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??OBJECTIVE To establish an oil bath method to determine the D values and Z value of biological indicators in spore suspension forms for moist heat sterilization. METHODS Spore suspension was sealed up in glass capillary, which was heated by thermostat oil bath. D value and Z value were determined by survivor curve method. RESULTS The D values of Geobacillus stearothermophilus ATCC7953 spores suspension at 117, 121 and 125 ?? were 7.04, 2.18 and 0.65 min, respectively, and the Z value was 7.75 ??. The D values of Clostridium sporogenes CMCC(B)64941 spores suspension at 95, 100 and 105 ?? were 11.36, 2.85 and 0.45 min, respectively, and the Z value was 7.14 ??. CONCLUSION By simulating the sterilization of aqueous liquid with oil bath method, the D values and Z values of biological indicators in spore suspension forms for moist heat sterilization can be determined conveniently and accurately(r² is above 0.980 0). The oil bath method can be used for heat resistance research of biological indicators in spore suspension form for moist heat sterilization.     

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??OBJECTIVE To study the chemical constituents from the rhizome of Drynaria fortunei and the protective effects of them on PC12 cells induced by A??_25-35. METHODS The compounds were isolated and purified by silica gel, Sephadex LH-20, ODS column chromatography, and their structures were identified on basis of spectroscopic methods, such as MS and NMR. PC12 cells were treated with A??_25-35 to establish the Alzheimer' s disease models. The compounds of different concentrations were added into culture medium to detect the protection. MTT assay was used to detect cell vitality and to observe the protective effects of compounds on PC12 cells induced by A??_25-35. RESULTS Nine compounds were isolated and identified as naringin(1), neoeriocitrin(2), 5,7-dihydroxychromone-7-neohesperidoside(3), (E)-4-O-??-D-glucopyranosyl caffeic acid(4), kaempferol(5), luteolin(6), protocatechoic acid(7), psoralen(8), and ??-sitosterol(9) . The cell experiments were performed on the compounds 1-8 and the results showed they can promote the proliferation of PC12 cells. The cell vitality increase with concentration rising, and the difference is statistically significant (P<0.05). CONCLUSION Compounds 1-8 play an important role in protecting A??_25-35-induced injury in PC12 cells and they are the main active components of Drynaria fortunei in the protection of central nervous function.     

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??OBJECTIVE To study the effect of lysine decarboxylase (LDC) gene on the accumulation of matrine(MA) and oxymatrine (OMA) in cotyledon of Sophora alopecuroides L. germinating seeds. METHODS The S.alopecuroides germinating seeds were stressed by different mass fractions of PEG 6000, and the contents of MA and OMA were determined by high performance liquid chromatography (HPLC) and the expression level of LDC was analyzed by real-time fluorescence quantitative PCR (qPCR) after 72 h treatment. RESULTS The contents of MA and OMA decreased in the cotyledon under light stress (PEG mass fraction<15%), while increased with the stress getting higher (PEG mass fraction>20%). The analysis of qPCR revealed that the LDC expression level was decreased first, and then increased with the stress rising. The changes of the contents of MA and OMA were parallel with the expression level of LDC especially under light and severe stress. CONCLUSION There is certain association between the accumulation of MA and OMA and the gene expression quantity of LDC. The results is of significance for illustrating the role of LDC in the biosynthetic pathways of MA and OMA.     

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??OBJECTIVE To investigate the factors influencing the adherence of asthma and chronic obstructive pulmonary disease (COPD) patients with inhaler drug device, and improve patients adherence. METHODS One hundred patients were collected and randomly divided into intervention group and control group. By seven steps form England in combination with the usage of Chinese patients with inhaler drug device, the suction operation was into ten steps and the reasons of the poor adherence were analyzed. Observed two groups of devices adherence, adverse reactions, the number of exacerbations greater than or equal to 2 times. RESULTS Compared with control group, 6 months after evaluation, the devices adherence of intervention group increased by 24.82%-35.09%. Incidence of adverse reactions decreased by 8.00%. The number of exacerbations greater than or equal to 2 times was reduced by 12.00%. CONCLUSION The adherence of inhaler drug device is associated with incidence of adverse reactions and the number of exacerbations. The pharmacists can improve patients adherence by intervene the operation of device . And the device adherece brought into the assessment of medication adherence is necessary.     

