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The in vitro and in vivo skin permeability of 16 drugs with a wide span of lipophilicity (log P ranging from -0.95 to 4.40) was evaluated with an ethanol/panasate 800 (tricaprylin) (40/60) system as a lipophilic vehicle. The ethanol/panasate 800 (40/60) binary vehicle remarkably improved the in vitro skin permeability of the drugs across excised hairless mouse skin compared with ethanol or panasate 800 as single vehicles. The in vivo skin permeability of the large majority of the drugs across abdominal rat skin also showed high permeation rates and short lag times. The relationship between lipophilicity and skin permeability of the drugs from the ethanol/panasate 800 (40/60) binary vehicle indicated parabolic shapes with their peaks at much greater hydrophilic range (log P: -0.88 for in vitro, -0.83 for in vivo) compared with other past references (log P: 2-3). The results suggest that the lipophilicity of a drug is a main factor for prediction of the skin permeability of the drug and that the ethanol/panasate 800 (40/60) lipophilic binary vehicle would be a good candidate as a vehicle for future clinical application of hydrophilic drugs.

The in vitro skin permeability of 16 drugs with a wide range of lipophilicity (log P ; -0.95-4.40) was evaluated by the use of an ethanol/water (60/40) binary vehicle with of without lauric acid as a permeation enhancer. The enhancing effect by the addition of lauric acid to the ethanol/water (60/40) binary vehicle could be observed from the aspect of both permeation rate and lag time. The permeation rate increased with an increase in the hydrophilicity of the drugs. It was considered that lauric acid exerts an effect on both the polar and nonpolar regions of lipids of the stratum corneum, and the cooperative interaction of ethanol and lauric acid increases the participation of the polar pathway of drugs. The relationship between lipophilicity and skin permeability of the drugs from the ethanol/water (60/40) binary vehicle with lauric acid showed a parabolic shape, with its peak at a more hydrophilic range (log P ; 0.19) compared with other past references (log P ; 2-3). The ethanol/water (60/40) binary vehicle with lauric acid appears to be a good candidate as a vehicle for transdermal therapeutic systems for hydrophilic drugs.

The in vitro skin permeation using hairless mouse and in vivo skin absorption using rat of alclofenac from ethanol/panasate 800 (tricaprylin) binary vehicle were investigated. The in vitro skin permeability of alclofenac was remarkably enhanced by the combination of ethanol and panasate 800. The greatest enhancement was obtained in the ethanol/panasate 800 (40/60) system. The results of in vivo skin absorption of alclofenac were shown almost the same tendency as that of the in vitro permeation. The skin permeation enhancement mechanism of alclofenac from the ethanol/panasate 800 (40/60) binary vehicle was evaluated by clarifying the different behavior of ethanol and panasate 800 for the diffusion process in the skin. It is suggested that ethanol increases permeation flux by increasing the uptake of alclofenac in the skin tissue and by gradually reducing the barrier function of stratum corneum. On the other hand, panasate 800 reduces lag time by increasing the uptake rate and diffusion of alclofenac in the stratum corneum and viable skin. Therefore, the enhancement effect of the ethanol/panasate 800 (40/60)binary vehicle is considered to be due to the mutual effect which is obtained by the effective interaction of the two vehicles.

A novel ethylcellulose gel preparation using an ethanol/panasate 800 (tricaprylin) (40/60) binary lipophilic vehicle was developed and applied to the transdermal delivery of theophylline. The in vitro skin permeability of theophylline across excised hairless mouse skin was improved by the use of this ethanol/panasate 800 (40/60) binary vehicle compared with either ethanol or panasate 800 as a single vehicle, and the addition of lauric acid as a permeation enhancer to the binary vehicle shortened the lag time and increased the permeated amount of theophylline up to 6 h (initial permeation amount). The in vitro permeability of theophylline from the ethanol/panasate 800 (40/60)-ethylcellulose gels decreased with an increase in the content of ethylcellulose in the gels. In the in vivo evaluation using abdominal rat skin, the ethanol/panasate 800 (40/60)-7% (w/w) ethylcellulose gel produced a good feature as a sustained-release preparation, with a relatively high bioavailability (BA) of theophylline, and dose dependency was observed.

