Tortuosity and viscosity of aqueous suspension of coarse particles under stirring were studied. Porosity, ε, was adjusted by changing the particle concentration tortuosity, q, was measured by the conductirity method, viscosity by a rotation viscometer, and apparent aggregation degree (γm/γo) by the sedimentation method. Pyrimidine-penicillin G (PYG) (primary particle radius γo, 1.8 and 13.2 μ), Nylon spheres (γo, 2.9 and 38 μ), glass spheres (γo, 45 and 100 μ), glass bars, and salicylic acid of various sizes (radius/length) were used as the suspending particles. Sodium dodecyl sulfate, and polyvinyl-pyrrolidone were used as the suspending agent. Horizontal tortuosity, qH, was independent of the stirring speed when the latter was over 2000 rpm in the case of glass bars (100 μm), while the qH value was constant in the entire range of the stirring speed in the case of PYG (1.8 μ). Vertical tortuosity, q, was constant against all the stirring speeds tested. It was not affected by the viscosity and temperature of the suspension medium, but it took higher value when the ε value or the primary particle radius, γo, was smaller, or in the presence of a dispersing agent. In the case of larger γo, the curves of q against ε were located near the theoretical curves of q=ε-1/4, which was derived from the two equations, f=ε3/2 and q=√(ε/f). The former had been derived by Tobias for concentrated suspensions. Reduced viscosity η1sp/C and structural viscosity index n showed higher values when ε and γo values were lower. Both η1sp/C and n decreased in the presence of dispersing agents. Both q and η1sp/C increased markedly for ε values of over 0.80, and also n increased markedly for ε values of over 0.70. Both η1sp/C and n increased when q value was over 1.15. It was concluded that q, -η1sp/C, and n are correlated with each other and vary according to the difference of ε, γo, and γm/γo.
4'-Dimethylamino-5, 5'-dioxo-1, 1'-diphenyl-2, 2', 3-trimethyl-N-(3'-pyrazolin-3'-ylmethylidene)-3-pyrazolin-4-ylamine (Schiff's base), which was found in the urine of rats and rabbits, and in the bile of rats after the administration of aminopyrine, inhibited the activity of the enzyme metabolizing aminopyrine, acetanilide, and amobarbital in rat liver 9000×g supernatants. When Schiff's base was administered orally to rats, the metabolism of these drugs by the 9000×g supernatants of the liver was inhibited and the biological half-life of aminopyrine and amobarbital in blood of rats was lengthened. By pretreating rats with Schiff's base, the activity of these drug-metabolizing enzymes in the liver 9000×g supernatants and the ratio of liver weight to body weight increased, and the activity of glucose-6-phosphatase was inhibited. The biological half-life of aminopyrine and amobarbital in blood of rats was shortened by their pretreatment with the Schiff's base.
The effectiveness of purines and pyrimidines as substrates for the induced production of uricase was studied in F-1 strain of Hyphomycetes, in a medium containing casamino acids, as a good nitrogen source for the growth of this strain. The purines were incorporated into the cells at a relatively early stage of the growth and then the enzyme was induced from all the substrates. No other substrates were found more effective than uric acid. The relationship between the amount of added uric acid and uricase production was examined in the following two cases : (1) The maximum concentration of uric acid in the medium was increased to 0.08% by dissolving uric acid into alkaline solution before adding it into the direct medium. Under this condition, the uricase production increased in proportion to the concentration of uric acid added. (2) The amount of uric acid added in the basal medium was increased to 0.30%, beyond its solubility, and undissolved uric acid precipitated in the bottom of Fernbach's culture vessel. In this experiment, there was no distinct relationship between the amount of uric acid added and uricase production. The precipitated uric acid started to dissolve slowly into the medium during the culture and its concentration in the medium increased markedly during the cultured process. Increase in the solubilizing capacity of the medium to uric acid was also observed as in the basal medium.
