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??OBJECTIVE To evaluate the effects of hormone replacement therapy(HRT) on the quality of life in climacteric women.METHODS The 202 patients were collected and divided into three groups according to whether or not they were treated with HRT: group 1 (not HRT), group 2 (HRT for the first time), group 3 (HRT for more than one year). All patients received follow-up visiting once per three months for one year. They were evaluated by the professionals through Kupperman index(KI), menopause-specific quality of life questionnaire(MENQOL), self-rating anxiety scale(SAS), self-rating depression scale(SDS). All patients were guided to improve the way of life.RESULTS After a year, KI, MENQOL and SAS in the three groups were improved significantly (P=0.003, 0.007, 0.014). KI and MENQOL were improved earlier than SAS. SDS was improved but not significantly(P=0.109). KI, MENQOL, SAS and SDS of patients in group 1 were improved significantly, but improved more weakly than those in group 2 and group 3. There is negative correlation between HRT and the values of every scale, and there is positive correlation between culture degree and SAS, SDS score values. CONCLUSION HRT canim prove the quality of life in climacteric women. The improvement in physical symptoms is earlier than that in mental symptoms. Anxiety and depression are more likely to occur in menopausal patients with high degree of education. Traditional Chinese medicine, exercise therapy and physical rehabilitation can be used as an auxiliary treatment for patients who are unable or unwilling to accept the HRT.     

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??OBJECTIVE To study the plasma protein binding rate of decapeptide in several species. METHODS Ultrafiltration was employed to separate the free and bound decapeptide, acetonitrile was used to precipitate protein, then the plasma concentration of decapeptide by HPLC-MS/MS. RESULTS The plasma protein binding rates of decapeptide at low, middle and high concentrations (50.0, 100.0, and 800.0 ng??mL^-1) were (95.9??1.1)%, (97.40??0.7)% and (94.9??0.6)% in SD rats,(96.8??0.8 )%, (97.8??0.2 )% and (96.9??0.5 )% in Beagle dogs, and (97.3??1.0 )%, (98.6??0.2 )% and (96.2??0.9)% in humans, respectively. The average plasma protein binding rate was 96.2% after subcutaneous administration at 200 ??g??kg^-1 in SD rats. And the average plasma protein binding rate was 97.1% after intramuscular injection at 320 ??g??kg^-1 in Beagle dogs. CONCLUSION Decapeptide has potent binding ability to plasma protein in several species. The plasma protein binding rate of decapeptide is independent of its plasma concentrations.     

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??OBJECTIVE To establish dose-related lung inflammatory injury in rats model with intratracheal atomization of lipopolysaccharide (lipopolysaccharides, LPS). METHODS Four groups of 4 rats were subjected to solvent or a single dose of LPS by intratracheal route using a IA-1B-2 inches-microsprayer. The male rats received 200 ??L solvent (control), LPS solutions (15, 5, 0.5 mg??kg^-1). All rats were sacrificed 24 h after dose administration, biochemical analysis and cell counts on bronchoalveolar lavage fluid (BALF) were performed on each rat. Lung, trachea and kidney were examined histologically. Serum chemistry profiles of creatinine, ALB, Na, K, Cl^- were detected. RESULTS Cell counts in BALF showed LPS groups had different degrees of inflammatory reaction. The alkaline phosphatase and total protein concentration were higher in LPS high dose group compared with other groups. In addition, the concentration of TNF-?? increased consistently with LPS dose and has statistical significance compared with the control group. Histopathology findings demonstrated that LPS produced an accumulation of foamy macrophages in the lungs and high degree of inflammation. CONCLUSION The results recommends intratracheally atomizing doses of LPS in rats model produced ranks of lung inflammatory injury.     

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??Dengue fever is one of the most important vector-borne human diseases caused by mosquito vector Aedes aegypti and Aedes albopictus. Dengue virus can cause dengue fever, dengue hemorrhagic fever and dengue shock syndrome. There are no approved drugs for the treatment of dengue disease so far. According to the mechanism of anti-dengue virus(anti-DENV) action, drugs under development for dengue disease can be divided into two categories:viral replication inhibitors and anti-cell factor pathway inhibitors. The former is further divided into DENV entry inhibitors, capsid protein inhibitors, NS3 protein inhibitors, NS5 protein inhibitors, and NS4B protein inhibitors; the latter is further divided into cell receptor inhibitors, lipid synthesis and metabolism inhibitors, and glucosidase inhibitors. The R&D of anti-DENV drugs is facing enormous challenges. Development of effective drugs which can be used for the treatment of four serotypes of dengue has a broad application prospect, and it will bring new hopes for dengue fever prevention and therapy.     

