法匹拉韦的合成

目的：设计并探索一条工艺稳定、收率较高的抗病毒化合物法匹拉韦（T-705）的合成工艺路线。方法以氨基丙二酸二乙酯盐酸盐为起始原料,氨水氨解后与乙二醛环合得到3-羟基-2-吡嗪酰胺、经硝酸钾硝化后制得3-羟基-6-硝基-2-吡嗪酰胺,再经三氯氧磷氯代、氟化钾氟代制得3,6-二氟-2-氰基吡嗪,水解成盐,最后经过氧化氢（双氧水）氧化制得目标化合物法匹拉韦。结果设计出的合成路线能有效制备目标化合物。结论该合成路线各步反应中除氟取代需要严格去水外,其余各步反应条件较温和且操作简单、收率稳定,适合规模制备。     

大黄贴敷联合复方聚乙二醇电解质散口服对便秘患者肠道准备给药时机的影响

目的探讨大黄贴敷神阙穴和天枢穴联合口服复方聚乙二醇电解质散(PGEP)在便秘患者肠道准备中的给药时机。方法选择行结肠镜检查的便秘患者300例,分3组,各100例。A组检查前1天晚上9点,行中药贴敷神阙穴和天枢穴,检查当天早上5~7点服完PGEP 139.12 g(2 000 ml);B组检查前1天晚上9点行中药贴敷神阙穴和天枢,检查当天上午10~12点服完相同剂量的PGEP;C组检查当天早上5点行中药贴敷神阙穴和天枢穴,早上5~7点服完相同剂量的PGEP。服药后4 h行结肠镜检查。应用Boston肠道准备量表(BBPS)评分,并对肠腔内气泡进行评分,比较3组患者肠道准备有效性、耐受性及安全性。结果 A组的肠镜检查时间(7.25±0.60)min明显短于B组(9.10±0.80)min和C组(10.50±0.55)min;A组的BBPS评分(8.50±0.35)分明显高于B组(7.35±1.25)分和C组(6.65±1.30)分;A组的肠腔内气泡评分(0.25±0.15)分明显低于B组(0.75±0.65)分和C组(0.55±0.50)分;A组肠道准备接受率、再次肠道准备接受率(96.00%、93.00%)明显高于B组(85.00%、70.00%)和C组(90.00%、88.00%);A组的总体不良反应评分(1.45±0.04)分明显低于B组(1.75±0.55)分和C组(1.60±0.25)分。差异均有统计学意义(P0.05)。结论检查前1天晚上9点大黄穴位贴敷联合检查当天早上5~7点口服PGEP对便秘患者行结肠镜检查肠道准备效果好。     

复方川芎滴丸制备工艺再探讨

目的优选复方川芎滴丸的最佳制备工艺。方法以药物与基质的配比、滴制温度、冷却液的温度为考察因素,采用正交试验设计,以滴丸的圆整度、丸重差异、溶散时限、外观质量的综合评分为评价指标,优选滴丸的成型工艺;以滴距、滴速为考察因素,优选最佳滴制工艺。结果滴丸制备的最佳条件为药物中间体与基质配比12,滴制温度80℃,冷却剂温度15~20℃,滴距5cm,滴速40gtt/min。结论该制备工艺合理,简便,易于控制,适用于本制剂的制备。     

HPLC测定复方氨肽素片中氨茶碱与马来酸氯苯那敏的含量及含量均匀度

目的 建立HPLC测定复方氨肽素片中氨茶碱与马来酸氯苯那敏的含量及含量均匀度。方法 色谱柱为YMC Hydrosphere C₁₈(4.6 mm×250 mm,5 μm),流动相为乙腈-0.5%磷酸溶液(用三乙胺调pH值至2.2)(10∶90),流速为1.0 mL·min^-1,柱温为30 ℃,检测波长为262 nm。结果 茶碱和马来酸氯苯那敏分别在0.06~0.58 mg·mL^-1和2.2~20.0 μg·mL^-1内线性关系良好,回收率分别为100.4%和101.2%,RSD分别为0.74%和1.40%(n=9)。结论 方法快速准确,重复性好,结果可靠,可同时测定氨茶碱及马来酸氯苯那敏,为产品质量标准提高提供基础。     

