岗梅根清喉颗粒的制备及临床疗效观察

目的研究岗梅根清喉颗粒的制备方法,并观察其临床疗效。方法与草珊瑚含片对照比较,观察其治疗咽喉炎症的临床疗效,并进行动物急性毒性试验。结果符合颗粒的质量要求。动物试验LD50>1208g生药/kg。治疗组与对照组总有效率均在85%以上,两者对咽喉炎症均具有明显的治疗作用。结论本颗粒组方合理,工艺可行,无毒性;临床疗效满意。     

硝酸甘油注射液稳定性研究

目的通过考察不同pH值的无水乙醇对硝酸甘油注射液稳定性的影响,筛选出最适于硝酸甘油注射液生产的无水乙醇。方法用高温加热破坏试验及长期试验的方法研究硝酸甘油注射液的稳定性,考察指标pH值和含量。结论碱性杂质含量低的无水乙醇配制的硝酸甘油注射液稳定性最好,适于硝酸甘油注射液的生产。     

四氢生物蝶呤反应性苯丙氨酸羟化酶缺乏症的临床与基因研究

目的 探讨四氢生物蝶呤（tetrahydrobiopterin,BH4）反应性苯丙氨酸羟化酶（phenylalanine hydroxylase,PAH）缺乏症临床表型和基因型的关系。方法 38例高苯丙氨酸血症（hyperphenylalaninemia,HPA）患儿均进行口服BH。负荷试验（20ms／kg）或Phe-BH。联合负荷试验,同时进行尿蝶呤谱分析、红细胞二氢蝶啶还原酶（dihyaropteridine reductase,DHPR）测定。对7例BH4反应性PAH缺乏症患儿采用聚合酶链反应（PCR）和单链构象多态性（single strand conformation polymorphism,SSCP）分析对PAH外显子进行突变筛检,并结合DNA直接测序方法进行突变分析。结果 确诊10例BH4反应性PAH缺乏症患儿,男6例,女4例;平均年龄7．8个月;生化代谢表型均为轻度或中度HPA。7例BH4反应性PAH缺乏症患儿PAH基因型分别为S70del／-、R241C／R243Q、S70del／A389G、Y166X／-、R11lX/-、EX6-96A〉G／R241C和IVS4-1G〉A／R241C。A389G是新发现的突变基因型。结论 BH4反应性PAH缺乏症多表现为轻、中度HPA生化代谢表型,R241C是BH4反应性相关突变基因型中较常见的一种类型。推测S70del可能是一种BH4反应性相关突变类型.     

Ruthenium-catalyzed asymmetric hydrogenation of aromatic and heteroaromatic ketones using cinchona alkaloid-derived NNP ligands

A series of cinchona alkaloid-based NNP ligands, including a new one, have been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various aromatic and heteroaromatic ketones were smoothly reacted, yielding valuable chiral alcohols with extremely high 99.9% ee. Moreover, a proposed reaction mechanism was discussed and verified by NMR.

A series of cinchona alkaloid-based NNP ligands including a new one has been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various ketones were smoothly reacted with up to 99.9% ee.

