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Showing papers in "Yakugaku Zasshi-journal of The Pharmaceutical Society of Japan in 1993"


Journal ArticleDOI
TL;DR: It was found that Japanese Zingiberis Rhizoma and fresh ginger root contained 6-gingerol (1), 6-dehydrogingerdione (6), and galanolactone (7) as major constituents, whereas 7 was not detected in imported Zingibis RhZoma and 6 was detected in Vietnamese ZediberisRhizoma.
Abstract: As a continuing study on the evaluation of various Zingiberis Rhizoma and the chemical characterization of the processing, a quantitative method by high performance liquid chromatography (HPLC) for 6, 8, 10-gingerol (1, 2, 3), 6,8-shogaol (4, 5), 6-dehydrogingerdione (6), and galanolactone (7) has been developed. By the use of this HPLC method, the contents of these compound in twenty kinds of Zingiberis Rhizoma [originating in China, Taiwan, Vietnam, and Japan (Shizuoka Prefecture)] and fresh ginger root cultivated in Shizuoka Prefecture were examined. It was found that Japanese Zingiberis Rhizoma and fresh ginger root contained 6-gingerol (1), 6-dehydrogingerdione (6), and galanolactone (7) as major constituents, whereas 7 was not detected in imported Zingiberis Rhizoma and 6 was detected in Vietnamese Zingiberis Rhizoma. Furthermore, the contents of 1 and 7 in fresh ginger root decreased remarkably during the processing procedure for Zingiberis Rhizoma. In addition, anti-ulcer sesquiterpene constituents in seven kinds of Zingiberis Rhizoma were analyzed by means of gas liquid chromatography (GLC).

48 citations


Journal ArticleDOI
TL;DR: It is suggested that GBE promotes the hair regrowth and could be used as a hair tonic.
Abstract: Effects of 70% ethanolic extract from leaves of Ginkgo biloba (GBE) on the hair regrowth in normal and high butter diet-pretreated C3H strain mice which posterior hair we shaved were investigated. GBE showed a promoting effect on the hair regrowth. GBE had the inhibitory effects on blood platelet aggregation, thrombin activity and fibrinolysis. GBE inhibited the increase of serum the triglyceride level in high cholesterol diet-treated rats. These results suggested that GBE promotes the hair regrowth and could be used as a hair tonic.

46 citations


Journal ArticleDOI
TL;DR: Hot water extracts of Lithospermum erythrorhizon and Prunella vulgaris showed the strongest anti-HIV-1 activities and suppressed the replication of HIV-1 growth more strongly than the cold water extracts.
Abstract: The anti-HIV-1 effects of 204 crude drugs of common use in Japan were evaluated in vitro. As a result, 45 samples inhibited HIV-1-induced cytopathogenicity in MT-4 cells. In particular, the hot water extracts of Lithospermum erythrorhizon (root) and Prunella vulgaris (spike) showed the strongest anti-HIV-1 activities. Their IC100 values were both 16 micrograms/ml. In general, the hot water extracts of the crude drug suppressed the replication of HIV-1 growth more strongly than the cold water extracts.

36 citations


Journal ArticleDOI
Takao Inoue1
TL;DR: The diarylheptanoid constituents of the titled plants and their close plants were reviewed and some biological activities of A. nikoense and M. rubra were described.
Abstract: The diarylheptanoid constituents of the titled plants and their close plants were reviewed. Many new diarylheptanoids and their glycosides named acerogenin and aceroside were isolated from the stem bark of Acer nikoense, A. griseum and A. triflorum. Myricanone, myricanol and its five new glycosides were isolated from the stem bark of Myrica rubra, and myricanone and galeon, from the stem of M. gale var. tomentosa. The structures of these compounds were determined on the basis of chemical and spectral evidence, and chemotaxonomy of the above plants was briefly discussed. In addition biosynthesis of acerogenin A, revision of the structure for isomyricanone derived from myricanone, and some biological activities of A. nikoense and M. rubra were described.

