灯盏花素心血管药理及临床研究进展

灯盏花素是从灯盏花中提取的黄酮类活性成分,为灯盏花甲素、灯盏花乙素的混合物,主要为灯盏乙素。灯盏花素具有增加血流量、改善微循环、扩张血管、降低血黏度、调节血脂、促纤溶、抗血栓、抗血小板聚集等作用。该文介绍了近10年灯盏花素心血管方面的药理及临床研究概况。     

灯盏花素注射液对肺心病的疗效观察

灯盏花素是从中药灯盏细辛中提取的灯盏甲素、灯盏乙素的混合物,主要为灯盏乙素,含黄酮成分,药理研究证明[1],灯盏花素有扩张血管、抗血小板聚集等作用.我们观察慢性肺心病患者使用灯盏花素治疗后,气喘、心悸、胸闷症状有明显改善,同时发现该注射液对肺血动脉压的降低、肺功能的改善有一定疗效,现报道如下.     

灯盏乙素和灯盏花素对急性心肌梗死的保护作用

目的研究灯盏乙素和灯盏花素对急性心肌梗死的保护作用。方法建立大鼠急性心肌梗死模型后,腹腔注射不同剂量灯盏乙素和灯盏花素,4h后取出心脏行氯化硝基四氮唑蓝（NBT）染色,测量心肌梗死面积,比较两种药物对心肌梗死面积影响的量效关系;建立犬急性心肌梗死模型,股静脉注射50mg/kg灯盏花素或灯盏乙素,记录不同时间点的心外膜电图,比较两种药物对心肌缺血程度和范围的影响。结果灯盏乙素单体能够降低心肌梗死面积,抑制梗死区心肌细胞的凋亡,50mg/kg灯盏乙素能够降低左冠状动脉前降支结扎后犬心外膜电图抬高的∑ST段。结论灯盏乙素单体是灯盏花素的主要药理活性成分,较灯盏花素具有更好的量效关系。     

野黄芩苷药动学研究进展

灯盏花素是从灯盏细辛中提取出来的黄酮类成分,主要由灯盏乙素和灯盏甲素组成,其公认的有效化学成分是灯盏乙素,又名野黄芩苷(Scutellarin),结构式为5,6,4′—三羟基黄酮-7-葡萄糖醛酸苷。目前,对灯盏花素的药理学活性研究主要是围绕其有效成分野黄芩苷进行。研究结果表明,野黄     

灯盏花素胃漂浮缓释片含量及释放度研究

目的 拟制备灯盏花素胃漂浮缓释片,研究剂型提高其生物利用度.方法 采用HPLC建立灯盏花素胃漂浮缓释片的体外分析方法,考察制剂的体外释放度和漂浮性能.结果 制备的3批灯盏花素胃漂浮缓释片中灯盏乙素的含量合格,RSD％为1.22;在偏碱性条件下,3批灯盏花素胃漂浮缓释片的释放性能基本稳定,均能达到胃漂浮缓释片体外累积释释放的要求.灯盏花素胃漂浮缓释片漂浮性能表明在胃液中持续漂浮达8h以上.结论 该制剂具有提高灯盏乙素利用率的优点,延长药物在胃中的滞留时间,有利于灯盏花素以原形药的形式吸收,为其临床应用提供依据.     

灯盏花素分散片在健康人体内的相对生物利用度研究

目的研究灯盏花素分散片与灯盏花素片在健康男性志愿者体内的相对生物利用度。方法采用随机双周期自身交叉对照试验设计,18名健康男性受试者分别经口给予受试制剂灯盏花素分散片和参比制剂灯盏花素片80 mg,采用LC-MS-MS法测定给药后不同时间异灯盏乙素的血药质量浓度。利用DAS软件计算药动学参数和进行统计分析,通过方差分析和双单侧t检验及90%置信区间法进行生物利用度评价。结果受试制剂与参比制剂中异灯盏乙素的ρmax为(75.81±23.24)、(62.17±17.82)μg.L-1,tmax为(6.50±1.34)、(7.78±1.52)h,AUC0→t为(454.1±194.7)、(403.9±133.3)μg.h.L-1,AUC0→∞为(460.1±199.8)、(410.3±137.1)μg.h.L-1。结论受试制剂ρmax比参比制剂大,疗效更高;受试制剂tmax比参比制剂小,起效更快;受试制剂对参比制剂的相对生物利用度(F,以AUC0-∞作为评价依据)为(116.5±43.5)%,灯盏花素分散片生物利用度较普通片高。     

