Wakunaga Pharmaceutical Co.

Hiroshima-shi, Japan

Wakunaga Pharmaceutical Co.

Hiroshima-shi, Japan
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Amano H.,Wakunaga Pharmaceutical Co. | Kazamori D.,Wakunaga Pharmaceutical Co. | Itoh K.,Wakunaga Pharmaceutical Co.
Biological and Pharmaceutical Bulletin | Year: 2016

Three major organosulfur compounds of aged garlic extract, S-allyl-L-cysteine (SAC), S-methyl-L-cysteine (SMC), and trans-S-1-propenyl-L-cysteine (S1PC), were examined for their effects on the activities of five major isoforms of human CYP enzymes: CYP1A2, 2C9, 2C19, 2D6, and 3A4. The metabolite formation from probe substrates for the CYP isoforms was examined in human liver microsomes in the presence of organosulfur compounds at 0.01-1 mM by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Allicin, a major component of garlic, inhibited CYP1A2 and CYP3A4 activity by 21-45% at 0.03 mM. In contrast, a CYP2C9-catalyzed reaction was enhanced by up to 1.9 times in the presence of allicin at 0.003-0.3 mM. SAC, SMC, and S1PC had no effect on the activities of the five isoforms, except that S1PC inhibited CYP3A4-catalyzed midazolam 1′-hydroxylation by 31% at 1 mM. The N-acetylated metabolites of the three compounds inhibited the activities of several isoforms to a varying degree at 1 mM. N-Acetyl-S-allyl-L-cysteine and N-acetyl-S-methyl-L-cysteine inhibited the reactions catalyzed by CYP2D6 and CYP1A2, by 19 and 26%, respectively, whereas trans-N-acetyl-S-1-propenyl-L-cysteine showed weak to moderate inhibition (19-49%) of CYP1A2, 2C19, 2D6, and 3A4 activities. On the other hand, both the N-acetylated and S-oxidized metabolites of SAC, SMC, and S1PC had little effect on the reactions catalyzed by the five isoforms. These results indicated that SAC, SMC, and S1PC have little potential to cause drug-drug interaction due to CYP inhibition or activation in vivo, as judged by their minimal effects (IC50>1 mM) on the activities of five major isoforms of human CYP in vitro. © 2016 The Pharmaceutical Society of Japan.


Shiraishi S.,Qualicaps Co. | Sakata Y.,Wakunaga Pharmaceutical Co. | Yamaguchi H.,Wakunaga Pharmaceutical Co.
International Journal of Pharmaceutics | Year: 2010

We have found that a cast film forms a white film when an aqueous solution comprising hydroxypropyl methylcellulose (HPMC) and calcium salts such as calcium lactate pentahydrate (CLP) and calcium chloride (CaCl2) is used. In contrast, the obtained white film was transformed into a transparent film by the addition of purified water. The transformation time for the change from the white film to the transparent film was dependent on film thickness. The relationship between the transformation time and the film thickness was significantly correlated, and it was found that the white film could be adaptable as time indicator. The formation of a white film comprising HPMC and calcium salts was strongly dependent on temperature conditions. The objective of the present study is to investigate the mechanism of the formation of this white film because of the interaction between HPMC and calcium salts. The DSC and XRPD results indicate that the calcium salts affect the HPMC polymer phase in the cast film comprising HPMC and calcium salts. By carrying out attenuated total reflection Fourier transform infrared (ATR FT-IR) analysis, we found that the white film could be formed by the calcium salts affecting the region associated with the C-O-C, C-O, and CH3 stretching of the HPMC polymer phase. © 2009 Elsevier B.V. All rights reserved.


Patent
Wakunaga Pharmaceutical Co. and Neugen Pharma Inc. | Date: 2011-07-15

An object of the present invention is to provide a pharmaceutical agent useful for treating and preventing neurological disease, having satisfactory solubility and oxidative stress-mediated cell death suppressive activity as well as capable of exhibiting excellent blood-brain barrier permeability. The present invention is directed to an acylaminoimidazole derivative represented by general formula (I) or a salt thereof, and a pharmaceutical and a therapeutic or preventive agent for neurological disease containing the same, as an active ingredient.


