CPA分光计算法同时测定多种维生素的研究

本文在矩阵法的基础上,研究了四组分紫外分光同时测定,采用CPA分光计算法对VB₁,VB₂,VB₆及烟酰胺混合组分同时定量,以BASIC语言编制计算程序,试样回收率在95～105%之间,均方根偏差为3.58%,为多种维生素同时测定提供简便、准确的方法。同时,对影响定量精度的测定误差与计算误差进行了较为详细的讨论。     

卡尔曼滤波分光光度法测定复方维生素B片四组分含量

复方维生素B片中的主要成分维生素B₁,B₂,B₆及烟酰胺各具有一定的不稳定性,且配方比例差较大,因而给多组分同时测定带来一定的困难。本文研究了应用卡尔曼滤波分光光度法同时测定复方维生素B片中的主要成分的可行性,并在处理由于分子间的相互作用引起的吸收度偏离Beer-Lambert定律的现象作了探索,得到较满意的结果。维生素B₁,B₂,B₆及烟酰胺的回收率分别是:100.2±0.90%(CV),100.3±1.7%(CV),101.1±3.3%(CV),99.90±0.65%(CV)。较已有的报道结果均好,表明方法可行。     

维生素B6电化学反应机理的研究

用循环伏安法和计时库仑法研究了维生素B₆(VB₆)在不同pH值的磷酸盐介质中的电化学行为。结果表明:VB₆经过一个有质子参与的4e不可逆电氧化反应;在碱性和中性介质中VB₆被电氧化为含有羰基结构的自由基;在酸性介质中VB₆被电氧化为γ-内酯。电氧化的产物均具电活性,可分别发生两步准可逆氧化还原反应。化学鉴定实验表明在碱性和中性介质中VB₆氧化后生成羰基化合物,而在酸性介质中VB₆氧化后无羰基生成。紫外吸收光谱电化学实验结果表明:VB₆在碱性和中性介质条件下随电解时间而变化的吸收光谱与在酸性介质条件下的不一样。在此基础上提出了VB₆在不同pH介质条件下可能的电化学反应历程。     

可变误差多面体法用于多种维生素的同时测定

本文基于对多元校正分析模型的简要讨论,探索了应用可变误差多面体法同时测定维生索B₁,B₂,B₆和烟酰胺的可行性。其结果准确度和精密度均较满意。维生素B₁,B₂,B₆及烟酰胺的回收率分别是99.8±0.9%(CV),100.1±0.8%(CV),100.2±2.1%,100.1±0.7%(CV)。结果表明,通过公式K_S=A_SC_S^T(C_SC_S^T)^-1计算校正系数矩阵K_S,并结合可变误差多面体法这一直接求解方法,能有效地提高分析结果的准确度,克服组分间的交互作用及病态,是多元校正分析的较佳策略之一。     

HPLC法同时测定复方三维右旋泛酸钙糖浆中4中维生素的含量

目的 建立高效液相色谱(HPLC)法同时测定复方三维右旋泛酸钙糖浆中维生素B₁、维生素B₂、维生素B₆和烟酰胺的含量。方法 采用外标法进行测定,色谱柱为Thermo Betasil C₁₈ Analytical(4.6 mm×250 mm, 5 μm),流动相为乙腈-5 mmol·L^-1十二烷基硫酸钠（含0.05%甲酸）水溶液梯度洗脱,流速1.0 mL·min^-1,检测波长260 nm,柱温30 ℃。分别测定10批复方三维右旋泛酸钙糖浆。结果 维生素B₁、维生素B₂、维生素B₆、烟酰胺4种成分的线性范围分别为5.76~115.2 μg·mL^-1(r=0.999 9)、1.16~23.20 μg·mL^-1(r=0.999 9)、1.72~34.4 μg·mL^-1(r=0.999 6)和5.76~115.2 μg·mL^-1(r=0.999 9),平均加样回收率为96.2%~98.4%(RSD为2.14%~3.42%)。不同批次复方三维右旋泛酸钙糖浆中维生素B₁、维生素B₂、维生素B₆、烟酰胺含量范围分别为0.133 7~0.155 9、0.027 86~0.030 71、0.039 05~0.047 7、0.138 7~0.148 2 mg·g^-1。结论 该方法为完善复方三维右旋泛酸钙糖浆的质量标准和加强质量控制提供了新的方法和依据。     

