银杏叶聚戊烯醇（GP）的分离和衍生物合成机理及生物活性研究
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摘要
银杏叶聚戊烯醇(GP)是银杏叶中新的有效类脂化合物，与人体多萜醇结构相似，参与糖蛋白的生物合成，目前国内外尚未开发利用。
本文以银杏叶为原料，研究GP提取分离机理和纯化工艺；聚戊烯基磷酸酯(GPP)衍生物的合成机理，探讨了GP和GPP保护肝损伤、抗肿瘤和抗病毒药效和药理，为GP保健制剂和新药开发提供基础。
首次系统研究GP分析的方法，建立了GP的TLC、RP-TLC定性和HPLC定量分析方法。以C95-prenol聚戊烯醇为外标法，分析不同树龄和采集时期的GP，GP富集在春季最低，在秋季增幅最快，最佳采集时间是9-10月。苗叶经过精制处理，GP精制品不仅得率在0.7％～0.9％间，而且含量在90％左右。
首次系统研究不同提取方式对提取GP的影响，超声波提取效果最好，GP提取率达90％左右，纯度达18.6％。索氏抽取法作为工业生产首选，GP提取率高达80％以上，纯度16％-19％。
采用皂化反应和溶剂冷冻分离聚戊烯醇不皂化物，皂化剂为5％NaOH-EtOH，石油醚软膏与皂化剂的比例为1：5(g／ml)。溶剂A冷冻温度-10℃至-20℃，溶剂B冷冻温度-20℃以下，溶剂A母液中聚戊烯醇为55.6％，GP回收率为98.5％，溶剂B沉淀物中聚戊烯醇含量64.7％，GP回收率为90％。
采用介质分离聚戊烯醇不皂化物，不同介质对GP分离的效果为硅胶＞氧化铝＞NKA-2＞聚酰胺＞D101。首次采用分子短程蒸馏分离聚戊烯醇不皂化物，馏余物中聚戊烯醇由不皂化物中的46.2％提高到83.7％，而且无溶剂残留，是工业化制备高纯度聚戊烯醇理想的分离方法。采用二级分子蒸馏分离和溶剂重结晶甾醇类化合物，银杏叶甾醇收率为0.03-0.08％，纯度大于95％。利用GC-MS分析，其中8个是甾醇类化合物，除β-谷甾醇外，其它银杏叶甾醇是首次报道。
首次以GP为原料，分别合成聚戊烯基氯磷酸酯、聚戊烯基磷酸单酯(GPP)和聚戊烯基磷酸二乙酯等衍生物，反应产物收率高于80％。由IR、~1H-NMR、~(13)C-NMR和高分辨质谱鉴定其化学结构。
首次研究GP保护肝脏、体内抗肿瘤和体外抗病毒的药效学和药理。结果表明GP无毒副作用，对CCl_4、D-Gal和酒精引起急性肝损伤有保护作用，能明显改善CCl_4致大鼠慢性肝损伤的肝功能，对肝组织羟脯氨酸和胶原蛋白含量明显降低，具有抗慢性肝细胞损伤和抗肝纤维化的作用。
GPP对移植性Heps、肉瘤S_(180)和艾氏癌EC荷瘤鼠的抑制作用明显好于GP。
GP能延长EC荷瘤鼠、荷人脑瘤SF763裸鼠和A549人肺腺癌荷瘤裸鼠的延命率，GP与CTX、PDD、ADM联合化疗Heps、S_(180)和EC荷瘤小鼠，具有很好的协同作同，明显提高联合化疗率，联合~(60)Co放疗Heps荷瘤鼠，其效果高于贞芪冲剂，具有辅助化放疗的作用。
GP能明显增加Heps荷瘤鼠胸腺指数，EC荷瘤鼠的脾指数和胸腺指数，GP可明显提高小鼠巨噬细胞的吞噬指数和吞噬功能，具有体液免疫作用；GP能提高S_(180)荷瘤小鼠肿瘤细胞凋亡指数(APO)至6.35，促进S_(180)荷瘤小鼠肿瘤细胞凋亡，使S_(180)荷瘤小鼠CD_4／CD_8比值接近正常小鼠；GP可通过降低端粒酶活性，促进肿瘤细胞凋亡，达到抑制肿瘤细胞增殖的药理作用。
GP对HepG 2215细胞和MDCK细胞无毒性，对HepG2215分泌的HBV DNA具有很好的抑制作用，GP为25μg／ml和12.5μg／ml的抑制率分别为75.9％和76.6％；GP对H_3N_2甲型流感病毒没有直接的杀灭作用，但能提高MDCK细胞的存活数量：100μg／mlGP对MDCK细胞的存活率为55.6％，具有明显的保护作用。
Polyprenols from ginkgo biloba L (GP) is new effective lipids in ginkgo biloba L, whichhave similar structure as dolichols(DH) in human. GP and DH mainly take part in thebiosynthsis of glycoprotein in vivo, but GP have'nt been developed yet.
The extraction and separation of GP have been studied in this dissertation. The synthesiticmechanism of polyprenyl monophosphates (GPP) was investigated from GP also. To develophealthyfood and new drugs of GP, the bioactives and pharmacology of GP and GPP forhepatoprotective properties, antitumor and antivirus were researched.
The dissertation investigated systemically the analysitic methodology of GP, andestablished qualitative and quantitative scheme of TLC, RP-TLC and HPLC for GP. The contentand seasonal variation of GP were studied with C_(95)-prenol as external standard, the resultsshowed that the content of GP was lowest in spring and highest in fall, the optimum collect timeis from sept. to oct.. The yield of GP was 0.7%～0.9% with about 90% polyprenol by treatmentwith seedlings.
The effection on GP with different extraction styles were systematically researched first.the ultrasonic extraction was best effective with short time, high yield and purity, itstechnological parameter was 40Khz, 150W, solid to liquid ratio (g/ml)1:10,30min,twice, theextract rate of GP was about 90% with purity 18.6%. Zauschneria extract was selected asindustrial production with over 80% yield of GP and 16%-19% polyprenols.
Non-saponifialble matter of GP was made and separated by saponification and solventrefrigeration., saponifier 5%NaOH-EtOH, ratio of paste of petroleum to saponifier 1:5 (g/ml).Solvent A got GP recovery of 98.5% with 55.6% polyprenols in the twice refrigerating fluids at-10℃to -20℃, solvent B got GP revovery of 90% with 64.7% polyprenols at below -20℃inthe twice precipitates while refrigerating.
Column chromatography was selected to purify non-saponifialble matter of GP. Theseperating effect was Silica gel＞alumina＞NKA-2＞polyamide＞D101. Molecular shortdistillation was first used to purify non-saponifialble matter of GP, total polyprenols could beraised from 46.2% to 83.7% in distilled remainder and there was no solvent residue, so it wouldbe the best ideal separation in industry.
Sterols in lipid of GP could be separated byⅡgrade molecular short distillation andrecrystallizatiion with a yield of 0.3-0.8% and over purity 95%. 8 sterols were identified byGC-MS, besidesβ-sitosterol, the other sterols were first reported in ginkgo biloba L.
The derivants of GP were synthesized first by reaction of acylation, hydrolysis and esterifywith phosphorus oxychloride, pyro-phosphoric acid and diethyl chlorophosphate as phosphatein wild alkali, the hydrolysate was purified by silicon gel chromatography and prepared byHPLC,and the yields of monopolyprenyl phosphate and polyprenyl diethyl phosphate andpolyprenylphosphatedichlordate were over 80%, and their structure was identified with IR、 ~1H-NMR、~(13)C-NMR and HRMS.
