三七总皂苷肠溶胶囊在比格犬体内的药代动力学

目的探讨三七总皂苷(PNS)肠溶胶囊在比格犬体内的药代动力学。方法比格犬采用随机交叉给药方案,口服PNS肠溶胶囊86.2 mg·kg-1或血栓通胶囊111.8 mg·kg-1后,用反相高效液相色谱法同时测定犬血浆中三七皂苷R1、人参皂苷Rg1和Rb1的血药浓度,采用3P97药动学软件计算药动学参数和基于曲线下面积(AUC0-∞)自定义权重系数整合血药浓度后的药动学参数。结果与参比制剂血栓通比较,受试制剂PNS R1、Rg1、Rb1的达峰时间延长:R10.18±0.09 vs(0.16±0.06)h,Rg12.03±0.76 vs(1.74±0.27)h,Rb1 0.76±0.39 vs(0.74±0.17)h;吸收延迟时间延长:R1 0.96±0.16 vs(0.50±0.11)h,Rg10.87±0.05 vs(0.02±0.01)h,Rb10.92±0.12 vs(0.44±0.07)h,3种成分及其整合后PNS的相对生物利用度分别为248.41%,107.19%,152.94%和155.31%。整合后,血栓通胶囊和PNS肠溶胶囊的主要药动学参数分别为:AUC0→t39.17±3.89 vs(46.91±3.86)mg.L-1.h,Lag时间0.45±0.18 vs(0.92±0.13)h,tmax0.74±0.17 vs(0.77±0.13)h,Cl(3.84±0.24 vs 1.84±0.97 L.kg-1.h-1)。结论本实验制备的PNS肠溶胶囊能提高PNS的口服生物利用度。     

三七三醇皂苷两种制剂在比格犬体内的药物动力学研究

目的 研究三七三醇皂苷的三七通舒胶囊和三七通舒胶囊(肠溶微丸)在比格犬体内的药动学特征.方法 采用双周期交叉试验设计,6只比格犬分别单剂量口服14粒三七通舒胶囊、10粒肠溶微丸,测定血浆样品中三七皂苷R1(R1)、人参皂苷Rg1(Rg1)、人参皂苷Re(Re)的含量,数据经3P87药动学软件处理.结果 三七通舒胶囊、肠...     

三七皂苷长循环纳米粒的肠吸收及药动学研究

目的:研究三七皂苷(PNS)长循环纳米粒(PNS-LCN)的肠吸收及药动学。方法:采用大鼠外翻肠囊实验,测定PNS、PNS-LCN和PNS-壳聚糖物理混合物(Cs)中三七皂苷R1、Rg1、Rb1在大鼠十二指肠、空肠、回肠、结肠的渗透系数(Papp);大鼠分别灌胃给予PNS、PNS-LCN、PNS-Cs后于不同时间点取血,测定大鼠血浆中R1、Rg1、Rb1的血药浓度。结果:与PNS比较,PNS-LCN中R1在十二指肠和空肠,Rg1在空肠和回肠,Rb1在回肠和结肠的Papp升高;PNS-Cs中R1在十二指肠,Rg1在十二指肠、空肠和回肠,Rb1在十二指肠、空肠、回肠和结肠的Papp升高,差异有统计学意义(P<0.01或P<0.05)。PNS-LCN中R1、Rg1、Rb1生物利用度分别为PNS的3.65、3.63、2.96倍;PNS-Cs中R1、Rg1、Rb1生物利用度分别为PNS的0.31、0.77、1.36倍。结论:PNS-LCN可以明显提高PNS中R1、Rg1、Rb1的生物利用度,是PNS-LCN提高PNS渗透性和延长PNS在大鼠体内消除时间等综合作用的结果。     

三七总皂苷及其活性单体药代动力学的研究进展

主要综述近五年三七总皂苷(PNS)及其活性单体三七皂苷R1、人参皂苷Rb1、人参皂苷Rg1的药动学研究进展.目前对PNS生物样品中人参皂苷Rg1,人参皂苷Rb1和三七皂苷R1等PNS活性单体的药物浓度多采用HPLC检测以评价PNS及其活性单体的药代动力学过程,现有的PNS药动学研究仅涉及PNS给药后2～3个单体皂苷,未能全面反映PNS的药动学变化规律,PNS血药浓度与药物效应关系不明确,今后的研究方向及重点应进一步研究PNS的化学成分及串联质谱法作分析手段的可行性并结合作用机制方面的研究以揭示其药动学特性及规律.     

