TW201121558A - Anti-influenza virus agent - Google Patents

Anti-influenza virus agent Download PDF

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Publication number
TW201121558A
TW201121558A TW099134529A TW99134529A TW201121558A TW 201121558 A TW201121558 A TW 201121558A TW 099134529 A TW099134529 A TW 099134529A TW 99134529 A TW99134529 A TW 99134529A TW 201121558 A TW201121558 A TW 201121558A
Authority
TW
Taiwan
Prior art keywords
influenza virus
influenza
agent
acid
alcohol
Prior art date
Application number
TW099134529A
Other languages
Chinese (zh)
Inventor
Haruki Yamada
Hiroaki Kiyohara
Takayuki Nagai
Tadamasa Ohmiya
Tadahiro Hiramoto
Original Assignee
School Juridical Person Kitasato Inst
Takasago Perfumery Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by School Juridical Person Kitasato Inst, Takasago Perfumery Co Ltd filed Critical School Juridical Person Kitasato Inst
Publication of TW201121558A publication Critical patent/TW201121558A/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • 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
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B9/00—Essential oils; Perfumes
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B9/00—Essential oils; Perfumes
    • C11B9/0042—Essential oils; Perfumes compounds containing condensed hydrocarbon rings
    • 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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Virology (AREA)
  • Nutrition Science (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Mycology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Physiology (AREA)
  • Botany (AREA)
  • Wood Science & Technology (AREA)
  • Oncology (AREA)
  • Pulmonology (AREA)
  • Zoology (AREA)
  • Polymers & Plastics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Food Science & Technology (AREA)
  • Molecular Biology (AREA)
  • Otolaryngology (AREA)
  • Communicable Diseases (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Cosmetics (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Detergent Compositions (AREA)

Abstract

Disclosed is a novel antiviral agent which is useful for prevention and treatment of influenza. Specifically disclosed is an anti-influenza virus agent which contains patchouli alcohol and/or a patchouli essential oil extract as an active ingredient.

Description

201121558 六、發明說明： 【發明所屬之技術領域】 本發明係關於一種對預防及治療流感病毒性疾病有效之 抗病毒劑，其包含唇形花科植物廣藿香（P〇g0stemon cablin Benth.)中所含有之成分。 【先前技術】 每年冬季流行之流感係由流感病毒引起之人畜共通傳染 病’其作為一種主要藉由飛沫傳染及接觸傳染而進行傳 染，並伴隨發燒、頭痛、肌肉痛、關節痛等強烈的全身症 狀之啤吸道傳染病而廣為人知。嬰幼兒、生理防禦功能低 下之高齡者、慢性呼吸道疾病或糖尿病等基礎疾病患者是 會因流感病毒傳染而引發腦炎、腦病或肺炎等預後不良之 併發症的高危險群。接種流感疫苗是防禦流感重症化之最 佳方法，但目前之疫苗預防傳染之效果較低。因此認為， 為防禦流感病毒傳染，較理想的是將疫苗與預防治療藥組 合之對策。 感病毒係屬於正黏液病毒科之RNA(ribonucleic acid， 核糖核酸）病毒，分為A、B及C型之3種類型（非專利文獻 1)。已知A〜C型病毒均係發生緩慢的抗原性之變化（連續變 異）以回避抗體之壓力’由於該現象，每年皆會發生A及b 型流感病毒之小規模流行（非專利文獻2及3)。 另一方面’ A型流感病毒發生不連續變異而導致新型病 毒之出現。作為由A型流感病毒引起之流感之大流行，有 1918年之西班牙流感（!11>11)、1957年之亞洲流感旧2犯）、 151403.doc 201121558 1968年之香港流感（H3N2)& 1977年之蘇聯流感（hini)，在 西班牙流感中，全世界之推定死亡者總數為2〜4千萬人， 曰本國内亦有38萬9千人死亡。 流感病毒向宿主細胞之傳染係由病毒表面之血球凝集素 (HA)識別並結合於宿主細胞表面之糖蛋白質或糖脂質等複 合糖質之糖鏈中的唾液酸[α伽3)'结合(鳥型)或α_(2 — 6)_ 結合（人型）]而開始、繼而，於病毒侵入至宿主細胞内，經 過與内體之融合、流感病毒基因之脫殼.複製、及流感病 毒粒子之重組最後發芽（出芽）的過程中，係進行下述過 程，即流感病毒表面之神經胺糖酸酶（ΝΑ)將血球凝集素 (ΗΑ)與唾液酸之結合水解，藉此流感病毒粒子自宿主細胞 游離（非專利文獻4及5)。業界以該等病毒傳染之各種過程 為對象而探索抗流感病毒活性物質，以丨998年之金剛烷胺 為開端，紫那米韋（Zanamivir)、奥司他韋（〇seltamivir)被 認可為日本之流感治療藥。但是，流感病毒具有回避抗體 等之外部壓力之手段即具備發生抗原性之連續變異的能 力，業界無可阻礙病毒獲得對該等流感治療藥之耐性機制 之技術。對於金剛烷胺，病毒係藉由M2蛋白膜通過部位 之特定胺基酸（26、27、30及31位）之變異而產生對其之耐 性，使用培養細胞進行研究時，於i次培養中，有約3〇% 之病毒獲得耐藥性。先前，現有之分離株中之對金剛烷胺 之对性度通常停留於10%以下，但於2〇〇5年末情況完全改 變’由於中國國内將該藥劑與普通藥混合等藥物亂用，於 亞洲分離之香港型（H3N2亞型）之A型流感病毒之耐藥性病 15I403.doc 201121558 毒劇增。於2004年，中國•香港之分離株之耐藥性株約佔 7〇°/〇，且該耐藥性病毒株正向全世界擴散（非專利文獻6)。 另一方面，已知對於作為神經胺糖酸酶抑制劑之紮那米 早及奥司他韋，病毒係藉由神經胺糖酸酶活性部位及血球 凝集素與唾液酸結合之部位的2種變異機制而產生耐藥性 (非專利文獻7)。先前，對該藥劑具有耐性之病毒之出現頻 率較低，但近年來，幼兒中耐奥司他韋性A型流感病毒之 出現頻率遠高於先前所認為之頻率，已明確：香港型 (H3N2亞型）達到18% ’蘇聯型（H1N1亞型）達到16%。進 而’根據來自世界衛生組織（WH〇，world Health 〇rganizati〇n)之報告，蘇聯型病毒中，於2〇〇8年之第c週 至第52週全世界分離之379個樣本中，有35〇個樣本檢測出 耐奥司他早性病毒，出現頻率高達92%。又，據報告，與 該專神經胺糖酸酶抑制藥對應之B型流感病毒，雖與a型 相比較耐藥性病毒之出現頻率較低（丨6%)但亦可能產生耐 藥丨生（非專利文獻7)。進而，對於磷酸奥司他韋，投予該藥 劑與精神•神經症狀（異常行為等）之關聯性亦成為社會問 題’對十幾歲之未成年人之使用設有限制。 就為抑制耐藥性病毒之產生而使用多劑併用療法，以及 需要回避現有流感藥之副作用之方面而言，需要開發新穎 之抗流感病毒藥。 近年來’各種天然藥之抗病毒效果亦受到關注。例如在 中國將夕種天然藥（廣藿香（Pogostemon cablin Benth.)、 蒼術（Atractylodis lanceae rhizoma)、白術（Atractylodes 151403.doc 201121558 rhizome)、大黃（Rheum rhabarbarum)、玲羊角（"if’-f 力、力乇 シ力角）、珊蝴菜（Glehniae radix cum rhizoma)、野菊 (Chrysanthemum indicum)、茅根（Imperatae rhizoma)、黃 芩（Scutellariae radix) ' 陳皮（Citrus Unshiu Peel)、甘草 (Glycyrrhiza)、半夏（Pinellia tuber)等）之混合天然藥製劑 作為對流感等呼吸道傳染病具有抗病毒作用之製劑而申請 專利（專利文獻1)’但並未特別指定成為其抗病毒活性之主 體之天然藥或其活性本體。 作為天然藥之廣藿香係將中國廣東省所栽培之唇形花科 植物廣藿香（Pogostemon cablin Benth.;亦稱為藿香）的葉 或全草乾燥後使用之中曰天然藥。中醫學上認為其對食慾 不振、消化不良、中暑、寒熱頭痛、嘔吐、腹瀉等有效。 其係含有精油成分（4〜5 %)作為主要成分（非專利文獻8 )。 ^是至今尚無廣藿香關於抗病毒作用之見解。中醫學 上，認為廣藿香發揮主要作用之中藥配方劑（藿香正氣散 係以於噁心、嘔吐、腹痛、腹瀉、腹脹感、胸悶、身體」 力、食慾不振、食無味、口發黏等症狀中伴隨惡寒、發 熱、頭痛等症狀之病情為適應症’作為臨床應用，已知可 用於胃腸型感冒、流行性腮腺炎等（非專利文獻9)。 另-方面’自廣藿香中獲得之精油(廣藿香油)係作為香 料而用於化妝品等。據報告作為廣董香油之主要香氣成分 之廣着香賴介U4(IL.4)之產生具有抑制效果，可用作 ^過敏劑或異位性皮膚炎之預防·改善劑（專利文獻2)。但 疋，未報告有廣藿香油或廣藿香醇顯示抗病毒作用之見 151403.doc 201121558 解。 先前技術文獻 專利文獻 專利文獻1 ··中國專利申請案公開第101095746號說明書 專利文獻2 :日本專利特開2000-309528號公報 非專利文獻 非專利文獻1 :清水一史，「流感病毒之抗原性變異機 制」，曰本臨床，曰本臨床社，55，ρ·2610-2616(1997) 非專利文獻2 :飛田清毅，「流感病毒之分類基準與命名 法」，日本臨床，日本臨床社，55，ρ.2512-2514(1997) 非專利文獻3 :西村秀一，「近來之a型、Β型流感病毒 之抗原變異」’日本臨床’日本臨床社，55，ρ. 2617-2626(1997) 非專利文獻4 :永武毅，「流感病毒向人傳染增殖之機 制」，日本臨床’日本臨床社，61，ρ.1892-1896(2003) 非專利文獻5 :本田文江、石浜明，「流感病毒之增殖· 基因組之轉錄與複製」’日本臨床，日本臨床社，55， P.2555-2561(1997) 非專利文獻6:齋藤玲子、鈴木宏，「耐藥性病毒之現狀 與展望」’綜合臨床，永井書店，55，p 2788_2793(2〇〇6) 非專利文獻7 .畠山修司、河岡義裕，「耐藥性獲得機制 與耐藥性病毒之現狀」，日本臨床，日本臨床社，64， P.1845-1852(2006) 非專利文獻8 ·難波恆雄，和漢藥百科圖鑒，v〇1 ^， 151403.doc 201121558 pp. 58-60，保育社（1980) 非專利文獻9 :神戶中醫學研究會譯，「中醫配方解 說」，醫齒藥出版（1979) 【發明内容】 發明所欲解決之問題 本發明之課題在於提供一種對於預防.治療病毒性疾 病、尤其是流感有用之新穎之抗病毒劑。 解決問題之技術手段 本發明者等人為解決上述課題反覆潛心研究’結果於自 廣藿香萃取之精油組分中發現抑制流感病毒之傳染過程之 活性’進而明確該組分所含之具有抗流感病毒活性之化合 物為倍半萜烯類之廣藿香醇（別名：薄荷醇），從而達成本 發明。 即，本發明包含以下者。 [1] 一種抗流感病毒劑’其係包含廣藿香醇及/或廣藿香 精油萃取物作為有效成分者。 [2] —種流感病毒傳染病之預防及/或治療用香料組合 物，其係含有如上述Π]之抗流感病毒劑者。 [3] —種流感病毒傳染病之預防及/或治療用之鼻腔或口 腔投予用組合物’其係含有如上述⑴之抗流感病毒劑或如 上述[2]之香料組合物者。 [4] 一種流感病毒傳染病之預防及/或治療用醫藥製劑， 其係含有如上述[1]之抗流感病毒劑或如上述[2]之香料組 合物者。 151403.doc 201121558 []種a感病帑傳染病之預防及/或治療用飲食品其 係含有如上述[11夕> '、 J <抗流感病毒劑或如上述[2]之香料组人 物者。 ’ σ []種抓感病毒傳染病之預防及/或治療用香妝品，其 糸3有如上述[1 ]之抗流感病毒劑或如上述[2]之香料組合 . 物者。 [7] —種流感病毒傳染病之預防及/或治療用之曰用雜貨 °»，其係含有如上述[丨]之抗流感病毒劑或如上述[2]之香 料組合物者。 本說明書包含作為本申請案主張優先權之基礎的曰本專 利申凊案之特願2009-235617號之内容。 發明之效果 若使用本發明之抗流感病毒劑’則可於較低之細胞毒性 下獲仔較南之抗流感病毒活性。 【實施方式】 以下’對本發明進行詳細說明。 工·廣藿香醇及/或廣藿香精油萃取物 本發明係關於一種含有廣藿香醇及/或廣藿香精油萃取 物作為有效成分之抗流感病毒劑及其用途。 • 廣藿香醇（patchouli alcohol)係具有藿香院（patchoulane) 骨架之獨特結構的倍半萜烯類化合物，其化學名為 (18)-2戸，5,5,8&〇1-四.甲基-10，60-亞曱基十氫萘-4&〇1-醇 ((1S)-2p,5,5,8aa-tetramethyl-lp,6P-methanodecalin-4aa-ol)。作為其生物活性，報告有抗氧化活性[A_ Wei, T. 151403.doc 201121558201121558 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to an antiviral agent effective for preventing and treating influenza virus diseases, which comprises a plant of the family Labiatae (P〇g0stemon cablin Benth.) The ingredients contained in it. [Prior Art] The flu that is prevalent every winter is a common disease caused by influenza virus. It is a kind of infection mainly caused by droplet infection and contact infection, accompanied by intense body such as fever, headache, muscle pain and joint pain. Symptoms of beer are widely known as infectious diseases. Infants and young children, elderly people with low physical defense function, patients with underlying diseases such as chronic respiratory diseases or diabetes are high-risk groups that cause complications such as encephalitis, encephalopathy or pneumonia due to influenza virus infection. Influenza vaccination is the best way to prevent flu from getting serious, but the current vaccine is less effective in preventing infection. Therefore, it is considered that in order to prevent influenza virus infection, it is desirable to combine vaccines with preventive and therapeutic drugs. The susceptible virus belongs to the ribonucleic acid (ribonucleic acid) virus of the genus Myxoviridae, and is classified into three types of types A, B, and C (Non-Patent Document 1). It is known that all of the A to C viruses undergo a slow antigenic change (continuous variation) to avoid the pressure of the antibody. Due to this phenomenon, small-scale epidemics of influenza A and B viruses occur every year (Non-Patent Document 2 and 3). On the other hand, the influenza A virus undergoes discontinuous mutations leading to the emergence of new viruses. As a pandemic of influenza caused by influenza A virus, there is the Spanish flu in 1918 (!11>11), the old flu of the Asian flu in 1957, 151403.doc 201121558 Hong Kong flu (H3N2) & 1968 In the Soviet flu (hini) in 1977, the total number of presumed deaths in the world was 2 to 40 million in the Spanish flu, and 389,000 in the country. The infection of the influenza virus into the host cell is recognized by hemagglutinin (HA) on the surface of the virus and binds to the sialic acid [α gamma 3]' in the sugar chain of the complex saccharide such as glycoprotein or glycolipid on the surface of the host cell ( Bird type) or α_(2 - 6)_ binding (human type)], and then, invade into the host cell, through fusion with the endosome, shelling of the influenza virus gene, replication, and influenza virions In the process of final germination (budulation), the following process is carried out, that is, the neuraminidase (ΝΑ) on the surface of the influenza virus hydrolyzes the binding of hemagglutinin (ΗΑ) and sialic acid, thereby taking the influenza virus particles from The host cells are free (Non-Patent Documents 4 and 5). The industry explores anti-influenza active substances for various processes of viral infection, starting with amantadine in 998, and Zanamivir and oseltamivir are recognized as Japan. Influenza treatment medicine. However, influenza viruses have the ability to avoid the external variability of antigenicity by means of avoiding external stress such as antibodies, and there is no technology in the industry that can prevent the virus from acquiring the tolerance mechanism of such influenza therapeutic drugs. For amantadine, the virus is resistant to the specific amino acid (26, 27, 30, and 31) of the M2 protein membrane passing through the site, and when cultured cells are used for the study, i culture is used. About 3% of the virus is resistant. Previously, the compatibility of the amantadine in the existing isolates usually stayed below 10%, but the situation completely changed at the end of the 2nd year's due to the indiscriminate use of drugs such as drugs mixed with common drugs in China. The Hong Kong-type (H3N2 subtype) type A flu virus-resistant disease isolated in Asia 15I403.doc 201121558 has increased dramatically. In 2004, the drug-resistant strain of the isolate of China and Hong Kong accounted for about 7〇/〇, and the drug-resistant virus strain was spreading to the whole world (Non-Patent Document 6). On the other hand, it is known that as a neuraminidase inhibitor, zanamivir and oseltamivir, the virus is composed of a site of a reactive portion of a neuraminidase and a site where hemagglutinin binds to sialic acid. Drug resistance is caused by the mutation mechanism (Non-Patent Document 7). Previously, the frequency of the virus with tolerance to the drug was low, but in recent years, the frequency of oseltamivir-type influenza A virus in children has been much higher than previously thought, and it has been clear: Hong Kong type (H3N2) Subtype) reached 18% 'Soviet type (H1N1 subtype) reached 16%. Furthermore, according to a report from the World Health Organization (WH〇, world Health 〇rganizati〇n), among the 379 samples of the Soviet-type virus that were isolated worldwide from week c to week 52 of 2-8 years, 35 One sample tested for the early-stage virus, which was up to 92%. In addition, it has been reported that the influenza B virus corresponding to the specific neuroglycosylase inhibitor has a lower frequency of occurrence of drug-resistant virus than the type a (丨6%), but may also produce drug-resistant twins. (Non-Patent Document 7). Further, in the case of oseltamivir phosphate, the association between administration of the drug and mental and neurological symptoms (abnormal behavior, etc.) has also become a social problem, and there is a restriction on the use of a juvenile. In order to suppress the production of drug-resistant viruses, the use of multiple doses of combination therapy, and the need to circumvent the side effects of existing influenza drugs, it is necessary to develop novel anti-influenza drugs. In recent years, the antiviral effects of various natural medicines have also received attention. For example, in China, the natural medicines (Pogostemon cablin Benth., Atractylodis lanceae rhizoma, Atractylodes 151403.doc 201121558 rhizome), Rhubarb (Rheum rhabarbarum), Ling Yangjiao ("if' -f force, force 角), Glehniae radix cum rhizoma, Chrysanthemum indicum, Imperatae rhizoma, Scutellariae radix 'Citrus Unshiu Peel, licorice (Glycyrrhiza) A mixed natural medicine preparation of Pinellia tuber or the like is applied as a preparation having an antiviral action against respiratory infectious diseases such as influenza (Patent Document 1)', but it is not specifically designated as a natural body of its antiviral activity. Medicine or its active body. As a natural medicine, the patchouli is a natural medicine used in the leaves or whole grasses of the Pogostemon cablin Benth. (also known as musk) cultivated in Guangdong Province, China. Traditional Chinese medicine believes that it is effective for loss of appetite, indigestion, heat stroke, cold and heat headache, vomiting, and diarrhea. It contains an essential oil component (4 to 5%) as a main component (Non-Patent Document 8). ^ There is no insight into the antiviral effect of patchouli. In traditional Chinese medicine, it is believed that patchouli plays a major role in traditional Chinese medicine formula (Zhuxiang Zhengqi Powder for nausea, vomiting, abdominal pain, diarrhea, bloating, chest tightness, body strength), loss of appetite, tastelessness, sticky mouth, etc. Symptoms of symptoms such as aversion to cold, fever, and headache are indications. As a clinical application, it is known to be used for gastrointestinal colds, mumps, etc. (Non-Patent Document 9). The obtained essential oil (Amaranthus oleifera) is used as a fragrance for cosmetics, etc. It is reported that the main aroma component of the dong fragrant oil is the inhibitory effect of the production of the scented scented scent U4 (IL.4), which can be used as an allergy. Agent or prevention and improvement agent for atopic dermatitis (Patent Document 2). However, it has not been reported that patchouli oil or patchouli alcohol exhibits antiviral action. 151403.doc 201121558 Solution. Prior Art Literature Patent Literature Patent Literature 1. Chinese Patent Application Publication No. 101095746, Patent Document 2: Japanese Patent Laid-Open No. 2000-309528, Non-Patent Literature Non-Patent Document 1: History of Clear Water, "Antigen of Influenza Virus Mutation mechanism", Sakamoto Clinical, Sakamoto Clinical Society, 55, ρ·2610-2616 (1997) Non-Patent Document 2: Fei Tian Qing Yi, "Classification and Nomenclature of Influenza Virus", Japanese Clinical, Japanese Clinical Society, 55, ρ.2512-2514 (1997) Non-Patent Document 3: Nishimura Hideyuki, "The recent antigenic variation of a type and sputum influenza virus" 'Japanese Clinical' Japanese Clinical Society, 55, ρ. 2617-2626 (1997) Non-Patent Document 4: Yong Wuyi, "Mechanism of Influenza Virus Transmission to Humans", Japanese Clinical 'Japan Clinical Society, 61, ρ.1892-1896 (2003) Non-Patent Document 5: Honda Wenjiang, Shi Yuming, "Influenza Virus Proliferation · Transcription and replication of genomes" 'Japan Clinical, Japanese Clinical Society, 55, P.2555-2561 (1997) Non-Patent Document 6: Saito Reiko, Suzuki Hiroshi, "Status and Prospects of Drug-Resistant Viruses" Clinical, Nagai Shoten, 55, p 2788_2793 (2〇〇6) Non-patent literature 7. Miyayama Shuji, Kawaoka Yoshihiro, "The status of drug resistance acquisition mechanism and drug-resistant virus", Japanese Clinical, Japanese Clinical Society, 64, P.1845-1852 (2006) Non-Patent Document 8 · Namba Constant , and Chinese Medicine Encyclopedia, v〇1 ^, 151403.doc 201121558 pp. 58-60, Conservation Society (1980) Non-Patent Document 9: Translation of the Kobe Chinese Medicine Research Association, "Chinese Medicine Formulation", Medical Tooth Drug Publishing (1979) SUMMARY OF THE INVENTION PROBLEM TO BE SOLVED BY THE INVENTION An object of the present invention is to provide a novel antiviral agent useful for the prevention and treatment of viral diseases, particularly influenza. The technical solution of the present invention has been made by the present inventors to solve the above problems. The result of the research is to discover the activity of the infection process of the influenza virus from the essential oil component of the patchouli extract, and to clarify that the compound having anti-influenza activity contained in the component is a sesquiterpene. Aroma alcohol (alias: menthol) to achieve the present invention. That is, the present invention includes the following. [1] An anti-influenza virus agent which comprises, as an active ingredient, a patchouli alcohol and/or patchouli essential oil extract. [2] A perfume composition for preventing and/or treating influenza virus infectious diseases, which comprises an anti-influenza agent as described above. [3] A composition for nasal or oral administration for the prevention and/or treatment of an influenza virus infectious disease, which comprises the anti-influenza virus agent of the above (1) or the flavor composition of the above [2]. [4] A pharmaceutical preparation for the prophylaxis and/or treatment of an influenza virus infectious disease, which comprises the anti-influenza virus agent of the above [1] or the perfume composition of the above [2]. 151403.doc 201121558 [] A food and drink for the prevention and/or treatment of a disease-causing infectious disease, which contains the above-mentioned [11 eve > ', J < anti-influenza virus agent or the spice group as described above [2] Character person. 'σ [] a cosmetic product for the prevention and/or treatment of a viral infection, such as the anti-influenza agent of the above [1] or the combination of the fragrances of the above [2]. [7] A groceries for use in the prevention and/or treatment of influenza virus infectious diseases, which is an anti-influenza virus agent as described above [丨] or a fragrance composition as described in [2] above. The present specification contains the contents of Japanese Patent Application No. 2009-235617, which is incorporated herein by reference. EFFECTS OF THE INVENTION The use of the anti-influenza virus agent of the present invention provides a relatively souther anti-influenza virus activity at a lower cytotoxicity. [Embodiment] Hereinafter, the present invention will be described in detail. The present invention relates to an anti-influenza virus agent containing as an active ingredient an extract of patchouli alcohol and/or patchouli essential oil and use thereof. • Patchouli alcohol is a sesquiterpene compound with a unique structure of the patriculane skeleton. Its chemical name is (18)-2戸,5,5,8&〇1-four. Methyl-10,60-arylene-decahydronaphthalene-4&-l-ol ((1S)-2p,5,5,8aa-tetramethyl-lp,6P-methanodecalin-4aa-ol). As its biological activity, it has been reported to have antioxidant activity [A_ Wei, T. 151403.doc 201121558

Shibamoto，J. Agric. Food Chem” 55，1737-1742 (2007)]、 止吐活性[Y. Yang et al” Phytomedicine，6，89-93 (1999)]及 基於Ca2+拮抗作用之腸道平滑肌收縮抑制作用[K Ichikawa et al.，Chem. Pharm· Bull” 37, 345-348 (1989)],但關於對 以流感病毒為代表之病毒之作用未有報告。倍半萜烯類係 作為不僅自植物中產生而且亦自微生物等中產生之結構多 樣性極尚之化合物群而廣為人知[田中治、野副重男、相 見則郎、永井正博編，天然物化學（修訂第6版），ρρ 1〇3_ 116(2002)]。作為來自植物之倍半萜烯類之抗病毒活性之 報告’於中醫使用之天然藥（中藥）中，具有與自雷公藤 (Tripterygium wilf0rdii Hook)中分離之廣藿香醇結構不同 之八氫-1-苯并氧雜環庚三烯骨架的20種倍半萜烯中，發現 卜U 7。卜7才士、：； > C-2對作為包膜病毒之類型I疱疹病毒 或巨細胞病毒具有抗病毒作用[K. Hayashi，T. Hayashi，K.Shibamoto, J. Agric. Food Chem" 55, 1737-1742 (2007)], antiemetic activity [Y. Yang et al" Phytomedicine, 6, 89-93 (1999)] and intestinal smooth muscle contraction based on Ca2+ antagonism Inhibition [K Ichikawa et al., Chem. Pharm· Bull" 37, 345-348 (1989)], but the role of the virus represented by influenza virus has not been reported. The sesquiterpene system is not only It is widely known as a group of compounds that are produced in plants and which are also extremely diverse in structure and production. [Tian Zhongzhi, No. Fuzhong, Xiangji, Lang, Nagai Masahiro, Natural Chemicals (Revised 6th Edition), ρρ 1〇3_ 116(2002)]. Report on the antiviral activity of sesquiterpenes from plants' In the natural medicine (Chinese medicine) used in traditional Chinese medicine, it has the structure of patchouli alcohol isolated from Tripterygium wilf0rdii Hook. Among the 20 sesquiterpenes of different octahydro-1-benzoxepanetriene skeletons, it was found that U 7 . Bu 7 士,:; > C-2 pairs as envelope type I Herpes virus or cytomegalovirus has antiviral effects [K. Hayashi, T. Hayashi K.

