抗瘤酮A_(10)的合成

以苯乙酰氯和L-谷氨酰胺为起始原料,经缩合和环合两步合成抗癌新药抗瘤酮A_(10),总收率40%。     

抗瘤酮A10在鼠体内的药物动力学研究

本文报道了~3H-抗瘤酮A10经1次灌胃及静脉注射后在鼠体内的药物动力学研究。实验给出了有关动力学参数,如t1/2β 16.5±3.5h,Vd61.42ml,β0.0435±0.0090h~(-1),α为0.1953±0.0745h~(-1);建立了数学模型;其血药浓度—时间曲线符合双室模型。抗瘤酮A10在体内分布以肝、肾、胃、生殖器、膀胱最高;在脂肪、肠、肌肉和脑中亦有较高浓度。     

抗瘤酮A10的酸酐交换法合成

抗瘤酮A_(10)(1)的合成,作者曾作过报道[本刊1988,19:198]。由于国内的L-谷酰胺(L-谷氨酸-5-酰胺)价格昂贵,来源困难,不适于生产。我们对合成工艺作了进一步改进,用价格便宜、来源方便的谷氨酸单钠盐(味精)代替L-谷酰胺,经缩合,酸酐交换和氨解三步反应合成了抗瘤酮A_(10),总收率12.3％。最后氨解一步,收率尚不满意。路线如下:     

抗瘤酮A10的化学修饰及抗肿瘤活性研究

设计合成了抗瘤酮Ａ１０（１）的类似物和衍生物２３个，包括光学活性的１。体Ｌ１２１０细胞试验表明，在浓度为１００μｇ／ｍｌ时，均显示微弱的抑制活性。     

抗瘤酮衍生物的合成和抗S—180活性

本文报道１４个抗瘤酮Ａ１０的衍生物的合成和抗Ｓ－１８０瘤株的活性，其中有两个化合物（Ｔ１－６Ｔ１－２）抑瘤率与抗瘤Ａ１０的相当或较高，比阿霉素的为低。除Ａ１－２外，其它均为未知物。     

抗瘤酮A10类似物的合成及抗肿瘤活性

合成了抗瘤酮Ａ１０类似物。通过元素分析和核磁对这８个席夫碱化合物进行了结构表征。并得到了化合物７ａ的单晶结构。抗肿瘤试验显示这些化合物在 １０~（－４） ｍｏｌ·Ｌ~（－１）浓度下对Ｐ３８８和Ａ－５４９有较好的抑制作用。     

抗瘤酮类似物的抗肿瘤活性

本文报道15个抗瘤酮A_(10)衍生物对临床分离的六株肿瘤的抑制活性测定结果,比较了它们同临床常用抗癌药物对临床分离的食道癌89111的抑制活性,并对比测定了化合物4、7和9同抗瘤酮A_1。对小鼠S_(160)瘤株的抑制活性。     

抗瘤酮A10对肝腹水Hep-A-22细胞的抑制活性的研究

通过抗瘤酮A     

抗肿瘤药物Antineoplaston A10新合成方法研究

报道了以１－谷氨酸为起始原料，经甲基化得１－谷氨酸－γ－甲酯，再经苯乙酰化，氨化和环合合成抗肿瘤药Ａｎｔｉｎｅｏｐｌａｓｔｏｎ Ａ１０的新方法，以１－谷氨酸－γ－甲酯计，总收率为４３％。产品经元素分析，红外光谱，核磁共振氢谱和质谱确证．     

Risk assessment for coenzyme Q10 (Ubiquinone)

