• 약학회지
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• 제41권6호
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• pp.737-748
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• 1997

Distribution of rhEGF in the skin, plasma and several organ tissues following topical application of $^{125}I-rhEGF$ (0.4${\mu}$Ci) solution in 25% Pluronic F-127 on 154$mm^2$ normal and damaged (burned and stripped) skins of hairless mice was examined. The radioactivity in the stripped skin tissues increased as a function of time, and was 10-20 times higher than that in the normal and burned skins. The fractions of intact drug in the skin tissues were 40-60% for the normal and burned skins, and 60-80% for the stripped skin. It indicates that the stratum corneum layer behaves as a barrier for the dermal penetration of the drug. The radioactivity in the plasma was much higher for the stripped skin than for the normal and burned skins. However, the concentration of intact drug in the stripped skin was comparable to those in the normal and burned skins indicating most severe degradation (or metabolism) of the drug in the stripped skin. As a result, the fraction of intact drug in the plasma was lowest for the stripped skin (<10%). Body organ distribution of the drug was much higher for the stripped skin. The concentration in the stomach. Both in total radioactivity and intact drug, showed more than 10-times higher value than in the other organs (liver, kidney and spleen). The fraction of intact drug in each organ tissue was below 10-20%. And generally lowest for the stripped skin. The lowest fraction of the drug for the stripped skin could not be explained by the activity of the aminopeptidases in the skin since it was lower for the stripped skin than for the normal skin. Thereover, the fraction of intact drug appears to be determined by the balance between dermal uptake and systemic elimination of the drug, for example. The mechanism of dermal uptake of rhEGF was examined by topical applying 200${\mu}$l of 25% Pluronic F-127 solution containing 0.4 ${\mu}$Ci of $^{125}I-rhEGF$ and 0.14${\mu}$Ci of $^{14}C$-inulin (a marker of passive diffusion). The radioactivity of $^{125}I-rhEGF$ at each sampling time point (0.5, 1, 2, 4 and 8hr) was correlated (p<0.05) with the corresponding radioactivity of $^{14}C$-inulin. It appears to indicate the rhEGF may be uptaken into the skins mainly by the passive diffusion. This hypothesis was supported by the constant specific binding of EGF to the skin homogenates regardless of the skin models. Receptor mediated endocytosis (RME) appears to contribute negligibly, if any, to the overall uptake process.

• 약학회지
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• 제41권6호
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• pp.730-736
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• 1997

Distribution of radioactivity in the skin tissues, subcutaneous tissues, blood and body organs was examined following topical application of $^{125}I-rhEGF$(0.4 ${\mu}Ci$), in the form of a Pluronic F-127 gel, on the normal and damaged (burned and stripped) skins of SD male rats. The radioactivity in the skin tissues and subcutaneous tissues was 3-5 times higher for the damaged skins than for the normal skin. But pretreatment of the skin with rhEGF (1${\mu}g$)) twice at 24 hr dose intervals affected the distribution of the radioactivity yielding the order of burned skin> stripped skin=normal skin. The decrease for the stripped skin by the pretreatment might be related either to the pathophysiological change of the skin or to the down regulation of the EGF receptor. Liver showed the highest radioactivity in amount following single and multiple administration of the drug to the normal and damaged skins. But,in concentration, the kidney and stomach showed higher value than the liver which is consistent with that kidney is a major eliminating organ of EGF and that EGF exerts its pharmacological effect specifically for the stomach.

• Journal of Pharmaceutical Investigation
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• 제25권3호spc1호
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• pp.53-59
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• 1995

Ethinylestradiol (EE)-containing matrix was fabricated with ethylene-vinyl acetate(EVA) copolymer to control the release of the drug, Effect of addition of PEG 400 as receptor solution, the stripping of skin and Azone pretreatment on skin on the permeation of EE through the excised mouse skin was also studied. The permeation rate of EE through the excised mouse skin was affected by the PEG 400 volume fraction. The Azone pretreatment on skin didn't affect on the steady state flux, however, the lag time was shortened. The permeation rate of EE through the stripped skin was much larger than that through the whole skin. It showed that the stratum corneum acts as a barrier of skin permeation. The fact that there is little difference in EE permeation between the intact skin and the stripped skin with EVA membrane shows the permeation of EE through the mouse skin is mainly controlled by the membrane.

