Updated on 2024/01/31

写真a

 
OTSUKA Yuta
 
Organization
Research Field in Dentistry, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Advanced Therapeutics Course Oral and Maxillofacial Rehabilitation Assistant Professor
Title
Assistant Professor

Degree

  • 博士(薬科学) ( 2018.3   徳島大学 )

Research Interests

  • バイオセラミックス、ケモメトリックス、機械学習

Research Areas

  • Informatics / Life, health and medical informatics

  • Life Science / Pharmaceutical analytical chemistry and physicochemistry

  • Life Science / Regenerative dentistry and dental engineering

Education

  • The University of Tokushima

    2015.4 - 2018.3

  • The University of Tokushima

    2013.4 - 2015.3

  • Konan University

    2008.4 - 2013.3

Research History

  • Tokyo University of Science   Assistant Professor

    2018.4 - 2022.5

Studying abroad experiences

  • 2023.8 - 2023.9   The University of New South Wales   Visiting Fellow

  • 2015.9 - 2016.3   テキサス大学アーリントン校   Visiting scholar

  • 2013.8 - 2013.9   シドニー工科大学   Visiting scholar

 

Papers

  • Otsuka Y., Sasaki D., Kusamori K., Nishikawa M., Ben-Nissan B. .  Investigation of the crystallinity change after the addition of magnesium hydroxides into the calcium phosphate during mechanochemical synthesis: an FTIR spectroscopy, XRD analysis, chemometrics, and cell culture .  Journal of the Australian Ceramic Society59 ( 5 ) 1373 - 1380   2023.12

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    Language:Japanese   Publisher:Journal of the Australian Ceramic Society  

    The aim of this study is to investigate the effect of the addition of Mg ion on calcium phosphate during mechanochemical synthesis. Ca(OH)2, dicalcium phosphate dihydrate (DCPD), and Mg(OH)2 were mechanochemically synthesized using ball milling with pure water. The prepared samples were evaluated by powder X-ray diffraction analysis (XRD), FT-infrared (IR) spectral analysis, and a TNF alpha test with murine macrophage-like cell line RAW264.7 cells for assessing the immune activation. The cell culture studies indicated that CaMg apatite can be used as bioceramic. Mg ion-doped Ca apatite, which also contains carbonated ions in the crystal, was identified based on the XRD patterns and FTIR spectra. The unique diffraction peaks of apatite at 211, 112, 300, and 202 decreased in the sample containing Mg(OH)2, suggesting a decrease in the rate of crystallization. In addition, the phosphate infrared bands of the samples were different from those of the carbonated apatite. To investigate the details of the effects of Mg ion, multiple spectra combining XRD patterns and FTIR spectra were prepared. The multiple spectra datasets were used for the estimation by multivariate curve resolution-alternating least squares (MCR-ALS). The effects of Mg ion on apatite as calcium phosphate were investigated by multiple spectra multivariate analysis. The analysis postulated that Mg ion decreased the apatite crystallinities possibly by adsorption at the growth sides and that these added ions strongly inhibited the formation of the thermodynamically most stable hydroxyapatite.

    DOI: 10.1007/s41779-023-00919-2

    Scopus

  • Otsuka Y., Ben-Nissan B., Kono H., Sasaki T., Kikuchi M. .  Mechanochemical synthesis and characterization of strontium substituted apatite for biomedical application .  Open Ceramics16   2023.12

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    Language:Japanese   Publisher:Open Ceramics  

    Strontium-substituted apatite has been proposed as a promising material for osteoporosis treatment. Several synthesis methods have been attempted in the past. In this study, we investigated a method known as the mechanochemical synthesis method. Characterization was carried out using different amounts of strontium ions in the hydroxyapatite (HAp) matrix with FT-IR spectral analysis, X-ray diffraction, lattice constant measurements, differential thermal analysis (DTA), terahertz spectroscopy, and investigation of the basic morphology using scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX). We report that the development and performance of mechanochemical synthetic pathways are more efficient and economical than other substituted apatite formation methods and are useful in the biomedical field to produce calcium phosphate-based clinical materials. The FTIR spectra, terahertz spectra, and XRD analysis results revealed that the mixture of dicalcium phosphate dihydrate (DCPD), Ca(OH)2 and Sr(OH)2 8H2O was phase-transformed into strontium-containing carbonate amorphous apatite by this simple and economical mechanochemical synthesis method.

