新型DTC金属配合物的抗肿瘤活性及构像研究

DTC是一类具有广泛生物活性的化合物。Piperazinedithioformates具有一定的抗肿瘤活性,但其溶解性却较差。本文对一系列新型的DTC金属配合物就人体六种癌细胞系进行了体外抗肿瘤作用研究,发现了两个有较好抗肿瘤活性的化合物;并对SRCu进行构像研究,第一次得到了其稳定构像。     

琥珀酸胆固醇酯作为脂质体膜稳定剂的研究及其在制备柴胡皂苷-D脂质体中的应用

目的研究琥珀酸胆固醇酯(CHEMS)对二棕榈酰磷脂酰胆碱(DPPC)脂质体的膜稳定作用以及作用机制；以CHEMS和DPPC为膜材制备柴胡皂苷-D(SSD)脂质体，考察其包封率和溶血性。方法差示扫描量热法(DSC)和荧光释放实验考察CHEMS的膜稳定作用，傅立叶红外(FT-IR)研究CHEMS与DPPC膜的作用机制，沉降实验研究CHEMS与SSD相互作用，溶血实验考察了以CHEMS为膜材包裹SSD脂质体的溶血性。结果CHEMS在膜稳定性上优于胆固醇(CHOL)，CHEMS与DPPC的极性端头同时有氢键和静电作用；CHEMS与SSD不会形成不溶性复合物(INCOM)，用DPPC和CHEMS为膜材制备了稳定的SSD包裹的脂质体，其溶血性大大降低。结论CHEMS对DPPC膜的稳定作用大于CHOL，并可取代CHOL作为制备胆固醇依赖性的溶血性皂苷脂质体的膜稳定剂。     

中药与日本汉方药原植物的差异比较及原因分析

依据 2000年版《中国药典》和第十四改《正日本药局方》收载植物类生药品种 ,列表比较了中药与日本汉方药原植物的差异 ,并对产生差异的现象和原因进行了分析和探讨。     

远志的化学成分研究Ⅱ

目的 :研究远志的化学成分。方法 :采用多种色谱方法进行分离 ,利用光谱数据结合理化分析进行结构鉴定。结果 :从远志根皮的正丁醇层中分离得到 4个蔗糖酯类化合物 ,分别鉴定为 :sibiricoseA₅(1) ,sibiricoseA₆(2 ) ,tenuifolisideA(3)和 3′ ,6 disinapoylsucrose(4 )。结论 :化合物 1和 2为首次从该植物中分离得到。     

A New Treatment for Epiphora Secondary to Submandibular Gland Transplantation: Transcutaneous Atropine Gel

PurposeTo explore whether topical application of atropine gel controls epiphora secondary to submandibular gland (SMG) transplantion for severe keratoconjunctivitis sicca.MethodsEighteen patients with epiphora after SMG transplantation participated in a double-blind, controlled, crossover study. Patients were treated with topical smear common atropine (CA) and modified atropine (MA) gels (intervals ≥1 day). The control effect of atropine gels was observed for 5 hours. Tear flow was quantified in resting and stimulated (after exercise) states using the Schirmer I test.ResultsWith the CA gel, tear flow decreased significantly at 10, 30, and 120 minutes. Average epiphora reduction rates (AERRs) were 22.37%, 18.14%, and 13.27%, respectively (P<.05). With the MA gel, tear flow decreased significantly from 5 minutes to 5 hours; AERRs increased from 24.06% to 42.67% (P<.05); Maximum efficacy was maintained from 15 minutes to 3 hours (P<.01); Tear flow gradually increased from 4 to 5 hours but was still lower than that before atropine use (P<.05). According to results of the Schirmer I test and AERRs, the control efficacy of the MA gel was significantly better than that of the CA gel (P<.05).ConclusionsTopical application of atropine gel could effectively control mild epiphora for patients with SMG transplantation for severe keratoconjunctivitis sicca. The efficacy of MA gel was much better than that of the CA gel.     

