p Review Article J Sasang Constitut Med 2014;26(1):98-109 http://dx.doi.org/10.7730/jscm.2014.26.1.098 熱多寒少湯관련기존연구분석 오혜원 신승원 장형진 * 안광석 * 이석근 * 이의주 고병희 이준희 경희대학교한방병원사상체질과, * 경희대학교한의과대학기초한의과학과, 경희대학교한의과대학사상체질과 Abstract Review of Studies on Taeumin Yeoldahanso-tang since 2000 Hye-Won Oh, Seung-Won Shin, Hyeung-Jin Jang *, Kwang-Seok Ahn *, Seok-Geun Lee *, Eui-Ju Lee, Byung-Hee Koh, Jun-Hee Lee Dept. of Sasang Constitutional Medicine, Kyung Hee Univ, Korean Medical Center * Dept. of Oriental Medicine, College of Korean Medicine, Kyung Hee Univ Dept. of Sasang Constitutional Medicine, College of Korean Medicine, Kyung Hee Univ. Objectives This paper was aimed to review experimantal and clinical articles on Yeoldahanso-tang(YDHS), figuring out the recent tendency and suggesting the future prospects of YDHS-related studies. Methods The articles published in Korean or English since 2000 were searched, screened, and classified into experimental or clinical studies. And we structured designs, methods and results of the included studies into each table for the experimental studies or the clinical studies. Especially tools to diagnose constitutions and patterns identified in clinical researches were also summarized in the tables. Results 28 articles are finally included. 14 experimental studies are mostly in vitro designs to show efficacy of YDHS. There are only 2 studies for the safety. Among 14 clinical studies, 12 case studies target disorders of central nervous system, viral infection, skin ulcer and so on. 2 studies are before and after studies on cerebral infarction and effects on liver function. Conclusions Based on the efficacy of YDHS on central nervous system, it acquires higher level of evidence such as randomized controlled trials in the future. In addition other diseases such as skin ulcer and so on, it needs to be done more specific experimental or clinical studies so that we can get statistically significant results. Key Words : Yeoldahanso-tang, Taeumin, Sasang Constitutional Medicine, Herbal Medicine, Review. Received March 12, 2014 Revised March 17, 2014 Accepted March 22, 2014 Corresponding Author Jun-Hee Lee Dept. of Sasang Constitutional Medicine, Kyung Hee Univ. Korean Medical Center, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-702, Korean Tel:02-958-9280 Fax: 02-958-9234 E-mail: ssljh@daum.net C The Society of Sasang Constitutional Medicine. All rights reserved. This is an open acess article distributed under the terms of the Creative Commons attribution Non-commercial License (http:// creativecommons.org/licenses/by-nc/3.0/)
HW Oh et al. 99 I. 緖論 熱多寒少湯은 東醫壽世保元辛丑本 에나오는處方으로葛根 4돈, 黃芩, 藁本각 2 錢, 蘿葍子, 桔梗, 升麻, 白芷각 1 錢으로구성되어있다. 熱多寒少湯은太陰人裏病證중燥熱證에대한주處方으로 1 燥熱證은 內經 燥病機에서의 澁枯涸皺揭 의形證과手指焦黑, 癍瘡, 手足無力, 引飮, 小便多, 大便秘, 虛勞夢泄및危亦林의陰血耗竭證인耳聾, 目暗, 脚弱, 腰痛등이주증상이된다 2. 熱多寒少湯은肝熱과肺燥의病理가함께있을때사용하며裏部의肝熱을除하고潤肺燥하는것을목표로하는處方이다 1. 기존에熱多寒少湯관련연구를살펴보면, 실험연구, 임상연구및문헌연구가있지만기존연구에대한전반적분석논문은없는실정이다. 문헌연구중에서熱多寒少湯의세포활성물질에대한영향을고찰한것이있으나 47, 특정효능에대한분석이므로기존연구에대한분석이라고보기에는미흡하다. 이에본연구는 2000년이후에熱多寒少湯관련연구에대한고찰을통해熱多寒少湯의효능및안정성에대해확인하고, 임상에서활용할수있는근거를 마련하여향후연구의방향을설정하는데도움이되고자하는바이다. Ⅱ. 硏究方法 1. 검색방법한글또는영문으로출판된논문중에서검색하였다. 한글로출판된논문의경우, 한국연구재단에서승인된등재학술지및등재후보학술지 19개를대상으로하였다 (Table 1). 