亚/超燃混合发动机模块间界面参数设计及数值实验

对轴对称双燃烧室冲压发动机亚/超燃模块间界面进行了初步设计研究。模拟了两股平行气流掺混的冷态流场,重点研究了台阶高度、台阶几何形状、亚燃模块流量比例等设计参数对掺混性能的影响规律,并提出了参数选择建议。在此基础上,给出了一个性能较优的设计方案,性能如下：马赫数4时掺混段出口马赫数为1.48,总压恢复系数为0.765,增压比为17.71,温升比为4.05;马赫数6时掺混段出口马赫数为2.08,总压恢复系数为0.502,增压比为28.03,温升比为4.67。     

Dose emission and aerodynamic characterization of the terbutaline sulphate dose emitted from a Turbuhaler at low inhalation flow

Previously, dose emission below 30?L min^?1 through DPI has not been routinely determined. However, during routine use some patients do not achieve 30?L min^?1 inhalation flows. Hence, the aim of the present study was to determine dose emission characteristics for low inhalation flows from terbutaline sulphate Turbuhaler.

Total emitted dose (TED), fine particle dose (FPD) and mass median aerodynamic diameter (MMAD) of terbutaline sulphate Turbuhaler were determined using inhalation flows of 10–60?L min^?1 and inhaled volume of 4?L.

TED and FPD increase significantly with the increase of inhalation flows (p <0.05). Flows had more pronounced effect on FPD than TED, thus, faster inhalation increases respirable amount more than it increases emitted dose. MMAD increases with decrease of inhalation flow until flow of 20L min^?1 then it decreases.

In vitro flow dependent dose emission has been demonstrated previously for Turbuhaler for flow rates above 30?L min^?1 but is more pronounced below this flow. Minimal FPD below 30?L min^?1 suggests that during routine use at this flow rate most of emitted dose will impact in mouth. Flow dependent dose emission results suggest that Pharmacopoeias should consider the use variety of inhalation flows rather than one that is equivalent to pressure drop of 4 KPa.     

毛细管电泳分离与测定大鼠血浆中尼群地平和尼莫地平对映体的浓度

目的:建立血浆中尼群地平和尼莫地平对映体的毛细管电泳的手性分离方法。方法:以对硝基苯甲酸为内标,血浆样品碱化后以乙醚溶剂提取2次,运行缓冲液为40 mmol.L-1磷酸二氢钠(用磷酸调节pH至2.96)-10 mmol.L-1磺丁基醚-β-环糊精(SBE-β-CD),检测波长为237 nm,尼群地平分离电压为-18 kV,尼莫地平分离电压为-15 kV,电动进样10 s。结果:尼群地平和尼莫地平两对映体均达到基线分离,且不受杂质干扰,尼群地平和尼莫地平浓度分别在28.4～568 ng.mL-1和27.4～548 ng.mL-1范围内线性良好,最低检测浓度分别为11.4 ng.mL-1和11.0 ng.mL-1。结论:本方法快速、简单及低耗,可适用于尼群地平和尼莫地平在体内立体选择性的研究。     

The investigation and the use of high flow column-switching LC/MS/MS as a high-throughput approach for direct plasma sample analysis of single and multiple components in pharmacokinetic studies

Recently direct plasma injection LC/MS/MS technique has been increasingly used in pharmaceutical research and development due to the demand for higher throughput of sample analyses. In this work, two on-line extraction methods including high flow LC/MS/MS and high flow column switching LC/MS/MS were investigated. The evaluations were conducted and focused on their performances with respect to peak responses, separation efficiency, and signal to-noise ratio in a multiple-component LC/MS/MS assay. Two HPLC pumps were used-with one for high flow delivery and one for gradient elution. A CTC autosampler was used to inject plasma samples. High flow LC was achieved by the use of 4 ml/min flow rate on a 1×50 mm Waters Oasis column. A 2×100 mm YMC column was coupled via a column-switching valve. The extracted analytes were analyzed in multiple-reaction-monitoring (MRM) mode using a triple quadrupole MS/MS. As a rapid and simple procedure, vortex-mixing plasma and internal standard directly in sample vials completed sample preparation. The high flow column switching method (two-column system) provided sharper peak shape than the conventional high flow method. This effect increased analyte signal-to-noise ratio and sensitivity. Narrower peak width resulted in much better separation efficiency, which was required for multiple compound (N-in-1) analysis. A 2 mm I.D. column resulted in better peak shape and resolution than using a smaller I.D. column. The selected method achieved acceptable recoveries for most of the compounds tested, and it was successfully applied to a 10-in-1 pharmacokinetic (PK) study. The results showed that the dynamic range, lower limit of quantitation, assay accuracy and precision were acceptable for all compounds. Rapid sample preparation eliminated labor intensive and time consuming processes and improved productivity. This high throughput on-line extraction high flow column switching method has been proven particularly useful for multiple component analysis in PK studies.     

Effects of chronic sympatho-inhibition on reflex control of renal blood flow and plasma renin activity in renovascular hypertension

Background and purpose:

We determined if chronic sympatho-inhibition with rilmenidine has functional significance for the kidney by altering responses of renal blood flow (RBF) and plasma renin activity (PRA) to stress and acute hypotension in rabbits with renovascular hypertension.

Experimental approach:

RBF to each kidney and renal sympathetic nerve activity (RSNA) to the left kidney were measured in rabbits in which a renal artery clip induced hypertension (2K1C) and in sham-operated rabbits. After 2 weeks, a subcutaneous minipump was implanted to deliver rilmenidine (2.5 mg·kg⁻¹·day⁻¹) to 2K1C rabbits for 3 weeks.

