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Pharmacology & Pharmacy 2013年第8期4卷 578-583页

作者： Hiroyuki Takabe Moriyuki Ohkuma yasunori iwao Shuji Noguchi Shigeru Itai Department of Pharmaceutical Engineering Graduate School of Pharmaceutical Sciences University of Shizuoka Shizuoka Japan. Drug Formulation Department Central Research Laboratories Kaken Pharmaceutical Co. Ltd. Shizuoka Japan Drug Formulation Department Central Research Laboratories Kaken Pharmaceutical Co. Ltd. Shizuoka Japan Department of Pharmaceutical Engineering Graduate School of Pharmaceutical Sciences University of Shizuoka Shizuoka Japan.

An initial burst is often observed during the release of active pharmaceutical ingredients (APIs) from poly-lactic-coglycolic-acid (PLGA) microparticles (MPs) which have been prepared by the emulsion-solvent evaporation method. Herein, we describe the development of a simple one-step coating method that suppresses the initial burst release process. This new method involves coating the PLGA-MPs with PLGA, with the coating process being performed through the phase separation of PLGA on the surface of PLGA-MPs using the emulsion-solvent evaporation method. Bovine serum albumin (BSA) was encapsulated in the PLGA-MPs as a model API. The coated MPs were spherical in shape with no pores on their smooth surface, whereas the non-coated PLGA-MPs had porous surfaces. An in vitro release study showed that the residual levels of BSA in the coated and non-coated PLGA-MPs after 1 h were about 99% and 16% of the original loads, respectively. The one-step coating method therefore represents a useful method for preparing PLGA-MPs that do not give an initial burst release of proteinaceous APIs.

关键词： Poly-Lactic-Co-Glycolic-Acid Microparticle Suppression of Initial Burst Release Coating Bovine Serum Albumin

Improving Flow Property of Nifedipine Loaded Solid-Lipid Nanoparticles by Means of Silica for Oral Solid Dosage Form

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Pharmacology & Pharmacy 2014年第12期5卷 1119-1129页

作者： Ranjan Kumar Barman yasunori iwao Shuji Noguchi Mir Imam Ibne Wahed Shigeru Itai Department of Pharmaceutical Engineering and Drug Delivery Science School of Pharmaceutical Sciences University of Shizuoka Shizuoka Japan Department of Pharmacy Faculty of Science University of Rajshahi Rajshahi Bangladesh

In this study, a new formulation of silica nanocomposite containing nifedipine (NI) loaded freeze-dried solid-lipid nanoparticles (NI-SLNs) and silica have been developed with improved flowability of powders, which can lead to the formulation of a widely acceptable oral dosage form. The stable NI-SLNs were prepared using two phospholipids, hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol mixed with 2.5% w/v trehalose as a cryoprotectant followed by lyophilization. We employed various grades of two types of silica, such as fumed and precipitated. Silica improved the poor flow property of NI-SLNs to good category as per USP-29. In addition, most of the silica nanocomposites showed the satisfactory results in their physicochemical properties such as particle size, polydispersity index, zeta potential, and recovered potency by around 100 nm, 0.3, -50 mV, and 80%, respectively. Furthermore, it was found that NI-SLNs were easily released form nanocomposites within 30 min, therefore, suggesting an improvement of drug dissolutions. Among them, precipitated silica cooperated fairly in improving the powder characteristics as well as the physicochemical, morphological, and pharmaceutical properties.

关键词： Silica Solid-Lipid Nanoparticle Solid Dosage Form Nifedipine Flowability

<i>In Vivo</i>Pharmacokinetic and Hemocompatible Evaluation of Lyophilization Induced Nifedipine Solid-Lipid Nanoparticle

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Pharmacology & Pharmacy 2014年第5期5卷 455-461页

作者： Ranjan Kumar Barman yasunori iwao Md. Rafiqul Islam Yuka Funakoshi Shuji Noguchi Mir Imam Ibne Wahed Shigeru Itai Department of Pharmaceutical Engineering and Drug Delivery Science Graduate School of Pharmaceutical Sciences University of Shizuoka Shizuoka Japan Department of Pharmacy Faculty of Biological Science and Technology Jessore University of Science and Technology Jessore Bangladesh Department of Pharmacy Faculty of Science University of Rajshahi Rajshahi Bangladesh

Nifedipine-solid-lipid nanoparticles lyophilized with trehalose (NI-SLN-Tre) were prepared by the high pressure homogenization of a roll mixture consisting of NI and hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol, and in vivo pharmacokinetic properties and their hemocompatibility were determined and compared with those of a NI-SLN suspension. The resulting pharmacokinetic data demonstrated that although no significant differences were observed between the time of peak concentration (Tmax), peak plasma concentration (Cmax), and the area under the curve (AUC0→∞) values of both administrated samples, NI tended to be absorbed to a much greater extent from the lyophilized NI-SLN-Tre suspensions because of the enhanced solvation of NI-SLN in gastrointestinal fluid, derived from formation of hydrogen bonds between the polar head groups of the lipids and the O-H groups of trehalose. Furthermore, the results of a hemolysis assay revealed that the NI-SLN and NI-SLN-Tre suspensions showed good hemocompatibility properties with hemolysis values of less than 5%. Taken together, the results of this study demonstrate that NI-SLN-Tre exhibits suitable pharmacokinetic properties and good biocompatibility.