含硫药物的氧瓶燃烧—电位滴定法测定

建立了一种测定含硫药物的方法。利用氧瓶燃烧法使分子中的硫元素转化为SO₄^2-,然后通过蒸发,加维生素C分解过氧化氢以及加入无水乙醇和1.4—二氧六环等步骤,再用硝酸铅标准溶液以铅离子选择性电极作指示电极进行电位滴定,籍此测定含硫药物的含量。用此法测定了一组含硫药物原料药和几种制剂,经与药典法比较,结果一致。方法简便,在混合物分析中有一定的选择性。     

UHILIC-MS/MS法同时测定复方三维右旋泛酸钙糖浆中5种维生素的含量

目的 建立一种超高效亲水作用色谱串联三重四极杆质谱法（UHILIC-MS/MS）,同时测定复方三维右旋泛酸钙糖浆中维生素B₁、维生素B₂、维生素B₆、烟酰胺和泛酸钙的含量。方法 采用超高效液相色谱仪,Waters ACQUITY BEHHILIC Amide色谱柱（2.1 mm×100 mm,1.7 μm）,以90%乙腈（含0.5%甲酸）-10 mmol/L甲酸铵水（含0.5%甲酸）为流动相,进行梯度洗脱,流速0.30 ml/min;在电喷雾（ESI）正离子模式下,用多反应监测（MRM）模式进行含量测定。结果 在5 min内,样品中5种维生素分别在各自考察的浓度范围内呈良好的线性关系,相关系数（r）均大于0.998 4;整体加样回收率在93.27%~100.39%之间,RSD为1.41%~4.96%;10批样品中维生素B₁、维生素B₂、维生素B₆、烟酰胺、泛酸钙的含量测定结果分别为32.40~38.91、7.002~8.462、9.677~11.17、33.64~39.58、3.276~3.771 mg/250 g。结论 本研究建立的UHILIC-MS/MS方法可快速实现对复方三维右旋泛酸钙糖浆中5种维生素类成分定性鉴定或定量检测,为复方三维右旋泛酸钙糖浆的开发利用和质量评价提供了可靠的技术检测方法。     

3-[p-ω-取代氨基烃氧基)-苯甲酰]-吲哚衍生物的合成

本文根据某些吲哚化合物具有抗生育活性,结合多数非甾体抗生育化合物联有碱性醚链的结构特征,设计并合成了以吲哚为母核的四种类型化合物(Ⅰ_1～7,Ⅱ_1～7,Ⅲ_1～7,Ⅳ₁)22个,并验证了三个熔点与文献报道不符的关键中间体。对小白鼠的初步药理试验表明:所合成的化合物均无抗着床作用;Ⅱ₁,Ⅱ₂,Ⅱ₄和Ⅱ₅有明显的镇痛作用;Ⅲ₂和Ⅲ₃则有较强的抗电休克作用。     

莨菪碱衍生物与M胆碱受体相互作用的构效关系

本文研究了一系列东莨菪碱衍生物对³H-QNB与大鼠脑M受体特异结合的影响。并通过比较它们的IC₅₀(用结合实验),药物—受体相互作用的解离常数K_B(抗乙酰胆碱引起的回肠收缩)以及抗震颤和抗匹罗卡品引起小鼠流涎的ED₅₀,分析了它们的构效关系。结果表明,K_B值与IC₅₀有很好的相关性(r=0.977),其线性回归的斜率为1.047;IC₅₀与抗震颤作用的ED₅₀之间相关性差,而log IC₅₀/ED₅₀值与它们的分配系数(logP)相关好(r=0.971),10号化合物的分配系数最大,中枢作用的选择性也最强。抗流涎ED₅₀与IC₅₀的相关系数为0.827。     

