We established a new method to quantitatively evaluate two types of consumed energies resulting from plastic deformation (Ep) and viscosity (Ev) of sample. To evaluate a new parameter (ΔE/ΔV), the tabletting velocity (V) dependence of Ev, was determined. We found that the total consumed energy (Et) consists of Ep and Ev, and the tabletting velocity dependence of Et is expressed as a simple first order equation, Et=a·V+b, where a and b mean ΔE/ΔV and Et, respectively. The parameter ΔE/ΔV is considered to express the grade of negative contribution of sample viscosity to the tabletting process.
Complementary Tristimulus Colorimetry (CTS method) which has the advantage of simultaneous determination of several components, was applied to the dissolution test of tablets. The test (National Formulary Method) was performed on EA tablets which contain two and Tridocelan tablets which contain three components. Our data indicated that the CTS method is useful in dissolution tests for each tablet component.
We describe the synthesis of derivatives of 10, 10-dimethyl-1, 2, 3, 4, 4a, 5, 10, 10a-octahydrobenzo [g] cinnoline. Reduction of 2, 3, 4, 4a, 5, 10-hexahydro-8-methoxy-10, 10-dimethyl-3-benzo [g] cinnolone (11) in the presence of PtO, gave a mixture of cis and trans-8-methoxy-10, 10-dimethyl-1, 2, 3, 4, 4a, 5, 10, 10a-octahydro-3-benzo [g] cinnolone (70% 3a and 30% 3b). This mixture could be separated by successive fractional crystallization. The assignment of stereochemistry of the ring fusion in 3a and 3b was based on nuclear magnetic resonance spectra and comparison of reactivity of these compounds with 3-methyl-2-butenyl bromide. The reaction of 3a and its derivatives with boron tribromide and sodium bis (2-methoxyethoxy) aluminium hydride are also described.
Thermal condensation of ethyl 2-ethoxycarbonylacetimidate (I') with 2-ethoxycarbonylacetamidine (II') provided a good yield of ethyl 6-amino-3, 4-dihydro-4-oxo-2-pyrimidine-acetate (IIIa). Treatment of the amidine (II') with β-dicarbonyl compounds under basic conditions exclusively afforded the corresponding ethyl 2-aminonicotinates. On the other hand, 2-(2-cyanoethyl)-2-ethoxycarbonylacetamidine (VIII) which was obtained by the Michael reaction of II' with acrylonitrile, reacted with acetylacetone to give ethyl 3-cyano-2-(4, 6-dimethyl-2-pyrimidinyl) butyrate (XVII). Similarly, ethyl 2-(4, 6-dimethyl-2-pyrimidinyl)-3-phenylpropionate (XX) was synthesized through the condensation of II' with benzyl chloride and successive treatment with acetylacetone.
The chemical constituents of the herbs of two gigantic types (A and B type) of Farfugium japonicum (L.) KITAM. (Compositae) were examined from the chemotaxonomical standing point. Two new non-steroidal 8-epi-eremophilenolides (II and III) and an eremophilenolide (I) in addition to three known terpenes (bakkenolide A, α-amyrin and brein) were isolated from Ligularia tussilaginea (BURM.) MAKINO var. gigantea MAKINO (A type). From Farfugium japonicum (L.) KITAM. var. giganteum (SIEB. et ZUCC.) KITAM. (B type), were isolated six constituents : I, II, bakkenolide A, α-amyrin, brein and phytol.
Lactobacillus acidophilus A-28, L. casei S-1, L. casei C-16, L. plantarum 11-35, L. arabinosus and L. fermenti F-4 were grown aerobically in a MRS glucose medium. The suspensions of each cell consumed oxygen in the presence of glucose. The oxygen consumption of lactobacilli takes place in a cytochrome-independent electron transport system with little inhibition by respiratory inhibitors such as KCN, NaN3 or antimycin A. Most lactobacilli except L. fermenti were grown aerobically also in a MRS mannitol medium. The suspensions of each cell consumed markedly more oxygen in the presence of mannitol than in the presence of glucose. L. acidophilus grown in a hexose (glucose, mannose, galactose or fructose) medium consumed more oxygen in the presence of hexose than in the presence of polyol (sorbitol or mannitol). L. acidophilus grown in a polyol medium consumed markedly more oxygen in the presence of polyol than in the presence of hexose. The activity of D-mannitol-1-phosphate : NAD oxidoreductase in cells grown in the mannitol medium was much higher than that of cells grown in the glucose medium. These results suggest that the increase of oxygen consumption of lactobacilli by repeated cultivations in a MRS polyol medium closely relates to the adaptive synthesis of the enzymes concerned with the polyol utilization.
