縮機、平板型漢縮機等，於減廢下 進行加熱的方法。於乾燥處理也可使用一般的裝置或 方法例如使用噴霧乾燥法（spray dry)、滾筒乾燥法、冷 凍真空乾燥（freeze dry)法、真空（減壓）乾燥法等。 =清蛋白分離物P丨）係將乳清的主要蛋白質等利用 離:交換樹脂法或電透析法等濃縮處理後進行乾燥處理而 獲仔者般而言，為固體成分約85%至約95%為乳清（whey) =白者的總稱。可藉由從乳清使乳糖或鹽類等減少，使乳 :蛋白質相對增加，使成為固體成分約90%(85%，%)而獲 得。 乳清蛋白分離物（wpi)的標準製造方法，如下所述。 將乳清進行膜分離或離子交換樹脂處理或電透析處理 後’進行遭縮的階段。或 =)將礼„進行膜分離或離子交換樹脂處理或電透析處 後，進行濃縮、乾燥的階段。 空基發罐般的裝置或方法，例如使用真 薄膜垂* )、真空釜、薄膜垂直上升管狀型濃縮機、 4膜垂直下降管狀型漠縮機、平板型濃縮機等，於減壓下 ::加:::法。一處理一般的= …=用嘴霧乾燥―…筒乾燥法、冷 -二乾知（freeze dry)法、真空（減屢）乾燥法等。 本發明中，丙酸菌的培養的較佳培養基纽成，可為如 12 201127389 的組成。以下所述數值均為重量比（w觸。以下， 表不組成犄’如無特別指明，為重量比(w/w%)。 蛋白質含量十5%，較佳為15〜4 〇% 糖含量：卜4%，較料1.5〜3.0% 以能得到如此的含量的方式，調整乳清粉末、乳清蛋 2這些的蛋白酶處理物的添加量。X，糖不是乳糖，較 佳為葡萄糖或將乳糖以乳糖酶處理後的單糖。 減養基的成本’而且獲得適於食用的培養 ’可❹乳清礦物質的乳糖酶處理液作為糖及礦物質的 ^給源。具體而言’可冑WPC作為蛋白f來源、乳清礦物 、作為糖來源及礦物質來源。若將兩者的最適化比率之混 合物利用作為培養基原才斗，則比起以乳清粉末作為培養基 原二的情形’更可以高濃度培養丙酸菌。用於培養丙酸菌 的詳細培養基製備方法如下所示。 ，將WPC(牛）還原後，以蛋白酶分解蛋白質。蛋白酶為 來自麴菌的内切型及外切型’使用量定為分解的蛋白質量 的3%。反應於50°c、pH7. 〇進行，持續攪拌3 5小時直到 觀察到pH不再下降。乳清礦物f，以乳糖酶將乳糖分解。 乳糖酶的使用量定為分解的糖量的2~8%，反應於5〇6〇t (55°C較佳）' pH5〜6進行，持續攪拌直到蛋白質完全分解。 接著，較佳為將此述的兩液混合使得最終的培養基濃 度為蛋白質濃度1〜5%(較佳為丨· 5〜4· 〇%)、糖濃度為 卜4%(較佳為1. 5〜3. 0%)。最後，在培養基中添加酵母萃取 物；^酸鈉、天冬醯胺酸等丙酸菌培養常用的成分，並將 13 201127389 PH調整成5〜8(較佳為5· 5〜7· 5)，完成培養基的製備。丙 酸菌的培養步驟如下所述。 亦即’培養基溫度定為20〜4(TC，以剛開始培養的活 菌數為107〜l〇8cfu/ml之菌元（starter)接種，培養3~4日。 pH以碳酸鉀水溶液保持在pH5. 5〜7· 5。於培養中也可追加 葡萄糖。以如此方式獲得的培養物中，丙酸菌達到以往的 約5倍。 如以上的培養條件’尤其適於乳酪用的丙酸菌的培 養。乳赂用丙酸菌，除了費氏丙酸桿菌 以外，可利用丙酸丙酸桿菌 {Propionibacterium acidipropionici、、每 t 两致辑隹 {Propionibacterium jensenii) ' 特氏两黢辑畜 (Propionibacterium theonii)等。良具體而言，在冬發明 中可利用以如下列菌株作為丙酸菌所獲得的培養物。 餐氏丙後择魯{Propionibacterium freudenreichii) 6207 費氏丙酸桿菌（户· /rei/i/e/jre/c/?//) ATCC 8262 費氏丙酸桿菌（八 /rei/i/e/7reyc/?/i·) IFO 12424 費氏丙酸桿菌（Λ /rez^e/7re/c/7//) IFO 12426 費氏丙酸桿菌（八 /rewi/eMe/c/?") IFO 12391 費氏丙酸桿菌（八 /rewcfenreyc/?//) ET-3 (FERM BP-8115) 這些丙酸菌可以單獨培養，也可將多數菌株混合並培 養。或者’也可將複數個微生物單獨培養後，將獲得的培 養物混合。以如此方式獲得的培養物，本身可直接供作飲 14 201127389 食。也可將其進一步進行粉末化或液 、— 的型態加工處理為機能性原料。亦即，：二：操作 養所獲得的培養物，可以直接由上相酸菌的培 組成物。 傻調配於本發明的 而且，該技術領域之人士為了 最適化，可適當調整培養基A知的方法更加 '持 土、成或培養條件。例如，就氮 源而吕，除了酪蛋白、WPC等以外， 轧 . 也了更添加各種胺其 .酸或其鹽，以提高丙酸菌的增殖 ^ 此力或流行性感冒感染症 的預防效果。不僅是調整培養Α σ餐基組成，也可調整培養停件 以達到最適化。培養條件，包含谇 來件 溫度、壓力等。 …養-體氣圍的氧濃度、 本發明的丙酸菌培養物，只要能夠維持流行性减冒病 毒感染的預防效果’也可使用其分離出來的部分。因此， 丙酸菌培養物’例如含有丙酸菌的培養物本身、典養上主 液、菌體、這些的萃取物、這些的乾燥粉末或㈣的稀^ 物等。在此，「丙酸菌的培養物本身」，係指丙酸菌心 養基成分處於混合狀態者。培養基成分中的丙酸菌分散狀 態是任意的。亦即，丙酸菌在培養基成分中為分散或沉殺 均無妨。另一方面，「培養上法饬 a " 脣，月液」通常係指利用過濾或 離心分離等’從「丙酸菌的培養物本身」將丙酸菌的菌體 除去的狀態。再者，「菌體」係指從「丙酸菌的培養物本 身」分離的丙酸菌。將培養基成分與丙酸菌的菌體分離時， 通常兩者的分離不完全者也是被容許的。因此，例如從培 養物分離的丙酸菌的菌體中混入培養基成分者也是被 15 201127389 的。 例如，丙酸菌培養物分離出來的部分在促進流行性感 冒疫苗接種後的中和抗體的誘導作用，比起相同丙酸菌的 培養物（分離前），為例如30%以上，較佳為5〇%以上，更佳 為70%以上時，則可說維持了培養物的流行性感冒病毒感 染的預防效果。 可將培養後的丙酸菌培養物進行殺菌而調配於本發明 的組成物。或者’也可將與乳發酵成分與調配後的組成物 進行殺菌。例如為牛奶時，依照乳等政府法令的規定，— 般進行以下的加熱殺菌處理。 低溫保持殺菌， 南溫保持殺菌， 高溫短時間殺菌， 超高溫瞬間殺菌。 本發明中的丙酸菌培養物或含有其的組成物，可適 這些殺菌法或滅菌法。殺菌處理可以批次單位進行，也 連續進行。根據殺菌方法，處理溫度、處理溫度不同， 佳為因應上述殺菌方法從5〇~2〇(rc、〇.丨秒小時的範 選擇。丙酸菌培養物的殺菌，希望保持在液中的溶氧』 低的狀態。因此’即使在加熱殺菌中，較佳為持續保持 性氣體氛圍。.隋性氣體’例如氮氣、氬氣 '二氧化碳氣 等其中II氣在空氣中大量存在，成本相對較低而且 全性已瑞認，不會影響飲食品的風味、品質，因此為較 的惰性氣體。本案發明人等，已確認滅菌後的丙酸菌培 16 201127389 物可維持流行性感冒的預防效果。 本發明中，丙酸菌培養物的流行性感冒感染症的預防 作用’在滅菌後仍然維持。通常，乳酸菌對於寄主的影響， 依存於活菌的作用。因此，發現滅菌後的培養物具有有用 的功能’是超越預想的見解。眾多報告益生菌（probi〇tics) 或益生源（prebiotics)會改善腸内環境並活化免疫系統。 —般而言’益生菌係指以活的狀態導入寄主腸内而帶來對 寄主有益的作用之微生物。相對於益生菌，益生源係指以 作用於原本棲息在腸内的微生物者，提供寄主有益作用的 物質。例如，特別於人類的試驗中，具有對流行性感冒疫 苗的中和抗體誘導之促進效果的益生菌之數種乳酸菌株已 有報告。但是，這些乳酸菌係以活菌作用的益生菌，因此 製造或品質管理不m，活菌製#卜般而言保存性有 限例如，於製造後即使將活菌製劑於低溫保存，也常 無法長期保存。 相對於乳酸菌，本發 q 口 V丨敗囷枵養物為益王鄉。經 減菌的培養物(益生源)中’不會因為微生物的活動造成品 =化。因此’於益生源中，能穩定維持流行性感冒感染 症的預防效果。亦_ ’本發明的組成物，在製造或品質管 再者，為益生源的本發明組成物，可在常溫長 、子又，一般而言期待經口投予而緙π ϋ 埒里& ?又卞而獲侍孔酸菌活菌的 4，必需考慮胃酸的影響。因 姑，丨、卜、 U马礼酸困會因為胃酸而 ,少，…、法將足夠量的活菌送達腸 文―門另一方面，本發明 中，丙酸菌的流行性感冒感染症的 叼頂防效果，不依存於活 17 5 201127389 菌的作用。因此’即使是經口投予仍能達成充分的流行性 感冒的預防效果。 丙酸菌的培養物，在殺菌後可以加工為粉末狀或液 狀。例如’可對於培養液添加適當的賦形劑，使培養基的 固體成分為30~40重量％後，使乾燥並粉末化。賦形劑可利 用脫脂奶粉、乳清粉末、生澱粉、糊精等。賦形劑除上述 以外’視需要也可使用WPC、乳清蛋白分離物（Whey pr〇tein folate : WPI)、加工澱粉。培養物的乾燥方法亦為公知。 例如’可將培養液直接喷霧乾燥。加工澱粉，具體而言， 例如糊精，除此以外，可利用可溶性澱粉、大英膠（Bri t丨讣 gum)、氧化澱粉、澱粉酯、澱粉醚等。或者，可將培養液 與賦形劑的還原液混合，濃縮至固體成分成為3〇〜4〇重量％ 後，進行噴霧乾燥。乾燥的培養物，可藉由於充填時進行 脫氧處理（封入氮氣或添加脫氧劑等）而能穩定地長期保 存。也可加工為經碾磨（triturati〇n)的製劑（〇2%碾磨粉 末）’使容易用在食品。 丙酸菌的培養物，已知具有乳酸菌的增殖促進作用。 具有如此作用的丙酸菌培養物或其加工品，稱為「雙岐桿 菌垮殖促逄物」（jind〇genjc Growth Stimulator.,机幻。 BGS，只要是在已接種流行性感冒疫苗的動物中，具有促進 對流行性感冒病毒的中和抗體的產生的作用者，即可在本 發明中作為丙酸菌的培養物利用。 本發明中的丙酸菌培養物，較佳為由丙酸菌而來的乳 清發酵物。例如’使產生雙岐桿菌增殖促進物（Bifid〇genic 18 201127389Zhu Q et al.). For a virus similar to the antigenicity of a virus vaccinated, the effect of preventing severe disease is high. It has been reported that the induction rate of the elderly is lower (l7_53%) than that of the vaccinated healthy adults (7〇_9〇%) (G(3Qdwin K, et In the elderly, the immunity is reduced. Therefore, if the infection is severe, it may cause death. Therefore, it is particularly important to increase the neutralizing antibody induction rate in the elderly. [Prior Art] Patent Document 1 ..W0 2001/028547 g 201127389 Patent Document 2: W0 2004/085364 Patent Document 3: W0 2007/023935 Patent Document 4: WO 2005/094850 Non-Patent Document 1: Sugawara Minji et al., Infectious Diseases, 2008, 82: 427-433 Non-patent literature 2: World Health Organization: Department of Communicable Disease Surveillance and Response Global Influenza Programmed, 2005. Non-Patent Document 3: C, Avendano et al., J Parenter Enteral Nutr. 2004; 28: 348-54. Non-Patent Document 4: ZhuQ, et al., Biochem Biophys Res Commun. 2005; 329: 87-94. Non-Patent Document 5: Goodwin K, et al., Vaccine. 2006 Feb 20:24(8): 1159-69. [Summary of the Invention] Problem to be solved) The subject of the present invention is Provided is a composition of a culture containing propionic acid bacteria. In particular, it is an object of the present invention to provide a composition having a preventive effect against influenza virus infection. Alternatively, it is an object of the present invention to provide a composition having an intestinal action. (The way to solve the problem) The prevention of viral infection by the catching of the flu vaccine is mainly dependent on the induction of neutralizing antibodies to the sputum. Because of the induction of the stimulation of neutralizing antibodies after vaccination, the kiss is a preventive effect against the vaccine. Or, when the virus sense 201127389 is dyed, a virus-neutralizing antibody induced by a general immune reaction is formed in the patient, which is one of the important biological defense functions of the patient. The inventor of the present invention can enhance the epidemic A study on the induction of the virus-neutralizing antibody produced by a cold vaccine or a viral infection. It was found that the induction of virus-neutralizing antibodies during influenza vaccination was enhanced in animals administered with specific microbial cultures. The present invention has been completed. That is, the present invention relates to the following compositions and uses thereof. [1] Seed flow Influenza infection prevention a composition comprising a culture of a propionic acid bacterium. [2] The preventive composition of influenza infection such as [1], in which propionate bacteria 夤K 丙 ★ 于 于 { {Propion 1 bacterium freudenrei chi. [3] The preventive composition of the influenza infection according to [1], which additionally includes either or both of the milk fermentation component and the oligosaccharide. [4] The preventive composition of an influenza infection according to [3], wherein the milk fermentation component is milk fermented by either or both of a lactic acid bacterium of the genus Lactobacillus and a lactic acid bacterium of the genus Streptococcus, or mixture. [5] A preventive composition for influenza infection such as [3] or [4], wherein the milk fermentation component is non-cooked cheese. [6] The preventive composition of influenza infection according to [3], wherein at least one of the sugars constituting the oligosaccharide is galactose. [7] A preventive composition for influenza infection according to [3] or [4], wherein the composition comprises a culture of propionic acid bacteria and a milk fermentation component, and both are sterilized. *=: 5 201127389 [8] The preventive component of influenza infection according to any one of [1] to [5] is for enteral administration to an animal vaccinated with influenza. [9] The preventive composition of influenza infection according to [3], which comprises the following nutrients: culture of propionic acid bacteria; milk fermentation ingredients; oligosaccharides; proteins; sugar; lipids; [10] The preventive composition of influenza infection according to [9], which further comprises at least one nutrient selected from the group consisting of vitamins, minerals, organic acids, and organic bases. [11] An inducer for neutralizing antibodies to influenza virus in an animal that has been inoculated with an influenza vaccine, comprising a culture of propionic acid bacteria. [12] A method for preventing influenza infection, comprising the steps of: (1) a step of administering a culture of propionic acid bacteria to an animal; and (2) a step of vaccinating the animal with an influenza vaccine. [13] The method for preventing influenza infection according to [12], wherein the step (1) is performed at least once in step (2), after or at the same time. [4] The method for preventing influenza infection according to [12] or [13], wherein in the step (1), the culture of the propionic acid bacteria is administered together with the milk fermentation component and the oligosaccharide or both . 201127389 Π5] A composition comprising the following components (a) to (c): (a) oligosaccharides, (b) milk fermentation components, and (c) cultures of propionic acid bacteria. [16] The composition according to [15], wherein at least one of the sugars constituting the oligosaccharide is galactose. [17] The composition of [15] or [16] is a composition for the whole intestine. (Effect of the Invention) The composition of the present invention enhances the neutralizing antibody-inducing action of the influenza vaccine. The composition of the present invention can be prepared to be produced by using only a liquid food or the like; Therefore, the composition of the present invention is highly secure. θ and ' can be administered not only to the composition of the present invention simultaneously with vaccination' but also to the composition of the present invention continuously before and after it. The induction promoting effect of neutralization by the composition of the present invention can be continuously expected by continuous administration. In order to enhance the immune response to viral vaccines derived from influenza viruses, adjuvants are often formulated in vaccines. Zoeji, who is vaccinating the vaccine, certainly requires Southern security. Careful safety testing is required when developing novel adjuvants for & On the other hand, the components constituting the composition of the present invention have been shown to be harmless since they have been continuously administered to the human being. Further, the composition of the present invention can be administered enterally by a combination of a known adjuvant. That is, not only is it safe, but the present invention is of great significance from the viewpoint of providing new options as an enhanced method of immune response to vaccines. The composition of the present invention, in a preferred aspect thereof, is provided by a combination of ingredients which are widely ingested by the liquid food 7 201127389 or food. By &, the composition of the present invention is continuously ingested as a liquid food, and the ability to induce neutralizing antibodies against influenza virus is often increased. Infecting people with influenza risk, such as elderly or hospitalized patients, is a serious problem. However, when the composition of the present invention is administered as a liquid food in a prophylactic manner, the ability of the entire population to prevent infection can be improved. [Embodiment] The present invention is directed to the culture containing propionic acid bacteria. A preventive component of influenza infection, or a preventive agent for influenza infection. The prophylactic or composition of the present invention comprises a culture of propionic acid bacteria. "Protonide of propionic acid" refers to a microorganism of the genus Propionibacterium (/ Grap-positive anaerobic bacterium of Vopj) which forms anaerobic anaerobic acid from a saccharide. Specifically, the following microbial culture can be added to the composition of the present invention. P. acidi propryonicus (/>.t force knife//) Bacillus (household./e/75^/7//) and so on. These propionic acid bacteria are microorganisms for producing cheese. In addition to the above, the following microorganisms can also be used as propionic acid bacteria. Greedy Propionibacterium (eight shi / (10)), Propionibacterium acnes (foot, 201127389 嗜 'P. aeruginosa (/ > · Lili / / (10)), Propionibacterium granulosus (eight wa / 7i / / 0lsa A method in which these microorganisms are isolated from nature or fermented milk is known. Propionibacterium can also utilize microorganisms used in the manufacture of Swi ss cheese. Propionate culture in the present invention means The culture of the propionic acid bacterium cultured under the appropriate culture conditions as described above is known. The culture method of the propionic acid bacteria is known. When the propionic acid bacteria are cultured, the conditions described in W003/016544A1 and the like can be applied. For example, the culture of propionic acid is applied. The culture medium of the fungus is known to have a composition such as a beer yeast extract added to the proteolytic treatment of skimmed milk powder or skim milk powder, and can be sterilized by inoculating Propionibacterium faecalis (Propionibacter jum fjreudenreichi i) in an appropriate medium. The culture of the propionic acid bacteria can be cultured under the conditions of the culture. Alternatively, the method of culturing the propionic acid bacteria at a high concentration may be added to the Whey Protein Concentrate (WPC) or its enzyme decomposition product. Minerals and monosaccharides culture medium propan-Open Patent Publication No. Laid level ™). For example, a culture obtained by culturing Propionibacterium faecalis (汾-❿/-m. (10)) in a medium containing a substance is preferable as a culture of the propionic acid bacteria of the present invention. Alternatively, in the efficiency culture method of the % propionic acid bacteria, there is a method in which the culture solution is circulated with a different culture medium from the propionate bacteria (Japanese Patent Laid-Open Publication No.). The propionic acid bacteria culture obtained by this culture method is a product. It is also formulated in the group of the present invention. For example, a whey processed product is added as a main component of the medium, and the propionic acid bacteria can be cultured at a high density of 9 201127389 degrees. The processed product of whey, for example, the following components. Whey powder, protease treatment of whey or whey powder. In addition to the addition of whey protein, a mixture of minerals and monosaccharides may be added to the medium. In order to reduce the concentration of sugar in the medium, a whey protein concentrate (hereinafter also referred to as WPC) may be added as a source of whey protein. Wpc can be obtained by reducing the lactose content by subjecting the whey to dialysis treatment. Whey egg = concentrate, which can further separate the protein component in high purity and become a whey protein isolate (hereinafter also referred to as WPI: ^, in addition to adding these components to the medium, it is also possible to add an appropriate amount of sugar and Insufficient minerals, the composition of the medium is used to culture propionic acid bacteria. The whey is a water-soluble component remaining when fat, casein, or fat-soluble vitamins are removed from cow's milk, for example, whey is generally natural. In the manufacture of milk road and rennet casein, cheese whey or rennet whey (also known as sweet whey) obtained as a by-product, or acid casein or quark milk from skim milk ( Quark Cheese) is obtained from road protein whey and quark whey (also known as sour whey). The main components of whey are protein (not-lactoglobulin, alpha-lactalbumin, etc.), lactose, water-soluble vitamins. The salt (mineral shell component), the individual characteristics' is more clear in the study of the milk component than the whey component. "Whey-related products", for example, the concentrated whey after concentrating the whey, Whey Whey Protein Concentrate: dried whey powder concentrate, whey main protein shell, etc., concentrated by concentrating (U1 traf i 1 trat i on : UF) method, and dried whey protein concentrate (Whey Protein Concentrate: 10 201127389 hereinafter referred to as WPC), whey using a microfiltration (Micr〇filtrati〇n: MF) method or a centrifugal separation method to remove fat, and then concentrated by UF method and then dried, defatted WPC (low fat, High protein), whey protein isolate (Whey Pr〇tein Isolate', also referred to as wpi), which is obtained by selective layering treatment of the main protein of whey by ion exchange resin method or gel filtration method. The desalted milk which is desalted after the desalting treatment by a nanofiltration (Nan〇filtrati〇n: NF) method or an electrodialysis method, and the mineral component from the whey is subjected to precipitation treatment, and then concentrated by centrifugation or the like. The treated mineral concentrates whey, etc. Among these, wpc containing 15% to 8〇% of the dry weight (solid content) of milk protein is used as a form of protein concentrated whey powder, according to Heisei 1 () March (4) Partial amendments to government regulations such as milk are defined as dairy products (for concentrated whey, whey powder, WPC, and pore clear protein concentrate powder, as long as it is a system of milk prescribed by government regulations such as milk, it is a dairy product, whether or not There is a de-salting step. The milk π protein concentrate (WPC) is obtained by subjecting the main protein of whey to a concentration treatment such as an ultrafilament (Ultrafiltrati〇n: UF) method, followed by drying treatment. A total of about 25% or more of the solid content is a whey protein. It can be obtained by reducing the lactose or the salt from the whey and increasing the relative amount of the milk/moon protein shell to a solid content of about 8 (10). In particular, 卯c containing 15% by dry weight of milk protein is defined as a protein-concentrated whey powder according to government regulations such as milk. Milk & Protein Concentrate (WPC) is the standard method for drying clothes. (1) The whey is subjected to membrane separation and concentrated. Or (7) After the whey is subjected to membrane separation, it is subjected to a stage of shrinking and drying. 11 201127389—In addition, the concentration treatment can use general equipment or methods, such as vacuum evaporation tank (evaporator), vacuum crucible, film vertical rise tubular type thickener, film vertical drop tubular type thickener, flat type Han shrinking machine, etc. , a method of heating under reduced waste. For the drying treatment, a general apparatus or method can be used, for example, a spray drying method, a drum drying method, a freeze dry method, a vacuum (depressurization) drying method, or the like. = albumin isolate P丨) is obtained by subjecting the main protein of whey to a concentration treatment such as an exchange resin method or an electrodialysis method, followed by drying treatment, and the solid content is about 85% to about 95 as a solid component. % is the general name of whey = white. By reducing the lactose or the salt from the whey, the milk: protein is relatively increased, and is obtained as a solid component of about 90% (85%, %). The standard manufacturing method of whey protein isolate (wpi) is as follows. The whey is subjected to membrane separation or ion exchange resin treatment or electrodialysis treatment to undergo a stage of contraction. Or =) the stage of concentration or drying after membrane separation or ion exchange resin treatment or electrodialysis. Empty space-like cans-like devices or methods, such as using true film hangs*, vacuum chamber, film vertical Ascending tubular type concentrator, 4 film vertical descending tubular type retracting machine, flat type concentrator, etc. under decompression: Add::: Method. One treatment is general = ... = Drying with mouth mist -... Tube drying method , freeze-dry method, vacuum (decrease) drying method, etc. In the present invention, a preferred medium for the culture of propionic acid bacteria may be a composition such as 12 201127389. The weight ratio (w touch. Below, the table does not constitute 犄', unless otherwise specified, is the weight ratio (w/w%). The protein content is 105%, preferably 15~4 〇%, sugar content: 4%, 1.5 to 3.0% of the material is adjusted so that the amount of the protease treatment product such as whey powder or whey egg 2 can be adjusted. X, the sugar is not lactose, preferably glucose or lactose is treated with lactase. After the monosaccharide. The cost of reducing the base 'and get a suitable culture for cooking' The lactase treatment solution of whey minerals is used as a source of sugar and minerals. Specifically, 'WPC can be used as a source of protein f, whey minerals, as a source of sugar and a source of minerals. If the ratio of the two is optimal The mixture is used as a medium, and the propionic acid bacteria can be cultured at a higher concentration than in the case where the whey powder is used as the medium. The detailed medium preparation method for culturing the propionic acid bacteria is as follows. After reduction (bovine), the protein is decomposed by protease. The protease is the endo-type and exo-type from the sputum, and the amount used is 3% of the amount of protein decomposed. The reaction is carried out at 50 ° C, pH 7. 〇, continuous stirring 3 5 hours until no more pH is observed. The whey mineral f decomposes lactose with lactase. The amount of lactase used is 2 to 8% of the amount of decomposed sugar, and the reaction is 5〇6〇t (55°). Preferably, C is carried out at pH 5 to 6 and stirring is continued until the protein is completely decomposed. Next, it is preferred to mix the two liquids so that the final medium concentration is 1 to 5% of the protein concentration (preferably 丨·5~4). · 〇%), sugar concentration is 4% (better 1. 5~3. 0%). Finally, the yeast extract is added to the medium; the commonly used ingredients of propionic acid bacteria such as sodium sulphate and aspartic acid are adjusted, and the pH of 13 201127389 is adjusted to 5~8 ( Preferably, 5·5~7·5), the preparation of the culture medium is completed. The culture step of the propionic acid bacteria is as follows. That is, the medium temperature is set to 20 to 4 (TC, and the number of viable cells just started to be cultured is 107). The cells are inoculated with a bacterium of ~1〇8cfu/ml, and cultured for 3 to 4 days. The pH is maintained at a pH of 5. 5~7·5. The culture may also be supplemented with glucose. The culture obtained in this way is obtained. Among them, propionic acid bacteria reached about 5 times as much as in the past. The above culture conditions are particularly suitable for the cultivation of propionic acid bacteria for cheese. For the milky propionate, in addition to Propionibacterium propioni, Proppronibacterium acidipropionici, Propionibacterium jensenii, Propionibacterium theonii, and the like can be used. Specifically, a culture obtained by using the following strain as a propionic acid bacterium can be utilized in the winter invention.食氏氏后鲁{Propionibacterium freudenreichii) 6207 Propionibacterium freundii (household /rei/i/e/jre/c/?//) ATCC 8262 Propionibacterium faecalis (eight/rei/i/e/ 7reyc/?/i·) IFO 12424 Propionibacterium faecalis (Λ /rez^e/7re/c/7//) IFO 12426 Propionibacterium faecalis (eight/rewi/eMe/c/?") IFO 12391 Propionibacterium faecalis (eight/rewcfenreyc/?//) ET-3 (FERM BP-8115) These propionic acid bacteria can be cultured alone or in combination with most strains. Alternatively, the plurality of microorganisms may be cultured separately, and the obtained cultures may be mixed. The culture obtained in this way can be directly used as a drink 14 201127389. It can also be further processed into a functional material by powdering or liquid-type processing. That is,: 2: The culture obtained by the operation of the nutrient can be directly composed of the culture medium of the upper phase acid bacteria. In addition, in the technical field, the person skilled in the art can appropriately adjust the method of the medium A to more appropriately hold soil, culture or culture conditions. For example, in addition to casein, WPC, etc., in addition to casein, WPC, etc., various amines and acids or their salts are added to increase the proliferation of propionic acid bacteria or preventive effects of influenza infection. . It is not only to adjust the composition of the Α σ meal base, but also to adjust the culture stop to optimize. Culture conditions, including 谇 temperature, pressure, etc. The oxygen concentration of the nutrient-body gas, and the propionic acid bacteria culture of the present invention can be used as long as it can maintain the preventive effect of the epidemic-reducing virus infection. Therefore, the propionic acid bacteria culture 'for example, the culture itself containing the propionic acid bacteria, the culture main liquid, the bacterial cells, the extracts of these, the dry powder of these, or the rare substance of (4). Here, the "culture of propionic acid bacteria" means that the propionic acid bacteria nutrient component is in a mixed state. The dispersion state of the propionic acid bacteria in the medium component is arbitrary. That is, the propionic acid bacteria may be dispersed or killed in the medium component. On the other hand, the "cultivation method" is a state in which the cells of the propionic acid bacteria are removed from the "culture of propionic acid bacteria" by filtration or centrifugation. In addition, "bacteria" means a propionic acid bacterium isolated from "the culture of propionic acid bacteria itself". When the medium component is separated from the cells of the propionic acid bacteria, it is usually permissible that the separation of the two components is incomplete. Therefore, for example, a person who mixes a medium component into a cell of a propionic acid bacterium isolated from a culture is also referred to as 15 201127389. For example, the induction of the neutralizing antibody after the influenza vaccination is promoted in the portion isolated from the culture of the propionic acid bacteria is, for example, 30% or more, preferably 30% or more, compared with the culture of the same propionic acid bacteria (before separation). When it is 5 % or more, and more preferably 70% or more, it can be said that the prevention effect of the influenza virus infection of the culture is maintained. The cultured propionic acid culture can be sterilized to be formulated in the composition of the present invention. Alternatively, the milk fermentation component and the formulated composition may be sterilized. For example, in the case of milk, the following heat sterilization treatment is carried out in accordance with the regulations of the government and other regulations such as milk. Keeping at low temperature, sterilizing at south temperature, sterilizing at high temperature for a short time, and sterilizing at ultra high temperature. The propionic acid bacteria culture or the composition containing the same in the present invention can be suitably subjected to these sterilization methods or sterilization methods. Sterilization can be carried out in batch units and continuously. According to the sterilization method, the treatment temperature and the treatment temperature are different, and the above sterilization method is selected from the range of 5 〇 to 2 〇 (rc, 〇. 丨 小时 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 丙 丙Oxygen is in a low state. Therefore, even in the case of heat sterilization, it is preferable to continuously maintain a gas atmosphere. An inert gas such as nitrogen gas, argon gas, carbon dioxide gas or the like, in which II gas is present in a large amount in the air, and the cost is relatively low. In addition, the inventors of the present invention have confirmed that the propionate culture after sterilization can maintain the preventive effect of influenza. In the present invention, the preventive action of the influenza virus infection of the propionic acid bacteria culture is maintained after sterilization. Usually, the effect of the lactic acid bacteria on the host depends on the action of the living bacteria. Therefore, it is found that the culture after sterilization has useful properties. The 'function' is an insight beyond expectations. Numerous reports of probi〇tics or prebiotics improve the intestinal environment and activate the immune system. 'Probiotics' refers to microorganisms that are introduced into the intestines of the host in a living state to bring about beneficial effects to the host. Relative to probiotics, probiotics refer to the beneficial effects of the microorganisms acting on the microorganisms originally inhabiting the intestines. For example, in human trials, several lactic acid strains having probiotics that promote the induction of neutralizing antibodies to influenza vaccine have been reported. However, these lactic acid bacteria are probiotics that act as live bacteria. Therefore, the manufacturing or quality management is not m, and the preservation property is limited. For example, even if the live bacterial preparation is stored at a low temperature after the production, it is often not stored for a long period of time. Compared with the lactic acid bacteria, the present invention has a V mouth. The defeated nutrient is Yiwang Township. In the culture of reduced bacteria (probiotics), 'the product will not be caused by the activity of microorganisms. Therefore, it can stably maintain the prevention of influenza infection in Yishengyuan. _ 'The composition of the present invention, in the manufacture or quality control, the composition of the present invention which is a probiotic source, can be long-lived at a constant temperature, and is generally expected to be orally administered. And 缂π ϋ 埒里 & 卞 卞 获 获 获 获 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍 侍A sufficient amount of live bacteria is delivered to the intestines. On the other hand, in the present invention, the effect of the topping prevention of influenza virus infection of propionic acid bacteria does not depend on the action of the bacteria. Therefore, even the Oral administration can still achieve sufficient preventive effects of influenza. Propionate cultures can be processed into powder or liquid after sterilization. For example, ' appropriate excipients can be added to the culture medium to make the medium After the solid content is 30 to 40% by weight, it is dried and pulverized. The excipient may be skim milk powder, whey powder, raw starch, dextrin, etc. Except the above, 'WPC, milk may be used as needed. Whey pr〇tein folate (WPI), processed starch. Methods of drying cultures are also known. For example, the culture solution can be spray dried directly. The processed starch, specifically, for example, dextrin, may be made of soluble starch, brit gum, oxidized starch, starch ester, starch ether or the like. Alternatively, the culture solution may be mixed with a reducing solution of the excipient, and concentrated to a solid content of 3 to 4% by weight, followed by spray drying. The dried culture can be stably stored for a long period of time by deoxidation treatment (sealing nitrogen or adding a deoxidizer) during filling. It can also be processed into a trituratin preparation (〇 2% milled powder) to make it easy to use in foods. The culture of propionic acid bacteria is known to have a proliferation promoting action of lactic acid bacteria. A propionic acid culture or a processed product thereof having such a function is called "jind〇genjc Growth Stimulator.", BGS, as long as it is an animal that has been inoculated with an influenza vaccine. Among them, those having a function of promoting the production of a neutralizing antibody against influenza virus can be used as a culture of propionic acid bacteria in the present invention. The propionic acid bacteria culture in the present invention is preferably propionic acid. Whey fermented from bacteria. For example, 'to produce Bifidobacterium proliferation promoters (Bifid〇genic 18 201127389

