低分子量壳聚糖的研制

研究了在酸性条件下过氧化氢对壳聚糖的氧化降解反应，讨论了过氧化氢浓度、温度及反应时间对氧化降解反应的影响。结果表明，用过氧化氢使壳聚糖氧化降解是制备药用低分子量壳聚糖的一种简便易行的方法。     

N-乙酰-L-半胱氨酸溶液氧化反应速率常数的测定

目的测定N-乙酰-L-半胱氨酸(NAC)在水溶液中氧化反应的速率常数。方法在一定温度下,向反应液中持续通入空气,以维持溶解氧浓度恒定,利用氧电极测定氧的浓度;采用碘量法测定NAC在水溶液中不同时刻的浓度,计算氧化反应降解速率常数。结果试验温度下,在pH9.0、pH6.8的缓冲溶液中,NAC与氧的反应均为表观零级反应,298.2 K时平均表观反应速率常数分别为8.03×10-3、0.08 mmol.L-.1h-1;而在pH4.0的缓冲溶液中,NAC与氧的反应为表观一级反应,298.2 K时,平均表观反应速率常数为0.02 h-1。结论弱碱性和中性条件下反应速率较慢,NAC的抗氧化能力较强;在弱酸性条件下反应速率较快,抗氧化能力较弱。在NAC溶液的初始浓度及pH相同条件下,温度升高,表观反应速率常数增大。     

抗氧剂L-抗坏血酸在水溶液中氧化反应速率常数的测定

目的测定抗氧剂L-抗坏血酸在3种缓冲溶液中与氧反应的速率常数。方法反应液中持续通入空气,在保证溶液中氧浓度恒定的情况下,用碘量法测定不同时刻抗坏血酸溶液的浓度,作出降解曲线,拟合降解公式并计算降解速率常数。结果抗坏血酸在中性和弱碱性溶液中为表观一级反应,氧化反应速率常数分别为(9.24±0.8)×10-3h-1,(100±1)×10-3h-1;在弱酸性溶液中为表观1/2级反应,氧化反应速率常数为(8.73±0.14)×10-5mol1/2·L-1/2·h-1。结论在弱碱性条件下L-抗坏血酸反应速率较快,抗氧化能力较弱;在中性和弱酸性条件下反应速率较慢,抗氧化能力较强。     

低聚氨基葡萄糖的研制

在中性条件下采用双氧水对脱乙酰壳多糖进行氧化降解,制备了分子量为１０００左右的药用低聚氨基葡萄糖。讨论了不同的双氧水浓度,配比,温度和反应时间对降解反应的影响,并用傅立叶红外分析表征了产物的结构。     

抗氧剂L-半胱氨酸盐酸盐在水溶液中的氧化反应速率常数

目的 测定抗氧剂L-半胱氨酸盐酸盐在水溶液中与氧反应的速率常数,并评价其抗氧化能力.方法 在25℃、35℃、45℃下,向反应液中持续通入空气以维持溶解氧浓度恒定,并用氧电极测定其浓度;用碘量法测定L-半胱氨酸盐酸盐在水溶液中不同时刻的浓度,做出降解曲线,计算各温度下的氧化降解速率常数.结果 25℃时,L-半胱氨酸盐酸盐在pH4.0、pH6.8缓冲溶液中与氧的反应均为表观零级反应,而在pH9.0缓冲溶液中为表观一级反应.3个不同pH条件下的表观反应速率常数分别为7.78、30.1μmol·L-1·h-1、5.03×10-2 h-1.结论 L-半胱氨酸盐酸盐在弱酸性条件下,反应速率较慢,抗氧化能力较弱;在中性和弱碱性条件下反应速率较快,抗氧化能力较强.     

