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TW200901954A - Antiviral composition - Google Patents

Antiviral composition Download PDF

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TW200901954A
TW200901954A TW097109281A TW97109281A TW200901954A TW 200901954 A TW200901954 A TW 200901954A TW 097109281 A TW097109281 A TW 097109281A TW 97109281 A TW97109281 A TW 97109281A TW 200901954 A TW200901954 A TW 200901954A
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Taiwan
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virus
antiviral agent
present
antiviral
influenza
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TW097109281A
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Chinese (zh)
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TWI363621B (en
Inventor
Kunitomo Watanabe
Mamoru Kouketsu
Tsugiya Murayama
Yuuzou Tsuchida
Kotarou Tsuchida
Daisuke Sakurai
Mitsuo Kawabe
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Yuuzou Tsuchida
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Priority claimed from TH801001299A external-priority patent/TH112912A/en
Priority claimed from PCT/JP2008/055087 external-priority patent/WO2008123102A1/en
Publication of TW200901954A publication Critical patent/TW200901954A/en
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Publication of TWI363621B publication Critical patent/TWI363621B/en

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Abstract

The present invention provides an antiviral composition having high antiviral activity and low side effect (cell toxicity). The antiviral composition contains at least one component selected from the group comprising 5, 7, 4'-trihydroxy-3', 5'-dimethoxyflavone, 3-hydroxypyridine, p-hydroxybenzaldehyde and vanillin as an active component.

Description

200901954 -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) ° 此專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)、膦甲酸(Foscarnet,亦即 PFA)、福米韋生(Fomivirsen)等。其中GCV係被廣泛使用, 5 320044 % 200901954 •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。200901954 - IX. Description of the invention: • [Technical field to which the invention pertains] - The present invention relates to an antiviral agent. [Prior Art] The virus system is incapable of self-propagation, and the parasitic proliferative animal or plant micro-pathogen can be classified into animal virus, plant virus, and microbial virus. Human cytomegalovirus is highly specific and does not proliferate in cells other than human-derived cells. For proliferation, various primary cultured cells such as human fetal 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, the virus that is latently infected is generally susceptible to infection due to immunosuppressive therapy, steroid use, and AIDS or cancer patients after inapparent infection. The sexual host is activated, causing severe opportunistic infections such as pneumonia, retinitis, and colitis. Antiviral agents for the prevention and treatment of diseases caused by this specialized virus 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% 200901954 • However, in recent years, the GCV-resistant virus system has become a problem. In addition, there is also a problem of strong (cytotoxicity) in the side effects, so there is no need for side effects and there is a demand for a drug-resistant virus-effective antiviral activity.

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烧胺(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,對於此等藥劑具有财藥性的 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 κ. 活性的藥劑係備受需求。 另一方面,已知箬竹(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 200901954 -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桿 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 (ferulic acid)、咖啡酸(coffeic acid)、香草搭等苯基丙酸類 (Phenylpropanoid)、3-經基11比咬等,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) ° 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 [專利文獻2]曰本特開2003-201247 [專利文獻3]日本特開2004-359626 [專利文獻4]曰本特開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 200901954 【發明内容】 (發明欲解決之課題) 本:明之目的係提供抗病毒劑。 主二;月:二目的係提供抗病毒活性高且副作用(細 胞毋性)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: ⑴一:抗病毒劑’係以選自5,7,4,-三羥基_3,,5,,_二甲氧 基黃酮、3-羥基吡啶、對-羥基苯甲醛以及香草醛所成 群組中之至少一種作為有效成分者。 ⑺-種抗病毒劑,係卩5,7,4,_三羥基_3,,5,,_二甲氧基黄 酮或3-羥基吡啶作為有效成分者。 (3) 一種抗病毒劑,係卩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⑴至(3)中任一項之抗病毒劑,其中,該病毒為 皰疹病毒(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 200901954 本發明中之「病毒」包括動物病毒、昆蟲病毒、植物 病毒、細菌病毒(嗟菌體),X其是指對於包含人類之哺乳 動物、包含烏類等之動植物會造成不良影響的病毒。 主本發明之2病毒劑可特別奏效之病毒,可列舉如皰疹 病毒、流感病毒,尤其可列舉如巨細胞病毒,特別是人類 巨細胞病毒、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:跑療病毒、 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】 ▲本案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,而將山白竹葉之敎水萃 =於各種㈣巾Μ,藉由各種分_製手段進行分離 精衣,針對各成分調查其抗病毒活性。 結果,發現5,7,4 稱為「,黃酮(Tricin)」)、3_經基吼咬、對-經基苯甲酸 :二香:酪’其中又以5j,4,_三羥基_3,,5,,_二甲氧基, 及3-經基。比咬,特別是5,7,4,_三經基_3,,5,,_二美^ (亦即麥黃酮)對於各種病毒顯示出優異之抗病毒活性, 320044 9 200901954 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)、 甘蔗、竹、芒草(Miscanthus)、蒲葦(pampas grass)、蘆葦 (Phragmites)等茅草類之葉或莖部含有大量之5,7,4’-三經 基-3’,5,’-二甲氧基黃酮(亦即麥黃酮),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、疏 草(Zizanialatifolia)、甘蔗、薏苡(ma-yuen)、蘆葦、芒草、 碁竹(Bamboo grass)、蘆竹(Arundo donax)、蒲葦、結縷草 (Zoysia japonica)。 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(例如曱醇、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’-三羥基-3’,5,’-二甲氧基黃酮)(於此說明書中亦稱為 10 320044 200901954 :二=之細以之;少—種作為有效成分的本發明之 组成:'广」:ί種“、來使用。例如適合作為黏膜保謹 裝置等之抗病毒劑。 相組成物、防腐劑、過遽 本發明之抗病毒劑之劑财為液體狀、 狀、膠體狀、氣溶膠狀中之任-種。本發明:抗 =哥劑可以經口投予、不經口投予之任一種 二經口投予型態可列舉如_、丸劑、粉劑、液劑、口 S糖、糖果、巧克力糖、麵包、餅乾、騫麥 種飲料鮮食品或飲料水溶液、調味料等型態: ’二口投予型产係可列舉如注射劑、局部投予劑(乳膏 :劑、陰道内投予型態(填塞棉球(_«) 1:«:::;^ ··—- /叩予戰媸3次本發明之抗病毒 =紅等化粧品或其他型態之化粧品(乳液、 匕 ^㈣乳霜⑽叫等)或人浴用劑含有本發明二S =叩成者’製成吴容液、洗髮精、沐浴乳 半: 二或液體之型態者等。