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??OBJECTIVE To proteins in toad venom. To investigate the by proteomic approach. METHODS The total proteins from the ear-side gland of toad were digested by trypsin, and the peptides were further analyzed by the NanoLC-linear trap quadropole (LTQ)-Orbitrap Velos Pro.. The raw data acquired by mass spectrometer were imported into MaxQuant software for the identification of peptides and proteins. The proteins were categorized based on gene ontology annotation in biological process, cellular component and molecular function. RESULTS A total of 407 protein groups and 880 peptides were identified. There were 76 pathways associated with the identified proteins in toad venom, including the 5-HT receptor mediated signaling pathway, beta adrenergic receptor signaling pathway, blood coagulation, cadherin signaling pathway, cholesterol biosynthesis, etc.. CONCLUSION This study lays the foundation for further exploration of the proteins in toad venom and their functions.     

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??OBJECTIVE To prepare ropivacaine ethosomal gel and study its transdermal permeation. METHODS The ropivacaine ethosomes were prepared by ethanol injection method. The formulation and the preparation method of ethosomes were optimized by orthogonal experiment. The particle size, morphology and encapsulation efficiency were evaluated,and the carbomer was added as the base for the preparation of the ethosomal gel. The penetration experiments of ropivacaine ethosomal gel through mouse skin were performed by Franz's cell. The cumulative penetration amount was calculated. RESULTS The obtained ethosomes were approximately spherical, the size were (127.6??4.8) nm. The entrapment efficiency of ropivacaine in ethosomes was (77.58??1.07)%. Accumulative permeation amount of ropivacaine ethosomal gel within 24 h was 73.07 ??g??cm^-2, which was about 1.56 times of normal gel. CONCLUSION The gel is feasible in preparation technique, controllable in quality and can significantly promote transdermal penetration of ropivacaine.     

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??OBJECTIVE To investigate the effects of combination treatment with L-carnitine and 5-fluorouracil on the proliferation and cell apoptosis of gastric cancer MGC803 cells. METHODS MGC803 cells were divided into control group, 5-fluorouracil group and the combination of L-carnitine and 5-fluorouracil group (L-carnitine+/??5-fluorouracil group) in vitro. The inhibitory rate of cells was measured by MTT assay. The apoptosis rate and cell cycle of cells were detected by FLOW. Western blot was used to analyzed the expression of Bcl-2, Bax, adenine nucleotide translocator1(ANT1) and cleaved-PARP. RESULTS Compared with 5-fluorouracil group, the inhibition rate of MGC803 cells was increased when cells were treated with the combination of L-carnitine and 5-fluorouracil. The apoptosis rate of cells was raised and the cells were blocked at S phase. In addition, the combination group can decrease the expression of Bcl-2 and increase the expression of Bax, ANT1 and cleaved-PARP. At the same time, the apoptosis rate of cells and the cell cycle were different with the different dosage regimen when treated with the combination. Compared with the L-carnitine+5-fluorouracil group, the apoptosis rate of cells was increased to (24.17??3.12)% from (19.60??1.06)% (P<0.05). The G₀/G₁ phase proportion of cells was decreased to (62.62??1.04)% from (72.95??0.91)%,and the S phase proportion of cells was increased to (37.35??1.03)% from (27.05??0.91)% (P<0.001). CONCLUSION Treatment with L-carnitine and 5-fluorouracil could enhance the inhibitory effect of 5-fluorouracil on MGC803 cells. The possible mechanism of action is achieved by regulating the expression of Bcl-2 protein family and influencing the cell cycle.     

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??OBJECTIVE The emergency practice and training program of food and drug safety in China's food and drug administration system is studied. METHODS The relevant situation of food and drug safety emergency drills and training in European Union and the emergency drills and training of food and drug in our country are learned. RESULTS The food and drug emergency drills and training programs in our country is explored and prospected, and the related thinking and enlightenment is put forward. CONCLUSION The food and drug safety emergency drills and training, innovation the exercise form and the content of the exercise should be vigorously strengthened, a hierarchical field emergency drill mechanism, prominent combat emergency drills will be established, and pay attention to emergency response drill assessment.     