注射用交联透明质酸钠凝胶的制备及其体外抗酶降解性的研究

目的筛选交联反应条件,制备强抗酶降解的注射用交联透明质酸钠(HA)凝胶(HA-凝胶),并建立其体外抗酶降解性的测定方法。方法用1,4-丁二醇二缩水甘油醚(BDDE)交联HA制备HA-凝胶,对其体外抗酶降解性的测定方法进行确证;采用正交试验考察6个因素对交联反应的影响,选择最佳反应条件。结果透明质酸酶(HAas)对HA-凝胶体外抗酶降解性测定方法无干扰,HAas在100~500 U/mL与产物显色后的吸光度呈线性关系(r=0.998 8)。正交试验极差分析和方差分析显示HA的起始反应浓度、BDDE与HA的比例对交联反应具有显著性影响,在氢氧化钠浓度1%、HA平均相对分子质量1.2×106、反应温度50℃、BDDE与HA的比例为1∶10(g/g)、反应时间4 h和HA浓度为15%的反应条件下,可得到抗酶降解性最好的HA-凝胶。结论选择适宜反应条件可以制备得到体外抗酶降解性强的HA-凝胶,为进一步开发注射美容和整形产品奠定了基础。     

光催化降解对氟苯氧乙酸的规律研究

以Pt／TiO2为光催化剂,研究了废水中对氟苯氧乙酸的光催化降解反应。考察了反应时间、溶液初始pH值以及污染物初始浓度对光催化反应的影响。实验表明,反应3h内,氟离子平均检出速率为2.64＆#215;10-5mol／（L· h）;在反应4～7h内,氟离子平均检出速率为5.38×10^-5mol／（ L· h）。反应液的紫外光谱图显示对氟苯氧乙酸浓度不断下降。在溶液初始pH值为3.44～4.95时,光催化生成氟离子的速率最大,在碱性范围内,氟离子的生成速率为零。当C0（对氟苯氧乙酸）＜1.00×10^-3 mol· L-1时,光催化降解反应速率随着对氟苯氧乙酸初始浓度的增大而急剧增大;当C0（对氟苯氧乙酸）＞8.00×10^-3 mol· L -1时,光催化降解速率与污染物初始浓度无关。     

微波辐射快速制备水溶性壳聚糖

目的快速制备水溶性壳聚糖。方法利用微波辐射 ,用过氧化氢作氧化剂 ,非均相降解高分子量壳聚糖。设计了正交试验法 ,得到最优化反应条件。结果最优反应条件为 5 %过氧化氢、5 %壳聚糖 ,微波辐射功率约40 0W ,辐射 3min ,所得水溶性壳聚糖分子量为 1 .1× 1 0 4 D ,收率可达 60 %。结论微波法制备低聚壳聚糖效果理想 ,可进一步扩展到壳聚糖的其它化学修饰     

不同相对分子质量壳聚糖的制备和部分性质研究

目的制备不同相对分子质量 (Mr)壳聚糖并研究其部分性质。方法在中性条件下 ,用过氧化氢氧化法制备不同Mr 的壳聚糖 ,并进行红外表征、热分析和稳定性等研究。结果探索到制备不同Mr 壳聚糖的最适宜条件。结论壳聚糖经过氧化氢降解后 ,结构没有明显变化 ,且随壳聚糖Mr 的降低 ,其稳定性增强     

盐酸阿莫罗芬在水溶液中的降解动力学研究

目的：研究盐酸阿莫罗芬在水溶液中的降解动力学。方法：建立HPLC法,测定盐酸阿莫罗芬在不同pH值、不同温度、不同离子强度的缓冲液中的降解动力学参数。结果：盐酸阿莫罗芬在水溶液中的降解呈现伪一级动力学特征,随着温度的增加,其降解速率增大;在37和60℃时,随着PH的增加,盐酸阿莫罗芬的降解速率明显增大（P〈0．05）,其半衰期和有效期明显减小（P〈0．05）,而随着离子强度的增大,其降解速率有所减小（P〉0．05）;在4和25℃时,盐酸阿莫罗芬在不同pH和不同离子强度的缓冲液中相对稳定;盐酸阿莫罗芬降解活化能随着pH的增大而增大。结论：盐酸阿莫罗芬在水溶液中的降解速率与温度、pH值和离子强度有关,其中温度对盐酸阿莫罗芬降解的影响较为明显。     

A novel accelerated oxidative stability screening method for pharmaceutical solids

