論文 - 藤堂 浩明
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Effect of liquid crystals with cyclodextrin on the bioavailability of a poorly water-soluble compound, diosgenin, after its oral administration to rats.
Okawara Masaki, Hashimoto Fumie, Todo Hiroaki, Sugibayashi Kenji, Tokudome Yoshihiro
Int J Pharm 472 ( 1-2 ) 257 - 261 2014年09月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Diosgenin, found in wild yam (Dioscorea villosa), has been shown to ameliorate diabetes and hyperlipidemia, increase cell proliferation in a human 3D skin model, and inhibits melanin production in B16 melanoma cells. It is also an active element in cosmeceutical and dietary supplements. Although the bioavailability of diosgenin is low due to its poor solubility and intestinal permeability, it was subsequently improved using a beta-cyclodextrin (beta-CD) inclusion complex. Recently liquid crystals (LCs) were shown to enhance the bioavailability of poorly water-soluble drugs. The purpose in the present study was to prepare diosgenin LCs and investigate the interaction between LC and beta-CD in order to improve its bioavailability of diosgenin. Crystallinity and particle diameters of LCs in water were determined by small angle X-ray scattering (SAXS) and Zetasizer. Pharmacokinetic parameters were calculated using the plasma content of diosgenin after its oral administration to Wistar rats. Regarding the formation of glyceryl monooleate (GMO) and phytantriol (PHY) LC, SAXS patterns showed the hexagonal and cubic phases, respectively. Bioavailability was significantly enhanced after oral administration of LCs prepared by GMO than after diosgenin alone. The bioavailability was further improved with the combination of LC and beta-CD than LC and water.
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Effect of emulsification on the skin permeation and UV protection of catechin. 査読あり
Sachie Yoshino, Tomoaki Mitoma, Keiko Tsuruta, Hiroaki Todo, Kenji Sugibayashi
Pharmaceutical development and technology 19 ( 4 ) 395 - 400 2014年06月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Effect of emulsification on the skin permeation and UV protection of catechin.
Yoshino Sachie, Mitoma Tomoaki, Tsuruta Keiko, Todo Hiroaki, Sugibayashi Kenji
Pharm Dev Technol 19 ( 4 ) 395 - 400 2014年06月
記述言語：英語 掲載種別：研究論文（学術雑誌）
An anti-aging effect may be obtained by skin application of tea catechins (Camellia sinensis) since they have high ultraviolet (UV)-protection activity. In this study, the skin permeation of catechin (C), epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECg) and epigallocatechin gallate (EGCg) was determined and compared, and the effect of emulsification on the skin permeation of C was measured. The UV-protective effect of C was also determined. The in vitro skin permeability of each catechin derivative was determined using side-by-side diffusion of cells. The UV-protective effect of C was determined by applying different concentrations of C to the solution or emulsion on a three-dimensional cultured human skin model or normal human epidermal keratinocytes with UV-irradiation. ECg and EGCg with gallate groups showed lower skin permeability than C, EC and EGC without gallate groups, suggesting that the skin permeability of catechin derivatives may be dependent on the existence of a gallate group. Interestingly, the skin permeation of C was increased by an o/w emulsification. In addition, the C emulsion showed a significantly higher UV-protective effect by C than that with its aqueous solution. These results suggest that the o/w emulsion of catechin derivatives is probably useful as a cosmetic formulation with anti-aging efficacy.
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Safety prediction of topically exposed biocides using permeability coefficients and the desquamation rate at the stratum corneum.
Sugino Masahiro, Todo Hiroaki, Suzuki Takamasa, Nakada Keiichi, Tsuji Kiyomi, Tokunaga Hiroshi, Jinno Hideto, Sugibayashi Kenji
J Toxicol Sci 39 ( 3 ) 475 - 485 2014年06月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Advances in the synthesis and utilization of new chemical compounds have led to improvements in our daily lives. However, new chemicals may be both beneficial and toxic. Thus, exposure to these new compounds should be restricted in an attempt to limit their potential toxicities. We predicted the safety of three biocides (p-cresol, diazinon and resmethrin) by comparing their skin permeability coefficients and desquamation rate (the counter flux of permeability coefficient for chemical compounds induced by skin turnover) following skin exposure. In vitro skin permeation experiments revealed that the permeability coefficients of diazinon and resmethrin were smaller than the desquamation rate; therefore, these biocides could not permeate the skin, which resulted in very low skin concentrations of these compounds. On the other hand, the skin concentration of p-cresol was high because of its higher permeability coefficient than the desquamation rate. Furthermore, low in vitro cell viability was reported for skin exposed to p-cresol. These results in the present study indicate that the method described herein is useful for predicting the toxicities of chemicals following their topical exposure.