关键词： Nifedipine Solid-Lipid Nanoparticles Lyophilization Pharmacokinetics Hemocompatibility

Preparation and Antidiabetic Effect of Orally Administered Nifedipine‐Loaded Solid Lipid Nanoparticles in Fructose-Induced Diabetic Rats

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Pharmacology & Pharmacy 2018年第10期9卷 457-471页

作者： Sabarni Sarker Md. Ashraf Ali Ranjan Kumar Barman Shuji Noguchi yasunori iwao Shigeru Itai Mir Imam Ibne Wahed Department of Pharmacy Faculty of Life and Earth Sciences Jagannath University Dhaka Bangladesh Department of Pharmacy Mawlana Bhasani University of Science of Technology Tangail Bangladesh Department of Pharmacy Faculty of Science University of Rajshahi Rajshahi Bangladesh Laboratory of Pharmaceutics Faculty of Pharmaceutical Sciences Toho University Tokyo Japan Department of Pharmaceutical Engineering and Drug Delivery Science School of Pharmaceutical Sciences University of Shizuoka Shizuoka Japan

The use of Nifedipine (NI), a dihydropyridine calcium channel blocker, is limited due to its poor aqueous solubility. However, NI loaded solid-lipid nanoparticles (NI-SLN) are known to exhibit suitable pharmacokinetic properties and good biocompatibility. The present investigation was designed to evaluate the effects of NI-SLN on glucose homeostasis, lipid metabolism and liver function in fructose-induced diabetic rats. NI-SLN was prepared by high pressure homogenization technique followed by lyophilization with trehalose as cryoprotectant. Diabetes was induced into rats by the administration of fructose (10%) in drinking water for six weeks. After induction of diabetes, rats were divided into four groups for the oral ingestion of NI, NI-SLN and/or vehicles and their effects on blood glucose levels, oral glucose tolerance test (OGTT), lipid profile, biochemical parameters, electrolytes and histopathology were observed. Single dose administration and treatment with NI-SLN showed significant glucose lowering efficacy in fructose-induced diabetic rats. Although NI and NI-SLN did not alter the fasting blood glucose level in normal rats, diabetic rats treated with NI-SLN resulted in significant reduction in glucose level for 24 hr. In OGTT, NI-SLN exhibited significant antihyperglycemic activity in both normal and diabetic rats. So, NI-SLN has better glucose lowering efficacy than that of pure NI in diabetic rats. The survival rates in rats among the treatment groups were 100%. Treatment with NI-SLN significantly improved lipid profiles than NI alone and the effect was dose-dependent. Administration of NI-SLN significantly reduced uric acid, creatinine levels and maintained a good cationic balance. After two weeks of NI-SLN treatment, hepatocytes regained their normal architecture, and the beneficial effect could be correlated with the reduction of SGOT and total bilirubin levels. Therefore, NI-SLN was found to be useful for the enhancement of bioavailability and exhibit

关键词： Formulation Solid Lipid Nanoparticle Calcium Channel Blocker Nifedipine Fructose Diabetes

Formulation Development and <i>In-Vivo</i>Evaluation of Atorvastatin Calcium Solid Dispersion in Streptozotocin Induced Diabetic Mice

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Pharmacology & Pharmacy 2018年第9期9卷 395-414页

作者： Md. Shahin Sarker Ranjan Kumar Barman Md. Ashraf Ali Shuji Noguchi yasunori iwao Shigeru Itai Mir Imam Ibne Wahed Department of Pharmacy Faculty of Science University of Rajshahi Rajshahi Bangladesh Department of Pharmacy Mawlana Bhasani University of Science of Technology Tangail Bangladesh Laboratory of Pharmaceutics Faculty of Pharmaceutical Sciences Toho University Chiba Japan Department of Pharmaceutical Engineering and Drug Delivery Science School of Pharmaceutical Sciences University of Shizuoka Shizuoka Japan