亦可製成 =固 霧劑等型態。 療用喷務劑、咽頭部炎症治療用喷 本發明之抗病毒劑係除了對人類有效之外 人類以外之哺乳類、烏類、魚貝類、Μ吏作為 棲類、艘蟲類等使用的抗病毒劑亦Ά虫類、兩 之抗病毒劑可用作此等動物用之r :因此,本發明 几病毋· μ (例如寵物用醫 320044 11 200901954 藥、動物用飼料、寵物食品等) ^ 毒劑除了對動物有效之外, V,本發明之抗病 毒劑,另外亦丄 '' ^ 於作為各種植物之抗病 毋片J另外亦,用於作為防腐劑。 若要製造本發明各種劑型 之上诚务人从、 之抗病势劑,則除了預定量 I化δ物以外,亦可使用通當殿# ± * a ,η .^ 、吊之i樂組成物、化粧品、 皮膚用、,且成物寺所用之油性成 腐劑等。 刀4基材成分、保濕劑、防 水等 佳。 抗病毒劑中所使用之水 ’並無特別限制,但一 ,可為自來水、天然水、精製 般以離子交換水等高純度水為 ―油性成分可列舉如M、牛油、豬油'馬油、羊毛脂、 晴動物性油;橄禮油、葡萄籽油、棕櫚 ::油(例如米胚芽油)、芝麻油、菜軒油、紅花油、沙拉 t寺植物性油;流動石蝶、高級脂肪酸酯(例如棕櫊酸辛 酉曰、標搁酸異丙g旨、肉豆該酿!装丄 Π五寇自义辛基十二烷酯)、聚矽氧油等 合成油、半合成油。 油1·生成刀可配合皮膚之保護、賦予潤膚性之效果(以薄 膜被覆皮膚表面,在防止錢之同時,亦賦^軟性、彈 力性的效果)、乾爽感等要求性能而適當組合使用。宣烷、 撖欖油及肉五蔻酸辛基十二烷酯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、 硬脂醯基醇、二十二烷酸(behenic acid)、鯨蠟醇(Cetan〇1)、 凡士林等固體油,較佳為組合使用硬脂酸與鯨蠟醇。 為了將本發明之抗病毒劑製造成乳膏組成物,可使用 320044 12 200901954 -將本發明之化合物、水、 • q客务*丨、,A· , 成仝4成乳貧狀的乳膏化劑。 :^亚扇限制’—般係將單 乳化型單硬脂酸甘油酯(亦 η自仃 化劑者)組合使用。t卩在早心酸甘㈣中添加乳 本發明之抗病毒劑亦可與其他抗病毒劑倂用。 在本發明之抗病毒密,丨中,& 7 ^ _ 化劑、保濕劑、創傷户㈣^ 需求可另含有安定 一—— 。癒4、防腐劑、界面活性劑等。The influenza virus (also known as flu virus) is a virus that infects humans and causes influenza infection, and has 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 chicken mites), both fatal and legally infectious, causing great damage to the chicken industry. In 2006, the anti-avian flu drugs used were three types: amantadine, Zanamivir, and Oseltamivir (trade name Tamiflu). On the other hand, amantadine-resistant influenza virus, zanamivir (osexetvir)-resistant influenza virus, and zanamivir and oseltamivir for these agents The emergence of a drug-resistant virus has also been reported. Therefore, a drug system having no side effects and having antiviral κ. activity which is also effective against a drug-resistant virus is in demand. On the other hand, the Bamboo grass extract is 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 an inhibitory activity against the liver cancer of the old 6 320044 200901954 - and many studies have been carried out in the direction of carcinogenic activity (Non-Patent Document 1). In addition, research has been conducted on the superior-different anti-corrosion effect (Non-Patent Document 2) and the antibacterial effect (Non-Patent Document 3) of H. chinensis. 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 are antibacterial to Escherichia coli, 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, and the like. These mixtures are antibacterial to Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa (Patent Document 4). However, the details of the components in the extract of the white bamboo extract and their antiviral activity are still unknown. [Patent Document 1] WO00/067707 [Patent Document 2] JP-A-2003-201247 [Patent Document 3] Japanese Laid-Open Patent Publication No. 2004-359626 [Patent Document 4] 曰本开开 2006-36731 [Non-Patent Document 1] M Shibata, K. Kubo, M. Onoda, Folia Pharmacol. Jpn, 72, 531-541 (1976) [Non-Patent Document 2] NV 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 200901954 [Summary of the Invention] Problem to be solved) Ben: The purpose of Ming is to provide antiviral agents. Main 2; Month: The second objective is to provide an antiviral agent with high antiviral activity and low side effects (cell sputum). (Method for Solving the Problem) The present invention provides an antiviral agent as follows: (1) A: an antiviral agent is selected from the group consisting of 5, 7, 4, -trihydroxy-3,5,-dimethoxy. At least one of a group consisting of flavonoids, 3-hydroxypyridine, p-hydroxybenzaldehyde, and vanillin is used as an active ingredient. (7) An antiviral agent which is quinone 5,7,4,-trihydroxy-3,5,-dimethoxyxanone or 3-hydroxypyridine as an active ingredient. (3) An antiviral agent which is quinone 5,7,4,-trihydroxy-3,5,-dimethoxyxanone as an active ingredient. (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 the above (1) to (3) 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 avian influenza virus. 320044 8 200901954 The "virus" in the present invention includes animal virus, insect virus, plant virus, bacterial virus (bacteria), and X refers to an adverse effect on animals and plants including humans, including blacks and the like. virus. The virus of the present invention 2 may be particularly effective, and examples thereof include herpes virus and influenza virus, and particularly, for example, cytomegalovirus, particularly human cytomegalovirus, monkey cytomegalovirus, mouse cytomegalovirus, etc. Cytomegalovirus; human influenza virus such as influenza A virus, influenza B virus, influenza C virus, or avian influenza virus. (Effect of the Invention) The antiviral agent of the present invention is useful for various viruses, in particular, a running virus, particularly a cytomegalovirus, more particularly a human cytomegalovirus; an influenza virus, particularly an influenza A virus, and an influenza B virus. The influenza C virus or the avian influenza virus has a high antiviral activity. The antiviral agent of the present invention has the advantage of low cytotoxicity. [Embodiment] ▲ In order to clarify the antibacterial effect of Sasa veitchii and specify its antibacterial active ingredient, the inventors of the present invention extracted the water from the leaves of the white bamboo leaves in various (four) frames, by various means. Means for separating the coats and investigating the antiviral activity of each component. As a result, it was found that 5,7,4 is called ","flavonoid", 3_base biting, p-benzoic acid: disaccharide: cheese, which is 5j,4,_trihydroxy_3 ,, 5,, -dimethoxy, and 3-carbyl. Specific bite, especially 5,7,4,_trisyl group_3,,5,, _ meimei (also known as flavonoid) shows excellent antiviral