대한한방소아과학회지제 27 권제 1 호 (2013 년 2 월 ) J Pediatrics of Korean Medicine, February, 2013;27(1):36-49 ISSN 1226-8038(Print), 2287-9463(Online), http://dx.doi.org/10.7778/jpkm.2013.27.1.036 아토피피부염외용제에관련된국내임상및실험논문고찰 민들레 박은정 강경하 원광대학교한의과대학소아과학교실 Abstract Review of Clinical and Experimental Studies on External Application Treatment for Atopic Dermatitis in the Korean Literature Min Deul Le Park Eun Jung Kang Kyung Ha Department of Pediatrics, College of Oriental Medicine, Wonkwang University Objectives The goal of this review is to investigate clinical and experimental studies on external application treatment for atopic dermatitis in Korean literature and to propose for the better method of clinical studies in order to seek more effective treatment. Methods Electronic researches were performed with KTKP, OASIS, National Assembly Library, Korean Medicine Database, KISS, DBpia, and KISTI. Results and Conclusions In Twenty six studies, the numbers of clinical and experimental studies are respectively 10 (38.46%) and 16 (61.54%). The numbers of studies that used herbal complex were 20 (76.92%), and out of that, 6 studies had used a single herbal medicine (23.08%). The external application with oriental medicine for the atopic dermatitis used with Phellodendri Cortex (7), Sophorae Radix (6), Scutellariae Radix (6), Lonicerae Flos (5), Coptidis Rhizoma (5) and so on. Among the clinical studies, the 5 studies were double-blind and randomized-controlled study (50%). The numbers of studies that used Hanifin and Rajka Diagnostic Criteria (1980) were 6 (60%), and that used the Diagnostic Criteria in Korean Atopic Dermatitis (2005) were 4 (40%). Among the clinical studies, categories to evaluate of atopic dermatitis are respectively SCORAD Index (80%), Total IgE (80%), Eosinophil count (70%) and so on. All of the clinical studies (100%) showed a statistically significant decline in atopic dermatitis according to the SCORAD Index, Modified SCORAD Index, the Clinic index score. Among the experimental studies, the numbers of studies that used NC/Nga mice were 9 (56.25%), and out of that 5 studies used BALB/c mice (31.25%). Most of the studies (68.75%) used DNCB as allergy inducing materials. The scales for evaluation of atopic dermatitis were Clinical skin severity score, Histopathologic examination, Immunohematologic examination, safety test and so on. In 12 cases (75%) of experimental studies, the IgE level of experimental group showed a statistically significant decline after using external application. In 8 study cases (50%), Clinical skin severity score of experimental group showed a statistically significant decline after using external application. Key words : Atopic dermatitis, External application Received: January 25, 2013 Revised: February 14, 2013 Accepted: February 15, 2013 Corresponding Author: Park Eun Jung Department of Pediatrics, Wonkwang University Jeonju Oriental Medicine Hospital, 99 Garyeonsan-ro, Deokjin-gu, Jeonju, Jeollabuk-do 561-851, Republic of Korea Republic of Korea Tel: +82-63-270-1019 Fax: +82-63-270-1594 E-mail: ejpark@wonkwang.ac.kr c The Association of Pediatrics of Korean Medicine. All rights reserved. This is an open-access article distributed under the tenus of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
아토피피부염외용제에관련된국내임상및실험논문고찰 37 Ⅰ. Introduction 아토피피부염은심한소양감과특징적인습진성피부병변을나타내는만성재발성의염증성피부질환으로 1), 연령에따라특징적인병변의분포와양상을보인다 2). 현재까지정확한원인과발병기전이밝혀져있지는않으나, 다양한가설로유전적요인, 환경적요인, 약리적요인, 심리적요인, 면역학적요인및표피투과장벽과항균장벽기능이상이중요한원인으로제시되고있다 3). 한의학에서아토피피부염은浸淫, 浸淫瘡, 乳癬, 奶癬, 胎斂瘡등으로불리며 4-6), 크게濕熱俱盛型, 脾虛濕盛型, 血虛風燥型으로변증분류하여 7) " 外病內治 " 의원칙하에다양한외치법도병용되고있다 8). 아토피피부염에있어피부장벽의역할이중요한데다양한원인에의해손상된피부장벽으로피부건조가유발되어소양감이생기고이로인하여피부를긁게되며, 피부를긁음으로써피부에상처가유발되고이를통하여다시소양감이나타나게되는 itch-scratch-itch 의악순환을반복하게된다. 따라서아토피피부염치료의기본은피부장벽기능의보강이라고볼수있으며 9), 이를위해서적절한피부외용제를통한적극적外治가필요하다. 이에저자는최근국내논문을중심으로아토피피부염외용제에대한선행연구들을조사, 검토해봄으로써아토피피부염치료에있어서외용제의단독적용을통한치료효과를확인해보고, 외용제연구에적절하리라생각되는본초및처방을정리한결과약간의지견을얻었기에보고하는바이다. Ⅱ. Materials and methods 연구자료수집은국내전자데이터베이스검색을통해수행하였다. 자료의수집을위해 한국전통지식포탈, 한국의학정보포탈, 국회도서관, 의학논문데이터베이스검색, 한국학술정보, DBpia, 과학기술학회마을 을중심으로 on-line 검색을하였으며 (Table 1), 검색어는 아토피, 아토피피부염, 외용, 외치, 도포, 화장품, 화장수 를조합하여사용하였고이중원문열람이가능한논문만을대상으로하였다. 