中药产业是构成我国医药工业可持续发展战略框架的重要组成部分，特别是新医改以来，中药产业整体保持良好势头，增速逐步提高。但由于中药材价格的持续上涨，及药品降价、招投标等多种不利因素的影响，也使中药企业面临前所未有的困难和挑战。本文从政策扶持，中药产品、生产技术的创新升级等方面，分析了我国中药产业的发展机遇。

Dissolution test plays a very important role in the development of oral solid formulations. A critical dissolution condition for distinguishing the dissolution behaviors of the products should be found. The paper describes how to choose a critical dissolution condition for showing the inherent properties of different solid products.

在市场经济时代，市场发展趋势决定企业品种的结构；具有中国特色的市场经济又被国家政策与制度所左右；因而探讨市场现状与解读政策是必须的。除众所周知的刚性因素外，还有全球经济、我国国民经济等因素造就中国医药行业成为一个朝阳行业；而品种低水平重复与市场无序化竞争决定此行业必须面临一场规模化、集约化的洗礼过程，兼并重组、做强做优将是今后几年行业发展的主旋律。

This review outlined the origin and the development of green process chemistry in modern pharmaceutical industry, list the key areas of green chemistry research, introduced the green techniques, skills and approaches with cases studies of several pharmaceutical products including celecoxib, sitagliptin, pregabalin, saxagliptin, aprepitant, esomeprazole and donepezil.

Statins can safely and effectively reduce the plasma level of low-density lipoprotein cholesterol (LDL-C), so that they are drugs of choice for the treatment of hypercholesterolemia. All approved statins share a common mechanism of action but their chemical structures are different. The chemical structures govern their water solubility and lipophilicity, which in turn affect their absorption, distribution, metabolism and excretion. The influences of the chemical structures and physicochemical properties of statins on their pharmacodynamics and pharmacokinetics are reviewed in this paper. All statins have hepatic first pass effects so that they can be enriched in liver. Among the approved statins, rosuvastatin has the stronger effect on reducing LDL-C level, followed by torvastatin, simvastatin and pravastatin.

The U.S. Food and Drug Administration (FDA) approved 45 new drugs into the market in 2015, including 32 chemical small molecules and 13 biological products. According to the prescription information for professionals and the related literature as well as patent information, this review describes the  descriptions, indications, mechanism of action, dosage form and strength, adverse reactions, and one synthetic route of the chemical small molecules, and brief information about biological products.

2012年1月，《国家药品安全“十二五”规划》正式将罕见病用药(即罕用药)的研发和生产纳入国家药品规划范畴。而由于罕用药自身的特殊供求关系，市场调节并不能有效起到促进该产业发展的作用，因此罕用药市场保障政策的建立和完善至关重要。本文从罕用药市场保障政策的必要性入手，分析我国目前的罕用药市场保障政策体系，并重点对我国目前的罕用药市场准入政策、数据保护政策和医疗保险政策的现状、不足和发展加以研究。

医疗器械行业涉及到医药、机械、电子、塑料等多个行业，是一个多学科交叉、知识密集、资金密集的高技术产业。高新技术医疗设备的基本特征是数字化和计算机化，跨领域的现代高技术的结晶，属于产品技术含量高，利润高的行业。在新医改的政策驱动及政府投入增大等外力推动下，结合人口老龄化、消费升级等内生动力的双重促进，将极大地推动基层医疗体制的建设，刺激中低端医疗器械市场需求。医疗器械产业已成为国家战略新兴产业的重要组成部分，国企产品结构调整已是当户之急，基层医院配备国产设备已成定局。政策倾斜与市场发展不但引起了业内人士的关注，更引发了投资者的兴趣。

The extraction process of procyanidine from pine needles by smashing tissue extraction was optimized by single factor experiment and orthogonal test. Smashing tissue extraction was compared with reflux extraction. The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) method was used to identify antioxidant activity of procyanidine from pine needles. The optimal extraction conditions were as follows: ethanol concentration of 60％, solid to liquid ratio of 1︰12, extraction time of 1.5 min and voltage of 80 V. Smashing tissue extraction was superior to reflux extraction in the extraction rate, extraction time and electricity consumption. The IC50 of procyanidine to DPPH was 5.44 μg/ml and its antioxidant activity was obviously higher than vitamin C.

In this paper, the esomeprazole magnesium polymorphs (dihydrate form A, dihydrate form B, tetrahydrate and trihydrate) were prepared. The polymorphs were characterized by powder X-ray diffraction, infrared spectroscopy and thermal gravimetric analysis. The identification of different polymorphs together with the conditions among their transformation was established.