activity against various viruses, 320044 9 200901954 and completed the present invention . Hereinafter, the present invention will be specifically described. The active ingredient of the invention 5,7,4'-trihydroxy-3',5,'-dimethoxyflavone, 3-hydroxypyridine, p-hydroxybenzaldehyde, and vanillin are extracted from the mountain white bamboo Out, but of course it can be a synthetic or a source from other sources. For example, plants other than white bamboo, especially most plants belonging to the family Poaceae, such as rice (rice), wheat, maize, barley, semale, sugar cane, bamboo, Miscanthus, pampas The leaves or stems of grasses such as grass and Phragmites contain a large amount of 5,7,4'-trisyl-3',5,'-dimethoxyflavone (also known as flavonoid). Extract from it. The specific plant names are as follows: rice, wheat, barley, oats, rye, panicum miliaceum, setaria italica, eucalyptus (Echinochloa esculenta), maize, Eleusine coracana, sorghum ( Sorghum bicolor), bamboo, Zizanialatifolia, sugar cane, ma-yuen, reed, miscanthus, bamboo grass, Arundo donax, pampas grass, Zoysia japonica. The leaves, stems, and the like of the above plants may be extracted with an appropriate solvent, and the flavonoids may be isolated and purified by separation and purification means 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, decyl alcohol, ethanol, aqueous sterol, aqueous ethanol), and the solid is dissolved in water by using ethyl acetate. It can be refined by distribution or the like. The above compounds (vanillin, p-hydroxybenzaldehyde, 3-hydroxypyridine, 5,7,4'-trihydroxy-3',5,'-dimethoxyflavone) (also referred to herein as 10 in this specification) 320044 200901954 : The composition of the present invention as an active ingredient: 'wide': "used". For example, it is suitable as an antiviral agent such as a mucous membrane retention device. The antiseptic agent and the antiviral agent of the present invention are any one of a liquid form, a colloidal form, a colloidal form and an aerosol form. The present invention: the anti-logic agent can be administered orally, and administered orally. Any of the two oral administration forms may be exemplified by _, pills, powders, liquids, S-sugars, candy, chocolate candy, bread, biscuits, buckwheat beverages, fresh foods or beverage aqueous solutions, seasonings, and the like. : 'Two-injection type of production line can be listed as injection, topical administration (cream: agent, intravaginal administration type (filling cotton ball (_«) 1: «:::; ^ ··-- / 叩 媸 媸 3 times of the invention anti-virus = red cosmetics or other types of cosmetics (emulsion, 匕 ^ (four) cream (10) called) or bath Containing the present invention, the two S = 叩成成's made Wu Rong liquid, shampoo, shower gel half: two or liquid type, etc. can also be made into = type of solid fog agent. In the treatment of pharyngeal head inflammation, the antiviral agent of the present invention is an antiviral agent used for mammals, urchins, fish and shellfish, cockroaches, and other insects, in addition to humans, and mites. The two antiviral agents can be used as r for such animals: therefore, the present invention has several diseases and μ (for example, pet medicine 320044 11 200901954 medicine, animal feed, pet food, etc.) ^ The poison is effective for animals. In addition, V, the antiviral agent of the present invention is also used as a preservative for the disease-resistant tablets J as various plants. To make the various dosage forms of the present invention, For the disease-resistant agent, in addition to the predetermined amount of δ-δ, you can also use the Tong Dian Dian #± * a , η .^ , the hanging i composition, cosmetics, skin, and used in the temple. Oily rot, etc. Knife 4 base material, moisturizer, waterproof, etc. Antiviral The water used in the medium is not particularly limited. However, high-purity water such as tap water, natural water, and ion-exchanged water can be used as an oily component, such as M, butter, lard, horse oil, and wool. Fat, clear animal oil; olive oil, grape seed oil, palm: oil (such as rice germ oil), sesame oil, vegetable oil, safflower oil, salad t plant oil; mobile stone butterfly, higher fatty acid ester (For example, citric acid palmitate, isopropyl gluconate, meat beans, 丄Π 寇 寇 寇 octyl octyl decyl ester), synthetic oils such as polyoxygenated oil, semi-synthetic oil. The knife can be used in combination with the protection of the skin, the effect of imparting emollient properties (the surface of the skin is covered with a film, the effect of softness and elasticity at the same time as the prevention of money), and the dry feeling. A combination of sulphate, eucalyptus oil and octyldodecyl pentanoate is one of the preferred examples. In order to adjust the hardness and the flow name of the antiviral agent, a solid oil such as stearic acid, stearyl alcohol, behenic acid, cetyl alcohol (Cetan〇1), petrolatum or the like may be used, preferably Stearic acid and cetyl alcohol are used in combination. In order to manufacture the antiviral agent of the present invention into a cream composition, 320044 12 200901954 can be used. The compound of the present invention, water, ?q, *, *, A, 4 into a milk-like cream Chemical agent. : ^ Sub-fan limitation 'Generally, a single emulsion type glyceryl monostearate (also known as η self-oxidizing agent) is used in combination. Adding milk to early heart acid (4) The antiviral agent of the present invention can also be used together with other antiviral agents. In the antiviral, sputum, & 7 ^ _ agent, moisturizer, wounded household (four) ^ requirements of the present invention may additionally contain stability one -. 4, preservatives, surfactants, etc.

