Biomedical subjects

Yoshiharu Machida

Publications and source records attributed to Yoshiharu Machida.

At least 19 recordsLinked to original sources

PubMed2006

Novel chitosan wound dressing loaded with minocycline for the treatment of severe burn wounds.

Novel wound dressings composed of chitosan (CH) film and minocycline hydrochloride (MH) were prepared using commercial polyurethane film (Tegaderm) as a backing. CHs with deacetylation degrees of 67%, 83% and 96% (mol/mol), named CH67, CH83 and CH96, respectively, were used. Wound dressing with a large piece of Tegaderm film (4 cm x 4 cm), named CH-MH-N, and wound dressing prepared by cutting CH-MH-N to the wound size, named CH-MH-A, were developed. As CH67-MH-N and CH83-MH-N showed the sustained release of minocycline in vitro, CH67 and CH83 were used as chitosan in the in vivo studies. Various formulations were applied to severe burn wounds in rats in the early stage, and the wound status and change in the wound surface area were examined. The use of 10mg of MH and complete sealing with Tegaderm had a negative effect. MH ointment was not effective, but Geben cream was fairly effective. However, CH83-MH-A containing 2mg of MH (CH83-MH2-A) and CH83 film showed an excellent effect. Considering the elimination of pus, CH83-MH2-A tended to be better than CH83 film. CH83-MH2-A is suggested as a useful formulation for the treatment of severe burn wounds.

Animals↗

PubMed2006

In vitro and in vivo evaluation of medicinal carbon granules and tablet on the adsorption of acetaminophen.

Medicinal carbon (MC) granules were prepared by wet granulation using maltitol (MT), and the MC tablet was produced by compression of the granules. The physical properties and the in vitro adsorption capacity for AA of the formulations were examined. Further, the effects of MC alone and the granules on gastrointestinal absorption of AA were examined in rats when they were administered intragastrically at 15 or 45 min after the intragastrical administration of AA. AA was rapidly adsorbed by MC, and the maximum adsorption capacity of MC was 0.329g AA per gram MC. The granules and tablet exhibited adequate strength, and the tablet disintegrated rapidly. The granules and tablet showed similar adsorption profiles, but somewhat lower adsorption capacity than MC alone. MC alone and granules administered at 15 min reduced the AUC(0-infinity) significantly against the control (no treatment); however, the suppression effect on the plasma concentration was lower with the granules than with MC alone. Thus, granules and tablet are useful as a compact dosage form of MC; though the reduced adsorption capacity must be taken into account in order to expect efficacy equivalent to that of MC alone.

Acetaminophen↗

PubMed2006

In vitro and in vivo characterization of nanoparticles made of MeO-PEG amine/PLA block copolymer and PLA.

The preparative method of a block copolymer of poly(dl-lactic acid) (PLA) and methoxypolyethylene glycol amine (MeO-PEG(N)), named PLA-(MeO-PEG), was refined. The degree of introduction of MeO-PEG(N) into PLA increased up to 55% (mol/mol) using a dichloromethane/methanol mixture (1:1, v/v) as a solvent at the reductive amination and taking all the fractions of the first peak in gel-chromatography. Plain and 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine (DiD)-loaded nanoparticles prepared using the PLA/PLA-(MeO-PEG) mixture of 45:55 (mol/mol) showed a mean size of 113 and 154 nm, respectively, and a positive zeta potential in water. DiD solution, i.v. administered, showed a lower plasma level and high distribution in liver, though DiD was distributed into the blood cells to a fair extent. Nanoparticles exhibited a higher plasma concentration of DiD than the DiD solution at 1 and 8h, though DiD was distributed into the liver and spleen to a fair extent. Nanoparticles made of the PLA/PLA-(MeO-PEG) mixture of 44:55 (mol/mol) showed better plasma retention than those made of the PLA/PLA-(MeO-PEG) mixture of 64:36 (mol/mol). It is suggested that the PLA/PLA-(MeO-PEG) mixture nanoparticles with a higher PEG/PLA ratio should be useful as a carrier for the elevation of the plasma concentration of lipophilic drugs.

Animals↗

PubMed2006

Preparation of double liposomes and their efficiency as an oral vaccine carrier.

