DNA alkylating agents generally kill tumor cells by covalently binding with DNA to form interstrand or intrastrand cross-links. However, in the case of cisplatin, only a few DNA adducts (<1%) are highly toxic irreparable interstrand cross-links. Furthermore, cisplatin is rapidly detoxified by high levels of intracellular thiols such as glutathione (GSH). Since the discovery of its mechanism of action, people have been looking for ways to directly and efficiently remove intracellular GSH and increase interstrand cross-links to improve drug efficacy and overcome resistance, but there has been little breakthrough. Herein, we hypothesized that the anticancer efficiency of cisplatin can be enhanced through iodo-thiol click chemistry mediated GSH depletion and increased formation of DNA interstrand cross-links via mild hyperthermia triggered by near-infrared (NIR) light. This was achieved by preparing an amphiphilic polymer with platinum(IV) (Pt(IV)) prodrugs and pendant iodine atoms (iodides). The polymer was further used to encapsulate IR780 and assembled into Pt-I-IR780 nanoparticles. Induction of mild hyperthermia (43 °C) at the tumor site by NIR light irradiation had three effects: (1) it accelerated the GSH-mediated reduction of Pt(IV) in the polymer main chain to platinum(II) (Pt(II)); (2) it boosted the iodo-thiol substitution click reaction between GSH and iodide, thereby attenuating the GSH-mediated detoxification of cisplatin; (3) it increased the proportion of highly toxic and irreparable Pt-DNA interstrand cross-links. Therefore, we find that mild hyperthermia induced via NIR irradiation can enhance the killing of cancer cells and reduce the tumor burden, thus delivering efficient chemotherapy.

混合式课程建设是目前我国高等教学的重要改革方向,主要论述在波谱解析课程教学中应用混合式课程建设,并将基于混合式教学模式试点班实践过程中的相关数据与没有进行该教学模式的普通班进行比较,探讨了混合式教学模式在波谱解析教学实践过程中体现的优势和问题,并为混合式教学的推广实施提出了建议,旨在提高学生学习积极性和改善教学效果.

Experimental teaching is a very important link of the college pharmaceutical education and the laboratory is an important platform for effective experimental teaching, which can cultivate students' ability and professional skills training.The original operation mode should be reformed and specification with the increase of teaching and scientific research tasks and the expansion of the experimental center.This paper carries on the exploration and practices based on the current problems in the operation of the laboratory, such as function module partition, experimental contents adjustment, system construction, personnel construction, safety prevention and control, etc.

随着网络技术的迅速发展,网络平台教学已逐渐成为一种新型的教学资源。从《新药设计与开发》课程的教学特点出发,详细地介绍了本门课程进行网络平台建设的背景、目的及网络平台建设的情况、应用的效果。

本文介绍了近几年关于红车轴草异黄酮药理作用的研究状况,并对红车轴草应用进行了展望.[

Objective:To establish an HPLC-ELSD specific chromatogram analysis method of natural Calculus Bovis with a comparative study of Calculus Bovis cultivated by glucuronidase.Methods:An HPLC-ELSD analysis was carried out on a Diamonsil C18 column(250 mm×4.6 mm,5 μm)with the mobile phase consisting of methanol(A)-0.1% acetic acid aqueous solution(B)in gradient mode.The flow rate was 0.8 mL·min-1.The temperature of drift tube was 110 ℃,flow rate of the gas was 2.0 L·min-1and the analytic time was 60 min.Results:Under the above chromatographic conditions,the mutual mode of HPLC specific chromatograms was set up,Calculus Bovis cultivated by glucuronidase had a similar specific chromatogram with the natural Calculus Bovis.Conclusion:The method is in good precision and reproducibility,which can be available for the identification of Calculus Bovis cultivated by glucuronidase.

OBJECTIVE To prepare the effervescent tablets of famotidine and establish its quality standards.METHODS The formulation was optimized by single factor screening experiments.Famotidine effervescent tablets were prepared using direct compression method,with poloxamer 188 as material carriers of solid dispersion of famotidine.Then the character,weight difference,disintegration time,acidity and the content were tested.RESULTS The optimal formulation was as follows: tartaric acid-sodium bicarbonate=1∶1,the percentage of disintegrant,PEG6000 and magnesium stearate was 60%,3%,0.3%,respectively.The tablets disintegrated entirely in 5 minutes.CONCLUSION The optimal formulation is feasible,the preparation techniques is simple,and can be widely used.

