生脉超微颗粒与其散剂的体外溶出度研究

目的：对生脉超微颗粒与其散剂中人参总皂苷、五味子醇甲、总多糖的体外溶出度及溶出动力学进行考察。方法：采用浆法，以自制生脉散为参比制剂，采用分光光度法测定了人参总皂苷、总多糖的体外累计溶出度；采用HPLC法测定了五味子醇甲的体外累计溶出度，并以Weibull方程进行溶出动力学模拟。结果：生脉超微颗粒中人参总皂苷、五味子醇甲、总多糖的的Td和T50均明显小于生脉散。结论：生脉超微颗粒的溶出度和溶出速率均优于生脉散。     

人工胃液酶解对五味子乙素溶出率的影响

目的:考察人工胃液对五味子乙素溶出率的影响,为合理使用五味子提供参考。方法:用人工胃液提取五味子,以水提取法作对照,用高效液相色谱法测定提取物中的五味子乙素,比较两种溶剂对五味子乙素的溶出率。结果:人工胃液提取溶出率为0.73%,水提法溶出率为0.57%。结论:人工胃液对五味子乙素的溶出率比水提取法高28.1%,能显著提高五味子乙素的溶出率,五味子经粉碎冲服或填装胶囊服用,可提高五味子乙素的生物利用度。     

不同产地野生五味子的含量研究

目的:建立不同产地野生五味子含量的客观评价方法。方法:采用物理筛分法进行分离并用显微鉴别法进行过筛后部位的确认,然后采用高效液相色谱法对区分样品分别进行五味子乙素和五味子醇甲的含量测定。结果:本试验建立的五味子乙素的含量测定方法准确度高,加样回收率为100.20%,RSD=1.61%(n=9)。辽宁葫芦岛产五味子中五味子乙素含量最高,吉林靖宇产五味子中五味子乙素含量最低;沈阳产五味子中五味子醇甲含量最高,吉林靖宇和辽宁铁岭产五味子中五味子醇甲含量最低。结论:不同产地五味子中五味子乙素和五味子醇甲的含量有明显差异,故应根据实际药用需要进行产地采购;在进行含量测定时应注意所取样品的代表性,否则会影响结果的客观、准确。     

超微粉碎对罗勒显微特征及总黄酮体外溶出的影响简

目的：对罗勒超微粉和常规粉中总黄酮的体外溶出、显微特征及粉体学性质进行考察.方法：采用比色法测定罗勒超微粉和常规粉中总黄酮体外溶出量和溶出速率,用生物显微镜进行显微特征观察,测定粉体休止角和堆密度.结果：罗勒超微粉和常规粉中总黄酮体外溶出量无显著性差异,超微粉体的溶出速率较常规粉体明显增加.罗勒超微粉颗粒均匀,基本无完整细胞存在.与常规粉相比,罗勒超微粉的休止角增大,堆密度减小.结论：超微粉碎不会影响总黄酮的体外溶出量,但可明显提高其溶出速率.植物细胞破壁率明显提高,但流动性和充填性变差,有待于在制剂生产中进行改进.     

不同粉碎度野生西洋参人参皂苷Rb_1的体外溶出度研究

目的采用体外溶出法考察野生西洋参细粉、极细粉与超微粉人参皂苷Rb1的溶出速率与溶出度。方法按2010年版《中国药典》规定进行不同粉碎度野生西洋参粉体外溶出度试验,绘制溶出曲线,考察不同粉碎度粉末的体外溶出行为及释药机制。结果前10 min,野生西洋参中人参皂苷Rb1的溶出速率为极细粉〉细粉〉超微粉,10 min后超微粉的溶出率最大,极细粉的溶出次之,而细粉溶出最慢。结论野生西洋参粉中人参皂苷Rb1的溶出速率与粉末本身的粒径和浸润有关,在粉末浸润后,超微粉的溶出最快。     

正交试验法优选五味子甲素和五味子乙素的超声提取工艺

目的:通过正交试验确定了五味子甲素和五味子乙素的超声提取工艺。方法:采用超声提取法提取五味子甲素和五味子乙素,以提取溶剂、超声时间、超声次数、溶剂用量为因素,以五味子甲素和五味子乙素提取率为考察指标,采用L9(34)正交表设计,用正交实验确定最佳提取条件,采用HPLC法分析2种成分。结果:在所考察的因素中,以五味子甲素与五味子乙素含量的均值为主要指标,确定最佳超声提取工艺为:以8倍体积甲醇为溶剂,超声提取3次,每次10min。结论:确定五味子最佳超声提取工艺,此法简单、快速、提取效率高;HPLC分析方法准确,灵敏度高,重现性好,可用于五味子有效成分的分析。     

