差示扫描量热法在药物多晶型定量分析中的应用

药物多晶型直接影响药物的安全性和质量可控性。因此仅对药物进行晶型的定性研究已不能满足要求。为了确保药品的疗效及安全性,测定原料药或制剂中有效晶型含量需要采用适当的方法对多晶型进行定量分析。本文具体综述了近年来传统差式扫描量热法、调制式差示扫描量热法及超高效差示扫描量热法在药物多晶型定量分析方面的应用,并对其优缺点进行了总结,展望了其应用前景。     

热分析法在医药品研究方面的应用

热分析法包括热重法、差示扫描量热法及其它。本文对热重法及差示扫描量热法在药物分析中的应用作一概述。     

复方新诺明片的热化学性质及差示扫描量热法测定

应用差示扫描量热法研究了 SMZ 和 TMP 低共熔混合物的组成,并对复方 SMZ 片中的主药进行含量测定,以 Kissinger 方程测定了复方 SMZ 片的热降解活化能。     

差示分光光度法测定诺氟沙星胶囊的含量

喹诺酮类合成抗生素诺氟沙星（Ｎｏｒｆｌｏａｃｉｎ）及其制剂的含量测定方法有紫外分光光度法［１］、ＨＰＬＣ法［２］、离子对比色法［３］、沉淀回滴法［４］、荧光分光光度法［５］、Ｃｒａｎ电位滴定法［６］,中国药典采用非水滴定法［７］测定带氟沙星胶囊的含量,终点不易观察。用差示分光光度法测定诺氟沙星胶囊的含量尚未见文献报道。本文利用诺氟沙星在０．１ｍｏｌ·Ｌ－１氢氧化钠溶液和０．１ｍｏｌ·Ｌ－１盐酸溶液中紫外光谱发生变化的特征,用差示分光光度法,通过测定差示吸收值（ＡＡ）直接测定诺氟沙星的含量,现报道…     

改良-差示酚硫法的建立及对淫羊藿多糖的含量测定

目的建立改良-差示酚硫法并测定淫羊藿多糖含量。方法在以往苯酚硫酸法、差示苯酚硫酸法的基础上进一步研究改进,建立新的可用于多糖含量测定的方法。结果改良-差示酚硫法的测定条件:样品可直接用未精制多糖提取物,反应应在2.5h内完成,测定波长λmax=490 nm,线性范围为30~400μg·mL-1,相关系数r=0.999 0,RSD=2.2%,回收率为98.9%。结论改良-差示酚硫法可用于多糖的含量测定,多糖不必进行繁琐的分离纯化,该法操作简捷、快速,精密度高。     

盐酸小檗碱的热特征分析

目的:观察盐酸小檗碱的热特征,并测定其水分。方法:利用热分析技术中的差示扫描量热法(DSC)和热重分析法(TGA)对盐酸小檗碱进行热特征分析并测定其游离水和结晶水含量。结果:国内不同生产企业生产的盐酸小檗碱热特征图谱不同,结晶水含量均为7%左右。结论:热分析用于药物晶型研究以及熔点、结晶水含量等的测量,具有用量少、快速、灵敏高、检测方便等优点。     

差示脉冲极谱法测定硝普钠含量的改进

硝普钠(Sodium Nitroprusside)是一种速效、强效而作用短暂的扩血管药物,主要用于治疗高血压危象及急性心力衰竭等.硝普钠口服无效,临床上多以静脉滴注给药,但其水溶液极不稳定,见光易分解.硝普钠定量分析,国内主要采用电位法、分光光度法等.本文参照国外文献,采用国产差示脉冲极谱仪测定硝普的溶液含量,灵敏度高,专一性好.     