Three quercetin glycosides, designated f1, f3, and f5, were obtained from the fruits of Rosa multiflora THUNB. The structures of f1 and f3, new flavonol glycosides, were determined to be quercetin 3-β-D-glucopyranosyl-(1→4)-α-L-ramnopyranoside (I) and quercetin 3-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl-(1→4)-α-L-ramnopyranoside (II), respectively, by means of acidic hydrolysis, enzymatic hydrolysis, hydrolysis of methylates, nuclear magnetic resonance measurement of trimethylsilyl ether and methanolysis of fully methylated compounds. f5 was identified with quercitrin (III).
Optical isomers of 5-(3-tert-butylamino-2-hydroxypropoxy)-3, 4-dihydrocarbostyril hydrochloride were synthesized and their anti-isoproterenol activity was examined in anesthetized dog. (S)(-)-isomer was about 20 times more active than (R)(+)-isomer.
An essential oil was obtained in 0.11% yield by steam distillation from the fresh fruit of Canarium album RAEUSCH The oil was treated successively with 5% sodium carbonate and 5% sodium hydroxide solution, and separated into neutral, sodium carbonate-soluble, and sodium hydroxide-soluble fractions. α-Pinene, camphene, β-pinene, myrcene, limonene, 1, 8-cineole, p-cymene, linalool, α-copaene, linalyl acetate, cis-p-2-menthen-1-ol, 1-terpinen-4-ol, trans-p-2-menthen-1-ol, β-caryophylene, citronellyl acetate, β-terpineol, α-terpineol, terpinyl acetate, neryl acetate, geranyl acetate, nerol, δ-cadinene, geraniol, δ-cadinol, elemol, 14 kinds of carboxylic acid, 6 kinds of phenolic compound, and alkane of C10 to C32 were identified from their infrared, mass, and nuclear magnetic resonance spectra, and by chemical methods.
Mixed membranes were prepared from gelatin and chondroitin sulfate C (chs) whose fractions (Xchs) were varied from 0 to 0.317. They were cross-linked by formaldehyde. The membrane potential across these membranes was measured in the systems of KCl, NaCl, LiCl, CaCl2, and MgCl2 solutions. The experimental temperature was 25°. The theoretical values of membrane potential were obtained by summing up a diffusion potential and Donnan potentials at membrane-solution interfaces. The experimental values were in agreement with the theoretical ones in a high concentration range of the solution. From these results, the membrane charge densities (θ) were determined. θ values obtained were negative and decreased with Xchs. They depended on the kind of electrolyte solutions, and this was considered to result from the difference in the bonding rate of cation to chs. The bonding order was [chemical formula]. pH dependence of θ was also examined in acidic region in which gelatin and chs from complexes. It was found that the pH making θ equal to 0 decreased with Xchs.
Thermal stability was examined of 11 kinds of organic adsorbents for sintered thin-layer chromatography, such as ion exchange resins, cellulose ion exchangers, and porous polymers under welding conditions of heating at 100-180° for 10-20 min. Physical, chemical, and mechanical properties of these adsorbents such as changes in color, shape profiles (by scanning electron microscopy), decomposition point (by thermogravimetric differential thermal analysis), ion exchange capacities, packing density, and sedimentation volume were examined under the welding conditions, and no changes in these properties were observed. Among the adsorbents examined, porous polymers such as Amberlite XAD-2 and Merck's microcrystalline cellulose were the most thermostable. Strong and weak acid cation exchangers were more stable than the corresponding anion exchangers. The salt form of these ion exchangers was more stable than corresponding free forms except Amberlite CG-50, CG-400, Machery-Nagel's ECTEOLA cellulose.
Several peptides, H-Lys-Thr-Pro-Arg-OH (VIII), H-Thr-Lys-Arg-Pro-OH (XII), H-Lys-Thr-Arg-Pro-OH (XIV), H-Thr-Pro-Lys-Arg-OH (XIX), and H-Thr-Lys-Pro-Pro-Arg-OH (XXIV), related to tuftsin were synthesized. VIII exhibited a phagocytosis-stimulating activity, to the same degree as tuftsin.