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??OBJECTIVE To establish an HPLC-MS method for the analysis of the impurity profile of cefotaxime sodium. METHODS Shimadzu-LCMS-IT-TOF was used with Waters XBridge Shield (RP18,4.6 mm??250 mm, 5 ??m) column. Mobile phase A was 20 mmol??L^-1 ammonium acetate (pH adjusted to 6.25)-methanol (92:8), and mobile phase B was set at 20 mmol??L^-1 ammonium acetate-methanol (60:40) (pH adjusted to 6.25).Gradient elution was performed at a flow rate of 1.0 mL??min^-1. ESI source was used.Positive and negative ion scanning was conducted in the range of m/z 150-900.The heating temperature was 200 ??, CDL temperature was maintained at 200 ??, atomization gas flow rate was 1.5 L??min^-1, dry gas pressure was 94.0 kPa, and the post-column diversion ratio was 1:4.Some related substances in cefotaxime sodium were identified by comparing the retention time in chromatography,[M+H]⁺ spectrum and MS² spectrum with those of reference substances, the others which haven't reference substances were deduced or speculated by analyzing the MS² or MSⁿ fragmentation with the help of a rule summarized from the MS² fragmentation of cefotaxime sodium and the reference substances of system suitability impurities. RESULTS Twenty-six related substances were separated and detected in the sample, all of which were identified or deduced. They were cefotaxime sodium isomeric compounds and homologs generated during the production process or degradation products. CONCLUSION The method can be applied in the identification and qualitative analysis of the related substances of cefotaxime sodium and the quality control and optimization of the synthesis of cefotaxime sodium.     

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目的以壳聚糖为酶触型结肠靶向给药系统的材料,研制可用于结肠靶向的多单元口服给药系统(迷你片),以期为结肠部位疾病治疗的药物输送提供重要参考。方法以结肠癌的治疗药物-吲哚美辛为模型药物,首先制备固体分散体,再采用直接压片法和包衣技术制备尤特奇-壳聚糖双层包衣结肠靶向迷你片,考察靶向迷你片在不同释放介质中的释药行为,采用小动物活体荧光成像技术考察制剂在体内的转运和吸收情况,并以比格犬为动物模型进行药动学研究和生物利用度评价。结果制备的壳聚糖多单元结肠靶向迷你片可以完整形态通过大鼠胃和小肠,并靶向在结肠部位缓慢释放,比格犬体内药动学数据表明,自制结肠靶向迷你片的释药时间显著延长,血药浓度平稳。结论本实验制备尤特奇-壳聚糖双层包衣多单元迷你片给药系统具有较好的结肠靶向性和缓释效果,可为治疗结肠疾病的制剂开发提供重要参考。     

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??OBJECTIVE To establish an HPLC-ELSD method for determination of mesaconine.METHODS Gemini C₁₈ 110A column (4.6 mm??150 mm,5 ??m) was adopted with the mobile phase consisting of methanol-0.1%TFA (25:75) at the flow rate of 0.6 mL??min^-1. The detector was Alltech ELSD 2000ES, with the drift tube temperature of 90 ?? and the airflow velocity of 2.3 L??min^-1. RESULTS Under this conditions, mesaconine and the related substances were well separated. The linear range of mesaconine was 0.40-0.60 mg??mL^-1 (r=0.999 6). RSD of injection precision and repeatability test were 0.04% (n=5) and 0.7% (n=6), the intra day and inter day precision RSD were 0.4% and 0.6%, respectively. The average recovery was 101.0% (RSD=1.1%, n=9). CONCLUSION The established method was specific, simple, accurate, and suitable for determination of mesaconine.     

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??OBJECTIVE To explore the mechanism of venlafaxine, paroxetine and St. John's wort extract by comparing the changes of endogenous metabolites profile in rat serum. METHODS These three drugs were employed to intervene in rats exposed to the chronic unpredictable mild stress (CUMS). Serum samples from all of rats were collected for a ¹H-NMR metabolomics analysis to find the differences of metabolic profile. RESULTS The resulting metabolic profiles demonstrated that these three antidepressants have an obvious difference effect on the endogenous metabolites in serum of the CUMS rats. It was also shown that the differential metabolites could be reversed in different degree. Six metabolites could be callback by venlafaxine while 4 metabolites by paroxetine and five metabolites by St. John's wort extract, in which lactate, choline, N-acetyl glycoprotein could be regulated to normal by all these three drugs. CONCLUSION The different drugs have difference regulation on the type and level of the endogenous metabolites, but also have similarities, which can provide a reference for the better understanding of the mechanism of antidepressant drugs.     