复方紫荆皮水杨酸溶液质量分析与评价

目的：建立客观评价复方紫荆皮水杨酸溶液质量分析的方法,为其质量控制提供参考。方法采用紫外分光光度法测定该品中水杨酸含量,检测波长530 nm,采用酸碱滴定法检测该品中苯甲酸含量。结果水杨酸线性方程为 Y ＝0．0118X －0．0004,r ＝0．9999,在18．08～54．24 mg·L －1的浓度范围内,其浓度与吸收度呈良好的线性关系,回收率在98．5％～101．0％之间,RSD 均小于1．0％,样品在24 h 内稳定;苯甲酸回收率在98．5％～101．5％之间,RSD 均小于2．0％。结论该方法简便、快速,测定结果准确可靠,重现性好,可用于复方紫荆皮水杨酸溶液的质量控制。     

复方九节茶乳膏的质量标准研究

目的：建立复方九节茶乳膏质量标准。方法采用薄层色谱法对九节茶和冰片进行鉴别;HPLC 双波长法测定复方九节茶乳膏中反丁烯二酸与迷迭香酸含量。采用 Kromasil C18色谱柱（250 mm ×4．6 mm,5μm）,流动相为0．1％甲酸乙腈溶液（B）—0．1％甲酸水溶液（D）,梯度洗脱[0～10 min,5％ B→20％ B;10～25 min,20％ B;25～30 min,20％ B→5％ B;30～35 min,5％ B],流速为1．0 mL·min －1,检测波长为210 nm 和330 nm,柱温为30℃。结果薄层鉴别斑点清晰,阴性无干扰;反丁烯二酸和迷迭香酸线性范围分别为6．53～65．28 mg·L －1（r ＝0．9999）和4．26～42．64 mg·L －1（r ＝0．9995）;平均加样回收率分别为98．3％（RSD ＝0．82％）和100．9％（RSD ＝0．63％）。结论该方法简单、准确、重复性好,能有效的控制该制剂的质量。     

复方丹参滴丸治疗糖尿病肾病疗效及安全性的Meta分析

目的：评价复方丹参滴丸治疗糖尿病肾病的疗效及安全性。方法计算机检索2006年9月至2014年9月,全面检索万方数据库、维普数据库、中国学术期刊全文数据库、中国生物医学文献数据库、Pubmed数据库,收集复方丹参滴丸治疗糖尿病肾病的试验,根据纳入和排除标准共纳入14项研究,1051例患者,选用空腹血糖、餐后2 h血糖、血肌酐、尿素氮、尿β2微球蛋白、尿微量白蛋白排泄率作为效应指标,使用RevMan5．0软件进行meta分析。结果（1）空腹血糖[WMD＝－0．15,95％的CI为（－0．38,0．09）,P＝0．22],差异无显著性;餐后两小时血糖[WMD＝－0．49,95％的CI为（－0．90,－0．08）,P＝0．02],差异具有统计学意义,治疗组均优于对照组（2）血肌酐[WMD＝－1．74,95％的CI为（－5．40,1．92）,P＝0．35],差异无显著性;尿素氮[WMD＝0．07,95％的CI为（－0．18,0．32）,P＝0．59],差异无显著性。（3）尿微量白蛋白排泄率[WMD＝－11．95,95％的CI为（－16．27,－7．64）,P＜0．00001],差异具有统计学意义,治疗组均优于对照组。结论证据表明,复方丹参滴丸治疗糖尿病肾病疗效性、安全性较高。     

The role of E255K/V-inclusive mutations in a Philadelphia-positive acute lymphoblastic leukemia with mutation evolution during sequential TKIs therapies: A case report

