盐酸美金刚胺的合成工艺改进

目的改进盐酸美金刚胺的合成工艺。方法以1,3-二甲基金刚烷为原料,在叔丁醇、乙腈、浓硫酸存在下,经Ritter反应生成1-乙酰胺基-3,5-二甲基金刚烷,再以聚乙二醇为溶剂,加入氢氧化钠水解得到美金刚胺,然后在异丙醇溶剂中盐酸化得到盐酸美金刚胺。总收率：70%。结果合成了具有良好化学纯度的盐酸美金刚胺（纯度99.9%,总收率70%）。结论改进的工艺明显提高了反应收率,工艺条件温和,合成步骤简洁,适合工业化生产。     

药用1,3-二甲基戊胺盐酸盐的合成工艺改进

目的合成1,3-二甲基戊胺盐酸盐并改进其工艺。方法 以乙酰乙酸乙酯和2-溴丁烷为原料,经4步合成反应得到1,3-二甲基戊胺盐酸盐,并采用单因素考察法对合成工艺进行改进。结果1,3-二甲基戊胺盐酸盐各步反应的收率均>40%,产物总收率达到12.3%。结论产物结构经1 H-NMR和13 C-NMR确认为1,3-二甲基戊胺盐酸盐。     

伊班膦酸钠合成工艺的改进

目的改进伊班膦酸钠的合成工艺。方法以N-甲基正戊胺为原料经加成、水解、成盐、膦酸化、水解、成盐得伊班膦酸钠。结果与结论改进的工艺明显提高了反应收率,工艺条件温和,合成步骤简洁,适合工业化生产。     

抗肿瘤药物泊马度胺的合成工艺改进

改进抗肿瘤药泊马度胺的合成工艺,以3-硝基邻苯二甲酸为原料,合成3-硝基邻苯二甲酸酐;再与谷氨酰胺反应,经氨解、缩合、还原得到目标产物泊马度胺,反应总收率60.8%。     

酒石酸托特罗定的合成研究

目的:合成酒石酸托特罗定并进行工艺改进。方法:以对甲苯酚为起始原料,经缩合、甲基化、还原、酯化、胺化、脱甲基化、拆分、精制等反应合成酒石酸托特罗定,并对脱甲基化反应进行了工艺改进。结果:通过改进工艺,总收率由9.23%提高到13.5%。结论:优化工艺后,收率提高,成本降低,解决了劳动保护和环保问题,更适合工业化生产。     

萘呋胺酯草酸盐的合成工艺改进

目的改进萘呋胺酯草酸盐的合成工艺。方法以糠醛和丙二酸二乙酯为起始原料经缩合、还原、烷基化、水解、脱羧和酯化等步骤制得萘呋胺酯草酸盐。结果目标化合物经1H-NMRI,R,MS谱确证,总收率在63.6%。结论改进后的工艺操作简便,成本低廉,有利于工业化生产     

因卡膦酸二钠的合成

目的：合成因卡膦酸二钠,并进行工艺改进。方法：即以环庚胺、亚磷酸二乙酯、原甲酸三乙酸为为起始原料,经二步反应合成因卡膦酸二钠。结果：避免了硅胶柱分离工艺,产物经IR、NMR、MS及元素分析、热分析确证了化学结构。结论：合成方便收率稳定,工艺简单。     

利奈唑胺合成工艺的改进

目的 改进利奈唑胺的合成工艺.方法 以3,4-二氟硝基苯为原料,经取代、还原、酰化、再与侧链双乙酰化合物缩合得到目标化合物.结果 合成总收率为62.7%.结论 改进后的方法操作时间缩短,溶剂量减少,后处理方便,成本降低.     

抗抑郁药盐酸托莫西汀的合成工艺改进

目的研究盐酸托莫西汀的合成工艺.方法以1-苯丙醇为起始原料,经氯代、溴代、醚化、胺化、拆分、氯化氢成盐6步反应合成盐酸托莫西汀.结果与结论合成盐酸托莫西汀的总收率为16.4%,比文献值提高了5.4%.改进了中间体5和6的合成工艺.     