각학회지의웹사이트에서 熱多寒少湯 을검색어로하여제목, 초록, 주제어의범위에서검색하였다. 영문으로출판된논문의경우 Pubmed에서 Yuldahansotang or Yeoldahansotang 을제목, 초록, 주제어의범위에서검색하였다. 기간은 2000 년 1월부터 2013년 12월까지출판된논문을대상으로하였다. 2. 포함기준 / 제외기준검색된논문의전문을읽고선별작업을시행하였다. 포함기준은 1) 熱多寒少湯을중재로사용한경 Table 1. List of Selected Journals in the Review Korean Journal of Acupuncture Korean Journal of Oriental Physiology & Pathology The Korea Journal of Herbology Journal of Pharmacoacupuncture Korean Journal for Oriental Preventive Medical Society Journal of Korean Acupuncture and Moxibustion Medicine Society(The Acupuncture) The Journal of Korean Oriental Internal Medicine The Journal of Oriental Obstetrics & Gynecology The Journal of Pediatrics of Korean Medicine The Korean Society of Oriental Neuropsychiatry The Journal of Korean Oriental Ophthalmology & Otorhinolaryngology & Dermatology The Journal of Korean Medical Classics Journal of Korean Medicine Journal of Sasang Constitutional Medicine Journal of Oriental Rehabilitation Medicine Journal of Korean Medicine Research in Daejeon University The Journal of The Korea Institute of Oriental Medical Diagnostics The Korean Journal of Oriental Medical Prescription The Journal of Korean Medical History
100 Review on Taeumin Yeoldahanso-tang since 2000 우 2) 동물을사용한실험연구 (in vivo, in vitro) 또는사람에게서유래된물질을사용한실험연구 (in vitro) 3) 임상연구 4) 熱多寒少湯이외의處方 ( 太陰人他處方, 非體質處方, 他體質處方 ) 과혼용하였다하여도熱多寒少湯을사용하였을때의효과를평가할수있는지표가명확히제시되어있으며熱多寒少湯이결과에의미있는영향을끼친경우이다. 제외기준은 1) 논문전문이없는경우 2) 四象體質病證으로診斷하지않고熱多寒少湯을사용한경우 3) 加味하여사용한약이太陰人약이아닌경우 4) 熱多寒少湯을사용한후에효과를평가할수있는지표가제시되어있지않는경우 5) 熱多寒少湯이외의處方 ( 太陰人他處方, 非體質處方, 他體質處方 ) 과혼용하였으며熱多寒少湯이결과에의미있는영향을끼치지않은경우 6) 熱多寒少湯加減方을사용하였으며加減한약재에주된효능이있는것으로판단되는경우 7) 문헌연구인경우이다. 3. 분류최종적으로선택된논문을형식에따라분류하였다. 우선실험연구와임상연구로분류하였으며실험연구는 in vivo, in vitro의두종류로분류하였다. 임상연구는증례및환자군연구, 전후연구, 무작위배정비교임상시험, 비무작위배정비교임상시험, 코호트연구, 환자- 대조군연구, 단면연구로분류하고자하였다. 분류기준은 2013년건강보험심사평가원에서개발한임상연구문헌분류도구인 DAMI 2.0을기준으로하였다. 4. 구조화실험연구는연구의목적, 연구디자인 (in vivo, in vitro), 대상질환및효능, 대상동물또는물질, 기간, 처치, 1차평가도구, 결과에대해정리하였다. 임상연구는연구디자인, 대상질환, 四象體質診斷기준, 體質病證, 대상자수, 기간, 處方, 기타치료, 평가도 구, 결과에대해정리하였다. 기간에대해, 실험연구에서대상에따라熱多寒少湯을처리한시간이다른경우에는시간을별도로적었으며, 임상연구에서다른處方과혼용하여사용한경우熱多寒少湯을쓴기간만계산하여정리하였다. 단, 熱多寒少湯의개념의확장으로太陰人裏熱病범주에서약을변경하여사용한경우에는熱多寒少湯이아닌處方 (ex. 葛根解肌湯, 淸血降氣湯, 淸肺瀉肝湯, 加減淸肝湯 ) 을사용한기간을총합쳐서기간으로계산하였다. 임상연구에서증례별로치료기간이다른경우에는반올림하여평균시간을적었으며, 논문에평균기간이기재되어있는것 3 은기재된대로썼다. Ⅲ. 結果 1. 검색결과검색결과 22개의학회지에서 52개의논문이검색되었다. 52개의논문중에서 24개의논문이제외되었다. 다른處方 ( 太陰人他處方, 非體質處方, 他體質處方 ) 과혼용하였으며熱多寒少湯이결과에의미있는영향을끼치지않은경우 4-14 가 11개로가장많았다. 그다음으로加味하여사용한약이太陰人약이아닌경우 15-18 가 4개로많았으며, 熱多寒少湯을사용한후에효과를평가할수있는지표가제시되어있지않는경우 19-21 가 3개, 四象體質病證으로診斷하지않고약을사용한경우가 2개였다. 이경우八體質 22 또는氣虛 23 로診斷하였다. 그밖에논문전문이없는경우 24 가 1개, 熱多寒少湯加減方을사용하였으며加減한약재에주된효능이있는것으로판단되는경우 25 가 1개, 문헌연구인경우 26,47 가 2개였다. 결과적으로포함된논문은총 28개이다. 최 27 의연구는임상연구와인체유래물을대상으로한 in vitro 실험연구가한논문에동시에포함되어있었으나제