The bioactives and pharmacology of GP for hepatoprotective properties showed that GP isinnocuity and has a powerful protective effect on acute hepatic injury induced by carbontetrachloride, D-galactosamine and alcohol; GP and YI Shanfu could significantly decreasedserum levels of AST and ALT and significantly improved degree of proliferation of hepaticfibrous tissue and declined content of hydrop roline and collagen. GP holds significant effectson the treatment of hepatic fibrosis of chronic liver injury induced by CCl_4 in Rats.
The bioactives and pharmacology of GP and GPP for antitumor showed that GPP havebetter inhibition than GP on mice transplanted tumor Heps, S_(180) and EC. GP couldsignificantly prolong survival time of mice transphtnted EC tumor, nude bearing SF763 tumorand nude bearing A549 tumor. GP has good synergistic reaction on mice transplanted tumors ofHeps, S_(180) and EC in combination with Fu-5, CTX, PDD and ADM, In particular the lowerdoses of GP with ~(60)Co radiotherapy had the best therapeutic effect on mice transplantedHeps, SoGP have distinct subsidiary effect on chemotherapy and radiotherapy and can reducetoxicity.
GP had higher the clearance than CTX, and could increase remarkablely the phagocyticfunction of the macrophages, increase the index of the thymus gland in mouse with Heps andindex of the spleen in mouse with EC, The APO level in mouse with S_(180) tumor in 5mg/kg GPwas 6.35, which made the rate of CD_4/CD_8 near to the normal mouse. GP have goodpharmacological functions of humoual immunity, inducing apoptosis and inhibitingproliferation.
The bioactives and pharmacology of GP for antivirus in vitro showed GP is no toxicityon cell HepG 2215 and MDCK, and has better inhibition on HBV DNA secreted by cell HepG2215, with inhibition for GP 75.9% at 25μg/ml and 76.6% at 12.5μg/ml; GP had directly nokill on H_3N_2 influenza virus, but GP can raise the survival numbers of cell MDCK, the survivalrate can be raised to 55.6% at GP100μg/ml.
本文以银杏叶为原料，研究GP提取分离机理和纯化工艺；聚戊烯基磷酸酯(GPP)衍生物的合成机理，探讨了GP和GPP保护肝损伤、抗肿瘤和抗病毒药效和药理，为GP保健制剂和新药开发提供基础。
首次系统研究GP分析的方法，建立了GP的TLC、RP-TLC定性和HPLC定量分析方法。以C95-prenol聚戊烯醇为外标法，分析不同树龄和采集时期的GP，GP富集在春季最低，在秋季增幅最快，最佳采集时间是9-10月。苗叶经过精制处理，GP精制品不仅得率在0.7％～0.9％间，而且含量在90％左右。
首次系统研究不同提取方式对提取GP的影响，超声波提取效果最好，GP提取率达90％左右，纯度达18.6％。索氏抽取法作为工业生产首选，GP提取率高达80％以上，纯度16％-19％。
采用皂化反应和溶剂冷冻分离聚戊烯醇不皂化物，皂化剂为5％NaOH-EtOH，石油醚软膏与皂化剂的比例为1：5(g／ml)。溶剂A冷冻温度-10℃至-20℃，溶剂B冷冻温度-20℃以下，溶剂A母液中聚戊烯醇为55.6％，GP回收率为98.5％，溶剂B沉淀物中聚戊烯醇含量64.7％，GP回收率为90％。
采用介质分离聚戊烯醇不皂化物，不同介质对GP分离的效果为硅胶＞氧化铝＞NKA-2＞聚酰胺＞D101。首次采用分子短程蒸馏分离聚戊烯醇不皂化物，馏余物中聚戊烯醇由不皂化物中的46.2％提高到83.7％，而且无溶剂残留，是工业化制备高纯度聚戊烯醇理想的分离方法。采用二级分子蒸馏分离和溶剂重结晶甾醇类化合物，银杏叶甾醇收率为0.03-0.08％，纯度大于95％。利用GC-MS分析，其中8个是甾醇类化合物，除β-谷甾醇外，其它银杏叶甾醇是首次报道。
首次以GP为原料，分别合成聚戊烯基氯磷酸酯、聚戊烯基磷酸单酯(GPP)和聚戊烯基磷酸二乙酯等衍生物，反应产物收率高于80％。由IR、~1H-NMR、~(13)C-NMR和高分辨质谱鉴定其化学结构。
首次研究GP保护肝脏、体内抗肿瘤和体外抗病毒的药效学和药理。结果表明GP无毒副作用，对CCl_4、D-Gal和酒精引起急性肝损伤有保护作用，能明显改善CCl_4致大鼠慢性肝损伤的肝功能，对肝组织羟脯氨酸和胶原蛋白含量明显降低，具有抗慢性肝细胞损伤和抗肝纤维化的作用。
GPP对移植性Heps、肉瘤S_(180)和艾氏癌EC荷瘤鼠的抑制作用明显好于GP。
GP能延长EC荷瘤鼠、荷人脑瘤SF763裸鼠和A549人肺腺癌荷瘤裸鼠的延命率，GP与CTX、PDD、ADM联合化疗Heps、S_(180)和EC荷瘤小鼠，具有很好的协同作同，明显提高联合化疗率，联合~(60)Co放疗Heps荷瘤鼠，其效果高于贞芪冲剂，具有辅助化放疗的作用。
GP能明显增加Heps荷瘤鼠胸腺指数，EC荷瘤鼠的脾指数和胸腺指数，GP可明显提高小鼠巨噬细胞的吞噬指数和吞噬功能，具有体液免疫作用；GP能提高S_(180)荷瘤小鼠肿瘤细胞凋亡指数(APO)至6.35，促进S_(180)荷瘤小鼠肿瘤细胞凋亡，使S_(180)荷瘤小鼠CD_4／CD_8比值接近正常小鼠；GP可通过降低端粒酶活性，促进肿瘤细胞凋亡，达到抑制肿瘤细胞增殖的药理作用。
GP对HepG 2215细胞和MDCK细胞无毒性，对HepG2215分泌的HBV DNA具有很好的抑制作用，GP为25μg／ml和12.5μg／ml的抑制率分别为75.9％和76.6％；GP对H_3N_2甲型流感病毒没有直接的杀灭作用，但能提高MDCK细胞的存活数量：100μg／mlGP对MDCK细胞的存活率为55.6％，具有明显的保护作用。
Polyprenols from ginkgo biloba L (GP) is new effective lipids in ginkgo biloba L, whichhave similar structure as dolichols(DH) in human. GP and DH mainly take part in thebiosynthsis of glycoprotein in vivo, but GP have'nt been developed yet.
The extraction and separation of GP have been studied in this dissertation. The synthesiticmechanism of polyprenyl monophosphates (GPP) was investigated from GP also. To develophealthyfood and new drugs of GP, the bioactives and pharmacology of GP and GPP forhepatoprotective properties, antitumor and antivirus were researched.
The dissertation investigated systemically the analysitic methodology of GP, andestablished qualitative and quantitative scheme of TLC, RP-TLC and HPLC for GP. The contentand seasonal variation of GP were studied with C_(95)-prenol as external standard, the resultsshowed that the content of GP was lowest in spring and highest in fall, the optimum collect timeis from sept. to oct.. The yield of GP was 0.7%～0.9% with about 90% polyprenol by treatmentwith seedlings.