之組劑而Λ’可列舉如缓乙婦聚合物與氫氧化鉀 d. ] 口 二乙—醇二硬脂酸酯((polyethylene giycoI glyclTl? ^ 〇 ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ (polyethylene -醇單硬二::ame)(亦即為聚乙二醇二硬腊酸醋與聚乙 一 _早硬月旨酸醋之彳、、日 至2〇〇〇〇),士 )(聚乙二醇之分子量為1,〇〇〇 為⑨其安定性高,且水與油不會分離,並且作 、:二二可有效地調節塗佈於皮膚時之硬度,故較佳。 物(尤以源自木立Μ之^;玻取尿;;1膠原、蘆蒼萃取 乙s之盧會卒取物(2)為佳)、尿素、1,3- 二海蒸糖一)、山梨醇、胺基酸… 甘草=!治癒劍而言,可列舉如尿囊素、甘草酸二納、 甘早卒取物、艾草萃取物等。 防腐劑係輔助用材料。 如對H I列舉如苯f義、對·絲Μ酸储院S旨(例 酸甲…基苯甲酸乙…基苯甲 一、各基本甲酸丁酯等被稱為對-羥基苯甲酸酯 320044 13 200901954 者)、丙酸鈉、混合脂肪酸酯(癸酸甘油酯(glyceryl caprate)、月桂酸聚甘油酯-2、月桂酸聚甘油酯_丨〇的混合 物)、苯氧基乙醇、感光素201號(黃色色素)、丨,2_戊二醇 專’又以對-經基苯甲酸S旨、混合脂肪酸醋、1,2 -戊二醇為 較佳。 就界面活性劑而言’可列舉如N-醯基-L-麵胺酸鈉、 聚氧伸乙基山梨醇酐單硬脂酸酯等。 依據需要亦可復含有香氣成分,例如橘油、檸檬油 雲杉油(spruce oil)、香料等。 含有本發明之抗病毒劑的黏膜保護組成物、病毒感染 預防及/或治療用組成物,可有效抑制病毒從眼、鼻、喉、 耳、肛門、陰部等之黏膜或創傷部位及皮膚侵入體内,並 有效地預防m療包含院内感染之病毒感染。病毒感染 及/或治療用組成物的更具體的型態,係可列舉如黏膜 保護布或口腔組成物。 黏膜保護布係藉由含浸、噴霧以法錢具有通氣七 之載脰(例如蠶絲、棉、麻等天然纖維;聚胺甲酸酉 人y:ethane)、聚乙烯、聚丙烯、尼龍、聚醋、丙稀酸奪 纖維本身戍線等之2種以上之混合 布二;=為了方便起見,此說明書中之「㈣ 1且:亦包含纖維本身、線、紙等者。 月經:衛=型Ϊ :言,除了紗布、口罩、眼罩、月經帶 細▼、衛生紙、缚瘡處置用紗布、耳塞、 320044 ]4 200901954 •液體_創膏等被if類為衛生用品而直接接觸㈣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、日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,手術用缝合線等醫療材料等會直接或間接接觸皮 膚的物品。 含有本發明之抗病毒劑的口腔組成物,可列舉如軟膠 ㈣麵y)、床踢(jelly)、漸溶錠劑(tr〇che)、糖果(candy/ 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、咽頭部炎症治療用喷霧劑等。 本發明之抗病毒劑之抗病毒活性高,本發明之化合物 僅以麵㈣至lppm左右之固形物濃度即可顯示 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5〇〇一,較佳為5至 2000mg’ 更佳為 1〇至 1〇〇 左右投予即可。 …-人或疋分成2至6:欠 若要使例如軟膠、,東膠、漸溶錠劑、糖果、口香糖、 巧克力糖、錠劑、丸劑(例如仁丹)、洗口劑、漱口劑、牙 貧、貼附黏膜之薄膜箄口脉^丄 厚膜4 口 ^組成物中含有本發明之化合 二St腔組成物之任一階段中,以使本發明之 :物=:上述投予量,適量添加至口腔組成物原料中。 二=之化合物之固形物較佳為添加…叫 貝里0左右,更佳為6至15Χ(1Π 1〇-5)質量%, 320044 15 200901954 最佳為8至12XO0-1至ΙΟ·5)質量%左右。 本發明之抗病毒劑之劑型’可列舉如膠囊劑、乾糖裝 (dry syrup)、錠劑、丸劑、粉劑、液劑,例如點鼻用之液 劑及凝膠劑、口腔喷霧劑等之氣溶勝等鼻腔或咽頭直接適 用之點鼻用製劑、軟膏劑、乳劑及乳f劑等經皮吸收用擊 劑。此等可依據常法調製。 衣 用以製造上述劑型之抗病毒劑的基劑成分,可列舉 如:葡萄糖、乳糖、嚴糖、水备、糊精、環糊精、殿粉等 賦形劑;阿拉伯膠、叛甲基纖維素納、結晶纖維素、勝基 材(gmn base)等結合劑;澱粉等崩解劑;硬脂酸鎂、斧= ㈣酸酷#潤滑劑;香料、葉綠素、薄荷、ι•薄荷腦等清 亦化劑’辛基十二烧醇等高級醇;肉豆謹酸異丙醋、己二 酸,異丙醋及掠櫚酸異丙醋等脂肪酸醋;聚山梨酸醋肋 及聚乳伸乙基硬化蓖麻油等懸濁化劑;缓乙婦聚合物、經 丙基纖維素、聚乙烯基吼嘻咬酮及玻尿酸納等高分子化合 …甘油丙一醇及^丁二醇等多元醇;二異丙醇胺、 虱减納、魏二氫_及鱗酸氫納等ρΗ調節劑;鱗酸氯 〆、.氧化鈉、硫代硫酸鈉、亞硫酸鈉及乙二胺四乙酸鈉 so^um edetate)等安定化劑;對-經基苯甲酸甲自旨 '對經 ;!V^S^SI ' ^^^^^(benzalkonium chloride)^ 本=权予(benzeih〇nium chl〇Hde)等防腐劑等。 ml n隻布之型恶來使用本發明之抗病毒劑時,只要 合物,黏膜或創傷部位之保護布(紗布等)含有本發明之化 天更換1至3次左右即可。當以手術用缝合線 320044 16 200901954 之型態來使用時,可有效地抑制病毒從缝合患部侵入,以 促進手術部位之回復。 當為了防止在醫院等之院内感染而以保護布之型態來 使用本發明之抗病毒劑時,本發明之抗病毒劑之感染防止 效果可存續長期間。當因洗滌而使該效果降低時,只要適 當地更換保護布、或是進行使保護布再次含有本發明之化 合物的處理即可。 當使用本發明之抗病毒劑作為口腔組成物時,在適宜 並需要之際,藉由預先將其含在口中,而可極度簡便地預 防病毒感染並抑制病毒增殖。另外,口香糖、糖果等缓釋 性型態之組成物,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2(^(10-1至10_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。 過濾裝置 本發明係亦提供一種含有本發明之化合物作為有效成 分之空氣過濾裝置。就具體之型態而言,可列舉如使用於 換氣扇、空調設備、汽車空調設備、空氣吸入口、空氣排 出口、紗窗、空氣清淨機等之空氣通過部位的過濾器。過 滤·器之基枯並無特別限制5可列舉如蠶絲、棉、羊毛、麻 等天然纖維;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、喷 17 320044 200901954 .:等::、而Λ此等過濾器含有本發明之化合物之水稀釋 以l秌即可。過濾器中之本發明之化合物的含量, •固形物較佳為2至20χΠο-〗石1Λ 5 5 , (1〇至10 )質量%左右,更佳為ό 至l)x(10 主;[〇5)質詈%,曰处* 量%左右。 )貝1/〇取佳為8至ΐ2χ(ι〇-ι至1〇-5)質 病毒之抗病毒作用) 竹萃取物對於皰疹病毒之 實施例1(山白竹萃取物對於皰疹 依據以下之方法,調查山白 抗病毒作用。 方法: 使經單層培養於培養皿之人類Μ肺纖維胚細胞 (Pulm〇nary flbroblast)(MRC_5)感染人類巨細胞病毒 =MV;標準株之τ_株以及更昔洛韋(G_ici叫耐 =性之別R株)後,添加市售之山白竹萃取 tTWEBS(固形物濃度%質量%))之稀釋水溶液= /辰度之從山白竹萃取物分離之精製物、以及含有市隹 毒劑之培養液,於5%二氧化碳培養器中開始培養。°几 ⑴在培養後第1天、第3天、第6天時,以顯微鏡觀察细 紀病變效應(cytopathic effeci ;亦即啦)之有無 況’評估各試料對於CPE之效果。 … ⑺將培養㈣6天時培養液巾職生之病録子數心 园斑法⑽que method)測定,評估各試料對於病工 (virus production)之效果。 ⑺在培養後第!天、第3天、第6天時,將各 染細胞溶解於料歸液巾m法絲蛋白質j 320044 18 200901954 -以西方點墨法來比較檢討病毒蛋白質之表現。尤其是針 -對在感染後數小時之初期即表現且接著作為病毒複譽 -之觸發蛋白⑻gger protein)而發揮作用的極重要的迅、 早期蛋白(immediate_earIy pr〇tein)、以及職合 素等晚期蛋白的表現,來比⑽估各試料之效果。 將使用山白竹萃取物(鳳凰堂販售之twebs(固形物 漠度50質量%))之稀釋水溶液時的細胞病變效應表示於第 1圖,並將病毒增紅㈣絲表示於第2圖。對於τ〇·6 株及93-m株這兩株,可確認到至少卩〇 4%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(尤其是麥黃酮)不僅對於通常 之巨細胞病毒有效’即使對於葛昔㈣耐隸病毒亦有效。 跑疹病喜…絲! 攸山白竹卒取物分離之精製物,係使用對-香豆酸(系 =1)、香草駿(系列2)、對·經基苯曱盤(系列3)、3_輕基吨 疋(系列4)、5,7,4 -二經基_3,,5,,_二甲氧基黃酉啦即麥黃 酮)(系列5)。 、 將各化合物之HCMV增殖抑制效果表示於第3圖。 一另外,將麥黃酉同濃度與病毒力價(νί·份叫的關係表 不於第4圖。可知當麥黃酮濃度為111//g/ml時,病毒之 增殖係幾乎完全被抑制。 主更進一步,將各種化合物之1(:^(50%抑制濃度)(細胞 )(g/ml)、EC50(50%有效濃度)(从 g/ml)、以及 §1(選擇 指數)表示於表1。 320044 19 200901954 [表i] 化合物 ic5〇 ec50 SI 對-香豆酸 187 8.2 22.8 香草醛 215 48.0 4.5 對-羥基苯曱醛 305 12.8 23.8 3 -經基°比σ定 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 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(ic5〇/ec5())顯著偏高。 