Patent
Neugen Pharma Inc. and Wakunaga Pharmaceutical Co. | Date: 2013-06-05

An object of the present invention is to provide a pharmaceutical agent useful for treating and preventing neurological disease, having satisfactory solubility and oxidative stress-mediated cell death suppressive activity as well as capable of exhibiting excellent blood-brain barrier permeability. The present invention is directed to an acylaminoimidazole derivative represented by general formula (I) or a salt thereof, and a pharmaceutical and a therapeutic or preventive agent for neurological disease containing the same, as an active ingredient.


Morihara N.,Wakunaga Pharmaceutical Co. | Hayama M.,Wakunaga Pharmaceutical Co. | Fujii H.,Sapporo Medical University
Plant Foods for Human Nutrition | Year: 2011

There is increasing evidence to suggest that many degenerative or pathological processes, such as aging, cancer, and coronary heart disease, are related to reactive oxygen species and radical-mediated reactions. We examined the effectiveness of aged garlic extract (AGE), a garlic preparation rich in water-soluble cysteinyl moieties, and its component for scavenging of superoxide by using the hypoxanthine-xanthine oxidase and human neutrophils. In the hypoxanthine-xanthine oxidase system, electron spin resonance showed that aged garlic extract scavenged superoxide radicals in a dose-dependent manner up to 54%. The EC 50 value of aged garlic extract for the superoxide radical scavenging effect was 0. 80 mg/ml. N-α-(1-deoxy-D-fructos-1-yl)-L-arginine (25. 9%) and (1S, 3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-1,3-dicarboxylic acid (20. 8%), water-soluble moieties of AGE, also exerted superoxide scavenging effects. Phorbol 12-myristate 13-acetate-activated human neutrophils produced superoxide radical of 56. 6 ± 9. 27 nmol/min/10 7 cells. Aged garlic extract (3 mg/ml) significantly inhibited superoxide production in comparison to the control. These data suggest that aged garlic extract may be useful for preventing diseases associated with reactive oxygen species. © 2011 Springer Science+Business Media, LLC.


Patent
Red Cross and Wakunaga Pharmaceutical Co. | Date: 2010-03-10

An object of the present invention is to provide a probe, primer, primer set and antibody for determining neonatal alloimmune thrombocytopenic purpura or the risk of developing it. According to the present invention, there is provided a probe, primer, primer set and antibody for use in the detection of the thymine residue at position 1297 in the GPIIIa.


Ohtani M.,Osaka Dental University | Oka T.,Wakunaga Pharmaceutical Co. | Ohura K.,Osaka Dental University
General and Comparative Endocrinology | Year: 2013

Adenosine A1, A2A, A2B and A3 receptor mRNAs were found to be expressed in mouse pancreatic islets and Beta-TC6 cells but their physiological or pharmacological actions are not fully clarified. We showed that adenosine (100μM) augmented insulin secretion by islets in the presence of either normal (5.5mM) or a high concentration of glucose (20mM). The augmentation of insulin secretion in the presence of high glucose was blocked by an A2A antagonist, but not by A2B and A3 antagonists, while an A1 antagonist potentiated the adenosine effect. An adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA) as well as A1, A2A and A3 receptor agonists also produced stimulation. On the other hand, an A3 agonist markedly reduced Beta-TC6 cell proliferation and the islet cell viability, while adenosine and NECA did not. The effect of A3 agonist was partially blocked by the A3 antagonist. In addition, treatment with the A3 agonist produced a small but significant extent of apoptosis in Beta-TC6 cells as judged by terminal transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. These results combined together suggested that like the A1 receptor, activation of A2A receptors by adenosine results in augmented insulin secretion, while the A3 receptor is involved in modulation of the survival of pancreatic β-cells. © 2013 Elsevier Inc.


