ASE-HPLC法快速测定决明子中大黄酚和橙黄决明素

摘 要 目的：建立快速溶剂萃取（ASE）及HPLC测定决明子中大黄酚和橙黄决明素的分析方法。方法: 利用正交试验对ASE350快速溶剂萃取系统进行提取方法的研究,采用HPLC法同时测定决明子中大黄酚和橙黄决明素的含量。色谱柱为ACE Excel C18 PFP柱(75 mm×2.1 mm,2.5 μm),流动相为乙腈 0.1%磷酸溶液梯度洗脱,流速为0.4 ml·min^-1,检测波长为284 nm,柱温为40℃。结果: 采用甲醇为萃取溶剂、萃取温度为120℃、静态萃取时间为5 min以及循环萃取3次的方法最优,可以很好地提取决明子中大黄酚和橙黄决明素,耗时仅为药典提取方法的1/9。大黄酚和橙黄决明素线性范围为0.73~58.57 μg·ml^-1(r=0.999 7)和1.09~87.29 μg·ml^-1（r=0.999 6),平均回收率分别为102.7%（RSD=0.8%）和98.2%（RSD=1.5%）。 结论:该方法能简便、快速、准确的测定决明子中的大黄酚和橙黄决明素。     

消白胶囊质量标准研究

摘 要 目的： 建立消白胶囊的质量标准。方法: 采用薄层色谱法对菟丝子、当归、白芍进行定性鉴别;建立补骨脂素、异补骨脂素的高效液相色谱含量测定方法。结果: 定性鉴别阴性无干扰,分离度高;补骨脂素线性范围为1.082～108.200 μg·mL^-1(r=0.999 8),平均回收率为99.82%,RSD=1.16%。异补骨脂素线性范围为0.818～81.800 μg·mL^-1(r=0.999 7),平均回收率为99.85%,RSD=1.81%。结论: 所建立的质量标准方法可行,可用于消白胶囊的质量控制。     

肾复康胶囊的质量标准研究

摘 要 目的： 建立肾复康胶囊的质量标准。方法: 采用显微鉴别法对肾复康胶囊中大黄、当归和全蝎进行定性鉴别;采用TLC法对肾复康胶囊中的大黄、何首乌、山茱萸、丹参、川牛膝、黄芪进行定性鉴别;采用HPLC法对制剂中大黄酚的含量。结果: 大黄、何首乌、山茱萸、丹参、川牛膝、黄芪薄层色谱斑点清晰、重现性好、专属性强、阴性对照无干扰。含量测定中大黄酚在1.712~17.120  μg·ml^-1范围内线性关系良好（r=0.999 9）,平均回收率为101.2%,RSD=0.34%（n=6）。结论:所建立的定性、定量方法简便易行,重复性好,为肾复康胶囊提供了质量控制方法。     

清肠合剂质量标准的建立

摘 要 目的：建立清肠合剂质量标准。方法: 采用TLC法对清肠合剂中当归、赤芍、黄柏进行定性鉴别;采用HPLC法,对清肠合剂中阿魏酸进行含量测定,色谱柱为Wondasil C18柱(250 mm×4.6 mm,5 μm),流动相为乙腈 0.1%磷酸水溶液（17∶83）,流速为1.0 ml·min^-1,检测波长为316 nm,柱温为30℃。结果: TLC斑点清晰,分离度好,阴性对照无干扰;阿魏酸在进样浓度39.6~316.8 μg·mL^-1范围内与峰面积呈良好线性关系（r=0.999 9）,平均加样回收率为98.75%,RSD为1.21%（n=9）。结论:该方法快速、准确、专属性强,可作为清肠合剂质量控制的方法。     

痤疮散质量标准的建立

摘 要 目的：建立痤疮散质量控制方法。方法: 采用薄层色谱法对制剂中的大黄、白芷和防风进行定性鉴别;采用气相色谱法同时测定制剂中百秋李醇、薄荷脑和冰片的含量。结果: 薄层色谱显色清晰且阴性对照无干扰。百秋李醇、冰片、薄荷脑分别在0.020 1~0.805 6 mg·mL^-1、0.010 0~0.401 6 mg·mL^-1、0.005 1~0.202 8 mg·mL^-1浓度范围内呈良好的线性关系,平均回收率（n=6）分别为102.03%（RSD=0.91%）、100.10%（RSD=1.94%）、103.15%（RSD=1.68%）。结论:本法操作简便,结果准确、重现性好,可用于痤疮散的质量控制。     

