Preparation of Fast Dissolving Films for Oral Dosage from Natural Polysaccharides

Fast-dissolving films (FDFs) were prepared from natural polysaccharides, such as pullulan, without heating, controlling the pH, or adding other materials. The release profiles of model drugs from the films were investigated. In the absence of a drug, the casting method and subsequent evaporation of the solvent resulted in the polysaccharide forming a circular film. The presence of drugs (both their type and concentration) affected film formation. The thickness of the film was controllable by adjusting the concentration of the polysaccharide, and regular unevenness was observed on the surface of 2% pullulan film. All films prepared with polysaccharides readily swelled in dissolution medium, released the incorporated compound, and subsequently disintegrated. The release of dexamethasone from the films was complete after 15 min, although this release rate was slightly slower than that of pilocarpine or lidocaine. Therefore, FDFs prepared from polysaccharides could be promising candidates as oral dosage forms containing drugs, and would be expected to show drug dissolution in the oral cavity.     

HPLC测定兔眼房水中匹罗卡品含量

 目的：建立高效液相色谱测定兔眼房水中匹罗卡品含量的方法；探讨匹罗卡品溶液、乳浊液在兔眼房水中经 时过程的异同。方法：色谱条件：硅胶柱，流动相为体积分数为80%的乙腈，检测波长217nm。36只兔均分两组，双眼滴入4 mg/ml匹罗卡品溶液或乳浊液35μl；测定滴眼后30，60，90，120，240 min眼房水中药物滞留量；试样用二氯甲烷提取。结果：0.10?4.80 μg/ml范围内线性良好；回收率81.7%;日内、日间RSD分别为1.7%和1.5%。结论：方法易行，重现性好，线性范围广。兔眼滴入匹罗卡品溶液和乳浊液后240 min以内，眼房水中药物经时过程无显著差异。     

一阶导数分光光度法测定1%硝酸匹鲁卡品眼膏的含量

目的：改进硝酸匹鲁卡品眼膏含量测定方法。方法：采用一阶导数分光光度法测定硝酸匹鲁卡品眼膏的含量。测定波长２２２ｎｍ,△λ为２ｎｍ。结果：样品浓度在１０～６０ｍｇ／Ｌ范围内呈良好线性关系,ｒ＝０．９９９８,平均回收率为９９．８３％,ＲＳＤ％〈１．０１％。结论：方法简便、准确,可用于测定硝酸匹鲁卡品眼膏的含量。     

4％毛果芸香碱凝胶单次应用治疗青光眼的临床观察

目的：比较４％毛果芸香碱凝胶（ｐｉｌｏｅａｒｐｉｎｅ ｇｅｌ,ＰＧ）和１％毛果芸香碱溶液（ｐｉｌｏｅａｒｐｉｎｅ ｓｏｌｕｔｉｏｎ,ＰＳ）的降眼压效果及安全性。方法：２０例（４０只眼）高眼压症及早期原发性开角型青光眼患者,采用自身对照,分别比较ＰＧ（每晚一次）和ＰＳ（每天４次）对日间多次眼压的降眼压效应,分别比较二者连续４周用药对某一时点（１０ＡＭ）的眼压、瞳孔及屈光度的影响,以及眼部副作用。结果     

Pilocarpine's effects on the blood-aqueous barrier of the human eye as assessed by high-resolution, contrast magnetic resonance imaging

The purpose of this research was to reassess the effects of topical pilocarpine on the integrity of the blood-aqueous barrier, using high resolution, magnetic resonance imaging, and the standard intravenous contrast agent gadolinium dimeglumine. It has long been known that topical pilocarpine gives rise to an increase in protein levels in the anterior chamber of the eye. This protein scatters light and is referred to clinically as 'flare'. Prior studies concluded that pilocarpine-induced flare resulted from disruption of the blood-aqueous barrier. These studies relied upon indirect methods that precluded direct visualization of the posterior chamber of the eye. Five normal, human volunteers (age 22-40) received a single drop of 3% pilocarpine in one eye, following baseline measurements of pupil size and anterior chamber 'flare'. These measurements were repeated every 15 min for 45 min. The subject was then positioned in the magnet and the eye that received pilocarpine was taped closed and covered with a 3 in.-diameter receive-only surface coil. The open contralateral eye focused on a target to maintain fixation of the imaged eye. A baseline image of the eye was obtained and the contrast agent was administered intravenously. A series of additional images was obtained during the following 60 min to track the movement of contrast material from the bloodstream into the tissues and compartments of the eye. Percent enhancement was calculated from selected regions of interest in the images, including the ciliary body, and the anterior and posterior chambers. Within the 45 min after administration of pilocarpine, pupil size in mm decreased from (mean+/-s.d.) 5.7+/-1.5 to 2.5+/-0.5 (p=0.0106). During this period, average flare/s.d. (photons msec-1) increased from 3.7+/-1.1 to 12.5+/-4.7 (p=0.0151). In all cases, MRI images showed rapid enhancement of the ciliary body, followed by a progressive increase in signal in the anterior chamber but not the posterior chamber. These studies confirm that topical pilocarpine gives rise to 'flare' in the anterior chamber. But the lack of enhancement in the posterior chamber strongly suggests that the presence of this added protein in the anterior chamber is not the result of increased permeability of the blood-aqueous barrier of the ciliary body. These studies also introduce the novel concept that not all clinically observed flare is the result of blood-aqueous barrier compromise.     

