Wakunaga Pharmaceutical Co.

Hiroshima-shi, Japan

Wakunaga Pharmaceutical Co.

Hiroshima-shi, Japan

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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.


Harauma A.,Wakunaga Pharmaceutical Co. | Harauma A.,Azabu University | Moriguchi T.,Wakunaga Pharmaceutical Co. | Moriguchi T.,Azabu University
Lipids | Year: 2011

Docosahexaenoic acid (DHA), is the major polyunsaturated fatty acid in the brain and is important for both the structure and the function of the nervous system. Mice were fed either an n-3 fatty acid deficient (n-3 Def) or adequate (n-3 Adq) diet for two generations. The mice were housed under two conditions, as a group or in isolation and the major point of the study was to determine whether n-3 fatty acid deficiency would enhance isolation-induced anxiety. Isolation stress was assessed using the novelty suppressed feeding paradigm (NSF) after a 3-week period and the test lasted a maximal duration of 10 min. The number of successful mice consuming food pellets within 5 min in the n-3 Def diet group was low in both housing conditions (group housing, 33% and isolated, 30%), but was 92% in the group housed and 50% in the isolated group when fed the n-3 Adq diet. In the subsequent 5 min period, the isolated housing group consuming the n-3 Adq diet increased up to 79% and the group housed animals fed the n-3 Def diet increased to 67%. However, those that consumed the n-3 deficient diet combined with isolation stress exhibited no increase. These results suggested that the n-3 deficient mice had increased anxiety that was enhanced by the chronic mild stress of social isolation. © 2011 AOCS.


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.


Sakata Y.,Wakunaga Pharmaceutical Co. | Yamaguchi H.,Wakunaga Pharmaceutical Co.
Journal of Non-Crystalline Solids | Year: 2011

Cast films comprising hydroxypropyl methylcellulose (HPMC) and calcium chloride (CaCl2) have higher flexibility than those with HPMC and calcium lactate pentahydrate (CLP). The aim of the present study was to investigate the relationship between the molecular behaviour and the film flexibility of HPMC cast films. In differential scanning calorimetry (DSC) measurements, the HPMC-only cast films exhibited a glass transition temperature (Tg) of 142.1-143.9 °C, which is similar that of HPMC/CLP cast films. In contrast, HPMC/CaCl2 cast films exhibited Tg of 76.1-77.3 °C, which is lower than that of HPMC-only and HPMC/CLP films. Thermal mechanical analysis (TMA) results indicated that the HPMC-only and HPMC/CLP cast films contracted strongly around the Tg calculated using DSC. In contrast, the cast films comprising HPMC/CaCl2 blends gradually contracted as the temperature increased; this behaviour is significantly different from that observed in the HPMC-only and HPMC/CLP films. The most probable mechanism for the film flexibility of HPMC/calcium salt blends was clarified through attenuated total reflection Fourier transform-infrared (ATR FT-IR) and thermogravimetric (TG) analysis. The analysis results suggest that the difference in the flexibility of the cast films in the presence of CaCl 2 or CLP depends on the difference affinity between calcium salts and water molecules. © 2010 Elsevier B.V.


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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