海藻酸钠在医学工程上的应用研究进展

介绍了海藻酸钠的性质和制备．阐述了其在医学工程上的应用．如用作药物载体、凝胶微球、缓释材料及外科创伤修复材料等，对其发展前景作了展望。指出：海藻酸钠用于开发缓释制剂是其发展的必然趋势，在耳科疾病局部治疗和人造软骨方面也有重要的应用前景．但是海藻酸钠水凝胶的强度和韧性却限制了其广泛应用。     

Growth dynamics in cystic fibrosis

The growth profiles of 28 cystic fibrosis patients, followed for at least three years, were analysed in order to study the dynamics of growth and to verify if any correlation with clinical events exists. Heights and weights were recorded at three-month intervals, and the patterns did not appear stable or linear, although a graphical smoothing might depict a linear pattern. Height and weight velocity profiles were plotted and all cases showed regular pulsatile patterns of height and weight velocity. By taking measurements at three-month intervals, the pulsatile rhythm was found to be associated with a circannual rhythm. When the appearance of clinical events was related to growth velocity profiles for each individual, the majority (71–82%) occurred during the descending phase of the growth velocity. An understanding of the individual pulsatile pattern of growth may actually increase the sensitivity of surveillance, and checks might be programmed according to the individual pattern, since the risk of developing an adverse clinical event is significantly greater during the slowing phase of the growth velocity.     

Relationship Between Gelation Rate of Controlled-release Acetaminophen Tablets Containing Polyethylene Oxide and Colonic Drug Release in Dogs

Purpose. We hypothesized that sufficient gelation of orally administered hydrophilic matrix tablets before they reach the colon could, as a result of continuous erosion of the gelated matrix, prevent the decrease in colonic drug release which normally occurs here. The purpose of this study was to elucidate the effect of gelation of hydrophilic matrices containing polyethylene oxide on colonic drug release in dogs using controlled-release (CR) acetaminophen tablets. Methods. Two types of CR tablets were prepared, a slow gelling tablet (SG) and a rapid gelling tablet (RG) containing an extra highly water soluble filler. In vitro and in vivo performance were examined. Results. SG and RG showed similar drug release behavior in vitro. In oral administration to dogs, the two formulations showed similar gastrointestinal transit, reaching the colon within 2–4 h after oral dosing. Further, they showed similar maximum plasma levels (Cmax) and time to Cmax (Tmax). In contrast, however, the two tablets produced different plasma levels from 2 h post-dosing, with plasma levels of RG higher than those of SG and with smaller individual variation. Directly observed colonic drug release behavior of RG was similar to in vitro drug release, whereas that from SG was suppressed. Conclusions. Colonic drug release is closely related to the gelation of hydrophilic matrix, and rapid gelation provides continuous in vivo drug release.     

Pulsatile tinnitus —a review of 84 patients

Pulsatile tinnitus can be annoying for a patient and can also be the only clue to a potentially devastating and life-threatening disease. In order to understand its clinical spectrum and management better we analysed the files of 84 patients seen at our institution over a 10-year period. Noninvasive techniques (ultrasound, computed tomography, magnetic resonance imaging) and angiography were employed as investigations tailored to the individual patient. A vascular disorder [i.e. arteriovenous fistula, dissection of the internal carotid artery (ICA), fibromuscular dysplasia, aneurysm of the ICA and sinus thrombosis] was found in 36 patients (42%), most commonly a dural arteriovenous fistula or a carotid-cavernous sinus fistula. In 26 patients with a vascular abnormality, pulsatile tinnitus was the presenting symptom. In 12 patients (14%), nonvascular disorders such as glomus tumour or intracranial hypertension with a variety of causes explained the tinnitus. We conclude that patients with pulsatile tinnitus should be investigated with noninvasive techniques. If these are negative or to clarify abnormal findings of noninvasive techniques selective angiography is needed for diagnosis and to guide treatment Received: 18 August 1997 Received in revised form: 29 October 1997 Accepted: 12 November 1997     

Pharmacokinetic and pharmacodynamic characteristics of a controlled-release formulation of trazodone versus the conventional formulation in healthy volunteers

The pharmacokinetic and pharmacodynamic characteristics of a controlled-release (CR) formulation of trazodone were evaluated in healthy subjects who received acutely 150 mg and 75 mg of the CR trazodone and equal amounts of the conventional formulation on separate occasions. Plasma trazodone concentrations were measured by HPLC. The pharmacokinetic profile of CR trazodone was characterized by a slower increase in drug plasma levels and a lower and retarded peak plasma concentration without any modification in the total amount of trazodone absorbed over 24 hrs. The side effects were less severe and less frequent than with the conventional formulation.

