一阶导数高速脉冲极谱法用于盐酸普鲁卡因的定量分析

研究了一阶导数高速脉冲极谱法,并运用于盐酸普鲁卡因及其注射制剂的定量分析。在-0.04 V(对 Ag/AgCl)处出现的良好导数峰,于1.0～6.0×10~(-4)mol/L 范围内,导数峰电流与浓度呈线性关系。检测限为3.0×10~(-8)mol/L。操作简便、快速、灵敏,结果准确。     

Electrophysiological properties of the propafenone-analogue GE 68 (1-[3-(phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol) in isolated preparations and ventricular myocytes of guinea-pig hearts

GE 68 ((Rac.)-1-[3-(Phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol hydrochloride) is structurally related to propafenone, and exerts negative inotropic and negative chronotropic effects similar to the parent drug, but lacks any β-adrenoceptor blocking activity contrary to propafenone. Thus, the electrophysiological effects of GE 68 were studied in papillary muscles, left atria, Purkinje fibres, sinoatrial nodes and ventricular myocytes of the guinea-pig heart with the intracellular microelectrode technique and the patch-clamp technique in the cell-attached mode. The decrease of the maximum upstroke velocity (V˙_max) by GE 68 (1 to 10 μM) was use- and frequency-dependent. V˙_max recovered from the use-dependent block with a time constant of 4.1 ± 0.6 s. In papillary muscles and Purkinje fibres action potential duration was shortened, while it was prolonged in left atria and sinoatrial nodes. Half-maximal steady-state inactivation of the sodium channels was shifted to more negative membrane potentials (control: –91.5 ± 0.8 mV, 10 μM GE 68: –97.9 ± 2.5 mV). The peak of the current-voltage relationship and the reversal potential were not changed by GE 68. The amplitude of the unitary current remained unaltered, while open state probability was decreased. The most striking effect of GE 68 was an increase of the number of sweeps without single channel openings (1 μM: 2 fold, 10 μM: 6 fold). GE 68 also caused a decrease of the mean open times, and an increase of the mean closed times in unmodified and pronase-modified sodium channels. Besides the lack of β-adrenoceptor blocking activity, data present a faster recovery from the use-dependent block by GE 68 and a lower affinity to inactivated sodium channels compared to the reference drug propafenone, as well as differences in the effect on single channel kinetics. Received: 25 July 1996 / Accepted: 14 October 1996     

新的高强度高选择性阿片μ受体激动剂[11C]-羟甲芬太尼的合成

羟甲芬太尼(I)是一个新的高强度高选择性阿片μ受体激动剂。本文用cis-A-N-[1-(2-羟基-2-苯乙基)-3-甲基-4-哌啶基]-苯胺(II)或cis-N-[1-(苯甲酰甲基)-3-甲基-4-哌啶基]-苯胺(III)作为前体合成了[¹¹C]-羟甲芬太尼,以便用正电子发射断层扫描(PET)来观察μ受体。通过水解cis-A-羟甲芬太尼(I)和cis-N-[1-(苯甲酰甲基)-3-甲基-4-哌啶]-N-苯基丙酰胺(cis-IV)的4-N-丙酰基分别获得II和III。溴乙烷的格氏试剂与回旋加速器产生的[¹¹C]-二氧化碳反应后继而直接加入邻苯二甲酸二酰氯和2,6-二叔丁基吡啶生成同位素标记中间体[¹¹C]-丙酰氯。[¹¹C]-丙酰氯与OH-前体(II)反应后再经HPLC分离纯化直接得[¹¹C]-羟甲芬太尼;[¹¹C]-丙酰氯与酮-前体(III)反应后,再用硼氢化钠甲醇溶液处理,然后进行HPLC分离纯化得[¹¹C]-羟甲芬太尼。两种方法均可获得ll.1～14.8GBq/μmol的特异性放射化学纯[¹¹C]-羟甲芬太尼。总共耗时为40～50min(EOB)。     

光动力学疗法与局部化疗联合治疗进展期食管贲门癌

作应用光动力学疗法（ＰＤＴ）对进展期食管贲门癌５５例进行治疗，并对其中１５例联合应用内镜下局部注射抗癌药物。对每一患均先静脉滴注血卟啉衍生物（ＨＰＤ）５ｍｇ／ｋｇ，于用药后２４，４８和７２ｈ分别用波长６３０ｎｍ的铜蒸汽激光照射肿瘤部位。联合治疗组除ＰＤＴ治疗外，于每次光照前肿瘤局部注射５－Ｆｕ２５０～５００ｍｇ。结果：联合治疗组的近期显效率高于单纯ＰＤＴ组（Ｐ〈０．０５）。病例随访６～１６月，     

