胃舒安颗粒治疗功能性消化不良的有效性和安全性多中心临床评价

目的：评价胃舒安颗粒治疗功能性消化不良的临床疗效和安全性。方法：试验采用分层区组、随机、双盲双模拟、阳性药平行对照、多中心临床研究方法，以西沙必利片作为对照药对比观察。共观察409例（3：1），其中试验组308例，对照组101例．其中脱落4例，剔除5例。结果：中医证候疗效：胃舒安颗粒组愈显率63．03％，总有效率95．70％；西沙必利片组愈显率62．38％，总有效率94．06％。痞满证候疗效：胃舒安颗粒组愈显率62．04％，总有效率92．07％；西沙必利片组愈显率54．45％，总有效率87．12％。胃排空试验胃舒安颗粒组愈显率60．78％，总有效率73．85％；西沙必利片组愈显率59．26％，总有效率70．37％。两组比较无统计学意义（P〉0．05）。结论：胃舒安颗粒治疗功能性消化不良疗效确切，未发现毒副作用。     

桃花止泻颗粒联合环丙沙星治疗感染性腹泻38例

目的观察桃花止泻颗粒治疗感染性腹泻的临床疗效,并评价其安全性。方法将38例住院患者作为治疗组,30例同期入院的患者为对照组。治疗组给予桃花止泻颗粒冲服,每次6 g,tid;合用环丙沙星口服,每次0.4 g,tid;对照组用双八面体蒙脱石散,po,tid;合用环丙沙星,每次0.4 g,po,tid;均5～7 d为1个疗程并观察疗效。结果治疗组总有效率97.37%,对照组总有效率96.67%,两组疗效差异无显著性（P＞ 0.05）。结论桃花止泻颗粒联合环丙沙星治疗感染性腹泻的临床疗效与双八面体蒙脱石散相当,是治疗腹泻安全、有效的中药制剂。     

复方甘草酸苷治疗斑秃32例

目的：观察复方甘草酸苷治疗斑秃的临床疗效。方法：治疗组32例，给予复方甘草酸苷片，每次3片，po，tid，3个月后改为每次2片，tid；对照组30例，给予胱氨酸，每次100 mg，po，tid，葡萄糖酸锌片，每次70 mg，po，tid。两组同时外搽中药生发酊剂，tid。总疗程均为5个月。结果：治疗组痊愈13例，总有效率81.2%；对照组痊愈6例，总有效率50.0%，差异有极显著性(P＜0.01)。结论：复方甘草酸苷片治疗斑秃疗效良好，且不良反应不明显。     

小剂量米非司酮治疗经前期综合征的随机双盲对照研究

目的：观察小剂量米非司酮治疗经前期综合征的临床疗效和安全性。方法：采用随机双盲安慰剂对照试验设计方法,选择80例经前期综合征患者,随机分为研究组和对照组,每组40例。每组均连续用药1个疗程（3个月经周期）,并予以随访3个月经周期。结果：研究组与对照组临床疗效的总有效率分别为92.5%（37/40）和45%（18/40）,2组比较有统计学差异（P〈0.05）,研究组优于对照组。研究组与对照组随访3个月经周期临床疗效的总有效率分别为90%（36/40）和37.5%（15/40）,2组比较有统计学差异（P〈0.05）,研究组优于对照组。研究组和对照组均无明显不良反应。结论：小剂量米非司酮能缓解经前期综合征症状,具有明显疗效,且副作用小,有一定安全性。     

金叶败毒颗粒治疗玫瑰糠疹58例疗效观察

目的：观察金叶败毒颗粒治疗玫瑰糠疹的疗效。方法：116例患者随机分为两组，治疗组58例用金叶败毒颗粒10g，po，tid，同时外用3％樟脑霜；对照组58例仅外用3％樟脑霜。疗程均为7d，3个疗程后观察疗效。结果：治疗组与对照组总有效率分别为93．10％和77．59％，P〈0．05。治疗组平均痊愈时间比对照组少3．5d。结论：金叶败毒颗粒内服能够有效控制玫瑰糠疹的症状和体征、缩短病程，且安全、有效。     

复方阿嗪米特联合伊托必利治疗功能性消化不良80例

目的：观察复方阿嗪米特联合伊托,Z-~q对功能性消化不良的疗效。方法：160例功能性消化不良患者根据就诊次序随机分为治疗组和对照组,治疗组应用复方阿嗪米特片,2片,po,tid,同时用伊托必利胶囊,50mg,po,tid;对照组应用伊托必利胶囊,50mg,po,tid,疗程均为4周;观察临床症状变化。结果：在14,28d,治疗组和对照组2组中总有效率分别为85．O％,90．0％;63．8％,67．5％,治疗组和对照组比较差异有统计学意义（／9〈0．05）。结论：复方阿嗪米特联合伊托必利治疗功能性消化不良疗效显著,无明显不良反应。     

