盐酸吉西他滨合成工艺改进

目的：提高盐酸吉西他滨合成收率。方法：通过对盐酸吉西他滨合成中的关键反应——胞苷形成反应条件的改进,进而提高胞苷形成反应的选择性,从而使产品收率提高。结果：对盐酸吉西他滨合成中的关键反应——胞苷的形成反应进行了优化,提高选择性,进而提高产品收率。结论：以苯甲醚为溶剂,氯化锂和硫酸钾为催化剂,在120～125℃下,反应选择性达到1/9,3β收率最高可达到81.2%。     

磷柳酸的制备工艺研究

目的：研究磷柳酸的制备工艺,确定最佳工艺条件,提高产品收率,方法：采用正交试验设计方法,对磷柳酸制备的反应条件进行优选,结果：最佳工艺条件为：室温反应1h,60-70度反应0．75h,75-80度1．5h,水解反应温度为10度,收率为92．5％,结论：优选后的工艺条件,反应缓和,收率高,水解温度提高,将进一步提高收率。     

吉非罗齐的合成

目的：合成吉非罗齐,并进行工艺改进。方法以２,５－二甲基苯酚为起始原料,与１－氯－３－溴丙烷反应,得３－（２,５－二甲基苯氧基）－１－氯丙烷,再与异丁酸钠锂作用,制得吉非罗齐。结果：通过两步反应制得产物,总收率４３．８％,醚化反应经优化后收率较文献提高３０％以上。合成产物经红外光谱,核磁共振谱及质谱确证。结论：缩短了反应步骤,提高了反应收率。     

盐酸西布曲明的合成

目的：研究盐酸西布曲明的合成方法。方法：以对氯氰苄为起始原料经环合、格氏反应、还原、氮上的氮甲基化、成盐５步反应合成盐酸西布曲明,并对反应的条件进行了优化。结果：经５步反应合成盐酸西布曲明,总收率为４０．６％。结论：反应条件温和,工艺简便,收率较高,适用于工业化生产。     

应用均匀设计研究2,4-二氟苯甲酸的制备工艺

目的：以2,4-二硝基甲苯为起始原料合成2,4-二氟苯甲酸;方法：应用均匀设计于标题化合物的工艺研究中;结果：反应总收率可达58．6％;结论：应用均匀设计优化反应条件,使收率显著提高。     

EFTA合成影响因素研究

目的：头孢替安中间体2-甲酰氨基-噻唑基-4-乙酸乙酯(EFTA)合成影响因素研究;方法：以2-氨基-噻唑基-4-乙酸乙酯(EATA)为原料,经氨基甲酰化反应得到EFTA．通过反应物摩尔配比、反应温度、反应终点PH等影响因素对EFTA含量、收率考察,利用正交设计优化工艺参数,产品用IR、H-NMR进行结构表征;结果：收率提高6．83％,含量均99％以上。结论：此反应条件温和,收率高,成本低,适合工业化生产。     

1-甲基-3-正丙基吡唑-5-甲酸乙酯的合成

目的：合成标题化合物,并进行工艺改进。方法：以2－戊酮和草酸二乙酯为原料,经三步反应合成了产物。结果：反应的总收率为47．7％。合成的各步产品经元素分析、红外和核磁共振光谱确证。结论：改进的工艺具有反应温度低、时间短等优点,并提高了收率。     

Epidepride的合成

目的：研究Epidepride的化学合成方法。方法：以3－甲氧基水杨酸为原料,经五步反应合成Epidepride。结果：得到的样品经IR,NMR,MS等波谱分析及元素分析证明该化合物为Epidepride,总收率为43％。结论：该合成方法简单,收率稳定,反应条件温和。     

α-呋喃丙烯酸酯类香料的合成

目的：通过化合得到酯类化合物；方法：两种化学物质在催化剂的作用下，反应得到的酯类化合物，此反应得到的化合物，可以提高产品的收率；结果：收率为51．2％;结论：该系列酯类备料具有香气，作为备料广泛用于防晒类化妆品。     

伊斑膦酸钠的合成

目的：合成伊斑膦酸钠,方法：以戊胺为原料,经缩合,甲基化,加成,水解,无溶剂膦酸化,中和反应合成。结果：合成了伊斑膦酸钠,总收率21．2％。结论：本方法提高了反应收率,降低了成本,简化了操作,是合成伊斑膦酸钠的有效途径之一。     