The effection on GP with different extraction styles were systematically researched first.the ultrasonic extraction was best effective with short time, high yield and purity, itstechnological parameter was 40Khz, 150W, solid to liquid ratio (g/ml)1:10,30min,twice, theextract rate of GP was about 90% with purity 18.6%. Zauschneria extract was selected asindustrial production with over 80% yield of GP and 16%-19% polyprenols.
Non-saponifialble matter of GP was made and separated by saponification and solventrefrigeration., saponifier 5%NaOH-EtOH, ratio of paste of petroleum to saponifier 1:5 (g/ml).Solvent A got GP recovery of 98.5% with 55.6% polyprenols in the twice refrigerating fluids at-10℃to -20℃, solvent B got GP revovery of 90% with 64.7% polyprenols at below -20℃inthe twice precipitates while refrigerating.
Column chromatography was selected to purify non-saponifialble matter of GP. Theseperating effect was Silica gel＞alumina＞NKA-2＞polyamide＞D101. Molecular shortdistillation was first used to purify non-saponifialble matter of GP, total polyprenols could beraised from 46.2% to 83.7% in distilled remainder and there was no solvent residue, so it wouldbe the best ideal separation in industry.
Sterols in lipid of GP could be separated byⅡgrade molecular short distillation andrecrystallizatiion with a yield of 0.3-0.8% and over purity 95%. 8 sterols were identified byGC-MS, besidesβ-sitosterol, the other sterols were first reported in ginkgo biloba L.
The derivants of GP were synthesized first by reaction of acylation, hydrolysis and esterifywith phosphorus oxychloride, pyro-phosphoric acid and diethyl chlorophosphate as phosphatein wild alkali, the hydrolysate was purified by silicon gel chromatography and prepared byHPLC,and the yields of monopolyprenyl phosphate and polyprenyl diethyl phosphate andpolyprenylphosphatedichlordate were over 80%, and their structure was identified with IR、 ~1H-NMR、~(13)C-NMR and HRMS.
The bioactives and pharmacology of GP for hepatoprotective properties showed that GP isinnocuity and has a powerful protective effect on acute hepatic injury induced by carbontetrachloride, D-galactosamine and alcohol; GP and YI Shanfu could significantly decreasedserum levels of AST and ALT and significantly improved degree of proliferation of hepaticfibrous tissue and declined content of hydrop roline and collagen. GP holds significant effectson the treatment of hepatic fibrosis of chronic liver injury induced by CCl_4 in Rats.
The bioactives and pharmacology of GP and GPP for antitumor showed that GPP havebetter inhibition than GP on mice transplanted tumor Heps, S_(180) and EC. GP couldsignificantly prolong survival time of mice transphtnted EC tumor, nude bearing SF763 tumorand nude bearing A549 tumor. GP has good synergistic reaction on mice transplanted tumors ofHeps, S_(180) and EC in combination with Fu-5, CTX, PDD and ADM, In particular the lowerdoses of GP with ~(60)Co radiotherapy had the best therapeutic effect on mice transplantedHeps, SoGP have distinct subsidiary effect on chemotherapy and radiotherapy and can reducetoxicity.
GP had higher the clearance than CTX, and could increase remarkablely the phagocyticfunction of the macrophages, increase the index of the thymus gland in mouse with Heps andindex of the spleen in mouse with EC, The APO level in mouse with S_(180) tumor in 5mg/kg GPwas 6.35, which made the rate of CD_4/CD_8 near to the normal mouse. GP have goodpharmacological functions of humoual immunity, inducing apoptosis and inhibitingproliferation.
The bioactives and pharmacology of GP for antivirus in vitro showed GP is no toxicityon cell HepG 2215 and MDCK, and has better inhibition on HBV DNA secreted by cell HepG2215, with inhibition for GP 75.9% at 25μg/ml and 76.6% at 12.5μg/ml; GP had directly nokill on H_3N_2 influenza virus, but GP can raise the survival numbers of cell MDCK, the survivalrate can be raised to 55.6% at GP100μg/ml.
引文
[1] 史清文，刘素云，张文素等，银杏叶的研究开发概况．天然产物研究与开花发，1995，7(1)：73～76
[2] HALER A, SRICHER O, MEIER D. Identification and determination of the flavonids from Ginkgo biloba by high-performance liquid chromatography. J chromatogr, 1992, (605):41
[3] 王成章，陈祥，谭卫红，银杏叶中黄酮类化合物及其分析方法，林产化学与工业，1998年，18(1)，83-88。
[4] 王成章，谭卫红，陈祥，银杏叶中萜内酯的化学成分及分析方法，林产化工通讯，1997，No．5，11-14．
[5] 黄雪悔，蔡军，银杏叶提取物的药理药用研究进展，数理医药学杂志，2005，18(6)：584-585．
[6] 谢燕，张钧寿，银杏叶提取物制剂研究概况，中草药，2005，36(8)：1267-1269．
[7] Rowland R., Latimer P. H., and Giles J. A., Characerization of solanesol, J. Amer. Chem. Soc., 1956, 78:4680.
[8] Lindgren B. o., Betulaprenol from Betula Verrucosa, Acta Chem. Scand, 1965, 19;1317.
[9] Wellburn A. R., Stevenson J., and Mirton R. A., The characterization and properties of ficaprenol-10, -11 and -12 from the leaves of Ficus elastica, Biochem. J., 1967, 102:325-330.
[10] Gough, D. P., et al., Biochem. J. 1970, 118:167-170.
[11] Zinkel, D. F., et al., Phytochemistry. J, 1972, 11: 3387
[12] Hannus, K., et al., Phytochemistry, 1974, 13:2563.
[13] Sasak, W., et al., FEBS Lett., 1976, 64:55.
[14] Ibata K., et al., Phytochemistry. J, 1984, 23:2517.
[15] Mafgorzata W, Ewa Sviezewska and Tadeusz Chojnachi, the diversity of polyprenols in leaves of fruit-trees in Poland, Acta Biochim Polon. 1998, 45, 811-818.
[16] T. Chojnachi, W. jankowski, T. Mankowski, Biochem. J, 1975, 69, 114.
[17] Swiezewska EWA, Long-chain polyrenols in gymnosperm plants, Acta BioChimica polonica. 1988, 35 (2), 131-147.
[18] Ibata, K., Mizuno, M., Tanaka T., long-chain polyprenols in the family pinceae, Phytochemistry, 1984, 23 (4), 783-786.
[19] Swiezewska, E., Sasak, W., Mankowski, T., the search for plant polyprenols. Acta Biochim Polon. 1994, 41, 221-260.
[20] Roslinska M., Walinska K., Swiezewska, E., Plant long-chain polyreaols as chemotaxonomic markers. Cell. Biol. Mol. Lett., 2001, 6(2).
[21] Rowland R., Latimer P. H., and Giles J. A., Characerization of solanesol, J. Amer. Chem. Soc., 1956, 78: 4680.
[22] Stone, K. J., Wellburn, A. R., Hemming, F. W. & Morton, R. A. The characterization of ficaprenol-10, -11 and -12 from leaves of Ficus elastica (decorative rubber plant). Biochem. J. 102, 1967), 313-324.
