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Preparation and Characteristics of Film Dosage Form Natural Polysaccharides  [PDF]
Yoshifumi Murata, Kyoko Kofuji, Norihisa Nishida, Ryosei Kamaguchi
Pharmacology & Pharmacy (PP) , 2011, DOI: 10.4236/pp.2011.23028
Abstract: We investigated preparation of film dosage form (FD) from natural polysaccharides using the casting method without organic solvents, heating or pH control. Ferulic acid (FA) and catechin were employed as model compounds incorporated in the FD, and the release profile of each compound from the form was investigated in the limited medium. Film formation was affected by the addition of the model compound to the polysaccharide solution. Rigid FD was obtained with 2% low-molecular-weight alginate (L-ALG; thickness, 65 µm), and it hardened after the addition of 0.5% polygalacturonic acid, although the thickness of the film did not change. The FDs immediately released the model compound, and the forms dissolved in phosphate-buffered saline. FD modification did not affect the FA release rate except in the early stage. FD would be a useful dosage form, especially for preventing or treating localized problems in the oral cavity.
Development of Film Dosage Forms Containing Miconazole for the Treatment of Oral Candidiasis  [PDF]
Yoshifumi Murata, Takashi Isobe, Kyoko Kofuji, Norihisa Nishida, Ryosei Kamaguchi
Pharmacology & Pharmacy (PP) , 2013, DOI: 10.4236/pp.2013.43047

Film dosage forms (FDs) containing miconazole (MCZ) for the treatment of oral candidiasis were prepared using water-soluble polysaccharides, and the dissolution profiles of MCZ from the FDs were investigated. In addition, the forms were modified by the addition of a surface active agent to accelerate the drug dissolution rate. Circular films incorporating MCZ were obtained using each polysaccharide. Most FDs were easy to handle and resistant to tearing. No diffraction peaks were observed in the X-ray diffractograms of FDs. FDs prepared with sodium alginate or pullulan immediately swelled and disintegrated in aqueous medium, whereas MCZ incorporated in the FD gradually dissolved. A marked acceleration in the MCZ dissolution rate was observed when FD was prepared with polysaccharide containing a surfactant. These results confirmed that modified FDs are useful for treating localized conditions in the oral cavity, such as oral candidiasis, and that FDs can simplify the administration of drugs to patients.

Uptake of Bile Acid into Calcium-Induced Alginate Gel Beads Containing β-Chitosan Weak Acid Salt  [PDF]
Yoshifumi Murata, Kyoko Kofuji, Norihisa Nishida, Ryosei Kamaguchi
Pharmacology & Pharmacy (PP) , 2014, DOI: 10.4236/pp.2014.54042

Recently, potential applications for β-chitosan (β-CS) have been examined. In the present study, calcium-induced alginate gel beads (Alg-Ca) containing weak acid salts of β-CS were prepared and examined with regard to their ability to adsorb bile acids in vitro. More than 70% of taurocholate dissolved in solution was taken up by Alg-Ca containing 100 mg β-CS, sim. ilar to the degree of uptake observed with Alg-Ca containing α-CS salt. The adsorption of bile acid was affected by the absolute amount of β-CS and/or the acid concentration of the preparation. A secondary bile acid, taurodeoxycholate, was also adsorbed by Alg-Ca containing weak acid salts of β-CS. Therefore, β-CS might be used to adsorb bile acids within the gastrointestinal tract in the same manner as an anion-exchange resin, and thus serve as a complementary means by which to prevent hyperlipidemia.

Preparation of Fast Dissolving Films for Oral Dosage from Natural Polysaccharides
Yoshifumi Murata,Takashi Isobe,Kyoko Kofuji,Norihisa Nishida,Ryosei Kamaguchi
Materials , 2010, DOI: 10.3390/ma3084291
Abstract: Fast-dissolving films (FDFs) were prepared from natural polysaccharides, such as pullulan, without heating, controlling the pH, or adding other materials. The release profiles of model drugs from the films were investigated. In the absence of a drug, the casting method and subsequent evaporation of the solvent resulted in the polysaccharide forming a circular film. The presence of drugs (both their type and concentration) affected film formation. The thickness of the film was controllable by adjusting the concentration of the polysaccharide, and regular unevenness was observed on the surface of 2% pullulan film. All films prepared with polysaccharides readily swelled in dissolution medium, released the incorporated compound, and subsequently disintegrated. The release of dexamethasone from the films was complete after 15 min, although this release rate was slightly slower than that of pilocarpine or lidocaine. Therefore, FDFs prepared from polysaccharides could be promising candidates as oral dosage forms containing drugs, and would be expected to show drug dissolution in the oral cavity.