    DOI: 10.1016/j.oceram.2023.100459

    Scopus

  • Otsuka, Yuta; Kono Hiroshi; Kikuchi, Masafumi .  Mechanochemical synthesis of cerium chlorapatite from a mixture of cerium chloride heptahydrate, dicalcium phosphate dihydrate, and calcium hydroxide for biomedical application .  Bio-Medical Materials and Engineering   2023.7Mechanochemical synthesis of cerium chlorapatite from a mixture of cerium chloride heptahydrate, dicalcium phosphate dihydrate, and calcium hydroxide for biomedical applicationReviewed

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    Authorship:Lead author, Corresponding author   Language:English  

    DOI: 10.3233/BME-230073

  • Kurosawa Y., Goto S., Mitsuya K., Otsuka Y., Yokoyama H. .  Interaction mode of hydroxypropyl-β-cyclodextrin with vaccine adjuvant components Tween 80 and Triton X-100 revealed by fluorescence increasing-quenching analysis .  Physical Chemistry Chemical Physics25 ( 8 ) 6203 - 6213   2023.1

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    Language:Japanese   Publisher:Physical Chemistry Chemical Physics  

    The nonionic surfactants Tween 80 (Tw80) and Triton X-100 (TX100), which are used as components of adjuvants, were used with bovine serum albumin (BSA) and hydroxfypropyl-β-cyclodextrin (HP-β-CD) as model antigens. The interaction patterns of Tw80 and TX100 with the hydrophobic cores of the model antigens were investigated. The fluorescence of 8-anilinonaphthalene-1-sulfonic acid (ANS), a hydrophobic fluorescent probe, was used to evaluate the effect of surfactants on each model antigen. A Hanes Woolf plot was used to analyze the adsorption of ANS to BSA, and an activator-inhibitor model was used to analyze the concentration-dependent increase and decrease of ANS fluorescence intensity. For BSA, TX100 occupies the ANS binding site inside the BSA hydrophobic core, while Tw80 does not contribute to the ANS binding site in the hydrophobic core. For HP-β-CD, the ANS concentration required for analyzable fluorescence intensity extended to the range where ANS concentration-dependent quenching was not negligible. Using the activator inhibitor model, we were able to separate the activators and inhibitors of ANS fluorescence and evaluate the affinity of ANS for HP-β-CD and surfactants. The results obtained showed that TX100 provided a hydrophobic environment to the ANS while being encapsulated by HP-β-CD, while Tw80 did not interact with HP-β-CD and provided a hydrophobic environment to the ANS independently of each other. The interpretations obtained were corroborated by the determination of the CMC of TX100 and Tw80, the effect of salt on ANS fluorescence, and 1H-NMR and ROESY. In summary, the results showed that the large hydrophilic head of Tween, composed of sorbitan and PEG chains, floated in the aqueous phase like a balloon, while Triton pierced the hydrophobic core of the antigen like a spear. In both BSA and HP-β-CD model antigens, TX100 impinged on the hydrophobic core.

    DOI: 10.1039/d3cp00094j

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  • Hiroshige R., Goto S., Tsunoda C., Ichii R., Shimizu S., Otsuka Y., Makino K., Takahashi H., Yokoyama H. .  Trajectory of the spectral/structural rearrangements for photo-oxidative reaction of neat ketoprofen and its cyclodextrin complex .  Journal of Inclusion Phenomena and Macrocyclic Chemistry102 ( 9-10 ) 791 - 800   2022.10

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    Language:Japanese   Publisher:Journal of Inclusion Phenomena and Macrocyclic Chemistry  

    Ketoprofen is a nonsteroidal anti-inflammatory drug used as mohrus tape which causes unwanted photosensitivity due to UV irradiation. In addition, photodegradation of ketoprofen induces its decarboxylation. Here, we aim to determine the effect of cyclodextrin on the photolysis of ketoprofen. Separation technique using HPLC confirmed that UV irradiation of ketoprofen produced multiple products. A unique reaction proceeded in the presence of β-cyclodextrin. Furthermore, characterization by UV spectroscopy was performed, and the obtained spectra were analyzed using singular value decomposition. By analyzing the trajectory of the singular vector space, we were able to reflect the difference in the reaction pathway of ketoprofen with and without cyclodextrin. This study uses a singular value decomposition analysis, which is useful as a novel approach for solutions of radical reactions and a promising technique for analysis of radical reactions in the future. Graphical abstract: [Figure not available: see fulltext.]

