Pharmacognostic Study of the Leaf of Heliotropium indicum Linn. (Boraginaceae)

Abstract

Heliotropium indicum Linn. (Fam. Boraginaceae) has many medicinal uses. The common trade name is Hatisunda. The plant has pubescent, exstipulate, ovate-elongate leaves with ranunculaceous stomata on both surfaces, near 21 stomatal index, various types of non-glandular and glandular hairs, about 6 palisade ratio, lacunar collenchyma in mid-veins, suberin at trichome bases and alkaloids in leaf extracts.     

Pharmacognostic Studies on Drug of Thlapsi bursa-pastoris Mench

Abstract

Microscopical studies on Thlapsi bursa-pastoris Moench (Cruciferae) have been done for its identification including the drug in powdered form. Diagnostic features include anisocytic stomata on both abaxial and adaxial epidermis; stomatal index 16.66 to 25.00; palisade ratio 1 to 1.5; stellate serrately thick-walled trichomes on leaves, each with a wide central circular-pore; sclerenchyma caps above and below vascular bundles in leaves; vessels with bordered pits and spiral thickenings; bast and wood fibres in xylem in roots; pericyclic sclerenchyma localised above primary vascular bundles in stem.     

Anatomical Identity Parameters of the Crude Drug Psidii guajavae folium

Abstract

The leaves of Psidii guajavae L. (Myrtaceae) (Guava) are popularly used in tropical countries to prepare a remedy for the treatment of patients suffering of liquid stools; this traditional use is now scientifically supported by the existence in the leaf of a group of quercetin-derived flavonoids with intestinal anti-motility, spasmolytic and anti-inflammatory properties. Consequently, herbal products prepared with Psidii guajavae folium are now clinically used to treat Acute Diarrheic Disease and some are commercialized as phyto-drugs. However, there are no studies on morphology of this plant drug, particularly to determine the anatomical characters required for quality control of the raw material used in the preparation of guava-leaf phytodrugs. The present paper provides the anatomical and morphological characters that help in the authentication of Psidii guajavae leaf. Guava leaf surfaces were dissected and stained with cresyle-violet; transversal cuttings of the lamina and petiole were stained using safranine-fast green; samples were studied using procedures of light, scanning-electron and laser-scanning con-focal microscopy. Anomocytic and anisocytic stomatas in the abaxial epidermis, long unicellular trichomes and schizolysigenous secretory cavities are proposed as anatomical parameters to establish authenticity of guava leaf crude drug.     

Pharmacognostic Study on Ecbolium Linneanum Kurz Var. Dentata Clarke

Abstract

Pharmacognostic characters of Echolium linneanum Kurz (Var. dentata Cl.) having Ayurvedic application in jaundice, menorrhagia, rheumatism, disuria etc. are: 1. Low shrubby habit with woody root stock, bluish bifid flowers in dense spikes, large imbricate 4-ranked bracts oblong lanceolate lamina tapering at both ends and very short petioles; 2. large oval glandular cells with dense contents, on leaf and stem periphery; 3. wood in stem ring porous with mostly solitary pores and with heterogeneous rays (type I of Jane, 1955) containing micro-crystals; 4. internal phloem; 5. leaves with caryophyllaceous stomata; palisade ratio: 4.07 (0.09), stomatal index: 16.52 (1.10) and vein-islet number: 7.00 (0.21); 6. roots with abundant thick-walled fibres in secondary xylem.     

Pharmacognostic Study on Ecbolium Linneanum Kurz Var. Dentata Clarke

Abstract

Pharmacognostic characters of Echolium linneanum Kurz (Var. dentata Cl.) having Ayurvedic application in jaundice, menorrhagia, rheumatism, disuria etc. are: 1. Low shrubby habit with woody root stock, bluish bifid flowers in dense spikes, large imbricate 4-ranked bracts oblong lanceolate lamina tapering at both ends and very short petioles; 2. large oval glandular cells with dense contents, on leaf and stem periphery; 3. wood in stem ring porous with mostly solitary pores and with heterogeneous rays (type I of Jane, 1955) containing micro-crystals; 4. internal phloem; 5. leaves with caryophyllaceous stomata; palisade ratio: 4.07 (0.09), stomatal index: 16.52 (± 1.10) and vein-islet number: 7.00 (0.21); 6. roots with abundant thick-walled fibres in secondary xylem.     

