• Journal of Pharmaceutical Investigation
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• v.33 no.1
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• pp.21-28
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• 2003

Ketorolac tromethamine(KT) is a nonsteroidal agent with potent analgesic and moderate anti-inflammatory activity. The lipid-water partition coefficient of KT was evaluated and KT gel was formulated as a gel containing different pH, different concentrations of polymer (poloxamer 407, carbopol 941), propylene glycol, ethanol and various enhancers. The resulting KT gels were evaluated with respect to their viscosity, in vitro drug permeation rate through hairless mouse skin and stability. In n-octanol and chloroform, the lipid-water partition coefficient of KT was the highest at pH 4 phosphate buffer. The apparent viscosity of KT gel increased with an increase in gel pH, polymer and enhancer concentration. But the apparent viscosity of KT gel decreased with an increase in ethanol concentration. The permeation rate of KT through hairless mouse skin from gels different pH was maximum at pH 4 which is close to KT $pK_{a}$ 3.54. The permeation rate decreased with an increase in polymer, propylene glycol concentration. But the permeation rate increased with an increase in ethanol. The increase of drug concentration from 1 to 3% induced linear increase in permeation rate. The best enhancer was the combination of $Labrasol^{\circledR},\;Transcutol^{\circledR}$, oleic acid and l-menthol. In the accelerated stability test(25, 40 and $50{\circ}C$), pH 5 gel was most stable and pH 4 gel was most unstable for 90 days.

• Journal of Pharmaceutical Investigation
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• v.35 no.5
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• pp.329-332
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• 2005

HPMC-based novel gel formulations for the transdermal delivery of testosterone (TS) were developed, and the effect of various skin permeation enhancers was studied in vitro and in vivo. In vitro hairless mouse skin permeation of TS from the gel was investigated using Keshary-Chien diffusion cells for 8 hours at $37^{\circ}C$. In vivo plasma concentration profiles of TS after applying the gel on the abdominal skin of rat were determined using a commercial radioimmunoassay kit. Hairless mouse skin permeation of TS increased with the addition of permeation enhancers both in vitro and in vivo. Combination of diethanolamine (2%) and N-methylpyrrolidone (NMP, 6%) was the most effective among tested. Plasma concentration of TS significantly increased for at least 24 hours with the addition of diethanolamine and NMP. These results suggest the feasibility of the development of a HPMC-based gel formulation for the transdermal delivery of TS.

• Journal of Pharmaceutical Investigation
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• v.36 no.2
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• pp.97-102
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• 2006

The aim of this study was to investigate the feasibility and optimize permeability of slim patch type as a transdermal delivery system of caffein. Slim patch type was formulated and tested in modified Franz diffusion cell across cellulose membrane and hairless mouse skin in pH 5.8 phosphate buffer solution (PBS). The effect of $Pharmsolv^{\circledR}$ and drug concentration on permeation at four model, 1,2% $Pharmsolv^{\circledR}$ with $0.12\;mg/cm^2$ caffein and 0.12, $1.2\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR}$ through hairless mouse skin was studied in vitro. The release of caffein from slim patch with various loading was fitted by the Higuchi's diffusion equation. The result showed that chemical $Pharmsolv^{\circledR}$ produced a large and significant increase of permeation. The effect of 2% $Pharmsolv^{\circledR}$ on permeation of caffein was greater about 10-fold greater than 1% $Pharmsolv^{\circledR}$ in first 60 minutes. The effect of drug concentration, however, was lower than that produced by chemical $Pharmsolv^{\circledR}$. Within the tested system, the most efficient combination for caffein slim patch type was $0.12\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR},$ although $1.2\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR}$ showed highest amounts permeation, because permeated percentages were significantly lower about $1/4{\sim}1/5$ times.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.741-762
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• 2003