검색은 2012년 12월까지출간된학회지논문으로한정하였으며, 아토피피부염에대하여외용제를단일치료도구로사용한증례보고, 임상시험연구, 동물실험연구논문을대상으로포함하여총 179편의논문중세포실험논문과처방내용을알수없는경우, 한약 Table 1. Lists of Search Engine Korean electric databases for this review Domain Korean Traditional Knowledge Portal http://www.koreantk.com Oriental Medicine Advanced Searching Integrated system http://oasis.kiom.re.kr National Assembly Library http://www.nanet.go.kr Korean Medicine Database http://kmbase.medric.or.kr Koreanstudies Information Service System http://kiss.kstudy.com DBpia http://www.dbpia.co.kr Korea Institute of Science and Technology Information http://society.kisti.re.kr Total 7 Table 2. Classification of Articles Associated with Atopic Dermatitis External Application Clinical Trials Animal Studies Case Reports Total before 2004 0 0 0 0 2005 0 1 (3.85%) 0 1 (3.85%) 2006 1 (3.85%) 1 (3.85%) 0 2 (7.69%) 2007 2 (7.69%) 0 0 2 (7.69%) 2008 2 (7.69%) 2 (7.69%) 0 4 (15.38%) 2009 1 (3.85%) 2 (7.69%) 0 3 (11.54%) 2010 2 (7.69%) 4 (15.38%) 0 6 (23.08%) 2011 1 (3.85%) 2 (7.69%) 0 3 (11.54%) 2012 1 (3.85%) 4 (15.38%) 0 5 (19.23%) Total (%) 10 (38.46%) 16 (61.54%) 0 26 (100%)
38 Review of Clinical and Experimental Studies on External Application Treatment for Atopic Dermatitis in the Korean Literature Table 3. Frequency of Herbs in Prescription Frequency Herbs Aroma Oil, Others 7 Phellodendri Cortex ( 黃柏 ) 6 Sophorae Radix ( 苦蔘 ), Scutellariae Radix ( 黃芩 ) 5 Lonicerae Flos ( 金銀花 ), Coptidis Rhizoma ( 黃連 ) 4 Angelicae Gigantis Radix ( 當歸 ), Rheum rhabarbarum L. ( 大黃 ), Houttuynia cordata Thunb ( 魚腥草 ), Forsythiae Fructus ( 蓮翹 ) Lavender 3 Glycyrrhizae Radix ( 甘草 ), Dictamni Radicis Cortex ( 白鮮皮 ), Paeoniae Radix ( 白芍藥 ), Lithospermum erythrorhizon siebold & zucc. ( 紫草 ), Gardeniae Fructus ( 梔子 ) Chamomile 2 Puerariae Radix ( 葛根 ), Portulaca oleracea L. ( 馬齒莧 ), Sanguisorba officinalis Linne ( 地楡 ), Kochia scoparia Schrader ( 地膚子 ), Torilis japonica (Houtt.) DC. ( 蛇床子 ), Schizonepeta tenuifolia Briquet ( 荊芥 ), Prunus yedoensis Rehder ( 樺皮 ), Rubus coreanus ( 覆盆子 ), Rehmannia glutinosa Libosch ( 生地黃 ), Astragali Radix ( 黃芪 ), Angelica dahurica ( 白芷 ), Camellia Sinensis ( 綠茶 ), Phellinus linteus ( 桑黃 ), Sesameseed Oil ( 胡麻油 ), Bees Wax ( 蜜蠟 ), Swine Oil ( 豚脂 ) Tea tree 1 Ginseng Radix ( 人蔘 ), Atractylodes macrocephala Koidzumi ( 白朮 ), Poria cocos ( 茯笭 ), Citrus Unshiu Markovich ( 陳皮 ), Chaenomeles sinensis ( 木瓜 ), Cimicifugae Rhizoma ( 升麻 ), Platycodi Radix ( 桔梗 ), Ponciri Fructus ( 枳實 ), Cnidium officinale makino ( 川芎 ), Corydalis Yanhusuo ( 玄胡索 ), Chamaecyparis obtusa ( 扁柏 ), Red ginseng ( 紅蔘 ), Hydnocarpi Semen ( 大風子 ), Sesami Semen ( 胡麻子 ), Momordicae Semen ( 木鼈子 ), Xanthii Fructus ( 蒼耳子 ), Eucommia Ulmoides Oliver ( 杜仲 ), Gypsum Fibrosum ( 石膏 ), Fossilia ossis Mastodi ( 龍骨 ), Borax ( 硼砂 ), Sepiae Os ( 烏賊骨 ), Sulfur ( 硫黃 ), Gynostemma Pentaphyllum Makino ( 七葉膽 ), Arctii Fructus ( 牛蒡子 ) Eucalyptus, Lemon, Snail Secretion Filtrate 재에서특성성분을추출하여사용한경우는연구대상에서제외하였으며, 기타치료도구 ( 한약복용, 침치료등 ) 를병용한논문을제외하여외용제단독사용효과를알아보는데에중점을두었다. 최종적으로연구주제에부합하는 26편의논문을선정하여분석하였다. 대상논문에대해연도별, 유형별분류를하였으며, 각논문에사용된치료법과평가도구를분석하였다. Ⅲ. Results 1. 연도및유형별분류연구를진행한 26편의논문을연도별로살펴보면 2012년 5편 (19.23%), 2011년 3편 (11.54%), 2010년 6편 (23.08%), 2009년 3편 (11.54%), 2008년 4편 (15.38%), 2007년 2편 (7.69%), 2006년 2편 (7.69%), 2005년 1편 (3.85%) 으로조사되었다. 이중임상시험연구논문은 10편 (38.46%), 동물실험논문은 16편 (61.54%) 이었으며, 외용제로단독치료한증례보고의경우는찾아볼수없었다 (Table 2). 외용제처방의경우복합처방논문이 20편 (76.92%), 단미처방논문이 6편 (23.08%) 이었다. 2. 외용제처방에관한분석외용제처방에사용된본초를살펴보면黃柏 (7), 苦 蔘 (6), 黃芩 (6), 金銀花 (5), 黃連 (5), 當歸 (4), 大黃 (4), 魚腥草 (4), 蓮翹 (4), 甘草 (3), 白鮮皮 (3), 白芍藥 (3), 紫草 (3), 梔子 (3) 등의순으로다용되었다 (Table 3). Aroma therapy에사용되는 essential oil은 Lavender (4), Chamomile (3), Tea tree (2), Eucalyptus (1), Lemon (1) 의빈도로사용되었다. 3. 임상논문분석임상논문이라함은인체를대상으로일정한처치를시행하여그에대한경과및효과를관찰, 분석한연구를편의상지칭한것으로 10), 증례보고와임상실험연구가이에해당한다고볼수있다. 본논문에서분석한 10편의주요내용은다음과같다 (Table 4, 5). (1) 연구방법에관한분석아토피피부염외용제관련임상실험연구총 10편가운데 5편 (50%) 만이실험군-대조군을설정하여무작위배정, 이중맹검으로진행된실험이었다. 연구대상의선정에있어서아토피피부염을진단하는기준으로 6편 (60%) 은 Hanifin and Rajka의진단기준 (1980) 11) (Table 6) 을사용했으며, 4편 (40%) 은대한아토피피부염학회의한국인아토피피부염진단기준 (2005) 12) (Table 7) 을사용했다. 또한각임상시험마다환자연령군과임상시험진행기간이다양하여일치되지않는경향을보였으며, 연령별로치료내용에명확한차이를설정한연구는찾아볼수없었다.