Ujita，Υ· Takaishi，J. Antimicrobial Chemothr·, 37，759-768 (1996)]，但未獲得關於來自其他植物之倍半萜烯之抗病毒 作用之見解。作為關於來自植物以外之天然原材料之倍半 萜烯之抗病毒活性的報告’自子嚢菌（葡萄穗黴 (Stachybotrys)屬 RF-7260)或海綿（Strongylophora bartmani van Soest)中單離出具有二環金合歡烷骨架之（乙醯基）_司 他弗林（（acetyl)-stachyflin)及只卜口 >半、y y A作為對 H1N1亞型之A型流感病毒之抗病毒活性成分[κ. Minagawa et al., J. Antibiotics, 55, 155-164 (2002) ； A. E. Wright et al·，J. Nat. Prod” 54，1108-1111 (1991)]。然而，該等具有 151403.doc •10- 201121558 抗流感病毒活性之倍半萜烯並不具有藿香烷骨架。本發明 係發現具備與具有抗流感病毒活性之現有之倍半祐烯不同 之結構的廣藿香醇、及含有其之廣藿香精油萃取物具有抗 流感病毒活性，且據此提供一種新穎之抗流感病毒劑。 本發明中’所謂「廣藿香醇」，係化學名為（18)_2β 5,5,8act-四甲基-1β，6β-亞曱基十氫萘_4aa-醇，由分子式 C^HwO所表示之分子量為222.37之倍半萜烯類化合物。廣 藿香醇可購貝市售品使用。或者廣藿香醇亦可使用自廣藿 香等植物中萃取並純化而獲得者。 已知’廣藿香醇最初為自廣藿香（Pogostemon cablin Benth.)中分離之化合物，但目前已知其亦包含於其他多種 植物中。本發明中’例如可自以下報告含有廣藿香醇之植 物中萃取廣藿香醇並加以純化而使用，即家蠅（Musca domestica L.)、蔓澤蘭（Milcania cordata (Burm. f.) Rob·)、 金盞花（Calendura officinalis)、漿果濱黎（Atriplex semibaccata)、番茉莉（Brunfelsia anstralis)、變色茉莉 (Brunfelsia pauciflora)、物蛛香（Valeriana jatamansi Jones)、Valeriana pancicii Halacsy & Bald、印度顯草 (Valeriana wallichii)、西歐甘松香（Valeriana celtica L· ssp. norica Vieth.)、練草（Valeriana officinalis L. s.l.)、薑黃 (Curcuma longa L.)、韻產巴（Trigonella foenum-graecum L.)、Salvia hydrangea DC. ex Benth. ' Haplopappus velutinus、Haplopappus illinitus、Haplopappus shumanni、 Haplopappus uncinatus、海茴香（Chrithmum maritimum L.) 151403.doc 201121558 等亦可使用自含有廣藿香醇之其他植物中萃取·純化之 廣藿香醇。廣藿香醇例如可藉由以各種精油萃取法自含有 廣藿香醇之植物中萃取精油萃取物，並按照公知之方法由 該精油萃取物純化而製備。廣藿香醇可藉由通常使用之管 柱層析法、液滴逆流分佈或使用各種溶劑之分佈法等自精 油萃取物中純化獲得。或者，廣藿香醇亦可藉由化學合成 而製備。藉由以上之各種方法製備之廣藿香醇可作為本發 明之抗流感病毒劑之有效成分而使用。 本發明中’廣藿香之精油萃取物亦含有大量之廣藿香 醇，因此亦可作為抗流感病毒劑之有效成分而使用。本發 明中，「精油萃取物」係指將植物供給至各種植物之精油 萃取法而獲得之含有精油成分之萃取物。本發明中，「廣 藿香精油萃取物」係指將廣藿香（通常為廣藿香之葉、包 含葉之一部分植物體、或全草（植物體整體）)供給至各種精 油萃取法而獲得之萃取物（精油萃取物）。 本發明中，「精油萃取物」亦包含例如藉由醇萃取法或 有機溶劑萃取法等溶劑萃取法而獲得之萃取物，藉由油脂 吸附萃取法（溫浸法或冷浸法）或超臨界流體萃取法等而獲 得之萃取物，以及藉由水蒸氣蒸餾法而獲得之典型之精油 (狹義之精油）。本發明中，「精油萃取物」亦包含植物精油 領域中之所謂原精、凝香體、精油樹脂、浸膏、酊劑等精 油萃取物。 本發明中’自包含廣藿香或廣藿香醇之其他植物中萃取 精油可藉由例如溶劑萃取法（醇萃取法、有機溶劑萃取法 151403.doc 201121558 等）、油脂吸附萃取法（溫浸法 宮 法、水蒸氣蒸餾法等任音之方法二又、超臨界流體萃取 矛仕思之方法而進行。該 法之詳細内容可參照「特許廳公 ，由卒取方 料)第-部，香料全隼」（平心u 慣用技術集(香 杲」（千成U(l"9)年1月29日絡— PP.4-2U2.H植物性香料^ 事典」，朝倉書店，2_年…。曰第 PP剔6⑷天然香料）等文獻或參考書。關於醇萃取Μ $機溶劑m亦可參照下述之實施例。料用於該等 举取之溶劑，並益限定，仓丨l 1 …、限疋，例如可列舉如下溶劑 取法 中主要使用之乙醇、甲醇、丙醇、異丙醇、丁醇等醇類， 或有機溶劑萃取法令主要使用之丙剩等極性相對較高之溶 劑至己烧等低極性有機賴（較佳為疏水性有機溶劑）。 本發明中’「精油萃取物」亦進而包含上述萃取物之純 化組分。該純化組分可藉由使用dIAI〇n队20等多孔性 顆粒、石夕膠或氧化銘等載體之疏水性或吸附層析法等各種 純化方法自上述萃取物中製備。 2·含有廣藿香醇及/或廣藿香精油萃取物之抗流感病毒劑 以上述方式製備之廣藿香醇及/或廣藿香精油萃取物具 有抗病毒活性’尤其具有抗流感病毒活性。 本發月提供@包含以上述方式製傷之廣蕾香醇及/或 廣藿香精油萃取物作為有效成分之抗流感病毒劑。以上述 方式製備之廣藿香醇及/或廣藿香精油萃取物亦可直接作 為本發明之抗流感病毒劑使用。或者，亦可利用適當之溶 解溶劑對該廣藿香醇及/或廣藿香精油萃取物 進行稀釋， 151403.doc -】3· 201121558 或進订滅菌等處理後作為抗流感病毒劑使用。本發明中， =可將於上述廣藿香醇及/或廣藿香精油萃取物中調配藥 4·上所谷„午之惰性成分（例如賦形劑、防腐劑、緩衝液等） 而成者作為抗流感病毒劑使用。 本發明之抗流感病毒劑之抗流感病毒活性並無限定，例 如可藉由下述實施例所例示之斑點形成法而加以確認。本 發明之抗流感病毒劑即便於流感病毒存在下亦可使細胞之 存活率顯著提昇，因此可用於治療流感傳染病。細胞存活 率之提昇亦表示自受到破壞之細胞之病毒釋放減少，因此 若使用本發明之抗流感病毒劑，則可抑制體内之病毒傳 染•增殖，亦可用於預防由流感病毒所引起的傳染病。 本發明之抗流感病毒劑可對Α型及Β型流感病毒使用， 較佳為對A型流感病毒使用。成為對象之較佳之a型流感 病毒尤其可列舉蘇聯型（H1N1亞型），亦可對該等之變異型 使用》 本發明之抗流感病毒劑之直接細胞毒性非常低或者完全 未發現細胞毒性，就該方面而言亦非常有用。 3·含有抗流感病毒劑之香料组合物 本發明亦提供一種含有本發明之抗流感病毒劑之流感病 毒傳染病之預防及/或治療用香料組合物。上述香料組合 物可為醫藥組合物》 作為本發明之抗流感病毒劑之有效成分的廣藿香醇為香 料成分，因此可藉由於本發明之抗流感病毒劑中調配製造 香料通常使用之添加劑（例如賦形劑、防腐劑、緩衝液等） 151403.doc •14· 201121558 而製備本發明之香料組合物。 介 ^ 或者’本發明之香料組合物 亦可糟由於本發明之括、·&片 机感病f劑中調配其他香料（香水 或香味劑（Flavor))而製備， A ^ 於上述2種以上之香料 e香料）中調配製造香料通當 ㊉使用之添加劑（例如賦形劑、 防腐劑、緩衝液等）而製備。 ^ ^ 上述本發明之香料組合物之Ujita, Υ Takaishi, J. Antimicrobial Chemothr., 37, 759-768 (1996)], but did not obtain insights into the antiviral action of sesquiterpene from other plants. As a report on the antiviral activity of sesquiterpene from natural raw materials other than plants, 'Secondary bacteria (Stachybotrys genus RF-7260) or Spongylophora bartmani van Soest have two rings The indomethacin skeleton (acetyl group) _ statin ((acetyl)-stachyflin) and only the mouth > half, yy A as an antiviral active ingredient of the influenza A virus of the H1N1 subtype [κ. Minagawa et al., J. Antibiotics, 55, 155-164 (2002); AE Wright et al., J. Nat. Prod" 54, 1108-1111 (1991)]. However, these have 151403.doc •10 - 201121558 The sesquiterpene which is active against influenza virus does not have a ruthenium skeleton. The present invention has found that it has a structure different from that of the existing sesquiterpene having anti-influenza virus activity, and has a wide range thereof. The musk essential oil extract has anti-influenza virus activity, and accordingly provides a novel anti-influenza virus agent. In the present invention, the so-called "blossom", the chemical name is (18)_2β 5,5,8act-four Base-1β,6β-arylene-decahydronaphthalene_4aa-alcohol, by molecular formula C The molecular weight represented by HwO is 222.37 sesquiterpene compounds. The scented scent can be purchased from the market. Alternatively, patchouli alcohol can be obtained by extracting and purifying from plants such as patchouli. It is known that the patchouli alcohol was originally a compound isolated from Pogostemon cablin Benth., but it is currently known to be included in many other plants. In the present invention, for example, the patchouli alcohol can be extracted and purified from the following plant containing the patchouli alcohol, that is, Musca domestica L., Milcania cordata (Burm. f.) Rob· ), Calendura officinalis, Atriplex semibaccata, Brunfelsia anstralis, Brunfelsia pauciflora, Valeriana jatamansi Jones, Valeriana pancicii Halacsy & Bald, Indian herb ( Valeriana wallichii), Valeriana celtica L. ssp. norica Vieth., Valeriana officinalis L. sl, Curcuma longa L., Trigonella foenum-graecum L., Salvia Hydrangeea DC. ex Benth. 'Haplopappus velutinus, Haplopappus illinitus, Haplopappus shumanni, Haplopappus uncinatus, sea fennel (Chrithmum maritimum L.) 151403.doc 201121558 etc. Can also be extracted and purified from other plants containing patchouli alcohol Aroma. The patchouli alcohol can be prepared, for example, by extracting an essential oil extract from a plant containing patchoulol by various essential oil extraction methods, and purifying the essential oil extract by a known method. Patchouli alcohol can be purified from essential oil extracts by column chromatography, droplet countercurrent distribution or distribution using various solvents. Alternatively, patchouli alcohol can also be prepared by chemical synthesis. The patchoulol prepared by the above various methods can be used as an active ingredient of the anti-influenza agent of the present invention. In the present invention, the extract of the essential oil of the patchouli also contains a large amount of patchouli alcohol, and therefore can also be used as an active ingredient of an anti-influenza virus agent. In the present invention, "essential oil extract" refers to an extract containing essential oil components obtained by supplying plants to essential oil extraction methods of various plants. In the present invention, "the patchouli essential oil extract" refers to a method in which patchouli (usually a leaf of patchouli, a part of a plant containing leaves, or a whole plant (whole plant)) is supplied to various essential oil extraction methods. The extract obtained (essential oil extract). In the present invention, the "essential oil extract" also includes an extract obtained by a solvent extraction method such as an alcohol extraction method or an organic solvent extraction method, by a fat adsorption extraction method (warm immersion method or cold immersion method) or supercritical An extract obtained by a fluid extraction method or the like, and a typical essential oil (narrowly defined essential oil) obtained by steam distillation. In the present invention, the "essential oil extract" also includes essential oil extracts such as so-called raw essence, aroma, essential oil resin, extract, and tincture in the field of plant essential oils. In the present invention, the essential oil extracted from other plants containing patchouli or patchouli alcohol can be obtained by, for example, solvent extraction (alcohol extraction, organic solvent extraction, 151403.doc 201121558, etc.), oil adsorption extraction method (warm immersion method). The method of the method of uterine method, steam distillation, etc., and the method of supercritical fluid extraction of the spears are carried out. For details of the method, please refer to the "Specialty of the Department of Graduation", the first part, spices隼 隼 ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( .... 曰 PP PP 6 (4) natural spices) and other literature or reference books. For the alcohol extraction Μ $ machine solvent m can also refer to the following examples. The material is used for these solvents, and benefits, 丨 丨1 , and the like, for example, an alcohol such as ethanol, methanol, propanol, isopropanol or butanol which is mainly used in the solvent extraction method, or a solvent having a relatively high polarity such as a residual solvent which is mainly used in an organic solvent extraction method may be mentioned. Low-polarity organic lysate (preferably hydrophobic organic solvent) In the present invention, the "essential oil extract" further comprises a purified component of the above extract. The purified component can be hydrophobic by using a porous particle such as dIAI〇n team 20, or a carrier such as shijiao or oxidized. Or various purification methods such as adsorption chromatography are prepared from the above extracts. 2. Anti-influenza agent containing patchouli alcohol and/or patchouli essential oil extract. Patchouli alcohol and/or patchouli prepared in the above manner. The essential oil extract has antiviral activity, especially anti-influenza virus activity. This month provides an anti-influenza virus agent containing as an active ingredient an extract containing the broad scented alcohol and/or patchouli essential oil produced in the above manner. The patchouli alcohol and/or patchouli essential oil extract prepared by the method may also be directly used as the anti-influenza virus agent of the present invention. Alternatively, the patchouli alcohol and/or patchouli essential oil may be extracted by using a suitable solvent. Dilute, use 151403.doc -] 3 · 201121558 or as an anti-influenza virus after treatment such as sterilization. In the present invention, = can be extracted from the above-mentioned patchoulol and / or patchouli essential oil Intermediate formulation 4·上上谷 „Inert ingredients (such as excipients, preservatives, buffers, etc.) are used as anti-influenza agents. The anti-influenza virus of the present invention has no anti-influenza activity. The definition can be confirmed, for example, by the speckle formation method exemplified in the following examples. The anti-influenza virus of the present invention can significantly improve the survival rate of cells even in the presence of influenza virus, and thus can be used for treating influenza infectious diseases. The increase in cell viability also indicates a decrease in the release of virus from the damaged cells. Therefore, if the anti-influenza virus agent of the present invention is used, it can inhibit the virus infection and proliferation in the body, and can also be used to prevent the infection caused by the influenza virus. Infectious Diseases The anti-influenza virus agent of the present invention can be used for sputum-type and sputum-type influenza viruses, preferably for influenza A virus. The preferred influenza A virus to be targeted is, in particular, the Soviet type (H1N1 subtype), and can also be used for such variants. The direct cytotoxicity of the anti-influenza agent of the present invention is very low or no cytotoxicity is found at all. It is also very useful in this respect. 3. Fragrance composition containing an anti-influenza virus agent The present invention also provides a perfume composition for preventing and/or treating an influenza virus infectious disease containing the anti-influenza virus agent of the present invention. The above-mentioned perfume composition may be a pharmaceutical composition. The patchoulol which is an active ingredient of the anti-influenza agent of the present invention is a perfume ingredient, and therefore, an additive which is usually used for the manufacture of a perfume by the formulation of the anti-influenza agent of the present invention (for example, Excipients, preservatives, buffers, etc.) 151403.doc • 14· 201121558 The perfume composition of the present invention is prepared. Or the 'perfume composition of the present invention can also be prepared by the method of the present invention, and the other ingredients (perfume or fragrance) are formulated in the tablet machine, and A ^ is in the above two kinds. The above-mentioned perfumes are formulated in the preparation of perfumes, such as excipients, preservatives, buffers and the like. ^ ^ The above perfume composition of the present invention

Ik方法亦包含於本發明之範圍令。 藉由將本發明之香料έ人 ’、’ 口物作為香料添加於各種製 中，可對該製品賦予香呋亦禾# 丁胥未或香氣，並且賦予 療流感病毒傳染病之效果。 戈~ 調配於本發明之香料組合 香料組合物中共存之香粗、十 感病毒劑之量根據 者汰〜 ， ’或香料組合物之使用目的等適 田’、疋卩可心較佳為以香料組合物 〇.〇1〜5.0質量％左右。 勹土半》又為 本發明之抗流感病毒劑具有易與多種其他香料（香水或 香味劑）融合之優點。並且 一 邴#姻入士、„、 發月之抗奴感病毒劑即便調 -;斗中’亦有無損該調合香料整體之香味之平衡 之優點。 _ 了與本發明之抗流感病毒劑共存之香料之具體例如下所 不 。 首先作為香料， 醛類、酚類、醚類 類、含硫化合物類 亦可使用天然香料 作為上述3旨類， 可列舉：酯類、醇類、醛類、酮類、縮 、内酯類、呋喃類、烴類、+氮化合物 、酸類等之合成香料等。再者，視需要 〇 例如可列舉：乙醯乙酸乙酯（f基、乙 1514〇3.cJ〇c 15 201121558 基等）、對甲氧基苯甲酸酯（甲基、乙基等）、苯甲酸酯（烯 丙基、異戊基、乙基、香葉草基、沈香基、苯基乙基、己 基、順-3-己烯基、苄基、甲基等）、鄰胺苯甲酸酯（苯烯丙 基、順-3-己烯基、甲基、乙基、沈香基、異丁基等）、辛 酸酯（烯丙基、異戊基、乙基、辛基、己基、丁基、甲 基、沈香基等）、辛烯酸酯（甲基、乙基等）、辛炔羧酸酯 (甲基、乙基等）、己酸酯（烯丙基、戊基、異戊基、甲基、 乙基、異丁基、丙基、己基、順_3-己烯基、反_2_己烯 基、沈香基、香葉草基、環己基等）、乙烯酸酯（甲基、乙 基等）、戊酸酯（戊基、異丙基、異丁基、乙基、順_3-己烯 基、反-2-己烯基、苯烯丙基、苯基乙基、曱基等）、肉桂 酸酯（烯丙基、乙基、甲基、異丙基、丙基、3_苯基丙基、 节基、環己基、甲基等）、乙酸酯（大茴香基、戊基、^戊 基苯烯丙基、異戊基、異丁基、異丙基、異胡薄荷基、異 福基、異丁香酚基、丁香酚基、2_乙基丁基、乙基、3_辛 基、香芹基、二氫香芹基、對曱苯基、鄰甲苯基、香葉草 基、或β-檀香基、環己基、環橙花基、二氫枯基、二曱 基苄基烴甲基、苯稀丙基、蘇合香基、癸基、十二统基、 松油基、胍基、橙花基、壬基、苯基乙基、苯基丙基、丁 基、糠基、丙基、己基、順_3_己烯基、反_2_己烯基、順-3-壬烯基、順-6-壬烯基、順-3,順_6_壬二烯基、3_曱基_2· 丁烯基、菫基、庚基、苄基、莅基、月桂稀基（mycenyi)、 一氫月桂烯基、桃金娘烯基、曱基、2曱基丁基、菫基、 沈香基、玫紅基等）、硬脂酸酯（乙基、丙基、丁基等）、乳 151403.doc -16 - 201121558 酸醋（異戊基、乙基、丁基等）、壬酸醋（乙基、苯基乙基、 甲基等）、經基己酸s旨（乙基 '甲基等）、苯基乙酸醋（異戍 異丁基乙基、香葉草基、香茅基、順·3_己烯基、甲 基等）等^ · 作為上述醇類，例如較佳可列舉：脂㈣醇（異戍醇、The Ik method is also included in the scope of the invention. By adding the flavoring agent of the present invention to the various flavors as a flavor, it is possible to impart a fragrance or aroma to the product, and to impart an effect of treating influenza virus infectious diseases. The amount of the fragrant and ten-sensitive virus agent coexisting in the flavoring composition of the present invention is based on the amount of the medicinal agent, and the purpose of the use of the flavoring composition, etc. The perfume composition is about 1 to 5.0% by mass. The smectite half is also an advantage of the anti-influenza agent of the present invention which is easy to fuse with a variety of other fragrances (perfume or fragrance). And a 姻 入 入 、 „ „ „ „ „ „ „ „ „ „ „ „ „ „ 发 发 发 发 发 发 ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; The specifics of the fragrances are as follows. First, as the fragrance, natural flavors may be used as the above-mentioned three types of aldehydes, phenols, ethers, and sulfur-containing compounds, and examples thereof include esters, alcohols, and aldehydes. a synthetic flavonoid such as a ketone, a condensed ester, a lactone, a furan, a hydrocarbon, a nitrogen compound or an acid, etc. Further, as needed, for example, ethyl acetonitrile (f-based, ethyl 1514 〇 3. cJ〇c 15 201121558 base, p-methoxybenzoate (methyl, ethyl, etc.), benzoate (allyl, isopentyl, ethyl, geranyl, agarwood, Phenylethyl, hexyl, cis-3-hexenyl, benzyl, methyl, etc.), o-amine benzoate (phenylallyl, cis-3-hexenyl, methyl, ethyl, agarwood Base, isobutyl, etc.), octanoate (allyl, isopentyl, ethyl, octyl, hexyl, butyl, methyl, agarwood, etc.), xin Ethyl ester (methyl, ethyl, etc.), octyne carboxylate (methyl, ethyl, etc.), hexanoate (allyl, pentyl, isopentyl, methyl, ethyl, isobutyl , propyl, hexyl, cis-3-hexenyl, trans-2-hexenyl, agarwood, geranyl, cyclohexyl, etc.), vinyl ester (methyl, ethyl, etc.), valerate (pentyl, isopropyl, isobutyl, ethyl, cis-3-hexenyl, trans-2-hexenyl, phenylallyl, phenylethyl, decyl, etc.), cinnamate Allyl, ethyl, methyl, isopropyl, propyl, 3-phenylpropyl, benzyl, cyclohexyl, methyl, etc.), acetate (anonyl, pentyl, pentylbenzene) Allyl, isopentyl, isobutyl, isopropyl, isopulegol, isofosyl, isoeugenol, eugenol, 2-ethylbutyl, ethyl, 3-octyl, fragrant Celery, dihydrocarvyl, p-phenylene, o-tolyl, geranyl, or β-santal, cyclohexyl, cycloandyl, dihydro cumyl, dinonylbenzyl hydrocarbon methyl, Benzylpropyl, sulphate, fluorenyl, decyl, terpine, sulfhydryl, neroli, Base, phenylethyl, phenylpropyl, butyl, decyl, propyl, hexyl, cis-3-enkenyl, trans-2-hexenyl, cis-3-nonenyl, cis-6 -decenyl, cis-3, cis_6-decadienyl, 3-fluorenyl-2-butenyl, fluorenyl, heptyl, benzyl, benzyl, mycenyi, monohydrogen Laurolyl, myrtenyl, decyl, 2-decylbutyl, decyl, agarwood, rose, etc.), stearate (ethyl, propyl, butyl, etc.), milk 151403. Doc -16 - 201121558 Sour vinegar (isopentyl, ethyl, butyl, etc.), citric acid vinegar (ethyl, phenylethyl, methyl, etc.), hexyl hexanoate (ethyl 'methyl group, etc.) , phenylacetic acid vinegar (isoisobutylethyl, geranyl, citronella, cis-3-hexenyl, methyl, etc.), etc., as the above alcohols, for example, preferably: Lipid (tetra) alcohol (isodecyl alcohol,

