• Journal of Pharmaceutical Investigation
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• 제35권4호
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• pp.233-241
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• 2005

Ursolic acid (UA), a bioactive triterpene acid, has been known to increase collagen content in human skin in addition to other actions such as anti-inflammatory, skin-tumor prevention and anti-invasion. However, it is poorly soluble in water. Therefore, we firstly prepared microemulsion system with benzyl alcohol, ethanol and Cremophor EL, RH 40 and Brij 35 as surfactant in order to increase solubility of UA and then prepared microemulsion was dispersed in o/w cream base for the topical delivery of UA in an effort to improve anti-wrinkle effect. The pseudo-ternary phase diagrams were developed and various microemulsion formulations were prepared using benzyl alcohol as an oil, Cremophor EL, RH 40 and Brij 35 as a surfactant. The droplet size of microemulsions was characterized by dynamic light scattering. The accumulation of VA in the skin from topical cream was evaluated in vitro using hairless mouse skins. The mean droplet size was $26.8{\pm}6.6$ nm for microemulsions II with Cremophor EL. All UA creams showed pseudoplastic flow and hysterisis loop in their rheogram, depending on the type of materials added in topical creams. The in vitro accumulation data demonstrated the UA topical cream prepared with the combination of Poloxamer 407 and Xanthan gum as a copolymer showed higher accumulation percentage than those prepared with either Poloxamer 407 or Xanthan gum. These results suggest that UA topical cream using microemulsion systems may be promising for the topical delivery of UA.

• Journal of Pharmaceutical Investigation
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• 제32권2호
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• pp.87-93
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• 2002

This study is to enhance drug penetration via skin and investigate anti-inflammation effect following adoption of ultrasound. For this goal gel containing triamcinolone was prepared and the skin penetration rate and the change effects of blood plasma ingredients and serum enzyme were investigated. Using Franz type diffusion cell and the skin of hairless mouse, the permeation enhancing effect of ultrasound was tested. After the injury by direct trauma, the blood test was performed by measuring WBC, lymphocyte, and neutrophyl, and by analyzing CPK and LDH. The ultrasound transducer whose technical specification is geometric area(GA) $1.4\;cm^2$, effective radiation area(ERA) $0.8\;cm^2$, and beam non-uniformity ratio(BNR) 6.0 max was used. The influence of frequency having an effect on skin permeation rate was higher in the case of using 1MHz and continuous treatment. The temperature of receptor phase was not influenced in skin permeation by phonophoresis. Skin permeation increase attended by intensity of ultrasound, the permeation of triamcinolone was accelerated at $2.5\;w/cm^2\;than\;1.0\;w/cm^2$. Following muscle injury phonophoretic group the number of WBC, neutrophil and lympholyte were decreased significantly as compared with both control group and ultrasound group. The result of variation of serum CPK and LDH activity conformed to the phonophoretic effect as same pattern with the variation of WBC, neutrophil and lymphocyte.

• Journal of Pharmaceutical Investigation
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• 제29권2호
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• pp.111-115
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• 1999

We have studied the transdermal flux of prostaglandin $E_1$ $(PGE_1)$ from a hydrogel patch through hairless mouse skin, to test the possibility of developing a transdermal delivery system. Karaya gum patch containing $PGE_1$ was prepared by casting method. $PGE_1$ was stable in the patch for 10 weeks. The effect of current application, enhancer (propylene glycol monolaurate : PGML), adhesive and patch thickness on the flux was studied using side-by-side diffusion cell. Passive flux of $PGE_1$ was negligible. Cathodal delivery increased the flux about 20 fold. As the concentrations of PGML increased, flux increased. When 5% PGML was used as the enhancer, maximum flux by cathodal iontophoresis was $55\;{\mu}g/cm^2\;hr$. It increased about 2 folds to $100\;{\mu}g/cm^2\;hr$, when the amount of PGML used was 9%. Large increase in flux and the decrease in time to reach maximum flux were observed when the skin was pretreated with neat PGML (maximum flux obtained was about $200\;{\mu}g/cm^2\;hr$). Use of adhesive decreased the flux significantly. To the contrary of our expectation, increase in current density decreased the flux. These flux data together with the stability data indicate that, though the onset of sufficient delivery occur after 1-2 hours of application, therapeutic amount of $PGE_1$ can be delivered through skin using iontophoresis and penetration enhancer.

