Several kinds of surface active agents-i.e., cationic : cetylmethyl diethyl ammonium methosulfate, cetylmethyl piperidinium methosulfate, non-ionic : Tween 20, Tween 60, and Span 20, anionic : dioctyl ester sodium sulfosuccinic acid, sodium oleate-were added according to the various steps of concentration to 0.01% solution of 4-n-cyclo-hexyl-6-chlororesorcinol (C. H. C. R.) in phosphate buffered, pH 7.5, frog-Ringers' solution. Then, the mortality percent of Spinicauda japonica Wilkie, a nematoda species inhabiting toad's large intestine, after immersed in these solutions for certain minutes, was observed by modified Lamson's method, and parallel measurement was carried out their interfacial tension against liquid-parrafin by Hillyer's drop method and du Nouy's ring method. The results obtained were : the soaps in dilute solution increased remarkably the biological activity of C. H. C. R. (as measured by the mortality percent) but when present in high 'concentration it decreased the activity. In these cases, the least concentration of soap to increase the biological activity of these solutions corresponded to the concentration at which the interfacial tenision bgins to fall, when measured by drop method, but not by ring method, but the maximum acceleration ot the activity occurred at the concentration where the interfacial tension by ring method indicated minimum. However, in the case of Tween, such acceleration of the biological activity of the solution was not observed throughout its concentrations, and the more concentrated the more markedly decreased. These results were discussed from the sufacechemical point of view.

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On the combinations between 4-cyclohexyl-6-chlororesorcinol. (C. H. C. R.) and 4-n-octyl-6-chlororesorcinol (O. C. R.), C. H. C. R. and 4-n-octylresorcinol (O. R.), remarkable potentiation of the efficiency in combating ascaris was observed in certain ratio of mixture. The most efficient ratio of mixture, in both cases lay within the rang e of from 90% of C. H. C. R. contained. Oral toxicity tomice, local irritant action (examined on conjunctiva of rabbits, human tongues and gastric mucosa of dogs and also clinical side effects of these mixtures of most efficatious ratios did not significantly differ from those of C. H. C. R., the fact revealing no potentiation in such aspects. These mixtures proved, to be superior in anthelmintic efficacy and less toxic and less irritant than hexylresorcinol. Some physical changes such as a fall of melting, point and a lowering of interfacial tension of solution are supposed to be important factors in the mechanism of anthelmintic potentiation of these mixtures.

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Experiments were performed under the normal physiological conditions on a caged rat with free access to water. The diuretic action and the amount of water drunk were compared at regular. intervals after the oral administration of diuretics of various kinds, such as coffein, theocin, urea, potassium chloride, potassium and sodium salts of acetic, succinic and suberic acid. All the experiments were planned statistically and carried out with the method, of uniformity test, and of cross test as, well : as with. Latin square method. First, in the method of uniformity test, 10 mg, 30 mg and 60, mg of. caffein, and, theocin were respectively administered per kg body. weight.but neither diuretic action nor an increase in the amount of water drunk were recognized. Then, 1, 000 mg of urea and 300 mg per kg of potassium chloride were administered. In the case of urea, a remarkable diuretic effect and an increase in the amount of water drunk were recognized. In the case of potassium chloride, temporary diuretic effect was found immediately after its administration and then, the amount of urine gradually decreased and in 5 or 6 days became smaller than before the administration. In the case where 23.5 mg of potassium acetate, 23 mg of potassium succinate and 30 mg of potassium suberate kneaded with a constant amount of wheat flour respectively (each dose is equimolar to the other) were administered, neither diuretic effect nor increase in amount of water drunk was observed, whereas with doses ten times as much as the doses of these compounds respectively, all caused distinct diuretic and increase in the amount of water drunk, although the effect of potassium succinate is less remarkable than those of the other two. Next, the experiments were made by the method of cross test. In this case, too, almost the same distinct diuretic effect and increase in the am ount of water were observed, by using potassium. acetate and potassium usberate. Furthermore, the results obtained by the Latin-square method with those compounds were the same as those of the above-mentioned two methods. When experiments were carried, out in the same, manner as before with their sodium salts instead of potassium salts, suberate showed a slight diuretic effect, while no diuretic action was. recognized in the cases of both acetate and succinate.