Ginsenosides, the major active ingredients of ginseng, show a variety of biomedical efficacies such as anti-aging, anti oxidation and anti-inflammatory activities. To understand the effects of compound K (20-O-D-glucopyranosyl-20 (S)-protopanaxadiol), one of the major metabolite of ginsenosides on the skin, we assessed the expression level of ∼ 100 transcripts in compound K-treated HaCaT cells using cDNA microarray analysis. Compound K treatment induced differential expression of 21 genes, which have been reported to be involved in the organization of ECM structure as well as defense responses in human skin cells. One of the most interesting findings is 2-fold increase in hyaluronan synthase2 (HAS2) gene expression by compound K. We found that change in expression of HAS2 gene represents a specific response of HaCaT cells to compound K because hyaluronan synthase 1, 3 was not changed by treatment with compound K. We also demonstrated that the compound K effectively induced hyaluronan synthesis in human skin cells and hairless mouse skin. The human clinical study indicates that topical application of compound K-containing oil-in-water emulsion showed improvement of xerosis, wrinkle and fine lines in the aged skin. We concluded that compound K has anti-aging effects by the induction of HAS2 gene expression and following hyaluronan synthase.

• Korean Chemical Engineering Research
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• v.46 no.2
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• pp.217-221
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• 2008

To investigate the enhancing effects in transdermal permeation of drug using newly designed ultrasound apparatus of 500 kHz, the transdermal permeation studies through the hairless mouse skin were conducted with lidocaine. The ultrasound apparatus of 500 kHz frequency and transducer were newly developed. The drug permeation studies were performed according to the ultrasound frequencies such as 1 MHz and 500 kHz at $1W/cm^2$ in intensity in continuous mode or pulsed mode, respectively. The results on transdermal permeation of lidocaine according to ultrasound intensity showed that the drug permeation increased as the intensity was higher.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.321-327
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• 2014

Collagen pentapeptide (Lys-Thr-Thr-Lys-Ser, KTTKS) and its palmitoylated derivative (pal-KTTKS) have received a great deal of attention as cosmeceutical ingredients for their anti-wrinkle effects. The objective of this study was to evaluate stability and permeability of KTTKS and pal-KTTKS in hairless mouse skin. In this study, a liquid chromatography-tandem mass spectrometric method was developed for the quantification of pal-KTTKS, and used for stability and permeability studies. Stability studies were performed using skin extracts and homogenates. Both KTTKS and pal-KTTKS were rapidly degraded, but pal-KTTKS was more stable than KTTKS. When protease inhibitors were added, the stability of both compounds (KTTKS and pal-KTTKS) improved significantly. In the skin permeation study, neither KTTKS nor pal-KTTKS was detected in the receptor solution, which indicates that neither compound could permeate through the full-thickness hairless mouse skin in the experimental conditions of this study. While KTTKS was not detected in any of the skin layers (the stratum corneum, epidermis, and dermis), pal-KTTKS was observed in all skin layers: $4.2{\pm}0.7{\mu}g/cm^2$ in the stratum corneum, $2.8{\pm}0.5{\mu}g/cm^2$ in the epidermis, and $0.3{\pm}0.1{\mu}g/cm^2$ in the dermis. In conclusion, this study indicated that pal-KTTKS had greater stability and permeability than that of un-modified KTTKS, and may be a useful anti-wrinkle and anti-aging cosmeceutical agent.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.35 no.4
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• pp.317-323
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• 2009

Chronic exposure of solar ultraviolet (UV) light to human skin results in photoaging with wrinkle formation. This study was performed to investigate anti-wrinkle effects of Lindera obtusiloba extract (LO) on UVB-induced wrinkle formation. We first measured cell proliferation and type I pN collagen synthesis activities in normal human dermal fibroblasts. Cell proliferation and type I pN collagen synthesis were increased by 33.8 % and 91.8 %, respectively, compared with no treatment control. SKH-1 hairless mice were topically applied 5 % LO solution for 10 weeks with UVB irradiation three times a week. After 10 weeks, a visual assessment and replica assay were performed on each mouse. According to visual assessment of close-up photos and skin replica, application of 5 % LO solution inhibited UV-induced wrinkle formation in mouse skin as compared to the vehicle-applied control mice. These results indicated that LO could protect skin wrinkle formation caused by chronic photo-irradiation in hairless mice.