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??OBJECTIVE To discuss the mode of grading pharmaceutical care on patients with asthma and chronic obstructive pulmonary disease (COPD). METHODS Combined with guidelines on patients with asthma and COPD, ,the standards for grading pharmaceutical services were formulated. Two hundred and fifth-six patients are divided into intervention group and control group. And patients were given different levels of pharmaceutical services with grading standard. Before the intervention, 3 months and 6 months after intervention, grading score, medication compliance and lung function index (FEV1/ FVC, FEV1% value) were expected to make the comparison between the two groups. The incidence of adverse reactions, the number of exacerbations greater than or equal to 2 times and clinical control rate were observed. RESULTS Compared with control group, 6 months after intervention, the proportion of first intervention decreased by 25%, the incidence of adverse reactions decreased by 7.82%, the number of exacerbations greater than or equal to 2 times was reduced by 7.81%, the rate of clinical effective increased by 23.43%, FEV1/FVC, FEV1% value and medication adherence has improved significantly (P<0.05). CONCLUSION The grading pharmaceutical care for patients with asthma and COPD, can help pharmacists find the crucial guardianship objects in the shortest time, and improve the quality of pharmaceutical care and clinical effect.     

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??OBJECTIVE To screen pressure sensitive adhesive system and penetration enhancer of rutaecarpine transdermal patch. METHODS The patch was prepared by solvent evaporation method. The ratio between pressure sensitive adhesive (Eudragit E100), crosslinking agent (succinic acid) and plasticizer (dibutyl sebacate) of the rutaecarpine patch were screened through Box-Behnken design by using adhesion (stick power, shear strength, peel force) as the index. The ratio between pressure sensitive adhesives and chemical enhancers (azone and oleic acid) were screened by adhesion and permeation experiments in vitro using custom design, which were carried out by using improved Franz diffusion cells through excised mice skin. RESULTS The optimized formulation of rutaecarpine transdermal patch consisted of 83% pressure sensitive adhesives (63.5% Eudragit E100, 5.5% succinic acid, 14% dibutyl sebacate), 10% azone, 6.4% oleic acid and 0.6% rutaecarpine. The stick power, shear strength, and peel force of the patch were 15 steel balls, (10.97??0.32) h and (0.16??0.02) kN??M^-1, respectively. The cumulative permeation amount and permeation rate of the patch were (29.71??1.19) ??g??cm^-2 and (1.36??0.10) ??g??cm^-2??h^-1, respectively. CONCLUSION The optimized rutaecarpine patch show increased permeation and appropriate adhesion. This study provides the basis for future research.     

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??Anthracyclines generally possess antitumor activities and they are clinically broad-spectrum anticancer antibiotics. But some of them have prominent toxicities and drug resistances. These limit their further development and applications. However, proper structural modifications can sometimes solve these problems. So lots of new anthacyclines are obtained through total-synthesis or partial-synthesis for the purpose of finding more effective new drugs. In this paper, combing with our previous work and referring the literatures, we briefly introduce the mechanism, drug resistance, cardiac toxicity of anthracycline, and mainly review the structure-activity relationships of ring A, sugar moieties and twin drugs of anthracyclines. These can provide powerful evidence for further developments of new anthracyclines.     

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??Recently, a new manner of cell death named ferroptosis is gradually accepted by researchers. It is characterized by cell death accompanied by a large accumulation of iron and lipid peroxidation. Numerous studies have shown that the manner of death are closely related to neurotoxicity, cancer, ischemia reperfusion injury, renal injury and iron metabolism related diseases,so the research of the mechanisms and regulative drugs for ferroptosis is particularly important. This paper reviewed the mechanisms, inducers, and inhibitors of ferroptosis and summarized the diseases related to ferroptosis, so that providing evidence for study the further mechanisms and development of new drugs for the ferroptosis-related diseases.     