Microbial transformation of asiatic acid by Alternaria longipes

Asiatic acid is a major pentacyclic triterpene isolated from Centella asiatica. It shows a variety of bioactivities. In order to obtain its derivatives, potentially useful for detailed pharmacological studies, the substrate was subjected to incubations with selected micro-organisms. In this work, asiatic acid was converted into three new compounds: 2α,3β,23,30-tetrahydroxyurs-12-ene-28-oic acid (1), 2α,3β,22β,23-tetrahydroxyurs-12-ene-28-oic acid (2), and 2α,3β,22β,23,30-pentahydroxyurs-12-ene-28-oic acid (3) by the fungus Alternaria longipes AS 3.2875. The structures of the three metabolites were determined by 1D and 2D NMR spectral data.     

Eight new bibenzyl derivatives from Dendrobium candidum

Eight bibenzyl derivatives, namely dendrocandins J–Q (1–8), were isolated from the stems of Dendrobium candidum. Their structures were elucidated by 1D and 2D NMR experiments and mass spectrometry. Compounds 1–8 were examined for antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay, and the IC₅₀ values were 36.8, 70.2, 45.0, 60.5, 87.6, 50.4, 22.3, and 30.3 μM, respectively.     

A Higher Dose of Dasatinib May Increase the Possibility of Crossing the Blood–brain Barrier in the Treatment of Patients With Philadelphia Chromosome–positive Acute Lymphoblastic Leukemia

PurposeDasatinib is a second-generation tyrosine kinase inhibitor with higher central nervous system (CNS) penetration compared with imatinib and nilotinib in in vitro studies. However, limited clinical data are available regarding the dosage and CNS penetration of dasatinib. The purpose of this study was to investigate the actual ability of dasatinib to cross the blood–brain barrier in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph⁺ ALL).MethodsPlasma and cerebrospinal fluid (CSF) samples collected from Ph⁺ ALL patients treated with dasatinib were analyzed by using an LC-MS/MS assay.FindingsOrally administered dasatinib 100 mg once daily was well absorbed by the patient but penetrated poorly into the CSF. The use of a higher drug dosage (140 mg/d) may increase systemic drug exposure and enhance the penetration of dasatinib into the CSF.ImplicationsBased on this study, the use of a higher dosage of dasatinib (140 mg/d) is recommended in patients at high risk of CNS relapse or patients who need treatment for CNS leukemia. ClinicalTrials.gov identifier: NCT02523976.     

Pharmacokinetics of Peptide–Fc Fusion Proteins

Peptide–Fc fusion proteins (or peptibodies) are chimeric proteins generated by fusing a biologically active peptide with the Fc-domain of immunoglobulin G. In this review, we describe recent studies that have evaluated the absorption, distribution, metabolism, and excretion characteristics of peptibodies. Key features of the pharmacokinetics of peptibodies include their extended half-life due to recycling by the neonatal Fc receptor (FcRn), a substantial contribution by renal excretion to total clearance and, for certain peptibodies, target-mediated drug disposition. The prolonged half-life of peptibodies permits less-frequent dose administration compared with small therapeutic peptides, thereby supporting patient convenience and compliance. Hence, a considerable number of peptibodies are currently in preclinical and clinical development. Investigation of the metabolism (biotransformation) of biologics is an evolving area of research: ligand-binding mass spectrometry techniques have been employed for the characterization of the peptibody romiplostim, providing a new approach to evaluation of the degradation products of biologics. Pharmacokinetic/pharmacodynamic modeling and simulation techniques have been used to predict the pharmacokinetics of peptibodies which can inform clinical decision-making, particularly selection of dosing regimens. This integrated review highlights the distinct pharmacokinetic characteristics of peptibodies and their influence on the drug development process for this emerging family of therapeutics. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:53–64, 2014