TWI363621B

TWI363621B - Antiviral composition

Info

Publication number: TWI363621B
Application number: TW097109281A
Authority: TW
Inventors: Kunitomo Watanabe; Mamoru Kouketsu; Tsugiya Murayama; Yuuzou Tsuchida; Kotarou Tsuchida; Daisuke Sakurai; Mitsuo Kawabe
Original assignee: Yuuzou Tsuchida
Priority date: 2007-03-19
Filing date: 2008-03-17
Publication date: 2012-05-11
Also published as: TW200901954A

Description

1363621 •-九、發明說明：【發明所屬之技術領域】；本發明係有關抗病毒劑。【先前技術】病毒係無法自體繁殖而寄生增殖於動植物或細菌的極微小病原體，可分成動物病毒、植物病毒、微生物病毒。人類巨細胞病毒（human cytomegalovirus)之種特異性強，在源自人類之細胞以外者係不會增殖。增殖可使用人 ®類胎兒皮膚、肌肉、包皮、肺等各種初級培養細胞，或是 -MRC-5、WI-38等株化細胞（established cell)系。在感染細胞中可確認到核内包涵體（intranuclear inclusion body)(驗性）及細胞質内包涵體（cytoplasmic inclusion body)。經胎盤感染（垂直感染）而成為死胎、早產之原因，又引起先天性感染症（CID，亦即 cytomegalic inclusion disease，巨細胞包涵體症）。亦被視為後天性之感染症，此時，一般係經過 •不顯性感染（inapparent infection)後，潛伏感染之病毒因免疫抑制治療、類固醇激素之使用、以及愛滋病患或癌症病患等易感染性宿主而被活性化，引起肺炎、視網膜炎、大腸炎等嚴重之機會性感染症（opportunistic infection disease) ° 此等病毒引起之疾病之各種預防治療用抗病毒劑正在進行開發。例如已知有葛昔洛韋（Ganciclovir，亦即GCV)、西多夫韋（Cidofovir，亦即CDV)、膦曱酸（Foscarnet，亦即 PFA)、福米韋生（Fomivirsen)等。其中GCV係被廣泛使用， 5 320044 1363621 ••但近年來GCV耐藥性病毒係成為問題。另外，亦有副作用（細胞毒性）強之問題，故無副作用且具有對耐藥性病毒 ; 亦有效之抗病毒活性的藥劑係備受需求。 / 流感病毒（influenzavirus，亦稱為flu virus)係感染人類 .而引起流行性感冒傳染病的病毒，有A型、B型、以及C 型。另外，一部分之流感病毒感染雞等家禽類而引起既為致死性傳染病亦為法定傳染病之高致病性禽流感（亦即雞 *瘟），對於養雞產業造成極大之損害。在2006年時，經實 •用化之抗禽流感藥有金剛烷胺（amantadine)、扎那米韋 (Zanamivir)、奥塞米韋（Oseltamivir)(商品名為克流感 (Tamiflu))三種類。另一方面，對於此等藥劑具有耐藥性的金剛烷胺耐藥性流感病毒 '扎那米韋（奥塞米韋）耐藥性流感病毒、對於扎那米韋與奥塞米韋兩種藥劑皆具耐藥性之病毒的出現亦已獲報。 • 因此，無副作用且具有對耐藥性病毒亦有效之抗病毒活性的藥劑係備受需求。另一方面’已知菩竹（Bamboo grass)萃取物具有抗菌性。例如，已獲報對於屬於創傷感染症之原因菌之細菌的金黃色葡萄球菌（Staphylococcus aureus)、綠膿桿菌 (Pdeudomonas aeruginosa)、大腸桿菌（Escherichia coli)的抗菌效果（專利文獻1、專利文獻2)，或是對於被視為胃潰瘍原因菌的幽門螺桿菌（Helicobacter pylori)的抗菌效果。戰後，因動物實驗而發現山白竹（Sasa veitchii)對於老 6 320044 1363621 •-鼠之肝癌具有抑制活性，從制癌活性之方向已進行許多藥理學之研究（非專利文獻1)。另外，關於山白竹所具有之優 :異防腐效果（非專利文獻2)、抗菌效果（非專利文獻3)亦已 /進行研究。然而，該等研究多僅為依據氣相層析法之有機酸分析，關於抗菌效果本體之分離精製的報告例較少。亦已知香豆酸（coumaric acid)及其衍生物對於大腸才干菌、金黃色葡萄球菌、綠膿桿菌具有抗菌性（專利文獻3)。此外，亦已知山白竹萃取物中含有香豆酸、阿魏酸鲁（ferulic acid)、咖啡酸（coffeic acid)、香草搭等苯基丙酸類 (Phenylpropanoid)、3·羥基吡咬等，此等混合物對於大腸桿菌、金黃色葡萄球菌、綠膿桿菌具有抗菌性（專利文獻 4) 〇然而，關於山白竹萃取物中之各成分之詳細内容及其抗病毒活性仍為未知。 [專利文獻 1] WO00/067707 鲁[專利文獻2]日本特開2003-201247 [專利文獻3]日本特開2004-359626 [專利文獻4]日本特開2006-36731 [非專利文獻 1] M. Shibata，K. Kubo，M. Onoda，Folia Pharmacol. Jpn, 72, 531-541(1976) [非專利文獻 2] N. V· Chuyen, T. Kurata, H. Kato, J. Antibact. Antifung. Agents, 11, 69-75(1983) [非專利文獻 3] N. V. Chuyen，H. Kato, Agric. Biol. Chem.， 46, 2795-2801(1982)3-1128(2004) 7 320044 •【發明内容】 .(發明欲解決之課題） .- 本發明之目的係提供抗病毒劑。〉· &本發明之另一目的係提供抗病毒活性高且副作用（細 .胞备性）低之抗病毒劑。 (解決課題之方法）本發明係提供如下所述之抗病毒劑： _ (1) 一種抗病毒劑，係以選自5,7,4，·三羥基_3，，5,，·二甲氧基頁酮、3-羥基吡啶、對·羥基苯曱醛以及香草醛所成 • 群組中之至少一種作為有效成分者。 -(2) 一種抗病毒劑，係以5,7,4，-三羥基_3，，5，，-二甲氧基黃 _或3·羥基他啶作為有效成分者。 (3) —種抗病毒劑，係以5,7,4，_三羥基_3，，5，，_二甲氧基黃酮作為有效成分者。 (4) 如上述（1)至（3)中任一項之抗病毒劑，其中，該病毒為籲皰療病毒（herpesvirus)者。 (5) 如上述（1)至（3)中任一項之抗病毒劑，其中，該病毒為巨細胞病毒(cytomegalovirus)者。 • (6)如上述（1)至（3)中任一項之抗病毒劑，其中，該病毒為 . 人類巨細胞病毒者。 (7) 如上述（3)之抗病毒劑’其中，該病毒為流感病毒者。 (8) 如上述（7)之抗病毒劑’其中，該病毒為a型流感病毒或B型流感病毒者。 (9) 如上述（7)之抗病毒劑’其中’該病毒為禽流感病毒者。 320044 8 1363621 '* 本發明中之「病毒」包括動物病毒、昆蟲病I、植物 •病毒、細菌病毒（噬菌體），尤其是指對於包含人類之哺乳 >動物、包含鳥類等之動植物會造成不良影響的病毒。 ,* I發明之抗病毒劑可特別奏效之病毒，可列舉如皰療 •病毒、流感病毒，尤其可列舉如巨細胞病毒，特別是人類旦細胞病毒、猴類巨細胞病毒、小鼠巨細胞病毒等巨細胞病毒，A型流感病毒、B型流感病毒、c型流感病毒等人類流感病毒或是禽流感病毒等。 ·(發明之效果）本發明之抗病毒劑對於各種病毒’尤其是：皰疹病毒、 -特別是巨細胞病毒、更特別是人類巨細胞病毒；流感病毒、特別是A型流感病毒、B型流感病毒、c型流感病毒或是禽流感病毒’具有高度之抗病毒活性。本發明之抗病毒劑具有細胞毒性低之優點。【實施方式】 Φ 本木發明人等為了闡明山白竹（Sasa veitchii)之抗菌效果本體並特定其抗菌有效成分，而將山白竹葉之熱水萃取物於各種溶媒中分餾，藉由各種分離精製手段進行分離精製，針對各成分調查其抗病毒活性。結果，發現5,7,4，-三羥基_3，，5，，_二曱氧基黃酮（以下亦稱為「麥黃酮（Tricin)」）、3_羥基吡啶、對_羥基苯曱醛' 以及香草醛，其中又以5,7,4，-三羥基-3，,5,，·二甲氧基黃酮及3-羥基吡啶，特別是5,7,4，_三羥基_3，，5，，_二曱氧基黃酮 (亦即麥黃綱）對於各種病毒顯示出優異之抗病毒活性，因 9 320044 1363621 •-而完成本發明。以下，具體說明本發明。；本發明之有效成分5,7,4’-三羥基_3，，5，’_二甲氧基黃 /酮、3-羥基吡啶、對-羥基苯曱醛、以及香草醛，係從山白竹中萃取出，但當然亦可為合成品或從其他來源獲取者。例如山白竹以外之植物’尤其是屬於禾本科（Poaceae)之多數植物，例如稻子（米）、小麥、玉蜀黍、大麥、黑麥（Secale)、甘蔬、竹、芒草（Miscanthus)、蒲葦（pampas grass)、蘆葦籲（Phragmites)等茅草類之葉或莖部含有大量之5,7,4，-三羥基-3’，5，’-二甲氧基黃g同（亦即麥黃酿J)，而可從其中萃取。 .具體之植物名係如下所述：稻子、小麥、大麥、燕麥、黑麥、黍（Panicum miliaceum)、小米（Setaria italica)、稗(Echinochloa esculenta)、玉蜀黍、鴨腳稗（Eleusine coracana)、高梁（Sorghum bicolor)、竹、菰草（212&1^1汪1^〇^)、甘嚴、薏苡（111&-71^11)、蘆葦、芒草、 φ 箬竹（Bamboo grass)、蘆竹（Arundo donax)、蒲葦、結縷草 (Zoysiajaponica) 〇可將上述植物之葉、莖等使用適當溶媒萃取，並使用 HPLC等分離精製手段而分離精製麥黃酮。例如可將水萃取物濃縮，再將固形物以醇類、含水之醇類（例如甲醇、乙醇、含水曱醇、含水乙醇）萃取，並將固形物溶解於水中，藉由與乙酸乙酯之分配等即可進行精製。以上述化合物（香草醛、對-羥基苯甲醛、3-羥基吡啶、 5，7,4’ -三經基- 3’，5，’-二曱氧基黃嗣）（於此說明書中亦稱為 C S ) 10 320044 1363621 +發明之化合物」）之至少一種作為有效成分的本發明之 .抗病毒劑，可以各種型態來使用。例如適合作為黏膜保護 :.組成物、病毒感染預防及/或治療用組成物、防腐劑、過濾 .、·裳置等之抗病毒劑。 . 本發明之抗病毒劑之劑型可為液體狀、固體狀、氣體狀、凝踢狀、膠體狀、氣溶膠狀中之任一種。本發明之抗病毒劑可以經口投予、不經口投予之任一種投予型態來投 _予，’二口技予型態可列舉如旋劑、丸劑、粉劑、液劑、口香糖、糖果、巧克力糖、麵包、餅乾、騫麥麵、烏龍麵等麵類各種飲料劑等食品或飲料水溶液、調味料等型態；非經口投予型態係可列舉如注射劑、局部投予劑（乳膏 (cream)、軟膏等）、栓劑、陰道内投予型態（填塞棉球〇卿⑻ 等）等。局部投予劑之劑型之例可列舉如：使天_維或合成纖維製之紗布等載體含浸本發明之抗病毒劑而成者；使口紅等化粧品或其他型態之化粧品（乳液、油、肥皂、化粧鲁水、化粧乳霜（Cream)等）或入浴用冑含有本發明之抗病毒劑而成者；製成美容液、洗髮精、沐浴乳、洗面乳等半固體或液體之型態者等。