Development of Film Dosage Form Containing Allopurinol for Prevention and Treatment of Oral Mucositis
Yoshifumi Murata,Kyoko Kofuji,Norihisa Nishida,Ryosei Kamaguchi
ISRN Pharmaceutics , 2012, DOI: 10.5402/2012/764510
Development of Film Dosage Form Containing Allopurinol for Prevention and Treatment of Oral Mucositis
Yoshifumi Murata,Kyoko Kofuji,Norihisa Nishida,Ryosei Kamaguchi
ISRN Pharmaceutics , 2012, DOI: 10.5402/2012/764510
Abstract: Film dosage forms (FDs) containing allopurinol (AP) were prepared using a casting method with water-soluble polysaccharides, such as sodium alginate (ALG), and the release profile of AP from FDs was investigated in limited dissolution medium. Some ALGs were able to form FDs incorporating AP, and the thickness was about 50?μm. All FDs were easy to handle, though the rheological properties varied with ALG species. AP was homogenously present throughout the FDs and was released with disintegration in 10?mL of physiological saline. These results confirmed that FDs are useful for preventing or treating localized problems in the oral cavity, such as mucositis. FDs are also useful for administering drugs to cancer patients receiving chemotherapy and/or radiotherapy. 1. Introduction The xanthine oxidase inhibitor allopurinol (AP) is a drug used for the treatment of gout. AP has also been used to prevent and treat oral mucositis (mouth ulcers) in cancer patients receiving chemotherapy and/or radiotherapy [1–3]. In the treatment of mucositis, direct application of AP to the oral mucosa is necessary to avoid the systemic action seen after gastrointestinal absorption as the antioxidant activity of AP will result in lowering the activity of anticancer drug such as methotrexate. For example, AP suspensions (1?mg/mL) are freshly prepared in the hospital, and the patient gargles with the preparation [4]. This method for preventing mucositis is simple and effective; however, these preparations are not stable for long-term preservation, and it is difficult to control the amount of AP during gargling, although the dose is not sufficiently high to induce systemic effects in the event of erroneous swallowing. Recently, oral disintegration (OD) dosage forms such as OD tablets have become widely utilized, as they are useful in patients who have difficulty swallowing regular tablets [5, 6]. Film dosage forms (FDs) are also anticipated to be useful in oral care [7–9]. The active compound present in FDs is spread in the oral cavity as the form disintegrates on contact with saliva, and the disintegration profile of FDs can be varied by modifying the film base [10]. However, the drug loading capacity of FDs is typically very low, and the drug incorporated into FDs should be selected carefully. FDs are generally prepared using a water-soluble polymer base for immediate dissolution in saliva. As various polysaccharides have been used as additives for drug preparation or food ingredients because of the safety on peroral administration, they are candidate materials for FD preparation.
The Mechanism of Decreased Serum Phosphorus Levels in Rats with Chronic Kidney Disease after Oral Administration of Bifidobacterium longum  [PDF]
Nobuo Nagano, Mayuko Futaya, Mamiko Kohno, Osami Nakano, Norihisa Nishida, Yoichi Matsuura, Mikiko Shimada, Kyoko Ito, Tetsuo Ando, Takaaki Tsutsui, Yoshitaka Ando, Kiyotsugu Omae, Kosaku Nitta, Hiroshi Sakura, Tetsuya Ogawa
Advances in Microbiology (AiM) , 2015, DOI: 10.4236/aim.2015.57055
Abstract: Chronic kidney disease (CKD) patients are prone to disturbances in the intestinal microbiota, which contributes to CKD progression and complications. We previously reported a reduction of serum phosphorus (P) levels in hemodialysis patients receiving oral encapsulated bifidobacteria. The present study was conducted to clarify the mechanisms of P-lowering effect of bifidobacteria on CKD rats. CKD was induced in rats by 5/6 nephrectomy. Five weeks later, the rats were fed for 4 weeks on a powder diet containing encapsulated bifidobacteria. At the end of the study, intestinal contents were sampled for analyses of pH, intestinal flora and short-chain fatty acids (SCFAs). Oral administration of bifidobacteria halted the onset and progression of hyperphosphatemia in CKD rats. The increased number of bifidobacteria was confirmed in the cecum. In addition, the increase in intestinal pH in CKD rats was decreased after bifidobacteria treatment, along with increases in some SCFAs. Furthermore, positive correlation between serum P levels and intestinal pH was observed. In conclusion, the mechanism for the P-lowering effect of bifidobacteria was supposed as follows: CKD conditions increase aerobic bacteria which hydrolyze urea into ammonia. Elevated pH decreases ionization of intestinal calcium (Ca) which leads to an increase in free phosphate ions through reduction of Ca phosphate crystal precipitation. Administered bifidobacteria fermented carbohydrates to produce SCFAs, resulting in acidification of the intestinal lumen. The resulting low intestinal pH increases Ca ionization, which binds with free phosphate ions as an intrinsic P binder, resulting in the reduction of serum P levels.