天然药物化学课程是药学专业中一门重要课程,作者总结了在天然药物化学教学中的经验,对于帮助学生克服学习中的障碍,激发学生的学习热情提出了几点建议。

Objective:To prepare in-situ thermosensitive gel containing berberine hydrochloride for ophthalmic use and study its pharmacokinetic parameters in aqueous humors of rabbit eyes.Methods:The in-situ thermosensitive gel of berberine hydrochloride was prepared using poloxamer 407 and poloxamer 188 as thermosensitive material,drug concentration in aqueous humors of rabbit eyes at different time was determined by HPLC.Aqueous humors concentration-time curve of berberine hydrochloride was plotted and pharmacokinetic parameters were calculated by the DAS(Drug and Statistics)soft.Results:The absorption and elimination of berberine hydrochloride were fitted to a two-compartment model with the main pharmacokinetic parameters as follows: t1/2 β,t1/2α,MRT,Tmax,Cmax,AUC0-τ and AUC0-∞ were 4.585 h,0.911 h,1.966 h,1 h,1.4 mg·L-1,2.561 mg·h·L-1 and 2.581 mg·h·L-1,respectively.Conclusion:This method can be used to determine the concentration of berberine hydrochloride in aqueous humors of rabbit eyes,and be suitable for the pharmacokinetic study of berberine hydrochloride in local ophthalmic system.

AIM:To develop an HPLC-PDA fingerprint analysis method of natural Calculus bovis in comparison with Calculus bovis cultivated by glucuronidase.METHODS:An HPLC analysis was carried out on a Diamonsil C18 column(4.6 mm ×250 mm,5 μm)with the mobile phase consisting Methanol(A)-chloroform-1% acetic acid aqueous solution in gradient mode.The detection wavelength was set at 370 nm.The flow rate was 1.0 mL.min-1 and the analytic time was 40 min.RESULTS:Under the above chromatographic conditions,the mutual mode of HPLC fingerprints was set up,Calculus bovis cultivated by glucuronidase had a similar fingerprint chromatogram to the natral Calculus bovis,but there was a little difference in their concent.CONCLUSION:The method is in good precision and reproducibility and could be available for the identification of various substitutes of Calculus bovis.

Objective To establish a HPLC-ELSD method for determining cholesterol and making a comparation of which between two kinds of calculus bovis. Methods A C18(250 mm×4.6 mm,5 μm)column was used with a mobile phase as acetonitrile-Isopropanol(1:1)flowing at 1.0 mL·min-1.The temperature of drift tube was 67.5 ℃,and the gas flow rate was 1.7 L·min-1. Results The cholesterol was in a good linear relationship in the range of 4.0-20.0 μg·mL-1,logA=1.541 2logC-2.525(r=0.999 2).The average recovery was 98.41%,100.04%,96.46%,respectively,and RSD was 0.63%,1.67%,1.03%,respectively. Conclusion The method is simple,accurate,specific and can be used for the quality control of cholesterol in natural calculus bovis,succedaneums and preparations.

s:Aim To observe the preventive effect of trifolium pratense isoflavones(TPIF)on retinoic acid induced osteoporosis in mice.Method The mouse osteoporosis was induced by given retinoic acid intragastrically for two weeks.The histomorphological features of bone were observed and biochemical indexes in serum(Ca,P,ALP,TRAP,E2,BGP)were determined after the mouse were given TPIF at the dose of 50,100,200 mg·kg-1 respectively.Results Trifolium pratense isoflavones could induce high turnover of osteoporosis.The levels of P,ALP,TRAP and BGP in the TPIF groups were lower than the model group,while the E2 level was higher than the model group.Conclusions Trifolium pratense isoflavones can prevent the loss bone in the experimental mice.The machanism may be that it improves the level of estrogenic hormone and inhibits the high bone turnover.

甜菜碱(betaine,Bet)又名甘氨酸甜菜碱、甜菜素,化学名称是三甲基氨基乙酸或三甲铵乙内酯,19世纪最早发现于欧洲,是一种季铵型水溶性生物碱,广泛存在于动植物和微生物体内.

Betaine,as a methyl donor,is distributed widely in animals,plants,and microorganisms.It participates in an important biochemical reaction——the methionine cycle in organism.Betaine can obviously improve the symptoms due to lacking of methyl group in organism,and can be used to treat hyperhomocysteine syndrome,protect liver and kidney,heart and blood vessels.It also has lots of other beneficial pharmacological effects such as inhibition of unceasingly growing tumor cells and protection of cells against hyperosmotic damage.This paper summarized the current status of studies on the pharmacodynamics of betaine and the possible mechanisms.