34 citations


Journal ArticleDOI
TL;DR: Three new phenolic compounds were isolated from methanol extracts of the leaves of Daphne pseudo-mezereum (Thymelaeaceae) and characterized as (-)-pinoresinol di-O-glucoside, together with six known compounds, using 1H- and 13C-NMR spectra.
Abstract: Three new phenolic compounds were isolated from methanol extracts of the leaves of Daphne pseudo-mezereum (Thymelaeaceae) and characterized as (-)-pinoresinol di-O-glucoside (1), 5-hydroxy-7-methoxy coumarin 8-O-beta-D-glucoside (2), diosmetin 7-O-beta-D-xylopyranosyl (1-->6) beta-D-glucopyranoside (3), respectively, together with six known compounds, using 1H- and 13C-NMR spectra.

27 citations


Journal ArticleDOI
TL;DR: The strategy for the development of a new universal vaccine which generates the antibody whose supervariable region mimics the common receptor sialo-sugar chains for all the subtypes of influenza viruses is also described.
Abstract: Influenza A, B viruses contain 2 viral specific, membrane associated glycoprotein antigens, hemagglutinin and sialidase. Hemagglutinin is essential for the initial binding of the virus to the cell membrane receptors that contain sialic acid such as gangliosides and sialo-glycoproteins. Hemagglutinin is also important for the intracellular viral uncoating by the low pH fusion processes. The evolution of the influenza viruses and host range variation come from the mutation of hemagglutinin and sialidase genes and change of their sialo-sugar chain recognition together with alteration in the antigenic epitopes. In this report, the molecular mechanism of the relationship between the evolutional change of the viral glycoproteins, especially hemagglutinin molecules and the change of the receptor binding specificity is reported, and also the strategy for the development of a new universal vaccine which generates the antibody whose supervariable region mimics the common receptor sialo-sugar chains for all the subtypes of influenza viruses is also described.

23 citations


Journal ArticleDOI
TL;DR: This article reviews the structure-activity relationships, biological properties and synthesis of two new oral cephalosporin antibiotics, cefixime (CFIX) and cefdinir (CFDN), and proposes mechanisms of intestinal absorption of CFIX and CFDN.
Abstract: This article reviews the structure-activity relationships, biological properties and synthesis of two new oral cephalosporin antibiotics, cefixime (CFIX) and cefdinir (CFDN). Our research into new oral cephalosporin antibiotics began in the late 1970's. The first goal of our research was to discover a new oral cephem possessing similar antibacterial activity and resistance to beta-lactamase as the 3rd generation injectable cephalosporins. We focused our attention on searching for a non-prodrug type cephem, that is, a new parent structure with high intrinsic absorption. We selected ceftizoxime (CZX) as a seed compound due to its relatively high excretion rate (8.5%) in the urine after oral administration to rats. We concentrated our research on the chemical modification of the oxime moiety in CZX based on our hypothesis for oral absorption, and discovered a lead compound with a carboxymethoxyimino group which displayed better urinary excretion (41.0%). Optimization studies led to a new oral cephem, CFIX. However, CFIX shows only low to moderate antibacterial activity against gram-positive bacteria such as S. aureus. Hence, the second goal of our research was to discover a new oral cephem with enhanced activity against gram-positive bacteria. From a consideration of structure-absorption relationships, we studied the activity and absorbability of cephems bearing other acidic functional groups at the oxime moiety of CFIX. As a result, we found a new oral cephem, CFDN with a hydroxyimino group at the 7-position. CFIX has excellent biological properties, displaying potent antibacterial activity against a wide range of gram-positive bacteria except S. aureus and gram-negative bacteria including opportunistic pathogens, high stability towards beta-lactamases and long acting efficacy. CFDN exhibits excellent and well balanced antibacterial activities against gram-positive and gram-negative bacteria. The pharmacokinetic of CFDN in healthy volunteers showed that serum levels were high enough to make CFDN as an effective antibacterial agent. The proposed mechanisms of intestinal absorption of CFIX and CFDN are briefly described. The efficient synthetic methods to CFIX and CFDN were achieved via a common intermediate, 7-amino-3-vinylcephalosporanic acid diphenylmethyl ester from 7-ACA.