[23] Khidyrova N. K. and Shakhidoyatov Kh. M., Plant polyprenols and their biological activity, Chemistry of Natural compounds, 2002, 38(2),
[24] Chijnacki T. Swiezewska EWA, and Vogtman T., Polyprenols from plants-structural analogues of mammalian dolochois, Chemica Scripta, 1987, 27:209-214. 17.
[25] 李永辉，欧阳臻，杨克迪，聚戊烯醇类化合物研究进展，时珍国医国约，2005，16(4)：304-306．
[26] lbata, K., Mizuno, M., Takigawa, T, Long chain betulaprenol-type polyprcnols from the leaves of Ginkgo biloba. Biochem. J., 1983 213, 305-311.
[27] 王成章，沈兆邦，陈祥，银杏叶聚戊烯孵化学研究，林产化学与工业，1994，12(4)：279-285
[28] Huh H., Supercritical fluid chromatographic analysis of polyprenols in ginkgo biloba L., J. Chromatogr., 1992, 600(2):314.
[29] 邓永智，袁东星，李权龙，银杏叶中聚戊烯醇酯的CO_2超临界流体提取及高效液相色谱分析，仪器分析，2005(1)，22-26．
[30] Chojnacki, T., and T. Vogtman. The occurrence and seasonaldistribution of C50-C60-polyprenols and of C100 and similar long-chain Polyprenols in leaves of plants. Acta Biochim. Pol. 1984. 31: 115-126.
[31] 王成章，沈兆邦，HPLC归一化法研究树叶中聚戊烯醇的含量，林产化工通迅，1994年第6期。
[32] 唐于平，楼风昌，徐笑萍，银杏叶中聚戊烯醇类化合物的研究进展，天然产物研究与开发．1998，11(6)，101-108．
[33] Thorne, K. J. I., and E. Kodieck. 1966. The structure of bactoprenol, lipid formed by lactobacilli from mevalonic acid. Biochem. J. 99: 123-127.
[34] Tanaka, Y., et al., Polymer, 1982b, 23: 1087-1090.
[35] Tanaka, Y., et al., Rubber Chem. Technol. 1983, 56.
[36] Doddrell, B. M., et al., J. Am. Chem. Soc., 1983.102:6388-6390.
[37] Noritoshi K, Takayuki I. Polyprenyl alcohol containing injections and use, GR3001793T, 1992.
[38] Keijo U, Masanori K, Polyprenyl alcohol composition for soft capsules, KR9300048, 1993.
[39] Okamoto, Y., et al., Polyprenols and polyprenyl phosphates for the inhibition of tumour motastasis, EP035080A2, 1989.
[40] Foster T P., et al., Oil composition of polyprenols, US5880163, 1997
[41] Danilov L. L, et al., Therapeutic compostion and methods, US6525035, 2003.
[42] Eggens I., Chojnack T., Kenne L, Separation, quantitation and distribution of dolichols and doilchyl phisphate in rat and human tissus, Biochimica et Biophysica Acta, 1983, 751, 355-368.
[43] Roshchin V., et al, Immungmodutating agent, RU2137479, 1999
[44] Kuznetsovs S. and Daugavietis M., Effects of plant polyprenols on P-388 leukemia cell sensitivity and chemotherapy resistance in vitro. 18th International Congress of Chemotherapy. Stockholm. p.170.
[45] Danilov L., et al, Antiviral drug. Rus. Pat. Appl. RU 2005475 C1., 1994.
[46] 国家外国专家局智力引进项目材料(2003年)：拉脱维亚医科院聚戊烯醇毒理研究报告。
[47] Roschin V., Immunomodulating agent, RU 2137479. 1999.
[48] Rubens J. et al. Immunomodulating active substances, US 5731357. 1998.
[49] Sanin A. et al. (1994) Antiviral drug, RU2005475.
[50] Safatov A. et. al. (2005) A prototype prophylactic anti-influenza preparation in aerosol form on the basis of Abies sibirica polyprenols, J Aerosol Med., 18 (1):55-62.
[51] Shishkina LN et al. (2002) Mechanisms of action of aerosol preparations based on Abies siberica polyprenols in experimental influenza infection Vopr. Virusol. 46:6 28-33.
[52] 澳大利亚Solagran公司公告, Russian pharmacological approval gained marketing approval pending for ropren, 2006, 9 February.
[53] Kageyu A. et 1l. (1987)Agent for improving hepatic function, JP 62029517.
[54] Yamatsu I. et al. (1985) Remedy and prevention for hepatic disease, JP 60136510.
[55] Yamatsu I. et al. (1988) Therapeutic and preventive agent containing dolichol, US 4791105.
[56] Keischs J. et al. (1997) Biochemical changes in patients with chronic liver diseases treated with plant polyprenols, Proceedings of Int. Conf. Natural Substances for health, Riga, pp53-54.
[57] 澳大利亚Solagran公司公告, Final results of polyprenlos Alzheimer's disease trial, 2005, 20 september.
[58] Rip J. et al. (1985) Distribution, metabolism and function of dolichol and Polyprenols, Prog. Lipid Res. Vol. 24 269-309.
[59] Rupar CA, et al. (1978) Occurrence of dolichol in human tissues Lipids, 13(4): 291-3.
[60] Pennich J. F., Hemming F., and Morton R., Bolichols:A naturally isoprenoid alcohol, Nature (London), 1960, 186:470-472.
[61] 王成章，沈兆邦，多萜醇的化学合成和药物开发，国外医药合成约，2001，6
[62] Imperiali, B., et al., Tetrahedron Lett, 1988, 29 (42), 5343.
[63] Tukigawa, T., et al., Chem. Phys. Lipids, 1989, 51(3-4), 171.
[64] Suzuki,. S., et al., Tetrahodron Lett, 1983 24(46), 5103.
[65] Danilov L, Sanin A, Narovlyanski J. Polyprenyl phosphate as antiviral drug. RU2005475 Cl, 1994.
[66] Sanin A. V., Danilov L. L, Maltsev S D, New immunomodulators of natural origin for therapy of acute viral infections. Abstr. International Immunol. Congr. Budapest, Hungary, 1992
[67] Danilov L. L, Maltsev S D., Deyeya A. V., Nurovlyansky A. N., Phosprenyl: A Novel Drug with Antiviral and Immunomodulatory Activity, Arch. Immunol. Ther. Exp. 1997. vol. 44. p395-400.
[68] Fumimaro T., et al, EP0166436A., 1987.
[69] Danilov. L. L, Maltsev S D. SU 1432065, 1988,
[70] Danilov L L., Chojnachi T., SHIBAEV, V., Phosphorylation of polyprenols via their trichloroacetimidates, Communications, 1984, May, 405.
[71] Danilov L L., Chojnachi T., A simple procedure for preparing dolicholyl monophosphate by the use of POCL3, Febs Letters, 1981, 131(2), 310-312.
[72] Tanaka Y, Ibata, K, USP4886904, 1989 USPS077046. 1991.
[73] 杨克迪，刘自力，童张法，银杏叶聚戊烯醇类化合物分离工艺研究，广西大学学报(自然科学版)，第27卷，第2期，2002年。
[74] 李永辉，宿树兰，杨克迪，银杏叶聚戊烯醇类化合物分离纯化研究，中药材，2004，27(25)，337-339，
[75] 杨小明，银杏聚戊烯醇提取技术研究，基层中药杂志2001年，15(5)，3-5
[76] Adair, W. L., Keller, R. K., Isolation and assay of dolichol and dolichyl phosphate. Methods Enzymol. 1985, 111:201-216.