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??OBJECTIVE To provide clinical reference for rational drug use by retrospectively reviewing oxaliplatin induced serious adverse reaction reports in Beijing area in recent 7 years and investigating the characteristics of these adverse reactions. METHODS Oxaliplatin induced adverse effect reports received by Beijing Municipal Drug Adverse Reaction Monitoring Center from January 1,2009 to December 31, 2015, were collected and analyzed. RESULTS Forty-one serious ADR reports were related with oxaliplatin, with one case evaluated as irrelevant,which accounted for 9.36% of the total reports. The 14 male and 26 female cases were reported, with an average age of (56.21??12.85) years old. One case occurred at the first cycle of chemotherapy and 14 cases did not occur at the first cycle. The occurrence time of the rest 25 cases was not clear. The manifestations of oxaliplatin induced adverse effect usually presented as systemic symptoms. The ADR onset was 0.5 min to 59 d after drug infusion which caused 2 cases of death, 1 case of sequelae, 9 cases of delayed disease duration, and 28 cases of no significant influence. CONCLUSION Careful monitoring is suggested especially for elderly people during oxaliplatin infusion. Attention is advised for patients requiring multi-cycles of chemotherapy, especially when they started a new round of treatment. Extending infusion time as well as using antihistamines and corticosteroids are believed to be effective to decrease the risk of ADR. Treatment plan needs to be modified by evaluating patients' adverse effect. The decision of dose reduction or withdrawal is to be made, if needed, to ensure the safety of drug use.     

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??OBJECTIVE To establish a method for determining the contents of saikosaponin a, b₁, b₂ and c in Radix Bupleuri formula granules by HPLC-MS/MS, and provide scientific basis for the quality standards. METHODS The samples were separated on a Kinetex C₁₈ column (2.1 mm??100 mm, 2.6 ??m) by gradient elution at the flow rate of 300 ??L??min^-1 using acetonitrile and 0.1% aqueous formic acid as the mobile phase. The column temperature was maitained at 40 ??. Multiple reaction monitoring scanning (MRM) was employed for the quantification with switching electrospray ion source polarity in negative mode. The ion spray voltage was set at -4 500 V and the turbo spray temperature was maintained at 550 ??. RESULTS There was significant correlation between the peak area and concentration of each compound within the test range (r??0.999 1). The average recoveries were from 97.44% to 100.56%. CONCLUSION Saikosaponin a, b₁, b₂ and c are determined by this method simultaneously. The method is available with good reproducibility and can control the quality of Radix Bupleuri formula granules effectively.     

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??OBJECTIVE To investigate the influence and mechanism of different doses of Yangxinshi on infarction region angiogenesis of Wistar rats after acute myocardial infarction. METHODS Sixty healthy male Wistar rats were randomly divided into five groups, named as follow:group A: rosuvastatin group (0.75 mg??kg^-1??d^-1), group B: high-dose Yangxinshi(0.27 g??kg^-1??d^-1),group C:mid-dose Yangxinshi group (0.18 g??kg^-1??d^-1),group D: Low-dose Yangxinshi group (0.09 g??kg^-1??d^-1),group E:saline control group. A, B, C, D group was respectively given the drug by gavage, group E received normal saline by gavage. The models of acute myocardial infarction can be established in the forth week . After continued drugs for 4 weeks, rats were killed before detected blood biochemicalindexes such as blood lipids, liver and kidney function. Myocardial tissue was sliced and stained infarcted myocardium by HE to observe the pathological changes, also extract ischemic and infarct myocardium tissue protein and test VEGF protein expression with immunohistochemistry. RESULTS Myocardial tissue HE staining were observed a lot of survival island cardiomyocytes and neonatal thin-walled capillaries in four treatment groups , however,control group exist less normal cardiomyocytes and capillaries mainly disappear. Immunohistochemistry RESULTS showed high-doses of Yangxinshi group express higher VEGF protein compared with mid-dose group, low-dose group and control group, the difference was statistically significant (P<0.05), VEGF protein expression was significantly increased the in mid-dose and high-dose Yangxinshi groups than rosuvastatin group, the difference was statistically significant (P<0.05). CONCLUSION Yangxinshi promote production of VEGF protein and angiogenesis of ischemic myocardium ,in addition its role and its dose is positive correlated. VEGF protein expression was significantly increased the in mid-dose and high-dose Yangxinshi groups than rosuvastatin group, the difference is statistically significant (P<0.05).     