灯盏花素对脑缺血再灌注损伤的细胞和分子保护机制研究现状

灯盏花素是从灯盏花中提取的黄酮类成分,以灯盏乙素为主,含有少量灯盏甲素。灯盏花素具有扩张血管、增加脑血流量和心脏冠脉流量、降低血液黏度、改善微循环等作用。临床上主要用于治疗心、脑血管等疾病,疗效确切。动物实验发现,灯盏花素对脑缺血再灌注损伤具有保护作用,但具体的细胞和分子保护机制报道较少。本文着重将其对脑缺血再灌注损伤中的作用及其可能的机制作如下综述。     

灯盏花治疗Ⅱ型糖尿病肾病短期临床观察

灯盏花是菊科飞蓬属植物短亭飞蓬的全草，其醇提物制成了灯盏花注射液。主要成分有黄酮、灯盏乙素、飞蓬甙、飞蓬双甙等。本文通过观察灯盏花注射液对糖尿病肾病尿蛋白的影响，观察其在防治糖尿病肾病中的作用。     

灯盏花素在制剂方面的研究分析

目的：分析研究灯盏花素在制剂方面的进展。方法：通过近些年有关灯盏花素在制剂方面的研究文献及书籍,结合本实验的研究成果进行概述。结果：热熔挤出滚圆制备灯盏花素口服缓释微丸能够大幅提高其生物利用度,工艺简单可行,将成为灯盏花素的一个新制剂。结论：国内对于灯盏花素在制剂方面的研究很多,甚至有扎堆研究现象,导致灯盏花素在制剂方面会有更深入的研究。     

灯盏花素的器官保护功能研究进展

灯盏花素是从天然植物灯盏花中提取的黄酮类活性成分,药理作用非常广泛,对心、脑、肝、肾等器官具有明显的保护作用,临床上常用于缺血性心、脑血管疾病的治疗,临床应用优势明显。本文主要综述灯盏花素的器官保护作用研究进展,以为临床进一步合理使用灯盏花素提供理论参考。     

口服缓控释制剂研究概况

本文综述了口服缓控释制剂研究概况。缓控释制剂有三种释药类型：定时、定速、定位释药。有多种剂型：包括骨架缓控释制剂、薄膜包衣缓控释制剂、渗透泵型缓控释制剂、胃内漂浮缓控释制剂、缓控释微丸、缓控释液体制剂等。口服缓控释释放系统的迅猛发展，为新药物的研制、老药新用途的开发提供了更为广阔的前景。     

硝苯地平缓控释制剂制备技术研究进展

目的总结近年来国内外硝苯地平缓控释制剂制备技术的研究进展,为硝苯地平缓控释制剂的开发研制提供参考。方法查阅了目前主要的硝苯地平缓控释制剂制备技术如缓控释片技术（骨架型技术、渗透泵技术、脉冲技术和薄膜包衣技术）、缓控释胶囊技术、微囊技术、微球技术、脂质体技术和纳米技术,以及一些新技术的文献和资料。结果和结论为了更好的满足高血压患者的用药需求,研制可以实现平穗给药和择时给药的硝苯地平缓控释制剂已经成为必然的趋势。     

Compression of coated drug beads for sustained release tablet of glipizide: formulation,and dissolution

Abstract

A promising glipizide formulation comprising compression of four-layer coated beads into tablets was prepared. The tablet offered the advantages of: a two-hour lag time before drug release, retaining sustained release characteristics and providing approximately zero-order drug release. Drug release was nearly independent of paddle speeds of 50 and 100?rpm releasing 80% over 14?h similar to the commercial glipizide osmotic pump tablet during dissolution testing while keeping the benefits of multiparticular dosage forms. The tablets contain beads with four layers: (1) the innermost layer consists of 2.5?g glipizide and 3.75?g solid ethylcellulose (Surelease®) coated onto 71.25?g of sugar beads; (2) next a hardening layer of 5?g of hypromellose; (3) the controlled release layer of 7.5?g of Surelease®:lactose at a solids ratio of 100:7 and (4) an outermost layer of 20?g of lactose:sodium starch glycolate (Explotab®) at a 2:1 ratio. Then, beads were compressed into tablets containing 11?mg of glipizide using 1500?lbs of compression pressure. The dissolution test similarity factor (f₂) was above 50 for all test conditions for formulation F13 and Glucotrol® with a high of 69.9. The two Surelease® layers both aid controlling drug release, with the Surelease®-drug layer affecting drug release to a greater extent.     