[77] Swiezewska, E., Chojnacki, T., Jankowski, W. J., The occurrence of long chain polyprenols in leaves of plants of Rosaceae family and their isolation by time-extended liquid chromatography. Biochem. Cell Biol., 1992, , 70 : 448-454
[78] Carlson, T., K. Skorupinska-Tudek, J. Hertel, T, Single polyprenol and dolichol isolationby semipreparative high-performance liquid chromatography technique. J. Lipid Res. 2000. 41: 1177-1180.
[79] Lindgren B. o., Betulaprenol from Betula Verrucosa, Acta Chem. Scand, 1965, 19; 1317.
[80] Sagami, H., A. Kurisaki, K. Ogura and T. Chojnacki. 1992. Separation of dolicholfrom dehydrodolichol by a simple two-plate thin-layer chromatography. J. Lipid Res. 33: 1857-1861.
[81] Eggens I., Chojnack T., Kenae L, Separation, quantitation and distribution of dolichols and dolichyl phisphate in rat and human tissues, Biochimica et Biophysica Acta, 1983, 751, 355-368.
[82] Huh H. Supercritical fluid chromatography analysis of polyprenols in ginkgo biloba L, Chromatogr. 1992. 600 (2), 314
[83] Bamba T, High-resolution analysis of polyprenls by supercritical fluid chromagraphy, Journal of Chromagraphy A, 2001, 911 (1):113-117.
[84] 中华人民共和国药典，2005年版，银杏叶提取物．
[85] 严伟，李淑芬，田松江．超声波协助提取技术[M]．化工进展，2002，21(9)：649-651．
[86] 应崇福，超声学[M]，北京：科学出版社，1990．
[87] 徐任生，中草药有效成分提取与分离[M]．上海科学出版社，1981．
[88] 张迪清．何照范，银杏叶资源化学研究[M]．中国轻工出版社，1999．
[89] 王军武，许松林，分子蒸馏技术的应用现状．化工展，2002，21(7)：499-501．
[90] 许松林，王军武，徐世民．短程蒸馏技术提纯药物的研究．化工学报，2003，54(9)：1343—1344
[91] V Piironen, D Lindsay, T Miettinen, Plant sterols: biosynthesis, biological function and their importance to hunman nutrition. J Sci Food Agric, 2000, 80: 939～966.
[92] 韩军花，冯妹元，王国栋等，常见谷类、豆类食物中植物甾醇含量分析，营养学报，2006，Vol．28 No．5 P．375-378
[93] 丁丽萍，银杏保健茶的制作．现代农业，2002，07
[94] 王成章，沈兆邦，银杏叶中脂肪酸含量及化学组成，林产化工通讯，2000．01
[95] 周雄尊，程从球，罗申·维·依，银杏叶与杉木绿冠提取物化学组分研究，林产化学与化工，1997，17，61-66。
[96] 李国兵，许松林，许春建，等．分子蒸馏过程模型化研究进展，化学工程，2002，30(3)：65—70．
[97] 高瑜莹，裘爱泳，植物甾醇的分析方法，中国油脂，2001年，26(1)，25-28
[98] 许文林．王雅琼，重结晶法精制植物甾醇的溶剂选择，扬州大学学报(自然科学版)．2002年2月第5卷第1期 Vol．5No．1
[99] Danilov L L., Chojnachi T.,, Chemistry and Physics of Lipids, 1989, 51:191-203.
[100] Makltscv S. D., Sizova O. V., Danilov L L., Russian Journal of Bioorganic Chemistry, 2001, 27 (6): 449-452.
[101] Yamatsu I, et al., Remedy and preventive for hepatic diseaes, JP60136510, 1985.
[102] Nekrasova V B., et al., Biologically active additive to food, RU2188563, 2002.
[103] 郑少雄，蔡文仪，邱明才等．血、尿羟脯氨酸测定的方法改进．中华医学检验杂志，1983，6(9)：5031
[104] 苗三明，主编．实验动物和动物实验技术．北京．中国中医药出版社 1997．200
[105] 李仪奎，主编．中药药理实验方法学．上海：上海科学技术出版社，1991．203
[106] 张均田，主编．现代药理实验方法．北京：北京医科大学中国协和医科大学联合出版社．1998．63-64
[107] Xia Z Q, Dong C, Lu S G. Method of liver perfusion for separating rat hepatocytes and primaryculture[J]. Acta Acad, Med Xuzhou, 1999, 19(6):458-459.
[108] 江正辉，王泰龄．酒精性肝病[M]．北京：中国医药科技出社，2001：26-29．
[109] 童英，姚小曼，吴少平．乙醇诱发急性肝损伤生物标记物的探讨．中国食品卫生杂志，1999，11(2)：12-14．
[110] Strubelt O, Younes M, Pentz R. Enhancement by glutathione depletion of ethanol-induced acute hepatotoxicityt in vitro and in vivo[J]. Toxicology, 1987, 45(2):213-223.
[111] 陈奇．中药药理实验方法学[M]．北京：人民卫生出版社，2000．846．
[112] Erystyna W., Tadeusz J., The errect of phosphate ester derivates of polyprenol on model membrane stability, Cell. Biol. Mol. Lett., 2001, vol. 6(2), 426.
[113] Tadeusz J., Teresa. J., Krzysztof N., The role of polyprenol in modulation of physical properties of model membranes. Current Topics in Biophysics, 2001, 25(1), 33.
[114] Rip W., Rupar C., Kothapalli R. and Carroli K. Distribution, metabolism and function of dolichol and polyprenols, Prog. Lipid Res. 1985, 24: 269-309
[115] Kuznetsovs S., Seleznovs J. , Daugayietis M. Urinary dolichol in breast cancer control, The European Journal of cancer, Vol. 30A, Suppl. 2., 1994,
[116] Kuznetsovs S., Seleznovs J., Mikhailovs V., Clinical usefulness of dolichol as a prognostic factor in cancer patients, Can. J. Intect. Diseases, Vol. 6., Suppl. 298: 1023, 1994.
[117] 王成章等，银杏叶聚戊烯醇抗肿瘤生物活性研究，天然产物研究与开发，2002，14(5)．
[118] 王成章等，银杏叶聚戊烯醇联合化疗药对Heps和EC荷瘤小鼠的抗癌作用，中国生化药物杂志，2003，24(3)．
[119] 王成章等，银杏叶聚戊烯醇联合化疗肿瘤的药效研究，林产化学与工业，2003，23(30)，15-18．
[120] Wu XH, Rush JS, Karaoglu D, et al. Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosmine-1 Phosphate Transferase (DPAGT1) Causes a Novel Congenital Disorder of Glycosylation Type 1j. Human Mutation, 2003, 22:144-150
[121] Chojnacki T. Dallner G., The biological role of dolichol, Biochemistry J. 1988, 251, 1-9.
[122] Rip J. et al. Distribution, metabolism and function of dolichol and polyprenols, Prog. Lipid Res. 1985, Vol. 24 269-309.
[123] Guerra CB, Busch R, Boebele RC, et al. Novel glycosytation of HLA-DR alpha disrupts antigen presentation wiuhout altering endosomal localization[J]. J Immunol, 1998, 160:4289
[124] Krajewska-Rychlik 1 (1985) Metabolism of exogenous polyisoprenoids by animal cells cultured in vitro Acta Biochim Pol 32:3 211-23.
