Toyama-shi, Japan
Toyama-shi, Japan

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Nishikawa M.,Hoshi University | Onuki Y.,Hoshi University | Okuno Y.,Ikeda Mohando Co. | Takayama K.,Hoshi University
Chemical and Pharmaceutical Bulletin | Year: 2011

This study investigated the relationship between the state of water and the dispersion stability of a skin cream formulation. Hydrophilic ointments treated with a high-pressure wet-type jet mill were used as model formulations. Spin-lattice relaxation times (T 1) were measured by magnetic resonance techniques to estimate the state of water in samples. A shorter T 1 relaxation time was obtained from samples with higher surfactant content, whereas the processing pressure of the jet mill and 1-week storage at 40°C did not influence the T 1 relaxation time. Observations using scanning electron microscopy (SEM) showed that coalescence occurred in samples with lower surfactant contents (1.0% by weight) following 1-week storage at 40°C. We also investigated samples prepared using a hydrophilic surfactant with a short polyethylene glycol (PEG) chain and with PEG-4000. From the change in T 1 relaxation times after removing the oil phase from samples by centrifugation, it was clarified that most of the surfactant was located on the surface of oil droplets. Furthermore, SEM observations showed that phase separation was facilitated as the PEG chain length of the surfactant shortened. Thus, a thin water layer over oil droplets is the most important factor for stabilizing their dispersion. This study provides proof-of-principle results on the contribution of the state of water to the dispersion stability of a skin cream formulation. © 2011 Pharmaceutical Society of Japan.


Nishikawa M.,Hoshi University | Onuki Y.,Hoshi University | Okuno Y.,Ikeda Mohando Co. | Takayama K.,Hoshi University
Drug Development and Industrial Pharmacy | Year: 2010

Background: A high-pressure wet-type jet mill is a powerful equipment used for the dispersion and emulsification of substances. In this study, we investigated its usefulness in the preparation of skin cream formulations. Method: We prepared a hydrophilic ointment base as a typical skin cream base, and then treated it with the wet-type jet mill under different conditions. Controllable factors of the wet-type jet mill included processing pressure, treatment cycle, and temperature of the treatment. Result: Treatment with the wet-type jet mill had a great impact on the rheological characteristics of the hydrophilic ointment base. The hysteresis areas and yield values of the treated ointments were significantly increased by increasing the processing pressure and temperature during the treatment. From scanning electron microscopic observations, the oil droplet size of the hydrophilic ointments decreased after treatment with the wet-type jet mill, suggesting that a decrease in oil droplet size mediates changes in the rheological characteristics. Conclusion: Because we can expect the wet-type jet mill to control the rheological characteristics of the ointment, it is a promising tool for the preparation of skin cream formulations. © Informa UK, Ltd.


Onuki Y.,Hoshi University | Horita A.,Ikeda Mohando Co. | Kuribayashi H.,Agilent Technologies | Okuno Y.,Ikeda Mohando Co. | And 2 more authors.
Drug Development and Industrial Pharmacy | Year: 2014

A non-destructive method for monitoring creaming of emulsion-based formulations is in great demand because it allows us to understand fully their instability mechanisms. This study was aimed at demonstrating the usefulness of magnetic resonance (MR) techniques, including MR imaging (MRI) and MR spectroscopy (MRS), for evaluating the physicochemical stability of emulsion-based formulations. Emulsions that are applicable as the base of practical skin creams were used as test samples. Substantial creaming was developed by centrifugation, which was then monitored by MRI. The creaming oil droplet layer and aqueous phase were clearly distinguished by quantitative MRI by measuring T1 and the apparent diffusion coefficient. Components in a selected volume in the emulsions could be analyzed using MRS. Then, model emulsions having different hydrophilic-lipophilic balance (HLB) values were tested, and the optimal HLB value for a stable dispersion was determined. In addition, the MRI examination enables the detection of creaming occurring in a polyethylene tube, which is commonly used for commercial products, without losing any image quality. These findings strongly indicate that MR techniques are powerful tools to evaluate the physicochemical stability of emulsion-based formulations. This study will make a great contribution to the development and quality control of emulsion-based formulations. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.


