Hydration, stability, and phase transformations of a new antitumor drug

We studied hydration equilibria and phase transformations in a cytotoxic drug (BBR3576). The original sample is a hydrated compound that undergoes a structural phase transition when it looses about half of its structural water. Such a structural transition is completely reversible: the partially dehydrated form is stable up to 130 degrees C (or up to 140 degrees C for several minutes) and reverts to the original form upon rehydration. Completely different phase relationships are observed if an original sample is fully dehydrated: when all water has been released, a metastable anhydrous phase forms, which undergoes an irreversible exothermic conversion to a stable phase. Upon rehydration at room temperature of such an anhydrous phase, a new hydrated form is obtained, which is definitely different from the original one.     

Ukrain: a novel antitumor drug

A review of the recent literature on the new anticancer drug Ukrain is provided herein. We review Ukrain, a thiophosphate derivative of alkaloids from Chelidonium majus L., its capacity to exert selective cytotoxic and cytostatic effects on tumor cells, simultaneously acting as an immune response modifier, its good tolerance and lack of side effects even after long-term application, perspectives of the application of this drug in oncology.     

抗肿瘤青蒿素衍生物的研究

目的:为抗肿瘤青蒿素衍生物的深入研究和开发提供参考.方法:查阅文献,对抗肿瘤青蒿素衍生物的研究新进展进行归纳总结.结果:高活性的抗肿瘤青蒿素衍生物多为C-10位取代物;青蒿素二聚体及三聚体的抗肿瘤活性可能优于单体衍生物.结论:青蒿素衍生物有望在不久的将来应用于肿瘤治疗.     

Rhein: a novel potential antitumor drug

Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) is an anthraquinone compound enriched in the rhizome of rhubarb (Rheum palmatum or Rheum tanguticum Maxim), a traditional Chinese medicine herb. Natural product compounds are a source of novel therapeutic agents. Rhein has been initially identified as an anti-inflammatory and anti-oxidant agent. Recent studies indicate that rhein may also have an antitumor effect. However, the molecular mechanisms are still unclear. This review aims to summarize the research of rhein to better understand the anti-tumor activities by targeting cell cycle arrest, apoptosis, invasion, and metastasis of cancer cells. Meanwhile, we also intend to give an overview of the mechanisms identified so far. The breakthrough findings may shed light on using rhein as a targeted-cancer therapy.     

抗肿瘤药米铂的合成工艺改进

目的 改进抗肿瘤药米铂的合成工艺。方法 以顺式-二碘-(1R,2R)-1, 2-环己二胺合铂(II)为起始原料,将顺式-二碘- (1R,2R)-1, 2-环己二胺合铂(II)与硝酸银水解合成含有硝酸根的水合物溶液,然后与阴离子树脂交换生成顺式-二羟基- (1R,2R)-1,2-环己二胺合铂(II)的水溶液,再与正十四碳酸的正丁醇溶液反应合成米铂。采用元素分析、质谱、红外光谱、核磁共振氢谱、热分析和比旋光度对其结构进行表征。结果与结论 合成的化合物结构与标题化合物一致,收率约75%。该方法便于操作,收率高。     

Studies on the metabolism of meptazinol,a new analgesic drug.

1 The absorption, metabolism and excretion of the new analgesic meptazinol has been studied in male volunteers following oral and intravenous administration of a mixture of the [1-14C] and [7-3H] labelled compound. 2 After oral dosage, absorption from the gastrointestinal tract was rapid as evidenced by the early attainment of peak plasma radioactivity levels and near complete as shown by only small amounts of radioactivity recovered in the faeces. 3 Although the absorption of the drug was good, the systemic bioavailability was relatively low. Plasma levels of the unchanged drug remained below the limit of detection (20 ng/ml) after an oral dose of 200 mg. However, after intravenous administration of only 20 mg the peak plasma level was approximately 58 ng/ml. Subsequent elimination was rapid and proceeded in an apparently mono exponential manner with a half-life of approximately 2 hours. 4 Excretion of radioactivity was rapid irrespective of the dosage route and took place chiefly via the urine. Over 60% of the administered radioactivity was recovered in the 0-24 h urine collection. Less than 10% of the administered dose was excreted in the faeces. 5 Less than 5% of the drugs was excreted unchanged. The major metabolite appeared to be the glucuronide conjugate of the parent drug. No evidence was found for N-demethylation of the compound. A minor metabolite of the drug which accounted for approximately 7% of the recovered radioactivity has been tentatively identified as 6-ethyl - 6 - (3-hydroxyphenyl) - 1 - methyl-hexahydroazepin - (2H)-2-ONE.     