Carbon-13 nuclear magnetic resonance spectrometry of acerinol (I) and its related compounds (IV, V) proposes a revised structure (Ia) for acerinol, which was obtained first from Cimicifuga acerina (SIEB. et ZUCC.) C.TANAKA, and from C. simplex WORMSK. and C. japonica SPRENGEL in the present work. 25-O-Methylacerinol (II), mp 146-148°, C31H48O5, was obtained from C. acerina, while acerionol (III), mp 248-249.5°, C30H46O5, and 24-O-acetylacerionol (IV), mp 201-202°, C32H48O6, were obtained from the above three species of Japanese Cimicifuga plants. Structures are proposed on the basis of their chemical and spectroscopic data.
Dose-response relationship of potentiation of contractile response of isolated vas deferens of a rat to norepinephrine (norepi) and acetylcholine (ACh) by seven potentiators, including cocaine, tripelennamine, diphenhydramine, and phentolamine, were examined. The maximum response of epididymal portion of vas deferens to both agonists was greater than that of prostatic portion and the degree of increase in maximum response induced by the potentiators was in reverse relation to the degree of maximum response. Potentiators increased the maximum response of vas deferens to norepi and ACh up to the same level of maximum response induced by transmural electrical stimulation, which was estimated to be the mechanical limit of contracture. The mechanism of increase in sensitivity and that in maximum response to norepi seemed to be different, but linear relation between increase in sensitivity and that in maximum response to ACh was recognized. Linear relation was also recognized between increase in maximum response to norepi and ACh. Dibenamine inhibited the increase in sensitivity of vas deferens to ACh by cocaine selectively. From these results, the supersensitization of vas deferens of a rat was classified into four groups : (1) Presynaptic catecholamine potentiation, (2) Dibenaminesensitive cocaine-induced supersensitivity, to ACh, (3) Dibenamine-insensitive supersensitivity to ACh, and (4) The so-called nonspecific increase in maximum response to norepi and ACh.
Dose-response relationship of the effect of various potentiators to contraction and relaxation of isolated tracheal preparation of a guinea pig was examined and following results were obtained. (1) Cocaine augmented both contraction and relaxation induced by norepinephrine or epinephrine, but relaxation induced by aminophylline or papaverine was not influenced and that by isoproterenol or trimetoquinol decreased by cocaine. (2) Relaxation induced by norepinephrine or epinephrine was potentiated by chlorpromazine, phentolamine, and Dibenamine, while contractile responses induced by these catecholamines were not influenced by chlorpromazine, and abolished by phentolamine and Dibenamine at the same concentration range for inducing a dose-dependent augmentation of relaxation. This indicates that adrenergic α-blocking activity of these potentiators does not contribute to the augmentation of relaxation induced by catecholamines. (3) Cocaine also increased the sensitivity of tracheal preparation to acetylcholine without any effect on the level of maximum response, but dose-response relationship of cocaine for the potentiation of response to acetylcholine was not coincident to that to norepinephrine. (4) Higher concentration of cocaine decreased the level of maximum response of tracheal preparation to acetylcholine in low-calcium medium, but the mechanism of this inhibitory action remains unsolved.
Studies were made on the effect of polyvinylpyrrolidone (PVP) and sodium carboxymethylcellulose (CMC) on the intestinal absorption of acridine system drugs in rats, and also on molecular interaction between acridine derivatives and the polymers. It was revealed that in the case of PVP-proflavine, PVP-acrinol and CMC-acrinol systems, whose in vitro binding ratio between acridine and polymer is relatively large, the intestinal absorption of acridine derivatives is inhibited by the relevant polymers, while no significant effect of polymer is observed in the case of PVP-quinacrine, CMC-proflavine, and CMC-quinacrine systems whose binding ratio is relatively small. Experimental results suggested that hydrophobic binding and ionic binding play important parts in the interaction between PVP and acridine derivatives and between CMC and acridine derivatives, respectively.