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Sommario Le caratteristiche farmacocinetiche e farmacodinamiche di una formulazione di trazodone a rilascio controllato (CR) sono state studiate in volontari sani ai quali furono somministrati, in quattro differenti occasioni, 150 mg e 75 mg di trazodone CR e dosi equivalenti di trazodone in formulazione convenzionale. Le concentrazioni plasmatiche di trazodone furono misurate mediante HPLC. Rispetto alla formulazione convenzionale, il trazodone CR esibì un profilo farmacocinetico caratterizzato da un incremento più graduale dei livelli plasmatici e da una concentrazione massima più bassa e più ritar-data. Nessuna differenza nella quantità totale di farmaco assorbita nelle 24 ore fu osservata tra le due formulazioni. Dopo somministrazione del trazodone CR, gli effetti collaterali indesiderati furono meno severi e meno frequenti rispetto alla formulazione convenzionale.

     

A comparison of withdrawal in rats implanted with different types of morphine pellets.

Time course and duration and physical dependence was investigated in rats implanted subcutaneously with 3 different types of morphine (M) pellets. Each was formulated according to the method of Gibson and Tingstand [8], but differed in surface area and hardness. Animals were maintained for 19 days after implantation and physical dependence was assessed every other day. Severity of naloxone (Nx)-induced withdrawal was quantified by the use of a composite symptom score and weight loss. Withdrawal severity was greatest following implantation of a pellet (Type C) of large surface area and low hardness rating, and least following implantation of a pellet (Type A) of small surface area and high hardness rating. Abstinence severity which resulted from implantation of a pellet (Type B) of moderate surface area and low hardness rating was intermediate. When 2 pellets were implanted the difference between Type C and B was amplified. It was concluded that formulation per se was not sufficient for specifying M pellet characteristics.     

Comparison of once-daily nifedipine controlled-release with twice-daily nifedipine retard in the treatment of essential hypertension

AIMS: Nifedipine is a short-acting calcium antagonist formulated into several different oral preparations, each of which may have different effects on haemodynamics and autonomic nervous function. We compared the effects of nifedipine controlled-release (CR) and nifedipine retard on 24-h blood pressure, heart rate, rate-pressure product, and power spectral measures of heart rate variability in patients with essential hypertension. METHODS: After 4 weeks of a drug-free period, 25 patients were randomized to receive either once-daily treatment with nifedipine CR (20-40 mg daily; 12 patients) or twice-daily treatment with nifedipine retard (20-40 mg daily; 13 patients) for 12 weeks. The ambulatory blood pressure, heart rate, and ECG R-R intervals were measured during a 24-h period using a portable recorder (TM-2425) at the end of the drug-free and the treatment periods. A power-spectral analysis of R-R intervals was performed to obtain the low-frequency (LF) and high-frequency (HF) components. RESULTS: Nifedipine CR and nifedipine retard reduced 24-h blood pressure significantly by 15.9 +/- 3.2 (SE)/8.7 +/- 1.4 mmHg and by 10.9 +/- 2.8/9.4 +/- 1.7 mmHg, respectively, after the 12-week treatment. Nifedipine CR did not change the 24-h heart rate significantly, while nifedipine retard increased it significantly by 3.9 +/- 2.1 beats min(-1). Nifedipine CR produced a significant reduction in rate-pressure product throughout a 24-h period, while nifedipine retard did not change the rate-pressure product significantly. In addition, nifedipine retard significantly decreased the 24-h and daytime average values of the LF and HF components, while nifedipine CR affected the nighttime LF component alone and did not change the HF component throughout a 24-h period. CONCLUSIONS: These results demonstrate that both nifedipine CR and nifedipine retard are effective as antihypertensive agents, but nifedipine CR has less influence on the autonomic nervous system and heart rate than nifedipine retard.     