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Analysis of hair follicle penetration of lidocaine and fluorescein isothiocyanate-dextran 4 kDa using hair follicle-plugging method. 査読あり
Horita Daisuke, Yoshimoto Masato, Todo Hiroaki, Sugibayashi Kenji
Drug Dev Ind Pharm 40 345 - 351 2014年03月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Analysis of hair follicle penetration of lidocaine and fluorescein isothiocyanate-dextran 4 kDa using hair follicle-plugging method.
Horita Daisuke, Yoshimoto Masato, Todo Hiroaki, Sugibayashi Kenji
Drug Dev Ind Pharm 40 ( 3 ) 345 - 351 2014年03月
記述言語：英語 掲載種別：研究論文（学術雑誌）
OBJECTIVE: Skin appendages including hair follicles (hfs) and the stratum corneum (sc) are beginning to be recognized as important permeation pathways for the skin permeation of drugs, but their detailed role is not yet clear. To investigate the contribution of hfs to drug permeation, we conducted skin permeation tests by controlling the hf contribution with a hf-plugging method. METHOD: Lidocaine (LC) and fluorescein isothiocyanate-dextran 4 kDa (FD-4) were selected as model drugs and pig ear skin was used as model skin. RESULTS: Skin permeabilities of ionized LC and FD-4 decreased with hf-plugging, whereas no change was observed for the skin permeation of unionized LC. A fairly good correlation was found for ionized LC and FD-4 between skin permeability and the number of hfs plugged. Permeation parameters of model drugs for both skin pathways were calculated utilizing Fick's second law of diffusion. Consequently, the sc pathway could highly contribute to the permeation of unionized LC, since unionized LC shows markedly high partition to the sc. In contrast, the hf pathway could contribute to the permeation of ionized LC and FD-4, since these had high distributions to the hf pathway in spite of its very small surface area relative to whole skin surface area. CONCLUSION: The hf pathway must be important for the skin permeation of ionized compounds and hydrophilic high molecular compounds. hf-plugging is also a useful method for assessing the skin permeability of compounds through the hf pathway.
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Analysis of the pretreatment effect of ethanol on the stratum corneum- and hair follicular-penetration of drugs using the hair follicle-plugging method.
Horita Daisuke, Todo Hiroaki, Sugibayashi Kenji
Chem Pharm Bull (Tokyo) 62 ( 6 ) 578 - 585 2014年
記述言語：英語 掲載種別：研究論文（学術雑誌）
The hair follicle-plugging method was used to analyze the effects of EtOH on skin permeation pathways. METHODS: In vitro permeation experiments were performed on 4 model drugs [isosorbide mononitrate (ISMN), ionized lidocaine (ionized LC), fluorescein (FL), and fluorescein isothiocyanate (FITC)-dextran 4 kDa (FD-4)] using excised pig ear skin. The skin permeations of ionized LC, FL, and FD-4 were decreased by hair follicle-plugging. Hair follicle-plugging prevented the skin permeation of FL and FD-4 in EtOH-pretreated skin, but did not prevent that of ISMN. On the other hand, the effect of hair follicle-plugging on the permeation of ionized LC was different among the pretreatment conditions. These results indicate that the EtOH pretreatment greatly affected the aqueous pathway in the stratum corneum and hair follicles.
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Usefulness of pressure-sensitive adhesives as a pretreatment material before application of topical drug formulations and a peeling tape for excess stratum corneum layers.
Kikuchi Keisuke, Todo Hiroaki, Sugibayashi Kenji
Chem Pharm Bull (Tokyo) 62 ( 6 ) 559 - 567 2014年
記述言語：英語 掲載種別：研究論文（学術雑誌）
Two unique pressure-sensitive adhesive (PSA) tapes (PSA-A, -B) with different adhesive properties of commercial PSAs were prepared and evaluated for their usefulness as a pretreatment material prior to the application of transdermal therapeutic systems or topical drug formulations and also as a peeling agent against excess layers of the stratum corneum. In the present study, in vitro permeation experiments were conducted using vertical type diffusion cells and excised hairless rat or porcine skin from which the stratum corneum had been stripped several times with PSAs. The results obtained revealed that PSA-A and -B had higher stripping or peeling effects than those of the marketed PSAs. Marked changes were observed in skin barrier function before and after stripping using PSAs, and the enhancement effect on the skin permeation of drugs achieved by stripping the stratum corneum was markedly different between the PSAs. PSA-A, in particular, markedly improved skin permeation and the skin concentration of topically applied chemical compounds because it removed many layers of the stratum corneum when skin was stripped only a few times. In contrast, when PSA-B was used to pretreat the skin surface, the extent of skin permeation and concentration of drugs was safely increased because only a few layers of the stratum corneum were removed, even with repeated stripping. The enhancement effect achieved by PSA-B was not as high as that by PSA-A. Thus, stripping with PSA-A can be used as a penetration enhancement tool, whereas PSA-B can be used as a peeling material against excess layers of the stratum corneum.