異胡薄荷醇、2-乙基己醇、1-辛醇、3-辛醇、卜癸醇、S 十二烷醇等）、帖烯醇、芳香族醇等。 作為上述酿類’例如可列舉：脂肪㈣、芳香族酸箱 烯醛等。 作為上述_類，例如可列舉m薄荷 H3，（piperitone)、α_、β·、γ♦突厥嗣、〇、卜或 丫_ 突厥烯酮、諾卡酮、2-第二丁基環己酮、麥芽糖醇、α-，β- 或γ-紫羅_ ' α·、甲基紫羅蘭嗣……異甲 基紫羅蘭酮等環式_，ι ^ 本乙酮、亞回香酮、覆盆子酮等芳 香族嗣，2,3 -丁 -雕|、η + ,]一駒、2-庚酮等鏈式酮等。 作為上述縮醛類，例如 ^ ^ 例如可列舉：乙醛二乙基縮醛、乙醛 -戍基祕、2.苯基㈣二甲縮酸等。 :為上述紛類，例如可列舉：丁㈣、異丁香盼、2·， _乙烯基料、瑞香_、㈣切等。 作為驗類，例如可列與. 桉樹腦、二㈤、氧:J二“腦、1洲 玫塊峻、香蘭基丁喊等/讀、乳化轉檬稀、橙花喊、 作為上述内：類’例如可列舉:咖癸内 酉曰、γ-壬内酯等。 I5I403.doc -17· 201121558 作為上述呋㈣’例如可列舉：呋喃 甲基呋喃、2·乙基呋σ南、2 南 甲其> 土土 ，二乙基四氫呋喃、3-羥基-2- 甲基四虱呋喃、乙酸糠酯等。 作=類，例如可列舉1品稀1品油歸、金合歡 烧、彳宁檬稀、羅勒烯、月桂 Θ桂油烯、α-或β-蒎烯等。 作為上述酸類，例如可列 稀酸、香葉草酸、十内 …癸酸、2·癸 .Α,δΑ ^ 肉豆謹酸、硬脂酸、乳酸、 本基乙@欠、丙酮酸、環己甲酸等。 及/戈端2香水例如可列舉：烴類、醇類、齡類、搭類 Γ:二類及/或縮，類，、合成靡香類、酸 ^、内_、醋類、含齒素化合物等Isopulegol, 2-ethylhexanol, 1-octanol, 3-octanol, diterpene alcohol, S-dodecanol, etc.), enol, aromatic alcohol, and the like. Examples of the above-mentioned brewings include fat (IV), aromatic acid tank aldehyde, and the like. Examples of the above-mentioned class include m peppermint H3, (piperitone), α_, β·, γ ♦ 厥嗣 厥嗣, 〇, 卜 or 丫 厥 厥 ketene, noca ketone, 2-t-butylcyclohexanone, Maltitol, α-, β- or γ-violet _ 'α·, methyl violet 嗣 嗣 ... isomethyl violet ketone and other ring _, ι ^ ethyl ketone, retinoic acid, raspberry ketone and other aromatic Clan, 2,3-but-carving|, η+,] chain ketones such as monoterpene and 2-heptanone. Examples of the acetal include, for example, acetaldehyde diethyl acetal, acetaldehyde-hydrazino group, and phenyl (tetra) dimethyl carboxylic acid. : For the above-mentioned genus, for example, D (four), different cloves, 2, _ vinyl, rugrant _, (four) cut, and the like can be cited. As a test class, for example, it can be listed with. Eucalyptus brain, two (five), oxygen: J two "brain, 1 continent rose block, Xianglanjiding shouting / reading, emulsified turn lemon, orange flower shout, as the above: class 'For example, curry mash, γ-decalactone, etc. I5I403.doc -17· 201121558 As the above fur (tetra)', for example, furanmethylfuran, 2·ethylfuran, 2 Nanjia It> soil, diethyltetrahydrofuran, 3-hydroxy-2-methyltetrafurfuran, decyl acetate, etc. As a class, for example, one product of dilute oil, acacia, and lemon Dilute, basilene, laurel, oleylene, α- or β-pinene, etc. As the above-mentioned acids, for example, dilute acid, geranic acid, decanoic acid, 2·癸.Α, δΑ ^ Acid, stearic acid, lactic acid, base B@ owed, pyruvic acid, cyclohexanoic acid, etc. and / Ge Du 2 perfume, for example, hydrocarbons, alcohols, ages, sputum Γ: second class and / Or shrinkage, class, synthetic musk, acid ^, internal _, vinegar, dentate compound, etc.

使用天然香料。 視恶要7Γ J 由碳與氣所構成之揮發性有機化合物則 :苯…烴類等。較佳為叫-院三婦、對-甲基異 別_、法m 斤烯卜石竹烯、蒎烯、△-蒈烯、 、’烯、羅勒烯、二氬月桂油烯、雙 柏木稀、“稀、“油烤 '瓦倫西二斯克㈣、 華按、 a爾四亞烯（valencene)、沒 /、月桂油烯、檸檬烯、金剛烷、莰烯等。 限發性有機化合物則無特別 族醇類等，較:可㈣類， 2’6-壬，、㈠三丁基環己醇、2乙=，、 醇、3,5,5-”基己醇、3·辛醇、3韻丙/己酵、2·庚 本基丙醇、醇、正 151403.doc 201121558 西亨 ^ ρ’α·—甲基苄醇、對第三丁基環己醇、對甲基二甲Use natural flavors.恶 要 Γ Γ Γ 由 由 由 由 由 由 由 由 由 由 由 由 由 由 由 由 由 挥发性 挥发性 挥发性Preferably, it is called - hospital three women, p-methyl singular _, method m mentene, carragene, decene, Δ-pinene, 'ene, basilene, diargonyl laurel, double cypress, "Sparse, "oily roasted" Valentino disk (four), Huazhan, avalencene (valencene), no /, laurel, limonene, adamantane, terpene and so on. There are no special alcohols in the limited organic compounds, such as: (4), 2'6-壬, (1) tributylcyclohexanol, 2 B =, alcohol, 3,5,5-" Alcohol, 3· octanol, 3 rhyme/enzyme, 2·heptyl propanol, alcohol, positive 151403.doc 201121558 Xiheng^ ρ'α·-methylbenzyl alcohol, p-tert-butylcyclohexanol Methyl dimethyl

基·苄基甲醇、I α，_3,3-二甲基-2-降福烷甲醇、α_正戊基桂皮 醇' α_葑醇、R贫I*古 丄 Ρ•本基乙知、大茴香醇、琥珀醇、龍涎醇、 ' 異葉綠醇、異胡薄荷醇、異葙醇、乙基沈香醇、 辛醇，香芹醇、香葉草醇、檀香醇、順-3_乙烯_丨_醇、順_ 締醇、香茅醇、二氫·α_松油醇、二氮香茅醇、二氣月 醇—氫沈香醇、二甲基苯基乙基甲醇、二甲基苄基 甲醇、桂皮醇、蘇合香醇、柏木醇、松油酵、松油稀-4-广 木倍醇、四氫香葉草醇、四氫月桂烤醇、四氫別羅 勒烯醇四氫沈香醇、橙花醇、橙花三級醇、壬醇 (n〇nan〇1)、壬醇（1101^1 alcohol)、諾卜醇、龍葵醇、白檀 醇金合歡醇、葉綠醇、苯基乙基甲基乙基甲醇、苯氧基 乙醇、糠醇、岩蘭草醇、紫蘇醇、苄基醇、馬氏醇 (mayol)、月桂烯醇、桃金孃烯醇、拉凡醇、沈香醇等。 上述酚類只要為酚性化合物及其衍生物且為具有香味之 有機化合物，則無特別限定，例如可列舉：一元、二元、 三兀•之酚性化合物、多酚類、或該等化合物之醚衍生物 等，較佳可列舉：對甲酚、甲佳味酚、丁香酚、檜木醇、 2’6-二曱氧基苯酚、4-乙基愈創木酚、4_甲基愈創木酚、 β-萘酚異丁基醚、異黃樟素、愈創木酚、黃樟素、二氫丁 香酚、瑞香草酚、生薑油等。 上述醛類或縮醛類只要為分子内具有醛基或縮醛基之揮 發性有機化合物則無特別限定，可列舉：脂肪族醛或縮 醛、萜烯系醛或縮醛、芳香族醛或縮醛等，較佳可列舉. 151403.doc •19- 201121558 1〇-十一烷烯醛、2,4-二甲基_4,43,5,91>-四氫茚幷[1，2£1]-1，3- 一％畊、2,4-癸二烯醛、2,6_壬二烯醛、2_ 丁基_4,4,6三 甲基_1，3-二氧代環己烷、2-己基-5-曱基_1，3_二氧雜環戊 烷、2-曱基壬乙醛、2·曱基壬乙醛二甲基乙縮醛、3•乙基 _2,4_二氧雜螺[5,5]十一 _8·烯、3_乙基 _8(9)11_二甲基 _24_ 一氧雜螺[5,5]十一-8-烯、3-丙基二環[2,2，1]-庚-5-烯-2-甲 酸4異丙基-5,5-二甲基-1，3-二氧代環己烧、4_庚稀酸、 %甲基-5-丙基-2_(1•曱基丁基二氧代環己烷、鄰甲氧 基桂皮醛、鄰甲氧基苯甲醛、對甲苯基醛、α_正己基桂皮 醛、α-戊基桂皮醛、乙醛、乙醛乙基沈香基縮醛、乙醛二 乙基縮酸、大茴香醛、醛c_1〇、醛^丨丨、醛c_12、醛匕 ό、搭 C-6 DEA、醛 C-6 DMA、醛 C-6 PG縮醛、醛 C-8、醛 C-8DEA、醛 C-8 DMA、醛 C-9、醛 C-9 DEA、醛 C-9 DMA、異環檸檬醛、乙香草醛、康辛醛、黃瓜醛、枯醛、 香葉醇、仙客來醛、順·6_壬烯醛、檸檬醛、香茅醛、香茅 氧基乙酿、中國橘醛、杜皮克醛、反_2_己烯醛、反_2_己 烯醛二乙基縮醛、女貞醛、撥花醛、2-苯基丙醛、香草 酿、經基香茅醛、苯基乙醛、苯基乙醛P.G.縮醛、苯基乙 酸二曱基縮醛、糠醛、對-乙基_α，α•二曱基羥基桂皮醛 (Floral〇zon)、胡椒醛、胡椒基丙醛、紫蘇醛、香檸檬醛、 香根縮醛、1-甲基-4-(4-甲基戊基）-3-環己烯曱醛 (Bemaldehyde)、苯甲醛、3-環己烯曱醛、柑菁醛、甜瓜 醛、新鈴蘭醛、鈴蘭醛等。 上述酮類或縮酮類只要為分子内具有酮基或縮酮基之揮 151403.doc •20· 201121558 發性有機化合物則無特別限定，可列舉… _、萜稀系酿I或縮酮、关巷 、_或縮 2-第二丁基環己酮、2•乙醯美。寺較佳可列舉·· G醞基-3,3-二甲基降花 基-5·曱基呋喃、2-乙醯A 儿、2-乙醯 嘅基_呋喃、2_ 丁基 [4,4]壬烧、2-己基環戊_ ，—氧雜螺 J -二甲其 ^ 喃酮、5-乙基-3-羥基·4_曱某)-呋 T基-2[5H]-呋喃g同、6_ 庚二烯-2-酮、d-胡薄荷_、L•香芽酮、鄰第三丁二’ _ 酮、對第三丁基環己，、對甲基苯乙酮、對甲氧：： 嗣、α•王㈣同、α__、β-甲基蔡基嗣、乙醯基柏^乙 苯乙酮、菌香酮、唏丙基·α_紫羅_、紫羅蘭酮、龍延 酉同、異茉莉酮、異突厥酮、異長葉烧綱、驚尾綱、乙基里 戊酮、乙基麥芽糖醇、開司米酮（Cashme叫、菩酮、二院 酉同、（2)-3,4,5,6,6-五？基_3_庚稀_2_嗣（&〇_叫、甲基产 戊稀醇酮、順-茉莉綱、二氫香序酮、二氫茉莉鋼、二； 基酮、柏木烯酮（Cedrenone)、葫蘆巴内酯、突厥酮突厥 烯酮、Trimofix 〇、諾卡酮、呋喃酮、藥香酮' 卜亞乙基 八氫-5,8-曱橋_2H_i苯并吡喃_2_調（F1〇rex)、甲基柏木酮 (vertofix) '馬鞭烯酮、二苯甲酮、麥芽糖醇、甲基紫羅蘭 酮、甲基環戊烯醇酮、甲基庚烯酮、堇酮、覆盆子酮等。 上述醚類只要為分子内具有醚基之揮發性有機化合物則 無特別限定，可列舉：脂肪族醚、萜烯系醚芳香族醚等。 較佳可列舉：1,4-桉樹腦、1，8-桉樹腦、對曱苯基曱醚、β_ 氧化石竹烯、β_萘基異丁醚、β-萘基乙醚、β-萘基甲喊、 大菌香腦、降龍涎香醚、異戊基苯基乙醚、異福基甲峻、 151403.doc -21 - 201121558Benzyl benzyl alcohol, I α, _3,3-dimethyl-2-norfosmin methanol, α-n-pentyl cinnamyl alcohol α-sterol, R-poor I* ancient 丄Ρ • BenQ, Anisanol, succinol, borneol, 'isophyllin, isopulegol, isodecyl alcohol, ethyl linalool, octanol, carvacrol, geraniol, sandalwood, cis-3_ Ethylene_丨-alcohol, cis-dehydration alcohol, citronellol, dihydro-α-terpineol, dinitrocitronellol, dihydrorhenol-hydrogeninol, dimethylphenylethylmethanol, dimethyl Benzyl benzyl alcohol, cinnamyl alcohol, sultry alcohol, cedarol, pine oil yeast, pine oil dilute - 4 wood xylool, tetrahydro geranyl alcohol, tetrahydro laurel alcohol, tetrahydro phenol enol Hydrogen saponin, nerol, nerolitriol, sterol (n〇nan〇1), sterol (1101^1 alcohol), nopol, Solanol, erythritol, farnesol, phytol , phenylethyl methyl ethyl methoxide, phenoxyethanol, decyl alcohol, sulphate, perillol, benzyl alcohol, mayol, myrcene, myrtenol, lamynyl, Invigorating alcohol, etc. The phenol is not particularly limited as long as it is a phenolic compound and a derivative thereof, and is an organic compound having a flavor, and examples thereof include a monovalent, binary, triterpene phenolic compound, a polyphenol, or the like. Examples of the ether derivative and the like include p-cresol, methicone, eugenol, eugenol, 2'6-dimethoxyphenol, 4-ethylguaiacol, and 4-methylate. Infectious lignin, β-naphthol isobutyl ether, isoxanthin, guaiacol, baicalein, dihydroeugenol, thymol, ginger oil, and the like. The aldehyde or acetal is not particularly limited as long as it is a volatile organic compound having an aldehyde group or an acetal group in the molecule, and examples thereof include an aliphatic aldehyde or an acetal, a terpene aldehyde or an acetal, an aromatic aldehyde or Acetal, etc., preferably exemplified. 151403.doc •19- 201121558 1〇-undecenalaldehyde, 2,4-dimethyl-4,43,5,91>-tetrahydroanthracene [1,2 £1]-1,3-one% tillage, 2,4-nonadienal, 2,6-nonadienal, 2_butyl-4,4,6-trimethyl-1,3-dioxo Cyclohexane, 2-hexyl-5-mercapto-1,3-dioxolane, 2-mercaptoacetaldehyde, 2-mercaptoacetaldehyde dimethyl acetal, 3•ethyl _2,4_Dioxaspiro[5,5]unda_8·ene, 3_ethyl_8(9)11_dimethyl_24_monooxaspiro[5,5]11-8 - alkene, 3-propylbicyclo[2,2,1]-hept-5-ene-2-carboxylic acid 4 isopropyl-5,5-dimethyl-1,3-dioxocyclohexane, 4_heptic acid, %methyl-5-propyl-2_(1•decyl butyl dioxocyclohexane, o-methoxycinnamic aldehyde, o-methoxybenzaldehyde, p-tolyl aldehyde, α _ n-hexyl cinnamic aldehyde, α-pentyl cinnamaldehyde, acetaldehyde, acetaldehyde ethyl emulsifiable acetal, acetaldehyde diethyl acetal, large Aromatic aldehyde, aldehyde c_1 〇, aldehyde oxime, aldehyde c_12, aldoxime, C-6 DEA, aldehyde C-6 DMA, aldehyde C-6 PG acetal, aldehyde C-8, aldehyde C-8DEA, aldehyde C-8 DMA, aldehyde C-9, aldehyde C-9 DEA, aldehyde C-9 DMA, isocyclic citral, ethyl vanillin, octanol, cucumber aldehyde, cumaldehyde, geraniol, cyclamen aldehyde, Shun·6_decenal, citral, citronellal, citronellyloxy, Chinese menthol, dupickaldehyde, trans-2-hexenal, trans-2-hexenal diethyl Aldehyde, cresol, valeraldehyde, 2-phenylpropanal, vanilla, citronellal, phenylacetaldehyde, phenylacetaldehyde PG acetal, dimercaptoacetal acetal, furfural, p-Ethyl-α,α•dimercaptohydroxy cinnamic aldehyde (Floral〇zon), piperonal, piperonyl propionaldehyde, perillaldehyde, bergamot, fragrant acetal, 1-methyl-4-(4 -Methylpentyl)-3-cyclohexenefurfural (Bemaldehyde), benzaldehyde, 3-cyclohexenefurfural, citrus phthalocyanal, melon aldehyde, neolinglialdehyde, lilac aldehyde, etc. The above ketone or ketal The class is as long as it has a keto group or a ketal group in the molecule. 151403.doc •20· 201121558 There are no special restrictions on the organic compound. , can be listed as ... _, 萜 酿 酿 I or ketal, Guan Xiang, _ or condensed 2 - second butyl cyclohexanone, 2 · 醯 醯 美. Temple is better to mention · · G 酝 -3, 3-dimethylnorphthyl-5-mercaptofuran, 2-acetamidine A, 2-ethylanthryl-furan, 2-butyl [4,4]pyrene, 2-hexylcyclopenta-, Oxyspiro-J-dimethyl ketone, 5-ethyl-3-hydroxy-4-indolyl-furo-T-yl-2[5H]-furan-g, 6-heptadien-2-one, d - Huteng _, L• ketone, o-butadiene ketone, p-tert-butylcyclohexane, p-methylacetophenone, p-methoxy:: 嗣, α•王(四)同, α__ , β-methyl zebyl hydrazine, acetaminophen acetophenone, acetophenone, coumarin, propyl propyl α, violet _, ionone, iridone, iso-jasmone, isoindolinone, iso-long Leaf sylvestris, scutellaria, ethyl valericone, ethyl maltitol, ketamine (Cashme called, oxatone, sylvestre, (2)-3, 4, 5, 6, 6-five?基_3_庚稀_2_嗣(&〇_叫, methyl pentyl ketone, cis-jasmine, dihydro ketone ketone, dihydro jasmine steel, bis; ketone, cedarlenone ( Cedrenone), fenugreek lactone, thioxanthone, Trimofix oxime, nocardanone, furanone, medicinal ketone 'Buethylene octahydro-5,8-anthracene bridge_2H_i benzopyran_2_ F1〇rex), methyl cedarone (vertofix) 'maphthenone, benzophenone, maltitol, methyl ionone, methylcyclopentenolone, methylheptenone, anthrone, raspberry ketone The ether is not particularly limited as long as it is a volatile organic compound having an ether group in the molecule, and examples thereof include an aliphatic ether and a terpene ether aromatic ether. Preferably, 1,4-cineole is used. 1,8-cineole, p-phenyl decyl ether, β_ oxidized carbenene, β-naphthyl isobutyl ether, β-naphthyl ether, β-naphthyl ketone, large bacteria fragrant brain, dandelion , isoamyl phenyl ether, isofosuccito, 151403.doc -21 - 201121558