盐酸特拉唑嗪的合成工艺改进

目的改进盐酸特拉唑嗪的合成工艺。方法以无水哌嗪为起始原料,经酰化、还原、胺化、成盐等反应制得盐酸特拉唑嗪。结果与结论降低了成本,提高了收率,适合工业化生产。     

Effects of methysergide, pizotifen and ergotamine in the monkey cranial circulation.

Internal and external carotid vascular resistances were measured, in anaesthetized monkeys, to asses the direct cranial vascular effects of i.v. methysergide, pizotifen and ergotamine, and their effects on the cranial vascular responses to the constrictors 5-hydroxytryptamine and noradrenaline and the dilators histamine, prostaglandin E1 and bradykinin. Methysergide reduced responses to 5-HT, and tended to potentiate the external carotid responses to noradrenaline. Pizotifen blocked responses to histamine; it tended to reduce internal carotid responses to 5-HT, but it potentiated external carotid 5-HT responses. Ergotamine reduced responses to 5-HT and noradrenaline, but this was probably related to its cranial vasoconstrictor effects, especially in the external carotid circulation. Methysergide induced weak transient cranial vasoconstriction and pizotifen had no direct effects. These findings may be relevant to the therapeutic actions of these drugs in migraine, since the doses used approximated to those used clinically.     

Further studies on the site of action of nicotinic blocking drugs

The effects of combinations of tubocarine and physostigmine, and of physostigmine and edrophonium alone, have been studied on the responses of the chick biventer cervicis muscle to nerve stimulation and to exogenous acetylcholine. The effects of hexamethonium, tetraethylammonium and triethylcholine have also been studied on the dose-response curves for acetylcholine, determined in the presence of low concentrations of physostigmine.Suitable combinations of tubocurarine and physostigmine reduced responses of the muscle to nerve stimulation, whilst leaving the responses to acetylcholine unaffected, whereas physostigmine and edrophonium augmented responses to acetylcholine, whilst leaving responses to nerve stimulation unaffected. These results indicate that the multiply innervated fibres of the muscle are particularly sensitive to inhibition of cholinesterase.Hexamethonium, tetraethylammonium and triethylcholine, drugs that are known to exhibit actions similar to that of the combination of tubocurarine and physostigmine, and also to possess anticholinesterase activity, depressed responses to acetylcholine determined in the presence of concentrations of physostigmine sufficiently low to possess a specific inhibitory action on cholinesterase. The results indicate that the neuromuscular block produced by large concentrations of these drugs is probably post-junctional in origin.     

A biologically based dynamic model for predicting the disposition of methanol and its metabolites in animals and humans.

A multicompartment biologically based dynamic model was developed to describe the time evolution of methanol and its metabolites in the whole body and in accessible biological matrices of rats, monkeys, and humans following different exposure scenarios. The dynamic of intercompartment exchanges was described mathematically by a mass balance differential equation system. The model's conceptual and functional representation was the same for rats, monkeys, and humans, but relevant published data specific to the species of interest served to determine the critical parameters of the kinetics. Simulations provided a close approximation to kinetic data available in the published literature. The average pulmonary absorption fraction of methanol was estimated to be 0.60 in rats, 0.69 in monkeys, and 0.58-0.82 in human volunteers. The corresponding average elimination half-life of absorbed methanol through metabolism to formaldehyde was estimated to be 1.3, 0.7-3.2, and 1.7 h. Saturation of methanol metabolism appeared to occur at a lower exposure in rats than in monkeys and humans. Also, the main species difference in the kinetics was attributed to a metabolism rate constant of whole body formaldehyde to formate estimated to be twice as high in rats as in monkeys. Inversely, in monkeys and in humans, a larger fraction of body burden of formaldehyde is rapidly transferred to a long-term component. The latter represents the formaldehyde that (directly or after oxidation to formate) binds to various endogenous molecules or is taken up by the tetrahydrofolic-acid-dependent one-carbon pathway to become the building block of synthetic pathways. This model can be used to quantitatively relate methanol or its metabolites in biological matrices to the absorbed dose and tissue burden at any point in time in rats, monkeys, and humans for different exposures, thus reducing uncertainties in the dose-response relationship, and animal-to-human and exposure scenario comparisons. The model, adapted to kinetic data in human volunteers exposed acutely to methanol vapors, predicts that 8-h inhalation exposures ranging from 500 to 2000 ppm, without physical activities, are needed to increase concentrations of blood formate and urinary formic acid above mean background values reported by various authors (4.9-10.3 and 6.3-13 mg/liter, respectively). This leaves blood and urinary methanol concentrations as the most sensitive biomarkers of absorbed methanol.     