Growth Stimulator; BGS)的費氏丙酸桿菌 (Projnombacteriu/π freudenrejcMi)以3 株以 乳清 粉還原液發酵獲得的丙酸菌培養物，可包含於本發明的組 成物中作為有效成分。例如，含有BGS的丙酸菌培養物， 稱為「Profec」，其係經許可作為特定保健用食品的參與 成分。含有「Profec」的組成物，有B.G S p〇wder(明治 乳業製，商品名）、腹活力錠（明治乳業製，商品名；「腹活 力」為明治乳業（股）公司的註冊商標）市售Q因此，「B. G. s powder」或「腹活力錠」，也可利用於作為本發明的組成 物。 尤其’含有Profec的BGS’為1，4-二經基-2-蔡曱酸 (1，4-dihydroxy-2-naphthoic acid (DHNA))與 2-胺基-3-羧基-1，4-萘酿（2-amino-3-carboxy-l，4-naphthoquinone (ACNQ))。其中，DHNA為微生物的維生素K2(menaquin〇ne) 的生合成中間體。這些物質將雙岐桿菌的能量代謝過程中 所生成的NADH有效率地再氧化而促進增殖。因此，丙酸菌 培養物’可利用以下成分（i)及（i i )任一者或兩者。亦即， 本發明提供一種流行性感冒感染症的預防劑，包含 (i) 1，4-一經基-2-萘甲酸（1，4-dihydroxy-2-naphthoic acid (DHNA))，及 (ii) 2 -胺基-3-叛基-1，4 -秦酿（2-amino-3-carboxy-l，4- naphthoquinone (ACNQ))任一者或兩者。 本發明中，含有上述成分（i)及/或（j_i)的流行性感冒 感染症之預防劑的投予量’通常對於成人，以丙酸菌培養 5 19 201127389 物中所含的DHNA量為指標時’一般而言，丙酸菌培養物中 所含的DHNA量為0. 01 g/kg-100mg/kg的範圍。視情形， 有時在此以下已足夠，又，反之’有時需要在此以上的用 量。又，也可於1日分成2〜4次投予。投予量可考慮年齡、 體重等患者的狀態、投予路徑 '期待的預防效果的程度等 而設定。Growth Stimulator; BGS) Propionyl Propionibacterium (Projnombacteriu/π freudenrejcMi) is a propionic acid culture obtained by fermenting three whey powder reducing solutions, and can be included in the composition of the present invention as an active ingredient. For example, a culture of propionic acid bacteria containing BGS is called "Profec", which is approved as a participating component of a specific health food. The composition containing "Profec" includes BG S p〇wder (made by Meiji Dairy Co., Ltd., trade name), abdomen vitality ingot (made by Meiji Dairy Co., Ltd., trade name; "Abdomen vitality" is a registered trademark of Meiji Dairy Co., Ltd.) Therefore, "BG s powder" or "abdominal vitality" can also be used as a composition of the present invention. In particular, the 'BGS' containing Profec is 1,4-dihydroxy-2-naphthoic acid (DHNA) and 2-amino-3-carboxy-1,4- 2-amino-3-carboxy-l, 4-naphthoquinone (ACNQ). Among them, DHNA is a biosynthetic intermediate of vitamin K2 (menaquin〇ne). These substances promote the proliferation by efficiently reoxidizing NADH produced during the energy metabolism of Bifidobacterium. Therefore, the propionic acid bacteria culture ' can use either or both of the following components (i) and (i i ). That is, the present invention provides a prophylactic agent for influenza infection comprising (i) 1,4-dihydroxy-2-naphthoic acid (DHNA), and (ii) Any one or both of 2-amino-3-carboxy-l, 4-naphthoquinone (ACNQ). In the present invention, the administration amount of the prophylactic agent for influenza infection containing the above components (i) and/or (j_i) is generally for adults, and the amount of DHNA contained in propionic acid culture 5 19 201127389 is In the case of the indicator, the amount of DHNA contained in the propionic acid culture is in the range of 0.01 g/kg to 100 mg/kg. Depending on the situation, sometimes it is sufficient here, and vice versa. Sometimes it is necessary to use more than this. Further, it may be divided into 2 to 4 injections on the 1st. The amount of administration can be set in consideration of the state of the patient such as the age and the body weight, and the degree of the expectation of the preventive effect.