    DOI: 10.1007/s10847-022-01160-3

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  • Takatsuka M., Goto S., Kobayashi K., Otsuka Y., Shimada Y. .  Evaluation of pure antioxidative capacity of antioxidants: ESR spectroscopy of stable radicals by DPPH and ABTS assays with singular value decomposition .  Food Bioscience48   2022.8

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    Language:Japanese   Publisher:Food Bioscience  

    Background: Among the antioxidant reactions, no correlation (R2 = 0.5468) has been observed between the logarithm of the reciprocal of EC50 obtained by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays, which can measure single electron transfer reactions. Therefore, we attempted to investigate the radical scavenging reaction of each antioxidant in the DPPH and ABTS assays by using electron spin resonance (ESR), and to study an analytical method that can eliminate other than that factor. Results: Singular value decomposition (SVD) of the spectra that were obtained by ESR measurements was used to separate the components and to determine the detailed changes of each component. We calculated the EC50 from the changes in the spectra of the first and second components owing to the change in the antioxidant concentration in the DPPH and ABTS assays to identify which component contributed more to the radical scavenging reaction. The results demonstrated a positive correlation (R2 = 0.8806) between the EC50s of the first component of each of the DPPH and ABTS assays. In this study, common spectral changes were observed for all compounds with radical scavenging activity, so the first component was considered to be radical scavenging activity. Conclusions: Through this study, we could calculate the EC50 that significantly contributed to the radical scavenging reaction by decomposing the spectra that were obtained from ESR measurements of the reactions by the DPPH and ABTS assays into specific values.

    DOI: 10.1016/j.fbio.2022.101714

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  • Kurosawa Y., Otsuka Y., Goto S. .  Increased selectivity of sodium deoxycholate to around Tryptophan213 in bovine serum albumin upon micellization as revealed by singular value decomposition for excitation emission matrix .  Colloids and Surfaces B: Biointerfaces212   2022.4

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    Language:Japanese   Publisher:Colloids and Surfaces B: Biointerfaces  

    In the present study, we investigated the effect of bile salts (sodium deoxycholate, NaDC) on the conformation of a globular protein (bovine serum albumin, BSA). The two Tryptophan (Trp) residues of BSA and the fluorescence energy of NaDC are in a three-way relationship, and singular value decomposition (SVD) was used to separate each element in the fluorescence spectra. SVD was used to separate the elements in the fluorescence spectra. SVD showed that NaDC had a particularly large effect on the microenvironment around Trp213 and that micellar NaDC enhanced the selectivity for Trp213. In addition, the Stern-Volmer plots of the warfarin (WAR) specific domain (domain I) and ketoprofen (KP) specific domain (domain II) in the presence and absence of NaDC showed that the effect of NaDC was selective for domain II, where Trp213 is located. These results indicate that NaDC induces a localized and selective conformational change in BSA, and that the selectivity varies depending on the aggregation state of NaDC.

    DOI: 10.1016/j.colsurfb.2022.112344

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  • Hiroshige R., Goto S., Ichii R., Shimizu S., Wada-Hirai A., Li Y.P., Shimada Y., Otsuka Y., Makino K., Takahashi H. .  Protective effects of cyclodextrins on edaravone degradation induced by atmospheric oxygen or additive oxidant .  Journal of Inclusion Phenomena and Macrocyclic Chemistry102 ( 3-4 ) 327 - 338   2022.4

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    Language:Japanese   Publisher:Journal of Inclusion Phenomena and Macrocyclic Chemistry  

    Abstract: Antioxidants scavenge free radicals and may help prevent disease. However, due to poor stability, continuous intake is required. This study investigates the ability of cyclodextrin inclusion to improve the stability of the novel antioxidant edaravone. Kinetic models of cyclodextrin protection against edaravone oxidative decomposition were assessed and the data obtained was analyzed using Hanes–Woolf plots and Scatchard plots. In addition, complexation was analyzed using phase-solubility diagrams. The results show that cyclodextrin inclusion can control the oxidation rate of antioxidant molecules such as edaravone. This paper also demonstrates a substantial variation in the quantitative stability constant when calculated using different methods. This observation is relevant to determining complexation during the many and varied applications of cyclodextrins. The study establishes mechanisms to enhance the stability of antioxidants, which in turn may be useful to improve their bioavailability and may have translational implications in future. Graphical abstract: [Figure not available: see fulltext.]