Yoshida N.,Tokyo University of Technology | Yoshida N.,Ikeda Mohando Co. | Sawada E.,Tokyo University of Technology | Imokawa G.,Tokyo University of Technology
Archives of Dermatological Research | Year: 2012

To examine factors that regulate ceramide production during keratinization of the human stratum corneum (SC), we developed a reconstructed human epidermal keratinization model in which a fresh layer of SC is newly formed within 1 week. Addition of the UDP-glucose: ceramide glucosyltransferase inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol significantly diminished SC ceramide levels (expressed as μg/mg protein) with decreased glucosylceramide levels. Desipramine hydrochloride, an inhibitor of sphingomyelinase, also significantly reduced SC ceramide levels. Similarly, conduritol B epoxide, an inhibitor of β-glucocerebrosidase, significantly down-regulated SC ceramide levels and significantly increased glucosylceramide levels. These results indicate the reliability of this model to elucidate ceramide synthesis regulating factors. Using this model, we assessed the effects of the inflammatory cytokine interleukin-1α (IL-1α), several bioactive sphingolipids and all-trans retinoic acid (RA) on ceramide levels in the SC. Whereas treatment with IL-1α (at 10 nM) significantly down-regulated ceramide levels, treatment with sphingosylphosphorylcholine (at 50 μM) or sphingosine-1-phosphate (at 10 or 20 μM) distinctly up-regulated ceramide levels. Interestingly, RA (at low as 10 nM) significantly up-regulated ceramide levels without affecting the formation of the SC or levels of keratinization-related proteins in the epidermis. The increased levels of ceramide were accompanied by a significantly increased secretion of granulocyte-macrophage colony-stimulating factor as well as by a significantly down-regulated expression of acid-ceramidase at both the gene and protein levels. Taken together, our results underscore the superiority of this reconstructed human epidermal keratinization model to analyze factors that regulate ceramide synthesis, especially in human SC. © 2012 Springer-Verlag.


Sawada E.,Tokyo University of Technology | Yoshida N.,Tokyo University of Technology | Yoshida N.,Ikeda Mohando Co. | Sugiura A.,Tokyo University of Technology | And 2 more authors.
Journal of Dermatological Science | Year: 2012

Background: Although the mechanism(s) involved in the ceramide deficiency in the stratum corneum (SC) of atopic dermatitis (AD) skin is unknown, Th2 type cytokines have been reported to down-regulate ceramide levels in the epidermis. However, almost all research to date has focused on ceramide levels in the whole epidermis, not just in the SC layers alone, which are predominantly responsible for the skin barrier function. Objective: We highlighted the effects of Th1/Th2 cytokines on ceramide levels in the SC. Methods: We developed a modified system of human epidermal equivalents in which epidermis without a SC is cultured for 1 week to generate complete SC layers after which ceramides are extracted from the separated SC layers and are then quantified as per SC protein. Results: The addition of Th2 cytokines (IL-4/IL-6) at a concentration of 10. nM resulted in a marked decrease in SC ceramide levels. The reduced ceramide content in the SC was accompanied by the down-regulated expression of the genes encoding serine-palmitoyl transferase-2, acid sphingomyelinase and β-glucocerebrosidase in the epidermis. In contrast, the addition of Th1 cytokines (GM-CSF/IFN-γ/TNF-α) at concentrations of 2.5 or 10. nM resulted in a slight increase in SC ceramide levels, which were accompanied by no change or an increase in the expression of those genes encoding sphingolipid metabolic enzymes in the epidermis. Conclusion: These findings suggest that the Th2 type of inflammation evoked in AD skin is one of the essential factors involved in down-regulating the levels of ceramide in the SC. © 2012 Japanese Society for Investigative Dermatology.


Horita D.,Josai University | Horita D.,Ikeda Mohando Co. | Hatta I.,Nagoya Industrial Science Research Institute | Hatta I.,Aichi Synchrotron Radiation Center | And 4 more authors.
Biochimica et Biophysica Acta - Biomembranes | Year: 2015