• Journal of Pharmaceutical Investigation
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• 제26권1호
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• pp.29-32
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• 1996

In vivo and in vitro skin permeation of $recombinant^{125}$ I-EGF through normal, stripped and the first degree burn skin were studied. The in vitro skin permeation rate through the first degree burn skin $(296\;cpm/cm^2/hr)$ and the stripped skin $(1131\;cpm/cm^2/hr)$ were 3.5 times and 13 times higher, respectively, as compared with the one through normal skin. In vivo absorption study with the first degree burn skin, the peak concentration of EGF in the skin was achieved at 1-3 hr and decreased afterward up to 8 hr with an elimination constant of $1.31{\times}10^{-3}\;g/ml/hr$. To investigate the higher elimination rate of EGF in burn skin, binding and metabolism studies were conducted. No significant metabolism of EGF in burn skin $(100^{\circ}C,\;5-second\;burning)$ was observed. With the presence or unlabelled-EGF $^{125}I-EGF$ permeation through the burn skin showed higher permeation rate than the one without unlabelled-EGF. The result nay indicate that EGF-receptor binding play a role in determining the skin permeation rate.

• Journal of Pharmaceutical Investigation
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• 제38권2호
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• pp.87-92
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• 2008

Wood vinegar is well known as a softening agent affecting on the stratum corneum that is easy to penetrate into the skin. In this study, we prepared mixed ursolic acid hydrogel with wood vinegar(1, 2, 5%) as a penetration enhancer. The accumulation of ursolic acid in the skin from hydrogels was evaluated in vitro hairless mouse skin and skin moisturizing effect of them was evaluated using the corneometer and the tewermeter. And the role of stratum corneum as a protective barrier was evaluated as well. The hydrogels were retained about 40% of water retention capacity 2hrs and had better effect on the stripped skin than full-thickness skin. The accumulation of ursolic acid through stripped skin from hydrogels with wood vinegar was not change compared to normal skin, which indicated the action site of wood vinegar and the accumulation site of ursolic acid would be stratum corneum. From these result, we could find wood vinegar seems to be a good enhancer for active materials with anti-wrinkle and anti aging effect such as ursolic acid, and can be a developed topical delivery system maintaining excellent water retention capacity.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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• pp.129-129
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• 1995

ASPS against TGF-${\beta}$ is developing as scar formation inhibitor. The scar was caused by undesired collagen deposition due to overexpression of TGF-${\beta}$ in wounded tissue. The in vitro percutaneous absorption of ASPS(25mer)was investigated by using Furanz Diffusion Cell. The flux of ASPS cannot be found through normal skin due to high molecular weight (MW 10,000) and polyanionic charge. However, the skin permeation of ASPS through tape-stripped damaged skin was markedly increased. The skin fluxs of ASPS were decreased in the following order; hairless mouse> rat >human cadaver skin.

• Archives of Pharmacal Research
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• 제19권2호
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• pp.116-121
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• 1996

Antisense oligonucleotides seem to provide a promising new tool for the therapy. Choi et al. (1995) reported antisense phosphorothioate oligonucleotides (PS-ODN, 25 mer) complementary to TGF-.betha. mRNA designed for scar formation inhibitor to eliminate scars, which was caused by undesired collagen deposition due to overexpression of TGF-.betha., in wounded skin. PS-ODN were evaluated in vitro for skin penetration using normal and tape-stripped damaged rat skin. The in vitro skin transports were carried out with partially modified PS-ODN (6S) and fully modified PS-ODN (25S). The cumulative amount of PS-ODN (6S) penetrated through normal rat skin was $0.234{\pm}0.041{\mu}g/cm^2$ and that of tape-stripped damaged rat skin was $1.077{\pm}0.301{\mu}g/cm^2$ over 8 hrs. PS-ODN (25S) can not be found in receptor medium through normal skin due to high molecular weight (Mol.Wt.=8,000) and polyanionic charge. However, the cumulative amount of PS-ODN (25S) penetrated across damaged rat skin in PBS was $0.340{\pm}0.296{\mu}g/cm^2$ over 8 hrs. The absense of dermis raised the cumulative amount of PS-ODN (6S) penetrated through rat skin. And the fluxes of PS-ODN (6S) and PSODN (25S) at 8hrs across damaged rat skin were $134.63{\pm}37.67{\mu}g/cm^2$ h, and $42.50{\pm}36.95ng/cm^2$ h, respectively. While PS-ODN (25S) was stable in 10% heat inactivated fetal bovine serum (FBS) during 24 hrs, PS-ODN (6S) was less stable than PS-ODN (25S), but was markedly stable than unmodified phosphodiester. It is suggested that the cumulative amount of PS-ODN (6S) penetrated through damaged rat skin is larger than that of PS-ODN (25S) since the former is easier to degrade by nuclease than the latter and then is apt to penetrate into skin. Thus, PS-ODN represents a logical candidate for further evaluation due to the potential for delivery into the wounded skin.