The usefulness of double liposomes (DL), liposomes containing liposomes inside, as an oral vaccine carrier was examined. Ovalbumin (OVA) encapsulating liposomes sized to 230 nm (small liposomes, SL) were prepared by the glass-beads (GB) method and sequential sonication and extrusion. For the purpose of stabilizing the model antigen, DL containing SL were prepared by the GB method and the reverse-phase evaporation (REV) method. They were named GB-DL and REV-DL, respectively. The morphological structure of DL was confirmed using confocal laser scanning microscopy and scanning electron microscopy by the freeze-fracture method. DL showed suppressed release of OVA and stabilized OVA in pepsin solution as compared with SL. BALB/c mice were immunized with OVA solution, SL and DL suspension by oral administration. Significantly higher levels of IgA in feces were observed in mice immunized with SL and REV-DL as compared with OVA solution, and REV-DL tended to show the higher level of IgA than SL. REV-DL elicited significantly higher anti-OVA IgG responses as compared with OVA solution. Furthermore, GB-DL tended to raise the IgG level as compared with SL. The results suggest that DL have the potential to be an effective carrier for oral immunization.

Administration, Oral↗

PubMed2006

Medicinal carbon tablets for treatment of acetaminophen intoxication: adsorption characteristics of medicinal carbon powder and its tablets.

Adsorption characteristics of medicinal carbon powder (JP 14) for acetaminophen were examined at 37 degrees C using conventional incubation in an attempt to obtain an effective oral dosage form. Hydroxypropyl cellulose (HPC) and maltitol (MT), being able to act as a binding agent, were tested as additives. Tablets of medicinal carbon were produced by the wet granulation method. The rate and extent of adsorption of the medicinal carbon powder were roughly similar in water, JP 14 1st fluid (pH 1.2) and JP 14 2nd fluid (pH 6.8). The relationship between concentrations of free and adsorbed acetaminophen indicated that the adsorption followed the Langmuir mode. The maximal adsorption of acetaminophen in water was 0.219 g per gram medicinal carbon powder, little influenced by the addition of MT, but slightly reduced by the addition of HPC. The tablet prepared using MT as a binding agent displayed a favorable hardness and adequate disintegration time. The tablet showed good adsorption potential for acetaminophen, though the adsorption rate and extent of the tablet were reduced to some extent as compared with powder.

Acetaminophen↗

PubMed2006

Evaluation of binders in the preparation of medicinal carbon tablets by wet granule compression.

Medicinal carbon (MC) tablets were prepared to obtain an oral dosage form that can be easily taken. The MC tablets were made by the wet granule compression method, in which hydroxypropyl cellulose (HPC), carboxymethyl cellulose sodium (CMC-Na) and maltitol (MT) were applied as binders. Brilliant Blue FCF (BB) was used as a model drug. The binders were evaluated in terms of formability of the granules and tablets, their strength, disintegration of the tablets, and their effect on the adsorption potential of MC. HPC and CMC-Na gave the strong granules at a fairly low concentration, but more MT was needed to obtain the strong granules. The tablets could be formed only when using MT at 120% (w/w) of the MC amount. The tablet displayed good hardness and rapid disintegration. The adsorption potential was not affected by CMC-Na, and slightly prevented by MT. However, the adsorption ability of MC was lowered more with the increase in HPC. The granules and tablets exhibited similar adsorption potentials, which were a little lower than that of MC suspended in MT aqueous solution. Similar adsorption characteristics were also observed in a real drug, acetaminophen. It is suggested that the MC tablets prepared by the wet granule compression using MT as a binder should be useful as a compact dosage form of MC.

Adjuvants, Pharmaceutic↗

PubMed2006

[Nanoparticles prepared with PLA derivatives].

Chemical modification of poly (DL-lactic acid) (PLA) is very important to give it various functionalities. When hydrophilic moieties are combined to PLA, the products tend to form the nanoparticles with the hydrophilic moieties as their shell and PLA as a core in aqueous medium. The nanoparticles produced with such PLA derivatives are also expected to exhibit various functions physicochemically and physiologically. Further, they can work well as a valuable depot of biologically active reagents. In this section, the preparative procedure of PLA derivaties and several nanoparticles prepared with PLA derivatives are introduced. Moreover, the physicochemical and biopharmaceutical characteristics of the nanoparticles are overviewed.

Chemical Phenomena↗

PubMed2005

Preparation of amoxicillin intragastric buoyant sustained-release tablets and the dissolution characteristics.

