Viviparus contectus로부터 콘드로이친 황산의 분리 및 화장품적 특성

김태양(Tae-Yang Kim),이강태(Ghang-Tai Lee),이춘몽(Chun-Mong Lee),이정노(Jung-Noh Lee),박성민(Sung-Min Park),이건국(Kun-Kook Lee) 한국화장품미용학회 2016 한국화장품미용학회지 Vol.6 No.2

Chondroitin sulfate, sulfated glycosaminoglycan(GAG), is an important structural component of cartilage and nowdays also used as a skin conditioning agent. It is obtained usually from animal sources, such as cow cartilage. However, there are some problems of acquisition of chondroitin sulfate from animal for its safety from bovine spongiform encephalopathy(BSE) and its efficient isolation method. In this study, we investigated the nature of chondroitin sulfate isolated from Viviparus contectus and confirmed its skin moisturizing effect. We studied the optimum condition for extracting chondroitin sulfate, cytotoxicity and its activity(cell proliferation , cell migration, collagen synthesis). The optimum extraction condition is under the 121℃ 15lb psi, 2 hours by autoclave and yield is 31.1%. By HPLC-GPC chromatograph, we found that the molecular weight of chodroitin sulfate is 360kDa. chondroitin sulfate showed no cytotoxicity up to 0.1% in human dermal fibroblast and promoted cell proliferation in a dose dependent manner. chondroitin sulfate increased type 1 procollagen synthesis 40% at 1% showing higher activity than L-ascorbic acid. Furthermore in the clinical test to study skin moisturizing effect by corneometer, chondroitin sulfate statistically increased skin moisturizing effect and moisture capacity of skin to 23.4% compared with sodium hyaluronate. These results indicate that chodroitin sulfate isolated from viviparus contectus showed no cytotoxicity, can improve collagen synthesis, cell proliferation and skin moisturizing effect. Therefore, we suggest this chondroitin sulfate to be a functional cosmetic material.

Developmental and Morphological Characterization of the Wild Silkmoth, Actias gnoma, in Korea

( Chun Woo Ryu ),( Mi Ae Kim ),( Nam Sook Park ),( Hung Dae Sohn ),( Sang Bong Park ),( Ho Oung Lee ),( Jae Yu Moon ),( Su Il Seong ),( Sang Mong Lee ) 한국잠사학회 2002 International Journal of Industrial Entomology Vol.5 No.1

Phenoxyethanol을 이용한 저자극 방부시스템 개발에 관한 연구

안기웅 ( Gi Woong Ahn ),이춘몽 ( Chun Mong Lee ),김형배 ( Heong Bae Kim ),정지헌 ( Ji Hean Jeong ),조병기 ( Byoung Kee Jo ) 대한화장품학회 2005 대한화장품학회지 Vol.31 No.1