實施例2 (麥黃嗣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 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 塑膠培養孤之MDCK細胞,使各病毒在室温中吸附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 200901954 *培養完畢後’以使細胞㈣’除 .〇观亞甲基藍液染色後,計㈣現之㈣斑數。 :添加有麥黃酮之實驗,且之嗟菌斑數⑽除以未添加 有麥頁酮之實驗組之嗟菌斑數(pc),計算出抗病毒作用(增 瘦抑制率=pt/pcxl〇〇%)。當麥黃酉同濃度為o.3/zg/ml時, 對於A型流感病毒之增殖抑制座生 ^^ a 曰直羊為)2%,對於β型流感病 毋之增殖抑制率為48%。結果係示於第5圖。 上料果充分示唉麥相對於禽流感等其他流感病毒 亦頦示咼增殖抑制作用。 製劑例1(膠囊劑) 將麥黃酮25〇mg置人艘_臺&制 製劑例2(錠劑) I囊内,衣成本發明之抗病毒劑。The grouping agent and Λ' can be exemplified by a slower ethyl polymer and potassium hydroxide d.] mouth diethyl-alcohol distearate ((polyethylene giycoI glyclTl? ^ 〇 ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ (polyethylene - alcohol single hard two:: ame) (that is, polyethylene glycol tartaric acid vinegar and polyethylene _ _ early hard moon vinegar, 2 to 2), ()) The molecular weight of polyethylene glycol is 1, and 〇〇〇 is 9, its stability is high, and water and oil are not separated, and 2:2 can effectively adjust the hardness when applied to the skin, so it is preferable. (especially from the root of Mu Lijun; glass to take urine;; 1 collagen, Lu Chong extract B s Lu will be a stroke (2) is better), urea, 1,3-two sea steamed sugar a), Yamanashi Alcohol, amino acid... Licorice =! For the cure of the sword, for example, allantoin, diammonium glycyrrhizinate, early pregnancy, wormwood extract, etc. Preservatives are auxiliary materials. Benzene f, 对 Μ Μ 储 储 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例 例Sodium propionate, mixed fat Ester (glyceryl caprate, lauric acid polyglyceride-2, lauric acid polyglycerol _ 丨〇 mixture), phenoxyethanol, photoreceptor No. 201 (yellow pigment), hydrazine, 2 y The diol is preferably used in the form of p-parabenbenzoic acid, mixed fatty acid vinegar, and 1,2-pentanediol. In the case of a surfactant, it may be exemplified by N-mercapto-L- faceamine. Sodium, polyoxyethylene ethyl sorbitan monostearate, etc., if necessary, may also contain aroma components, such as orange oil, lemon oil spruce oil, spices, etc. Containing the antiviral agent of the present invention The mucosal protective composition, the virus infection prevention and/or therapeutic composition can effectively inhibit the virus from invading the mucous membrane or the wound site and the skin of the eyes, nose, throat, ears, anus, genitals, etc., and effectively prevent m Treatment includes viral infections of nosocomial infections. More specific forms of viral infections and/or therapeutic compositions are exemplified by mucosal protective cloths or oral compositions. Mucosal protective fabrics are ventilated by impregnation and spraying. Seven of the 脰 (such as silk, cotton, hemp and other natural Dimensional; y: ethane), polyethylene, polypropylene, nylon, polyester, acrylic acid, fiber, and other two or more mixed cloths; = for convenience, in this specification "(4) 1 and: also includes the fiber itself, thread, paper, etc. Menstruation: Wei = type Ϊ: words, except gauze, mask, eye mask, menstrual belt fine ▼, toilet paper, gauze for the treatment of sore, earplugs, 320044] 4 200901954 • Liquid _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Articles such as articles, sheets, quilt covers, pillow covers, bed supplies, etc., interior decorations such as curtains, wallpapers, carpets, interior decoration materials, medical materials such as surgical sutures, etc., which directly or indirectly contact the skin. Examples of the oral composition containing the antiviral agent of the present invention include soft gelatinous (y) face y), bed kick (jelly), gradual dissolution tablet (tr〇che), candy (candy/chewing gum, chocolate candy, lozenge, Pills, mouthwashes, mouthwashes, toothpastes, films attached to mucous membranes, sprays for the treatment of pharyngeal head inflammation, etc. The antiviral agent of the present invention has high antiviral activity, and the compound of the present invention is only in the range of (4) to 1 ppm. The anti-viral activity can be exhibited by the concentration of the solids on the left and right. When the antiviral agent of the present invention is used in humans, it is considered that the symptoms, age, and body weight of the adult are from i to 5, preferably from 5 to 2000 mg per day. More preferably, it can be administered from about 1 to about 1 inch. ...