HW Oh et al. 101 Figure 1. Screening and classification of identified publications 목을고려하여임상연구에포함시켜분석하였다. 배 28 의연구는 in vitro, in vivo 연구가한논문에동시에포함되어있었으며, 분류상실험연구중 in vitro연구로포함하였다. 결과실험연구 14개, 임상연구 14개가포함되었다. 실험연구중에서 in vitro 연구 12개, in vivo 연구 2개가포함되었으며, 임상연구중에서증례연구 12개, 전후연구 2개가포함되었다 (Figure 1). 2. 熱多寒少湯관련실험연구분석 14개의실험연구중에서 2개의연구 29,30 는熱多寒少湯의안정성에대한연구였고나머지는효능에대한연구였다. 대부분의논문은디자인상 in vitro 연구였으며 2개의연구만 in vivo 연구였다 29,31 (Table 2). 효능에대한연구에서다수의연구는독성을유발한세포에대한熱多寒少湯의세포활성물질조절효과에대한연구였다. 결과熱多寒少湯은항산화효능, 알츠하이머병의병인으로알려진베타-아밀로 이드가유발하는뇌신경독성에대한보호효능, UPS(ubiquitin-proteasome system) 의기능부전을유발한신경에대한보호효능, 저산소증에의해유발된신경세포독성에대한보호효능, 항염증효능, 항동맥경화효능, 항비만효능이있었다. 세포활성물질조절작용과관련하여熱多寒少湯이독성물질이유발된뇌신경세포에대해어떠한작용을하는지에대한것을알고, 궁극적으로는뇌신경계질환의치료효능을밝히고자하는의도를가진실험연구가가장많았다 32-37. 이외에 in vivo 연구에서 Allergy성접촉피부염에대해면역과민반응억제효능과항염증효능, 파킨슨에대한신경보호효능이있음을밝혔다. 안정성과관련된연구에서는熱多寒少湯이약물의대사에핵심적역할을하는 CYP450 활성에미치는영향을평가하였으며, 결과 CYP2D6 및 CYP2E1에의해대사되는양약과熱多寒少湯이상호작용을할
102 Review on Taeumin Yeoldahanso-tang since 2000 Table 2. Structured Basic Information of Experimental Studies on Yeoldahanso-tang Author Objectives Design Target Disease or Effect Laboratory Animal or Molecules Duration Treatment (Year) Choi, JS Regulating effect on cytokine LPS and SP stimulated Human (2001) 32 Efficacy in vitro 24 hrs * Preincubated with secretion astrocytes(ccf-sttg1 cells) Hong, JA Protective effect on oxidative Preincubated with (2001) 33 Efficacy in vitro Spinal sensory neuron of mouse 3hrs process Lee, JH Preventive effect on the (2002) 35 Efficacy in vitro damage by hydrogen peroxide Hippocampal cell of rat 3hrs Preincubated with Kim, MS (2002) 31 Efficacy in vivo Allergic contact dermatitis BALB/c rats 72hours Administered orally Choi, JS Regulating effect on cytokine LPS and SP stimulated Human Preincubated with (2002) 48 Efficacy in vitro 24 hrs production astrocytes(ccf-sttg1 cells) Park, SJ Protective effect on cerebral Cerebral neurons from mouse and (2003) 34 Efficacy in vitro NA NA neurons damaged by hypoxia SK-N-MC cells Han, BS Antioxidant capacity, (2004) 37 Efficacy in vitro PC12 cells Preincubated with NA antiperoxidation effect Bae, NY Protective effect on β-amyloid (2009) 36 Efficacy in vitro PC12 cells 24 hrs Preincubated Induced cytotoxicity Ma, JY Toxicity (2009) 29 in vivo Acute toxicity ICR mouse 14days Administered orally and Safety Lee, JA (2010) 49 Efficacy in vitro Anti-inflammatory effects LPS -stimulated RAW 264.7 cells 18 hrs Preincubated in vitro Neuroprotective effect PC12 cells Preincubated with 2 hrs Bae, N (2011) 28 Efficacy in vivo Neuroprotective C57BL/6 mice 3 days Administered orally effect(parkinson s disease) Jin, SE Interaction potential on (2012) 30 Safety in vitro CYP CYP450 NA NA 450 isozymes Kim, OS ABTS, DPPH #, LDL **, LDL / 30min/ 30min/ Preincubated with (2012) 50 Efficacy in vitro Anti-atherosclerotic effect LPSstimulatedRAW264.7cells 6hrs/ 24hrs Yoo, SR Preincubated with (2012) 51 Efficacy in vitro Anti-obesity effect 3T3-L1 cells NA Abbreviations; * NA: Not Applicable, PC12 cells: Rat pheochromocytoma cells, LPS: Lipopolysaccharide, SP: Substance P CYP: Cytochrome P, ABTS: 3-ethyl-benzothiazoline-6-sulfonic acid, # DPPH: 1-1-diphenyl-2-picrylhydrazyl, ** LDL: Low Density Lipoprotein 수있다고하였다 30. 또다른연구에서熱多寒少湯을쥐에게경구투여한결과어떠한독성증상도관찰되지않았다 29. 평가방법과결과는표에요약되어있다 (Table 3). 3. 熱多寒少湯관련임상연구분석 1) 증례보고 12개의증례연구가포함되었다. 體質診斷방법으로 QSCCII, 體形氣像, 容貌詞氣, 性質才幹, 素證, 病證藥理, 전문가의診斷등의방법을사용한경우 가많았다. 病證診斷으로는太陰人燥熱證으로診斷한경우가가장많았으며그중에서도太陰人癍瘡病으로診斷한경우도있었다 38,39,40. 증례연구에서는 1-2명을대상으로, 짧게는 10일에서길게는 397일까지치료하였다. 대상질환으로는뇌경색, 부신백질이영양증, 뇌경색후무도병, 파킨슨병과같은중추신경계뇌질환과, Ramsay Hunt Syndrome, 대상포진과같은바이러스감염질환, 망상청피반, 당뇨병성족부병변같은피부궤양질환, 기타안면마비, 만성기침, 역류성식도염이있었다. 기타치료로양약병행, 침치료, 뜸치료, 약침, 이침, 부항, 물리치료를시행한