최근, 민감성 피부가 증가함에 따라 화장품의 안전성이 매우 중요시되고 있으며, 특히 방부제는 화장품 사용에 따른 부작용을 일으킬 수 있는 주요 자극원의 하나로 알려져 있다. 하지만, 방부제의 세포 독성 피부 투과, 유/수 분배, 항균력 비교 및 이를 통한 피부 자극과의 상관성 분석에 관한 연구는 전무한 실정이다. 본 연구의 목적은 상기의 여러 factor를 고려하여 화장품에서 빈번히 사용되고 있는 방부제의 하나인 phenoxyethanol을 이용한 저자극 방부시스템 개발에 관한 것이다. MTT assay를 통하여 human norm기 fibroblast cell에 대한 독성을 평가해 본 결과, 세포 독성은 propylparaben > butylparaben > ethylparaben > methylparaben > triciosan > phenoxyethanol 순으로 확인되어 phenoxyethanol이 다른 방부제에 비해 낮은 세포 독성을 나타낸 반면, 피부 일차자극을 알아보기 위하여 수행한 인체 첩포시험에서는 triclosan, methylparaben에 비해 높은 피부 자극을 나타내었다. 5~8 주령의 웅성 무모생쥐의 피부를 적출하여 in vitro Franz diffusion cell system을 이용한 방부제의 피부 투과도를 측정하여 본 결과, 피부 투과도는 phenoxyethanol > methylparaben > ethylparaben > propylparaben > butylparaben > triclosan 순으로 확인되어 세포 독성이 낮은 phenoxyethanol의 높은 피부 자극이 높은 피부 투과도와 연관성이 큰 것을 확인하였다. 따라서, 본 연구에서는 비교적 독성이 낮은 phenoxyethanol의 피부 투과도를 감소시킬 수 있는 방법을 찾고자 하였으며, 연구 결과, 제형내 polarity가 낮은 oil을 사용할 경우 phenoxyethanol의 피부 투과가 현격히 감소하며, 피부 자극도 감소함을 알 수 있었다. Oil polarity에 따른 Phenoxyethanol의 유/수 분배 측정 결과, Polarity가 낮은 oil에서는 70% 이상의 Phenoxyethanol이 수상에 존재한 반면, polarity가 높은 oil에서는 약 70~90%의 phenoxyethanol이 유상에 존재하였다. 또한, 미생물에 대한 항균력도 phenoxyethanol이 수상에 많이 존재할수록 증가하는 경향을 나타내었다. 따라서, 제형 내 oil tomposition을 변화시킴으로써 phenoxyethanol의 사용량을 줄일 수 있을 뿐만 아니라, 피부 투과를 감소시켜 보다 피부 자극이 적은 저자극 방부시스템 개발이 가능하리라 보여 진다. Recently, according as people who have sensitive skin increase, we've been giving more importance to the safety of cosmetics. Especially, preservative is known to be one of the main stimuli which cause side-effects of cosmetics. However, there have been few reports describing cell cytotoxicity, skin penetration, oil-aqueous phase partition, anti-microbial activity of preservatives and their correlation with skin irritation. The study is aimed to develop low irritable preservative system with phenoxyethanol, one of the most commonly used preservatives in cosmetics, considering various factors mentioned above. According to our results of cell cytotoxicity against human normal fibroblasts by means of MTT assay, phenoxyethanol showed the lowest cytotoxicity when compared to other preservatives tested (cytotoxicity: pro-pylparaben > butylparaben > ethylparaben > methylparaben > triclosan > phenoxyethanol), but human patch test for assessing shin primary irritation revealed that phenoxyethanol has higher skin irritation than methylparaben and triclosan. We performed in vitro skin penetration test using horizontal Franz diffusion cells with skin membrane prepared from hairless mouse (5~8 weeks, male) to evaluate the rate of skin penetration of preservatives. From the results, we found that the higher irritable property of phenoxyethanol in human skin correlates with its predominant permeability (skin penetration: phenoxyethanol > methylparaben > ethylparaben > propylparaben > butylfaraben > triclosan). Therefore, we made an effort to reduce skin permeability of phenoxyethanol and found that not only the rate of skin penetration of phenoxyethanol but also its skin irritation is dramatically reduced in formulas containing oils with low polarity. In the experiments to investigate the effect of oil polarity on the oil-aqueous phase partition of phenoxyethanol, more than 70% of phenoxyethanol was partitioned in aqueous phase in formulas containing oils with low polarity, while about 70~90% of phenoxyethanol was partitioned in oil phase in formulas containing oils with high polarity. Also, in aqueous phase phenoxyethanol showed greater anti-microbial activity. Conclusively, it appears that we can develop less toxic preservative system with reduced use dosage of phenox-yethanol and its skin penetration by changing oil composition in formulas.