秀丽斑叶兰的植物形态和显微鉴定

目的 对秀丽斑叶兰进行生药鉴定,明确其原植物形态和显微特征。方法 采用生药学鉴定的方法观察秀丽斑叶兰原植物形态和组织构造。结果 秀丽斑叶兰叶片卵形,叶上表面深绿色,具白色网状叶脉或叶脉不明显,中肋有一条白色的带,叶背面紫红色;花较小,花瓣白色,中部绿色,斜倒披针形;唇瓣白色,卵形,基部凹陷呈囊状,内面具多数腺毛。结论 这些特征可为秀丽斑叶兰的生药鉴别和资源开发利用提供参考依据。     

中药老鹳草的形态组织学研究

报告了三种供药用的老鹳草—牛儿苗Erodiumstephanianum Willd.、尼泊尔老鹳草GeraniumnepalenseSweet和鼠掌老鹳草G。sibiricumL.的形态组织学研究结果,并列表比较鉴别特征和写出生药检索表。     

The Role of the Drug/Excipient Particle Size Ratio in the Percolation Model for Tablets

Purpose. In previous papers, a linear relationship between drug particle size and drug percolation threshold was found in inert matrix tablets. The main objectives of the present work are: to study the influence of the excipient particle size on the drug percolation threshold and to investigate if the change in the drug percolation threshold is due either to the absolute or to the relative drug particle size. Methods. Matrix tablets have been prepared using KC1 (7 different particle size fractions) as a drug model and Eudragit^® RS-PM (4 granulommetric fractions) as matrix forming material. In vitro release assays were carried out on the 66 lots of tablets. The drug percolation thresholds were estimated following the method of Bonny and Leuenberger. Results. The particle size of the excipient has shown an opposite effect to the drug size on the drug percolation threshold. Nevertheless, the influence of drug and excipient sizes on the drug percolation threshold are of the same magnitude. Conclusions. The drug percolation threshold depends linearly on the relative drug particle size. This finding is in agreement with percolation theory and can facilitate the use of the percolation threshold as a preformulation parameter to improve the pharmaceutical dosage forms design.     

基于标准化模型构建药品质量风险管控体系的研究

目的 探索构建一套切实可操作的制度化、数据化药品质量风险管控标准化模型及运行体系。方法 从风险评估、风险控制、风险交流、风险审核等方面阐述药品质量风险管控的应用研究。结果 宁波市药品监管部门将药品质量风险信息标准化、风险评估指标体系实践应用于药品生产、流通、不良反应监测、药品检验、社会共治等环节。结论 药品质量风险管控体系化建设不断完善,并提出实施药品质量风险管控标准化体系建设工作的建议,为当前的药品监管提供科学的创新思路。     

Wound healing activity of Pluchea indica leaf extract in oral mucosal cell line and oral spray formulation containing nanoparticles of the extract

Context: Pluchea indica (L.) Less (Asteraceae) is an herb used as a traditional medicine for wound healing. The chemical compounds found in Pluchea indica leaves are phenolic acids, flavonoids, anthocyanins and carotenoids.

Objective: This study investigates the effect of Pluchea indica leaf ethanol extract and its nanoparticles (NPs) on cytotoxicity, cell survival and migration of human oral squamous carcinoma cell line.

Materials and methods: Cell viability was measured using MTT assay to assess the effect of Pluchea indica leaf extract and NPs (1–500?μg/mL) on cytotoxicity and cell survival. The effect of Pluchea indica leaf extract and NPs on cell migration was determined by scratch assay. The % relative migration was calculated after 24, 48 and 72?h of treatment.