HW Oh et al. 103 Table 3. Summaries of Main Outcomes in Experimental Studies on Yeoldahanso-tang Author Target Disease or Effect Main Method of Evaluation Results (Year) Significantly inhibited IL-1, IL-4, IL-6, TNF-α secretion induced by LPS and SP concentraion-dependently. Choi, JS Regulating effect on cytokine (2001) 32 IL * -1, IL-4, IL-6,TNF -α IFN -γ, IL-2 secretion TNF-α secretion was stimulated simultaneously by LPS and SP, mediated by IL-1. Hong, JA Protective effect on oxidative Cell viability, The cell death, neurofilament, LDH # Had efficacy of increasing neurofilament, LDH activity. (2001) 33 process activity Lee, JH Preventive effect on the damage by hydrogen peroxide synthesis. Had efficacy of increasing a amount of neurofilament, DNA (2002) 35 Neurofilament, DNA synthesis Had less ear swelling, hyperplasia of epidermis, migration Change of cutaneous shape, histochemistry, immunohistochemistry, dis- Had lower number of mastocyte, apoptotic cells and Bax of inflammatory cells, damage of epidermis than control group. Kim, MS (2002) 31 Allergic contact dermatitis tribution of apoptotic cells and Fas than control group. Had more distribution of Bcl-2 than control group Choi, JS Regulating effect on cytokine (2002) 48 IL * -1,IL-4,IL-6,TNF -α IFN -γ, IL-2 production Significantly inhibited IL-1, IL-4, IL-6, TNF-α secretion induced by LPS and SP concentraion-dependently. TNF-α secretion was stimulated simultaneously by LPS and SP, mediated by IL-1. Park, SJ Protective effect on cerebral Cell viability, catalase, SOD ** activity, Inhibited the decrease of the catalase, SOD activity and apoptosis (2003) 34 neurons damaged by hypoxia TNF-αand PKC activity via caspase activation induced by hypoxia. Han, BS Antioxidant capacity, antiperoxidation effect rate ing of ROS. Antioxidant activity, MDA formation Had antioxidant and antiperoxidantion properties for scaveng- (2004) 37 Had protective effect of on PC12 cells cytotoxity induced Protective effect on Bae, NY Cell viability, The cell death, the expression level of LC 3Ⅰ, LC3Ⅱ proteins Pharmacologically induced autophagy in PC12 cells. by Aβ25-35. (2009) 36 β-amyloid Induced cytotoxicity Induced autophagy on Aβ25-35-induced injury in PC12 cells. Ma, JY Survival rates, general toxicity, change (2009) 29 Acute toxicity of body weight and autopsy, LD50 ## Free from the toxicity and safety problems. Lee, JA (2010) 49 Anti-inflammatory effects Productions of NO ***,PGE2. Had effect on NO inhibition, no effect on PGE2 inhibition. Bae, N (2011) 28 Neuroprotective effect Neuroprotective effect (Parkinson s disease) Jin, SE Interaction potential on (2012) 30 CYP450 isozymes Kim, OS (2012) 50 Anti-atherosclerotic effect Yoo, SR (2012) 51 Anti-obesity effect Significantly provided neuroprotection, partially mediated by Cell viability, induction of autophagy autophagy enhancement. TH positive neurons in the substantia Significantly inhibited both the loss of TH-positive neurons nigra pars compacta, reduction of the optical density of TH-IR(tyrosine hydrox- in