ONYX-I: Efficacy of Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir in South Korean and Taiwanese Patients with HCV Genotype 1b Infection and without Cirrhosis

( Jeong Heo ),( Wan-Long Chuang ),( Yan Luo ),( Mong Cho ),( Chi-Jen Chu ),( Kwang-Hyub Han ),( Jia-Horng Kao ),( Seung Woon Paik ),( Chun-Yen Lin ),( Jin-Woo Lee ),( Cheng-Yuan Peng ),( Young-Suk Lim 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Background: Approximately 45-50% of Hepatitis C virus (HCV) infections in South Korea and Taiwan are genotype (GT) 1b. Previous phase 3 studies demonstrated that the direct-acting antiviral (DAA) regimen of ombitasvir (OBV), ritonavir-boosted paritaprevir (PTV/r; identified by Abbvie and Enanta) and dasabuvir (DSV) was well tolerated and achieved sustained virologic response at post-treatment week 12 (SVR12) in 99% of treatment-naive and 100% of treatment- experienced patients with HCV GT1b. ONYX-I (NCT02517515) was designed to evaluate efficacy and safety in Asian patients with HCV GT1b infection without cirrhosis. Methods: Treatment-naive and IFN-based therapy-experienced patients with HCV GT1b infection in South Korea, Taiwan, and China were randomized 1:1 to receive either OBV/PTV/r (25 mg/150 mg/100 mg once daily) and DSV (250 mg twice daily) or placebo for 12 weeks during the double-blind (DB) period. Patients in the placebo arm subsequently received OBV/PTV/r + DSV for 12 weeks during the open-label period. Patients will be followed for 48 weeks after last dose of study drugs. The primary objectives are to compare the SVR12 rates for the treatment-naive and -experienced patients to corresponding historical SVR rates of telaprevir + peg-interferon and ribavirin therapy, and assess the safety of the OBV/PTV/r + DSV regimen. Presented are results from the South Korean and Taiwanese populations. Results: In both South Korea and Taiwan, 120 patients were randomized and treated. Of South Korean patients, 45% were male, 33% were treatment-experienced and 89% had F0-F1 fibrosis. Of Taiwanese patients, 39% were male, 33% were treatment-experienced, and 87% had F0-F1 fibrosis. Safety data and SVR at post-treatment week 4 will be presented. Conclusions: The ONYX-I study is evaluating the safety and efficacy of DAA regimen, OBV/PTV/r + DSV, in Southeast Asian patients without cirrhosis infected with HCV GT1b. Resultant data may help inform treatment guidelines for HCV GT1b in this population.

바이오틴 함유 나노리포좀의 안정성에 관한 연구

양성준 ( Seong Jun Yang ),김태양 ( Tae Yang Kim ),이춘몽 ( Chun Mong Lee ),이광식 ( Kwang Sik Lee ),윤경섭 ( Kyung-sup Yoon ) 대한화장품학회 2020 대한화장품학회지 Vol.46 No.2

본 연구는 용해도가 낮은 수용성 활성물질인 바이오틴(biotin)의 안정화 및 용해도 증가를 목적으로 나노리포좀을 활용하였다. 이번 실험을 통해 바이오틴 나노리포좀의 안정성에 pH가 큰 영향을 준다는 사실을 확인할 수 있었으며, pH 상승이 바이오틴 활성에 튼 영향을 미치지 않음을 확인하였다. 또한 제타사이저(zetasizer)로 입자크기, 제타전위(zeta potential) 및 다분산지수(polydispersity index)를 측정하여 안정성을 평가하였다. 입자크기는 평균 100 ∼ 250 nm, 제타전위 -80 ∼ -30 mV로 나노리포좀 제조가 가능함을 확인하였다. 바이오틴 나노리포좀 내의 바이오틴 캡슐화율(capsulation efficiency)을 측정하기 위해 dialysis membrane method (DMM)를 이용하여 평가하였으며, 이를 통해 알지닌을 첨가시킨 바이오틴 나노리포좀이 일반 바이오틴 나노리포좀보다 캡슐화율이 5 배 높은 것으로 측정되었다. 바이오틴 나노리포좀의 경피흡수율을 측정하기 위해 in vitro franz diffusion cell method를 통해 확인하였으며, cryogenic transmission electron microscopy (cryo - TEM)을 통해 바이오틴 나노리포좀이 잘 형성되었는지 확인하였다. 본 논문을 통하여 모발건강과 밀접한 관계가 있는 것으로 소개된 바이오틴을 약물전달체(drug delivery carrier)인 나노리포좀에 캡슐화시켜 기존의 낮은 용해도 및 석출되는 문제를 보완한 바이오틴 나노리포좀을 만들 수 있음을 확인하였다. This study utilized nano-liposomes for the purpose of stabilizing and increasing the solubility of biotin, a water-soluble active material with low solubility. The particle size, zeta potential, and polydispersity index were confirmed with a nano zetasizer. It was possible to manufacture nano liposomes at 100 to 250 nm of particle size and -80 to -30 mV of zeta potential. Dialysis membrane method (DMM) was used to measure the capsulation efficiency of biotin in biotin nano-liposomes, and results showed that pH increased biotin nano-liposomes had higher capsulation efficiency than normal biotin nano-liposome. Through this experiment, it was confirmed that the pH has a great influence on the stability of biotin nano-liposomes. In vitro franz diffusion cell method was used to measure in vitro skin absorption rate of biotin nano-liposomes. The shape of the formulation and biotin solubility in nano-liposome was observed by cryogenic transmission electron microscopy (cryo-TEM). Through this study, we confirmed that biotin, which is introduced as closely related to hair health, can be incorporated into a nano-liposome drug delivery system, to make biotin nano-liposome with improved solubility and precipitation problems.