莫达非尼在小鼠体内的药动学-药效学联合研究

对莫达非尼 (modafinil, MOD) 在小鼠体内的药动学和药效学进行联合研究, 以阐明其关联性, 为临床合理用药提供依据。以莫达非尼120 mg·kg⁻¹对小鼠灌胃给药, 采集给药后不同时间点血浆样本, 用HPLC检测血浆药物浓度, 分析平均血药浓度经时变化并计算药动学参数。以小鼠自主活动计数为药效学指标, 观测MOD 120 mg·kg⁻¹灌胃给药后不同时间段内小鼠自主活动量 (计数) 的变化, 分析与血浆药物浓度变化的相关性。结果显示, MOD在小鼠体内药动学过程符合二室模型, t_1/2α, t_1/2β, t_max, C_max, AUC_0−∞分别为0.42 h, 3.10 h, 1.00 h, 41.34 mg·L⁻¹和142.22 mg·L⁻¹·h。MOD使小鼠自主活动明显增多, 持续约4 h, 且与血浆药物浓度呈同步变化, 二者间存在明显的相关性。     

The use of inverse gas chromatography to assess the acid-base contributions to surface energies of cefditoren pivoxil and methacrylate copolymers and possible links to instability

It is known that acids and bases when mixed together have the potential to react, however, there is complexity when materials are in the solid state, as the surface of the solids may not have all functional groups of the molecule expressed in equal proportions. Conceptually a drug that is acidic when in solution could have a crystal surface that is largely basic (if the acid groups are aligned away from the surface). The interaction of cefditoren pivoxil (a basic drug when dissolved) and various Eudragit polymers was studied. The drug was chemically unstable with Eudragit EPO (basic) and stable with Eudragit L100 or S100 (both acidic). Thus, the hypothesis of this work was that the surface of these materials had a different nature to the dissolved molecules, such that solid state reactions do not proceed in line with the expectation from the solution state. Inverse phase gas chromatography (IGC) was used to investigate the cefditoren pivoxil and the Eudragits. The basic to acidic parameter ratios (K(D)/K(A)) on the powder surface of the samples by IGC revealed that surface nature was in keeping with the tendency to react, such that the incompatibility could be due to the acid-base interaction between any carbonyl groups having an amphoteric nature on the surface of cefditoren pivoxil crystal and dimethylaminoethyl groups having a basic nature on the powder surface of Eudragit EPO. This study indicated that IGC would be suitable to elucidate the cause of incompatibility between two different solids.     

The influence of incubation temperature and surfactant concentration on the interaction between dimyristoylphosphatidylcholine liposomes and poloxamer surfactants

Differential scanning calorimetry and photon correlation spectroscopy have been used to study the interaction between poloxamers P338 and P407 and dimyristoylphosphatidylcholine (DMPC) liposomes. The extent of the interaction was found to be dependent on the incubation temperature in addition to the poloxamer concentration. At low poloxamer concentrations (0.1-1.0% w/v) an interaction with the phospholipid bilayer was detected by a reduction of the pre-transition enthalpy of DMPC. At higher concentrations (2.0-5.0% w/v), the main phase transition temperature of the liposomes decreased and the endotherm broadened with a shoulder on the high temperature side, indicative of phase separation. Maximum increases in the diameter of small freeze-thaw extruded liposomes were shown to occur at temperatures close to the poloxamer critical micelle temperatures. At higher temperatures and surfactant concentrations there was evidence of solubilization of phospholipid into mixed micelles.     