亦可製成點眼劑、教口劑等型態。亦可列舉如創傷部位治療用喷霧劑、咽頭部炎症治療用喷霧劑等型態。 ' 本發明之抗病毒劑係除丁對人類有效之外，即使作為人類以外之哺乳類、鳥類、魚貝類、甲殼類、昆蟲類、兩樓類、欣蟲類等使用的抗病毒劑亦為有效。因此，本發明之抗病毒劑可用作此#動物用之抗病毒劑（例如寵物用醫 320044 11 1363621 •藥、動物用飼料、寵物食品等毒劑除了對動物J ^步本發明之抗两毒巧，另外介' ，亦噶用於作為各種植物之抗病毋劑三料亦有用於作為防腐劑。之上述：:：:：明亦各種劑型之抗病毒劑，則除了預定量腐成物等所用之油性成分等基材成分、保濕劑、防水等Iff中所使用之水’可為自來水、天然水、精製 .佳。〜特別限制’但—般以離子交換水等高純度水為二性成分可列舉如牛油、褚油、馬油、羊毛脂、 =:=物性油;橄欖油、葡萄籽油、棕櫚油、荷荷巴油、油等措如Λ肢芽油）、芝麻油、菜軒油' 紅花油、沙拉 .、，油，流動石蠟、高級腊肪酸酯（例如棕櫚酸辛酉曰、棕櫊酸異丙酯、肉豆蔻酸奈其.一 _合成油、半合成油。辛基十-院酯）、聚石夕氧油等藤分可配合皮膚之保護、賦予潤膚性之效果（以薄、被覆皮膚表面，在防止乾燥之同時，亦賦予柔軟性、彈 ==)、乾爽感等要求性能而適當組合使用。望烧、橄欖油及肉豆蔻酸辛基十二絲之組合為較佳例之一。為了調節抗病毒劑之硬度、流動姓，可使用硬脂酸、硬脂酿基醇、二十二㈣（behenie aeid)、_醇（⑽咖心凡士林等固體油，較佳為組合使用硬脂酸與料醇。、為了將本發明之抗病毒劑製造成乳膏組成物，可使用 121363621 •- Nine, invention description: [Technical field to which the invention pertains]; The present invention relates to an antiviral agent. [Prior Art] The virus system is incapable of self-propagating and parasitic to the extremely small pathogens of animals, plants or bacteria, and can be classified into animal viruses, plant viruses, and microbial viruses. Human cytomegalovirus is highly specific and does not proliferate in cells other than human-derived cells. For the proliferation, various primary cultured cells such as human skin, muscle, foreskin, and lung, or - established cells such as -MRC-5 and WI-38 can be used. An intranuclear inclusion body (intestinal) and a cytoplasmic inclusion body can be confirmed in the infected cells. Transplacental infection (vertical infection) is the cause of stillbirth, premature birth, and causes congenital infection (CID, also known as cytomegalic inclusion disease, giant cell inclusion body disease). It is also considered as an acquired infection. At this time, it is generally caused by immunosuppressive therapy, steroid use, and AIDS patients or cancer patients after inapparent infection. Infectious hosts are activated, causing serious opportunistic infections such as pneumonia, retinitis, and colitis. Antiviral agents for the prevention and treatment of diseases caused by such viruses are under development. For example, Ganciclovir (i.e., GCV), Cidofovir (i.e., CDV), foscarnet (i.e., PFA), and Fomivirsen are known. Among them, GCV is widely used, 5 320044 1363621 •• However, in recent years, the GCV-resistant virus system has become a problem. In addition, there is also a problem that the side effect (cytotoxicity) is strong, so that there is no side effect and there is a drug-resistant virus; and an effective antiviral activity is also required. / Influenza virus (also known as flu virus) is a virus that causes infection in humans, and causes influenza virus infections, including type A, type B, and type C. In addition, some of the influenza viruses infect chickens and other poultry and cause highly pathogenic avian influenza (also known as chickens), which are both fatal and legal infectious diseases, causing great damage to the chicken industry. In 2006, there were three types of anti-avian flu drugs: amantadine, Zanamivir, and Oseltamivir (trade name: Tamiflu). . On the other hand, the amantadine-resistant influenza virus 'Zanamivir (Oxemide)-resistant influenza virus resistant to these agents, for zanamivir and oseltamivir The emergence of a drug-resistant virus has also been reported. • Therefore, a drug system that has no side effects and has an antiviral activity that is also effective against a drug-resistant virus is in demand. On the other hand, 'Bamboo grass extracts are known to have antibacterial properties. For example, the antibacterial effect of Staphylococcus aureus, Pdeudomonas aeruginosa, and Escherichia coli against bacteria belonging to the cause of traumatic infection has been reported (Patent Document 1 and Patent Document 2) ), or the antibacterial effect of Helicobacter pylori, which is considered to be a cause of gastric ulcer. After the war, it was found in the animal experiment that Sasa veitchii has inhibitory activity against the liver cancer of the old 6 320044 1363621 • mouse, and many pharmacological studies have been carried out in the direction of carcinogenic activity (Non-Patent Document 1). In addition, it is excellent in the effect of the mountain white bamboo: the different anti-corrosion effect (Non-Patent Document 2) and the antibacterial effect (Non-Patent Document 3) have been studied. However, most of these studies are only organic acid analysis based on gas chromatography, and there are few reports on the separation and purification of the antibacterial effect body. It is also known that coumaric acid and its derivatives have antibacterial properties against colonic bacteria, Staphylococcus aureus, and Pseudomonas aeruginosa (Patent Document 3). In addition, it is also known that the extract of the white bamboo contains coumaric acid, ferulic acid, coffeic acid, vanillin, etc., and hydroxypyrazole. The