Grisalva(3a-ethyl-dodecahydro-6,6,9a-trimethyl naphto[2,1 -b]furan，3α-乙基十二氫-6,6,9α-三甲基萘幷[2，l-b]呋喃）、 Cyclamber(13-oxa-bicyclo[10.3.0]pentadecane，13-氧雜二環 [10.3.0]十五烧）、二苯謎、柏木甲醚（£^(^311156]*)、甲基柏 木醚（cedryl methyl ether)、茶螺烷（theaspirane)、燈花 麵、甲苯基乙醚、1-甲基環十二烧基曱驗（Madrox)、氧化 务樟醇、白檸檬環_、胡椒鍵（Rhubofix)、Rhouboflor、玫 瑰醚、玫瑰呋喃等。 上述合成麝香類只要為具有麝香之香氣或類似麝香之香 氣之有機化合物則無特別限定，可列舉：1 〇-氧雜十六烷内 酯、11-氧雜十六烷内酯、12-氧雜十六烷内酯、黃葵内 S旨' 5-環十六稀-1 -酮（ambretone)、環十五烧醋、環十五烧 酮、佳樂麝香（galaxolide)、環十六院内酯 (cyclohexadecanolide)、環十五烷内酯、環十五烷酮、香 寒苗酿I (civetone)、麝香内酯（cervolide)、薩利麝香 (celestolide)、吐納麝香（tonalide)、粉檀麝香 (phantolide)、十五烷内酯、曱醯基乙基四甲基四氛萘 (formylethyltetramethyltetralin)、麝香酮（muscone)、萬山 麝香（versalide)等。 上述酸類只要為分子内具有叛基之有機化合物則無特別 限定’可列舉：苯乙酸、2-乙基丁酸、2-乙基己酸、2·癸 烯酸、2-曱基丁酸、2-甲基庚酸、十一烷酸、十一院烯 酸、肉豆蔻酸、乳酸、亞麻油酸（linolic acid)、次亞麻油 酸（linolenic acid)、順丁稀二酸、丙二酸等。 151403.doc -22· 201121558 物類只要為分子内具有内醇基之揮發性有機化合 L、特別限定’可列舉：脂肪族内酿、結烯系内 香族’較佳可列舉：6_甲基香豆素、γ_正丁内醋、 γ-十-内冑、γ-己内醋、γ_庚内酷 '以癸烯内酿二· decenoUctone)、香豆素、二氫茉莉酮内醋、茉莉内酷 (jasmine iactone)、茉莉内酯（jasm〇Uct〇ne)、八氫香豆 素、二氫香豆素、3_丙基酞内酯等。 上述知類只要為分子内具有酯基之揮發性有機化合物則 無特別限定，可列舉：脂肪族酯、萜烯系酯、芳香族醋 等，較佳可列舉：乙酸-1-乙炔基環己酯、乙酸_丨_辛烯_3 基酯、乙酸-2-乙基己酯、異丁酸_2-苯氧基乙酯、乙酸_L_ 堇酯、丙酸-L-菫酯、乙酸鄰第三丁基環己酯、乙酸對第 三丁基環己酯、乙醯異丁香酚、乙醯丁香酚、乙酸大苗香 酯、水楊酸戊酯、戊酸戊酯、過氧化乙酸烯丙基環己醋、 肉桂酸稀丙S旨、苯氧乙酸烯丙醋、丁酸稀丙g旨、肉.桂酸異 戊S旨、異戊酸異戊S旨、異丁酸異戊醋、十一烧烯酸異戍 酯、辛酸異戊酯、水楊酸異戊酯、肉桂酸異戊酯、癸酸異 戊酯、十二酸異戊酯、丁酸異戊酯、丙酸異戊酯、己酸異 戊酯、辛酸異戊酯、肉桂酸異丁酯、戊酸異丁酯、苯乙酸 異丁酯、丁酸異丁酯、丙酸異丁酯、己酸異丁酯、苯甲酸 異丁醋、乙酸異胡薄荷S旨（isopulegyl acetate)、乙酸異丙 酯、丙酸異葙酯、2-第三丁基環己基碳酸乙醋、鄰甲氧基 苯甲酸乙S旨、對茴香酸乙醋（ethyl p-anisate)、乙酸乙δ旨、 乙醯乙酸乙酯、異戊酸乙酯、異丁酸乙醋、辛炔幾酸乙醋 151403.doc •23- 201121558 (ethyl octyne carbonate)、肉桂酸乙酯、戊酸乙酯、苯乙酸 乙酯、丁酸乙酯、丙酸乙酯、庚酸乙酯、庚炔羧酸乙酯、 壬酸乙醋、苯甲酸乙醋、十二碳二酸乙二醋（ethylene dodecanedioate)、十三碳二酸乙二酯、苯乙酸丁香紛酯、 乙酸辛酯、異戊酸辛酯、異丁酸辛酯、辛酸辛酯、丁酸辛 酯、庚酸辛酯、甲酸辛酯、乙酸羅勒烯酯、乙酸石竹烯 酯、甲酸石竹烯酯、乙酸香芹酯、乙酸愈創木紛酯、乙酸 枯酯、乙酸香葉草酯、異戊酸香葉草酯、異丁酸香葉草 酯、惕各酸香葉草酯（geranyl tiglate)、苯乙酸香葉草酯、 丁酸香葉草酯、乙酸檀香酯、己二酸二乙酯、琥珀酸二乙 酯、癸二酸二乙酯、酒石酸二乙酯、苯二曱酸二乙酯、乙 酸環己酯、異戊酸環己酯、乙酸環己基乙酯、巴豆酸環己 酯、丙酸順-3 -己稀酯、苯甲酸順-3 -己烯醋、甲酸順-3-己 烯酯、乳酸順-3-己烯酯、乙酸擰檬酯、乙酸香茅酯、苯乙 酸香茅S旨、丁酸香茅S旨、乙酸二氫香芽g旨（dihydrocarvyl acetate)、乙酸二氫枯酯、乙酸二氫松油酯、乙酸二氫月 桂烯酯、丁二酸二甲酯、1,1-二曱基-3-苯基丙醇乙酸酿 (dimethylphenylethylcarbinyl acetate)、甲酸松油酯、甲酸 十氫-β -萘盼S旨、乙酸癸S旨、丁酸四氫糖醋、乙酸四氫香葉 草酯、三乙酸甘油酯、檸檬酸三乙酯、乙酸三環癸醋、乙 酸橙花酯、異丁酸橙花酯、丁酸橙花酯、丙酸橙花酯、乙 酸丁醋、己酸丁醋、乙酿丙酸丁醋（butyl levulinate)、乙 酸糠酯、乙酸胡椒酯、2 -甲基丁酸苄酯、乙酸苄醋、異戊 酸苄酯、異丁酸苄酯、丙烯酸苄酯、水楊酸苄酯、肉桂酸 151403.doc -24- 201121558 苄酯、惕各苄酸、十二酸苄酯、戊酸苄酯、苯乙酸苄s旨、 丁酸苄酯、丙酸苄酯、己酸苄酯、苯甲酸苄酯、甲酸笮 酯、水揚酸戊酯、水楊酸甲酯、環辛基甲基碳酸酯、環香 葉烯酸甲酯、環松油烯酸甲酯、二氫茉莉酸曱酯、茉莉酸 甲酯、肉桂酸甲酯、癸酸曱酯、2-癸炔酸曱酯、肉桂酸沈 香酯、丁酸沈香酯、丙酸沈香酯、己酸沈香酯、苯曱酸沈 香酯、芳樟醇曱酸酯、苯乙酸玫瑰酯、丁酸玫瑰酯、丙酸 玫瑰酯、甲酸香草酯等。 上述含齒素化合物只要為分子中含有鹵素之有機化合物 則無限定，可列舉：對二氯苯、溴代蘇合香烯等。 該等香味劑及香水可使用1種，亦可混合使用2種以上。 4·含有抗流感病毒劑之鼻腔或口腔投予用組合物 本發明亦提供一種含有本發明之抗流感病毒劑之流感病 毒傳染病預防及/或治療用之鼻腔或口腔投予用組合物。 本發明之抗流感病毒劑於保護有流感病毒傳染•增殖之危 險的鼻腔或口腔細胞不受流感病毒侵害之方面尤其有效。 上述組合物可為醫藥組合物。 奉發明之「鼻腔或口腔投予用組合物」係指用於以外用 之方式於鼻腔及/或口腔（包括咽喉）之局部投予之組合物。 本發明之鼻腔或口腔投予用組合物典型的是鼻腔或口腔投 予用製劑，例如可調配於口腔外用醫藥品、鼻咽喉外用醫 藥品、口腔外料藥品、及鼻咽喉相準藥品、以及清洗 劑、芳香劑、或浴用劑等(具體而言，例如滴鼻劑、洗鼻 劑、牙膏、口腔清洗料、口含錠、口香糖類等）中而作為 151403.doc •25· 201121558 有效成分使用。本發明之鼻腔或口腔投予用組合物可用於 以改善由流感病毒傳染病導致的發熱或咳嗽等各種症狀、 預防在流感病毒傳染流行期患上該傳染等為代表之流感病 毒傳染病之預防及/或治療。然而，「流感病毒傳染病之預 防及/或治療用」之用途並非僅限於應用於該等症狀、患 病、病情，亦包括對與流感病毒傳染相關之所有病情之應 用。 本發明之鼻腔或口腔投予用組合物可以含嗷劑、喷霧劑 4劑型使用。於作為含嗽劑之情形時，除漱口藥之劑型以 外’亦可使用特殊之器具直接喷附於咽喉部。又，於喷霧 劑之情形時’可採用直接滴至鼻腔之投予方法，亦可使用 嗔霧器向鼻腔内投予。又，本發明之鼻腔或口腔投予用組 合物亦可包裝成含有壓縮推進劑之氣溶膠組合物。 5.含有抗流感病毒劑之流感病毒傳染病之預防及/或治療用 製品 本發明亦提供含有本發明之抗流感病毒劑作為有效成分 且用以供流感病毒傳染病之預防及/或治療之（即，流感病 毒傳染病之預防及/或治療用）製品。作為上述製品，例如 可列舉醫藥製劑、飲食品、香妝品、及日用•雜貨品等。 本發明亦提供一種包含含有本發明之抗流感病毒劑作為 有效成分之香料組合物且用以供流感病毒傳染病之預防及/ 或治療之（即’流感病毒傳染病之預防及/或治療用）製品。 作為上述製品，例如可列舉醫藥製劑' 飲食品、香妝品、 及曰用•雜貨品等。 151403.doc • 26 - 201121558 作為醫藥製劑，包括 订別與.樂οβ及準樂品，並無限定，例如 了歹）舉.貼劑或軟膏劑等 #丨、士制^ 及贗外用劑、叙劑、顆粒劑、散 霧劑，劍等各種劑二劑、糖漿劑、喷 /之1劑。本發明之醫藥製劑可為 絰口製劑亦可為非經口 劑。作為鼻腔或口腔投予二=0腔投予用製 。、富m 則又予用製劑’可列舉：口腔外用醫藥 二等。喉外用醫藥品、口腔外用準藥品、鼻咽喉外用準 外=製劑除Ϊ有本發明之抗流感病毒劑或香料組合物以 載體、可3有樂學上所容許之載體或添加劑等。作為上述 齊例ΓΓ:黏合劑、賦形劑、潤滑劑、崩解劑、㈣ =例=水、藥學上所容許之有機溶劑、膠原蛋白、聚乙 =聚乙稀基。比㈣鲷、缓乙烯基聚合物、海藻酸納、 水浴性聚葡萄糖、羧甲基澱粉鈉 视 α 妙—仙膠、阿拉伯 修、路蛋白、明膠、瓊脂、 丄从 由丙二醇、聚乙二醇、凡 :石蠘、硬脂醇、硬脂酸、人血清蛋白、甘露醇、山 、m甲基纖維素^作為添加劑之例，可列舉 定劑、緩衝劑、調味劑、防腐劑、芳香劑、著色劑等二 =之載體或添加劑可根據製劑之劑形適當選擇或組合選 作為飲食品，並無限定，例如可列舉：果汁飲料類 實酒類、碳酸飲料、清涼飲料、飲料劑類、乳飲 枓類；霜洪淋類、㈣類、冰棒類等冷;東甜點類； 果汁來等甜品類；巧克力、口香糖等西式點心類；羊囊等 151403.doc -27· 201121558 曰本式點心類；果醬類；糖果類；菜莉茶等花。 作為香妝品，並無限定，例如可列舉：香水製品 化妝品、㈣化妝品、頭髮化妝品、日曙化妝品1 妝品、護髮製品等。 用化 作為日用·雜貨品’並無限定’例如可列舉：肥矣 體清洗劑、洛用劑、洗務劑、柔順護理劑、清洗劑 用洗條劑、漂白劑、氣溶膠劑、除臭•芳香劑、驅蟲劑、 其他雜貨類等。 若列舉更具體之例，則如下所述。 •香水製品：香水 '淡香精、淡香水、线水等。 •基礎化妝品：洗面乳、粉底霜、潔面霜、冷霜、按摩 霜、乳液、化妝水、美容液、覆劑、卸妝劑等。 •修飾化妝品：粉底、散粉、粉餅、爽身粉、口紅、唇 膏、肥紅、眼線、睫毛膏、眼影、眉墨、眼膜、指甲油、 洗甲水等。 •頭髮化妝品：髮膏劑、美髮油、定型液、貼片式無痕接 髮（hair stick)、髮蠟、髮油、修護素、髮乳、生髮水整 髮液、喷霧髮膠、髮膠、養髮劑、染髮劑等。 •防曬化妝品：曬黑製品、防曬製品等。 •藥用化妝品.止汗劑、鬚後水及鬚後膏、燙髮劑、藥用 肥皂、藥用洗髮精、藥用皮膚化妝料等。 •濩髮製品：洗髮精、潤絲精、二合一洗髮精、護髮素、 修護素、髮膜等。 •肥皂：化妝皂、浴用皂、香水皂、透明皂、合成皂等。 151403.doc •28· 201121558 •身體清洗劑：沐浴乳、沐浴露、洗手液等。 .浴用劑：入浴劑（浴鹽、沐浴片、沐浴液等）、泡沫浴（氣 泡浴等）、沐浴油（沐浴香料、沐浴膠囊等）、牛奶浴、沐浴 膏、沐浴香精塊等。 •洗滌劑：衣料用重質洗滌劑、衣料用輕質洗滌劑、液體 洗滌劑、洗衣皂、壓縮洗滌劑、肥皂粉等。 •柔順護理劑：柔軟劑、傢俱護理劑等。 •清洗劑：清潔劑、房屋清洗劑、盥洗室清洗劑、浴室用 清洗劑、玻璃清洗劑、除菌劑、排水管用清洗劑等。 •厨房用洗蘇劑：料用肥皂、廚房用合肥皂、食器用洗 滌劑等。 •漂白劑：氧化型漂白劑（氯系漂白劑、氧系漂白劑等）、 還原型漂白劑（硫系漂白劑等）、光學漂白劑等。 •氣溶膠劑：霧劑類型、粉末喷劑等。 •除臭·芳香劑：固體狀類型 '凝膠狀類型、液體類型 .驅蟲劑：氣溶膠、噴霧劑、錠劑、凝膠狀類型等。 •作為其他雜貨類’可列舉：衛生紙、廟紙、面膜等。 將本發明之抗流感病毒劑或含有本發明之抗流感病毒劑 作為有效成分之香料組合物用於上述各種製品之情形時， :根據製品之種類或製品之最終形態(例如液體狀、固體 用η、凝膠狀、霧狀、氣溶膠狀等製品形態)直接 、'广σ(糟由添加、調配、附加或塗佈等)。本發明之抗 流感病毒劑或香料組合物亦可溶解於例如醇類，丙二醇、 15I403.doc •29- 201121558 甘油等多元醇類而以液體狀進行添加或供給 拉伯膠、黃蓍膠等天然膠質方了使用阿 肪酸醋、薦糖脂肪酸醋等非離子界面活性劑、二= 活性劑、陽離子界面活性劑、 ，面 ，合解 刀散之溶解狀或分散狀而使用。進而，本發明 :抗=病：劑或香料組合物可利用阿拉伯膠等天 類、明膠、糊精等賦形劑形成為具有被膜之粉末狀而使 用’亦可利用膠囊化劑進行處理形成為微膠囊狀而使用。 進而’亦可藉由㈣糊精等包藏劑進行包藏而使本發明 之抗流感病毒劑或香料組合物變得穩定並賦予其緩釋性而 加以使用。 製中的本發明之抗流感病毒劑或香料組合物之使用量 可根據製品之種類或形態、製品所謀求之抗流感病毒效果 或作用#料組合物中之抗流感病毒劑之含量等而進行調 整0 於製品為醫藥製劑或飲食品之情形時，通常相對於製品 之質量（將製品質量設為100質量％)，本發明之抗流感病毒 劑之使用量並無限定，較佳為0 〇〇〇〇〇〇〇1質量質量％ 左右。含有本發明之抗流感病毒劑作為有效成分之香料組 合物之使用量並無限定，較佳為約0 〇〇〇5〜2〇質量％左右， 尤佳為0.001〜5質量％左右。就使本發明之抗流感病毒劑之 優異之上述效果良好地發揮之方面而言，該等製品中，相 對於製品之質量，含有抗流感病毒劑作為有效成分之香料 組合物之使用量較佳為0.001〜1質量。/〇，尤佳為0.01〜0 5質 151403.doc •30· 201121558 量％，抗流感病毒劑之使用量較佳為〇 〇〇〇〇〇〇一〇 〇5質量 %，尤佳為0.000001〜0.01質量％。 又，於製品為香妝品或日用•雜貨品等，例如香水製 品、基礎化妝品、修飾化妝品、頭髮化妝品、日曬化妝 品、藥用化妝品、護髮製品、肥4、身體清洗劑、浴用 劑、洗蘇劑、柔順護理劑、清洗劑、厨房用洗滌劑、漂白 劑、氣溶膠劑、除臭•芳香劑、驅蟲劑、其他雜貨等之情 形時，含有本發明之抗流感病毒劑作為有效成分之香味· 香氣組合物之添加量或供給量通常相對於製品之質量（將 製品質量設為100質量％)較佳為約〇〇〇1〜25質量％左右尤 佳為0.01〜0.5質量％左纟，本發明之抗流感病毒劑或含有 其作為有效成分之香料組合物並無限定。就使本發明之抗 机感病毒劑之優異之上述效果良好地發揮之方面而言點， 該等製品中，相對於製品之質量，含有抗流感病毒劑作為 有效成分之香料組合物之使用量較佳為〇 〇“〜〗質量％，尤 佳為0_01〜0.5質量％，抗流感病毒劑之使用量較佳為 0.0000001-0.05 質量 ％ ’ 尤佳為 〇 〇〇〇〇〇1〜〇 〇1 質量 ％。 進而本發明亦提供一種流感之預防或治療方法，其包 括：將含有廣f香醇及/或廣f香精油萃取物作為有效成 分之抗流感病毒劑，含有該抗流感病毒劑之流感病毒傳染 病之預防及/或治療用香料組合物，含有該抗流感病毒劑 或香料組合物之鼻腔或口腔投予用組合物，含有該抗流感 病毒劑或香料組合物之醫藥製劑、飲食品、香妝品或日 用雜貨〇σ用於兩要預防或治療之被試驗體。本發明尤其 151403.doc •31 - 201121558 k供一種包括將本發明之抗流感病毒劑以對預防及/或治 療流感（流感病毒之傳染病）有效之量，投予至需要預防< 治療之被試驗體的流感之預防或治療方法。 本發明之抗流感病毒劑之投予量根據作為投予對象之被 試驗體的年齡及體重、投予路徑、投予次數而不同，可根 據業者之斟酌判斷於較大範圍内變更。例如，本發明之抗 流感病毒劑之投予量以其所包含之廣藿香醇量計，適當的 是1〜1000 mg/kg/day之量。本發明之抗流感病毒劑可一次 性投予’亦可以6〜8小時之間隔反覆地投予。 投予本發明之抗流感病毒劑之被試驗體並無限定，較佳 為包括人、家畜、玩賞動物、實驗（試驗）動物等哺乳動 物。另外，作為本發明之被試驗體，患流感或疑似患流感 之哺乳動物，傳染有流感病毒、疑似傳染有流感病毒或傳 染流感病毒之風險較高之哺乳動物亦較佳。本發明之抗流 感病毒劑與先前之藥劑相比細胞毒性較低，副作用之顧慮 較少，因此非常有用。 實施例 以下，利用實施例對本發明進行更具體的說明。但是， 本發明之技術範圍並非僅限於該等實施例。 [實施例1]廣藿香精油萃取物（醇萃取物、正己烷萃取物）及 廣藿香醇之製備 (1)醇萃取物之製備 相對於切碎成0.5〜2毫米見方左右之碎片狀的廣藿香 (Pogostemon cablin Benth.)之全草} g，添加 1〇〇% 甲醇 10 151403.doc •32- 201121558 mL，花費約3天於室溫下進行萃取。將萃取液過濾後’再 次以同樣方法自殘逢中進行萃取’混合所得之各萃取液並 進行減壓乾燥，獲得殘渣作為醇萃取物。 (2) 正己烷萃取物之製備 相對於切碎成0.5 ~2毫米見方左右之碎片狀的廣藿香 (Pogostemon cablin Benth.)之全草 1 g，添加 100%正己院 1〇 mL ’花費約3天於室溫下進行萃取。將萃取液過濾後’再 次以同樣方法自殘潰中進行萃取，混合所得之各萃取液並 進行減壓乾燥，獲得正己烷萃取物。 (3) 廣藿香醇之製備 藉由利用矽膠管柱層析[矽膠60 N(370 mm><36 mm I.D·)] 之階段式溶出，對以上述方式獲得之正己烷萃取物（3 g)進 行區分。階段式溶出係依序使用作為正己烷與乙酸乙酯之 混合溶劑的正己烷：乙酸乙酯=100 : 0之溶劑（600 mL)、 50 : 1之溶劑（300 mL)、10 : 1 之溶劑（300 mL)、5 : 1之溶 劑（3 00 mL)、1 : 1 之溶劑（300 mL)及 0 : 1 之溶劑（3〇〇 mL)，最後使用曱醇（300 mL)。將溶出組分以1〇 mL為單位 而分裝之後，進而利用薄層層析（TLC)(溶劑系，正己烷： 乙酸乙酯=10 : 1)，將觀察到具有相近之Rf值之點的組分 分別合併’獲得9種組分（Fr· 1-9)。 根據下述實施例2對所得之9種組分有無抗流感活性進行 確認。將9種組分中確認到抗流感病毒活性之正己烷：乙 酸乙酯=5 : 1之溶出組分（Fr.4，產量：713.3 mg，自正己 烧萃取物之產率：0.7%)進而供給於矽膠管柱層析[矽膠6〇 151403.doc -33· 201121558 N(120 mmx42 mm I.D) ’正己烷：乙酸乙酯混合溶劑（2〇 : 1 ’ 2 L)] ’將溶出組分以1 〇 mL為單位而分裝後，藉由 TLC ’將具有相近之Rf值之組分分別合併而獲得6種組分 (Fr.4-1 〜4-6)。對於 Fr.4_4(產量：18 mg)(RF值為 0.22〜0.40 之點），藉由逆相HPLC(high performance liquid chromatography， 咼效液相層析）[X-Bridge Prep ODS(150 mmx 10 mm I.D.)， 9 5%之乙腈’檢測器波長：210 nm]而進行區分，從而獲得 廣藿香醇純化物（產量：16.1 mg，產率：0.3%)(保持時 間：約8.2分鐘）。 對所得之廣藿香醇進行性狀觀察、質譜分析及核磁共振 (NMR)光譜分析。藉此顯示之物理及化學性質如下所述。 1) 性狀：無色固體狀 2) 比旋光度：[a]D25 0;-l〇5.4(c=0.724，曱醇（MeOH)) 3) 低解析度質譜分析（70 ev，電子衝擊質譜分析計）： m/z 222(M+, 100%), 207(62.8), 161(78.2), 138(100), 125(90.4)，98(100)，83(100)，81(86.5)，41(50.6)。 4) 高解析度質譜分析（70 eV，電子衝擊質譜分析計）： 計算值：222.1984 (Cl5H260)，實測值：222.1991 5) 核磁共振 核磁共振（NMR)光譜（§值，ppm，400 ΜΗζ，β比唆-d5): l. 834 (1H, ddd, J=13.6, 6.0, 0.9, H-2ax), 1.888 (1H, ddd, J=13.6, 2.2, 1.8, H-2eq), 1.416 (2H, m, H-3), 1.967 (1H, m, H-4), 1.415 (1H, m, H-5), 1.260 (1H, m, H-6ax), 1.974 (1H, m, H-6eq), 1.182 (1H, m, H-7), 1.283 (1H, m, H-8ax), 1.505 151403.doc •34· 201121558 (1H, ddd, J=15.6, 5.7, 2.7, H-8eq), 1.007(1H, ddd, J=13.6, 11.2, 1.8, H-9eq), 2.246 (1H, ddd, J=13.6, 11.2, 8.4, H-9ax), 0.813 (3H, d, J=6.9, H-12), 1.057 (3H, s, H-13), 1.330 (3H, s, H-14), 1.138 (3H, s, H-15), 4.638 (1H, bs, OH) 13C核磁共振（NMR)光譜（δ值，ppm，100 MHz，°比咬-d5): 74.687 (C-l), 33.282 (C-2), 29.147 (C-3), 28.631 (C-4), 44.071 (C-5), 25.103 (C-6), 39.716 (C-7), 25.178 (C-8), 29.534 (C-9), 38.191 (C-10), 40.930 (C-ll), 19.017 (C-12), 21.620 (C-13), 28.107 (C-14), 24.845 (C-15) [實施例2]廣藿香之醇萃取物及正己烷萃取物之抗流感病毒 活性之評價 (1)流感病毒之培養 將添加有10%之非活化胎牛血清（熱滅活FBS)、青黴素 (200單位/mL)-鏈黴素（0.2 mg/mL)溶液及兩性黴素B(5 pg/mL)溶液之MEM培養基（20 mL)中之Madin-Darby狗腎臟 (MDCK)細胞懸浮液（3 X 1 05個細胞/mL)分注於96孑L培養板 中（100 pL/孔）後，於5%之C02條件下且37t下培養2〜4天 直至融合為止。將融合之96孔培養板内之MDCK細胞之培 養上清液除去之後，利用填酸緩衝化生理鹽水（PBS)(200 μί/孔）清洗MDCK細胞2次。於該96孔培養板之下部4段 (E~H列）之孔中，添加將A型流感病毒原液（A/Puerto Rico/8/34，H1N1亞型）利用包含乙醯胰蛋白酶（1萬單位/ mg/mL)、10%之葡萄糖（0.4 mL)、2倍濃度之MEN培養基 (20 mL)及注射用水（19 mL)之傳染用培養基稀釋1〇45倍所 151403.doc •35· 201121558 得之流感病毒稀釋液〇8〇 孔）β另一方面，於96孔培養 板之上部4段（Α〜D列）之孔中添加上述傳染用培養基（18〇 μΐ^/孔）。進而，於上段及下段之各孔群中，分別以2〇 — 孔添加溶解於10%之甲醇中之由實施例丨製備完成之廣藿 香精油萃取物.（醇萃取物或正己烷萃取物）或丨〇%甲醇（對照 〇 )又作為陽性對照’以20 μυ孔添加1 pg/mL之紮那 米韋（zanamivir)e其次，於5%之c〇2條件下且3rc下將96 孔培養板培養3天。 (2)抗流感病毒活性之測定 (2-1)流感病毒量之測定 將以上述（1)之方式培養之96孔培養板之各孔中的培養 上/月液（50 μ!7孔）於無菌條件下轉移至另一 ％孔微量滴定 盤之各孔中。繼而，添加PBS(5〇 pL/孔）及〇」mMi4甲基 傘形酮-N·乙醯神經胺糖酸（4MU_NeuAc)水溶液（5〇叫/孔） 並立即利用培養板授拌器（plate mixer)授拌後，使用 Fluoroskan(大日本住友製藥股份有限公司）使其於37<>c下 反應10刀鐘。於動力學模式（Kinetics m〇dei)下測定藉由本 反應時間内顯示流感病毒唾液酸酶活性之螢光強度（激發 波長：355 nm，測定波長：460 nm)而作出的酶反應曲線 之斜率（使用軟體：Delta soft 3)。各孔之培養上清液中之 相對流感病毒值係藉由以下之計算式而算出。 培養上清液之流感病毒值 上述計算式中，Α表示添加廣藿香精油萃取物時流感病 毒存在下之培養上清液中的唾液酸酶活性（酶反應曲線之 151403.doc -36 - 201121558 斜率）’B表示未添加廣藿香精油萃取物時流感病毒存在下 之培養上清液中的唾液酸酶活性（酶反應曲線之斜率），c 表不未添加廣藿香精油萃取物時流感病毒不存在下之培養 上清液中的唾液酸酶活性（未添加試驗樣品，背景）。 又，由用量-流感病毒唾液酸酶活性之直線，算出各廣 藿香精油萃取物對流感病毒增殖之5〇%抑制濃度（IC5〇)。 以上之測定結果示於下述表1。 (2-2)流感病毒存在下之MDCK細胞之存活率之測定丁丁 法） 將以上述（1)之方式培養之96孔培養板之培養上清液除 去之後，利用PBS(200 μί/孔）將培養板上之MDCK細胞清 洗1次。於該培養板中，以1〇〇 μ£/孔添加3_(45二甲基·2_ 噻唑基）-2,5-二苯基溴化四唑（MTT)2PBS溶液（1 mg/mL)， 於5%之C〇2條件下且37t下培養2小時後，利用抽氣器抽 吸除去MTT溶液。進而向培養板中添加〇 〇4 N之含有鹽酸 之異丙醇（100 pL/孔）並攪拌，於培養板攪拌器上混合，藉 此將生成之甲臢溶解之後，向其中添加純化水（丨〇〇 pL/孔） 並輕輕攪拌。利用微盤分析儀（大日本住友製藥股份有限 公司）測定反應液之吸光度，作為]^1)(：反細胞數之指標（測 定波長：570 nm，補償波長：630 nm)。 MDCK細胞之存活率（MTT法）係藉由以下之計算式而算 出。 MDCK細胞之存活率（％)=(Α/Β)χ1〇〇 式中，Α表示於流感病毒存在下之添加有廣藿香精油萃 151403.doc -37· 201121558 取物之情形時之吸光度，B表示於流感病毒不存在下之未 添加廣藿香精油萃取物之情形時之吸光度。 所得之結果示於下述表i。 (2-3 )廣藿香精油萃取物之細胞毒性之檢驗 於流感病毒不存在下，以與上述相同之條件，於實 施例1製備之廣藿香精油萃取物（廣藿香之醇萃取物或正己 烷萃取物）之存在下或不存在下，對MDCK細胞進行培養之 後，依據上述（2-2)之方法，藉由MTT法測定成為河〇(：艮細 胞數（殘存MDCK細胞數）之指標的吸光度。繼而，藉由下 述計算式算出流感病毒不存在下且廣藿香精油萃取物存在 下之MDCK細胞之死亡率，即廣藿香精油萃取物之細胞毒 性。 廣藿香精油萃取物對MDCK細胞之細胞毒性（％)=(A_ Β)/Αχ100 式中，A表示未添加有廣藿香精油萃取物之情形時之吸 光度，B表示添加有廣藿香精油萃取物之情形時之吸光 度。 (3)廣藿香精油萃取物之抗流感病毒活性及細胞毒性 以上述方式獲得之廣藿香精油萃取物（廣藿香之醇萃取 物及正己烷萃取物）之抗流感病毒活性及細胞毒性如表 示0 151403.doc •38· 201121558 [表i] 廣藿香之醇萃取物及正己烷萃取物之MDCK細胞的抗流感病毒活性、 及該萃取物對MDCK細胞之直接細胞毒性 抗流感病毒活性 病毒不存在下之對 MDCK細胞之細胞 毒性(％) 流感病毒值 (%) 病毒存在下之MDCK細 胞存活率(％) 廣藿香之醇萃 取物 (10 pg/mL) 0.2 97.5 -12.0〜~~ 廣藿香之正己 烧萃取物 (10 pg/mL) 0.1 76.1 10.0 紮那米韋 (1 pg/mL) 0.1 〜0.3 112.9 〜113.3 -29.4 〜25.5 ----- 表中，紮那米韋係已知之具有抗流感病毒活性之化合 物，其係作為陽性對照而使用者。 如表1所示，已明確：廣藿香之醇萃取物及正己烷萃取 物幾乎不顯示細胞毒性，且顯示可顯著地抑制流感病毒增 殖之抗流感病毒活性，因此可作為抗流感病毒劑而使用。 [實施例3]廣藿香醇之抗流感病毒活性之評價 將添加有10%之非活化胎牛血清、青黴素（200單位 鏈黴素（0.2 mg/mL)溶液及兩性黴素B(5 pg/mL)溶液之MEM 培養基（20 mL)中的Madin-Darby狗腎臟（MDCK)細胞懸浮 液（3xl05個細胞/mL)分注於6孔培養板（2 mL/孔）中之後， 於5%之C〇2條件下且37°C下培養2〜4天直至融合為止。將 融合之6孔培養板内的培養MDCK細胞之培養上清液除去 151403.doc -39- 201121558 之後，利用PBS(2 mL/孔）清洗MDCK細胞！次。清洗後，於 各孔中以100 pL/孔添加以與實施例2同樣之方式製備之流 感病毒稀釋液（A/Puerto Rico/8/32’HlNl亞型，1〇3·7倍稀 釋液），於5%之C〇2條件下且37t下培養3〇分鐘。於上述 各孔中，以2 mL/孔添加向多層用瓊脂培養基（126 mL)中 加入以ίο%甲醇稀釋之廣藿香醇（參照實施例丨）溶液（14 mL)而製備之試驗樣品溶液，於室溫下放置直至瓊脂固化 為止。進而，將該培養板倒置，於5%2C〇2條件下且”艽 下培養3天。又，除代替試驗樣品溶液而添加水以外以與 上述相同之方式進行試驗（流感病毒存在下，未添加廣蕾 香醇）作為對照。進而，除代替試驗樣品溶液而添加1〇%之 甲醇以外，以與上述相同之方式進行試驗作為陰性對照， 又，除代替試驗樣品溶液而添加紮那米韋水溶液以外，以 與上述相同之方式進行試驗作為陽性對照。 繼而，將6孔培養板之上下方還原，於其各孔中重疊染 色用瓊脂培養基[向2倍濃度之MEM培養基（2〇 mL)中添加 〇·1°/。之中性紅水溶液（4 mL)，並添加瓊脂培養基（向〇 32 g 瓊脂中添加注射用水16 mL而製備）而成者](1 mL/孔）之 層，並於室溫下放置直至瓊脂固化為止。進而，將該培養 板倒置，於5%之C〇2條件下且37t：下培養9〇分鐘之後，目 視數出作為未染色之點而觀察到的溶解之死細胞（斑點）之 數。將其結果之一例示於圖1。 如圖1所示，於基於目視計數之評價中，顯示出於將未 添加廣藿香醇之情形（對照）設為100%時，廣藿香醇可使死 151403.doc • 40· 201121558 細胞（斑點）數降低至約25%。 又’關於以同樣方式形成斑點並數出斑點數之試樣，藉 由以下之計算式以相對於對照品之斑點數相對值（％)而算 出抗流感病毒活性。 斑點數相對值（％)=(A/B)xl〇〇 式中，Α表示流感病毒存在下之添加有廣藿香醇之情形 時之平均斑點數，B表示流感病毒存在下之未添加有廣藿 香醇之情形時之平均斑點數。將其結果之一例示於圖2。 如圖2所示，於斑點數相對值（％)之評價中，顯示出當將 未添加有廣藿香醇之情形（對照）時之死細胞數設為1〇〇% 時’廣藿香醇可使死細胞（斑點）數降低至約40〇/〇。 圖1與圖2之結果之差異係由斑點形成法中通常出現之 20%左右之實驗誤差所導致。圖}及圖2所示之結果均顯示 可成功地顯著減少死細胞（斑點）數。 又’藉由圖2所示之樣品用量-斑點數相對值之曲線，算 出廣藿香醇對流感病毒增殖之50%抑制濃度（1C5 廣着 香醇對流感病毒增殖之50%抑制濃度（IC5〇)為〇 639 pg/mL。 根據以上之結果明確，由於廣藿香醇顯示可顯著地抑制 流感病毒增殖之抗流感病毒活性，因此可作為抗流感病毒 劑使用。 [實施例4]廣藿香醇對流感病毒唾液酸酶之抑制活性之坪價 業界已知於流感病毒之傳染過程中，來自病毒之唾液酸 酶在病毒之出芽過程中發揮重要之作用，故而開發出以該 151403.doc •41 - 201121558 酶作為標靶之抗流感病毒藥紮那米韋及奥司他韋。 因此，為研究本發明之廣藿香醇是否與該等已知之抗流 感病毒藥同樣地作用於標靶分子，而評價廣藿香醇對流感 病毒之唾液酸酶活性之抑制活性。 首先，於96孔微量滴定盤中添加PBS(90 μί/孔）之後，添 加廣藿香醇（10 pL/孔）之10°/。曱醇溶液、及含有來自流感病 毒之唾液酸酶作為病毒蛋白抗原之流感疫苗（A/New Caledonia/20/99 ’ H1N1亞型，50 pL/孔），以培養板授拌器 攪拌之後，於室溫下培養30分鐘。向該反應液中添加〇1 mM之4MU-NeuAc水溶液（50 pL/孔）並立即以培養板搜拌器 攪拌之後，使用Fluoroskan(大日本住友製藥股份有限公 司）於37C下使之反應10分鐘。於動力學模式下測定反應 時間内之螢光強度（激發波長：355 nm，測定波長：460 nm)之變化，藉此以酶反應曲線之斜率而算出唾液酸酶活 性（使用軟體：Delta soft 3)。 其次，藉由以下之計算式算出流感病毒之相對唾液酸酶 活性。Grisalva(3a-ethyl-dodecahydro-6,6,9a-trimethyl naphto[2,1 -b]furan,3α-ethyldodecahydro-6,6,9α-trimethylnaphthoquinone [2,lb]furan ), Cyclamber (13-oxa-bicyclo [10.3.0] pentadecane, 13-oxabicyclo[10.3.0] fifteen), diphenyl mystery, cedar methyl ether (£^(^311156)*), A Cedryl methyl ether, theaspirane, nectarine, tolyl ether, 1-methylcyclododelation (Madrox), oxidized sterol, white lemon ring _, pepper (Rhubofix), Rhouboflor, rose ether, rose furan, etc. The above-mentioned synthetic musk is not particularly limited as long as it is an organic compound having a musky aroma or a musky-like aroma, and is exemplified by 1 〇-oxahexadecanolide, 11-oxahexadecanolide, 12-oxahexadecanolide, yellow sunflower, S-'5-cyclohexadecan-1-one (ambretone), ring fifteen vinegar, ring fifteen Ketone, galaxolide, cyclohexadecanolide, cyclopentadecanolide, cyclopentadecanone, civetone, cervolide, sali musk (celestol Ide), tonalide, phantolide, pentadecyl lactone, formylethyltetramethyltetralin, muscone, versalide The above-mentioned acid is not particularly limited as long as it is an organic compound having a repulsive group in the molecule, and examples thereof include phenylacetic acid, 2-ethylbutyric acid, 2-ethylhexanoic acid, 2-decenoic acid, and 2-mercaptobutylene. Acid, 2-methylheptanoic acid, undecanoic acid, eleventh oleic acid, myristic acid, lactic acid, linolic acid, linolenic acid, cis-succinic acid, C 151403.doc -22· 201121558 The substance is a volatile organic compound L having an internal alcohol group in the molecule, and is particularly limited to 'exemplified as: an aliphatic internal brewing or an aromatic internal aromatic group'. :6_methylcoumarin, γ_n-butyrolactone, γ-deca-endoin, γ-hexine vinegar, γ_genecoin's terpene decenoUctone), coumarin, two Hydrogen jasmonone vinegar, jasmine iactone, jasmine lactone (jasm〇Uct〇ne), octahydrocoumarin, dihydrocoumarin, 3_ Phthalocyanine lactone group. The above-mentioned known class is not particularly limited as long as it is a volatile organic compound having an ester group in the molecule, and examples thereof include an aliphatic ester, a terpene ester, an aromatic vinegar, and the like, and preferably an acetate-1-ethynylcyclohexane Ester, acetic acid _ 丨 octene _3 base ester, acetic acid 2-ethylhexyl acetate, isobutyric acid _2-phenoxyethyl ester, acetic acid _L_ decyl ester, propionic acid-L- decyl ester, acetic acid neighbor Tertiary butylcyclohexyl ester, acetic acid p-tert-butylcyclohexyl ester, ethyl eugenol, eugenol eugenol, eugenyl acetate, amyl salicylate, amyl valerate, acetyl acetate Base hexane vinegar, cinnamic acid sulphuric acid, phenoxyacetic acid propylene vinegar, butyric acid, propyl ketone, meat, sulphuric acid, sulphuric acid, isovaleric acid, isobutyric acid, isovaleric acid Isodecyl enoate, isoamyl octanoate, isoamyl salicylate, isoamyl cinnamate, isoamyl decanoate, isoamyl dodecanoate, isoamyl butyrate, isoamyl propionate Ester, isoamyl hexanoate, isoamyl octanoate, isobutyl cinnamate, isobutyl valerate, isobutyl phenylacetate, isobutyl butyrate, isobutyl propionate, isobutyl hexanoate, benzene Isobutyl acetonate Isopulegyl acetate, isopropyl acetate, isodecyl propionate, 2-tert-butylcyclohexyl carbonate, ethyl orthomethoxybenzoic acid, ethyl p-anisate (ethyl p- Anisate), ethyl acetate, ethyl acetate, ethyl isovalerate, ethyl isobutyrate, octanoic acid ethyl citrate 151403.doc • 23- 201121558 (ethyl octyne carbonate), ethyl cinnamate, Ethyl valerate, ethyl phenylacetate, ethyl butyrate, ethyl propionate, ethyl heptanoate, ethyl