-People or sputum is divided into 2 to 6: if it is to be made, for example, soft rubber, east gum, gradual dissolution lozenge, candy, chewing gum, chocolate candy, ingot Agent, pill (such as Rendan), mouthwash, mouthwash, tooth-poor, film attached to the mucous membrane, 箄 脉 丄 丄 4 thick film 4 mouth ^ composition containing the compound of the two St cavity composition of the present invention In the stage, in order to make the present invention: the above-mentioned dosage, the appropriate amount is added to the oral cavity In the raw material, the solid matter of the compound of the second= is preferably added...called Berry 0 or so, more preferably 6 to 15 Χ (1Π 1〇-5)% by mass, 320044 15 200901954 Best 8 to 12XO0-1 to ΙΟ · 5) About % by mass. The dosage form of the antiviral agent of the present invention may, for example, be a capsule, a dry syrup, a tablet, a pill, a powder, a liquid, such as a liquid or gel for nasal spray, an oral spray, or the like. It is suitable for percutaneous absorption of nasal preparations, ointments, emulsions and emulsions, such as nasal sprays and pharyngeal heads. These can be modulated according to the usual method. The base component for preparing the antiviral agent of the above dosage form may, for example, be an excipient such as glucose, lactose, Yan sugar, water preparation, dextrin, cyclodextrin, and temple powder; gum arabic, methylidene fiber Bonding agents such as sodium, crystalline cellulose, gmn base; disintegrants such as starch; magnesium stearate, axe = (4) sour cool # lubricant; spices, chlorophyll, mint, ι•Menthol, etc. High-alcohol such as octyl dodecyl alcohol; fatty acid vinegar such as isopropyl vinegar, adipic acid, isopropyl vinegar and isopropyl vinegar; polysorbate ribs and polyemulsion Base-hardening castor oil and other suspending agents; slow-growth polymer, propyl cellulose, polyvinyl ketone ketone and sodium hyaluronic acid and other macromolecules... glycerol propanol and butyl glycol; Diisopropanolamine, guanidine reduction, Wei Dihydrogen and guanidine hydrochloride, etc.; chlorate citrate, sodium oxide, sodium thiosulfate, sodium sulfite and sodium edetate so^um edetate) Anteinizing agent; p-parabenzic acid A from the purpose of 'the passage;! V^S^SI ' ^^^^^(benzalkonium chloride)^ this = right to (be Preservatives such as nzeih〇nium chl〇Hde). When the antiviral agent of the present invention is used in the case of the mold of the present invention, the protective cloth (gauze, etc.) of the mucosa or the wound site may be replaced by the use of the present invention for about 1 to 3 times. When used in the form of surgical suture 320044 16 200901954, the virus can be effectively inhibited from invading the affected part to promote the recovery of the surgical site. When the antiviral agent of the present invention is used in a form of a protective cloth in order to prevent infection in a hospital such as a hospital, the anti-viral agent of the present invention can have an infection preventing effect for a long period of time. When the effect is lowered by washing, the protective cloth may be appropriately replaced or the protective cloth may be further contained in the compound of the present invention. When the antiviral agent of the present invention is used as an oral composition, it is extremely easy to prevent viral infection and inhibit virus proliferation by appropriately preliminarily containing it in the mouth. Further, it is advantageous that the composition of a sustained-release type such as chewing gum or candy can exhibit an effect 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. It is extremely easy to prevent viral infection and inhibit virus proliferation by previously applying an emulsion or oil containing the compound of the present invention in an amount of 2 to 2 (1 (10-1 to 10_5)% by mass of the solid matter to the skin or the like. Filtration device The present invention also provides an air filtration device containing the compound of the present invention as an active ingredient. In a specific form, it can be exemplified, for example, for use in a ventilation fan, an air conditioner, an automobile air conditioner, an air intake, an air exhaust. Filters for air passage parts such as outlets, screens, air cleaners, etc. There is no particular limitation on the basis of the filter. 