mixture is antibacterial to Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa (Patent Document 4). However, the details of each component in the extract of the white bamboo extract and its antiviral activity are still unknown. [Patent Document 1] WO00/067707 [Patent Document 2] JP-A-2003-201247 [Patent Document 3] JP-A-2004-359626 [Patent Document 4] JP-A-2006-36731 [Non-Patent Document 1] M. Shibata, K. Kubo, M. Onoda, Folia Pharmacol. Jpn, 72, 531-541 (1976) [Non-Patent Document 2] N. V· Chuyen, T. Kurata, H. Kato, J. Antibact. Antifung. Agents , 11, 69-75 (1983) [Non-Patent Document 3] NV Chuyen, H. Kato, Agric. Biol. Chem., 46, 2795-2801 (1982) 3-128 (2004) 7 320044 • [Summary of the Invention] (Question to be Solved by the Invention) - The object of the present invention is to provide an antiviral agent. 〉· & Another object of the present invention is to provide an antiviral agent having high antiviral activity and low side effects (fine cell preparation). (Method for Solving the Problem) The present invention provides an antiviral agent as described below: _ (1) An antiviral agent selected from the group consisting of 5, 7, 4, · trihydroxy _3, 5, dimethyl At least one of the group consisting of oxypage ketone, 3-hydroxypyridine, p-hydroxybenzaldehyde, and vanillin is used as an active ingredient. - (2) An antiviral agent which is an active ingredient of 5,7,4,-trihydroxy-3,5,-dimethoxy yellow or 3-hydroxyhistidine. (3) An antiviral agent which is an active ingredient of 5,7,4,3-trihydroxy-3,5,-dimethoxyxanthone. (4) The antiviral agent according to any one of the above (1) to (3) wherein the virus is a herpesvirus. (5) The antiviral agent according to any one of the above (1) to (3) wherein the virus is a cytomegalovirus. (6) The antiviral agent according to any one of (1) to (3) above, wherein the virus is a human cytomegalovirus. (7) The antiviral agent according to (3) above, wherein the virus is an influenza virus. (8) The antiviral agent according to (7) above, wherein the virus is an influenza A virus or a influenza B virus. (9) The antiviral agent according to (7) above, wherein the virus is an avian influenza virus. 320044 8 1363621 '* "Virus" in the present invention includes animal virus, insect disease I, plant virus, bacterial virus (phage), and especially refers to animals and plants including humans, animals, birds and the like, which cause bad The virus that affects. , * I antiviral agent can be particularly effective virus, such as blister, virus, influenza virus, in particular, such as cytomegalovirus, especially human dendritic virus, monkey cytomegalovirus, mouse giant cell A cytomegalovirus such as a virus, a human influenza virus such as influenza A virus, influenza B virus, or influenza C virus, or avian influenza virus. (Effects of the Invention) The antiviral agent of the present invention is specific for various viruses 'especially: herpes virus, especially cytomegalovirus, more particularly human cytomegalovirus; influenza virus, particularly influenza A virus, type B Influenza virus, influenza C virus or avian influenza virus has a high degree of antiviral activity. The antiviral agent of the present invention has the advantage of low cytotoxicity. [Embodiment] Φ In order to clarify the antibacterial effect of Sasa veitchii and to specify its antibacterial active ingredient, the inventors of the present invention fractionate the hot water extract of the mountain white bamboo leaves in various solvents and purify them by various separations. The method was isolated and purified, and the antiviral activity of each component was investigated. As a result, 5,7,4,-trihydroxy-3,5,-dioxaxyflavone (hereinafter also referred to as "Tricin"), 3-hydroxypyridine, p-hydroxybenzofural was found. And vanillin, which in turn is 5,7,4,-trihydroxy-3,5,1,dimethoxyflavone and 3-hydroxypyridine, especially 5,7,4,_trihydroxy-3, The 5,-dioxaxyflavone (i.e., scutellaria) exhibits excellent antiviral activity against various viruses, and the present invention has been completed by 9 320044 1363621. Hereinafter, the present invention will be specifically described. The active ingredient of the present invention 5,7,4'-trihydroxy-3,5,'-dimethoxy yellow/ketone, 3-hydroxypyridine, p-hydroxybenzaldehyde, and vanillin are from the mountain Extracted from white bamboo, but of course it can be synthetic or obtained from other sources. For example, plants other than the white bamboo are especially the majority of plants belonging to the Poaceae family, such as rice (rice), wheat, maize, barley, semale, sweet and sour, bamboo, Miscanthus, and pampas grass. Pampas grass), Phragmites and other grassy leaves or stems contain a large amount of 5,7,4,-trihydroxy-3',5,'-dimethoxy yellow g (also known as wheat yolk J), from which it can be