아토피피부염외용제에관련된국내임상및실험논문고찰 39 Table 4. Methods of Treatment and the Types of Study in the Clinical Studies No. 1st Author (year) Article Publication journal Treatment Subjects Duration Age The types of study 1 Joo H.A. (2012) A Clinical study for the effect of cosmetic cream containing Samwhangsejegamibang Extracts on Atopic dermatitis patients Otolaryngology& Dermatology cosmetic cream containing Samwhangsejegamiba ng extracts 43 4weeks 5~25yr A double-blind, randomized, placebo-controlled intervention 2 O M.J. (2011) A Clinical study for the effect of ointment contained Takrisodok-Eum on recovering the damaged skin barrier by Atopic dermatitis Otolaryngology& Dermatology ointment contained Takrisodok-Eum 37 8weeks 5~50yr A double-blind, randomized-controll ed intervention 3 Jung H.J. (2010) Research about Herbal Cosmetics containing Phellinus linteus Extracts in Atopic Dermatitis patients Otolaryngology& Dermatology herbal cosmetics containing Phellinus linteus extracts 35 4weeks 2~65yr Uncontrolled clinical trial 4 Oh M.J. (2010) The Effects of Snail Secretion Filtrate on the damaged skin barrier s recovery of the Atopic dermatitis Otolaryngology& Dermatology Snail Secretion Filtrate 15% 20 4weeks 15±9.1yr A double-blind, randomized-controll ed study 5 Kang S.J. (2009) The Enhancing effect of Atopic Dermatitis by cosmetics containing estern medical herbs Journal of academia-industrial technology toner and cream using estern medical herbs 16 6weeks 5~50yr Uncontrolled clinical trial 6 Yun D.C. (2008) Clinical research of Atopic Dermatitis treated by Hwangryeonhaedok-Tang in Cosmetics Korean J. Oriental Physiology & Pathology ointment that contain Hwangryeonhaedok-T ang 31 4weeks 16yr~ A double-blind, randomized-controll ed study 7 Kim S.H. (2008) A Clinical research of Atopic Dermatitis treated by Yeongyuseungmatang in cosmetics Otolaryngology& Dermatology cosmetics with Yeongyuseungmatang 33 4weeks 16yr~ A double-blind, Randomized-control led study 8 Hwang S.Y.(2007) A Clinical study of Atopic Dermatitis treated by external application with Gynostemma Pentaphyllum MAKINO in cosmetics Otolaryngology& Dermatology cosmetics with Gynostemma Pentaphyllum MAKINO 46 (laboratory 44) 4weeks 6~40yr Prospective open study 9 Kim C.H. (2007) Clinical efficacy of External Preparation containing Herbal Extracts in Atopic Dermatitis patients Otolaryngology& Dermatology the 4 items of Medibebe (cream, lotion, soap, and body cleanser) 50 4weeks 1~60yr Uncontrolled clinical trial 10 Yoon J.M. (2006) Effect of Taeyeol-go on Atopic Dermatitis Daejeon University, Institute of korean medicine.thesis Collection Taeyeol-go (TYG) 10 1week 3~37yr Uncontrolled clinical trial
40 Review of Clinical and Experimental Studies on External Application Treatment for Atopic Dermatitis in the Korean Literature Table 5. Methods of Evaluation, Results and Conclusions in the Clinical Studies No. Methods of evaluation Results Conclusions Comparison of changes in Scorad Index, depending on the perspective, the SCORAD Index, image experimental group showed a statistically significant decline than the placebo group. photographing, moisture Comparison of change in IGA, depending on the perspeαive, the experimental group content, oil content of Cosmetic cream containing showed a statistically significant decline than the placebo group. skin, wrinkled skin, Samwhangsejegamibang 1 Comparison of change in moisture content, oii content of skin and wrinkled skin, Change in IgE & extracts have a positive effect on both the experimental group and the placebo group showed level elevation but Eosinophil, IGA atopic dermatitis patients. there was no statistically significant change. (Investigator s Global Comparison of change in IgE and Eosinophil, both the experimental group and Assesment) the placebo group showed no statistical significance. 2 3 4 5 6 SCORAD Index, image photograhing, skin hydration, TEWL, skin ph, Total IgE, Eosinophil count, IL-4,10,13, IFN-r Modified SCORAD Index, TEWL, skin moisture content, pruritic degree SCORAD Index, Image photopgraphing, TEWL, skin hydration, skin ph, total IgE, Eosinophil count, Global assesment of efficacy SCORAD Index, skin hydration, TEWL, skin ph, Total IgE, Eosinophil count, Global assesment of efficacy SCORAD Index, Image photographing, skin temperature, TEWL, skin hydration, skin ph, total IgE, eosinophil count, global assesment of In the primary endpoint, SCORAD Index showed a statistically significant decline in experimental group. In the secondary endpoint index of skin hydration, both the experimental group and the control group showed statistical significance. In the secondary endpoint index of TEWL, the experimental group showed greater statistical significance than the control group. In the secondary endpoint index of skin ph, skin ph showed a statistically significant decline in both the control group and the experimental group within the normal range. In the secondary endpont index of Total IgE, Eosinophil count, IL-10, IL-13, both the experimental group and the control group showed no statistical significance. To evaluate the safety of the products for the human body, hematological examination and hematological biochemical examination, vital sign check were conducted; both control group and experimental group showed no abnormal level. And There were no severe adverse events during this study. Therefore, it is suggested that the safety of the products, if used for certain period, should be safe for the human body. Statistically, herbal cosmetics containing Phellinus linteus extracts showed siginificant effect on transepidermal water loss, skin moisture content, modified scorad index of atopic dermatitis and pruritic degree (p<0.05). And satisfaction after using herbal cosmetics was near good. In the primary endpoint, SCORAD Index showed a statistically significant decline in both the control group and the experimental group. However, the experimental group showed greater statistical significance than the control group. In the secondary endpoint index of skin hydration, both the control group and the experimental group did not show a statistically significant increase. However, the degree of skin hydration in the experimental group is greater than in the control group. In global assessment of efficacy, it was higher in the experimental group than in the control group for both the subjects and the researchers. To evaluate the safety of the products for the human body, hematological examination and hematological biochemical examination were conducted; both the control group and the experimental group showed no abnormal level. Therefore, the safety of the products, if used for so long a time, proved to be safe for the human body. Product satisfaction was higher in the experimental group than in the control group. The result was a decrease in SCORAD index(26.9±11.8 to 14.9 ± 9.7 (p<0.05)), IgE (641.9 ± 1294.6 to 565.8 ± 1076.8), Eosinophil count (246.7 ± 203.5 to 203.3 ± 130.7 (p<0.05)) and TEWL (16.7 ± 5.1 to 15.4 ± 8.7 (p<0.05)). And skin hydration was increased (36.6 ± 10.0 to 44.0 ± 10.3 (p<0.01)) maintaining skin ph level. The patient's and physician's global assessment also improved. Takrisodok-Eum should be effective for the Atopic dermatitis. Herbal cosmetics containing Phellinus linteus extracts have the remarkable effects on atopic dermatitis. Snail Secretion Filtrate was effective on the Atopic dermatitis. Estern medical herbs may play a role in treatment of atopic dermatitis. After 4 weeks of external application treatment, SCORAD Index in experimental group was significant statistically decreased compared with control group. After Cosmetics with 4 weeks of external application treatment, total IgE of both groups were decreased and eosinophil count in control group was decreased but experimental group was unstatistically decreased. Unstatistically, both groups didn't showed significant effect on Skin Temperature. Transepidermal Water Loss (TEWL) in both groups Hwangryeonhaedok-Tang has some therapeutical effects in mitigating the symptoms of Atopic Dermatitis.