血塞通软胶囊溶出度的研究

目的:考察血塞通软胶囊中三七皂苷R1和人参皂苷Rg1,Rb1在两种不同介质中的溶出行为。方法:参照日本《医疗用药品品质情报集》中的溶出度试验条件,并根据血塞通软胶囊处方成分的理化性质对溶出介质进行选择,分别考察了血塞通软胶囊在p H6.8磷酸盐缓冲液和水中的体外溶出行为,采用高效液相蒸发光散射法(HPLC-ELSD)测定血塞通软胶囊中三七皂苷R1和人参皂苷Rg1,Rb1三者总和的溶出度,并通过相似因子(f2)法对3种成分的溶出度曲线进行相似性比较。结果:三七皂苷R1和人参皂苷Rg1,Rb1的线性范围分别为0.8~16.0 mg·L-1(r=0.999 6),3.0~60.0 mg·L-1(r=0.999 8),4.0~80.0 mg·L-1(r=0.999 7);在介质p H 6.8磷酸盐缓冲液和水中,以三七皂苷R1为参比,血塞通软胶囊中人参皂苷Rg1和Rb1的f2均大于50。结论:该方法简便、准确,重复性好,可用于该胶囊的溶出度测定;血塞通软胶囊中三七皂苷R1和人参皂苷Rg1,Rb1具有相似的溶出特点。     

HPLC法测定活血舒脉胶囊中人参皂苷Rg_1、Rb_1及三七皂苷R_1的含量

目的考察活血舒脉胶囊中人参皂苷Rg1、Rb1及三七皂苷R1的含量,为制订活血舒脉胶囊质量标准提供科学的实验依据。方法采用HPLC法对10个批号的活血舒脉胶囊中人参皂苷Rg1、Rb1及三七皂苷R1进行含量测定。结果10批样品中人参皂苷Rg1、Rb1、三七皂苷R1最低含量分别为14.862、14.258、2.864mg.g-1;RSD分别为2.53%、1.12%、2.11%。结论10批样品测定结果表明各成分含量稳定,RSD均小于3.0%,可以作为制订活血舒脉胶囊质量标准的依据。     

三七总皂甙提取工艺研究进展

三七总皂甙（PNS）（又称三七总皂苷）为五加科人参属植物三七根部提取的有效成分,它含有人参皂甙Rb1、Rb2、Rc、Rd、Re、Rf、Rg1、Rg2、Rh、三七皂甙R1、1／2、R3、R4、R5、R6等20多种皂甙成分,其中以人参皂甙Rb1、Rg1、三七皂甙R1含量最高Ⅲ。三七总皂甙对中枢神经系统有明显的抑制作用和镇痛作用。     

三七总皂苷对细胞免疫炎症因子作用的研究进展

三七总皂苷（PNS）系从我国中药材三七Panaxnotoginseng（Burk）F．H．Chen的根茎中提取出来的主要药理成分,主要由人参皂苷Rg1、Rb1,三七皂苷R1、R2等40多种皂苷组成。三七总皂苷是中药三七的主要活性成分。     