不同粉碎度野生西洋参人参皂苷Rb1的体外溶出度研究

目的 采用体外溶出法考察野生西洋参细粉、极细粉与超微粉人参皂苷Rb₁的溶出速率与溶出度。方法 按2010年版《中国药典》规定进行不同粉碎度野生西洋参粉体外溶出度试验,绘制溶出曲线,考察不同粉碎度粉末的体外溶出行为及释药机制。结果 前10 min,野生西洋参中人参皂苷Rb₁的溶出速率为极细粉>细粉>超微粉,10 min后超微粉的溶出率最大,极细粉的溶出次之,而细粉溶出最慢。结论 野生西洋参粉中人参皂苷Rb₁的溶出速率与粉末本身的粒径和浸润有关,在粉末浸润后,超微粉的溶出最快。     

人工胃液对五味子甲素的溶出率考察

目的：考察人工胃液对五味子甲素溶出率的影响,为五味子优选最佳提取方法提供参数。方法：用人工胃液提取五味子,用水提取法做对照,用高效液相色谱法测定提取物中的五味子甲素,比较两种溶剂对五味子甲素的溶出率。结果：60min时人工胃液提取溶出率为0.483%,水提法溶出率为0.362%。结论：人工胃液对五味子甲素的溶出率比水提取法高33.4%,能显著提高五味子甲素的溶出率。     

延胡索细粉与超微粉溶出度比较

目的:考察并比较延胡索细粉和超微粉的溶出度,为改进、提高药品的生物利用度提供依据。方法:以桨法制备供试品溶液,高效液相色谱法测定延胡索乙素的含量,计算延胡索细粉和超微粉的溶出率。结果:延胡索超微粉的溶出度和溶出率均大于细粉。结论:微粉化有利于药物有效成分的溶出。     

HPLC法测定太太静心助眠口服液中五味子醇甲、五味子甲素和五味子乙素的含量

目的 采用HPLC法建立同时测定太太静心助眠口服液中五味子醇甲、五味子甲素和五味子乙素的方法.方法 色谱柱Waters C18柱(250 mm× 4.6 mm,5μm),流动相为甲醇-水(梯度洗脱),检测波长为254 nm.结果 五味子醇甲浓度在2.022～101.1 μg/mL范围内与峰面积呈良好的线性关系,r为0.999 9;五味子甲素浓度在2.004～100.2 μg/mL范围内与峰面积呈良好的线性关系,r为0.9999;五味子乙素浓度在2.030～101.5 μg/mL范围内与峰面积呈良好的线性关系,r为0.9999.五味子醇甲加样回收率的平均值为101.9％,RSD=1.9％;五味子甲素加样回收率的平均值为101.9％,RSD=1.2％;五味子乙素加样回收率的平均值为100.4％,RSD=1.0％.结论 本方法简便、准确可靠,适用于太太静心助眠口服液中五味子醇甲、五味子甲素和五味子乙素三个主要有效成分的测定.     

超微粉碎对蒙药文冠木中总黄酮的体外溶出度影响

目的采用紫外分光光度法对文冠木普通粉和超微粉中主要有效成分总黄酮的溶出度进行比较。方法采用桨状搅拌法,紫外分光光度法在500 nm处测定文冠木普通粉与超微粉总黄酮的体外溶出度。结果文冠木超微粉中总黄酮在单位时间内的溶出速率明显高于普通粉,且溶出量较普通粉提高了约20%。结论微粉化技术能明显提高文冠木中主要有效成分总黄酮的体外溶出度。     

麻黄超微粉体与常规粉体的体外溶出研究

目的对麻黄的超微粉体和常规粉体中麻黄碱的体外溶出进行考察。方法采用HPLC法测定麻黄超微粉体与常规粉体中麻黄碱的溶出量和溶出速度。结果麻黄超微粉体与常规粉体中麻黄碱溶出量具有显著性差异,超微粉体的溶出速度较常规粉体明显增加。结论麻黄超微粉体的溶出量和溶出速度均优于其常规粉体。     