아토피피부염외용제에관련된국내임상및실험논문고찰 41 7 8 9 No. Methods of evaluation Results Conclusions efficacy SCORAD Index, Image photographing, Skin temperature, TEWL, skin hydration, skin ph, Total IgE, Eosinophil count, Global assesment of efficacy Clinical index score, Total IgE, eosinophil count, Total Availability SCORAD Index, Quality of Life (skindex-29), Total IgE 10 SCORAD Index were increased but experimental group was significant decreased compared with control group. Skin Hydration in experimental group was significant statistically increased compared with control group. Statistically, both groups didn't showed significant effect on Skin ph. Only experimental group showed little increase. After 4 weeks of external application treatment, experimental group showed significant effect on global assesment of efficacy. After 4 weeks of external application treatment, SCORAD Index in Yeongyuseungmatang was significant statistically decreased compared with control group. After 4 weeks of external application treatment, eosinophil count in Yeongyuseungmatang was significant statistically decreased compared with control group but total IgE was very increased both Yeongyuseungmatang and control group. Statistically, Yeongyuseungmatang and control group didn't showed significant effect on Skin Temperature was measeured by Thermometer SM815. Transepidermal Water Loss (TEWL) in Yeongyuseungmatang was significant statistically decreased compared with control group measured by Tewameter TM300. Skin Hydration in Yeongyuseungmatang was significant statistically increased compared with control group measured by Corneometer CM825. Statistically, Yeongyuseungmatang and control group didn't showed significant effect on Skin ph was measured by Skin-pH-Meter PH905. After 4 weeks of external application treatment, Yeongyuseungmatang showed significant effect on global assesment of efficacy. There are 46 patients we could check by clinic index score and 44 patients by laboratory. In the 46 case clinic index score was significantly decreased between the beforeand after-external application treatment periods (P<0.01). The 46 cases was devided into two types (moist heat type and blood dryness type) by intensity. External application of Gynostemma Pentaphyllum MAKINO in cosmetics did not significant change by two types. In the 44 laboratory cases, the number of eosinophil counts was decreased but the number of IgE was significantly increased. After 4 weeks' use of Medibebe, SCORAD index showed a decrease of 20.0 ± 10.2 (95% C.I:17.1-22.9) compared with when it was not applied, which is a statistically meaningful change (p-value<0.0001). Subjective pruritus and Sleeping loss reported after both 2 and 4 weeks' use of Medibebe decreased in a statistically meaningful way (p-value<0.0001) compared with before the application. but, 2 cases out of all 50 subjects for the clinical trial were excluded on the way. 10 patients (4 male, 6 female), 3 to 37 years of age (mean 14.6 ± 9.52 years old), 2 to 31 years of onset (mean 11.4 ± 8.54 years), finished study. After treatment extent (p<0.01), intensity (p<0.005), subjective symptom (p<0.002) and total SCORAD index (p<0.002) was significantly decreased than before treatment. Cosmetics with Yeongyuseungmatang has some therapeutical effects in mitigating the symptoms of atopic dermatitis. Cosmetics with Gynostemma Pentaphyllum MAKINO have the remedical effect for Atopic Dermatitis. 4 items of Medibebe (cream, lotion, soap, and body cleanser) can be used by atopic patients safely and effectively with almost no side-effect. TYG is an effective therapeutic method for atopic dermatitis. (2) 평가항목에관한분석아토피피부염의상태를평가하기위해사용된 scale 로서 SCORAD Index가 8편 (80%) 으로가장많이사용되었으며, Modified Scorad Index, Clinical index score가사용된논문이각각 1편 (10%) 씩조사되었다. 아토피피부염평가 scale 외에혈액학적검사로 8편 (80%) 의연구에서 Total IgE를측정하였고, 7편 (70%) 의연구에서 Eosinophil count를시행하여아토피피부염의정도를평가하는데참고하였다. 이외에사진촬영을통해병변부위상태를관찰, 기록한경우가 5편 (50%) 이었고, 피부진단기기를사용하여피부의수분 함유량, 표피수분손실량 (TEWL), 피부산성도등을측정한경우가 7편 (70%) 이었다. 유효성평가를시행한경우가 6편 (60%) 이었고기타 IL-4, IL-10, IL-13, IFN-γ 를측정한경우, skindex-29를통하여삶의질을평가한보고도있었다. (3) 결과에관한분석임상시험논문 10편 (100%) 모두에서아토피피부염의상태를평가하기위해사용된주요 scale (SCORAD Index, Modified SCORAD Index, Clinic index score) 이유의성있게감소하였다. 피부수분함유량이유의성있게
42 Review of Clinical and Experimental Studies on External Application Treatment for Atopic Dermatitis in the Korean Literature Table 6. Hanifin and Rajka Diagnostic Criteria(1980) 11) : at least three of 4 major features and three of 23 minor features Major features 1. Pruritus 2. Typical morphology and distribution : Flexural lichenification or linearity in adults Facial and extensor involvement in infants and children 3. Chronic or chronically relapsing dermatitis 4. Personal or family history of atopy Minor features 1. Xerosis 2. Ichthyosis / palmar hyperlinearity / keratosis pilaris 3. Immediate (type 1) skin test reactivity 4. Elevated serum IgE 5. Ear1y age of onset 6. Tendency towards cutaneous infections 7. Tendency towards non-specific hand or foot dermatitis 