Results: The sizes of Pluchea indica leaf extract NPs were in a range of nanometers. NPs possessed negative charge with the polydispersity index (PDI) smaller than 0.3. After the treatment for 24, 48 and 72?h, Pluchea indica leaf extract had IC₅₀ value of 443.2, 350.9 and 580.5?μg/mL, respectively, whereas the IC₅₀ value of NPs after the treatment for 24, 48 and 72?h were 177.4, 149.2 and 185.1?μg/mL, respectively. The % relative migration of cells was significantly increased when the cells were treated with 62.5 and 125?μg/mL of the extract and 62.5?μg/mL of NPs.

Discussion and Conclusions: NPs increased cytotoxicity of the Pluchea indica leaf extract, increased the migration of cells at low concentration and increased colloidal stability of the extract in an oral spray formulation.     

基于主成分分析对于不同产地黄芩茎叶提取物紫外指纹图谱的鉴别研究

目的 建立黄芩茎叶提取物紫外指纹图谱的研究方法。方法 利用紫外谱线组法对不同产地黄芩茎叶提取物的乙酸乙酯、三氯甲烷、乙醇、水提取液建立黄芩茎叶提取物紫外指纹图谱,并利用simca-p+11分析软件,对不同产地黄芩茎叶提取物的紫外吸收数据进行主成分分析,根据它们的紫外指纹图谱峰位置的差异及主成分分析的结果,为黄芩茎叶提取物的质量控制提供实验依据,对于不同产地的黄芩茎叶提取物加以区分鉴别。结果 不同产地黄芩茎叶提取物的成分存在一定的差异性,可以有效控制不同产地黄芩提取物的质量的稳定性。由主成分分析选出的各产地的黄芩茎叶提取物的主成分吸收波长,可以明显的区分不同产地的黄芩茎叶提取物。结论 建立了黄芩茎叶提取物产地与紫外谱线组的相关性研究方法,对于鉴别黄芩原产地也具有一定的指导意义。     

蜡梅不同部位精油化学成分分析及其体外抑菌活性研究

目的 研究蜡梅Chimonanthus praecox（Linn.）Link根、叶、果皮中精油的化学组成及其抑菌活性。方法 采用气相色谱-质谱联用（GC-MS）技术对水蒸气蒸馏法提取的蜡梅根、叶、果皮精油进行成分分析,并分别采用肉汤二倍稀释法和菌丝生长法测试蜡梅不同部位精油对细菌和病原真菌的抑制活性。结果 鉴定了蜡梅根精油中的37种成分、蜡梅叶精油中的48种成分、蜡梅果皮精油中的38种成分,蜡酶不同部位精油中具有相同的化合物15种,分别占各部位精油总量的84.05%,36.83%,64.46%。抑菌实验结果表明蜡梅不同部位精油对受试菌均有不同强度的抑制作用。结论 蜡梅根精油对革兰氏阳性菌和病原真菌具有较强的抑菌活性,抑菌谱较广,且该精油含有多种生物活性成分,具有较高的药用价值及开发前景。     

Glycobiology of the Leishmania parasite and emerging targets for antileishmanial drug discovery

Importance of the field: Parasitic diseases that pose a threat to human life include leishmaniasis – caused by protozoa of Leishmania species. Existing drugs have limitations due to deleterious side effects like teratogenicity and factors like cost and drug resistance, thus furthering the need to develop this area of research.

Areas covered in this review: We came across drug targets, very recently characterised, cloned and validated by genomics and bioinformatics. We bring these promising drug targets into focus so that they can be explored to their fullest.

What the reader will gain: In an effort to bridge the gaps between existing knowledge and future prospects of drug discovery, we found interesting studies validating drug targets and paving the way for better experiments to be designed. In a few cases, novel pathways have been characterized, while in others, well established pathways when probed further, led to the discovery of new drug targets.