the substantia nigra pars compacta and the reduction of the optical density of TH-IR fibers in the striatum. ylase-immunoreact) fibers in the striatum. Had Inhibitory effects on CYP2D6 and CYP2E1-mediated IC50 values metabolism, week inhibition on CYP3A4 and CYP2C19 relatively. Fragmentation of apolipoprotein B-100 (ApoB), foam cell formation Oil Red O staining, GPDH ### activity,triglyceridecontents,leptinproduction Showed suppressive effect on LDL oxidation, significantly inhibited foam cell formation in LDL/LPS stimulated RAW 264.7 cells. Remarkably prevented lipid accumulation with no cytotoxicity in the differentiated 3T3-L1 cells, Decreased contents of triglyceride 3T3-L1 adipocytes. Significantly inhibited GPDH activity and leptin production in a dose-dependent manner. Abbreviations; * IL:Interleukin TNF : Tumor Necrosis Factor IFN : Interferon LPS : :Lipopolysaccharide SP: Substance P # LDH: Lactate Dehydrogenase Enzyme, ** SOD:superoxidedismutase, PKC: protein kinase C, MDA: Malondialdehyde, LC: light chain, Aβ25-35: β-amyloid peptide, ## LD50:LethalDose50, *** NO:NitricOxide, PGE2: Prostaglandin E2, IC50: Half maximal inhibitory concentration, LDL: Low Density Lipoprotein, LPS: Lipopolysaccharide, ### GPDH:glycerol-3-phosphatedehydrogenase
104 Review on Taeumin Yeoldahanso-tang since 2000 Table 4. Structured Method of Clinical Studies on Yeoldahanso-tang Author (year) Design * B&A Choi, YK (2000) 27 in vitro Target disease Cerebral infarction Constitution Diagnosis QSCC II, specialists' diagnosis Regulatory effects on cytokine production NR Pattern Identified NR Mean Number of Patients Duration 8 3 weeks LPS -activa preincubated for ted PBMC 30minutes YDHS # Prescription NR Other Treatments Kwon, K Ramsay Hunt AT, pharmaco- 46 CR** NR NR 2 9days YDHS (2001) Syndrome AT, Moxa-Tx Yoo, JS (2001) 38 CR Livedo Reticularis NR TE-BCB Auricular 1 80 days YDHS AT(AAT), AT QSCCII, specialists' diagnosis, LDHP, 1 71 days YDHS Mx ## T E Go, WS (2002) 39 CR Diabetic foot SMPC, OS TE-BCB AT, Mx, Kim, YJ (2003) 40 CR CVA with Diabetic SMPC, PC *** TE LDHP, 1 9 days YDHS Moxa-Tx, Foot TE-BCB Nega-Tx Kim, HS (2004) 41 CR Facial palsy QSCCII, SMPC, AMS TE LDHP 2 12days YDHS,PC YDHS Lee, KR (2004) 52 CR Chronic cough QSCCII, SMPC, AMS, PC, OS TE LDHP 1 70 days Nokyoungdaejo-tang Galgeunhaegi-tang QSCCII, SMPC, Lim, JH (2004) 53 CR Adrenoleukodystrop AMS, PC, OS, TE LDHP 1 397 days hy(ald) PSTP Gagamchungan-tang YDHS Galgeunhaegi-tang Cheongpaesagan-tang Cheonghyeolgangi-tang AT, Nega-Tx, physical-tx QSCCII, SMPC, Han, DY (2005) 42 CR Chorea after Cerebral AMS, PC, OS, TE LDHP 1 infarction PSSC-2004 15 days YDHS NR Kim, TH Effects on liver function 3 B&A NR (2007) NR 25 36 days YDHS Mx Lee, JW (2009) 1 CR Hand tremor, heat QSCCII, SMPC, flash, dysarthria AMS, PC, OS TE LDHP 1 10 days Cheongsimyeonja-tang AT, Moxa-Tx, YDHS Mx Kim, YH (2011) 43 CR Gastro-esophageal reflux disease(gerd) AMS, PC, OS QSCCII, SMPC, TE LDHP 1 11 weeks YDHS AT, Mx Choi, JS (2012) 44 CR Parkinson`s Disease QSCCII, SMPC, TE LDHP AMS, PC, OS 1 11 months YDHS AT, Mx Kim, ST (2012) 45 CR Herpes Zoster QSCCII, SMPC, TE LDHP AMS, PC, OS 1 15 days YDHS AT