海洋多糖药物PS916的荧光标记及其药代动力学研究
|
摘要
海洋硫酸多糖PS916是以来源于海洋的甲壳质为基础原料,经多步分子修饰而得到的一种硫酸氨基多糖,化学名为β-(1,4)-3-氧-硫酸基-6-氧-硫酸基-6′-氧-羧甲基醚钠盐,英文名为β-(1,4) polyglycosamine-3-O-sulfate-6-O-sulfate-6′-O- carboxylmethyl ether sodium,药效学研究结果表明PS916具有调血脂、抗脂质过氧化、抑制血管平滑肌细胞增殖等作用,具有多途径抗动脉粥样硬化作用,系正在进行系统研究的I类新药。本文对PS916在大鼠体内的药代动力学、组织分布及排泄进行了研究,初步阐明了PS916在大鼠体内的吸收,分布及排泄过程,为新药开发和临床用药提供了一定的理论依据。本论文主要研究工作如下:
一、PS916的荧光标记研究
PS916为多糖类物质,在分子结构中缺乏发色团和荧光团,不能直接用紫外或荧光法进行检测,质谱法也不适合多糖的定量分析。因此,我们以异硫氰酸荧光素(FITC)为荧光标记试剂,对PS916进行了荧光标记,标记后的PS916的荧光最大激发波长Ex为480nm,最大发射波长Em为515nm;荧光标记的PS916中含FITC 0.74%;以高效凝胶色谱法测定PS916分子量及分子量分布,测定结果表明,标记后的PS916平均分子量及分子量分布宽度与标记前比较均未发生显著变化。
二、PS916的体内外稳定性研究
以荧光标记的PS916为研究对象,采用高效凝胶色谱法考察PS916在磷酸盐缓冲液(PBS)及大鼠血浆中的稳定性。PS916体外在PBS、大鼠血浆及大鼠尿液中37℃孵育1h、20h,其分子量及分子量分布宽度均未发生变化,荧光强度也未发生变化,表明PS916体外在PBS、大鼠血浆及大鼠尿液中稳定。同时,对大鼠以口服和静脉注射两种给药方式给药后PS916在血浆、尿液和粪便中的稳定性进行了研究,体内大鼠口服PS916后血浆和粪便中PS916均以原型形式存在;PS916静脉注射给药后尿液中以原型形式从尿液中排泄,说明大鼠口服和静脉注射PS916后,主要以原型的形式吸收代谢。
三、PS916在生物样品中的定量分析方法研究
建立了生物样品中PS916的荧光定量分析方法,PS916的血浆浓度在0.2-20μg/mL的浓度范围内PS916的荧光强度与浓度具有良好的线性关系,线性方程为:y =22.951x– 3.3561,相关系数r2=0.9991,血浆中PS916最低定量限为0.2μg/mL;低、中、高(0.2、2.0、20.0μg/mL) 3种浓度的日内精密度在1.52–7.83%之间,日间精密度在2.14–8.42%之间,组内回收率在84.3-108.0%之间,组间回收率在88.7-100.1%之间;血浆样品稳定性考察显示PS916在-70℃条件下放置4周相对稳定。PS916在组织、尿液及粪便中的线性、精密度、准确度及稳定性分析均符合生物样品体内定量分析的要求。证明本实验方法适用于PS916在大鼠血浆、组织等生物样品中含量的测定。
四、PS916在大鼠体内的药代动力学研究
1、大鼠口服和静脉给药PS916后,血药浓度-时间曲线数据采用非房室模型计算药代动力学参数,通过Cmax和AUC与给药剂量的相关性分析结果表明,大鼠口服和静脉给药后,PS916在大鼠体内呈线性动力学特征。
2、大鼠口服PS916后,三种剂量的平均Tmax为3.28±0.58h,可知PS916在大鼠体内吸收较慢,达峰迟缓。大鼠口服三种剂量下平均消除半衰期t1/2为7.84±0.12h,大鼠静脉注射三种剂量下平均消除半衰期t1/2为8.74±1.01h,口服和静脉给药后的t1/2无统计学差异(P>0.05),PS916在大鼠体内的半衰期较长,
3、大鼠口服和静脉给药后,用AUC0-∞计算PS916绝对生物利用度为9.06%,显示大鼠口服PS916吸收较差,生物利用度较低。
4、在大鼠连续给药实验中,口服50mg/kg剂量PS916多次给药与单次给药相比,药-时曲线基本吻合,首、末次给药后的t1/2和AUC0-∞值均无统计学差异,提示PS916多次给药体内不易蓄积,且对其代谢酶无诱导抑制作用。
5、大鼠单次口服PS916后,组织分布实验表明,给药后1h,药物能分布到大部分组织中,在肠和胃中分布最高,另外主要分布在血流充足的肝和肺组织;给药6h后,肠和胃组织中药物浓度明显下降,肾脏中药物浓度明显升高,表明PS916吸收入血后的药物主要经肾脏随尿液排出;给药24h后,大部分组织中药物浓度均明显降低。给药后脑组织中可检测到药物,说明PS916能透过血脑屏障,向脑内分布。
6、大鼠单次静脉给予PS916后,组织分布实验表明,PS916静脉给药后在大鼠各主要组织中广泛分布。给药后1h,PS916在大鼠肾脏、肝脏、血浆中的浓度较高,在肾脏中浓度最高,在肠中亦有相对较高浓度,在肾脏中含量高说明该药物主要经肾排泄。PS916静脉注射6h后,肾脏中药物浓度在3个时间点中最高,在肾脏、肝脏、肠、心、肺、胃、脾等组织中的浓度均大于其血浆浓度,说明PS916的组织分布比例较大。给药后PS916在脑中亦可检出,说明PS916能透过血脑屏障,向脑内分布。
7、大鼠口服给予PS916后,主要以原型从粪便和尿液中排出体外,给药72h后,尿中PS916的累积排泄量占给药剂量百分比为1.288±0.958%;粪中PS916的累积排泄量占给药剂量百分比为78.974±5.498%;灌胃给药后72h内,有相当于给药量80.26%的药物以原型的形式随尿粪排出体外,灌胃给药后PS916主要是从粪便中排出。
8、大鼠静脉注射给予PS916后,主要以原型从粪便和尿液中排出体外,给药72h后,尿中PS916的累积排泄量占剂量百分比为54.388±11.832%;粪中PS916的累积排泄量占剂量百分比为6.286±1.938%;静脉注射给药后72h内,有相当于给药量60.67%的药物以原型的形式随尿粪排出体外,静脉给药后PS916主要是从尿液中排出体外。
PS916 is a new form of sulfated amino polysaccharide that is derived from marine chitin and by ways of molecular modifications. It is characterized by 1, 4-linkedβ-D-glucosamine with an average of 1.0 sulfate and 0.5 carboxylmethyl groups per unit monosaccharide. The average molecular weight of PS916 is 7000 Da and the distribution width of molecular weight is less than 1.5. Systematic pharmacodynamic research shows that PS916 has good antiatherosclerotic activity and was authorized to enter clinical trial in China. This paper was designed to evaluate the pharmacokinetics features of PS916 in rats to provid scientific data for the new drug development and clinic use.
1. The flurocescent labeling of PS916
PS916, similar to other polysaccharides such as glucosan, possesses few chromophoric or fluorophoric structurally, so derect detection is impossible with violet-visible (UV-Vis) or flurocescence method, Mass spectra method is unsuitable to quantification analysis of polysaccharides either. Fluorescein-isothiocyanate (FITC) is a fluroscent labeling regent usually used to label protein, so we chose it to label PS916 because just like protein there is amino group in its structure. UV-Vis and flurocescence spectroscopy demonstrated the labeling of FITC to PS916. The maxium excition wavelength of labeled PS916 is 480nm, and the maxium emission wavelength is 515nm. Furthermore, labeled PS916 was determined spectrophotometrically by visible absorption at 490nm with reference to FITC, the content of FITC in labeled PS916 was 0.71% (w/w). The molecular weight of labeled PS916 was examined by high performance gel permeation chromatography (HPGPC). The average molecular weight and the distribution width of molecular weight of labeled PS916 were not signifficent different from that of unlabeled PS916.
2. The stability of PS916 in vitro and in vivo
The stability of PS916 in vitro and in vivo was investigated using HPGPC method with fluorescesent labeled PS916. After 1, 20h incubation in phosphate buffer, rat plasma and rat urine at 37℃, the molecular weight and the width of molecular weight distribution were not changed, that showed PS916 was stable in vitro. After oral administration of PS916 to rats, PS916 was in its original form in rat plasma and rat feces, meanwhile after an intravenous administration of PS916 to rats, PS916 was also excreted in its original form in rat urine, that demonstrated PS916 metabolized in its original form.
3. The establishment of analytical method of PS916 in biological matrix
A rapid, sensitive fluroescence method was developed to determine PS916 in biological matrix. The linear calibration curve was obtained in the range of 0.2-20μg/mL in rat plasma. The lower limit of quantitation (LLOQ) was 0.2μg/mL. The inter-day CV% at 0.2, 2.0 and 20μg/mL of PS916 was 6.35%, 3.81% and 1.68%, respecttively. The intra-day CV% at the above concentrations was 8.42%, 4.38% and 2.14%, respectively. One-way analysis of variance (ANOVA) was carried out with grouping variable“day”to assess precision at 95% level. The result was non-significant when data for each day was compared with other days and within the same day. The calibration curves were also linear in other biological sample such as tiusse, urine and feces, range with correlation coefficient all above 0.99. The established method is suitable for PS916 pharmacokinetics studies.
4. The pharmacokinetics study of PS916
Individual plasma-concentration data were analyzed by non-compartmental in this paper.
After intravenous and oral administration of PS916 to rats, the proportionality between dosage and Cmax or AUC was calculated,A good correlation was found between the dosage and AUC and Cmax, PS916 exhibited dose-proportional pharmacokinetics with linear kinetic character.
Following oral administration, the average Tmax of three dosages was 3.28±0.58 h, that means the absorption of PS916 was slowly. After intravenous and oral administration, the average t1/2 were 7.84±0.12h and 8.74±1.01h,respectively, PS916 had a long terminal half-life.
The absolute oral bioavailability of PS916 was 9.06%,which was calculated by compared the AUC0-∞of oral administration to the AUC0-∞of intravenous administration at the dose of 25mg/kg. The bioavailability of PS916 was low.
After multiple dosage of PS916 at 50mg/kg, the plasma concentration–time profile was basically the same as that of signal dosage, t1/2 and AUC0-∞were non-significant between the first and the last dosage, that mean PS916 was not accumulated in rats. PS916 was widely distributed to tissues of most organs in rats 1h after oral administration of PS916, such as stomach, intestine, liver, kidneys, lung and heart. The concentration in stomach and intestine was the most highest in all tissues, the concentration in lung and liver was higher than other tissues. The concentration in stomach and intestine degraded rapidly, and increased rapidly in kidney 6h after oral administration of PS916, that show PS916 was excreted mainly by kidney after absorption. For all tissues, PS916 concentrations had significantly decreased at the time point of 24 h after oral administration. PS916 was also be detected in brain, that mean PS916 could also across blood-brain barrier.
PS916 was widely distributed to tissues of most organs in rats 1h after intravenous administration of PS916, such as liver, kidneys, lung, heart and intestine. The concentration in kidney, liver and plasma was higher, the most highest in kidney, that show PS916 was excreted mainly by kidney. The concentration in most tissues such as liver, kidney, lung, heart, spleen and intestine was higher than that of plasma, that mean PS916 was widely distributed to tissues. PS916 was also be detected in brain, that mean PS916 could also across blood-brain barrier.
PS916 was mainly excreted in its original form from feces and urine after oral administration. Cumulative amounts percentage of PS916 in feces at 72 h after an oral dose was 78.974±5.498%. Cumulative amounts percentage of PS916 in urine at 72 h after an oral dose was 1.288±0.958%. Drug which was excreted totally in urine and feces in 72 h after an oral administration of PS916 was equal to 80.26% of given dose. PS916 was mainly excreted from feces after oral administration.
PS916 was mainly excreted in its original form from feces and urine after oral administration. Cumulative amounts percentage of PS916 in urine at 72 h after an oral dose was 54.388±11.832%. Cumulative amounts percentage of PS916 in feces at 72 h after an oral dose was 6.286±1.938%%. Drug which was excreted totally in urine and feces in 72 h after an oral administration of PS916 was equal to 60.67% of given dose. PS916 was mainly excreted from urine after oral administration.