The state of aspirin mixed in the solid Macrogol was examined. Macrogol-6000 and 30% (w/w) aspirin were mixed at 70°, 90°, and 110°, and aged at the same temperature. After the mixture cooled, various tests were carried. As the aging time became longer and the temperature higher, the sample became more transparent and had less consistency by both transparency test and thermal analysis. When a high temperature was used or long time spent for aging, X-ray diffraction patterns and infrared (IR) spectra indicated that aspirin in the mixture was in a liquid state at room temperature. The presence of acetylated Macrogol in the mixture was estimated from nuclear magnetic resonance (NMR) and IR spectra, and by a stoichiometric method, and the presence of salicylic acid was confirmed from ultraviolet ( UV) spectra. It is concluded that transesterification between aspirin and Macrogol 6000 decomposed part of aspirin to salicylic acid, and formation of acetylated Macrogol from Macrogol. Lowering of consistency and increased transparency of the mixture may be due to one of the following three reasons : (1) Dissolution of aspirin into Macrogol, of lower molecular weight formed by lowering of molecular weight of Macrogol 6000 due to heating in the presence of aspirin, (2) complicated lowering of the melting point by four ingredients (aspirin, Macrogol, salicylic acid, and acetylated Macrogol), and (3) delay of crystal growth of aspirin in the mixture.
The moisture sorption and volume expansion of anhydrous α- and β-lactose tablets were examined under various conditions of relative humidity. In the case of anhydrous α-lactose tablets, the moisture sorption and expansion of tablets occurred even at a relatively low humidity, leading to the formation of the α-monohydrate. The rate of moisture sorption and expansion increased with an increase in water vapor pressure and with a lowering in temperature. The effect of tablet thickness and of compaction pressure in tablet making were also examined using anhydrous α-lactose tablets. β-Lactose was less hygroscopic at below 90% relative humidity (R.H.). Moisture uptake was small and the expansion of tablets was not observed. When the water vapor pressure rose to almost saturation, β-lactose absorbed a large amount of moisture to form the α-monohydrate gradually.
Two new methods for the determination of gentiopicroside in gentian radix and Gentiana scabra radix were developed by the combination of thin-layer chromatography (TLC) and spectrophotometry. In the preparative TLC-ultraviolet (UV) method, gentiopicroside contained in the methanol extract ofsamples is quantitatively separated by preparative TLC (detection by a PAN UV lamp) and the amount is determined from the absorbance at 270 nm by using a calibration graph. In the TLC-densitometer (DM) method, the methanol extract containing gentiopicroside is developed on the TLC plate, and the amount of gentiopicroside (Rf=ca. 0.4) is measured by TLC densitometry using a dual-wavelength TLC scanner. By these two methods, the content of gentiopicroside vras determined as 1-2% in gentian idix (Osaka market product), 1-3% in Gentiana scabra radix (Osaka market product), and 7-10% in the fresh root of Gentiana scabra BUNGE.
The Chinese crude drug Qinjao ( ?? 〓) is the root of Gentiana macrophylla PALL. and Gentiana dahurica FISCH. As a continuation of studies on the crude drugs originating from gentianaceous plants, bitter principle of Qinjao was examined and gentiopicroside was isolated as its tetraacetate. The content of gentiopicroside in commercial Qinjao was determined as 0.2-1.5% in Gentiana macrophylla radix (in Hongkong and Peking markets) and 0.2-1.4% in Gentiana dahurica radix (in Hongkong market). Gentianine, major alkaloid previously isolated by Fu, et al.4) seems to be an artefact produced from gentiopicroside during the isolation procedure.
An examination was made to find a simple method for discriminating the contamination of other bitter crude drugs in the dried whole herb of Swertia japonica. Thin-layer chromatography was carried out on the extractives of Swertia herb, and bitter crude drugs likely to be mixed in it, such as gentian radix, Gentiana scabra, radix Sophora angustifolia radix, Isodon herb, and Picrasma wood. It was thereby found that these crude drugs, if contaminated in Swertia herb in 10-20% by weight, would readily be detected by thin-layer chromatography.