Abbreviations; * B&A: Before-after study QSCC: Questionnaire for Sasang Constitution Classification, NR: Not Reported, LPS: Lipopolysaccharide, PBMC : peripheral blood mononuclear cells # YDHS:Yeoldahanso-tang, ** CR: Case Report, AT: Acupuncture Therapy, BCB: Banchangbyung( 癍瘡病 ),,SMPC: Somatic Morphology and Physical Comportment( 體形氣像 ), OS: Ordinary Symptoms( 素證 ), LDHP: Liver Dryness Heat Pattern( 肝燥熱證 ), ## Mx:Medication, *** PC:Proclivity and Capacity( 性質才幹 ), AMS:Appearance and Manner of Speech( 容貌詞氣 ), PSTP:Pathological Symptomatology and Therapeutic Principle( 病證藥理 ) NR AT 경우도있었다 (Table 4). 결과는대부분증상의호전으로표현하였으며, 평가도구로 VAS 1,41-45, DITI 38,44 를사용하기도하였으며, 질환특이적으로 EGG 43, 안면마비평가점수 41,46 를사용한경우가있었다. 대부분의경우증세가호 전되었다. 평가방법과결과는표에요약되어있다 (Table 5). 2) 전후연구 2개의전후연구가포함되었다. 이중최 27 의연구
HW Oh et al. 105 Table 5. Summaries of Main Outcomes in Clinical Studies on Yeoldahanso-tang Author (year) Design * B&A Choi, YK (2000) 27 in vitro Target disease Cerebral infarction Regulatory effects on cytokine production Method of Evaluation IFN -γ, IL -2, IL-4, IL-6, Ig E, TNF -α Results Plasma levels of IFN-γ, IL-2 elevated significantly, IL-4, IL-6 reduced significantly, IgE reduced significantly. Release of IFN-γ, IL-2, IL-6 decreased. Kwon, K (2001) 46 CR # Ramsay Hunt House-Brackmann system, Grades considerably improved, Syndrome Yanagihara's system Yoo, JS (2001) 38 CR Livedo Reticularis DITI ** Symptoms improved.,symptomsprogress (feet became warm, ulceration has disappeared.) Go, WS Symptoms improved (2002) 39 CR Diabetic foot Symptoms progress (ulceration had nearly disappeared and could save toes) Kim, YJ (2003) 40 CR CVA with Diabetic Foot Symptoms progress Consciousness and objective symptoms improved. Kim, HS Symptoms progress(facial (2004) 41 CR Facial palsy muscle paralysis, VAS Symptoms improved. ) Lee, KR Change of sweating coughing, (2004) 52 CR Chronic cough Sweating condition improved, chronic cough decreased. and other symptoms Lim, JH Change of subjective symptoms (2004) 53 CR Adrenoleukodystrophy(ALD) May have an effect on management of ALD. and general conditions. Han, DY Chorea after Cerebral Choreiform movement(vas, (2005) 42 CR Symptoms improved. infarction frequency) Kim, TH ALP, AST, ALT, γ-gt, total Values of ALP, AST, ALT, γ-gt, total bilirubin were within (2007) 3 B&A Effects on liver function bilirubin normal range or decreased for most patients,. Lee, JW Hand tremor, heat flash, (2009) 1 CR Symptoms progress(vas) VAS score dropped, general conditions improved. dysarthria Kim, YH Gastro-esophageal reflux Symptoms progress(vas), Bradygastria parameters in fed EGG significantly increased (2011) 43 CR disease(gerd) EGG of %. Power ratio significantly increased. Choi, JS DITI, symptoms (2012) 44 CR Parkinson`s Disease Chief complaints and symptoms were improved. progress(vas) Kim, ST Symptoms progress(vas), (2012) 45 CR Herpes Zoster The vesicles were cleared and symptoms improved pictures of the affected part Abbreviations; * B&A: Before-after study, IL:Interleukin, TNF : Tumor Necrosis Factor, IFN : Interferon, Ig: immunoglobulin, # CR: Case Report, ** DITI:Digital Infrared Thermal Imaging, VAS: Visual Analogue Scale, EGG: Electrogastrography 내에는전후연구와 in vitro 연구가동시에있었으나형식별분류기준에서언급하였듯이제목에비중을두어전후연구로분류하였다. 