heptynecarboxylate, ethyl citrate, ethyl benzoate, ethylenedicarbonate (ethylene dodecanedioate), ethylene terephthalate, clofenac phthalate, octyl acetate, octyl isovalerate, octyl isobutyrate, octyl octanoate, octyl butyrate, octyl heptate, octyl formate Ester, basilene acetate, acetate resin, carotenoid ester, carvacrol acetate, guaiac acetate, cumyl acetate, geranyl acetate, geranyl isovalerate, isobutyric acid Geranyl tartlate, geranyl tiglate, geranyl phenylacetate, geranyl butyrate, sandalwood acetate, Diethyl adipate, diethyl succinate, diethyl sebacate, diethyl tartrate, diethyl benzoate, cyclohexyl acetate, cyclohexyl isovalerate, cyclohexyl acetate Cyclohexyl crotonate, cis-3-hexyl propionate, cis-3-hexene benzoate, cis-3-hexene carboxylic acid, cis-3-hexenyl lactate, citric acid acetate, Citronella acetate, citric acid citronella S, citric acid butyrate, dihydrocarvyl acetate, dihydroacetic acid acetate, dihydroterpineol acetate, dihydromyrcene acetate , dimethyl succinate, dimethylphenylethylcarbinyl acetate, terpineate, formic acid, decahydro-β-naphthalene, Tetrahydrobutyric acid butyrate, tetrahydrogeranyl acetate, triacetin, triethyl citrate, tricyclic vinegar acetate, neryl acetate, erysyl isobutyrate, neryl butyrate, Nectar propionate, butyl vinegar, butyl vinegar, butyl levulinate, decyl acetate, piperazine acetate, benzyl 2-methylbutyrate, benzyl acetate, different Benzyl methacrylate, benzyl isobutyrate, benzyl acrylate, benzyl salicylate, cinnamic acid 151403.doc -24- 201121558 Benzyl ester, benzylic acid, benzyl dodecanoate, benzyl valerate, phenylacetic acid Benzyl, benzyl butyrate, benzyl propionate, benzyl hexanoate, benzyl benzoate, decyl carboxylate, amyl salicylate, methyl salicylate, cyclooctyl methyl carbonate, ring fragrant Methyl oleate, methyl cyclopentene enoate, decyl jasmonate, methyl jasmonate, methyl cinnamate, decyl decanoate, decyl 2-decanoate, agaric acid cinnamate, butyl Acidic acid ester, propionate, propionate, benzoic acid, benzoic acid, linalyl phthalate, rose phenyl acetate, rose succinate, rose propionate, vanillyl formate, and the like. The dentate-containing compound is not limited as long as it is an organic compound containing a halogen in the molecule, and examples thereof include p-dichlorobenzene and bromothene. These flavoring agents and perfumes may be used alone or in combination of two or more. 4. Nasal or Oral Administration Composition Containing Anti-Influenza Virus Agent The present invention also provides a nasal or oral administration composition for the prevention and/or treatment of influenza virus infectious diseases containing the anti-influenza virus agent of the present invention. The anti-influenza virus of the present invention is particularly effective in protecting nasal or oral cells which are at risk of influenza virus infection and proliferation from influenza virus. The above composition may be a pharmaceutical composition. The "nasal or oral administration composition" as used in the invention means a composition for topical administration to the nasal cavity and/or the oral cavity (including the throat) for external use. The nasal or oral administration composition of the present invention is typically a nasal or oral administration preparation, for example, an oral preparation for external use, a nasal and external medicine, an oral preparation, and a nasopharyngeal medicine, and a cleaning agent, a fragrance, a bathing agent, etc. (specifically, for example, nasal drops, nasal washes, toothpastes, mouth rinses, buccal tablets, chewing gums, etc.) as 151403.doc •25· 201121558 active ingredients use. The composition for nasal cavity or oral administration of the present invention can be used for the prevention of various symptoms such as fever or cough caused by influenza virus infection, and prevention of influenza virus infectious diseases represented by the infection during the epidemic of influenza virus infection. And / or treatment. However, the use of "prevention and/or treatment of influenza virus infections" is not limited to the application to such symptoms, illnesses, conditions, but also to all conditions associated with influenza virus infection. The nasal cavity or oral administration composition of the present invention can be used in the form of an elixir or a spray. In the case of a gargle, it may be sprayed directly onto the throat using a special device, except for the dosage form of the gargle. Further, in the case of a spray, a method of directly dropping into the nasal cavity can be employed, and a mister can be used for administration into the nasal cavity. Further, the nasal cavity or oral administration composition of the present invention may be packaged as an aerosol composition containing a compressed propellant. 5. A preventive and/or therapeutic product for influenza virus infectious diseases containing an anti-influenza virus agent. The present invention also provides an anti-influenza virus agent containing the present invention as an active ingredient and used for the prevention and/or treatment of influenza virus infectious diseases. (ie, for the prevention and/or treatment of influenza virus infectious diseases). Examples of the above-mentioned products include pharmaceutical preparations, foods and drinks, cosmetics, daily necessities, and the like. The present invention also provides a perfume composition comprising the anti-influenza virus agent of the present invention as an active ingredient and used for the prevention and/or treatment of influenza virus infectious diseases (ie, for the prevention and/or treatment of influenza virus infectious diseases) )product. Examples of the above-mentioned products include pharmaceutical preparations such as 'drinks, cosmetics, cosmetics, and miscellaneous goods. 151403.doc • 26 - 201121558 There are no restrictions on pharmaceutical preparations, including subscriptions, music, music, and prescriptions. For example, 歹), patches, ointments, etc. #丨,士制^ and 赝 external preparations, Recipe, granules, aerosols, swords and other two agents, syrup, spray / 1 agent. The pharmaceutical preparation of the present invention may be a mouthwash preparation or a parenteral preparation. As a nasal cavity or oral administration, a two-zero cavity administration system was administered. And rich m is also used in the preparation of 'may be listed: oral medicine second-class. The extracorporeal medicinal product, the oral external use quasi-drug, and the nasopharyngeal external preparation = preparation, in addition to the anti-influenza virus or perfume composition of the present invention, may be a carrier, or a carrier or an additive which is arbitrarily acceptable. As the above example, a binder, an excipient, a lubricant, a disintegrator, (4) = an example = water, a pharmaceutically acceptable organic solvent, collagen, a polyethylene group = a polyethylene group. ( (4) 鲷, slow vinyl polymer, sodium alginate, water-bath polydextrose, sodium carboxymethyl starch α 妙 仙 仙 仙 、, Arabic repair, road protein, gelatin, agar, 丄 from propylene glycol, polyethylene glycol Where: Dendrobium, stearyl alcohol, stearic acid, human serum albumin, mannitol, mountain, m methyl cellulose ^ as an example of additives, can be listed as a fixative, buffer, flavor, preservative, fragrance The carrier or the additive of the coloring agent or the like may be appropriately selected or selected as a food or drink according to the dosage form of the preparation, and is not limited, and examples thereof include a fruit juice beverage, a carbonated beverage, a refreshing beverage, a beverage, and a milk. Drinking sputum; frost Honglin, (four), popsicles and other cold; East desserts; juices and other desserts; chocolate, chewing gum and other Western-style snacks; sheepskins, etc. 151403.doc -27· 201121558 曰 式 点心; jams; candy; vegetables, tea and other flowers. The cosmetic product is not limited, and examples thereof include perfume products, cosmetics, (4) cosmetics, hair cosmetics, Japanese cosmetics, cosmetics, hair care products, and the like. The use of the product as a daily or miscellaneous product is not limited, and examples thereof include a fat body cleaning agent, a lozenge agent, a detergent, a soft care agent, a detergent stripper, a bleaching agent, an aerosol agent, and the like. Stinky, aromatics, insect repellents, other miscellaneous goods, etc. If a more specific example is given, it is as follows. • Perfume products: perfume 'light fragrance, eau de toilette, line water, etc. • Basic cosmetics: facial cleanser, foundation cream, cleansing cream, cold cream, massage cream, lotion, lotion, beauty lotion, coating, makeup remover, etc. • Modified cosmetics: foundation, loose powder, powder, talcum powder, lipstick, lip balm, fat red, eyeliner, mascara, eye shadow, eyebrow ink, eye mask, nail polish, nail polish, etc. • Hair cosmetics: hair cream, hair oil, styling liquid, patch type hair stick, hair wax, hair oil, repairing conditioner, hair lotion, hair styling lotion, spray hair gel, hair gel, raising Hair spray, hair dye, etc. • Sunscreen cosmetics: tanning products, sunscreen products, etc. • Medicated cosmetics. Antiperspirant, aftershave and after shave cream, perm, medicinal soap, medicated shampoo, medicated skin cosmetics, etc. • Hair products: shampoo, moisturizing essence, two-in-one shampoo, conditioner, repairing conditioner, hair mask, etc. • Soap: cosmetic soap, bath soap, perfume soap, transparent soap, synthetic soap, etc. 151403.doc •28· 201121558 • Body cleansers: shower gel, shower gel, hand soap, etc. Bathing agents: bathing agents (bath salts, shower tablets, body washes, etc.), foam baths (bubble baths, etc.), bath oils (bathing perfumes, bathing capsules, etc.), milk baths, bath creams, bathing essences, etc. • Detergent: heavy detergent for clothing, light detergent for clothing, liquid detergent, laundry soap, compressed detergent, soap powder, etc. • Soft care agent: softener, furniture care agent, etc. • Cleaning agents: detergents, house cleaners, bathroom cleaners, bathroom cleaners, glass cleaners, disinfectants, drain cleaners, etc. • Kitchen detergent: soap for kitchen, soap for kitchen, detergent for food, etc. • Bleach: oxidized bleach (chlorine bleach, oxygen bleach, etc.), reduced bleach (such as sulfur bleach), optical bleach, and the like. • Aerosol: type of aerosol, powder spray, etc. • Deodorant • Fragrance: Solid type 'gel type, liquid type. Insect repellent: aerosol, spray, lozenge, gel type, etc. • As other miscellaneous goods, you can mention: toilet paper, temple paper, mask, etc. When the anti-influenza virus agent of the present invention or the perfume composition containing the anti-influenza virus agent of the present invention as an active ingredient is used in the above various articles, according to the type of the product or the final form of the product (for example, liquid or solid) η, gel, mist, aerosol, and other product forms) direct, 'wide σ (defective addition, blending, addition or coating, etc.). The anti-influenza virus or perfume composition of the present invention can also be dissolved in a liquid such as an alcohol, propylene glycol, propylene glycol, 15I403.doc •29-201121558 glycerin, etc., or added to a natural material such as labo gum or tragacanth. The gum is used by using a non-ionic surfactant such as a fatty acid vinegar, a sugar fatty acid vinegar, a second active agent, a cationic surfactant, a surface, and a dissolved or dispersed form. Further, the present invention: an anti-disease agent or a perfume composition can be formed into a powder having a film by using an excipient such as gum arabic, gelatin or dextrin, and can be processed by using an encapsulating agent. Microcapsules are used. Further, the anti-influenza virus agent or the fragrance composition of the present invention can be stabilized by the inclusion of an occlusion agent such as dextrin, and can be used for its sustained release property. The amount of the anti-influenza virus or perfume composition of the present invention to be used may be determined according to the type or form of the product, the anti-influenza virus effect sought by the product, or the content of the anti-influenza agent in the composition. When the product is a pharmaceutical preparation or a food or beverage, the amount of the anti-influenza agent of the present invention is not limited, and is preferably 0 相对 with respect to the quality of the product (the mass of the product is set to 100% by mass). 〇〇〇〇〇〇 1 mass% or so. The amount of the perfume composition containing the anti-influenza virus agent of the present invention as an active ingredient is not limited, but is preferably about 0 〇〇〇 5 to 2 % by mass, and more preferably about 0.001 to 5% by mass. In terms of the excellent effects of the above-described anti-influenza agent of the present invention, the amount of the perfume composition containing the anti-influenza agent as an active ingredient is preferably used in comparison with the quality of the product. It is 0.001~1 mass. /〇, especially good is 0.01~0 5 quality 151403.doc •30· 201121558%, the amount of anti-influenza agent is preferably 〇〇5〇〇%, especially preferably 0.000001~ 0.01% by mass. In addition, the products are cosmetic products or daily necessities, such as perfume products, basic cosmetics, cosmetic cosmetics, hair cosmetics, sun cosmetics, cosmeceuticals, hair care products, fertilizers 4, body cleansers, bath agents. The anti-influenza agent of the present invention is contained in the case of a detergent, a softening agent, a cleaning agent, a kitchen detergent, a bleach, an aerosol, a deodorant, a fragrance, an insect repellent, or the like. Aroma of the active ingredient. The amount or supply amount of the aroma composition is usually preferably about 1 to 25% by mass, particularly preferably 0.01 to 0.5 by mass, based on the mass of the product (the mass of the product is 100% by mass). % left 纟, the anti-influenza virus of the present invention or a perfume composition containing the same as an active ingredient is not limited. In terms of the excellent effects of the above-described antiviral agent of the present invention, the amount of the perfume composition containing the anti-influenza agent as an active ingredient relative to the quality of the product is used. Preferably, it is 〜"~〗 mass%, especially preferably 0_01~0.5% by mass, and the amount of anti-influenza virus agent is preferably 0.0000001-0.05% by mass ' 尤佳为〇〇〇〇〇〇1~〇〇1 The present invention also provides a method for preventing or treating influenza, which comprises: an anti-influenza virus agent containing an extract of a wide-flavored alcohol and/or an aromatic essential oil as an active ingredient, and the influenza containing the influenza virus-containing agent A cosmetic composition for preventing and/or treating a viral infectious disease, a nasal or oral administration composition containing the anti-influenza virus agent or a fragrance composition, a pharmaceutical preparation containing the anti-influenza virus agent or a fragrance composition, and a food or drink. , cosmetic or household groceries 〇 σ for two subjects to be prevented or treated. The present invention, in particular, 151403.doc • 31 - 201121558 k for an anti-influenza virus comprising the present invention To be effective in preventing and/or treating influenza (infectious diseases of influenza virus) < A method of preventing or treating influenza of a subject to be tested. The dose of the anti-influenza agent of the present invention varies depending on the age and body weight of the subject to be administered, the administration route, and the number of administrations, and can be changed within a wide range according to the discretion of the practitioner. For example, the dose of the anti-influenza agent of the present invention is suitably from 1 to 1000 mg/kg/day based on the amount of the patchouli alcohol contained therein. The anti-influenza virus agent of the present invention can be administered in a single dose, or it can be administered repeatedly at intervals of 6 to 8 hours. The test subject to which the anti-influenza virus agent of the present invention is administered is not limited, and preferably includes mammals such as humans, domestic animals, animal animals, and experimental (test) animals. Further, as the subject of the present invention, mammals suffering from influenza or suspected influenza, and mammals infected with influenza virus, suspected of being infected with influenza virus or transmitting influenza virus are also preferred. The anti-fluviral agent of the present invention is very useful because it has lower cytotoxicity than prior agents and has fewer side effects. EXAMPLES Hereinafter, the present invention will be more specifically described by way of examples. However, the technical scope of the present invention is not limited to the embodiments. [Example 1] Preparation of patchouli essential oil extract (alcohol extract, n-hexane extract) and patchouli alcohol (1) Preparation of alcohol extract relative to chopped into pieces of 0.5 to 2 mm square Whole plant of Pogostemon cablin Benth. g, add 1% methanol 10 151403.doc • 32- 