HPLC 法同时测定复方血栓通胶囊中5种皂苷类成分

目的：建立 HPLC 法同时测定复方血栓通胶囊中人参皂苷 Rg1、Re、Rb1、Rd 和三七皂苷 R1含量的方法。方法采用YMC －Pack Pro C18柱（250 mm ×4．6 mm,5μm）,以乙腈为流动相 A,水为流动相 B 进行梯度洗脱,检测波长为203 nm,流速为1．0 mL·min －1,柱温为35℃。结果测得三七皂苷 R1在50．10～501．00 ng、人参皂苷 Rg1在151．02～1510．20 ng、人参皂苷Re 在32．01～302．10 ng、人参皂苷 Rb1在102．23～1022．30 ng、人参皂苷 Rd 在16．32～163．20 ng 范围内线性关系良好（r ＝0．9999）;精密度、稳定性、重复性 RSD 均小于3％;平均加样收回率在95％～105％之间。结论该法简便、准确、重复性好,可用于复方血栓通胶囊的质量控制。     

HPLC测定复方丹参片中三七总皂苷的含量

目的建立复方丹参片中三七有效成分的含量测定方法。方法采用HPLC法测定本品中三七中人参皂苷Rg1、人参皂苷Rb1、三七皂苷R1的含量。结果人参皂苷Rg1、人参皂苷Rb1、三七皂苷R1线性范围分别依次为0.850～8.524、0.922～9.013、0.377～3.317μg;平均回收率分别为101.1%、101.2%、103.2%,RSD分别为1.5%、1.6%、1.8%。结论本方法简便可靠,结果稳定,可用于丹心舒胶囊中三七的有效成分的含量测定。     

Self-micelle formation and the incorporation of lipid in the formulation affect the intestinal absorption of Panax notoginseng

The purpose of this research is to evaluate the effect of self-micelle formation and incorporation of lipid in the formulation on absorption of ginsenosides Rg1 and Rb1 from intestinal tract in rats. Ginsenosides Rg1 and Rb1 were extracted from Panax notoginseng saponins (PNS). The critical micellar concentration (CMC) of PNS in deionzied water was determined to be 0.339 mg/ml. At normal physiological ionic strengths, PNS was salted out from the solution above the CMC. The particle size of the micelle grows as PNS concentration increases. By in situ injection to a closed loop of the rat jejunum, AUC0-6h obtained after administration of low concentration solution (12 mg/ml) was 3.61 times for ginsenoside Rg1 and 3.84-folds for ginsenoside Rb1 compared with high concentration solution (120 mg/ml). The release rate of ginsenosides in aqueous medium was too slow to complete in 24h, especially for Rb1. The data suggested that the self-micelle formation tendency in ginsenosides might prevent them from permeation or absorption through the cell membrane of gastrointestinal (GI) tract. To inhibit the formation of micelles, lipid was incorporated in the PNS formulation. The intraduodenal bioavailability in rats showed that the bioavailability was enhanced remarkably relative to the aqueous solution. AUC 0-infinity of ginsenoside Rg1 and Rb1 in the lipid-based formulation were 207.52+/-53.95 and 1961.72+/-686.60 microg ml(-1) h, compared with 7.87+/-2.85 and 148.58+/-36.73 microg ml(-1) h, respectively from its aqueous solution. These findings suggested a new strategy to increase the absorption of amphiphilic saponins.     

普萘洛尔药物树脂缓释混悬剂在Beagle犬体内的药动学

目的考察普萘洛尔药物树脂缓释混悬剂在Beagle犬体内的缓释行为及其体内外相关性研究。方法采用双周期交叉试验设计,6只健康Beagle犬口服市售缓释胶囊或自制缓释混悬剂后,用HPLC法测定血药浓度,计算2制剂的药动学参数,进行生物利用度比较,用不同的体外释放量对体内吸收量进行线性拟和。结果自制缓释混悬剂的药动学参数计算结果为AUC_(0-24)(1031±s 63)μg·h·L~(-1),c_(max)(87±4)μg·L~(-1),t_(max)(6.5±1.2)h,市售缓释胶囊的计算结果相应为AUC_(0-24)(989±99)μg·h·L~(-1),c_(max)(85±3)μg·L~(-1),t_(max)(7.2±0.7)h,2制剂的3项药动学参数没有显著差异(P>0.05),自制缓释混悬剂对市售缓释胶囊的平均相对生物利用度为(106±9)%,以0.5mol·L~(-1) NaCl溶液中所得体外溶出数据与体内吸收量相关性较好(r=0.937 7)。结论普萘洛尔药物树脂缓释混悬剂在Beagle犬体内达到明显的缓释效果,与参比制剂相比具生物等效性,可用一定的体外释放条件进行体内行为的预测。     