The effects of an ethanol/panasate 800 (tricaprylin) (40/60) system as a lipophilic vehicle, and an ethanol/water (60/40) system as a hydrophilic vehicle, with or without permeation enhancers for in vitro skin permeation and in vivo skin absorption of tegafur, alclofenac and ibuprofen with different lipophilicity, were evaluated.The in vitro and in vivo skin permeability of tegafur, alclofenac and ibuprofen was enhanced by the use of ethanol/panasate 800 (40/60) or ethanol/water (60/40) binary vehicles as a donor composition. However, the two vehicles showed contrastive properties in relation to the extent of permeation enhancement of the three drugs : tegafur > alclofenac > ibuprofen for the ethanol/panasate 800 (40/60) system, and ibuprofen ≥ alclofenac > tegafur for the ethanol/water (60/40) system. When lauric acid, as a permeation enhancer, was added to both of the binary vehicles, the in vitro and in vivo skin permeability of three drugs further increased, and the in vivo absorption rate of the drugs from the ethanol/water (60/40) system was larger than that from the ethanol/panasate 800 (40/60) system. In conclusion, it was suggested that the ethanol/panasate 800 (40/60) lipophilic binary vehicle is useful for hydrophilic drugs, and conversely, the skin absorption of lipophilic drugs can be improved by the use of the ethanol/water (60/40) hydrophilic binary vehicle with or without lauric acid as a permeation enhancer.

Five cases of infants, who had Peanuts as foreign bodies of bronchi, were reported.It was proposed that in treating peanuts as bronchial foreign bodies, following notices must beborn in mind:1) Precise and thorough informations must be inquired from the infant or persons accompanied, as to history of present illness, possibility of aspiration of peanuts, and situation of onset of coughor stridor.2) Chest X-ray examination should be performed especially both in inspiratory and expiratory states.Differences in chest roentgenogram taken in inspiratory and expiratory states as well as atelectasis, emphysema of lung or deviation of mediastinum would often suggest lodging site of foreign bodyof bronchus.3) Ventilation bronchoscopy must be carried out under total anaesthesia as soon as possible.4) In removing peanuts through bronchoscope, fenesterated forceps are recommended to beused, not to crush peanuts softened during long lodging in the bronchus. The tip of forceps mustbe corrected to the gap around peanuts in bronchial wall.5) In case remaining of a part of peanuts suspected, re-examination of ventilation bronchoscopyshould not be hesitated.Postoperative course of the infant must be watched strictly and carefully.

Ama is a professional sea-diving woman for fishing and her occupational disease has been reported in some localities of her body, especially in the ear.This report was compiled as a result of the otological examination of Ama at Hekura Island in Ishikawa Prefecture. The number of Ama interviewed was 40, The results were as follows:1) Ages ranged from 15 to 58, all of them female.2) The main complaints in the auditory organ were otalzia, blockade of the ear and tinnitus, but deafness in few subjects.3) The abnormal view of eardrums was found 75% by the otological examination, most of which showed sinking, turbidness or roughness.Especially we found the exostosis in external ear canal in 7 Ama.4) The resulting loss of hearing was indicated in half of them, whose type was generally sensorineural deafness and increased with ages.5) In almost all, the inflation of the auditory tube was good.6) Ama are considered to indicate that all these symptoms were caused by external agents in the sea, namely the water pressure equilibration of the ear during diving.

Nine hundred and fifty one cases of epistaxis were observed for the past 7 years. Epistaxis was observed more frequently in males than in females and was frequently observed in children.It occured more frequently from May to August, showing a peak in June.The negative correlation was observed statistically between the frequency of epistaxis and the atmospheric pressure.Hemorrhagic diathesis was examined in 114 cases. About 28 per cent of them showed abnormality, especially in the capillaly fragility.Children with nasal bleeding showed the tendency of disliking of foods containing vitamine C.