一、PS916的荧光标记研究
PS916为多糖类物质,在分子结构中缺乏发色团和荧光团,不能直接用紫外或荧光法进行检测,质谱法也不适合多糖的定量分析。因此,我们以异硫氰酸荧光素(FITC)为荧光标记试剂,对PS916进行了荧光标记,标记后的PS916的荧光最大激发波长Ex为480nm,最大发射波长Em为515nm;荧光标记的PS916中含FITC 0.74%;以高效凝胶色谱法测定PS916分子量及分子量分布,测定结果表明,标记后的PS916平均分子量及分子量分布宽度与标记前比较均未发生显著变化。
二、PS916的体内外稳定性研究
以荧光标记的PS916为研究对象,采用高效凝胶色谱法考察PS916在磷酸盐缓冲液(PBS)及大鼠血浆中的稳定性。PS916体外在PBS、大鼠血浆及大鼠尿液中37℃孵育1h、20h,其分子量及分子量分布宽度均未发生变化,荧光强度也未发生变化,表明PS916体外在PBS、大鼠血浆及大鼠尿液中稳定。同时,对大鼠以口服和静脉注射两种给药方式给药后PS916在血浆、尿液和粪便中的稳定性进行了研究,体内大鼠口服PS916后血浆和粪便中PS916均以原型形式存在;PS916静脉注射给药后尿液中以原型形式从尿液中排泄,说明大鼠口服和静脉注射PS916后,主要以原型的形式吸收代谢。
三、PS916在生物样品中的定量分析方法研究
建立了生物样品中PS916的荧光定量分析方法,PS916的血浆浓度在0.2-20μg/mL的浓度范围内PS916的荧光强度与浓度具有良好的线性关系,线性方程为:y =22.951x– 3.3561,相关系数r2=0.9991,血浆中PS916最低定量限为0.2μg/mL;低、中、高(0.2、2.0、20.0μg/mL) 3种浓度的日内精密度在1.52–7.83%之间,日间精密度在2.14–8.42%之间,组内回收率在84.3-108.0%之间,组间回收率在88.7-100.1%之间;血浆样品稳定性考察显示PS916在-70℃条件下放置4周相对稳定。PS916在组织、尿液及粪便中的线性、精密度、准确度及稳定性分析均符合生物样品体内定量分析的要求。证明本实验方法适用于PS916在大鼠血浆、组织等生物样品中含量的测定。
四、PS916在大鼠体内的药代动力学研究
1、大鼠口服和静脉给药PS916后,血药浓度-时间曲线数据采用非房室模型计算药代动力学参数,通过Cmax和AUC与给药剂量的相关性分析结果表明,大鼠口服和静脉给药后,PS916在大鼠体内呈线性动力学特征。
2、大鼠口服PS916后,三种剂量的平均Tmax为3.28±0.58h,可知PS916在大鼠体内吸收较慢,达峰迟缓。大鼠口服三种剂量下平均消除半衰期t1/2为7.84±0.12h,大鼠静脉注射三种剂量下平均消除半衰期t1/2为8.74±1.01h,口服和静脉给药后的t1/2无统计学差异(P>0.05),PS916在大鼠体内的半衰期较长,
3、大鼠口服和静脉给药后,用AUC0-∞计算PS916绝对生物利用度为9.06%,显示大鼠口服PS916吸收较差,生物利用度较低。
4、在大鼠连续给药实验中,口服50mg/kg剂量PS916多次给药与单次给药相比,药-时曲线基本吻合,首、末次给药后的t1/2和AUC0-∞值均无统计学差异,提示PS916多次给药体内不易蓄积,且对其代谢酶无诱导抑制作用。
5、大鼠单次口服PS916后,组织分布实验表明,给药后1h,药物能分布到大部分组织中,在肠和胃中分布最高,另外主要分布在血流充足的肝和肺组织;给药6h后,肠和胃组织中药物浓度明显下降,肾脏中药物浓度明显升高,表明PS916吸收入血后的药物主要经肾脏随尿液排出;给药24h后,大部分组织中药物浓度均明显降低。给药后脑组织中可检测到药物,说明PS916能透过血脑屏障,向脑内分布。
6、大鼠单次静脉给予PS916后,组织分布实验表明,PS916静脉给药后在大鼠各主要组织中广泛分布。给药后1h,PS916在大鼠肾脏、肝脏、血浆中的浓度较高,在肾脏中浓度最高,在肠中亦有相对较高浓度,在肾脏中含量高说明该药物主要经肾排泄。PS916静脉注射6h后,肾脏中药物浓度在3个时间点中最高,在肾脏、肝脏、肠、心、肺、胃、脾等组织中的浓度均大于其血浆浓度,说明PS916的组织分布比例较大。给药后PS916在脑中亦可检出,说明PS916能透过血脑屏障,向脑内分布。
7、大鼠口服给予PS916后,主要以原型从粪便和尿液中排出体外,给药72h后,尿中PS916的累积排泄量占给药剂量百分比为1.288±0.958%;粪中PS916的累积排泄量占给药剂量百分比为78.974±5.498%;灌胃给药后72h内,有相当于给药量80.26%的药物以原型的形式随尿粪排出体外,灌胃给药后PS916主要是从粪便中排出。
8、大鼠静脉注射给予PS916后,主要以原型从粪便和尿液中排出体外,给药72h后,尿中PS916的累积排泄量占剂量百分比为54.388±11.832%;粪中PS916的累积排泄量占剂量百分比为6.286±1.938%;静脉注射给药后72h内,有相当于给药量60.67%的药物以原型的形式随尿粪排出体外,静脉给药后PS916主要是从尿液中排出体外。
PS916 is a new form of sulfated amino polysaccharide that is derived from marine chitin and by ways of molecular modifications. It is characterized by 1, 4-linkedβ-D-glucosamine with an average of 1.0 sulfate and 0.5 carboxylmethyl groups per unit monosaccharide. The average molecular weight of PS916 is 7000 Da and the distribution width of molecular weight is less than 1.5. Systematic pharmacodynamic research shows that PS916 has good antiatherosclerotic activity and was authorized to enter clinical trial in China. This paper was designed to evaluate the pharmacokinetics features of PS916 in rats to provid scientific data for the new drug development and clinic use.
1. The flurocescent labeling of PS916
PS916, similar to other polysaccharides such as glucosan, possesses few chromophoric or fluorophoric structurally, so derect detection is impossible with violet-visible (UV-Vis) or flurocescence method, Mass spectra method is unsuitable to quantification analysis of polysaccharides either. Fluorescein-isothiocyanate (FITC) is a fluroscent labeling regent usually used to label protein, so we chose it to label PS916 because just like protein there is amino group in its structure. UV-Vis and flurocescence spectroscopy demonstrated the labeling of FITC to PS916. The maxium excition wavelength of labeled PS916 is 480nm, and the maxium emission wavelength is 515nm. Furthermore, labeled PS916 was determined spectrophotometrically by visible absorption at 490nm with reference to FITC, the content of FITC in labeled PS916 was 0.71% (w/w). The molecular weight of labeled PS916 was examined by high performance gel permeation chromatography (HPGPC). The average molecular weight and the distribution width of molecular weight of labeled PS916 were not signifficent different from that of unlabeled PS916.
2. The stability of PS916 in vitro and in vivo
The stability of PS916 in vitro and in vivo was investigated using HPGPC method with fluorescesent labeled PS916. After 1, 20h incubation in phosphate buffer, rat plasma and rat urine at 37℃, the molecular weight and the width of molecular weight distribution were not changed, that showed PS916 was stable in vitro. After oral administration of PS916 to rats, PS916 was in its original form in rat plasma and rat feces, meanwhile after an intravenous administration of PS916 to rats, PS916 was also excreted in its original form in rat urine, that demonstrated PS916 metabolized in its original form.
3. The establishment of analytical method of PS916 in biological matrix
A rapid, sensitive fluroescence method was developed to determine PS916 in biological matrix. The linear calibration curve was obtained in the range of 0.2-20μg/mL in rat plasma. The lower limit of quantitation (LLOQ) was 0.2μg/mL. The inter-day CV% at 0.2, 2.0 and 20μg/mL of PS916 was 6.35%, 3.81% and 1.68%, respecttively. The intra-day CV% at the above concentrations was 8.42%, 4.38% and 2.14%, respectively. One-way analysis of variance (ANOVA) was carried out with grouping variable“day”to assess precision at 95% level. The result was non-significant when data for each day was compared with other days and within the same day. The calibration curves were also linear in other biological sample such as tiusse, urine and feces, range with correlation coefficient all above 0.99. The established method is suitable for PS916 pharmacokinetics studies.
4. The pharmacokinetics study of PS916
Individual plasma-concentration data were analyzed by non-compartmental in this paper.
After intravenous and oral administration of PS916 to rats, the proportionality between dosage and Cmax or AUC was calculated,A good correlation was found between the dosage and AUC and Cmax, PS916 exhibited dose-proportional pharmacokinetics with linear kinetic character.
Following oral administration, the average Tmax of three dosages was 3.28±0.58 h, that means the absorption of PS916 was slowly. After intravenous and oral administration, the average t1/2 were 7.84±0.12h and 8.74±1.01h,respectively, PS916 had a long terminal half-life.
The absolute oral bioavailability of PS916 was 9.06%,which was calculated by compared the AUC0-∞of oral administration to the AUC0-∞of intravenous administration at the dose of 25mg/kg. The bioavailability of PS916 was low.
After multiple dosage of PS916 at 50mg/kg, the plasma concentration–time profile was basically the same as that of signal dosage, t1/2 and AUC0-∞were non-significant between the first and the last dosage, that mean PS916 was not accumulated in rats. PS916 was widely distributed to tissues of most organs in rats 1h after oral administration of PS916, such as stomach, intestine, liver, kidneys, lung and heart. The concentration in stomach and intestine was the most highest in all tissues, the concentration in lung and liver was higher than other tissues. The concentration in stomach and intestine degraded rapidly, and increased rapidly in kidney 6h after oral administration of PS916, that show PS916 was excreted mainly by kidney after absorption. For all tissues, PS916 concentrations had significantly decreased at the time point of 24 h after oral administration. PS916 was also be detected in brain, that mean PS916 could also across blood-brain barrier.
PS916 was widely distributed to tissues of most organs in rats 1h after intravenous administration of PS916, such as liver, kidneys, lung, heart and intestine. The concentration in kidney, liver and plasma was higher, the most highest in kidney, that show PS916 was excreted mainly by kidney. The concentration in most tissues such as liver, kidney, lung, heart, spleen and intestine was higher than that of plasma, that mean PS916 was widely distributed to tissues. PS916 was also be detected in brain, that mean PS916 could also across blood-brain barrier.
PS916 was mainly excreted in its original form from feces and urine after oral administration. Cumulative amounts percentage of PS916 in feces at 72 h after an oral dose was 78.974±5.498%. Cumulative amounts percentage of PS916 in urine at 72 h after an oral dose was 1.288±0.958%. Drug which was excreted totally in urine and feces in 72 h after an oral administration of PS916 was equal to 80.26% of given dose. PS916 was mainly excreted from feces after oral administration.
PS916 was mainly excreted in its original form from feces and urine after oral administration. Cumulative amounts percentage of PS916 in urine at 72 h after an oral dose was 54.388±11.832%. Cumulative amounts percentage of PS916 in feces at 72 h after an oral dose was 6.286±1.938%%. Drug which was excreted totally in urine and feces in 72 h after an oral administration of PS916 was equal to 60.67% of given dose. PS916 was mainly excreted from urine after oral administration.
引文
[1].张树政.糖生物学与糖生物工程.第一版.北京:清华大学出版社,2002.1-2.
[2]. Deka RK, Machius M, Norgard MV, Tomchick DR. Crystal Structure of the 47-kDa Lipoprotein of Treponema pallidum Reveals a Novel Penicillin-binding Protein J Biol Chem.2002,277 (44):41857- 41864
[3]. Blix G., Gottschalk A., Klenk E. Proposed nomenclature in the field of sialic. Nature, 1957,175: 340-341.
[4]. Stanley P., Ioffe E. Glycosyltransferase mutants: Key to new insights in glycobiology. FASEB J. 1995, 9:1436-1444.
[5]. Rademacher T.W., Parekh R.B., Dwek R.A. Glycobiology. Annu. Rev. Biochem. 1988, 57:785-838.
[6]. Zhang Y X, Xang S T, Zhou J H. Effects of Lycium barbarum polysaccharides and their combination with Corybacterium parvum on the peritoneal macrophages in mice. Chinese Journal of Pharruacology and Toxicology, 1989, 3 (3): 169-174.
[7].张俊平,钱定华.商陆多糖抗瘤活性及对小鼠产生肿瘤坏死因子的作用.中国药理学报,1990, 14(6):542-544
[8].赵俊,吴宏,王亚平.人参多糖的化学与药理学研究进展.国外医学中医中药分册,2004, 26 (2):79-81.
[9].刘彦平,毛辉青,李萍,张玉叶.枸杞多糖对小鼠T淋巴细胞亚群和淋巴细胞转化作用的研究.青海医学院学报, 2000,21(4):4-5.
[10]. Ren, DL; Wang, JZ; Noda, H; Amano, H; Ogawa, S. The effects of an angal polysaccharide from Gloiopeltis tenax on transplantable tumors and immune activities in mice. Planta Med,1995, 61 (2) : 120-125.
[11]. Kiho T, Ookubo K, Usui S, Ukai S, Hirano K. Structural features and hypoglycemic activity of a polysaccharide (CS-F10) from the cultured mycelium of Cordyceps sinensis. Biol Pharm Bull, 1999, 22(9):966-970.
[12]. Lei L S, Lin Z B. Effect of Ganoderma Polysaccharides on T cell subpopulations and production of interieukin 2 in mixed lymphonyte. Acta Pharm Sin Acta Pharm Sin, 1992, 27(5): 33l-334.