extracted. The specific plant names are as follows: Rice, wheat, barley, oats, rye, Panicum miliaceum, Setaria italica, Echinochloa esculenta, maize, Eleusine coracana, sorghum (Sorghum bicolor), bamboo, yarrow (212 & 1^1wang 1^〇^), Gan Yan, 薏苡 (111 & -71^11), reed, Miscanthus, φ Bamboo grass, Luzhu ( Arundo donax), scutellaria, and Zoysiajaponica 〇 The leaves and stems of the above plants can be extracted with a suitable solvent, and the flavonoids can be isolated and purified by separation and purification methods such as HPLC. For example, the aqueous extract can be concentrated, and the solid matter is extracted with an alcohol, an aqueous alcohol (for example, methanol, ethanol, aqueous sterol, aqueous ethanol), and the solid is dissolved in water by using ethyl acetate. It can be refined by dispensing or the like. The above compounds (vanillin, p-hydroxybenzaldehyde, 3-hydroxypyridine, 5,7,4'-trisyl-3',5,'-didecyloxyxanthine) (also referred to in this specification) The antiviral agent of the present invention which is at least one of CS) 10 320044 1363621 + a compound of the invention") as an active ingredient can be used in various forms. For example, it is suitable for mucosal protection: an antiviral agent such as a composition, a viral infection prevention and/or therapeutic composition, a preservative, a filter, and a shelf. The antiviral agent of the present invention may be in the form of a liquid, a solid, a gas, a gel, a gel, or an aerosol. The antiviral agent of the present invention can be administered by oral administration or by any of the administration forms which are not administered orally. The two-component technology can be exemplified by a spinner, a pill, a powder, a liquid, a chewing gum, For food, beverage aqueous solutions, seasonings, etc., such as candy, chocolate candy, bread, biscuits, soba noodles, oolong noodles, etc.; non-oral administration forms such as injections, topical administration Agents (creams, ointments, etc.), suppositories, intravaginal administration (filling cotton balls (8), etc.). Examples of the dosage form of the topical administration agent include, for example, a carrier such as a gauze made of a ray or a synthetic fiber, which is impregnated with the antiviral agent of the present invention; a cosmetic such as a lipstick or other type of cosmetic (emulsion, oil, Soap, make-up Lu, water, cream, etc.) or bathing gel containing the antiviral agent of the present invention; semi-solid or liquid type such as cosmetic liquid, shampoo, shower gel, facial cleanser, etc. State and so on. It can also be made into eye-type agents, esthetics, and the like. For example, a spray for treating a wound site or a spray for treating a pharyngeal head inflammation may be mentioned. The antiviral agent of the present invention is effective as an antiviral agent for use in mammals, birds, fish and shellfish, crustaceans, insects, two-story, and insects, except for humans. . Therefore, the antiviral agent of the present invention can be used as the antiviral agent for the animal (for example, the pet doctor 320044 11 1363621 • the poison of the medicine, the animal feed, the pet food, etc., in addition to the anti-drug of the animal of the invention In addition, it is also used as a preservative for various plant anti-disease agents. The above::::: Anti-viral agents of various dosage forms, except for a predetermined amount of rot The water used in the base material such as the oil component such as the oil component and the humectant, water repellency, etc. can be tap water, natural water, or refined. It is particularly limited. However, high-purity water such as ion-exchanged water is used. The sexual ingredients may be, for example, tallow, eucalyptus oil, horse oil, lanolin, =:=physical oil; olive oil, grape seed oil, palm oil, jojoba oil, oil, etc., such as radish sesame oil), sesame oil,菜轩油' safflower oil, salad, oil, mobile paraffin, high-grade tartaric acid ester (such as palmitic acid bismuth, isopropyl palmitate, myristic acid Nai. a synthetic oil, semi-synthetic oil. Rattan of octyl ten-yard ester), Ju Shixi Oxygen Oil can match the skin It is used in combination with the protective effect and the emollient effect (the thin surface, the surface of the skin is covered, and the softness, elasticity ==), dryness, and the like are required to be combined. A combination of simmering, olive oil and octyl 12-filament of myristic acid is one of the preferred examples. In order to adjust the hardness and flow name of the antiviral agent, stearic acid, stearyl alcohol, behenie aeid, _alcohol ((10) solid oil such as chiagrass may be used, preferably hard fat is used in combination. Acid and feed alcohol. In order to manufacture the antiviral agent of the present invention into a cream composition, 12 can be used.