    DOI: 10.1007/s10847-021-01122-1

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  • Kinoshita T., Tsunoda C., Goto S., Hasegawa K., Chatani H., Fujita M., Kataoka H., Katahara Y., Shimada Y., Otsuka Y., Komatsu K., Terada H. .  Enthalpy-Entropy Compensation in the Structure-Dependent Effect of Nonsteroidal Anti-inflammatory Drugs on the Aqueous Solubility of Diltiazem .  Chemical and Pharmaceutical Bulletin70 ( 2 ) 120 - 129   2022.2

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    Language:Japanese   Publisher:Chemical and Pharmaceutical Bulletin  

    Certain combinations of acidic and basic drugs can cause significant changes in physicochemical properties through the formation of ionic liquids, eutectic mixtures, or deep eutectic solvents. In particular, combining indomethacin and lidocaine is known to result in apparent increases in both the partition coefficients (hydrophobicity) and aqueous solubilities (hydrophilicity). The physicochemical interactions between drugs change the water solubility of the drugs and affect the bio-availability of active pharmaceutical ingredients. Therefore, we need to clarify the mechanism of changes of water solubility of drugs through the physicochemical interactions. In the present study, we identified a thermodynamic factor that regulates the dissolution of a basic drug, in the presence of various acidic nonsteroidal anti-inflammatory drugs. The results demonstrated that enthalpy-entropy compensation plays a key role in the dissolution of drug mixtures and that relevant thermodynamic conditions should be considered.

    DOI: 10.1248/cpb.c21-00834

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  • Kinoshita Takatoshi, Tsunoda Chihiro, Goto Satoru, Hasegawa Kanji, Chatani Hitoshi, Fujita Momoko, Kataoka Hikaru, Katahara Yuta, Shimada Yohsuke, Otsuka Yuta, Komatsu Kazushi, Terada Hiroshi .  Enthalpy-Entropy Compensation in the Structure-Dependent Effect of Nonsteroidal Anti-inflammatory Drugs on the Aqueous Solubility of Diltiazem(和訳中) .  Chemical & Pharmaceutical Bulletin70 ( 2 ) 120 - 129   2022.2Enthalpy-Entropy Compensation in the Structure-Dependent Effect of Nonsteroidal Anti-inflammatory Drugs on the Aqueous Solubility of Diltiazem(和訳中)

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    Language:English   Publisher:(公社)日本薬学会  

  • Mitsuya K., Goto S., Otsuka Y., Kawano Y., Hanawa T. .  Saturated adsorption of lidocaine and coal tar dyes onto porous polytetrafluoroethylene .  RSC Advances12 ( 4 ) 1914 - 1921   2022.1

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    Language:Japanese   Publisher:RSC Advances  

    Polytetrafluoroethylene (PTFE) has excellent physical properties and has been used in a wide range of applications in various fields. Adsorption research on PTFE is essential as primary research for the further application of PTFE. We attempted to adsorb coal tar dyes and model drugs such as lidocaine onto PTFE as a guideline to search for medicines that adsorb onto PTFE. Saturation curves were obtained after analyzing the adsorption of coal tar dyes on PTFE using the Hanes-Woolf plot. In addition, we collected multiple cases of ATR-FTIR spectral changes and/or retention depending on TPM derivatives and other adsorbates. Lidocaine matched some coal tar dye for the apparent spectral changes between the adsorbed molecules and its crystalline powder. The apparent spectral changes are blue-shifted, suggesting a hydrophobic interaction between the dyes/lidocaine and porous PTFE. This work provides a promising strategy for further application of PTFE.