右旋酮洛芬氨丁三醇和酮洛芬双盲对照治疗类风湿关节炎

目的：比较右族酮洛芬氨丁三醇和酮洛芬治疗类风湿关节炎的疗效和安全性。方法：采用随机、双盲、平行对照的方法治疗类风湿关节炎120例。试验组61例予右旋酮洛芬氨丁三醇25mg，po，tid；对照组59例予酮洛芬50mg，po，tid，疗程均为4周。结果：右旋酮洛芬氨丁三醇能明显改善患者的临床症状和体征，治疗有效率63．9％，与对照组(55．9％)相比无显著差异。右旋酮洛芬氨丁三醇的不良反应少量轻微，其中胃不适症状发生率两药相比有显著差异(分别为4．9％和18．6％)。结论：右旋酮洛芬治疗类风湿关节炎疗效与酮洛芬相近，耐受性优于酮洛芬。     

驱白巴布期片治疗白癜风疗效观察

目的：观察驱白巴布期片治疗白癜风的临床疗效。方法：148例患者随机分为2组,治疗组76例服用驱白巴布期片5片,po,tid;对照组72例服用白蚀丸2g,po,tid;两组同时外用驱白巴布期喷剂。6个月后分别观察疗效。结果：治疗组总有效率60．53％,明显高于对照组（41．67％）,P〈0．05。结论：驱白巴布期片治疗白瘢风有明显疗效,值得临床推广应用。     

复方甘草酸苷联合消银颗粒治疗玫瑰糠疹65例

［摘要］目的探讨复方甘草酸苷片联合消银颗粒治疗玫瑰糠疹的疗效。方法123例玫瑰糠疹患者随机分为两组，治疗组65例，口服复方甘草酸苷75 mg，po，tid； 同时联合消银颗粒3.5 g， po，tid；对照组58例，给予复方甘草酸苷75 mg，po，tid，两组均外用醋酸曲安奈德尿素乳膏，bid。疗程均为2周。结果治疗组总有效率为90.77% ，对照组总有效率为68.97%（P＜O.01）。两组均未见不良反应。结论复方甘草酸苷联合消银颗粒治疗玫瑰糠疹疗效确切，疗程短，治愈率高，不良反应少。     

银丹心脑通软胶囊治疗中风后遗症临床观察

目的：观察银丹心脑通软胶囊治疗中风后遗症的疗效。方法：采用随机双盲法将100例中风后遗症患者分为2组，每组各50例。治疗组给予银丹心脑通软胶囊，每次3粒，tid，po对照组给予复方丹参片，每次3片，tid，po。2组均以4周为1个疗程。观察2组治疗前后神经功能缺失评分及临床疗效评定，进行对比分析。结果：治疗组的神经功能缺失评分及临床疗效评定均优于对照组，差异有显著性（P〈0．05）。结论：银丹心脑通软胶囊对中风后遗症有较好的疗效。     

Polymorphism, pseudopolymorphism, and amorphism of peracetylated alpha-, beta-, and gamma-cyclodextrins

Polymorphism, pseudopolymorphism, and amorphism of hexakis(2,3,6-tri-O-acetyl)-alpha-cyclodextrin (TAalphaCyD), heptakis(2,3,6-tri-O-acetyl)-beta-cyclodextrin (TAbetaCyD), and octakis(2,3,6-tri-O-acetyl)-gamma-cyclodextrin (TAgammaCyD) were investigated using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffractometry (XRPD), Fourier transform infrared spectroscopy (FTIR) and optical microscopy. An anhydrous and a bi-hydrate crystalline forms of TAalphaCyD, two monotropic anhydrous polymorphs and three pseudopolymorphs (i.e. methanolate, hydrate, and isopropanolate-hydrate) of TAbetaCyD, as well as two monotropic anhydrous polymorphs and isostructural pseudopolymorphs (e.g. hydrate and isopropanolate-hydrate) of TAgammaCyD were isolated and characterized. The amorphous forms of each TACyD were also obtained. Thermal data for desolvation of TAalphaCyD.2H2O and TAbetaCyD.CH3OH were reconciled with their crystal packing features. Melting temperatures and enthalpies of the crystalline forms of each TACyD can be referred to for possible solid-state interactions with drugs.     