5, for example, natural fibers such as silk, cotton, wool, and hemp; polyamine phthalate, polyethylene, Synthetic fibers such as polypropylene, nylon, polyester, acrylic, etc.; semi-synthetic fibers; or woven fabrics, fabrics, non-woven fabrics, papers, etc. of a mixture of two or more of these, as long as by impregnation, spray 17 320044 200901954 .: And the like: and the filter containing the compound of the present invention is diluted with water. The content of the compound of the present invention in the filter, • the solid content is preferably 2 to 20 χΠ ο - Stone 1Λ 5 5 , (1〇 to 10)% by mass, more preferably ό to l)x(10 main; [〇5) 詈%, 曰*%%. ) 1 / 〇 佳 佳 佳 佳 佳 佳 佳 佳 佳 佳 佳 佳 佳 佳 佳 佳 佳 佳 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 The method of investigating the antiviral effect of the mountain white. Method: Infecting human cytomegalovirus=MV with human porphyry fibroblast (MRC_5) cultured in a single culture dish in a culture dish; And ganciclovir (G_ici called resistance = sex strain R), adding a commercially available mountain white bamboo extract tTWEBS (solid content concentration%% by mass)) diluted aqueous solution = / Chendu from the mountain white bamboo extract separation The purified product and the culture solution containing the municipal cockroach were started to be cultured in a 5% carbon dioxide incubator. ° (1) On the first day, the third day, and the sixth day after the culture, the effect of the cytopathic effeci (ie, y) was observed by a microscope to evaluate the effect of each sample on CPE. (7) The effect of each sample on the virus production was evaluated by cultivating (4) the number of the disease records of the cultivating liquid wipes at 6 days. (7) After training! On days, 3rd, and 6th, each dyed cell was dissolved in a liquid returning liquid m-filament protein j 320044 18 200901954 - The performance of viral proteins was compared by Western blotting. In particular, the needle--important early-early protein (immediate_earIy pr〇tein), which functions in the early days after infection and which is the trigger protein (8) gger protein, which plays a role in viral recognition, and the occupational protein, etc. The performance of late proteins is compared to (10) the effect of each sample. The cytopathic effect in the case of using a dilute aqueous solution of the extract of the white bamboo extract (twebs sold by the phoenix hall (solid matter 50% by mass)) is shown in Fig. 1 and the virus red (four) filament is shown in Fig. 2. For both of the τ〇·6 strain and the 93-m strain, it was confirmed that at least %4% of the concentration inhibited the cytopathic effect and the virus proliferation effect. This fact indicates that the present invention firstly found that the components (especially flavonoids) in the extract of S. chinensis are effective not only for the usual cytomegalovirus, but also for the virulence virus. Run a rash, hi... silk! The refined product of the separation of the white bamboo and bamboo shoots was made using p-coumaric acid (system=1), vanilla (series 2), p-benzopyrene plate (series 3), and 3_light base tons ( Series 4), 5,7,4 -di-based _3,,5,,-dimethoxyxanthine, ie, flavonoids) (Series 5). The HCMV proliferation inhibitory effect of each compound is shown in Fig. 3. In addition, the relationship between the same concentration of wheat scutellariae and the viral power price (vί·份) is not shown in Fig. 4. It can be seen that when the concentration of flavonol is 111//g/ml, the proliferation of the virus is almost completely suppressed. Further, 1 (: (50% inhibitory concentration) (cell) (g/ml), EC50 (50% effective concentration) (from g/ml), and § 1 (selection index) of various compounds are shown in Table 1. 320044 19 200901954 [Table i] Compound ic5〇ec50 SI p-coumaric acid 187 8.2 22.8 Vanillin 215 48.0 4.5 p-Hydroxybenzaldehyde 305 12.8 23.8 3 - ratio σ 263 3.4 77.4 Flavonoid 2050 1.7 1205.8 Gemcyclovir 0.3 to 0.8 According to Table 1, the compounds of the present invention, especially flavonoids (flavonoid derivatives), have a significantly low cytotoxicity and a low effective concentration (high activity). Therefore, the selection index (ic5〇/ec5()) was significantly higher. Example 2 (Antiviral effect of wheat scutellariae against influenza virus) The antiviral effect of flavonoids against influenza virus was investigated according to the following method: Cell: MDCK cell influenza virus Type: A/Hiroshima/52/2005, H3N2 B/Malaysia/2506 /2004 After each virus was propagated to MDCK cells and the viral power was determined, it was stored frozen in a freezer at -80 ° C, and used after thawing at the time of use. Method: According to the usual plaque method, The MDCK cells were cultured in a plastic culture medium in a 5% carbon dioxide incubator, and the viruses were adsorbed for 1 hour at room temperature. After removing the unadsorbed virus, the pancreas containing various concentrations of flavonoids was added thereto. 