8. Nipple eczema 9. Cheilitis 10. Recurrent conjunctivitis 11. Dennie-Morgan infraorbital fold 12. Keratoconus 13. Anterior subcapsular cataracts 14. Orbital darkening 15. Facial pallor / facial erythema 16. Pityriasis alba 17. Anterior neck folds 18. Itch when sweating 19. Intolerance to wool and lipid solvents 20. Perifollicular accentuation 21. Food intolerance 22. Course influenced by environmental / emotional factors 23. White dermographism / delayed blanch Table 7. Atopic Dermatitis Research Group (2005) 12) : diagnostic criteria in Korean (at least two of 4 major features and four of 14 minor features) Major features 1. Pruritus 2. Typical morphology and distribution 1) Under the age of 2 years : face, trunk and extensor involvement 2) Over the age of 2 years : face, neck and flexural involvement 3) Personal or family history (atopic dermatitis, asthma, allergic rhinitis) Minor features 1. Xerosis 2. Pityriasis alba 3. Periorbital eczema or orbital darkening 4. Periauricular eczema 5. Cheilitis 6. Tendency towards non-specific hand or foot dermatitis 7. Scalp scale 8. Perifollicular accentuation 9. Nipple eczema 10. Itch when sweating 11. White dermographism 12. Skin prick test reactivity 13. Elevated serum IgE 14. Tendency towards cutaneous infections 증가한논문이 5편 (50%), 표피수분손실량 (TEWL) 이유의성있게감소한논문이 4편 (40%), 총괄적유효성평가에서실험군이대조군에비해유의성있게높게나타난논문이 3편 (30%), Eosinophil이유의성있게감소한논문이 2편 (20%) 으로나타났다. 4. 동물실험논문분석 (Table 8) 아토피피부염외용제관련동물실험연구총 16편가운데대상동물로 NC/Nga mice를사용한논문이 9편 (56.25%), BALB/c mice로실험한논문이 5편 (31.25%), 기타 hairless mice, Sprague-Dawley rat를사용한논문이각각 1편씩있었다. 아토피피부염유발물질로 1-chloro 2,4-dinitrochlorobenzene (DNCB) 를사용한경우가 11편 (68.75%) 으로가장많았으며, Biostir Mite antigen cream (BMAC) 을사용한경우가 2편 (12.5%), 2,4,6-trinitrochlorobenzene (TNCB), Ovalbumin (OVA), Dermatophagoides farinae (Df) extract를사용한경우가각각 1편씩있었다. 외용
아토피피부염외용제에관련된국내임상및실험논문고찰 43 Table 8. Methods of Treatment and Evaluation in the Animal Experimentation 1 st Author (year) Article Publication journal Species of animals Allergy Inducing Materials & Treatments Methods of evaluation Conclusions Choi Y.Y. (2012) Anti-inflammatory effects of HC001 on atopic dermatitis-like skin lesions in mice The Korean Journal Of Oriental Prescription 1) BALB/c mice 3) HC001 histologic analysis (hyperplasia), western blot assay (NF-κB) HC001 may be useful as an external application agent for atopic dermatitis based on reductions of various inflammatory responses. Hwang C.Y. (2012) The External use effects of Samwhangsejegami Extract on Atopic dermatitis of NC/Nga mice Ophthalmology & Otolaryngology & Dermatology 1) NC/Nga mice 3) Samwhangsejegami Extract clinical skin severity score, IgE, IL-4,5,6 level, expression of filaggrin, serine almitoyltransferase (SPT), COX-2 Samhwangsaejaegami extract can be promising candidate for anti-atopic dermatitis treatment Lee G.S. (2012) Lee Y.J. (2012) Cho H.C. (2011) Song J.S. (2011) Effects of Herbal Complex, YJ-1, on Atopic Dermatitis Yakhak Hoeji in NC/Nga mice model Study on the modulation of immune system of CPS in atopic dermatitis induced animal models Topical application of Herbal-mixed Extract on back skin suppresses inflammation in Ovalbumin-induced Atopic Dermatitis Effects of Scrophulariae Radix (SR) on Allergic Contact Dermatitis (ACD) induced by DNCB in mice Daejeon University, Institute of korean medicine.thesis Collection Kor. J. Oriental Preventive Society Ophthalmology & Otolaryngology & Dermatology 1) NC/Nga mice 3) YJ-1 (Herbal Complex) 1) NC/Nga mice 2) TNCB 3) CPS (chunggipadoksan) 1) BALB/c mice 2) OVA (Ovalbumin) 3) Herbal-mixed Extract (CP001, CP002) 1) BALB/c mice 3) Scrophulariae Radix (SR) The ointment of YJ-1 may Weight, Water and feed, enhance the process of AD Scratching counts, Clinical skin healing by alleviating allergic severity, Spleen weight, Serum IgE & reaction and has potential for IL-4 level therapeutic reagent for the treatment of AD. safety test (cell viability, AST, ALT, BUN), Clinical skin index Immune cell count of DLN & Dorsal skin, IL-4,5,6,13, TNF-α level in splenocytes The results strongly indicated the significant immune modulatory effect of CPS and thus clinical application of CPS on AD treatment Herbal extracts (CP001 and Histopathologic Analysis, Blood CP002) could be potential analysis, Immunostaining, Real-time candidate for the treatment of PCR, IgE level chronic atopic dermatitis Clinical aspects on the skin, Histopathological changes, Mast cell distribution, Immune cell infiltration in tissue, spleen/body ratio, production levels of serum cytokines, cell viability, release of b-hexosaminidase and histamine SR can decrease symptoms of ACD, then SR is useful to treat patient with ACD Mok J.Y. (2010) Anti-inflammatory effects of Effective Microorganism Fermentation Substance on Atopic Dermatitis- like NC/Nga mouse model Korean J. Oriental Physiology & Pathology 1) NC/Nga Mice 2) Dermatophagoides farinae (Df) extract 3) EM-S (Effective Microorganism Fermentation Substance) Clinical severity score, Skin tissue analysis, Immunohistochemical Staining, Serum IgE & Th2 chemokine productions Topical application of EM-S may be improve the AD-like skin lesion by suppressing IgE and Th2 chemokines Kim H.A. (2010) Effects of Lavender, Lemon and Eucalyptus essential Oil on Th2 related Factors of DNCB-induced Atopy dermatitis in NC/Nga mice model Journal of Korean institute of pharmacopunct ure 1) NC/Nga Mice 3) ELL (lavender, lemon, eucalyptus) with one carrier oil (jojoba) cell viability, skin clinical score, the ELL was effective on atopy level of serum IgE, IgG1, IL-4,13 and dermatitis by modulating Th2 IFN-r related factors
