• Journal of Pharmaceutical Investigation
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• v.29 no.4
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• pp.329-335
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• 1999

Clenbuterol, a selective ${\beta}_2-adrenergic$ receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic bronchitis and pulmonary emphysema. For the purpose of developing a transdermal preparation for clenbuterol, we attempted to select an optimal solvent system and permeation enhancer among fatty acids and fatty alcohols which are known to accelerate the penetration of various drugs in permeation experiments using hairless mouse skin and Franz diffusion cell. Apparent partition coefficient of clenbuterol was increased as pH of buffer solution was increased and solubility of clenbuterol was increased as the percent of propylene glycol(PG) in buffer solution(pH 10) was increased. Permeability of clenbuterol from different buffer(pH 10)/PG solvent mixtures was decreased as the percent of PG in pH 10 buffer solution was increased and among the various enhancers studied, lauryl alcohol was found to be the most effective enhancer, increasing the permeability of clenbuterol approximately 76-fold compared with control. Lauryl alcohol$(0{\sim}2%)$ enhanced the permeability of clenbuterol concentration-dependently. In this study, the optimal solvent system for the penetration of clenbuterol was found to be 50/50 buffer(pH 10)/PG solvent mixture containing 2% lauryl alcohol.

• Journal of Microbiology and Biotechnology
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• v.25 no.1
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• pp.74-80
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• 2015

Skin is the soft outer covering of vertebrates that provides protection from pathogenic infection, physical damage, or UV irradiation, and controls body temperature and water content. In this study, we examined the effects of oral intake of kimchi-derived Lactobacillus plantarum K8 lysates on skin moisturizing. In an in vitro study, we observed that the hyaluronic acid content increased in HaCaT cells treated with L. plantarum K8 lysates. Oral administration of L. plantarum K8 lysates effectively attenuated the horny layer formation and decreased epidermal thickening in DNCB-treated SKH-1 hairless mice skin. The damage to barrier function was reduced after 8 weeks of oral administration of L. plantarum K8 lysates as compared with that in the atopic dermatitis mice. For the test with volunteers, we manufactured experimental candy containing 2.1% L. plantarum K8 lysates, while control candy did not contain bacterial lysate. A significant increase in hydration in the experimental candy-administered group as compared with the control candy-administered group was observed on the face after 4 and 8 weeks, and on the forearm after 4 weeks. Decreases in horny layer thickness and TEWL value were observed on the face and forearm of the experimental group. Together, the in vitro cell line and in vivo mouse studies revealed that L. plantarum K8 lysates have a moisturizing effect. A clinical research study with healthy volunteers also showed an improvement in barrier repair and function when volunteers took L. plantarum K8 lysates-containing candy. Thus, our results suggest that L. plantarum K8 lysates may help to improve skin barrier function.

• Journal of Sasang Constitutional Medicine
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• v.29 no.4
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• pp.347-368
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• 2017

The aim of this study is to investigate the effect of Zizyphus jujuba var. spinosa Composite oil(ZjJ-C_oil) and Aralia cordata var. continentalis Composite oil(ARC-C_oil) to NC/Nga mice induced in Atopic dermatitis-like skin lesions by DNCB. NC/Nga mice which have been induced to Atopic dermatitis-like skin lesions by DNCB are divided into 4 groups, the first is the mice which have been spread with izyphus jujuba var. spinosa Composite oil(ZjJ-C_oil), the second is the mice which have been spread with Aralia cordata var. continentalis Composite oil(ARC-C_oil), the third is which have been spread with dexamethasone (Dexa.) 0.5% on their Atopic lesion, the last is the control group. Then We analyzed skin clinical score, blood sample of each group of measure state of the dorsal skin, the number of immunocytes, and resect the skin lesion to anlayze the state of cells. There are meaningful results of measuring the number of IgE, IL-4, IL-13, $IFN-{\gamma}$, IL-5, the total cells in ALN, dorsal skin, CD4+ Th, CD11b+/Gr-1+ in PBMCs, CD4+ Th, B220+/CD23+ in ALN, $CD4^+$, $CD8^+$ Th in dorsal skin, the level of COX-2, $TNF-{\alpha}$, $TGF-{\beta}1$, IL-4, IL-13 mRNA, the state of the skin lesion and cells in the group with ZjJ-C_oil, ARC-C_oil cream in comprarison with the control group.