Sustained-release delivery systems, I: Phase diagram studies of dapsone and selected derivatives

In order to develop slowly dissolving particles containing the antileprotic drug dapsone (4,4'-sulfonylbisbenzamine, that would be suitable for a sustained-release intramuscular injection, the dilauryl and monolauryl derivatives of dapsone, N,N'-didodecanoyl-4,4'-sulfonylbisbenzamine and N-dodecanoyl-4,4'-sulfonylbisbenzamine, respectively, were studied for their ability to form solid dispersions with the parent compound. The 1:2 binary phase diagram showed these two compounds were partially miscible in the liquid state, leading to the coexistence of a monotectic and a eutectic system in the phase diagram. The 1:3 phase diagram showed that these compounds were completely miscible in the liquid state and formed discontinuous solid solutions in the solid state. At a cooling rate of 2.5 degrees C min-1, eutectic mixtures lying on the dapsone side of the eutectic point formed glass solutions. Taken as a whole, the results demonstrate that the molecular interactions between 1 and 3 are stronger than those between 1 and 2. Accordingly, 3 would appear to be the better carrier for reducing the rate of dissolution of dapsone from a solid dispersion.     

Solid state chemistry of proteins IV. what is the meaning of thermal denaturation in freeze dried proteins?

This research addresses the thermodynamic significance of the denaturation endotherm observed during differential scanning calorimetry (DSC) scans of proteins in dry formulations, such as freeze dried solids. Human growth hormone formulations are the chosen representative examples. We employ observations of denaturation temperature, glass transition temperature, and the differences between estimated molecular mobilities to argue that unfolding is under partial thermodynamic control. Further, unfolding during a DSC scan is simulated using a three state kinetic model, which is a two state unfolding model followed by aggregation. Kramers-type rate constants are used, where the preexponential term is dominated by viscous forces. Simulation results are in qualitative agreement with experiment, and clearly show that while the denaturation endotherm is impacted by irreversibility, caused by nonzero scan rate and aggregation, the position of the endotherm peak is changed only slightly. Thus, the denaturation peak is a good approximation for the thermodynamic denaturation temperature. Using data for denaturation temperature, heat of denaturation, and heat capacity of denaturation, free energy versus temperature curves were calculated. We find that even formulations with added saccharides are thermodynamically unstable near ambient temperature; significant denaturation in the solid state is prevented by low mobility.     

银杏达莫注射液干预治疗老年糖尿病高黏血症及周围血管病变的临床研究

目的探讨银杏达莫注射液在老年糖尿病高黏血症及周围血管病变中的治疗作用。方法将符合1999年WHO诊断标准的98例老年糖尿病合并高黏血症及周围血管病变的患者随机分为两组:干预组50例,对照组48例,2组均给予控制血糖、血压、糖尿病教育的基础治疗,干预组予银杏达莫注射液15～25 ml/d静脉滴注,15d为1个疗程;对照组口服Vit B_1、Vit B_6、复方丹参片治疗。观察治疗前后2组患者的血液流变学、眼底病变、下肢足背动脉搏动、皮肤颜色、温度、痛、温、触觉等相关指征及血糖、血压、HbA_1c、TG、TC、HDL—C、心脑血管事件发生率等。结果干预组患者血液流变学及周围血管病变的好转率高,恶性发展率低,心脑血管事件发生率低。血脂、血液流变学、下肢血管多普勒彩超及眼底病变等好转改善率明显,与对照组比较,差异有统计学意义(P<0.05)。结论银杏达莫注射液对老年糖尿病的高黏血症及周围血管病变的干预治疗疗效显著,有较重要的临床意义。     

丙二醇与丙三醇红外光谱鬼峰的研究

目的：发现丙二醇与丙三醇红外光谱中鬼峰出现的缘由,建立方法去除鬼峰的干扰。方法：比较不同含水量样品的红外图谱膜法得到的红外光谱,分析鬼峰出现的原因;通过加热膜法控制鬼峰。结果：膜法制图1645cm^-1处有中等强度吸收峰,且含水量越高该峰强愈大;加热膜法制图该吸收峰消失或峰强显著降低。结论：鬼峰为水的吸收峰,采用加热膜法可避免鬼峰出现或有效控制鬼峰强度。     