尼莫地平微粉化物双层渗透泵控释片的制备

目的 制备尼莫地平微粉化物双层渗透泵控释片。方法 以尼莫地平为模型药物,将微粉化增溶技术应用于控释双层渗透泵剂型中,设计并制备体外控释12 h的尼莫地平双层渗透泵片,采用相似因子法（f₂）对不同处方释药行为的相似性进行评价,并对处方进行优化。结果 成功制备了尼莫地平微粉化物双层渗透泵控释片,零级释放特征明显,符合渗透泵的释药机制。结论 将微粉化增溶技术与控释双层渗透泵技术相结合,显著提高了难溶性药物尼莫地平的体外释放,成功制备了控释制剂。     

Modulating drug release profiles by lipid semi solid matrix formulations for BCS class II drug – an in vitro and an in vivo study

Abstract

The main objective of the study was to alter the dissolution profile of a practically insoluble Biopharmaceutics Classification System class II drug, aceclofenac, by formulating into lipid semisolid matrix (SSM) formulations using liquid filling technology in hard gelatin capsules, for both immediate and sustained release. SSM formulations of aceclofenac were prepared by melt fusion technique, using Gelucires (44/14, 50/13, 33/01 and 43/01), polyethylene glycols (4000 and 6000) and Poloxamer 188 at different levels. Role of additives like docusate sodium, Tween 80, Aerosil 200 and polyvinylpyrrolidone K-30 in enhancement of drug release was investigated. The optimized immediate and sustained SSM capsules were characterized in terms of assay, in vitro drug release, moisture uptake and differential scanning calorimetry. More than 80% of the drug was released within 15?min in various dissolution media studied, from Gelucire 44/14-based immediate release formulations. Incorporation of docusate sodium and Tween 80 provided further enhancement in drug dissolution when compared to plain drug and marketed tablet. SSM formulations based on Gelucire blends of 50/13 and 43/01 and 44/14 and 43/01 sustained the release of the drug for a period of 24?h following zero-order kinetics. The in vivo study of the optimized immediate release and sustained release formulations revealed significant enhancement in anti inflammatory activity (p?<?0.01) in rats. From these findings, liquid fill technique in hard gelatin capsules using Gelucire and their blends might be an efficacious approach for designing immediate or sustained drug release profiles for poorly soluble drugs like aceclofenac.     

Correlation between the viscoelastic properties of the gel layer of swollen HPMC matrix tablets and their in vitro drug release

Abstract

Drug release from hydroxypropyl methylcellulose (HPMC) hydrophilic matrix tablets is controlled by drug diffusion through the gel layer of the matrix-forming polymer upon hydration, matrix erosion or combination of diffusion and erosion mechanisms. In this study, the relationship between viscoelastic properties of the gel layer of swollen intact matrix tablets and drug release was investigated. Two sets of quetiapine fumarate (QF) matrix tablets were prepared using the high viscosity grade HPMC K4M at low (70?mg/tablet) and high (170?mg/tablet) polymer concentrations. Viscoelastic studies using a controlled stress rheometer were performed on swollen matrices following hydration in the dissolution medium for predetermined time intervals. The gel layer of swollen tablets exhibited predominantly elastic behavior. Results from the in vitro release study showed that drug release was strongly influenced by the viscoelastic properties of the gel layer of K4M tablets, which was further corroborated by results from water uptake studies conducted on intact tablets. The results provide evidence that the viscoelastic properties of the gel layer can be exploited to guide the selection of an appropriate matrix-forming polymer, to better understand the rate of drug release from matrix tablets in vitro and to develop hydrophilic controlled-release formulations.     

Formulation and In vitro assessment of sustained release terbutaline sulfate tablet made from binary hydrophilic polymer mixtures

In the present systematic study, a sustained release of terbutaline sulfate tablet (TBS) was developed and optimized by employing the hydrophilic polymers; chitosan and xanthan gum mixed with sodium bicarbonate as a release modifying agent. This formulation was developed using direct compression technology. In vitro release studies indicated rapid swelling and drug release in the initial period of the acid stage from a matrix composed of chitosan and xanthan gum solely. Addition of sodium bicarbonate to the matrix resulted in sustained drug release. Various formulation factors such as polymer to polymer ratio, polymer viscosity and particle size were altered and their effect on dissolution pattern was illustrated. Manufacturing variables such as compression force and lubricant percentage were investigated and found not to influence the drug release profile of the resulted tablets. The release mechanism follows Korsmeyer-Peppas equation with n value indicating non-Fickian diffusion. The release profiles were analyzed using statistical method (one-way ANOVA) and f₂ metric values and found to be similar to the commercial product Bricanyl^®. Reproducible data were obtained when scale-up of the formulation was performed.     