• 한방안이비인후피부과학회지
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• 제21권2호
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• pp.39-45
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• 2008

Objective : Skin barrier protects skin against harmful environment. Its function includes antimicrobial barrier as well as physical barrier. But there are few studies about the factors which improve skin barrier recovery after injury. The aim of this study is to investigate the factors which improve skin barrier recovery. Method : Nine hairless mice was anesthetized by inhalation and we tape stripped them. We used thermometer to know temperature one day ago, before anesthesia, before tape stripping, and after tape stripping. Vapometer was used to know transepidermal water loss before tape stripping, after tape stripping. And we used doppler flowmeter to measure blood flow before tape stripping, after tape stripping. Result : After analyzed data, we concluded that temperature was lower after anesthesia than before anesthesia and after tape stripping than before tape stripping. We could know that transepidermal water loss was lower after tape stripping than before tape stripping and more blood flowed after tape stripping. Conclusion : In our study, it was observed that temperature, transepidermal water loss, blood flow changed after tape stripping. But we thought lowered temperature was pathologic situation, more blood flow was to recover after injury. In traditional korean medicine, cold(寒) and imbalance of blood flow(血行) don't only make many skin diseases, but cold(寒) also obstructs blood flow. So we need to study how to warm cold(寒) and improve blood flow.

• Journal of Pharmaceutical Investigation
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• 제31권2호
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• pp.107-112
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• 2001

In order to reduce the systemic side effects and gastrointestinal irritation after its oral adminitration, ketoprofen was formulated as water-soluble packs. The effects of fatty acids and fatty alcohols on the penetration of ketoprofen through excised rat skins were evaluated. The role of stratum corneum as a protective barrier was also investigated. Fatty acids and fatty alcohols were generally effective in promoting ketoprofen penetration. The flux of ketoprofen through rat skin was maximized when oleic acid or lauryl alcohol was used as an enhancer. As the concentration of fatty acids and fatty alcohols varied from 0% to 10%, the amounts of ketoprofen penetrated were in direct proportion to that of fatty acids but those had no relationship with that of fatty alcohols. The penetration of ketoprofen through stripped skin was enhanced compared to normal skin irrespective of enhancer type, which indicated that the action site of enhancers would be stratum corneum.

• 대한화장품학회지
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• 제38권1호
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• pp.75-82
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• 2012

천연보습인자(NMF, natural moisturizing factor)는 정상 피부 내의 각질층에 존재하는 수용성, 친수성 성분을 총칭하는 말로 외부로부터 수분을 흡수하고 각질층의 수분보유능을 증가시키며 피부가 건조해지는 것을 방지하여 피부의 유연성과 가수성을 유지하는 기능을 한다. NMF는 주로 아미노산과 아미노산의 대사산물로 구성되며 이들은 필라그린(filaggrin)이 분해되면서 생성된다. 본 연구에서는 피부 각질층의 22종의 개별 아미노산의 함량분석을 통하여 피부보습능과 개개의 아미노산과의 상관관계를 연구하였다. 15명의 건강한 지원자들의 전박과 이마로부터 tape stripping한 각질 시료 중 22종의 아미노산 함량을 UPLC-PDA를 이용하여 동시 분석하였다. 그 결과 각질 표면보다는 안쪽에서의 아미노산들의 함량이 높음을 확인하였다. 또한 신체 부위별 비교에서 전박이 이마에 비해 아미노산 함량이 1.5배 정도 높음을 확인하였다. 전박부위의 아미노산 총 함량과 보습능(TEWL)과의 상관 관계분석을 통해서는 보습능이 클수록 총아미노산 함량이 높은 것으로 확인되었으며 특히 Ser, Glu, Gly, Ala 및 Thr은 각질 내 존재하는 주요 아미노산 성분으로 보습에 긍정적인 영향을 주는 성분으로 확인되었다. 이상의 결과로써 NMF의 주성분인 아미노산의 함량은 각질 생리기능과 밀접한 관련을 가지고 있음을 확인할 수 있었으며 본 연구를 통해 얻은 각질층의 아미노산의 통합적인 분석법은 보습, 노화, 미백, 피부 염증질환 등 다양한 피부 상태와 아미노산류들의 변화와의 관계를 깊이 이해하고 피부 기능과 관련된 새로운 분자적 타겟을 발굴하고 증명하는데 기초적인 방법으로써 사용될 수 있을 것으로 사료된다.