姜黄素-赖氨酸共晶在无水乙醇中的热力学研究

目的：考察在三元体系中各条件下的平衡状态,计算姜黄素共晶的相关热力学常数,探讨无水乙醇作为特异性溶剂的合理性。方法：采用溶液法分别测定姜黄素在不同温度下、不同浓度赖氨酸的无水乙醇中的溶解度,通过数学推导,得出姜黄素共晶的热力学常数。结果：绘制了姜黄素-赖氨酸-无水乙醇的三元相图,并求得了Ksp、Kll、△G°、△H及△S等热力学参数。结论：无水乙醇可以作为特异性溶剂用于提取姜黄素共晶中混杂的姜黄素单体。     

药物共晶的筛选技术及热力学研究进展

综述药物共晶的筛选技术及热力学研究进展。研究共晶筛选技术和共晶热力学的目的是提高共晶筛选效率,节省试验成本。共晶具有改良药物原有理化特性的优势,且新的药物共晶可获得知识产权保护,因此可延长原有药物的市场周期,具有广阔的研发及应用前景。     

咖啡因在新生儿中的临床应用

咖啡因是中枢神经系统兴奋药,通过刺激呼吸中枢、阻断腺苷受体和改善呼吸肌功能等发挥作用。其具有肺保护作用,可以减低早产儿呼吸暂停的发生危险,提高撤机成功率,同时具有脑保护作用。该药应用时无需常规监测血药浓度,但极早产儿及频繁呼吸暂停、出现中毒症状的患儿仍有必要定期监测血药浓度。     

药物共晶在药学中的应用

根据晶体工程学原理将活性药物成分（active pharmaceutical ingredient，API）与其他生理可接受的酸、碱、非离子化合物，以氢键等非共价键形式结合在同一晶格中，形成药物共晶。具有改变药物理化性质、提高稳定性和生物利用度等优点，已成为研发新药的一种新的途径。现对药物共晶的设计、制备方法及其在药学领域的应用进行综述。     

不同维持剂量枸橼酸咖啡因在早产儿呼吸暂停中的应用效果

目的：探讨不同维持剂量枸橼酸咖啡因在早产儿呼吸暂停中的应用效果。方法：选取2020年2月—2023年2月蚌埠市第三人民医院新生儿科收治的96例28～34周胎龄早产儿为研究对象,按照随机数字表法分为对照组和观察组,各48例。2组均在出生后24 h内予以首剂20 mg/kg枸橼酸咖啡因治疗,24 h后对照组每间隔24 h给予5 mg/kg低剂量枸橼酸咖啡因治疗,观察组每间隔24 h给予10 mg/kg高剂量枸橼酸咖啡因治疗,比较2组患儿治疗有效率、疗效评价指标、炎症指标、不良反应及并发症发生率。结果：观察组有效率为93.75%,高于对照组的83.33%,差异有统计学意义(P<0.05);观察组撤机失败率为12.50%,低于对照组的29.17%,差异有统计学意义(P<0.05);观察组呼吸暂停次数、用氧时间、住院时间、持续气道正压通气(CPAP)使用时间分别为(5.33±0.40)次、(12.54±0.87)d、(26.73±1.00)d、(6.27±0.46)d,均低于对照组的(7.08±0.48)次、(15.60±1.15)d、(29.71±1.08)d、(8.38±0.72...     

绿茶在不同采收期茶多酚及咖啡因的含量

目的:测定不同采收期绿茶中茶多酚和咖啡因的含量。方法:使用 Inertsil ODS-3色谱柱(2.1 mm×150 mm,5μm),以甲醇-水(含0.2%甲酸)梯度系统为流动相,流速为0.4 mL·min~(-1),用 HPLC 外标法测定不同采收期绿茶中 EGCG 和咖啡因的含量,根据 HPLC—MS 提供的质谱分子量信息,确定 EGC、ECG 的色谱峰,再根据 EGCG 的含量测定 EGC、ECG 的相对含量。结果:EGCG 和咖啡因在10～800μg·mL~(-1)的范围内线性关系均良好(r_(EGCG)=0.9998;r_(咖啡因)=0.9999)。平均加样回收率分别为99.3%,98.2%。EGCG 的最高含量为干茶重的18.04%,咖啡因的最高含量为干茶重的3.76%。结论:该测定方法结果准确,选择性好,操作简单。在日照产绿茶中,EGCG 的含量在10月份达到最高,而咖啡因的含量在4月最高。     

枸橼酸咖啡因在早产儿原发性呼吸暂停中的临床价值研究

目的 分析枸橼酸咖啡因在早产儿原发性呼吸暂停中的临床应用价值.方法 68例原发性呼吸暂停早产儿,根据治疗方法不同分为常规组(31例)与观察组(37例).常规组予以氨茶碱进行治疗,观察组予以枸橼酸咖啡因进行治疗.比较两组药物起效时间、住院时间、不良反应发生率、疗效.结果 观察组药物起效时间(32.31±5.31)h、住院...     