Background: Garlic and its processed preparations contain numerous sulfur compounds that are difficult to analyze in a single run using HPLC. Objective: The aim of this study was to develop a rapid and convenient sulfur-specific HPLC method to analyze sulfur compounds in aged garlic extract (AGE). Methods: We modified a conventional postcolumn HPLC method by employing a hexaiodoplatinate reagent. Identification and structural analysis of sulfur compounds were conducted by LC-mass spectrometry (LC-MS) and nuclear magnetic resonance. The production mechanisms of cis-S-1-propenylcysteine (cis-S1PC) and S-allylmercaptocysteine (SAMC) were examined by model reactions. Results: Our method has the following advantages: Less interference from nonsulfur compounds, high sensitivity, good correlation coefficients (r > 0.98), and high resolution that can separate > 20 sulfur compounds, including several isomers, in garlic preparations in a single run. This method was adapted for LC-MS analysis. We identified cis-S1PC and γ-glutamyl- S-allyl-mercaptocysteine in AGE. The results of model reactions suggest that cis-S1PC is produced from trans-S1PC through an isomerization reaction and that SAMC is produced by a reaction involving S-allylcysteine/S1PC and diallyldisulfide during the aging period. Conclusion: We developed a rapid postcolumn HPLC method for both qualitative and quantitative analyses of sulfur compounds, and this method helped elucidate a potential mechanism of cis-S1PC and SAMC action in AGE. © 2016 American Society for Nutrition.


Morihara N.,Wakunaga Pharmaceutical Co. | Hino A.,Wakunaga Pharmaceutical Co. | Yamaguchi T.,Wakunaga Pharmaceutical Co. | Suzuki J.-I.,Wakunaga Pharmaceutical Co.
Journal of Nutrition | Year: 2016

Background: Aged garlic extract (AGE) has been shown to retard the progression of coronary calcification in patients with coronary artery disease. Objective: To clarify the mechanism of AGEs action to retard atherosclerosis, we investigated whether AGE suppresses the formation and progression of atherosclerosis in Apolipoprotein E (Apoe)-knockout (ApoE-KO) mice. Methods: Male C57BL/6J mice (control mice, 5 wk old) were fed a standard diet, whereas male ApoE-KO mice (5 wk old) were fed a standard diet with or without 3% AGE for 12 or 24 wk. After the treatment, blood samples, aortas, and spleens were collected from allmice. Concentrations of total cholesterol (TC), HDL cholesterol, and triglycerides (TGs) in serumwere measured. The area of atherosclerotic lesion in the aorta was examined by Oil Red O staining. The relative abundances of monocytes plus macrophages (CD11b+ cells) and interferon-g-producing CD4+ T cells in spleen were assessed by flow cytometric analysis. Results: The atherosclerotic lesion areas in the aortas of ApoE-KO mice were 87 and 114 times as great (P < 0.01) as those in control mice at 12 and 24 wk, respectively. AGE feeding significantly inhibited the progression of atherosclerotic lesion area in ApoE-KO mice by 22% (P < 0.05) at 12 wk. In addition, serum concentrations of TC and TGs in ApoE-KO mice were significantly higher than those in control mice at 12 and 24 wk. Treatment with AGE significantly suppressed the increases in serum concentrations of TC and TGs in ApoE-KO mice by 21% (P < 0.05) and 19% (P < 0.05) at 24 wk, respectively, and reduced the relative abundance of CD11b+ cells in ApoE-KO mice by 24% (P < 0.05) at 12 wk. Conclusion: These data suggest that the antiatherosclerotic activity of AGE is at least partly due to the suppression of inflammation and lipid deposition in the vessels during the early stage of atherosclerotic development in ApoE-KO mice. © 2016 American Society for Nutrition.


Patent
Wakunaga Pharmaceutical Co. | Date: 2012-05-30

A method is provided for producing a sugar-coated preparation including a solid composition containing a pharmacologically active ingredient and a sugar coating layer. The method comprises a step of forming the sugar coating layer with a sugar coating composition containing one or more sugar-alcohols selected from the group consisting of mannitol and erythritol and a polyvinyl alcohol-based resin. The sugar-coated preparation includes a solid composition containing a pharmacologically active ingredient and a sugar coating layer, wherein the sugar coating layer is made of a sugar coating composition containing one or more sugar-alcohols selected from the group consisting of mannitol and erythritol and a polyvinyl alcohol-based resin.

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