    DOI: 10.1039/d1ra09086k

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  • Kasai T., Wada T., Iijima T., Minami Y., Sakaguchi T., Koga R., Shiratori T., Otsuka Y., Shimada Y., Okayama Y., Goto S. .  Comparative study of the hydrophobic interaction effect of pH and ionic strength on aggregation/emulsification of Congo red and amyloid fibrillation of insulin .  BBA Advances2   2022.1

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    Language:Japanese   Publisher:BBA Advances  

    Amyloid fibrillation is provoked by the conformational rearrangement of its source. In our previous study, we claimed that the conformational rearrangement of hen egg white lysozyme requires intermolecular aggregation/packing induced. Our proposed causality of the aggregation and amyloid formation was demonstrated by the quantitative dependence of amyloid fibrillation on pH difference from its isoelectric point (pI) and on the square root of ionic strength in order to reduce the intermolecular repulsion due to the shielding effect of electrolytes (DLVO effect). When Congo red has dianionic form at the pH higher than its pKa, it forms ribbon-like micelle colloids under lower ionic strength, while it loses electrostatic repulsion and aggregates to be emulsified in the octanolic phase under the higher ionic strength. These behaviors of Congo red were resembling to molecular assembly of surfactants. In contrast, the amyloid formation of insulin was proportional to the square root of ionic strength at the pH lower than its isoelectric point. Therefore, the trigger for conformational rearrangement of amyloid fibrillation is predominantly gripped by hydrophobic hydration and an electrostatic shielding effect. We concluded that the both behaviors of Congo red and insulin were derived from a driving force related to the hydrophobic hydration.

    DOI: 10.1016/j.bbadva.2021.100036

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  • Otsuka Y., Goto S. .  Dry mechanochemical synthesis of ethenzamide and saccharin 1:1 cocrystal and their evaluation using powder X-ray diffraction and FT-MIR and NIR spectroscopy .  Journal of Drug Delivery Science and Technology67   2022.1

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    Language:Japanese   Publisher:Journal of Drug Delivery Science and Technology  

    The purpose of this study was to evaluate effects of dry mechanochemical synthesizes on ethenzamide (EZ) and saccharin (SA) mixture. EZ and SA mixture were evaluated after grinding by mid and near infrared spectroscopy, powder X-ray diffraction (PXRD) and thermal analysis. During the grind, EZ and SA mixture was transformed into their 1:1 cocrystal form. Measurement time course data was applied to multi variate analysis of principal component analysis (PCA). Their cocrystallization could decompose two steps reactions. At first, EZ crystal transform into amorphous phase and their amorphous react with SA molecules after them, hydrogen bond networks were constructed and produce cocrystal was suggested. Combination PCA and several measurement data enable to extract useful chemical information.

    DOI: 10.1016/j.jddst.2021.102918

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  • Otsuka Y., Goto S. .  Dry and Wet Mechanochemical Synthesis of Piroxicam and Saccharin Co-Crystals and Evaluation by Powder X-Ray Diffraction, Thermal Analysis and Mid- and Near- Infrared Spectroscopy .  Journal of Pharmaceutical Sciences111 ( 1 ) 88 - 94   2022.1

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    Language:Japanese   Publisher:Journal of Pharmaceutical Sciences  

    The purpose of this study is to investigate the effects of dry and wet mechanochemical synthesis on piroxicam (PX) and saccharin (SA) mixtures. For this purpose, PX and SA mixtures prepared by wet mechanochemical processes using three solvents and by dry mechanochemical synthesis were evaluated by mid-and near-infrared spectroscopy, powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). The mixtures of wet-type products were transformed into PX/SA 1:1 co-crystals. The effect of the solvent was key to the co-crystallization of PX and SA. The products from the dry process were transformed into the amorphous phase. For the sample of the amorphous mixture, two exothermic peaks due to crystallization were observed in the thermal analysis. Bulk PX was ground for the same number of times for transformation, but was not successfully transformed to the amorphous bulk; the same was observed for SA. It is suggested that the mutual existence of PX and SA promotes mutual amorphization.