[13].邵树军,刘彩玉,刘雄伯,王天元.牛膝多糖对小鼠免疫功能影响的研究.肿瘤防治杂志,2002,9(1):57-58
[14].冯仲联,孙秀华.人参多糖治疗恶性胸腔积液的临床研究.中国新药杂志, 1999, 8(9):619-621
[15]. Kodama N, Harada N, Nanba H. A polysaccharide, extract from grifola frondosa, induces Th-1 dominant responses in carcinoma-bearing BALB/c mice. Japanese Journal of Pharmacology, 2002, 90 (4) :357-360.
[16].刘俊栋,刘海霞,李建基.当归多糖对免疫系统作用的研究.四川畜牧兽医,2003, 3: 34-35.
[17].郭随章.中药多糖的抗癌研究与临床应用进展.医药导报,2004, 23 (11):848-848.
[18]. Kajimura, K; Takagi, Y; Miyano, K; Sawabe, Y; Mimura, M; Sakagami, Y; Yokoyama, H; Yoneda, K. Polysaccharide of Astragali Radix enhances IgM antibody production in aged mice. Biol. Pharm. Bull.1997,20(11):1178-1182.
[19]. Okai, Y.; Higashi-Okai, K.; Ishizaka, S.; Ohtani, K.; Matsui-Yuasa, I.; Yamashita, U. Possible immunodulating activities in an extract of edible brown alga, Hijikia fusiforme (Hijiki). Journal of science of food and agriculture, 1998, 76 (1):56-62.
[20]. Yamada, H.; Kiyohara, H.; Cyong, J.C.; Kojima, Y.; Kumazawa, Y.; Otsuka, Y. Studies on polysaccharides from Angelica acutiloba. 1. Fractionation and biological properties of polysaccharides. Planta Med. 1984, 50(2): 163-167.
[21].董爱琴.多糖的免疫调节作用及作用机制研究进展.中华今日医学杂志, 2003, 3(5): 87-88.
[22]. Chun, H; Shin, D H; Hong, B S; Cho, H Y; Yang, H C. Purification and biological activity of acidic polysaccharide from leaves of Thymus vulgaris L. Biol. Pharm. Bull., 2001,24(8):941-946.
[23]. Chun, H; Shin, D H; Hong, B S; Cho, H Y; Yang, H C. Purification and biological activity of acidic polysaccharide from leaves of Thymus vulgaris L. Biol. Pharm. Bull., 2001,24(8):941-946.
[24]. Peyroux, J.; Rossignol, P.; Delaveau, P. Anti-edematous and anti-hyperhemiant properties of Calendula officinalis L. Plantes medicinales et phytotherapie., 1981,15(4):210-216.
[25]. Nagashima, H.; Fukuda, I. Low molecular weight carbohydrates in Cyanidium caldarium andsome related algae. Phytochemistry., 1981,20(3):439-442.
[26]. Prcciarini F., Ghezzi S., Pinnr D., Sulfated KS Eschenchia coli polysaccharide derivatives inhibit human immunodeficiency virus HIV transmission. New Mcrobiol, 2004,27(2 Suppl 1):5-9.
[27]. Sastry G, HariA S , Sudeep ta A., Isolation of a previously unidentified polysaccharide (MAR-10) from hyssopofficinalis that exhibits strong activity against human immunodeficiency virus type. Biochem Biophy Res Commun, 1995, 210:145 - 151.
[28]. Nakano, M; Itoh, Y; Mizuno, T; Nakashima, H. Polysaccharide from Aspalathus linearis with strong anti-H IV activity. Biosci Biotechnol Biochem, 1997, 61(2): 267-271.
[29].耿美玉,辛现良,管华诗.海洋硫酸多糖类药物911抗艾滋病毒作用及其机理研究.中国药理学会通讯,2001,18(1):9-13
[30].辛现良,丁华,耿美玉,梁平方,李英霞,管华诗.海洋硫酸多糖911抗艾滋病毒作用及其机理研究-体内对猴免疫缺陷病毒(SIV)增殖的影响.中国海洋药物杂志,2000,19(6):4-8.
[31]. Watson, K; Gooderham, N J; Davies, D S; Edwards, R J. Interaction of the transactivating protein HIV-1 Tat with sulphated polysaccharide. Biochem Pharmaco, 1999, 57(7): 775-783.
[32]. Baba, M; de Clercq, E; Schols, D; Pauwels, R; Snoeck, R; Van Boeckel, C; Van Dedem, G; Kraaijeveld, N; Hobbelen, P. Novel sulfated polysaccharides: Dissociation of anti-human immunodeficiency virus activity from antithrombin activity. J Infect Dis, 1990, 161 (2) : 208-213.
[33]. Collins, RA; Ng, Tzi Bun. Polysaccharopeptide from Coriolus versicolor has potential for use against human immunodeficiency virus type 1 infection. Life Sci. 1997, 60(25): 383-387.
[34].田庚元,李寿桐,宋麦丽,郑民实,李文.牛膝多糖硫酸醋的合成及其杭病毒活性,药学学报,1995, 30(21): 107-111.
[35].郭长占,马俊良.猪苓多糖对HBV转基因小鼠HbsAG表达的影响.中国实验临床免疫学杂志, 1999,11(6):48-50.
[36]. Hoshino, T; Hayashi, T; Hayashi, K; Hamada, J; Lee, J-B; Sankawa, U. An Antivirally Active Sulfated Polysaccharide from Sargassum horneri (Turner) C. Agardh Biol Pharm Bull. 1998, 21 (7) : 730 - 734.
[37].佟丽;黄添友;李吉来;吴波;梁谋;梁念慈.植物多糖对S180、K562细胞增殖和唾液酸、磷酸、胆固醇含量的影响.中国中西医结合杂志,1994, 14 (8) : 482-484.
[38].吴迪.茯苓多糖抗肿瘤作用与机理的实验研究.中国药理学通报, 1994, 10 (4) : 30-33.
[39].杨江苏;秦旭平;张娜;颜卉君.两种真菌多糖对HL260细胞酪酸蛋白磷酸化作用的影响.中国药学杂志, 2000, 35 (5) : 303-305.
[40].魏小龙,茹祥斌.低分子质量地黄多糖体外对Lewis肺癌细胞p53基因表达的影响.中国药理学通报, 1998, 14 (3) : 245247.
[41].吕怀盛,张红梅,张波.枸杞多糖对PG细胞株增殖及凋亡的影响.宁夏医学院学报, 2002, 24 (1) : 10-12.
[42].陈彻;王镜;李兴玉;席亚明.梁金菇多糖促人急性早幼粒细胞白病细胞系(HL260)细胞凋亡的研究.中国新药与临床杂志,2002, 21 (6) : 349-352.
[43].戴伟娟;仲伟法;司端运;王绍红;刘善庭.无花果多糖可提高荷S180小鼠血清的MDA、SOD和GSH2px的影响.济宁医学院学报, 2002, 25(1) : 20-22.
[44].王炳岩,季宇彬.海藻多糖对白血病L615小鼠LPO含量及GR、GSH2px、CAT、SOD酶活性影响.中医药信息, 1994, 12 ( 5 ) :43-45.
[45].金山久.茯苓菌丝体抗肿瘤活性多糖研究Ⅲ抗小鼠肿瘤活性.国外医学·中医中药分册, 1987, 9 (6) : 29-30.
[46].宋为民,法京.人参和绞股蓝的抗突变作用.中草药, 1992,23 (3) : 136-138.
[47].丁健.抗肿瘤药物的研究新进展.中国新药杂志, 2000, 17(3) : 150-152.
[48]. Takahashi Y, Kitadai Y,Bucana C D. Expression of VEGF and its receptor KDR. Correlates with vascu-laritymetastasis and proliferation of human colon cancer. Cancer Research, 1995, 55 ( 4) :3964-3970.
[49]. Geng YJ, Hellst rand K. Apoptotic death of human leukemic cells induced by vascular cells expressing tricocide Syntheses in response to gamma-interferon and tumor necrosis factoralpha. Cancer Res, 1996, 56 (4) : 866-870.
[50].李家琦,夏英.中药诱导干扰素作用的探索.上海中医药杂志, 1994, 28 (1) : 34-37.
[51]. Kajimura, K; Takagi, Y; Miyano, K; Sawabe, Y; Mimura, M; Sakagami, Y; Yokoyama, H; Yoneda, K. Polysaccharide of Astragali Radix enhances IgM antibody production in aged mice. Biol. Pharm. Bull. 1997,20(11):1178-1182.
[52].许爱霞,张振明,葛斌,蒲君峰.党参多糖抗衰老作用机制的实验研究.中国现代应用药学杂志, 2006年,23(8): 729-731.
[53].黄正良,红芪多糖抗衰老作用的实验研究.中草药, 1992, 23(9):469-471.
[54].左绍远.螺旋藻多糖对D-半乳糖所致衰老小鼠的作用.中国生化药物杂志, 1998, 19 (1) : 15-18.
[55].张振明,葛斌,许爱霞,蔡曦光.女贞子多糖的抗衰老作用.中国药理学与毒理学杂志, 2006,20 (2) : 108– 111.
[56].姚文兵.大黄的生化学研究:波叶大黄多糖抗衰老作用的实验研究.中国药科大学学报.1991, (3):167-169.
[57].王建华,王汉中,张民,张声华.枸杞多糖延缓衰老的作用.营养学报, 2002, 24(2):189-192.
[58].李国莉,任彬彬,杨建军.枸杞多糖对小鼠耐力及体内抗氧化酶活性的影响.辽宁中医杂志,2002,29(10):634-638.
[59].凌小曼;丁虹;罗顺德;张晓健;张连和.当归多糖对血癖证动物免疫功能和抗氧化功能的影响.中国医院药学杂志,2002,22(10):584-586.
[60]. Yoshida, I; Kiho, T; Usui, S; Sakushima, M; Ukai, S. Polysaccharides in fungi. XXXVII. Immunomodulating activities of carboxymethylated derivatives of linear (1 arrow right 3)- alpha -D-glucans extracted from the fruiting bodies of Agrocybe cylindracea and Amanita muscaria . Biol Pharm Bull ,1996,19(1) :114-121.
[61]. Bopanna K.N.,Kannan, J.,Gadgil, S,Balaraman, R., Rathod, S.P. Antidiabetic and antihyperlipemic effects of neem seed kernel powder on alloxan-diabetic rabbits.Indian J. Pharmaco1,1997, 29:162-167.
[62]. Kumari, K., Mathew, B.C., Augusti, K.T. Antidiabetic and polipidemic effects of S-methyl cysteine sulfoxide isolated from Allium ceps linn. Indian J. Biochem. Biophys. 1995, 32: 49-54.
[63]. M. Shanmugam and K. H. Mody. Heparinoid-active sulphated polysaccharides from marine algae as potential blood anticoagulant agents. CURRENT SCIENCE, 2000,79,12, 25:1672-1683.
[64]. Glombitz, K.W., Mahran, G.H., Mirhom, Y.M., Michel, K.G., Motawi, T.K. Hypoglycemic and antihyperglycemic effect of Zaphus spanachrastt in rats. Plants Med. 1994, 60: 244-247.
[65]. Khan, B.A,Abraham, A., Leelamma, S. Hypoglycemic action of Murraya Koeraaghi (curry leaf) and Brassta juracea (mustard): mechanism of action. Indian J. Biochem. Biophys. 1995,32: 106-108.
[66]. Itoh, T; Itoh, Y; Mizutani, M; Fujishiro, K; Furuichi, Y; Komiyami, T; Hibasami, H Hot-water extracts from adzuki beans (Vigna angularis) suppress not only the proliferation of KATO III cells in culture but also benzo(a)pyrene-induced tumorigenesis in mouse forestomatch. Journal of Nutritional Science and Vitaminology, 2004,50 (4):295-299.
[67]. Spiller R.C. Pharmacology of dietary fiber. Pharmacology and Therapeutics, 1994, 62: 407-427.
[68]. Silverman H.M. Metabolic effects of fiber supplementation(Part II). Journal of Practical Nursing,1990, 40: 41-48.
[69]. Lairon D. Dietary fibres: effects on lipid metabolism and mechanisms of action. European Journal of Clinical Nutrition, 1996, 50(3): 125-133.
[70]. Wursch P., Pi-Sunier F.X. The role of viscous soluble fiber in the metabolic control of Diabetes. Diabetes Care, 1997, 20: 1774-1780.
[71].吴建芬;冯磊;张春飞;李印彩.茶多糖降血糖机制研究.浙江预防医学, 2003,15 (9):10-13.
[72]. Basnet, P.; Kadota, S.; Shimizu, M.; Takata, Y.; Kobayashi, M.; Namba, T. Bellidifolin stimulates glucose uptake in rat 1 fibroblasts and ameliorates hyperglycemia in streptozotocin (STZ)-induced diabetic rats. Planta medica., 1995,61(5):402-405.
[73]. Konno C, Sugiyama K, Kano M, Takahashi, M., Hikino, H. Isolation and hypoglycaemic activity of panaxans A, B, C, D and E, glycans of Panax ginseng roots. Planta Med, 1984,50 (5) : 434-436.
