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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 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.     

�й�ʳҩ��ϵͳʳƷҩƷ��ȫӦ����������ѵ��Ŀ����̽��

??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 optimize the preparation process of liquiritigenin injection. METHODS Single factor experiment was carried out to determine the solvents, dosage of adjuvants, pH of solution, pyrogen removal method and sterilization process. RESULTS The optimal conditions were determined as follows: liquiritigenin was dissolved in 40% propylene glycol solution at pH 4.0-6.0. Ultrafiltration was employed to remove bacterial endotoxin. The solution was sterilized at 121 ??(97 kPa) for 15 min. CONCLUSION The established preparation process of liquiritigenin injection is reasonable and suitable for industrialized production.     

2009~2015�걱���а�ɳ���������ز�����Ӧ�������

??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).     

盐酸青藤碱醇质体的制备及其性质考察

目的研究盐酸青藤碱醇质体的最佳制备工艺,并考察不同促渗剂对其体外经皮渗透的影响和该制剂的皮肤过敏性。方法采用注入法制备盐酸青藤碱醇质体,以包封率为评价指标,通过正交设计优化最佳制备工艺;同时对其形态、Zeta电位、粒径大小进行分析;以氮酮为阳性促渗剂,研究丁香精油等不同促渗剂预处理离体小鼠腹部皮肤24 h后,对盐酸青藤碱24 h累积渗透量的影响。以豚鼠为动物模型,进行皮肤过敏性试验。结果所得青藤碱醇质体平均包封率为(66.18±1.84)%,平均粒径为(102.2±10.4)nm,Zeta电位为(52.4±1.5)mV。2%丁香酚预处理皮肤组,盐酸青藤碱醇质体24 h的累积渗透量为412.493 2μg/cm2,大约是醇质体组(未促渗)的1.6倍、水溶液组(未促渗)的5.8倍。该制剂外用对皮肤无致敏性。结论优选得到的盐酸青藤碱醇质体处方和制备工艺合理,醇质体稳定性良好,经皮给药安全。2%丁香酚可显著提高盐酸青藤碱的体外渗透效果。     

醇质体在经皮给药方面的应用

对一种新型经皮给药载体——醇质体进行综述研究分析.根据近10年国内外文献,总结醇质体的制备方法、性质、促透机制及应用进展.醇质体性质稳定,制备简单,包封率高,适用于各种性质的药物,与普通脂质体相比,显著提高了透皮速率,能传递药物至皮肤深层,增加药物在皮肤深层的滞留量.醇质体的制备工艺简单,可以包载各种类型的药物(包括水溶性、脂溶性、两亲性以及蛋白多肽类),并能达到较高的包封率.与普通脂质体相比,醇质体可以携带药物到达皮肤深层,并提高其经皮吸收速率;与传递体相比,醇质体更稳定;醇质体还可制成凝胶、贴剂、乳膏等方便临床用药的制剂,因而在局部用药和药物经皮吸收方面具有很好的应用前景.     

秋水仙碱醇质体的制备及体外经皮渗透研究

 目的制备秋水仙碱醇质体并考察醇质体作为秋水仙碱经皮给药载体的可行性。方法采用注入法制备秋水仙碱醇质体,紫外法测定其包封率,并以包封率为指标,利用正交试验法优化处方和制备工艺;采用TYJ-6A型透皮扩散实验仪,用小鼠腹部皮肤进行体外经皮渗透实验;比较不同给药形式对秋水仙碱经皮渗透的影响。结果最佳处方为乙醇3.3mL,豆磷脂0.25g和秋水仙碱0.025g,用注入法注入4min即可,包封率达57.0%。秋水仙碱醇质体的经皮渗透速率(6.54μg·cm^-2·h^-1)是水溶液的5.59倍,是普通脂质体的3.14倍,是体积分数为30%乙醇溶液的1.24倍。10h后皮肤中药物的滞留量大小顺序为:醇质体>体积分数为30%乙醇溶液>普通脂质体>饱和水溶液。结论醇质体能提高秋水仙碱的透皮速率,增加药物在皮肤中的滞留量。     

熊果酸醇质体的制备和体外透皮研究

目的:制备熊果酸醇质体并考察醇质体作为熊果酸经皮给药载体的渗透特性.方法:采用乙醇注入法制备熊果酸醇质体,并对其形态及粒径进行分析;采用TP-3型透皮扩散实验仪进行体外透皮吸收试验,比较熊果酸10%异丙醇溶液、熊果酸醇质体、熊果酸脂质体的经皮累积渗透量和渗透速率.结果:此方法制得的醇质体平均包封率为(95.83±0.86)%,平均粒径为(87.5±7.5)nln,Zata电位为-(38.4±3.6)mV.醇质体12 h的累积透过量为146.49μg·cm-2,12 h的渗透速率为12.17μg·cm-2.h-1.结论:醇质体包封率高,稳定性好,可显著促进熊果酸的透皮吸收.     