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??OBJECTIVE To investigate the preventive protective effect of matrine(MT) on ??-naphthl isocyanate(ANIT)-induced cholestasis in rat, and to explore its possible mechanism. METHODS Thirty SD rats were randomly divided into five groups with six rats in each group: normal control group, model group, low dose matrine(5 mgkg^-1), high dose matrine group(10 mgkg^-1) and positive control group(ursodeoxycholic acid 100 mgkg^-1), which were administered continuously for 7 d. All groups except the normal control group were given 60 mgkg^-1 ANIT at the fifth day. After the last administration, all rats were fasted 24 h and arterial blood were collected to detect the indexes of total bilirubin(TBIL), aspartate aminotransferase(AST), alanine aminotransferase(ALT) and alkaline phosphatase(ALP). The livers were picked for HE staining, immunohistochemistry(IHC) analysis and Western blot(WB), to indentify the protein expressions of CYP3A4 and PXR. RESULTS Compared to model group, low-dose and high-dose matrine decreased TBIL, AST, ALT and ALP significantly; IHC analysis showed that the expression of CYP3A4 in high-dose group was significantly higher than that in model group(P??0.05). The results of WB showed that the expressions of CYP3A4 and PXR in two matrine groups were significantly higher than that in model group(P??0.05), however, only CYP3A4 expression in UDCA group was significantly higher than that in model group(P??0.05). CONCLUSION Matrine could improve cholestatic liver injury in rats and its mechanism might be related to the upregulation of CYP3A4 expression controled by inducing PXR expression.     

药用硫化汞理化性质及药效、毒理学研究

对药用硫化汞的形态结构、理化性质、含量测定及药效毒理学进行了归纳,查阅了国内外文献30篇,探讨了药用硫化汞中汞元素的体内存在形态、体内含量对其毒性的影响。研究发现,朱砂、银朱等药物中的硫化汞为具旋光性的红色结晶,在体外的存在形式通常是不溶于水的Hg2+,还有一部分可溶性的Hg2+,Hg+,含汞药物产生毒性的原因主要是其中的可溶性汞,而主要成分是硫化汞的药物,如朱砂,在肠道中可能以汞与硫各种形式的配合物存在,多硫化汞配合物是其中的一种重要形式,多硫化汞的形式降低了游离汞的含量,毒性降低。药效毒理的研究发现,含汞药物的临床用量一般情况下不会引起中毒。实践表明,通过采取现代分析手段制定相应规范,可以在保证药效的基础上,提高含汞药物的安全性。     

壳聚糖修饰的丹皮酚PEG-PLGA纳米粒的制备及其体外释药性能考察

目的:制备壳聚糖修饰的丹皮酚聚乙二醇-(聚乳酸-羟基乙酸共聚物)(PEG-PLGA)纳米粒,对其体外性质进行表征,考察纳米粒的体外释药性能,为丹皮酚的新型纳米制剂研究提供参考。方法:以PEG-PLGA为载体材料,壳聚糖为表面修饰剂,采用纳米沉淀法制备了壳聚糖修饰的丹皮酚PEG-PLGA纳米粒,利用正交试验优化处方工艺,并对其体外性质进行表征。以p H 7.4磷酸盐缓冲液为释放介质,考察壳聚糖修饰的丹皮酚PEG-PLGA纳米粒的体外释药行为。结果:载药纳米粒经壳聚糖修饰后,Zeta电位由负电荷转为正电荷且更加稳定,粒径略有增加。制备出的纳米粒外观呈球形,平均粒径和Zeta电位分别为(96.6±3.2)nm,(30.61±0.34)m V,载药量及包封率分别为10.87%和79.37%。体外释药试验表明载药纳米粒24 h的累计释放率62.4%。结论:按优选的处方成功制备了壳聚糖修饰的丹皮酚PEG-PLGA纳米粒,该制剂的体外性质良好且具有一定的缓释特性。     