Profec由於可專一性地增加人類腸内雙岐桿菌 ，因此被認可為特定保健用食品的參與 成分（依田伸生：ILSI，No· 80，5-13(2004))。現在含有 Prof ec的組成物，已有「B. G. S powder」或「腹活力錠」 市售。因此取得並無困難。然而’藉由對於已接種流行性 感冒疫苗的動物投予pro fee，而強化中和抗體的誘導為未 知。亦即，本發明提供一種對於已接種流行性感冒疫苗的 動物之中和抗體的誘導促進劑，包含 (i) 1，4-二羥基-2-萘甲酸（l，4-dihydr〇Xy-2-naphth〇ic acid (DHNA))，及 (Π) 2-胺基-3-羧基-1，4-萘醌（2-amino-3-carb〇xy-l，4- naphthoquinone (ACNQ))任一者或兩者。 或者，本發明關於一種用於促進已接種流行性感冒疫 苗的動物中的中和抗體的誘導之醫藥組成物，包含上述成 分（i)及（ii)任一者或兩者。 本發明的組成物中，調配i，4_二羥基一2_萘甲酸（DHNA) 時，希望組成物的溶氧程度為低保持。因為溶氧使MNA分 解，造成保存中其濃度降低。使含有MNA的組成物中的溶 20 201127389 乳私度降低的方法為公知⑽2004/85364)。具體而言，組 ^物為液狀時’藉由以不含氧的氣體對於該液體組成物打 包’可將溶氧取代為氧以外的氣體。不含氧的氣體，以 乳乳較佳。而且’藉由將具有抗氧化性的化合物與MNA同 時添加，可將溶氧程度遷低。具有抗氧化性的化合物，可 ^公知的抗氧化劑。具體而言’作為抗氧化劑為公知的 :、次亞^I酸 '抗壞血酸（維生素〇、異抗壞血酸、胡蘿葡 、生月酚、具有抗氧化作用的多酚類。 多酶類，除了人忐σ 夕认 Γ 口成〇口以外，也可利用來自於天然物的 夕盼。例如，茶類、葡萄、擰檬、咖啡、紫字、大 源的多酚為公知0可蔣入亡夕θ ^ 水 了將3有夕罝廷些多酚的果實類或薜荽 種子類'植物葉片等的梓汁液，或這些的萃取：二 劑配於本發明的組成物。例如，可利用水或有機溶 a:::獲得多齡萃取物。又，這些含有天然多盼的製 -之_物或精製物、乾燥物，也可作為多酴使用。 心氧化劑的添加量，葙始 抗氧化用it使㈣^ θ 以通常作為 的添加I之等量或以上添加，可使溶氧& 度降低。例如，杏不—法&产 忧冷氧柽 酸單獨 田 订‘“生虱體的打氣泡’而將抗壞血 的她重曰於組成物以期待DHNA的安定性時’相對於溶液 〜1，可添加0.01重量%以上 可在添加DHNA於组成物之火天t 柷虱化劑 DHNA同時添加於組成物 了與 血酸作為"㈣性 u解。例如添加抗壞 乍為抗乳化劑時’其添加量I膽⑺ l〇〇g)，例如可為成物母 通韦為150 // g-1· 5g，較佳為 § 21 201127389 lmg-500mg 左右 〇 丙酸菌的培養物，相對於組成物全體，例如可以 0. 00卜20%的比例調配，通常為〇· 〇1〜15%，較佳為 0.01-10%。或者，本發明的組成物全體所含的乳發酵成分， 以添加夸克乳酪作為乳發酵成分時，夸克乳酪的蛋白質部 分的濃度，相對於組成物全體，可定為約〇· 〇1%〜約3〇% , 較佳為約0. 1 %〜約2 0 % ’更佳為〇 · 5 %〜約1 〇 %。 本發明的組成物可為液狀、糊狀或乾燥的固體物等任 意劑型。本發明的組成物可對於丙酸菌的培養物調配適於 經腸投予的、或藥學上可容許的載體而製成組成物。更具 體而言，可製劑化為錠劑、膠囊劑' 顆粒劑、散劑、糖漿 劑等。或者，也可以將丙酸菌培養物分散於乳發酵成分的 狀態供給。這些各種製劑，可依照常法，對於主劑使用賦 形劑、黏結劑、崩散劑、潤滑劑、矯味劑、溶解輔助劑、 懸ί子劑、包覆劑、溶劑、等張化劑等醫藥的製劑技術領域 中通常可使用的已知輔助劑而製劑化。又，也可含有適量 的鈣等礦物質。再者，也可添加適量的維生素、礦物質、 有機酸、糖類、胺基酸、胜肽類等。有機酸包含短鏈脂肪 酸等脂肪酸類》 丙酸菌的乳清發酵物，可期待優異的整腸作用一事已 為公知。但是，丙酸菌培養物的流行性感冒感染症的預防 作用為未知。 本發明的組成物，更可額外地添加乳發酵成分或寡 糖亦即，本發明係關於一種組成物，包含以下成分 22 201127389 (a)〜（c): (a) 寡糖 (b) 乳發酵成分，及 (c) 丙酸菌培養物。 一般而言，寡糖也稱為少糖類，係指2〜2〇個楗键以糖 苷鍵鍵結的化合物。例如，本發明中，可利用以卞的糖類 作為养糖。 乳果募糖、 異麥芽寡糖、 果募糖、 半乳募糖、 木寡糖、 大豆寡糖、 黑麴黴寡糖、 龍膽寡糖、 乳糖、 蔗糖、 麥芽糖等。 募糖之中，存在容易於酸性條件分解的化合物。因此， 本發明的組成物或含有本發明組成物的食品為酸性時，宜 使用於酸性條件下穩定的寡糠。例如，構成糖含有半乳糖 的暴糖’宜作為於酸性條件調配的寡糖β本發明中，構成 糖含有半軋糖的募糖，包含2〜20個糖以糖苷鍵鍵結的化合 物，且也包含構成化合物的糖包含丨個或複數個半乳糖Profec is recognized as a component of specific health foods because it can specifically increase Bifidobacterium intestines in humans (Yita Shinsei: ILSI, No. 80, 5-13 (2004)). The composition containing Prof ec is now commercially available as "B. G. S powder" or "abdominal vitality". Therefore, there is no difficulty in obtaining it. However, the induction of enhanced neutralizing antibodies was not known by administering a pro fee to animals that had been inoculated with a pandemic influenza vaccine. That is, the present invention provides an inducer for neutralizing antibodies to an animal which has been inoculated with an influenza vaccine, comprising (i) 1,4-dihydroxy-2-naphthoic acid (1,4-dihydr〇Xy-2) -naphth〇ic acid (DHNA)), and (Π) 2-amino-3-carb-1,4-naphthoquinone (2-amino-3-carb〇xy-l,4-naphthoquinone (ACNQ)) One or both. Alternatively, the present invention relates to a pharmaceutical composition for promoting the induction of neutralizing antibodies in an animal which has been inoculated with an influenza vaccine, comprising either or both of the above components (i) and (ii). In the composition of the present invention, when i,4-dihydroxy-2-naphthoic acid (DHNA) is formulated, it is desirable that the degree of dissolved oxygen of the composition is kept low. Since dissolved oxygen causes the MNA to be decomposed, its concentration is lowered during storage. A method for reducing the solubility of a solution in a composition containing MNA is known (10) 2004/85364). Specifically, when the composition is in a liquid state, the dissolved oxygen can be replaced with a gas other than oxygen by encapsulating the liquid composition with a gas containing no oxygen. Oxygen-free gas is preferred for breast milk. Further, by adding a compound having oxidation resistance to MNA at the same time, the degree of dissolved oxygen can be lowered. A compound having an antioxidant property, which is a well-known antioxidant. Specifically, 'as an antioxidant, it is well known: sub-Asian acid' ascorbic acid (vitamin oxime, erythorbic acid, carrot, gynomolol, polyphenols having antioxidant effects. Multi-enzymes, except humans σ 夕 Γ Γ Γ Γ Γ 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 以外 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 ^ Water has 3 kinds of polyphenolic fruits or alfalfa seeds 'plant leaves, etc., or extracts of these: two doses are formulated with the composition of the present invention. For example, water or organic can be used. Dissolve a::: Obtain multi-aged extracts. In addition, these products contain natural ingredients, refined or dried substances, and can also be used as polysaccharides. The amount of heart oxidizing agent is used to prevent oxidation. Adding (4)^ θ to the same amount or more as the usual addition of I, can reduce the dissolved oxygen & degree. For example, apricot does not - method & worry about cold oxynitride alone field set '' Bubbles' while she is concentrating on the composition of the blood stasis in anticipation of the stability of DHNA The solution ~1 can be added in an amount of 0.01% by weight or more. DHNA can be added to the composition at the same time as the composition of the composition, and the DHNA is added to the composition at the same time as the "acidic acid" as a <(4)-degree solution. For example, adding anti-gangrene to the anti-gangrene In the case of an emulsifier, the amount of the addition is I (6) l〇〇g), for example, it can be 150 // g-1·5g, preferably § 21 201127389 lmg-500mg. The composition may be formulated in a ratio of 0.00% to 20%, usually from 1 to 15%, preferably from 0.01 to 10%, based on the total amount of the composition. Alternatively, the emulsion of the composition of the present invention may be contained. 5%%, preferably about 0.1%, with respect to the total composition of the composition of the composition of the composition of the composition of ~ about 20% 'more preferably 〇 · 5 % ~ about 1 〇%. The composition of the present invention may be any formulation such as a liquid, a paste or a dried solid. The composition of the present invention may be used for propionic acid bacteria. The culture is formulated into a composition suitable for enteral administration or a pharmaceutically acceptable carrier. More specifically, It can be formulated into tablets, capsules, granules, powders, syrups, etc. Alternatively, the culture of propionic acid bacteria can be dispersed in the state of the milk fermentation component. These various preparations can be used according to the usual method for the main agent. Known adjuvants commonly used in the field of pharmaceutical preparations such as excipients, binders, disintegrating agents, lubricants, flavoring agents, solubilizing aids, suspensions, coating agents, solvents, isotonic agents, and the like In addition, it may contain an appropriate amount of minerals such as calcium. In addition, an appropriate amount of vitamins, minerals, organic acids, sugars, amino acids, peptides, etc. may be added. Organic acids include short-chain fatty acids. Fatty Acids The whey fermented product of propionic acid bacteria is well known for its excellent intestinal function. However, the prevention of influenza infection in propionic acid bacteria cultures is unknown. The composition of the present invention may additionally be additionally added with a milk fermentation component or an oligosaccharide. That is, the present invention relates to a composition comprising the following ingredients 22 201127389 (a) to (c): (a) oligosaccharide (b) milk Fermentation ingredients, and (c) propionic acid bacteria cultures. In general, oligosaccharides, also referred to as oligosaccharides, refer to compounds in which 2 to 2 oxime bonds are bonded by glycosidic bonds. For example, in the present invention, a sugar having a hydrazine can be used as a sugar. Milk fruit, sugar, isomalto-oligosaccharide, fruit sugar, semi-milk sugar, xylooligosaccharide, soybean oligosaccharide, black sclerotium oligosaccharide, gentian oligosaccharide, lactose, sucrose, maltose, and the like. Among the sugar-raising substances, there are compounds which are easily decomposed by acidic conditions. Therefore, when the composition of the present invention or the food containing the composition of the present invention is acidic, it is preferred to use a oligosaccharide which is stable under acidic conditions. For example, the oligosaccharide constituting the sugar containing galactose is preferably used as the oligosaccharide β which is formulated under acidic conditions. In the present invention, the sugar constituting sugar contains a half-milled sugar, and the compound containing 2 to 20 sugars is glycosidically bonded, and The sugar also comprising the constituent compound contains one or more galactose

S 23 201127389 者。更具體而言’較佳的寡糖例如棉子糖族寡糖（大豆寡 糖）、半乳寡料H半乳寡糖為本發財較佳的寡糖。 —本發明中，半乳寡糖係指主要以半乳糖作為構成糖的 寡糖。半乳寡糖之例，包括以乳糖（Gal⑷_4)Gic)作為基 本構造，具有於其鍵結卜數個半乳糖殘基構造的寡糖，或 半乳糖與葡萄糖以万-丨’3鍵結等的雙糖類（轉移雙糖 類）、GaHGai)n-Glc(n=H8)、GaHGal)n一Gai(n+ 18)。本發明中，構成半乳寡糖的半乳糖殘基的數目，通常 為1 20較佳為卜1〇，更佳為卜8。又，構成半乳寡糖的 半乳糖的比例’相對於構成半乳寡糖的單糖的總數，例如 可為10%以上，較佳為30%以上，更佳為50%以上。半乳寡 糖的製造方法’例如使半乳糖轉移能力高#厂半乳糖普 酶作用於乳糖（澤人淑人’半乳寡糖的機能及對於食品的應 用，Food style 21，2, pp76-78(1 998)。/?-半乳糖苷酶， 可利用例如羅倫隱球酵母、環 形芽孢桿菌（如£7y"i/S Cjr>Cday?iS)等微生物來源者。 又，特定保健用食品（規格基準型）制度中的規格基 準’將從乳糖利用半乳糖㈣（/g_D_galactoside galaCt〇hydr〇lase，E.c. 3.2.1.23,隱球菌屬酵母來源） 的作用生成的寡糖，定義為半乳寡糖。如此生成的半乳寡 糖’係在乳糖的半乳糖殘基上以糖苷鍵鍵結1個或複數個 半乳糖的寡糖，且以4’ _半乳糖苷基乳糖（（Gal(/5卜4)Gal 曰4)Glc)為主成分（平成17年7月ί日食安發第070100 號厚生勞動省醫藥食品局食品安全部長通知、「特定保健 24 201127389 用食品（規格基準型）制度創設配套的規格基準的設定 等」）。 在母乳中含有半乳募糖，具有適性增加腸内的雙岐桿 菌的效果，已知為不易消化吸收的糖。又，已知胃切除手 術後的礦物質補給’半乳寡糖為有用者（國際公開 98/1 51 96)。而且，相對於果糖募糖在強酸性下會水解（中 村厚子，使用果糖寡糖的糖醋豬肉或煮物中的糖的變化， 東π豕政學院大學紀要，43，叩49_53(2〇〇3))，半乳寡糖 具有在酸性條件下或加熱條件下不易因為分解產生衰減的 性質（澤入淑人，半乳寡糖的機能及對於食品的應用，FoodS 23 201127389. More specifically, preferred oligosaccharides such as raffinose oligosaccharide (soy oligosaccharide) and galacto-oligosaccharide H galactooligosaccharide are preferred oligosaccharides. - In the present invention, galactooligosaccharide means an oligosaccharide mainly composed of galactose as a constituent sugar. Examples of galactooligosaccharides include lactose (Gal(4)_4) Gic) as a basic structure, oligosaccharides having a structure in which several galactose residues are bonded, or galactose and glucose in a 10,000-丨3 linkage. Disaccharides (transfer disaccharides), GaHGai) n-Glc (n=H8), GaHGal) n-Gai (n+ 18). In the present invention, the number of galactose residues constituting the galactooligosaccharide is usually preferably from 1 to 20, more preferably from 8. Further, the ratio of the galactose constituting the galactooligosaccharide is, for example, 10% or more, preferably 30% or more, and more preferably 50% or more, based on the total number of the monosaccharides constituting the galactooligosaccharide. The method for producing galactooligosaccharides is, for example, high in galactose transfer ability. The plant galactose-producing enzyme acts on lactose (the function of Zeren Shuren's galacto-oligosaccharide and its application to food, Food style 21, 2, pp76- 78(1 998)./?-galactosidase, which can be used, for example, by microorganisms such as Cryptococcus marinus and Bacillus circulans (such as £7y"i/S Cjr> Cday?iS). The standard reference in the food (standard-based) system is defined as oligosaccharide from the action of lactose using galactose (4) (/g_D_galactoside galaCt〇hydr〇lase, Ec 3.2.1.23, Cryptococcus yeast). Oligosaccharide. The galactooligosaccharide thus produced is linked to one or a plurality of galactose oligosaccharides by a glycosidic bond on the galactose residue of lactose, and is 4'-galactosyl lactose ((Gal( /5B 4)Gal 曰4)Glc) is the main ingredient (July 17th, ί日食安发 No. 070100, Minister of Health and Welfare, Food and Drug Administration, Food Safety Minister, "Special Health 24 201127389 Food (Specification Type) ) The setting of the standard basis for the establishment of the system, etc." It contains half-milk sugar, which has the effect of increasing the intestinality of Bifidobacterium in the intestine. It is known as a sugar that is not easily digested and absorbed. Moreover, it is known that the mineral supplement after the gastrectomy is 'half oligosaccharide is useful (International Publication 98/1 51 96). Moreover, it is hydrolyzed under strong acidity with respect to fructose. (Changes in sugar in the sweet and sour pork or boiled in fructose oligosaccharides using the fructose oligosaccharide, East 豕 豕 学院 大学 大学, 43 , 叩49_53(2〇〇3)), galactooligosaccharide has the property of being not easily attenuated by decomposition under acidic conditions or under heating conditions (the function of succulent, galactooligosaccharide and application to food, Food

Style 21’ 2, pp76-78(1 998)。藉由在本發明的組成物中 添加募糖’可更強化組成物的整腸作肖。亦即，本發明的 、、且成物’可為整腸用的組成物而利用。下病等胃腸症狀， 為流灯性感f病毒的代表性感染症狀之…因&，兼具整 腸作用的組成物，可說是流行性感冒感染症的預防用組成 物希望有的特徵。 本發明的組成物中含有的寡糖濃度，相對於組成物全 體的含量’約0.0。卜約隐較佳為約0·05'約11%，更 ::約0.卜約寡糖的調配量，可因應劑型、症狀、體 置等而調整。 本發明的組成物，…有丙酸菌的培養物， 有暴糖及乳發酵成分之任一者或兩者。 本發明中，礼發酵成分，係指將動 或酵素作用發酵成的加工品。本發明中，動：十以微生物 令赞明中，動物乳汁包含牛 25 5 201127389 乳、水牛乳、山羊乳、羊乳及馬乳等。其中， 由於可輕異摧p夕曰 孔i午礼）’ 分，不僅s Γ >的原料礼’於經濟面有利。乳發酵成 X者而製：。生乳採集的乳，也可由其分離的部分或經加 脫"L 礼的分離部分或加工品，例如部分脫脂乳、 脫月曰礼、還原全乳、還原脫脂乳、還原部分脫脂乳、乳清、 酪蛋白、脫脂奶粉、乳清蛋白濃 物则、奶油、白脫乳、鮮奶油等…L:蛋白分離 〇 士士 吁奶，由寺k些的乳來源的加工 :::有時稱為原料乳。原料乳與可以單獨或混合不 料乳，作為乳發酵成分的原料。 本發明中，乳發酵成分’可在乳中加入微生物使發酵 後的培養物㈣得。微生物的培養物，只要是調配丙酸菌 時具有流行性感冒感染症的預防效果，則其分離出來的部 分可作為本發明中的乳發酵成分利用。以發酵為目的加入 乳的微生物般稱為菌元（starter)。乳發酵使用的微生 物宜為乳酸菌或雙岐桿菌。具體而言，例如如下述屬的乳 酸菌或雙岐桿菌可作為菌元獲得乳發酵成分。 I 敗稈亀{Lactobacillus')屬、 鏈球菌（屬、 乳球菌（Lactococcus)屬、 念珠兔ILeuconostoc)屬，反 先珠蛰 QPediococcus)Μ> 蓴。 更具體而言’由以下的微生物而來的乳發酵成分為公 知。由這些微生物獲得的乳發酵成分，宜為本發明中作為 乳發酵成分。 ^ 26 201127389 乳酸菌： 乳酸鍵球菌（Sfrepiococcws lactis) ' 乳酿键球菌（Sfrepfococcz/s cremoris)、 雙乙醯鏈球菌（iSYrepfococci/s diacetylactis)、 腸 J求菌（iV? ie/'ococcz/s faecium)、 I 陽珠摄{Enterococcus faecalis)、 今败含L 薇择窗{Lactobacillus acidophilus)、 短乳酸桿菌（Z/acic^ac"/"·? Z?_reF/>s)、 凱氏乳酸桿菌（Zacf<9Z?ac/7/z/>s case/)、 瑞士乳後择舊{Lactobacillus helveticus)、 德氏乳酸桿菌保加利亞亞種de7Z?ri/ec/ry/ subsp. bulgaricus) ' 德氏乳酸桿菌乳酸亞種（ZacfoZ?ac//7z/ t/e/Z?ri/ec/r// subsp. 1 actis)、 加氏乳酸桿菌（Zacic^ac/7/i/s 、 黏液乳酸桿菌（ZacioZ?ac///ws /z/i/cosae)、 替、乳鳆择窗（Lactobaci 1 lus murinus)、 胚箐乳鳆择隹 iLactobaci 11 us piantarum)、 口乳酸桿菌（Zacor/s)、 洛德乳酸桿菌rei/ieW)，及 鼠李糖乳酸桿菌（Lactobacillus rhamnosus) 雙岐桿菌： 1板雙士 择窗{Bifidobacterium 1 on gum)、 分 k 雙 4 择遠（Bifidobacterium bi fidum)，反 5 27 201127389 紅雙呔椁蛰（Bifidobacterium bi'eve) 將這些微生物從自然界或發酵乳單離的方法為公知。 或者可從細胞庫等分讓已經單離的微生物而取得。再者， 用於獲得乳發酵成分的乳酸菌菌&，已有市售。利用市售 的乳酸ϋϋ元製造的乳發酵成分也可利用於本發明的組 成物。依照生成的發酵乳的ρΗ或物理性狀差異有多數製 品在販售。發酵乳的物理性狀，係指硬度或滑順度 (smoothness)。市售的乳酸菌菌元，只要是與丙酸菌培養 物同時投予時，能促進由於流行性感冒疫苗而來的中和抗 體的誘V，即可利用為作為用於獲得本發明中乳發酵成分 的乳酸菌菌元。 本發明中，為了獲得乳發酵成分，可將如下的微生物 接種於原料乳中作為乳酸菌菌元。 保加利亞乳酸桿菌（Z.如/^rycws)、 啥熱鏈球菌（51. Mer/z/dp/zi/i/s)、 乳酸乳球菌（Z. /act/s)、 一般的發酵乳製造中，原料乳中也可添加這些乳酸菌 以外的選自乳酸菌或酵母菌之1種或2種以上。但是，本 發明中’利用在CODEX規格中規格化為優酪乳菌元的保加 利亞乳酸桿菌U.如與嗜熱鏈球菌（$ tAermopJn’ jus)的混合菌元為佳。而且，加入額外的微支物 時’也可於該混合菌元中’考慮目的發酵乳的發酵溫度或 發酵條件而混合追加的微生物。額外混合於混合菌元的微 生物，例如加氏乳酸桿菌（Z· gassery)或雙咬桿菌 28 201127389 (Bifidobacterium)等矣他的乳歡菌。 本發明中’作為混合菌元添加於原料乳的微生物也可 從寄存於細胞庫的微生物中選擇。能利用為混合菌元的希 望菌株例如以下：Style 21' 2, pp76-78 (1 998). The intestines of the composition can be further enhanced by the addition of sugar in the composition of the present invention. That is, the present invention can be utilized as a composition for the whole intestine. The gastrointestinal tract such as the disease is a representative symptom of the infection of the fluorescent f virus. It is a composition that is a preventive component of influenza infection. The concentration of the oligosaccharide contained in the composition of the present invention is about 0.0 with respect to the content of the entire composition. Preferably, the dose is about 0. 05', about 11%, and more: about 0. The amount of oligosaccharide can be adjusted according to the dosage form, symptoms, and body. The composition of the present invention, ... has a culture of propionic acid bacteria, and has either or both of a saccharide and a milk fermentation component. In the present invention, the term "fermentation component" refers to a processed product obtained by fermenting the action of an animal or an enzyme. In the present invention, the action is: in the microbial order, the animal milk contains cow 25 5 201127389 milk, buffalo milk, goat milk, goat milk and horse milk. Among them, because of the singularity, it is not only s Γ 孔 > Milk is fermented into X and made: Milk collected from raw milk, which may also be separated from parts of it, or separated parts or processed products such as partially skimmed milk, eclipse, reduced whole milk, reduced skim milk, reduced partial skim milk, milk Clear, casein, skimmed milk powder, whey protein concentrate, cream, buttermilk, fresh cream, etc... L: Protein separation, gentleman, milk, processing by the milk source of the temple::: sometimes called It is a raw milk. The raw milk may be used alone or in combination with milk as a raw material for the milk fermentation component. In the present invention, the milk-fermented component ' can be added to the milk to obtain the culture (4) after fermentation. The microorganism culture can be used as the milk fermentation component in the present invention as long as it has a preventive effect against influenza infection when it is formulated with propionic acid bacteria. A microorganism that is added to milk for the purpose of fermentation is called a starter. The microorganism used in the milk fermentation is preferably lactic acid bacteria or Bifidobacterium. Specifically, for example, lactic acid bacteria or Bifidobacterium which are genus of the following gene can obtain a milk fermentation component as a fungus. I genus {Lactobacillus'), Streptococcus (genus, genus Lactococcus, genus Ileuconostoc), genus QPediococcus) 莼. More specifically, a milk fermentation component derived from the following microorganisms is known. The milk fermentation component obtained from these microorganisms is preferably used as a milk fermentation component in the present invention. ^ 26 201127389 Lactic acid bacteria: Sfrepiococcws lactis' Sfrepfococcz/s cremoris, iSYrepfococci/s diacetylactis, intestinal J (iV? ie/'ococcz/s faecium ), I yangzhu photo {Enterococcus faecalis), today's ruin contains L-Lactobacillus acidophilus, Lactobacillus acidophilus (Z/acic^ac"/"·? Z?_reF/>s), Kjeldahl Bacillus (Zacf<9Z?ac/7/z/>s case/), Swiss Lactobacillus helveticus, Lactobacillus delbrueckii subspecies de7Z?ri/ec/ry/subsp. bulgaricus) Lactobacillus subsp. lactis (ZacfoZ?ac//7z/t/e/Z?ri/ec/r//subsp. 1 actis), Lactobacillus kawaii (Zacic^ac/7/i/s, mucin lactic acid Bacillus (ZacioZ?ac///ws/z/i/cosae), Lactobaci 1 lus murinus, iLactobaci 11 us piantarum, Lactobacillus (Zacor/s) , Lactobacillus rei/ieW), and Lactobacillus rhamnosus Bifidobacterium: 1 plate doubles window {Bifidobacterium 1 on gum), sub-k double 4 Far (Bifidobacterium bi fidum), anti-double red tie 527201127389 coffin sting (Bifidobacterium bi'eve) These microorganisms isolated from nature or fermentation process of milk isolated well known. Alternatively, it can be obtained by aliquoting the cells from the cell bank. Further, lactic acid bacteria & for obtaining milk fermentation ingredients are commercially available. A milk fermentation component produced by using a commercially available lactic acid lanthanum can also be used in the composition of the present invention. Most of the products are sold in accordance with the difference in the pH or physical properties of the fermented milk produced. The physical properties of fermented milk refer to hardness or smoothness. The commercially available lactic acid bacteria can be used as a milk fermentation for obtaining the present invention as long as it is administered simultaneously with a culture of propionic acid bacteria to promote the inducing V of the neutralizing antibody derived from the influenza vaccine. Ingredients of lactic acid bacteria. In the present invention, in order to obtain a milk fermentation component, the following microorganism may be inoculated into the raw material milk as a lactic acid bacteria. Lactobacillus bulgaricus (Z. such as /^rycws), Streptococcus thermophilus (51. Mer/z/dp/zi/i/s), Lactococcus lactis (Z. /act/s), general fermented milk manufacturing One or two or more kinds selected from the group consisting of lactic acid bacteria or yeasts other than the lactic acid bacteria may be added to the raw material milk. However, in the present invention, it is preferable to use a mixed bacterium of Lactobacillus bulgaricus U., which is standardized as a yoghurt in the CODEX standard, such as Streptococcus thermophilus ($tAermopJn' jus). Further, when additional micro-branches are added, the additional microorganisms may be mixed in the mixed bacteria to consider the fermentation temperature or fermentation conditions of the fermented milk of interest. Additional microorganisms mixed with the mixed fungus, such as Z. gassery or Bifidobacterium 28 201127389 (Bifidobacterium), etc. In the present invention, the microorganism added as a mixed fungus to the raw material milk can also be selected from microorganisms deposited in the cell bank. Hope strains that can be utilized as mixed fungi are as follows:

保加利亞乳酸桿菌（Z· JCM 1 002T 嗜熱鏈球菌（S. t/zer卯ATCC 1 9258 由以下的微生物的混合培養物構成的乳酸菌菌元： 嗜熱鏈球 g (Sirepiococcw i/zeryz/op/zy/iys) OLS 3059 (FERM BP-10740) 嗜熱鏈球菌0LS3294 (NITE P-77) 德氏乳酸桿菌保加利亞亞種 {Lactobacillus delbrueckii subspecies bulgaricus) OLL 1073R-1 (FERM BP-10741) 德氏乳酸桿菌保加利亞亞種 subspecies bulgaricus) OLL 1255 (NITE BP-76) 由這些微生物的發酵獲得的乳酪、天然乳酪、優路乳、 發酵乳、乳清（whey)發酵物、乳清乳酪等，包含於本發明 的乳發酵成分。用於調配於本發明組成物的乳發酵成分， 例如減少發酵乳（優酪乳）的水分（乳清）者（例如日本特許 第3, 179, 555號）。發酵乳（優酪乳）來源的蛋白質，胺基酸 級數為100 ’經發酵使蛋白質的消化吸收性增加，營養價 值面。 這些乳發酵成分當中’例如乳酪為本發明較佳乳發酵 29 201127389 成分。例如，可腺你〃 J將使用1種或組合2 製備的液狀乳以乳酸菌發酵 液狀乳原料而 為凝乳（currH 4、加酵素或酸而使成 為疑礼（curd)。乳酪係從凝乳除 化或熟成，從凝乳除去，… 月者。無論有無固體 攸熒礼除去札清者稱為乳酪。乳 製造後經過熟成步驟的熟成乳： 刀成 ^ ^ m , ^ ^ . 、…、成礼酪◎乳酪的熟 成步驟，通*進行乳酸菌或真菌 ^ ^ ^ 闽^貧殖^發酵：^並形成各 種礼特有的風味。相對於熟成⑽，維持從凝乳除去乳 清的狀態的乳赂為非熟成該。非熟成乳路（新鮮乳路）， 且為本發月中之乳發酵成分。非熟成乳酪(新鮮乳酪)有鄉 村乳赂（cottage cheese)、夸克乳路（叫㈣、絲 狀乳酪（string cheese)、納紗泰爾乳酪 cheese)、鮮奶油乳酪、莫札瑞啦乳酪（m〇zzareiia cheese)、缟可達乳酪（ric〇tta cheese)、瑪斯卡波乳酪 (mascarpone)等許多種類。這些新鮮乳酪之中，本發明較 佳為使用夸克乳酪。夸克乳酪的製造方法為公知（例如曰本 特開平 6-228013， Cheese and Fermented Milk Foods，Lactobacillus bulgaricus (Z·JCM 1 002T Streptococcus thermophilus (S. t/zer卯ATCC 1 9258 lactic acid bacteria consisting of the following mixed cultures of microorganisms: thermophilic chain g (Sirepiococcw i/zeryz/op/zy /iys) OLS 3059 (FERM BP-10740) Streptococcus thermophilus 0LS3294 (NITE P-77) Lactobacillus delbrueckii subspecies bulgaricus OLL 1073R-1 (FERM BP-10741) Lactobacillus delbrueckii Bulgaria Subspecies bulgaricus) OLL 1255 (NITE BP-76) Cheese, natural cheese, yoghurt, fermented milk, whey fermented product, whey cheese, etc. obtained by fermentation of these microorganisms, are included in the present invention. Milk fermentation ingredients. A milk fermentation component to be formulated in the composition of the present invention, for example, a water (whey) which reduces fermented milk (young butter) (e.g., Japanese Patent No. 3, 179, 555). Fermented milk (yoghurt)-derived protein, the amino acid grade is 100 ′. Fermentation increases the digestion and absorption of the protein, and the nutritional value. Among these milk fermentation ingredients, for example, cheese is a preferred milk fermentation 29 201127389 component of the present invention. For example, it is possible to use a liquid milk prepared by using one type or combination 2 as a curd liquid to ferment a liquid milk material (currH 4, add an enzyme or an acid to make a curd). The curd is removed or matured, and it is removed from the curd.... The person who has the solid 攸 攸 除去 除去 除去 除去 除去 除去 除去 除去 除去 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 ..., yoghurt ◎ cheese ripening step, through lactic acid bacteria or fungi ^ ^ ^ 闽 ^ poor fermentation ^: and form a variety of special flavor. Relative to ripening (10), maintain the state of whey removal from curd The milk is unripe. It is a non-cooked milk road (fresh milk road), and it is the milk fermentation ingredient of the month. Non-cooked cheese (fresh cheese) has cottage cheese, quark milk road (called (4), string cheese, cheese, whipped cream cheese, m〇zzareiia cheese, ric〇tta cheese, mascarpone (mascarpone) and many other types. Among these fresh cheeses, this hair Best use than quark cheese. The method for producing quark cheese are well known (e.g., Japanese Patent said present 6-228013, Cheese and Fermented Milk Foods,

Volume I: Origins and Principles, Frank V, Kosikowski and Vikram V. Mistry, F. V. Kosikowski, L. L.C., 1 999, pp 147-161)。夸克乳酪為一種乳酪（一般名），其營養學的 組成已經明瞭（Milk and Dairy Product Technology， Edgar Spreer; Axel Mixa， Marcel Dekker Inc, 1998， pp.245-249)。 以下說明非熟成乳酪的一般製造法。首先，從原料乳 製造凝乳。在原料乳中接種菌元並培養後，再添加粗凝乳 30 201127389 轉製成凝乳(略在製造凝乳之前，視需要可將原料乳 進仃則處理，如’為了使製造批次之間的品質差異減小， 可混合多種乳原料而進行品質調節。此種處理稱為標準 化。又，也可將乳中的脂肪球進行機械性破壞的均質化 〇—)處理。或者，為了去除混入乳原料的微生物， 也可施行離心除菌或加熱處理。 從獲得的凝乳（curd)將乳清（whey)分離而獲得的固體 成分’為非熟成乳路(新鮮乳路）。利用離心分離或膜分離 從凝乳分離乳清的方法為公知。例如， 離心分離機利用於乳清的分離。或者， 乳切斷或利用加溫使得分離過程有效率 可將夸克分離機等 可視需要預先將凝 更具體而言’以如下的原料與步驟可獲得的新鮮乳 酪在本發明中作為乳發酵成分較佳。以下步驟中，發酵 主要使用保加利亞乳酸桿菌（Zaci〇如c///w如& 反 / 氙嗜氨遨束蛰{Streptcoccus thennophi lus、。 將脫脂牛奶進行加熱殺菌； 接種0. 5〜5%乳酸菌菌元開始發酵； 從pH到達4· 6而形成的凝乳分離乳清； 將已分離乳清的凝乳冷卻，獲得非熟成乳酪。 以如此方式可製造的非熟成乳路，一般也有人稱為夸 克（Quark)乳酪。非熟成乳酪的組成的一例，如下所述。 總固體成分17〜19%、 蛋白質11〜13%、 脂肪1%以下（亦即〇 —1%)、Volume I: Origins and Principles, Frank V, Kosikowski and Vikram V. Mistry, F. V. Kosikowski, L. L.C., 1 999, pp 147-161). Quark cheese is a cheese (general name) whose nutritional composition is well understood (Milk and Dairy Product Technology, Edgar Spreer; Axel Mixa, Marcel Dekker Inc, 1998, pp. 245-249). The general manufacturing method of non-cooked cheese is described below. First, curd is produced from raw milk. After the inoculum is inoculated into the raw milk and cultured, the curd is added to the curd 30 201127389 to be converted into a curd. (Before the curd is made, the raw milk can be processed as needed, such as 'to make the manufacturing batch The quality difference between the two is reduced, and a plurality of kinds of milk raw materials can be mixed for quality adjustment. This treatment is called standardization, and the fat ball in the milk can also be treated by homogenization of mechanical damage. Alternatively, in order to remove microorganisms mixed with the milk raw material, centrifugal sterilization or heat treatment may be performed. The solid component obtained by separating the whey from the obtained curd is a non-cooked milk road (fresh milk road). A method of separating whey from curd by centrifugation or membrane separation is known. For example, a centrifugal separator utilizes the separation of whey. Alternatively, the milk cut or the use of warming makes the separation process efficient. The quark separator or the like can be pre-conceived in advance. More specifically, the fresh raw cheese obtainable by the following raw materials and steps is used as the milk fermentation component in the present invention. good. 5〜5%。 In the following steps, the fermentation mainly used Lactobacillus bulgaricus (Zaci 〇 c / / 如 如 如 反 Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str Str The lactic acid bacteria start to ferment; the whey is separated from the curd which has reached the pH of 4.6; the curd which has been separated from the whey is cooled to obtain the non-cooked cheese. The non-cooked milk road which can be manufactured in this way is also generally called Quark cheese. An example of the composition of non-cooked cheese is as follows. The total solid content is 17 to 19%, the protein is 11 to 13%, and the fat is 1% or less (that is, 〇-1%).