44 Review of Clinical and Experimental Studies on External Application Treatment for Atopic Dermatitis in the Korean Literature 1 st Author (year) Jung J.Y. (2010) Kim G.E. (2010) Ju Y.E. (2009) Kim B.A. (2009) Yeo E.J. (2008) Kim B.A. (2008) Kim S.C. (2006) Kim C.J. (2005) Article Effect of Phellinus igniarius Quel Extract on the Anti-inflammatory, Anti allergy, Anti-oxidant, Anti-wrinkle reaction Anti-acne and Anti-atopic Dermatitis Effect of Plant extracts including Eucommia ulmoides Oliv and Phellodendron amurense Effects of Atopy Cream-combined with Jawoongo Ointment on the Development of Atopic Dermatitis-like skin lesions in NC/Nga mouse Effect of Hwangryunhaedok-tang Extracts on DNCB-induced Allergic Contact Dermatitis Topical application of Atopy cream-jawoogo ointment (A-J) of Ointment Inhibits Biostir mite antigen cream induced Atopy Dermatitis by local action in NC/Nga mice Inhibitory studies of Hwangryunhaedok-tang on development of Atopic Dermatitis in NC/Nga mice Effect of Lonicerae Flos-Skin on Contact Hypersensitivity induced by repeat elicitation of DNCB The Effects of Sophorae Radix and Coptidis Rhizoma - Iontophoresis in Allergic Contact Dermatitis Publication journal Korean Oriental Otolaryngology & Dermatology Korean Chem. Eng. Res. J. Korean Oriental Pediatrics Kor. J. Herbology Daejeon University, Institute of korean medicine.thesis Collection Kor. J. Herbology Kor. J. Herbology Ophthalmology & Otolaryngology & Dermatology Species of animals Allergy Inducing Materials & Treatments 1) NC/Nga Mice 3) BPE (Betula platyphylla var. japonica extract) 1) hairless mice 3) Plant Extracts including Eucommia ulmoides Oliv. and Phellodendron amurense 1) NC/Nga Mice 2) Biostir Mite antigen cream (Mite Ext.) 3) A-J (Atopy Cream-combined with Jawoongo Ointment) 1) BALB/c mice 3) HRHDT extract, HRHDT lotion 1) NC/Nga Mice 2) BMAC (Biostir Mite antigen cream 3) Atopy cream- Jawoogo ointment (A-J) 1) NC/Nga mice 3) Hwangryunhaedoktang 1) BALB/c mice 3) Lonicerae Flos-Skin 1) Sprague-Dawley rat 3) Sophorae Radix and Coptidis Rhizomaiontophoresis Methods of evaluation Cell viability, NO, TNF-α, IL-1β,2,4,5,6,8, IFN-γ, COX-2 production and gene expression, MAPK Western Blotting, Skin severity score, Weight, Water and feed, Blood test, Weight of organs, Histological change, Serum total IgE and Histological change of main organs Anti-oxidation effect (DPPH free radical scavenging activity) Anti-bacterial effect (disc diffusion method) Anti-atopic dermatitis effect (skin condition observation, IgE concentration) Clinical skin score, Hematology and Serum total IgE, IgG1 level, Cytokine level, total cell number, Immunohistochemical staining, Histological features of ALN, DLN, PBMCs and dorsal skin tissue Histopathologic examination, Serum IgE level Clinical skin severity score, Serum IgE, IgG1 level TEWL Assay, Erythema Assay, Skin histopathologic examination, Serum IgE level. Contact hypersensitivity Serum IgG & IgE level Contact hypersensitivity assay, Video microscope, Melanin-erythema levels, ph levels, Hydration levels, Blood test, Serum total IgE level, Skin tissue sample analysis Conclusions Phellinus igniarius Quel extract could be applicable for improvement of several skin functions Plant extracts indicated strong anti-acne and anti-atopic dermatitis effect, and showed strong potential for cosmetics and skin related medicine A-J was the successful treatment of atopic dermatitis in a NC/Nga mouse model HRHDT-skin could be used as a pharmaceutical material with antiinflammatory effects by reducing IgE in contact hypersensitivity dermatitis Balb/c mice by DNCB A-J can be an effective therapeutic method for atopic dermatitis. HRHDT could be used as pharmaceutical material with anti-atopic dermatitis effect by reducing IgE in contact hypersensitivity atopic dermatitis NC/Nga mice model by DNCB. Lonicerae Flos-skin could be used as a pharmaceutical material with antiinlammatory effects by reducing IgG and IgE in contact hypersensitivity mouse model by DNCB Sophorae Radix and Coptidis Rhizoma-iontophoresis had some anti-allergy, anti-inflammatory effects on allergic contact dermatitis, but had no effects on melanin-erythema levels, ph levels and hydration levels of skin