[74]. Hikino H, Konno C, Mirin Y, Hayashi, T, Isolation and Hypoglycemic Activity of Ganoderans A and B, Glycans of Ganoderma lucidum Fruit Bodies1. Planta Med,1985, 51(4): 339-340.
[75]. Oshima, Y; Ohsawa, T; Oikawa, K; Konno, C; Hikino, H., Structures of Dianosides A and B, Analgesic Principles of Dianthus superbus var. longicalycinus Herbs1. Planta Med, 1984,50 (1): 40-43.
[76]. Konno C., Hikino H., Isolation and hypoglycemic activity of panaxans M, N, O and P, glycans of Panax ginseng roots. Int J Crude Drug Res, 1987, 25(1): 53-57.
[77]. Konno C, Murakami M, Oshima Y, Hikino, H., Isolation and hypoglycemic activity ofpanaxans Q, R, S, T and U, glycans of Panax ginseng roots. J Ethno-pharmacol 1985, 14 (1) : 69-74.
[78]. Takahashi M., Konno C., Hikino H. Isolation and hypoglycemic activity of saccharans A, B, C, D, E and F, glycans of Saccharum officinarum stalks. Planta Med, 1985, 51(3) : 258-260.
[79]. Konno C, Mizuno T, Hikino H., Isolation and Hypoglycemic Activity of Lithospermans A, B and C, Glycans of Lithospermum erythrorhizon Roots1. Planta Med, 1985, 51(2) : 157-158.
[80]. Hikino H., Takahashi M., Oshima Y., Konno C. Isolation and hypoglycemic activity of oryzabrans A, B, C and D, glycans of Oryza sativa bran. Planta Med, 1988, 54 (1) : 1-3.
[81]. Kiho, T; Kochi, M; Usui, S; Hirano, K; Aizawa, K; Inakuma, T. Antidiabetic effect of an acidic polysaccharide (TAP) from Tremella aurantia and its degradation product (TAP-H). Biological & pharmaceutical bulletin, 2001,24(12):1400-1403.
[82]. Kondo, Y; Nakatani, A; Hayashi, K; Ito, M Low molecular weight chitosan prevents the progression of low dose streptozotocin-induced slowly progressive diabetes mellitus in mice. Biol. Pharm. Bull., 2000,23(12):1458-1464.
[83]. Hayashi K, Ito M. Antidiabetic action of Low molecular weight chitosan in genetically obese diabetic KK-Ay mice. Biol. Pharm. Bull., 2002,25(2):188-193.
[84].吴昊姝;徐建华;陈立钻;孙继军.铁皮石斛降血糖作用及其机制的研究.中国中药杂志. 2004,29(2):160-163.
[85]. Yang, Jeong-Lye; Kim, Young-Hwa; Lee, Hyun-Sook; Lee, Mak-Soon; Moon, Yangha Kim Barley beta-glucan lowers serum cholesterol based on the up-regulation of cholesterol 7 alpha-hydroxy-lase activity and mRNA abundance in cholesterol-fed rats . J Nutr Sci Vitaminol,2003 , 49(6) :381-387.
[86].张信岳;程敏;孟倩超;叶小弟;郑高利;李士敏.羊栖菜多糖降血脂作用研究.中国海洋药物,2003,5:27-31.
[87].童红莉;田亚平;汪德清;邓心新;董振南.黄芪多糖对高脂血症大鼠血脂的调节.中国临床康复, 2006, 10(11): 68-70.
[88].尹俊青;宋淑珍;田亚平;汪德清黄芪多糖对健康人群血脂水平的干预效应.中医康复研究, 2005, 9(31): 160-161.
[89].吴建芬;冯磊;张春飞;李印彩.茶多糖降血糖机制研究,浙江预防医学,2003,15(9): 10-12.
[90]. Xue C., Fang Y, Lin H. Chemical characters and antioxidative properties of sulfated polysaccharides from Laminaria japonica. J. Appl. Plrycol., 2001, 13, 67-70.
[91].黄飞.山楂叶多糖的功能活性测定研究.广西轻工业, 2001, 2:47-49.
[92].王常青,杨桂兰.两种海藻多糖对大鼠脂质代谢和血小板功能的比较.中国预防医学杂质. 1998,31(6):342-346.
[93].黄晓青,瞿伟箐,张晓玲.沙棘多糖对小鼠试验性高脂血症的影响.营养学报, 2004,26(3):222-224.
[94]. Hosseinzadeh H., Sadeghi A. Antihyperglycemic Effects of Morus Nigra and Morus Alba in Mice[P]. Japan: 97140351,1995-11-21.
[95].姚思宇,赵鹏,刘荣珍,等.虫草多糖降血脂作用的动物试验研究.中国热带医学, 2004,4(2):197-198.
[96].罗琼,李瑾玮,张声华.枸杞及其多糖对家兔血脂的影响.食品科学, 1997,18(4):5-7.
[97]. Lindsay, J O; Whelan, K; Stagg, A J; Gobin, P; Al-Hassi, H O; Rayment, N; Kamm, M A; Knight, S C; Forbes, A Clinical microbiological and immunological effects of fructo-oligosaccharide in patients with Crohn’s disease. Gut , 2006 , 55 (3) :348-355.
[98]. Akindele A.J., Adeyemi O.O. Antiinflammatory activity of the aqueous leaf extract of Byrsocarpus coccineus. Fitoterapia , 2007,78(1) :25-28.
[99]. Guzmán, S; Gato, A; Lamela, M; Freire-Garabal, M; Calleja, J M Anti-inflammatory and immu-nomodulatory activities of polysaccharide from Chlorella stigmatophora and Phaeodactylum tricornutum. Phytother Res , 2003 , 17(6) :665-670.
[100]. da Silva BP , Silva GM, Mendes TP , et al . Structural characteristics of a bioactive polysaccharide from Sorghum arundinaceum. Z Naturforsch , 2003 , 58 (526) :342-346.
[101]. Lee JH , ShimJS , Lee JS , et al . Pectin-like acidic polysaccharide from Panax ginseng with selective antiadhesive activity against pathogenic bacteria. Carbohydr Res , 2006 , 341 ( 9) : 1154-1163.
[102]. Kasper DL, Onderdonk AB, Crabb J , et al . Protective efficacy of immunization with capsular antigen against experimental infection with Bacteroides fragilis. J Infect Dis,1979, 140 :724-731.
[103]. Pereda2Miranda R , Kaatz GW, Gibbons S , et al . Polyacylated oligosaccharides from medicinal Mexican morning glory species as antibacterials and inhibitors of multidrugresistance in Staphylococcus aureus. J Nat Prod , 2006 , 69 (3) :406-409.
[104]. Sun C , Shan CY, Gao XD , et al . Protection of PC12 cells from hydrogen peroxide-induced injury by EPS2 , an exopolysaccharide from a marine filamentous fungus Keissleriella sp. YS4108J [ J ] .Biotechnol , 2005 , 115 (2) :137-1441.
[105]. Chicoine LM, Bahr BA. Excitotoxic protection by polyanionic polysaccharide: evidence of a cell survival pathway involving AMPA receptor2MAPK Interactions[J ] . J Neurosci Res , 2007 , 85 (2) :294-3021.
[106].方积年,丁侃.夹竹桃花多糖及其制备方法和应用:中国,ZL 99125746.4[P].20032122031.
[107]. Yu MS, Lai SW, Lin KF. Characterization of polysaccharides from the flowers of Nerium indicum and their neuroprotective effects. Int J Mol Med , 2004,14(5) :9172-9241.
[108].徐德生,冯怡,林晓.麦冬多糖MDG21的分离纯化和结构分析.药学学报,2005,40(7) :636-6391.
[109]. Chen YJ , Yang YC. A novel polysaccharide of black soybean promotes myelopoiesis and reconstitutes bone marrow after 52flurouraciland irradiation2induced myelosuppression. Life Sci , 2005,77( 4) :400-413.
[110]. Rocha HA , Moraes FA , Trindade ES , et al . Structural and hemostatic activities of a sulfated galactofucan from the brown alga Spatoglossum schroederi . An ideal antithrombotic agent. J Biol Chem ,2005 , 280(50) :41278-41288.
[111]. Tsujita T, Takaichi H, Takaku T, et al . Inhibition of lipase activities by basic polysaccharide . J Lipid Res , 2007 , 48 (2) :358-365.
[112]. Ermerk IM, Barabanova AO , Kukarskikh TA , et al . Natural polysaccharide carrageenan inhibits toxic effect of gram2negative bacterial endotoxins. Bull Exp Biol Med, 2006, 141(2) :230-232.
[113]. Kaji Y, Hiraoka T , Oshika T , et al . Potential use of (1,3)-beta-D-glucan as target of diagnosis and treatment of keratomycosis. Cornea , 2004 , 231 :36-41.
[114]. Maeda H , Zhu X, Suzuki S , et al . Structural characterization and biological activities of an exopolysaccharide kefiran produced by Lactobacillus kefiranofaciens WT22B (T). J Agric Food Chem ,2004 , 52(17) :5533-5538.
[115]. Sakaguchi I , Ishimoto H , Matsuo M, et al . The water soluble extract of Illiciumanisatum stimulates mouse vibrissae follicles in organ culture. Exp Dermatol , 2004 , 13(8) :499-504.
[116]. Kardosova A , Ebringerova A , Alfoldi J , et al . A biologically active fructan from the roots of Arctium lappa L. , var. Herkules. Int J Biol Macromol , 2003 , 33(123) :135-140.
[117]. Takada T , Katagiri T , Ifuku M, et al . Sulfated polysaccharides enhance the biological activities of bone morphogenetic proteins. J Biol Chem , 2003 , 278 (44) :43229-43235.
[118]. Guyard C , Dehecq E , Tissier JP , et al . Involvement of [ beta ]-glucans in the wide-spectrum antimicrobial activity of Williopsis saturnus var. mrakii MUCL 41968 killer toxin. Mol Med , 2002 , 8 (11) :686-694.
[119]. Schachter H. Molecular cloning of glycosyltransferase genes. In Molecular Glycobiology. Oxford: IRL Press,1994.
[120]. Varki A. Biological roles of oligosaccharides: all of the theories are correct[J]. Glycobiology.1993,(3):97-101.
[121]. Meinjohanns E. Meldal M, Paulsen H, et al. Novel sequentiall solid-phase synthesis of N-linked glycopeptides from natureal sources . J. Chem Soc.Perkin Trans I, 1998,549-555.
[122]. Gilbert M, Bayer R, Cunningham A M, et al.The synthesis of sialylated oligosaccharides using a CMP-neu5Ac synthetase/sialyltransferase fusion. Nature Biotechnol, 1998, (16):769-776.
[123].辛月坤.肝素临床应用回顾.中国医学文摘,2002,23(1):131-134.
[124].张治云,凌沛学,王凤山,张天民.低分子肝素药理作用研究进展.食品与药品,2006,8(1): 7-9.
[125]. Goa K.L.,Benfield P. Hyaluronic acid: A review of its pharmacology and use as surgical aid in ophthalmology, and its therapeutic potential in joint disease and wound healing. Drugs, 1994,47:536-566.
[126].卢京光,姬胜利,张尊建.硫酸软骨素及其衍生物的研究进展.中国海洋药物杂志, 2006,25(1):59-63.
[127].田庚元,冯宇澄,多糖类免疫调节剂的研究和应用.化学进展, 1994,6(2):114-122.
[128]. Franz, G. Polysaccharides in pharmacy: current in applications and future concepts. Plant Medical. 1989,55:493-497.
[129].梅建民.高渗盐水右旋糖酐液抗失血性休克机理的研究进展.国外医学创伤与外科基本问题分册,1994,1:10-12.
[130]. Zeerleder, Sacha; Mauron, Thomas; L?mmle, Bernhard; Wuillemin, Walter A. Effect of low-molecular weight dextran sulfate on coagulation and platelet function tests. Thrombosis research, 2002 ,105(5):441-446.
[131]. Bobek, G; Scott, CD; Baxter, RC. Radioimmunoassay of soluble insulin-like growth factor-II/mannose 6-phosphate receptor: Developmental regulation of receptor release by rat tissues in culture. Endocrinology. 1992,130(6):3387-3394.
[132]. Acemannan. CARN 1000, CARN 750, polymannoacetate, Aliminase, Alovex, Carrisyn. Drugs in R&D, 1999,1(3):251-252.
[133].罗善高.藻酸双酯钠的临床应用.医学文选, 2001,20(3):379-380.
[134].张平;夏泉;赵新民.甘糖酯的药理及临床应用研究进展.江苏药学与临床研究, 2001,9(1):38-40.
[135]. Baron A. D.,Postprandial hyperglycaemia andα-glucosidase inhibitors. Diabetes Research and Clinical Practics, 1998, 40(Suppt):51-55.
[136]. Blickle J.F,Andies E,Mogul J.M., Current status of the treatment of type 2 diabetes mellitus alpha-glucosidase inhibitors. Rev Med lnterne, 1999,20(Suppl.3):375-383.
[137]. Stephen P. C., Clive E. Acarbose a preliminary review of its pharmacodynamic and pharmacolinetic properties and therapeutic potential. Drugs, 1988, 35: 214.
[138]. Elbein A.D. Inhibitors of the biosynthesis and processing of N-linked oligosaccharides.CRC Crit.Rev.Biochem.1984,16:21-49.