S 31 201127389 碳水化合物2~8%、 乳糖2%以下（亦即〇__2〇/q) 乳發酵成分的調配量，來自於乳發酵成分的蛋白質， :目對：組成物全體，例如…〇"。%，通… 0.卜20/。’較佳為約〇.5〜1〇%的比例調配。又，組成物肩 胸’可調配ο.(π，、0.卜22g、〇 5〜Ug，較佳為2七 更佳為2.5〜4. 5g。或者，本發明的組成物全體所含的來自 於乳發酵成分的蛋白質’相對於組成物全體的蛋白質賓 量，可為約o.woo%，較佳約卜丨⑽％，更佳為約3〇%〜1〇〇% 除此之外，也可將在經加熱殺菌的脫脂乳中加入屬龙 乳球菌（hdococws)屬的乳酸菌作為乳酸菌菌元並使智 酵的乳發酵成分，製成本發明的非熟成乳酪。更具體而言 也可利用將以下微生物混合而成的乳酸菌菌元。 乳酸乳球菌（Zaciococcws /acii.s)、 乳脂乳球菌（Zacbcoccws cre/zzor/s)，及 乳酸鏈球菌屬的微生物。 混合上述微生物的乳酸菌菌元添加到經過加熱殺菌的 脫脂乳培養，可獲得凝乳（curd)。也可從乳發酵成分除去 乳清而成為非熟成乳酪《事先將以發酵獲得的凝乳以裁刀 切斷’一面加溫一面分離乳清而獲得的非熟成乳酪，也包 含在本發明的乳發酵成分。 此外，在原料乳中添加粗凝乳酶（rennet)使凝固者， 包含於本發明之非熟成乳酪中。粗凝乳酶係指以凝乳酶 (<：1^111〇3丨11，£0 3.4.23.4)為主成分的乳酪等的製造原料。 32 201127389 本發明的組成物可經腸投予。經腸投予，係指將本發 明的組成物送達腸管n不僅是經口料，注腸投予 或利用各種經管餵食（tube feeding)的投予方法也包含在 經腸投予。經管館食是對於難以經σ攝食的患者，通過管 子直接投予流質食物等到消化管的方法。由於管子設置方 法的不同，有以下的投予路徑。 經鼻腔（nasal feeding) 外屢（external fistula) 胃屢（percutaneous endoscpic gastr〇st〇my; pEG) 空腸屢（jejunostomy)。 ^外屢（externai flstula)係指管子從腹壁外通到消化 吕内含胃屢或空腸f再者，將組成物從肛門注入直 腸内的注腸投予，也包含在經腸投予中。經口投予時，組 成物的劑型為任意。但是’ 4 了經管投予或注腸投予，本 發明的組成物以糊狀、半固體化或液狀為有利。 九本發明的組成物，對於預防動物的流行性感冒病毒 染有用。本發明中，動物係、指為流行性感冒病毒寄主的 =物或烏類。哺乳類’以人為首、豬等，已知有流行 感冒病毒的感染例。除了豬以外，牛、山羊、羊、鬲、 牛、路乾以外，也適用在寵物或動物_養的動物或家畜 又丄鳥類’在雞等家禽或多數野鳥也觀察到有流行性感 病毒的感染。這些動物種’均可期待藉由投予本發明的 成物而有流行性感冒感染症的預防效果。本發明的組成 對於動物投予時，可將本發明的組成物調配於飼料中投号 33 201127389 對於本發明的組成物 成分的投予（攝取）量，】s 酵成分的情形’孔發酵 β 日以體重每1公斤以固體成分含 !计，為例如約一'約2〇g，較佳為約1〇呵'約❿ 為約5〇mg'叫投予量可因應劑型、症狀、性 體重等調整。 齡 例如，將乳發酵成分調配於本發明組成物而投予人 時’投予量一般為每曰以固體成分含量計，為例如約。.05g〜 約1500g’較佳為約。·〇5g'約i〇〇〇g，更佳為約2斗約 8〇〇g。對於必需利用本發明組成物促進中和抗體誘導者， 可：次或分次在餐前、餐後、餐間及/或睡前適當投予。投 予量可分別因應受投予者的年齡、體重及投予目的而適當 調整。也可將本發明的組成物用於取代餐食，也可利用作 為餐飲的輔助。 構成本發明組成物的丙酸菌培養物，或可額外地添加 的礼發酵成分或寡糖，肖已利用作為營養劑或流質食物的 成分。因此，調配含有這些成分的營養劑或流質食物而， 也可作為本發明的組成物。例如，含有BGS的丙酸菌培養 物稱為「Prof ec」，已許可作為特定保健用食品的參與成 刀商0口名「B. G. S. powder」或「腹活力錠」，包含以丙 酸菌發酵的乳清發酵物「Profec」。又，商品名「Fibren YH」 (月/α乳業）係含有乳發酵成分的流質食物。因此，將這些 商品依照如上述調配比調配，也可獲得本發明的組成物。 再者’組合含有丙酸菌培養物的組成物與含有乳發酵 成分的組成物，也可構成流行性感冒感染症的預防用套 34 201127389 ”，组。亦即，本發明係關於一種流行性感冒感染症的預防用 套組，由 (a) 含有丙酸菌培養物的組成物，及 (b) 含有乳發酵成分的組成物，所構成。 或者，本發明提供一種促進已接種流行性感冒疫苗的 動物中流行性感冒病毒的中和抗體誘導的套組包含上述 組成物U)及（b)。本發明的套組，例如可組合含有丙酸菌 培養物的營養組成物與含有乳發酵成分的營養組成物所構 成。這些營養組成物，以流質食物或營養劑的形式流通。 /案發明人等發現，攝取了丙酸菌培養物的人因接種 流行性感冒疫苗所形成的中和抗體的誘導被增強。亦即， 本發明提供含有丙酸菌培養物之組成物，用於對接種流行 性感冒疫苗的動物經腸投予。或者，本發明提供一種已接 種流行性感冒疫苗的動物中流行性感冒病毒的中和抗體的 誘導促進劑，含有丙酸菌培養物。本發明的組成物或中和 抗體的誘導促進劑，在較佳態樣中可額外含有乳發酵成分 與券糖之兩者之一或兩者。 而且，本發明關於將丙酸菌培養物使用於已接種流行 性感冒疫苗的動物中流行性感冒病毒的中和抗體的誘導促 進劑之製造。或者，本發明關於將丙酸菌培養物於促進已 接種亍性感冒疫苗的動物中之中和抗體的誘導之使用。 而且本發明關於一種已接種流行性感冒疫苗的動物中的 中和抗體的誘導促進劑之製造方法，包含調配丙酸菌培養 物與藥學上可容許知載體的步驟。 35 201127389 而且’本發明關於將丙酸菌培養物於流行性感冒感染 症預防劑之製造的用途。或者，本發明關於將丙酸菌培養 物於流行性感冒感染症的預防之使用。 或者，本發明提供一種用於促進已經接種流行性感冒 病毒疫苗的動物中流行性感w病毒的中和抗體的誘導之醫 藥組成物，包含丙酸菌培養物。更者，本發明提供一種丙 酸菌培養物之使用，用於促進已經接種流行性感冒病毒疫 苗的動物中流行性感冒病毒的中和抗體的誘導之醫藥組成 物的製造。本發明的醫藥組成物，包含藥學上有效量的丙 酸菌培養物。本發明的醫藥組成物，可調配適於經口投予 或經腸投予的載體。本發明的醫藥組成物，能以誘導已接 種流行性感冒疫苗的動物中的中和抗體的誘導之目的與 流質食物一起投予。 本發明中’流行性感冒疫苗包含以預防流行性感冒病 毒感染或預防感染後重症化的目的所投予的疫苗。現在在 日本實用化的不活化疫苗或在海外實用化的經鼻疫苗，包 含於本發明之流行性感冒疫苗中。不活化疫苗，—般係以 皮下 '皮内或肌肉内投予。另一方面，經鼻疫苗，為活的 病毋疫苗。經鼻疫苗，以鼻腔内喷霧誘導氣道黏膜中病毒 感染的預防效果高的IgA抗體為目的。 或者，本發明提供一種流行性感冒感染症的預防方 法，包含以下步驟： (1)對動物投予丙酸菌培養物之步驟；及 (2 )對動物接種流行性感冒疫苗之步騾。 36 201127389 本發明中，流行性感冒感染症的預防，具體而言，包 含防止流行性感冒病毒感染及防止流行性感冒病毒感染後 的重症化之兩者之-或兩者。流行性感冒感染症，係由於 病原體流行性感冒病毒的感染所帶來的各種症狀所伴隨的 感染性疾病。本發明中，有時流行性感冒感染症僅記載為 「流行性感冒」。流行性感冒感染症的重症化，包含 狀態： 感染症狀嚴重化、 感染症狀的種類增加、 病毒感染組織或感染細胞增加、 病毒於生體内增殖。 因此’阻礙這些狀態之至少—種者，意味著本發明中 之流行性感冒感染症之預防。本發明巾，流行性感冒感染 症之預防’包含流仃性感冒病毒感染的防。更具體而古， 強化病毒中和抗體的誘導者’包含在流行性感冒病毒感。染 的預防。#由流行性感冒疫苗的接種而誘導活體内的中和 抗體，隨時間其產生的程度會降低。防止中和抗體的降低 者’則對流行性感冒感染症的預防有貢獻。因&，防止中 和抗體產生的程度降低，也包含在病毒中和抗體的誘導促 進中。 中和抗體，對防止流行性感冒病毒在體内的感染組織 或感染細胞的擴大具有貢獻1用本發明的組成物或本發 明的方法，可期待流行性感冒感染症的預防效果的動物種 為流行性感冒病毒的寄主動物。更具體而言，例如人類或 201127389 包含人類的動物或人類以外的動物。 又’由於本發明的組成物所具有的流行性感冒感染症 的預防效果’不依存於流行性感冒病毒的抗原性。因此， 對於各種種類的流行性感冒病毒的感染預防有效^尤其， 對於A型及其亞型的流行性感冒病毒，為本發明中作為預 防感染的流行性感冒病毒為佳。更具體而言，以人、豬、 鳥等為寄主的A型流行性感冒病#，為本發明之適當的預 防對象。 中和抗體的誘導的促進，例如可利用下述方法確認。 亦即，對於已投予本發明組成物的群組及未投予的群組， 同樣投予流打性感冒疫苗，彳比較在兩群組的病毒中和抗 體的誘導H此時，各群組的構成成員，除了組成物投 予以外’其餘的條件相同。亦即，希望群組之中的健康狀 態、年齡、體格、性別比等條件是以無偏頗的方式配置。 遺傳的特徵也儘可能均質者為理想。因此，以人類為對象 時希望人種為同群組。在非人類動物中择認預防效果時， 儘可能利用遺傳上為同一群組。 牡如此的條件 列々啕砰組以相同時程施行姐取 物的投予及疫苗的接藉β . 旳接種並且’在已投予本發明組成物的 群組中，當中和抗體的誘導顯签择 守顯考增強時’可確認該組成物 的流行性感冒感染症預防效杲 用防政果。在此，所謂中和抗體的誘 導增強，例如下述者可確認。 Α I'所不指標中，中和抗體 價’可藉由比較例如超過群纟日pg Μ η 文迟群組間的阻止感染抗體價的個體 比例（表現率）而評估。 38 201127389 當中和抗體的抗體價的上升快逮時， 當中和抗體的產生長期持續時或 達到高的中和抗體價時， η此’猎由投予本發 ' ^ 八个u吨§忍此迷之 -的效果的個體數顯著增加時，則可確認該組成物的流行 性感冒感染症的預防效果。用於定量評價中和抗體價的方 法為公知。例如，利用感染性流行性感f病毒與培養細胞， 可確認抗體的感染阻礙效果。#由將抗體系列稀釋，可定 量地比較感染阻礙作用。 本發明中，丙酸菌的培養物，可在疫苗接種的前後或 接種同時投予。較佳為，從疫苗接種前至後，連續投予丙 酸菌的培養物。亦即，本發明提供含有丙酸菌培養物的組 成物，用於在疫苗接種前後連續經腸投予接種流行性感冒 疫苗的動物。所謂疫苗接種的前後，以疫苗接種日為第〇 日，係指例如-150〜+ 150日，通常為_60〜+ 6〇日，或_8週 〜+ 8週。 於該期間中’本發明的組成物，以藥學上有效量每工 日至少投予1次。每1日的投予量，也可分成數次投予。 或者，也可每隔1日投予。再者，本發明中，也可將丙酸 菌培養物的有效量，組合其調配比不同的多種組成物而投 予。 實際上，本案發明人等’確認在流行性感冒疫苗投予 前後攝取丙酸菌培養物的人，疫苗所產生的中和抗體的誘 導受到促進。因此’本發明提供在已投予流行性感冒疫苗 39 201127389 的動物中促進或增強中和抗體的誘導之方&，包含以下步 驟（1)及（2)。 (1) 對動物投予丙酸菌培養物之步驟.及 (2) 對動物接種流行性感冒疫苗之步驟。 本發明的組成物，不僅可期待在疫苗接種時促進中和 抗體的誘導，而且可期待病毒感染時強化中和抗體的誘導 之作用。因此’本發明的組成物，在感染流行性感冒病毒 的心者中’也能提尚患者本身的病毒中和抗體的產生能 力：抑制患者體内病毒感染擴大而緩和症狀。尤其當感染 強毒性病毒時’預測不僅是呼吸道感染，有引發全身症狀 的危險性。本發明的組成物’藉由使患者持續攝取，可期 待提高對感染病毒的中和抗體的誘導能力，防止重症化的 作用。 本發明的'组成物能以醫藥。口。或飲食品任一帛的形態利 用。例如’藉由以醫藥品的形式直接投予，能增強流行性 感冒疫苗的中和抗體的誘導。或纟，期待流行性感冒疫苗 的預防效果的增強’也可以作為特定保健用食品等特別用 途食品或營養機能食品攝取。又，也可不問液狀、糊狀、 固體、粉末等形態’添加於各種飲食品，料食品攝取。 作為飲食品，可例如牛奶、清涼飲料、發酵乳、優路乳、 乳路、麵包、軟餅乾、薄脆餅乾、比薩麵餅皮、調製奶粉、 流質食物、病人用食品、營養食品、冷凌食品、食品組成 物加工κ οσ等其他市售食品等。本發明的組成物製成酸 性醫藥品或飲食品的形態時，其ρΗ可定為ρΗ2.〇〜ρΗ6.〇, 40 201127389 較佳為pH3. 〇〜pH5. 0。 尽發明的組成 〜％町’乜1為營香劑或飲 食品或飼料投予。本發明的組 丁个《 J，'且成物作為營養劑或飲食品或 飼料投予時’除了調配乳發酵成分與丙酸菌培養物之外， 藉由調配額外的營養素，可調整其營養學的組成。本發明 中，附加的營養素’可使用水、蛋白質、糖、脂質、維生 ㈣、鑛物質類、有機酸、短鍵脂肪酸、有機驗、果汁、 香料類等。這些營養素’可使用如下的成分。 m(動物性蛋白質或植物性蛋白質，或這些的分解物） 月曰奶粕、脫脂奶粉、部分脫脂奶粉、酪蛋白、乳清、乳 月泰末礼/月蛋白質、乳清蛋白濃縮物、乳清蛋白分離物、 路蛋白、沒-路蛋白、路蛋白、沒-乳球蛋白、乳鐵 蛋白、大豆蛋白質'雞蛋蛋白質、肉蛋白質等。 乳來源的脂質或糖類等：奶油、乳清礦物質、鮮奶油、非蛋 白質態氮、唾液酸、磷脂質、乳糖等各種乳來源成分等 胜肽或胺基酸類：酪蛋白磷酸胜肽、精胺酸、離胺酸等胜肽 或各種胺基酸 糖類：加工澱粉（糊精（麥芽糊精、難消化糊精等）、可溶性 澱粉、大英澱粉、氧化澱粉、澱粉酯、澱粉醚等）、食物纖 維等 < 油脂類:豬脂、魚油等、這些的分別油、氫化油、酯交換油 等動物性油脂；棕櫚油、葵花油、玉米油、菜籽油、椰子油、 這些的分別油'氲化油、酯交換油等植物性油脂等 維生素類：維生素A、胡蘿蔔素類、維生素B群、維生素 41 201127389 維生素D群、維生素E、維生素K群、維生素P、維生素q 於驗、於驗酸、泛酸、生物素、肌醇'膽驗、葉酸等 礦物質類：妈、碟、斜、氯、鎂、鈉、銅、鐵、餘、鋅、碼 鉻、鉬等 有機酸類：蘋果酸、檸檬酸、乳酸、酒石酸等 短鏈脂肪酸類：乙酸、丙酸、丁酸、戊酸、己酸等 這些額外的營養素，可利用化學合成者或天然物來源 的成分之一。或者’也可將含有目的成分的食品作為原材 料進行調配。這些成分，可與目的營養劑的組成一併以 至少一種或組合2種以上進行調配。組成物的形態，可為 固體也可為液體。又，也可為凝膠狀或半固體等。因此， 營養劑為流質食物投予也可以。 實際上’如後述實施例所示，本發明的組成物，藉由 攝取含有丙酸菌培養物的流質食物，促進已接種流行性感 冒疫苗的I主動物巾流行性感冒病毒中和抗體的誘導。因 此’具有已調配丙酸菌培養物的流質食物之組成的組成 物’為本發明之較佳態樣之一。，亦即，本發明關於一種促 進已攝取流行性感冒疫苗的對象中流行性感冒病毒中和抗 體的誘導之流質食物的製造方法’包含將丙酸菌培養物調 配於抓質食物的步驟。或者，本發明提供—種對於流質 =賦予促進已攝取流行性感f疫苗的對象中流行性感冒 毒中和抗體的誘導能力之方法，包含將丙酸菌培養物調 於流質食物的步驟。爯去，士政。。， 再者，本發明提供一種流行性感冒 染症的預防組成物，包含以下營養素。 42 201127389 •• 丙酸菌培養物； 乳發酵成分； 寡糖； 蛋白質； 糖； 脂質；及 食物纖維。 上述组成中，丙酸菌的培養物’可為例如 (i) 1，4-二羥基 _2-萘甲酸（l，4-dihydroxy-2一naphthoic acid (DHNA))，及 (ii) 2-胺基-3-羧基-1，4-萘醌（2-amino-3-carboxy-l，4- naphthoquinone (ACNQ))兩者之一或兩者。又，上述組成 中的乳發酵成分含有蛋白質時，蛋白質也可再調配額外不 同來源的蛋白質。例如，除乳發酵成分以外，也可調配乳 成分。同樣地，上述組成中的糖也可調配寡糖以外的糖。 構成本發明組成物的各成分，可因應流質食物投予的 對象體格、年齡、性別等各條件適當調整。更具體而言， 一般組成可例示如下述之組成（每1〇〇mL)。 丙酸菌培養物：lmg〜22g，通常為10mg〜17g ,較佳為 l〇mg〜llg ，或 .DHNA 直為 〇. 〇1 y g〜i5mg， 通常為0. 5 // g〜i〇mg， 較佳為0. 5从g~〇. img; 乳發酵成分._〇.〇lg〜33g，通常為〇 lg〜22g，較佳為 43 201127389 0· 5s~llg(就蛋白質質量而言）; 為 0.l"g; 較佳為〇.5g〜 寡糖：lmg〜20g，通常為50mg~llg’較佳 蛋白質：0.01g〜50g，通常為〇.lg~30g， 15g; 糖：0. lg〜40g ’通常為〇.5g〜30g ’較佳為lg〜25 脂質：0. lg~20g，通常為〇. 3g~15g，較佳為η ^ 6S-l〇g 食物纖維：0〜15g，通常為0〜10g，較佳為〇〜8g。 上述組成中，在調配含有DHNA的丙酸菌培養物時，舌 培養物的量，a DHNA換算，可調配成如上述組成者。、同= 地上述组成中調配的寡糖，也可作為糖的—部分調配7 亦即’养糖構成上述組成中的糖一部分。 本發明的組成物中，也可以更額外地調配選自由維生 素類、確物質類、有機酸或短鏈脂肪酸及有機驗構成之群 組中之至）1個營養素。調配這些成分時的組成，可因應 流質食物的投予對象㈣格、年齡、㈣等各條件適當調 整。更具體而言’一般組成例如以下組成(每。 %，文住馮U~bUUmg 維生f類：〇〜2g，通常為 礦物質類:〇，’通常為〇，，較佳為0〜2g; 2g 有機酸或短鏈脂肪酸：〇，，通常為㈠g，較佳為 亦即’本發明提供一種用 形成的中和抗體的誘導之流質 述組成調配上述營養素的步驟 於增強因流行性感冒疫苗所 食物的製造方法，包含以上 。依照本發明製造的流質食 44 201127389 物，顯示該流質食物於流行性感冒疫苗接種前後投予已接 種流行性感冒疫苗的對象，會促進對象中對 毒的中和抗體的誘導。 鐵9病 本發明的組成物，可將丙酸菌培養物與例如藥學上可 容許的載體調配而製備。在調配額外的成分時，上述糖、 蛋白質、脂質等作為a糖 ‘、、、載體或作為流質食物混合，均質混 σ而製備。乳發酵述八愈系缺过 赞酵成刀與丙酸菌培養物 成物中的蛋白質之約】番θ 〇/、 7贪白質以組 以上的t γ丨. 置。以上的比例，例如約3〇重量％ 比例，更佳為約〗：重二：的蛋白f 7〇重量%以上的 備為流質食物時，希望1°心：調製。本發明的組成物製 為U最31。又，混=為母1ml為0，較佳 質類及食物纖維所構m €可添加由維生素類或鑛物 纖維分成水、为H人、名外成分之至少1種以上。食物 用。具體而：:：=:與不溶性食物纖維，兩者皆可使 果膠(原果膠二 可為例如以下成分。 果膠、果膠酿酸、果膠酸）、 瓜爾膠水解物、 葡甘露聚糖、 半乳糖甘露聚糖、 P度車前子(Psyllium)、 玉米纖維、 藻酸、 藻酸分解物、 鹿角菜膠、 20U27389 難消化性糊精 不溶性食物纖維例如結晶纖 等 又 心u , 木纖維、小I無 二'::使用果膠、瓜爾膠水解物、難消化性糊精。 子月形也可添加香料或其他調配物。 上述之各種成分混合後充填於容器，視 殺菌處理’可製成流質食物或經腸營養劑。組成物^^ 酸性時’加熱處理可於較通常更溫和的條件進行。例如： 中性流質食物的加熱殺菌處理為蒸餾器殺菌條件12(M3〇 C、2〇_40分鐘，間接殺菌條件140-145。(：、4-10秒，本 發明組成物可於80-9(ΤΓ眘*& 1C； 〇η 。 ◦貫轭15-30刀鐘的蒸餾器殺菌或 11〇 C實她20-6。秒的間接殺菌。由於溫和的殺菌條 件’可使風味良好，也容許調配對熱不耐的成分。又，本 發明的組成物可利用瓊脂或明膠製成凝膠狀，或利用喷霧 乾燥製成顆粒狀食品、醫藥，口 ’或甚至固體的食品、醫藥 品° 本發明的組成物，可根據流質食物或經腸營養劑的領 域公知的方法製造。例如，將液狀組成物預先加熱滅菌後 再無囷充填於容器的方法（例如，併用ΜΤ殺菌法及無菌包 裝法的方法）’或將液狀組成物充填於容器後和容器一起加 熱滅菌的方法（例如蒸餾器法、高壓釜法）等。亦即，組成 物的使用形態為液狀時’依據該組成物的均質化物（殺菌液 沒過均質化者）視需要再度於約120〜145 °C加熱殺菌約 1〜10秒後’冷卻再進行無菌充填，或充填於罐容器或軟質 袋後進行蒸館器殺菌。組成物的使用形態為粉末時，該均 46 201127389 質化物進行例如喷霧乾燥或冷涑乾燥。 以下對於本發明詳細說明，但β' 形態。本發明中，調和（添加、混入二本發明不限於下述各 若調和溫度為m：等的高溫時時，係加溫調和。 若調和溫度為rc等的低溫時，蛋蛋白白：會凝固(凝乳化)， 水等。因此，啁和+驟蛋白貝不易溶解或分散於 此調和步驟，㈣ C，又更佳為25〜55t 更佳為15 75 虐嘴知、广士 佳為35〜5(TC。又，此時，宜考 慮調和液中的細菌（污染1 間。 s 7且秣用適當的調和時 再者，本發明中，將調和 古、 一、 ’進仃咼溫殺菌後進行均皙 化。兩溫殺菌（加熱）時蛋白 、 吟蛋白貝會變性而黏度增加（增黏）， 一疋藉由尚溫殺菌後進行均皙 ^ , ^ 9質化，此減低其增黏程度。 ，進行高溫殺菌後均質化， 亡姑从— 係才日進仃尚溫殺菌後，在 充填於容器等製品前進行 在 可為2次以上的複數_欠。二化其次數不限於1次，也 —黛 χ 例如，將調和液殺菌後，直接進 订·人杈菌時，在該第2次殺菌後也進行均質化。又， =調和液殺菌後均質化’再於第2次時也殺菌時，在 該第2次殺菌後重新第 諮德始睹儿 “均質化。又，也可於調和液殺 -、，且不殺新第2次均質化。亦即， :中，將調和液進行高溫殺菌後，在充填於容器等而製^ 製，為止’即使1次均質化也是重要。 y 方面將經過鬲溫殺菌後的調和液（殺菌液）均質 化後’只要是㈣液未増黏的程度，則可再度殺菌。例如、， 可將調和液殺菌後均質化，並且不高溫殺菌而重新第2次 41 201127389 终此時，高溫殺菌步驟’例如為相當於溫度W50 C、保持時間為卜3〇秒，較佳為115145。〇、卜別秒，更 佳為120〜㈣'1，秒’又更佳為⑵〜職、卜5秒的 2歷。若高溫殺菌，則蛋白質會變性，殺菌液容易增黏。 “之’若不高溫殺g，則殺菌後的混合液不易增黏。因 此’利用均質化減低增黏程度的效果，於進行高溫殺菌時 可說是特別有效。 又，進行高溫殺菌時等，也可對調和液調整壓力（加麼 或減幻。此時，通常為了防止調合液滞騰等目的，例如， :菌壓力定為約H〇kg/心右。因此，本發明的高溫殺 '’除了溫度(加熱）’也可施加如此的壓力。高溫殺菌裝 。二如：·式t交換器、管式熱交換器、蒸氣注入式殺菌 益瘵ι輸式殺菌機、通電加熱式殺菌機等。另一方面， =質化時，使用均f機，例如較溫度為㈤1G〜6(TC、济 量為約100〜1〇〇〇〇L/h，則壓力$ 1〇〜lOOMPa，較佳2 20 80MPa ’更佳為3〇〜7〇Mpa ’又更佳為2〇 5_a。又若 有需要’也可改變高溫殺菌或均f化等的操作， 數次處理。 、運仃 =下對於本發明舉更詳細的例子說明，但是本發 Pf於3 _和步驟中’將前述溫度的溫水在槽内搜掉 考慮混合維生素混合物(維生物的混合 ’ 散容易度，依序添加、混合、授摔，製成調二=擴 今易此合 '擴散的投入順序，視原料量或特性而不、料 此，可因應組成，將各主調配成分一次或分…因 合種順 48 201127389 序投入。具體而言，例如，有依序投人糖、蛋白質、油脂、 礦物質的方法。又—例，有依序投入—部分糖、蛋白質、 其他糖類、礦物質、、古 、 貞油月曰的方法。又另一例，有依序投入 油月曰、蛋白質、糖、礦物暂的古土 噸物質的方法。將該調和液以蒸氣注 入式加熱殺菌後，以始哲 句質機均質化（以2階段壓力均質 、,成殺菌液。對於此殺菌液添加維生素混合物(維生 素的混成成分)、風味劑(香料)等並混合，製成最終的殺菌 液。將該最終殺菌液再以蒸氣灌輸式加熱殺菌（二階段殺菌） 後乂句質機均質化(以二階段壓力均質化)，獲得組成物。 本發明的組成物，可彳七氣 了作為具有〜行性感冒感染症的預 防效果之經腸營卷密，丨南丨田 養萬丨引用亦即，本發明組成物調配於流 質食物或經腸營養劑時’流質食物或經腸營養劑本身具有 流行性感冒感染症的預防效果，因此，不單是食品，也可 =於流行性感冒感染症的預防目的。具有下述機能之至 少-種的食品’例如可作為特定保健用食品、營養機能食 品等保健機能食品使用。 流行性感冒感染症的預防作用、 中和抗體的誘導增強作用，或 防止疫苗接種後的中和抗體價降低的作用。 在老年人或醫院住院患者多的設施，可考慮 流行性感冒疫苗的感染預防效果的預防方法等。或者，也 可利用於作為乳幼兒用的流行性感冒預防用的嬰兒食品、 一般用的流行性感冒感染症的預防用營養食品。又，本發 明組成物的希望態樣，可製成具有整腸作用的組成物。因 49 201127389S 31 201127389 Carbohydrate 2~8%, lactose 2% or less (that is, 〇__2〇/q) The amount of milk fermentation ingredients, derived from the protein of the milk fermentation component, : Objective: The whole composition, for example...〇 ". %, pass... 0. Bu 20/. ‘It is preferably a ratio of about 5.5 to 1〇%. Further, the composition of the shoulder of the composition of the composition of the present invention is 0.25. The amount of protein from the milk fermentation component may be about o.woo%, preferably about 10%, more preferably about 3% to 1%, relative to the total amount of protein of the composition. Alternatively, a lactic acid bacterium belonging to the genus Lactococcus (Hdococws) may be added to the heat-sterilized skim milk as a lactic acid bacterium and the milk of the virgin milk may be fermented to form the non-cooked cheese of the present invention. More specifically, it may be A lactic acid bacteria cell which is obtained by mixing the following microorganisms: Lactobacillus lactis (Zaciococcws / acii.s), Lactobacillus lactis (Zacbcoccws cre/zzor/s), and microorganisms of the genus Streptococcus. It can be obtained by adding to the heat-sterilized skim milk to obtain a curd. It is also possible to remove the whey from the milk fermentation component and become a non-cooked cheese. "Pre-heating the curd obtained by fermentation with a knife" Non-cooked cheese obtained by separating whey, The milk-fermenting component of the present invention is further included. The rennet is added to the raw milk to cause the coagulant to be included in the non-cooked cheese of the present invention. The rennet is referred to as chymosin (< :1^111〇3丨11, £0 3.4.23.4) A raw material for the production of cheese or the like as a main component. 32 201127389 The composition of the present invention can be administered by the intestine. Intestinal administration means the composition of the present invention. The delivery of the intestines n is not only a trans-oral administration, but also a bolus administration or a tube feeding method is also included in the enteral administration. The tube-feeding is for patients who are difficult to pass σ, and the tube is directly passed through the tube. The method of administering liquid food to the digestive tract. Due to the different methods of setting the tube, the following route of administration is given. nasal feeding (external fistula) (percutaneous endoscpic gastr〇st〇my; pEG) jejunum Repeatedly (jejunostomy). ^External flutula (external flstula) refers to the tube from the outside of the abdominal wall to the digestive lenium containing the stomach or jejunum f, and the composition is injected into the rectum from the anus into the intestine, also included in the Intestinal administration. Oral At the time of administration, the dosage form of the composition is arbitrary. However, the composition of the present invention is advantageous in the form of a paste, a semi-solid or a liquid by administration or injection. The composition of the present invention is In the present invention, an animal system, which is a host or a genus of influenza virus, is known as a human being, and a mammal is known as a case of infection with a cold virus. In addition to pigs, cows, goats, sheep, donkeys, cows, and roads are also suitable for pets or animals. Animals or livestock and ostriches. Infected with epidemic viruses in poultry or most wild birds. . These animal species can be expected to have a preventive effect against influenza infection by administering the product of the present invention. When the composition of the present invention is administered to an animal, the composition of the present invention can be formulated into a feed. In the feed No. 33 201127389, the amount of the composition of the composition of the present invention is administered (intake), the case of the s-fermented ingredient 'porous fermentation β The daily dose is, for example, about one gram of about 1 〇g, preferably about 1 〇 ' ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ 可 叫 ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ Adjustments such as weight. For example, when the milk fermentation component is formulated in the composition of the present invention and administered to a human, the amount of administration is generally, for example, about the solid content per guanidine. .05g~about 1500g' is preferably about. · 〇 5g 'about i 〇〇〇 g, more preferably about 2 buckets about 8 〇〇 g. For those who must utilize the compositions of the invention to promote the induction of neutralizing antibodies, they may be administered in a sub- or post-meal, pre-meal, inter-meal and/or bedtime. The amount of administration may be appropriately adjusted depending on the age, weight and purpose of the applicant. The composition of the present invention can also be used to replace meals, and can also be used as an aid to catering. The propionic acid bacteria culture constituting the composition of the present invention, or an additionally added fermentable ingredient or oligosaccharide, has been utilized as a nutrient or a liquid food. Therefore, a nutrient or a liquid food containing these components can be formulated as a composition of the present invention. For example, the culture of propionic acid bacteria containing BGS is called "Prof ec", and it has been approved as a special health food for the participation of the knife-making company in the name of "BGS powder" or "abdominal vitality", including fermentation with propionic acid bacteria. Whey fermented product "Profec". Further, the trade name "Fibren YH" (month/alpha dairy) is a liquid food containing a milk fermentation component. Therefore, the composition of the present invention can also be obtained by blending these products in accordance with the above-described blending ratio. Further, 'the composition containing the culture of the propionic acid bacteria and the composition containing the milk fermentation component may also constitute a preventive sleeve for influenza infection 34 201127389", that is, the present invention relates to a prevalence. The kit for preventing cold infection is composed of (a) a composition containing a culture of propionic acid bacteria, and (b) a composition containing a milk fermentation component. Alternatively, the present invention provides a promotion of vaccination against influenza. The neutralizing antibody-inducing kit of influenza virus in the vaccine animal comprises the above-mentioned compositions U) and (b). The kit of the present invention, for example, can combine a nutrient composition containing a propionic acid culture and a milk-containing fermentation The nutrient composition of the ingredients is distributed in the form of a liquid food or a nutrient. / The inventors found that the human ingestion of the culture of propionic acid bacteria is neutralized by the influenza vaccine. The induction of the antibody is enhanced. That is, the present invention provides a composition comprising a culture of propionic acid bacteria for enteral administration to an animal vaccinated with influenza vaccine. An inducer for neutralizing antibodies against influenza virus in an animal that has been inoculated with an influenza vaccine, comprising a culture of propionic acid bacteria. The composition of the present invention or an inducer for neutralizing antibodies, in a preferred aspect One or both of the milk fermentation component and the vouchers may be additionally contained in the present invention. Moreover, the present invention relates to the use of a culture of propionic acid bacteria for neutralizing antibodies against influenza virus in an animal vaccinated with influenza vaccine. Production of an induction promoter. Alternatively, the present invention relates to the use of a culture of propionic acid bacteria to promote the induction of antibodies in an animal that has been inoculated with a flu vaccine. Moreover, the present invention relates to an animal that has been vaccinated with influenza vaccine. A method for producing an induction promoter for neutralizing antibodies, comprising the step of formulating a culture of propionic acid bacteria and a pharmaceutically acceptable carrier. 35 201127389 Furthermore, the present invention relates to the prevention of infection of influenza virus by Propionibacterium culture. Use of the agent for production. Alternatively, the present invention relates to the use of a propionic acid bacteria culture for the prevention of influenza infection. Provided is a pharmaceutical composition for promoting the induction of a neutralizing antibody against a pancreatic w virus in an animal that has been inoculated with an influenza virus vaccine, comprising a propionic acid bacteria culture. Further, the present invention provides a propionic acid bacteria culture. The use of a pharmaceutical composition for promoting the induction of a neutralizing antibody against an influenza virus in an animal that has been vaccinated with an influenza virus vaccine. The pharmaceutical composition of the present invention comprising a pharmaceutically effective amount of a propionic acid culture The pharmaceutical composition of the present invention may be formulated with a carrier suitable for oral administration or enteral administration. The pharmaceutical composition of the present invention can induce the induction of neutralizing antibodies in an animal which has been inoculated with an influenza vaccine. In the present invention, the influenza vaccine contains a vaccine which is administered for the purpose of preventing influenza virus infection or preventing post-infection, and is currently in use in Japan. A practical nasal vaccine is included in the influenza vaccine of the present invention. The vaccine is not activated, and is usually administered subcutaneously or intramuscularly. On the other hand, the nasal vaccine is a live disease vaccine. The nasal vaccine is intended to induce IgA antibodies with high prophylactic effect of viral infection in the airway mucosa by intranasal spray. Alternatively, the present invention provides a method for preventing influenza infection, comprising the steps of: (1) a step of administering a propionic acid bacteria culture to an animal; and (2) a step of vaccinating the animal with an influenza vaccine. 36 201127389 In the present invention, the prevention of influenza infection includes, in particular, prevention of influenza virus infection and prevention of severe illness after infection with influenza virus - or both. The influenza infection is an infectious disease accompanied by various symptoms caused by the infection of the pathogen influenza virus. In the present invention, influenza infection is sometimes only described as "influenza". Intensive influenza infection, including status: Severe infection symptoms, increased types of infection symptoms, increased viral infection or infected cells, and proliferation of viruses in the body. Therefore, the term "obstructing at least" of these states means prevention of influenza infection in the present invention. The present invention, the prevention of influenza infection, contains the prevention of a flu virus infection. More specifically, the inducer of the virus-inhibiting antibody is included in the influenza virus. Prevention of dyeing. #Inducing neutralizing antibodies in vivo by vaccination with influenza vaccine, the degree of production will decrease with time. Preventing the reduction of neutralizing antibodies' contributes to the prevention of influenza infection. Since &, the degree of prevention of the production of neutralizing antibodies is lowered, and it is also included in the induction promotion of virus-neutralizing antibodies. The neutralizing antibody contributes to the prevention of the spread of the infectious tissue or the infected cells in the body of the influenza virus. 1 The animal of the present invention can be expected to have the preventive effect of influenza infection by the composition of the present invention or the method of the present invention. The host animal of the influenza virus. More specifically, for example, human or 201127389 contains human animals or animals other than humans. Further, the preventive effect of the influenza infection caused by the composition of the present invention does not depend on the antigenicity of the influenza virus. Therefore, it is effective for the prevention of infection of various types of influenza viruses. In particular, the influenza virus of type A and its subtypes is preferably an influenza virus for preventing infection in the present invention. More specifically, Type A influenza A, which is hosted by humans, pigs, birds, etc., is an appropriate prevention target of the present invention. The promotion of induction of the neutralizing antibody can be confirmed, for example, by the following method. That is, for the group to which the composition of the present invention has been administered and the group that has not been administered, the influenza vaccine is also administered, and the induction of the neutralizing antibody in the two groups is compared. The constituent members of the group, except for the composition, are given the same conditions. That is, it is desirable that conditions such as health status, age, physique, and sex ratio in the group are configured in an unbiased manner. Genetic characteristics are also ideal for homogenization. Therefore, when human beings are targeted, people are expected to be in the same group. When selecting preventive effects in non-human animals, use genetically the same group as much as possible. The condition of the sputum group was administered by the same time course for the administration of the sister and the vaccination of the vaccine. 旳 vaccination and 'in the group in which the composition of the present invention has been administered, the induction of the neutralizing antibody When the signing of the test is enhanced, it can be confirmed that the composition of the influenza infection prevention effect can be used for prevention. Here, the induction of the neutralizing antibody is enhanced, for example, as follows. In the indicator of Α I', the neutralizing antibody valence ' can be evaluated by comparing, for example, the proportion (indicating rate) of individuals who block the price of the infected antibody between the group of pg Μ η and the group. 38 201127389 When the antibody price of the neutralizing antibody rises rapidly, when the production of the neutralizing antibody persists for a long time or reaches a high neutralizing antibody price, η this 'hunting by the present hair' ^ eight u tons § this When the number of individuals of the effect of the fascination is remarkably increased, the preventive effect of the influenza infection of the composition can be confirmed. Methods for quantitatively evaluating the price of neutralizing antibodies are well known. For example, the infection-inhibiting effect of an antibody can be confirmed by using an infectious epidemic f virus and cultured cells. # By diluting the antibody series, the infection inhibition effect can be compared quantitatively. In the present invention, the culture of propionic acid bacteria can be administered simultaneously before or after vaccination. Preferably, the culture of propionibacterium is continuously administered from before to after vaccination. That is, the present invention provides a composition comprising a culture of propionic acid bacteria for continuous enteral administration of an influenza vaccinated animal before and after vaccination. Before and after the vaccination, the vaccination date is the third day, which means, for example, -150 to +150 days, usually _60 to +6 days, or _8 weeks to +8 weeks. During this period, the composition of the present invention is administered at least once a pharmaceutically effective amount per working day. The amount of administration per day can also be divided into several doses. Alternatively, it may be administered every other day. Further, in the present invention, an effective amount of the culture of the propionic acid bacteria may be administered in combination with a plurality of compositions having different blending ratios. In fact, the inventors of the present invention have confirmed that the induction of neutralizing antibodies produced by the vaccine is promoted by those who have taken the culture of propionic acid bacteria before and after the administration of the influenza vaccine. Thus, the present invention provides a method for promoting or enhancing the induction of neutralizing antibodies in an animal to which influenza vaccine 39 201127389 has been administered, comprising the following steps (1) and (2). (1) The steps of administering a propionic acid culture to an animal. And (2) the step of vaccinating the animal with an influenza vaccine. The composition of the present invention can be expected not only to promote the induction of neutralizing antibodies at the time of vaccination but also to enhance the induction of neutralizing antibodies in the case of viral infection. Therefore, the composition of the present invention can also enhance the ability of the patient's own virus-neutralizing antibody to be produced in the heart of the influenza virus infection: it suppresses the expansion of the viral infection in the patient and alleviates the symptoms. Especially when infected with a highly virulent virus, it is predicted that it is not only a respiratory infection but also a risk of causing systemic symptoms. The composition of the present invention can be expected to improve the inducing ability of neutralizing antibodies against infectious viruses by preventing the patient from continuously ingesting, and to prevent the effect of severe disease. The 'composition of the present invention can be used in medicine. mouth. Or the use of any form of food or drink. For example, by direct administration in the form of a pharmaceutical product, the induction of a neutralizing antibody against a pandemic influenza vaccine can be enhanced.纟 纟 纟 纟 期待 期待 期待 期待 流行 流行 流行 流行 流行 ’ ’ ’ ’ ’ ’ ’ ’ ’ ’ ’ ’ ’ ’ ’ ’ ’ ’ ’ ’ ’ ’ Further, it is also possible to add to various foods and drinks, and to ingest foods, regardless of the form such as liquid, paste, solid, or powder. As food and drink, for example, milk, refreshing drink, fermented milk, yoghurt, milk road, bread, soft biscuits, crackers, pizza dough, prepared milk powder, liquid food, patient food, nutritious food, cold food , food composition processing κ οσ and other commercial foods. When the composition of the present invention is in the form of an acidic pharmaceutical or a food or drink, the pH may be ρΗ2.〇~ρΗ6.〇, 40 201127389 is preferably pH 3. 〇~pH5. The composition of the invention is ~% 町'乜1 for the camping agent or drink food or feed. In the case of the group of the present invention, when J, 'and the product is administered as a nutrient or a food or drink or a feed, in addition to formulating the milk fermentation component and the propionic acid bacteria culture, the nutrition can be adjusted by blending additional nutrients. The composition of learning. In the present invention, the additional nutrient' may use water, protein, sugar, lipid, vitamins (4), minerals, organic acids, short-chain fatty acids, organic tests, fruit juices, spices, and the like. These nutrients can use the following ingredients. m (animal protein or vegetable protein, or a decomposition product of these) Moonworm milk, skimmed milk powder, partially skimmed milk powder, casein, whey, milk moon taiyue/month protein, whey protein concentrate, milk Albumin isolate, road protein, no-road protein, road protein, galactin, lactoferrin, soy protein 'egg protein, meat protein, etc. Milk-derived lipids or sugars, etc.: creams, whey minerals, fresh cream, non-protein nitrogen, sialic acid, phospholipids, lactose and other milk-derived ingredients such as peptides or amino acids: casein phosphopeptides, fine Amino acid, lysine and other peptides or various amino acid sugars: processed starch (dextrin (maltodextrin, indigestible dextrin, etc.), soluble starch, British starch, oxidized starch, starch ester, starch ether, etc.) , dietary fiber, etc. < Oils and fats: pig fat, fish oil, etc., these oils, hydrogenated oils, transesterified oils and other animal fats; palm oil, sunflower oil, corn oil, rapeseed oil, coconut oil, these Oils such as vegetable oils such as eucalyptus oil and transesterified oil: vitamin A, carotene, vitamin B group, vitamin 41 201127389 Vitamin D group, vitamin E, vitamin K group, vitamin P, vitamin q, For acid testing, pantothenic acid, biotin, inositol 'biliary test, folic acid and other minerals: mother, dish, oblique, chlorine, magnesium, sodium, copper, iron, residual, zinc, code chromium, molybdenum and other organic acids: apple Acid, citric acid, Short-chain fatty acids such as lactic acid and tartaric acid: acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, etc. These additional nutrients can be used as one of chemical-derived or natural-derived ingredients. Alternatively, a food containing a target ingredient may be formulated as a raw material. These components may be formulated in combination of at least one kind or a combination of two or more kinds together with the composition of the intended nutrient. The form of the composition may be either a solid or a liquid. Further, it may be a gel or a semi-solid or the like. Therefore, the nutrient can also be administered as a liquid food. In fact, as shown in the examples below, the composition of the present invention promotes the induction of neutralizing antibodies against the influenza virus of the I main animal towel which has been inoculated with the influenza vaccine by ingesting the liquid food containing the culture of the propionic acid bacteria. . Therefore, the composition of the composition of the liquid food having the culture of the propionic acid bacteria has been made one of the preferred aspects of the present invention. That is, the present invention relates to a method for producing an inducible liquid food for promoting influenza virus neutralizing antibodies in a subject who has ingested an influenza vaccine. The method comprising the step of arranging a propionic acid culture to a grasping food. Alternatively, the present invention provides a method for imparting an ability to induce influenza-neutralizing neutralizing antibodies in a subject who has been ingested with a prevalent influenza f vaccine, and includes a step of adjusting a culture of propionic acid bacteria to a liquid food. Go, gossip. . Further, the present invention provides a preventive composition for influenza infection comprising the following nutrients. 42 201127389 •• Propionate culture; milk fermentation ingredients; oligosaccharides; proteins; sugars; lipids; In the above composition, the culture of propionic acid bacteria may be, for example, (i) 1,4-dihydroxy-2-naphthoic acid (DHNA), and (ii) 2- Either or both of 2-amino-3-carboxy-l, 4-naphthoquinone (ACNQ). Further, when the milk fermentation component of the above composition contains a protein, the protein may be further mixed with a protein of a different source. For example, in addition to the milk fermentation ingredients, the milk ingredients can also be formulated. Similarly, the sugar in the above composition may also be formulated with a sugar other than the oligosaccharide. The components constituting the composition of the present invention can be appropriately adjusted depending on the conditions of the subject, age, sex, and the like to be administered to the liquid food. More specifically, the general composition can be exemplified as the following composition (per 1 mL). Propionate culture: lmg~22g, usually 10mg~17g, preferably l〇mg~llg, or .DHNA is directly 〇. 〇1 yg~i5mg, usually 0. 5 // g~i〇mg , preferably from 0.5 to g. im. img; milk fermentation ingredients. _ 〇 〇 lg ~ 33g, usually 〇 lg ~ 22g, preferably 43 201127389 0 · 5s ~ llg (in terms of protein quality) 0.l"g; preferably 〇.5g~ oligosaccharide: lmg~20g, usually 50mg~llg' preferred protein: 0.01g~50g, usually 〇.lg~30g, 15g; sugar: 0 Lg~40g 'usually 〇5g~30g' is preferably lg~25 lipid: 0. lg~20g, usually 〇. 3g~15g, preferably η ^ 6S-l〇g dietary fiber: 0~ 15 g, usually 0 to 10 g, preferably 〇 8 g. In the above composition, when the culture of propionic acid bacteria containing DHNA is formulated, the amount of the tongue culture can be adjusted to be the above composition in terms of a DHNA. The oligosaccharide blended in the above composition can also be used as a sugar-partial blending 7 , that is, the sugar constituting a part of the sugar in the above composition. In the composition of the present invention, one nutrient selected from the group consisting of vitamins, substances, organic acids or short-chain fatty acids, and organic tests may be further added. The composition of these ingredients can be adjusted according to the conditions (4), age, and (4) of the liquid food. More specifically, the general composition is, for example, the following composition (per. %, Wenzhu von U~bUUmg, vitamin class f: 〇~2g, usually minerals: 〇, 'usually 〇, preferably 0~2g 2g organic acid or short-chain fatty acid: hydrazine, usually (a) g, preferably, ie, the present invention provides a step of formulating the above nutrients with the induced flow characterization of the formed neutralizing antibody to enhance the influenza vaccine The method for producing the food includes the above. The liquid food 44 201127389 manufactured according to the present invention shows that the liquid food is administered to a subject who has been vaccinated with influenza vaccine before and after influenza vaccination, and promotes the poisoning in the subject. And induction of antibodies. Iron 9 disease The composition of the present invention can be prepared by blending a culture of propionic acid bacteria with, for example, a pharmaceutically acceptable carrier. When the additional ingredients are formulated, the sugar, protein, lipid, etc. are used as a sugar. ',,, carrier or as a liquid food mixture, homogenized and mixed with σ. Preparation of milk fermentation, the yakiyu system lacks the protein of the yeast and the culture of propionic acid bacteria. 7 The greedy white matter is set to t γ 丨. Above the ratio, for example, about 3 〇 wt%, more preferably about 〗 〖: heavy two: protein f 7 〇 wt% or more when prepared for liquid food, hope 1 ° heart: modulation. The composition of the present invention is U-31. In addition, the mixed = mother 1ml is 0, preferably the quality and the dietary fiber structure m can be added by the vitamin or mineral fiber into water, At least one or more of the H and the external ingredients. For food: specific:::=: and insoluble dietary fiber, both of which can make pectin (the original pectin 2 can be, for example, the following ingredients. Pectin, pectin Stearic acid, pectic acid), guar hydrolysate, glucomannan, galactomannan, Psyllium, corn fiber, alginic acid, alginic acid decomposition, carrageenan, 20U27389 Indigestible dextrin insoluble dietary fiber such as crystalline fiber, etc., wood fiber, small I have no two:: use pectin, guar hydrolysate, indigestible dextrin. Other preparations. The above ingredients are mixed and filled in the container, depending on the sterilization treatment. It is a liquid food or enteral nutrient. Composition ^^ When acidic, 'heat treatment can be carried out under milder conditions. For example: Heat sterilization of neutral liquid food is retort sterilization condition 12 (M3〇C, 2 〇 _ 40 minutes, indirect sterilization conditions 140-145. (:, 4-10 seconds, the composition of the present invention can be 80-9 (ΤΓ慎* &1C; 〇η. ◦ yoke 15-30 knives of distillation Sterilization or 11〇C indirect sterilization of 20-6 seconds. Due to mild sterilization conditions, the flavor can be good, and it is also allowed to adjust to the ingredients that are not heat resistant. Moreover, the composition of the present invention can utilize agar or gelatin. It can be made into a gel form, or can be spray-dried to form a granulated food, a medicine, a mouth or a solid food or a pharmaceutical product. The composition of the present invention can be obtained according to a method known in the art of a liquid food or an enteral nutrient. Manufacturing. For example, a method in which a liquid composition is preheated and sterilized and then filled in a container (for example, by a method of sterilizing and aseptic packaging) or a liquid composition is filled in a container and heated and sterilized together with the container. Methods (for example, a distiller method, an autoclave method) and the like. That is, when the use form of the composition is liquid, 'the homogenate of the composition (the sterilizing liquid is not homogenized) is heat-sterilized again at about 120 to 145 ° C for about 1 to 10 seconds, as needed, and then cooled. Sterile filling, or filling in a tank container or a soft bag, and then steaming the museum. When the form of use of the composition is a powder, the amount of the product is, for example, spray drying or cold drying. The invention is described in detail below, but in the form of β'. In the present invention, the blending (addition and blending) are not limited to the following high temperature when the blending temperature is m: etc., and the temperature is adjusted. If the blending temperature is a low temperature such as rc, the egg white: solidifies. (condensed emulsified), water, etc. Therefore, 啁 and + 蛋白 protein shells are not easily dissolved or dispersed in this blending step, (4) C, and more preferably 25~55t, more preferably 15 75, the mouth is known, and Guangshijia is 35~ 5 (TC. Also, at this time, it is advisable to consider the bacteria in the liquid (contaminating 1 s 7 and using the appropriate reconciliation, in the present invention, the reconciliation of the ancient, one, 'into the sputum temperature after sterilization The homogenization is carried out. When the two-temperature sterilization (heating), the protein and the prion protein will be denatured and the viscosity will increase (growth), and once the temperature is sterilized, the homogenization will be carried out, and the quality will be reduced. After the high-temperature sterilization, the homogenization is carried out, and the death is performed after the temperature is sterilized, and before the product is filled in a container or the like, the number of times may be two or more times. The number of times is not limited to one time. Also—黛χ, for example, after sterilizing the solution, when directly ordering the human bacterium, After homogenization, the homogenization is carried out after the second sterilization. In addition, the homogenization is carried out after the sterilization of the confluent liquid, and when it is sterilized in the second time, the homogenization is repeated after the second sterilization. It is also possible to reconcile the liquid to kill - and not to kill the second homogenization. In other words, the mixture is subjected to high-temperature sterilization, and then filled in a container or the like to be prepared, even if it is homogenized once. It is also important. y is to homogenize the conditioned liquid (sterilization liquid) after sterilizing, as long as it is not viscous, it can be sterilized again. For example, the conditioned liquid can be sterilized and homogenized, and The second time 41 201127389 At the end of this time, the high temperature sterilization step 'for example, corresponds to the temperature W50 C, and the holding time is 3 seconds, preferably 115145. 〇, 别别秒, more preferably 120~ (4) '1, second' is better (2) ~ job, Bu 5 seconds of 2 calendar. If high temperature sterilization, the protein will be denatured, the sterilizing liquid will easily become sticky. "If you do not kill g at high temperature, then the mixture after sterilization The liquid is not easy to be viscous. Therefore, the effect of using homogenization to reduce the degree of viscosity increase is carried out. It can be said to be particularly effective at the time of high-temperature sterilization. In addition, when high-temperature sterilization is performed, the pressure can be adjusted to the conditioning liquid (adding or reducing the illusion. In this case, usually, in order to prevent the turbidity of the mixing liquid, for example, the pressure of the bacteria is determined. It is about H〇kg/heart right. Therefore, the high temperature killing of the present invention can also apply such pressure in addition to temperature (heating). High temperature sterilization equipment, such as: · type t exchanger, tube heat exchanger, Vapor-injection sterilization, Yiqi ι-type sterilizer, electric heating sterilizer, etc. On the other hand, when the quality is reduced, the machine is used, for example, the temperature is (5) 1G~6 (TC, the quantity is about 100~1) 〇〇〇〇L/h, the pressure is $1〇~lOOMPa, preferably 2 20 80MPa 'better than 3〇~7〇Mpa' and more preferably 2〇5_a. If necessary, the operation of high-temperature sterilization or uniformization can be changed, and the treatment is performed several times.仃 仃 = 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下 下In order to add, mix, and drop, make a second adjustment = expansion of the current easy to this 'diffusion of the input order, depending on the amount of raw materials or characteristics, and this, according to the composition, the main components of the primary allocation or ... In particular, for example, there are methods for sequentially injecting sugar, protein, oil, and minerals. In another case, there are sequential inputs—partial sugars, proteins, other sugars, and minerals. , ancient, and oily moon bream method. In another case, there is a method of sequentially inputting oily glutinous rice, protein, sugar, and minerals in the ancient soil. After the heat treatment is steam-injected, the solution is The philosophical machine is homogenized (the homogenization is carried out in two stages, and the sterilizing liquid is added. The vitamin mixture (mixture of vitamins) and flavor (fragrance) are added to the sterilizing liquid and mixed to prepare a final sterilizing liquid. The final The sterilizing liquid is then subjected to steam infusion type heat sterilization (two-stage sterilization), and the sputum synthesizer is homogenized (by two-stage pressure homogenization) to obtain a composition. The composition of the present invention can be used as a tangential property. The effect of the prevention of cold infections is the enthusiasm of the intestines. The composition of the present invention is formulated in liquid foods or enteral nutrients. 'The liquid food or enteral nutrition itself is popular. In addition to the food, it can be used for the prevention of influenza infections. The foods having at least the following functions can be used as health care products such as specific health foods and nutritional foods. The use of functional foods. The prevention of influenza infection, the enhancement of the induction of neutralizing antibodies, or the prevention of the reduction of the price of neutralizing antibodies after vaccination. Consider the epidemic in facilities for elderly or hospital inpatients. It is a preventive method for the prevention of the infection of a cold vaccine, etc. Alternatively, it can also be used as a baby food for the prevention of influenza for infants and young children. Generally used to prevent influenza infection with nutritious food. Further, the present invention desired composition aspect, a composition can be made having a function of intestines. 49201127389 by