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The chronic actions of antihistaminics were studied on the mice, injected daily with Restamin (β-dimethylamino-ethylbenzohydryl-ether-HCl) or Anergen (N-dimethylaminoethylphenothiazine-HCl) for 80-120 days, and the combined actions of antihistaminics and central paralytics or stimulants were observed. The results obtained were as follows : (1) Restamin was found to have excitative and paralytic action on the mice, while Anergen showed only a paralytic action. The acute toxicity of Restamin was stronger on the mice than that of Anergen, but by the chronic toxicity it was reversed. Antagonism of histamine to antihistaminics was observed obscurely on the mice treated with Restamin. (2) The combination of Restamin and the central paralytics increased the sedative action and decreased the Restamin toxicity, while the combination of Restamin and the central stimulants increased the stimulant action. resulting convulsions and the Restamin toxicity. On the contrary, the combination of Anergen and the central paralytics exerted no obvious potentiation in their sedative actions; Anergen was, however, observed antagonistic to the convulsions due to the central stimulants. (3) Antagonism between histamine and Restamin was observed on the isolated intestine of mice treated with Restamin, but not proved, on mice with Anergen. (4) By the experiments. on the tissue respiration the. liver, intestine and. brain of mice injected with Restamin for a short time, became hypersensitive to Restamin, after repeated 80-130 times of injections of Restamin, however, these tissues became hyposensitive. On the contrary, the tissues of the Anergen mice maintained continuously the hypersensitiveness to Anergen. (5) The distribution pattern of Restamin in the bodies of the Restamin mice was observed to be differed from controls.

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The actions of Restamin (see no. 18 of this Breviaria) and histamine on the isolated uteri of rabbits, gninea pigs and rats were studied and the influences of ovarial hormones thereupon were examined. Result : (1) Histamine showed a stimulating action on the rabbit's and guinea pig's uterus but a paralytic action on the rat's. The paralytic action was not due to the smooth muscle paralysis. (2) Restamin showed an accelerating action on the uterus of rabbit and guinea pig, but in a lower concentration either accelerated or inhibited the motility of the rat's uterus and only suppressed it in a higher concentration. (3) Antagonism between histamine and Restamin was observed on the isolated uterus of rabbit and guinea pig, while not on the rat's uterus. (4) The effect of Ovahormon on the actions of histamine and Restamin was not obvious, while Oophormin controlled the stimulant actions of these two drugs and increased their paralytic actions. (5) Actions of histamine and. Restamin had little to do with the estrus.

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Because of the insolubility of sulfathiazol, and thus poor absorption from wound surface little therapeutic effect is expected from external application. Therefore, in order to find the best method for external application of the drug the absorp tion of. the drug was tested by using different vehicles. Sulfathiazol (S) was mixed at a concentration of 10 % in 3 ointment bases, i.e. LV (lanolin 10+vaselin 90), HO (hydrophilic ointment) and PC (propylene glycol 50-carbowax (4000) 50).The S ointment were spread 2×2 cm squares of oil-paper and applied on the surface of wounds on the leg skin of a rabbit. Then the concentration of S in blood and urine was measured. with Tsuda's method at certain intervals of times. The results obtained were as follows : (1) When a small amount (0.1 g) of each ointment was applied, there were only slight differences between the three vehicles in the drug concentration in blood and in the quantity of the drug excreted in urine. (2) Although LV and HO increase the absorption and excretion of the drug in triple doses, doubling the dose did not influence the absorption and excretion. The ratio of the quantity excreted in urine to the dose (excretion ratio) was lower, the larger the dose. (3) When the dose of the PC-S ointment was tripled, the S concentration in blood was raised and the quantities excrted in urine and the duration of excretien were increased. The excretion ratio in this case was higher, the larger the dose.

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Quantitative estimations of free santonin were determined in-the urine and intestinal tract of a rabbit following oral, subcutaneous and intravenous administration. The analytic method for this purpose was previously reported in detail (Nagasaki Igakkai Zassi in press).. The results obtained were as follows : (1) The ratio of the quantity of santonin excreted in the urine to the dose amounted to 6.7 27.7 % after oral administration ; to 64.9 77.4%; after subcutaneous administration of sodium santonin ; to 673-82.8 % after intravenous administration of the salt. Since individual variations in the excretion of santonin are great, the same rabbit was used to avoid experimental error. (2) Most of the santonin was excreted within the first 9 hrs. after oral administration, and in the first 3 hrs. after injection of sodiums santoninate. (3) Whenever oral administration of santonin was repeated in a rabbit excreting a large quantity of the drug at the first administration, the amount excreted in the urine, fell to a constant value after several administrations. (4) No santonin could be detected in the feces, but a qualitative test for santonin was positive in the bile and intestinal tract. (5), Seven rug of santonin (1%) was found in the bile of a rabbit whose liver and kidneys were injured by repeated large doses of santonin.