Despite the fact that oxidation is the second most frequent degradation pathway for pharmaceuticals, means of evaluating the oxidative stability of pharmaceutical solids, especially effective stress testing, are still lacking. This paper describes a novel experimental method for peroxide-mediated oxidative stress testing on pharmaceutical solids. The method utilizes urea-hydrogen peroxide, a molecular complex that undergoes solid-state decomposition and releases hydrogen peroxide vapor at elevated temperatures (e.g., 30°C), as a source of peroxide. The experimental setting for this method is simple, convenient, and can be operated routinely in most laboratories. The fundamental parameter of the system, that is, hydrogen peroxide vapor pressure, was determined using a modified spectrophotometric method. The feasibility and utility of the proposed method in solid form selection have been demonstrated using various solid forms of ephedrine. No degradation was detected for ephedrine hydrochloride after exposure to the hydrogen peroxide vapor for 2 weeks, whereas both anhydrate and hemihydrate free base forms degraded rapidly under the test conditions. In addition, both the anhydrate and the hemihydrate free base degraded faster when exposed to hydrogen peroxide vapor at 30°C under dry condition than at 30°C/75% relative humidity (RH). A new degradation product was also observed under the drier condition. The proposed method provides more relevant screening conditions for solid dosage forms, and is useful in selecting optimal solid form(s), determining potential degradation products, and formulation screening during development.     

Synthesis and Pharmacological Activity of the Oxidized Fractions of Arabinogalactan from Siberian Larch (<Emphasis Type="Italic">Larix sibirica L.</Emphasis>)

Aqueous solutions of arabinogalactan from Siberian larch (Larix sibirica L.) were subjected to oxidative destruction by a hydrogen peroxide – molecular oxygen system. The obtained high- and low-molecular-weight fractions of oxidation products were characterized by chemical and spectral methods and tested for pharmacological activity. The results of experiments on animals showed evidence for significant antiulcer and antiinflammatory properties of the preparations studied. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 8, pp. 23 – 26, August, 2005.     

Competitive oxidation of 6-hydroxydopamine by oxygen and hydrogen peroxide.

Simultaneous oxygen electrode and conventional polarographic measurements show the net concentration of hydrogen peroxide produced by air oxidation of 6-hydroxydopamine is considerably less than that predicted from the known stoichiometry of the reaction. This is due to competitive oxidation of 6-hydroxydopamine by the generated hydrogen peroxide. The presence of ascorbic acid in this reaction also results in significant decreases of hydrogen peroxide under most conditions. The implications of these results to the molecular mechanism of 6-hydroxydopamine neurotoxicity are discussed.     

Degradation of microcystin-RR by UV radiation in the presence of hydrogen peroxide.

Experiments were conducted to investigate the degradation of microcystin-RR in order to assess the effectiveness and feasibility of the combined UV/H(2)O(2) catalytic system for purification of water polluted by microcystins. The operating parameters such as hydrogen peroxide dosage, pH value, UV light intensity, initial concentration of microcystin-RR and reaction time were evaluated, respectively. The degradation efficiency increased nonlinearly with increasing UV light intensity and hydrogen peroxide dosage, respectively. There existed an optimal hydrogen peroxide dosage, beyond which the reagent exhibited an inhibitory effect, for degrading microcystin-RR. The degradation process could be fitted by both of the pseudo-first-order and second-order kinetics well and primarily followed a mechanism of both direct photolysis and hydroxyl radical oxidation. Compared with the treatment using UV radiation and hydrogen peroxide individually, the combined UV/H(2)O(2) system could significantly enhance the degradation efficiency due to the synergetic effect between UV radiation and hydrogen peroxide oxidation. The observed rate constants decreased and the corresponding half-lives prolonged as the concentrations of microcystin-RR increased. The combined UV/H(2)O(2) process provides an effective technology for the removal of microcystins from drinking water supplies.     

Studies with primaquine in vitro: superoxide radical formation and oxidation of haemoglobin.

1. The production of superoxide radicals from primaquine diphosphate in aqueous solution has been demonstrated, using as indicator the reduction of cytochrome C with inhibition of the reaction by superoxide dismutase. 2. Primaquine-mediated oxidation of haemoglobin to methaemoglobin was reduced by the addition of catalase and increased by superoxide dismutase. Mannitol, a hydroxyl radical scavenger, abolished the increase in methaemoglobin observed in the presence of superoxide dismutase. EDTA reduced the oxidation of haemoglobin with and without superoxide dismutase. 3. Although the oxidation of haemoglobin in the presence of primaquine includes the effects of hydrogen peroxide, superoxide and hydroxyl radicals and metal ions, the results indicate that hydrogen peroxide, rather than the superoxide radical, is the main oxidizing species. The increase in haemoglobin oxidation occurring with superoxide dismutase may result from the augmented rate of hydrogen peroxide formation from superoxide radicals.     

