Periploca sepium is listed in the Japanese and Chinese Pharmacopoeia and has been widely used as a tonic. As the original plants of this drug, more than seventeen plants are recorded, most of which belong to Araliaceae, but only one, Periploca sepium BUNGE belongs to Asclepiadaceae (1). A few Asclepiadaceae plants of Indian origin having therapeutic value were reported (2). The volatile components of several Chinese crude drugs have been investigated in our research on flavour compounds or flavour ingredients (3-9). In earlier papers, various glycosides and 4-methoxysalicylaldehyde have been reported from P. sepium (10-13), but so far there is no attempt has been made to study the volatile oil from this plant, has not yet been reported. In this report, the chemical composition of volatile oil from the P. sepium was investigated. 2 Experimental 2 1 Material Commercially available air-dried root bark of P. sepium was obtained from matsuura kanpo Co., Ltd, (Aichi japan). 2 2 Isolation of Volatile Oil The root bark of P. sepium (200g) was cut into small pieces, hydrodistilled in a Likens-Nickerson type apparatus, with diethyl ether to yield 199 mg, 0.10% of essential oil, which was dried over anhydrous sodium sulphate. 2 3 Gas Chromatography GC was carried out using Hewlett-packard 5890 equipped with a flame ionization detector (FID) on a capillary column (DB-5, 30 m 0.25 mm i.d.
ABSTRACT-Effect of subchronically administered GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine di hydrochloride], a selective nicotinic agonist, on neuronal cell loss caused by nucleus basalis magnocellularis (nBM) lesion was studied in rats. After 2 weeks of bilateral nBM excitotoxic lesion, GTS-21 was orally administered once daily for 20 weeks. Neuronal cell loss was observed in layers 11-111 of the parietal cortex in the lesioned control rats. GTS-21 significantly attenuated the neuron loss in these layers. These results suggest that GTS-21 exhibits a protective action against the neuronal cell death in the parietal cortex and may have a beneficial effect on neurodegenerative disorders such as an Alzheimer-type disease. (1) have found neuronal cell loss and cytopathological abnormalities in the nucleus basalis magnocellularis (nBM) in AD patients. These authors also have demonstrated a strong correlation be tween the frequency of neuritic plaques in the cerebral cortex and the neuronal loss in the nBM. Moreover, the decrease of nicotinic receptors in the frontal cortex has been shown in AD patients (2). These findings suggest that the nicotinic receptor system plays an important role in cognitive and neurophysiological function.The recent report by Newhouse et al. (3) has demon strated that the intravenous administration of nicotine partially improves cognitive performance in AD patients, suggesting the role of central nicotinic acetylcholine receptors in cognitive and pathophysiological changes in AD. Moreover, their findings give rise to the possibility that stimulation of the remaining nicotinic receptors can alleviate the cognitive deficits induced by dysfunction of central cholinergic systems.GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine di hydrochloride], a selective nicotinic agonist, reportedly improves the learning performance in nucleus basalis lesioned rats (4). Moreover, a recent study indicates that nicotinic drugs exert a protective activity against fimbrial transection-induced neuronal cell loss when administered systemically 1 hr before and every 12 hr after the transec tion (5).In rodents, an injection of ibotenic acid, an excitotox in, into the nBM causes a decrease in the number of neuro nal cells in the cerebral cortex and attenuates the cortical cholinergic activities in rats (6, 7). This nBM lesion is also known to impair memory-related behaviors. Thus, the nBM-lesioned rats provide an animal model with brain dysfunction similar to that observed in AD and have been used to elucidate the therapeutic potential of drugs in AD patients.In the present study, to elucidate this possibility, we examined whether per orally administered GTS-21 exerts a protective action against neocortical neuronal cell loss caused by bilateral nBM-lesion in rats.Male Wistar rats (8-weeks-old; Clea Japan, Inc., Tokyo) were housed 3 4 per cage at least for 1 week be fore the start of the experiments. The housing was thermo statically maintained at 21 ± 1 C with a constant humidity (45-6507o) and a 12-hr light-da...
Neither the pharmacokinetics nor the pharmacodynamics of tofogliflozin was affected by any of the anti-T2DM drugs evaluated in this study, nor was the pharmacokinetics of any of the anti-T2DM drugs affected by tofogliflozin in healthy male volunteers.
Effects of GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride], a selective nicotinic agonist, on locomotor activity and dopamine turnover were examined and compared to those of nicotine to test if GTS-21 exhibits side effects similar to those of nicotine. GTS-21 had no effect on locomotor activity in mice or dopamine turnover in rats. In contrast, nicotine produced a biphasic effect on locomotor activity. It also enhanced dopamine turnover rates in the striatum and cerebral cortex, suggesting the involvement of dopaminergic systems in the nicotine-induced changes in locomotor activity. GTS-21 exhibits fewer adverse effects, suggesting that it has therapeutic potential for cognitive disorders related to central cholinergic dysfunction.
Biologics manufacturing technology has made great progress in the last decade. One of the most promising new technologies is the single-use system, which has improved the efficiency of biologics manufacturing processes. To ensure safety of biologics when employing such single-use systems in the manufacturing process, various issues need to be considered including possible extractables/leachables and particles arising from the components used in single-use systems. Japanese pharmaceutical manufacturers, together with single-use suppliers, members of the academia and regulatory authorities have discussed the risks of using single-use systems and established control strategies for the quality assurance of biologics. In this study, we describe approaches for quality risk management when employing single-use systems in the manufacturing of biologics. We consider the potential impact of impurities related to single-use components on drug safety and the potential impact of the single-use system on other critical quality attributes as well as the stable supply of biologics. We also suggest a risk-mitigating strategy combining multiple control methods which includes the selection of appropriate single-use components, their inspections upon receipt and before releasing for use and qualification of single-use systems. Communication between suppliers of single-use systems and the users, as well as change controls in the facilities both of suppliers and users, are also important in risk-mitigating strategies. Implementing these control strategies can mitigate the risks attributed to the use of single-use systems. This study will be useful in promoting the development of biologics as well as in ensuring their safety, quality and stable supply.
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