壳聚糖修饰的雷公藤甲素聚乙二醇-聚乳酸纳米粒的制备及质量评价

 目的制备壳聚糖修饰的雷公藤甲素聚乙二醇-聚乳酸纳米粒,并对其质量进行评价。方法通过降解反应合成低相对分子质量壳聚糖,采用黏度测定法和酸碱滴定法测定其黏均相对分子质量和脱乙酰度;以聚乙二醇-聚乳酸为载体材料,低相对分子质量壳聚糖为修饰剂,采用乳化溶剂挥发法制备壳聚糖修饰的雷公藤甲素聚乙二醇-聚乳酸纳米粒;并比较壳聚糖修饰前后纳米粒的性质;以纳米粒形态、粒径、Zeta电位、包封率、载药量及体外释放度为指标评价其质量。结果壳聚糖的黏均相对分子质量为20000,脱乙酰度为90%;经壳聚糖修饰后,纳米粒的粒径和Zeta电位均增大,包封率几无变化;所制备的纳米粒外观呈圆形或类圆形,平均粒径、Zeta电位、包封率和载药量分别为（202.62±1.52）nm、（0.17±0.12）mV、（58.20±2.43）%和（1.25±0.13）%。体外释放实验表明,纳米粒体外释放t_1/2为1.1h,在10.0h累积释放率达到74.0%。结论壳聚糖修饰对纳米粒的粒径及Zeta电位影响较大;制备的纳米粒包封率较高,粒径小,体外释放具有一定缓释特征。     

蝇蛆壳聚糖急性毒性实验

目的观察蝇蛆壳聚糖的急性毒性反应。方法蝇蛆壳聚糖以最大浓度及最大给药体积的药液灌胃连续给药3次。连续观察14d,记录小鼠毒副反应情况。蝇蛆壳聚糖腹腔注射给药1次,连续观察14d,记录小鼠毒副反应情况。结果观察14d,灌胃给药全部动物健存,小鼠体重与空白对照组差异无显著性,未见任何毒性反应。计算蝇蛆壳聚糖最大给药量为2700mg／kg体重,相当于成人日用量的67．5倍。腹腔注射给药亦未见任何毒性反应。结论蝇蛆壳聚糖毒性较小。     

白藜芦醇壳聚糖纳米粒的制备及理化性质

 目的建立白藜芦醇壳聚糖纳米粒的制备方法。方法以三聚磷酸钠作为离子聚合剂,在弱酸性条件下制备白藜芦醇壳聚糖纳米粒;考察pH值、壳聚糖与离子聚合剂浓度、白藜芦醇加入顺序、搅拌时间及探头超声等因素对纳米粒性质的影响,确定最佳制备工艺。结果在透射电子显微镜下,制备的白藜芦醇壳聚糖纳米粒呈球形;平均粒径为38nm,多分散指数为0.13;包封率与载药量分别为(61.6±2.3)%和(13.1±1.1)%;与白藜芦醇壳聚糖溶液相比,白藜芦醇壳聚糖纳米粒显示了明显的缓释效应。结论离子聚合法可用于小粒径壳聚糖纳米粒的制备。     

盐酸青藤碱壳聚糖纳米粒的制备及体外释放性能的研究

目的:制备盐酸青藤碱壳聚糖纳米粒,并考察其性质和体外释药特性。方法:通过微乳液-离子交联法制备盐酸青藤碱壳聚糖纳米粒,考察纳米粒的形态、粒径和zeta电位,紫外分光光度法测定其载药量和包封率,透析法研究其体外释药特性。结果:制得的纳米粒呈球形或类球形,平均粒径为98.3nm,包封率为67.2%,体外模拟释药结果表明载药纳米粒药物释放速率在24h内持续稳定。结论:微乳液-离子交联法制备盐酸青藤碱壳聚糖纳米粒简便可靠,体外释药具有明显的缓释作用。     