复方黄槐片质量标准的提高

摘 要 目的：提高并完善复方黄槐片的质量标准。方法: 采用TLC法对制剂中槐米、黄芩、赤芍、大黄、白茅根、鸡血藤、薏苡仁、夏枯草等8味药材进行定性鉴别;采用HPLC法测定芦丁的含量：色谱柱为DIKMA Spursil C18柱（250 mm×4.6 mm,5 μm),以甲醇 0.2%磷酸（45∶〖KG-*2〗55）为流动相;检测波长为350 nm;柱温为25℃;流速为1.0 ml·min^-1 ,进样量为20 μl。结果: TLC鉴别斑点清晰,阴性对照无干扰;芦丁在0.011 6～0.185 9 mg·ml^-1的浓度范围内有良好的线性关系(r=0.999 9),平均回收率为98.93%（RSD=1.14%,n=6）。结论: 提高后的质量标准具有操作简单、专属性强、重复性好的特点,可用于该制剂的质量控制。     

HPLC法同时测定祛喘胶囊中木兰脂素、欧前胡素、异欧前胡素的含量

摘 要 目的： 建立祛喘胶囊中对木兰脂素、欧前胡素和异欧前胡素的HPLC测定方法。方法: 采用日本资生堂CAPCELL PAK C₁₈ 色谱柱（150 mm×4.6 mm,5 μm）,以乙腈-水为流动相进行梯度洗脱,柱温为30℃,流速为1.0 ml·min^-1,检测波长在0～25 min为278 nm,25～70 min为248 nm,进样量为10 μl。结果: 木兰脂素在6.126～55.134 μg·mL^-1范围内线性关系良好（r=0.999 7）,平均回收率为101.5%,RSD为1.4%;欧前胡素在9.862～88.758 μg·mL^-1范围内线性关系良好（r=0.999 8）,平均回收率为99.6%,RSD为1.2%;异欧前胡素在4.830～43.470μg·mL^-1范围内线性关系良好（r=0.999 8）,平均回收率为100.2%,RSD为1.7%。结论:本法操作简便、结果准确,可用于祛喘胶囊的质量控制。     

HPLC法同时测定云南红大戟中三种蒽醌类化合物的含量

摘 要 目的：建立HPLC法同时测定红大戟药材中芦西定、5 羟基巴戟醌与红大戟素的含量。方法: 采用 Waters Xbridge C18色谱柱（250 mm×4.6 mm,5 μm）,以0.05%磷酸为流动相A,以乙腈为流动相B,梯度洗脱;流速为1.0 ml·min^-1,检测波长为280 nm,柱温为30℃。 结果: 芦西定、5 羟基巴戟醌、红大戟素的线性范围分别为0.147～29.400 μg·mL^-1(r=0.999 6)、0.126～25.200 μg·mL^-1 (r=0.999 9)、0.135～27.000μg·mL^-1 (r=0.999 5),平均加样回收率分别为98.50%（RSD=1.20%）、98.72%（RSD=0.73%）、101.10%（RSD=1.12%）(n=6)。结论:本文建立的方法经方法学验证可用于评价红大戟药材质量。     

欣梦安神颗粒质量控制方法的建立

摘 要 目的：建立欣梦安神颗粒的质量控制方法。方法: 采用TLC法对方中的丹参、桑椹、酸枣仁（炒）、落花生枝叶及五味子进行定性鉴别;以HPLC法分别对丹参中的原儿茶醛和酸枣仁（炒）中的斯皮诺素进行含量测定。结果: 薄层斑点清晰,分离良好,阴性无干扰。原儿茶醛、斯皮诺素分别在3.972～198.600 μg·mL^-1（r=0.999 9）、7.070～226.240 μg·mL^-1（r=0.999 9）范围内呈现良好的线性关系;平均回收率分别为98.46％,RSD=1.18%（n=9）和98.20%,RSD=0.90%（n=9）。结论:本研究建立的质量控制方法准确、操作简便,重复性好,专属性强,可有效用于欣梦安神颗粒的质量控制。     