    DOI: 10.1016/j.xphs.2021.06.024

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  • Otsuka Y., Pal S. .  Predictive evaluation of multicomponent direct compress model tablets by integrating sphere UV-Vis spectroscopy and chemometrics .  Bio-Medical Materials and Engineering33 ( 3 ) 209 - 219   2022

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    Language:Japanese   Publisher:Bio-Medical Materials and Engineering  

    BACKGROUND: Control of the pharmaceutical manufacturing process and active pharmaceutical ingredients (API) is essential to product formulation and bioavailability. OBJECTIVE: The aim of this study is to predict tablet surface API concentration by chemometrics using integrating sphere UV-Vis spectroscopy, a non-destructive and contact-free measurement method. METHODS: Riboflavin, pyridoxine hydrochloride, dicalcium phosphate anhydrate, and magnesium stearate were mixed and ground with a mortar and pestle, and 100 mg samples were subjected to direct compression at a compaction pressure of 6 MPa at 7 mm diameter. The flat surface tablets were then analyzed by integrating sphere UV-Vis spectrometry. Standard normal variate (SNV) normalization and principal component analysis were applied to evaluate the measured spectral dataset. The spectral ranges were prepared at 300-800 nm and 500-700 nm with SNV normalization. Partial least squares (PLS) regression models were constructed to predict the API concentrations based on two previous datasets. RESULTS: The regression vector of constructed PLS regression models for each API was evaluated. API concentration prediction depends on riboflavin absorbance at 550 nm and the excipient dicalcium phosphate anhydrate. CONCLUSION: Integrating sphere UV-Vis spectrometry is a useful tool to process analytical technology.

    DOI: 10.3233/BME-211269

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  • Shiratori T., Goto S., Sakaguchi T., Kasai T., Otsuka Y., Higashi K., Makino K., Takahashi H., Komatsu K. .  Singular value decomposition analysis of the secondary structure features contributing to the circular dichroism spectra of model proteins .  Biochemistry and Biophysics Reports28   2021.12

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    Language:Japanese   Publisher:Biochemistry and Biophysics Reports  

    Amyloid fibril formation occurs in restricted environment, such as the interface between intercellular fluids and bio-membranes. Conformational interconversion from α-helix to β-structure does not progress in fluids; however, it can occur after sedimentary aggregation during amyloid fibril formation induced by heat treatment of hen egg white lysozyme (HEWL). Secondary structures of various proteins and denatured proteins titrated with 2,2,2-trifluoroethanol (TFE) were examined using their CD spectra. Gaussian peak/trough and singular value decompositions (SVD) showed that the spectral pattern of the α-helix comprised a sharp trough at wavelength 207 nm and a broad trough at 220 nm. Conversely, we distinguished two patterns for β-sheet—a spread barrel type, corresponding to ConA, and a tightly weaved type, corresponding to the soybean trypsin inhibitor. Herein, we confirmed that the spectral/conformational interconversion of the heat-treated HEWL was not observed in the dissolved fluid.

    DOI: 10.1016/j.bbrep.2021.101153

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  • Wada-Hirai A., Shimizu S., Ichii R., Tsunoda C., Hiroshige R., Fujita M., Li Y.P., Shimada Y., Otsuka Y., Goto S. .  Stabilization of the Metastable α–Form of Indomethacin Induced by the Addition of 2-Hydroxypropyl-β-Cyclodextrin, Causing Supersaturation (Spring) and Its Sustaining Deployment (Parachute) .  Journal of Pharmaceutical Sciences110 ( 11 ) 3623 - 3630   2021.11

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    Language:Japanese   Publisher:Journal of Pharmaceutical Sciences  

    The purpose of this study is to find that a small amount of 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) can produce a parachute effect on indomethacin (INM). From the examination of dissolution curves and concentration after several days, the supersaturation of INM was observed for the mixtures containing HP-β-CD at a molar ratio ≤ 0.5, and the sustained deployment of supersaturation was found not only in equimolar mixtures but also in mixtures with a shortage of HP-β-CD. In the solid state, it was compared the physical properties of INM/HP-β-CD mixtures using two different mixing methods and determined the stoichiometry of INM and HP-β-CD. Differential scanning calorimetry (DSC) revealed that the polymorphs of INM were converted by HP-β-CD into an amorphous state. Furthermore, X-ray powder diffraction (XRPD) and DSC–XRPD demonstrated that INM crystals from the INM/HP-β-CD mixture prepared from an EtOH solution were metastable. In conclusion, these phenomena may be considered the "spring" and "parachute" effects of mixtures with a shortage of HP-β-CD, as they depended on the presence of the metastable α-form of INM. The addition of 1/3 to 1/20 equivalents of HP-β-CD to INM enhanced INM solubility.