• Journal of Pharmaceutical Investigation
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• 제40권1호
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• pp.23-31
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• 2010

In our previous work on levodopa delivery at pH 2.5 using iontophoresis, we found that cathodal delivery showed higher permeation than anodal delivery and electroosmosis plays more dominant role than electrorepulsion. In this work, we studied the transdermal transport of levodopa at very low pH (pH=1.0) where all levodopa molecules are cations, and evaluated some factors which affect the transdermal transport. The transport study at pH 2.5 was also conducted for comparison. The contribution of electrorepulsion and electroosmosis on flux was also evaluated. Using stable aqueous solution, the effect of electrode polarity, current density, current type and drug concentration on transport through skin were studied and the results were compared. We also investigated the iontophoretic flux from hydroxypropyl cellulose (HPC) hydrogel containing levodopa. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell. Full thickness hairless mouse skin were used. Current densities applied were 0.2, 0.4 or $0.6\;mA/cm^2$. Contrary to the pH 2.5 result, anodal delivery showed higher flux, indicating that electrorepulsion is the dominant force for the transport, overcoming the electroosmotic flow which is acting against the direction of electrorepulsion. Cumulative amount of levodopa transported was increased as the current density or drug concentration was increased. When amount of current dose was constant, continuous current was more beneficial than pulsed current in promoting levodopa permeation. Similar transport results were obtained when hydrogel was used as the donor phase. These results indicate that iontophoretic delivery of zwitterion such as levodopa is much complicated than that can be expected from small ionic molecules. The results also indicate that, only at very low pH like pH 1.0, electrorepulsion can be the dominant force over the electroosmosis in the levodopa transport.

• Macromolecular Research
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• 제17권12호
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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.

• 대한임상전기생리학회지
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• 제4권1호
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• pp.49-61
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• 2006

This study conducted the following experiment to examine and compare transdermal permeation effects according to parameters of ultrasound and physiochemical characteristics of meloxicam. Permeation by ultrasound among these experimental drugs was relatively higher and it was involved in COX-2 inhibition unlike other drugs. Recently use of oral agents has been rapidly increased, but it was not generalized to transdermal agent and this study selected meloxicam that transdermal permeation research using ultrasound was not performed and conducted transdermal permeation experiment with skin of hairless mouse and analyzed permeation with HPLC. It made gel first and analyzed permeation depending on frequency and intensity of ultrasound of meloxicam with the same experimental procedures as the above experiment. The results of this study can be summarized as follows. Transdermal permeation by ultrasound frequency was higher in 1.0 MHz and it was higher as intensity increased. In comparison by parameters of ultrasound, there was similar permeation in $1.0\;W/cm^2$ of continuous mode and $3.0\;W/cm^2$ of pulsed mode and it was effective to high intensity for using pulsed mode. It was found that duty cycle of ultrasound affected transdermal permeation in meloxicam gel used in this experiment and transdermal permeation was higher in used ultrasound as phonophoresis than non-ultrasound for anti-inflammatory effects.

• Biomolecules & Therapeutics
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• 제25권4호
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• pp.434-440
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• 2017

S-methyl-$\small{L}$-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of -3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.

• 약학회지
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• 제56권3호
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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.

