Fluidity parameters (angle of repose, fluidity index K, coefficient of internal friction, cohesive force, and flow rate) of pharmaceutical powders with various mixing ratios of two components and three components of powders were measured in order to investigate the possibility of estimating and evaluating the fluidity of mixed powders. Changes in the pattern of the mixing ratio and fluidity depended on whether corn starch was included or not in the mixed powders, and fluidity index K of mixed powders including corn starch showed a minimum value at the mixing ratio of corn starch of 60%. Relation between fluidity index K and mixing ratio of mixed powders excluding corn starch showed nearly a straight line. This study showed that, if the fluidity index K of each pharmaceutical powders was known, there would be a possibility of estimating the fluidity of multi-component mixed powders.
The powder of aspirin and sulfisomezole were sieved into three classes, L, M, and S in the order of their grain size, and used for making tablets. Disintegration time of these tablets was measured for containing various amounts of corn starch. The minimum content of corn starch (critical content) for tablet disintegration was determined and the distance between starch grains in a tablet was calculated from the critical content of disintegrant. The calculations for the distance were based on the following conditions of crystal size : (a) aspirin and sulfisomezole crystals are much larger than starch grains and (b) aspirin and sulfisomezole crystals are nearly the same with starch grains in size. The tablet of small particles required a larger amount of corn starch to disintegrate in water, i. e., tablets of crystal size S showed larger value of the critical content than those of the sizes L and M, but the calculated distance was nearly the same in tablets of L, M, and S size grains. The critical content and the distance were affected by the wetting of crystals. For the tablet of sulfisomezole, which was coated with Aerosol OT, the distance between starch grains necessary for tablet disintegration did not vary with particle size of sulfisomezole. The distance in the tablets of treated crystals was longer than those in tablets of intact crystals.
Examinations were made to clarify the structure of products formed by autoxidation of an antioxidant, ethyl protocatechuate. Irradiation of the antioxidant in ethanol or in methyl oleate with ultraviolet ray resulted in the formation of 5'-ethoxycarbonyl-3, 3', 4-trihydroxybiphenyl-2, 2'-carbolactone which was inactive as an antioxidant, unlike oxidation products of butyl hydroxyanisole. Effect of the substrate and variation in the amount of oxidation products formed are also discussed.
The structures of β-(3-hydroxy-4-methoxyphenyl) ethylbenzene (I) and 1, 2-bis (3-hydroxy-4-methoxyphenyl) ethane (II) were determined by single-crystal X-ray diffraction method. The sweet compound I was synthesized as the essential structure for the sweet taste of phyllodulcin, while the tasteless compound II was synthesized as the chemical modification product of I. Between the structures of I and II, there are distinct differences in the dihedral angles made by the two planes of phenyl group and in the conformation of ethylene bridges. The structure of II is similar in conformation to that of dibenzyl while that of I is not.
In guinea pigs, chlorphenesin carbamate (CPC), a centrally acting skeletal muscle relaxant, was excreted rapidly in urine after oral administration of the 14C-labeled compound. During 5 days, about 93% of the dose administered was recovered from urine and only 2% appeared in feces. The glucuronide of CPC was the major metabolite which accounted for about 87% of the total radioactivity excreted in 48 hr urine and only 2.5% of the urinary radioactivity was excreted as the acidic metabolites including p-chlorophenoxylactic acid, p-chlorophenoxyacetic acid and p-chlorophenol. The biliary excretion of CPC after intravenous administration was less than 10% of the dose administered in guinea pigs, while it was about 42% in rats. The major metabolite found in the bile was the glucuronide in both species. In common bile duct-ligated rats, CPC markedly inhibited the spinal reflex but duration of the action was shorter than that in intact rats. A temporary rise of radioactivity, followed by rapid fall in blood and rapid excretion in urine were observed by the ligation of common bile duct after administration of 14C-CPC, as compared to those in intact rats. CPC was excreted mostly as its glucuronide and the excretion of acidic metabolites decreased markedly in these bile duct-ligated rats. Urinary acidic metabolites increased to a greater extent after oral administration than by a subcutaneous route.
The metabolic fate of biliary chlorphenesin carbamate (CPC) glucuronide after administration to rats was examined. After intraduodenal administration of the bile containing 14C-CPC glucuronide to bile fistula rats, about 21% of radioactivity administered was excreted into the bile during 48 hr. After intravenous injection of 14C-CPC to intact rats, both the unconjugate and glucuronide were recovered in the intestine and only the unconjugate in portal blood. Hydrolysis of CPC glucuronide by the intestinal content was demonstrated in vivo and in vitro. The rate of disappearance of radioactivity from the looped intestines, to which the glucuronide of 14C-CPC was injected, increased from the jejunum to colon. 14C-CPC was incubated with the everted sacs of rat small intestine at pH 7.4, and a small amount of the hydrolyzed product of CPC, chlorphenesin, was detected in the serosal fluid. Oral administration of synthetic 14C-chlorphenesin to rats and guinea pigs revealed that the compound was converted readily to acidic metabolites of CPC, p-chlorophenoxylactic acid and p-chlorophenoxyacetic acid, in both species. The acidic metabolites of CPC had no muscle relaxant activity. In relation to the urinary excretion of large amount of acidic metabolites in rats, the enterohepatic circulation of CPC and a particularly high activity converting CPC to chlorphenesin in the intestinal wall are discussed.