[139]. Elbein A.D. Inhibitors of the biosynthesis and processing of N-linked oligosaccharide chains. Annu.Rev.Biochem.1987,56:497-534.
[140]. Humphries M.J.,Matsumoto K.,White S.L.,and Olden K.Inhibition of experimental metastasis by castanospermine in mice:Blockage of two distinct stages of tumor colonization by oligosaccharide processing inhibitors. Cancer Res.1986,46:5215-5222.
[141]. Dennis J.W., White S.L., Freer A.M., and Dime D. Carbonoyloxy analogs of anti-metastatic drug swainsonine. Activation in tumor cells b esterases. Biochem. Pharmacol. 1993,46: 1459-1466.
[142]. Harris E.M., Aleshin A.E., Firsov L.M., and Honzatko R.B. Refined structure for the complex of 1-deoxynojirimycin with glucoamylase from Aspergillus awamori var. X100 to2.4-àresolution. Biochemisty, 1993, 32:1618-1626.
[143]. Goss P.E., Baptiste J., Fernandes B., Baker M., and Dennis J.W. Aphase I study of swainsonine in patients with advanced malignancies. Cancer Res. 1994,54:1450-1457.
[144]. Jacob G.S. Glycosylation inhibitors in biology and medicine. Curr. Opin. Struct. Biol. 1995,5:605-611.
[145]. Kang M.S., Liu P.S., Bernotas R.C., Harry B.S., and Sunkara P.S. Castanospermine analogues: Their inhibition of glycoprotein processingα-glucosidases from porcine kidney and B16F10 cells. Glycobiology, 1995,5:147-152.
[146]. Asano N., Kato A.,Matsui K., Watson A.A., Nash R.J., Molyneux R.J., Hackett L., Topping J., and Winchester B. The effect of calystegines isolated from edible fruits and vegetables on mammalian liver glycosidases. Glycobiology, 1997,7:1085-1088.
[147]. Platt F.M., Reikensmeier G., Dwek R.A., and Butters T.D. Extensive glycosphingolopid depletion in the liver and lymphoid organs of mice treated with n-butyldeoxynojirimycin. J.Biol.Chem. 1997,272;19365-19372.
[148]. Platt F.M., Butters T.D. New therapeutic prospect for the glycosphingolipid lysosomal storage diseases. Biochem. Pharmacol. 1998,56:421-430.
[149]. Von Itzstein, M; Wu, Wen-Yang; Kok, GB; Pegg, MS; Dyason, JC; Jin, B; Phan, Tho Van; Smythe, ML; White, HF; Oliver, SW. Rational design of potent sialidase-based inhibitors of influenza virus replication Nature, 1993,363(6428):418-423.
[150]. Calfee, D P; Hayden, F G New approaches to influenza chemotherapy. Neuraminidase inhibitors. Drugs, 1998,56(4):537-553.
[151]. Sahasrabudhe, A; Lawrence, L; Epa, VC; Varghese, JN; Colman, PM; McKimm-Breschkin, JL Substrate, Inhibitor, or Antibody Stabilizes the Glu 119 Gly Mutant Influenza Virus Neuraminidase. Virology, 1998,247(1):14-21.
[152]. Mendel, D B; Tai, C Y; Escarpe, P A; Li, W; Sidwell, R W; Huffman, J H; Sweet, C; Jakeman, K J; Merson, J; Lacy, S A; Lew, W; Williams, M A; Zhang, L; Chen, M S; Bischofberger, N; Kim, C U Oral administration of a prodrug of the influenza virus neuraminidase inhibitor GS 4071 protects mice and ferrets against influenza infection. Agents Chemother,1998,42(3):640-646.
[153]. Li, W; Escarpe, P A; Eisenberg, E J; Cundy, K C; Sweet, C; Jakeman, K J; Merson, J;Lew, W; Williams, M; Zhang, L; Kim, C U; Bischofberger, N; Chen, M S; Mendel, D BIdentification of GS 4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor GS 4071.Agents Chemother,1998,42(3):647-653.
[154]. Collins P M, Ferier R J . Natural products related to and containing monosaccharides. In Monosaccharides: Their Chemistry and their Roles in Natural Products. Chichester: Wiley,1995.
[155]. Gaisser S, Leadlay P F. Sugaring the pill by design. Nature Biotechnol,1998,16(1):19-20.
[156]. Ajit Varki, Richard Cummings, Jeffrey Esko, Hudson Freeze, Gerald Hart, Jamey Marth. Essential of .glycobiology. New York: Cold Spring Harbor Laboratory Press,1999.562-568.
[157].卞广兴.糖工程:糖基化对治疗蛋白性质的影响.国外医学.药学分册,2006,33(4):266-268.
[158]. Ronin C. Remodiling of glycoprotein and carbohydrate antigens. Clin Chem Lab Med,1998,57:785-789.
[159]. Dsouza V T, Lipkowitz K B.Cyclodetrin. Cyclodextrins Chem Rev,1998,98:2045-2052.
[160]. Lee YC, Lee RT, Neoglycoconjugates. San Diego, Academic Press,1994,53-57.
[161].刘昌孝,孙瑞元.药物评价实验设计与统计学基础.军事医学科学出版社,1999.
[162].钟大放.药物代谢与药物动力学基础研究展望.辽宁药物与临床.2000,3(4):145-148.
[163].陈淑娟,曾繁典.抗心律失常药物体内代谢及其临床影响因素.中国临床药理学杂志, 2000,16(2):146-150.
[164]. Shah, V P; Midha, K K; Findlay, J W; Hill, H M; Hulse, J D; McGilveray, I J; McKay, G; Miller, K J; Patnaik, R N; Powell, M L; Tonelli, A; Viswanathan, C T; Yacobi, A. Bioanalytical method validation--a revisit with a decade of progress. Pharmaceutical research, 2000, 17(12):1551-1557.
[165].张琪,王广基.蛋白多肽类药物药代动力学分析方法研究进展.药物生物技术, 2000,7(2):126-128.
[166].王克夷.分子生物学前沿技术,联合出版社,1998.
[167]. N., Laforest et al., Pharmacokinetics and biodistribution of technetium 99m labeled atandard heprin and a low molecular weight heparin after intravenous injection in normalvolunteers. British J Haemat 1991,77:201.
[168]. Huhil etal. Comparison of three heparin bovine serum albumin binding methods for production of antiheparin antibidies. Semi Thromb Hesomst, 1994,20(2):193-198.
[169]. Huhil etal. Monoclonal antibodies against heparin and heparinoids. Semi Thromb Hesomst, 1997,23(1):17-21.
[170]. L Robert etal. Pharmacokinetic profile of 14C-labelled clopidogrel. Semi Thromb Hesomst,1999,25(suppl):29-35.
[171]. R Malsch etal. Measurement of fluorensent–labblee LMN-heparin in biological fluid using protamine-linked microbeads. Semi Thromb Hesomst, 1997,23(1):23-30.
[172]. U Cornelli, etal. Human pharmacokinetics of low molecular weight heparins. Semi Thromb Hesomst, 1999,25(supp):57-66.
[173]. J Fareed, Pharmacokinetics of low molecular weight heparins in animal models. Semi Thromb Hesomst, 1999,25(supp):51-58.
[174]. L Piazolo, Comparison of the pharmacodynamic and Pharmacokinetic profiles of two low-molecular-mass heparins in rats. Semi Thromb Hesomst, 1997,23(2):109-116.
[175]. B Boneu, Pharmacokinetics and tolerance of the natural pentasaccharide with high affinity to antihrombinⅢin man. Thromb Hesomst, 1995,74(6):1468-1473.
[176]. Smolec, JoMarie; DeSilva, Binodh; Smith, Wendell; Weiner, Russell; Kelly, Marian; Lee, Ben; Khan, Masood; Tacey, Richard; Hill, Howard; Celniker, Abbie; Shah, Vinod; Bowsher, Ronald; Mire-Sluis, Anthony; Findlay, John W A; Saltarelli, Mary; Quarmby, Valerie; Lansky, David; Dillard, Robert; Ullmann, Martin; Keller, Stephen; Karnes, H Thomas Bioanalytical method validation for macromolecules in support of pharmacokinetic studies. Pharmaceutical research, 2005,22(9):1425-1431.
[177]. P. Oreste, M. Peruzzi and P. Stella Micromethod for the determination of heparin in plasma after intravenous and subcutaneous administration. Analytical Biochem, 1993,210(1):136-139.
[178]. Yong Huang, Yukio Washio, Mutsumi Hara, Hidenao Toyoda, Ichiro Koshiishi, Toshihiko Toida and Toshio Imanari Simulataneous determination of dermatan sulfate and oversulfated dermatan sulfate in plasma by HPLC with postcolumn fluorenscence derivatization. Analytical Biochem, 1996,240(2):227-234.
[179].郑年新,姚新生.六味地黄多糖在小鼠体内的吸收.中国药理学通报.2000,16(4):403-405.
[180]. Volpi, Nicola , Separation of capsular polysaccharide-K4- and defructosylated-K4-derived disaccharides by high-performance liquid chromatography and postcolumn derivatization with 2-cyanoacetamide and fluorimetric detection. Analytical biochemistry, 2004,330(2):359-61.
[181]. O’Hara Y., Fate of lentinan(antitumor polysaccharide)I: Fate of lentinan in mice, rats and dogs. J. Toxicol. Sci. 1980,5:59-72.
[182].谢炳华,张年宝,茯苓聚糖的氚离子束标记及其在小鼠体内的药物动力学研究.核技术, 1990,13:693-695.
[183].盛少虎;李应全;马剑峰;袁玮.甘糖酯在小鼠体内的药代动力学研究.中国海洋药物杂志, 1995,14(2): 15-17.
[184]. Robert A., Shiv C., Rajesh K., James K., Francesca C.L., Garret A. Oral delivery of anticoagulant dose of heparin a randomized, double-blind, controlled study in humans. 1998,98:1610-1615.
[185].王睿,方翼,柴栋,裴斐,李桂玲,耿美玉、谭兰,陈升杰,管华诗.单次静滴D-聚甘酯注射液在中国男性健康志愿者的药代动力学.中国临床药理学杂志,2006,22(3):192-194.
[186].丁华;祝清芬;徐鲁源;吴葆杰;李英霞;吕志华.几丁糖酯抗动脉粥样硬化研究.中国海洋药物.2001,1:12-17.
[187].胡金凤;耿美玉;陈昆;冉忠梅;徐家敏;管华诗.甲壳质衍生物916对家兔实验行动脉粥样硬化的预防作用.中国海洋药物.2000,3:18-21.
[188].王妍婷;吕志华;王远红.海洋硫酸多糖916在2种酶作用下稳定性的研究.中国海洋大学学报, 2004, 34(6):955-958.
[189]. Han Y.H., Lv Z.H., Jiang T.F., Wang Y.H. Bioanalysis and pharmacokinetics of chitosan ester in rabbit serum by HPLC with postcolumn fluorescence derivatization. Journal of Chromatography B, 2007, 845:138–142.
[190]. Pangburn SH. Trescony PV. Heller J. Lysozyme degradation of partially deacetylated chtin. Its films and hydrogels. Biomaterials 1982, 3:105-108.
[191]. Yomata C. Komuro T. Kimura T. Studies on the degradation of chitosan films bylysozyme and release of loaded chemicals. Yakugaku zasshi 1990:110:442-448.
[192]. Hiraku O. Yoshiharu M. Biodegradation and distribution of water-soluble chitosan in mice. Biomaterials. 1999, 20: 175-182.
[193]. Shah VP, Midha KK, Findlay JW, Hill HM, Hulse JD, McGilveray IJ, McKay G. Bioanalytical method validation-A revisit with a decade of progress. Pharm. Res. 2000, 17: l 551-1557.
[194]. Kames HT, March C. Precision, accuracy and data acceptance criteria in biopharmaceutical analysis. Pharm. Res. 1993, 10: 1420-1422.
[195].萧参,陈坚行.生物药剂分析方法的认证.中国药学杂志,1993, 24; 425-426.
[2]. Deka RK, Machius M, Norgard MV, Tomchick DR. Crystal Structure of the 47-kDa Lipoprotein of Treponema pallidum Reveals a Novel Penicillin-binding Protein J Biol Chem.2002,277 (44):41857- 41864
[3]. Blix G., Gottschalk A., Klenk E. Proposed nomenclature in the field of sialic. Nature, 1957,175: 340-341.
[4]. Stanley P., Ioffe E. Glycosyltransferase mutants: Key to new insights in glycobiology. FASEB J. 1995, 9:1436-1444.
[5]. Rademacher T.W., Parekh R.B., Dwek R.A. Glycobiology. Annu. Rev. Biochem. 1988, 57:785-838.
[6]. Zhang Y X, Xang S T, Zhou J H. Effects of Lycium barbarum polysaccharides and their combination with Corybacterium parvum on the peritoneal macrophages in mice. Chinese Journal of Pharruacology and Toxicology, 1989, 3 (3): 169-174.
[7].张俊平,钱定华.商陆多糖抗瘤活性及对小鼠产生肿瘤坏死因子的作用.中国药理学报,1990, 14(6):542-544
[8].赵俊,吴宏,王亚平.人参多糖的化学与药理学研究进展.国外医学中医中药分册,2004, 26 (2):79-81.