核磁共振和差示扫描量热法作为研究药物-膜相互作用的工具

核磁共振(NMR)和差示扫描量热法(DSC)是研究药物与人工膜相互作用方便而灵敏的工具。差示扫描量热法该方法可用于研究相转变性质随药物/脂比率的函数而变化。两个参数对描述药物-磷脂之间的相互作用特别有用,主相转变温度的变化,定义为凝胶-液晶吸热线的峰值T_c,以及相转换曲线的半高宽△T_t。前者表示膜流动性的改变,后者是磷脂     

黄体酮的热特性分析

目的:观察黄体酮药物的热特性,并测定其纯度。方法:利用差示扫描量热法(DSC)和导数热重法(DTG)测定黄体酮的熔点、纯度及挥发性物质,在氮气氛下升温速率分别为1.5,10,20℃·min~(-1)。结果:用差示扫描量热法,升温速率为1.5℃·min~(-1),测定黄体酮的熔点为130℃,在程序控温下对其吸热峰进行分析,其纯度为99.8%,与高效液相色谱测定的结果(99.9%)一致。用导数热重法可准确测定其挥发性物质包括水分在内的变化,以及推测其降解历程。结论:该分析法简便、快捷,可测定黄体酮的晶型、水分及纯度,并为研究降解机理及开发新剂型提供参考。     

羟丙基-β-环糊精对双氯芬酸钠的包合作用研究

目的:研究羟丙基-β-环糊精对双氯芬酸钠的包合作用。方法:采用紫外扫描、差示扫描量热分析法对包合物进行确定,通过相溶解度法确定包合比例。并观察包合物对家兔股四头肌注射的刺激性。结果:含量测定结果证明包合物主、客分子比为1:1,药物溶解度由原来的9.78增至52.2mg·mL~(-1)。包合物与原药相比,肌肉刺激性明显降低。结论:双氯芬酸钠经包合后溶解度增加、肌肉刺激性降低。     

Inhibitory effect of free fatty acids on plasma protein binding of disopyramide in haemodialysis patients

Summary The plasma (or serum) protein binding of disopyramide (DSP) in five haemodialysis patients was studied using an ultrafiltration technique. There was an increase in the free fraction of DSP in the plasma on dialysis days in comparison to the levels on interdialysis days, which was associated with an elevation of the free fatty acid levels in the plasma together with the increase of the free fraction of DSP. The inhibitory effect of free fatty acids on DSP binding in an in vitro study was enhanced in proportion to their concentrations, and was shown to be due to competition at one binding site by experiments with oleic acid as a representative displacer. Certain endogenous organic acids, such as indoxyl sulphate, 2-hydroxyhippuric acid and hippuric acid, which are characteristically elevated in chronic renal failure, scarcely affected the protein binding of DSP. The findings indicate that free DSP should be monitored in patients with elevated plasma free fatty acid levels, such as those on haemodialysis therapy.     

Regulatory effect of dosiinpartner on high-fat diet-induced obesity in C57BL/6J mice

Dosiinpartner (DSP) is a newly developed dietary functional food to help control weight. The aim of this study was to evaluate whether DSP combined with a high-fat (HF) diet could influence body weight, fat accumulation, and plasma glucose levels. Mice were fed for 8 weeks with normal diet, HF diet, and HF+10% or 20% DSP diet. Body weight was recorded at 1 week, and plasma levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and glucose were analyzed at the end of the study. Weight increases in the 10% or 20% DSP group were significantly less than in the HF diet group (p<0.05). Plasma total cholesterol and LDL cholesterol levels decreased by 48.3% and 26.8% in the 10% DSP group and by 42.9% and 34.9% in the 20% DSP group, respectively. However, the HDL cholesterol level was unchanged. Glucose levels also decreased by 80.6% in the 10% DSP group but was almost the same in the HF and 20% DSP groups. Our findings indicate that DSP may be beneficial in the regulation of high-fat diet-induced overweight and other complications such as circulatory disorders and diabetes mellitus.     