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??OBJECTIVE To prepare sulfadiazine solid dispersion, determine its solubility and dissolution in vitro, and investigate its physical properties. METHODS Using in vitro dissolution as an index, single factor test and orthogonal design were used to optimize the preparation process of sulfadiazine solid dispersion. The existing state of sulfadiazine was identified by DSC, IR spectroscopy, and powder X-ray diffraction. RESULTS The solubility and dissolution rate of sulfadiazine solid dispersion prepared by the optimized preparing process were increased by 17 times and 3 times respectively than crude sulfadiazine. Sulfadiazine existed in an amorphous state as shown by phase identification. CONCLUSION The solid dispersion prepared by the solvent-molten method with PEG4000 as the carrier can significantly improve the solubility and the dissolution rate of sulfadiazine.     

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??OBJECTIVE To improve the dissolution rate of fenofibrate (FNB) by using starch source mesoporous carbon (SMC) as a carrier and achieve controlled release of the drug by utilizing double-layer osmotic pump technology to improve the oral bioavailability. METHODS FNB was loaded into the mesoporous of NMS by adsorption method to prepare the drug loading system (FNB-SMC). Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXDR) were used to characterize the present state of the drug before and after being loaded. The dissolution rate of FNB-SMC was investigated by in vitro dissolution test, and the formulation of the double-layer osmotic pump tablets of FNB-SMC was optimized. The oral bioavailability of the self-made tablet was investigated by in vivo experiment in rabbits. RESULTS FNB existed in the mesoporous of SMC in an amorphous state. The in vitro dissolution test showed that NMS could significantly increase the dissolution rate of FNB, and the double-layer osmotic pump technology could achieve Zero-order release of the drug. The in vivo experiments showed that the oral bioavailability of the self-made tablets was significantly improved. CONCLUSION The combination of starch source mesoporous carbon carrier and double-layer osmotic pump technology prevente the burst effect and significantly improve the oral absorption of FNB.     

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??Drug solubility is the key factor that restricts the forming and clinical application of drugs in class II of the biopharmaceutics classification system (BCS). At present, making drugs into solid dispersion is an effective method to improve the dissolution rate. And with the research and development of mesoporous materials, using porous materials as the carrier to prepare solid dispersion becomes a hot research topic in recent years because of their unique structure advantages. Therefore,this paper elaborates the concept and characteristics of porous materials, summarizes the effects of pore size and ordered and surface groups on drug release properties, introduces the preparation method of solid dispersions with porous materials as the carrier, and finally summarizes the classification,characteristics and applications of the common porous materials in order to promote the application of porous materials in the pharmaceutical preparation of poorly water-soluble drugs and improve their bioavailability.     

基于聚合物无定形固体分散体技术的难溶性药物口服固体制剂开发

水难溶性是大部分药理活性成分难以开发成口服固体制剂的主要原因。聚合物无定形固体分散体(polymeric amorphous solid dispersion,PASD)能大大提高难溶性药物的表观溶解度及溶出速率,已经成为提高难溶性药物口服生物利用度的常用手段。然而由于PASD中药物处于高表面自由能的无定形态,在储存过程和溶出过程中易于向晶态药物转变从而丧失相应制剂优势。笔者从PASD的处方角度和制备技术角度,为研制质量稳定且后期开发风险低的PASD制剂提供结构化开发思路,并通过分析PASD的上市产品和专利趋势阐述了PASD技术在提高难溶性药物口服固体制剂生物利用度上的应用前景。     