用两步超滤法制备伸筋草注射液的实验研究

实验考察了伸筋草注射液制备过程中特别是超滤精制时药液的pH值、浓度等条件对注射液质量的影响，发现较强酸性、较低浓度的药液在超滤时有效成分的滤过率高，反之则滤过率低，并依此制定出一种能在不同条件下分别除去药液中的大分子杂质和小分子杂质的新的精制方法──两步超滤法，提高了注射剂的质量，减少了有效成分的损失。文中还对两步超滤法的机理进行了初步探讨。     

盐酸消旋山莨菪碱注射液处方的优化研究

目的 优化盐酸消旋山莨菪碱注射液工艺处方,提高产品稳定性。方法 盐酸消旋山莨菪碱注射液工艺处方改为预先配制盐酸溶液,再将消旋山莨菪碱缓缓加入盐酸溶液中,成盐时pH值控制在5.0～5.2。结果 工艺处方更改后,可降低产品的有关物质,提高稳定性。结论 经处方优化后,盐酸消旋山莨菪碱注射液可在室温条件下稳定储存。     

不同剂型去甲斑蝥素肝脏注射急性毒性比较

目的：比较去甲斑蝥素缓释注射课题与普通注射液肝脏注射的急性毒性、为缓释剂型的临床肝脏注射应用提供实验依据。方法：６０只小鼠及１８只大鼠各随机分为３组,分别肝脏注射等量去甲斑蝥素缓释溶液,普通水剂及药物缓释辅料泊洛沙姆４０７溶液,观察小鼠行为状态、生存情况及大鼠肝脏病理形态学变化。结果;注射去甲斑螯素缓释溶液组小鼠死亡率低于普通水溶液组;泊洛沙姆４０７小鼠肝脏注射的ＬＤ５０〉６２５ｍｇ／ｋｇ,缓释制     

克班宁注射剂制备工艺的初步研究

目的制备性质稳定的克班宁注射剂,优选最佳制备工艺.方法采用正交试验法,以可见分光光度法对其色泽变化进行考察.结果配制0.25%克班宁注射剂的最佳工艺为:以盐酸为成盐用酸,pH为4.4,NaHSO3为抗氧剂,熔封通CO2且避光保存.以该法配制的克班宁注射剂沸水加热6 h,强光照射1 2 h,色泽无变化.结论按上述方法配制的克班宁注射剂稳定性较好.     

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??OBJECTIVE To investigate the compatibility of dexamethasone sodium phosphate injection and ondansetron hydrochloride injection. METHODS The dexamethasone sodium phosphate injection and ondansetron hydrochloride injection were dissolved with 5% glucose injection and 0.9% sodium chloride injection respectively at commonly used concentrations in clinic. The contents of dexamethasone sodium phosphate and ondansetron hydrochloride were determined by HPLC at 0,3,6,and 24 h after the preparation of solution. Meanwhile,the pH and number of indiscerptible particles in these solutions were also determined. RESULTS The mixtures of the two drugs were highly stable within 24 h,without obvious change in pH and color. The numbers of insoluble particles greater than 10 and 25 ??m were acceptable. CONCLUSION Dexamethasone sodium phosphate injection is compatible with ondansetron hydrochloride injection.     

活性炭对生脉注射液人参皂苷Re的吸附作用

目的　观察活性炭对生脉注射液中人参皂苷 Re的吸附。方法　设计影响活性炭吸附人参皂苷 Re的因素如加炭量、p H值、温度等进行试验 ,用高效液相色谱法测定人参皂苷 Re的含量的变化。结果　实验证明 ,活性炭对生脉注射液中的人参皂苷 Re有明显的吸附作用 ,并随加入量的增大而明显增强 ,温度对吸附有一定的作用 ,p H值对吸附影响不大。结论　配制生脉注射液时要严格控制活性炭的加入量     