Since the well-known failure of using racemic thalidomide, attention has been paid to the manufacture of optically pure compounds as effective components in pharmaceuticals and agrochemicals. Asymmetric hydrogenation of ketones, especially heteroaromatic ketones, has emerged as a popular facile route to approach enantiopure secondary alcohols as essential intermediates for the construction of biologically active molecules.^1–4 Knowles et al.⁵ pioneered the production of enantioenriched chiral compounds in 1968, and Noyori and co-workers^6–8 laid the cornerstone of asymmetric hydrogenation in 1990s. Subsequently, numerous catalytic systems have been developed. Ru-BICP-chiral diamine-KOH was developed and proved to be effective for asymmetric hydrogenation of aromatic ketones by Xumu Zhang.⁹ Cheng-yi Chen reported asymmetric hydrogenation of ketone using trans-RuCl₂[(R)-xylbinap][(R)-daipen] and afforded secondary alcohol in 92–99% ee.¹⁰ Mark J. Burk and Antonio Zanotti-Gerosa disclosed Phanephos-ruthenium-diamine complexes catalyzing the asymmetric hydrogenation of aromatic and heteroaromatic ketones with high activity and excellent enantioselectivity.¹¹ Qi-Lin Zhou et al. designed and synthesized chiral spiro diphosphines as a new chiral scaffold applied in the asymmetric hydrogenation of simple ketones with extremely high activity and up to 99.5% ee.^12–15 Similarly, Kitamura and co-workers have developed a set of tridentate binan-Py-PPh₂ ligands for the asymmetric hydrogenation of ketones affording excellent results.¹⁶ Recently, chiral diphosphines and tridentate ligands based on ferrocene have been developed for the asymmetric hydrogenation of carbonyl compound with a remarkable degree of success.^17–21 Despite many ligands for asymmetric hydrogenation of ketones have been reported, expensive reagent and multistep complicated reactions were employed to synthesize most of them.^22–24 In light of increasing industrial demand, easily obtained, cheap and practical chiral ligands are still highly desirable. In addition to chiral ligands, the selection of metals was essential for asymmetric hydrogenation.^25–27 Although Mn,^28–30 Fe,^31–34 Co,^35–37 Ni^38,39 and Cu^40,41 metals were proved to be effective for asymmetric hydrogenation in recent years, Rh,^42–44 Ir^45,46 and especially Ru remained the most preferred metals. Ruthenium^47–51 was chosen owing to its superior performances in terms of low price, selectivity and activity. Takeshi Ohkuma,⁵² Hanmin Huang^53,54 and Johannes G. de Vries⁵⁵ all successfully used ruthenium catalysts for asymmetric hydrogenation of ketones. Admittedly, there is a continuing interest in the development of cheaper, simpler and more efficient catalysts for the asymmetric hydrogenation of ketones under mild conditions to access corresponding secondary alcohols. Recently, we developed new NNP chiral ligands derived from cinchona alkaloid for the asymmetric hydrogenation of various ketones in extremely excellent results using a iridium catalytic system.⁵⁶ Prompted by these encouraging results, we were interested in exploring a ruthenium-catalyzed asymmetric hydrogenation of ketones with NNP chiral ligands derived from cinchona alkaloid. Here, we showed that changing from iridium to ruthenium, with the same simple synthetic ligands, delivered a catalyst catalyzed asymmetric hydrogenation of ketones to give the industrially important chiral alcohols with up to 99.9% ee. Although the catalytic activity of ruthenium catalyst was not as high as that of the iridium catalyst, the enantioselectivity could be maintained, and even showed higher enantioselectivity in the hydrogenation of some substrates.Chiral tridentate ligand NNP (L1–L10) were synthesized and characterized as reported in our previous publication. With tridentate ligands in hand, we began to evaluate the catalytic performance in benzylidene-bis(tricyclohexylphosphine) dichlororuthenium-catalyzed asymmetric hydrogenation of acetophenone employed as a standard substrate (Fig. 2). MeOH was found to be a better one as the conversion and enantioselectivity were 99.9% and 98.2%, respectively. Bases screening showed that Ba(OH)₂ was superior to the others, giving >99.9% conversion and 98.8% ee in the present catalytic system (Fig. 1). Ligand screening revealed that the configuration of chiral centers of cinchona alkaloids of the ligand markedly affected the catalytic performance. NNP ligands derived from cinchonine and quinidine appeared to benefit both the reaction rate and enantioselectivity, while those derived from cinchonidine and quinine had the opposite effect. Further, different NNP ligands that bearing different substituents on the phenyl rings were evaluated. Similar to our previous research, ligands with electron-withdonating substituents showed better catalytic performance than those with electron-withdrawing substituents. However, it was noted that the more electron-withdonating substituents furnished lower activity but same enantioselectivity. The optimal ligand L5 derived from quinidine with one methoxy group on benzene ring provided the corresponding chiral alcohol with 99.9% conversion and 98.8% ee. Considering that L3 derived from cinchonine had similar catalytic performance to L4 derived from quinidine, new ligand L10 similar to L5 with one methoxy group on benzene ring was synthesized and applied to the asymmetric hydrogenation of template substrate. 99.6% conversion and 97.6% ee was obtained. Hence, L5 was employed as better ligand in subsequent experiments.Open in a separate windowFig. 1The effect of different bases for the asymmetric hydrogenation of acetophenone (substrate/Ru/L5 = 500/1/2, ketones: 0.429 mol L⁻¹, base: 0.15 mol L⁻¹, MeOH: 2 mL, 30 °C, 6 MPa, 2 h.).Open in a separate windowFig. 2The effect of different solvents for the asymmetric hydrogenation of acetophenone. (substrate/Ru/L5 = 1000/1/2, ketones: 0.858 mol L⁻¹, Ba(OH)₂: 0.15 mol L⁻¹, solvent: 2 mL, 30 °C, 6 MPa, 2 h.).The effect of different ligand for the asymmetric hydrogenation of acetophenone^a