When an ion permeates through cellulose membrane in mixed electrolyte solutions. it can overshoot if ionic flux, driven by the diffusion potential gradient, is large enough upon the concentrations reaching the equilibrium value. Ionic permeation through cellulose membrane was measured for the HCl-CaCl2-H2O ternary system at 25°. The concentration change for permeation was determined at various times. We concluded that overshooting can occur not only with the fastest H+ ion, but also the slowest Ca2+ ion. The condition of ionic overshooting was revealed theoretically for the ternary systems which contain two kinds of cations and one kind of anions. Moreover, permeation patterns with passage of time was studied in connection with reverse permeation and overshooting.
Optical isomers of 4-ethyl-5 or 6-methyl-2, 3-dioxopiperazine were prepared from (S) or (R)-alanine, respectively, and subjected to synthesis of the penicillin derivatives (R1=CH3 of II, III, IV, V) via the phenylglycine derivatives (XVI). 6-Alkyl-4-ethyl-2, 3-dioxopiperazine derivatives were prepared and these phenylglycine derivatives (XXVI) were separated to diastereomers XXVIa, XXVIb by silica gel column chromatography. Their configurations were determined on the basis of the correlation of thin-layer chromatography (TLC) Rf values and optical rotations. The corresponding penicillin derivatives (II, III) were prepared from XXIVa, XXIVb. These penicillin derivatives showed in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Klebsiella pneumoniae and Serratia marcescens, the activity being in the order of II, piperacillin IV, V, III. In (S)-6-alkyl derivatives (II), the stability against β-lactamase increased with increasing the number of carbons of the 6-alkyl group.
A series of 21-methyl-20, 21-diketocorticosteroids (1-10), 21-methylprednisolone derivatives (11-19) and 21-hydroxymethylcorticosteroids (20-22) were tested for anti-inflammatory activity in the carrageenin edema test, carrageenin abscess test and granuloma pouch test in rats. 11β, 17α-Dihydroxy-21-methylpregna-1, 4-diene-3, 20, 21-trione 17-acetate (1), 17-propionate (2), 17-n-butyrate (3) and 17-benzoate (4) showed potent or slightly less activity compared to that of prednisolone, while 17-deacylated compound i.e. 11β, 17α-dihydroxy-21-methylpregna-1, 4-diene-3, 20, 21-trione (5), did not show any significant activity at the dose tested. 6α-Methylation (6) or 9α-fluorination (7) of 1 potentiated the activity of 1 but the simultaneous introduction of 9α-fluorine and 16α-methyl groups (8) into 1 failed to potentiate its activity. 21-Methylprednisolone 17-acetate (13), 17-propionate (14), 17-n-butyrate (15), 17-benzoate (16) and 21αF-acetate (17) or 21βF-acetate (18) showed potent activity, but 21-methylprednisolone per se, 21αF-ol (11) or 21βF-ol (12), did not show any significant activity at the doses tested. 21-Hydroxy-methyldexamethasone (22) showed weak anti-inflammatory activity, and 21-hydroxymethylprednisolone (20) and 21-bis (hydroxymethyl) prednisolone (21) did not have any significant activity.
We developed a highly sensitive and specific method for the quantitative determination of N1, N1-anhydrobis (β-hydroxyethyl) biguanide (ABOB) in human serum and urine. A triazine derivative derived from ABOB was analyzed by mass fragmentography and a similar triazine derivative from 1-n-butylbiguanide (buformin) was synthesized and used as an internal standard. The molecular ions of ABOB and buformin triazine derivatives, m/e 249 and 235, respectively, were recorded after elution from the gas chromatographic column, and ABOB in biological fluid was determined. Mass fragmentographic analysis requires less than 5 min and allows an accurate determination of ABOB in the range of 0.02-1 μg/ml of human serum. The standard deviation is less than 12% in the 0.1-1 μg/ml range. A time course study of blood concentration and elimination rate and urinary excretion following a single oral 500 mg dose of ABOB or repeated administration for 6 days was performed.