201121558 mL, and take about 3 days to extract at room temperature. After the extract was filtered, 'the extract was again extracted in the same manner from the residue.' Each of the obtained extracts was mixed and dried under reduced pressure to obtain a residue as an alcohol extract. (2) Preparation of n-hexane extract 1 g of whole grass of Pogostemon cablin Benth., which is chopped into pieces of about 0.5 to 2 mm square, and added 100% Zhengjiyuan 1 mL' The extraction was carried out at room temperature for 3 days. After the extract was filtered, it was extracted again by the same method from the residue, and each of the obtained extracts was mixed and dried under reduced pressure to obtain a n-hexane extract. (3) Preparation of patchouli alcohol by gel column chromatography [矽 60 N (370 mm) The staged dissolution of <36 mm I.D·)] was distinguished from the n-hexane extract (3 g) obtained in the above manner. The stage elution system uses n-hexane as a mixed solvent of n-hexane and ethyl acetate: a solvent of ethyl acetate = 100:0 (600 mL), a solvent of 50:1 (300 mL), a solvent of 10:1 (300 mL), 5:1 solvent (300 mL), 1:1 solvent (300 mL), and 0:1 solvent (3 〇〇mL), and finally decyl alcohol (300 mL). After dissolving the eluted fraction in units of 1 mL, and then using thin layer chromatography (TLC) (solvent, n-hexane: ethyl acetate = 10:1), points having similar Rf values were observed. The components were combined to obtain '9 components (Fr·1-9). The presence or absence of anti-influenza activity of the obtained nine components was confirmed according to the following Example 2. The n-hexane having an anti-influenza virus activity was confirmed among the nine components: the eluted component of ethyl acetate = 5:1 (Fr. 4, yield: 713.3 mg, yield from the extract of n-hexane): 0.7% Supply to 矽 rubber column chromatography [矽胶6〇151403.doc -33· 201121558 N (120 mmx42 mm ID) 'n-hexane: ethyl acetate mixed solvent (2〇: 1 ' 2 L)] 'The dissolution component is After dispensing in units of 〇mL, the components having similar Rf values were separately combined by TLC to obtain six components (Fr. 4-1 to 4-6). For Fr.4_4 (yield: 18 mg) (RF value 0.22 to 0.40), by high performance liquid chromatography [X-Bridge Prep ODS (150 mm x 10 mm) ID), 95% acetonitrile 'detector wavelength: 210 nm> was distinguished to obtain a patchouliol purified product (yield: 16.1 mg, yield: 0.3%) (holding time: about 8.2 minutes). The obtained patchoulol was subjected to property observation, mass spectrometry and nuclear magnetic resonance (NMR) spectral analysis. The physical and chemical properties thus shown are as follows. 1) Properties: colorless solid 2) Specific optical rotation: [a] D25 0; -l 5.4 (c = 0.724, decyl alcohol (MeOH)) 3) Low-resolution mass spectrometry (70 ev, electron impact mass spectrometer ): m/z 222 (M+, 100%), 207 (62.8), 161 (78.2), 138 (100), 125 (90.4), 98 (100), 83 (100), 81 (86.5), 41 ( 50.6). 4) High-resolution mass spectrometry (70 eV, electron impact mass spectrometer): Calculated value: 222.1984 (Cl5H260), measured value: 222.1991 5) Nuclear magnetic resonance NMR (NMR) spectrum (§ value, ppm, 400 ΜΗζ, β唆-d5): l. 834 (1H, ddd, J=13.6, 6.0, 0.9, H-2ax), 1.888 (1H, ddd, J=13.6, 2.2, 1.8, H-2eq), 1.416 (2H, m, H-3), 1.967 (1H, m, H-4), 1.415 (1H, m, H-5), 1.260 (1H, m, H-6ax), 1.974 (1H, m, H-6eq) , 1.182 (1H, m, H-7), 1.283 (1H, m, H-8ax), 1.505 151403.doc •34· 201121558 (1H, ddd, J=15.6, 5.7, 2.7, H-8eq), 1.007 (1H, ddd, J=13.6, 11.2, 1.8, H-9eq), 2.246 (1H, ddd, J=13.6, 11.2, 8.4, H-9ax), 0.813 (3H, d, J=6.9, H-12 ), 1.057 (3H, s, H-13), 1.330 (3H, s, H-14), 1.138 (3H, s, H-15), 4.638 (1H, bs, OH) 13C nuclear magnetic resonance (NMR) spectroscopy (δ value, ppm, 100 MHz, ° ratio bite-d5): 74.687 (Cl), 33.282 (C-2), 29.147 (C-3), 28.631 (C-4), 44.071 (C-5), 25.103 (C-6), 39.716 (C-7), 25.178 (C-8), 29.534 (C-9), 38.191 (C-10), 40.930 (C-ll), 19.017 (C-12), 21.620 ( C-13), 28.107 (C-14), 24.845 (C-15) [Implementation 2] Evaluation of anti-influenza activity of patchouli alcohol extract and n-hexane extract (1) Influenza virus culture will be supplemented with 10% non-activated fetal bovine serum (heat inactivated FBS), penicillin (200 units) /mL)-Streptomycin (0.2 mg/mL) solution and amphotericin B (5 pg/mL) solution in MEM medium (20 mL) in Madin-Darby dog kidney (MDCK) cell suspension (3 X 1 05 cells/mL) were dispensed into a 96-L culture plate (100 pL/well), and cultured for 2 to 4 days at 37 ° C under 5% CO 2 until confluence. After the culture supernatant of the MDCK cells in the fused 96-well culture plate was removed, the MDCK cells were washed twice with acid-buffered saline (PBS) (200 μί/well). Add the influenza A virus stock solution (A/Puerto Rico/8/34, H1N1 subtype) to the acetaminophen trypsin (10,000) in the lower 4 segments (E~H column) of the 96-well culture plate. Unit / mg / mL), 10% glucose (0.4 mL), 2 times concentration of MEN medium (20 mL) and water for injection (19 mL) were diluted 1 to 45 times with 151403.doc •35· 201121558 The resulting influenza virus dilution 〇8〇孔)β On the other hand, the above-mentioned infectious medium (18 μμΐ^/well) was added to the wells of the upper 4 stages (Α~D column) of the 96-well culture plate. Further, in each of the upper and lower sections, the patchouli essential oil extract prepared by the example 溶解 dissolved in 10% methanol was added to each of the pore groups of the upper and lower sections. (Alcohol extract or n-hexane extract Or 丨〇% methanol (control 〇) as a positive control 'add 1 pg/mL of zanamivir e with 20 μ pupil, then 96 well at 3 rc and 3 rc The plate was cultured for 3 days. (2) Measurement of anti-influenza virus activity (2-1) Measurement of influenza virus amount Culture supernatant/month liquid (50 μ! 7 well) in each well of a 96-well culture plate cultured in the manner of the above (1) Transfer to each well of another % well microtiter plate under sterile conditions. Then, add PBS (5 〇 pL / well) and 〇 "mMi4 methyl umbelliferone - N · acetaminosamine (4 MU_NeuAc) aqueous solution (5 / / hole) and immediately use the culture plate feeder (plate Mixer) After mixing, use Fluoroskan (Daichi Sumitomo Pharmaceutical Co., Ltd.) to make it at 37 <>c The reaction was 10 knives. The slope of the enzyme reaction curve determined by the fluorescence intensity (excitation wavelength: 355 nm, measurement wavelength: 460 nm) showing the influenza virus sialidase activity in the reaction time was measured under Kinetics mode (Kinetics m〇dei) Use software: Delta soft 3). The relative influenza virus value in the culture supernatant of each well was calculated by the following calculation formula. Influenza virus value of the culture supernatant In the above formula, Α indicates the sialidase activity in the culture supernatant in the presence of influenza virus when the extract of patchouli oil is added (Enzyme reaction curve 151403.doc -36 - 201121558) Slope) 'B indicates the sialidase activity in the culture supernatant in the presence of influenza virus without the addition of patchouli essential oil extract (slope of the enzyme reaction curve), c indicates the flu without the addition of patchouli essential oil extract The sialidase activity in the culture supernatant in the absence of virus (no test sample added, background). Further, from the line of the dose-influenza virus sialidase activity, the inhibitory concentration (IC5 〇) of the extract of the essential oil of the genus eucalyptus oil against the proliferation of the influenza virus was calculated. The above measurement results are shown in Table 1 below. (2-2) Measurement of Survival Rate of MDCK Cells in the Presence of Influenza Virus: The culture supernatant of the 96-well culture plate cultured in the manner of the above (1) was removed, and then PBS (200 μί/well) was used. The MDCK cells on the culture plate were washed once. In the culture plate, 3_(45 dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) 2 PBS solution (1 mg/mL) was added at 1 μμ£/well. After incubation for 2 hours at 37 ° C under 5% C 〇 2 conditions, the MTT solution was removed by aspirator suction. Further, 〇〇4N-containing isopropyl alcohol (100 pL/well) containing 〇〇4 N was added to the culture plate, and the mixture was stirred and mixed on a plate stirrer to dissolve the produced formazan, and then purified water was added thereto (丨〇〇pL/hole) and stir gently. The absorbance of the reaction solution was measured using a microplate analyzer (Japan Sumitomo Pharmaceutical Co., Ltd.) as an indicator of the number of anti-cells (measurement wavelength: 570 nm, compensation wavelength: 630 nm). Survival of MDCK cells The rate (MTT method) is calculated by the following formula: MDCK cell survival rate (%) = (Α / Β) χ 1 〇〇 where Α indicates the addition of patchouli oil extract in the presence of influenza virus 151403.doc -37· 201121558 Absorbance in the case of taking the object, B is the absorbance in the absence of the patch extract of the patchouli essential oil in the absence of influenza virus. The results obtained are shown in the following table i. -3) Test for cytotoxicity of patchouli essential oil extract In the absence of influenza virus, the extract of patchouli essential oil prepared in Example 1 under the same conditions as above (alcohol extract of patchouli or ginseng) After the MDCK cells were cultured in the presence or absence of the alkane extract, the number of sputum cells (the number of remaining MDCK cells) was determined by the MTT method according to the method of (2-2) above. Absorbance. Then, by Calculate the mortality of MDCK cells in the absence of influenza virus and in the presence of patchouli essential oil extract, ie the cytotoxicity of patchouli essential oil extract. Cytotoxicity of patchouli essential oil extract on MDCK cells (%) =(A_ Β)/Αχ100 where A represents the absorbance in the case where the patchouli essential oil extract is not added, and B represents the absorbance in the case where the patchouli essential oil extract is added. (3) Patchouli essential oil Anti-influenza activity and cytotoxicity of the extract The anti-influenza activity and cytotoxicity of the extract of the patchouli essential oil (the extract of patchouli alcohol and n-hexane extract) obtained in the above manner are as follows: 0 151403.doc • 38· 201121558 [Table i] Anti-influenza activity of MDCK cells of patchouli alcohol extract and n-hexane extract, and direct cytotoxicity of the extract against MDCK cells Anti-influenza virus active virus in the absence of MDCK Cell cytotoxicity (%) Influenza virus value (%) MDCK cell survival rate in the presence of virus (%) Patchouli alcohol extract (10 pg/mL) 0.2 97.5 -12.0~~~ Patchouli sinensis extraction (10 pg/mL) 0.1 76.1 10.0 Zanamivir (1 pg/mL) 0.1 to 0.3 112.9 to 113.3 -29.4 to 25.5 ----- In the table, zanamivir is known to have anti-influenza activity. The compound was used as a positive control for the user. As shown in Table 1, it was confirmed that the alcohol extract of patchouli and the n-hexane extract showed almost no cytotoxicity, and showed anti-influenza which significantly inhibited the proliferation of influenza virus. The virus is active and therefore can be used as an anti-influenza agent. [Example 3] Evaluation of anti-influenza virus activity of patchouli alcohol 10% of non-activated fetal bovine serum, penicillin (200 units of streptomycin (0.2 mg/mL) solution and amphotericin B (5 pg/) were added. mL) of Madin-Darby dog kidney (MDCK) cell suspension (3xl05 cells/mL) in MEM medium (20 mL) was dispensed into 6-well culture plates (2 mL/well) at 5% The culture supernatant of the cultured MDCK cells in the fused 6-well culture plate was removed under C〇2 conditions and cultured at 37 ° C for 2 to 4 days until 151403.doc -39 - 201121558, and PBS (2) was used. MDCK cells were washed once in mL/well. After washing, the influenza virus dilution (A/Puerto Rico/8/32'HlNl subtype prepared in the same manner as in Example 2 was added at 100 pL/well in each well. , 1〇3·7-fold dilution), cultured for 3 〇 at 37 ° C under 5% C〇2. Add 2 mL/well to the multi-layer agar medium (126 mL) in each well. A test sample solution prepared by adding a solution of patchouli alcohol (refer to Example 丨) diluted with ίο% methanol (14 mL) was allowed to stand at room temperature until the agar solidified. Further, the culture plate was inverted, and cultured under the conditions of 5% 2 C 〇 2 and under the armpit for 3 days. Further, the test was carried out in the same manner as above except that water was added instead of the test sample solution (in the presence of influenza virus) In addition, except for adding 1% by mole of methanol instead of the test sample solution, the test was carried out in the same manner as above as a negative control, and in addition to the test sample solution, Zanamid was added. In addition to the aqueous solution of Wei, the test was carried out in the same manner as above as a positive control. Then, the 6-well culture plate was reduced above and below, and the staining agar medium was superimposed on each well [to a 2-fold concentration of MEM medium (2 mL) Add 〇·1°/. neutral red aqueous solution (4 mL), and add agar medium (prepared by adding 16 mL of water for injection to 〇32 g agar)] (1 mL/well) And the mixture was allowed to stand at room temperature until the agar was solidified. Further, the plate was inverted and cultured under 5% of C 2 conditions at 37 t: for 9 minutes, and visually observed as unstained spots. of The number of dead cells (spots) was determined. One of the results is shown in Fig. 1. As shown in Fig. 1, in the evaluation based on the visual count, it was shown that the case where the patchoulol was not added (control) was set as At 100%, patchouli alcohol can reduce the number of cells (spots) of 151403.doc • 40· 201121558 to about 25%. Also, 'for the sample that forms spots in the same way and counts the number of spots, by the following calculation The formula calculates the anti-influenza virus activity with respect to the relative value (%) of the number of spots of the control. The relative value of the number of spots (%) = (A / B) xl 〇〇 where Α indicates the average number of spots in the presence of scented scented scented scented alcohol, and B indicates that the presence of influenza virus is not added The average number of spots in the case of musk alcohol. An example of the result is shown in Fig. 2 . As shown in Fig. 2, in the evaluation of the relative value (%) of the number of spots, it was shown that when the number of dead cells in the case where the patchoulol was not added (control) was set to 1%, the patchouli alcohol was Reduce the number of dead cells (spots) to about 40 〇 / 〇. The difference between the results of Fig. 1 and Fig. 2 is caused by an experimental error of about 20% which usually occurs in the spot formation method. Both the results shown in Fig. 2 and Fig. 2 show that the number of dead cells (spots) can be successfully reduced significantly. In addition, the 50% inhibitory concentration of patchouli alcohol against influenza virus proliferation was calculated by the curve of the relative amount of sample-spot number shown in Fig. 2 (50% inhibitory concentration of 1C5 scented alcohol on influenza virus proliferation (IC5〇) It is 639 pg/mL. According to the above results, since patchouli alcohol exhibits anti-influenza activity which can significantly inhibit the proliferation of influenza virus, it can be used as an anti-influenza virus agent. [Example 4] Patchouli alcohol against influenza The valerase activity of the virus sialidase is known in the industry. In the process of infection of influenza virus, the sialidase from the virus plays an important role in the budding process of the virus, so it was developed to use the 151403.doc •41 - 201121558 The enzyme is used as a target for the anti-influenza virus zanamivir and oseltamivir. Therefore, in order to study whether the patchoulol of the present invention acts on the target molecule in the same manner as the known anti-influenza virus, the evaluation is wide. Inhibitory activity of muscarinic alcohol on sialidase activity of influenza virus. First, after adding PBS (90 μί/well) to a 96-well microtiter plate, add 10% of patchouli alcohol (10 pL/well). //. sterol solution, and influenza vaccine containing sialidase from influenza virus as viral protein antigen (A/New Caledonia/20/99 'H1N1 subtype, 50 pL/well), stirred with a culture plate stirrer Thereafter, the mixture was incubated at room temperature for 30 minutes, and a 1 mM aqueous solution of 4 MU-NeuAc (50 pL/well) was added to the reaction solution, and immediately stirred with a plate stirrer, and then Fluoroskan (a large Japanese Sumitomo Pharmaceutical Co., Ltd. limited) was used. The company was allowed to react for 10 minutes at 37 C. The change in fluorescence intensity (excitation wavelength: 355 nm, measurement wavelength: 460 nm) during the reaction time was measured in a kinetic mode, thereby calculating the slope of the enzyme reaction curve. Sialidase activity (using software: Delta soft 3) Next, the relative sialidase activity of the influenza virus was calculated by the following calculation formula.