Atorvastatin calcium (ATV) is a selective competitive inhibitor of HMG CoA reductase characterized by poor aqueous solubility leading to inadequate bioavailability. The present study was designed to develop solid dispersion of atorvastatin (SDA) to improve the solubility and dissolution properties of ATV and evaluation of its in-vivo efficiency in streptozotocin (STZ) induced diabetic mice. Formulations of SDA were prepared by solvent evaporation method using PEG-4000 alone and/or mixture of PEG-4000 and Carplex-80 as carrier in different ratios. Solid-state analyses of SDA were performed to characterize the physicochemical properties of newly developed SDA by differential scanning calorimetry (DSC), powder x-ray diffractometry (PXRD), fourier transformed infrared spectra (FTIR) and scanning electron microscopy (SEM). DSC and PXRD showed that the crystallinity of drugs was notably decreased during the preparation of SDA. FTIR and SEM also demonstrated the conversion of ATV from amorphous to crystalline state resulting in improved solubility. Among formulations, SDA-5 showed significant enhancement of in-vitro drug release (around 2 fold higher) as compared to pure ATV. Further, in-vivo study was conducted to evaluate the effects of a newly developed ATV loaded solid dispersion on glycemic control, lipid profile, liver enzyme and histopathology in STZ induced diabetic mice. Oral administration of SDA significantly lowered the blood glucose levels during the course of treatment. Treatment with SDA significantly improved lipid profiles better than ATV alone and the effect was dose-dependent. After one week of SDA treatment significantly decreased liver weights as result of lipid clearance and the hepatocytes regained their normal architecture, and these beneficial effects can be correlated with the reduction of SGPT levels. The results demonstrated that, SDA exerted better glycemic control, lipid lowering effect and organ protection (liver and pancreas) than that of co

关键词： Solid Dispersion Atorvastatin Poor Aqueous Solubiity Streptozotocin Diabetic Mice

Interaction between hepatitis C virus and metabolic factors

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World Journal of Gastroenterology 2014年第11期20卷 2888-2901页

作者： yasunori Kawaguchi Toshihiko Mizuta Department of Internal Medicine Saga Medical SchoolSaga 849-8501Japan

Hepatitis C virus (HCV) infection disrupts the normal metabolism processes, but is also influenced by several of the host’s metabolic factors. An obvious and significantly detrimental pathophysiological feature of HCV infection is insulin resistance in hepatic and peripheral tissues. Substantial research efforts have been put forth recently to elucidate the molecular mechanism of HCV-induced insulin resistance, and several cytokines, such as tumor necrosis factor-α, have been identified as important contributors to the development of insulin resistance in the distant peripheral tissues of HCV-infected patients and animal models. The demonstrated etiologies of HCV-induced whole-body insulin resistance include oxidative stress, lipid metabolism abnormalities, hepatic steatosis and iron overload. In addition, myriad effects of this condition have been characterized, including glucose intolerance, resistance to antiviral therapy, progression of hepatic fibrosis, development of hepatocellular carcinoma, and general decrease in quality of life. Metabolic-related conditions and disorders, such as visceral obesity and diabetes mellitus, have been shown to synergistically enhance HCV-induced metabolic disturbance, and are associated with worse prognosis. Yet, the molecular interactions between HCV-induced metabolic disturbance and host-associated metabolic factors remain largely unknown. The diet and lifestyle recommendations for chronic hepatitis C are basically the same as those for obesity, diabetes, and metabolic syndrome. Specifically, patients are suggested to restrict their dietary iron intake, abstain from alcohol and tobacco, and increase their intake of green tea and coffee (to attain the beneficial effects of caffeine and polyphenols). While successful clinical management of HCV-infected patients with metabolic disorders has also been achieved with some anti-diabetic (i.e., metformin) and anti-lipid (i.e., statins) medications, it is recommended th

关键词： Hepatitis C virus Insulin resistance Diabetes Lipid metabolism abnormality Hepatic steatosis Iron overload Oxidative stress Visceral obesity

Distortion-free PCA on sample space for highly variable gene detection from single-cell RNA-seq data

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Frontiers of Computer Science 2023年第1期17卷 133-142页

作者： Momo MATSUDA yasunori FUTAMURA Xiucai YE Tetsuya SAKURAI Department of Computer Science University of TsukubaTsukuba 305-8573Japan

Single-cell RNA-seq (scRNA-seq) allows the analysis of gene expression in each cell, which enables the detection of highly variable genes (HVG) that contribute to cell-to-cell variation within a homogeneous cell population. HVG detection is necessary for clustering analysis to improve the clustering result. scRNA-seq includes some genes that are expressed with a certain probability in all cells which make the cells indistinguishable. These genes are referred to as background noise. To remove the background noise and select the informative genes for clustering analysis, in this paper, we propose an effective HVG detection method based on principal component analysis (PCA). The proposed method utilizes PCA to evaluate the genes (features) on the sample space. The distortion-free principal components are selected to calculate the distance from the origin to gene as the weight of each gene. The genes that have the greatest distances to the origin are selected for clustering analysis. Experimental results on both synthetic and gene expression datasets show that the proposed method not only removes the background noise to select the informative genes for clustering analysis, but also outperforms the existing HVG detection methods.