영지버섯추출물 및 에르고스테롤의 냉감 수용체 TRPM8 (Transient Receptor Potential Cation Channel Melastatin Subtype 8) 발현 유도 효과

유화선 ( Hwa Sun Ryu ),정지연 ( Jiyeon Jeong ),전원옥 ( Weon-ok Jeon ),이춘몽 ( Chun Mong Lee ),이정노 ( Jung-no Lee ),박성민 ( Sung-min Park ) 대한화장품학회 2018 대한화장품학회지 Vol.44 No.1

UV 뿐 아니라 가시광선, 적외선에 의해 발생된 열로 인해 피부 온도 상승, MMP-1의 증가에 따른 피부 노화가 진행된다. 따라서 열에 의한 노화에서 피부 온도 조절은 노화 억제에 중요한 핵심 요소이다. 일시적인 수용체 전위 통로인 TRPM8은 멘솔 수용체(CMR1)로써 25 ℃ 이하의 온도에서 활성화되고 시원한 감각을 발생시키는 냉 수용체로 보고되어 있다. TRPM8 조절을 통해 시원한 감각과 피부 온도를 조절하는 연구가 활발히 진행되고 있다. 본 연구에서는 천연물인 영지버섯을 이용하여 냉 수용체인 TRPM8 발현에 어떠한 영향을 주는지 확인하였다. 영지버섯추출물 및 용매 분획물의 TRPM8 발현에 대한 영향을 측정한 결과, 영지버섯추출물, n-hexane 분획물 및 water 분획물에서 농도의존적으로 TRPM8 발현이 증가함을 확인하였다. Hex 분획물에서 유효성분을 찾고자 크로마토그래피를 실시하여 1개의 화합물을 분리하였으며 ¹H 및 ¹³C NMR spectrum 분석을 통하여 화학구조를 동정하였다. 분리된 화합물은 에르고스테롤로 TRPM8 발현 증가에 효과가 있음을 확인하였다. 결과를 토대로, 영지버섯추출물 및 에르고스테롤은 화장품 분야에서 새로운 쿨링 소재로서 개발가능성이 있다고 사료된다. Skin-aging is accelerated by the increased expression of MMP-1 caused by the increased skin temperature induced by IR/visible light as well as UV. Thus, the control of skin temperature is important to inhibit heat-induced aging. Many studies have been conducted to lower the skin temperature through the controlling transient receptor potential melastatin 8 channel (TRPM8), which is known as the cold and menthol receptor 1 (CMR1) and is activated at temperature below 25 ℃. In this study, we first investigated the effect of Ganoderma lucidum extract (GLE) on the TRPM8 expression. Results showed that GLE, hexane (Hex) fractions and water fractions increased the TRPM8 expression in a dose dependent manner. Active compound in Hex fractions were separated by chromatography and analyzed by ¹H and ¹³C NMR spectroscopy. The isolated compounds were identified as ergosterol and it also significantly increased the TRPM8 expression. Taken together, these results strongly suggest that G. lucidum extract and ergosterol have the potential as a new cooling ingredient in the cosmetics.