Take home message: The review constitutes a comprehensive report on upcoming drug targets, with emphasis on glycosylphosphatidylinositol (GPI)-anchored glycoconjugates along with related biochemistry of enolase, glycosome and purine salvage pathways, as we strive to bring ourselves a step closer to being able to combat this deadly disease.     

论《药品管理法》修订背景下的药品犯罪立法完善

目的： 结合《药品管理法》相关条款的修订，分析其对刑法药品犯罪罪名适用的影响，并确立药品犯罪条款的立法完善思路。方法： 检索新修订《药品管理法》与药品犯罪相关的条文，分析其修订目的，对照刑法和药品犯罪相关司法解释，分析新修订《药品管理法》对药品犯罪的司法适用造成的冲击与影响，并提出相应的立法完善性思路。结果与结论： 新修订《药品管理法》重新界定了假药和劣药，导致生产、销售假药罪和生产、销售劣药罪适用范围的限缩，但是不能简单化理解为将进口国内未上市的药品行为除罪化，同时在二元化立法模式下，《药品管理法》部分处罚条款的适用范围会非常狭窄，而假药、劣药证据标准的提高会给刑事司法造成直接的冲击。应结合新修订《药品管理法》，对刑法相关条文和刑法司法解释进行修改和更新。     

Charged liposomes as carriers to enhance the permeation through the skin

Introduction: In recent years, there has been increased interest in developing charged liposomes as carriers for transdermal drug delivery. It is necessary to modify the basic composition of the liposomes in order to enhance the penetration properties of the vesicles through the skin. Charged liposomes offer several advantages compared with previous drug delivery systems.

Areas covered: This paper provides a brief overview of the different drug delivery systems that exist which aim to improve the permeation of drugs through the skin, focusing on the use of charged liposomes for transdermal delivery. We propose a classification of such liposomes based on the origin of the charge given to the vesicles.

Expert opinion: Despite the advances that are occurring in the design of charged liposomes for transdermal drug delivery, the long-term stability continues to be a drawback in such systems. The presence of charge on the surface of the vesicles favors the electrostatic repulsion among them, creating a ζ potential positive or negative that prevents their aggregation and flocculation. However, there is loss of the encapsulated drug, which limits the in vivo use of these systems. It should be emphasized that charged liposomes are indeed a promising candidate for use in gene therapy and vaccine targeting, in a great diversity of diseases, for which drugs are administered by the percutaneous route.     

Skin Penetration and Mechanisms of Action in the Delivery of the D2-Agonist Rotigotine from Surfactant-Based Elastic Vesicle Formulations

Purpose. This study was performed to investigate the effect of elastic and rigid vesicles on the penetration of the D₂ dopamine agonist rotigotine across human skin and to further elucidate the mechanisms of action of the elastic vesicles. Methods. A series of rotigotine-loaded vesicles were prepared, ranging from very elastic to very rigid. The drug penetration from these vesicles across human skin was studied in vitro using flow-through diffusion cells. Micelle and buffer solutions were investigated as controls. For the most elastic vesicle composition, two additional variables were investigated. Coapplication of drug and vesicles was compared to pretreatment, and the effect of the drug entrapment efficiency was investigated. Results. The very elastic vesicle formulation L-595/PEG-8-L (50/50) gave steady-state fluxes of 214.4 ± 27.8 ng/(h · cm²). This formulation was the most effective formulation and significantly better than the rigid vesicle formulations as well as the micelle and buffer controls. However, coapplication and a high drug entrapment efficiency were essential factors for an optimal drug delivery from elastic vesicle formulations. Conclusions. Elastic vesicles are promising vehicles for transdermal drug delivery. It is essential that drug molecules are applied together with and entrapped within the vesicles themselves, suggesting that elastic vesicles act as drug carrier systems and not solely as penetration enhancers.     