三七皂苷的口服吸收机制

目的研究三七总皂苷(PNS)的口服吸收机制。方法采用Caco-2细胞和动物等模型研究PNS中人参皂苷Rb_l(Rb_l)和人参皂苷Rg_l(Rg_l)的胃肠道内稳定性、肠道黏膜吸收机制及吸收过程中胃、肠及肝对药物的影响。结果Rb_l和Rg_l在胃液酸性环境下易被破坏，而在近中性环境内基本保持稳定。Rb_l和Rg_l在大肠内容物中易降解，尤以Rb_l降解较为明显；二者在小肠内容物中则相对稳定。Rb_l和Rg_l在Caco-2细胞层的摄取受温度的影响，而pH的变化及环孢菌素A的加入对二者摄取均无显著性影响。在实验考察的浓度范围内，细胞内Rb_l(或Rg_l)的摄取量随Rb_l(或Rg_l)的浓度的增加而呈线性增加，Rb_l(或Rg_l)单体与总皂苷中的Rb_l(或Rg_l)在Caco-2细胞模型中的吸收特性无明显差异。而Rg_l的细胞摄取量［(1.07±0.16) μg·mg^-1(protein)］(C₀=1 mg·mL^-1)相对Rb_l［(0.77±0.03) μg·mg^-1(protein)］(C₀=1 mg·mL^-1)较高。Caco-2细胞转运实验表明，Rb_l和Rg_l单体的转运透过系数(P_app)分别为(5.9±1.0)×10^{-8cm·s-1和(2.59±0.17)×10-7 cm·s-1(C₀=1 mg·mL-1)，二者转运都不受环孢菌素A影响。PNS溶液灌胃、十二指肠及门静脉给药后测得Rb_l大鼠绝对生物利用度分别为0.71%，2.75%和65.77%；Rg_l分别为3.29%，6.60%和50.56%。结论三七总皂苷(包括Rb_l和Rg_l)的肠道吸收机制为单纯被动扩散，吸收过程不受细胞膜内P-gp和MRP外排载体的调控，PNS中其他成分对Rb_l或Rg_l的吸收特性无明显影响。胃液的酸性环境、大肠菌丛产生的酶及肝脏的首过作用均对其口服吸收产生影响，而肠道黏膜的透过性低是其口服吸收差的主要影响因素。}     

番茄红素微囊的体内外药剂学行为

目的考察番茄红素微囊的体外释放、番茄红素原料及番茄红素微囊在家犬体内的药代动力学、体外释放和体内吸收的相关性。方法用分光光度法测定释放介质中番茄红素的含量。用HPLC法测定家犬体内的番茄红素含量，数据用3P87程序处理，得到各主要药代动力学参数。体内吸收与体外释放进行点点相关。结果微囊体外释放呈肠溶性，原料及番茄红素微囊的T_1/2α分别为7.30和15.06 h；T_1/2β分别为28.10和46.76 h；T_max分别为22.32和41.03 h；AUC_0-∞分别为1.67和2.08 μg·h·L^-1。体内外相关性良好。结论微囊较原料药呈现缓释特征，体内外相关性结果表明可以根据体外释放情况预测体内的吸收。     

三七总皂苷脉冲迟释片体外释放度影响因素研究

目的：考察三七总皂苷脉冲迟释片的体外释放度,初步判断其主药成分人参皂苷 Rg1在体内的吸收速率和程度。方法制备三七总皂苷脉冲迟释片,考察其在不同介质、不同方法及不同转速下人参皂苷 Rg1的释放度。结果溶出介质的 pH 对释放度无显著影响,释药时滞会随介质黏度的增加而延长;转篮法较桨法稳定,更适合该制剂的释放度研究;不同转速对释药时滞无显著影响,对释药速率略有影响。所制备的三七总皂苷脉冲迟释片在体外释放过程中延迟4~5 h 后,快速脉冲式地释药。结论根据时辰药理学原理,三七总皂苷脉冲迟释片的体外释放符合其用于心血管疾病预防和治疗的目的。     