Evidence for the presence of P1-purinoceptors on cholinergic nerve terminals in the guinea-pig ileum

The inhibitory effects of adenosine, ATP, 5'-adenylyl methylene diphosphonate (beta, gamma-meATP) and adenosine 5'-alpha, beta-methylene triphosphonate (alpha, beta-meATP) were compared on the cholinergic twitch responses to transmural stimulation of the guinea-pig ileum. Adenosine, ATP and beta, gamma-meATP reduced the twitch responses in a concentration dependent manner. Theophylline antagonized and dipyridamole potentiated the inhibitory responses to adenosine, ATP and beta, gamma-meATP. Inhibitory responses to alpha, beta-meATP were usually preceded by an enhancement in twitch height. Contractions of the unstimulated ileum to alpha, beta-meATP were blocked by atropine and tetrodotoxin while those elicited by ATP were unaffected, which suggests that the initial excitatory effects of alpha, beta-meATP may be due to its ability to release ACh from cholinergic nerve terminals. Use of high pressure liquid chromatography and bioluminescence assay techniques demonstrated the ability of the tissue to degrade ATP and beta, gamma-meATP and, at a much slower rate, alpha, beta-meATP. Inhibitory responses to ATP, AMP and beta, gamma-meATP were reduced by adenosine deaminase, which also abolished responses to adenosine. 5'-AMP deaminase abolished responses to AMP and adenosine, and reduced those to ATP and beta, gamma-meATP. The results suggest that the inhibitory effect of ATP on cholinergic neurotransmission is due to its rapid breakdown to AMP or adenosine, which act on prejunctional P1-purinoceptors.     

Addressing the workforce crisis: the professional aspirations of pharmacy students in Ghana

Objective A lack of skilled health professionals, and net migration from developing to more developed countries, are widely recognised as barriers to the delivery of effective health care. However, few studies have investigated this issue from the perspective of pharmacists, although they are increasingly viewed as a potentially valuable and underexploited health care resource. The objectives of this study were to examine the professional aspirations and perceived opportunities of final year pharmacy students in a developing country; and consider what developments may encourage them to remain in, and contribute to, health care in their home country. Method Final year pharmacy students from the Faculty of Pharmacy, KNUST, Kumasi, Ghana, were randomly selected and invited to participate in in-depth interviews. These were audio-recorded (with permission of respondents) and transcribed verbatim to enable a qualitative analysis. Main outcome measure: professional aspirations, and perceived opportunities and barriers to their achievement in Ghana and abroad. Results Participants viewed themselves, and wished to be viewed by others, as health professionals. They described a commitment to applying their clinical knowledge and to education beyond their first degree. However, they identified significant barriers to the achievement of professional aspirations in Ghana, which would diminish their opportunities to contribute to health care. Whilst most students expressed the expectation or desire to travel at some point, usually early, in their career, they all demonstrated a commitment to their country and stated a wish to return. Conclusion Overall the study highlighted prospective pharmacists in Ghana as ambitious, committed potential health professionals. The study indicates that a lack of attention by policy makers and professional bodies to ways of exploiting the contribution of pharmacists to public health, may represent a lost potential human resource for health in developing countries.     