Psychosedative action of seven derivatives of 4-substituted 2-amino-6-trifluoromethyl-s-triazines was examined. Among these, 4-[4-(2-hydroxyethyl)piperazin-1-yl] (X) and 4-(4-methylpiperazin-1-yl) (IX) derivatives showed considerable cataleptogenic, antimethamphetamine, and taming effects in mice, in addition to depression of exploratory behavior in rats. 4-Isopropylamino-(I), 4-cyclohexylamino-(IV), and 2-dimethylamino-4-(4-methylpiperazin-1-yl) (XXXIX) derivatives also depressed the exploratory behavior in rats and antagonized the stimulating action of cocaine and caffeine, but they had a very weak activity in other experiments relevant to psychosedative action. 2-Methylamino-4-isopropylamino derivative (XLIII) only inhibited the stimulating action of cocaine and 4-(p-chloroanilino) derivative (VI) slightly depressed the stimulating action of methamphetamine, cocaine, and caffeine. A slight loss of righting reflex in mice was observed only at the lethal dose of the seven derivatives. Judging from these results, the type of action of X and IX was considered to be similar to that of neuroleptics. It seems that piperazine substituent in the triazines played some role for the manifestation of such pharmacological properties as neuroleptics.
From the ether-soluble fraction of the aqueous extract of the leaves of Scutellaria baicalensis GEORGI, two flavanone derivatives, carthamidin (4', 5, 7, 8-tetrahydroxyflavanone) and isocarthamidin (4', 5, 6, 7-tetrahydroxyflavanone) were isolated for the first time as natural products.
2-Mercapto-(I), 2-methylthio-(II), 2-hydrazino-(III), and 2-(3, 5-dimethyl-1-pyrazolyl)-5-alkyl-6-hydroxypyrimidines (IV) were synthesized and their anti-influenza virus activity was examined. Among the tested compounds, inhibitory activity was observed only in the 5-propyl compound (IVb) (50% inhibitory concn. 4.7 μg/ml, index 4.8) and 5-hexyl compound (IVc) (339 μg/ml, 6.3). However, almost all the compounds exhibited a virucidal activity, and especially 5-octyl (Id) (50% virucidal concn. 90 μg/ml, index 8.8) and 5-hexyl (IIIc) (130 μg/ml, 7.7) compounds were considerably active. Compounds which showed toxic concentration of more than 125 μg/ml against HeLa cells were tested in infected mice. When intraperitoneally administered at a level of 100 mg/kg, 5-decyl (Ie), 5-methyl (IIa), and 5-propyl (IIb) compounds and amantadine hydrochloride respectively showed 71, 62, 62, and 55% inhibition of the virus multiplication in the lungs. However, Ie was inactive when administered orally.
Reaction of primary aromatic amines (I) with malonaldehyde bis(diethyl acetal) derivatives (II, V) in ethanol gave malonaldehyde dianil derivatives (III, IV). Treatment of III with bromine afforded bromomalonaldehyde dianil (IV). III reacted with acetic anhydride to give β-(N-acetylamino)acrolein (VII) and acetylamine (VIII). Acetylation of III with acetyl chloride afforded N-acetates (VI), which reacted with acetic anhydride to give VIIb and VIIIb.
Four substances were produced when 4-benzyloxy-2'-hydroxy-4', 5', 6'-trimethoxy-chalcone was irradiated with a high-pressure mercury lamp in ethanolic phosphoric acid under refluxing for over 50 hr. They were isolated and their structures confirmed from spectral data and other syntheses as 3'-benzyl-4'-hydroxy-5, 6, 7-trimethoxyflavanone, 4'-benzyloxy-5, 6, 7-trimethoxyflavanone, 4'-hydroxy-5, 6, 7-trimethoxyflavanone, and 2', 4-dihydroxy-4', 5', 6'-trimethoxychalcone.