甘草浸膏胶囊质量标准的建立

摘 要 目的：建立甘草浸膏胶囊中两种有效成分质量控制标准。方法: 采用TLC法对方中甘草进行鉴别;测定样品中甘草苷和甘草酸铵的含量。色谱条件：色谱柱为Inertsil C18柱(150 mm×4.6 mm,5 μm);流动相：乙腈(A) 0.2%磷酸(B) (0～8 min:20%A～20%A;8～34 min:20%A～50%A;34～35 min:50%A～100%A;35～40 min:100%A～20%A);流速为1.0 ml·min-1;检测波长：237 nm;柱温：25℃。结果: 薄层定性鉴别的斑点清晰,分离效果良好;甘草苷在0.002 0～0.100 0 mg·mL^-1浓度范围内线性关系良好（r=0.999 5）,平均加样回收率为100.29％,RSD为2.94％(n=6);甘草酸铵在0.002 0～0.100 0 mg·mL^-1浓度范围内线性关系良好（r=0.999 8）,平均加样回收率为101.46％,RSD为2.33％(n=6)。结论: 所建立方法快速简便,重复性好,专属性强,可作为该制剂的质量控制方法。     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

Self-stimulation and amphetamine: Tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Isolation and characterization of glycosylated and non-glycosylated prolactins from alligator and crocodile

Two molecular forms of prolactin (PRL). glycosylated and non-glycosylated, were isolated from pituitary glands of two reptiles, alligator and crocodile. The reptilian PRLs were extracted under alkaline conditions from the precipitate obtained after pituitaries were first extracted with 0.25 m sucrose, 1 mM NH₄HCO₃, pH 6.3. Purification was performed by ion exchange chromatography on DE-52, gel filtration on Sephadex G-75 superfine, and reversed phase high performance liquid chromatography. Two forms of both alligator and crocodile PRL, designated PRLI and PRLII, with molecular weights of 26000 and 24000 were isolated. Alligator and crocodile PRLI and PRLII were stained specifically in immunoblots with anti-sea turtle PRL and anti-ostrich PRL. Sequence analysis revealed that both forms of alligator and crocodile PRLs consisted of 199 amino acid residues with a glycosylation consensus sequence (Asn-Ala-Ser) at position 60 in alligator and crocodile PRLs with a molecular weight of 26000 (PRLI). In contrast, Thr was substituted for Asn at position 60 in the PRLs with a molecular weight of 24000 (PRLII). The sequences of alligator PRLs differed from crocodile PRLs only in position 134: Val for alligator PRLs and He for crocodile PRLs. There is a high degree of structural conservation between the reptilian PRLs isolated in this study and avian PRL; each showed 92% sequence identity with chicken PRL and 89% with turkey PRL.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

Benzodiazepines,amnesia and sedation: Theoretical and clinical issues and controversies

The amnestic effect of benzodiazepines, first described in 1965, and the subsequent attempts to identify the precise nature of this effect, are reviewed. The difficulty in deciding to what extent this effect is secondary to the sedative action of these drugs is shown by the lack of agreement between studies. Nevertheless, it is concluded that, given the right experimental design, all benzodiazepines can be shown to cause an anterograde amnesia which is probably primarily a result of reduced attention or rehearsal and secondary to sedation. Its onset, degree and duration are influenced by dose, rate of absorption, route of administration, potency and the receptor occupancy rate of the particular benzodiazepine involved, but plasma elimination t_½ appears to be relatively unimportant. The clinical relevance of this for the long-term use of hypnotics and anxiolytics is not clear. Tolerance appears to be greater than for the anxiolytic but less than the sedative or anticonvulsant effect of benzodiazepines. It seems that transient amnestic effects could occur in chronic users related to post-dose, peak benzodiazepine levels. The great variability in individual response means that transient amnesia is a potential adverse drug reaction in certain individuals taking benzodiazepines.