Norihisa Tonami
Iranian Journal of Nuclear Medicine , 1997,
Abstract: This study was undertaken to examine the ability of SPECT in differentiation of a pulmonary lesion suspecions of lung cancr. A total of 170 patients with suspected lung cancer were studied. A dose of Tl-201 chloride {148-296 MBq) was injected intravenously and tomographic early and delayed scans were obtained at 15 miniutes and 3 hours post injection, respectively. Delayed Tl-201 SPECT visulized all of the 147 malignant pulmonary lesions which were clearer than those obtained by the early SPECT. Tl-201 SPECT seems to be a useful method for assessing pulmonary tumors and it offeres the retention index useful for differentiating malignant from benign lesions, and mediastinal involvement from lung cancer.
The chemical mechanism of oxidative stress due to the non-transferrin-bound iron (NTBI)  [PDF]
Yuzo Nishida
Advances in Bioscience and Biotechnology (ABB) , 2012, DOI: 10.4236/abb.2012.327131
Abstract: Plasma iron is normally bound to the iron transport protein transferrin, but there are some iron ions not associated with transferrin. The latter ions are generally termed as non-transferrin-bound iron (NTBI) or labile plasma iron. The NTBI has been thought to play an important role in iron-induced cell damage with resultant peroxidation of cell membrane lipids and other biomolecules, and such oxidative damage is implicated as an important contributor in the pathogenesis of cancer, cardiovascular disease, aging and other degenerative disorders, but little is understood about the chemical composition of NTBI and the origin of toxicity due to NTBI. In this review, we demonstrated the several chemical models for NTBI, and elucidated the chemical mechanism of iron toxicity due to NTBI in human body on the basis of my concept on the mechanism of oxygen activation in biological oxygenases. This has lead to the conclusion that 1) NTBI are divided into two groups, water-in-soluble and water-soluble ones, 2) some of the water-soluble NTBI react with oxygen or hydrogen peroxide, changing these molecules to those exhibiting the reactivity similar to singlet oxygen (1△g), and this is the main reason for NTBI to induce the oxidative stress, and 3) the responsibility of hydroxyl radical or free singlet oxygen is negligible as a “reactive oxygen species” in the human body. Based on the discussions described in this article we have proposed a new technique to prevent the oxidative damage due to NTBI. In order to achieve the purpose, we have synthesized the new superpolyphenols which contain more than 100 molecules of catechol derivative in one polymeric compound; these are sometimes water-insoluble, and in another cases, water-soluble. We have observed that some of these compounds can eliminate NTBI effectively from the plasma, and also some of these derivatives can remove hydrogen peroxide from the solution. Thus, we can hope that our new super-polyphenols should depress greatly the oxidative stress due to NTBI, which may be consistent with the facts that the Japanese tea catechins which contain polyphenols exhibit high preventing effects against lifestyle-related diseases, and that some polyphenols have been known to protect the pathogenesis of Alzheimer’s disease. We also discussed the antioxidative function by zinc(II) ion, which depresses the oxidative damage by NTBI by promoting the formation of iron deposition.
Hamiltonian Representation of Higher Order Partial Differential Equations with Boundary Energy Flows  [PDF]
Gou Nishida
Journal of Applied Mathematics and Physics (JAMP) , 2015, DOI: 10.4236/jamp.2015.311174
Abstract: This paper presents a system representation that can be applied to the description of the interaction between systems connected through common boundaries. The systems consist of partial differential equations that are first order with respect to time, but spatially higher order. The representation is derived from the instantaneous multisymplectic Hamiltonian formalism; therefore, it possesses the physical consistency with respect to energy. In the interconnection, particular pairs of control inputs and observing outputs, called port variables, defined on the boundaries are used. The port variables are systematically introduced from the representation.
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