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[In vitro and in silico approaches to evaluate usefulness and safety of chemical compounds applied or exposed on skin].
Sugibayashi Kenji, Todo Hiroaki, Kadhum Wesam R
Yakugaku Zasshi 134 ( 1 ) 27 - 32 2014年
記述言語：日本語 掲載種別：研究論文（学術雑誌）
Recently, animal experiments become very difficult to be done in the research and development of cosmetics and cosmeceuticals due to animal welfare and 3Rs (replacement, reduction, refinement) concept. However, usefulness and safety of these preparations must be strictly guaranteed before human use. We thus proposed three sets of extrapolation methods to estimate in vivo profiles from in vitro and in silico approaches, to evaluate permeation profiles through real human skin from those through animal skin and cultured human skin model, and to estimate responses such as usefulness and safety of cosmetics and cosmeceuticals from their skin permeation and concentration profiles. Although we need more data and discussion, the present extrapolation methods must be very useful for estimation of cosmetics and cosmeceuticals without using animal experiments.
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Effect of beta-cyclodextrin derivatives on the diosgenin absorption in Caco-2 cell monolayer and rats.
Okawara Masaki, Tokudome Yoshihiro, Todo Hiroaki, Sugibayashi Kenji, Hashimoto Fumie
Biol Pharm Bull 37 ( 1 ) 54 - 59 2014年
記述言語：英語 掲載種別：研究論文（学術雑誌）
Orally administrated diosgenin, a steroidal saponin found in the roots of Dioscorea villosa, improves reduced skin thickness in ovariectomized mice, and plays an important role in the treatment of hyperlipidemia. Diosgenin has been noticed as an active element in cosmeceutical and dietary supplements. We have already elucidated that the absolute oral bioavailability of diosgenin is very low; however, a high skin distribution of diosgenin was also observed. The aim of the present study was to examine and compare the effects of beta-cyclodextrin (beta-CD) and 3 kinds of its derivatives such as hydroxypropyl beta-CD on the diosgenin permeability using a Caco-2 model and rat jejunal perfusion. These derivatives of beta-CD greatly improved the low solubility of diosgenin. No significant increase was observed in the lactate dehydrogenase leakage from Caco-2 cell, while a slight decrease was found on the transepithelial electrical resistance by diosgenin and beta-CD derivatives. However, beta-CD derivatives, especially hydroxyethyl beta-CD and hydroxypropyl beta-CD, markedly enhanced diosgenin permeability across the Caco-2 monolayer and rat jejunum. The bioavailability of diosgenin in the presence of beta-CD derivatives were about 4 to 11 fold higher than diosgenin suspension. The mechanisms of these enhancement effects may be due to improvements in solubility and tight junction opening.
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Enhancement of diosgenin distribution in the skin by cyclodextrin complexation following oral administration.
Okawara Masaki, Tokudome Yoshihiro, Todo Hiroaki, Sugibayashi Kenji, Hashimoto Fumie
Biol Pharm Bull 36 ( 1 ) 36 - 40 2013年
記述言語：英語 掲載種別：研究論文（学術雑誌）
Orally administrated diosgenin, a steroidal saponin found in several plants including Dioscorea villosa, recovers skin thickness reduced in ovariectomized mice, and plays an important role in the treatment of hyperlipidemia. Thus, diosgenin is an active element of cosmeceutical and dietary supplements. However, we have already elucidated that the skin distribution and absolute oral bioavailability of diosgenin is very low. The aim of this study is to evaluate the efficacy of diosgenin-cyclodextrin (CD) complexes in improving the skin concentration of diosgenin. The formation of the CD complex was indicated by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and scanning electron microscope (SEM) studies. Oral administration of the diosgenin/beta-CD complex resulted in a significant enhancement in terms of the skin distribution of diosgenin, maximum plasma level (C(max)), area under the plasma concentration-time curve (AUC), and absolute oral bioavailability over those of the drug alone. These results suggest that the inclusion complex of diosgenin/beta-CD can be used to improve low skin content of diosgenin.