Sustained release formulations of rhVEGF165 produce a durable response in a murine model of peripheral angiogenesis

Local delivery of therapeutic angiogenic agents that stimulate blood vessel formation represents a promising strategy for the treatment of peripheral vascular disease (PVD). At present, requirements for temporal and spatial parameters for localized delivery are unclear, with a variety of sustained delivery approaches being examined. Two polymer-based sustained formulations containing the 165 amino acid isoform of human recombinant vascular endothelial growth factor-A (rhVEGF₁₆₅) were evaluated for their potential application in the treatment of PVD following intramuscular injection. Microspheres prepared from a 50:50 ratio of polylactic-co-glycolic acid (PLGA) and a gel of PLGA polymer solubilized in N-methyl pyrrolidone (PLGA:NMP) were each loaded with rhVEGF₁₆₅ and tested in vitro and in vivo. PLGA microspheres averaged ∼30 μm in diameter and contained 8.9% (w/w) rhVEGF₁₆₅, while the PLGA:NMP gel was formulated with varying amounts of spray freeze-dried rhVEGF₁₆₅ to result in final gel formulations having concentrations of 0.36, 0.72, or 3.6 mg/mL rhVEGF₁₆₅. In vitro release of rhVEGF₁₆₅ from PLGA microspheres showed ∼10% cumulative release by day 6, whereas the cumulative release of rhVEGF₁₆₅ from the PLGA:NMP gel matrices (0.65% w/w loading) was less than 0.25% at this same time point. While the in vitro release characteristics of these two sustained release formulations were broadly different, the plasma rhVEGF₁₆₅ concentration-time profiles following hind-limb intramuscular (IM) injection of these formulations in non-compromised rats revealed similar in vivo pharmacokinetics. Three-dimensional resin casts of vascular architecture were prepared at days 3, 7, 14, 21, 28, 60, and 75 following a single IM dosing of these sustained release microsphere and gel matrix formulations in the gastrocnemius muscle of immune-compromised mice. Scanning electron microscopic visualization of these vascular casts demonstrated spatial arrangement of capillary sprouts and vessel enlargement consistent with profound vascular changes occurring within 3 days of dosing that persisted for 2 months, approximately 1 month beyond the anticipated completion of rhVEGF₁₆₅ release from these sustained delivery formulations. Vascular re-modeling events were correlated with histological and immunohistochemical parameters attributed to known biological actions of rhVEGF₁₆₅ signaling. Together, these pharmacokinetic and pharmacodynamic results support the use of sustained release PLGA-based formulations for the local delivery of rhVEGF₁₆₅ to achieve a durable vascular re-modeling response.     

替硝唑原位固化缓释凝胶的处方研究

目的:应用Box-Behnken法设计并优化替硝唑原位固化缓释凝胶处方.方法:通过体外释放度的单因素影响试验确定考察因素与水平,以凝胶粘度、遇水固化时间、释放时间为响应变量,应用Box-Behnken法进行处方筛选与优化.结果:优化处方为35.3%(w/w)单甲氧基聚乙二醇-聚乳酸(mPEG-PDLLA 10/90),5.9% (w/w)替硝唑和58.8% (w/w)N-甲基-2-吡咯烷酮(NMP).该凝胶体外释放时间达192 h,无突释现象.结论:通过Box-Behnken法成功实现了替硝唑原位固化缓释凝胶的处方筛选.     

Application of dynamic neural networks in the modeling of drug release from polyethylene oxide matrix tablets

The main objective of this study was to demonstrate the possible use of dynamic neural networks to model diclofenac sodium release from polyethylene oxide hydrophilic matrix tablets. High and low molecular weight polymers in the range of 0.9–5 × 10⁶ have been used as matrix forming materials and 12 different formulations were prepared for each polymer. Matrix tablets were made by direct compression method. Fractions of polymer and compression force have been selected as most influential factors on diclofenac sodium release profile. In vitro dissolution profile has been treated as time series using dynamic neural networks. Dynamic networks are expected to be advantageous in the modeling of drug release. Networks of different topologies have been constructed in order to obtain precise prediction of release profiles for test formulations. Short-term and long-term memory structures have been included in the design of network making it possible to treat dissolution profiles as time series. The ability of network to model drug release has been assessed by the determination of correlation between predicted and experimentally obtained data. Calculated difference (f₁) and similarity (f₂) factors indicate that dynamic networks are capable of accurate predictions. Dynamic neural networks were compared to most frequently used static network, multi-layered perceptron, and superiority of dynamic networks has been demonstrated. The study also demonstrated differences between the used polyethylene oxide polymers in respect to drug release and suggests explanations for the obtained results.