Several drug delivery systems, such as nanoparticles, microspheres, liposomes,  in stiu  hydrogel, and micro- or submicro-emulsions are endowed with the advantages of lessening degradation of drugs in vitro  and  in vivo  and  achieving controllable release profile. Thus, preparation of novel injections based on these delivery systems has been a hot spot in the drug development area. The dosage characteristics of these novel injections marketed abroad in recent years
and these clinical applications are reviewed, and some new injection devices are introduced.

Computational fluid dynamics has become an important tool for study fluid flowing state and the mass and heat transfer process based on the numerical simulation, which aims at working out the equations of fluid momentum, heat and mass to obtain the thermodynamic parameters of the flowing fluid. In this paper, computational fluid dynamics technology is briefly introduced and its application to spray dryer chamber design, optimizing process parameters and reducing the wall deposition in the spray drying operation are reviewed.

A TLC method was established for the simultaneous qualitative analysis of 48 banned pigments in traditional Chinese medicine. Sample powders were extracted by ultrasonication with acetonitrile, 0.1％ formic methanol solution and methanol∶0.1％ formic acid (3∶2), respectively. The acetonitrile extraction and the liposoluble pigments reference solution were applied to a silica gel plate separately and developed with petroleum ether∶diethyl ether∶ formic acid (80∶20∶1). The 0.1％ formic methanol solution extraction and the basic pigments reference solution were developed with ethyl acetate∶ethanol∶water∶amonia (12∶1∶1∶1.2), and the methanol∶0.1％ formic acid (3∶ 2) extraction and the acid pigments reference solution were developed with ethyl acetate∶ethanol∶water∶amonia (6∶ 4∶2∶0.2). The plates were observed under daylight. The limits of detection of 48 banned pigments were 0.025 - 0.6 μg. This method, with simple pretreatment and rapid analysis, was suitable for the simultaneous scan of pigments in traditional Chinese medicine.

Physicochemical properties of active pharmaceutical ingredients (API) can influence manufactory process and quality of final products so that they are the important part of performulation study. Salts formation, solvation and polymorphism screening are traditional methods to improve physicochemical properties of slightly soluble compound.Recently, co-crystal, which is designed by crystal engineering, attracts more attention on improving physicochemical
properties and patent protection of API. The screening methods, physicochemical properties, industrial production and prospects of co-crystals are reviewed in this paper.

The anti-inflammatory activity fractions were isolated from Callicarpa kwangtungensis Chun. and purified by column chromatographies, such as AD-8 macroporous resin, Sephadex LH-20, C18 and silica gel. Their structures were identified on the basis of physiochemical properties and spectroscopic methods (1H NMR, 13C NMR, HMBC and ESI-MS). Five C-glycosylflavones were isolated and identified as 5,7,3',4'-tetrahydroxy-8-C-β-Dglucopyranosyl
flavone(Ⅰ), 5,7,3',4'-tetrahydroxy-6-C-[α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranosyl flavone (Ⅱ), 5,7,3',4'-tetrahydroxy-8-methoxy-6-C-β-D-glucopyranosyl flavone(Ⅲ), 5,4'-dihydroxy-6,7-dimethoxy-8-C-[β-Dxylopyranosyl-( 1→2)]-β-D-glucopyranosyl flavone(Ⅳ) and 5,4'-dihydroxy-6,7-dimethoxy-8-C-β-D-glucopyranosyl flavone(Ⅴ). CompoundⅠwas isolated from Callicarpa kwangtungensis Chun. for the first time while the others were found from Callicarpa for the first time. The preliminary anti-inflammatory activities of the five compounds were investigated. The results showed that compounds Ⅰ, Ⅱ and Ⅲ had significant in vitro anti-inflammatory activity.

The liposomes loaded with 10-hydroxycamptothecine were prepared by thin film hydration and high pressure homogenize method. The liposomes and free drug were separated by Sephadex G-75, the encapsulation efficiency was determined by HPLC. The eutectic points and glass transition temperatures of liposomes containing different lyoprotectants were determined by differential scanning calorimeter. The appearance, encapsulation efficiency and particle size before and after lyophilization of the products were compared to optimize the process and lyoprotectants. The results showed that 6％ sucrose was the suitable lyoprotectant, and the lyophilization process moved from prefreezing condition of 4 ℃ for 1 h，-18 ℃ for 12 h and -35 ℃ for 5 h, then lyophilized at -54 ℃ for 24 h. The lyophilized product was of good appearance, the encapsulation efficiency was (87.0±2.7)％ . The particle size varied little before and after lyophilization.