达托霉素新杂质及其来源研究

达托霉素是一种正在临床使用的新型抗耐药菌抗生素。由于结构特点，其具有很多结构类似的杂质。在达托霉素样品中，通过HPLC分析发现了一种新的杂质，相对保留时间为0.82。经过分离纯化，获得了纯化的新杂质。UPLC-MS检测发现新杂质的分子量为1617。核磁共振分析，确定新杂质的侧链含有双键，推定新杂质为N-(3-癸烯酰基)-L-色氨酰基-D-天冬酰胺酰基-L-天冬氨酰基-L-苏氨酰基-甘氨酰基-L-鸟氨酰基-L-天冬氨酰基-D-丙氨酰基-L-天冬氨酰基-甘氨酰基-D-丝氨酰基-苏-3甲基-L-谷氨酰基-L-3-邻氨基苯甲酰基-L-丙胺酸-ε1-内脂。根据杂质的化学结构，推测该杂质可能来源于发酵过程中补加的癸酸。因此通过GC-MS分析了起始原料癸酸，发现其中含有少量癸烯酸，该结果证实了本研究的推测。     

Cancer gene therapy--first international conference. 8-9 July 1999, Hammersmith Hospital, London, UK

The failings of the cancer gene therapies that have so far been tested in clinical trials are that they do not reach sufficient target cells and are not toxic enough. The eventual success of many strategies may also depend on their ability to elicit a strong antitumor immune response. Unsurprisingly, therefore, the focus of this meeting, the first of the International Society of Cancer Gene Therapy, was on new strategies currently in preclinical development that address these problems, and relatively little new clinical information was presented. There was much interest in a new class of therapeutic genes, those encoding fusogenic membrane glycoproteins, which are very toxic and have the potential to elicit a potent bystander effect and a strong immunogenic response. The aim of another strategy that shows considerable promise is to improve the toxicity of replication-conditional adenoviruses by replacing deleted adenoviral genes with cytotoxic or suicide genes. Disappointingly, there was little discussion of new vector systems that might improve gene delivery. The most exciting development in ex vivo immunogene therapies presented was progress towards the development of a streamlined 'off the shelf' immunogene therapy for relapsing leukemia patients who have undergone bone marrow transplants. In addition, a few promising immunotherapies were discussed that may provide several starting points for the development of new gene therapies that are effective in eliciting tumor immunogenicity.     

Decongestant activity of a new formulation of xylometazoline nasal spray: a double-blind,randomized versus placebo and reference drugs controlled,dose-effect study

Xylometazoline hydrochloride is an imidazoline derivative commonly used in topical application to relieve nasal congestion associated with acute or chronic rhinitis, common cold, sinusitis and hay fever or other allergies. To reduce the negative effects on the mucosal defensive mechanism, a new formulation of xylometazoline (Rhinostop) with inactive preservatives and hyaluronic acid (HA) was studied. The most appropriate concentration of xylometazoline and its decongestant activity in the new formulation were investigated in a double-blind, dose-effect study. The new formulation at three different concentrations of xylometazoline (0.025%, 0.05% and 0.1%) was compared with a placebo formulation, three equivalent aqueous solutions containing xylometazoline (without HA) and a reference formulation, containing benzalkonium chloride as preservative. The drugs' efficacy in reducing airflow resistance was also evaluated. The effects of xylometazoline on inspiratory and expiratory nasal resistance were found to be concentration-dependent. Indeed, the new formulation at a concentration of 0.05% was more effective than the new formulation at a concentration of 0.025%, but was statistically equivalent to the new formulation at a concentration of 0.1%; therefore, the 0.05% concentration of xylometazoline seemed to achieve maximal decongestant activity. These findings were confirmed by the observation that the efficacy of the new formulation at a concentration of 0.05% was also statistically comparable to that of the reference formulation and the aqueous solution of xylometazoline 0.1%. HA seems to act as an enhancer/carrier of the active principle, xylometazoline, as already demonstrated for other drugs. The new formulation at a concentration of 0.05% was therefore selected for further clinical development.     