    DOI: 10.1016/j.xphs.2021.07.002

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  • Otsuka Y., Makino K., Takahashi H. .  Experimental study on the raman spectra of imine emulsification with chemometrics .  Journal of Oleo Science70 ( 8 ) 1109 - 1114   2021.8

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    Language:Japanese   Publisher:Journal of Oleo Science  

    In this study, we aimed to investigate imine emulsification using Raman spectroscopy with chemometrics. The imine emulsification samples were obtained by mixing aldehydes and amines in methanol and aqueous methanol. The Raman spectra of the samples were measured over time between 400 and 2300 cm–1 every 40 s using a Raman spectrometer. The obtained spectra were regarded as a dataset matrix. A multivariate curve resolution with alternating least squares was applied to the dataset. A multivariate analysis based on the Raman spectrum revealed that raw materials, emulsions, and products were decomposed when the water-rich samples were emulsified. Additionally, we evaluated the kinetics of the synthesis. The effect of water content on emulsification was investigated using Raman spectroscopy. The molecular dynamics of the co-solvent model were also investigated. The phase-layer construction was consistent with the phase transition in the water-methanol imine samples.

    DOI: 10.5650/jos.ess21073

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  • Otsuka Y., Kuwashima W., Tanaka Y., Yamaki Y., Shimada Y., Goto S. .  Effects of Heat Treatment on Indomethacin-Cimetidine Mixture; Investigation of Drug-Drug Interaction Using Singular Value Decomposition in FTIR Spectroscopy .  Journal of Pharmaceutical Sciences110 ( 3 ) 1142 - 1147   2021.3

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    Language:Japanese   Publisher:Journal of Pharmaceutical Sciences  

    This study investigated the effect of phase transformation on indomethacin (IMC), cimetidine (CIM), and their 1:1 eutectic mixture, using FTIR spectra and multivariate analysis. The IMC form γ, CIM form A, and IMC-CIM 1:1 mixture molar ratio samples were heated on a hot plate at 303–453 K for 5 min and cooled till room temperature. The prepared samples were investigated by powder X-ray diffraction analysis and infrared spectroscopy with KBr powder. The PXRD patterns suggested the bulk IMC form γ, bulk CIM form A, and 1:1 physical mixture samples phase transformed into low-crystallinity IMC form γ, amorphous CIM, and eutectic mixture, respectively. FTIR spectra combined with singular value decomposition (SVD) suggested by absorbance peak shifts of several vibration modes that the polymorphic transformations of the samples affect their molecular interactions. The estimated melting points of heated samples were evaluated by sigmoid fitting based on the SVD results. The principal components of SVD show that the process of phase transformation of IMC-CIM 1:1 mixture samples affect the IR vibration of the C[dbnd]O stretch of IMC and the C-C stretch and C-H bending of CIM. These results suggest that molecular interaction is an important factor in the eutectic condition of IMC-CIM 1:1 mixture. This observation enables to evaluate for in co-amorphous formulations or stability of drug combinations in a poly pill.

    DOI: 10.1016/j.xphs.2020.09.049

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  • Mai N.N.S., Otsuka Y., Goto S., Kawano Y., Hanawa T. .  Effects of polymer molecular weight on curcumin amorphous solid dispersion; at-line monitoring system based on attenuated total reflectance mid-infrared and near-infrared spectroscopy .  Journal of Drug Delivery Science and Technology61   2021.2

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    Language:Japanese   Publisher:Journal of Drug Delivery Science and Technology  

    The aim of this study was to investigate the effects of the molecular weight (Mw) of hydroxypropyl cellulose (HPC) and grinding duration on solid dispersions (SDs) formation and their characteristics. In this study, ternary amorphous SD systems containing curcumin (CUR), HPC, and sodium dodecyl sulfate (SDS) were developed using the milling method and characterized their physicochemical and mechanochemical properties. After 120-min grinding, the particle size reduced to under 1 μm and the GMs totally transformed into amorphous phase. The release behavior of CUR depended on the grade of HPCs due to their Mw and corresponding viscosity. During the SD formation process, the grinding time and Mw of HPC could be monitored by analyzing data obtained from MIR and NIR spectra based on chemometrics. There were two steps in SD formation: (1) simple dispersion with grinding time under 30 min and (2) random dispersion of mixtures with grinding time from 30 to 120 min. The HPC-M (700,000 Da) resulted in more effectively forming SD systems.

