缓释力足踝矫形器的研制及临床应用

目的:制作缓释力足踝矫形器,探索伴有腓肠肌或跟腱挛缩的足下垂的非手术性矫治方法。方法:用半成品高分子纤维材料制作足托,楔形去除足托之踝关节转动中心处两侧的材料,以此为轴使之具有似折叶的活动性。用弹性牵引带于足托的足尖部自前面与足托的小腿部上端胫骨前相连,利用弹性带的回缩力,起到缓慢的持续牵引作用,使跟腱和腓肠肌的挛缩、踝关节的粘连得到逐渐松解,踝关节背屈活动度得到逐渐增加,足下垂得到逐渐矫正。结果:缓释力足踝矫形器有较好的肢体适应性。由于具有良好的透气性能,故穿戴舒适,能起到缓慢的小剂量持续牵引作用。对伴有腓肠肌和跟腱挛缩以及踝关节纤维性粘连的足下垂有较好的矫正作用,22例足下垂患者,踝关节跖屈固定角度和踝关节被动活动范围分别由治疗前的44.91±5.35和3.54±1.63,恢复到治疗后的17.59±10.04和28.09±9.26,治疗前后比较差异均有显著性意义(P<0.05)。结论:缓释力足踝矫形器是一种设计合理、具有良好疗效的非手术性足下垂矫治工具。

减载缓释机构缓释特性的上限法分析

为了提高发射可靠性,我国未来的运载火箭中拟采用牵制释放系统。文章以一种新型强制式牵制释放系统为例,建立了分析该系统中减载缓释机构缓释特性的上限模型。该模型可以考虑缓释销拉拔过程中截面缩减率的变化、拉拔模芯表面的摩擦、缓释销材料的硬化以及死区的形成等因素对缓释力曲线的影响。所得上限解与实验数据符合较好,可为减载缓释机构的合理设计提供理论依据。

运载火箭牵制释放发射研究

为提高发射可靠性,运载火箭采用牵制释放系统。以连杆式牵制释放机构和套筒-缓释销型减载缓释放机构组成的牵制释放系统为例,运用Adams多体动力学软件和Abaqus有限元软件,研究运载火箭牵制释放发射时牵制力的特性,对比连杆之间角度不同时气缸力的变化,仿真缓释销从套筒内拔出的过程并得到缓释力曲线,比较有无减载缓释放机构时火箭起飞的运动规律。研究表明,连杆机构能大大减小气缸力的设计要求,连杆之间的夹角对气缸力有较大的影响,减载缓释放机构能为火箭提供递减的缓释力,减小突然释放时对箭体的冲击。研究结果对运载火箭牵制释放发射具有一定的参考价值。

膨胀性软岩隧道支护结构受力特性及缓释方法

隧道工程中因软岩的膨胀性而诱发的隧道支护结构失稳现象十分普遍。以膨胀性软岩导致隧道围岩结构非均匀受力为出发点,研究膨胀性软岩隧道支护结构的受力特性,试图建立一种膨胀性软岩隧道支护结构受力缓释方法。在初期支护与二次衬砌之间植入团粒膨润土作为缓冲层,开展室内缩尺物理模型试验。通过MIDAS GTS NX软件建立三维数值模型,对比分析加入缓冲层前、后的膨胀性软岩隧道支护结构的受力特性。根据隧道力学理论推导构建膨胀性软岩隧道支护结构受力缓释模型,得到缓释系数表达式,据此验证膨胀性软岩隧道支护结构受力缓释方法的实用性。研究结果表明:加入缓冲层后,支护结构的变形及围岩膨胀力较加入前明显变小,变形均呈拱顶下沉、拱底向上隆起、拱腰向内收敛的特征;缓冲层通过对抗、弱化、传递以减小作用于支护结构上的围岩膨胀力,使单一的集中受力体系转变为均布荷载体系;通过缓释模型计算得出缓释系数为30%~50%,表明在初期支护与二次衬砌之间植入团粒膨润土作为缓冲层可以起到缓释膨胀力的作用,可为解决软岩隧道膨胀问题提供参考。

Preparation and Pharmacokinetic Characterization of Sustained Release Melatonin Tablet

Aim To prepare the sustained release melatonin tablet with HPMC matrix and study its pharmacokinetics and bioavailatility. Methods HPMC was used as matrix to formulate the sustained release tablet. The influences of the size of melatonin, type and amount of HPMC, drug loading, type and amount of additives, and compressing pressure were investigated. Plasma concentration of melatonin in dogs after intravenous injection of two doses and oral administration of sustained release tablets and unmodified release capsules was detected by HPLC using fluorescence detector. Results The drug release from sustained release tablets was influenced by the size of melatonin, type and amount of HPMC, drug loading, and type and amount of additives. Melatonin was found to fit two compartment model after intravenous injection, AUC was proportional to doses, and t(1/2β) of two doses has no significant difference. Relative bioavailability of melatonin sustained release tablet to normal capsule was 83.8%, and absolute bioavailability was 3.75% for sustained release tablet and 4.49% for capsule. Conclusion The melatonin sustained release tablet was well formulated. The absolute bioavilability for oral administration of either sustained release tablet or unmodified release capsule of melatonin was less than 5%. The bioavailability of melatonin sustained release tablet was lower than that of unmodified release capsule, but MRT of sustained release tablet was significantly longer than that of capsule.