전후연구에서대상질환은각각뇌경색과熱多寒少湯의간기능에대한영향이었다. 세포활성물질, 간기능검사로결과를평가하였으며, 결과熱多寒少湯은급성기뇌경색증환자의세포활성물질의불균형을조절하였으나통계적으로유의하지는않았다. 또熱多寒少湯복용후대부분의경우간기능검사수치가정상범위또는감소하였으나통계적으로유의하지는않았다. 평가방법과결과는표에요약되어있다 (Table 5). Ⅳ. 考察 熱多寒少湯은肝熱熱證溫病, 燥熱病, 手指焦黑癍瘡病, 虛勞夢泄등을主治로한다 1. 연구경향을보면실험연구중에는 in vitro 연구가대부분이며, 주로독성을유발한세포에대해熱多寒少湯이세포활성물질을조절하는효능을확인함으로써, 熱多寒少湯의뇌신경질환에대한치료효과를입증하고자하는목적을가진경우가많았다. 임상연구에서도뇌신경질환을대상으로한경우가있었으며, 문헌에근거하여癍瘡病으로診斷하여피부궤양에적
106 Review on Taeumin Yeoldahanso-tang since 2000 용한경우도있었다. 한편熱多寒少湯의안정성과관련한실험연구에서熱多寒少湯이 CYP2D6 및 CYP2E1에의해대사되는양약과상호작용을할수있다는결과가있었다. 따라서이러한양약과동시에熱多寒少湯을處方시주의해야한다고하였다. 쥐에게熱多寒少湯을경구투여한경우어떠한독성도발견되지않았다. 임상연구에서안정성과관련하여간기능에미치는영향을확인한결과간기능검사수치는정상또는감소하였으나통계적으로유의하지않았다. 이를통해정리해보면, 현재까지熱多寒少湯과관련하여 in vivo 연구가적은편이며기존의안정성및효능에대한연구에서통계적으로유의한결과를얻은경우가많지않다. 또한대조군과의비교를통한무작위배정비교임상시험과같은좀더근거수준이높은연구가진행된적이없다. 따라서현재까지실험및임상연구로밝혀진熱多寒少湯의뇌신경질환에대한효과를근거로향후무작위배정비교임상시험과같은근거수준이높은연구가진행되고, 기타피부질환을비롯한다양한질환및안정성에대한실험연구및임상연구가더욱진행된다면熱多寒少湯의효능및안정성에대해통계적으로유의한결과를얻을수있을것으로보인다. Ⅴ. 感謝의글 이연구는 2012년도경희대학교연구비지원에의한결과임 (KHU-20131087). Ⅵ. 參考文獻 1. Lee JW, Jang HS, Kim YH, Lee JH, Lee EJ, Koh BH. A Case Study of 1 Taeeumin Patient Experiencing Hand Tremor, Heat Flash, and Dysarthria Treated Successfully with Yeoldahansotang. J Sasang Constitut Med. 2009;21(1):254-262. 2. Lee JH, Lee EJ, Koh BH. The Study on the Energy and Fluid Metabolism and the Pathology and Symptomatology of Taeeumin based on The Discourse on Viscera and Bowels of Donguisusebowon. J Sasang Constitut Med. 2012;24(4):1-16. 3. Kim TH, Hong SY, Han DN, Lim EC. The Effects of Constant Use of Yeoldahanso-tang on Liver Function. J Sasang Constitut Med. 2007;19(3):217-226. 4. Kim TY, Lee BJ, Jeon JH, Lew JH. A Case of Amyotrophic Lateral Sclerosis. The Journal of Korean Oriental Internal Medicine. 2000;21(4):661-665. 5. Roh GH, Choi DJ, CHo KH, Kim YS. The Clinical Report about Two Stroke Patients who Developed Hiccups after Purgation Therapy. Journal of Korean Medicine. 2000;21(1):109-113. 6. Kim CH, Kim HG. The Clinical case study of facial palsy. The Journal of Korean Oriental Ophthalmology & Otorhinolaryngology & Dermatology. 2001;14(2): 262-270. 7. Kim HS, Lee SW, Park HS, Kim KY. A Case Study about Treatment of Taeumin Patient diagnosed as Lateral medullary syndrome(wallenberg syndrome). J Sasang Constitut Med. 2001;13(2):182-189. 8. Ko JC, Park JY, Jun CY, Han YH. A Case of paralytic ileus and Urinary Tract Infection with cerebral infarction. The Journal of Korean Oriental Internal Medicine. 2001;22(3):471-476. 9. Lee JH, Kim SB, Park GS, Jeong YJ, Lee SK, Lee EJ, et al. A Case Report on 'fever of unknown origin, abdominal distension and diarrhea' of Taeumin. J Sasang Constitut Med. 2001;13(3):121-125. 10. Shin JA, Son DH, Yu KS, Lee JG, Lee YG. 2 Cases of Lower Limb Monoplegia due to Brain Cortical Infarction. The Journal of Korean Oriental Internal Medicine. 2001;22(2):263-269. 11. Yun BH, Lim CW, Kim KH, Park YJ, Park JH. The Clinical Study on a Abnormal Liver Function