超微粉固体分散技术对丹参片指标成分溶出度的影响

目的：采用超微粉固体分散技术制备丹参片,并考察其溶出特征。方法：按《中国药典》2015年版丹参片制备方法制得丹参片DSP1作为对照品,用超微粉固体分散技术制得丹参片DSP2。高效液相色谱（HPLC）法测定2种丹参片中的丹酚酸B、丹参酮Ⅱ_A的含量,并在不同溶出介质测定各成分的溶出度,绘制溶出曲线,采用f₂相似因子法进行比较分析。结果：DSP1、DSP2的丹酚酸B含量分别为11.20,18.90 mg·g^-1原药材,丹参酮Ⅱ_A含量分别为0.45,0.71 mg·g^-1原药材;丹酚酸B、丹参酮Ⅱ_A在0.1 mol·L^-1的盐酸溶液介质中溶出曲线的相似因子分别为40,32,在0.5%十二烷基硫酸钠（SDS）水溶液中溶出曲线的相似因子分别为43,35,f₂<50,两种丹参片的溶出度有显著差异。结论：超微粉固体分散技术能显著高丹参片中的丹酚酸B、丹参酮Ⅱ_A溶出度,同时提高丹参药材的利用率,值得进一步研究推广。     

麻黄常规粉体与超微粉体中麻黄碱在小鼠肺部药物浓度的比较研究

目的测定麻黄常规粉体与超微粉体中麻黄碱在小鼠肺部的浓度,探讨不同粒径麻黄粉体对麻黄碱在小鼠肺部浓度的影响。方法小鼠以相同剂量灌胃给予常规与超微2种麻黄粉体后,在规定的时间点摘取肺,匀浆处理后用HPLC法测定其中麻黄碱的含量。结果超微粉体组肺内麻黄碱含量明显高于常规粉体组。结论超微粉体可提高麻黄药物在小鼠肺内的药物浓度。     

灯盏生脉胶囊联合依那普利治疗2型糖尿病早期肾病的临床研究

目的探讨灯盏生脉治疗2型糖尿病早期肾病的临床疗效。方法将90例2型糖尿病早期肾病患者随机分为2组,每组45例。A组为治疗组,采用灯盏生脉+依那普利治疗,B组为对照组,单用依那普利治疗。观察尿微量清蛋白排泄率(UALB)、血糖、血脂,比较2组患者的疗效。结果 2组患者治疗后UALB较治疗前均降低,差异均有统计学意义(P<0.01)。2组患者治疗后疗效比较,差异有统计学意义(P<0.05),A组优于B组。2组治疗前血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、差异均无统计学意义(P>0.05);但2组治疗后上述指标比较,差异有统计学意义(P<0.05),其中A优于B组。结论灯盏生脉与依那普利均能降低2型糖尿病早期肾病患者的UALB,但灯盏生脉联合依那普治疗效果优于单用依那普利,且灯盏生脉有改善血脂的作用。     

当归超微粉的药剂学研究

目的:比较当归超微粉和普通粉的粉体学特征及溶出特点,探索超微粉碎技术在中药当归中的应用。方法:通过重压式超微粉碎机制备当归超微粉末;通过扫描电子显微镜(SEM)观察超微粉和普通粉的形貌和细胞特征,用激光粒度分析仪对2种粉末进行粒径分布测定,并对粉体学参数休止角和堆密度进行测定;采用高效液相色谱法测定阿魏酸的含量;用恒温搅拌溶出法对2种粉末主要成分溶出特点的关系进行研究。结果:当归超微粉和普通粉的粉体学特征、表面形态、溶出成分含量差异显著;通常情况下当归超微粉相应成分溶出的速度与浓度要高于普通粉。结论:微粉化能促进当归有效成分的充分利用,超微粉碎技术应用于当归具有可行性和必要性。     

Isothermal Microcalorimetry as a Quality by Design Tool to Determine Optimal Blending Sequences

This study was designed to assess the value of isothermal microcalorimetry (ITMC) as a quality by design (QbD) tool to optimize blending conditions during tablet preparation. Powder mixtures that contain microcrystalline cellulose (MCC), dibasic calcium phosphate dihydrate (DCPD), and prednisone were prepared as 1:1:1 ratios using different blending sequences. ITMC was used to monitor the thermal activity of the powder mixtures before and after each blending process. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) were performed on all final powder mixtures. Final powder mixtures were used to prepare tablets with 10 mg prednisone content, and dissolution tests were performed on all tablet formulations. Using ITMC, it was observed that the powder mixtures had different thermal activity depending on the blending sequences of the ingredients. All mixtures prepared by mixing prednisone with DCPD in the first stage were associated with relatively fast and significant heat exchange. In contrast, mixing prednisone with MCC in the first step resulted in slower heat exchange. Powder mixture with high thermal activity showed extra DSC peaks, and their dissolution was generally slower compared to the other tablets. Blending is considered as a critical parameter in tablet preparation. This study showed that ITMC is a simple and efficient tool to monitor solid-state reactions between excipients and prednisone depending on blending sequences. ITMC has the potential to be used in QbD approaches to optimize blending parameters for prednisone tablets.     