Vitamin-C as anti-Helicobacter pylori agent: More prophylactic than curative- Critical review

Potential of nonantibiotic therapies for treatment of Helicobacter pylori-related acid peptic disease remains underexplored. Several clinical studies have shown that higher prevalence of H. pylori infection is associated with low Vitamin C (Vit C) level in serum and gastric juice. However, there is no consensus regarding the usefulness of Vit C supplementation in the management of H. pylori infection. Surveying the existing literature we conclude that high concentration of Vit C in gastric juice might inactivate H. pylori urease, the key enzyme for the pathogen's survival and colonization into acidic stomach. Once infection established, urease is not very important for its survival. The role of Vit-C as anti-H. pylori agent in peptic ulcer diseases appears to be preventive rather than curative. Rather than supplementing high dose of Vit C along with conventional triple therapy, it is preferable to complete the conventional therapy and thereafter start Vit C supplementation for extended period which would prevent reinfection in susceptible individuals, provided the patients are not achlorhydric. Further studies are required to prove the role of Vit C in susceptible population.     

A study of amorphous molecular dispersions of indomethacin and its sodium salt.

Amorphous solid dispersions of indomethacin (IMC) and sodium indomethacin (NaIMC) over a range of compositions were prepared by physically mixing amorphous IMC and amorphous NaIMC, as well as by coprecipitation from methanol solution. Measurement of glass transition temperatures, T(g), for the physical mixtures revealed two values indicating, as expected, phase separation. In contrast, all samples of coprecipitated materials exhibited one value of T(g), which was greater than that predicted for ideal miscibility in the formation of a molecular dispersion. Such nonideality suggests a stronger acid-salt interaction in the amorphous state than that between acid-acid and salt-salt. FTIR spectroscopic analysis provides evidence for interactions between NaIMC and IMC through a combination of hydrogen bonding and ion-dipole interactions between the carboxylic group of the acid and the carboxylate anion of the salt. The inhibition of isothermal crystallization of IMC by NaIMC only when in molecular dispersion is believed to result from the interaction between the acid and the salt, which prevents the formation of hydrogen-bonded carboxylic acid dimers for IMC, required for the formation of crystal nuclei and crystallization.     

2-取代苯基-5-(3′-吲哚基)-噁唑衍生物的合成及其抗氧化活性

目的　合成 5 ( 3′ 吲哚基 ) 唑衍生物并研究其抗氧化活性。方法　以色氨酸为原料 ,与取代的苯甲酸在DCC催化下脱水缩合得到酰胺 ,再通过DDQ苄位氧化和分子内环合生成 5 ( 3′ 吲哚基 ) 唑。用DPPH体外抗氧化模型测定化合物的抗氧化活性。结果　合成了 11个 2 取代苯基 5 ( 3′ 吲哚基 ) 唑衍生物 ,其中化合物 2 1和 2 2的活性比维生素E强约 3～ 4倍 ;化合物 2 9的活性与维生素E相近。结论　合成的目标化合物中有 3个化合物有较好的抗氧化活性 ,有可能开发成为良好的抗氧化剂。     

2-取代苯基-5-(3′-吲哚基)-唑衍生物的合成及其抗氧化活性

目的合成5-(3′-吲哚基)-唑衍生物并研究其抗氧化活性。方法以色氨酸为原料,与取代的苯甲酸在DCC催化下脱水缩合得到酰胺,再通过DDQ苄位氧化和分子内环合生成5-(3′-吲哚基)-唑。用DPPH体外抗氧化模型测定化合物的抗氧化活性。结果合成了11个2-取代苯基-5-(3′-吲哚基)-唑衍生物,其中化合物21和22的活性比维生素E强约3～4倍;化合物29的活性与维生素E相近。结论合成的目标化合物中有3个化合物有较好的抗氧化活性,有可能开发成为良好的抗氧化剂。