相對唾液酸酶活性WXA/BhWO 式中，A表示添加有試驗樣品之情形時之螢光強度曲線 之斜率，B表示未添加有試驗樣品之情形時之螢光強度曲 線之斜率。 將所算出之結果示於表2。 151403.doc -42- 201121558 [表2] 廣藿香醇對A型流感病毒唾液酶活性之影響 濃度(Pg/mL) (廣藿香醇/紮那米 韋） _ 相對唾液酸酶活性(0/〇) 對照=100.0(%) 廣藿香醇 紮那米韋 0.015625 11.9 • 0.03125 4.5 — 0.0625 2.8 • 0.125 1.9 _ 0.25 -0.2 通 0.5 0.2 - 1.0 -0.4 15.6 102.7 31.25 97.4 62.5 98.7 125.0 101.4 . 250.0 96.5 . 500.0 99.7 1000.0 101.6 - -:未測定 如表2所示，即便以較顯示抗病毒活性之濃度進而高3〇 倍以上之濃度即I5.6〜1〇〇〇 kg/mL之濃度的用量添加廣藿 香醇，亦完全未對病毒唾液酸酶活性產生影響。因此，可 知廣藿香醇之抗流感病毒活性並非基於唾液酸酶抑制作 用。 [配方例] 以下，揭示含有本發明之抗流感病毒劑之化妝料、醫藥 151403.doc •43· 201121558 品、食品等之配方例。 (配方例1)敷劑 分別將以下之A相、B相、C相均勻地溶解之後，向A相 中添加B相並溶解，繼而添加C相並均勻地溶解而製造敷 劑0 (成分） (質量％) (A相)二丙二醇 5.0% 聚氧乙烯氫化蓖麻油 5.0% (B相)橄欖油 5.0% 乙酸生育酚酯 0.2% 對羥基苯甲酸酯 0.2% (C相)聚乙烯醇 13.0% 抗流感病毒劑#1) 0.2% 乙醇 7.0% 花香香料 0.05% 純化水 剩餘部分 合計 100.0% * 1):使用廣藿香醇作為抗流感病毒劑（以下相同）。 (配方例2)固形粉底 利用攪拌器將下述成分（1)〜(7)均勻地混合，向其中添加 (8)〜（13)，進行充分地混練而製造固形粉底。 151403.doc • 44· 201121558 (成分） (質量％) (1)滑石粉 42.4% (2)高嶺土 15.7% (3)絹雲母 10.3% (4)鋅白 7.0% (5)二氧化鈦 3.8% (6)氧化鐵黃 2.8% ⑺氧化鐵黑 0.3% (7)氧化鐵黑 0.3% (8)角鯊烧 8.0% (9)異硬脂酸 4.0% (10)聚氧乙烯山梨糖醇酐單油酸酯 3.1% (11)辛酸異鯨蠟基酯 2.0% (12)花香香料 0.1% (13)抗流感病毒劑％ 0.2% 合計 100.0% *2):使用來自廣藿香之醇萃取物作為抗流感病毒劑（以 下相同）。 (配方例3)肥皂 使用下述成分並藉由常法製造肥皂。 151403.doc -45 - 201121558 (成分） (質量％) (1)肥皂生坯 53.2% (2)只夕 口一/1/ 19.4% (3)花香之未加工香料 0.25% (4)抗流感病毒劑#3) 0.2% (5)還原蜂蜜液 0.25% (6)濃甘油 6.5% (7)羥基亞乙基二膦酸 0.15% (8)純化水 剩餘部分 合計 100.0% *3):使用來自廣藿香之精油萃取物作為抗流感病毒劑 (以下相同）。 (配方例4)洗髮精 將下述成分加熱並均勻地混合而製造洗髮精。 (成分） (質量％) (1)N-椰子油脂肪酸麩胺酸三乙醇胺 25.0% (2)月桂酸二乙醇醯胺 5.0% (3)肉豆蔻酸鉀 5.0% (4)二硬脂酸乙二醇酯 2.0% (5)聚乙二醇4〇0 15.0% (6)甘油 1.0% (7)抗流感病毒劑 0.1% (8)抗流感病毒劑#3) 0.1% (9)氯二曱酚 0.1% (10)維生素E 0.1% (11)對羥基苯甲酸酯 0.2% (12)花香香料 0.3% (13)純化水 剩餘部分 合計 100.0% 151403.doc -46- 201121558 (配方例5)潔面凝膠 將下述成分（1)〜(3)於70°C下加熱溶解而形成A液，另將 (4)〜（7)及（9)於70°C下加熱溶解而形成B液之後，向A液中 添加B液並攪拌均勻。一面攪拌一面冷卻至50°C，添加成 分（8)而製造潔面凝膠。 (成分） (質量％) (1)六聚甘油單肉豆證酸醋 20.0% (2)液態石躐 59.7% (3)對羥基苯甲酸酯 0.3% (4)抗流感病毒劑 0.075% (5)抗流感病毒劑％ 0.075% (6)濃甘油 5.9% (7)山梨糖醇 5.0% ⑻香料 0.1% (9)純化水 剩餘部分 合計 100.0% (配方例6)化妝水 將下述成分（5)〜（8)混合溶解而形成A液。另外，將下述 成分（1)〜(4)及（9)混合溶解而形成B液。將A液與B液均勻地 混合而製備化妝水。 151403.doc • 47- 201121558 (成分） (質量％) (1)榲棹籽萃取物 8.0% (2)甘油 3.0% (3)1，3-丁二醇 5.0% (4)抗流感病毒劑〜 0.15% (5)聚氧乙烯山梨糖醇酐月桂酸酯 1.2% (6)乙醇 5.0% (7)對羥基苯曱酸曱酯 0.2% (8)甜橘香料 0.1% (9)純化水 剩餘部分 合計 100.0% (配方例7)乳霜 將下述成分（1)〜（1〇)於75°C下加熱溶解而獲得A液，另將 下述成分（11)〜（15)於75°C下加熱溶解而獲得B液。向A液 中添加B液進行乳化，一面攪拌一 面冷卻至50°c，添加成 分（16)而製備乳霜。 (成分） (質量％) (1)蓖麻油 3.0% (2)角鯊烧 2.0% (3)曱基聚矽氧烷 0.5% (4)硬脂醇 0.5% (5)鯨蠟醇 0.5% (6)三(辛酸/癸酸)甘油酯 12.5% (7)單硬脂酸甘油酯 5.0% (8)單硬脂酸二甘油酯 1.5% 151403.doc • 48 · 201121558 (9)十聚甘油單硬脂酸酯 3.0% (10)對羥基苯甲酸丙酯 0.1% (11)三仙膠 0.1% (12)抗流感病毒劑+3) 0.05% (13)1,3-丁二醇 5.0% (14)對羥基苯甲酸曱酯 0.2% (15)花香香料 0.05% (16)純化水 剩餘部分 合計 100.0% (配方例8)乳液 將下述成分（1)〜（10)於75°C下加熱溶解而獲得Α液，另 下述成分（11)〜（14)及（16)於75°C下加熱溶解而獲得B液 向A液中添加B液進行乳化， 一面攪拌一面冷卻至50°c 添加成分（15)而製備乳液。 (成分） (質量％) (1)蓖麻油 1.0% (2)角鯊烧 2.0% (3)山蓊醇 1.0% (4)三(辛酸/癸酸)甘油酉旨 2.0% (5 )四甘油縮合亞油酸酉旨 0.1% (6)單油酸丙二醇 0.5% (7)單硬脂酸甘油酉旨 1.0% 151403.doc -49- 201121558 (8)六聚甘油單肉豆蔬酸酯 1.0% (9)十聚甘油單肉豆蔻酸酯 0.5% (10)對羥基苯甲酸丙酯 0.1% (11)榲棹籽萃取物 5.0% (12)抗流感病毒劑+3) 0.03% (13)1，3-丁二醇 3.0% (14)對羥基苯曱酸甲酯 0.1% (15)玫瑰香料 0.1% (16)純化水 剩餘部分 合計 100.0% (配方例9)浴用劑 使用下述成分，藉由常法製造浴用劑。 (成分） (質量％) (1)乾燥硫酸鈉 40.0% (2)碳酸氫鈉 57.5% (3)橄欖油 0.2% (4)抗流感病毒劑Μ) 0.1% (5)輕質矽酐 0.3% (6)花香香料 1.7% (7)黃色202號之乾燥硫酸鈉 0.2% 合計 100.0% 151403.doc -50- 201121558 (配方例10) 口香糖 藉由常法並利用捏合機對下述配方之成分進行混練，製 造口香糖。 (成分） (質量％) (1)碳酸鈣 5.0% (2)抗流感病毒劑” > 0.2% (3)原膠 31.8% (4)赤藻糖醇 10.0% (5)木糖醇 40.0% (6)麥芽糖醇 12.5% (7)水果香料 0.5% 合計 100.0% (配方例11)檸檬香料 藉由常法將下述配方之成分混合， 1並藉由常法製造檸檬 香料。 (成分） (質量％) (1)桉葉油 10.0% (2)大茴香腦 2.0% (3)擰檬油 1.0% (4)1-蓋醇 25.0% (5)1-香芹_ 25.0% (6)綠薄荷油 10.0% (7)抗流感病毒劑 0.02% (8)乙醇 剩餘部分 合計 100.0% 151403.doc -51 · 201121558 (配方例12) 口香糖 藉由常法並利用捏合機對下述配方之成分進行混練，製 造口香糖。 (成分） (質量％) (1)碳酸鈣 5.0% (2)抗流感病毒劑 0.2% (3)原膠 31.8% (4)赤藻糖醇 10.0% (5)木糖醇 40.0% (6)麥芽糖醇 12.5% ⑺配方例11之檸檬香料 0.5% 合計 100.0% (配方例13)糖果 藉由常法對下述配方之成分進行混練 ，並藉由常法製造 糖果。 (成分） (質量％) (1)抗流感病毒劑〜 0.2% (2)木糖醇 8.0% (3)麥芽糖醇 10.0% ⑷阿斯巴甜 0.1% (5)柑橘香料 0.2% ⑹異麥芽糖醇 剩餘部分 合計 100.0% 151403.doc -52- 201121558 (配方例14)薄荷香料 藉由常法將下述配方之成分混合，並藉由常法製造薄荷 香料。 (成分） (質量％) (1)胡椒薄荷油 20.0% (2)大茴香腦 6.0% (3)擰檬油 1.0% (4)綠薄荷油 10.0% (5)1-香芹酮 23.0% (6)抗流感病毒劑+1) 0.01% (7)1-堇醇 剩餘部分 合計 100.0% (配方例15)糖果 藉由常法對下述配方之成分進行混練 ，並藉由常法製造 糖果。 (成分） (質量％) (1)抗流感病毒劑 0.2% P)木糖醇 8.0% (3)麥芽糖醇 10.0% ⑷阿斯巴甜 0.1% (5)配方例14之薄荷香料 0.2% (6)異麥芽糖醇 剩餘部分 合計 100.0% 151403.doc •53- 201121558 (配方例16)牙膏 藉由常法將下述配方之成分混合，並藉由常法製造牙 膏。 (成分） (質量％) (1)填酸氫鈣 30.0% (2)甘油 10.0% (3)山梨糖醇 20.0% (4)羧曱基纖維素鈉 1.0% (5)月桂基硫酸鈉 1.5% (6)鹿角菜膠 0.5% (7)糖精鈉 0.1% (8)柑橘薄荷香料 1.0% (9)苯曱酸鈉 0.3% (10)抗流感病毒劑Φ1) 0.2% (11)純化水 剩餘部分 合計 100.0% (配方例17)牙膏 藉由常法將下述配方之成分混合， 並藉由常法製造牙 膏。 (成分） (質量％) (1)構酸氫鈣 30.0% (2)甘油 10.0% (3)山梨糖醇 20.0% (4)羧甲基纖維素鈉 1.0% (5)月桂基硫酸鈉 1.5% 151403.doc • 54· 201121558 ⑹鹿角菜膠 0.5% (7)糖精鈉 0.1% (8)配方例14之薄荷香料 1.0% (9)苯曱酸鈉 0.3% (10)純化水 剩餘部分 合計 100.0% (配方例18)滴鼻劑 藉由常法將下述配方之成分混合， 並藉由常法製造滴鼻 劑。 (成分） (質量％) (1)氣化苯二曱烴銨 0.01% (2)抗流感病毒劑#1) 0.2% (3)擰檬酸 適量 (4)檸檬酸鈉 適量 (5)D-山梨糖醇 適量 (6)純化水 剩餘部分 合計 100.0% (配方例19)洗鼻劑 藉由常法將下述配方之成分混合， 並藉由常法製造洗鼻 劑。 (成分） (質量％) (1)對羥基苯曱酸酯 0.08% (2)抗流感病毒劑+1) 0.2% (3)胡椒薄荷香料 0.1% (4)純化水 剩餘部分 合計 100.0% 151403.doc -55- 201121558 (配方例20)胡椒薄荷香料 藉由常法將下述配方之成分混合， 並藉由常法製造胡椒 薄荷香料。 (成分） (質量％) (1)水楊酸乙酯 10.0% (2)含柴魚乾之樹脂 1.0% (3)1-茧醇 30.0% (4)薄荷白油 5.0% (5)抗流感病毒劑#1) 0.01% (6)胡椒薄荷油 剩餘部分 合計 100.0% (配方例2 1)洗鼻劑 藉由常法將下述配方之成分混合， 並藉由常法製造洗鼻 劑。 (成分） (質量％) (1)對羥基苯甲酸酯 0.08% (2)配方例20之胡椒薄荷香料 0.12% (3)純化水 剩餘部分 合計 100.0% (配方例2 2 )漱口劑 藉由常法將下述配方之成分混合，並藉由常法製造漱口 劑0 151403.doc -56- 201121558 (成分） (質量％) (1)乙醇 14.0% (2)甘油 7.0% (3)SDS(十二烷基硫酸鈉） 6.0% (4)堇醇 0.5% (5)胡椒薄荷香料 0.5% (6)抗流感病毒劑〜 0.2% (7)純化水 剩餘部分 合計 100.0% (配方例23)漱口劑 藉由常法將下述配方之成分混合， 1並藉由常法製造漱口 劑。 (成分） (質量％) ⑴乙醇 14.0% (2)甘油 7.0% (3)SDS 6.0% (4)配方例20之胡椒薄荷香料 1.0% (5)純化水 剩餘部分 合計 100.0% (配方例24)漱口液 藉由常法將下述配方之成分混合，並藉由常法製造漱口 液。 151403.doc -57- 201121558 (成分） (質量％) (1)月桂基硫酸鈉 0.80% (2)月桂酸二乙醇醯胺 0.80% (3)甘油 12.0% (4)糖精鈉 0.2% (5)薄荷香料 0.80% (6)精胺酸 0.10% (7)填酸氫二鈉 0.50% (8)填酸氫二鉀 0.08% (9)抗流感病毒劑 0.2% (10)純化水 剩餘部分 合計 100.0% (配方例25)漱口液 藉由常法將下述配方之成分混合， 1並藉由常法製造漱口 液。 (成分） (質量％) (1)月桂基硫酸鈉 0.80% (2)月桂酸二乙醇醯胺 0.80% (3)甘油 12.0% (4)糖精鈉 0.2% (5)配方例14之薄荷香料 0.80% (6)精胺酸 0.10% (7)填酸氫二鈉 0.50% (8)填酸氫二鉀 0.08% (9)純化水 剩餘部分 合計 100.0% 151403.doc -58 - 201121558 (配方例2 6 )食品•旋劑 藉由常法將下述配方之成分混合，並藉由常法製造食 品·鍵劑。 (成分） (質量％) ⑴澱粉 98.5% (2)薄荷粉末香料 0.8% (3)蔗糖脂肪酸酯 0.5% (4)抗流感病毒劑+1) 0.2% 合計 100.0% (配方例27)薄荷粉末香料 藉由常法將下述配方之成分混合， 並藉由常法製造薄荷 粉末香料。 (成分） (質量％) (1)胡椒薄荷油 10.0% (2)抗流感病毒劑 0.05% (3)阿拉伯膠 30.0% ⑷糊精 剩餘部分 合計 100.0% (配方例28)食品•錠劑 藉由常法將下述配方之成分混合，並藉由常法製造食 品·鍵劑。 151403.doc -59- 201121558 (成分） (質量％) (1)澱粉 98.7% (2)配方例27之薄荷粉末香料 0.8% (3)蔗糖脂肪酸酯 0.5% 合計 100.0% (配方例29)含果汁之飲料 藉由常法將下述配方之成分混合，並藉由常法製造含果 汁之飲料。 (成分） (質量％) (1)橘子水(糖度(Brix) : 10.8，酸度:0.38)果糖葡萄糖液糖 10.7% (2)檸檬酸 0.1% (3)檸檬酸鈉 0.03% (4)橘子濃縮果汁 5.2% (5)橘子香料 0.1% (6)CCF溶液 0.01% (7)抗流感病毒劑+1) 0.02% ⑻純化水 剩餘部分 合計 100.0% (配方例30)橘子香料 藉由常法將下述配方之成分混合，並藉由常法製造橘子 香料。 151403.doc •60- 201121558 (成分） (質量％) (1)大茴香腦 2.0% (2)桉葉油 10.0% (3)橘子油 1.0% (4)1-香芹酮 25.0% (5)1-蓋醇 25.0% (6)綠薄荷油 10.0% (7)抗流感病毒劑 0.02% (8)乙醇 剩餘部分 合計 100.0% (配方例31)含果汁之飲料 藉由常法將下述配方之成分混合，並藉由常法製造含果 汁之飲料。 (成分） (質量％) ⑴橘子水(糖度(Brix) : 10.8，酸度:0.38)果糖葡萄糖液糖 10.7% (2)檸檬酸 0.1% (3)檸檬酸鈉 0.03% (4)橘子濃縮果汁 5.2% (5)配方例30之橘子香料 0.1% (6)CCF溶液 0.01% (7)純化水 剩餘部分 合計 100.0% (配方例32)運動飲料 藉由常法將下述配方之成分混合，並藉由常法製造運動 飲料。 151403.doc •61 - 201121558 (成分） (質量％) ⑴砂糖 3.1% (2)葡萄糖 1.57% (3)檸檬酸 0.1% (4)乳酸鈣 0.0679% (5)擰檬酸鈉 0.03% (6)氯化納 0.028% (7)氣化鉀 0.022% (8)維生素C 0.0864% (9)L-麩胺酸鈉 0.003% (10)於驗酸 0.0013% (11)泛酸鈉 0.0007% (12)維生素B6 0.00022% (13)維生素B12 〇.〇〇〇〇〇〇6% (14)檸檬香料 0.1% (15)CCMF 溶液 0.01% (16)抗流感病毒劑〜 0.02% (17)純化水 剩餘部分 合計 100.0% (配方例3 3 )運動飲料 藉由常法將下述配方之成分混合，並藉由常法製造運動 飲料。 151403.doc -62- 201121558 (成分） (質量％) ⑴砂糖 3.1% (2)葡萄糖 1.57% (3)擰檬酸 0.1% (4)乳酸鈣 0.0679% (5)檸檬酸鈉 0.03% (6)氣化鈉 0.028% ⑺氯化鉀 0.022% (8)維生素C 0.0864% (9)L-麩胺酸鈉 0.003% (10)於驗酸 0.0013% (11)泛酸鈉 0.0007% (12)維生素B6 0.00022% (13)維生素B12 〇.〇〇〇〇〇〇6% (14)配方例11之檸檬香料 0.1% (15)CCMF 溶液 0.01% (16)抗流感病毒劑”] 0.02% (17)純化水 剩餘部分 合計 100.0% 產業上之可利用性 廣藿香醇及廣藿香之油性萃取物顯示出抗流感病毒活 性，並且為自天然化合物衍生之化合物，安全性亦較高， 因此含有本發明之廣藿香醇及/或廣藿香萃取物之抗流感 病毒劑不僅可用作流感之預防或治療藥，而且可用於製造 流感之預防或治療用準藥品及飲食品。本發明之抗流感病 151403.doc -63- 201121558 毒劑對流感病毒傳染本身及/或由該傳染病引起之發熱、 惡寒、關節疼痛等各種症狀、病情之預防或治療有用。 本說明書中引用之全部出版物、專利及專利申請案係藉 由引用而將其全文併入於本說明書中。 【圖式簡單說明】 圖1係表示根據利用斑點形成法計數之流感病毒傳染 MDCK細胞數（斑點數），評價廣藿香醇之抗流感病毒活性 之結果之圖。圖中之紮那米韋為已知之具有抗流感病毒活 性之藥劑’其係作為陽性對照使用。 圖2係將廣着香醇之抗流感病毒活性以相對於對照品之 斑點數相對值（〇/〇)示於圖中之圖。橫轴表示廣藿香醇或紮 那米韋之濃度，縱轴表示相對於對照品（流感病毒存在 下，代替廣藿香醇而添加相同量之1〇%曱醇水溶液）之斑點 數相對值黑色圓表示添加廣藿香醇之結果，白色圓 表示添加紮那米韋之結果。 151403.doc • 64·Relative sialidase activity WXA/BhWO wherein A represents the slope of the fluorescence intensity curve when the test sample is added, and B represents the slope of the fluorescence intensity curve when the test sample is not added. The calculated results are shown in Table 2. 151403.doc -42- 201121558 [Table 2] Effect of patchouli alcohol on salivary activity of influenza A virus (Pg/mL) (Pallanol/zanamivir) _ Relative sialidase activity (0/〇 Control = 100.0 (%) Patcholine zanamivir 0.015625 11.9 • 0.03125 4.5 — 0.0625 2.8 • 0.125 1.9 _ 0.25 -0.2 Pass 0.5 0.2 - 1.0 -0.4 15.6 102.7 31.25 97.4 62.5 98.7 125.0 101.4 . 250.0 96.5 . 500.0 99.7 1000.0 101.6 - -: Not determined As shown in Table 2, the patchouli alcohol was added at a concentration higher than the concentration showing the antiviral activity and further 3 times higher than the concentration of I5.6 to 1 〇〇〇 kg/mL. There was also no effect on viral sialidase activity at all. Therefore, it is known that the anti-influenza virus activity of patchouli alcohol is not based on sialidase inhibition. [Formulation Example] Hereinafter, a formulation example containing the anti-influenza agent-containing cosmetic of the present invention, medicine 151403.doc, 43·201121558, food, and the like will be disclosed. (Formulation Example 1) The coating agent is uniformly dissolved in the following A phase, B phase, and C phase, and then phase B is added to the phase A and dissolved, and then the phase C is added and uniformly dissolved to prepare a coating agent 0 (component). (% by mass) (A phase) dipropylene glycol 5.0% polyoxyethylene hydrogenated castor oil 5.0% (phase B) olive oil 5.0% tocopheryl acetate 0.2% p-hydroxybenzoate 0.2% (C phase) polyvinyl alcohol 13.0 % Anti-influenza virus #1) 0.2% Ethanol 7.0% Floral fragrance 0.05% The remaining portion of purified water is 100.0% in total * 1): Patchouli alcohol is used as an anti-influenza virus agent (the same applies hereinafter). (Formulation Example 2) Solid Foundation The following components (1) to (7) were uniformly mixed by a stirrer, and (8) to (13) were added thereto, and sufficiently kneaded to obtain a solid foundation. 151403.doc • 44· 201121558 (ingredient) (% by mass) (1) talc powder 42.4% (2) kaolin 15.7% (3) sericite 10.3% (4) zinc white 7.0% (5) titanium dioxide 3.8% (6) Iron oxide yellow 2.8% (7) Iron oxide black 0.3% (7) Iron oxide black 0.3% (8) Squalene burning 8.0% (9) Isostearic acid 4.0% (10) Polyoxyethylene sorbitan monooleate 3.1% (11) Isocetyl octanoate 2.0% (12) Floral fragrance 0.1% (13) Anti-influenza agent% 0.2% Total 100.0% *2): Use alcohol extract from patchouli as an anti-influenza virus Agent (the same below). (Formulation Example 3) Soap The soap was produced by the usual method using the following ingredients. 151403.doc -45 - 201121558 (Ingredient) (% by mass) (1) Soap greens 53.2% (2) 夕口一/1/ 19.4% (3) Floral unprocessed spices 0.25% (4) Anti-influenza virus Agent #3) 0.2% (5) Reduced honey liquid 0.25% (6) Concentrated glycerin 6.5% (7) Hydroxyethylene diphosphonic acid 0.15% (8) Total remaining part of purified water 100.0% *3): Use from wide The essential oil extract of Musk is used as an anti-influenza virus agent (the same applies hereinafter). (Formulation Example 4) Shampoo The following ingredients were heated and uniformly mixed to prepare a shampoo. (Component) (% by mass) (1) N-coconut oil fatty acid glutamic acid triethanolamine 25.0% (2) lauric acid diethanol decylamine 5.0% (3) potassium myristate 5.0% (4) distearate B Glycol ester 2.0% (5) Polyethylene glycol 4〇0 15.0% (6) Glycerin 1.0% (7) Anti-influenza virus 0.1% (8) Anti-influenza virus #3) 0.1% (9) Chlorodiquinone Phenol 0.1% (10) Vitamin E 0.1% (11) Paraben 0.2% (12) Floral Fragrance 0.3% (13) Total remaining water of purified water 100.0% 151403.doc -46- 201121558 (Formulation 5) Cleansing gel The following components (1) to (3) are heated and dissolved at 70 ° C to form liquid A, and (4) to (7) and (9) are heated and dissolved at 70 ° C to form liquid B. Thereafter, the liquid B was added to the liquid A and stirred uniformly. The mixture was cooled to 50 ° C while stirring, and a component (8) was added to prepare a cleansing gel. (Ingredient) (% by mass) (1) Hexaglycerol single meat bean vinegar 20.0% (2) Liquid sarcophagus 59.7% (3) Parahydroxybenzoate 0.3% (4) Anti-influenza virus 0.075% ( 5) Anti-influenza virus% 0.075% (6) Concentrated glycerin 5.9% (7) Sorbitol 5.0% (8) Perfume 0.1% (9) The remaining portion of purified water is 100.0% in total (Formulation 6) The lotion will have the following ingredients ( 5) ~ (8) mixed and dissolved to form liquid A. Further, the following components (1) to (4) and (9) were mixed and dissolved to form a liquid B. A lotion was prepared by uniformly mixing the A liquid and the B liquid. 151403.doc • 47- 201121558 (ingredients) (% by mass) (1) 榲棹 seed extract 8.0% (2) glycerin 3.0% (3) 1,3-butanediol 5.0% (4) anti-influenza agent~ 0.15% (5) Polyoxyethylene sorbitan laurate 1.2% (6) Ethanol 5.0% (7) Oxime phthalate 0.2% (8) Sweet orange flavor 0.1% (9) The remaining part of purified water 100.0% in total (Formulation Example 7) Cream The following components (1) to (1) were heated and dissolved at 75 ° C to obtain solution A, and the following components (11) to (15) were further added at 75 ° C. The solution B was obtained by heating under heat. The liquid B was added to the liquid A to be emulsified, and the mixture was cooled to 50 ° C while stirring, and the component (16) was added to prepare a cream. (Ingredient) (% by mass) (1) Castor oil 3.0% (2) Sharks burn 2.0% (3) Mercapto polyoxyalkylene 0.5% (4) Stearyl alcohol 0.5% (5) Cetyl alcohol 0.5% ( 6) Tris(octanoic acid/capric acid) glyceride 12.5% (7) glyceryl monostearate 5.0% (8) diglyceryl monostearate 1.5% 151403.doc • 48 · 201121558 (9) Decaglycerol single Stearate 3.0% (10) Propylparaben 0.1% (11) Sanxianjiao 0.1% (12) Anti-influenza virus +3) 0.05% (13) 1,3-butanediol 5.0% ( 14) Ethyl p-hydroxybenzoate 0.2% (15) Floral fragrance 0.05% (16) Total remaining portion of purified water 100.0% (Formulation 8) Emulsion The following components (1) to (10) were heated at 75 ° C. The solution is dissolved to obtain a mash, and the following components (11) to (14) and (16) are heated and dissolved at 75 ° C to obtain a liquid B. The liquid B is added to the liquid A to be emulsified, and the mixture is cooled to 50 ° C while stirring. The emulsion was prepared by adding the component (15). (Ingredient) (% by mass) (1) Castor oil 1.0% (2) Sharks burn 2.0% (3) Kaempferol 1.0% (4) Tris(octanoic acid/capric acid) glycerin 2.0% (5) Tetraglycerin Condensed linoleic acid 0.1 0.1% (6) glycerol monooleate 0.5% (7) glyceryl monostearate 1.0% 151403.doc -49- 201121558 (8) hexaglycerol mono-soybean acid 1.0% (9) Decaglycerol monomyristate 0.5% (10) Propylparaben 0.1% (11) Quercetin extract 5.0% (12) Anti-influenza agent +3) 0.03% (13)1 3-butanediol 3.0% (14) methyl p-hydroxybenzoate 0.1% (15) rose perfume 0.1% (16) 100.0% of the remaining portion of purified water (Formulation 9) Bathing agent The following ingredients were used. A bath agent is produced by a conventional method. (Component) (% by mass) (1) Dry sodium sulfate 40.0% (2) Sodium hydrogencarbonate 57.5% (3) Olive oil 0.2% (4) Anti-influenza virus Μ) 0.1% (5) Light phthalic anhydride 0.3% (6) Floral Fragrance 1.7% (7) Yellow Sodium Chloride No. 202 0.2% Total 100.0% 151403.doc -50- 201121558 (Formulation Example 10) Chewing gum The ingredients of the following formulations were prepared by a conventional method using a kneading machine. Mix and make chewing gum. (Component) (% by mass) (1) Calcium carbonate 5.0% (2) Anti-influenza virus agent > 0.2% (3) Raw gum 31.8% (4) Erythritol 10.0% (5) Xylitol 40.0% (6) Maltitol 12.5% (7) Fruit flavor 0.5% Total 100.0% (Formulation 11) Lemon flavor The ingredients of the following formula were mixed by a usual method, and a lemon flavor was produced by a usual method. (%) (1) eucalyptus oil 10.0% (2) aniseed brain 2.0% (3) lemon oil 1.0% (4) 1-galen 25.0% (5) 1-carnation _ 25.0% (6) green Peppermint oil 10.0% (7) Anti-influenza virus 0.02% (8) Total ethanol remaining 100.0% 151403.doc -51 · 201121558 (Formulation 12) Chewing gum The ingredients of the following formula were prepared by a conventional method using a kneading machine. Kneading, making chewing gum. (Ingredient) (% by mass) (1) 5.0% calcium carbonate (2) 0.2% anti-influenza virus (3) 31.8% original gum (4) erythritol 10.0% (5) Xylitol 40.0% (6) Maltitol 12.5% (7) Lemon flavor of Formulation Example 11 0.5% Total 100.0% (Formulation Example 13) Confectionery The ingredients of the following formula were kneaded by a usual method, and the confectionery was produced by the usual method. ) %) (1) anti-influenza agent ~ 0.2% (2) xylitol 8.0% (3) maltitol 10.0% (4) aspartame 0.1% (5) citrus flavor 0.2% (6) the remaining part of isomalt total 100.0% 151403.doc -52- 201121558 (Formulation Example 14) Mint Flavor The ingredients of the following formula are mixed by a conventional method, and a mint flavor is produced by a conventional method. (Component) (% by mass) (1) Peppermint oil 20.0% (2) Aniseed brain 6.0% (3) Lemon oil 1.0% (4) Spearmint oil 10.0% (5) 1-carvone 23.0% (6) Anti-influenza agent +1) 0.01% (7)1 - A total of 100.0% of the remainder of the sterol (Formulation Example 15) The confectionery was kneaded by the usual method, and the confectionery was produced by a conventional method. (Ingredient) (% by mass) (1) Anti-influenza virus agent 0.2 % P) xylitol 8.0% (3) maltitol 10.0% (4) aspartame 0.1% (5) Mint Spice 0.2% of Formulation Example 14 (6) Total amount of isomaltol total 100.0% 151403.doc • 53- 201121558 (Formulation Example 16) Toothpaste The ingredients of the following formulas were mixed by a usual method, and toothpaste was produced by a usual method. (Component) (% by mass) (1) Calcium hydrogenate 30.0% (2) Glycerol 10.0% (3) Sorbitol 20.0% (4) Carboxymethyl cellulose sodium 1.0% (5) Sodium lauryl sulfate 1.5% (6) Carrageenan 0.5% (7) Sodium saccharin 0.1% (8) Citrus mint spice 1.0% (9) Sodium benzoate 0.3% (10) Anti-influenza virus Φ1) 0.2% (11) Remaining part of purified water A total of 100.0% (Formulation Example 17) Toothpaste The ingredients of the following formulations were mixed by a usual method, and toothpaste was produced by a usual method. (Component) (% by mass) (1) Calcium hydrogenate 30.0% (2) Glycerol 10.0% (3) Sorbitol 20.0% (4) Carboxymethylcellulose sodium 1.0% (5) Sodium lauryl sulfate 1.5% 151403.doc • 54· 201121558 (6) Carrageenan 0.5% (7) Sodium saccharin 0.1% (8) Mint spice 1.0% of formula 14 (9) Sodium benzoate 0.3% (10) Total remaining part of purified water 100.0% (Formulation Example 18) Nasal Drops The ingredients of the following formulations were mixed by a usual method, and nasal drops were produced by a usual method. (Component) (% by mass) (1) Gasified benzodiazepine ammonium 0.01% (2) Anti-influenza virus #1) 0.2% (3) Molybdenum amount (4) Sodium citrate (5) D- Appropriate amount of sorbitol (6) Total remaining portion of purified water 100.0% (Formulation 19) Nasalizing agent The ingredients of the following formulations were mixed by a usual method, and a nasal wash was prepared by a usual method. (Component) (% by mass) (1) p-hydroxybenzoic acid ester 0.08% (2) anti-influenza virus agent +1) 0.2% (3) peppermint flavor 0.1% (4) total remaining portion of purified water 100.0% 151403. Doc-55-201121558 (Formulation Example 20) Peppermint Spice The ingredients of the following formula are mixed by a usual method, and peppermint flavor is produced by a usual method. (Component) (% by mass) (1) Ethyl salicylate 10.0% (2) Resin containing dried fish 1.0% (3) 1-decyl alcohol 30.0% (4) Mint white oil 5.0% (5) Anti-flu Viral Agent #1) 0.01% (6) Total 100.0% of the remainder of the peppermint oil (Formulation Example 2 1) Nasalizing agent The ingredients of the following formulations were mixed by a usual method, and a nasal wash was prepared by a usual method. (Component) (% by mass) (1) p-hydroxybenzoic acid ester 0.08% (2) Formulation Example 20 peppermint flavor 0.12% (3) Total amount of purified water remaining 100.0% (Formulation Example 2 2) Mouthwash The ingredients of the following formulas are mixed by a conventional method, and a mouthwash is produced by a conventional method. 0 151403.doc -56- 201121558 (ingredient) (% by mass) (1) 14.0% of ethanol (2) 7.0% of glycerol (3) SDS (sodium lauryl sulfate) 6.0% (4) sterol 0.5% (5) Peppermint spice 0.5% (6) Anti-influenza virus ~ 0.2% (7) Total remaining portion of purified water 100.0% (Formulation 23 The mouthwash is prepared by mixing the ingredients of the following formula by a conventional method, and a mouthwash is produced by a usual method. (Component) (% by mass) (1) Ethanol 14.0% (2) Glycerol 7.0% (3) SDS 6.0% (4) Peppermint spice 1.0% of Formulation Example 20 (5) Total remaining part of purified water 100.0% (Formulation Example 24) The mouthwash is mixed by the usual method, and the mouthwash is produced by a usual method. 151403.doc -57- 201121558 (Ingredient) (% by mass) (1) Sodium lauryl sulfate 0.80% (2) 0.80% lauric acid diethanolamine (3) Glycerin 12.0% (4) Sodium saccharin 0.2% (5) Mint spice 0.80% (6) arginine 0.10% (7) disodium hydrogenate 0.50% (8) dipotassium hydrogenate 0.08% (9) anti-influenza agent 0.2% (10) purified water remaining part total 100.0 % (Formulation Example 25) Mouthwash The ingredients of the following formulations were mixed by a usual method, and a mouthwash was produced by a usual method. (Component) (% by mass) (1) Sodium lauryl sulfate 0.80% (2) 0.80% of lauric acid diethanolamine (3) Glycerin 12.0% (4) Sodium saccharin 0.2% (5) Mint flavor of formula 14 0.80 % (6) arginine 0.10% (7) disodium hydrogenate 0.50% (8) dipotassium hydrogenate 0.08% (9) the remaining part of purified water total 100.0% 151403.doc -58 - 201121558 (Formulation 2 6) Foods and Rotating Agents The ingredients of the following formulas are mixed by a usual method, and foods and keys are produced by a usual method. (Component) (% by mass) (1) Starch 98.5% (2) Peppermint powder flavor 0.8% (3) Sucrose fatty acid ester 0.5% (4) Anti-influenza virus agent +1) 0.2% Total 100.0% (Formulation 27) Peppermint powder The perfume is mixed with the ingredients of the following formula by a conventional method, and a mint powder flavor is produced by a usual method. (Ingredient) (% by mass) (1) Peppermint oil 10.0% (2) Anti-influenza virus 0.05% (3) Gum arabic 30.0% (4) Dextrin remaining 100.0% (Formulation 28) Foods and lozenges by A common method is to mix the ingredients of the following formula, and to manufacture a food-key agent by a conventional method. 151403.doc -59- 201121558 (Component) (% by mass) (1) Starch 98.7% (2) Mint powder flavor of Formulation Example 27 0.8% (3) Sucrose fatty acid ester 0.5% Total 100.0% (Formulation 29) The juice beverage is mixed with the ingredients of the following formula by a conventional method, and a juice-containing beverage is produced by a conventional method. (Component) (% by mass) (1) Orange water (Brix: 10.8, acidity: 0.38) Fructose glucose liquid sugar 10.7% (2) Citric acid 0.1% (3) Sodium citrate 0.03% (4) Orange concentrate Juice 5.2% (5) Orange spice 0.1% (6) CCF solution 0.01% (7) Anti-influenza agent +1) 0.02% (8) The remaining part of purified water is 100.0% (Formulation 30) Orange flavor is prescribed by the common method The ingredients of the formula are mixed and the orange flavor is produced by a conventional method. 151403.doc •60- 201121558 (Ingredient) (% by mass) (1) Aniseed brain 2.0% (2) Eucalyptus oil 10.0% (3) Orange oil 1.0% (4) 1-carvone 25.0% (5) 1-monanol 25.0% (6) Spearmint oil 10.0% (7) Anti-influenza virus 0.02% (8) Total ethanol remaining 100.0% (Formulation 31) Juice-containing beverage The following formula was prepared by the usual method. The ingredients are mixed and the juice-containing beverage is produced by a conventional method. (Component) (% by mass) (1) Orange water (Brix: 10.8, acidity: 0.38) Fructose glucose liquid sugar 10.7% (2) Citric acid 0.1% (3) Sodium citrate 0.03% (4) Orange juice concentrated juice 5.2 % (5) Formulation Example 30 Orange Spice 0.1% (6) CCF solution 0.01% (7) Total remaining portion of purified water 100.0% (Formulation 32) Sports drink The ingredients of the following formula were mixed by the usual method, and borrowed Sports drinks are made by conventional methods. 151403.doc •61 - 201121558 (Ingredient) (% by mass) (1) Sugar 3.1% (2) Glucose 1.57% (3) Citric acid 0.1% (4) Calcium lactate 0.0679% (5) Sodium citrate 0.03% (6) Chlorinated sodium 0.028% (7) Calcium carbonate 0.022% (8) Vitamin C 0.0864% (9) L-glutamate 0.003% (10) Acid test 0.0013% (11) Pantothenic acid 0.0007% (12) Vitamin B6 0.00022% (13) Vitamin B12 〇.〇〇〇〇〇〇6% (14) Lemon flavor 0.1% (15) CCMF solution 0.01% (16) Anti-influenza virus ~ 0.02% (17) Total amount of purified water remaining 100.0% (Formulation Example 3 3) Sports drink The ingredients of the following formula were mixed by a usual method, and a sports drink was produced by a usual method. 151403.doc -62- 201121558 (Ingredient) (% by mass) (1) Sugar 3.1% (2) Glucose 1.57% (3) Lemon acid 0.1% (4) Calcium lactate 0.0679% (5) Sodium citrate 0.03% (6) Gasification sodium 0.028% (7) Potassium chloride 0.022% (8) Vitamin C 0.0864% (9) L-glutamate 0.003% (10) Acid test 0.0013% (11) Pantothenic acid 0.0007% (12) Vitamin B6 0.00022 % (13) Vitamin B12 〇.〇〇〇〇〇〇6% (14) Formulation Example 11 Lemon Flavor 0.1% (15) CCMF solution 0.01% (16) Anti-influenza virus"] 0.02% (17) Purified water A total of 100.0% of the total industrially available oily extracts of patchouli and patchouli exhibit anti-influenza activity and are compounds derived from natural compounds, which are also highly safe and therefore contain a wide range of the present invention. The anti-influenza virus agent of muscadin and/or patchouli extract can be used not only as a prophylactic or therapeutic agent for influenza, but also as a quasi-drug and food or drink for the prevention or treatment of influenza. The anti-influenza disease of the present invention 151403. Doc -63- 201121558 Poisoning agent for influenza virus infection itself and / or fever, aversion to cold caused by the infectious disease All the symptoms, the prevention of the disease, or the treatment of the pain are useful. All the publications, patents, and patent applications cited in the specification are hereby incorporated by reference in their entirety in the specification. This is a graph showing the results of the anti-influenza activity of patchouli alcohol based on the number of MDCK cells (spots) of influenza virus infection counted by the speckle formation method. The zanamivir is known to have anti-influenza activity. The agent 'is used as a positive control. Figure 2 is a graph showing the relative anti-influenza activity of the broad-spectrum alcohol in the figure relative to the reference number of spots (〇 / 〇). The horizontal axis represents patchouli alcohol or The concentration of zanamivir, the vertical axis indicates the relative number of spots relative to the control (in the presence of influenza virus, the same amount of 1% sterol aqueous solution was added instead of patchool). The black circle indicates the result of adding patchouli alcohol. The white circle indicates the result of adding zanamivir. 151403.doc • 64·

