硫酸吗啡口腔崩解片的制备及处方工艺研究

目的:制备硫酸吗啡口腔崩解片,优化其处方工艺条件。方法:采用直接压片法制备硫酸吗啡口腔崩解片,以崩解时间和口感为指标采用单因素试验法筛选片剂硬度、硬脂酸镁用量、甜菊苷用量范围等,再以崩解时限为指标采用星点设计法优化微晶纤维素(SMCC)、交联羧甲基纤维素钠(CCMC-Na)、甜菊苷用量,并对最优处方所制制剂进行验证。结果:最优处方组成为(片质量60 mg):硫酸吗啡16.67%、SMCC 35.77%、CCMC-Na 8.94%、甜菊苷2.85%、硬脂酸镁1%、甘露醇34.77%。所制口腔崩解片硬度为3 kg,能在12 s内完全崩解,且味微甜、口感良好。结论:该制剂制备方法简便、可行。     

咪达那新口腔崩解片的制备及处方优化

目的 研究咪达那新口腔崩解片的处方与制备工艺.方法采用粉末直压 升华干燥制备法,以崩解剂的种类与用量、助崩解剂用量、升华剂用量等为考察因素,以物料休止角、片剂润湿时间、崩解时间等为考察指标,通过单因素试验进行处方筛选,确定最优处方.在最优处方的基础上考察片剂硬度对口崩片崩解时间的影响,从而制得孔隙率较高脆碎度较好的咪达那新口腔崩解片.结果处方以甘露醇为填充剂,微晶纤维素40%、交联聚维酮5%为崩解剂,另加入10%的碳酸氢铵为升华剂,压制硬度4.0～6.0 kg的咪达那新口腔崩解片,于60 ℃真空恒温干燥箱干燥90 min.结论该优选的制备工艺简单可行.     

硝苯地平咀嚼片的制备工艺研究

目的:制备硝苯地平咀嚼片。方法:采用单因素试验对硝苯地平咀嚼片的填充剂、矫味剂、润滑剂、崩解剂及黏合剂进行优选;以外观、口感、片重差异、脆碎度、硬度和崩解时限为评价指标,采用正交试验优化咀嚼片的填充剂(甘露醇-蔗糖)、矫味剂(阿斯巴甜)、崩解剂(交联聚维酮)和润滑剂(硬脂酸镁)的用量,并进行中试验证工艺。结果:硝苯地平咀嚼片的最佳制备工艺处方(1 000片)为:硝苯地平5.0 g、甘露醇106.7 g、蔗糖53.3 g、预胶化淀粉26 g、阿斯巴甜2.0 g、聚乙烯吡咯烷酮水溶液2%、柑桔香精0.3%、交联聚维酮3.0%、硬脂酸镁1.0%;制得片剂的外观、口感、片重差异、脆碎度、硬度和崩解时限等质量指标均符合2010年版《中国药典》的有关规定。结论:硝苯地平咀嚼片制备工艺合理、可行。     

黄花倒水莲口腔速崩片的制备及体外溶出行为考察

目的:制备黄花倒水莲口腔速崩片并考察其体外溶出行为。方法:采用粉末直接压片制备速崩片。以崩解时限为评价指标,通过单因素及正交试验对处方中填充剂甘露醇与崩解剂微晶纤维素用量比、药材浸膏加入量、润滑剂硬脂酸镁加入量等影响因素进行考察。通过体外溶出度试验(以水为溶出介质,桨法)对优化后处方所制速崩片的溶出效果(以远志皂苷元为对照品)进行评价。结果:最优处方为药材浸膏加入量15%、甘露醇与微晶纤维素用量比1.5∶1、硬脂酸镁加入量1.0%;所制片剂崩解时限为(31±4)s、硬度为(3.4±0.2)kg、脆碎度为(0.23±0.07)%(RSD均小于0.11%,n=3);5 min内总皂苷累积溶出度达到90%以上,溶出参数T_(50)=0.84 min、T+d=1.77 min。结论:制备的黄花倒水莲口腔速崩片在水溶液中可快速崩解和溶出。     

盐酸昂丹司琼口腔崩解片的制备以及崩解时间影响因素的考察

目的考察影响盐酸昂丹司琼口腔崩解片崩解时间的因素。方法采用湿法制粒压片法制备盐酸昂丹司琼的口腔崩解片,浆法测定崩解时间,考察了口腔崩解片的硬度、交联聚维酮（PVPP）和微晶纤维素（MCC）的用量对崩解时间的影响。结果片剂硬度与崩解时间成正比,交联聚维酮和微晶纤维素的用量与崩解时间成反比。调节片剂硬度为4．6kg／mm、交联聚维酮的用量为15～20mg／片和微晶纤维素的用量为50-70mg／片,可获得较理想的崩解时间和良好的片剂性质。结论湿法制粒压片法简便易行;制备的盐酸昂丹司琼口腔崩解片符合质量要求。     