[125] Yasugi E, Yokoyama Y, Seyama Y, et al. Biochem Blophys Res Commun, 1995, 216 (3): 8482853.
[126] Dohi T, Yasugi E, Shima M. Biochem Biophys Res Commun. 1996, 224 (1):87291.
[127] Guerra CB, Busch R, Doebele RC, et al. Novel glycosylation of HLA-DR alpha disrupts antigen presentation without altering endosomal localization. J Immunol, 1998, 160: 4289
[128] Rudd PM, Elliott T, Cresswell P, et at. Glycosylation and the immune system. Science, 2001, 291:2370
[129] Shay JW, Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer, 1997, 33 (5):7872791.
[130] Shay JW. Wright WE. Telomerase activity in humman cancer. Curr Opin Oucol, 1996, 8 (1):66271.
[131] Brandt S, Heller H, Schuster KD, Tamoxtfen induces suppression of cell viability and apoptosis in the human hepatoblastoma cell line HepG via down regulation of telomerase activity. Liver Int, 2004, 24 (1):46254.
[132] pronin A. V, Sanin A. V, Deyeva A, Antipov Y., Sachek M., Depot-from of phosphopolyprenols as protective remedy for influenza. "Options for the control of influenza". Conf. Cairs, North Queensland, Australia 4-9 May 1996, p1-11
[133] 陆德源．医学微生物学．第5版．北京：人民卫出版社，2001，268．
[134] 黄祯祥．医学病毒学基础与实验技术．北京：科学出版社，1990．122，152．
[135] 张其威，张楚瑜．抗病毒中药研究的最新进展．中成药，2005，27(1)：118．
[136] Chojnacki T. and Daltner G., The uptake of dietary polyprenols and their modification to active dolichols by the rat liver, J. Biol. Chem. 258: 2, 916-922, 1983.
[137] Sanin A. V., Danilov L. L, Maltsev S D., Study of the phosphorilated isoprenoids as novel anti HIVA-1 compounds with a potent antiviral activity. Abstr. Ⅸ International conference on AIDS, Berlin, June 1993. Abstr. No. 4593.
[2] HALER A, SRICHER O, MEIER D. Identification and determination of the flavonids from Ginkgo biloba by high-performance liquid chromatography. J chromatogr, 1992, (605):41
[3] 王成章，陈祥，谭卫红，银杏叶中黄酮类化合物及其分析方法，林产化学与工业，1998年，18(1)，83-88。
[4] 王成章，谭卫红，陈祥，银杏叶中萜内酯的化学成分及分析方法，林产化工通讯，1997，No．5，11-14．
[5] 黄雪悔，蔡军，银杏叶提取物的药理药用研究进展，数理医药学杂志，2005，18(6)：584-585．
[6] 谢燕，张钧寿，银杏叶提取物制剂研究概况，中草药，2005，36(8)：1267-1269．
[7] Rowland R., Latimer P. H., and Giles J. A., Characerization of solanesol, J. Amer. Chem. Soc., 1956, 78:4680.
[8] Lindgren B. o., Betulaprenol from Betula Verrucosa, Acta Chem. Scand, 1965, 19;1317.
[9] Wellburn A. R., Stevenson J., and Mirton R. A., The characterization and properties of ficaprenol-10, -11 and -12 from the leaves of Ficus elastica, Biochem. J., 1967, 102:325-330.
[10] Gough, D. P., et al., Biochem. J. 1970, 118:167-170.
[11] Zinkel, D. F., et al., Phytochemistry. J, 1972, 11: 3387
[12] Hannus, K., et al., Phytochemistry, 1974, 13:2563.
[13] Sasak, W., et al., FEBS Lett., 1976, 64:55.
[14] Ibata K., et al., Phytochemistry. J, 1984, 23:2517.
[15] Mafgorzata W, Ewa Sviezewska and Tadeusz Chojnachi, the diversity of polyprenols in leaves of fruit-trees in Poland, Acta Biochim Polon. 1998, 45, 811-818.
[16] T. Chojnachi, W. jankowski, T. Mankowski, Biochem. J, 1975, 69, 114.
[17] Swiezewska EWA, Long-chain polyrenols in gymnosperm plants, Acta BioChimica polonica. 1988, 35 (2), 131-147.
[18] Ibata, K., Mizuno, M., Tanaka T., long-chain polyprenols in the family pinceae, Phytochemistry, 1984, 23 (4), 783-786.
[19] Swiezewska, E., Sasak, W., Mankowski, T., the search for plant polyprenols. Acta Biochim Polon. 1994, 41, 221-260.
[20] Roslinska M., Walinska K., Swiezewska, E., Plant long-chain polyreaols as chemotaxonomic markers. Cell. Biol. Mol. Lett., 2001, 6(2).
[21] Rowland R., Latimer P. H., and Giles J. A., Characerization of solanesol, J. Amer. Chem. Soc., 1956, 78: 4680.
[22] Stone, K. J., Wellburn, A. R., Hemming, F. W. & Morton, R. A. The characterization of ficaprenol-10, -11 and -12 from leaves of Ficus elastica (decorative rubber plant). Biochem. J. 102, 1967), 313-324.
[23] Khidyrova N. K. and Shakhidoyatov Kh. M., Plant polyprenols and their biological activity, Chemistry of Natural compounds, 2002, 38(2),
[24] Chijnacki T. Swiezewska EWA, and Vogtman T., Polyprenols from plants-structural analogues of mammalian dolochois, Chemica Scripta, 1987, 27:209-214. 17.
[25] 李永辉，欧阳臻，杨克迪，聚戊烯醇类化合物研究进展，时珍国医国约，2005，16(4)：304-306．
[26] lbata, K., Mizuno, M., Takigawa, T, Long chain betulaprenol-type polyprcnols from the leaves of Ginkgo biloba. Biochem. J., 1983 213, 305-311.
[27] 王成章，沈兆邦，陈祥，银杏叶聚戊烯孵化学研究，林产化学与工业，1994，12(4)：279-285
[28] Huh H., Supercritical fluid chromatographic analysis of polyprenols in ginkgo biloba L., J. Chromatogr., 1992, 600(2):314.
[29] 邓永智，袁东星，李权龙，银杏叶中聚戊烯醇酯的CO_2超临界流体提取及高效液相色谱分析，仪器分析，2005(1)，22-26．
[30] Chojnacki, T., and T. Vogtman. The occurrence and seasonaldistribution of C50-C60-polyprenols and of C100 and similar long-chain Polyprenols in leaves of plants. Acta Biochim. Pol. 1984. 31: 115-126.
[31] 王成章，沈兆邦，HPLC归一化法研究树叶中聚戊烯醇的含量，林产化工通迅，1994年第6期。
[32] 唐于平，楼风昌，徐笑萍，银杏叶中聚戊烯醇类化合物的研究进展，天然产物研究与开发．1998，11(6)，101-108．
[33] Thorne, K. J. I., and E. Kodieck. 1966. The structure of bactoprenol, lipid formed by lactobacilli from mevalonic acid. Biochem. J. 99: 123-127.
[34] Tanaka, Y., et al., Polymer, 1982b, 23: 1087-1090.
[35] Tanaka, Y., et al., Rubber Chem. Technol. 1983, 56.
[36] Doddrell, B. M., et al., J. Am. Chem. Soc., 1983.102:6388-6390.