关键词： single-cell RNA-sequencing feature selection principal component analysis highly variable gene detection background noise clustering analysis

Study of photoexcited-carrier dynamics in GaAs photoconductive switches using dynamic terahertz emission microscopy

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Photonics Research 2016年第3期4卷 9-15页

作者： Hironaru Murakami Shogo Fujiwara iwao Kawayama Masayoshi Tonouchi Institute of Laser Engineering Osaka University

We propose dynamic terahertz(THz) emission microscopy(DTEM) to visualize temporal–spatial dynamics of photoexcited carriers in electronic materials. DTEM utilizes THz pulses emitted from a sample by probe pulses irradiated after pump pulse irradiation to perform time-resolved two-dimensional mapping of the THz pulse emission, reflecting various carrier dynamics. Using this microscopy, we investigated carrier dynamics in the gap region of low-temperature-grown Ga As and semi-insulating Ga As photoconductive switches of the identical-dipole type. The observed DTEM images are well explained by the change in the electric potential distribution between the electrodes caused by the screening effect of the photoexcited electron-hole pairs.

关键词： Ga Study of photoexcited-carrier dynamics in GaAs photoconductive switches using dynamic terahertz emission microscopy As THz

Shearing Mechanism of Straight Thin Copper Wires at Connecting Terminal due to Lightning Current

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Plasma Science and Technology 2007年第6期9卷 752-755页

作者：胡小博 Takahiro OTSUKA Toru iwao Tsuginori INABA Chuo University Tokyo 112-8551Japan Toko Electric Corporation Saitama 349-0192Japan Musashi Institute of Technology Tokyo 158-8557Japan

When a lightning current is impressed through a copper wire, the copper wire would be melted. A straight thin copper wire with a diameter of 0.1 mm,~ is melted due to the specific melting Joule heating （j^2t）m in an adiabatic condition. However, it has been recognized in the experiment that the thicker copper wires of φ1 mm are not completely melted, but sheared mainly at the connecting terminal by a relatively low impulse current. Electro-magnetic mechanical shearing stress, etc. are discussed in addition to the conventional Joule heating. New broken mechanisms were presumed and proved in the additional experiments.

关键词： lightning copper wire broken

Therapeutic response assessment of RFA for HCC:Contrast-enhanced US,CT and MRI

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World Journal of Gastroenterology 2014年第15期20卷 4160-4166页

作者： yasunori Minami Naoshi Nishida Masatoshi Kudo Department of Gastroenterology and Hepatology Kinki University Faculty of MedicineOsaka 589-8511Japan

Radiofrequency ablation (RFA) is commonly applied for the treatment of hepatocellular carcinoma (HCC) because of the facile procedure, and the safety and effectiveness for the treatment of this type of tumor. On the other hand, it is believed that HCC cells should spread predominantly through the blood flow of the portal vein, which could lead to the formation of intrahepatic micrometastases. Therefore, monitoring tumor response after the treatment is quite important and accurate assessment of treatment response is critical to obtain the most favorable outcome after the RFA. Indeed, several reports suggested that even small HCCs of ≤ 3 cm in diameter might carry intrahepatic micrometastases and/or microvascular invasion. From this point of view, for preventing local recurrences, RFA should be performed ablating a main tumor as well as its surrounding non-tumorous liver tissue where micrometastases and microvascular invasion might exist. Recent advancement of imaging modalities such as contrast-enhanced ultrasonic, computed tomography, and magnetic resonance imaging are playing an important role on assessing the therapeutic effects of RFA. The local recurrence rate tends to be low in HCC patients who were proven to have adequate ablation margin after RFA; namely, not only disappearance of vascular enhancement of main tumor, but also an adequate ablation margin. Therefore, contrast enhancement gives important findings for the diagnosis of recurrent HCCs on each imaging. However, hyperemia of non-tumorous liver surrounding the ablated lesion, which could be attributed to an inflammation after RFA, may well obscure the findings of local recurrence of HCCs after RFA. Therefore, we need to carefully address to these imaging findings given the fact that diagnostic difficulties of local recurrence of HCC. Here, we give an overview of the current status of the imaging assessment of HCC response to RFA.

关键词： Hepatocellular carcinoma Micrometastasis Microvascular invasion Radiofrequency ablation Safety margin