Effect of different ointment bases on ocular disposition of ethylphenylephrine in rabbit eyes

The influence of vehicle composition on the ocular disposition of ethylphenylephrine, a mydriatic drug used for the treatment of wide-angle glaucoma, has been studied. The vehicles investigated consisted of a hydrocarbon base, an absorption base (10% lanolin in a paraffin base) and a water-soluble base (polyvinyl alcohol, PVA, 15% in water). The albino rabbit was chosen as the animal model. The disposition of the drug in conjunctiva, cornea, iris-ciliary body and aqueous humor of the rabbit was monitored at 1, 2 and 4 h post-installation using extraction technique. At the early time period (1 h post-administration) both oleaginous and water-soluble bases were judged to perform adequately in that they provided approximately the same drug concentrations in various ocular tissues at the aqueous vehicle. However, after 4 h, the oleaginous base provided the highest concentrations of drug in the conjunctiva. The water-soluble PVA formulation gave significantly lower levels in the conjunctiva and the cornea. At this same point, the absorption base containing lanolin produced the highest drug concentration in the cornea, iris-ciliary body and aqueous humor. Collectively, these data suggest that of the 3 bases studied, the oleaginous base and the absorption base show most promise as vehicles to extend the residence time of ethylphenylephrine in the eye. Obviously the final choice of vehicle will also be influenced by factors such as the physical and chemical stability of the drug in the formulation chosen and patient acceptance.     

新疆昆仑雪菊水溶性总黄酮的含量测定

目的建立检测新疆昆仑雪菊中水溶性总黄酮含量的方法。方法以芦丁为对照品,用分光光度计进行全波长扫描并在510nm波长处测定吸光度,计算总黄酮含量。结果昆仑雪菊总黄酮在0.008-0.080mg.mL^-1浓度范围内具有良好的线性关系,方法操作简便,重现性好,r=0.9999,平均加样回收率92.80%,RSD为1.91%（n=9）,总黄酮平均含量为18.62%。结论昆仑雪菊总黄酮含量较高;该实验方法可适用于昆仑雪菊及其制剂的质量控制。     

紫杉醇类前药的研究进展

紫杉醇(paclitaxel)及其半合成类似物多西紫杉醇(docetaxel) 是迄今为止发现的最为有效的抗癌药物之一,然而该类药物对正常组织、系统具有严重的毒性,而且水溶性较低以及对多药耐药 (MDR) 细胞几乎无活性等,使其临床应用受到限制。近年来,在提高紫杉醇类前药生物利用度和靶向性以及解决紫杉醇对于多药耐药肿瘤细胞无效等方面的研究和开发取得了很大进展。该文对近十几年来紫杉醇类前药的研究进展进行综述。 关键词：紫杉醇;前药;轭合物;水溶性;靶向性 中图分类号:     

Carboxylated mesoporous carbon microparticles as new approach to improve the oral bioavailability of poorly water-soluble carvedilol

The main objective of this study was to develop carboxylated ordered mesoporous carbon microparticles (c-MCMs) loaded with a poorly water-soluble drug, intended to be orally administered, able to enhance the drug loading capacity and improve the oral bioavailability. A model drug, carvedilol (CAR), was loaded onto c-MCMs via a procedure involving a combination of adsorption equilibrium and solvent evaporation. The physicochemical properties of the drug-loaded composites were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and HPLC. It was found that c-MCM has a high drug loading level up to 41.6%, and higher than that of the mesoporous silica template. Incorporation of CAR in both drug carriers enhanced the solubility and dissolution rate of the drug, compared to the pure crystalline drug. After loading CAR into c-MCMs, its oral bioavailability was compared with the marketed product in dogs. The results showed that the bioavailability of CAR was improved 179.3% compared with that of the commercial product when c-MCM was used as the drug carrier. We believe that the present study will help in the design of oral drug delivery systems for enhanced oral bioavailability of poorly water-soluble drugs.     

Using water-soluble chitosan for flavour microencapsulation in food industry

The aim of this work is to investigate the possibility of producing flavour microparticles, by means of water-soluble chitosan, considering all the advantages of this natural polymer (non-toxic, biocompatibility, biodegradability, anticholesterolemic), with or without a crosslinking agent (tripolyphosphate (TPP)). The microparticles were prepared by spray drying and characterized by their particle size, surface morphology and zeta potential. Structural analysis of the surface of the particles was performed by scanning electron microscopy (SEM). Significant differences were found in the surface structure of the crosslinked and non-crosslinked particles. Chemical characterization of the microparticles was performed by Fourier transform infrared spectroscopy (FTIR), the results being significant and proving the success of flavour microencapsulation. This work shows that it is possible to encapsulate peach flavours using water-soluble chitosan, through a spray-drying process.     

The neuroprotective effects of intraperitoneal injection of hydrogen in rabbits with cardiac arrest

Objective

The purpose of this study was to investigate the neuroprotective effects of intraperitoneal injection of hydrogen (H₂) in rabbits with cardiac arrest (CA).

Methods

A rabbit model of CA was established by the delivery of alternating current between the esophagus and chest wall to induce ventricular fibrillation. Before CA, the animals were randomly divided into four groups: a sham group (no CA), a CA group, a CA + low dose (10 ml/kg) H₂ group (CA + H₂ group 1), and a CA + high dose (20 ml/kg) H₂ group (CA + H₂ group 2). In the first experiment, animals were observed for 72 h after the restoration of spontaneous circulation (ROSC). The neurological scores were assessed at 24, 48 and 72 h after ROSC. The rabbits that survived until 72 h were sacrificed using an overdose of anesthetic, and the brain tissues were collected and Nissl-stained to observe nerve cell damage in the hippocampal CA1 area. In addition, TUNEL assay was performed to detect apoptosis. In the second experiment, animals were observed for 6 h after ROSC. Blood samples and brain hippocampal tissues were collected, and differences in oxidative stress indicators were compared among the four groups.