Coenzyme Q10 (CoQ10) widely occurs in organisms and tissues, and is produced and used as both a drug and dietary supplement. Increasing evidence of health benefits of orally administered CoQ10 are leading to daily consumption in larger amounts, and this increase justifies research and risk assessment to evaluate the safety. A large number of clinical trials have been conducted using a range of CoQ10 doses. Reports of nausea and other adverse gastrointestinal effects of CoQ10 cannot be causally related to the active ingredient because there is no dose-response relationship: the adverse effects are no more common at daily intakes of 1200 mg than at a 60 mg. Systematic evaluation of the research designs and data do not provide a basis for risk assessment and the usual safe upper level of intake (UL) derived from it unless the newer methods described as the observed safe level (OSL) or highest observed intake (HOI) are utilized. The OSL risk assessment method indicates that the evidence of safety is strong at intakes up to 1200 mg/day, and this level is identified as the OSL. Much higher levels have been tested without adverse effects and may be safe, but the data for intakes above 1200 mg/day are not sufficient for a confident conclusion of safety.     

辅酶Q_(10)高产酵母菌SY-3发酵工艺的研究

目的为了获得比较高的辅酶Q10产量,以一株酵母菌SY-3作为辅酶Q10的生产菌,研究不同的发酵条件对辅酶Q10产量的影响。方法用皂化法提取,用高效液相检测。结果与结论蔗糖是较好的碳源,蛋白胨是较好的氮源,通过均匀设计初步确定的发酵培养基为:蔗糖4.2%,蛋白胨2.8%,KH2PO40.13%。接种量2%,500mL三角瓶中装液量40mL,pH值4.0,温度26℃,转速240 r/m in,在此发酵条件下,发酵液中菌体生长量达到10g/100mL,辅酶Q10产量达到84.6mg/L。     

高效液相色谱法测定辅酶Q_(10)含量的研究

应用色谱技术，建立了辅酶Q_10(CoQ_10)含量测定的高效液相色谱方法.并从多个影响保留时间的因素中选出三个水平、三个因子进行正交设计，从而确定了CoQ10。含量测定的最佳条件。本法选用碳十八硅烷为固定相，检测波长为275um，经过多批COQ10。测定，其回收率大于99．6％，RSD小于0．07％，方法简便快速、灵敏度高、特异性强，适用于该药品的含量分析检测。     

米诺环素软膏治疗慢性牙周炎的疗效及对患者龈沟液中超敏C反应蛋白和白介素-10水平影响

目的:观察米诺环素软膏局部用药对慢性牙周炎患者龈沟液中超敏C反应蛋白(hs-CRP)和白介素-10(IL-10)水平的影响及其疗效。方法:慢性牙周炎患者72例(96颗牙)随机分为观察组(36例,47颗牙)和对照组(36例,49颗牙)。两组患者均常规予以龈上洁治、龈下刮治和根面平整等牙周基础治疗。观察组予米诺环素软膏注满牙周袋内;对照组予复方碘甘油液适量注入牙周袋内。1次/周,连用4周。观察两组患者治疗前后龈沟液中hs-CRP和IL-10水平的变化,比较两组临床疗效。结果:治疗4周后,两组患者龈沟液中hs-CRP水平均明显下降,IL-10水平均明显上升(P<0.01或0.05),且观察组下降或上升值较对照组更明显(P<0.05)。观察组临床总有效率为94.44%,明显优于对照组的77.78%(P<0.05)。结论:米诺环素软膏局部用药治疗慢性牙周炎的效果良好,能降低龈沟液中hs-CRP水平,升高IL-10水平,从而有效控制牙周组织的炎性破坏,改善牙周局部炎症反应状况。     

Preparation, characterization and biodistribution of the lactone form of 10-hydroxycamptothecin (HCPT)-loaded bovine serum albumin (BSA) nanoparticles