• 대한화장품학회지
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• 제22권1호
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• pp.60-69
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• 1996

3-APPA는 생체내 물질 Υ-amino butyric acid와 유사한 구조를 갖는 물질로서 human fibroblasts 3-dimensional culture system 등의 in vitro 시험에서 collagen 합성촉진 효과, 세포증식 효과를 나타내며, hairless mouse를 이용한 동물시험에서도 collagen 합성이 증가되는 것으로 보고된 바 있다. 또한 피부 안정성에서도 우수한 결과를 보여줌으로서 화장품 분야에서 새로운 노화억제 물질로서 주목을 받게 되었다. 본 시험에서는 180명의 피검자를 대상으로 3개월간의 임상시험을 통하여 새로운 노화억제 물질인 3-APPA의 효능을 기존의 GABA 유사물질, aminopropane sulfonic acid와 비교하였다. 본 시험은 double-blind, randomized, vehicle-controlled clinical study로서 180명의 피검자를 APSA군, 3-APPA군, vehicle군으로 분류한 후 3개월간 매일 저녁 취침 전, 안면에 시험제품을 사용하도록 하였으며, 사용 전, 사용 1주후, 2주후, 6주후, 12주후 5회 설문지를 통하여 피부상태를 조사하였다. 각 설문내용은 피부 건조도, 피부 탄력도, 피부 주름량, 피부 윤기도, 피부 거칠기 정도에 대한 5개 질문으로 구성된 효능에 관한 질문과 흡수정도, 끈적임, 매끄러움, 보습력, 보습지속성, 전체적인 사용감에 대한 6개 질문으로 구성된 사용성에 관한 것이었다. 각 질문에 대하여는 매우 좋음 1점, 좋은 2점, 보통임 3점, 나쁨 4점, 매우 나쁨 5점 사이에서 답할 수 있도록 하였다. 시험 결과 APSA군은 6주와 12주후 피부 건조도, 피부 거칠기 항목에서 사용전에 비하여 유의한 차이를 나타내었다. 3-APPA군은 6주후 피부 건조도, 피부 거칠기, 피부 탄력도 항목에서 시료사용전에 비해 유의한 차이를 나타내었으며 12주후에는 피부 건조도, 피부 탄력도, 피부 윤기도, 피부 거칠기 항목에서 유의한 차이를 나타내었다. 12주후 APSA군은 피부 주름, 피부 탄력도 항목에서 vehicle 사용 피검자군에 비하여 유의적인 차이를 나타내었으나 3-APPA군은 피부 탄력도, 피부 주름량, 피부 윤기 항목에서 vehicle군에 비하여 유의적인 차이를 나타내었다. 결론적으로 3-APPA와 APSA 사이에 유의적인 차이가 있지는 않았으나 3-APPA군은 APSA군에 비하여 6주, 12주에서 사용전과 유의한 차이를 나타내는 항목이 많았으며 12주에서 vehicle과 유의적인 차이를 나타내는 항목도 많으므로 3-APPA가 APSA 보다 광범위한 피부노화 억제 효과를 갖는 물질이라고 할 수 있다.

• 대한화장품학회지
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• 제25권4호
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• pp.145-154
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• 1999

A novel retinol derivative, polyethoxylated retinamide(Medimin A) was synthesized, as an anti-aging agent. Collagen synthesis, skin permeation, stability, and toxicity of Medimin A were evaluated and compared with those of retinol and retinyl palmitate. In vitro collagen synthesis was evaluated by quantitative assay of $[^3H]-proline$ incorporation into collagenase sensitive protein in fibroblast cultures. For in vitro skin permeation experiments, Franz diffusion cells(effective diffusion area: 1,766 $cm^2$) and the excised skin of female hairless mouse aged 8 weeks were used, The stabilities of retinoids were evaluated at two different temperature($25^{\circ}C\;and\;40^{\circ}C$) and under UV in solubilized state and in O/W emulsion. To estimate the safety, acute oral toxicity, acute dermal toxicity, primary skin irritation, acute eye irritation and human patch test were performed. The effect of Medimin A on collagen synthesis was similar to that of retinol. The skin permeability of Medimin A was higher than those of retinol and retinyl palmitate. The Medimin A was more stable than retinol and retinyl palmitate. Medimin A was nontoxic in various toxicological tests. These results suggest that Medimin A would be a good anti-aging agent for enhancing bioavailability and stability.