    DOI: 10.1016/j.jddst.2020.102278

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  • Takatsuka M., Goto S., Kobayashi K., Otsuka Y., Shimada Y. .  Leading individual features of antioxidant systematically classified by the ORAC assay and its single electron transfer and hydrogen atom transfer reactivities; analyzing ALS therapeutic drug Edaravone .  BBA Advances1   2021.1

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    Language:Japanese   Publisher:BBA Advances  

    Many natural compounds mop up radicals and limit radical reactions and may prove useful in reducing or preventing oxidative stress-related diseases in vivo. Several assays have been developed to measure antioxidant or anti-radical activity. Here, we measured the anti-radical activities of representative antioxidants using different assays. The oxygen radical absorption capacity (ORAC) assay has two mechanistic stages. We classified antioxidant behavior using two characteristic values thought to be related to the two stages — peroxyl radical formation time (lag time) and fluorescein annihilation rate (kobs) — by applying Voronoi polyhedral division. We focused on four class-representative antioxidants, Trolox ®, vitamin C, L-cysteine, and 2,6-di‑tert‑butyl‑p-cresol, and compared their characteristic activities with those of edaravone. Our analysis indicates that edaravone is in the same group as cysteine and may function via a similar mechanism. Our results suggest that analyzing lag time and kobs is a useful method to characterize antioxidants.

    DOI: 10.1016/j.bbadva.2021.100030

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  • Takahashi T., Watanabe M., Otsuka Y., Tanaka H., Takeuchi M. .  Rapid flow injection analysis by partial least squares regression –validation by a spectrophotometric determination of iron with 1,10-phenanthroline– .  Bunseki Kagaku70 ( 7-8 ) 451 - 457   2021

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    Language:Japanese   Publisher:Bunseki Kagaku  

    We applied a partial least squares regression (PLS) to overlapped peaks to develop a rapid flow injection analysis by the PLS method (RFP method) that quantifies the analytes of interest both accurately and rapidly. Spectrophotometric determination of Fe2+ with 1,10-phenanthroline was used as an evaluation model of the RFP method. Two Fe2+ standard samples (S1 and S2) were sequentially injected at a 30-sec interval, and the overlapped peaks were obtained. A calibration curve was constructed by applying the PLS to the overlapped peaks. The slopes of the calibration curve for S1 and S2 were both almost unity with good linearity. The concentrations of Fe2+ in surface water samples were determined by the RFP method. The Fe2+ concentrations measured were in good agreement with the values calculated by applying an absolute calibration curve method to non-overlapped peaks (ACC method). The sample throughput of the RFP method was about 1.7-times faster than that of the ACC method. We concluded that the RFP method achieves both accurate and rapid quantification.

    DOI: 10.2116/bunsekikagaku.70.451

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Books

  • Synthesis of Hydroxyapatite: Crystal Growth Mechanism and Its Relevance in Drug Delivery Applications Reviewed

    Yuta Otsuka( Role: Sole author)

    ( ISBN:978-981-16-7435-8

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    Total pages:1-356   Responsible for pages:213-229   Language:English Book type:Scholarly book

    DOI: 10.1007/978-981-16-7435-8_7

Presentations

  • Otsuka Y, Ito S, Kono H, Noguchi K, Kikuchi M   Investigation of self-setting apatite cement system using NIR spectroscopy with principal component analysis   Invited International conference

    2023.12 

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    Event date: 2023.12

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:Viet Nam  

  • Synthesis of strontium carbonate apatite by mechanochemical method and characterization by terahertz spectroscopy  

    2023.3 

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    Event date: 2023.3

  • 大塚裕太,河野博史,菊地聖史   セリウム含有アパタイトのメカノケミカル法による合成とその評価  

    第 81 回日本歯科理工学会学術講演会  2023.4