Results

Intraperitoneal injection of H₂ improved the 72-h survival rate and neurological scores, reduced neuronal injury and inhibited neuronal apoptosis. Intraperitoneal injection of H₂ reduced oxidative stress indicators in the plasma and hippocampal tissues and enhanced antioxidant enzyme activity. No significant difference was observed between the two CA groups treated with different doses of H₂.

Conclusions

Intraperitoneal injection of H₂ is a novel hydrogen administration method and can reduce cerebral ischemia-reperfusion injury and improve the prognosis of cardiopulmonary cerebral resuscitation in a rabbit model of CA.     

Characterization of recrystallized itraconazole prepared by cooling and anti-solvent crystallization

The objective of the present study was to alter the crystal habit of itraconazole (ITZ) by cooling and anti-solvent crystallization and characterize its properties. ITZ was recrystallized in different solvents and the effects of each solvent on morphology of crystals, dissolution behavior and solid state of recrystallized drug particles were investigated. The results revealed that ITZ crystals recrystallized by cooling and anti-solvent crystallization showed the different crystal habits from the untreated ITZ. Using cooling crystallization tended to provide needle-shaped crystals while the crystals obtained from anti-solvent crystallization showed more flaky, plate shape. This indicated the importance of preparation method on nucleation and crystal growth. No change in drug polymorphism was observed, according to determination of thermal property and crystalline state by differential scanning calorimetry and powder X-ray diffractometry, respectively. The recrystallized ITZ showed higher drug dissolution than untreated ITZ and the highest drug dissolution was observed from the samples recrystallized in the presence of PEG 200, which provided the small plate-shaped crystals with tremendously increased in surface area. However, the increasing of drug dissolution is relatively small, therefore, further development may be required.     

UPLC-Q-TOF/MS分析孟河医派特色猪心血丹参炮制前后化学成分的变化

目的:分析猪心血丹参炮制前后的化学成分变化情况,为深入阐明该饮片的炮制机制提供科学依据。方法:采用超高效液相色谱-四级杆-飞行时间质谱联用技术(UPLC-Q-TOF/MS),色谱条件为ACQUITY UPLC~ C_(18)色谱柱(2.1 mm×100 mm,1.7μm),流动相0.1%甲酸水溶液(A)-0.1%甲酸乙腈溶液(B)梯度洗脱(0~1 min,8%B;1~1.5 min,8%~20%B;1.5~4 min,20%B;4~5 min,20%~60%B;5~9 min,60%~70%B;9~10 min,70%~95%B;10~13 min,95%B),柱温40℃,流速0.3 m L·min~(-1);质谱分析使用电喷雾离子源(ESI),分别在正、负离子模式下扫描,扫描范围均为m/z 50~1 200,采用对照品比对、质谱数据、数据库匹配和文献参照对各离子峰进行归属,通过比较猪心血丹参炮制前后离子峰数目和峰面积,研究其化学成分变化。结果:猪心血丹参炮制前后共鉴别出59个成分,未发现有新的成分产生。猪心血炮制丹参后,共有25种化学成分峰面积发生显着变化,其中丹参水溶性成分原儿茶醛,丹酚酸C,F,G和脂溶性成分丹参醛,丹参二醇A,丹参酮Ⅰ和氨基酸类成分L-苯丙氨酸峰面积显著增高。结论:猪心血丹参炮制前后化学成分的含量变化显著,其中丹参部分水溶性、脂溶性和氨基酸类成分产生了量变,推测这可能与猪心血促进丹参治疗脑缺血的作用有关。     

A novel core-shell lipid nanoparticle for improving oral administration of water soluble chemotherapeutic agents: inhibited intestinal hydrolysis and enhanced lymphatic absorption

The oral administration of water-soluble chemotherapeutical agents is limited by their serious gastrointestinal side effects, instability at intestinal pH, and poor absorption. Aiming to solve these problems, we chose topotecan (TPT) as a model drug and developed a novel lipid formulation containing core-shell lipid nanoparticle (CLN) that makes the water-soluble drug to ‘dissolve’ in oil. TPT molecules can be encapsulated into nanoparticles surrounded by oil barrier while avoiding the direct contact with intestinal environment, thus easing the intestinal hydrolytic degradation and gastrointestinal (GI) irritation. Microstructure and mean particle size of TPT-CLN were characterized by Transmission Electron Microscope (TEM) and Dynamic Light Scattering (DLS), respectively. The average size of nanoparticles was approximately 60?nm with a homogeneous distribution in shapes of spheres or ellipsoid. According to in vitro stability studies, more initial form of TPT was observed in presence of lipid nanoparticle compared with free topotecan solution in artificial intestinal juice (pH 6.5). After oral administration of TPT-CLN in rats, AUC and C_max of TPT were all increased compared with free TPT, indicating significant enhancement of oral absorption. Intestinal lymphatic transport was confirmed as the major way for CLN to enhance oral absorption of TPT by the treatment of blocking chylomicron flow. Lower GI irritation of TPT-CLN was observed in the gastrointestinal damage studies. The in vivo antitumor activity of TPT-CLN showed an improved antitumor efficacy by oral treatment of TPT-CLN compared to free TPT. From the obtained data, the systems appear an attractive progress in oral administration of topotecan.