The epithelium capsule was regarded as a composed membrane composed of a negatively charged and positively charged membranes in order to determine the charge density θ*e of this epithelium layer which was found to be -0.0101 mol/l in NaCl solution and -0.0120 mol/l in KCl solution.
Following the previous work on a simulation of powder compaction on two-dimensional model, where 400 discs were used and the cohesion probability P' and insertion probability P" were introduced, 1600 discs (40×40) were used and it was assumed that discs did not shift to the hole present in the lower layer when the coordination number of a disc or the probability variable (R) related to the coordination number was greater than a given value (q). The elimination or jumping probability P'" were newly introduced. Almost all the data of porosity and tapping number followed the first-order rate equation and the rate constant k increased with decreasing the probability P' and with increasing the probability P". As the tapping number increased, the porosity approached a definite value, which varied according to the magnitude of the values of q and P"'.
Addition of arachidonic acid (0.1 mM) to a washed platelet suspension obtained from guinea pigs resulted in platelet aggregation and formation of malonyldialdehyde in vitro. These were inhibited by 2-(5H- benzopyrano [2, 3-b] pyridin-7-yl) propionic acid (pranoprofen), indomethacin and acetylsalicylic acid. The concentrations causing a 50% inhibition of malonyldialdehyde formation were 0.35 μM for indomethacin, 4.6 μM for pranoprofen, and 77 μM for acetylsalicylic acid. Oral treatment of guinea pigs with pranoprofen (0.01 mg/kg), indomethacin (1 mg/kg), or acetylsalicylic acid (10 mg/kg) resulted in inhibition of platelet aggregation induced by the addition of arachidonic acid (0.1 mM). The increased pulmonary pressure with a concomitant decrease of platelet counts induced by the intravenous injection of arachidonic acid (400 μg/kg) to guinea pigs was inhibited by oral treatment with the above agents. These results suggest that pranoprofen inhibits the platelet aggregation by affecting the pathway concerned with prostaglandin synthesis, and may have an antithrombotic activity.
Essential oils of Magnolia denudata DESR. (Magnoliaceae) were examined in detail. The yields of oils were 0.03-0.05% in the fresh shoots (branchlets and leaves), 0.04-0.05% in the leaves, 0.29-0.67% in the flower buds, and 0.08-0.09% in the flower in full bloom. The main components of essential oils of the fresh leaves were β-caryophyllene and (+)-nerolidol, while those of the branchlets and barks were 1, 8-cineole, (+)-terpinen-4-ol, and (-)-α-terpineol, and that of the flower and flower buds was 1, 8-cineole.
The binding of seven commercial sulfonylureas (tolbutamide, chlorpropamide, acetohexamide, carbutamide, chlorpentazide, azepinamide, and tolazamide) by bovine serum albumin (BSA) was investigated using an equilibrium dialysis procedure. The Scatchard plots of the data of six sulfonylureas except tolazamide indicated the presence of two kinds of binding sites. Assuming both concentrations of BSA and sulfonylureas are 5×10-4M, the results of calculation demonstrated that tolbutamide has large binding percentages (97.2%) and tolazamide is relatively small (88.8%). Although the effect of pH and ionic strength of solvent was investigated, the exact mechanism of binding could not be elucidated. A good correlation was observed between the logarithms of BSA binding constants and octanol-water partition coefficients for sulfonylureas. It seemed that their molecular structure that leads to a higher lipophilicity will result in an enhanced BSA binding.
Ferric hydroxide was peptized by pouring the precipitate into an aqueous solution of various organic acids and boiling for 8 hr. The degree of peptization was evaluated by the concentration of ferric hydroxide in the sol thus formed by chelatometry after decomposition of the colloidal particles into ferric ions. The adsorption of these organic acids on ferric hydroxide particles was also measured. In the case of formic, acetic, and propionic acids, the degree of peptization increased with increasing amount of the organic acid adsorbed. However, no peptization took place in the case of butyric and valeric acids. The adsorption isotherms followed Langmuir's scheme, and the minimum acid concentration required for peptization was found to depend on the adsorption constant (k) in the case of formic, acetic, and propionic acids. The addition of a small amount of hydrochloric acid increased the degree of peptization by butyric acid, which can be ascribed to the decrease in dissociation of the latter. It was thus concluded that the adsorption of organic acids promotes, while that of their ions prevents, the peptization.
The aglycon of lagertannin, 3, 4-di-O-methylellagic acid (I), was synthesized from gallic acid and methyl 3-O-methylgallate (II) which was obtained in a fairly good yield by one-step method according to the two layer procedure of Bredereck.