以杯[4]芳烃衍生物为载体的钾离子选择电极的研究

目的：研制新的以杯[4]芳烃衍生物为载体的PVC膜钾离子选择电极。方法：以3种杯[4]芳烃衍生物为载体，癸二酸二辛酯或邻苯二甲酸二辛酯为增塑剂，四（4－氯）苯硼钾为离子定域体制得了PVC膜钾离子选择电极，测试了该类电极对钾离子的响应性能和对7种阳离子的选择性系数。结果：以5，11，17，23－四叔丁基－25，26，27，28－四[2-(乙氧基羰基）苄氧基]杯[4]芳烃为载体所制得的电极（电极Ⅰ）对钾离子有良好的能斯特响应，该电极的选择性系数优于电极Ⅱ和Ⅲ。分别用电极Ⅰ，Ⅱ，Ⅲ对青霉素V钾中的钾含量进行了测定，其结果均与原子吸收法基本一致。结论：所制得的上述电极是一类新的钾离子选择电极，有实用价值。     

Synthesis and cytotoxic activity of new alkyl[3-(2-chloroethyl)ureido]benzene derivatives

Several alkyl[3-(2-chloroethyl)ureido] (CEU) benzene derivatives were prepared as potential anticancer agents. These new compounds were readily prepared in good yields by addition of anilines to 2-chloroethylisocyanate. Their cytotoxic activity was evaluated on human breast cancer (MDA-MB-231), human colon adenocarcinoma (LoVo) and mouse lymphocytic leukemia (P388D₁) tumor cell lines. Several new CEUs were significantly more cytotoxic than the nitrogen mustard chlorambucil. The biological activity of these aromatic urea derivatives seems to be related to the nature and position of the alkyl substituents on the aromatic ring. Substitution by branched alkyl groups on position 4 of the aromatic ring led to cytotoxic molecules which are up to 5 times more potent than the standard chlorambucil.     

Structural variations in the crystal structures of two homologous DL-Leu and Δ-Leu containing peptides+

The similar conformations and interaction modes of Ac-DL-Leu-Nme₂ and Ac-Δ-Leu-NMe₂ molecules in the solid state allow the comparison of their geometrical parameters. The most evident variations are essentially restricted to the α,β-unsaturated side-chain which adopts the Z-disposition. The dimensions of the peptide backbone are much less sensitive to α,β-unsaturation, with a small shortening by 0.04 Å and 0.02 Å of the N-C^α and C^α-C′ bonds, respectively, and an increase by 6° of the N-C^α- C′ bond angle. The ethylenic and amide groups in the Δ-Leu derivative are far from coplanarity, and a significant electronic conjugation of the π-orbital is likely to be rejected.     

一阶导数光谱法测定丙吡胺尿药浓度及其缓释片的相对生物利用度

本文报道了用导数光谱法测定磷酸丙吡胺的尿药浓度,本方法能消除尿中杂质干扰,测定结果准确。6名受试者交叉口服磷酸丙吡胺缓释片和普通片,测得尿药浓度计算消除速度常数K,排泄速率(Δx/Δt)_(max) 所需时间,证明缓稀片药物排泄慢,药效维持时间长,且缓释片的相对生物利用度与普通片基本相同。     

二阶导数光谱法测定尿中呋喃妥因浓度

本文采用有酸性条件下用乙酸乙酯萃取呋喃妥因后，通过二阶导数光谱法测定尿中呋喃妥因的浓度。该法定量信息为３７４￣３７７ｎｍ处的峰谷之间距离，最低检出浓度为１．５ｍｇ／Ｌ，回收率为９８％，相对标准差小于３％；本法与ＨＰＬＣ法进行了对照性研究。两法具有明显的相关性（ｒ＝０．９９９１）。本法可用于呋喃妥因药动学的研究。     

血卟啉衍生物对癌细胞钠泵活性和糖酵解的光动力效应

血卟啉衍生物(YHpD)合并照光对S180瘤细胞摄取~(86)Rb,瘤细胞的钠泵活性及糖酵解具有明显的抑制作用,且抑制程度随YHpD剂量的增大而增强。瘤细胞的总ATP酶和(Na-K)-ATP酶活性对YHpD的光动力效应也较敏感.YHpD对Mg—ATP酶活性有轻度抑制作用。YHpD并用哇巴因,对瘤细胞摄取~(86)Rb的光动力效应比两种药物单独应用的抑制作用大。