10-Hydroxycamptothecin (HCPT) is insoluble in both water and physiological acceptable organic solvents and tends to change into its carboxylate form, which shows minimal anticancer activity and several unpredictable side effects. The goal of this study is to exploit an appropriate delivery system for HCPT to improve the stability of its lactone form. Bovine serum albumin (BSA) nanoparticles entrapping HCPT were prepared by reformative emulsion-heat stabilization technique. During this process, HCPT transformed from lactone to carboxylate and finally back to lactone form successfully. A simple reversed-phased HPLC method was developed to analyze both lactone and carboxylate forms of HCPT synchronously. Mean particle size and the ratio of lactone and carboxylate forms of HCPT were evaluated to investigate the effects of the formulations and preparation conditions. It was indicated the percentage of lactone form of HCPT in resultant BSA nanoparticles could be improved over 95% through adjusting the concentration of NaOH solution and the stirring time after high-speed emulsification. This drug delivery system was also characterized by dynamic light scattering (DLS) and light microscopy. The investigations on drug loading, in vitro release and body distribution in rats after intravenous (i.v.) administration were also carried out. It was found that the obtained nanoparticles showed spherical shape with the mean particle size of around 600 nm, and drug loading content, encapsulation efficiency and yield achieved 2.21%, 57.5% and 90.5% with the optimal preparation conditions, respectively. The in vitro release behavior exhibited a sustaining release manner and was affected by the trypsin in medium. HCPT could release more than 90% within 20 h in the medium of pH 7.4 PBS containing 750 U/ml trypsin, but only 25% within 40 h in the pure pH 7.4 PBS. The results of body distribution study in rats showed the liver targeting potential of HCPT–BSA nanoparticles that 59.6%, 52.9% and 55.3% of the examined amount of lactone HCPT accumulated in livers at 1, 4 and 24 h after injection, respectively. These results suggest that the HCPT–BSA nanoparticles seem to be a stable delivery system for poorly soluble HCPT or its derivatives.     

辅酶Q_(10)口服胶囊治疗频发性室性早搏59例

本文报告辅酶Q_(10)口服胶囊用双盲对照治疗频发室性早搏59例的疗效,计有效率为88％、显效率为68％,均较安慰剂对照组为显著(p<0.01)。此外,对辅酶Q_(10)的药理及其抗心律失常的机理也作了探讨。     

The pharmacological properties of the novel peptide BPC 157 (PL-10)

The reported beneficial effects of the gastric mucosal derived pentadecapeptide BPC 157 (Gly Glu Pro Pro Pro Gly Lys Pro Ala Asp Asp Ala Gly Leu Val, M.W. 1419) on different organ lesions are reviewed. Apart from the effects on various gastrointestinal lesions, the potentially beneficial effect on pancreas, liver injuries, endothelium and heart damage, i.e. dysrhythmias following reoxygenation, and blood pressure, along with effect on experimental acute/chronic inflammation, wound and fracture (pseudoarthrosis) healing are described. It appears that these beneficial effects all together provide a particular network reflecting activity of a special peptidergic defence system. In support of this concept, it appears that there are interactions of this pentadecapeptide with many important systems (namely, dopamine-, NO-, prostaglandin-, somatosensory neurone-systems), that could provide a basis for the observed protective effects. Moreover, since disturbance of these systems’ functions (i.e. dopamine-, NO-, somatosensory neuronal-system) which manifest either over-activity or as inhibition, may contribute to the multiple lesions in different organs. The reported evidence that this pentadecapeptide is able to counteract both their over-action, and their inhibition, may suggest this pentadecapeptide as a new, but most probably essential physiological defence system and that should be further investigated. This work under the direction of Prof. Sikiric involved the following authors: Gorana Aralica, Josip Aralica, Gojko Buljat, Valentina Coric, Vedran Coric, Bozidar Duplancic, Miroslav Gjurasin, Zeljko Grabarevic, Miroslav Hanzevacki, Stipislav Jadrijevic, Vjekoslav Jagic, Pasko Konjevoda, Martina Lovric, Anton Marovic, Pavle Miklic, Darko Mikus, Stjepan Mise, Darko Perovic, Marijan Petek, Ivo Rotkvic, Rudolf Rucman, Bozidar Sebecic, Sven Seiwerth, Jadranka Separovic, Zoran Simec, Zoran Slobodnjak, Dinko Stancic-Rokotov, Branko Turkovic, Tomislav Ziger, Ivan Zoricic.