甘草苷体内暴露特征及体外跨膜转运机制研究

目的总甘草素是甘草苷在体内的主要暴露形式,对两者在大鼠体内暴露特征及体外跨膜转运机制进行研究,为以甘草苷单体为新药的进一步开发提供依据。方法采用LC-MS/MS分析方法测定大鼠给药后不同时间点血浆样品中的总甘草素浓度,并应用WinNonlin.6.3软件采用非房室模型的统计矩法计算药代动力学参数;同时测定大鼠ig给药后组织匀浆中的浓度,考察不同类型甘草素在各组织中的暴露特征;应用体外MDCK-MDR1细胞模型,研究甘草苷、甘草素的跨膜转运能力及其机制。结果 ig给药后在大鼠体内,甘草苷不呈线性动力学特征;血浆和大部分组织中主要以甘草素的II相结合产物存在,肝、子宫、卵巢、胃和肠组织中主要为游离甘草素;总甘草素暴露量排序为肠血浆肝肾肺胃子宫卵巢脂肪心脾肌肉睾丸,且不易产生组织蓄积现象;甘草素跨膜转运能力较甘草苷良好,且均不是P-gp转运体的底物。结论甘草苷不呈线性动力学吸收特征;甘草素在组织中暴露特征表现为不同组织中甘草素的存在形式和分布程度差异较大,总甘草素不易产生组织蓄积现象;两者均为被动扩散跨膜转运方式。     

葫芦素毫微粒冻干针剂的研究

目的 :制备稳定的、易再分散的葫芦素聚乳酸毫微粒 (Cu-PLA-NP)冻干针剂。方法 :选用适宜填充剂制备Cu-PLA-NP冻干针剂 ,并评价其相关理化性质。结果 :冻干前后毫微粒形态、粒径、pH、包封率及载药量无明显变化 ,再分散性良好 ,制剂稳定 ,含水量合格。其临界相对湿度为 69.52%。结论 :在适宜的处方及工艺条件下制备的Cu-PLA-NP冻干针剂是可行的。     

全缘千里光碱脂质体凝胶剂制备工艺的研究

 目的制备具有高包封率和良好稳定性的全缘千里光碱(INT)脂质体,并将其制成凝胶剂。方法以离心-超滤法测定脂质体的包封率。以包封率为主要指标筛选脂质体制备工艺、主要辅料磷脂与处方中磷脂-胆固醇比例;通过均匀设计法优选制备脂质体的工艺条件;考察药脂比包封率;通过pH梯度主动载药法提高脂质体的包封率;确定脂质体及其凝胶剂的处方工艺,并进行质量与稳定性评价。结果制备INT脂质体的最适方法为薄膜分散法,最适的磷脂为注射级大豆磷脂,处方中磷脂-胆固醇的最佳比例为4∶1;药脂比为1∶10时,薄膜分散法制备INT脂质体的最佳工艺参数为:成膜温度46.3℃,水化液用pH4.0柠檬酸缓冲液(CBS4.0),体积为15.0mL,包封率可达57.45%;药脂比由1∶20增加1∶2,包封率均在60%左右;pH梯度主动载药可显著提高脂质体的药物包封率,主动载药中较合适的水化液为CBS4.0。优选的脂质体包封率为75.21%,平均粒径为284nm,Zeta电位为2.23mV,稳定性实验证明,该脂质体及其凝胶剂稳定性良好。结论薄膜分散法结合pH梯度载药可以制备稳定且高包封率的INT脂质体凝胶剂。     

基于物质基础组分结构的消癌平注射液多维结构质量控制的研究思路

中药制剂的质量控制一直是中药国际化发展道路上所关注的一个重要问题。中药成分的复杂性特点,使得中药制剂生产及其质量控制成为一大难点,如何实现制备质量稳定、可控的中药制剂是当前中药制剂领域所急需解决的关键问题。作者认为,结合中药制剂制备工艺特点,采取生产过程多维、动态的质量控制模式可能成为解决中药制剂质量可控的方法之一。因此,作者提出基于中药物质基础组分结构的多维结构质量控制的研究思路,该文主要是针对如何在整个变化动态过程中(工艺过程生产中间体的成分分析监控、药材源头、生产中间体到最后制剂成品)控制中药制剂质量的稳定性。作者以消癌平注射液为例,阐述消癌平注射液多维质量控制过程,希望该方法可以为中药现代制剂的质量控制提供新的思路。