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The influence of liver function on the urinary excretion of unchanged santonin was investigated in rabbits. The results obtained were as follows. After the liver was damaged by CCl₄ the urinary excretion of santonin increased markedly over the control ; it was decreased when the function of liver was stimulated by dehydrocholic acid or sodium thiosulphate. These results showed conversely the same relation that oxysantonin was excret. ed in the urine proportionally to the function of liver, and it was accordingly considered that santonin would be changed to oxysantonin in liver.

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The anticonvulsive activities of such drugs as o-tolylglycerylether (Myanesin), guaiacol glycerylether, isotetradrin ammonium hydroxide, isotetrandrin ammonium chloride, isotrilobin and d-tubocurarine were comparatively examined by the head-drop dose of rabbits and mice and discussed on the superiority of the former method with rabbits to the latter.

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It has been known that p-hydroxy-camphor has a cardio-stimulating action. This drug used for the author's experiment has been prepared from campherol, being separated from the urine of a dog taking camphor. The drug seemed to have the action to get rabbits sleep naturally by this experiment. In the case in which it was used with a barbiturate such as evipal, the author found it to be certain that, as the former would have the antagonistic action in part against the : latter, the paralytic action diminished and consequently sleep came on naturally in rabbits with the simultaneous application of both drugs. In the case in which these two drugs were administered together to the human body in the same way as bebore, it seemed certainly that they would act also antagonistically to each other at the site of action, so that their side actions diminished and they, therefore, caused sleep more naturally their synergistic action on the other hand. It may be said that sleep would come on with change of the state of two centers, sleeping and awaking; p-hydroxy-camphor excites the sleeping center, while barbiturates inhibit the awaking center, so that the human being would be taken in the natural sleep if he used these two drugs together.

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The 4-hours method by frogs as bioassay of digitalis was formally adopted on Pharmacopoeia Japonica VI (1951). This method indicates to give each group of 3 frogs each dose, which has the difference of 20 % (secondly 10%) to successive dose, but this way is not so adequate experimentally or theoretically. We gave to frogs (Rana nigromaculata) subcutaneously 3.2 % solution extracted from many different digitalis leaves by methanol and investigated the time needed to produce the heart standstill. We found from the above results interpolated from 800 cases that all deviations of the time needed to produce the action express completely the normal distribution and that Gaddum's standard deviation, λ is±0.155, 2λ=±0.31. As the products of time and dose are mostly constant in the above dose, the deviation of time should represent that of sensitivity of frogs to digitalis. Calculating the error by the above values of the deviation, the 2ε of determination of digitalis by 4-hours method is about 25 % to the true value of the standard preparation. If we would calculate the error by the method which assigned to give each group of 5 frogs a certain dose, which has the difference of 10 % between each dose, adopted on Deutsches Arzneibuch, it is ± 20% to the former and ±24% to the latter.Even in sucha case that the frog number of one group was more than 5 and the difference between each dose was smaller than 10 %, we could not find the lower value of the error than 15 %.When frogs are few, we can make the error small, if we compute the mean between the median culculated by Kärber's method and the geometrical median of two doses, the one is the large dose that frogs dies almost and the other is the smaller dose that they tolerated almost.

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Analyzing the fators of “Cocaineinactivation” by rabbit's liver the following results were obtained. (1) By the biological estimation of cocaine it was demonstrated that the liver extract of rabbits could inactivate cocaine and its important mechanism was suggested to be destruction. (2) Its destructive products, methyl alcohol, bezoic acid and ecgonine, were chemically demonstrated. (3) The quantitative micro-determination of benzoic acid was testified to be albe to measure benzoic acid derived from cocaine by rabbitt's liver extract. (4) Using this method, it could be proved that the production of benzoic acid was enzymatically performed. (5) The destructive ability was compared among the tissues of rabbits and the livers of several animals, and the liver of rabbits showed the most active destruction.

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