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Mathematical model to predict skin concentration after topical application of drugs.
Todo Hiroaki, Oshizaka Takeshi, Kadhum Wesam R, Sugibayashi Kenji
Pharmaceutics 5 ( 4 ) 634 - 651 2013年
記述言語：英語 掲載種別：研究論文（学術雑誌）
Skin permeation experiments have been broadly done since 1970s to 1980s as an evaluation method for transdermal drug delivery systems. In topically applied drug and cosmetic formulations, skin concentration of chemical compounds is more important than their skin permeations, because primary target site of the chemical compounds is skin surface or skin tissues. Furthermore, the direct pharmacological reaction of a metabolically stable drug that binds with specific receptors of known expression levels in an organ can be determined by Hill's equation. Nevertheless, little investigation was carried out on the test method of skin concentration after topically application of chemical compounds. Recently we investigated an estimating method of skin concentration of the chemical compounds from their skin permeation profiles. In the study, we took care of "3Rs" issues for animal experiments. We have proposed an equation which was capable to estimate animal skin concentration from permeation profile through the artificial membrane (silicone membrane) and animal skin. This new approach may allow the skin concentration of a drug to be predicted using Fick's second law of diffusion. The silicone membrane was found to be useful as an alternative membrane to animal skin for predicting skin concentration of chemical compounds, because an extremely excellent extrapolation to animal skin concentration was attained by calculation using the silicone membrane permeation data. In this chapter, we aimed to establish an accurate and convenient method for predicting the concentration profiles of drugs in the skin based on the skin permeation parameters of topically active drugs derived from steady-state skin permeation experiments.
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Effect of direction (epidermis-to-dermis and dermis-to-epidermis) on the permeation of several chemical compounds through full-thickness skin and stripped skin.
Oshizaka Takeshi, Todo Hiroaki, Sugibayashi Kenji
Pharm Res 29 ( 9 ) 2477 - 2488 2012年09月
記述言語：英語 掲載種別：研究論文（学術雑誌）
PURPOSE: Compound permeation through stratum corneum-stripped skin is generally greater than that through full-thickness skin. In addition, epidermis-to-dermis permeation profile should be the same as dermis-to-epidermis permeation profile. However, stripped skin permeability of some compounds was lower than full-thickness skin permeability and different permeabilities were found for some compounds between the two directions of skin permeation. The reasons for these findings were investigated in this study. METHODS: Full-thickness or stripped hairless rat skin was set in a Franz-type diffusion cell, and a solution of compound was applied on the epidermis or dermis side to determine the in vitro skin permeability. RESULTS: Although the stripped skin permeability of pentyl paraben (PeP) with extremely high logK(o/w) was lower than full-thickness skin permeabilities, the addition of 3% ethanol resulted in the expected permeation order. Epidermis-to-dermis permeation of PeP through full-thickness skin was higher than dermis-to-epidermis permeation. Epidermis-to-dermis permeations of fluorescein isothiocyanate dextran (FD-4) and isosorbide 5-mononitrate with negative logK(o/w) were also higher than those in the opposite direction. CONCLUSIONS: Morphological observation of skin after FD-4 permeation suggested that a conically shaped trans-follicular permeation pathway model could be advocated to explain the difference between the epidermis-to-dermis permeation and that in the opposite direction.
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Effects of soybean peptide and collagen peptide on collagen synthesis in normal human dermal fibroblasts.
