计算机在临床医药学中的应用

计算机在临床医药学中的应用尹海峰胡丹红（湖北医科大学临床药学研究室武汉４３００６０）计算机在临床医药学中的应用是六十年代开始的。由于计算机具有运算速度快、存储容量大，具有记忆和逻辑分析能力，所以在临床医药学的科学计算、数据处理、过程控制等方面有很广...     

抗磷脂抗体检测在系统性红斑狼疮中的临床应用

目的评估抗磷脂抗体包括抗心磷脂抗体(Acl)和抗β2糖蛋白Ⅰ抗体(anti-β2GPⅠ)在系统性红斑狼疮(SLE)中的临床应用价值。方法采用酶联免疫吸附法(ELISA)对确诊的120例SLE和100例健康体检者血清Acl(IgG、IgM、IgA)和anti-β2GPⅠ(IgA/G/M)水平表达进行测定,并分析其对SLE的敏感度和特异度,及血清Acl和anti-β2GPⅠ水平间的相关性。统计学分析采用χ~2检验。结果 SLE组血清Acl-IgG、Acl-IgM、Acl-IgA、AclIgG/IgM、anti-β2GPⅠ阳性率分别为6.7%、4.2%、1.7%、5%、18.3%,均高于健康对照组,差异有统计学意义(P<0.05)。结论 anti-β2GPⅠ抗体对SLE的敏感度高于Acl,建议两种抗体联合检测,有助于提高检出率。     

毛细管电泳在医药学中的应用

本文综述了近年来毛细管电泳在医药学领域中的应用。在药学领域,主要介绍了毛细管电泳在药物中主药成分分析,药物中相关杂质的检测,中药中活性成分的分析,中药指纹图谱分析,手性药物分析等方面的应用;在临床医学中,毛细管电泳的应用主要包括临床疾病诊断,临床药物监测、滥用药物分析及临床微生物检测等。     

抗心磷脂抗体在习惯性流产中的检查应用

目的为查出习惯性流产的免疫学原因.方法用酶联免疫吸附试验,对曾于1996年2月至10月间来我院检测习惯性流产史者96例,检查流产原因.正常妇女组30例,有一次人流史者20例,这两组作为对照组.对所有检测对象进行ACL-IgG检查.结果正常妇女中无1例阳性.一次人流史者中也无1例阳性,习惯性流产96例中有34例阳性,检出率为35.4%.结论抗心磷脂抗体阳性是习惯性流产的原因之一.     

烷基咪唑类离子液体在分子印迹聚合物中的应用

分子印迹聚合物是具有高选择性的仿生识别材料。以烷基类离子液体为单体、致孔剂或助溶剂合成分子印迹聚合物或制备分子印迹柱,可缩短分子印迹时间,降低分子印迹柱背压,改善水溶性,提高吸附容量、选择性、识别能力和分子印迹柱渗透性,加快吸附平衡,拓宽了其在药物分离分析中的应用范围。     

脂质体及其类似物在基因治疗中的应用

脂质体及其类似物在基因治疗中有着广阔的前景。本文对阳离子脂质体,聚阳离子脂质体,阴离子脂质体,ｐＨ敏感型脂质体,融合脂质体,立体稳定脂质体,以及其类似物在基因治疗中的应用进行综述,并着重介绍阳离子脂质体的药动学特征及其在遗传病和肿瘤的治疗等方面的临床应用。     

聚合物胶团在肿瘤治疗中的应用

聚合物胶团(polymeric micelles)是近几年来,在药剂学领域崭露头角的一类新型的纳米载体[1],聚合物胶团由于其增溶性、靶向性、低毒性和长循环性引起了人们的广泛重视.     

甲壳素及其衍生物的生物学特性和医药学应用研究进展

甲壳素及其衍生物是一类来源广泛的具有多种优越性能的生物材料。近年来,随着对其生物学特性研究的不断深入,其在医药中的用途也得到相应的开发。本文综述甲壳素及其衍生物在药学以及医学材料方面的研究。     

荧光光纤传感器在医药学中的应用研究

荧光光纤化学传感器因其敏感、特异及可远程、在位、连续检测等优点,已在医学、药学、化学反应监测等方面得到了较广泛应用.本文主要就荧光光纤传感器在医药学分析方面的应用研究进行综述.     