아토피피부염외용제에관련된국내임상및실험논문고찰 45 제는대부분도포하는방식이었고 1편에서이온삼투요법 (iontophoresis) 으로해당약물을피부에침투시키는방식을사용하였다. 아토피피부염외용제의효과를평가하기위해사용된도구로는 Clinical skin severity score, 조직병리학적평가, 면역혈액학적검사, 안전성검사등이있었다. IgE level이유의성있게감소한논문이 12편 (75%) 이었고, Clinical skin severity score가유의성있게감소한논문이 8편 (50%), IL-4 level이유의성있게감소한논문이 5편 (31.25%) 으로나타났다. 이외에도피부과각화증완화, IL-4, IL-5, IL-6, IL-13 분비및발현감소, TNF-α 분비및발현감소, IgG level 감소, IFN-γ 생성증가, COX-2 유전자발현억제등의효과를보고한논문들이있었다. Ⅳ. Discussion 한의학에서아토피피부염은浸淫, 浸淫瘡, 乳癬, 奶癬, 胎斂瘡등으로불리며 4-6), 吳謙의 < 醫宗金鑑 > 에서는奶癬을胎斂瘡이라하여가려워白屑이일어나는乾斂과가려움이甚하여黃水가浸淫하여퍼져가는濕斂으로나누어설명하여오늘날아토피피부염과가장유사하게표현하고있다 13). 아토피피부염을크게濕熱俱盛型, 脾虛濕盛型, 血虛風燥型으로변증분류하는데 7), 한의학적으로아토피피부염의병리기전은체질적으로脾胃氣虛때문에濕熱의邪氣를感受하기쉽게되어胃의痰飮이일어나고脾胃의건전한기능이손상을입은體質虛弱한소아가外部의영향을받아腠理에濕熱症을일으킨다고보고있다. 또한先天的으로虛寒하며脾의건전한運行機能을상실한사람에게風熱邪가皮膚에浸潤해서발생되고발작을반복해서치유되지않으면결국脾虛血燥로되어피부의영양실조를일으킨다고보았다 14). 아토피피부염은심한소양감과특징적인습진성피부병변을나타내는만성재발성의염증성피부질환으로 1), 완치가가능한치료법이없기때문에보습제및국소 steroid, 국소 tacrolimus, 항히스타민제, 항알러지제, cyclosporine 투여등을증상경감또는제어하는목적으로이용하고있다 15,16). 그러나 steroid의사용은항염증작용, 면역억제작용외에각질형성세포와섬유세포의증식을억제하여피부위축을초래하고초기에는혈관수축을일으키지만결국혈관확장을일으키며그 외에여드름을유발하고면역억제작용에따른세균및진균감염을초래하는등여러가지부작용을일으킬수있다 17). 피부외용제에의한부작용사례연구 에서, 1년미만의연구기간동안피부외용제에의한부작용사례가무려 1257건으로보고되었으며이중부작용의빈도가가장많았던외용제는스테로이드연고로서전체외용제의약 83% 에달하였다 18). 최근아토피피부염의병인은피부장벽및염증반응에관여하는다양한유전적인원인과함께후천적으로다양한피부장벽의손상및항원의노출에의해병변이발현되는 Genotype-phenotype relation으로이해되고있다 19). 즉, 아토피피부염환자에서장벽기능을회복시키는치료는아토피피부염치료의핵심으로생각된다. 실제로이는자체의치료효과뿐아니라다양한문제를유발할수있는국소스테로이드제의사용을감소시킬수있다 20). 아토피피부염의치료원칙은악화요인을피하고피부를청결하고건조하지않도록잘관리하는것인데 21) 이를위해서적절한외용제사용이권장되며, 국소외용제를잘활용하면아토피피부염환자의삶의질을향상시키는데도움이된다 22). 이에저자는최근국내논문을중심으로아토피피부염외용제에대한선행연구들을조사, 검토해봄으로써아토피피부염치료에있어서외용제의단독적용을통한치료효과를확인해보고, 외용제연구에적절하리라생각되는본초및처방을정리해보고자본연구를진행하였다. 논문분류에있어분류방법이다양하여임의로문헌논문, 임상논문, 실험논문의세종류로분류하였고, 본연구는임상논문과실험논문을중심으로진행하였다. 여기에서임상논문은인간을대상으로실험하였거나치료경과를발표한논문, 실험논문은사람이외의동물이나기타생물을대상으로실험하여나타난결과를발표한논문을말한다 10). 연구를진행한 26편의논문을연도별로살펴보면 2012년 5편 (19.23%), 2011년 3편 (11.54%), 2010년 6편 (23.08%), 2009년 3편 (11.54%), 2008년 4편 (15.38%), 2007년 2편 (7.69%), 2006년 2편 (7.69%), 2005년 1편 (3.85%) 으로조사되었다. 이중임상시험연구논문은 10편 (38.46%), 동물실험논문은 16편 (61.54%) 이었으며, 외용제로단독치료한증례보고의경우는찾아볼수없었다. 외용제처방의경우복합처방논문이 20편 (76.92%), 단미처방논문이 6편 (23.08%) 이었다. 일반적으로사용되어온한의학적약물요법을종합
46 Review of Clinical and Experimental Studies on External Application Treatment for Atopic Dermatitis in the Korean Literature 적으로살펴보면內治法으로濕熱型은淸熱利濕養血祛風하며生地黃, 淡竹葉, 防風, 蒼朮, 白鮮皮, 燈心草, 赤芍藥, 連翹, 車前子, 蟬蛻등의약물이주로사용되고, 脾虛濕盛型은健脾利濕消導淸熱하며白朮, 茯笭, 白扁豆, 薏苡仁, 澤瀉, 地膚子, 牧丹皮등의약물이주로사용되고, 血燥型은養血潤燥淸熱解毒하며生地黃, 牧丹皮, 當歸, 梔子, 黃柏, 麥門冬, 白茅根, 紫草등의약물이주로사용된다 23). 본연구에서외용제처방에사용된본초를살펴보면黃柏 (7), 苦蔘 (6), 黃芩 (6), 金銀花 (5), 黃連 (5), 當歸 (4), 大黃 (4), 魚腥草 (4), 蓮翹 (4), 甘草 (3), 白鮮皮 (3), 白芍藥 (3), 紫草 (3), 梔子 (3) 등의순으로다용되었다. Aroma therapy에사용되는 essential oil은 Lavender (4), Chamomile (3), Tea tree (2), Eucalyptus (1), Lemon (1) 의빈도로사용되었다. 아토피피부염외용제관련임상실험연구총 10편가운데 5편 (50%) 만이실험군-대조군을설정하여무작위배정, 이중맹검으로진행된실험이었다. 연구대상의선정에있어서아토피피부염을진단하는기준으로 6 편 (60%) 은 Hanifin and Rajka의진단기준 11) 을사용했으며, 4편 (40%) 은대한아토피피부염학회의한국인아토피피부염진단기준 (2005) 12) 을사용했다. 환자연령군과임상시험진행기간은각임상시험마다다양하여일치되지않는경향을나타내었으며연령별로치료내용에명확한차이를설정한연구는찾아볼수없었다. 이처럼한의학연구에있어질환별관련임상시험에대한명확한기준이마련되어있지않고, 연구를진행하는데있어서방법론적인인식이부족하다는점이아직까지의한계로지적될수있다. 특히아토피피부염은주로영아와유아에서많이발생하며나이가들어감에따라유병율및질환의강도가감소하는질환으로 24), 연령별로각기특징적인병변의양상이나분포를보이므로 2) 향후대상연령을고려한체계적인연구가이루어질필요가있다. 논문의객관성을위해서는자료수집방법의객관성이중요하므로, 이를위해타당성있고신뢰도있는척도를이용하는것이바람직하다. 이에본연구에서는각논문에사용된평가척도들을살펴보았다. 아토피피부염의상태를평가하기위해사용된 scale로서임상실험연구총 10편가운데 SCORAD Index가 8편 (80%) 으로가장많이사용되었으며, Modified Scorad Index가 1편 (10%), Clinical index score가사용된논문이 1편 (10%) 이었다. 아토피피부염평가 scale 외에혈액 학적검사로 8편 (80%) 의연구에서 Total IgE를측정하였고, 7편 (70%) 의연구에서 Eosinophil count를시행하여아토피피부염의정도를평가하는데참고하였다. 이외에사진촬영을통해병변부위상태를관찰, 기록한경우가 5편 (50%) 이었고, 피부진단기기를사용하여피부의수분함유량, 표피수분손실량 (TEWL), 피부산성도등을측정한경우가 7편 (70%) 이었다. 유효성평가를시행한경우가 6편 (60%) 이었고기타 IL-4, IL-10, IL-13, IFN-γ를측정한경우, skindex-29를통하여삶의질을평가한보고도있었다. 임상시험논문 10편 (100%) 모두에서아토피피부염의상태를평가하기위해사용된주요 scale (SCORAD Index, Modified SCORAD Index, Clinic index score) 이유의성있게감소하였다. 외용제사용으로피부수분함유량이유의성있게증가한논문이 5편 (50%), 표피수분손실량 (TEWL) 이유의성있게감소한논문이 4편 (40%), 총괄적유효성평가에서실험군이대조군에비해유의성있게높게나타난논문이 3편 (30%), Eosinophil 이유의성있게감소한논문이 2편 (20%) 으로나타났다. 이처럼환자의상태를평가함에있어많은수의논문에서 scale과함께혈액학적검사, 피부진단기기를통한측정등을병행하여좀더객관적인평가를내리고자하는시도가이루어지고있다. 논문의객관성확보를위한노력이점차가시화되고있다는점에서긍정적으로사료된다. 동물실험은연구자의통제가쉽고표본추출과대조군의설정이간편하므로현재한의학계에서도연구가많이이루어지고있는추세이다. 아토피피부염외용제관련동물실험연구총 16편가운데대상동물로 NC/Nga mice를사용한논문이 9편 (56.25%), BALB/c mice로실험한논문이 5편 (31.25%), 기타 hairless mice, Sprague-Dawley rat를사용한논문이각각 1편씩있었다. 아토피피부염유발물질로 DNCB를사용한경우가 11편 (68.75%) 으로가장많았으며, Biostir Mite antigen cream을사용한경우가 2편 (12.5%), 2,4,6-trinitrochlorobenzene (TNCB), Ovalbumin (OVA), Dermatophagoides farinae (Df) extract를사용한경우가각각 1편씩있었다. 외용제는대부분도포하는방식이었고 1편에서이온삼투요법 (iontophoresis) 으로해당약물을피부에침투시키는방식을사용하였다. 아토피피부염외용제의효과를평가하기위해사용된도구로는 Clinical skin severity score, 조직병리학적평가, 면역혈액학적검사, 안전성검사등이있었다. 외용제처리후 IgE level이유의성