20 citations


Journal ArticleDOI
TL;DR: Results indicate that quercitrin might have an inhibitory effect on acute inflammation.
Abstract: Anti-inflammatory activities of quercitrin (Qu) were studied using various experimental models in mice, rats and guinea pigs. Qu (50, 100 and 200 mg/kg, p.o.) inhibited the rat hind paw edema induced by various phlogistics (carrageenin, dextran, histamine, serotonin and bradykinin) in a dose-dependent manner, and 200 mg/kg of this compound also inhibited the scald edema induced by hot water (54 degrees C). Qu did not show any significant inhibition of the ultraviolet light-induced erythema in guinea-pigs and of the increase of vascular permeability induced by acetic acid in mice. Qu did not affect the granuloma formation in a cotton pellet and the development of adjuvant arthritis in rats. These results indicate that Qu might have an inhibitory effect on acute inflammation.

19 citations


Journal ArticleDOI
TL;DR: To evaluate the bioequivalence between Coptidis Rhizoma and cultured cells, it is important that the values of Tmax, Cmax and AUC24h of berberine after oral administration of both extracts are not different, and about the same values of berbertine by the combined use of both Extracts and the aqueous extract of other crude drugs are required.
Abstract: The present study was carried out to evaluate the bioequivalence between Coptidis Rhizoma and the cultured cells of Coptis japonica Makino var. dissecta Nakai to compare the concentration of berberine in the rat plasma after oral administration of both aqueous extracts. The concentration of berberine in the plasma after oral administration of both extracts was determined by HPLC. It was found that the values of time required for the maximum concentration (Tmax), the maximum concentration (Cmax) and the area under the plasma-time curve (AUC24h) of berberine in the rat plasma after oral administration of both extracts were about the same. It was also found that the values of Tmax, Cmax and AUC24h of berberine after oral administration of both extracts and an aqueous extract of Glycyrrhizae Radix were about the same as that of individual administration of both extracts. From these results, to evaluate the bioequivalence between Coptidis Rhizoma and cultured cells, it is important that the values of Tmax, Cmax and AUC24h of berberine after oral administration of both extracts are not different, and about the same values of berberine by the combined use of both extracts and the aqueous extract of other crude drugs are required.

17 citations


Journal ArticleDOI
TL;DR: In this paper, the serum 4-O-methylpyridoxine (MPN) levels in a 21 months-old patient with gin-nan food poisoning were determined by HPLC.
Abstract: The serum 4-O-methylpyridoxine (MPN) levels in a 21 months-old patient with gin-nan food poisoning were determined by HPLC. The blood of the patient was taken at 8.5 and 15.5 h after taking about 50 ginkgo albumens. After deproteinization of the serum, the supernatant was pretreated with Sep-pak C18 cartridge and was applied to HPLC. HPLC was performed with a Hibar LiChrosorb RP-18 (4.0 mm i.d. x 250 mm, 7 microns) using a fluorescence detector (wave length of excitation and fluorescence; 290 and 400 nm, respectively). The serum MPN level was determined by the absolute calibration method. The determination limit of MPN in the serum was 0.05 micrograms/ml. The serum MPN concentration was 0.09 micrograms/ml at 8.5 h after taking ginkgo seeds, and was less than the determination limit of MPN (0.05 micrograms/ml) at 15.5 h. MPN, isolated from the seed of Ginkgo biloba L., is responsible for "gin-nan food poisoning," and its cardinal symptoms are mainly tonic and/or clonic convulsions and loss of consciousness. Infants are particularly vulnerable. This method may be available for proving the gin-nan food poisoning, chemically.

17 citations


Journal ArticleDOI
TL;DR: The analysis has shown that the presence of the 1,4- and 1,2-hydroquinone in A-ring and/or B-ring of flavonoids and hydrophobicity of the molecule are responsible for the in vitro inhibitory activity.
Abstract: 145 flavonoids were studied for their inhibitory effects on the iron-induced lipid peroxidation in mitochondria obtained from rat livers. Of these compounds tested, 30, 57, 59, 67, 70, 72, 77, 102 and 110 (ED50 < or = 0.5 nmol/mg prot) showed distinctly more potent inhibitory activity than baicalein (ED50 < or = 5 nmol/mg prot) and 59 and 72 (ED50 < or = 0.05 nmol/mg prot) exhibited the most potent activity. In order to elucidate the relationships between substituents on the flavonoid skeleton and the biological activity, the quantitative structure-activity relationships (QSAR) were analyzed by the adaptive least-squares (ALS) method for 142 flavonoids. The analysis has shown that the presence of the 1,4- and 1,2-hydroquinone in A-ring and/or B-ring of flavonoids and hydrophobicity of the molecule are responsible for the in vitro inhibitory activity.