Tokudome Yoshihiro, Nakamura Kyosuke, Kage Madoka, Todo Hiroaki, Sugibayashi Kenji, Hashimoto Fumie
Int J Food Sci Nutr 63 ( 6 ) 689 - 695 2012年09月
記述言語：英語 掲載種別：研究論文（学術雑誌）
The collagen present in the dermis of the skin is a fibrous protein that fills the gaps between cells and helps maintain tissue flexibility. Effectively increasing the collagen present in the skin is an important goal for cosmetic research. Recent research has shown that soybean peptide (SP) has anti-fatigue activity, antioxidant activity, and the ability to increase type I collagen, while collagen peptide (CP) has the ability to enhance corneal moisture content and viscoelasticity, as well as to increase levels of hyaluronic acid synthesizing enzymes in human skin. Little documented research, however, has been conducted on collagen formation in relation to these peptides. Therefore, this research applied SP and CP with molecular weights primarily around 500 and preparations containing both SP and CP to normal human dermal fibroblasts together with magnesium ascorbyl phosphate (VC-PMg), and used real-time PCR to determine the gene expression of type I collagen (COL1A1), which contributes to collagen synthesis, and Smad7, which contribute to collagen breakdown. In addition, enzyme linked immuno sorbent assay (ELISA) was used to measure collagen content in the media. COL1A1 gene expression at 24 h after sample addition showed higher tendency in all samples and increased with time at 4, 8 and 24 h after addition. Smad7 gene expression was not substantially different at 4 h after addition. matrix metalloproteinase-1 gene expression was higher following SP addition, but was lower after the addition of CP and SP+CP. Medium collagen content was higher in all samples and increased with time at 8 h after addition. Collagen levels were higher when SP and CP were added together.
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Measurement of skin permeation/penetration of nanoparticles for their safety evaluation. 査読あり
Biological & pharmaceutical bulletin 35 ( 9 ) 2012年04月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Measurement of skin permeation/penetration of nanoparticles for their safety evaluation.
Kimura Eriko, Kawano Yuichiro, Todo Hiroaki, Ikarashi Yoshiaki, Sugibayashi Kenji
Biol Pharm Bull 35 ( 9 ) 1476 - 1486 2012年
記述言語：英語 掲載種別：研究論文（学術雑誌）
The aim of the present study was to quantitatively evaluate the skin permeation/penetration of nanomaterials and to consider their penetration pathway through skin. Firstly, penetration/permeation of a model fluorescent nanoparticle, Fluoresbrite(R), was determined through intact rat skin and several damaged skins. Fluoresbrite(R) permeated through only needle-punctured skin. The permeation profiles of soluble high molecular compounds, fluorescein isothiocyanate-dextrans (FITC-dextrans, FDs), with different molecular weights were also measured for comparison. The effects of molecular sizes and different skin pretreatments on the skin barrier were determined on the skin penetration/permeation of Fluoresbrite(R) and FDs. Fluoresbrite(R) was not permeated the intact skin, but FDs were permeated the skin. The skin distribution of titanium dioxide and zinc oxide nanoparticles was also observed after topical application of commercial cosmetics. Nanoparticles in sunscreen cosmetics were easily distributed into the groove and hair follicles after their topical application, but seldom migrated from the groove or follicles to viable epidermis and dermis. The obtained results suggested that nanoparticles did not permeate intact skin, but permeated pore-created skin. No or little permeation was observed for these nanomaterials through the stratum corneum.
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[Safety and skin penetration of nanoparticles].
Kimura Eriko, Todo Hiroaki, Sugibayashi Kenji
Yakugaku Zasshi 132 ( 3 ) 319 - 324 2012年
記述言語：日本語 掲載種別：研究論文（学術雑誌）
Human beings are exposed or otherwise a subjected to a various chemical compounds. Various nanomaterials are contained in the chemical compounds which are used in many fields. Nanomaterials are also used in cosmetics: titanium dioxide and zinc oxide are examples. Consumers who apply cosmetics to their skin as well as workers at industrial plants may thus be exposed to these nanoparticles. Therefore, it is of great importance to evaluate the safety of these nanoparticles. In this review, we describe the possibility of nanoparticle penetration to skin following exposure, which makes it urgent to evaluate the safety factors. In general, it is necessary to take account of the desquamation rate of the stratum corneum and the permeation pathway and size of nanoparticles when considering such penetration. One layer of the human stratum corneum is peeled off per day. Therefore, a chemical compound of which the skin penetration is lower than the desquamation rate does not permeate through the skin, when the compound infiltrates the stratum corneum. Hence, compounds with a molecular weight of more than 500 Daltons do not permeate through the stratum corneum. However, we must also pay attention to the appendage routes, although the aforementioned layer is the primary permeation route of nanoparticles. The contribution of appendage routes must be taken into consideration.
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Influence of skin thickness on the in vitro permeabilities of drugs through Sprague-Dawley rat or Yucatan micropig skin.