地塞米松磷酸钠滴眼液的稳定性考察

目的:考察地塞米松磷酸钠滴眼液的稳定性,预测其有效期。方法:采用高效液相色谱法测定地塞米松磷酸钠滴眼液中地塞米松磷酸钠的含量,以初匀速法预测其稳定性。结果:地塞米松磷酸钠检测浓度的线性范围为18~70μg.mL-1(r=0.999 9),平均回收率为99.74%,RSD=0.37%;滴眼液随温度的升高以及存放时间延长其含量下降,但pH变化不明显。计算得25℃时其有效期为70d,4℃冷藏其有效期可延长至438d。结论:本品4℃存放稳定性较好。     

肠包衣地塞米松脂质体壳聚糖胶囊对炎性结肠组织MPO活性的影响

目的评价肠包衣地塞米松(DSP)脂质体冻干剂壳聚糖胶囊对大鼠炎性结肠组织髓过氧化酶(MPO)活性的影响。方法用2,4,6-三硝基苯磺酸钠(TNBS)诱导大鼠结肠炎,建立反应结肠炎症程度的结肠组织MPO浓度的测定方法,观察口服各种DSP制剂对MPO的抑制程度。结果TNBS灌肠后d 5时MPO达到最高值;各种DSP制剂均有降低TNBS诱导的实验性大鼠结肠炎结肠组织MPO的效果,但DSP脂质体壳聚糖胶囊具有最好的抑制作用。结论肠包衣DSP脂质体冻干剂壳聚糖胶囊在治疗结肠炎中可能具有较大的应用前景,值得进一步开发研究。     

葡聚糖-精胺阳离子聚合物基因载体体外基因转染的研究

本文研究了葡聚糖-精胺阳离子聚合物(DSP)基因载体的性能及其对体外细胞基因的转染效率。氧化葡聚糖与精胺通过还原胺化法反应制得DSP，所得DSP与质粒pEGFP通过静电吸附形成复合物；当DSP/DNA质量比在4∶1至20∶1，能形成稳定的复合物，复合物粒径为162.6～187.9 nm，zeta电位则从+8.45 mV增至+39.6 mV；DSP能有效保护DNA不受核酸酶I降解，同时在一定pH范围内载体具有较强的缓冲能力；复合物在质量比为8∶1时对SMMC-7721肝癌细胞、BHK-21细胞的转染率分别达到最高，其效果均与Lipofectamine 2000相当。该研究表明葡聚糖-精胺阳离子聚合物是一种高效的基因载体。     

Physical and Chemical Stability of Dexamethasone Sodium Phosphate in Intravenous Admixtures Used to Prevent Chemotherapy-Induced Nausea and Vomiting

Purpose: Dilute intravenous (IV) admixtures of dexamethasone sodium phosphate (DSP) are becoming increasingly used in antiemetic regimens to prevent chemotherapy-induced nausea and vomiting (CINV). Based on its chemical structure and previous studies, DSP is known to be susceptible to hydrolysis and oxidation under certain conditions. There are limited data to directly support the selection of IV diluents, storage conditions, and beyond-use dates for the dilute IV solutions of DSP used in the antiemetic regimens. This study was designed to investigate these parameters. Methods: A stability-indicating high-performance liquid chromatography (HPLC) method was first developed for the analysis of DSP. Commercially available 100 mg/10 mL DSP injection vials were used to prepare the IV admixtures of DSP in 0.9% sodium chloride injection or 5% dextrose injection. The final DSP concentrations were 0.08 or 0.4 mg/mL, which bracketed the range commonly used in antiemetic regimens. These admixtures were packaged in 50-mL polyvinylchloride (PVC) bags and stored at room temperature or under refrigeration for 14 days. Samples from each IV bag underwent visual, pH, and HPLC assessments on days 0, 1, 3, 7, and 14. Results: Immediately after preparation, the IV admixtures of DSP appeared clear, colorless, and free of particulate matters. The initial pH values were 6.4 to 6.8 and 7.0 to 7.8 for samples in 0.9% sodium chloride and 5% dextrose, respectively. The initial DSP concentrations of all samples were within 96% to 100% of the expected values. Over the 14 days of storage at room temperature or refrigeration, no significant change was observed for the visual appearance of any IV bags. The pH of all samples remained within one pH unit from the initial values. The HPLC results confirmed that all samples retained 94% to 100% of original drug concentrations and that no significant degradation products were observed. Conclusions: Intravenous admixtures of DSP at 0.08 to 0.4 mg/mL are compatible with 0.9% sodium chloride and 5% dextrose in PVC bags. These admixtures are also chemically and physically stable when stored at room temperature or under refrigeration for up to 14 days.     