[37] Noritoshi K, Takayuki I. Polyprenyl alcohol containing injections and use, GR3001793T, 1992.
[38] Keijo U, Masanori K, Polyprenyl alcohol composition for soft capsules, KR9300048, 1993.
[39] Okamoto, Y., et al., Polyprenols and polyprenyl phosphates for the inhibition of tumour motastasis, EP035080A2, 1989.
[40] Foster T P., et al., Oil composition of polyprenols, US5880163, 1997
[41] Danilov L. L, et al., Therapeutic compostion and methods, US6525035, 2003.
[42] Eggens I., Chojnack T., Kenne L, Separation, quantitation and distribution of dolichols and doilchyl phisphate in rat and human tissus, Biochimica et Biophysica Acta, 1983, 751, 355-368.
[43] Roshchin V., et al, Immungmodutating agent, RU2137479, 1999
[44] Kuznetsovs S. and Daugavietis M., Effects of plant polyprenols on P-388 leukemia cell sensitivity and chemotherapy resistance in vitro. 18th International Congress of Chemotherapy. Stockholm. p.170.
[45] Danilov L., et al, Antiviral drug. Rus. Pat. Appl. RU 2005475 C1., 1994.
[46] 国家外国专家局智力引进项目材料(2003年)：拉脱维亚医科院聚戊烯醇毒理研究报告。
[47] Roschin V., Immunomodulating agent, RU 2137479. 1999.
[48] Rubens J. et al. Immunomodulating active substances, US 5731357. 1998.
[49] Sanin A. et al. (1994) Antiviral drug, RU2005475.
[50] Safatov A. et. al. (2005) A prototype prophylactic anti-influenza preparation in aerosol form on the basis of Abies sibirica polyprenols, J Aerosol Med., 18 (1):55-62.
[51] Shishkina LN et al. (2002) Mechanisms of action of aerosol preparations based on Abies siberica polyprenols in experimental influenza infection Vopr. Virusol. 46:6 28-33.
[52] 澳大利亚Solagran公司公告, Russian pharmacological approval gained marketing approval pending for ropren, 2006, 9 February.
[53] Kageyu A. et 1l. (1987)Agent for improving hepatic function, JP 62029517.
[54] Yamatsu I. et al. (1985) Remedy and prevention for hepatic disease, JP 60136510.
[55] Yamatsu I. et al. (1988) Therapeutic and preventive agent containing dolichol, US 4791105.
[56] Keischs J. et al. (1997) Biochemical changes in patients with chronic liver diseases treated with plant polyprenols, Proceedings of Int. Conf. Natural Substances for health, Riga, pp53-54.
[57] 澳大利亚Solagran公司公告, Final results of polyprenlos Alzheimer's disease trial, 2005, 20 september.
[58] Rip J. et al. (1985) Distribution, metabolism and function of dolichol and Polyprenols, Prog. Lipid Res. Vol. 24 269-309.
[59] Rupar CA, et al. (1978) Occurrence of dolichol in human tissues Lipids, 13(4): 291-3.
[60] Pennich J. F., Hemming F., and Morton R., Bolichols:A naturally isoprenoid alcohol, Nature (London), 1960, 186:470-472.
[61] 王成章，沈兆邦，多萜醇的化学合成和药物开发，国外医药合成约，2001，6
[62] Imperiali, B., et al., Tetrahedron Lett, 1988, 29 (42), 5343.
[63] Tukigawa, T., et al., Chem. Phys. Lipids, 1989, 51(3-4), 171.
[64] Suzuki,. S., et al., Tetrahodron Lett, 1983 24(46), 5103.
[65] Danilov L, Sanin A, Narovlyanski J. Polyprenyl phosphate as antiviral drug. RU2005475 Cl, 1994.
[66] Sanin A. V., Danilov L. L, Maltsev S D, New immunomodulators of natural origin for therapy of acute viral infections. Abstr. International Immunol. Congr. Budapest, Hungary, 1992
[67] Danilov L. L, Maltsev S D., Deyeya A. V., Nurovlyansky A. N., Phosprenyl: A Novel Drug with Antiviral and Immunomodulatory Activity, Arch. Immunol. Ther. Exp. 1997. vol. 44. p395-400.
[68] Fumimaro T., et al, EP0166436A., 1987.
[69] Danilov. L. L, Maltsev S D. SU 1432065, 1988,
[70] Danilov L L., Chojnachi T., SHIBAEV, V., Phosphorylation of polyprenols via their trichloroacetimidates, Communications, 1984, May, 405.
[71] Danilov L L., Chojnachi T., A simple procedure for preparing dolicholyl monophosphate by the use of POCL3, Febs Letters, 1981, 131(2), 310-312.
[72] Tanaka Y, Ibata, K, USP4886904, 1989 USPS077046. 1991.
[73] 杨克迪，刘自力，童张法，银杏叶聚戊烯醇类化合物分离工艺研究，广西大学学报(自然科学版)，第27卷，第2期，2002年。
[74] 李永辉，宿树兰，杨克迪，银杏叶聚戊烯醇类化合物分离纯化研究，中药材，2004，27(25)，337-339，
[75] 杨小明，银杏聚戊烯醇提取技术研究，基层中药杂志2001年，15(5)，3-5
[76] Adair, W. L., Keller, R. K., Isolation and assay of dolichol and dolichyl phosphate. Methods Enzymol. 1985, 111:201-216.
[77] Swiezewska, E., Chojnacki, T., Jankowski, W. J., The occurrence of long chain polyprenols in leaves of plants of Rosaceae family and their isolation by time-extended liquid chromatography. Biochem. Cell Biol., 1992, , 70 : 448-454
[78] Carlson, T., K. Skorupinska-Tudek, J. Hertel, T, Single polyprenol and dolichol isolationby semipreparative high-performance liquid chromatography technique. J. Lipid Res. 2000. 41: 1177-1180.
[79] Lindgren B. o., Betulaprenol from Betula Verrucosa, Acta Chem. Scand, 1965, 19; 1317.
[80] Sagami, H., A. Kurisaki, K. Ogura and T. Chojnacki. 1992. Separation of dolicholfrom dehydrodolichol by a simple two-plate thin-layer chromatography. J. Lipid Res. 33: 1857-1861.
[81] Eggens I., Chojnack T., Kenae L, Separation, quantitation and distribution of dolichols and dolichyl phisphate in rat and human tissues, Biochimica et Biophysica Acta, 1983, 751, 355-368.
[82] Huh H. Supercritical fluid chromatography analysis of polyprenols in ginkgo biloba L, Chromatogr. 1992. 600 (2), 314
[83] Bamba T, High-resolution analysis of polyprenls by supercritical fluid chromagraphy, Journal of Chromagraphy A, 2001, 911 (1):113-117.
[84] 中华人民共和国药典，2005年版，银杏叶提取物．
[85] 严伟，李淑芬，田松江．超声波协助提取技术[M]．化工进展，2002，21(9)：649-651．
[86] 应崇福，超声学[M]，北京：科学出版社，1990．
[87] 徐任生，中草药有效成分提取与分离[M]．上海科学出版社，1981．
[88] 张迪清．何照范，银杏叶资源化学研究[M]．中国轻工出版社，1999．
[89] 王军武，许松林，分子蒸馏技术的应用现状．化工展，2002，21(7)：499-501．
[90] 许松林，王军武，徐世民．短程蒸馏技术提纯药物的研究．化工学报，2003，54(9)：1343—1344
[91] V Piironen, D Lindsay, T Miettinen, Plant sterols: biosynthesis, biological function and their importance to hunman nutrition. J Sci Food Agric, 2000, 80: 939～966.