아토피피부염외용제에관련된국내임상및실험논문고찰 47 있게감소한논문이 12편 (75%) 이었고, Clinical skin severity score가유의성있게감소한논문이 8편 (50%), IL-4 level이유의성있게감소한논문이 5편 (31.25%) 으로나타났다. 연구결과다수의외용제가아직생쥐를이용한동물실험단계에머무르고있어인간에게적용되기까지는보다많은연구가필요하다고생각된다. 현재까지동물실험에서조사한다양한외용제들을인체에적용할수있도록이후임상시험의체계적인 guideline과 protocol을개발하여기존의치료법을개선시키고보완해야할것이다. 또한잘설계된연구 protocol에의한질높은연구에근거한정보가임상치료지침으로서의가치를가질수있도록향후의임상연구설계에있어연구의근거수준강화에힘써야할것이다. 한의학계에서는한약복용을통한각종실험적연구와임상연구는비교적활발히이루어지고있는편이지만, 상대적으로외용제에대한연구는부족한편이며실제임상에서는보조요법정도로인식되고있는실정이다. 아토피피부염환자의대부분을차지하는유소아들의경우한약특유의맛과향으로인해복용하기힘들어하는경우가많고장기간의한약복용을힘들어하는경우가많다 25). 또한극심한가려움증을참지못하고긁어상처가생기기쉬우며이로인한 2차감염의우려도있어심한소양감을완화시킬수있는효과적인외용제의개발및연구가더욱필요한상황이다. 아토피피부염에대한한방외용제개발을위한약재및처방선택에있어상기의빈용약물들을우선적으로연구하는것이좋을것으로보이며, 향후각약재에대한실험적연구를비롯한치료군-대조군설정을통한임상연구등이충분히이뤄져야할것이다. 또한동물실험에이어인체를대상으로한임상연구도단계적으로진행되어야할것으로생각된다. 실제임상에서쓰이는 steroid 연고의경우증상의경중도에따라다양한농도로나뉘어져있기때문에이를고려한추가적인비교연구도시행되어야할것으로사료된다. 이번연구는인터넷검색엔진을통해국내논문을대상으로검색이이루어져국내저자가국외학술지에발표한논문들은연구대상에서제외되어근거수준이높은연구들이누락되었을가능성이있다. 또한현재까지아토피피부염치료제로외용제를단독으로적용한경우가다른치료법에비해상대적으로적어분석대상에한계가있었다. 그러나국내논문을중심으로외용제의단독적용을통한치료효과를확인해보고연구방법을분석하여향후효과적인아토피피부염외용제개발을위한하나의기초자료가될수있을것으로생각된다. Ⅴ. Conclusion 아토피피부염외용제에대하여 한국전통지식포탈, 한국의학정보포탈, 국회도서관, 의학논문데이터베이스검색, 한국학술정보, DBpia, 과학기술학회마을 을중심으로 on-line 검색을통해국내실험및임상논문들을고찰한결과다음과같은결론을얻었다. 1. 연구를진행한 26편의논문을연도별로살펴보면 2012년 5편 (19.23%), 2011년 3편 (11.54%), 2010 년 6편 (23.08%), 2009년 3편 (11.54%), 2008년 4 편 (15.38%), 2007년 2편 (7.69%), 2006년 2편 (7.69%), 2005년 1편 (3.85%) 으로조사되었다. 이중임상시험연구논문은 10편 (38.46%), 동물실험논문은 16편 (61.54%) 이었으며, 외용제로단독치료한증례보고의경우는찾아볼수없었다. 2. 외용제처방의경우복합처방논문이 20편 (76.92%), 단미처방논문이 6편 (23.08%) 이었다. 처방에사용된본초는黃柏 (7), 苦蔘 (6), 黃芩 (6), 金銀花 (5), 黃連 (5), 當歸 (4), 大黃 (4), 魚腥草 (4), 蓮翹 (4) 등의순으로다용되었다. 3. 아토피피부염외용제관련임상실험연구총 10 편가운데 5편 (50%) 만이실험군-대조군을설정하여무작위배정, 이중맹검으로진행된실험이었다. 연구대상선정에있어서아토피피부염을진단하는기준으로 6편 (60%) 은 Hanifin and Rajka 의진단기준을사용했으며, 4편 (40%) 은대한아토피피부염학회의한국인아토피피부염진단기준 (2005) 을사용했다. 4. 아토피피부염의상태를평가하기위해사용된 scale로서 SCORAD Index가 8편 (80%) 으로가장많이사용되었으며, 혈액학적검사로 8편 (80%) 의연구에서 Total IgE를측정하였고, 7편 (70%) 의연구에서 Eosinophil count를시행하여아토피피부염의정도를평가하는데참고하였다. 임상시험논문 10편 (100%) 모두에서아토피피부염의상태를평가하기위해사용된주요 scale (SCORAD Index, Modified SCORAD Index, Clinic index score)
48 Review of Clinical and Experimental Studies on External Application Treatment for Atopic Dermatitis in the Korean Literature 이유의성있게감소하였다. 5. 아토피피부염외용제관련동물실험연구총 16 편가운데대상동물로 NC /Nga mice를사용한논문이 9편 (56.25%), BALB/c mice로실험한논문이 5편 (31.25%) 이었으며, 아토피피부염유발물질로 DNCB를사용한경우가 11편 (68.75%) 으로가장많았다. 아토피피부염외용제의효과를평가하기위해사용된도구로는 Clinical skin severity score, 조직병리학적평가, 면역혈액학적검사, 안전성검사등이있었다. 외용제처리후 IgE level이유의성있게감소한논문이 12편 (75%) 이었고, Clinical skin severity score가유의성있게감소한논문이 8편 (50%) 으로나타났다. Ⅵ. Acknowledgement 이논문은 2013학년도원광대학교의교비지원에의해서수행됨. References 1. Gil KM, Sampson HA. Psychological and social factors of atopic dermatitis. Allergy. 1989;25:39-44. 2. Korean Dermatological Association Textbook Compilation Committee. 5th Edition Dermatology. Seoul:Ryomoongak, P.Co. 2008:170. 3. Lee EH, Lee SE, Lee SH. Diagnosis and recent advances in treatment of Atopic dermatitis. J Skin Barrier Res. 2010;12(1):104. 4. Hong WS. Jeonggyo Huang Di Nei Jing Su Wen. Seoul: Dong Yang Ui Hak Yeon Gu Won Press, 1985:72-80, 246-8. 5. Song SG. Jin Gui Yao Lue Guang Zhou Xiao Quan. Beijing: Ren Min Wei Sheng Publishing Co, 1994:221-5. 6. Chao YF. Chao Shi Zhu Bing Yuan Hou Lun. Seoul: Dae Sung Publishing Co, 1992:251-3. 7. Kwon MW, Lee HJ, Park EJ, Hwang WJ. The Clinical study Of atopic Dermatitis and eosinophil cationic protein in Atopic Dermatitis. J Korean Orient Med 2000;14(2):121-32. 8. Choi YY, Kim MH, Km CJ, Choi YJ, Hwang MK. Anti-inflammatory effects of HC001 on atopic dermatitis-like skin lesions in mice. J Korean Orient Med Prescription. 2012;20(1):41-9. 9. Kim HJ, Jeong SK, Lee SH. Allergen and skin barrier in atopic disease. J Skin Barrier Res. 2008;10(2): 38-45. 10. Park JW, Park CK. A Statistical study on the contents of theses of Oriental Medicine. J Korean Med Classics. 1994;7:161-97. 11. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol(Stockh) Suppl. 1980; 92:44-7. 12. Park YL, Kim HD, Kim KH, Kim MN, Kim JW, Ro YS, Park CW, Lee KH, Lee AY, Cho SH, Choi JH. Report from ADRG: A Study on the Diagnostic Criteria of Korean Atopic Dermatitis. Korean J Dermatol. 2006;44(6):659-63. 13. Wu Q. Yi Zong Jin Jian. Vol 3. Beijing: Ren Min Wei Sheng Publishing Co, 1982:443-4, 451-2. 14. Zhong DY. Pibugwa Hanbangchiryo. Busan: Il Jung Sa Publishing Co, 1991:68-71. 15. Katayama I, Kohno Y, Akiyama K, Ikezawa Z, Kondo N, Tamaki K, Kouro O; Japanese Society of Allergology. Japanese Guideline for Atopic Dermatitis. Allergol Int. 2011;60:205-20. 16. Schmitt J, Schüel K, Schmitt N, Meurer M. Systemic treatment of Severe Atopic Eczema: a Systematic Review. Acta Derm Venereol. 2007;87:100-11. 17. Baumann L, Kerdel F. Topical glucocorticoids. In:Freedberg IM, Eisen AZ, Wolff K. Austen KF, Goldsmith LA, Katz SI, et al, editors. Dermatology in general medicine. 6th ed. New York:McGraw-Hill. 2003:2324-8. 18. Kim SC, Ahn KJ, Hann SK, Kim JW, Sung KJ, Kye YC, Kim NI, Cho KH, Kim KJ, Youn JI. Clinico- Epidemiologic study on the abuse, misuse, and adverse effects of topical dermatologic drugs. Korean J dermatol. 2003;41(9):1129-35. 19. Bieber T. Atopic dermatitis. Ann Dermatol. 2010; 22:125-37. 20. Kim HJ, Jeong SK, Lee SH. Allergen and skin barrier in atopic disease. J Skin Barrier Res. 2008;10(2):38-45. 21. Kim DH, Kang KH, Kim KW, Yoo IY. Management of children with Atopic Dermatitis. J Korean Acad Pediatr Allergy Respir Dis. 2008;18(2):148-57.
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