I (S 320044 •發明之化合物、水、油性成分製成乳膏狀的乳膏化劑。 h化劑亚無#別限制，—般係將單硬脂酸甘油醋與自行 =單硬脂酸甘油醋(亦即在單硬脂酸甘油醋中添加乳化劑者）组合使用。本發明之抗病毒劑亦可與其他抗病毒劑併用。 π制在本發狀抗病毒劑中，為了因應需求可另含有安定化Ί濕劑、創傷治癒劑、防腐劑、界面活性劑等。就安定化劑而言，可列與 1列舉如羧乙烯聚合物與氫氧化鉀，、且。、聚乙一醇二硬脂酸酉旨（(polyethylene g】yC0l rteame))等。尤其是聚乙二醇倍半硬脂酸醋㈣吻lene 二醢„D qulstearate)(亦即為聚乙二醇二硬脂酸酯與聚乙 ;= 脂酸醋之？混合物)(聚乙二醇之分子量為⑽。矣暮，由於其安定性高’且水與油不會分離，並且作礼r組成物可有效地調節塗佈於皮膚時之硬度，故較佳。就保濕劑而言，可石，丨與i p丄了列舉如玻尿酸鈉、膠原、蘆薈萃取 •(二源自木立蘆薈之i薈萃取物⑺為佳)、尿素、二'海㈣Μ—)、山梨醇、胺基酸、吨洛疋酉同缓酸鈉等。 ‘甘草治癒劑而言，可列舉如尿囊素、甘草酸二鈉、甘早卒取物、艾草萃取物等。防腐劑係輔助用材料。如對H了列，如笨甲酸鈉、對铺笨甲酸低級燒_ 酸丙7 '對七基苯甲酸乙酷、對-經基苯曱 -曰S 、·搜基笨甲酸丁酯等被稱為對_羥基笨曱酸酯 320044 13 1363621 a )、丙酸鈉、混合脂肪酸酯（癸酸甘油酯（glycew • aprate)、月桂酸聚甘油酯·2、月桂酸聚甘油酯-10的混合、，）、苯氧基乙醇、感光素201號（黃色色素）、1，2-戊二醇 ♦等，又以對-羥基苯甲酸酯、混合脂肪酸酯、丨，2_戊二較佳。馬取产就界面活性劑而言’可列舉如Ν醯基_L_麩胺酸鈉、小氧α伸乙基山梨醇酐單硬脂酸酯等。 W依據需要亦可復含有香氣成分，例如橘油、擰樣油、雲杉油（spruce oil)、香料等。含有本發明之抗病毒劑的黏臈保護組成物、病毒感染預防及/或治㈣組成物，可有效抑制病毒從眼、鼻、喉、、耳、肛Η、陰料之㈣或創傷部位及皮膚侵人體内，並有效地預防及/或治療包含院内感染之病毒感染。病毒感华預防及/或治療用組成物的更具體的型態，係可列舉如勘膜保護布或口腔組成物。、I (S 320044 • The compound, water and oily ingredients of the invention are made into a creamy creaming agent. The h-reducing agent is not #, and the general-purpose monostearic acid glycerin and self-single-stearic acid Glycerin (that is, an emulsifier added to monostearic acid glycerin) is used in combination. The antiviral agent of the present invention may also be used in combination with other antiviral agents. π is prepared in the hair growth antiviral agent, in order to meet the demand Further, it may contain a stabilizer, a wound healing agent, a preservative, a surfactant, etc. In terms of the stabilizer, one can be listed, for example, a carboxyvinyl polymer and potassium hydroxide, and a polyethylenol. Di-stearic acid ((polyethylene g) yC0l rteame)), especially polyethylene glycol sesquilique vinegar (four) kiss lene two „D qulstearate) (also known as polyethylene glycol distearate Ester and polyethyl; = mixture of fatty acid vinegar) (polyethylene glycol has a molecular weight of (10). 矣暮, because of its high stability' and water and oil will not separate, and the composition of the r can be effectively adjusted The hardness when applied to the skin is preferred. As far as the humectant is concerned, the stone, 丨 and ip are listed as glass. Sodium, collagen, aloe extract • (two from the aloe vera extract (7) is good), urea, two 'sea (four) Μ-), sorbitol, amino acid, tons of strontium and sodium sulphate. For the licorice healing agent, for example, allantoin, disodium glycyrrhizinate, early pregnancy, wormwood extract, etc. Preservatives are auxiliary materials. For example, for H, such as sodium benzoate, Low-grade benzoic acid _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ , sodium propionate, mixed fatty acid esters (glycew • aprate, lauric acid polyglyceryl ester 2, lauric acid polyglyceryl ester-10 mixed,,), phenoxyethanol, photoreceptor 201 (yellow pigment), 1,2-pentanediol ♦, etc., and further preferably p-hydroxybenzoic acid ester, mixed fatty acid ester, hydrazine, and 2-pentylene. In terms of surfactant, horse can be used as a surfactant. For example, sulfhydryl-L-glutamic acid sodium, small oxygen alpha-extension ethyl sorbitan monostearate, etc. may also contain aroma components, such as orange oil, as needed. Squeezing oil, spruce oil, spices, etc. The adhesive protective composition containing the antiviral agent of the present invention, the virus infection prevention and/or treatment (4) composition, can effectively inhibit the virus from the eyes, nose and throat , ear, anal fistula, vaginal material (4) or wound site and skin invading the body, and effectively prevent and / or treat viral infections including nosocomial infections. More specific aspects of viral sensation prevention and / or therapeutic composition The type may be, for example, a film protective cloth or an oral composition.

黏膜保護布係藉由含浸、喷料方法而使具有通氣性之載體(例如蠶絲、棉、麻等天然纖，维；聚胺，酸顆 (P〇lyUrethane)、聚乙埽、聚丙稀、尼龍、聚醋、丙烯酸系專合成纖維；半合成纖維；或此等之2種以上之混合物的纖維本身或線 '或其織布、編布、不織布、㈣）含有本發明之化合物而成者。為了方便起見，此說明書中之「保^ 布」除了.布以外，亦包含纖維本身、線、紙等者。就具體之型態而言，除了紗布罩、眼罩、月經帶 · ”八个.乃、令王« 月經用衛生棉、端帶、衛生咕、、痒忠各術王、，、氏、痔瘡處置用紗布、耳塞 320044 14 1363621 •-液體絆創膏等被歸類為衛生用品而直接接觸黏膜或皮膚的 .保護布以外，亦可列舉如白衣等衣服類，手套、帽子、襪；子、曰式足袋襪等衣料小物品，床單、棉被罩、枕罩、床 .··用品等寢具類，窗簾、壁紙、地毯等室内裝飾品及室内裝 -修材料，手術用縫合線等醫療材料等會直接或間接接觸皮膚的物品。The mucosa protective cloth is made of a ventilating carrier by means of impregnation and spraying methods (for example, natural fibers such as silk, cotton, hemp, vitamins, polyamines, P〇lyUrethane, polyethylene, polypropylene, nylon). , polyester, acrylic synthetic fiber; semi-synthetic fiber; or a mixture of two or more of these fibers or the wire 'or its woven fabric, braided fabric, non-woven fabric, (four)) containing the compound of the present invention. For the sake of convenience, the "protective cloth" in this specification includes, in addition to the cloth, the fiber itself, the thread, the paper, and the like. In terms of the specific type, in addition to gauze cover, eye mask, menstrual belt, "eight. Nai, Ling Wang" sanitary napkins for menstruation, end belts, sanitary sputum, itch loyalty, s, acne treatment Use gauze and earplugs 320044 14 1363621 • Liquid enamel cream, etc., which are classified as sanitary products and directly contact the mucous membrane or skin. In addition to the protective cloth, clothes such as white clothes, gloves, hats, socks, and squat-foot bags are also listed. Small items such as socks, quilts, quilts, pillow covers, beds, etc., bedding, curtains, wallpapers, carpets, etc., interior decorations, interior materials, surgical materials, surgical sutures, etc. Or indirect contact with skin.

