The experiments were carried out to observe the influence of PG (propylene glycol) and PEG (polyethylene glycol) as vehicles in the penetration of furan derivative ointments (furacin, guanofuracin, parafuracin, paraguanofuracin). Staphylococcus aureus Teracshima, Streptococcus hemolyticus, Diplococcus pneumonia, Bacillus coli, Bacillus typhosus, Bacillus paratyphosus A, Bacillus paratyphosus B and Bacillus dysenteria were tested as strains and the ointment paper disc agar plate method was used. The results obtained were : (1) PG (15%) added to the Unguentum simplex base increased about ten times the penetration of furacin and guanofuracin as compared to the action with only Ung. simplex base. Streptococcus hemolyticus was the only exception, and here the hemolytic activity was increased by the combination with PG (See Table 1 and 2). (2) in studying the penetration of 0.2 % furacin in various bases, PEG was most effective of all. The hydrophilic ointment as well as vaseline bases were weakest in effectiveness (Table 3). (3) The penetrating action of a lower concentration (0.05%) of furacin in the PEG-ointment base was just as effective as a higher concentration (0.2 %) in other bases (Table 4). (4) The penetrations of parafuracin and paraguanofuracin were made more effective by PG and PEG as vehicles (Table 5). (5) The penetration of furacin derivatives was strengthened by PG and PEG in the agar plate culture medium, and the application of these results to the human body was discussed.
The relation between the cerebrospinal pressure and the circulation was investigated on rabbits anaesthetized with urethane. The fluid pressure at the Cisterna cerebellomedularis was measured by Harada's method in which the pressure measured with Hg-manometer was calculated in terms of water-pressure and drawn on a kymograph. To observe the cerebral blood flow, the modified “thermocouple method” of Takenaka was used. The results obtained : (1) The cerebrospinal fluid pressure measured in 450 rabbits varied between 55-89 mm water, the majority were between 65-85 mm water. (2) There is no alternation in the brain circulation when the pressure is raised to 650 mm water or is lowered to-120 mm water. (3) A rise or fall of the cerebrospinal pressure does not influence the amplitudes of the pressure curve. (4) Adrenaline at first increases the pressure as well as the blood flow in the brain and later it decreases them, although they differ in the extent and duration after various doses (See Fig. 1). (5) Inhalation of ether increases the cerebral blood flow and the cerebrospinal pressure. (6) Barium chloride causes a transient increase of the pressure and blood flow and then it decreases markedly the blood flow while only a slight fall of the pressure occurs (Fig. 2). (7) Acetylcholine increases the blood flow and the pressure (Fig. 3). (8) The changes in the blood flow measured with the thermocouple method is revealed a short time after the pressure changes. (9) The extent of a rise.of the pressure is proportionate to an increase of the blood flow, but it decreases out of proportion to the pressure.
Pearl-barley (Coix Lacryma-jobi L. var. frumentacea Makino) contains a fatty oil in 5.9-9.8 %. The main ingredient of unsaturated acids in the oil is _??_-octadecenic acid (Bp5 2350), -I call it coixic acid-and the saturated one, palmitic acid. The fatty oil has some effects on blood vessels and respiration, while palmitic acid has special effects on the sympathetic nerve endings of blood vessels, uterus and intestine just like ergotamine. It excites the respiration owing to its stimulant action on the respiratory center and on the motor nerve endings of respiratory tracts. It lessens the fatigue because of the stimulation of the motor activity. In addition it controls the outflow of urine, but has no action on heart directly.
In present report the influence of PG (propylene glycol) as a solvent on the penetration of furan derivatives were investigated by the one-dimensional diffusion method. Another experiment was carried out to determine the action of PG as a vehicle strengthening the effect of drugs. The results obtained are as follows : (1) The antibacterial zones in agar tube culture media were markedly increased by the drug (furacin, guanofuracin, parafuracin, paraguanofuracin) when PG was used as a solvent. Staphylococcus aureus Terashima, Diplococcus pneumonia, Bacillus coil, Bacillus typhosus, Bacillus paratyphyphsus A, Bacillus paratyphosus B, Bacillus dysenteria were used as tested strains (See Table 1). (2) The penetrative activity of the furan derivatives in solvents containing various concentration of PG was increased in proportion to PG concentration (Table 2). (3) When PG-furacin solution was exposed to sunlight, its colour turned to red. orange and the antibacterial potency decreased, but this did not-occur if the solution were kept in a dark place (Table 3). (4) The antibacterial activity of furacin was increased in culture media containing increased concentration of PG. The same results were obtained by both the one dimensional diffusion method and the ointment paper disc plate method (Table 5). PG potentiates the antibacterial action of furacin, especially in a lower concentration of the furacin. (5) PG and PEG aid in the furacin soluble and therefore increase its penetration, so they play a role as a drug carrier. Furthermore, the antibacterial activity of furan derivatives especially in a lower concentration is supported by synergism with the antibacterial activity of PG. (6) The penetration of furacin in the gelatin medium was increased by PG and PEG, similar to the situation using agar medium (Table 6).