Journal ArticleDOI
TL;DR: The structure of the newly isolated minor lupin alkaloid from the seeds of S. flavescens was determined as (-)-leontalbinine N-oxide from its spectral comparison with the authentic sample, and seems to be specific to the reaction of (+)-matrine N- oxide with ferrous reagents.
Abstract: The possibility of the biomimetic transformation of (+)-matrine N-oxide, a main alkaloid in Sophora flavescens var. angustifolia, under various oxidative conditions was examined by the use of several metallic ions. When (+)-matrine N-oxide was warmed with FeSO4, or Fe(COOH)2 in MeOH-H2O at 40 degrees C, (-)-7, 11-didehydromatrine [(-)-leontalbinine], a minor alkaloid in the same plant, was obtained along with (+)-matrine. This selective formation of (-)-leontalbinine seems to be specific to the reaction of (+)-matrine N-oxide with ferrous reagents. In addition, the structure of the newly isolated minor lupin alkaloid from the seeds of S. flavescens. was determined as (-)-leontalbinine N-oxide from its spectral comparison with the authentic sample.

Journal ArticleDOI
TL;DR: The combination of CyD derivatives and pharmaceutical additives was also useful to modify the release rate of various drug molecules.
Abstract: Hydrophobic cyclodextrin (CyD) derivatives, such as 2,6-di-O-ethyl-beta-CyD (DE-beta-CyD), 2,3,6-tri-O-ethyl-beta-CyD (TE-beta-CyD), carboxymethylethyl-beta-CyDs (CME-beta-CyDs) with different degrees of substitution, 2,3,6-tri-O-acyl-beta-CyDs with different alkyl chains (C1-C12) were prepared and their chemical structures and physicochemical properties were elucidated. Furthermore, possible utilities of hydrophilic and hydrophobic CyD derivatives as modified-release drug carriers were evaluated on the basis of in vitro/in vivo correlations. The results obtained in this study are as follows: (1) Hydrophilic CyDs such as 2-hydroxypropyl-beta-CyD are useful as immediate-release type carriers for poorly water-soluble drugs such as nifedipine. (2) Hydrophobic CyDs such as ethylated and acylated beta-CyDs can be used as prolonged-release type carriers for water-soluble drugs such as diltiazem hydrochloride, buserelin acetate and molsidomine. (3) Enteric CME-beta-CyD derivatives are useful as delayed-release type carriers, and also as stabilizers for prostaglandin E and carmofur which are labile under alkaline conditions. (4) Various release rates can be obtained by combining hydrophilic and hydrophobic CyD derivatives in appropriate mixing ratios, e.g., double-layer tablets consisting of beta-CyD complex and DE-beta-CyD/CME-beta-CyD complexes released drugs rapidly at an initial stage, followed by slow release. The combination of CyD derivatives and pharmaceutical additives was also useful to modify the release rate of various drug molecules.

Journal ArticleDOI
TL;DR: Protective effects of 41 Taiwan crude drugs on rat hepatic injuries caused by carbon tetrachloride (CCl4) and alpha-naphthylisothiocyanate (ANIT) were investigated and water extracts showed higher protective potency than the methanol extracts.
Abstract: Protective effects of 41 Taiwan crude drugs on rat hepatic injuries caused by carbon tetrachloride (CCl4) and alpha-naphthylisothiocyanate (ANIT) were investigated. The methanol extracts of Elephantopi Herba and Lonicerae Flos inhibited the release of intrahepatic enzymes and histological changes by CCl4. The methanol extracts of Canarii Radix, Arecae Pericarpium, Cynomorii Caulis, Polygoni Cuspidati Radix, Phyllodii Herba, Junci Caulis Medulla, Rubiae Herba and Rhinacanthi Herba protected the hepatic injury by ANIT. Among them, the water extracts of Cymorii Caulis and Junci Caulis Medulla showed higher protective potency than the methanol extracts. And them this two crude drugs also protected the cholestasis by ANIT.