Erythrocyte membrane stabilizing fraction (EMSF) was purified from the acetone extract of the mycelium of Streptomyces sp. F4818 by the combination of chromatography on silica gel and preparative thin-layer chromatography on silica gel. 1) Heat-induced hemolysis was significantly inhibited by EMSF at a concentration of 2 μg/ml and the hypotonic hemolysis was also inhibited by about 50% at a concentration of 12 μg/ml of EMSF. 2) EMSF showed high anti-inflammatory activity for carrageenin-induced edema in the hind paw of rats at the oral dose of 50 mg/kg. 3) It was proved that EMSF was a fatty acid mixture, consisting of C14 : 0, iso- or anteiso-C14 : 0, C15 : 0, iso C15 : 0, C16 : 0, iso-C16 : 0, iso- or anteiso-C17 : 0, C18 : 0, and C18 : 1 from the result of gas chromatography-mass spectra (GC-MS) analysis on their methyl esters. 4) Palmitic acid, the main fatty acid component in EMSF, markedly suppressed the heat-induced, hypotonic hemolysis in vitro and carrageenin-induced edema in vivo.
Anti-inflammatory effect of C10-C20 saturated fatty acids was examined by using heat-induced hemolysis, hypotonic hemolysis, heat-induced denaturation of bovine serum albumin (BSA), and carrageenin-induced paw edema as the experimental systems. 1) Several fatty acids, including C13 : 0 to C17 : 0, were found to protect erythrocytes from heat-induced hemolysis, and C12 : 0 to C16 : 0 significantly inhibited hypotonic hemolysis in vitro. 2) All fatty acids tested showed a significant effect on heat-induced denaturation of BSA at a concentration of 5.0 μg/ml in vitro, but C16 : 0 methyl ester did not show any inhibitory effect at the same concentration. 3) Palmitic acid, its methyl ester, and oleic acid suppressed carrageenin-induced paw edema in rats by oral administration at the dosage of 200 mg/kg, but C16 : 0 methyl ester did not suppress it by intraperitoneal injection. 4) In adrenalectomized rats, palmitic acid also suppressed carrageenin-induced paw edema. 5) Palmitic acid inhibited the granuloma formation caused by felt-pellet at the dose of 100 mg/kg/day (oral) for 5 days, but did not show a significant effect on either exudation into the granuloma pouch or on formation of pouch wall.
Thiourea dioxide, readily obtained by the treatment of thiourea with hydrogen peroxide, has been proved to be a useful reducing agent for the preparation of some kinds of substituted aromatic amino compounds from the corresponding nitro compounds. Reduction of nitrobenzene (I) to aniline (IV) in an alkaline solution, showed that hydrazobenzene (VII) was formed from nitroso- (II), azo- (VI), and azoxy-benzene (V) in a good yield. Some substituted hydrazobenzenes were formed from the corresponding azobenzenes.
Studies were made on the effect of purine nucleosides and nucleotides on the photodecomposition of riboflavine, riboflavine 5'-phosphate, and flavine-adenine dinucleotide, and also on the intermolecular interaction between flavines and purine derivatives. The photodecomposition of flavines was found to be inhibited by purine derivatives, and the inhibitory effect was compared in terms of apparent first-order rate constant (K) of photodecomposition of flavines. The intermolecular interaction was studied from the point of fluorescence quenching of flavines by purine derivatives, and the quenching effect was compared in terms of association constant (KA) of the flavine-purine complexes. Irrespective of the kind of flavines involved, values of K and KA were in parallel, with decreasing order of guanosine, adenine, adenosine, 5'-guanylic acid, 5'-adenylic acid, adenosine triphosphate, inosine, and inosinic acid.
In the presence of platinized palladium-carbon catalyst, 3, 3'-ethylenedipyridine did not undergo intramolecular dehydrogenation and condensation at 2- and 2'-positions with oxygen from aromatic amine N-oxides but reacted at 6-position to give a dimer and a trimer.
Berberine in Coptidis Rhizoma and Oriental pharmaceutical preparations was determined with a small standard deviation and a small coefficient of variation. The sample solution was separated by two-dimensional thin-layer chromatography on a plate (20×20 cm) with two different developing solvents, n-BuOH : AcOH : H2O=7 : 1 : 2, and cyclohexane : diethylamine=9 : 1. The berberine portion was scraped off from the plate and extracted with 1% HCl·methanol. The extract solution was placed in a test tube. After evaporation of the solvent, 5 ml of phosphate buffer (pH 8.0) and 2 ml of phosphate tetrabromophenolphthalein ethyl ester (TBPE) solution (4.0×10-4M) were added to the residue, and the solution was shaken with 5 ml of 1, 2-dichloroethane. Berberine was extracted into the organic layer as a 1 : 1 ion-pair complex with TBPE. Color of organic layer was yellowish green (λmax 610 nm). The quantitative determination of berberine in the range of 4.3-21.6 μg is possible by the mesurement of this coloration at 610 nm.