An intragastric buoyant sustained-release tablet (IGB-T) containing 100 mg of amoxicillin (AMX) was prepared to eradicate gastric Helicobacter pylori. A tablet prepared by compressing the mixture of hydroxypropylcellulose-H (HPC-H), citric acid (17.2 mg), sodium hydrogen carbonate (22.8 mg) and AMX was employed as the basic system for preparing IGB-T. The weight and diameter of the tablets were designed to be about 300 mg and 10 mm, respectively. IGB-T containing 5 mg of AMX and HPC-H (255 mg) was buoyant and showed a sustained-release pattern in water. However, when AMX was increased and HPC-H decreased to maintain the tablet weight (300 mg), there was no apparent sustained-release pattern. To prepare IGB-T containing 50 mg of AMX, the surface of the tablet was coated with HPC-H after a tablet was prepared from the mixture of AMX (50 mg), HPC-H (210 mg), citric acid (17.2 mg), and sodium hydrogen carbonate (22.8 mg). This tablet (IGB-T50-Coating) was buoyant and showed a sustained-release pattern in water. However, to complete IGB-T with 100 mg of AMX, it was necessary not only to coat the surface of the tablet but also to use granulated AMX with a particle size of 300-500 microm (IGB-T100-Coating-300-500G). IGB-T100-Coating-300-500G was confirmed to be buoyant for 24 h while maintaining a tablet shape and showed a sustained-release pattern in water and buffer solutions of pH 1.2 and 6.8.

Amoxicillin↗

PubMed2005

Evaluation of Eudragit-coated chitosan microparticles as an oral immune delivery system.

Chitosan microparticles containing ovalbumin (OVA), OVA-containing chitosan microparticles (Chi-OVA), were prepared, coated with Eudragit L100 (ER), and evaluated as oral vaccine. Chi-OVA with an OVA content of 34.4% (w/w) and a mean particle size of 2.3 microm were used for experiments in vitro and in vivo. ER-coated Chi-OVA (ER-Chi-OVA) contained 3.6-20.5% (w/w) OVA and had a particle size of 47.9-161.1 microm. Chi-OVA dissolved readily in JP 14 first fluid, but not in JP 14 second fluid. The release of OVA from Chi-OVA was suppressed extensively in JP 14 second fluid. ER-Chi-OVA did not dissolve in JP 14 first fluid, and the release of OVA was suppressed greatly in JP 14 first and second fluids. OVA solution, Chi-OVA and ER-Chi-OVA (200 and 800 microg OVA/mouse) were administered to Balb/C mice twice at a 1-week interval. At 7 d after the second administration, plasma OVA-specific IgG and fecal OVA-specific IgA levels were measured. OVA-specific IgG tended to be enhanced in Chi-OVA and ER-Chi-OVA, but was the highest in OVA solution. OVA-specific IgA was induced significantly more efficiently by ER-Chi-OVA than the others. These suggested that ER-Chi-OVA should be possibly useful to induce an intestinal mucosal immune response.

Administration, Oral↗

PubMed2005

Preparation of a PLA-PEG block copolymer using a PLA derivative with a formyl terminal group and its application to nanoparticulate formulation.

A novel poly(DL-lactic acid) (PLA) derivative with a diethoxy propanol ester at the end, named PLA-acetal, was synthesized by ring opening polymerization using DL-lactide and 3,3-diethoxy propanol. PLA-acetal was hydrolyzed to a PLA derivative with a formyl group, named PLA-aldehyde, by acid treatment. Reductive amination between PLA-aldehyde and methoxypolyethylene glycol amine (MeO-PEG(N)) gave the block copolymer (PLA-(MeO-PEG(N))). Nanoparticles were prepared by emulsification-solvent evaporation or solvent diffusion using PLA-(MeO-PEG(N)) or a conventional methoxypolyethylene glycol-PLA block copolymer, PLA-(MeO-PEG(O)). PLA-(MeO-PEG(N)) nanoparticles had a particle size of 60-340 nm, dependent on the preparative procedure, while PLA-(MeO-PEG(O)) nanoparticles prepared by solvent diffusion showed a particle size of 60 nm. The PLA-(MeO-PEG) nanoparticles with a smaller PEG introduction degree exhibited a more negative zeta potential. 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate (DiD) could be incorporated efficiently in PLA-(MeO-PEG(N)) nanoparticles. It is suggested that PLA-aldehyde should be useful as a functional intermediate for derivatization of PLA, and PLA-(MeO-PEG(N)) can be used for the preparation of PEG-coated PLA nanoparticles.

Chemistry, Pharmaceutical↗

PubMed2005

Preparation and in vitro evaluation of chitosan microspheres containing prednisolone: comparison of simple and conjugate microspheres.