熊果酸共晶固体分散体的体外特性研究

目的 采用共晶与固体分散体技术相结合策略,筛选合适的载体材料制备熊果酸共晶的固体分散体,更进一步提高熊果酸的溶解度、溶出度,以更好地改善其生物利用度。方法 选择泊洛沙姆188（F68）、聚维酮S630（PVP-S630）、硬脂酸聚烃氧（40）（S40）和羟丙甲纤维素（HPMC）4种载体材料,采用溶剂法,分别将原药、熊果酸-哌嗪共晶（UA-PP）与不同载体制成固体分散体。测定溶解度,进行体外溶出实验,比较并评价熊果酸制成共晶和固体分散体后改善生物利用度的潜力。结果 熊果酸共晶和熊果酸固体分散体均能增加熊果酸的溶解度和溶出度。共晶制成固体分散体后能进一步提高熊果酸的溶解度,加快其体外溶出。结论 将熊果酸共晶制成固体分散体后其溶解度和溶出度显著优于熊果酸共晶和熊果酸固体分散体。     

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??OBJECTIVE To prepare epalrestat (EP) solid dispersion by holt-melt extrusion (HME) technique in order to enhance its dissolution rate.METHODS Optimal formula was obtained by screening the carrier type and drug proportion. The dispersion state of EP in the solid dispersion and physical mixture were studied with differential X-ray diffraction (X-RD), Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) analysis techniques.RESULTS Poloxamer 188 was selected as the carrier with the optimal ratio of Poloxamer188 to EP of 1??3. The final solid powder product was homogeneous dispersion in light yellow color without any agglomerate.CONCLUSION The carrier of EP solid dispersion has significant impact on the dissolution behavior and state of EP. Using Poloxamer 188 as the carrier, holt-melt extrusion is an effective technology for improving the in vitro dissolution of EP.     

青黛脂溶性提取物固体分散体制备及溶解性研究

目的考察共研磨技术对难溶性药物的增溶能力。方法分别利用共研磨技术和共沉淀法制备青黛脂溶性提取物的固体分散体,并以靛玉红为指标,采用HPLC测定其表观溶解度。结果共研磨技术和共沉淀法有效提高了靛玉红的表观溶解度,不同载体研究表明共研物中亲水载体的羟基对改善难溶性药物的溶解度有着重要的影响。结论共研磨技术能有效地提高难溶药物的溶解度。     

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??OBJECTIVE To investigate the effect of copovidone (PVP/VA ), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and hydroxypropylmethylcellulose (HPMC) on drug dispersion and in vitro dissolution of solid dispersion by using nifedipine as model drug. METHODS Nifedipine solid dispersion was prepared by hotmelt extrusion (HME) technology, and the drug dispersion was evaluated by differential scanning calorimetry (DSC) and dissolution test. RESULTS DSC analysis RESULTS showed that nifedipine was amorphous in all HME extruders. Drug release from solid dispersion prepared with HPMCAS reached 100% in 30 min, but was only 75% for PVP/VA solid dispersion. Adding 5% HPMC E5 to PVP/VA extruders before dissolution test could raise the drug release from 75% to 90%. CONCLUSION HPMCAS or combination of PVP/VA and HPMC E5 are desirable polymers for nifedipine solid dispersion.     

热熔挤出技术制备固体分散体的辅料研究进展

热熔挤出技术（HME）是一种制备固体分散体的新技术。固体分散体的制备和性质主要依赖于辅料的选择。HME的辅料应具有较强的热塑性、较高的热稳定性、适宜的熔融黏度和原辅料的相容性。依据辅料的用途,HME的辅料主要分为载体、塑化剂和功能性辅料。依据载体溶解能力的不同,载体又分为水溶性、难溶性和肠溶性3类,对应制备出速释、缓控释功能的固体分散体。通过塑化剂和功能性辅料的修饰和辅助,进一步优化固体分散体的稳定性和释放特性。主要从载体、塑化剂和功能性辅料等方面对HME的辅料进行综述,旨在为固体分散体载体的选择、固体分散体的制备提供参考和依据。     

人参皂苷Rg3固体分散体的制备与体外特性研究

目的 采用固体分散技术,比较3种不同载体对人参皂苷Rg3的溶解度和体外溶出度的作用.方法 分别以泊洛沙姆188(F68)、聚维酮k29/32(PVP)和聚乙二醇6000(PEG)为载体,采用熔融法或溶剂法,制备人参皂苷Rg3固体分散体,测定溶解度,进行溶出度试验,并采用差热量热分析(DSC)法鉴别药物在固体分散体中的存在状态.结果 各种固体分散体均能显著增加人参皂苷Rg3的溶解度,加快其体外溶出.人参皂苷Rg3可充分分散在载体中并形成低共熔物.结论 F68作为载体制成固体分散体,对增加人参皂苷Rg3的溶解度和体外溶出度的效果优于PEG和PVP.