含有本發明之抗病毒劑的口腔組成物，可列舉如軟膠 (gummy)、凍膠(jdly)、漸溶錠劑（tr〇che)、糖果扑/ 口香糖、巧克力糖、錠劑、丸劑、洗口劑、漱口劑、牙膏、貼附黏膜之薄膜、咽頭部炎症治療用噴霧劑等。本發明之抗病毒劑之抗病毒活性高，本發明之化合物僅以1_鹏至lppm左右之固形物濃度即可顯示充抗病毒活性。當本發明之抗病毒劑使用於人類時，只要考慮症狀、年齡、體重’令成人每天將i至5〇〇〇mg，較佳為5 2000mg，更佳為10至1000叫，以1次或是分成2至“ 左右投予即可。若要使例如軟膠、；東膠、漸溶鏡劑、糖果、口香糖、 =克力糖、錠劑'丸劑（例如#)、洗口劑、漱口劑月、貼附黏膜之薄膜等口腔組成物中含有物丄則要在製造口腔組成物之任—階財，以使样^ ::物述投予量，適量添加至口腔組成物。例如’本發明之化合物之固形物較佳為添至1〇 )質量%左右’更佳為6〜至 320044 15 1363621 最佳為8至仏⑽1至ίο·5)質量％左右。本發明之抗病毒劑之劑型，可列舉 ^ rdry svrun'l > ^ , 膠囊劑、乾糖漿 t 劑、丸劑、粉劑、液劑，例如點魯用$洛劑及凝膠劑、口腔噴霧劑，·_ ·-、用之點鼻用製劑、款膏劑、乳或咽頭直接適劑。此等可依據常法調製。h劑4經皮吸收用製 :::造上述劑型之抗病毒劑的基劑成分二二乳糖、嚴糖，、糊精、環糊精、澱粉等 : '阿拉伯膠、致甲基纖維素納、結晶纖維素、膠基材（gum base)等結合劑；澱粉等崩解劑；硬脂酸脂肪酸酯等潤滑劑；香料、荦、庶微、、1刺m 丁叶某，、录素、厚何、1-薄荷腦等清 π θ ,辛土十二烷醇等高級醇；肉豆蔻酸異丙酯、己二酸二異丙酯及椋櫚酸異丙醋等脂肪酸醋；聚山梨酸醋⑽ 及聚乳伸乙基硬化寬麻油等懸濁化劑；幾乙稀聚合物、羥丙基纖維素、聚乙烯基対咬酮及破尿酸納等高分子化入 •物；甘油、丙二醇及U·丁二醇等多元醇；二異丙醇胺^ 氫氧^鈉、磷酸二氫鉀及磷酸氫鈉等pH調節劑；磷酸氫鈉、氯化鈉、硫代硫酸鈉、亞硫酸鈉及乙二胺四乙酸鈉 (sodium edetate)等安定化劑；對-羥基苯甲酸甲酯、對-羥基苯甲酸丙s旨、氨化苯甲烴録（benzaIk〇nium chI〇dde)及氯化本錄松f (benzethonium chloride)等防腐劑等。當以保護布之型態來使用本發明之抗病毒劑時，只要使接觸黏膜或創傷部位之保護布（紗布等）含有本發明之化。物’並一天更換1至3次左右即可。當以手術用缝合線 .320044 16 1363621 型態來使用時，可有致地抑制病促進手術部位之回復。〜口-邛知入，以㈣了防止在醫院等之院内感染而以保護布之型能來使用本發明之抗病毒劑時，本發明之抗病 = 效果可存續長期間。當 i之感木b止. 隸心，使該效果降低時，只要適田地更換㈣布、或是進行使合物的處理即可。人3有本發明之化 :使用本發明之抗病毒劑作為口腔組成物時，在適宜藉由預先將其含在口中，而可極度簡便地預 :病：“並抑制病毒增殖。料，口香糖、糖果等緩釋 i·生U、之組成物’可長時間發揮效果而為有利。本發明之抗病毒劑亦可以乳液或油之型態使用。藉由預先將以固形物為2至20χ㈤·！至！〇·5)質量％之量含有本發明之化合物的乳液或油塗佈於皮膚等，可極度簡便地預防病毒感染並抑制病毒增殖。過濾裝詈本發明係亦提供一種含有本發明之化合物作為有效成分^空氣過遽裝置。就具體之型態而言，可列舉如使用於換虱扇.、空調設備、汽車空調設備、空氣吸入口、空氣排出、’〆自、空氣清淨機等之空氣通過部位的過濾器。過濾器之基材並無特別限制，可列舉如蠶絲、棉、羊毛、麻等=然纖維；聚胺曱酸酯、聚乙烯、聚丙烯、尼龍、聚酯、丙烯酸系等合成纖維；半合成纖維；或此等之2種以上之混合物的織布、編布、不織布、紙等。只要藉由含浸、噴 320044 17 1363621 以西方點墨法來比較檢討病毒蛋白質之表現。尤並是針對在感染後數何之㈣即表現且接著作為病毒複製之觸發蛋白（tngger pn)tein)而發揮作用的極重要的迅早期蛋白(immediate·^ pr〇tein)、以及職合成酵素等晚期蛋白的表現’來比較評估各試料之效果。The oral composition containing the antiviral agent of the present invention may, for example, be a gummy, a jelly (jdly), a gradual tablet (tr〇che), a candy puff/chewing gum, a chocolate candy, a lozenge or a pill. A mouthwash, a mouthwash, a toothpaste, a film attached to a mucous membrane, a spray for treating pharyngeal inflammation, and the like. The antiviral agent of the present invention has high antiviral activity, and the compound of the present invention exhibits antiviral activity only at a solid concentration of from about 1 to about 1 ppm. When the antiviral agent of the present invention is used in a human, as long as the symptoms, age, and body weight are considered, the adult will be i to 5 mg, preferably 5 2000 mg, more preferably 10 to 1000, per day, or 1 time. It is divided into 2 to "can be administered left and right. To make, for example, soft rubber, east rubber, gradual coating agent, candy, chewing gum, gram sugar, lozenge 'pill (such as #), mouthwash, 漱The mouth composition, the film attached to the mucous membrane, and the like, which are contained in the oral composition, are required to be used in the manufacture of the oral composition, so that the amount of the substance can be added to the oral composition. The solid matter of the compound of the present invention is preferably added to about 1% by mass. More preferably, it is 6 to 320,044, and 15 1363621 is preferably 8 to 仏(10)1 to ίο·5)% by mass. For the dosage form of the poison, exemplify ^ rdry svrun'l > ^ , capsules, dry syrup t, pills, powders, liquids, such as lingluo and gel, oral spray, ·_ ·- Use nasal preparations, ointments, milk or pharyngeal direct preparations. These can be prepared according to common methods. System:: The base ingredient of the above-mentioned antiviral agent is dilactose, strict sugar, dextrin, cyclodextrin, starch, etc.: 'Arabic gum, methyl cellulose, crystalline cellulose, gum base A binder such as a gum base; a disintegrant such as starch; a lubricant such as stearic acid fatty acid ester; a fragrance, a sputum, a sputum, a thorn, a stalk, a phlegm, a thick, a 1-menthol The brain is equal to π θ , higher alcohol such as dodecyl alcohol; fatty acid vinegar such as isopropyl myristate, diisopropyl adipate and isopropyl palmitate; polysorbate (10) and polyemulsion Emulsifying agent such as ethyl hardened broad sesame oil; macromolecular polymers such as ethylene glycol, hydroxypropyl cellulose, polyvinyl ketone and sodium urate; glycerin, propylene glycol and U·butanediol a pH adjuster such as a polyhydric alcohol; diisopropanolamine, sodium hydroxide, potassium dihydrogen phosphate or sodium hydrogen phosphate; sodium hydrogen phosphate, sodium chloride, sodium thiosulfate, sodium sulfite, and sodium edetate ( Sodium edetate) and other stabilizers; methyl p-hydroxybenzoate, p-hydroxybenzoic acid, ammoniated benzate (benzaIk〇nium chI〇dde And a preservative such as chlorinated benzethonium chloride. When the antiviral agent of the present invention is used in the form of a protective cloth, the protective cloth (gauze, etc.) contacting the mucous membrane or the wound site is included. The invention can be replaced by one to three times a day. When used in the surgical suture. 