Synthesis,anti-inflammatory,analgesic, and antibacterial activities of some triazole,triazolothiadiazole, and triazolothiadiazine derivatives

This study is concerned with the synthesis of new 1,2,4-triazoles, 1,3,4-thiadiazoles, and 1,3,4-thiadiazines derivatives. Derivatives 3a–i were obtained by condensation of 4-amino-3-(4-pyridine)-5-mercapto-1,2,4-triazole 1 with the appropriate aldehyde. Compounds 4a–i were synthesized in a one pot reaction involving compounds 3a–i, formaldehyde, and morpholine. Condensation of compound 1 with the appropriate acids or 4-substituted phenacyl bromide gave compounds 6a–d and 8a–f respectively. The chemical structures of the newly synthesized derivatives were elucidated using different spectral and elemental methods of analysis. All compounds were evaluated for their anti-inflammatory activity and the most potent derivatives were tested for their analgesic activity using indomethacin as a reference drug. In addition, ulcerogenicity and LD₅₀ for the most active compounds were evaluated. Moreover, the antibacterial activities of the newly synthesized derivatives were investigated.     

New synthesis of benzo-delta-carbolines, cryptolepines, and their salts: in vitro cytotoxic, antiplasmodial, and antitrypanosomal activities of delta-carbolines, benzo-delta-carbolines, and cryptolepines

The paper describes, in its first part, a new synthesis of benzo-delta-carbolines, cryptolepines, and their salts. The strategy is based on the association between halogen-dance and hetero-ring cross-coupling. It is fully convergent and regioselective with interesting overall yields from 27% to 70%. A halogen-dance mechanism in quinoline series is also proposed. The formal synthesis of potential antimalarial compounds and the first total synthesis of 11-isopropylcryptolepine are also described. In the second part, cytotoxic activity against mammalian cells and activities against Plasmodium falciparum and Trypanosoma cruzi of benzo-delta-carbolines and delta-carbolines were evaluated in vitro to study the structure-activity relationships. For benzo-delta-carbolines, methylation at N-5 increases the cytotoxic and antiparasitic activities. A further alkylation on C-11 generally increases the cytotoxic activity but not the antiparasitic activity, cryptolepine and 11-methylcryptolepine being the most active on both parasites. Taking advantage of the fluorescence of the indoloquinoline chromophore, cryptolepine was localized by fluorescence microscopy in parasite DNA-containing structures suggesting that these compounds act through interaction with parasite DNA as proposed for cryptolepine on melanoma cells. For delta-carbolines, methylation at N-1 is essential for the antimalarial activity. 1-Methyl-delta-carboline specifically accumulates in the intracellular parasite. It has weak cytotoxic activity and can be considered as a potential antimalarial compound.     

Pharmacokinetics of Liquiritigenin in Mice,Rats, Rabbits,and Dogs,and Animal Scale-Up

Pharmacokinetics of liquiritigenin (LQ) and its two glucuronide metabolites, M1 and M2, in mice, rats, rabbits, and dogs and animal scale-up of the pharmacokinetic parameters of LQ were evaluated. After intravenous administration of LQ, the AUC (AUC_0?t) values of LQ, M1, and M2 were proportional to LQ doses in all animals studied. Animal scale-up of some pharmacokinetic parameters of LQ was performed based on the parameters after its intravenous administration (20 mg/kg; in the linear pharmacokinetic range) to the four species. Linear relationships were obtained (r > 0.968) between log CL (or CL/f_u) (L/h) and log species body weight (W) (kg) [CL (or CL/f_u) = 3.29 (34.0) W^{0.723 (0.789)}] and log V_ss (or V_ss/f_u) (L) and log W (kg) [V_ss (or V_ss/f_u) = 0.340 (3.52) W^{0.882 (0.948)}]. Interspecies scale-up of plasma concentration–time data of LQ using apolysichron (complex Dedrick plots) resulted in similar profiles, and plasma concentration–time profile of humans were predicted using the well-fitted four animal data. Our results indicate that the LQ data obtained from laboratory animals could be utilized to generate preliminary estimates of the pharmacokinetic parameters of LQ in humans. These parameters can serve as guidelines for better planning of clinical studies. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4327–4342, 2009     

Comparison of natriuretic, uricosuric, and antihypertensive properties of tienilic acid, bendrofluazide, and spironolactone.

