【作者】 张国刚；

【导师】 徐绥绪；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2002， 博士

【摘要】 本文综述了有关抗病毒药物的一般筛选方法及抗病毒中药及天然药物的研究概况。 以抗合胞病毒及腺病毒为活性筛选指标，采用CPE法筛选并确定了抗病毒2号和抗病毒6号两个中药复方的有效部位并对其进行了化学成分研究。通过大孔吸附树脂色谱、硅胶柱色谱、硅胶制备薄层色谱、聚酰胺色谱和Sephadex LII-20等各种色谱手段，从有效部位中分离得到28种单体化合物，通过理化常数测定、波谱数据分析等方法鉴定了25个化合物。分别为：连翘酸{2-(1′，4′-二羟基环己基)-乙酸[2-(1′，4′-dihydroxy cyclohexanyl)-acetic acid]}(1)。其它已知化合物为：连翘醇(Rengynol，2)，连翘苷(phillyrin，3)，连翘酯苷A(Forsythoside A，4)，连翘脂素(phillygenin，5)，黄芩素(baicalein，6)，黄芩苷(baicalin，7)，6-甲氧基-5、7、4′-三羟基异黄酮(6-methoxy-5、7、4′-trihydroxyisoflavone，8)，6、3′-二甲氧基-5、7、4′-三羟基异黄酮(6、4′-dimethoxy-5、7、4′-trihydroxyisoflavone，9)，7-甲氧基-5、4′-二羟基二氢黄酮醇(7-methoxy-5、4′-dihydroxyflavanonol，10)，7、3′—二甲氧基—5、4′—二羟基黄酮醇(7、3′-dimethoxy-5、4′-dihydroxyflavonol，11)，4′-甲氧基-8-异戊烯基-7-葡萄吡喃糖基-黄酮醇-3-O-α-L-鼠李糖苷(4′-methoxy-8-isopentenyl-7-glucopyranosyl-flavonol-3-O-α-L--rhamnoside)，12)，氧化苦参碱(Oxymatrine，13)，苦参碱(Matrine，14)，槐定碱(Sophoridine，15)，3—乙酰基—α—香树脂醇(3-acetyl-α-amyranol，16)，3—乙酰基—β—香树脂醇(3-acetyl-β-amyranol，17)，齐墩果酸(Oleanolic acid，18)，熊果酸(Ursolic acid，19)，3—甲氧基—4—羟基—苯甲酸(3-methoxy-4-hydroxy-benzoic acid，20)，3—甲氧基—4—羟基—苯甲醛(3-methoxy-4-hydroxy-benzaldehyde，21)，苯甲酸(benzoic acid，22)，硬脂酸—2、3—双(十四烷酸)—三甘油酯(Octadecanoic acid，2,3-bis[(1-oxotetradecyl)oxy]propyl ester，23)，棕榈酸-α，α’-双甘油酯(Hexadecanoic acid，2-hydroxy-1，3-propanediyl ester，24)，β-谷甾醇(β-sitosterol，25)。其中黄酮类化合物7个，生物碱类化合物3个，其它类化合物15个。化合物1为一新化合物，命名为连翘酸(Rengynic acid)。化合物8、9、10、11及12为处方所含药材的原植物中首次分离得到的已知化合物，沈阳药科大学博士学位论文 摘要 同时本文采用体外抗病毒哈胞病毒、腺病毒）及体内抗炎二个药理指标，应用均匀设计试验方法对抗病毒6号中各提取部位的抗病毒、抗炎等活性进行了综合评价。初步确定了其最佳的有效部位为总酸性物和总碱性物，采用体外CPE方法选择确定化合物连翘酸，连翘酯昔A和 Z－23；Z－54；Z－64为主要活性成分，其中抑制RSV的 IC。；；分别为：9 9，12．7，10．2，5．6，7．in g／ml。将得到的有效部位总酸性物【）和总碱性物（11）按均匀设计试验方法，以抗病毒、抗炎二个药理活性为指标，重新进行抗病毒制剂处方比例筛选，确定了抗病毒制剂的最佳处方。并己经申请了国家专利（申请号：01 106196．0）。 本文首次研究了处方中的主要药材之一即若参的指纹图谱。更多还原

【Abstract】 The subject presented in this disquisition is regarding the normal method of screening for antivirotic medicine, and the status of study on antivirotic Traditional Chinese Medicine and natural pharmaceutical as well.According to the screening standards of Human respiratory syncytial virus (RSV), Human adenovirus C (ADV III), both screening on the effective parts of anti-virus No.2 and anti-virus No.6 have been done by CPE and we also have done further research on the chemical constituents of them. Through all kinds of chromatographic methods such as porous resin(D101), silica gel, preparative TLC and HPLC, polyamide and Sephadex LH-20 etc., we separated 28 individual compounds. Among them, 25 compounds, including 7 flavonoids, 3 alkaloids and 15 other compounds, have been authenticated by chemical and spectral methods. One of the compounds, which is named as Rengynic acid, is a new compound. Compounds 8, 9, 10, 11 and 12 were isolated from these plants for the first time.The New compound named as rengynic acid [ 2-(l ’ ,4 ’ -dihydroxy cyclohexanyl )-acetic acid ] (1), and known compounds: rengynol (2), phillyrin(3), forsythoside A(4), phillygenin(5), baicalein(G), baicalin(7), 6-methoxy-5, 7, 4’ -trihydroxyisoflavone (8), 6, 4’ -dimethoxy, 7, 4’ -trihydroxyisoflavone(9), 7-methoxy-5, 4’ -dihydroxyflavanonol (10), 7, 3’ -dimethoxy-5, 4’ -dihydroxyflavonoK 11), 4’-methoxy-8-isopentenyl-7- glucopyranosyl-flavonoI-3-O-u-L-- rhamnoside (12), oxymatrine (13), matrine (14), sophoridine (15), 3-acetyl- a - amyranol (16), 3-acetyl- & -amyranol (17), oleanolic acid (18), ursolic acid ( 19 ) , 3-methoxy-4-hydroxy-benzoic acid ( 20 ) , 3-methoxy-4-hydroxy-benzaldehyde (21), benzoicacid (22), octadecanoicacid, 2,3-bis [(1-oxotetradecyl) oxy] propyl ester ( 23 ) , hexadecanoic acid, 2-hydroxy-l,3-propanediyl ester (24), -sitosterol (25).Meanwhile, according to the two standards of anti-virus, anti-inflammation,general assessment on activities including anti-virus, anti-inflammation etc. toward every extracts in anti-virus No.6 has been presented in the disquisition by anti-virus method in vitro, anti-inflammation in vivo and uniform design method. The best effective parts, total flavonoids and alkaloids extracts, have been determined initially. For these effective parts, all flavonoids and alkaloids extracts, we carried through proportion screening of anti-virus prescription over again and confirmed the best prescription of anti-virus pharmacy by uniform design method according to the standards of three pharmacological data including anti-virus, anti-inflammation. Then we made Antivirus Powder Injection (API) by a certain technics according to the best prescription of anti-virus pharmacy we got. We have applied for the national patent of this anti-virus pharmacy ( Applying No.: 01106196.0)Chromatographic fingerprint of the part Chinese medicinal materials used in anti-virus pharmacy had been studied in this disquisition.更多还原