0.6% acacia medium of trypsin, solidified at room temperature, and then cultured in an incubator for 2 days with 5% carbon dioxide. 20 320044 200901954 * After the culture is completed, 'to make the cells (4)' remove. After the liquid staining, count (4) the current (four) plaque number: the experiment with the addition of flavonoids, and the number of plaques (10) divided by the number of plaques (pc) of the experimental group without melamine, calculate the resistance The role of the virus (slimation inhibition rate = pt / pcxl 〇〇%). When the same concentration of wheat scutellariae is o.3 / zg / ml, for the proliferation inhibition of influenza A virus ^ ^ a 曰 straight sheep is) 2% The inhibition rate of proliferation of β-flu sputum was 48%. The results are shown in the 5th. The toppings fully show that buckwheat also shows the inhibition of proliferation of sputum against other influenza viruses such as avian flu. Formulation Example 1 (capsule) Putting flavonoids 25 〇mg into a vessel _ Taiwan & Preparation Example 2 (ingot Agent) I in the capsule, the cost of the antiviral agent of the invention.

將麥黃嗣與乳糠混合、成型,製成1錠中含有麥黃嗣 100mg之錠劑。 ^ ^ J 【圖式簡單說明】 [弟1圖]係頌不山白竹萃取物(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 ^ 2圖]係顯不山白竹萃取物(twebs)對於病毒增殖之 市!1圖 [第3圖]係顯示山白 病毒增狀抑制圖卒取物(TWEBS)中之分離成分對於 [弟4圖]係顯示麥普納^廿 , '、狗(頁酮衍生物)對於人類巨細胞病毒 增殖之抑制圖 丙母 [第5圖]係顯示麥黃鋼野於流感病毒增殖之抑制圖 320044 21 200901954 【主要元件符號說明】The wheat sassafras and the yam are mixed and molded to prepare a tablet containing 100 mg of wheat scutellaria in one tablet. ^ ^ J [Simple description of the schema] [Diagram 1] Microscopic photo of the inhibition of cytopathic effect of virus-infected white bamboo extract (twebs) on virus infection ^ 2 Figure] ) For the city of virus proliferation! 1Fig. [Fig. 3] shows the separation components in the TWEBS, and shows the Maipu Na, ', dog Inhibition of human cytomegalovirus proliferation by benzyl ketone derivatives [Fig. 5] shows inhibition of proliferation of virgin virus in influenza virus 320044 21 200901954 [Description of main component symbols]

Claims (1)

200901954 •十、申請專利範圍: 3抗病毋:'卜其係以選自5,7,4,-三羥基-3,,5,,-二曱氧 -土尹、酮3,基〇比咬、對_經基苯甲盤、以及香草盤所成 群組中之至少一種作為有效成分者。 2. —種抗病毒劑,其心5,7,4,_三減_3,,5,,_二甲氧基黃 酮或3-羥基吡啶作為有效成分者。 3. 種抗病毋劑,其係以5,7,4、三經基_3,,5,,_二甲氧基黃 S同作為有效成分者。 •:申明專利範圍第1項至第3項中任-項之抗病毒劑, 中該病毋為皰療病毒(herpesvirus)者。 5·如申請專利範圍第1項至第3項中任一項之抗病毒劑, ’、中’該病毒為巨細胞病毒(cytomegalovirus)者。 6. 如申請專利範圍第1項至第3項中任一項之抗病毒劑, 其中’該病毒為人類巨細胞病毒者。 7. 如申請專利範圍第3項之抗病毒劑,其中,該病毒為流 感病毒者。 8. 如申請專利範圍第7項之抗病毒劑,其中,該病毒為A 型流感病毒或B型流感病毒者。 9. 如申請專利範圍第7項之抗病毒劑,其中,該病毒為禽 k感病毒者。 23 320044200901954 • Ten, the scope of application for patents: 3 anti-disease: 'Bu is selected from 5,7,4,-trihydroxy-3,,5,,-dioxa-o, ketone 3, ketone ratio At least one of a group consisting of a bite, a benzoic benzoate disk, and a vanilla dish as an active ingredient. 2. An antiviral agent having 5, 7, 4, _3 minus _3, 5, dimethyl diketone or 3-hydroxypyridine as an active ingredient. 3. An anti-disease agent which is the active ingredient of 5, 7, 4, and tri-based _3,5,-dimethoxy yellow S. •: The antiviral agent of any of items 1 to 3 of the patent scope, wherein the disease is herpesvirus. 5. The antiviral agent according to any one of claims 1 to 3, wherein the virus is a cytomegalovirus. 6. The antiviral agent according to any one of claims 1 to 3, wherein the virus is a human cytomegalovirus. 7. The antiviral agent of claim 3, wherein the virus is an influenza virus. 8. The antiviral agent according to claim 7, wherein the virus is a type A influenza virus or a type B influenza virus. 9. The antiviral agent of claim 7, wherein the virus is an avian k virus. 23 320044
TW097109281A 2007-03-19 2008-03-17 Antiviral composition TWI363621B (en)

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JP2007071409 2007-03-19
TH801001299A TH112912A (en) 2008-03-17 Antiviral component
PCT/JP2008/055087 WO2008123102A1 (en) 2007-03-19 2008-03-19 Anti-viral agent

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