氯诺昔康和羟丙基-β-环糊精在缓冲液中的相互作用及热力学特征

目的研究氯诺昔康和羟丙基-β-环糊精（HP-β-CD）在pH7．4缓冲液中的相互作用及热力学特征。方法采用紫外-可见光谱扫描法研究氯诺昔康与HP-β-CD在溶液中的相互作用,采用摩尔连续递变法测定复合物化学计量学特征,根据溶解度相图斜率及截距测定热力学参数。结果氯诺昔康在HP-β-CD中的溶解相图为AL型,△H=-5．9889kJ·MOl^-1,△s=7．6305J·Mol^-1·K^-1溶液中HP-β-CD影响氯诺昔康的紫外可见吸收特征,当其摩尔分数为0．5时,相同浓度氯诺昔康溶液的吸收度差异最大。结论HP-β-CD与氯诺昔康在溶液中存在明显的相互作用,复合物的化学计量学特征为1：1（摩尔比）,作用力主要为Van der Waals-London分散力和疏水性相互作用。     

On the thermodynamics of cocrystal formation

The thermodynamics underpinning cocrystal formation are derived. The results provide the pharmaceutical scientist with the foundation to experimentally assess the thermodynamic stability of a cocrystal with respect to its component forms. Data for the carbamazepine-nicotinamide system are discussed as an example.     

不同纯度的有机溶剂对2株肿瘤细胞的抑制作用

目的 给脂溶性的抗肿瘤药物筛选高溶解性、低细胞毒性的有机溶剂.方法 采用MTT法,按照不同纯度,对8种能溶于水的有机溶剂,测试其对黑色素瘤B16、人胃癌细胞SGC-7901两种细胞株的细胞毒性.结果 不同有机溶剂对不同细胞株的抑制皆不同,甲醇与丙酮对两种细胞株的毒性相对都较弱,纯度越高的有机溶剂对细胞毒害越小.结论 光谱纯的甲醇与丙酮是脂溶性抗肿瘤药物有效的有机溶剂.     

Cholesterol solubility in organic solvents.

The 37 degree cholesterol solubilities in over 50 solvents, including the homologous n-alkanols through dodecanol and homologous ethyl carboxylates through the undecanoate, and the 37 degree beta-sitosterol solubilities in the n-alkanols through decanol are reported. Additionally, solubility data for cholesterol at 7, 17, and 27 degrees in the alcohol series were obtained. These measurements allowed the calculation of heats of solution for cholesterol in the alkanols, which range from 7.5 kcal for methanol to 4.3 kcal for decanol and which tend to decrease, although irregularly, with increasing alkanol chain length. A solubility maximum in all of these series for both solutes was observed between a chain length of six and seven. A surprisingly irregular, odd-even alternating solubility pattern was noted for cholesterol in the alkanols at all four temperatures. Experimental evidence indicated that this pattern was due to solvent-induced crystalline changes, presumably solvate formation, in each alkanol solvent through C10. Overall, the solubility studies screened solvents for their utility in dissolving cholesterol and, thus, cholesterol gallstones. To these ends, some limited dissolution experiments were performed, which indicated that the solution rate is directly related to the measured solubility in organic solvents. The dissolution behavior is thus different from micellar bile salt solutions, in which a significant interfacial barrier controls kinetics.     

Occupational exposure to different levels of mixed organic solvents and colour vision impairment

Mixed organic solvents have a broad range of applications in industry. Occupational exposure to organic solvents has been shown to be associated with colour vision impairment. The study was designed to determine the impact of chronic occupational exposure to organic solvent mixtures on colour vision of car industry painters. 408 workers of assembly location and 2 different paint locations of a car manufacturing company were included in the study. The workers were studied in three groups. The first group consisted of those working in the assembly location with no exposure to organic solvents. The second and third groups included those working in the new and old paint locations, exposed to organic solvents at lower and higher levels than the permissible level, respectively. The Lanthony D-15 desaturated (LD-15) test was used for screening acquired colour vision impairment. The frequency of acquired colour vision impairment was 44.28% for workers of the old paint location, 29.31% for workers of the new paint location, and 3.90% for workers of the assembly location, indicating a significant difference (p < 0.001). The results of logistic regression indicated there was a significant relationship between colour confusion index (CCI) and exposure to organic solvents (p < 0.001) for the old and new paint locations. We suggest that chronic occupational exposure to organic solvents at higher and even lower levels than the permitted levels may lead to acquired colour vision impairment. It is recommended that LD-15 test would be implicated in the early diagnosis of nervous system disorders in workers exposed chronically to organic solvents.     