Journal ArticleDOI
TL;DR: 3-Methoxycoumarin-3'-carbonyl)-benzoxazoline-2-thione was synthesized as a precolumn fluorescent labeling reagent for amantadine for use in high-performance liquid chromatography (HPLC) and derivatized quantitatively into a fluorescent compound through the amino group.
Abstract: 3-(7'-Methoxycoumarin-3'-carbonyl)-benzoxazoline-2-thione (MCBT) was synthesized as a precolumn fluorescent labeling reagent for amantadine for use in high-performance liquid chromatography (HPLC). Amantadine was derivatized quantitatively into a fluorescent compound through the amino group by treatment with MCBT at room temperature for 5 min in aqueous 95% acetonitrile solution in the presence of 4-dimethylaminopyridine. The derivative was subjected to HPLC on TSK gel ODS-80TM (250 x 4.6 mm i.d.) with methanol-water (10:1) as the mobile phase and monitored with an excitation wavelength of 355 nm and an emission wavelength of 405 nm. The limit of detection was 2.0 micrograms/ml in the urine. This method was satisfactory with respect to simplicity and precision to quantify amantadine spiked in the urine.

Journal ArticleDOI
TL;DR: The results suggest that MT is produced in the myocardium after Isp administration, and that the roles of MT in the heart and the liver are different.
Abstract: The amounts of myocardial metallothionein (MT) and heavy metal (Zn, Cu) levels during the early stage of the experimental myocardial infarction model induced by isoproterenol (Isp) administration were measured by an atomic absorption spectrophotometry. MT was measured by the Cd-hem method. Myocardial infarction was induced by the administration of 75 mg/kg i.p. of Isp to rats weighing 270 +/- 10 g. Thirty minutes after Isp injection, Zn and Cu levels began to decrease and 12 h later, reached the minimal values compared with the control value. The level of MT began to increase 3 h after the Isp injection and reached the maximal value at 12 h, although MT remained undetectable in the control myocardial tissue by the Cd-hem method. MT levels in the liver increased and total Zn and Cu were elevated compared with the control value 12 h after Isp administration. These results suggest that MT is produced in the myocardium after Isp administration, and that the roles of MT in the heart and the liver are different. It was thought that a rise in MT was induced for the protection of the myocardial cells to injury.

Journal ArticleDOI
TL;DR: The data indicated that the hypoglycemic effect of selenium might be due to the acceleration of glucose metabolism and the inhibition of glucose synthesis in the liver, suggesting a decrease in a source of precursor supply for the gluconeogenesis.
Abstract: We studied the effect of selenium on the glycolysis and gluconeogenesis system in the rat liver. Significant decreases in glucose level in the serum were observed from the 4th day after daily intraperitoneal (i.p.) administration of selenite (173 micrograms/kg, 78.9 micrograms/kg of selenium base equivalent). Selenium was also effective in reducing a precursor of gluconeogenesis, lactate, alanine or glycerol, in the serum. Moreover, there were significant decreases in the activities of pyruvate carboxylase and glucose-6-phosphatase, a rate-limiting enzyme of gluconeogenesis, in the liver of selenium-treated rates. On the contrary, the activities of glycokinase and phosphofructokinase, a rate-limiting enzyme of glycolysis, in the liver of rat treated with selenium significantly increased in comparison with the control group. These data, therefore, indicated that the hypoglycemic effect of selenium might be due to the acceleration of glucose metabolism and the inhibition of glucose synthesis in the liver, suggesting a decrease in a source of precursor supply for the gluconeogenesis.

Journal ArticleDOI
TL;DR: Epidermal growth factor (EGF) in the milk fat globule membrane (MFGM) emulsion enhanced the absorption of this factor from the intestine, especially to the intestinal lymph, suggesting that this dosage form increased the absorptionof EGF, protected the degradation of EGF in the intestine or promoted theabsor of intact EGF.
Abstract: Epidermal growth factor (EGF) in the milk fat globule membrane (MFGM) emulsion enhanced the absorption of this factor from the intestine, especially to the intestinal lymph. Most of the radioactive EGF administered was degraded to small molecular weight materials. These degraded materials were absorbed and appeared in both the intestinal lymph and portal vein blood. However, a certain portion of EGF, although small, appeared in the lymph maintaining the original molecular mass. The MFGM emulsion used enhanced the lymphatic absorption of intact EGF, suggesting that this dosage form increased the absorption of EGF, protected the degradation of EGF in the intestine or promoted the absorption of intact EGF. The enhancing effect on the absorbed dose percentage of EGF recovered using MFGM emulsion was also observed in the portal vein plasma. However, the effect on the absorption of intact EGF was much larger in the lymph than in the portal vein.