Pharmacokinetics and Relative Bioavailability ofsustained-release Tablets of Diclofenac Sodiumin Male Volunteers

The pharmacokinetics of a sustained- release formulation and an enteric- coated tablet of diclofenac sodium were studied on 8 healthy male volunteers in an open,randomized crossover study.Drug level in serum was assayed by HPLC method.The changes in serum concentration were conformed to a l-compartment open model.The t_1/2 (Ke)averaged 2.15±0.17 and ll.60 ± l.95 h,and the areas under the drug concentration curves were 5.87 ± 0.67 and 5.55 ± 0.57μgh/ml for enteric-coated and sustained-release tablet of diclofenac sodium,respectively. The mean relative bioavailability of sustained-release tablet was 0.95 to that of enteric-coated tablet.

Pharmacokinetics of Moclobemide Sustained Release Tablets after Multiple Oral Dose Administration in Healthy Volunteers

To investigate the pharmacokinetic characteristics of moclobemide sustainedrelease tablets after multiple oral dose administration in healthy Chinese volunteers. MethodsMoclobemide sustained release tablets were given as a multiple oral dose regimen of 300 mg oncedaily for five consecutive days to 12 healthy volunteers. The concentrations of moclobemide inplasma were determined by reversed-phase high performance liquid chromatography. The partialpharmacokinetic parameters were calculated using 3p97 pharmacokinetic program. Results Theconcentration-time profile fitted an one-compartment model best. The steady-state pharmacokineticparameters of moclobemide sustained release tablets after multiple oral doses were as follows:C_(max) was (1 950 +- 156) μg· L^(-1), T_(max) was (6.00 +-1.55) h, T_(1/2(kel)) was (3.14 +-0.12)h, AUC_(ss 0-24) was (22 836 +- 1 842) μg·h· L^(-1), MRT was (7.68+-0.36) h, CL/F_((s)) was(20.2+-2.1) L·h^(-1), and V/F_((c)) was (91.4+-9.4) L, respectively. No marked adverse events werenoted during this study. Conclusion The formulation has a sustained-release effect and goodtolerance in the healthy volunteers, which provides useful information for clinical practice.

Bistability Analysis of Excitatory-Inhibitory Neural Networks in Limited-Sustained-Activity Regime

Bistable behavior of neuronal complex networks is investigated in the limited-sustained-activity regime when the network is composed of excitatory and inhibitory neurons.The standard stability analysis is performed on the two metastable states separately.Both theoretical analysis and numerical simulations show consistently that the difference between time scales of excitatory and inhibitory populations can influence the dynamical behaviors of the neuronal networks dramatically,leading to the transition from bistable behaviors with memory effects to the collapse of bistable behaviors.These results may suggest one possible neuronal information processing by only tuning time scales.

Hydroxy Propyl Methyl Cellulose： Different Aspects in Drug Delivery

Among the various research works going on nowadays, designing of controlled release dosage form is of great importance. For the development of suitable controlled release dosage form, a proper matrix needs to be formed from which the drug release generally occur by polymer swelling, polymer erosion, drug dissolution/diffusion mechanism. HPMC （hydroxy propyl methyl cellulose）, also known as hypromellose, is one of the best known cellulosic polymers used in the development of controlled released drug delivery. It is available in various grades. Cellulosic polymers are ingredients that contain units linked together which help to retain water. Due to its high water absorptive capacity, it acts as an excellent hydrophilic gel forming polymer. HPMC generally hydrates on the outer surface to form a gelatinous layer which is critical to prevent wetting and rapid drug release from the matrices. If the drug is sparingly soluble in the system, the release of drug from the system is slow and helps in formulation of controlled release dosage form. In the ophthalmic dosage form, HPMC is used as a matrix that swells and expands after absorbing water and expand the thickness of the tear film.

Preparation of lomustine loaded liposomes and studies of its pharmacokinetics and tissue distribution properties

Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes （CCNU-Lips） and evaluate its physicochemical properties and the tissue targeting after intravenous （i.v.） injection. CCNU-Lips were prepared by film dispersion method. In vitro drug release was investigated in phosphate-buffered saline （pH 6.8） at 37℃. The concentrations of CCNU in selected organs were determined using reversed-phase high-performance liquid chromatography （HPLC） following i.v. administration of CCNU-Lips and inclusion complex solution of CCNU with hydroxypropyl-β-cyclodextrin （CCNU-Sol）. CCNU-Lips had an average diameter of （189.8±28.5） nm with a zeta potential of （-19.13±0.12） mV and the in vitro drug release was monitored for up to 3 d, and the release behavior was in accordance with Weibull-equation. The CCNU-Lips exhibited a longer elimination half life （t1/2β） in vivo compared with CCNU-Sol after i.v. injection to New Zealand rabbits. The encapsulation of lomustine in liposomes also changed its biodistribution in mice. CCNU-Lips showed significant brain targeting with AUC, Te and Re of the brain all showing obvious elevation. These results indicated that CCNU-Lips were promising passive targeting formulation to the brain.

A novel o-nitrobenzyl-based photocleavable antitumor prodrug with the capability of releasing 5-fluorourail

An o-nitrobenzyl-based photocleavable antitumor prodrug with a terminal carboxyl group was designed and synthesized.The photolysis properties of the prodrug were investigated by means of1H NMR,HPLC,UV,and MTT methods.The results showed that the toxicity of the anticancer drug was effectively shielded before release.However,the prodrug effectively regained the antitumor capability against cancer cells by release of 5-fluorouracil when it was exposed to ultraviolet irradiation.