• Journal of Environmental Health Sciences
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• v.42 no.1
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• pp.61-70
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• 2016

Objectives: The purpose of this study is to determine the exposure risk to tattoo components by analyzing skin absorption using the in vitro method. Tattoos are commonly used for cosmetic purposes, and the skin of not only the operator but of the people who are undergoing the cosmetic procedure is continuously exposed to hazardous chemicals. Methods: Skin permeation risk determination was conducted by the in vitro Franz diffusion cell method according to the ingredient types of tattoo dyes, such as volatile organic compounds (VOCs), non-volatile organic compounds and heavy metals, using hairless mouse full skin and human cadaver epidermis. Results: The major components with good skin penetration for each type of tattoo dye ingredient were clarified. Among the tatto dye ingredients, 1,2-Dichlorobenzene, Zn, Al, Pb and Ti showed good skin penetration. Most of the skin transmission rates were higher in hairless mouse full skin than in human cadaver epidermis. Conclusion: A possible exposure risk to hazardous substances in tattoo dyes was confirmed from this study. These results are expected to provide a positive contribution to the establishment of management regulations for tattoo dyes.

• Nutrition Research and Practice
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• v.12 no.1
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• pp.29-40
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• 2018

BACKGROUND/OBJECTIVES: Ultraviolet radiation (UV) is a major cause of skin photoaging. Previous studies reported that ethanol extract (PET) of Prunus persica (L.) Batsch flowers (PPF, peach flowers) and its subfractions, particularly the ethylacetate (PEA) and n-butanol extracts (PBT), have potent antioxidant activity and attenuate the UV-induced matrix metalloproteinase (MMP) expression in human skin cells. In this study, we investigated the protective activity of PPF extract against UV-induced photoaging in a mouse model. MATERIALS/METHODS: Hairless mice were treated with PET or a mixture of PEA and PBT either topically or orally along with UV irradiation. Histological changes and biochemical alterations of mouse skin were examined. Major phenolic compounds in PPF extract were analyzed using an ACQUITY UPLC system. RESULTS: The overall effects of topical and oral treatments with PPF extract on the UV-induced skin responses exhibited similar patterns. In both experiments, the mixture of PEA and PBT significantly inhibited the UV-induced skin and epidermal thickening, while PET inhibited only the UV-induced epidermal thickening. Treatment of PET or the mixture of PEA and PBT significantly inhibited the UV-induced MMP-13 expression, but not type I collagen expression. Topical treatment of the mixture of PEA and PBT with UV irradiation significantly elevated catalase, superoxide dismutase (SOD) and glutathione-peroxidase (GPx) activities in the skin compared to those in the UV irradiated control group, while oral treatment of the mixture of PEA and PBT or PET elevated only catalase and SOD activities, but not GPx. Thirteen phytochemical compounds including 4-O-caffeoylquinic acid, cimicifugic acid E and B, quercetin-3-O-rhamnoside and kaempferol glycoside derivatives were identified in the PPF extract. CONCLUSIONS: These results demonstrate that treatment with PET or the mixture of PEA and PBT, both topically or orally, attenuates UV-induced photoaging via the cooperative interactions of phenolic components having anti-oxidative and collagen-protective activities.

• Journal of Pharmaceutical Investigation
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• v.36 no.5
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• pp.321-329
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• 2006

Albuterol, a selective ${\beta}_2$-adrenergic receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease, chronic bronchitis and pulmonary emphysema. The percutaneous permeation of albuterol sulfate was investigated in hairless mouse skin in vitro with and without pretreatment with enhancers. The enhancing effects of ethanol and various penetration enhancers such as terpenes, non-ionic surfactants, pyrrolidones, and fatty acids on the permeation of albuterol sulfate were evaluated using Franz diffusion cells. Among terpenes studied, 1,8-cineole was the most effective enhancer, which increased the permeability of albuterol sulfate approximately 33-fold compared with the control without enhancer pretrement, followed by d-limonene with enhancement ratio of 21.79. 2-Pyrrolidone-5-carboxylic acid increased the permeability of albuterol sulfate approximately 5.5-fold compared with the control. Other pyrrolidones tested showed only slight permeability enhancing effect with enhancement ratio less than 2.8. Nonionic surfactants showed moderate enhancing effects. Lauric acid increased the permeability of albuterol sulfate approximately 30-fold with decreasing the lag time from 2.85 to 0.64 hr. Oleic acid and linoleic acid showed enhancement ratio of 24.55 and 22.91, respectively. These findings would allow a more rational approach for designing formulations for the transdermal delivery of albuterol sulfate and similar drugs.