本說明書。以下其你香, 用的營養輔助醫藥品或流行性感 而利用。 所有先前技術文獻，作為參照納入 土於實％例對於本發明更具體說明 冒疫苗後的抗體 實施例1:對於經管餵食患者㈣㈣性感 價測定： [方法] 將經官餵食患者分成試驗群與對照群兩群，評價丙酸 菌坨養物對流行性感冒疫苗之中和抗體的誘導的影響。對 =群與試驗群的患者背景如表1所示。以Students’ t檢 定（等分散）或Welch檢定（非等分散）分析，認為患者背景 在群組間沒有顯著差異。 對照群與試驗群的患者背景 [表1 ] 性^ --- 對照群 男性 女性 〇 11 平均+SD 試驗群 男性 女性 2 9 年齡(years) 身高(cm) 體重(kg) ΒΜΪ ---- 84. 5+7. 5 145. 0+6. 6 36. 6+2. 9 17. 4+1.1 平均+SD 78. 7+9. 6 145.1+9. 6 37. 7+7. 3 17.8+2.5 統。十學上的顯著差異，以Students’ 1：檢定（等分散）或This manual. The following is the use of your fragrance, nutritional supplements or popular sex. All prior art documents, as a reference for inclusion in the soil, are more specifically described for the present invention. The vaccinated antibody is described in detail. Example 1: For the administered patient (4) (4) Sensitive price measurement: [Method] The officially fed patients are divided into test groups and controls. Two groups were evaluated to evaluate the effect of propionic acid trophozoites on the induction of neutralizing antibodies to influenza vaccine. The background of the patients in the = group and the experimental group is shown in Table 1. The Student's background was evaluated by (Standard Dispersion) or Welch's Assay (non-equal dispersion) analysis, and the patient background was considered to be not significantly different between the groups. Background of the control group and the test group [Table 1] Sex ^ --- Control group Male female 〇 11 Average + SD test group Male female 2 9 Age (years) Height (cm) Weight (kg) ΒΜΪ ---- 84 5+7. 5 145. 0+6. 6 36. 6+2. 9 17. 4+1.1 Average + SD 78. 7+9. 6 145.1+9. 6 37. 7+7. 3 17.8+2.5 System. Significant differences in the 10th grade, with Students’ 1: Verification (equal dispersion) or