[9].刘彦平,毛辉青,李萍,张玉叶.枸杞多糖对小鼠T淋巴细胞亚群和淋巴细胞转化作用的研究.青海医学院学报, 2000,21(4):4-5.
[10]. Ren, DL; Wang, JZ; Noda, H; Amano, H; Ogawa, S. The effects of an angal polysaccharide from Gloiopeltis tenax on transplantable tumors and immune activities in mice. Planta Med,1995, 61 (2) : 120-125.
[11]. Kiho T, Ookubo K, Usui S, Ukai S, Hirano K. Structural features and hypoglycemic activity of a polysaccharide (CS-F10) from the cultured mycelium of Cordyceps sinensis. Biol Pharm Bull, 1999, 22(9):966-970.
[12]. Lei L S, Lin Z B. Effect of Ganoderma Polysaccharides on T cell subpopulations and production of interieukin 2 in mixed lymphonyte. Acta Pharm Sin Acta Pharm Sin, 1992, 27(5): 33l-334.
[13].邵树军,刘彩玉,刘雄伯,王天元.牛膝多糖对小鼠免疫功能影响的研究.肿瘤防治杂志,2002,9(1):57-58
[14].冯仲联,孙秀华.人参多糖治疗恶性胸腔积液的临床研究.中国新药杂志, 1999, 8(9):619-621
[15]. Kodama N, Harada N, Nanba H. A polysaccharide, extract from grifola frondosa, induces Th-1 dominant responses in carcinoma-bearing BALB/c mice. Japanese Journal of Pharmacology, 2002, 90 (4) :357-360.
[16].刘俊栋,刘海霞,李建基.当归多糖对免疫系统作用的研究.四川畜牧兽医,2003, 3: 34-35.
[17].郭随章.中药多糖的抗癌研究与临床应用进展.医药导报,2004, 23 (11):848-848.
[18]. Kajimura, K; Takagi, Y; Miyano, K; Sawabe, Y; Mimura, M; Sakagami, Y; Yokoyama, H; Yoneda, K. Polysaccharide of Astragali Radix enhances IgM antibody production in aged mice. Biol. Pharm. Bull.1997,20(11):1178-1182.
[19]. Okai, Y.; Higashi-Okai, K.; Ishizaka, S.; Ohtani, K.; Matsui-Yuasa, I.; Yamashita, U. Possible immunodulating activities in an extract of edible brown alga, Hijikia fusiforme (Hijiki). Journal of science of food and agriculture, 1998, 76 (1):56-62.
[20]. Yamada, H.; Kiyohara, H.; Cyong, J.C.; Kojima, Y.; Kumazawa, Y.; Otsuka, Y. Studies on polysaccharides from Angelica acutiloba. 1. Fractionation and biological properties of polysaccharides. Planta Med. 1984, 50(2): 163-167.
[21].董爱琴.多糖的免疫调节作用及作用机制研究进展.中华今日医学杂志, 2003, 3(5): 87-88.
[22]. Chun, H; Shin, D H; Hong, B S; Cho, H Y; Yang, H C. Purification and biological activity of acidic polysaccharide from leaves of Thymus vulgaris L. Biol. Pharm. Bull., 2001,24(8):941-946.
[23]. Chun, H; Shin, D H; Hong, B S; Cho, H Y; Yang, H C. Purification and biological activity of acidic polysaccharide from leaves of Thymus vulgaris L. Biol. Pharm. Bull., 2001,24(8):941-946.
[24]. Peyroux, J.; Rossignol, P.; Delaveau, P. Anti-edematous and anti-hyperhemiant properties of Calendula officinalis L. Plantes medicinales et phytotherapie., 1981,15(4):210-216.
[25]. Nagashima, H.; Fukuda, I. Low molecular weight carbohydrates in Cyanidium caldarium andsome related algae. Phytochemistry., 1981,20(3):439-442.
[26]. Prcciarini F., Ghezzi S., Pinnr D., Sulfated KS Eschenchia coli polysaccharide derivatives inhibit human immunodeficiency virus HIV transmission. New Mcrobiol, 2004,27(2 Suppl 1):5-9.
[27]. Sastry G, HariA S , Sudeep ta A., Isolation of a previously unidentified polysaccharide (MAR-10) from hyssopofficinalis that exhibits strong activity against human immunodeficiency virus type. Biochem Biophy Res Commun, 1995, 210:145 - 151.
[28]. Nakano, M; Itoh, Y; Mizuno, T; Nakashima, H. Polysaccharide from Aspalathus linearis with strong anti-H IV activity. Biosci Biotechnol Biochem, 1997, 61(2): 267-271.
[29].耿美玉,辛现良,管华诗.海洋硫酸多糖类药物911抗艾滋病毒作用及其机理研究.中国药理学会通讯,2001,18(1):9-13
[30].辛现良,丁华,耿美玉,梁平方,李英霞,管华诗.海洋硫酸多糖911抗艾滋病毒作用及其机理研究-体内对猴免疫缺陷病毒(SIV)增殖的影响.中国海洋药物杂志,2000,19(6):4-8.
[31]. Watson, K; Gooderham, N J; Davies, D S; Edwards, R J. Interaction of the transactivating protein HIV-1 Tat with sulphated polysaccharide. Biochem Pharmaco, 1999, 57(7): 775-783.
[32]. Baba, M; de Clercq, E; Schols, D; Pauwels, R; Snoeck, R; Van Boeckel, C; Van Dedem, G; Kraaijeveld, N; Hobbelen, P. Novel sulfated polysaccharides: Dissociation of anti-human immunodeficiency virus activity from antithrombin activity. J Infect Dis, 1990, 161 (2) : 208-213.
[33]. Collins, RA; Ng, Tzi Bun. Polysaccharopeptide from Coriolus versicolor has potential for use against human immunodeficiency virus type 1 infection. Life Sci. 1997, 60(25): 383-387.
[34].田庚元,李寿桐,宋麦丽,郑民实,李文.牛膝多糖硫酸醋的合成及其杭病毒活性,药学学报,1995, 30(21): 107-111.
[35].郭长占,马俊良.猪苓多糖对HBV转基因小鼠HbsAG表达的影响.中国实验临床免疫学杂志, 1999,11(6):48-50.
[36]. Hoshino, T; Hayashi, T; Hayashi, K; Hamada, J; Lee, J-B; Sankawa, U. An Antivirally Active Sulfated Polysaccharide from Sargassum horneri (Turner) C. Agardh Biol Pharm Bull. 1998, 21 (7) : 730 - 734.
[37].佟丽;黄添友;李吉来;吴波;梁谋;梁念慈.植物多糖对S180、K562细胞增殖和唾液酸、磷酸、胆固醇含量的影响.中国中西医结合杂志,1994, 14 (8) : 482-484.
[38].吴迪.茯苓多糖抗肿瘤作用与机理的实验研究.中国药理学通报, 1994, 10 (4) : 30-33.
[39].杨江苏;秦旭平;张娜;颜卉君.两种真菌多糖对HL260细胞酪酸蛋白磷酸化作用的影响.中国药学杂志, 2000, 35 (5) : 303-305.
[40].魏小龙,茹祥斌.低分子质量地黄多糖体外对Lewis肺癌细胞p53基因表达的影响.中国药理学通报, 1998, 14 (3) : 245247.
[41].吕怀盛,张红梅,张波.枸杞多糖对PG细胞株增殖及凋亡的影响.宁夏医学院学报, 2002, 24 (1) : 10-12.
[42].陈彻;王镜;李兴玉;席亚明.梁金菇多糖促人急性早幼粒细胞白病细胞系(HL260)细胞凋亡的研究.中国新药与临床杂志,2002, 21 (6) : 349-352.
[43].戴伟娟;仲伟法;司端运;王绍红;刘善庭.无花果多糖可提高荷S180小鼠血清的MDA、SOD和GSH2px的影响.济宁医学院学报, 2002, 25(1) : 20-22.
[44].王炳岩,季宇彬.海藻多糖对白血病L615小鼠LPO含量及GR、GSH2px、CAT、SOD酶活性影响.中医药信息, 1994, 12 ( 5 ) :43-45.
[45].金山久.茯苓菌丝体抗肿瘤活性多糖研究Ⅲ抗小鼠肿瘤活性.国外医学·中医中药分册, 1987, 9 (6) : 29-30.
[46].宋为民,法京.人参和绞股蓝的抗突变作用.中草药, 1992,23 (3) : 136-138.
[47].丁健.抗肿瘤药物的研究新进展.中国新药杂志, 2000, 17(3) : 150-152.
[48]. Takahashi Y, Kitadai Y,Bucana C D. Expression of VEGF and its receptor KDR. Correlates with vascu-laritymetastasis and proliferation of human colon cancer. Cancer Research, 1995, 55 ( 4) :3964-3970.
[49]. Geng YJ, Hellst rand K. Apoptotic death of human leukemic cells induced by vascular cells expressing tricocide Syntheses in response to gamma-interferon and tumor necrosis factoralpha. Cancer Res, 1996, 56 (4) : 866-870.
[50].李家琦,夏英.中药诱导干扰素作用的探索.上海中医药杂志, 1994, 28 (1) : 34-37.
[51]. Kajimura, K; Takagi, Y; Miyano, K; Sawabe, Y; Mimura, M; Sakagami, Y; Yokoyama, H; Yoneda, K. Polysaccharide of Astragali Radix enhances IgM antibody production in aged mice. Biol. Pharm. Bull. 1997,20(11):1178-1182.
[52].许爱霞,张振明,葛斌,蒲君峰.党参多糖抗衰老作用机制的实验研究.中国现代应用药学杂志, 2006年,23(8): 729-731.
[53].黄正良,红芪多糖抗衰老作用的实验研究.中草药, 1992, 23(9):469-471.
[54].左绍远.螺旋藻多糖对D-半乳糖所致衰老小鼠的作用.中国生化药物杂志, 1998, 19 (1) : 15-18.
[55].张振明,葛斌,许爱霞,蔡曦光.女贞子多糖的抗衰老作用.中国药理学与毒理学杂志, 2006,20 (2) : 108– 111.
[56].姚文兵.大黄的生化学研究:波叶大黄多糖抗衰老作用的实验研究.中国药科大学学报.1991, (3):167-169.
[57].王建华,王汉中,张民,张声华.枸杞多糖延缓衰老的作用.营养学报, 2002, 24(2):189-192.
[58].李国莉,任彬彬,杨建军.枸杞多糖对小鼠耐力及体内抗氧化酶活性的影响.辽宁中医杂志,2002,29(10):634-638.
[59].凌小曼;丁虹;罗顺德;张晓健;张连和.当归多糖对血癖证动物免疫功能和抗氧化功能的影响.中国医院药学杂志,2002,22(10):584-586.
[60]. Yoshida, I; Kiho, T; Usui, S; Sakushima, M; Ukai, S. Polysaccharides in fungi. XXXVII. Immunomodulating activities of carboxymethylated derivatives of linear (1 arrow right 3)- alpha -D-glucans extracted from the fruiting bodies of Agrocybe cylindracea and Amanita muscaria . Biol Pharm Bull ,1996,19(1) :114-121.
[61]. Bopanna K.N.,Kannan, J.,Gadgil, S,Balaraman, R., Rathod, S.P. Antidiabetic and antihyperlipemic effects of neem seed kernel powder on alloxan-diabetic rabbits.Indian J. Pharmaco1,1997, 29:162-167.
[62]. Kumari, K., Mathew, B.C., Augusti, K.T. Antidiabetic and polipidemic effects of S-methyl cysteine sulfoxide isolated from Allium ceps linn. Indian J. Biochem. Biophys. 1995, 32: 49-54.
[63]. M. Shanmugam and K. H. Mody. Heparinoid-active sulphated polysaccharides from marine algae as potential blood anticoagulant agents. CURRENT SCIENCE, 2000,79,12, 25:1672-1683.
[64]. Glombitz, K.W., Mahran, G.H., Mirhom, Y.M., Michel, K.G., Motawi, T.K. Hypoglycemic and antihyperglycemic effect of Zaphus spanachrastt in rats. Plants Med. 1994, 60: 244-247.
[65]. Khan, B.A,Abraham, A., Leelamma, S. Hypoglycemic action of Murraya Koeraaghi (curry leaf) and Brassta juracea (mustard): mechanism of action. Indian J. Biochem. Biophys. 1995,32: 106-108.
[66]. Itoh, T; Itoh, Y; Mizutani, M; Fujishiro, K; Furuichi, Y; Komiyami, T; Hibasami, H Hot-water extracts from adzuki beans (Vigna angularis) suppress not only the proliferation of KATO III cells in culture but also benzo(a)pyrene-induced tumorigenesis in mouse forestomatch. Journal of Nutritional Science and Vitaminology, 2004,50 (4):295-299.
[67]. Spiller R.C. Pharmacology of dietary fiber. Pharmacology and Therapeutics, 1994, 62: 407-427.
[68]. Silverman H.M. Metabolic effects of fiber supplementation(Part II). Journal of Practical Nursing,1990, 40: 41-48.