Possible involvement of oxidative stress in hypoxia-induced adrenomedullin secretion in cultured rat cardiomyocytes

Although hypoxia induces adrenomedullin gene expression in cultured rat cardiac myocytes, it is still unknown whether oxidative stress is involved in the hypoxia-induced adrenomedullin production. We investigated whether oxidative stress might participate in hypoxia-induced adrenomedullin secretion and whether adrenomedullin might have a protective effect on damaged myocytes. Hypoxia increased adrenomedullin secretion and its gene expression in cardiac myocytes, but not in nonmyocytes. Furthermore, oxidative stress (hydrogen peroxide) also increased adrenomedullin secretion from myocytes. N-acetyl-L-cysteine, a free radical scavenger, completely inhibited the stimulation of adrenomedullin secretion by hydrogen peroxide, and this agent reduced the stimulation of adrenomedullin secretion by hypoxia. Lactate dehydrogenase leakage, a marker of cell injury, was significantly increased with the exposure to hydrogen peroxide and adrenomedullin significantly reduced this leakage. These findings suggest that an oxidative stress may be involved, in part, in the increased adrenomedullin secretion from cardiac myocytes under hypoxic condition. Adrenomedullin secreted from myocytes may play a cell protective role in an autocrine manner.     

Antioxidant and prooxidant effects of quercetin on glyceraldehyde-3-phosphate dehydrogenase.

Anti- and prooxidant properties of quercetin under different conditions were investigated using glyceraldehyde-3-phosphate dehydrogenase, a glycolytic enzyme containing essential cysteine residues. Quercetin was shown to produce hydrogen peroxide in aqueous solutions at pH 7.5, this resulting in the oxidation of the cysteine residues of the enzyme. Quercetin significantly increased oxidation of GAPDH observed in the presence of ferrous ions, particularly when FeSO(4) was added to the solution containing GAPDH and quercetin. The results suggest the formation of hydroxyl radical in the case of the addition of FeSO(4) to a quercetin solution. At the same time, quercetin protects GAPDH from oxidation in the presence of ascorbate and Fe(3+). In the absence of metals, quercetin protects SH-groups of GAPDH from oxidation by the superoxide anion generated by the system containing xanthine/xanthine oxidase.     

Inactivation of anthracyclines by serum heme proteins

We have previously shown that the anticancer agent doxorubicin undergoes oxidation and inactivation when exposed to myeloperoxidase-containing human leukemia HL-60 cells, or to isolated myeloperoxidase, in the presence of hydrogen peroxide and nitrite. In the current study we report that commercial fetal bovine serum (FBS) alone oxidizes doxorubicin in the presence of hydrogen peroxide and that nitrite accelerates this oxidation. The efficacy of inactivation was dependent on the concentration of serum present; no reaction was observed when hydrogen peroxide or serum was omitted. Peroxidase activity assays, based on oxidation of 3,3',5,5'-tetramethylbenzidine, confirmed the presence of a peroxidase in the sera from several suppliers. The peroxidative activity was contained in the >10000 MW fraction. We also found that hemoglobin, a heme protein likely to be present in commercial FBS, is capable of oxidizing doxorubicin in the presence of hydrogen peroxide and that nitrite further stimulates the reaction. In contrast to intact doxorubicin, the serum + hydrogen peroxide + nitrite treated drug appeared to be nontoxic for PC3 human prostate cancer cells. Together, this study shows that (pseudo)peroxidases present in sera catalyze oxidation of doxorubicin by hydrogen peroxide and that this diminishes the tumoricidal activity of the anthracycline, at least in in vitro settings. Finally, this study also points out that addition of H2O2 to media containing FBS will stimulate peroxidase-type of reactions, which may affect cytotoxic properties of studied compounds.     

碳酰胺过氧化氢的制备及临床应用

目的 :探讨碳酰胺过氧化氢的制备及质量控制方法。方法 :采用碳酰胺与过氧化氢在—5℃～—10℃条件下形成1∶1分子复合物 ,经低温干燥为白色结晶性物质 ,用于固化氧分子。结果 :碳酰胺过氧化氢中过氧化氢含量可达34 90 % ,为标示量的97 00 %以上。结论 :该制剂制备工艺简单 ,质量易于控制 ,临床应用方便。