Ethanol (EtOH) is one of the bases in topically applied medicines that promote the skin permeation of drugs. Although the effects of EtOH have been attributed to structural modifications in the stratum corneum, the underlying mechanisms, especially the influence of different concentrations of EtOH, have not been examined extensively. Structural modifications in the stratum corneum of hairless mouse due to the application of EtOH/water mixture were herein investigated at the molecular level using synchrotron X-ray diffraction. The results revealed that all EtOH concentrations examined greatly modified the short lamellar structures containing the aqueous layer in intercellular lipids and the structure of keratin fibrils in corneocytes, which can take up hydrophilic compounds. However, the long lamellar and the hydrocarbon-chain packing structures were unaffected by EtOH. Changes to the short lamellar structures were not proportional to the concentration of EtOH. However, the keratin fibril structures changed gradually with increasing EtOH concentration. The X-ray diffraction experiments enabled the effects of different EtOH concentrations on the morphology of the stratum corneum to be assessed by using a number of experimental samples to avoid variations due to individual differences. The results indicated that alterations to the short lamellar structures appeared to be related to the skin permeability of drugs with the application of EtOH/water mixture, and monotonous structural changes in the keratin fibrils with an increase in EtOH concentration may contribute to this permeation as supplement. These results will be useful for the development of new drug formulations containing EtOH. © 2015 Elsevier B.V.


Trademark
Ikeda Mohando Co. | Date: 2012-01-24

PHARMACEUTICAL PREPARATIONS, NAMELY, ANTI-INFLAMMATORY OINTMENTS, ANTI-ITCH OINTMENTS, ANTI-ITCH CREAM; PHARMACEUTICAL PREPARATIONS FOR SKIN CARE AND FOR TREATING SKIN DISORDERS; OIL EMULSION PAPER DRESSINGS; WAFER BAGS SOLD EMPTY FOR USE IN WRAPPING POWDERED MEDICINE TO MAKE IT EASIER TO SWALLOW; GAUZE FOR DRESSINGS; CAPSULES SOLD EMPTY FOR PHARMACEUTICALS; EYE PATCHES FOR MEDICAL PURPOSES; SURGICAL EAR BANDAGES; SANITARY PADS; ABSORBENT COTTON WOOL FOR MEDICAL PURPOSES; STICKING PLASTERS; BANDAGES FOR DRESSINGS; ANTISEPTIC LIQUID BANDAGES; BREAST-NURSING PADS; DENTAL COMPOSITE MATERIALS.


Horita D.,Josai University | Horita D.,Ikeda Mohando Co. | Yoshimoto M.,Josai University | Todo H.,Josai University | Sugibayashi K.,Josai University
Drug Development and Industrial Pharmacy | Year: 2014

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. © 2014 Informa Healthcare USA, Inc.


Horita D.,Josai University | Horita D.,Ikeda Mohando Co. | Todo H.,Josai University | Sugibayashi K.,Josai University
Chemical and Pharmaceutical Bulletin | Year: 2014

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. © 2014 The Pharmaceutical Society of Japan.


PubMed | Ikeda Mohando Co.
Type: Journal Article | Journal: Journal of dermatological science | Year: 2012

Trichophyton-induced superficial skin mycosis is a common infectious human disease, but the immunological mechanism against Trichophyton infection is unclear with regard to many points. Since Trichophyton cannot colonize mice, guinea pigs were used in previous experiments on Trichophyton infection. However, it is difficult to perform immunological and genetic analyses in guinea pigs.The objective of this study was to establish a mouse Trichophytin-associated inflammation model of superficial skin mycosis in which immunological and genetic analyses can be performed.We established a mouse Trichophyton-induced contact hypersensitivity model by applying Trichophytin, the Trichophyton antigen, extracted from Trichophyton mentagrophytes, to mice. Using a Th1-dominant strain, C57BL/6, and a Th2-dominant strain, BALB/c, we investigated the expression of inflammatory cytokines and receptors of the innate immune system for fungi, TLR4, TLR2, and dectin-1, and their influences on responses of the acquired immune system.In C57BL/6 mice, expressions of IFN- and IL-17 A in regional lymph nodes and IL-1, IFN-, IL-6, and IL-23 in the inflammatory auricular skin were enhanced by Trichophytin challenge, suggesting that not only Th1 cells but also Th17 cells were induced. In BALB/c mice, expressions of IL-4 in regional lymph nodes, and TSLP and IL-4 in the auricular skin were enhanced by Trichophytin challenge. Interestingly, dectin-1-neutralizing antibody inhibited the promotion of IFN- production in C57BL/6 mice, and dectin-1-expressing immune cells had crucial actions in Trichophyton-induced IFN- production.These results suggest that inflammatory mediators differently regulate Trichophytin-induced contact hypersensitivity on the basis of the status of host immunity.

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