The purpose of the present study was to obtain a novel microparticulate formulation of prednisolone, which was adequate for the treatment of inflammatory bowel disease (IBD). The formulations prepared were evaluated in vitro. Two types of chitosan microspheres containing prednisolone, named Ch-Pred and Ch-SP-MS, were prepared by an emulsification-solvent evaporation method using a chitosan-prednisolone mixture and a chitosan-succinyl-prednisolone conjugate (Ch-SP), respectively. Ch-Pred and Ch-SP-MS were obtained in almost spherical shape. Ch-Pred showed a relatively high drug content of 13.2% (w/w), but the particle size was distributed from 10 to 45 microm, and a large initial burst release of approximately 60% was observed. On the other hand, although Ch-SP-MS exhibited a fairly low drug content of 3.5% (w/w), their particle size ranged from several hundred nanometers to 20 microm, with the mean diameter of 5 microm, and a gradual drug release profile was achieved. These characteristics on particle size and in vitro release suggested that Ch-SP-MS should have good potential as a microparticulate system for the treatment of IBD.

Anti-Inflammatory Agents↗

PubMed2005

Novel mucoadhesive oral patch containing diazepam.

The oral patch of diazepam (DZ) was developed to achieve a rapid absorption of DZ for the emergency treatment of epileptic seizure or anxiety disorder. The patch was composed of the outer mucoadhesive Carbopol 934 region, central drug region, and Tegaderm backing film. DZ (3 mg) was dissolved in propylene glycol (PG) alone or PG containing oleic acid (OA) at 5.6% (w/w), and used as the drug region. The patches with and without OA were attached to the mucosa of cheek in rats. The patch with OA exhibited the plasma level of more than 200 ng/mL at 10 min after administration, then the plasma concentration decreased gradually. The patch without OA displayed a plasma level of less than 30 ng/mL during 40 min after administration. To the contrary, in the in vitro drug permeation using a cellulose membrane, the patch without OA showed a three times faster permeation rate than the patch with OA, suggesting that the direct action of OA to mucosa might be associated with absorption enhancement. It was demonstrated that the patch with OA showed a good adhesion to oral mucosa and worked efficiently for rapid absorption of DZ.

Absorption↗

PubMed2005

Stability of spironolactone in rat plasma: strict temperature control of blood and plasma samples is required in rat pharmacokinetic studies.

The stability of spironolactone (SPN) in rat plasma was studied and its degradation was found to be an apparent first-order reaction. The apparent first-order rate constants (k(obs)) at 37, 23.5 and 0 degrees C were 3.543+/-0.261 (h-1, mean+/-S.D., n=3), 6.278+/-0.045 (x10(-1) h-1), and 7.336+/-0.843 (x10(-2) h-1), respectively. The half-lives were 0.20 h, 1.10 h, and 9.53 h. The degradation rate of SPN in rat plasma was markedly decreased when NaF, an esterase inhibitor, was added to the plasma, and the degradation was catalyzed by esterase in the plasma. These results indicated that not only plasma but also blood and serum samples in rat pharmacokinetic studies should be cooled to 0 degrees C, the temperature maintained, and treated as soon as possible. In pharmacokinetic studies reported previously, the temperature control of plasma, blood, and serum samples was not described. The pharmacokinetic study in rats after intravenous administration of SPN at 20 mg/kg was performed with strict temperature control of plasma and blood samples. The AUC, MRT, CL and Vd(ss) values (mean+/-S.E. of 4 rats) for SPN were 4100.8+/-212.9 ng h/ml, 0.29+/-0.01 h, 4915.7+/-248.0 ml/h/kg, and 1435.4+/-48.4 ml/kg, respectively. The AUC value was much larger than that previously reported. The AUC, MRT, Cmax and Tmax values (mean+/-S.E. of 4 rats) of canrenone, an active metabolite of SPN, after the administration of SPN were 4196.1+/-787.5 ng h/ml, 1.99+/-0.13 h, 1546.3+/-436.4 ng/ml and 1.0+/-0.0 h, respectively. This AUC value was almost identical to the value previously reported.

Animals↗

PubMed2005

PLGA implant tablet of ketoprofen: comparison of in vitro and in vivo releases.

An implant tablet of ketoprofen (KP) was developed in order to achieve its sustained supply for approximately one week, and its release was evaluated in vitro and in vivo. Implant tablets (30 mg) containing 1 and 5 mg of ketoprofen, prepared using poly(DL-lactic acid-co-glycolic acid) copolymer (PLGA; MW 10000; lactic acid : glycolic acid=1 : 1 (mol/mol)) as a matrix, exhibited similar week-long sustained release in vitro. Plasma concentration was monitored after the implant tablet (5 mg of KP) and a KP solution (0.5 mg of KP) were administered subcutaneously to rats, and in vivo release rate was analyzed by deconvolution. The release rate from the implant tablet was faster in vivo than in vitro in the initial phase, but much lower in vivo than in vitro in the later phase. The plasma level decreased to the level less than the minimal effective concentration at 96 h after administration. However, the calculated plasma concentration given by convolution based on in vitro release rate was more than 7 times greater than the minimal effective concentration even at 96 h after administration. As the implant displayed the discrepancy between in vitro and in vivo release rates, the improvement of the in vivo release rate is required.