Esomeprazole magnesium, a proton pump inhibitor, was synthesized from 2-hydroxymethyl-3,5-dimethyl-4-nitropyridine by chlorination, condensation, asymmetric oxidation, methoxylation and then reacted with magnesium chloride. The overall yield was 73.6％(based on 2-hydroxymethyl-3,5-dimethyl-4-nitropyridine).

Polyphenols existing in plants have the antioxidant, anti-tumor, anti-inflammatoryand hypoglycemic as well activities as other pharmacological effects. In recent years, pomegranate attracted widespread attention because of its high content of polyphenols, which are mostly present in the peels. The progress of pomegranate polyphenols in kinds, extraction, separation, purification, pharmacological efects and toxicity are reviewed in this paper.

仿制药一致性评价是近期制药行业最重要的一项改革政策之一，正本清源，提高药品审评审批质量，调整制药产业品种结构，促进药品出口，提升国际竞争力，实现药品质量和价格的联动改革，促进医疗和医保的可持续发展，具有非常重要的意义。本文系统梳理了仿制药的定义和政策沿革，分析了仿制药一致性评价对医药、医疗和医保的影响，并提出企业相应的应对策略。

Vortioxetine hydrobromide was synthesized from 1-fluoro-2-nitrobenzene by nucleophilic substitution with 2,4-dimethylbenzenethiol to give 2-(2,4-imethylphenylthio)nitrobenzene, which was subjected to Pd/C-catalyzed hydrogenation to afford 2-[(2,4-dimethylphenyl)thio]aniline, followed by condensation with bis(2-chloroethyl)amine hydrochloride and salt formation with an overall yield of about 49％.

实施基本药物制度是推行新医改的重大措施之一，自安徽省推出基本药物集采方案以来，对此模式各方的评论褒贬不一。国务院出台国家级的基本药物集采政策后，各地又出现不同的变异。许多制药企业为此迷茫，有些甚至无所适从。本文详述了基本药物集采模式，以便制定2012年更好的营销策略。

The extraction of the antitumor constituents from Tibetan medicinal herb Phyllanthus emblica L. was optimized by orthogonal design with the in vitro efficacy as the index. The optimal process was as follows: 10 times of 70％ ethanol for 2 times, 2 h for each time. An HPLC method with muti-wavelength fusion was established for the determination of gallic acid (1), epicatechin (2) and ellagic acid (3) in antitumor constituents of Phyllanthus emblica L.. A C18 column was used with the mobile phase of 0.2％ phosphoric acid-acetonitrile by gradient elution at the detection wavelengths of 230 nm (1), 254 nm (2) and 280 nm (3). The calibration curves were linear in the ranges of 0.88 - 5.28 μg, 0.30 - 1.80 μg and 0.28 - 1.68 μg. Their average recoveries were 98.5％, 98.6％ and 98.2％, with RSDs of 1.02％, 1.00％ and 1.06％, respectively.

The fluidity and compressibility of several commonly used pharmaceutical excipients for direct compression, which were microcrystalline cellulose (Vivapur® PH 301, Ceolus™ KG-802 and Celldone® 200), lactose (Cellactose® 80 and Flowlactose® 100) and copovidone (Plasdone® S-630), had been evaluated. The fluidity and filling property of these excipients were characterized by Hausner ratio, Carr's index, angle of repose and Kawakita equation parameters. The tensile strength-pressure regression equation and the Kawakita equation were employed to characterize the compressibility. The results showed that compressibility of Plasdone® S-630 and Ceolus™ KG-802 were good among these excipients, but their fluidity and filling property were general. The fluidity and filling property of Cellactose® 80 and Flowlactose® 100 were excellent, but their compressibility were general. The fluidity, filling property and compressibility of Vivapur® PH 301 and Celldone® 200 were moderate. Through fully understanding of the powder properties of these excipients, it was good to contribute to a more reasonable choice direct compression excipients.

Imatinib mesylate was synthesized by reaction from 3-acetylpyridine(2) and N,N-dimethylformamide dimethyl acetal(3) to give 3-dimethylamino-1-(3-pyridinyl)-2-propylene-1-one(4), which was subjected to cyclization, reduction, acylation with 4-chloromethylbenzoyl chloride and reaction with N-methylpiperazine, followed by salt formation with an overall yield of about 58％(based on 2).