[69]. Lairon D. Dietary fibres: effects on lipid metabolism and mechanisms of action. European Journal of Clinical Nutrition, 1996, 50(3): 125-133.
[70]. Wursch P., Pi-Sunier F.X. The role of viscous soluble fiber in the metabolic control of Diabetes. Diabetes Care, 1997, 20: 1774-1780.
[71].吴建芬;冯磊;张春飞;李印彩.茶多糖降血糖机制研究.浙江预防医学, 2003,15 (9):10-13.
[72]. Basnet, P.; Kadota, S.; Shimizu, M.; Takata, Y.; Kobayashi, M.; Namba, T. Bellidifolin stimulates glucose uptake in rat 1 fibroblasts and ameliorates hyperglycemia in streptozotocin (STZ)-induced diabetic rats. Planta medica., 1995,61(5):402-405.
[73]. Konno C, Sugiyama K, Kano M, Takahashi, M., Hikino, H. Isolation and hypoglycaemic activity of panaxans A, B, C, D and E, glycans of Panax ginseng roots. Planta Med, 1984,50 (5) : 434-436.
[74]. Hikino H, Konno C, Mirin Y, Hayashi, T, Isolation and Hypoglycemic Activity of Ganoderans A and B, Glycans of Ganoderma lucidum Fruit Bodies1. Planta Med,1985, 51(4): 339-340.
[75]. Oshima, Y; Ohsawa, T; Oikawa, K; Konno, C; Hikino, H., Structures of Dianosides A and B, Analgesic Principles of Dianthus superbus var. longicalycinus Herbs1. Planta Med, 1984,50 (1): 40-43.
[76]. Konno C., Hikino H., Isolation and hypoglycemic activity of panaxans M, N, O and P, glycans of Panax ginseng roots. Int J Crude Drug Res, 1987, 25(1): 53-57.
[77]. Konno C, Murakami M, Oshima Y, Hikino, H., Isolation and hypoglycemic activity ofpanaxans Q, R, S, T and U, glycans of Panax ginseng roots. J Ethno-pharmacol 1985, 14 (1) : 69-74.
[78]. Takahashi M., Konno C., Hikino H. Isolation and hypoglycemic activity of saccharans A, B, C, D, E and F, glycans of Saccharum officinarum stalks. Planta Med, 1985, 51(3) : 258-260.
[79]. Konno C, Mizuno T, Hikino H., Isolation and Hypoglycemic Activity of Lithospermans A, B and C, Glycans of Lithospermum erythrorhizon Roots1. Planta Med, 1985, 51(2) : 157-158.
[80]. Hikino H., Takahashi M., Oshima Y., Konno C. Isolation and hypoglycemic activity of oryzabrans A, B, C and D, glycans of Oryza sativa bran. Planta Med, 1988, 54 (1) : 1-3.
[81]. Kiho, T; Kochi, M; Usui, S; Hirano, K; Aizawa, K; Inakuma, T. Antidiabetic effect of an acidic polysaccharide (TAP) from Tremella aurantia and its degradation product (TAP-H). Biological & pharmaceutical bulletin, 2001,24(12):1400-1403.
[82]. Kondo, Y; Nakatani, A; Hayashi, K; Ito, M Low molecular weight chitosan prevents the progression of low dose streptozotocin-induced slowly progressive diabetes mellitus in mice. Biol. Pharm. Bull., 2000,23(12):1458-1464.
[83]. Hayashi K, Ito M. Antidiabetic action of Low molecular weight chitosan in genetically obese diabetic KK-Ay mice. Biol. Pharm. Bull., 2002,25(2):188-193.
[84].吴昊姝;徐建华;陈立钻;孙继军.铁皮石斛降血糖作用及其机制的研究.中国中药杂志. 2004,29(2):160-163.
[85]. Yang, Jeong-Lye; Kim, Young-Hwa; Lee, Hyun-Sook; Lee, Mak-Soon; Moon, Yangha Kim Barley beta-glucan lowers serum cholesterol based on the up-regulation of cholesterol 7 alpha-hydroxy-lase activity and mRNA abundance in cholesterol-fed rats . J Nutr Sci Vitaminol,2003 , 49(6) :381-387.
[86].张信岳;程敏;孟倩超;叶小弟;郑高利;李士敏.羊栖菜多糖降血脂作用研究.中国海洋药物,2003,5:27-31.
[87].童红莉;田亚平;汪德清;邓心新;董振南.黄芪多糖对高脂血症大鼠血脂的调节.中国临床康复, 2006, 10(11): 68-70.
[88].尹俊青;宋淑珍;田亚平;汪德清黄芪多糖对健康人群血脂水平的干预效应.中医康复研究, 2005, 9(31): 160-161.
[89].吴建芬;冯磊;张春飞;李印彩.茶多糖降血糖机制研究,浙江预防医学,2003,15(9): 10-12.
[90]. Xue C., Fang Y, Lin H. Chemical characters and antioxidative properties of sulfated polysaccharides from Laminaria japonica. J. Appl. Plrycol., 2001, 13, 67-70.
[91].黄飞.山楂叶多糖的功能活性测定研究.广西轻工业, 2001, 2:47-49.
[92].王常青,杨桂兰.两种海藻多糖对大鼠脂质代谢和血小板功能的比较.中国预防医学杂质. 1998,31(6):342-346.
[93].黄晓青,瞿伟箐,张晓玲.沙棘多糖对小鼠试验性高脂血症的影响.营养学报, 2004,26(3):222-224.
[94]. Hosseinzadeh H., Sadeghi A. Antihyperglycemic Effects of Morus Nigra and Morus Alba in Mice[P]. Japan: 97140351,1995-11-21.
[95].姚思宇,赵鹏,刘荣珍,等.虫草多糖降血脂作用的动物试验研究.中国热带医学, 2004,4(2):197-198.
[96].罗琼,李瑾玮,张声华.枸杞及其多糖对家兔血脂的影响.食品科学, 1997,18(4):5-7.
[97]. Lindsay, J O; Whelan, K; Stagg, A J; Gobin, P; Al-Hassi, H O; Rayment, N; Kamm, M A; Knight, S C; Forbes, A Clinical microbiological and immunological effects of fructo-oligosaccharide in patients with Crohn’s disease. Gut , 2006 , 55 (3) :348-355.
[98]. Akindele A.J., Adeyemi O.O. Antiinflammatory activity of the aqueous leaf extract of Byrsocarpus coccineus. Fitoterapia , 2007,78(1) :25-28.
[99]. Guzmán, S; Gato, A; Lamela, M; Freire-Garabal, M; Calleja, J M Anti-inflammatory and immu-nomodulatory activities of polysaccharide from Chlorella stigmatophora and Phaeodactylum tricornutum. Phytother Res , 2003 , 17(6) :665-670.
[100]. da Silva BP , Silva GM, Mendes TP , et al . Structural characteristics of a bioactive polysaccharide from Sorghum arundinaceum. Z Naturforsch , 2003 , 58 (526) :342-346.
[101]. Lee JH , ShimJS , Lee JS , et al . Pectin-like acidic polysaccharide from Panax ginseng with selective antiadhesive activity against pathogenic bacteria. Carbohydr Res , 2006 , 341 ( 9) : 1154-1163.
[102]. Kasper DL, Onderdonk AB, Crabb J , et al . Protective efficacy of immunization with capsular antigen against experimental infection with Bacteroides fragilis. J Infect Dis,1979, 140 :724-731.
[103]. Pereda2Miranda R , Kaatz GW, Gibbons S , et al . Polyacylated oligosaccharides from medicinal Mexican morning glory species as antibacterials and inhibitors of multidrugresistance in Staphylococcus aureus. J Nat Prod , 2006 , 69 (3) :406-409.
[104]. Sun C , Shan CY, Gao XD , et al . Protection of PC12 cells from hydrogen peroxide-induced injury by EPS2 , an exopolysaccharide from a marine filamentous fungus Keissleriella sp. YS4108J [ J ] .Biotechnol , 2005 , 115 (2) :137-1441.
[105]. Chicoine LM, Bahr BA. Excitotoxic protection by polyanionic polysaccharide: evidence of a cell survival pathway involving AMPA receptor2MAPK Interactions[J ] . J Neurosci Res , 2007 , 85 (2) :294-3021.
[106].方积年,丁侃.夹竹桃花多糖及其制备方法和应用:中国,ZL 99125746.4[P].20032122031.
[107]. Yu MS, Lai SW, Lin KF. Characterization of polysaccharides from the flowers of Nerium indicum and their neuroprotective effects. Int J Mol Med , 2004,14(5) :9172-9241.
[108].徐德生,冯怡,林晓.麦冬多糖MDG21的分离纯化和结构分析.药学学报,2005,40(7) :636-6391.
[109]. Chen YJ , Yang YC. A novel polysaccharide of black soybean promotes myelopoiesis and reconstitutes bone marrow after 52flurouraciland irradiation2induced myelosuppression. Life Sci , 2005,77( 4) :400-413.
[110]. Rocha HA , Moraes FA , Trindade ES , et al . Structural and hemostatic activities of a sulfated galactofucan from the brown alga Spatoglossum schroederi . An ideal antithrombotic agent. J Biol Chem ,2005 , 280(50) :41278-41288.
[111]. Tsujita T, Takaichi H, Takaku T, et al . Inhibition of lipase activities by basic polysaccharide . J Lipid Res , 2007 , 48 (2) :358-365.
[112]. Ermerk IM, Barabanova AO , Kukarskikh TA , et al . Natural polysaccharide carrageenan inhibits toxic effect of gram2negative bacterial endotoxins. Bull Exp Biol Med, 2006, 141(2) :230-232.
[113]. Kaji Y, Hiraoka T , Oshika T , et al . Potential use of (1,3)-beta-D-glucan as target of diagnosis and treatment of keratomycosis. Cornea , 2004 , 231 :36-41.
[114]. Maeda H , Zhu X, Suzuki S , et al . Structural characterization and biological activities of an exopolysaccharide kefiran produced by Lactobacillus kefiranofaciens WT22B (T). J Agric Food Chem ,2004 , 52(17) :5533-5538.
[115]. Sakaguchi I , Ishimoto H , Matsuo M, et al . The water soluble extract of Illiciumanisatum stimulates mouse vibrissae follicles in organ culture. Exp Dermatol , 2004 , 13(8) :499-504.
[116]. Kardosova A , Ebringerova A , Alfoldi J , et al . A biologically active fructan from the roots of Arctium lappa L. , var. Herkules. Int J Biol Macromol , 2003 , 33(123) :135-140.
[117]. Takada T , Katagiri T , Ifuku M, et al . Sulfated polysaccharides enhance the biological activities of bone morphogenetic proteins. J Biol Chem , 2003 , 278 (44) :43229-43235.
[118]. Guyard C , Dehecq E , Tissier JP , et al . Involvement of [ beta ]-glucans in the wide-spectrum antimicrobial activity of Williopsis saturnus var. mrakii MUCL 41968 killer toxin. Mol Med , 2002 , 8 (11) :686-694.
[119]. Schachter H. Molecular cloning of glycosyltransferase genes. In Molecular Glycobiology. Oxford: IRL Press,1994.
[120]. Varki A. Biological roles of oligosaccharides: all of the theories are correct[J]. Glycobiology.1993,(3):97-101.
[121]. Meinjohanns E. Meldal M, Paulsen H, et al. Novel sequentiall solid-phase synthesis of N-linked glycopeptides from natureal sources . J. Chem Soc.Perkin Trans I, 1998,549-555.
[122]. Gilbert M, Bayer R, Cunningham A M, et al.The synthesis of sialylated oligosaccharides using a CMP-neu5Ac synthetase/sialyltransferase fusion. Nature Biotechnol, 1998, (16):769-776.
[123].辛月坤.肝素临床应用回顾.中国医学文摘,2002,23(1):131-134.
[124].张治云,凌沛学,王凤山,张天民.低分子肝素药理作用研究进展.食品与药品,2006,8(1): 7-9.
[125]. Goa K.L.,Benfield P. Hyaluronic acid: A review of its pharmacology and use as surgical aid in ophthalmology, and its therapeutic potential in joint disease and wound healing. Drugs, 1994,47:536-566.
[126].卢京光,姬胜利,张尊建.硫酸软骨素及其衍生物的研究进展.中国海洋药物杂志, 2006,25(1):59-63.
[127].田庚元,冯宇澄,多糖类免疫调节剂的研究和应用.化学进展, 1994,6(2):114-122.
[128]. Franz, G. Polysaccharides in pharmacy: current in applications and future concepts. Plant Medical. 1989,55:493-497.
[129].梅建民.高渗盐水右旋糖酐液抗失血性休克机理的研究进展.国外医学创伤与外科基本问题分册,1994,1:10-12.
[130]. Zeerleder, Sacha; Mauron, Thomas; L?mmle, Bernhard; Wuillemin, Walter A. Effect of low-molecular weight dextran sulfate on coagulation and platelet function tests. Thrombosis research, 2002 ,105(5):441-446.
[131]. Bobek, G; Scott, CD; Baxter, RC. Radioimmunoassay of soluble insulin-like growth factor-II/mannose 6-phosphate receptor: Developmental regulation of receptor release by rat tissues in culture. Endocrinology. 1992,130(6):3387-3394.