Transfection activity of layer-by-layer plasmid DNA/poly(ethylenimine) films deposited on PLGA microparticles

In this study, the dynamics of powder flow upon griseofulvin-self-emulsified drug delivery system (SEDDS) addition to silica and silicates and the effect of these adsorbents on drug release were investigated. SEDDS was adsorbed at SEDDS/adsorbent ratios from 0.25:1 to 3:1 on magnesium aluminum silicate [5 and 80 microm], calcium silicate [25 microm], and silicon dioxide [3.6, 20, and 300 microm]. Powder flow was evaluated using the powder rheometer and compared to angle of repose. Release of drug from a 1:1 SEDDS/adsorbent powder was determined by dissolution using USP Type 2 apparatus. Powder rheometer profiles indicated that effect of SEDDS on the flow behavior of the adsorbents could be correlated to stepwise or continuous growing behavior as observed in wet granulation process. However, due to their porous nature, adsorbents exhibited an initial lag phase during which no change in flow was observed. Dissolution of drug from adsorbed-SEDDS was found to be dependent on pore length and nucleation at the lipid/adsorbent interface. Increase in dissolution rate was observed with an increase in surface area and was independent of the chemical nature of the adsorbents. Therefore, in order to manufacture free flowing powder containing liquid SEDDS, special attention should be given to particle size, specific surface area, type and amount of adsorbent.     

生脉方治疗心力衰竭的药理作用研究进展

心力衰竭是威胁人类健康的重大疾病之一,其病理机制复杂,中医药防治心衰具有显著特色。中医理论认为气阴两虚是心衰患者的主要证候之一,生脉散为益气养阴的代表方。目前根据生脉散研制的中成药包括注射用益气复脉、生脉注射液、生脉散、生脉饮、参麦注射液、生脉胶囊等,被广泛用于治疗心脑血管疾病。从生脉方改善线粒体功能、抑制心室重塑、减轻心肌细胞的炎性反应3个方面综述了生脉方治疗心衰的研究进展,以期为心衰的防治提供依据。     

Casein Hydrolysate as a Rapid and/or Enteric Dissolving Additive for Oral Drugs

ABSTRACT

Two types of casein hydrolysates, casein A (mean peptide length 3.3) and casein B (mean peptide length 17.4) were prepared by the enzymatic hydrolysis of casein, and their effects on in vitro dissolution rates and oral bioavailability of drugs were evaluated. The in vitro dissolution behavior of the kneaded mixture of three drugs (diclofenac acid, diazepam, and prednisolone) with caseins A and B were significantly improved compared to the drugs alone, even at 1:1 weight ratio of drug and casein hydrolysate, even though casein A and casein B did not interact with drug molecules in the kneaded mixture. Only diclofenac, an acidic drug, showed an increased dissolution rate with added casein hydrolysates, and a more rapid dissolution with casein A than with casein B was observed. When the dissolution of prednisolone from kneaded mixture was compared at pH 1.2 and 6.8, the dissolution rate of prednisolone from the casein A kneaded mixture was considerably higher than that of prednisolone powder at both pHs, and the rate from the casein B kneaded mixture was higher only at pH 6.8. The plasma concentration-time profile showed that prednisolone was completely and rapidly absorbed from the casein A kneaded mixture as well as the prednisolone solution. In addition, prednisolone in the kneaded mixture with casein B was more difficult to absorb up to 1 hr after administration in comparison to prednisolone powder. The slow and lowered absorption of prednisolone by casein B might be explained by conversion of casein B to a shorter soluble peptide in the gastrointestinal tract and by the slow dissolution of prednisolone at acidic conditions. The toxicological tests revealed that casein hydrolysate is a safe drug carrier. Consequently, casein hydrolysates might be safely used to control the dissolution rate and bioavailability of a variety of drugs, depending on the peptide length of the casein fragments.