大鼠脑组织磷脂色谱随龄性变化的研究

为探讨脑组织磷脂分子组成含量随龄性变化,采用簿层色谱扫描仪测定了30只,7～9月龄、14～17月龄及24～28月龄Wistar大鼠的磷脂酰胆碱(PC)、磷脂酰乙醇胺(PE)、磷脂酰丝氨酸(PC)和鞘磷脂(SM)含量。并计算了PE/PC与SM/PC比值。结果表明:SM含量、PE/PC、SM/PC比值随增龄而增高,PE、PC含量随增龄而降低。     

高效液相色谱在中药研究中的应用

高效液相色谱法在中药分析中有广阔的应用和发展前景。本文查阅国内近年来的相关文献资料,综述了高效液相色谱的发展状况以及近年来该技术在中药质量控制和中药药物动力学等方面的应用。     

奥沙利铂磷脂复合物及其纳米混悬剂的制备

目的研究奥沙利铂磷脂复合物及其纳米混悬液的制备方法。方法以奥沙利铂与磷脂的复合率为指标,采用单因素和正交试验设计优化了奥沙利铂磷脂复合物的制备工艺。采用逆相蒸发法结合高压均质技术,将奥沙利铂磷脂复合物制成纳米混悬液,并进行理化性质考察。结果奥沙利铂与磷脂的复合率可达100%。制备的纳米混悬液载药量提高到10 g.L-1,平均粒径为(126±17)nm,具有良好的物理稳定性。结论磷脂复合物改善了奥沙利铂的理化性质及溶解性能,用其制备的纳米混悬剂可静脉给药。     

HPLC-ELSD测定大豆磷脂中溶血磷脂酰胆碱的含量

目的:采用HPLC-ELSD法测定大豆磷脂中溶血磷脂酰胆碱(LPC)的含量。方法:采用NH2柱(150 mm×4.6 mm,5μm),柱温为30℃,流速为0.8 mL.min-1,进样量为10μL。流动相:甲醇-氯仿(97∶3)为流动相A,草酸-乙醇(16∶84)为流动相B,A∶B=7∶3;蒸发光散射检测,ELSD漂移管温度:80℃,雾化气:空气,气体流量:2.0 L.min-1。结果:在选定的色谱条件下,大豆磷脂和溶血磷脂酰胆碱之间可达到很好分离。溶血磷脂酰胆碱进样量在0.2~3.2 mg范围内与峰面积的线性关系良好(r=0.999 3),最低检测限为80 ng(S/N=3),3个浓度水平下溶血磷脂酰胆碱的平均回收率(n=9)为100.1%。结论:该方法灵敏、快速、准确,可用于产品的质量控制。     

Preparation and characterization of semi-solid phospholipid dispersions and dilutions thereof

Highly concentrated, viscous to semi-solid phospholipid dispersions with phosphatidylcholine (PC) contents up to 600 mg/g or 780 mM were obtained by high-pressure homogenization. Dilution of these pastes with excess buffer led to ‘classical' liposome dispersions. The dilution technique determined the homogeneity of the liposome dispersions. Handshaking yielded heterogeneous dispersions, which according to cryo-electron microscopy contained large multivesicular vesicles (MVVs) as well as small unilamellar vesicles (SUVs). By using a ball mill for dilution, however, the phospholipid pastes could be completely transferred into uniform SUVs with mean diameters of about 20–40 nm. The absence of bigger particles could be demonstrated both by a membrane filtration test through 0.2 μm pore filters and photon correlation spectroscopy. Lipid paste formation and subsequent dilution into liposomes led to high encapsulation efficiencies of the hydrophilic model compound 5,6-carboxyfluorescein. For true SUV dispersions, encapsulation efficiencies rose with increasing lipid contents up to a maximum of over 45% at original lipid contents of 600 mg/g. According to geometrical considerations, the packing of SUVs reaches densest sphere packing at this lipid content. In conclusion, semi-solid, vesicular PC pastes can be diluted by ball milling into homogeneous SUV dispersions with high encapsulation efficiency for hydrophilic compounds.     

磷脂固体分散体对槲皮素溶出促进作用的研究

目的研究磷脂固体分散体对槲皮素溶出的促进作用。方法用溶剂法制备了不同比例的槲皮素的磷脂固体分散体 ,与其相应的物理混合物及槲皮素的PVP或PEG4 0 0 0 (1∶1)固体分散体并进行了溶出的对比研究。结果所制得固体分散体均可改善槲皮素的溶出 ,而质量比为 1∶1的槲皮素 磷脂固体分散体的溶出促进作用最为显著。DSC和X射线粉末衍射的研究表明 ,在质量比为1∶1的槲皮素 磷脂固体分散体中 ,槲皮素以无定形的状态分散于载体磷脂中 ,其熔点吸热峰消失。结论槲皮素溶出度的增大与其无定形的存在状态、磷脂对其的润湿作用以及磷脂在水中可形成脂质体有关     

Automated synthesis and use of N-chloroacetyl-modified peptides for the preparation of synthetic peptide polymers and peptide-protein immunogens

A method to incorporate N-chloroacetyl moieties at the amino termini of synthetic peptides using a standard program with an automated peptide synthesizer has been developed. The N-chloroacetyl-modified peptides react well with sulfhydryl containing proteins such as 4-mercaptobutyrimide-modified bovine serum albumin to form stable protein-peptide conjugates. By incorporating cysteine into the synthetic peptide, autopolymerization or cyclization of the synthetic peptide occurs by reaction of the free sulfhydryl with the chloroacetyl group. N-Chloroacetyl-derivatized peptides may be useful as reagents for potential peptide immunogens and vaccines.     