Effect of some organic solvents on oxidative phosphorylation in rat liver mitochondria: Choice of organic solvents

The effect of acetone, acetonitrile, dimethyl sulfoxide (DMSO), ethanol and methanol on oxidative phosphorylation (ATP synthesis) in rat liver mitochondria has been studied. All the organic solvents inhibited the oxidative phosphorylation in a concentration dependent manner, but with differences in potencies. Among the tested organic solvents, acetonitrile and acetone were more potent than ethanol, methanol, and DMSO. There was no significant difference in oxidative phosphorylation, compared to controls, when the concentrations of acetone was below 1% (v/v), of acetonitrile below 2% (v/v), of DMSO below 10% (v/v), of ethanol below 5% or of methanol below 2%, respectively. There was complete inhibition of oxidative phosphorylation at 50% (v/v) of acetone, acetonitrile and ethanol. But in the case of DMSO and methanol there were some residual activities observed at the 50% concentration level. DMSO showed least effect on oxidative phosphorylation with an IC₅₀ value of 13.3 ± 1.1% (v/v), followed by methanol (IC₅₀ value 8.3 ± 1.0), ethanol (IC₅₀ value 4.6 ± 1.1), acetone (IC₅₀ value 4.3 ± 1.0) and finally acetonitrile (IC₅₀ value 2.1 ± 1.0).All the organic solvents showed modulatory effects on 2,4-dinitrophenol (DNP) mediated inhibition of oxidative phosphorylation with potentiation of the action of DNP. Acetonitrile showed the highest potentiation effect followed by acetone, ethanol, methanol, and DMSO in presence of DNP. The use of organic solvents for investigation of the effects of compounds on oxidative phosphorylation in mitochondria should therefore include the use of relevant concentrations of the organic solvent in order to validate the contribution.     

Formation mechanism of a new carbamazepine/malonic acid cocrystal polymorph

A new 2/1 carbamazepine (CBZ)/malonic acid (MA) cocrystal polymorph form C was formed using a vibrational rod mill, whereas the known cocrystal polymorph form A was prepared using a ball mill. IR measurements showed that the interaction between CBZ and MA in cocrystal form C was formed by amide-carboxylic acid heterosynthons, similar to that in cocrystal form A. However, NMR results showed that the molecular states of CBZ at the dibenzazepine ring appeared to be different, which could be due to variation in either the conjugation of the aromatic rings or the π-π interaction of CBZ. Factors affecting the formation of cocrystal polymorphs, such as heat and force, were investigated to clarify the formation mechanism.     

卡培他滨中有机残留溶剂的检测

目的建立气相色谱法测定卡培他滨原料药中二氯甲烷、乙醇、甲醇和乙酸乙酯4种有机溶剂。方法采用DB-624毛细管柱,FID检测器,以DMSO为溶剂。结果各有机溶剂的平均加样回收率为93.7%～97.6%,RSD为2.5%～3.7%。结论该方法稳定准确,可用于卡培他滨中有机溶剂残留的检测。     

Tolerance during inhalation of organic solvents

Inhalation of several different halogenated solvents stimulated motor activity in mice. During prolonged exposure acute tolerance developed. The development of tolerance depended both on the schedule of exposure, and on the solvent. Exposure to trichloroethylene induced both stimulation and tolerance while the same degree of stimulation induced by 1,1,1-trichloroethane caused no tolerance. Thus the mechanisms which induce stimulation do not always initiate tolerance. Slow steady increases in the concentration of trichloroethylene could be maintained for several hours without any stimulation of motor activity. At the end of such exposures concentrations were reached which, if applied directly, would have induced considerable stimulation. Thus tolerance may develop without motor stimulation. Inhalation of ethanol also stimulated motor activity initially. During constant exposure the stimulation was followed by a considerable reduction in motor activity. This resulted in a hypoactive period, which in turn was followed by a second increase in motor activity, indicating the existence of not only two but several counteracting mechanisms. Development of metabolites with sedative effects counteracting the stimulating effect of the pure solvents seems to be one explanation for the results.