Journal ArticleDOI
TL;DR: It is suggested that small peptide isolated from soybean might have some pharmacological effects of anti-fatigue, anti-obesity, and hypoglycemia.
Abstract: The present research was an attempt to determine the pharmacological actions as for anti-fatigue, anti-obesity and hypoglycemia of small peptide isolated from soybean in mice. Small peptide administration prevented the decrease in sporting movement induced by concussion stress for 3 h in mice. In addition, it should be noted that the recovery rate of fatigue in 60 min after small peptide administration was over one hundred percentage in comparison with that after pretreatment, while the equivalent dose administration of amino acid mixture with the same small peptide amino acid composition did not prevent the decrease in sporting movement. In gold-thioglucose (500 mg/kg (i.p.))-induced obese mouse body weight gain, liver weight and body lipid level around uterine were significantly reduced by the chronic oral administration of small peptide (200, 1000 mg/kg). Administration in 1000 mg per kg of small peptide significantly lowered hyperglycemia in 30 and 120 min after glucose (3 g/kg (p.o.)) administration, whereas the equivalent amino acid mixture showed no effect. In conclusion, it suggested that small peptide isolated from soybean might have some pharmacological effects of anti-fatigue, anti-obesity, and hypoglycemia.

Journal ArticleDOI
TL;DR: The interactions of camptothecin and its derivatives (CPT-11 and SN-38) with human plasma proteins (serum albumin (HSA) and alpha 1-acid glycoprotein (alpha 1-AGP)) were studied mainly by means of ultraviolet and fluorescence spectroscopy.
Abstract: The interactions of camptothecin (CPT) and its derivatives (CPT-11 and SN-38) with human plasma proteins (serum albumin (HSA) and alpha 1-acid glycoprotein (alpha 1-AGP)) were studied mainly by means of ultraviolet and fluorescence spectroscopy. The binding constants of lactone ring-opened forms (A form) of CPT and CPT-11 with HSA were larger than those of the intact lactone forms (L form). In the case of SN-38, there was no difference in the constants between A form and L form. The binding constant of CPT (A form) with HSA was larger than those of CPT-11 and SN-38. The presence of cisplatin, which is presumed to be coadministered with CPT derivatives, did not affect the interaction of CPT derivatives with HSA. Only L form of CPT-11 among the CPT derivatives examined interacted with alpha 1-AGP, followed by quenching the fluorescence of alpha 1-AGP.

Journal ArticleDOI
TL;DR: The antitumor activity of a preparation of heat-killed cells of Enterococcus faecalis, FK-23, prolonged the lifespan of C3H/He N mice which were intraperitoneally inoculated with MM46 mammary carcinoma and inhibited the growth of these carcinomas inoculated intradermally.
Abstract: The antitumor activity of a preparation of heat-killed cells of Enterococcus faecalis, FK-23. Intraperitoneal injection of the preparation prolonged the lifespan of C3H/He N mice which were intraperitoneally inoculated with MM46 mammary carcinoma. Not only intraperitoneal but also oral administration of the FK-23 preparation inhibited the growth of these carcinomas inoculated intradermally. The tumor-bearing mice produced tumor necrosis factor (TNF) in their sera 2 h after intravenous injection of OK432. This TNF level increased after the mice were fed with food supplemented with the FK-23 preparation. Additionally, the FK-23 preparation inhibited the growth of Meth A fibrosarcoma in cyclophosphamide-treated BALB/c mice.