植物源抗菌活性成分的研究进展

介绍近年来国内外研究发现的多种已知结构类型及新结构类型的植物源抗菌活性成分。简要归纳了其抗菌活性及其相应的MIC值。同时对构效关系进行了分析。并对其中抗菌活性较强。具有进一步研究开发价值的化合物及结构类型进行了概括。     

奥美拉唑雷尼替丁预防颅脑损伤术后应激性胃出血比较

目的：探讨奥美拉唑,雷尼替丁预防颅脑损伤手术后应激性胃出血的效果。方法;将中,重型颅脑损伤（GCS12－4分）的手术后患者随机分为3组,各30例,奥美拉唑组,雷尼替丁组在对照组用药的基础上分别静脉滴注奥美拉唑40mg,qd,和雷尼替丁150mg,bid,观察临床出血程度,结果：奥美拉唑组,雷尼替丁组的预防效果分别为96．7％,93．3％,与对照组（76．7％）比较差异有统计学意义（P＜0．05）,在使用额外剂量后,奥美拉唑组的5例出血均停止,雷尼替丁组7例出血中仍有4例不能止血,结论：奥美拉唑,雷尼替丁均有预防颅脑损伤手术后应激性胃出血的作用,且预防效果几乎相等,但奥美拉唑较雷尼替丁的止血作用强。     

补脾益气方药对哮喘大鼠血清白细胞介素-4和γ-干扰素含量的影响

本研究采用卵蛋白等敏大鼠哮喘模型,观察正常组、哮喘和中药治疗组大鼠血清中总ＩｇＥ、白细胞介素－４和γ－干扰素的含量变化。结果表明：哮喘大鼠血清总ＬｇＥ水平、ＩＬ－４含量明显增加（Ｐ〈０．０１）,血清中ＩＦＮ－γ含量明显降低（Ｐ〈０．０１）,而补脾益气方药可显著降低哮喘大鼠ＩｇＥ水平及ＩＬ－４含量（Ｐ〈０．０１）,提高ＩＦＮ－γ的含量（Ｐ〈０．０１）。     

中国近视患者的角膜厚度与屈光度关系的研究

目的　了解我国近视眼患者角膜厚度 ,及其与屈光度的相互关系 ,并给出由屈光度预测角膜厚度的回归方程 ,为准分子激光原位角膜磨镶术 (LASIK)手术设计提供参考依据。方法　应用OrbscanⅡ眼前节系统对 45 9例近视眼患者角膜厚度进行检测 ,包括角膜中央直径为 2mm及角膜中周部上方、颞上、颞侧、颞下、下方、鼻下、鼻侧、鼻上、上方 9个直径为 2mm的测量区 (距视轴3mm)的平均角膜厚度 ;屈光度由 -0 5D至 -2 3 5D不等 ;并对各方位角膜厚度与屈光度作直线相关 ,如有相关性则进行回归分析。结果　中国近视眼患者角膜厚度以中央区最薄 ,鼻上方最厚 ,近视眼患者角膜最薄点多位于颞下方 ( 5 2 72 % ) ;颞下及颞侧角膜厚度与屈光度呈线性负相关 (相关系数r分别为 -0 117、 -0 10 7,P <0 0 5 0 ) ;其它部位与屈光度无相关关系 ;角膜厚度彩色地形图中均为圆形最多 ,依次为椭圆形、偏心圆形、偏心椭圆形。结论　中国近视眼患者角膜厚度的改变多位于颞下及颞侧 ,且角膜厚度随近视度数增加有变薄倾向 ;而最薄点、中央区、颞上、鼻下、鼻侧、鼻上、上方、下方角膜厚度与近视度数增加无关 ;OrbscanⅡ眼前节系统能了解角膜厚度分布情况 ,在角膜屈光手术中具有广泛应用前景