两种秋水仙碱醇质体的制备及评价

 目的 比较分别用不饱和磷脂和饱和磷脂为膜材,不同溶剂制得的秋水仙碱醇质体理化特性的差别。方法 采用注入法制备秋水仙碱醇质体, 正交设计法筛选处方。比较不饱和磷脂与饱和磷脂对其形态学、包封率、稳定性和经皮渗透的累积透过量的影响。结果 制备的两种醇质体形状呈圆球形或类圆形,结构完整。含不饱和磷脂醇质体平均粒径为100 nm,粒径分布较窄,包封率达58%;含饱和磷脂醇质体平均粒径为50 nm,粒径分布较宽,包封率达63%;含饱和磷脂醇质体的稳定性受高温和光照的影响都要明显小于含不饱和磷脂醇质体。含饱和磷脂醇质体的药物单位面积累计透过量和药物在皮肤中的滞留量也明显高于含不饱和磷脂醇质体的透过量和滞留量。结论 经初步评价,用氢化磷脂、乙醇和Tween 80所制备的秋水仙碱醇质体在包封率、稳定性和经皮渗透的累积透过量方面明显优于用大豆磷脂和异丙醇所制备的秋水仙碱醇质体。
     

炔雌醇醇质体凝胶的经皮渗透研究

 目的考察醇质体凝胶作为炔雌醇透皮给药载体的可行性。方法采用注入法制备炔雌醇醇质体,进而用卡波姆制备成凝胶,采用TK-6H型透皮扩散试验仪用人皮进行体外经皮渗透实验;以HPLC测定药物含量求算累积渗透量及稳态透皮速率,并测定药物在皮肤表皮和真皮中的滞留量。结果炔雌醇醇质体凝胶的经皮渗透速率(3.59μg·cm^-2·h^-1)是其水溶液的9.97倍,是体积分数为30%乙醇溶液的1.69倍,是凝胶制剂(含醇量30%)的1.45倍。24 h后皮肤中药物滞留量大小顺序为:醇质体凝胶>体积分数为30%乙醇溶液>凝胶>饱和水溶液。结论醇质体凝胶能提高炔雌醇的透皮速率,增加药物在皮肤内的滞留量。     

雷公藤甲素阿魏酸醇质体的制备与评价

目的研究雷公藤甲素阿魏酸醇质体最佳制备工艺,并考察其制剂性能和体外透皮特性。方法 MTT法确定雷公藤甲素与阿魏酸的配伍比例。采用注入法制备雷公藤甲素阿魏酸醇质体,在单因素实验结果的基础上,采用Box-Behnken设计优化处方,并对其粒径、包封率、电位、分析方法学及体外释放行为进行研究。采用改良的Franz扩散池进行醇质体的体外透皮实验。结果雷公藤甲素与阿魏酸的配伍比例为1∶100。醇质体优化处方为乙醇体积分数为20%,磷脂质量分数为2.2%,超声时间为90 s,制备出的醇质体外观为澄清液体,微有蓝色乳光,平均粒径为(46.75±2.39)nm,Zeta电位为(-46.32±3.76)m V,包封率为(67.72±1.10)%。醇质体中阿魏酸、雷公藤甲素的体外透皮行为均符合Higuchi方程。结论醇质体粒径小、分布均匀、稳定性良好,有良好透皮吸收特性,可为雷公藤有效成分的局部透皮制剂开发提供一定依据。     

十一酸睾酮醇质体制备及其体外经皮渗透研究

醇质体作为透皮给药的新载体,能明显促进药物的经皮渗透,该文以十一酸睾酮为主药,制备十一酸睾酮醇质体并对其形态、粒径、包封率、膜的流动性进行测定,同时以小鼠皮肤进行体外透皮实验,考察醇质体作为十一酸睾酮经皮给药载体的渗透特性,并比较了十一酸睾酮醇质体、脂质体及其醇溶液中的透皮行为.     

非那甾胺醇质体的体外经皮渗透研究

 目的考察醇质体作为非那甾胺经皮给药载体的渗透特性。方法分别采用注入法和薄膜分散法制备非那甾胺醇质体(ethosomes)和脂质体;用透射电镜观察所得醇质体和脂质体的形态;采用改良的TK-6A型Franz扩散池,用人皮进行体外经皮渗透实验;以HPLC测定一定时间点接受室中药物浓度,求算累积渗透量及稳态透皮速率,并测定药物在表皮层和真皮层中的滞留量。结果非那甾胺醇质体经皮渗透速率(134μg·cm^-2·h^-1)是其水饱和溶液的74倍,是脂质体的32倍,是30%乙醇溶液的26倍。24h时药物在皮肤中滞留量大小顺序为醇质体>30%乙醇溶液>脂质体>水饱和液。结论醇质体能显著促进脂溶性药物非那甾胺的经皮渗透,增加药物在皮肤中的蓄积,有望成为一类新型的皮肤给药制剂。     

�Ȼ���̼���׹ܸ��ع�ʶ��ص��Ʊ���͸Ƥ�����о�

??OBJECTIVE To study the preparation of carboxylated multi-walled carbon nanotubes loaded with podophyllotoxin (PPT-CNTs-COOH) as well as the characteristics of the in vitro transdermal penetration.METHODS PPT-CNTs-COOH was prepared by freezing milling method; IR, UV, XRD, and TGA were used to characterize the PPT-CNTs-COOH; HPLC method was used for determination of the content of podophyllotoxin loaded in the carboxylated multi-walled carbon nanotubes; franze diffusion cells method was used to determine the drug transdermal penetration rate.RESULTS The IR spectrum of PPT-CNTs-COOH showed the main absorption peaks of PPT and CNTs-COOH and the peaks changed obviously. Compared with free PPT, the UV absorption peaks of PPT-CNTs-COOH changed obviously. The PPT content in the CNTs-COOH gel was 58.0 ??g??mg^-1; the transdermal penetration rate of PPT gel was 7.08 ??g??cm^-2??h^-1 and that of the PPT-CNTs-COOH gel was 3.03 ??g??cm^-2??h^-1; the skin retention of PPT-CNTs-COOH gel was 3.04 ??g??cm^-2, far less than the 1.52 ??g??cm^-2 of PPT gel. Mild irritation developed within 24 h following removal of the PPT-CNTs-COOH gel, and disappears after 72 h.CONCLUSION Podophyllotoxin can successfully be loaded into the carboxylated multi-wall carbon nanotubes by using the frozen ball milling method. The product has remarkable sustained release effect in vitro and high retention in skin, which is beneficial to transdermal delivery.