一个耦合双曲-抛物系统的全局光滑解

考虑一个源自生物学的耦合双曲-抛物模型的初边值问题. 当动能函数为非线性函数以及初始值具有小的$L^2$能量但其$H^2$能量可能任意大时, 得到了初边值问题光滑解的全局存在性和指数稳定性. 而且, 如果假定非线性动能函数满足一定的条件, 在对初值没任何小条件假定下得到光滑解的全局存在性. 通过构造一个新的非负凸熵和做精细的能量估计得到了结果的证明.     

Hopfield型连续神经网络模型的稳定性

利用单调流方法得到一类 Hopfield型连续神经网络模型存在唯一全局渐近稳定正平衡态的充分条件     

一类艾滋病传播动态模型的稳定性

文(1)介绍了一类艾滋病多群组传播动态模型,给出了无传染病平衡态的稳定性结论,但传染病平衡态的稳定性未解决。本文指出一定条件下,传染病平衡态的存在性与稳定性。     

一类多传染阶段的艾滋病模型

当前国内外对艾滋病传染模型的研究引起了广泛的重视，在各种不同的假设下，建立了各种不同的模型。随着研究的深入，所建立的模型正在逐步接近实际。本文在文〔１〕、〔２〕和〔３〕的基础上作进一步的讨论，除了考虑将ＨＩＶ感染者分成ｎ个不同感染阶段外，还对性接触数不为常数而是性活动积极者总数Ｎ的函数的情况，来建立模型和进行分析，以得出复发数与疾病消除平衡态及流行平衡态之关系的阈值定理。     

水葫芦生态系统状态反馈控制

本文研究一类以Logistic增长为基础的具有群体防御的水葫芦生态系统.首先得到无脉冲作用的系统定性结论.其次对具有状态反馈控制的脉冲系统,利用微分方程几何理论中后续函数法得到系统的阶一周期解存在的充分条件,证明该周期解是轨道渐近稳定的,同时利用数值模拟讨论了系统生态意义.     

亚纯系数的高阶线性微分方程的解的增长性

本文研究亚纯系数的高阶线性微分方程,当方程系数满足一定条件时,得到方程的每一非零亚纯解具有无穷级且超级为n.此外,还研究了非齐次线性微分方程的亚纯解.     

精神药物临床安全选择简表

到目前为止,对精神障碍的治疗主要仍以药物治疗为主,临床治疗时需在很多药物(特别是在同一类)中选择最合适的药物。治疗时既要考虑药物的适应证,又要考虑每种药品的优缺点、禁忌、慎用、不良反应和相互作用(主要是避免不良的相互作用)等注意事项。笔者参考药品说明书及有关资料,按临床应用分类进行归纳组合,就每类药品的禁忌、慎用、不良的相互作用汇总出一个表格化的资料,供临床医师参考,以便能便捷、正确地选择药物,见表1。精神药物临床安全选择简表@樊学敏$天津市安定医院!天津300074 @毕玉丽$天津市安定医院!天津300074 @孙津津$天…     

非线性扰动偏微分方程混合边值问题的可解性

研究具有混合边界条件的非线性扰动偏微分摄动方程的可解性.得到原问题的摄动解并证明解的展开式的一致有效性.     

半线性椭圆方程正解的等周不等式

证明了一类半线性椭圆方程正解满足等周不等式, 并得到了此解的最佳上界估计.     

一类一阶非线性微分方程的求解方法

利用稳定性理论得到了一类一阶非线性方程的求解方法,得到了相应的显式解或隐式解,并对结果进行了推广。     

The stability of hydrochlorothiazide and cyclopenthiazide in various dosage forms. 4. Stability of hydrochlorothiazide injection solutions II

The hydrolytic decomposition of hydrochlorothiazide (1) in an optimized dispensing with polyethyleneglycol 400/ethanol as solvent led to an equilibrium in the isothermic short-term test as well as in the long-term stability test. Corresponding equilibrium concentrations were obtained for forward and back reaction. When comparing the precalculated equilibrium values with the long-term results the evaluation after Van't Hoff proved superior compared with an evaluation after the Arrhenius plot which is only applicable when the equilibrium concentrations are taken into consideration. By adding the decomposition product aminodisulfamide (2) the hydrolysis of 1 can be inhibited completely.     

Über die Struktur eines photochemischen Reaktionsproduktes des Nardosinons

Structure of an Irradiation Product of Nardosinone For an irradiation product of nardosinone (1) , which is also formed in the reaction of isonardosinone (4) with hydrogen peroxide in alkaline solution, the structure of a hydroxy ketone, which is in equilibrium with a four-membered cyclic hemiacetal (2a,b) was proposed²⁾. Based on chemical reactions and spectroscopic data, the structure of a diepoxy ketone, which is in equilibrium with a six-membered cyclic hemiacetal 7a,b is now suggested.     