Comparison of sustained-release morphine with sustained-release oxycodone in advanced cancer patients

The antinociceptive effect of morphine and oxycodone is mediated preferentially at micro and kappa receptors, respectively. The aim of this study was to evaluate the analgesic profile of the combination of morphine and oxycodone in cancer pain, compared to the standard administration of morphine alone. Controlled-release formulations of oxycodone (CRO) and morphine (CRM) were compared in 26 patients. The study started with an open-label, randomised titration phase to achieve stable pain control for 7 days, followed by a double-blind, randomised crossover phase in two periods, 14 days each. At any point, patients were allowed to use oral immediate-release morphine (IRM) as needed, in order to keep visual analogue scale < or =4. Pain, satisfaction, adverse effects and number of daily rescue morphine tablets were assessed. A total of 22 patients were evaluated. The weekly upload consumption ratio in morphine/oxycodone was 1 : 1.8 (1.80, 1.83, 1.76, 1.84). The weekly IRM consumption was higher in patients having CRM compared to patients having CRO (ratio morphine/oxycodone: 1.6, 1.6, 1.6, 1.7) (P<0.05). Patients receiving oxycodone complained of less nausea and vomiting. The rescue morphine analgesic consumption was 38% higher in patients receiving only morphine, compared to patients receiving both morphine and oxycodone. The results suggest that the combination of morphine/oxycodone (opioids with differential preferential sites of action) can be a useful alternative to morphine alone, resulting in a better analgesia profile and less emesis.     

天香丹对大鼠心肌缺血再灌注损伤的保护作用研究

目的:探讨天香丹冲剂预处理对大鼠急性心肌缺血再灌注损伤的保护作用。方法:Wistar大鼠40只,随机分为正常对照组(不做任何处理)、实验对照组(生理盐水灌胃)以及天香丹低、高剂量组(天香丹分别为0.38g/250g体重、1.5g/250g体重,灌胃10d),实验对照组和天香丹低、高剂量组手术致心肌缺血,检测复灌后各组心电图ST段的变化、左室内压上升和下降最大速率(±dp/dtmax),复灌结束后颈动脉取血并切取心脏,心脏切片后0.1%TTC染色,检测心肌梗死范围及各组血清中谷胱甘肽过氧化物酶(GSH-Px)的活性和丙二醛(MDA)含量。结果:与实验对照组相比,天香丹高剂量组心肌梗死面积减小较为显著,ST段回落明显(P<0.05~0.01),±dp/dtmax明显升高,GSH-Px的活性明显增强,MDA含量降低(P<0.01);天香丹低剂量组GSH-Px活性和MDA含量没有明显变化。结论:天香丹冲剂预处理对大鼠心肌缺血再灌注损伤有一定的保护作用。     

液相色谱-串联质谱法测定犬血浆中布地奈德

建立液相色谱-串联质谱法测定犬血浆中布地奈德。血浆样品碱化后，经乙酸乙酯液-液萃取，以乙腈-5 mmol·L^-1醋酸铵(60∶40，v/v)为流动相，Capcell Pak C₁₈ MG柱分离；采用电喷雾电离源，以多反应监测(MRM)方式进行负离子检测，用于定量分析的离子反应分别为m/z 489→m/z 357(布地奈德)和m/z 493→m/z 413(内标，曲安奈德)。测定血浆中布地奈德方法的线性范围为25.0～2 000 pg·mL^-1，定量下限为25.0 pg·mL^-1，日内、日间精密度(RSD)均小于15%，准确度(RE)在-8.1%～-1.7%。应用本法研究6只比格犬单次和多次给予布地奈德缓释胶囊9 mg后的药代动力学结果显示：单次给药后T_max为(3.5±3.3) h，C_max为(786±498) pg·mL^-1；多次给药后C_max为(2 142±1 515) pg·mL^-1。该法选择性强、灵敏度高、操作简便，适用于布地奈德缓释制剂的药代动力学研究。