식도의 과립상 세포종 1 예

김상현(Sang Hyun Kim),최성호(Seong Ho Choi),전국진(Kook Jin Chun),이선희(Sun Hee Lee),조몽(Mong Cho),양웅석(Ung Suk Yang),허윤(Yoon Huh),문한규(Han Kyu Moon) 대한내과학회 1993 대한내과학회지 Vol.45 No.1

Granular cell tumor of esophagus is a rare neoplasm. It is almost invariably benign in character and is of still disputed histogenesis. Although endoscopy permits recongnition of this tumor and supports its benign nature, only histologic examination of the endoscopic biopsy specimen permits one to determin its precise nature. The endoscopic appearance of esophageal granular cell tumor ranges from a plaque like thickening of the mucosa to a polypoid mass. We describe here one case of granular cell tumor of esophagus in 62 years-old male who complain anterior chest pain those managed successfully by endoscopic polypectomy, We believe the actual incidence of this tumor in this location might be greater if every esophagus were given as much attention at endoscopic examination and autopsy.

Vanillic Acid Stimulates Anagen Signaling via the PI3K/Akt/ β-Catenin Pathway in Dermal Papilla Cells

( Jung-il Kang ),( Youn Kyung Choi ),( Young-sang Koh ),( Jin-won Hyun ),( Ji-hoon Kang ),( Kwang Sik Lee ),( Chun Mong Lee ),( Eun-sook Yoo ),( Hee-kyoung Kang ) 한국응용약물학회 2020 Biomolecules & Therapeutics(구 응용약물학회지) Vol.28 No.4

The hair cycle (anagen, catagen, and telogen) is regulated by the interaction between mesenchymal cells and epithelial cells in the hair follicles. The proliferation of dermal papilla cells (DPCs), mesenchymal-derived fibroblasts, has emerged as a target for the regulation of the hair cycle. Here, we show that vanillic acid, a phenolic acid from wheat bran, promotes the proliferation of DPCs via a PI3K/Akt/Wnt/β-catenin dependent mechanism. Vanillic acid promoted the proliferation of DPCs, accompanied by increased levels of cell-cycle proteins cyclin D1, CDK6, and Cdc2 p34. Vanillic acid also increased the levels of phospho(ser473)- Akt, phospho(ser780)-pRB, and phospho(thr37/46)-4EBP1 in a time-dependent manner. Wortmannin, an inhibitor of the PI3K/ Akt pathway, attenuated the vanillic acid-mediated proliferation of DPCs. Vanillic acid-induced progression of the cell-cycle was also suppressed by wortmannin. Moreover, vanillic acid increased the levels of Wnt/β-catenin proteins, such as phospho(ser9)- glycogen synthase kinase-3β, phospho(ser552)-β-catenin, and phospho(ser675)-β-catenin. We found that vanillic acid increased the levels of cyclin D1 and Cox-2, which are target genes of β-catenin, and these changes were inhibited by wortmannin. To investigate whether vanillic acid affects the downregulation of β-catenin by dihydrotestosterone (DHT), implicated in the development of androgenetic alopecia, DPCs were stimulated with DHT in the presence and absence of vanillic acid for 24 h. Western blotting and confocal microscopy analyses showed that the decreased level of β-catenin after the incubation with DHT was reversed by vanillic acid. These results suggest that vanillic acid could stimulate anagen and alleviate hair loss by activating the PI3K/Akt and Wnt/β-catenin pathways in DPCs.