In the quality study of cefminox sodium sterile, a new impurity was identified by HPLC-MS. Its structure was speculated to be sodium (6R,7S)-7-[[[[(2S)-2-amino-2-carboxyethyl]thio]acetyl]amino]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-7-methylthio-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, and it was synthesized via substitution, acylation, deprotection and substitution from benzhydryl (6R,7S)-7-amino-7-methoxy-3-[(1-methyl-1H-tetrazol-5-ylthio)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate and methanthiol. The structure was confirmed by 1H NMR and MS. It had the same peak retention time as the new impurity of cefminox sodium.

The determination, extraction and purification of resveratrol from herbal residues of Polygonum cuspidatum Sieb. et Zucc. were investigated. The extraction process was optimized by orthogonal design with the content of resveratrol as index. The resveratrol in extract was separated by macroporous adsorptive resin and chromatography and then purified by recrystallization. The optimal extraction process was as follows: the herbal residues were extracted by 90％ ethanol with solid-liquid ratio of 1∶10 at 85 ℃ (reflux) for three times in 1.5, 1 and 0.5 h, respectively. The resveratrol in the extract dissolved in water was enriched by D101 macroporous adsorptive resin, followed with separation by silica column chromatography and recrystallization in acetone. The purity of final product was above 99％.

Metabolomics is a branch of system biology developed in recent years. It aims to reveal the variation of endogenous metabolic profiles in biological samples, such as body fluids, cells, and tissues, when subjected to external stimuli. Gas chromatography-mass spectrometry (GC-MS) has high resolution and detection sensitivity, with a standard spectral library to facilitate identification of endogenous metabolites. Thus, GC-MS has been widely employed in metabolomics. This review introduces key technologies in GC-MS based metabolomics, including derivatization, identification of metabolites, and data analysis. Meanwhile, typical applications in GC-MS metabolomics describing metabolic profiles of low-molecular-weight metabolites, such as amino acids, fatty acids, organic acids, and sugars are described.

虽然医药行业在我国所有工业中一枝独秀，并且即将出台的国家“十三五”规划也对医药工业发展有明显的支持力度，但随着新医改的深入及相关政策的相继出台，使医药产业链的上游医药工业发展受到了一定影响。比如，政府有关部门对公立医院的医院用药与医保用药实行2 个总量控制；在医改试点城市中，社保部门对医院用药金额实行总额预付制；分级诊疗组成各种医联体推进中实行按人头付费，临床治疗路径按病种付费的趋势更为明朗；政府主管部门又宣布对医院实施药占比的限制；抗菌药物分级管理已成为常态化且更趋严厉；各省市药品招标中的药品价格还是呈下降态势等，使医药工业的发展举步维艰。国家又对药品审评趋严，药品一致性评价进展速度加快，对GMP、GSP、GLP、GAP 监管力度加大，医保支付标准向通用名靠拢，互联网销售药品的目录清单至今未能出台等。这些政策制度迫使我国医药工业一定会在产品结构、药物创新、企业管理、销售模式等方面出现根本性变化，而这些医药产业链出现的变化肯定会给制药企业带来机遇与挑战。

Nanosuspensions in pharmaceutical field have been increasingly concerned with the rapid development of nanotechnology. Nanosuspensions are colloid dispersion system composed of pure drug sub-micron particles, which depend on surfactants to remain stability. The physical stabilities of  nanosuspensions, including sedimentation, agglomeration, crystal growth and crystal transition are summarized in this paper. The mechanism of stability and main solutions of the problems are briefly reviewed.

Gefitinib was synthesized from 3-hydroxy-4-methoxybenzaldehyde via conversion of aldehyde to nitrile, condensation with N-(3-chloropropy1)morpholine, nitration and reduction to give 2-amino-4-methoxy-5-(3-morpholin-4-ylpropoxy)benzonitrile, which was subjected to amidination with 3-chloro-4-fluoroaniline and cyclization in the presence of formic acid with an overall yield of about 44％.

4-Methoxy-5-(3-morpholinopropoxy)-2-nitrobenzonitrile was converted into the mixture of 2-amino-4-methoxy-5-(3-morpholinopropoxy)benzamide and 2-amino-4-methoxy-5-(3-morpholinopropoxy)benzonitrile via the transfer hydrogenation catalyzed by Pd/C, and then the mixture was transformed to N'-[2-cyano-5-methoxy-4-(3-morpholin-4-ylpropoxy)phenyl]-N,N-dimethylformamidine (5) in the presence of DMF and phosphoric chloride. Gefitinibwas finallyobtained through the Dimroth rearrangement of 5 with 3-chloro-4-fluoroaniline.The overall yield was about 66％.