右佐匹克隆口腔崩解片的制备及处方优化

目的:制备右佐匹克隆口腔崩解片,并优化其处方。方法:采用粉末直接压片法制备右佐匹克隆口腔崩解片,以物料休止角、崩解时限、口感评价为指标,单因素试验筛选处方中填充剂、崩解剂、润滑剂、矫味剂种类或用量;以崩解时限为指标,正交试验优化处方中填充剂比例、崩解剂用量、润滑剂用量、矫味剂用量,并考察最优处方所制右佐匹克隆口腔崩解片的硬度和主成分含量。结果:最优处方中填充剂甘露醇-微晶纤维素质量比为1∶4、崩解剂交联聚维酮用量为15%、润滑剂硬脂酸镁用量为1.0%、矫味剂甜菊苷用量为3.0%。所制3批右佐匹克隆口腔崩解片的表面光滑、口感微甜,崩解时限分别为(26.7±1.2)、(26.7±0.6)、(27.6±0.9)s,硬度分别为(3.59±0.19)、(3.49±0.18)、(3.27±0.16)kg,右佐匹克隆含量分别为(99.47±0.15)%、(99.53±0.05)%、(99.46±0.20)%,RSD均≤0.87%(n=3)。结论:所制右佐匹克隆口腔崩解片各项质量指标均符合口腔崩解片的要求。     

五味子软胶囊制剂成型工艺研究

目的:优选五味子软胶囊的最佳成型工艺。方法:以明胶、甘油、水的用量及溶胶温度为考察因素,以崩解时限和加速试验崩解时限的综合评分为评价指标,采用正交试验优选软胶囊囊壳工艺;利用单因素试验考察药物粒度、基质种类及用量、助悬剂种类及用量。结果:最佳软胶囊囊壳工艺为甘油、明胶、水的用量分别为100、220、200g,溶胶温度为80℃;成型工艺为药物细粉与大豆油的比例1∶1.2,蜂蜡占药粉用量的15%,药物粒度为100目。结论:所得工艺稳定、质量可控,适合工业化生产。     

均匀设计法优化生脉分散片处方

摘 要 目的：探讨生脉分散片的处方与制备工艺参数。方法: 以分散片的制粒情况,崩解时限,脆碎度,口感等为考察指标,采用均匀设计法优选生脉分散片的处方与成型工艺。结果: 最佳生脉分散片处方为：浸膏粉25%、 MCC 58%、CCMC-Na8%、CMS-Na 4%、L-HPC 2%、硬脂酸镁2%、甜菊糖1%,其中L-HPC、硬脂酸镁外加,片硬度为25N;优选出的分散片处方崩解时限小于3 min。结论:优选的生脉分散片处方与制备工艺参数稳定可靠,重复性较好,工艺可行。     

银黄口腔崩解片的制备工艺研究及体外评价

目的:优选银黄口腔崩解片的处方和制备工艺。方法:采用单因素考察和星点设计-效应面法,以崩解时限为主要评价指标,优选最佳制备工艺和处方;采用体外溶出度实验考察制备的口崩片与普通片剂的溶出度差异。结果:经效应面法筛选出了最佳处方组合,以优选出的处方,制备3批银黄口崩片,片面光洁圆整、均匀无斑点,口感良好,片重差异在±5%以内,硬度在40N左右,体外崩解时间为(29±0.3)s,口腔内崩解时间为(28±0.5)s。体外溶出度实验表明,所制备的口崩片在15 min内累积溶出达到80%以上,30 min累积溶出达90%以上,明显优于普通片剂。结论:制备的银黄口腔崩解片达到设计要求,硬度适中,崩解迅速,口感良好,服用方便,工艺简单易行。     

温脾补肾片的成型工艺研究

目的 研究温脾补肾片的最佳成型工艺.方法 通过单因素重复试验,考察填充剂、润湿剂和润滑剂的种类及用量对本制剂成型性能的影响,以颗粒的吸湿性、片剂的外观、颗粒的流动性、片剂的硬度、片剂的崩解度等为指标,优选出最佳成型工艺.结果 最佳成型工艺为选用淀粉为填充剂(浸膏粉与淀粉的配比为5:1),以90%乙醇(20%)为润湿剂制软材,并用硬脂酸镁(0.5%)为润滑剂.结论 制得的片剂符合<中国药典>2010版有关项下的规定.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

---

Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.