Transdermal delivery of triptolide–phospholipid complex to treat rheumatoid arthritis

The aim of this study was to develop and evaluate a triptolide phospholipid complex (TPCX) for the treatment of rheumatoid arthritis (RA) by transdermal delivery. TPCX was prepared and characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR) analysis, transmission electron microscope (TEM), and scanning electron microscope (SEM). The solubility of TPCX was determined. Then, a TPCX cream was prepared to evaluate its percutaneous permeability and the antiarthritis effect. The transdermal permeability was determined using the Franz method, and a microdialysis system was used for skin pharmacokinetic study. A rat model of RA was prepared to evaluate the pharmacological effects. TPCX increased the solubility of triptolide in water, and the percutaneous permeability of TPCX cream was greatly enhanced compared with triptolide cream. The skin pharmacokinetic study indicated that TPCX cream has a longer biological half-life (t_1/2) and mean residence time (MRT), but it has a shorter T_max than that of triptolide cream in vivo. The area under the curve (AUC_0–t)/AUC_0–∞) and the peak concentration (C_max) of TPCX cream were obviously higher than those of triptolide cream. The TPCX-loaded cream alleviated paw swelling and slowed down the progression of arthritis by inhibiting the inflammatory response by down regulating the TNF-α, IL-1β, and IL-6 levels, thus exhibiting excellent antiarthritic effects. In summary, the prepared TPCX effectively increases the hydrophilicity of triptolide, which is good for its percutaneous absorption and enhances its effect on RA rats. TPCX can be a good candidate for the transdermal delivery to treat RA.     

The use of multifunctional polymers for non-invasive peptide and protein application

For the efficient delivery of peptide and protein drugs by non-invasive routes various strategies have been pursued to overcome enzymatic and mucosal barriers to gain sufficient bioavailability. Among such delivery systems multifunctional polymers have received considerable attention, which is reflected by numerous publications and patents. They are able to provide a controlled release for therapeutic peptides and proteins being embedded in the polymeric network either based on a simple diffusion process or on the biodegradation of the carrier matrix. Additionally, polymers such as polyacrylates display an inhibitory effect towards various proteases located on the absorption membrane. In combination with enzyme inhibitors, this protective effect towards enzymatic attack may further be improved. Moreover, polyacrylates and chitosan display a permeation enhancing effect, in particular for the paracellular uptake of peptide drugs from mucosal tissues. If these polymers also exhibit mucoadhesive properties, the concentration gradient of the drug on the mucosa can be increased and in the case of oral delivery the presystemic enzymatic degradation of the (poly)peptide drug in the intestine between the delivery system and the absorption membrane can be reduced. Delivery systems utilising multifunctional polymers include formulations such as nano- and microspheres, pellets and matrix-tablets.     

Actions of neuroleptics on the acetylcholine-induced phospholipid effect in rat neostriatal homogenates

The proposal that the severity of extrapyramidal side effects of neuroleptics are inversely related to their potency as musearinic antagonists was tested using a unique biochemical assay of cholinergic receptor activity. This assay is based on reported findings that the stimulation in vivo and in vitro of cholinergic muscarinic receptors results in increased incorporation of radiolabelled inorganic phosphate into certain phospholipids in the CNS. This cholinergie “phospholipid effect” as it is known, appears to be a biochemical event which occurs with, or soon after, the initial transmitter-receptor interaction, probably prior to the receptor-mediated cyclic GMP response, to which it may be related. Anticholinergic agents and neuroleptics show the following relative potencies of inhibition of the phospholipid effect in rat neostriatal homogenates: benztropine > atropine > trihexyphenidyl > clozapine > thioridazine > chlorpromazine > pimozide > haloperidol > fluphenazine. The results agree well quantitatively with those reported using a radioligand binding displacement assay of muscarinic receptors and those using the muscarinic receptor-mediated cyclic GMP response, thereby providing additional support for the hypothesis. In addition, these and other studies indicate that the phospholipid effect is a sensitive, specific, accurate, and reasonably simple biochemical assay of muscarinic, α-adrenergic and H₁-histaminic receptor activity which may be utilized to evaluate the actions of psychopharmacological agents.