雷公藤甲素壳聚糖纳米粒的制备与初步评价

目的:制备包载雷公藤甲素的壳聚糖纳米粒系统(triptolide-chitosan nanoparticles,TP-CS NPs),并考察其理化性质及体外释药性能。方法:采用非溶剂辅助络合-化学交联法制备壳聚糖纳米粒。利用透射电镜、粒度仪、HPLC法等对制备的纳米粒性质进行表征。结果:制得的纳米粒呈球形,平均粒径为(151.2±5.4)nm,Zeta电位(20.1±1.2)m V,纳米粒收率(78.0±3.3)%,包封率(77.0±1.2)%,载药量(2.0±0.4)%,体外模拟释药结果表明载药纳米粒药物释放速率在24 h内持续稳定。结论:非溶剂辅助络合-化学交联法制备的雷公藤甲素壳聚糖纳米粒简便可靠,体外释药具有明显的缓释作用。     

两种克班宁长循环纳米粒的急性毒性与抗心律失常作用研究

目的 对两种经PEG修饰载体材料(PELGE、PLGA)制备的克班宁(Crebanine,Cre)长循环纳米粒(PELGE-Cre-NPs、PLGA-Cre-NPs)进行急性毒性试验与抗心律失常作用研究,探讨其增效减毒的效果。方法 采用Bliss法对PELGE-Cre-NPs与PLGA-Cre-NPs进行小鼠急性毒性试验,求半数致死量(LD₅₀);采用氯仿诱发小鼠心室纤颤模型、氯化钡(BaCl₂)及乌头碱致心律失常大鼠模型对两种纳米粒进行药效作用考察。结果 PLGA-Cre-NPs与PELGE-Cre-NPs静脉注射的LD₅₀分别为13.619 mg·kg^-1与14.839 mg·kg^-1,均比克班宁静脉注射的LD₅₀ (9.382 mg·kg^-1)明显增加。与模型对照组比较,两种纳米粒均能明显对抗氯仿诱发的小鼠心室纤颤、对抗氯化钡诱导的大鼠心律失常,明显提高乌头碱诱发大鼠室性早搏(VPB)、室性心动过速(VT)、心室纤颤(VF...     

紫杉醇脂质体的制备及初步毒性、药效学研究

 目的 制备紫杉醇脂质体并对其理化性质、毒性及药效学进行初步研究。方法 将大豆卵磷脂（soybean Phosphatidylcholine,SPC）、培化磷脂酰乙醇胺（mPEG2000-DSPE）及紫杉醇以100∶0.5∶5（摩尔比）混合并溶解于氯仿中,采用油水相研磨成乳,然后高压均质的方法制备脂质体。采用低速离心法测定包封率,动态光散射法测定粒度分布,KM鼠进行毒性实验,H22/KM小鼠为模型进行药效实验。结果 脂质体平均粒径为（140±10） nm;药脂摩尔比在3%～6%内包封率均大于95%;毒性实验表明,紫杉醇脂质体（Pac-lipo）和紫杉醇游离药（Pac-free）对KM雄性小鼠的最大耐受剂量（MTD）分别为64.8和29.4 mg·kg^-1;药效实验表明,紫杉醇脂质体剂量依赖性的抑制鼠肝癌H22肿瘤生长。结论 紫杉醇脂质体具有较高包封率,与紫杉醇游离药相比可以显著提高治疗指数。     

姜黄素偶联O-羧甲基壳聚糖纳米粒的制备及抗癌活性考察

目的: 制备姜黄素偶联O-羧甲基壳聚糖纳米粒(Cur-OMCS)并考察其对HepG2细胞的抑制能力。方法: 通过酯化反应将姜黄素和O-羧甲基壳聚糖键合在一起,利用紫外、红外、核磁及透射电镜对Cur-OMCS进行表征,通过MTT考察Cur-OMCS对肿瘤细胞的抑制效果。结果: Cur-OMCS在水中自组装成纳米粒,平均粒径319 nm,粒径分布指数0.488,Zeta电势-26.1 mV,水溶液呈黄色澄清透明,姜黄素在水中质量浓度提高了300倍。姜黄素载药量1.5%,Cur-OMCS的临界胶束质量浓度0.040 g·L^-1,Cur-OMCS对HepG2细胞的抑制效果明显优于游离姜黄素,当Cur-OMCS中姜黄素质量浓度15 mg·L^-1时,细胞生长抑制率达80%。结论: Cur-OMCS在水中可自组装形成纳米粒子,极大地提高了姜黄素的肿瘤细胞抑制能力。