The antihypertensive properties of the new diuretic tienilic acid were investigated. Thirteen previously untreated hypertensive patients took part in a double-blind crossover study in which 30 days' treatment with tienilic acid 250 mg, bendrofluazide 5 mg, and spironolactone 100 mg were compared. Bendrofluazide caused the greatest natriuresis on the first treatment day and the most rapid fall in blood pressure. The ultimate antihypertensive effect of all three drugs was similar. Tienilic acid caused a noticeable reduction in serum urate concentrations and a rise in urate clearance, in contrast to the other two agents, which caused slight urate retention. Tienilic acid and bendrofluazide caused falls and spironolactone a rise in plasma potassium concentrations. No untoward effects were seen from any of the drugs. It is concluded that tienilic acid is a moderately potent diuretic that lowers plasma urate concentrations. It may be the drug of first choice for hypertensive patients who already have gout or are likely to develop it when taking thiazide diuretics.     

Stereospecific and circadian-phase-dependent kinetic behavior of d,l-, l-, and d-propranolol in plasma, heart, and brain of light--dark-synchronized rats

In light--dark-synchronized male rats, the kinetic behavior of d,l-, l-, and d-propranolol after single (1.78 and 8.89 mg/kg) or multiple drug administration (6 X 8.89 mg/kg) was studied in plasma, heart, and brain both in the light period (L) and in the dark period (D). With either dosage regimen the kinetics of racemic propranolol displayed a temporal dependency, elimination half-lives in plasma, heart, and brain being shorter during D than during L. This was observed with the stereoisomers only after single drug application with no circadian phase dependency at steady-state concentrations. On the other hand, the kinetic behavior of l- and d-propranolol exhibited pronounced stereospecificity in that t1/2 Beta, Vdbeta, plasma clearance, and drug accumulation in heart and brain were greater for l-propranolol than for the d-isomer. Stereospecific differences in t1/2 beta and elimination rate were more pronounced during D. In the light of the flow-dependent hepatic extraction of propranolol it is unlikely that daily variations in microsomal liver enzyme activity are responsible for the chronopharmacokinetics of propranolol. It is assumed that daily variations in liver blood flow, which is more effectively reduced by beta-receptor blockade in the period of increased sympathetic tone during D, are mainly responsible for the chronopharmocokinetics of the therapeutically used d,l-propranolol.     

PCP, THC, ethanol, and morphine and consumption of palatable solutions

Water-deprived rats were given daily opportunities (2.0-hr sessions) to take water or a sweet solution (20% or 24% sugar-water). After stable intakes of each fluid were achieved, the effects of phencyclidine hydrochloride (PCP), delta-9-tetrahydrocannabinol (THC), ethanol (E), and morphine (M) on intakes were tested. PCP, THC, and M all enhanced intake of the sweet solution, while E produced varying effects across doses tested. With other rats, nearly the same procedure was used except that the test solution presented with water was 0.9% sodium chloride. Doses of PCP enhanced intake of the salty solution. These data, combined with the data from similar studies of the effects of opioids and benzodiazepines, indicate that a wide variety of agents that are self-administered also modify intake of ingesta.     

Storage,release, uptake,and inactivation of purines

Adenine nucleotides are released into the interstitial space during platelet thrombus formation and neurotransmission. ATP has also been reported to be released from the heart and endothelial cells in some studies. Ecto ATPase, ADPase, and 5′-nucleotidase activities capable of hydrolyzing ATP sequentially to adenosine are present in many cell types and may serve to terminate the actions of the nucleotides. The opposing effects of adenosine and ATP on the same cell types have suggested a modulatory role for adenosine of the actions of extracellular ATP and that the rates of hydrolysis of nucleotides might be regulated. Consistent with this it has been found that the balance between feedforward inhibition of 5′-nucleotidase by ADP and/or ATP and preferential delivery of AMP from ADPase to 5′-nucleotidase determines the rate of adenosine production and that this differs in different cell types. Alternatively, adenosine may be produced intracellularly as a result of an imbalance between energy demand and supply. There are at least two different cytosolic forms of 5′-nucleotidase. Degradation of ATP during increased metabolic activity results in an increase in intracellular AMP concentration. Either cytosolic enzyme has a high KM (2–5 mM) and would thus respond to this increase with a proportional rise in the rate of adenosine production. The nucleoside transporter is essential to allow the diffusion of adenosine to extracellular receptor sites. In general, adenosine must be taken up via the nucleoside transporter before it is inactivated either by phosphorylation by adenosine kinase in the micromolar range or by deamination by adenosine deaminase at higher concentrations. © 1993 Wiley-Liss, Inc.