[132]. Acemannan. CARN 1000, CARN 750, polymannoacetate, Aliminase, Alovex, Carrisyn. Drugs in R&D, 1999,1(3):251-252.
[133].罗善高.藻酸双酯钠的临床应用.医学文选, 2001,20(3):379-380.
[134].张平;夏泉;赵新民.甘糖酯的药理及临床应用研究进展.江苏药学与临床研究, 2001,9(1):38-40.
[135]. Baron A. D.,Postprandial hyperglycaemia andα-glucosidase inhibitors. Diabetes Research and Clinical Practics, 1998, 40(Suppt):51-55.
[136]. Blickle J.F,Andies E,Mogul J.M., Current status of the treatment of type 2 diabetes mellitus alpha-glucosidase inhibitors. Rev Med lnterne, 1999,20(Suppl.3):375-383.
[137]. Stephen P. C., Clive E. Acarbose a preliminary review of its pharmacodynamic and pharmacolinetic properties and therapeutic potential. Drugs, 1988, 35: 214.
[138]. Elbein A.D. Inhibitors of the biosynthesis and processing of N-linked oligosaccharides.CRC Crit.Rev.Biochem.1984,16:21-49.
[139]. Elbein A.D. Inhibitors of the biosynthesis and processing of N-linked oligosaccharide chains. Annu.Rev.Biochem.1987,56:497-534.
[140]. Humphries M.J.,Matsumoto K.,White S.L.,and Olden K.Inhibition of experimental metastasis by castanospermine in mice:Blockage of two distinct stages of tumor colonization by oligosaccharide processing inhibitors. Cancer Res.1986,46:5215-5222.
[141]. Dennis J.W., White S.L., Freer A.M., and Dime D. Carbonoyloxy analogs of anti-metastatic drug swainsonine. Activation in tumor cells b esterases. Biochem. Pharmacol. 1993,46: 1459-1466.
[142]. Harris E.M., Aleshin A.E., Firsov L.M., and Honzatko R.B. Refined structure for the complex of 1-deoxynojirimycin with glucoamylase from Aspergillus awamori var. X100 to2.4-àresolution. Biochemisty, 1993, 32:1618-1626.
[143]. Goss P.E., Baptiste J., Fernandes B., Baker M., and Dennis J.W. Aphase I study of swainsonine in patients with advanced malignancies. Cancer Res. 1994,54:1450-1457.
[144]. Jacob G.S. Glycosylation inhibitors in biology and medicine. Curr. Opin. Struct. Biol. 1995,5:605-611.
[145]. Kang M.S., Liu P.S., Bernotas R.C., Harry B.S., and Sunkara P.S. Castanospermine analogues: Their inhibition of glycoprotein processingα-glucosidases from porcine kidney and B16F10 cells. Glycobiology, 1995,5:147-152.
[146]. Asano N., Kato A.,Matsui K., Watson A.A., Nash R.J., Molyneux R.J., Hackett L., Topping J., and Winchester B. The effect of calystegines isolated from edible fruits and vegetables on mammalian liver glycosidases. Glycobiology, 1997,7:1085-1088.
[147]. Platt F.M., Reikensmeier G., Dwek R.A., and Butters T.D. Extensive glycosphingolopid depletion in the liver and lymphoid organs of mice treated with n-butyldeoxynojirimycin. J.Biol.Chem. 1997,272;19365-19372.
[148]. Platt F.M., Butters T.D. New therapeutic prospect for the glycosphingolipid lysosomal storage diseases. Biochem. Pharmacol. 1998,56:421-430.
[149]. Von Itzstein, M; Wu, Wen-Yang; Kok, GB; Pegg, MS; Dyason, JC; Jin, B; Phan, Tho Van; Smythe, ML; White, HF; Oliver, SW. Rational design of potent sialidase-based inhibitors of influenza virus replication Nature, 1993,363(6428):418-423.
[150]. Calfee, D P; Hayden, F G New approaches to influenza chemotherapy. Neuraminidase inhibitors. Drugs, 1998,56(4):537-553.
[151]. Sahasrabudhe, A; Lawrence, L; Epa, VC; Varghese, JN; Colman, PM; McKimm-Breschkin, JL Substrate, Inhibitor, or Antibody Stabilizes the Glu 119 Gly Mutant Influenza Virus Neuraminidase. Virology, 1998,247(1):14-21.
[152]. Mendel, D B; Tai, C Y; Escarpe, P A; Li, W; Sidwell, R W; Huffman, J H; Sweet, C; Jakeman, K J; Merson, J; Lacy, S A; Lew, W; Williams, M A; Zhang, L; Chen, M S; Bischofberger, N; Kim, C U Oral administration of a prodrug of the influenza virus neuraminidase inhibitor GS 4071 protects mice and ferrets against influenza infection. Agents Chemother,1998,42(3):640-646.
[153]. Li, W; Escarpe, P A; Eisenberg, E J; Cundy, K C; Sweet, C; Jakeman, K J; Merson, J;Lew, W; Williams, M; Zhang, L; Kim, C U; Bischofberger, N; Chen, M S; Mendel, D BIdentification of GS 4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor GS 4071.Agents Chemother,1998,42(3):647-653.
[154]. Collins P M, Ferier R J . Natural products related to and containing monosaccharides. In Monosaccharides: Their Chemistry and their Roles in Natural Products. Chichester: Wiley,1995.
[155]. Gaisser S, Leadlay P F. Sugaring the pill by design. Nature Biotechnol,1998,16(1):19-20.
[156]. Ajit Varki, Richard Cummings, Jeffrey Esko, Hudson Freeze, Gerald Hart, Jamey Marth. Essential of .glycobiology. New York: Cold Spring Harbor Laboratory Press,1999.562-568.
[157].卞广兴.糖工程:糖基化对治疗蛋白性质的影响.国外医学.药学分册,2006,33(4):266-268.
[158]. Ronin C. Remodiling of glycoprotein and carbohydrate antigens. Clin Chem Lab Med,1998,57:785-789.
[159]. Dsouza V T, Lipkowitz K B.Cyclodetrin. Cyclodextrins Chem Rev,1998,98:2045-2052.
[160]. Lee YC, Lee RT, Neoglycoconjugates. San Diego, Academic Press,1994,53-57.
[161].刘昌孝,孙瑞元.药物评价实验设计与统计学基础.军事医学科学出版社,1999.
[162].钟大放.药物代谢与药物动力学基础研究展望.辽宁药物与临床.2000,3(4):145-148.
[163].陈淑娟,曾繁典.抗心律失常药物体内代谢及其临床影响因素.中国临床药理学杂志, 2000,16(2):146-150.
[164]. Shah, V P; Midha, K K; Findlay, J W; Hill, H M; Hulse, J D; McGilveray, I J; McKay, G; Miller, K J; Patnaik, R N; Powell, M L; Tonelli, A; Viswanathan, C T; Yacobi, A. Bioanalytical method validation--a revisit with a decade of progress. Pharmaceutical research, 2000, 17(12):1551-1557.
[165].张琪,王广基.蛋白多肽类药物药代动力学分析方法研究进展.药物生物技术, 2000,7(2):126-128.
[166].王克夷.分子生物学前沿技术,联合出版社,1998.
[167]. N., Laforest et al., Pharmacokinetics and biodistribution of technetium 99m labeled atandard heprin and a low molecular weight heparin after intravenous injection in normalvolunteers. British J Haemat 1991,77:201.
[168]. Huhil etal. Comparison of three heparin bovine serum albumin binding methods for production of antiheparin antibidies. Semi Thromb Hesomst, 1994,20(2):193-198.
[169]. Huhil etal. Monoclonal antibodies against heparin and heparinoids. Semi Thromb Hesomst, 1997,23(1):17-21.
[170]. L Robert etal. Pharmacokinetic profile of 14C-labelled clopidogrel. Semi Thromb Hesomst,1999,25(suppl):29-35.
[171]. R Malsch etal. Measurement of fluorensent–labblee LMN-heparin in biological fluid using protamine-linked microbeads. Semi Thromb Hesomst, 1997,23(1):23-30.
[172]. U Cornelli, etal. Human pharmacokinetics of low molecular weight heparins. Semi Thromb Hesomst, 1999,25(supp):57-66.
[173]. J Fareed, Pharmacokinetics of low molecular weight heparins in animal models. Semi Thromb Hesomst, 1999,25(supp):51-58.
[174]. L Piazolo, Comparison of the pharmacodynamic and Pharmacokinetic profiles of two low-molecular-mass heparins in rats. Semi Thromb Hesomst, 1997,23(2):109-116.
[175]. B Boneu, Pharmacokinetics and tolerance of the natural pentasaccharide with high affinity to antihrombinⅢin man. Thromb Hesomst, 1995,74(6):1468-1473.
[176]. Smolec, JoMarie; DeSilva, Binodh; Smith, Wendell; Weiner, Russell; Kelly, Marian; Lee, Ben; Khan, Masood; Tacey, Richard; Hill, Howard; Celniker, Abbie; Shah, Vinod; Bowsher, Ronald; Mire-Sluis, Anthony; Findlay, John W A; Saltarelli, Mary; Quarmby, Valerie; Lansky, David; Dillard, Robert; Ullmann, Martin; Keller, Stephen; Karnes, H Thomas Bioanalytical method validation for macromolecules in support of pharmacokinetic studies. Pharmaceutical research, 2005,22(9):1425-1431.
[177]. P. Oreste, M. Peruzzi and P. Stella Micromethod for the determination of heparin in plasma after intravenous and subcutaneous administration. Analytical Biochem, 1993,210(1):136-139.
[178]. Yong Huang, Yukio Washio, Mutsumi Hara, Hidenao Toyoda, Ichiro Koshiishi, Toshihiko Toida and Toshio Imanari Simulataneous determination of dermatan sulfate and oversulfated dermatan sulfate in plasma by HPLC with postcolumn fluorenscence derivatization. Analytical Biochem, 1996,240(2):227-234.
[179].郑年新,姚新生.六味地黄多糖在小鼠体内的吸收.中国药理学通报.2000,16(4):403-405.
[180]. Volpi, Nicola , Separation of capsular polysaccharide-K4- and defructosylated-K4-derived disaccharides by high-performance liquid chromatography and postcolumn derivatization with 2-cyanoacetamide and fluorimetric detection. Analytical biochemistry, 2004,330(2):359-61.
[181]. O’Hara Y., Fate of lentinan(antitumor polysaccharide)I: Fate of lentinan in mice, rats and dogs. J. Toxicol. Sci. 1980,5:59-72.
[182].谢炳华,张年宝,茯苓聚糖的氚离子束标记及其在小鼠体内的药物动力学研究.核技术, 1990,13:693-695.
[183].盛少虎;李应全;马剑峰;袁玮.甘糖酯在小鼠体内的药代动力学研究.中国海洋药物杂志, 1995,14(2): 15-17.
[184]. Robert A., Shiv C., Rajesh K., James K., Francesca C.L., Garret A. Oral delivery of anticoagulant dose of heparin a randomized, double-blind, controlled study in humans. 1998,98:1610-1615.
[185].王睿,方翼,柴栋,裴斐,李桂玲,耿美玉、谭兰,陈升杰,管华诗.单次静滴D-聚甘酯注射液在中国男性健康志愿者的药代动力学.中国临床药理学杂志,2006,22(3):192-194.
[186].丁华;祝清芬;徐鲁源;吴葆杰;李英霞;吕志华.几丁糖酯抗动脉粥样硬化研究.中国海洋药物.2001,1:12-17.
[187].胡金凤;耿美玉;陈昆;冉忠梅;徐家敏;管华诗.甲壳质衍生物916对家兔实验行动脉粥样硬化的预防作用.中国海洋药物.2000,3:18-21.
[188].王妍婷;吕志华;王远红.海洋硫酸多糖916在2种酶作用下稳定性的研究.中国海洋大学学报, 2004, 34(6):955-958.
[189]. Han Y.H., Lv Z.H., Jiang T.F., Wang Y.H. Bioanalysis and pharmacokinetics of chitosan ester in rabbit serum by HPLC with postcolumn fluorescence derivatization. Journal of Chromatography B, 2007, 845:138–142.
[190]. Pangburn SH. Trescony PV. Heller J. Lysozyme degradation of partially deacetylated chtin. Its films and hydrogels. Biomaterials 1982, 3:105-108.
[191]. Yomata C. Komuro T. Kimura T. Studies on the degradation of chitosan films bylysozyme and release of loaded chemicals. Yakugaku zasshi 1990:110:442-448.
[192]. Hiraku O. Yoshiharu M. Biodegradation and distribution of water-soluble chitosan in mice. Biomaterials. 1999, 20: 175-182.
[193]. Shah VP, Midha KK, Findlay JW, Hill HM, Hulse JD, McGilveray IJ, McKay G. Bioanalytical method validation-A revisit with a decade of progress. Pharm. Res. 2000, 17: l 551-1557.
[194]. Kames HT, March C. Precision, accuracy and data acceptance criteria in biopharmaceutical analysis. Pharm. Res. 1993, 10: 1420-1422.
[195].萧参,陈坚行.生物药剂分析方法的认证.中国药学杂志,1993, 24; 425-426.