Claims (1)

201121558 七 1. 2. 3. 4. 5. 6. 7. 、申請專利範圍： 1種抗流感病毒劑，其係包含廣藿香醇及/或廣藿香精油 萃取物作為有效成分者。 一種流感病毒傳染病之預防及/或治療用香料組合物，其 係含有如請求項1之抗流感病毒劑者。 一種流感病毒傳染病之預防及/或治療用之鼻腔或口腔投 予用組合物，其係含有如請求項丨之抗流感病毒劑或如 請求項2之香料組合物者。 一種流感病毒傳染病之預防及/或治療用醫藥製劑，其係 3有如求項1之抗流感病毒劑或如請求項2之香料組合 物者。 一種流感病毒傳染病之預防及/或治療用飲食品，其係含 有如β求項1之抗流感病毒劑或如請求項2之香料組合物 者。 一種流感病毒傳染病之預防及/或治療用香妝品，其係含 有如請求項1之抗流感病毒劑或如請求項2之香料組合物 者。 一種流感病毒傳染病之預防及/或治療用之日用·雜貨 品’其係含有如請求項1之抗流感病毒劑或如請求項2之 香料組合物者。 151403.doc201121558 VII 1. 2. 3. 4. 5. 6. 7. Scope of application: An anti-influenza virus agent containing as an active ingredient extracts of patchouli and/or patchouli essential oils. A perfume composition for preventing and/or treating influenza virus infectious diseases, which comprises the anti-influenza agent of claim 1. A nasal or oral administration composition for the prevention and/or treatment of an influenza virus infectious disease, which comprises the anti-influenza agent as claimed or the fragrance composition according to claim 2. A pharmaceutical preparation for the prevention and/or treatment of an influenza virus infectious disease, which is the anti-influenza agent of claim 1 or the fragrance composition of claim 2. A food or drink for the prevention and/or treatment of an influenza virus infectious disease, which comprises an anti-influenza virus agent such as β-item 1 or a flavoring composition according to claim 2. A cosmetic preparation for the prevention and/or treatment of an influenza virus infectious disease, which comprises the anti-influenza virus agent of claim 1 or the perfume composition of claim 2. A daily-use/groceries for the prevention and/or treatment of an influenza virus infectious disease, which comprises the anti-influenza virus agent of claim 1 or the perfume composition of claim 2. 151403.doc
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JP5871235B2 (en) * 2012-04-27 2016-03-01 高砂香料工業株式会社 6a, 7,7-Trimethyldecahydro-1,4-methanocyclopropa [de] naphthalen-1-ol
GB2506174A (en) 2012-09-24 2014-03-26 Wolfson Microelectronics Plc Protecting a MEMS device from excess pressure and shock
EP2925412B1 (en) 2012-12-03 2017-07-26 Colgate-Palmolive Company Compositions and methods for treating dental caries
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CN101485647B (en) * 2009-02-27 2013-04-24 东莞广州中医药大学中医药数理工程研究院 Use of patchouli alcohol in preparing medicament

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