Key results:

After 5 weeks of renal artery stenosis, mean arterial pressure (MAP) was 23% higher and PRA 3-fold greater than in sham-operated rabbits. Blood flow and renal vascular conductance in the stenosed kidney were lower (−75% and −80%) compared with sham, and higher in the non-clipped kidney (68% and 39%). Responses of RBF and PRA to hypotension were similar in 2K1C and sham rabbits. Airjet stress evoked a greater increase in MAP in 2K1C rabbits than sham controls. Chronic rilmenidine normalized MAP, reduced RSNA and PRA, and did not reduce RBF in the stenosed kidney. Responses of RBF (clipped and non-clipped kidney), RSNA and PRA to hypotension and airjet were little affected by rilmenidine.

Conclusions and implications:

Our observations suggest that chronic sympatho-inhibition is an effective antihypertensive therapy in renovascular hypertension. It normalizes MAP and reduces basal PRA without compromising blood flow in the stenosed kidney or altering responses of MAP, haemodynamics and PRA to acute hypotension and stress.     

Temporal responses of cutaneous blood flow and plasma catecholamine concentrations to histamine H1- or H2-receptor stimulation in man

Summary We have studied the effect of histamine and H₁- or H₂-receptor antagonists on cutaneous blood flow and catecholamine release in man.Histamine was infused alone or in combination with mepyramine, an H₁-antagonist or cimetidine, an H₂-antagonist for 2 h. Cutaneous blood flow was measured continously with a laser Doppler flowmeter, and noradrenaline and adrenaline concentrations were determined in blood samples drawn every 15 min.The infusion of histamine caused an immediate and sustained vasodilatation. The Concomitant infusion of mepyramine prevented the immediate vasodilatation, but had no effect on the sustained response. The Concomitant infusion of cimetidine was without effect on the immediate vasodilatation, but abolished the sustained response. Infusion of the antagonists alone had no effect on cutaneous blood flow.Histamine caused a rapid and sustained increase in plasma noradrenaline, while the increase during concomitant H₁-receptor blockade was delayed but achieved the level observed during the histamine infusion. The response to histamine during H₂-receptor blockade was small and transient. The rise in plasma adrenaline was not significant.These findings suggest that histamine causes an immediate cutaneous vasodilatation through H₁-receptors and a more sustained response through H₂-receptors. The vasodilatation is accompanied by an increase in plasma catecholamine concentrations. Despite the continuous infusion of histamine, blood flow decreased during the last hour of histamine infusion, while the plasma noradrenaline concentration was still elevated.     

Acute effects of a new vasodilator,Ro 12-4713, on blood pressure,plasma renin activity,aldosterone and catecholamine levels,and renal function in hypertensive and normal subjects

Summary Selected cardiovascular and endocrine effects of the new oral vasodilator Ro 12-4713 have been evaluated in an acute single dose study. In five patients with essential hypertension, Ro 12-4713 caused a dose-dependent decrease in supine and upright blood pressure and an increase in heart rate. Initial effects occurred one to 2 h after drug ingestion and maximal effects were noted after five hours and persisted for at least 8 h. Blood pressure was normalized, and the antihypertensive and chronotropic effects persisted for 24 h after a dose of about 300 mg/1.73 m². Plasma and urinary norepinephrine and plasma renin levels tended to be raised, whereas plasma and urinary epinephrine and plasma aldosterone did not change. Changes in supine heart rate were inversely correlated with changes in mean blood pressure (r=–0.60; P<0.02), and positively with those in plasma norepinephrine (r=0.55; P<0.05) and renin (r=0.62, P<0.01); changes in supine plasma renin level were also inversely correlated with those in mean blood pressure (r=–0.65; P<0.01), and positively with those in plasma norepinephrine (r=0.58; P<0.05). 24 h-urinary sodium excretion was significantly (P<0.001) decreased; it was positively correlated with mean blood pressure (r=0.51; P<0.05) and inversely with supine plasma renin activity (r=–0.63; P<0.01). In six normal subjects and six patients with essential hypertension, effective renal plasma flow and the renal clearance of sodium, potassium, calcium and uric acid were not significantly altered five hours after a dose of Ro 12-4713 of about 250 mg/1.73 m²; glomerular filtration rate tended to be slightly decreased, and filtration fraction was significantly (P<0.05) reduced in the hypertensive patients. At the same time blood pressure was decreased and plasma norepinephrine (P<0.01) and renin (ns) were slightly increased in both groups. Ro 12-4713 in a single oral dose of about 300 mg appeared to be a potent, long acting, hypotensive vasodilator.     

The effects of dopamine and a low protein diet on glomerular filtration rate and renal plasma flow in the aged kidney

Summary The aims of this study were to determine the effects of dopamine and a low protein diet on glomerular filtration rate and effective renal plasma flow in the aged kidney. Effective renal plasma flow was measured using ¹²⁵I-labelled hippuran and glomerular filtration rate using ⁵¹Cr-labelled EDTA.Low-dose continuous intravenous dopamine 3 g·kg^–1·min^–1 in 10 healthy elderly volunteers caused a significant increase in effective renal plasma flow but not in the mean glomerular filtration rate when compared with baseline. However, glomerular filtration rate did increase substantially in 5 subjects (mean 14.4, SD 1.3). This implied that the elderly kidney was working maximally without reserve capacity in half the elderly. Since renal function is likely to be even more reduced in elderly patients with congestive cardiac failure, dopamine infusions may have little place in this condition in some older patients.A low protein diet (0.69 g·kg^–1) in the same volunteers reduced glomerular filtration rate, suggesting that protein restriction may help to reduce the increased filtration rate in the remaining nephrons, thereby leading to structural and functional preservation in the aged kidney.