320044 16 1363621 type, it can effectively inhibit the disease and promote the recovery of the surgical site. (4) When the antiviral agent of the present invention is used to prevent infection in hospitals such as hospitals and to protect the cloth, the disease resistance of the present invention may last for a long period of time. When i feels the wood b. When the effect is lowered, it is only necessary to replace the (four) cloth or the treatment of the compound. Human 3 has the invention: when the antiviral agent of the present invention is used as an oral composition, it can be extremely easily pre-prepared by pre-existing it in the mouth: "and inhibiting virus proliferation.", chewing gum It is advantageous that the composition of the present invention can be used for a long period of time. The antiviral agent of the present invention can also be used in the form of an emulsion or an oil. The solid content is 2 to 20 预先 (5) in advance. !·5 to 5% by mass. The emulsion or oil containing the compound of the present invention is applied to the skin or the like to prevent viral infection and inhibit virus proliferation in an extremely simple manner. The present invention also provides a method for containing the present invention. The compound of the invention is used as an active ingredient in an air-passing device. For specific types, it can be exemplified, for example, for use in changing fans, air conditioning equipment, automobile air conditioning equipment, air intake, air discharge, 'self-cleaning, air cleanliness The filter for passing the air through the machine, etc. The substrate of the filter is not particularly limited, and examples thereof include silk, cotton, wool, hemp, etc.; polyamine phthalate, polyethylene, polypropylene, and nylon. Synthetic fibers such as polyester or acrylic; semi-synthetic fibers; or woven fabrics, fabrics, non-woven fabrics, papers, etc. of a mixture of two or more of these, as long as they are compared by Western blotting by impregnation and spraying 320044 17 1363621. Reviewing the performance of viral proteins, especially the very important early-stage protein (immediate·^ pr〇tein) that plays a role in the post-infection (4) expression and works as a trigger protein for viral replication (tngger pn) tein) ), as well as the performance of advanced proteins such as synthetic enzymes, to compare the effects of each sample.

將使用山白竹萃取物（鳳凰堂販售之twebs(固形物濃度5〇質量⑽之稀釋水溶液時的細胞病變效應表示於第 1圖，並將病毒增殖之抑制效果表示於第2圖。對於丁〇職株及⑸R株這兩株，可確認到至少以Q4%之濃度抑制細胞病變效應以及病毒增殖的效果。此事實顯示本發明首先發現山白竹萃取物中之成分（尤其是麥黃裥）不僅對於通常之巨細胞病毒有效’即使對於葛昔洛韋耐藥性病毒亦有效。從一山白竹萃取物免跑疹病毒的抗症表你田從山白竹萃取物分離之精製物，係使用對·香豆酸（系The cytopathic effect of the extract of the white bamboo extract (twebs (the solid concentration of 5 〇 mass (10)) is shown in Fig. 1 and the inhibitory effect of virus proliferation is shown in Fig. 2. Both the delinquent strain and the (5) R strain confirmed the effect of inhibiting the cytopathic effect and the virus proliferation at least at a concentration of Q4%. This fact indicates that the present invention firstly found the components (especially wheat jaundice) in the extract of the white bamboo extract. It is effective not only for the usual cytomegalovirus, but also for the gluoxivir-resistant virus. The anti-disease table of the extract of the white bamboo extract from the mountain is extracted from the extract of the white bamboo extract. P-coumaric acid

列1)、香草醛（系列2)、對-經基苯甲醛（系列3)、3_經基吡唆（系列4)、5,7,4，-三經基_3，，5，，_二甲氧基黃酮（亦即麥黃酮）（系列5)。將各化合物之HCMV增殖抑制效果表示於第3圖。另外，將麥汽酮濃度與病毒力價（virus titer)的關係表示於第4圖。可知當麥黃酮濃度為m#g/ml時，病毒之增殖係幾乎完全被抑制。更進一步，將各種化合物之IC5q(5〇%抑制濃度）（細胞毒性）U g/ml)、EC50(50%有效濃度）（a g/ml)、以及SI(選擇指數）表示於表1。Column 1), vanillin (series 2), p-parabenzaldehyde (series 3), 3_pyridinium (series 4), 5,7,4,-trisyl groups _3,,5, - Dimethoxyflavone (also known as flavonoids) (Series 5). The HCMV proliferation inhibitory effect of each compound is shown in Fig. 3. Further, the relationship between the concentration of the vaginal ketone and the virus titer is shown in Fig. 4. It is understood that when the concentration of flavonoids is m#g/ml, the proliferation of the virus is almost completely suppressed. Further, IC5q (5 〇% inhibitory concentration) (cytotoxicity) U g/ml), EC50 (50% effective concentration) (a g/ml), and SI (selection index) of various compounds are shown in Table 1.