[92] 韩军花，冯妹元，王国栋等，常见谷类、豆类食物中植物甾醇含量分析，营养学报，2006，Vol．28 No．5 P．375-378
[93] 丁丽萍，银杏保健茶的制作．现代农业，2002，07
[94] 王成章，沈兆邦，银杏叶中脂肪酸含量及化学组成，林产化工通讯，2000．01
[95] 周雄尊，程从球，罗申·维·依，银杏叶与杉木绿冠提取物化学组分研究，林产化学与化工，1997，17，61-66。
[96] 李国兵，许松林，许春建，等．分子蒸馏过程模型化研究进展，化学工程，2002，30(3)：65—70．
[97] 高瑜莹，裘爱泳，植物甾醇的分析方法，中国油脂，2001年，26(1)，25-28
[98] 许文林．王雅琼，重结晶法精制植物甾醇的溶剂选择，扬州大学学报(自然科学版)．2002年2月第5卷第1期 Vol．5No．1
[99] Danilov L L., Chojnachi T.,, Chemistry and Physics of Lipids, 1989, 51:191-203.
[100] Makltscv S. D., Sizova O. V., Danilov L L., Russian Journal of Bioorganic Chemistry, 2001, 27 (6): 449-452.
[101] Yamatsu I, et al., Remedy and preventive for hepatic diseaes, JP60136510, 1985.
[102] Nekrasova V B., et al., Biologically active additive to food, RU2188563, 2002.
[103] 郑少雄，蔡文仪，邱明才等．血、尿羟脯氨酸测定的方法改进．中华医学检验杂志，1983，6(9)：5031
[104] 苗三明，主编．实验动物和动物实验技术．北京．中国中医药出版社 1997．200
[105] 李仪奎，主编．中药药理实验方法学．上海：上海科学技术出版社，1991．203
[106] 张均田，主编．现代药理实验方法．北京：北京医科大学中国协和医科大学联合出版社．1998．63-64
[107] Xia Z Q, Dong C, Lu S G. Method of liver perfusion for separating rat hepatocytes and primaryculture[J]. Acta Acad, Med Xuzhou, 1999, 19(6):458-459.
[108] 江正辉，王泰龄．酒精性肝病[M]．北京：中国医药科技出社，2001：26-29．
[109] 童英，姚小曼，吴少平．乙醇诱发急性肝损伤生物标记物的探讨．中国食品卫生杂志，1999，11(2)：12-14．
[110] Strubelt O, Younes M, Pentz R. Enhancement by glutathione depletion of ethanol-induced acute hepatotoxicityt in vitro and in vivo[J]. Toxicology, 1987, 45(2):213-223.
[111] 陈奇．中药药理实验方法学[M]．北京：人民卫生出版社，2000．846．
[112] Erystyna W., Tadeusz J., The errect of phosphate ester derivates of polyprenol on model membrane stability, Cell. Biol. Mol. Lett., 2001, vol. 6(2), 426.
[113] Tadeusz J., Teresa. J., Krzysztof N., The role of polyprenol in modulation of physical properties of model membranes. Current Topics in Biophysics, 2001, 25(1), 33.
[114] Rip W., Rupar C., Kothapalli R. and Carroli K. Distribution, metabolism and function of dolichol and polyprenols, Prog. Lipid Res. 1985, 24: 269-309
[115] Kuznetsovs S., Seleznovs J. , Daugayietis M. Urinary dolichol in breast cancer control, The European Journal of cancer, Vol. 30A, Suppl. 2., 1994,
[116] Kuznetsovs S., Seleznovs J., Mikhailovs V., Clinical usefulness of dolichol as a prognostic factor in cancer patients, Can. J. Intect. Diseases, Vol. 6., Suppl. 298: 1023, 1994.
[117] 王成章等，银杏叶聚戊烯醇抗肿瘤生物活性研究，天然产物研究与开发，2002，14(5)．
[118] 王成章等，银杏叶聚戊烯醇联合化疗药对Heps和EC荷瘤小鼠的抗癌作用，中国生化药物杂志，2003，24(3)．
[119] 王成章等，银杏叶聚戊烯醇联合化疗肿瘤的药效研究，林产化学与工业，2003，23(30)，15-18．
[120] Wu XH, Rush JS, Karaoglu D, et al. Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosmine-1 Phosphate Transferase (DPAGT1) Causes a Novel Congenital Disorder of Glycosylation Type 1j. Human Mutation, 2003, 22:144-150
[121] Chojnacki T. Dallner G., The biological role of dolichol, Biochemistry J. 1988, 251, 1-9.
[122] Rip J. et al. Distribution, metabolism and function of dolichol and polyprenols, Prog. Lipid Res. 1985, Vol. 24 269-309.
[123] Guerra CB, Busch R, Boebele RC, et al. Novel glycosytation of HLA-DR alpha disrupts antigen presentation wiuhout altering endosomal localization[J]. J Immunol, 1998, 160:4289
[124] Krajewska-Rychlik 1 (1985) Metabolism of exogenous polyisoprenoids by animal cells cultured in vitro Acta Biochim Pol 32:3 211-23.
[125] Yasugi E, Yokoyama Y, Seyama Y, et al. Biochem Blophys Res Commun, 1995, 216 (3): 8482853.
[126] Dohi T, Yasugi E, Shima M. Biochem Biophys Res Commun. 1996, 224 (1):87291.
[127] Guerra CB, Busch R, Doebele RC, et al. Novel glycosylation of HLA-DR alpha disrupts antigen presentation without altering endosomal localization. J Immunol, 1998, 160: 4289
[128] Rudd PM, Elliott T, Cresswell P, et at. Glycosylation and the immune system. Science, 2001, 291:2370
[129] Shay JW, Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer, 1997, 33 (5):7872791.
[130] Shay JW. Wright WE. Telomerase activity in humman cancer. Curr Opin Oucol, 1996, 8 (1):66271.
[131] Brandt S, Heller H, Schuster KD, Tamoxtfen induces suppression of cell viability and apoptosis in the human hepatoblastoma cell line HepG via down regulation of telomerase activity. Liver Int, 2004, 24 (1):46254.
[132] pronin A. V, Sanin A. V, Deyeva A, Antipov Y., Sachek M., Depot-from of phosphopolyprenols as protective remedy for influenza. "Options for the control of influenza". Conf. Cairs, North Queensland, Australia 4-9 May 1996, p1-11
[133] 陆德源．医学微生物学．第5版．北京：人民卫出版社，2001，268．
[134] 黄祯祥．医学病毒学基础与实验技术．北京：科学出版社，1990．122，152．
[135] 张其威，张楚瑜．抗病毒中药研究的最新进展．中成药，2005，27(1)：118．
[136] Chojnacki T. and Daltner G., The uptake of dietary polyprenols and their modification to active dolichols by the rat liver, J. Biol. Chem. 258: 2, 916-922, 1983.
[137] Sanin A. V., Danilov L. L, Maltsev S D., Study of the phosphorilated isoprenoids as novel anti HIVA-1 compounds with a potent antiviral activity. Abstr. Ⅸ International conference on AIDS, Berlin, June 1993. Abstr. No. 4593.