In this pilot study we treated cerebral vasospasm in patients with subarachnoid haemorrhage to assess intra-arterial fasudil hydrochloride. We analysed effects of intra-arterial infusion on angiographically evident cerebral vasospasm in 10 patients including 3 with symptoms of vasospasm. Over 10 to 30 min 15 to 60 mg was administered via the proximal internal carotid artery or vertebral artery following standard angiography, without superselective techniques. A total of 24 arterial territories (21 internal carotid, 3 vertebral) were treated. Angiographic improvement of vasospasm was demonstrated in 16 arterial territories (local dilation in 2, diffuse dilation in 14) in 9 patients. In 2 symptomatic patients, intra-arterial fasudil hydrochloride was associated with resolution of symptoms without sequelae. In the third symptomatic patient the benefit of fasudil hydrochloride was only temporary, and a large cerebral infarction occurred. All asymptomatic patients showed no progression of angiographic to symptomatic vasospasm after treatment with intra-arterial fasudil hydrochloride. No adverse effect was encountered.
Quinine hydrochloride, ticlopidine hydrochloride and sucrose were purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). Eperizone hydrochloride, donepezil hydrochloride and azelastine hydrochloride were manufactured by Eisai Co., Ltd. (Tokyo, Japan); k-, i-, and l-carrageenan and agar were gifts from Ina Food Industry Co., Ltd. (Nagano, Japan). The carrageenans are a polysaccharide family built up from subunits consisting of two galactose rings that carry an electric charge of up to three unit charges derived from dissociated sulfate groups. The ideal structures indicate that the k-, i-, and l-carrageenans should be characterized by one, two, or three charge units, respectively, per subgroup. 25) LM pectin was purchased from Sansho Co., Ltd. (Osaka, Japan); Ludiflash ® , a granulated product developed by BASF for production of ODTs by the direct tabletting The purpose of this study was to demonstrate the usefulness and wide applicability of a taste sensor and a new disintegration testing apparatus in the development and/or evaluation of orally disintegrating tablets (ODTs). In this paper, we described methods for the effective utilization of a taste sensor in the development of a new medicine. First we predicted the taste of propiverine hydrochloride, a model drug substance whose taste is unknown, using a taste sensor. Then we screened masking agents for their ability to suppress the bitterness of propiverine hydrochloride, and manufactured ODTs of propiverine hydrochloride with various masking agents. The tastes of these ODTs were then evaluated in chronological order by combining the taste sensor with the new disintegration testing apparatus, ODT-101, to resemble the oral cavity. As a result, we were able to evaluate the taste of propiverine hydrochloride and the effectiveness of various masking agents in ODTs. The result using this combination of taste sensor and ODT-101 shows good agreement with the results of human gustatory sensation testing, thus demonstrating the usefulness and applicability of the taste sensor and disintegration testing apparatus, ODT-101, in the development of new medicine. A New Method for Evaluating the Bitterness of Medicines in Development Using a Taste Sensor and a Disintegration Testing Apparatus
The aim of this study was to develop a simple and suitable disintegration method specific for rapid disintegrating tablets (RDTs). The new disintegration method that we propose employs a rotary shaft to exert mechanical pressure on the RDT. To assess our method, we manufactured several placebo RDTs and exposed them to severe storage conditions (60 degrees C/75%RH for 1 week) in order to obtain RDTs with a wide range of disintegration times. These placebo RDTs were utilized to compare the disintegration times obtained by several methods, including the proposed method. As expected, the disintegration time of the placebo RDTs in human sensory test varied widely. The disintegration times determined by the conventional disintegration test were in good correlation to those in human sensory test, but the slope was far from 1 (0.241). There was no correlation between the disintegration time of RDTs in human sensory test and those determined by the conventional dissolution test. In contrast, we acquired good correlation between the disintegration times obtained with the new method and those in human sensory test, and the slope was very close to 1 (0.858). We attribute this to the use of mechanical stress in the new method, similar to that the RDT is subject to in the oral cavity. We therefore concluded that the proposed method was suitable for the measurement of the disintegration time of RDTs. This new method might provide a valuable approach for the establishment of the official disintegration test for RDTs in the future.
The essential components which impart the favorable “brothy taste” as the characteristic flavor of beef bouillon were investigated. Broth prepared from beef was performed successively by dialysis, electrodialysis, gel filtration chromatography, chelate affinity chromatography, and carbon partition chromatography, and finally three fractions which gave the “brothy taste” were obtained. Among these, one fraction, A8, contained the component responsible for this taste in highest purity. Structural analysis was carried out using FAB-MS and various NMR methods, and the main compound of A8 was thus elucidated to be the novel compound N-(1-methyl-4-hydroxy-3-imidazolin-2,2-ylidene)alanine. Keywords: Beef; extract; sour; brothy; taste; amino acid derivative
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