Toru Tonegawa

Tokyo Institute of Technology, Tokyo, Tokyo-to, Japan

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Publications (14)12.53 Total impact

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    ABSTRACT: Type A carbonate apatite powder, in which carbonate ion was completely substituted for the hydroxyl site, was synthesized by heating a low crystalline and stoichiometric hydroxyapatite powder under flow of a dry carbon dioxide gas at 1000 °C for 24 h. Its chemical formula was determined to be Ca10(PO4)6(CO3)0.93±0.06 from compositional and infrared spectroscopic analyses. The X-ray and neutron diffraction patterns of type A carbonate apatite showed the extra diffractions attributed to monoclinic symmetry with the space group Pb. The thermal expansion property of the type A carbonate apatite was determined from neutron powder diffraction data at 25, 200, 400 and 500 °C. The extra diffractions attributed to the monoclinic symmetry were not diminished at the high temperatures. The thermal lattice expansion coefficients were, for the first time, calculated to be αa = 13.1 × 10−6 °C−1, αb = 34.9 × 10−6 °C−1 and αc = 8.1 × 10−6 °C−1 by using a Le Bail refinement.
    Materials Science and Engineering B 10/2010; 173(1-3):171-175. DOI:10.1016/j.mseb.2010.02.008 · 2.17 Impact Factor
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    ABSTRACT: Complete carbonate substitution at A-sites (OH) of low-crystallinity hydroxyapatite with near stoichiometric composition (i.e. Ca/P ratio of 1.65) was achieved by heating in a dry carbon dioxide flow at 1173K for 64h. The carbonate content was analysed by thermogravimetry and infrared absorption spectrometry; the chemical composition was determined to be Ca9.9±0.1(PO4)6.00±0.1(CO3)0.9±0.1. The crystal structure and atomic configuration of the carbonate ion were determined by Rietveld refinement using X-ray powder diffraction data. This analysis revealed that the space group was monoclinic Pb with a=0.9571(1), b=1.9085(2), c=0.68755(3) nm and γ=119.847(7)°. The triangular planes of the carbonate ions were oriented parallel to the c- and a-axes, though there were two independent carbonate sites with occupancy factors of 0.56(1) and 0.34(1), where the triangles were oppositely rotated about the corresponding carbon atoms by 23° and −18°, respectively. The arrangement of the ions was disordered, which explains the lack of a thermal phase transition below 623K.
    Journal of Materials Science 05/2010; 45(9):2419-2426. DOI:10.1007/s10853-010-4209-x · 2.37 Impact Factor
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    ABSTRACT: The recombinant human erythropoietin (rhEPO) is used for the treatment of patients with renal anemia. However, rhEPO should be administered subcutaneously or intravenously three times a week. The repetitive injections of rhEPO result in burdens to patients. To resolve this problem, we investigated the sustaining release methods using an rhEPO-hydroxyapatite (HAp) made by spray-drying technique as the drug delivery system. Two types of rhEPO-HAp formulations were prepared; zinc (Zn) formulation and Zn and poly-L-lactic acid (PLA) formulation. These formulations were examined in genetically anemic model, ICGN (ICR-derived glomerulonephritis) mice. According to in vivo release test of rhEPO from HAp in ICGN mice, elevated plasma concentration of rhEPO could be maintained for more than 7 days. These mice showed the amelioration of anemia for more than 3 weeks post-administration without causing any side effect. In conclusion, Zn or Zn/PLA formulation of HAp was considered to be one of the useful carriers of rhEPO for long-term improvement of anemia.
    Journal of Veterinary Medical Science 10/2009; 71(10):1365-71. DOI:10.1292/jvms.001365 · 0.78 Impact Factor
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    ABSTRACT: For chronic kidney disease patients with renal anemia, recombinant human erythropoietin (rHuEPO) is a very effective drug; however, the treatment regime is troublesome, requiring multiple administrations each week. In the present study, we examined the efficiency of hydroxyapatite (HAp) as a drug delivery carrier for the sustained release of erythropoietin (EPO) to reduce the frequency of administration. Spray-dried HAp microparticles, formed from zinc-containing HAp (Zn-HAp) and Zn-HAp calcined at 400 degrees C, were used as carriers of EPO, and five Zn-HAp formulation samples incorporating EPO were prepared; no formulation, poly-L-lactic acid (PLA) formulation, zinc (Zn) formulation, Zn/PLA formulation, and calcined/Zn/PLA formulation. ICR mice were administered these samples or commercial rHuEPO (Epogin) as a control from dorsal neck subcutaneous, and hematological and histopathological analyses, including enzyme-linked immunosorbent assay for plasma EPO concentration, were performed. An increase in the blood EPO level was detected on days 3 and 8 post-administration. Peak hematopoiesis was delayed and higher hematological values were obtained on day 14 post-administration with no serious adverse reactions compared with the control. The Zn/PLA formulation sample was found to be most effective in reducing the initial peak while sustaining the delayed release of EPO. In conclusion, the Zn-HAp formulation samples were considered to be useful carriers for the sustained release of EPO, and the Zn/PLA formulation appears to be the most effective of five Zn-HAp formulation samples in sustaining EPO release.
    Journal of Veterinary Medical Science 07/2009; 71(6):729-36. DOI:10.1292/jvms.71.729 · 0.78 Impact Factor
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    ABSTRACT: Elemental distribution of calcium, phosphorus, oxygen, and carbon in a single collagen fibril obtained from tilapia fish scales was identified with an electron energy-loss spectroscopy and an energy-filtered transmission electron microscopy, for the first time. The carbon intensity profile of the single collagen fibril showed the specific D-periodic pattern at 67 nm of type I collagen fibrils. The calcium L(2,3)-edge and oxygen K-edge peak positions were detected at 347/350 eV and 137 eV, respectively, and these positions were identical to those of hydroxyapatite. Calcium, phosphorus, and oxygen were present in the hole zones as the amorphous phase, while carbon was present in the overlap zone. Our results indicated that the hole zones preferentially attract calcium and phosphate ions and thus serve as possible nucleation sites for mineralization.
    Micron 05/2009; 40(5-6):665-8. DOI:10.1016/j.micron.2009.04.001 · 1.99 Impact Factor