Journal ArticleDOI
TL;DR: A simple and precise method was established for the simultaneous determination of daidzin and puerarin and the determination ofdaidzein in oriental pharmaceutical decoctions containing Puerariae Radix using high-performance liquid chromatography with tetra-n-heptylammonium bromide (THA) as an ion-pair reagent.
Abstract: A simple and precise method was established for the simultaneous determination of daidzin and puerarin and the determination of daidzein in oriental pharmaceutical decoctions containing Puerariae Radix using high-performance liquid chromatography with tetra-n-heptylammonium bromide (THA) as an ion-pair reagent. Daidzin and puerarin were eluted within 45 min without interference with co-existing components using an ODS column and a mixture of 10 mM phosphate buffer (pH 6.5)-methanol (68:32) containing 5 mM THA as a mobile phase. Daidzein was eluted within 35 min without interference with co-existing components using an ODS column and a mixture of 10 mM phosphate buffer (pH 6.5)-acetonitrile (72:28 or 68:32) containing 5 mM THA as a mobile phase.

Journal ArticleDOI
TL;DR: In this paper, various substituted 2,3-bis(4-methoxyphenyl)pyridines were synthesized by the cycloaddition retro Diels-Alder reaction.
Abstract: 4,5-Diphenyl-2-ethoxypyrimidine (1), 3,4-diphenyl-6-ethoxypyridazine (2) and 2,3-diphenyl-5-ethoxypyrazine (3) were evaluated for inhibitory activity towards arachidonic acid-induced aggregation of rabbit blood platelet in vitro. 2,3-Diphenyl-5-ethoxypyrazine (3) exhibited significant inhibitory activity. Thus, various 5-substituted 2,3-bis(4-methoxyphenyl)pyrazines were synthesized by the nucleophilic substitution reaction of 5-chloro-2,3-bis(4-methoxyphenyl)pyrazine (9). In a similar manner, substituted 2,3-bis(4-methoxyphenyl)pyridines were prepared from 2,3-bis(4-methoxyphenyl)-6-methylsulfonylpyridine (17), which was synthesized by the cycloaddition retro Diels-Alder reaction of 5,6-bis(4-methoxyphenyl)-3-methylsulfonyl-1,2,4-triazine (16) with norbornadiene. Among the compounds prepared, 6-isopropoxy-2,3-bis(4-methoxyphenyl)-pyrazine (10f) showed the most potent inhibitory activity, which was more than the activity of anitrazafen[5,6-bis(4-methoxyphenyl)-3-methyl-1,2,4-triazine.

Journal ArticleDOI
TL;DR: Adriamycin ointment for local chemotherapy to breast cancer prepared using polyethylene glycol, ammonium polyacrylate and hydroxypropyl cellulose according to an optimum formulation showed an excellent clinical effect in spite of a decreased drug content.
Abstract: Topical drug delivery is important from the view points of improvement of therapeutic effect and reduction of systemic side effects. Utilization of polymeric materials seemed to be as a key for the development of new topical dosage forms including targeting drug delivery systems. Adriamycin ointment for local chemotherapy to breast cancer prepared using polyethylene glycol, ammonium polyacrylate and hydroxypropyl cellulose (HPC) according to an optimum formulation showed an excellent clinical effect in spite of a decreased drug content. Double-layered mucoadhesive sticks for the treatment of uterine cervix cancer were prepared by direct compression of powder mixture of bleomycin, HPC and carboxyvinyl polymer (CP). Drug release property of the sticks could be controlled by the weight of outer layer, drug combining ratio to each layer and coating of core layer. The results suggested a possibility of a "once-a-week" treatment that is preferable for the patients. Magnetic granules for the treatment of esophageal cancer were prepared using ferrite, HPC and CP. Magnetic guidance and retainment of the granules on esophageal mucosa were confirmed using rabbits in vivo. Buoyant sustained release preparations were prepared using chitosan, soybean protein, HPC and other polymers. Usefulness of the buoyant preparations was suggested from the results in vitro and in vivo. Insulin microspheres (IMS) for targeting delivery to the small intestine were prepared by the newly developed method. Employment of enteric coating material (Eudragit) and combination of protease inhibitor protected insulin from enzymatic attack and gave decreased levels of blood glucose by oral administration.