We 1 ch檢定（非等分散）分析。 對於各群组投予的流質食物如下。 對照群（11位）：一般組成的流質食物 50 201127389 »式驗群（11位’但便性級數與菌叢的分析係以丨2位為 對线行）：將試驗的流質食物與丙酸菌培養物同時投予。 般流質食物」為含有乳蛋白質作為蛋白質，且不 含乳發酵成分或丙酸菌培養物的流質食物。 另方面，试驗的流質食物，為含有乳發酵成分 (3.8g/100kcal)作為蛋白質的流質食物。試驗的流質食物 中所3的礼發酵成分，係在利用保加利亞乳酸桿菌（众 與嗜熱鏈球菌（s广心门⑽抑使脫脂乳發 酵並濃縮者，添加蜂·密、祕全 刀蝉蚕維生素 '礦物質、食用油脂、食 物纖維、糊精並殺菌。 丙酸菌培養物為丙酸菌的費氏丙酸桿菌。X，丙酸菌 的坨養物中含有丙酸菌的培養物來源成分的dhna(1, 4_ dihydroxy-2-naphthoic acid)。試驗的流質食物與丙酸菌 培養物的同時投予’視為投予含有乳發酵成分與丙酸菌培 養物的新穎營養組成物。寡糖使用半乳寡糖。 試驗的流質食物除了含有乳發酵成分以外，在-般流 質食物與試驗流質食物之間本質上沒有不同。在實施例的 最後’顯示這些流質食物的組成（平均）（表6>以對照群（一 般組成的流質食物投予群組）與試驗群（試驗的流質食物投 予群組）在卡路里基礎上沒有顯著差異地投予各組成物。其 、··。果對於4驗群的患者，各別投予下列量的乳發酵成分 與丙酸菌培養物。 乳發酵成分：平均33g/day 為約 £ 丙醚菌培養物：平均1g/day(換算為DHNA量 51 201127389 13^g/day’或每攝取100kcal+路里的μνα量為丨 對於各群組開始投予上述流質食物的日定為第_4週 (分群時）’於4週之後（第〇週），在上腕皮下接種流行性 感冒疫苗0.5mL(HlNl型、H3N2型、B型的疫苗）（化血研）（圖 1)。於疫苗接種的4週前及4週後，計數糞便中的雙岐桿 菌，比較腸内菌叢。以如下時程從各群組的所有受試者採 血，測定對於疫苗的抗體價及血中的細胞激素濃度。為了 測定血中的細胞激素濃度，依照以下時程採血。 分各群組之日（第-4週）、 接種流行性感冒疫苗時（第〇週），及 接種疫苗2週後（第2週）及6週後（第6週） 中和抗體以紅血球凝集抑制試驗（ΙΠ法）測定，血中細 胞激素的測定方法為EL ISA ，便中的雙岐桿菌數以即時 PCR法測定。將測定結果於兩群組間、分群組前後，及接 種疫苗第2週與第6週比較。此時’抗體價小於1〇，為5。 又，便性的級數值，係從分群組時（第-4週）起，依照 布氏便形狀級別（表2 )，每日記錄，以各患者1週的平均 級數進行分析。布氏便形狀級別有1〜7的7階段，1為最 硬的便’ 7為水狀的便，3及4為正常便。 統計分析以如下方式進行。阻止感染抗體表現率在統 計學上的顯著差異，以chi-square檢定分析。關於中和抗 體力價，係計算1 ogl 〇(抗體價）後，兩群組間在統計學上 的顯著差異以Mann-Whitney U檢定分析，疫苗接種後以 W i 1 coxon符號排序和檢定分析。關於腸内菌叢及血中細胞 52 201127389 激素濃度，兩群組間在統計學上的顯著差異以S t u d e n t s ’ t 檢定（等分散）或Wei ch檢定（非等分散）分析，試驗前與試 驗中各週在統計學上的顯著差異以有對應的t檢定分析。 便性級數在統計學上的顯著差異，兩群組間以 Mann-Whitney U檢定分析’試驗前與試驗中在統計學上的 顯著差異以Wi 1 coxon符號排序和檢定分析。 巧.f?座狀級別（Bristol Stool Chgrt) 第2型：香腸形狀但是凹凸不平β 』 第3型：像香腸但在表面上有裂縫。 第4型：像香腸或蛇，平滑且柔軟。 第5型：有銳利邊緣的柔軟團（容易通過）。 第6型：有粗糙邊緣的鬆軟破片，為糊狀糞便。 夹m尊砗苎二完全是液體。 .......二：：：：：：：：：:：：：：：：：：：：：： [結果] 將阻止感染抗體價定為40以上（K〇jimaharaN，etal.，We 1 ch test (non-equal dispersion) analysis. The liquid foods administered to each group are as follows. Control group (11th place): general composition of liquid food 50 201127389 » Type test group (11-digit 'sufficiency level and flora analysis line 丨 2 position as the line): test liquid food with C The acid bacteria culture was administered at the same time. A liquid food is a liquid food containing milk protein as a protein and containing no milk fermentation or propionic acid culture. On the other hand, the tested liquid food is a liquid food containing a milk fermentation component (3.8 g/100 kcal) as a protein. The fermented ingredients in the liquid foods of the test are based on the use of Lactobacillus bulgaricus (the group and the Streptococcus thermophilus (s), which are fermented and concentrated by skim milk, adding bee, secret, and snail Vitamin 'mine, edible oil, dietary fiber, dextrin and sterilization. Propionate culture is propionic acid bacteria Propionibacterium faecalis. X, propionic acid bacteria contain propionate culture source The component of dhna (1, 4_ dihydroxy-2-naphthoic acid). The test of the liquid food and the propionic acid culture simultaneously administered 'considered to be administered a novel nutritional composition containing the milk fermentation component and the propionic acid culture. The oligosaccharide uses galactooligosaccharides. The tested liquid foods, in addition to the milk-fermented ingredients, are essentially the same between the normal liquid food and the test liquid food. At the end of the example, the composition of these liquid foods is shown (average). (Table 6> The control group (the general composition of the liquid food administration group) and the test group (the experimental liquid food administration group) were administered to each composition without significant difference on the basis of calories. For the patients in the 4 groups, the following amounts of milk fermentation components and propionic acid bacteria cultures were administered separately. Milk fermentation ingredients: average 33 g/day for about £ propyl ether culture: average 1 g/day (converted to The amount of DHNA 51 201127389 13^g/day' or the amount of μνα per 100kcal + path is 丨 The day when the above-mentioned liquid food is started in each group is set to the 4th week (at the time of grouping)' after 4 weeks (the first 〇 Weekly, inoculate 0.5 mL of influenza vaccine (HlNl, H3N2, and B vaccine) (Hua Xueyan) under the upper wrist (Fig. 1). Count the feces 4 weeks before and 4 weeks after vaccination. Bifidobacterium in the middle, comparing the intestinal flora. Blood was collected from all subjects in each group in the following time course, and the antibody price and the cytokine concentration in the blood were determined for the vaccine. In order to determine the concentration of cytokines in the blood, Blood was collected according to the following schedules. The day of each group (week -4), the influenza vaccine (week week), and the vaccination 2 weeks (week 2) and 6 weeks (week 6) Neutralizing antibodies are measured by erythrocyte agglutination inhibition test (ΙΠ method), measurement of blood cytokines The method is EL ISA, and the number of Bifidobacterium in the stool is determined by real-time PCR method. The results are compared between the two groups, before and after the group, and between the second week and the sixth week of the vaccination. 1〇, is 5. In addition, the level of the stool level is recorded from the group (week - 4), according to the Brinell shape level (Table 2), daily record, with an average of 1 week for each patient. The number of stages is analyzed. The Brinell shape has a 7-stage of 1 to 7, and 1 is the hardest one. '7 is watery, and 3 and 4 are normal. Statistical analysis is performed as follows. The rate was statistically significant and analyzed by chi-square assay. Regarding the neutralizing antibody valence, after calculating 1 ogl 〇 (antibody valence), the statistically significant difference between the two groups was analyzed by Mann-Whitney U assay, and the W i 1 coxon symbol was sorted and assayed after vaccination. . About intestinal flora and blood cells 52 201127389 Hormone concentration, statistically significant difference between the two groups by Student's test (equal dispersion) or Wei ch test (non-equal dispersion) analysis, pre-test and test Statistically significant differences in each week were analyzed with corresponding t-tests. Statistically significant differences in the number of stools were analyzed by Mann-Whitney U assay between the two groups. Statistically significant differences between pre-test and trial were analyzed by Wi 1 coxon symbol ordering and assay. (Bristol Stool Chgrt) Type 2: Sausage shape but unevenness β 』 Type 3: Like sausage but cracked on the surface. Type 4: Like a sausage or snake, smooth and soft. Type 5: Soft group with sharp edges (easy to pass). Type 6: A soft fragment with rough edges, which is a paste-like stool. The m m 砗苎 2 is completely liquid. .......二::::::::::::::::::::: [Results] will prevent the price of infected antibodies to be above 40 (K〇jimaharaN, etal.,

Vaccine. 2006;24:5966-9, Scharpe J, et al., Am JVaccine. 2006;24:5966-9, Scharpe J, et al., Am J

Hdney Dis. 2009;54:77_85 )，以分群組（第 _4 週）與疫 苗接種時（第0週）的平均值求取抗體價小於4〇的受試者的 疫苗接種後第2週及第6週的阻止感染抗體表現率。以 cM-square衫分析獲得的結果。關於_、麵的抗 原’第2週及第6週的兩個時點均為試驗群較對照群達到 阻止感染抗體價的受試者表現率較高。關⑨Μ抗原，第 6週兩群組均有9%的表現率 ^ ± 1疋孓弟2週時，試驗群 的表現率高於對照群。又，饼 對兩群組間進行顯著差里檢定 時’ H3N2抗原於第6週時， '、 吁忒驗群組的阻止感染抗體價表 5 53 201127389 現率顯著較高（表3)。 因此，由本次的比較實驗’瞭解藉由同時攝取乳發酵 成分及丙酸菌培養物，使流行性感冒疫苗所產生的中和抗 體的誘導增強。 阻止感染抗體的表現率 [表3] H1N1 Η3Ν2 Β-1 η數 2週 6週 η數 2週 6週 η數 2週 6週_ 11 18%(2) 9%(ΓΓ 對照群 10 30%(3)10°/〇(1) 10 50%(5)10°/〇(1) 試驗群 9 44%(4) 44%(4) 11 64°/〇(7) 64°/〇(7) 11 27°/〇(3) 9%(1)' P值 0.86 0.24 0.85 0.04 1 1 比較於第2週及第6週的流行性感冒疫苗接種後的中 和抗體力價’抗H1N1與H3N2抗原的抗體力價，對照群中， 第6週比起第2週顯著降低。另一方面，於試驗群中，於 第2週及第6週之間’中和抗體力價未變化（圖2A、圖2B)。 其次’分析流行性感冒疫苗接種前後的腸内菌叢，於 °式驗群中’腸内雙岐桿菌數（log 10(菌數/g糞便）從 6·⑻土1. 91增加到7. 37^2. 40，但是於對照群組，從 6. 65土2. 97 到 6. 18丸2· 8〇，未變化（表 4)。 腸内雙岐桿菌數的變化（單位：糞便重量每lg的菌數的對 數值） .[妻 4] ——.........一 Β驗開始2個月後 R ιοίο ^ 6. 39+ί. 91 又 試驗群的第-i 1、2、6週的便性級數值，比 54 201127389 . 起分群組時（第-4週）顯著下降，可見到便性的改善。另一 方面，對照群在投予期間中的級數值，比起投予開始時未 有顯著降低（圖3)。又，關於便性的級數，試驗群比起對 照群’在第3週及第6週有顯著降低。 關於血液中的細胞激素的濃度變化，針細 素，在試驗群與對照群之間未見到大的變化。但是'，關於 IL-7’試驗群中，第6週比起攝取前（第_4週）有顯著上升。 此-時的對照群，於第-4週及第6週未見到濃度有變化。 [IL-7] 試驗群中，第6週比起第_4週（分群組時或第】次採 血時）’ IL-7濃度顯著上升，但是，於對照群，比起第 週未有顯著變化（圖4)。又，在對照群與試驗群之間也未 見到顯著差異。 [IL-17] 試驗群、對照群均為，帛6週比起第_4週（分群組時 或第1次採血時）IL-17濃度降低（對照群：p<〇〇5，試驗 群：P>0.05)(圖4)。在對照群與試驗群之間未見到顯著差 異。 [TGF-yS 1] 兩群均為，血中濃度投予期間中相對於第4 週未見到顯著變化。另―方面，試驗群比起對照群，在第 〇週與第2週有顯著上升。但是，於分群組時（第^週）， 試驗群已經比起對照群的血中Tm濃度有較高的傾向 (Ρ = 0·074)，因此，可認為兩群組間對於血中TGF_々i濃声 55 201127389 的影響沒有差異（圖4)。 由以上的結果可知，乳發酵成分與丙酸菌培養物複合 投予時，對於流行性感冒疫苗接種時的中和抗體的誘導有 專一性的增強作用。又，乳發酵成分與丙酸菌培養物的複 合投予’顯示明顯的整腸作用。 實施例2 :新穎流質食物的製造方法 調和步驟為，先將溫水在槽内攪拌好，考慮維生素混 合（維生素的混合成分）以外的原料（表5)混合、擴散的容 易度，依序投入油脂、乳發酵成分蛋白質、糖、礦物質' 丙酸菌培養物。乳發酵成分，係使用以下微生物作為乳酸 菌菌元利用乳酸發酵製備。 嗜熱鏈球菌卯於以“）〇LS 3〇59 (FERM BP-1 0470)，及德氏乳酸桿菌保加利亞亞種 Uactotacillus delbrueckii subsp. bulfgaricus ) OLL l〇73R-l(FERM BP-10741)。 將該調和液，以瘵氣注入式加熱殺菌後，以均質機均 質化（以一段壓力均質化）’作為殺菌液。對於該殺菌液添 加維生素混合物（維生素的混合成分）、風味劑（香料）並混 合，作為最終的殺菌液。將該最終殺菌液，再以蒸氣灌輸 …殺菌（一#又权囷）後，以均質機均質化（以二段壓力均 質化）獲得組成物。該組成物的品質或風味良好。 56 201127389 [表5] 新穎流質食物的組成： (均為每lOOkcal的組成) 新穎流質食物 (平均組成） 蛋白質（g) 3.8 脂質（g) 2.7 糖(g) 14.6 食物纖維(g) 1.6 灰分(g) 0.7 維生素類： 維生素A(//g) 109. 4(*) 維生素Bl(mg) 0.1 維生素B2(mg) 0.2 維生素B6(mg) 0.3 維生素B12(//g) 0.6 維生素C(mg) 15.4 維生素D(/zg) 0.5 維生素E(mg) 2.9 維生素K(/zg) 1.9 於驗(mg) 1.5 葉酸(//g) 48.0 泛酸(mg) 0.6 礦物質類 鈉（mg) 96.6 鈣(mg) 77.0 鐵(mg) 1.0 填(mg) 81.9 鎂（mg) 19.2 鉀(mg) 99.8 銅（//g) 48.0 鋅(mg) 1.0 氯(mg) 105.6 來自乳發酵成分 蛋白質（g) 3.8 DHNA(βg) 1.6 寡糖(合計g) 0.5 (*):維生素A的量以視醇當量表示。Hdney Dis. 2009;54:77_85), the average of the group (week 4) and vaccination (week 0) for the second week after vaccination for subjects with antibody titers less than 4〇 And the 6th week of blocking infection antibody performance. The results obtained were analyzed by cM-square shirt. Regarding the _, the surface of the antigen, the two weeks of the second week and the sixth week were higher in the test group than in the control group to prevent the price of the infected antibody. 9 Μ antigen, 9% of the two groups in the sixth week of the performance rate ^ ± 1 疋孓 2 weeks, the performance of the test group was higher than the control group. In addition, when the cake was tested for significant difference between the two groups, the H3N2 antigen was significantly higher at the 6th week, and the rate of the anti-infective antibody price list was significantly higher (Table 3). Therefore, it is understood from the comparative experiment of this time that the induction of neutralizing antibodies produced by the influenza vaccine is enhanced by simultaneously ingesting the milk fermentation component and the propionic acid bacteria culture. The rate of inhibition of infected antibodies [Table 3] H1N1 Η3Ν2 Β-1 η number 2 weeks 6 weeks η number 2 weeks 6 weeks η number 2 weeks 6 weeks _ 11 18% (2) 9% (ΓΓ Control group 10 30% ( 3) 10°/〇(1) 10 50%(5)10°/〇(1) Test group 9 44%(4) 44%(4) 11 64°/〇(7) 64°/〇(7) 11 27°/〇(3) 9%(1)' P value 0.86 0.24 0.85 0.04 1 1 Neutralizing antibody titer after anti-vaccination at weeks 2 and 6 'anti-H1N1 and H3N2 antigens The antibody titer was significantly lower in the control group than in the second week. On the other hand, in the test group, the neutralizing antibody did not change between the 2nd week and the 6th week (Fig. 2A) Figure 2B). Secondly, 'analysis of the intestinal flora before and after influenza vaccination, in the ° test group 'the number of Bifidobacteria in the intestine (log 10 (number of bacteria / g feces) from 6 · (8) soil 1. 91 increased to 7. 37^2. 40, but in the control group, from 6.65 soil 2.97 to 6.18 pills 2·8〇, unchanged (Table 4). Changes in the number of Bifidobacteria in the intestine (Unit: the logarithm of the number of bacteria per lg of fecal weight). [Wife 4] ——.........After 2 months from the start of the test, R ιοίο ^ 6. 39+ ί. 91 The value of the level of the -i 1, 2, and 6 weeks of the group is significantly lower than that of the group of 54 201127389. When the group is divided (the 4th week), the improvement of the convenience is seen. On the other hand, the control group is investing. The value of the grade in the period of the period was not significantly lower than that at the start of the administration (Fig. 3). Further, regarding the number of stages of the stool, the test group showed a significant decrease in the third week and the sixth week as compared with the control group. Regarding the change in the concentration of cytokines in the blood, needle fines did not show a large change between the test group and the control group. However, in the IL-7' test group, the sixth week was compared to before the ingestion (the first There was a significant increase in _4 weeks. The control group at this time did not see any change in concentration at weeks -4 and 6. [IL-7] In the test group, week 6 was compared to week _4 ( IL-7 concentration increased significantly at the time of grouping or at the time of the first blood collection, but there was no significant change in the control group compared to the first week (Fig. 4). Again, there was no comparison between the control group and the test group. Significant differences were observed. [IL-17] Both the test group and the control group were at 6 weeks compared with the _4 weeks (when subgroup or the first blood collection), and the IL-17 concentration was decreased (control group: p< 〇5, test group: P > 0.05) (Fig. 4). No significant difference was observed between the control group and the test group. [TGF-yS 1] Both groups were in the blood concentration during the administration period relative to the first No significant changes were seen in 4 weeks. On the other hand, the test group showed a significant increase in the second week and the second week compared to the control group. However, in the subgroup (week), the test group has a higher tendency to the Tm concentration in the blood of the control group (Ρ = 0·074), so it can be considered that TGF is in the blood between the two groups. There is no difference in the impact of _々i loud voice 55 201127389 (Figure 4). From the above results, it is understood that when the milk fermentation component is compounded with the propionic acid bacteria culture, the induction of the neutralizing antibody at the time of influenza vaccination is specifically enhanced. Further, the combined administration of the milk fermentation component and the propionic acid bacteria culture showed a significant intestinal effect. Example 2: Method for preparing novel liquid foods The mixing step is to first stir the warm water in the tank, and consider the ease of mixing and diffusion of the raw materials other than vitamins (mixed components of vitamins) (Table 5). Oil, milk fermentation ingredients protein, sugar, minerals 'propionic acid bacteria culture. The milk fermentation component was prepared by lactic acid fermentation using the following microorganisms as lactic acid bacteria. Streptococcus thermophilus “ 〇 LS 3〇59 (FERM BP-1 0470), and Lactobacillus delbrueckii Uactotacillus delbrueckii subsp. bulfgaricus ) OLL l〇73R-l (FERM BP-10741). The hydrating solution is sterilized by helium gas injection, and homogenized (synthesized by one pressure) as a sterilizing liquid. A vitamin mixture (mixed component of vitamins) and a flavor (fragrance) are added to the sterilizing liquid. Mixing, as the final sterilizing liquid, and then injecting the final sterilizing liquid with steam, sterilizing (one #又囷), and homogenizing the homogenizer (homogenizing by two-stage pressure) to obtain a composition. Good quality or flavor 56 201127389 [Table 5] Composition of novel liquid foods: (both for every lOOkcal composition) Fresh liquid food (average composition) Protein (g) 3.8 Lipid (g) 2.7 Sugar (g) 14.6 Food fiber ( g) 1.6 Ash (g) 0.7 Vitamins: Vitamin A (//g) 109. 4(*) Vitamin Bl (mg) 0.1 Vitamin B2 (mg) 0.2 Vitamin B6 (mg) 0.3 Vitamin B12 (//g) 0.6 Vitamin C (mg) 15.4 Vitamin D (/ Zg) 0.5 Vitamin E (mg) 2.9 Vitamin K (/zg) 1.9 Test (mg) 1.5 Folic acid (//g) 48.0 Pantothenic acid (mg) 0.6 Mineral sodium (mg) 96.6 Calcium (mg) 77.0 Iron (mg 1.0 Fill (mg) 81.9 Magnesium (mg) 19.2 Potassium (mg) 99.8 Copper (//g) 48.0 Zinc (mg) 1.0 Chlorine (mg) 105.6 Protein derived from milk fermentation (g) 3.8 DHNA(βg) 1.6 Oligosaccharide (Total g) 0.5 (*): The amount of vitamin A is expressed as an equivalent of an alcohol.