Takeuchi Hiroyuki, Ishida Masahiro, Furuya Atsushi, Todo Hiroaki, Urano Hidetoshi, Sugibayashi Kenji
Biol Pharm Bull 35 ( 2 ) 192 - 202 2012年
記述言語：英語 掲載種別：研究論文（学術雑誌）
The purpose of this study was to clarify the influence of skin thickness on the in vitro permeabilities of 3 model drugs with different physicochemical properties (nicorandil (NR), isosorbide dinitrate (ISDN) and flurbiprofen (FP)) through Sprague-Dawley rat (rat) or Yucatan micropig (YMP) skin. Intact, dermis-split, stratum corneum-stripped or stratum corneum-stripped and dermis-split rat or YMP skin (rat skin thickness: approximately 0.4, 0.9 or 1.2 mm; YMP skin thickness: approximately 0.4, 0.9, 1.8 or 2.8 mm) were set in Franz-type diffusion cells to determine the permeation rate, lag time and resistance ratio of the viable epidermis and dermis against whole skin (R(ved)/R(tot)) of the drugs. The YMP skin permeabilities of the drugs decreased with an increase in the skin thickness, and significant differences were observed in the permeation rates and lag times between intact and dermis-split (0.4 mm) YMP skins. The decreases in the permeabilities of the drugs through the YMP skin were larger than those through the rat skin. The influence of resistances of ISDN and FP through the dermis-split rat or YMP skin was greater at 0.9 mm skin thickness than 0.4 mm skin thickness. The R(ved)/R(tot) values for the YMP skins were relatively large for lipophilic drugs (ISDN and FP), and these ratios increased with an increase in the dermis thickness. These results suggest that in vitro skin permeation studies must be done using dermis-split (0.4 mm) skin with the thinnest dermis for predicting in vivo human percutaneous absorption rate.
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[Evaluation of efficacy and safety of drugs absorbed through skin using their physicochemical parameters].
Oshizaka Takeshi, Todo Hiroaki, Sugibayashi Kenji
Yakugaku Zasshi 132 ( 11 ) 1237 - 1243 2012年
記述言語：日本語 掲載種別：研究論文（学術雑誌）
Skin has been paid attention as a site of application of prescription drugs, over-the-counter drugs (non-prescription drugs) and cosmetics. Skin permeation and skin concentration of the compounds should be considered after topical administration, as well as their blood concentration to evaluate efficacy and safety. Since the evaluation of the amount of drugs permeated through skin is important for topically applied drugs, studies on the skin permeation has been greatly advanced. In addition, many reports proved that skin permeabilities of drugs could be predicted from physicochemical parameters of drugs. On the other hand, few reports have been found on the prediction of skin concentration of drugs. Furthermore, many experimented problems are left to determine the skin concentration of drugs: severe consume of human or animal skins, difficult removal of applied drugs from the skin surface, low drug extraction ratio from skin and low sensitivity to determine skin concentration of drugs, and requirement of long time measurement. Thus, fast and accurate measurement of skin concentration of applied drugs are urgently required. This report describes the relationship between skin permeation and skin concentration, and the prediction of skin concentration of drugs using skin permeation parameters of drugs.
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Evaluation of the skin blanching of topically applied steroids using a chroma meter in animals.
Ishii Hiroshi, Fujino Konomi, Todo Hiroaki, Sugibayashi Kenji
Exp Anim 61 ( 2 ) 147 - 156 2012年
記述言語：英語 掲載種別：研究論文（学術雑誌）
We evaluated the utility of animal skins for determining the skin blanching of steroids. A Chroma Meter was used to determine the skin blanching of steroids. Hydrophilic creams containing clobetasol propionate (CP) or prednisolone (PS) were selected as model steroid formulations. Skin blanching, a*, was determined using a Chroma Meter after the application of 0.005, 0.01, 0.1, or 1.0% CP or PS hydrophilic cream to the back skin of guinea pigs and hairless rats for 24 h. The relationships between Deltaa*(6h) and the skin concentrations of the steroids were determined at 6 h after removal of the cream. Deltaa*(6h) was markedly decreased after the application of CP hydrophilic cream to guinea pigs, and a good linear relationship was observed between Deltaa*(6h) and skin concentration (r=0.98). In contrast, no relationship was observed between these parameters after the application of CP cream to the hairless rats. Although skin blanching was observed after PS cream application in guinea pigs, no relationship was observed between Deltaa*(6h) and skin concentration of PS in each animal. These results suggest that the skin blanching effect of CP in guinea pigs is greater than that of PS and that its blanching effect in guinea pigs was stronger than that in hairless rats. Guinea pigs were found to be a good animal model for determining the skin blanching produced by steroid creams. In addition, Chroma Meters can be effectively used in skin vasoconstrictive tests in guinea pigs.