• The Journal of Pediatrics of Korean Medicine
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• v.29 no.4
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• pp.97-107
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• 2015

Objectives Hataedock is the treatment that dispels toxic heat and meconium gathered at the fetus for the new born baby by orally administered herbal extracts. The purpose of this study was to evaluate whether Hataedock alleviate inflammatory skin damages in AD-induced NC/Nga mice through regulating of skin barrier maintain and Th2 differentiation. Methods We established an AD model in the 3-week-old NC/Nga mice through the repeated application of DNFB (dinitrochlorobenzene) on days 28, 35, 42 after Hataedock treatment which was orally administered. We identified the changes of skin barrier and Th2 differentiation through the histological and immunohistochemical changes of protein kinase C (PKC), interleukin (IL)-4, degranulated mast cell, Substance P and MMP-9. Results Our results suggested that Hataedock treatment significantly down-regulated levels of PKC by 82% (p < 0.001), as well as IL-4 by 56% (p < 0.001). Hataedock also suppressed mast cell infiltration, ear edema formation. and Substance P in the tissue of NC/Nga mice were decreased by 57% (p < 0.001), and MMP-9 by 55% (p < 0.001). Conclusions These results suggest that Hataedock alleviates AD through the down-regulation of PKC and Th2 cytokines, which are involved in the initial steps of AD development. Hataedock have potential application for the treatment of AD.

• Toxicological Research
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• v.34 no.1
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• pp.7-12
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• 2018

Laboratory animal models have been developed to investigate preventive or therapeutic effect of medicinal products, or occurrence or progression mechanism of atopic dermatitis (AD), a pruritic and persistent inflammatory skin disease. The murine model with immunologic phenomena resembling human AD was introduced, which demonstrated skewedness toward predominance of type-2 helper T cell reactivity and pathophysiological changes similar as human AD following 2,4-dinitrochlorobenzene (DNCB) sensitization and challenge. Molecular mechanism on the DNCB-mediated AD was further evaluated. Skin tissues were collected from mice treated with DNCB, and each tissue was equally divided into two sections; one for protein and the other for mRNA analysis. Expression of filaggrin, an important protein for keratinocyte integrity, was evaluated through SDS-PAGE. Level of mRNA expression for cytokines was determined through semi-quantitative reverse transcriptase polymerase chain reaction. Expression of filaggrin protein was significantly enhanced in the mice treated with DNCB compared with the vehicle (acetone : olive oil = 4 : 1 mixture) treatment group or the normal group without any treatment. Level of tumor necrosis factor-alpha and interleukin-18 mRNA expression, cytokines involved in activity of type-1 helper T ($T_H1$) cell, was significantly downregulated in the AD group compared with other control groups. These results suggest that suppression of $T_H1$ cell-mediated immune response could be reflected into the skin tissue of mice treated with DNCB for AD induction, and disturbance of keratinocyte integrity might evoke a compensatory mechanism.

• Korean Journal of Pharmacognosy
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• v.25 no.3
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• pp.249-257
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• 1994

The cytotoxic and antitumor activity of Perilla frutescens extract on cultured 3T3 fibroblast and skin melanoma cells were evaluated by tetrazolium MTT (MTT) and neutral red (NR) colorimetric assay methods. Lactate dehydrogenase activity was also measured. The light microscopic study was carried out to observe morphological changes of cultured mouse fibroblast and skin melanoma cells. The results were as follows: 1. Water and ether extracts showed a significant cytotoxicity in 3T3 fibroblast and all extracts exhibited a significant anti-tumor activity in skin melanoma cells. Methanol, ethyl acetate and ethanol extracts showed low cytotoxic effects, but exhibited a high anti-tumor activity. 2. The MTT absorbance in 3T3 fibroblast was significantly decreased by treatment with ether, water, chloroform and ethanol extracts and skin melanoma cells was significantly decreased by treatment with all extracts. The difference in MTT absorbance in two cell types was most remarkable when treated with methanol and ethanol extracts. 3. Methanol and ethyl acetate extracts showed the strongest effect in growth inhibition of melanoma cells. These results indicated that methanol extract possessed a low cytotoxicity and a strong anti-tumor activity.