Rationale:Until recently, the survival rate in patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) was approximately 30%. Tyrosine kinase inhibitors (TKIs), which are a new class of drugs that target BCR-ABL fusion protein, have shown to be effective in treating Ph+ ALL in adults. However, the resistance mechanisms that promote the disease recurrence have altered the initial success of these revolutionary agents.Patient concerns:A 71-year-old Chinese female patient who suffered from severe shoulder and back pain for 1 week.Diagnosis:The patient was diagnosed with Ph+ ALL (B–cell) because of the following items. Complete blood count showed extremely abnormal white blood cell count (26.26×10⁹/l), hemoglobin concentration (65 g/l) and platelet count (14×10⁹/l). And because that Bone marrow aspirate showed 72.5% lymphoblasts and 59.30% lymphoblasts were confirmed by flow cytometry (FCM). At mean time, Real-time fluorescent quantitative PCR analysis confirmed that the P190 BCR/ABL fusion gene expression was 5.9%. Karyotype analysis indicated the following: 45, XX, −7, t (922) (q34; q11) [cp3].Interventions:The patient was treated with chemotherapy and different TKIs including imatinib, dasatinib, ponatinib, and bosutinib.Outcomes:The patient achieved complete remissions with different TKIs after diagnose but relapsed afterward and died of infection.Lessons:Multidrug-resistant mutations within the BCR-ABL1 kinase domain are an emerging clinical problem for patients receiving sequential TKIs therapy. Acquisition of E255K/V-inclusive mutations is usually associated with ponatinib resistance, thus it is necessary to screen out new real pan-inhibitor compounds for all BCR/ABL mutations and figure out the potential efficacy of asciminib-based drug combinations in the future.     

Deciphering Subtype-Selective Modulations in TRPA1 Biosensor Channels

The transient receptor potential (TRP) proteins are a family of ion channels that act as cellular sensors. Several members of the TRP family are sensitive to oxidative stress mediators. Among them, TRPA1 is remarkably susceptible to various oxidants, and is known to mediate neuropathic pain and respiratory, vascular and gastrointestinal functions, making TRPA1 an attractive therapeutic target. Recent studies have revealed a number of modulators (both activators and inhibitors) that act on TRPA1. Endogenous mediators of oxidative stress and exogenous electrophiles activate TRPA1 through oxidative modification of cysteine residues. Non-electrophilic compounds also activate TRPA1. Certain non-electrophilic modulators may act on critical non-cysteine sites in TRPA1. However, a method to achieve selective modulation of TRPA1 by small molecules has not yet been established. More recently, we found that a novel N-nitrosamine compound activates TRPA1 by S-nitrosylation (the addition of a nitric oxide (NO) group to cysteine thiol), and does so with significant selectivity over other NO-sensitive TRP channels. It is proposed that this subtype selectivity is conferred through synergistic effects of electrophilic cysteine transnitrosylation and molecular recognition of the non-electrophilic moiety on the N-nitrosamine. In this review, we describe the molecular pharmacology of these TRPA1 modulators and discuss their modulatory mechanisms.     

复方半枝莲防治二乙基亚硝胺诱发大鼠肝癌的研究

目的 :研究复方半枝莲 (SBC)对二乙基亚硝胺 (DEN)诱发大鼠肝癌的防治作用。方法 :利用免疫组化、流式细胞仪、血清和组织生化等检测方法 ,分别在第 14周和第 2 4周观察 SBC对 DEN诱发的肝癌形成过程的影响。结果 :中药组 14周时大鼠肝脏异型性增生灶明显较模型组少 ,2 4周时形成的肝癌结节小而少 ,模型组、中药组肝癌发生率分别为 75 .0 %、5 0 .0 % ;免疫组化显示中药组大鼠肝组织谷胱甘肽 - S-转移酶胎盘型阳性灶面积明显低于模型组 ;肝组织匀浆上清液谷胱甘肽 - S-转移酶含量以及血清 λ-谷氨酰转移酶、碱性磷酸酶、谷丙转氨酶含量也明显低于模型组 ;流式细胞仪检测结果显示 ,中药组大鼠肝细胞 G0 - G1 期比例下降 ,G2 - M期比例升高。结论 :SBC能抑制癌前病变 ,延缓肝癌的形成 ,降低肝癌发病率 ,其作用机制之一可能为阻滞 G2 - M期细胞进展 ,从而抑制DEN引起的肝细胞的去分化和恶性增殖