Acute effects of glaucoma medications on rat intraocular pressure

The rat has been used increasingly in glaucoma research, but many aspects regarding the regulation of its intraocular pressure (IOP) are still unknown. For example, it is not clear whether glaucoma medications can lower IOP in the rat similarly to human. This information will be valuable in evaluating this animal model for its usefulness in predicting drug effects in patients. Hence, we tested the acute IOP effects of selected glaucoma drugs topical administered onto the rat eye. In these studies, IOP was measured using the Tono-Pen XL tonometer. After a correlation between the IOP reported by the Tono-Pen and actual IOP was established, IOP measurements were obtained in slightly sedated adult rats. Effects of glaucoma medications were tested in two groups of animals. One group (12 h/L) was housed in a 12-h/12-h light/dark cycle. The other (24 h/L) was housed under constant light. Exposure of the animals to constant light increased their basal IOP from 20.5+/-0.6 mmHg (mean+/-S.E.M., n=12) to 32.0+/-0.5 mmHg. At 3 h after topical administration, Betoptic S lowered IOP by 4.3+/-1.7 mmHg (n=6) and 3.7+/-0.3 mmHg (n=6) in the 12 and 24h/L rats, respectively. Pilocarpine did not affect rat IOP. Xalatan produced a biphasic response in the rat. At 3h after topical administration, it increased IOP by 7.9+/-1.4 and 7.0+/-1.0 mmHg in the 12 and 24 h/L rats, respectively. By the next day, it decreased IOP by 3.0+/-1.0 and 6.0+/-0.8 mmHg in the 12 and 24 h/L rats, respectively. The IOP-enhancing effect of Xalatan was dose-dependent. The present study indicates that IOP responses of the rat to different pharmacological agents are not identical to those of the human. In the rat, Betoptic S, but not pilocarpine, lowered IOP. Xalatan initially increased then decreased IOP.     

Impaired activation of CA3 pyramidal neurons in the epileptic hippocampus

We employed in vitro and ex vivo imaging tools to characterize the function of limbic neuron networks in pilocarpine-treated and age-matched, nonepileptic control (NEC) rats. Pilocarpinetreated animals represent an established model of mesial temporal lobe epilepsy. Intrinsic optical signal (IOS) analysis of hippocampal-entorhinal cortex (EC) slices obtained from epileptic rats 3 wk after pilocarpine-induced status epilepticus (SE) revealed hyperexcitability in many limbic areas, but not in CA3 and medial EC layer III. By visualizing immunopositivity for FosB/ΔFosBrelated proteins—which accumulate in the nuclei of neurons activated by seizures—we found that: (1) 24 h after SE, FosB/ΔFosB immunoreactivity was absent in medial EC layer III, but abundant in dentate gyrus, hippocampus proper (including CA3) and subiculum; (2) FosB/ΔFosB levels progressively diminished 3 and 7 d after SE, whereas remaining elevated (p<0.01) in subiculum; (3) FosB/ΔFosB levels sharply increased 2 wk after SE (and remained elevated up to 3 wk) in dentate gyrus and in most of the other areas but not in CA3. A conspicuous neuronal damage was noticed in medial EC layer III, whereas hippocampus was more preserved. IOS analysis of the stimulus-induced responses in slices 3 wk after SE demonstrated that IOSs in CA3 were lower (p<0.05) than in NEC slices following dentate gyrus stimulation, but not when stimuli were delivered in CA3. These findings indicate that CA3 networks are hypoactive in comparision with other epileptic limbic areas. We propose that this feature may affect the ability of hippocampal outputs to control epileptiform synchronization in EC.     

锂-匹罗卡品致颞叶癫痫小鼠模型的建立及苔藓纤维出芽的实验研究

目的探讨腹腔注射锂-匹罗卡品建立小鼠颞叶癫痫(EP)模型方法及其行为学改变与苔藓纤维出芽的关系。方法小鼠腹腔注射锂-匹罗卡品建立颞叶EP模型,应用ZnSe金属自显影技术(AMG)检测3d、7d、15d、30d及60d的苔藓纤维出芽情况。结果锂-匹罗卡品注射后,约40%的小鼠呈现癫痫持续状态,并出现慢性自发发作。形态学检查发现海马齿状回分子层苔藓纤维出芽,并且随着时间的延长,苔藓纤维出芽逐渐增多。结论腹腔注射锂-匹罗卡品小鼠模型是一种理想的颞叶EP动物模型,苔藓纤维出芽可作为判断SE模型是否成功的形态学标准。     

激活乙酰胆碱作用靶标对血管内皮细胞基因表达的影响

目的　研究激活乙酰胆碱作用靶标 (ETA)对血管内皮细胞基因表达的影响。方法　采用人类cDNA表达谱芯片 ,比较氨甲酰胆碱和毛果芸香碱对人冠脉内皮细胞基因表达的影响及其生物学功能。结果　既激活ETA又激活M受体的氨甲酰胆碱 ,以及仅激活M受体的毛果芸香碱 ,在 10 0μmol·L-1浓度下与内皮细胞共孵育 10h ,以含有 14 0 0 0条人类unigene的BiostarH 14 112ScDNA表达谱芯片检测内皮细胞基因表达的变化 ,发现差异基因共 80 1条。两药共同诱导的差异基因 4 91条 ,上调 2 0 5条 ,下调 2 86条。两药诱导差异基因存在很大差别 ,其中氨甲酰胆碱诱导上调基因 119条 ,下调基因 191条 ,这些差异基因均不受毛果芸香碱的影响。进一步分析氨甲酰胆碱特异性诱导差异基因的功能 ,发现有受体与G蛋白、离子通道、血栓、动脉粥样硬化相关基因等七大类。结论　氨甲酰胆碱特异性诱导的差异基因与ETA及其效应器系统以及激活ETA产生抗动脉粥样硬化和抗血栓的分子机制相关。