Journal ArticleDOI
TL;DR: The results suggest that the pharmacological action of bithionol, a phenolic anthelmintic, depends on the inhibition of the electron transport system by the competition with RQ.
Abstract: To elucidate the mechanism of anthelmintic action of bithionol, the inhibitory effect of the drug on NADH-fumarate reductase (NADH-FR) of Ascaris lumbricoides suum was examined. NADH-FR, an enzyme of anaerobic carbohydrate metabolic pathway was solubilized from the mitochondria of the worm's muscle with deoxycholate, and then partially purified with the monoethanolamine-Sepharose 4B column chromatography. Rhodoquinone (RQ), which is required for the electron transfer from NADH to fumarate, was separated from the enzyme protein and phospholipids. Although the enzyme protein fraction eluted from the above column did not show NADH-FR activity, this enzyme was reactivated by the addition of purified RQ and phosphatidylcholine. The IC50 value of bithionol for reconstituted NADH-FR was 18 +/- 2 microM. The inhibition type was competitive to RQ. Bithionol inhibited at most 30% NADH-ferricyanide reductase, which did not require RQ, even at high concentration of 150 microM. These results suggest that the pharmacological action of bithionol, a phenolic anthelmintic, depends on the inhibition of the electron transport system by the competition with RQ.

Journal ArticleDOI
TL;DR: A simple method using ion-pair high-performance liquid chromatography was established for the rapid and precise simultaneous determination of honokiol and magnolol in oriental pharmaceutical decoctions containing Magnolia bark.
Abstract: A simple method using ion-pair high-performance liquid chromatography was established for the rapid and precise determination of honokiol(3',5-di-2-propenyl-1,1'-biphenyl-2,4'-diol) and magnolol(5,5'-di-2-propenyl-1,1'-biphenyl-2,2'-diol) in eighteen species of oriental pharmaceutical decoctions containing Magnolia bark. An ODS column and a mixed solvent system of water involving 10 mM tetra-n-amyl-ammonium bromide (TAA) and acetonitrile (4:6) as a mobile phase were used for the separation. Honokiol and magnolol were eluted without interference of other coexisting components within 12 min.

Journal ArticleDOI
TL;DR: The commercial health-supplemental foods of five companies were investigated for the contents of gymnemic acids as DAGA and there were large differences from 38 to 251 mg in the dosage per day recommended by each company.
Abstract: A method of the quantitative analysis was established for the determination of deacylgymnemic acid (DAGA) in the alkaline hydrolysate of the sample containing gymnemic acids which are ingredients of Gymnema sylvestre R. BR. leaves, by means of high-performance liquid chromatography. This method was used for comparing the contents of gymnemic acids in various samples. The amount of gymnemic acids analyzed as DAGA in 70% ethanol extract of dry leaves was about twice that in hot water extract. The commercial health-supplemental foods of five companies were investigated for the contents of gymnemic acids as DAGA and there were large differences from 38 to 251 mg in the dosage per day recommended by each company.


Journal ArticleDOI
TL;DR: The effect of protamine on the stability of AsA in various pH solutions (pH 1-10) was examined after standing for 90 min at 30 degrees C and the effect of Protamine (60 mumol/l) on the stabilized AsA was observed above pH 5 and degradation of As a was controlled at higher pH.
Abstract: Protamine was found to stabilize ascorbic acid (AsA) in aqueous solution. The concentration of AsA (50 mumol/l) dissolved in 0.05 M phosphate buffer, pH 7, decreased by 57% after standing for 90 min at 30 degrees C, whereas 91% of AsA remained under the same conditions in the presence of 60 mumol/l protamine. When 0.5 mumol/l of copper ion (II) was added to the above AsA solution (0.05 M phosphate buffer, pH 7) in the absence of protamine, AsA decreased by 5% after standing for 15 min at 30 degrees C. On the other hand, 91% of AsA remained after 15 min and 52% of AsA remained after 90 min under the same conditions in the presence of 60 mumol/l protamine. Furthermore, the effect of protamine on the stability of AsA in various pH solutions (pH 1-10) was examined after standing for 90 min at 30 degrees C. Degradation of AsA was accelerated by increasing the pH from 1 to 10. On the other hand, the effect of protamine (60 mumol/l) on the stabilization of AsA was recognizable above pH 5 and degradation of AsA was controlled at higher pH. When 0.5 mumol/l of copper ion (II) was added to the above solutions in the absence of protamine, degradation of AsA was greatly accelerated above pH 5. When 60 mumol/l of protamine was added to the solutions, the effect of protamine on the stabilization of AsA was observed above pH 5 and degradation of AsA was controlled at higher pH.