改良的人乳腺癌细胞三维培养模型及药敏性考察

目的：建立适用于高通量药物筛选的人乳腺瘪MCF-7细胞三维培养模型,考察其药敏性。方法：在传统的liquidoverlay法和直接混合法基础上,建立新型锚定法,制备MCF-7细胞的三维培养系统;以二维培养和直接混合法制备的三维培养系统作对照,通过倒置显微镜观察其中细胞形态学特征,绘制细胞生长曲线,使用顺铂并采用MTT法进行药敏试验。结果：采用新型锚定法成功制备MCF-7细胞的三维培养系统,不同于二维培养系统．其中MCF-7细胞形成典型的直径为160um左右的葡萄样多细胞球：与直接混合法制备的三维培养系统相比．其中MCF-7细胞生长速度明显更快（P〈0．05）：与二维培养系统相比,其中MCF-7细胞对顺铂的敏感性显著降低,即顺铂对MCF-7细胞的增殖抑制率明显降低（P〈0．01）。结论：该新型锚定法制备的乳腺癌细胞三维培养系统更接近体内肿瘤生长环境,其中肿瘤细胞能模拟体内实体瘤的耐药特征,故其更适用于抗癌药物的活性筛选。     

清洁消毒新方法的建立及在腮腺炎疫苗车间的应用

 目的  以酸性/碱性苯酚盐作为常规消毒剂,在腮腺炎疫苗生产车间建立新的清洁消毒方法。方法  每月轮换使用酸性/碱性苯酚盐溶液进行擦拭,且每周使用杀孢子剂进行熏蒸。检测新消毒方法的消毒效果,并与原消毒方法进行比较。 结果  新方法的消毒效果好于原方法,使用新方法消毒后,腮腺炎疫苗车间的沉降菌检出率下降,而且腮腺炎疫苗单收液和原液的污染率分别降至0.1%和0.0%。  结论  新消毒方法可用腮腺炎疫苗生产车间的日常清洁消毒。     

Cerebral muscarinic acetylcholine receptors interact with three kinds of GTP-binding proteins in a reconstitution system of purified components

A new GTP-binding protein, which serves as a substrate for pertussis toxin, was prepared from porcine brain. The new G protein was separated from other GTP-binding proteins, Gi and Go, by an anion-exchange column chromatography. The mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the alpha subunit of the new G protein was between those of alpha subunits of Gi and Go. Evidence that the alpha subunit is not a proteolytic fragment of the alpha subunit is not a proteolytic fragment of the alpha subunit of Gi or Go was provided by experiments involving partial hydrolysis of these G proteins with thermolysin and their interaction with an antibody raised against the amino terminal peptide of the alpha subunit of Gi. In addition, the gamma subunit of the new G protein was indicated to be different from the gamma subunits of Gi and Go, because the latter were found to be phosphorylated by protein kinase C but the former was not. GTP-sensitive high affinity binding of muscarinic receptors with acetylcholine was observed when muscarinic receptors purified from porcine cerebrum were reconstituted in phospholipid vesicles with the new G protein as well as with Gi or Go. The proportion of the high affinity sites increased with the concentrations of the G proteins, the potency of the new G protein being similar to that of Gi but a little lower than that of Go. This GTP-sensitive high affinity binding was not observed when each G protein was pretreated with pertussis toxin and then reconstituted with muscarinic receptors. Acetylcholine accelerated the dissociation of [3H]GDP from the new G protein as well as from Gi and Go, which were reconstituted with muscarinic receptors. These results indicate that muscarinic receptors interact with at least the above three kinds of G proteins, in a pertussis toxin-sensitive manner.     

固体火箭发动机的一种点火药量估算方法

针对传统经验公式估算点火药量存在的不足,从固相点火理论出发,推导得到固体发动机点火药量的计算公式。对不同配置的固体火箭发动机进行点火药量验算的结果表明,该公式估算的点火药量与发动机真实试验药量基本一致,估算精度明显优于传统经验公式,且公式通用性较好。     

δ型吲哚拉新新晶型的制备与鉴别

用氯仿作为溶剂,制备了吲哚拉新的一种新晶型———δ型,并通过差热分析,红外吸收分光光度法及Ｘ射线粉末衍射等鉴别方法,确定了吲哚拉新药物除前物文献报道的α,β,γ３种晶型外,还存在一种新晶型———δ型．