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    ABSTRACT: Insulin delivery carriers using low crystalline porous zinc hydroxyapatite (ZnHAp) microparticles with different crystal sizes and novel formulation method of poly (lactic acid) (PLA) have been developed to achieve the sustained-release of insulin. The adsorption isotherm curves of insulin dissolved into acetic acid of pH4.5 onto ZnHAp nanocrystals show non-Langmuir type due to the dissolution of the ZnHAp microparticles; the adsorption amounts were increased with the increase of crystalline sizes. The PLA formulation, coating the outer layer of microparticles, showed the apparent reduction of initial burst for insulin. The amounts of initial release of insulin decreased with the increase of crystalline sizes of ZnHAp, which could be attributed to the different meso-porous structure depending on its crystal sizes.
    Key Engineering Materials 01/2009; 396-398:507-510. DOI:10.4028/ · 0.19 Impact Factor
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    ABSTRACT: Hydroxyapatite (HAp) sensor, available for quartz crystal microbalance with dissipation (QCM-D) technique, has been fabricated by an electrophoretic deposition method. The method of re-usability of the sensor after adsorption of fibrinogen and the biological apatite (BAp) growth on the sensor with and without the adsorption of feral bovine serum (FBS) from 1.5 simulated body fluid were investigated. The re-usability of the sensor, cleaning with the combination of ammonia and hydrogen peroxide mixture and UV/ozone treatment, achieved ten times reuses. BAp was grown on the HAp surface but not on the gold surface at 37.5 °C for 40 hours. The viscoelastic property (ΔD/Δf value) of the BAp layer on the HAp sensor showed harder than that of the protein adsorption films from FBS. The amount of the BAp grown on the HAp sensor adsorbed FBS is lower than that on the HAp sensor. The adsorption of FBS proteins on the HAp surface strongly inhibited the BAp growth.
    Key Engineering Materials 01/2009; 396-398:89-92. DOI:10.4028/ · 0.19 Impact Factor
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    ABSTRACT: Real time adsorption behaviors of six proteins with different isoelectric points on hydroxyapatite (HAp) nanocrystal surfaces have been investigated by using HAp sensors for quartz crystal microbalance with dissipation technique (QCM-D). The dissipation (D)) - frequency (f) plots clearly showed that the different types of protein adsorption behaviors; the D-f plots of acidic proteins lie on one straight line with a constant slope under all initial protein concentrations, while those of neutral and basic proteins lie on two straight lines with different slopes. The acidic proteins formed a monolayer, while the neutral and basic proteins could cause conformational changes with the adsorbed amount of proteins. The QCM-D technique with novel HAp nanocrystal sensor is useful for the liquid phase changes of proteins on the surface.
    Key Engineering Materials 01/2008; 361-363:1119-1122. DOI:10.4028/ · 0.19 Impact Factor
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    ABSTRACT: The adsorption properties of metal ions containing hydroxyapatite (Ca 10(PO4)6(OH)2, HAp) were elucidated for the development of protein drug carrier. As-prepared metal ion containing HAp nanocrystal showed plate-like morphology with 10-20nm in length and 5-10nm in width. The metal ion containing HAp microparticles had higher specific surface area than the HAp microparticle. The adsorption amount per unit area of HAp showed higher than those of metal ion containing HAp. The adsorption behavior followed the Langmuir curves for each protein, indicating the monolayer adsorption. The loaded amount of proteins could be one of the most important properties for the application of drug delivery carrier.
    Key Engineering Materials 01/2008; 361-363:187-190. DOI:10.4028/ · 0.19 Impact Factor
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    ABSTRACT: Drug-supported spherical microparticles with below 3 microm in diameter of calcium carbonate (CC) nanocrystals were precipitated by a complex decomposition method from Na2CO3 and CaCl2 solutions with hydrocortisone phosphate (HyC). The HyC was completely incorporated into the microparticles and was adsorbed on the surface of nanocrystals. The crystal phases of vaterite and calcite were controlled by the addition of magnesium ions. Spherical microparticles of calcite cores and petal-shaped hydroxyapatite (HAp) outer layers were fabricated by soaking calcite into the SBF, or a supersaturated solution of phosphate ions to enhance the crystal growth of HAp.
    Journal of Nanoscience and Nanotechnology 04/2007; 7(3):822-7. DOI:10.1166/jnn.2007.523 · 1.56 Impact Factor
  • Toru Tonegawa · Toshiyuki Ikoma · Guoping Chen · Junzo Tanaka ·
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    ABSTRACT: Zinc and/or iron ions containing hydroxyapatite (HA) microparticles, which had twice as high specific surface area and higher pore volumes compared with the pure HA, were fabricated by a spray drying method; the zinc and/or iron ions were incorporated into the constitutional nanocrystals with below 20 nm in size in preparing. The small amount of carbonate ions was substituted in the phosphate group. The particle sizes were distributed in the range of 1 to 20 microm in diameter and its averaged size was approximately 6 microm. The microparticles with a spherical shape showed a single phase of HA and, after treated at higher temperature than 800 degrees C, had the high crystallite HA and the other phase of metal oxide such as ZnO or Fe2O3. The microparticles with higher specific surface area will be applicable for the drug delivery carriers of proteins.
    Journal of Nanoscience and Nanotechnology 04/2007; 7(3):839-43. DOI:10.1166/jnn.2007.526 · 1.56 Impact Factor
  • Toru Tonegawa · Toshiyuki Ikoma · Guo Ping Chen · Junzo Tanaka ·
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    ABSTRACT: Control of protein release without the initial burst from zinc containing hydroxyapatite porous microparticles (Zn-HAp) was investigated with a novel formulation method. The formulation method was a coat of polyL(L-lactide; PLA) on the microparticle with nano-thickness, which obviously suppressed the initial burst of protein release compared with the microparticles without the formulation, the coat of PLA. The HAp/PLA microparticle with 1-20μm of the size distribution was available for the drug delivery carrier of proteins without the degradation.
    Key Engineering Materials 01/2007; 330-332:857-860. DOI:10.4028/ · 0.19 Impact Factor