This experiment was to observe whether headache and vomiting is due to the change of cerebral blood flow and cerebrospinal fluid pressure. The methods were the same in the previous report (no. 8 of this Breviaria). The experiment was done with drugs closely related to headache or vomiting in the human body, i. e. histamine, antipyrin, sulpyrin, apomorphine, etc. The results obtained are as follows : (1) Histamine, antipyrin, sulpyrin, and apomorphine increased the cerebral blood flow and raised the fluid pressure (See Fig. 1, 4 and 6). (2) The cerebral blood flow and the fluid pressure was slightly increased by agroclavin (an alkaloid from the cultivated ergot), but after a minute they began to decrease markedly. (3) The intravenous injection of a large dose of caffeine (10 mg) increased the blood flow and the fluid pressure but the subcutaneous injection of the same dose decreased them. (4) An emetic drug (apomorphine) increased the cerebral blood flow and the fluid pressure but agroclavin (acting emetic in over-doses) decreased them. Therefore there is no relation between vomiting, and the blood flow and cerebrospinal pressure.
The time needed to produce a regular action by the various drugs (digitalis, strophanthine, strychnine, picrotoxin, guanidine, chloral hydrate and urethane) was measured at intervals of 5°C at the temperature of 10°C to 30°C or 35°C. In this case the dosage of each drug was changed at each temperture over a wide range, and thus temperature coefficient at each range of temperature was calculated. The results are as follows : (1) Between 15°C and 30°C temperature coefficient was not remarkably different in any drugs, increased in proportion to increase of dosage of drugs and its value was about 2. (2) In the experimental examples at 30°C to 35°C the value ot temperature coefficient (Q10) was fairly large in picrotoxin and strophanthine and on the contrary Q10 was small in urethane. At the low temperature of 10°C to 15°C Q15 became abruptly large but became reversely small in urethane. So the changing point seemed to be in the range of the above temperature. This changing point in strophanthine was about 13°C. (3) In the experiment which the surrounding temperature was artificially changed Q10 coincided with the above results. Therefore increase or decrease of the time needed to produce the action by the seasonal change seems chiefly to be due simply to the difference of the surrounding temperature. (4) The little difference of temperature coefficient among each drug should prove that the chemical change of drugs themselves or the direct participation of drugs to cellular metabolism must not be the essential quality of action of drugs. The reason which Van't Hoff's law can be applied to action of drugs may be thought that the rate of adsorption of drugs into the active point of cells is under the influence of temperature. (5) Temperature coefficient of action of drugs injected subcutaneously takes the genuine value near by the minimum effective dosage. When the time needed to the gradual increase of concentration in blood in proportion to the increase of dosage of drugs is permitted, temperature coefficient takes the larger value than the genuine one, and the process which drugs are absorbed into the blood vessel through the part injected subcutaneously does not give an influence to temperature coefficient, because in this case there may be not adsorption. (6) When the relation between the minimum effective dosage of each drug and temperature at 15°C aud 25°C was investigated, it was found that the minimum effective dosage hardly changed by the difference of temperature but had possibility to become slightly small at high temperature. (7) After all temperature coefficient of action of drugs is not nearly estimated from the active dosage, but is determined by the comparison of the time needed to produce the action of a certain dosage of drugs.
The mode of action of glycols as vehicle and solvent to the penetration. of antibacterial activity of furan derivatives was previously investigated (See no. 8 and 11 of this Breviaria). in this study we observed influences of surface active agents [Tween 80, Span 80, Emasol 110, Aerosol 1B] in vehicles (carbowax (PEG, ) petrolatum, Unguentum simplex) and solvents [water, propylene glycol (PG, ) olive oil] on the antibacterial penetration of furacin. The paper disc agar plate method known in quantitative analysis of penicillin and the one dimensional diffusion method widely used as a biological method for assaying antibiotics were used as in the previous experiment. Staphylococcus aureus Terashima was used as a test strain. The results obtained were as follows : (1) The penetration of furacin in PEG-base was not influenced or slightly by the concentration of 10% each agent contained in the base. (2) The penetration of furacin in petrolatum and Ung. simplex was increased a little by Tween 80, Span 80 and Emasol 110 though it was not by Aerosol 1B. (3) Furacin in water, 30%FG-water solution and F G penetrated more markedly in the presence of Aerosol 1B than in the presence of Tween 80, Span 80 or Emasol 110. (4) When olive oil was used as a solvent, the penetration of furacin was decreased by Tween 80, Span 80 and Emasol 110 but it was not affected by Aerosol 1B.