Studies on the peripheral pharmacology of fenazoxine, a potential antidepressant drug

1. The action of fenazoxine, a cyclized analogue of orphenadrine, has been studied on peripheral tissues innervated by adrenergic and cholinergic nerves. The hypothesis that cyclization of the alkyl amino chain of orphenadrine results in a molecule which retains the noradrenaline sensitizing action of orphenadrine but lacks the antimuscarinic activity has been investigated.2. The antimuscarinic activity of fenazoxine, on guinea pig ileum, was approximately 1/30 that of orphenadrine.3. Fenazoxine, desmethylimipramine and cocaine potentiated the response to noradrenaline and sympathetic nerve stimulation on the cat nictitating membrane, isolated rabbit ear artery and isolated driven atrial strip preparations.4. On the driven atrial strip preparation, fenazoxine at concentrations of 5 x 10(-7)M and 1 x 10(-6)M produced a small potentiation of the inotropic response to isoprenaline. At 5 x 10(-6)M and 5 x 10(-5)M fenazoxine antagonized the inotropic response to tyramine.5. Chronic denervation of the cat nictitating membrane abolished the potentiating action of fenazoxine.6. The results presented suggest that fenazoxine inhibits the uptake of catecholamines in a manner similar to that reported for desmethylimipramine and cocaine.7. Evidence is also presented which suggests that fenazoxine, like desmethylimipramine, possesses anti-noradrenaline activity at higher concentrations.     

Studies on the effect of pilocarpine incorporation into a submicron emulsion on the stability of the drug and the vehicle.

In order to obtain a novel ocular formulation with a potential for prolonging pilocarpine activity, the drug (2.0%) was incorporated into a submicron emulsion containing soya-bean oil and lecithin as emulgator. The effect of drug incorporation into the emulsion on its physical stability and on the other hand, the potential of the vehicle to reduce drug degradation at pH higher than 5.0 was studied. The pH was adjusted to 6.5 or 5.0 and the physicochemical stability of the formulations was observed. The mean diameter of oily particles in the resulting emulsions measured by a laser diffractometer was 0.6-0.7 micron and this was larger than in a drug-free emulsion where a 0.33 micron value was measured. The formulations were physically stable for 6 months at 4 degrees C, but progressing chemical degradation of pilocarpine was noted at pH 6.5. At that pH nearly 8% of pilocarpine was degraded to isopilocarpine and pilocarpic acid, both in the emulsion and in the solution. Thus, it may be concluded that pilocarpine in submicron emulsion is not protected against degradation. The presence of pilocarpine changes the physical stability of the vehicle since the formulation was easily destabilized during autoclaving or at room temperature. In the presence of higher concentration of lecithin (2.4%) or co-emulgators (poloxamer 2.0% or Tween 80 0.5%) the mean droplet size in the emulsions was the same as in a drug-free system. However the emulsions containing poloxamer were not stable during storage. Viscosity of pilocarpine emulsions can be increased by addition of methylcellulose or sodium carmellose (1.0%), but an intensive creaming occurs in these systems. Pilocarpine base is less suitable for emulsion preparation than hydrochloride salt, and emulsions prepared at pH 5.0 show the most satisfying stability.     

Studies on the mode of action of hexobendine, a prospective anti-anginal drug

1. In cats anaesthetized with pentobarbitone sodium, hexobendine (0·25 mg/kg) markedly increased myocardial blood flow (measured using a heat clearance technique) and usually decreased myocardial metabolic heat production, without influencing cardiac contractility or systemic arterial blood pressure. These effects lasted for about 45 min.     

抗肿瘤新药布立尼布的合成

目的:合成抗肿瘤新药布立尼布,并对其工艺进行改进。方法:以3-甲基-1H-吡咯-2,4-二甲酸乙酯为原料,经N-氨基化,环合,格氏反应,氧化重排,乙酰化,卤化,亲核取代,脱保护和亲核取代反应制得布立尼布。结果与结论:目标产物结构经1H-NMR和MS确证,总收率为21.6%,ee值为99.3%。改进后的制备工艺反应条件温和,适合工业化生产。     

Studies on the antitumor activity ofDuchesnea indicae Herba

As a part of finding the biologically active components fromDuchesnea indica (Andr.)Focke (Rosaceae), antitumor activities of its water soluble fractions have been studied. The fractions were examined for antitumor activity against sarcoma 180 implanted in mice. The antitumor inhibition ratios of the water soluble fractions fromDuchesnea indica were 17.9, 37.1, 62.7, 60.1, 62.4%, respectively.     

Studies on the absorption, distribution, and elimination of amiquinsin hydrochloride, a hypotensive drug

A sensitive and specific spectrophotofluorometric procedure is described for the determination of amiquinsin hydrochloride, a hypotensive drug, in biologic materials. Results are presented which show that either oral or parenteral dosage of amiquinsin HCl to dogs yields blood drug levels which are dose related and linear urinary drug dose responses. At least of the dose usually is recovered in urine under these conditions. Intravenous administration of amiquinsin HCl to dogs results in a biphasic drug disappearance curve in blood. Only low concentrations of amiquinsin HCl were detectable in the bile, aqueous humor, and cerebrospinal fluid of the dog. Although no major specific tissue binding sites were apparent for amiquinsin HCl in the dog, the drug was found in most tissues at levels greater than those currently present in blood. Evidence is also presented which indicates that there is placental transfer of amiquinsin HCl in the guinea pig, rabbit, dog, and sheep.