Preparation and In Vitro and In Vivo Evaluation Of Panax Notoginseng Saponins-loaded Nanoparticles Coated with Trimethyl Chitosan Derivatives

In this study, novel Panax notoginseng saponins (PNS)-loaded nanoparticles coated with the Trimethyl chitosan (TMC) derivatives TMC-VB₁₂ and TMC-Cys (PPTT-NPs) were developed to improve the oral absorption of the constituents. PPTT-NPs were prepared by the double emulsion method and showed different encapsulation effects on the major components, including Rg1, Rb1, and R1, in PNS. In vivo, the absorption rate constant and apparent absorption coefficient of PPTT-NPs were higher than PNS solution. These findings preliminarily proved that PPTT-NPs can promote intestinal absorption to a certain extent. The pharmacokinetic results indicated that the blood concentration and the area under the curve of Rg1 and Rb1 in the PPTT-NPs were higher than Xueshuantong capsules. The cell viability of PPTT-NPs was above 90% within 25-150 μg/mL. PPTT-NPs promoted the cellular uptake of PNS by receptor-mediated endocytosis. In summary, NPs coated with TMC-VB₁₂ and TMC-Cys can be used as promising drug delivery systems.     

Absorption profiles of sanchinoside R1 and ginsenoside Rg1 in the rat intestine.

Panax notoginseng is used as a therapeutic agent in Chinese medicine for stopping hemorrhage and also as a general health remedy. Although Panax notoginseng saponins (PNS) are currently attracting attention due to their hemorheological properties, the absorption profiles of PNS have still not been fully investigated. In the present study, an in situ intestinal perfusion rat model was used to investigate the absorption mechanism of sanchinoside R1 (R1) and ginsenoside Rg1 (Rg1), two main components of PNS. Quantitative analysis methods for R1 and Rg1 were first established, then concentrations of R1 and Rg1 in the perfusate were measured in real time through assessment of circulating perfusate in the rat small intestine. The absorption rate constant (k(a)) values for R1 were 0.1223, 0.0946 and 0.0904 h(-1) at a dose of 1, 10 and 100 mg respectively, while those of Rg1 were 0.1169, 0.1134 and 0.1089 h(-1) at a dose of 1, 10 and 100 mg respectively. The optimal absorption site for both of these compounds was found to be the duodenum, which indicated that the bioavailability of the orally administered PNS preparation was relatively low. Finally, the effect of certain absorption promoters on the absorption rates of R1 and Rg1 was investigated. It was found that carbomer and borneol could enhance the permeability of R1 and Rg1 on the intestinal wall (P < 0.05), which indicated that a suitable absorption promoter could improve the absorption of PNS and increase its bioavailability.     

Effects of combination of Salvia miltiorrhiza and Panax notoginseng on the pharmacokinetics of their major bioactive components in Beagle dog

After oral administration of Salvia miltiorrhiza (Danshen in Chinese), Panax notoginseng (Sanqi in Chinese) and Danshen Sanqi combination suspensions to Beagle dogs, the plasma concentration-time profiles of danshensu, tanshinone II(A), cryptotanshinone, notoginsenoside R1, ginsenoside Rg1 and Rb1 were analyzed by LC-MS/MS. Pharmacokinetic parameters were calculated and analyzed with BAPP 2.0 software. The results showed that the Cmax and AUC of danshensu, notoginsenoside R1, ginsenoside Rg1 and Rb1 in Danshen Sanqi combination group all decreased in comparison with those of Danshen or Sanqi given alone, while the CLz/F and Vz/F increased to some extent. No significant differences of the pharmacokinetics of tanshinone II(A) and cryptotanshinone were observed between groups.