Development of in vitro systems for nanotoxicology: methodological considerations

Due to the rapid development of a diverse array of nanoparticles, used in a wide variety of products, there are now many international activities to assess the potential toxicity of these materials. These particles are developed due to properties such as catalytic reactivity, high surface area, light emission properties, and others. Such properties have the potential to interfere in many well-established toxicity testing protocols. This article outlines some of the most frequently used assays to assess the cytotoxity and biological reactivity of nanoparticles in vitro. The article identifies key issues that need to be addressed in relation to inclusion of relevant controls, assessing particles for their ability to interfere in the assays, and using systematic approaches to prevent misinterpretation of data. The protocols discussed range from simple cytotoxicity assays, to measurement of reactive oxygen species and oxidative stress, activation of proinflammatory signaling, and finally genotoxicity. The aim of this review is to share knowledge relating to nanoparticle toxicity testing in order to provide advice and support for guidelines, regulatory bodies, and for scientists in general.     

Effect of variable power levels on the yield of total aerosol mass and formation of aldehydes in e-cigarette aerosols

The study objective was to determine the effect of variable power applied to the atomizer of refillable tank based e-cigarette (EC) devices. Five different devices were evaluated, each at four power levels. Aerosol yield results are reported for each set of 25 EC puffs, as mass/puff, and normalized for the power applied to the coil, in mass/watt. The range of aerosol produced on a per puff basis ranged from 1.5 to 28 mg, and, normalized for power applied to the coil, ranged from 0.27 to 1.1 mg/watt. Aerosol samples were also analyzed for the production of formaldehyde, acetaldehyde, and acrolein, as DNPH derivatives, at each power level. When reported on mass basis, three of the devices showed an increase in total aldehyde yield with increasing power applied to the coil, while two of the devices showed the opposite trend. The mass of formaldehyde, acetaldehyde, and acrolein produced per gram of total aerosol produced ranged from 0.01 to 7.3 mg/g, 0.006 to 5.8 mg/g, and <0.003 to 0.78 mg/g, respectively. These results were used to estimate daily exposure to formaldehyde, acetaldehyde, and acrolein from EC aerosols from specific devices, and were compared to estimated exposure from consumption of cigarettes, to occupational and workplace limits, and to previously reported results from other researchers.     

加强医院药品的质量管理

加强药品质量管理,为医院提高医疗质量,保证患者用药安全提供了有效保障。根据医疗、科研的实际需要,以中华人民共和国《药品管理法》和《医院药剂管理办法》的规定,加强医院药剂管理,严把药品采购、保管、使用关。通过加强医院药品质量管理,贯彻优质、合理、高效、低耗的原则,使医院达到有效、安全、经济、方便地使用药品。加强医院药品的质量管理,对促进医院健康、稳定的发展具有重要意义。     

The nootropic concept and its prospective implications

Giurgea, C.E. : The nootropic concept and its prospective implications. Drug. Dev. Res. 2:441–446, 1982. The nootropic concept emerged about 10 years ago essentially from the unusual pharmacology of piracetam, which later on was confirmed and extended to human pharmacoclinics and therapeutics. A nootropic drug is characterized by a direct functional activation of the higher integrative brain mechanisms that enhances cortical vigilance, a telencephalic functional selectivity, and a particular efficiency in restoring deficient higher nervous activity. In contradistinction to other psychotropic drugs, nootropics do not induce direct reticular, limbic, or other subcortical events. Little is known with regard to nootropic, neurochemical mechanisms of action except that they interact with factors that contribute to the neuronal membrane stability, and possibly with the brain 5-HT. Main therapeutical indications seem to be in children with speech disorders, in the posttraumatic, and posthypoxic sequelae, in vertigo of central origin, and in geriatric, moderately impaired, possibly dysmnesic patients. Other drugs, such as pyritinol, meclofenoxate, and, to some extent, hydergine and vincamine, do show partially nootropic activities. The nootropic line of research is by now multifaceted to deepen the neurochemical and neurophysiologic comprehension of nootropics' mode of action; to make clearer their clinical differential profile; to enlarge the nootropic framework to some other existing drugs, clinically if not pharmacologically related to piracetam; and to find new, more potent, and possibly more selective nootropic agents. The general aim of nootropic research is to find new drugs capable of enhancing directly the efficiency of the cognitive, noetic activity of the brain, thus compensating various neuro-psychologic deficits such as, but not exclusively, those related to aging.