Incorporation of the Model Drug Ubidecarenone into Solid Lipid Nanoparticles

Purpose. The impact of drug incorporation on melt-homogenized tripalmitin nanoparticles is investigated with ubidecarenone as a model drug. The dispersions are studied with respect to their drug loading capacity, localization and physical state of the drug as well as to potential changes of the nanoparticle properties due to interactions between drug and triglyceride matrix. Methods. The investigations were carried out using photon correlation spectroscopy, differential scanning calorimetry, synchrotron radiation X-ray diffraction, ultracentrifugation, and cryo- and freeze-fracture transmission electron microscopy. Results. Ubidecarenone can be incorporated into the dispersions in concentrations higher than 50% of the dispersed phase. The drug is associated with the nanoparticles such that small drug amounts are bound tightly to the carrier matrix while excess drug adheres as a liquid phase to the crystalline particles. Drug incorporation lowers the crystallization and melting temperature of the particle matrix and accelerates the transition of the triglyceride into the stable -polymorph after crystallization. Conclusions. Drug incorporation may significantly alter important physicochemical parameters of solid lipid nanoparticles. Slow release of ubidecarenone may only be possible for the fraction of drug which is tightly bound to the matrix while the liquid fraction should be rapidly released.     

药品管理法律责任的制度创新

目的：评析2019年版《药品管理法》中的法律责任制度的创新,明确药品市场主体的主体责任和药品监管者的监管责任,以期减少药品违法事件的发生,保证公众用药安全。方法：对比2001年版《药品管理法》,结合行政法原理,加之比较法的视角,对2019年版《药品管理法》进行解析。结果与结论：2019年版《药品管理法》强化了法律责任的重要性,设定了更为严格的法律责任,通过体系化的制度设计和完善的法律责任机制,提高了违法者的违法成本,有助于遏制和惩戒违法行为。     

Mechanistic models enable the rational use of in vitro drug-target binding kinetics for better drug effects in patients

Introduction: Drug-target binding kinetics are major determinants of the time course of drug action for several drugs, as clearly described for the irreversible binders omeprazole and aspirin. This supports the increasing interest to incorporate newly developed high-throughput assays for drug-target binding kinetics in drug discovery. A meaningful application of in vitro drug-target binding kinetics in drug discovery requires insight into the relation between in vivo drug effect and in vitro measured drug-target binding kinetics.

Areas covered: In this review, the authors discuss both the relation between in vitro and in vivo measured binding kinetics and the relation between in vivo binding kinetics, target occupancy and effect profiles.

Expert opinion: More scientific evidence is required for the rational selection and development of drug-candidates on the basis of in vitro estimates of drug-target binding kinetics. To elucidate the value of in vitro binding kinetics measurements, it is necessary to obtain information on system-specific properties which influence the kinetics of target occupancy and drug effect. Mathematical integration of this information enables the identification of drug-specific properties which lead to optimal target occupancy and drug effect in patients.     

HPMC-Matrices for Controlled Drug Delivery: A New Model Combining Diffusion,Swelling, and Dissolution Mechanisms and Predicting the Release Kinetics

Purpose. The purpose of this study was to investigate the drug release mechanisms from hydroxypropyl methylcellulose (HPMC)-matrices, and to develop a new model for quantitative predictions of controlled drug delivery. Methods. The dissolved mass of pure HPMC-matrices and the drug release rate from propranolol HCl-loaded HPMC-matrices were determined experimentally. Based on Fick's second law of diffusion for cylinders, the transport of water and drug were modeled considering (i) both radial and axial diffusion, (ii) concentration-dependent drug diffusivities, (iii) matrix swelling and (iv) HPMC dissolution. Results. Good agreement between theory and experiment (dissolved mass and drug release studies) was obtained, proving the validity of the presented model. The water and drug diffusivities are strongly dependent on the matrix swelling ratio. Diffusion, swelling and dissolution are the governing mechanisms involved in the overall drug release process. Conclusions. The practical benefit of the presented model is to identify the required shape and dimensions of drug-loaded HPMC-matrices in order to achieve desired release profiles, thus facilitating the development of new controlled drug delivery products. This will be demonstrated in a future study.