Myristoleic Acid Promotes Anagen Signaling by Autophagy through Activating Wnt/β-Catenin and ERK Pathways in Dermal Papilla Cells

( Youn Kyung Choi ),( Jung-il Kang ),( Jin Won Hyun ),( Young Sang Koh ),( Ji-hoon Kang ),( Chang-gu Hyun ),( Kyung-sup Yoon ),( Kwang Sik Lee ),( Chun Mong Lee ),( Tae Yang Kim ),( Eun-sook Yoo ),( H 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.2

Alopecia is a distressing condition caused by the dysregulation of anagen, catagen, and telogen in the hair cycle. Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Myristoleic acid (MA) increases Wnt reporter activity in DPCs. However, the action mechanisms of MA on the stimulation of anagen signaling in DPCs is not known. In this study, we evaluated the effects of MA on anagen-activating signaling pathways in DPCs. MA significantly increased DPC proliferation and stimulated the G2/M phase, accompanied by increasing cyclin A, Cdc2, and cyclin B1. To elucidate the mechanism by which MA promotes DPC proliferation, we evaluated the effect of MA on autophagy and intracellular pathways. MA induced autophagosome formation by decreasing the levels of the phospho-mammalian target of rapamycin (phospho-mTOR) and increasing autophagy-related 7 (Atg7) and microtubule-associated protein 1A/1B-light chain 3II (LC3II). MA also increased the phosphorylation levels of Wnt/β-catenin proteins, such as GSK3β (Ser⁹) and β-catenin (Ser⁵⁵² and Ser⁶⁷⁵). Treatment with XAV939, an inhibitor of the Wnt/β-catenin pathway, attenuated the MA-induced increase in β-catenin nuclear translocation. Moreover, XAV939 reduced MA-induced effects on cell cycle progression, autophagy, and DPC proliferation. On the other hand, MA increased the levels of phospho (Thr²⁰²/Tyr²⁰⁴)-extracellular signal regulated kinases (ERK). MA-induced ERK phosphorylation led to changes in the expression levels of Cdc2, Atg7 and LC3II, as well as DPC proliferation. Our results suggest that MA promotes anagen signaling via autophagy and cell cycle progression by activating the Wnt/β-catenin and ERK pathways in DPCs.

Original Article : Rescue therapy with adefovir in decompensated liver cirrhosis patients with lamivudine-resistant hepatitis B virus

( Hyun Young Woo ),( Jong Young Choi ),( Seung Kew Yoon ),( Dong Jin Suh ),( Seung Woon Paik ),( Kwang Hyub Han ),( Soon Ho Um ),( Byung Ik Kim ),( Heon Ju Lee ),( Mong Cho ),( Chun Kyon Lee ),( Dong 대한간학회 2014 Clinical and Molecular Hepatology(대한간학회지) Vol.20 No.2

Background/Aims: Adefovir dipivoxil (ADV) is a nucleotide analogue that is effective against lamivudine-resistant hepatitis B virus (HBV). The aim of this study was to determine the long-term clinical outcomes after ADV rescue therapy in decompensated patients infected with lamivudine-resistant HBV. Methods: In total, 128 patients with a decompensated state and lamivudine-resistant HBV were treated with ADV at a dosage of 10 mg/day for a median of 33 months in this multicenter cohort study. Results: Following ADV treatment, 86 (72.3%) of 119 patients experienced a decrease in Child-Pugh score of at least 2 points, and the overall end-stage liver disease score decreased from 16±5 to 14±10 (mean ± SD, P<0.001) during the follow-up period. With ADV treatment, 67 patients (56.3%) had undetectable serum HBV DNA (detection limit, 0.5 pg/ mL). Virologic breakthrough occurred in 38 patients (36.1%) and 9 patients had a suboptimal ADV response. The overall survival rate was 89.9% (107/119), and a suboptimal response to ADV treatment was associated with both no improvement in Child-Pugh score (≥2 points; P=0.001) and high mortality following ADV rescue therapy (P=0.012). Conclusions: Three years of ADV treatment was effective and safe in decompensated patients with lamivudineresistant HBV. (Clin Mol Hepatol 2014;20:168-176)