S 57 201127389 實施例3 :新穎流質食物的製造方法 使用以下微生物作為乳酸菌菌元利用乳酸發酵製備乳 發酵成分，除此以外，與實施例2同樣進行，獲得組成物。 與實施例2同樣，該組成物的品質或風味良好。 作為乳酸菌菌元利用的微生物： 今熱遑珠 ％ {Streptococcus thermophi 1 us) (ΝΙΤΕ Ρ-77)，及 德氏乳酸桿菌保加利亞亞種 subspecies bulgaricus) OLL 1255(NITE BP-76) 實施例4 :新穎流質食物的製造方法 使用乳酸菌菌元（為了製造明治乳業公司製「明治 Bulgaria yogurt」而接種保加利亞乳酸桿菌 {Lactobacillus 與嗜熱 鏈球菌 利用乳酸發酵製備乳發 酵成分，除此以外，與實施例2同樣進行，獲得組成物。 與實施例2同樣，該組成物的品質或風味良好。 58 201127389 ‘ [表 6] 用於比較的流質食物的組成 (均為每lOOkcal的組成） .................................—^組成流質食物試驗流質食物+丙酸菌培養物 (平均組成） （平均組成） 蛋白質（g) 脂質（g) 糖(g) 食物纖維(g) 灰分(g) 維生素類： 維生素A(//g) 維生素Bl(mg) 維生素B2(mg) 維生素B6(mg) 維生素B12(/zg) 維生素C(mg) 維生素D(//g) 維生素E(mg) 維生素K(/zg) 菸驗(mg) 葉酸（/zg) 泛酸(mg) 礦物質類 納（mg) 鈣(mg) 鐵(mg) 填(mg) 鎂（mg) 鉀(mg) 銅（//g) 鋅(mg) 氯(mg) 4 9 3.8 2.7 14.6 1.6 0.7 109_4(*) 5 6 L 4 3 2 6 7 5 0 5 2 7 8 2 2 3 5 2 7 4 0 9 3 9 7 9 5 2 4 3 6 ο· 4 LCJ -- 5 9 9 5 οώ 1χ Ίχ 48 ο 6 6 0 0 9 2 8 0 6 7 _； ι—- 9 9 8 9 7 8 19 4 來自乳發酵成分 8 6 5 蛋白質（g) - DHNA(//g) - 0.1 59 201127389 [產業利用性] 本發明所提供之含有丙酸菌培養物的組成物，藉由與 乳發酵成”起投+，可作為流行性感冒⑤$症的預防劑 利用。本發明的組成物’增強已接種流行性感冒疫苗的動 物中流行性感冒病毒的中和抗體的誘導。因此，對於接種 流打性感冒疫苗的動物投予本發明的組成物，可提高疫苗 的重症化或感染預防效果。本發明的組成物，調配於流質 食物等營養劑或食品，可製成能期待流行性感冒預防作用 的經口攝取用組成物。本發明的組成物可更含有額外的乳 發酵成分與养糖。藉由投予該組成物，也可期待整腸作用。 【圖式簡單說明】 圖1顯示實驗流程（各流質食物的投予時間、疫苗接種 及抗體測定時點，及腸内菌叢分析時點）。 圖2顯示乳發酵成分與丙酸菌培養物的投予對接種疫 苗後的中和抗體價的影響。圖中，縱軸表示抗體力價的對 數值（loglO)，橫轴表示接種疫苗後的時間（週數）。對照群 與試驗群 2群間的統計學上的顯著差異，利用 Mann-Whitney U檢定分析，接種疫苗後第2週及第6週之 間的統計學上的顯著差異，利用Wilcoxon符號排序和檢定 分析。*表示第6週相對於第2週在感.染中和抗體價有顯著 差異（p<0.05)°A:對於H1N1的中和抗體價，B:對於H3N2 的中和抗體價，C :對於B1抗原的中和抗體價。 60 201127389 圖3顯不試驗期間中的糞便級數的變化。圖中，縱輕 表示布氏糞便級別（1-7)，橫軸表示各流質食物的投予時間 (週）。對照群與試驗群2群間的統計學上的顯著差異，利 用Mann-WhitneyU檢定分析，試驗前與試驗中各週的統卄 學上的顯著差異，利用Wilc〇x〇n符號排序和檢定分析。木 表示對照群與試驗群有顯著差異（P<〇. 05)，且a表示相對 於分群時（-4週）有顯著差異（p<〇. 〇5)。 圖4顯示乳發酵成分與丙酸菌培養物對於流行性感冒 疫苗接種時的血中細胞激素濃度的影響。圖中，縱輛表厂 a/l-7 濃度（pg/ml)、B:IL_17 濃度（pg/ml)，及 c:tgf 濃度（ng/inl)。橫軸表示以分群時定為_4時，採血時的 間（週）。對照群與試驗群2群間的統計學上的顯著差異以S 57 201127389 Example 3: Method for producing a novel liquid food A composition was obtained in the same manner as in Example 2 except that the following microorganisms were used as the lactic acid bacteria to prepare a milk fermentation component by lactic acid fermentation. As in Example 2, the composition was excellent in quality or flavor. Microorganisms used as lactic acid bacteria: % Streptococcus thermophi 1 us (ΝΙΤΕ 77-77), and Lactobacillus subsp. bulgaricus OLL 1255 (NITE BP-76) Example 4: Novel In the same manner as in the second embodiment, the lactic acid bacteria (in order to produce the Meiji Bulgarian yogurt manufactured by the Meiji Dairy Co., Ltd.) and the Lactobacillus bulgaricus (Lactobacillus and Streptococcus thermophilus were fermented by lactic acid to prepare a milk fermentation component) The composition was obtained, and the quality or flavor of the composition was good as in Example 2. 58 201127389 ' [Table 6] The composition of the liquid food for comparison (both composition per lOOkcal) ...... ...........................—^ Composition of liquid food test liquid food + propionic acid bacteria culture (average composition) (average composition) protein (g) Lipid (g) Sugar (g) Food fiber (g) Ash (g) Vitamins: Vitamin A (//g) Vitamin Bl (mg) Vitamin B2 (mg) Vitamin B6 (mg) Vitamin B12 (/zg ) Vitamin C (mg) Vitamin D (//g) Vitamin E (mg) Vitamin K (/z g) Smoke test (mg) Folic acid (/zg) Pantothenic acid (mg) Minerals (mg) Calcium (mg) Iron (mg) Fill (mg) Magnesium (mg) Potassium (mg) Copper (//g) Zinc (mg) Chlorine (mg) 4 9 3.8 2.7 14.6 1.6 0.7 109_4(*) 5 6 L 4 3 2 7 7 5 0 5 2 7 8 2 2 3 5 2 7 4 0 9 3 9 7 9 5 2 4 3 6 ο· 4 LCJ -- 5 9 9 5 οώ 1χ Ίχ 48 ο 6 6 0 0 9 2 8 0 6 7 _; ι—- 9 9 8 9 7 8 19 4 From milk fermentation ingredients 8 6 5 Protein (g) - DHNA(//g) - 0.1 59 201127389 [Industrial Applicability] The composition containing the culture of propionic acid bacteria provided by the present invention can be used as the influenza 5$ disease by fermenting with milk. The use of the prophylactic agent. The composition of the present invention enhances the induction of a neutralizing antibody against an influenza virus in an animal that has been inoculated with an influenza vaccine. Therefore, the composition of the present invention is administered to an animal inoculated with a influenza vaccine. The composition of the present invention can be formulated into a nutrient or a food such as a liquid food, and can be used as an orally ingestible composition which can anticipate the prevention of influenza. The composition of the present invention may further contain additional milk fermentation ingredients and sugar. The intestine action can also be expected by administering the composition. [Simple description of the diagram] Figure 1 shows the experimental procedure (the time of administration of each liquid food, the time of vaccination and antibody determination, and the time of analysis of intestinal flora). Figure 2 shows the effect of the administration of the milk fermentation component and the propionic acid bacteria culture on the neutralizing antibody price after inoculation. In the figure, the vertical axis represents the logarithm of the antibody valence (loglO), and the horizontal axis represents the time (week) after vaccination. Statistically significant differences between control and test group 2, using the Mann-Whitney U assay, statistically significant differences between weeks 2 and 6 after vaccination, using Wilcoxon symbol ordering and assays analysis. * indicates that there is a significant difference in the sensitizing and neutralizing antibody valence at week 6 relative to week 2 (p < 0.05) ° A: neutralizing antibody valency for H1N1, B: neutralizing antibody valence for H3N2, C: for The neutralizing antibody valency of the B1 antigen. 60 201127389 Figure 3 shows the change in the number of stools during the test period. In the figure, the lightness indicates the Brinell stool level (1-7), and the horizontal axis indicates the administration time (week) of each liquid food. The statistically significant difference between the control group and the test group 2 was analyzed by Mann-Whitney U assay, and the statistically significant differences between the pre-test and the week of the experiment were analyzed using Wilc〇x〇n symbol sorting and assay. Wood indicates that the control group is significantly different from the test group (P < 〇. 05), and a indicates a significant difference (p < 〇. 〇 5) relative to the grouping (-4 weeks). Figure 4 shows the effect of milk fermentation components and propionic acid bacteria cultures on blood cytokine concentrations during influenza vaccination. In the figure, the vertical plant has a/l-7 concentration (pg/ml), B:IL_17 concentration (pg/ml), and c:tgf concentration (ng/inl). The horizontal axis indicates the time (week) at the time of blood collection when the grouping is _4. Statistically significant difference between the control group and the test group 2

Students，t檢定（等分散）或^丨叻的檢定（非等分散')= 析’試驗前與試驗中各週間的統計學上： 的t檢定分析。 考差異以對應 【主要元件符號說明】 itt. 〇 “》、 61Students, t-test (equal dispersion) or ^丨叻 test (non-equivalent dispersion) = analysis 'pre-test and weekly weeks of the test: t-test analysis. Test the difference to correspond to [Main component symbol description] itt. 〇 "", 61

Claims (1)

201127389 七、申請專利範圍： 1.種 <亍1·生感冒感染症的預防組成物，包含丙酸菌 的培養物。 2 ·如申請專利筋[f|楚1 tS a > 軏圍第1項之流行性感冒感染症的預防 組成物，其中丙酸菌 馬 W K两後大干齒〈pr〇plonibacterjum freudenreichii)。 3. 如申請專利範圍第1項之流行性感胃感染症的預防 組成物’更㈣地包含乳發酵成分及寡糖的任-者或兩者。 4. 如申明專利範圍第3項之流行性感冒感染症的預防 組成物，其中乳發酵成分係以乳酸桿菌屬 的乳酸菌及鏈球菌屬的乳酸菌的任一者 或兩者傈乳發酵的乳、或其混合物。 5. 如申請專利範圍第3項之流行性感f感染症的預防 組成物’其中乳發酵成分為非熟成乳酪。 6. 如申請專利範圍第3項之流行性感冒感染症的預防 組成物，其中構成該寡糖的糖之至少一種為半乳糖。 7. 如申請專利範圍第3項之流行性感冒感染症的預防 組成物’其中該組成物包含丙酸菌的培養物及乳發酵成 分，且兩者經過殺菌。 8. 如申請專利範圍第1項之流行性感冒感染症的預防 組成物，係用於對接種流行性感冒疫苗的動物經腸投予。 9·如申請專利範圍第3項之流行性感冒感染症的預防 組成物’包含下述營養素： 丙酸菌的培養物； 62 201127389 > 乳發酵成分； 寡糖； 蛋白質； 糖； 脂質；及 食物纖維* 10.如申請專利範圍第9項之流行科 IL仃性感冒感染症的預 防組成物，更額外地包含選自由維生+ # ' 夂I頰、礦物質類、有 機酸及有機鹼所構成的群組中之至少1種營養素。 Π. —種於已接種流行性感冒疫苗& ㈢仪田的動物中的流行性 感冒病毒的中和抗體之誘導促進劑，句人 巴含丙酸菌的培養物。 1 2. —種流行性感冒感染症的預防太、土 J J只防万法，包含以下步 驟： (1) 對動物投予丙酸菌的培養物之步驟.及 (2) 對動物接種流行性感冒疫苗之步驟。 13. 如申請專利範圍第12項之流行性感f感染症的預 防方法’其中在步驟⑵之前、後或同時，至少進行（次步 驟⑴。 14. 如申請專利範圍第12項之流行性感冒感染症的預 —其中在步驟⑴中’ @酸菌的培養物與乳發酵成分 及寡糖任一者或兩者一起投予。 I5· 一種組成物，含有以下成分（a)〜（C): (a )券糖、 (b)乳發酵成分，及 63 201127389 (C)丙酸菌的培養物。 1 6.如申請專利範圍第1 5項之組成物，其 寡糖的糖之至少一種為半乳糖。 17.如申請專利範圍第1 5項之組成物，係 物。 中，構成該 整腸用組成 64201127389 VII. Patent application scope: 1. Kind of <亍1·Prophylactic composition of cold infection, including culture of propionic acid bacteria. 2 · If you apply for a patent rib [f|楚1 tS a > 軏 第 第 第 第 之 第 第 第 第 第 第 第 第 第 第 第 第 第 第 第 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 流行 〇 〇 〇 〇 〇 3. The preventive composition of the epidemic-type gastric infection according to the first aspect of the patent application includes the milk fermentation component and the oligosaccharide or both. 4. The preventive composition of influenza infection according to item 3 of the patent scope, wherein the milk fermentation component is a milk fermented by any one or both of a lactic acid bacterium of the genus Lactobacillus and a lactic acid bacterium of the genus Streptococcus; Or a mixture thereof. 5. The preventive composition of the epidemic-type f infection of the third paragraph of the patent application' wherein the milk-fermented ingredient is non-cooked cheese. 6. The composition for preventing influenza infection according to item 3 of the patent application, wherein at least one of the sugars constituting the oligosaccharide is galactose. 7. The composition for preventing influenza infection according to item 3 of the patent application wherein the composition comprises a culture of propionic acid bacteria and a milk fermentation component, and both are sterilized. 8. The preventive composition of influenza infection according to item 1 of the patent application is for enteral administration to an animal vaccinated with influenza. 9. The preventive composition of influenza infection according to item 3 of the patent application scope contains the following nutrients: culture of propionic acid bacteria; 62 201127389 > milk fermentation ingredients; oligosaccharides; proteins; sugars; Food fiber* 10. The preventive composition of the epidemic IL, a cold infection, as in the ninth application of the patent scope, further includes a vitamin, a mineral, an organic acid and an organic base selected from the group consisting of vitamins + # ' 夂I At least one nutrient in the group formed. Π. A vaccine for the induction of neutralizing antibodies to influenza viruses that have been vaccinated against influenza vaccines and (3) animals in the field, and a culture of propionate bacteria. 1 2. Prevention of Influenza Infectious Diseases, Soil JJ is only a defensive method, including the following steps: (1) the steps of administering a culture of propionic acid bacteria to animals. And (2) cultivating the epidemic of animals. The steps of the cold vaccine. 13. The method for preventing prevalence of sexually transmitted infections in the patent application section 12, wherein at least before step (2), or at the same time, at least (substep (1). 14. Influenza infection according to item 12 of the patent application scope Pre-existing - wherein in step (1), the culture of '@ acid bacteria is administered together with either or both of the milk fermentation ingredients and the oligosaccharides. I5· A composition comprising the following components (a) to (C): (a) vouchers, (b) milk-fermented ingredients, and 63 201127389 (C) Cultures of propionic acid bacteria. 1 6. As in the composition of claim 15 of the patent application, at least one of the oligosaccharide sugars is Galactose. 17. The composition of claim 15 of the patent application, in the composition.
TW099143199A 2009-12-10 2010-12-10 Production of Propionic Acid Bacteria in the Preparation of Preventive Agents for Influenza Infectious Diseases and Induction Promoters for Neutralizing Antibodies TWI476000B (en)

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