Assessment of a five-layer laminate technique to measure the saturation solubility of drug in pressure-sensitive adhesive film

A five-layer laminate technique is used to determine the saturation solubility of a drug in a thin polymer film, c(p)(s), of pressure-sensitive adhesive (PSA) used to prepare transdermal patches. A drug-loaded donor polymer film is attached via a separating membrane to an initially drug-free acceptor polymer film. Diffusion of drug occurs into the acceptor up to saturation solubility equilibrium. This systematic study of the technique using the drug tamsulosin and the PSA Duro Tak 87-4098 was a kinetic analysis of the diffusion process. It was found that the technique gives an equilibrium value for c(p)(s) in a PSA polymer film in the presence of crystalline phase of the drug in the donor. A highly permeable Perthese-separating membrane caused overshoot in the acceptor, most likely induced by initial supersaturation of the donor. Change to a less-permeable ethylene-vinyl-acetate-separating membrane avoided overshoot, but gave a prolonged time, >300 days, to equilibrium. Preloading the acceptor accelerated the equilibration process to approximately 50 days with the Perthese. Suitable experimental conditions are identified that, if performed correctly, allow the technique to give an equilibrium value for c(p)(s).     

Quantitative determination of tautomeric FK506 by reversed-phase liquid chromatography

The quantitative determination of FK506, an immunosuppresant for organ transplants, was studied by using reversed-phase high performance liquid chromatography. There were three peaks corresponding to FK506 and its tautomeric compounds on the chromatogram obtained from aqueous solution. Interconversion among these compounds due to epimerization occurs and then reaches an equilibrium in aqueous solution. An increase in the water content in water-solvent solutions caused by the peak areas of FK506 and Tautomer I to decrease and that of Tautomer II to increase. For quantitative analyses of aqueous solutions this creates a problem because the composition of the mixture at equilibrium varies with the water content. A simple method, using a solution of polyoxyethylene lauryl alcohol ether (Brij-35) as a diluent, has been developed to provide a constant equilibrium. By diluting the sample with the Brij-35 diluent, it is possible to quantify FK506 in aqueous solutions. The reliability of the proposed method was confirmed with samples extracted from fermentation broth.     

Solubility and stability of anhydrate/hydrate in solvent mixtures

In this paper, the thermodynamics of the anhydrate/dihydrate carbamazepine (CBZA/CBZH) in ethanol-water mixtures was studied by measuring the solubility of anhydrate and dihydrate carbamazepine at 0-60 degrees C. Both stable form solubility and metastable form solubility were measured, the latter with the assistance of Raman immersion probe. The thermodynamic properties of the anhydrate/dihydrate system, such as the relative stability, and enthalpy and entropy of dissolution, were estimated by plotting the measured solubility data according to the van't Hoff equation. The anhydrate/dihydrate carbamazepine showed an enantiotropic relationship in the studied mixtures and temperature ranges. It was shown that at a certain temperature, there was an equilibrium water activity value at which the anhydrate and dihydrate carbamazepine were in equilibrium. This equilibrium water activity value depends significantly on the temperature. The lower the temperature, the smaller is the water activity value needed to attain equilibrium between anhydrate and dihydrate. The obtained results are useful in determining crystallization parameters to achieve a desired anhydrate or hydrate phase. The approach can be applied to other anhydrate and hydrate systems.     

Tissue binding affects the kinetics of theophylline diffusion through the stratum corneum barrier layer of skin

New data sets on both (i) equilibrium theophylline (TH) partitioning/binding in stratum corneum and (ii) transient TH diffusion through human epidermis are explained by an extended partition-diffusion model with reversible binding. Data conform to a linear binding isotherm within the tested concentration range (0-2000 μg/mL) with an equilibrium ratio of bound-to-free solute of approximately 1.4. The permeability coefficient for TH is 4.86 × 10(-5) cm/h, and the lag time is 20.1 h. Binding occurs as a slow process, significantly affecting the kinetics of dermal penetration.     