Animals↗

PubMed2005

Transdermal absorption of propofol in rats.

Propofol (PF), a highly lipophilic anesthetic, has several desirable properties, such as the rapid onset and cessation of its effects upon intravenous infusion. In this study, the transdermal absorption of PF was investigated with the aim of the development of an alternative route of administration. PF solutions containing isopropyl myristate (IPM), ethanol or propylene glycol (PG) at various concentrations were prepared and applied to the abdominal skin of rats. Petrolatum and fatty alcohol propylene glycol (FAPG) ointments containing PF were also prepared and applied to the dorsal skin. Eyelid opening was measured and the ratio of the measured value to the initial value was calculated to evaluate the level of the pharmacological effect of the preparation. The PG solution containing 80% PF achieved higher plasma PF concentrations than the 100% PF solution. The PF-FAPG ointment produced a higher plasma PF concentration than the PF-petrolatum ointment. Furthermore, a drowsy state was confirmed after transdermal administration of 42% PF-FAPG ointment. These results indicate that the combination of PF and PG was appropriate for the transdermal absorption of PF, and PF was absorbed through the rat skin to an extent sufficient to cause a continuous sedative effect.

Administration, Cutaneous↗

PubMed2005

Macromolecular and nanotechnological modification of camptothecin and its analogs to improve the efficacy.

Camptothecin (CPT) and its analogs are some of the most potent antitumor agents known. However, their poor water-solubility and high toxicity require changes of their physicochemical and biological characteristics. Active lactone forms have provoked interest in the utility of CPT and its analogs again. Macromolecular chemical modifications and nanotechnological formulations have been used to obtain improved systems of CPT-related compounds. In these systems, one of the most important concepts is the enhanced permeability and retention (EPR) effect. The outcomes obtained by these approaches are displayed by introducing concrete examples.

Animals↗

PubMed2004

Development of implant tablet for a week-long sustained release.

An implant tablet for a week-long sustained release was developed by the direct compression method using poly-DL-lactic acid (PLA) and poly(DL-lactic acid-co-glycolic acid) copolymer (PLGA) as a matrix and phenol red (PR) as a model drug. The in vitro release was affected by formulations, especially by drug content and polymer species. The release rate correlated with the rate of absorption of water. The implant tablet (30 mg) containing 1 mg of PR, prepared using PLGA (MW 10,000; lactic acid/glycolic acid=1:1, mol/mol) by compression at 50 kg/cm(2) for 10 s, was found to efficiently exhibit a week-long sustained release in vitro, and applied in vivo. The remaining amount or plasma concentration of PR after s.c. administration of the implant tablet to rats demonstrated that the implant tablet showed a week-long sustained release in vivo. The present implant tablet is suggested to be useful as a drug delivery system for supplying drugs for approximately 1 week.

Animals↗

PubMed2004

Evaluation of antitumor and toxic side effects of mitomycin C-estradiol conjugates.

The antitumor and toxic side effects of mitomycin C-estradiol conjugates (EB-glu-MMC and E-glu-MMC) were evaluated in detail for solutions in propylene glycol and suspensions in 10% (v/v) propylene glycol. Tumor growth, body weight and number of leukocytes were examined after i.p. administration to sarcoma 180 solid tumor-bearing mice. Body weight and number of leukocytes were also examined in normal mice after i.p. administration of the solution. In solution dosage forms, the two conjugates had almost the same suppressive effect on tumor growth at 30 mg MMC eq./kg as MMC at 5 mg/kg, did not lower body weight significantly, but reduced the number of leukocytes at 30 mg MMC eq./kg. MMC, lethally toxic at 10 mg, significantly lowered the body weight and leukocyte number. In the suspension dosage forms, these conjugates had a greater suppressive effect on tumor growth at 50 mg MMC eq./kg than MMC at 5 mg/kg, and reduced the body weight and leukocyte number, with E-glu-MMC more toxic than EB-glu-MMC. The presence of the tumor itself influenced the body weight and leukocyte number. However, toxic side effects could be evaluated from the body weight and leukocyte number to almost the same extent between tumor-bearing and normal mice.

Animals↗