C 320044 19 1363621 [表 1] 化合物 IC5〇 ec5〇 SI 對-香豆酸 187 8.2 22.8 香草醒· 215 48.0 4.5 對-羥基苯曱醛 305 12.8 23.8 3 -經基α比咬 263 3.4 77.4 麥黃酮 2050 1.7 1205.8 葛昔洛韋 0.3 至 0.8 由表1可知，本發明之化合物，尤其是麥黃酮（黃酮衍籲生物），其細胞毒性顯著偏低，有效濃度亦低（高活性），因 -此，選擇指數（ic50/ec5〇)顯著偏高。 .實施例2(麥黃酮對於流感病毒之抗病毒作用）依據以下之方法，調查麥黃酮對於流感病毒之抗病毒作用。細胞：MDCK細胞流感病毒之種類：A/Hiroshima/52/2005，H3N2 φ B/Malaysia/2506/2004 使各病毒增殖於MDCK細胞並求出病毒力價後，將其冷凍保存在-80°C之冰凍機中，使用時解凍後使用。 . 方法：依照通常之噬菌斑法亦即，對於已在5%二氧化碳培養器中經單層培養於塑膠培養皿之MDCK細胞，使各病毒在室溫中吸附1小時。除去未吸附之病毒後，於其中加入添加有包含各種濃度之麥黃酮的胰蛋白酶(trypsin)之0.6%洋菜培養基，於室溫使洋菜固化後，以5%二氧化碳在培養器中培養2天。 20 320044 1363621 •培養完畢後，以1 〇〇/0曱搭使細胞固定，除去洋苐，再以〇.〇3°/〇亞甲基藍液染色後，計數出現之噬菌斑數。 r 將添加有麥黃酮之實驗組之噬菌斑數（pt)除以未添加 ·.·有麥黃酮之實驗組之噬菌斑數（pc)，計算出抗病毒作用（增 -殖抑制率tpt/pedOO%)。當麥黃酮濃度為0.3/zg/ml時，集於A型流感病毒之增瘦抑制率為52%，對於b型流感病毒之增殖抑制率為48%。結果係示於第5圖。上述結果充分示唆麥黃酮對於禽流感等其他流感病毒胃亦顯示高增殖抑制作用。製劑例1(膠囊劑）將麥黃酮250mg置入膠囊内，製成本發明之抗病毒劑。製劑例2(錠劑）將麥黃酮與乳糖混合、成型’製成1旋中含有麥黃酮 lOOmg之鍵劑。【圖式簡單說明】籲[第1圖]係顯示山白竹萃取物（TWEBS)對於病毒感染後之細胞病變效應抑制情形的顯微鏡照片 [第2圖]係顯示山白竹萃取物（TWEbS)對於病毒增殖之抑 .制圖 [第3圖]係顯示山白竹萃取物（TweBS)中之分離成分對於病毒增瘦之抑制圖 [第4圖]係顯示麥黃酮（黃酮衍生物）對於人類巨細胞病毒增殖之抑制圖 [第5圖]係顯示麥黃酮對於流感病毒增殖之抑制圖 320044 1363621 【主要元件符號說明】C 320044 19 1363621 [Table 1] Compound IC5〇ec5〇SI p-coumaric acid 187 8.2 22.8 Vanilla awake 215 48.0 4.5 p-Hydroxybenzaldehyde 305 12.8 23.8 3 -Phase alpha ratio bite 263 3.4 77.4 Flavonoid 2050 1.7 1205.8 Gemcyclovir 0.3 to 0.8 As can be seen from Table 1, the compounds of the present invention, especially flavonoids (flavonoids), have a significantly low cytotoxicity and a low effective concentration (high activity), because - The selection index (ic50/ec5〇) was significantly higher. Example 2 (Antiviral action of flavonoids against influenza virus) The antiviral action of flavonoids against influenza virus was investigated according to the following method. Cells: MDCK cell type of influenza virus: A/Hiroshima/52/2005, H3N2 φ B/Malaysia/2506/2004 After each virus was propagated to MDCK cells and the viral power was determined, it was cryopreserved at -80 °C. In the freezer, use it after thawing. Method: Each virus was allowed to adsorb at room temperature for 1 hour in accordance with the usual plaque method, i.e., for MDCK cells which had been cultured in a plastic dish in a 5% carbon dioxide incubator. After removing the unadsorbed virus, 0.6% acacia medium supplemented with trypsin containing various concentrations of flavonoids was added thereto, and the leaves were solidified at room temperature, and then cultured in an incubator with 5% carbon dioxide. day. 20 320044 1363621 • After the culture was completed, the cells were fixed with 1 〇〇/0 ,, the artichokes were removed, and the number of plaques was counted after staining with 〇.〇3°/〇 methylene blue solution. r The number of plaques (pt) of the experimental group to which flavonoids was added was divided by the number of plaques (pc) of the experimental group without flavonoids, and the antiviral effect (increased inhibition rate) was calculated. Tpt/pedOO%). When the concentration of flavonoids was 0.3/zg/ml, the leanness inhibition rate of influenza A virus was 52%, and the proliferation inhibition rate of influenza B virus was 48%. The results are shown in Figure 5. The above results fully demonstrate that buckwheat flavonoids also exhibit high proliferation inhibition effects on the stomach of other influenza viruses such as avian influenza. Formulation Example 1 (Capsule) 250 mg of flavonoids was placed in a capsule to prepare an antiviral agent of the present invention. Formulation Example 2 (tablet) A mixture of malt flakes and lactose was molded and formed into a spinner containing 100 mg of flavonoids. [Simplified illustration] [ [Fig. 1] shows a micrograph of the inhibition of cytopathic effect of virus extract (TWEBS) on viral infections [Fig. 2] shows that white bamboo extract (TWEbS) is for viruses. The inhibition of proliferation. Mapping [Fig. 3] shows the inhibition of virus thinning by the isolated components in the extract of T. chinensis (Fig. 4). The flavonoids (flavonoid derivatives) are shown to be human cytomegalovirus. Inhibition map of proliferation [Fig. 5] shows the inhibition of flavonoids on the proliferation of influenza virus. 320044 1363621 [Description of main components]

Claims

1363621 100. 5. Patent application No. 97109281 TDU year 3 pairs of Japanese amendments Replacement page Year of the month Announcement This book is still filled with ten, the scope of patent application 1. An antiviral agent, which is 5,7,4'-three The hydroxydi-foxy-xanthene is the active ingredient* and the virus is a running virus or an influenza virus. 2. The antiviral agent according to claim 1, wherein the virus is a herpesvirus. 3. The antiviral agent of claim 2, wherein the virus is a cytomegalovirus. 4. The antiviral agent according to claim 2, wherein the virus is a ganciclovir-resistant cytomegalovirus. 5. The antiviral agent of claim 2, wherein the virus is a human cytomegalovirus. 6. The antiviral agent of claim 1, wherein the virus is an influenza virus. 7. The antiviral agent according to claim 1, wherein the virus is a type A influenza virus or a type B influenza virus. 8. The antiviral agent of claim 6, wherein the virus is an avian influenza virus. 23 320044 Amendment