Plasma free fatty acids and protein binding of disopyramide during haemodialysis

Summary The binding of disopyramide (DSP) to plasma (or serum) proteins was determined using an ultrafiltration technique in three patients undergoing haemodialysis.An increase in the free fraction (FF) of DSP during dialysis occurred together with elevation of the free fatty acid (FFA) level in plasma. The effect of FFA on protein binding in vitro was examined using DSP- and FFA-spiked solutions containing human ₁-acid glycoprotein and serum albumin. The FF of DSP rose in proportion to increasing FFA levels, supporting the in vivo observations.The findings suggest that the free concentration of DSP should be routinely monitored, especially in haemodialysis patients.     

Effects of inescapable shock and norepinephrine depletion induced by DSP4 on escape performance

The potential contribution of dorsal bundle norepinephrine (NE) in the induction of escape disturbances engendered by inescapable shock was evaluated following administration of the NE neurotoxin, DSP4. Treatment with DSP4 produced marked NE reductions in the hippcampus and cortex, a moderate reduction of NE in the locus coeruleus, but only small effects on hypothalamic NE. In contrast to the effect of inescapable shock, DSP4 was found not to influence escape behavior among naive mice or mice that had received inescapable shock. Moreover, DSP4 was without effect on escape performance irrespective of whether animals were individually or group housed, a treatment that has been shown to be sensitive to manipulations that influence escape performance. Treatment with DSP4 was found not to influence the escape interference ordinarily provoked by either haloperidol or -MpT. Interestingly, the escape interference ordinarily engendered by the dopamine--hydroxylase inhibitor, FLA-63, was eliminated among mice that had been pretreated with DSP4. The interference effect induced by inescapable shock is probably not attributable to NE alterations in the hippocampus and locus coeruleus. Serial or parallel effects of shock on more than a single transmitter system are likely to be responsible for the behavioral interference.     

The hindlimb extension reflex is not a reliable marker of post-decapitation convulsions or spinal noradrenaline depletion in rats

The degree of hindlimb extension reflex (ER), post-decapitation reflex (PDR) and noradrenaline (NA) depletion was measured under various treatment regimens involving the neurotoxins DSP4 and 6-OHDA. Neither neonatal 6-OHDA treatment, direct application of 6-OHDA to the locus coeruleus nor DSP4 treatment produced a blockade of ER that could be associated with the loss of PDR and the spinal NA depletion, whereas intrathecal 6-OHDA treatment caused a strong loss of both ER and PDR related to severe spinal NA depletion. No correlation was obtained between the ER and PDR in a large number of DSP4-treated rats.     

Accumulation and depuration of okadaic acid esters in the European green crab (Carcinus maenas) during a feeding study.

Soft shell crab is a seafood delicacy in many parts of the world. In Denmark, it has been investigated whether a commercial production of soft shell European green crabs (Carcinus maenas) would be feasible. In relation to this, a feeding study was performed to examine if occurrence of DSP toxins in the product could be a food safety problem. The crabs were fed with mussels containing DSP toxins (2500 microg total okadaic acid equivalents/kg) for 17 days and then fasted for 19 days. The content of total okadaic acid equivalents in the digestive organs was on average 27 times higher than the corresponding content in the body meat. The highest level of total okadaic acid equivalents measured was 12 microg/kg in body meat and 503 microg/kg in digestive organs. The results show that the content of DSP toxins in a commercial product of soft shell European green crab (without digestive organs) could be regarded as negligible.