• Journal of Pharmaceutical Investigation
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• v.41 no.1
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• pp.9-17
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• 2011

The objective of this work is to study transdermal delivery of calcitonin using iontophoresis and to evaluate various factors which affect the transdermal transport. We have studied the effect of polarity, current density, drug concentration, penetration enhancers (isopropyl myristate [IPM] and ethanol) and laser treatment on transdermal flux and the results were compared. We also investigated the iontophoretic flux from microemulsions containing calcitonin together with oleic acid (OA) or IPM. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell and full thickness hairless mouse skin. Anodal delivery at pH 3.0 was much larger than cathodal and passive delivery, due to the positive charge of calcitonin. Cumulative amount delivered (CUM) by cathodal or passive delivery was close to zero for 10 hours. The pretreatment of skin by neat IPM markedly increased the CUM anodically. CUM increased as the current density, drug concentration or the duration of IPM treatment increased. Microemulsion containing IPM or oleic acid was prepared and the phase diagram was constructed. CUM also increased when IPM was incorporated into a microemulsion. OA microemulsion showed similar enhancing effect to IPM microemulsion. The delivery of calcitonin from 70% (v/v) ethanol aqueous solution showed a large increase in flux. Laser treatment of skin before flux experiment exhibited about 2 fold increase in total calcitonin amount transported for 12 hours, when compared to that delivered by IPM microemulsion. Based on these results, we have evaluated the possibility of delivering enough amount of calcitonin to reach the therapeutic level. The data suggest that it is highly possible to deliver clinically effective amount of calcitonin using iontophoresis patch with small area (<10 $cm^2$).

• Macromolecular Research
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• v.17 no.12
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• pp.969-975
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• 2009

This article describes the topical delivery and localization of budesonide through the hairless mouse skin. Two poly(ethylene oxide)-block-poly($\varepsilon$-caprolactone)-block-poly(ethylene oxide) (PEO-PCL-PEO) triblock copolymers (T 222 and T 252) having different CL:EO ratios were added in the preparation of budesonide particles stabilized with poly(vinyl alcohol) (PVA) and Tween 80 under ultrasonication. For comparison, a commercial PEO-PPO-PEO triblock copolymer (F68) was studied under the same condition. To demonstrate the effects of the triblock copolymer, the particle size of budesonide emulsion, entrapment efficiency, and in vitro release were measured and compared. The budesonide particles stabilized by the triblock copolymers had a diameter of ca. 350 nm with entrapment efficiencies of 66-76%. The In vitro release profiles of all samples showed an initial burst followed by sustained release. The skin penetration and permeation of budesonide were analyzed by using a Frantz diffusion cell. T 222 and T 252 exhibited higher total permeation amounts, but lower budesonide penetration amounts, than F68. The results suggest that the partitioning of budesonide in each skin layer can be adjusted in order to avoid skin thinning and negative immune response arising from the penetration of budesonide in blood vessels.

• YAKHAK HOEJI
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• v.48 no.2
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• pp.122-129
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• 2004

NDM hair tonic is composed of several plant extracts which are known to be used in oriental medicine. This study was carried out to investigate the effect of NDM hair tonic on hair regrowth in an alopecia model of C57BL6 mice. Hair of six-weeks old mice were trimmed by electric clippers and electric shavers, so as not to damage the skin. The next day, mice without visible scraches were selected, randomized and separated in groups of 6 mice. There were four experimental groups including saline (negative control), 50% ethanol (vehicle control), 3% minoxidil (MXD), and NDM tonic. The test compounds were topically treated with 0.15 $m\ell$ per mouse per day for 2 weeks. The hair regrowth was determined photographically and histologically and the quantity of endocrine factors, IGF-1 and TGF-$\beta$, in the skin of mice was measured by PCR. No clinical signs were found in all animals. The topical treatment of NDM tonic for 2 weeks to dorsal skin accelerated hair regrowth faster than either the controls or MXD treatment. The NDM tonic treatment also promoted hair follicle development and elongation as compared with the controls or MXD treatment. Both NDM tonic and MXD treatment significantly increased the expression of IGF-1 and TGF-$\beta$ in the skin of C57BL6 mice as compared with the controls (p<0.05). These results suggest that NDM tonic has a hair growth activity and be useful for the treatment of baldness or alopecia.

• YAKHAK HOEJI
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• v.56 no.3
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• pp.152-157
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• 2012

Angelica gigas is one of the most widely used herbal medicines in Asia. Root extract of Angelica gigas is known to have anti-oxidant activity and skin whitening effect. The aim of this study was to prepare microemulsion system of root extracts of Angelica gigas for topical delivery. Microemulsion was successfully prepared by using MCT (medium chain triglyceride) as an oil phase, Labrasol as a surfactant, and the mixture of propyleneglycol and phosphatidylcholine (4 : 1) as a cosurfactant. In vitro and in vivo skin permeation and deposition of decursin, as a marker, was determined using hairless mouse. Microemulsion significantly increased the in vitro skin permeation of decursin for up to 12 hours and was significantly higher than the control (water). Moreover, microemulsion formulation showed significantly higher skin deposition of decursin compared to the control in both in vitro and in vivo studies. Thus, microemulsion could be a useful vehicle for topical application of root extracts of Angelica gigas.