Penetration of a series of phenothiazine derivatives (PTZ) dissolved in phosphate buffer (pH 6.92, ionic strength 0.1) into dipalmitoyl lecithin (DPL) monolayer was studied by the meaeurement of surface pressure (F)-surface area (A) relationships. The surface pressure increase (ΔF) by the penetration of each PTZ into the monolayer under a constant PTZ concentration (10-5M) at a constant molecular area occupied by DPL (75 Å2/molecule) was assumed to be a characteristic parameter on each PTZ, which represents the difference in hydrophile-lipophile balance and affinity to DPL molecule in liquid-expanded state. Relationships between ΔF and some physico-chemical parameters and pharmacological activities, were examined and discussed from the view point of the possibility of employing ΔF as a new physico-chemical parameter which correlates with the pharmacological and clinical potency of psychotropic drugs. The surface pressure increase (ΔF) was found to be correlated with the partition coefficient in n-octanol/water system and also with the surface activity at air-water interface and the protein binding capacity. The correlation between ΔF and some pharmacological activities was also confirmed. Thus, ΔF was suggested to be a valuable parameter, likewise the partition coefficient in oil/water system, which represents quantitatively the difference in pharmacological potency of a series of phenothiazine derivatives.
Carboxylic acid esters (II-VI) of pentazocine (I) and aminoalkylcarboxylates (VIII-XI) of acetaminophen (VII), phenolic hydroxy compounds, were synthesized and their hydrolysis studied. The aminoalkylcarboxylates (XIII-XV) of bucetin (XII), alcoholic hydroxy compounds, were also synthesized and their hydrolysis rates compared with those of VIII-XI. Similarly, the hydrolysis rates of these derivatives in pH 7.4 phosphate buffer with 1% rabbit plasma were measured. The results showed that t1/2 values of the hydrolysis rates of II, III and VI in the buffer with plasma were 8-120 times faster than those in the buffer alone.
Proton magnetic resonance spectra of several ethyl indole-2-carboxylate derivatives in the presence of a shift reagent, tris (dipivalomethanato)-europium [Eu (DPM)3], were measured in CDCl3 and good straight lines were obtained on plotting induced shift vs. concentration of Eu (DPM)3 for each signal. Application of the McConnell-Robertson equation to interpret pseudocontact shifts of the indole derivatives gave good agreement between measured and predicted shifts. The relationship between substituents of indoles and the position of the co-ordinated Eu atom is discussed.
A new method was developed for quantitative analysis of deuterium-labelled and endogenous bile acids in human serum, urine, bile and feces. The conventional extraction method was modified to improve the recovery of the sulfated bile acids. The sulfated and nonsulfated bile acids were adsorbed on an Amberlite XAD-2 column, eluted with methanol containing 20 mM NaOH, and separated on a Sephadex LH-20 column. Sulfated bile acids were dissolved in ethanol (pH 1)-acetone (1 : 9, v/v) and solvolysed for 3 hr at 37°. A new alkaline hydrolysis method was also devised ; bile acids were dissolved in 4 N NaOH-methanol (1 : 1, v/v) and hydrolyzed in a screw-capped Pyrex glass tube at 80° for 16 hr. After extraction with ether, bile acids were converted to methyl ester propionate derivatives. The determination of endogenous and deuterium-labelled bile acids was accomplished by gas chromatography-mass fragmentography. The reproducibility of the present method was good (3-8% of relative standard deviation for endogenous bile acid in serum) and 11, 12-2H2-chenodeoxycholic acid was determined up to 1% of the coexisting chenodeoxycholic acid. Endogenous bile acid levels in biological materials were measured and compared with previously reported results. The present method was sensitive and useful for the quantitation of minute amounts of bile acids. Further, this was a recommendable method for the determination of pool size of bile acids by using deuterium-labelled bile acids.
We used high-speed liquid chromatography in the quantitative analysis of paeoniflorin content in Paeonia Radix. Sufficient separation of paeoniflorin was obtained under appropriate conditions (HITACHI Gel 3010, eluted with 50% MeOH). We observed the monthly variation of paeoniflorin content and found that the best month for collecting Paeony root is November because of the maximum paeoniflorin content. Comparison of paeoniflorin content among several products in various habitats was also examined. We also discovered that one-year cultivated Paeony root contains more paeoniflorin than three-year cultivated one.
An attempt was made to prepare 3H-dihydromorphine as a labeled hapten antigen. Catalytic reduction of morphine with tritium gas, using colloidal palladium as a catalyst, removal of radioactivity contamination by the use of H-H type reaction vessel, and final purification with neutral activated alumina afforded a product with specific radioactivity of 97.47 mCi/mmol.
Prunuside from purgative drugs, the fruits of Prunus japonica THUNB. was identified with multiflorin A [kaempferol-3-(6-O-acetyl)-β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranoside]. In addition, three compounds, ursolic acid (II), vanillic acid (III), proto-catechuic acid (IV) and four known flavonoids, afzelin (V), kaempferitrin (VI), multiflorin B(VII) and multinoside A (VIII) were isolated.