Ultraviolet light-induced photorelaxation of agonist-contracted rabbit aorta: Further characterization and the estimation of drug-receptor rate constants

Isolated strips of rabbit thoracic aorta, contracted to a steady-state isometric tension by measured doses of α-adrenoceptor agonists, exhibit a transient loss in tension when exposed to a flash of ultraviolet light. This response consists of an initial decrease in tension followed by a spontaneous restoration to equilibrium tension. The time course of the return to equilibrium from maximum relaxation is a biphasic exponential, resolvable into a fast phase and a slow phase. Previous work has shown that the fast phase of recovery is drug-independent, but that the slow phase of recovery is drug-dependent; i.e., the rate of return to equilibrium tension is unique for each agonist used to produce the initial contraction. When a system in equilibrium is perturbed in a manner such as this, the return to equilibrium is characterized by a time constant that is a function of the drug concentration. A plot of this time constant against drug consentration yields a straight line of slope and y-intercept equal to the forward and reverse rate constants, respectively, of the chemical reaction. In this study, equilibrium perturbation by UV light was used to determine the forward and reverse rate constants (k₁ and k₂) of the drug-receptor interaction and the dissociation constants (K_A = k₂/k₁) of each of three α-adrenoceptor agonists, norepinephrine, phenylephrine, and methoxamine. The values of K_A reported here for all three agents and for different degrees of passive stretch (0.25-g and 10-g preload for norepinephrine, 10-g preload for phenylephrine and methoxamine) are not significantly different from the corresponding values reported using the method of partial irreversible blockade of receptors. These findings are compatible with the hypothesis that the radiation disrupts the drug-receptor equilibrium. Regardless of mechanism, however, the photorelaxation phenomenon may provide an additional tool for classifying vasoactive compounds.     

Evaluation of a Catenary PBPK Model for Predicting the In Vivo Disposition of mAbs Engineered for High-Affinity Binding to FcRn

Efforts have been made to extend the biological half-life of monoclonal antibody drugs (mAbs) by increasing the affinity of mAb–neonatal Fc receptor (FcRn) binding; however, mixed results have been reported. One possible reason for a poor correlation between the equilibrium affinity of mAb–FcRn binding and mAb systemic pharmacokinetics is that the timecourse of endosomal transit is too brief to allow binding to reach equilibrium. In the present work, a new physiologically based pharmacokinetic (PBPK) model has been developed to approximate the pH and time-dependent endosomal trafficking of immunoglobulin G (IgG). In this model, a catenary sub-model was utilized to describe the endosomal transit of IgG and the time dependencies in IgG–FcRn association and dissociation. The model performs as well as a previously published PBPK model, with assumed equilibrium kinetics of mAb–FcRn binding, in capturing the disposition profile of murine mAb from wild-type and FcRn knockout mice (catenary vs. equilibrium model: r ², 0.971 vs. 0.978; median prediction error, 3.38% vs. 3.79%). Compared to the PBPK model with equilibrium binding, the present catenary PBPK model predicts much more moderate changes in half-life with altered FcRn binding. For example, for a 10-fold increase in binding affinity, the catenary model predicts <2.5-fold change in half-life compared to an ～8-fold increase as predicted by the equilibrium model; for a 100-fold increase in binding affinity, the catenary model predicts ～7-fold change in half-life compared to >70-fold increase as predicted by the equilibrium model. Predictions of the new catenary PBPK model are more consistent with experimental results in the published literature.     

Numerical solution for 5-layer laminate technique to determine saturation solubility of a drug in a thin film of pressure sensitive adhesive

Abstract

A numerical solution of the one-dimensional diffusion equation is presented to describe the 5-layer laminate technique for estimating the saturation solubility of a drug in a thin polymer film. The boundary and initial conditions encompass a donor layer, a separating membrane, and an acceptor layer. Alteration of the drug’s partition coefficient between donor and separating membrane has little influence on drug accumulation with the acceptor. The diffusivity in the separating membrane should be high to promote a short experimental time to achieve saturation equilibrium in the acceptor layer. The essential parameter to give rapid equilibrium is the thickness of the acceptor polymer film. For values of diffusivity typical for drugs of molecular weight around 500 an acceptor layer thickness of 10?µm–20?µm is required to achieve equilibrium within less than 10?d. These simulations allow the selection of suitable experimental conditions to make the 5-layer laminate technique a viable method for routine use.     

Development of a high throughput equilibrium dialysis method

The identification of large numbers of biologically active chemical entities during high throughput screening (HTS) necessitates the incorporation of new strategies to identify compounds with drug-like properties early during the lead prioritization and development processes. One of the major steps in lead prioritization is an assessment of compound binding to plasma proteins, because it affects both the pharmacokinetics and pharmacodynamics of the compound in vivo. Equilibrium dialysis is the preferred method to determine the free drug fraction, because it is less susceptible to experimental artifacts. However, even low-volume standard equilibrium dialysis is currently not amenable to the HTS format. Those considerations dictate the development of a high throughput equilibrium dialysis device, without compromising the analytical quality of the data. The present paper demonstrates successful development of a 96-well format equilibrium dialysis plate. Plasma protein binding of three drugs, propranolol, paroxetine, and losartan, with low, intermediate, and high binding properties, respectively, were chosen for assay validation. The data indicate that the apparent free fraction obtained by this method correlates with the published values determined by the traditional equilibrium dialysis techniques.