中药新药研发一直是以高投入、高风险著称。本论文通过对2010 ～ 2015 年间我国中药新药注册申报获批品种数量、分类、品种剂型进行系统地对比分析，结果发现剂型选择适当的4 类、5 类、6 类中药新药获批的成功率较高，如果以这几类新药为研发重点，其研发风险将会显著降低。此外，选择注册分类与易批剂型两者间的最佳结合点，也可大幅提高中药新药注册申报的成功率。

Nano spray drying is a novel one-step granulation technology for the preparation of nanoparticles with narrow distribution. The biologically active molecule can maintain its structure and activity because of the mild preparation process. So this technology is suitable for the preparation of thermosensitive and sparingly soluble drugs. The principle, process parameters and the pharmaceutical applications in recent years of the nano spray drying technology are reviewed in this paper.

Hyaluronic acid (HA) possesses lots of advantages such as non-toxicity, low immunogenicity and biodegradability. The active targeting effect can be achieved through the interaction between HA and its receptors, especially CD 44. The purpose of this paper is to review the formulations, physicochemical and biological properties of HA-based targeted nano-drug delivery systems, such as HA-drug conjugates, nanogels, nanomicelles and nanoparticles. Trends and prospects of developments and applications of HA are introduced.

本文详尽阐述了进行仿制药研发时有关物质的研究思路，并针对目前业内出现的一些研发现状，提出了深刻诠释与理性观点。同时，根据自身工作经验提出了几点有关物质研究中的试验技巧与注意事项，为相关研究人员的工作开展与优化提供了有价值的参考。

Prostaglandins are important endogenous compounds with mutiple bioactivities. There have been 14 prostaglandin analogues approved by FDA in the market for the treatment of glaucoma, ulcer, early pregnancy, constipation, hypertension etc. Recent advances in the total synthesis of prostaglandins were reviewed, including the key intermediates such as Corey lactone, cyclopentenone derivatives, bicyclic enal. The seven-step process of prostaglandin PGF2α via the intermediate bicyclic enal starting from succinaldehyde is expected to greatly reduce the production cost of related drugs.

(3R,4S)-4-[4-(Benzyloxy)phenyl]-1-(4-fuorophenyl)-3-[[(2S,3R)-3-(4-fuorophenyl)oxiran-2-yl]methyl]azetidin-2-one(10) was synthesized from 4-fluorobenzaldehydevia Wittig reaction, hydrolysis, condensation with (S)-4-phenyloxazolidin-2-one, addition with N-[4-(benzyloxy)benzylidene]-4-fluoroaniline and cyclization in the presence of BSA and TBAF·3H2O. Compound 10 was converted to ezetimibe by Shi reaction, ring-opening with diphenyldiselenide and Pd/C catalytic hydrogenation with an overall yield of about 7％ and (S)-hydroxyl de > 99％.

Tofacitinib, an anti-rheumatoid arthritis drug, was synthesized from N-[(3R,4R)-1-benzyl-4-methylpiperidin-3-yl]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine(7) by removing the benzyl group and condensing with ethyl cyanoacetate in one-pot synthesis. The intermediate 7 could be obtained from 4-chloro-7H-pyrrolo[2,3-d]pyrimidine(2) by protection, substitution and deprotection. The total yield of tofacitinib was about 57％(based on compound 2) with purity of 99.4％.

基于2006～2010年的上市医药公司年报的相关数据，构建多元回归模型以研究专利产出与公司业绩之间的相关性与时滞性。回归分析的结果表明：专利产出对公司业绩具有一定的促进作用，却无法确定时滞期。提高医药专利成果的转化效率对促进公司业绩具有重要作用，因此，企业应当增加专利投入，提高专利管理水平，并制定符合自身发展需要的专利战略。

Mesoporous silica nanoparticles (MSNs) are novel multifunctional inorganic nanosized materials, which have been extensively applied to develop the controlled-release drug delivery systems owing to their unique pore structures, large specific surface area, narrow and adjustable pore size distribution as well as ease of surface modification. The drug loading of MSNs is dependent on their mesopore volume. After surface modification, MSNs have the properties of controlled-release and targeted delivery. Meanwhile, the biological safety of MSNs comes in the spotlight with more chances and more time that the public expose under them. This paper reviews the application of MSNs to drug delivery system through consulting related literatures at home and abroad in recent decade, the influence factors on their biological safety are also systematically summarized.