  • Key Engineering Materials 01/2007; 330-332:1343-1346. DOI:10.4028/ · 0.19 Impact Factor
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    ABSTRACT: Hydroxyapatite (HAp) also shows the high absorption ability for proteins with low degradations. In this study, to modify the absorption ability and to obtain high surface area, metal ions (Zn, Mg, Fe) were introduced in preparing the HAp nanocrystals, and porous microparticles were subsequent fabricated by a spray drying method. HAp microparticles with Zn, Mg, Fe ions had a single phase of low crystalline HAp. The specific surface area of the HAp, Mg-HAp, Fe-HAp and Zn-HAp were 87, 150, 152, 167 m2/g, respectively. In the adsorption experiment of a lysozyme as a basic proteine, Zn-HAp showed the highest adsorption ability. On the other hand, the HAp microparticles witn metal ions showed higher adsorption ability for BSA as a acitic protein than pure HAp microparticles.
    Key Engineering Materials 01/2006; 309-311:81-84. DOI:10.4028/ · 0.19 Impact Factor

Publication Stats

118 Citations
12.53 Total Impact Points


  • 2008-2010
    • Tokyo Institute of Technology
      • • Graduate School of Science and Engineering
      • • Department of Metallurgy and Ceramics Science
      Tokyo, Tokyo-to, Japan
  • 2009
    • National Institute for Materials Science
      • International Center for Young Scientist (ICYS)
      Tsukuba, Ibaraki, Japan
  • 2007
    • University of Tsukuba
      • Graduate School of Pure and Applied Sciences
      Tsukuba, Ibaraki, Japan