HW Oh et al. 107 Patients Caused by Obesity. The Journal of Korean Oriental Internal Medicine. 2001;22(4):547-555. 12. CHoi WJ, Kim DW, Shin SH, Lee UJ, Choi JY, Shin HS, et al. Effects of the Renal Function of Complex Herbal Medication in 20 Diabetic Nephropathy Patients. Korean Journal of Oriental Physiology & Pathology. 2003;17(2):580-584. 13. Ock MK, Lim WK, Yoon HS, Sun YJ, Moon JH, Kim CH. Four Cases of Stroke Patients with Defective Vision Treated with Venesection on Palpebral Conjunctiva. The Journal of Korean Oriental Ophthalmology & Otorhinolaryngology & Dermatology. 2004;17(3):107-113. 14. Oh KM, Yang DH, Kim BK. A Clinical report of cerebral infarction patient with schizophrenia. The Korean Society of Oriental Neuropsychiatry. 2007; 18(3):209-224. 15. Jung HS, Lee JY. A Study on the alteration of general characteristics and therapeutic effect of Gami Yeoldahansotang in patients with Atopic Dermatitis. The Journal of Pediatrics of Korean Medicine. 2001; 15(3):177-188. 16. Cho GI, Han MA, Lee JY, Choi JY, Kim DW, Jung DY, et al. Case Reports about Brainstem Infarction. Korean Journal of Oriental Physiology & Pathology. 2002;16(6):1291-1296. 17. Kim JJ, Kim MG, Choi JR, Park SS. A Clinical Study about Treatment of a Abdominal Distention in Stroke. J Sasang Constitut Med. 2004;16(1):148-154. 18. Cho JS, Yim CH, Kim HS, Kwon SM, Kim S, Kim IH, et al. The Clinical Study on 2 Case of Patient with Tremor. J Sasang Constitut Med. 2008;20(3):208-217. 19. Son DH, Jang IS, Yu KS, Lee JG, Yun HS, Lee YG, et al. A Clinical Study on the Patients Admitted at the Acute Stage of Stroke. The Journal of Korean Oriental Internal Medicine. 2000;21(2):203-212. 20. Koh KH, Park SY, Choi HG, So KS, Hwang WJ, Lee KM, et al. Clinical Study on treatment of HIVD of lumbar spine using Scolopendrid herbal acupuncture. Korean Journal of Acupuncture. 2002;19(3):192-206. 21. Kwon EM, Jung YH, Kim EH, Seo YK, Lee SK, Kim DR, et al. A Clinical Case of Liver Injury with Administration of Yeoldahanso-tang plus Rheum rhabarbarum. J Sasang Constitut Med. 2009;23(3): 209-215. 22. Cho SH, Jee SY. A Clinical Study on Allergic rhinitis. Journal of Pharmacoacupuncture. 2001;14(2):173-182. 23. Choi YS, Park SJ, Lee HK, Cho MY, Yu JY, Baek DG, et al. A Case Report of Fever of Unknown Origin Treated with Yeoldahansotang-gamibang. The Journal of Korean Oriental Internal Medicine. 2012;10(4): 316-323. 24. Lee YJ, Rhim EK, Hwang SI, Baek DG, Yun JM, Hong SH, et al. A case report of facial palsy and eyeball movement disturbances with Yuldahansotang, Jungmyung and Jium acupuncture point in modified lateral inferior pontine syndrome resulting from pontine infarction. The Journal of Korean Oriental Internal Medicine. 2003;24(3):681-687. 25. Kim MG, Choi JR, Bae HS, Park SS. A Case study of multiple myositis. J Sasang Constitut Med. 2003; 15(2):117-123. 26. Kim DJ, Kim JR, Kim DR. A Bibliographical Research of the Correlation Among Sasang Constitutional Disease and the Pulse Diagnosis. Journal of Pharmacoacupuncture. 2003;6(3):23-37. 27. Choi YK, Kim KY. Studies on the Regulatory Effect of Cytokine Production in Patients with Cerebral Infarction by Yuldahansotang. J Sasang Constitut Med. 2000;12(1):201-215. 28. Bae N, Ahn T, Chung S, Oh MS, Ko H, Oh H,
108 Review on Taeumin Yeoldahanso-tang since 2000 et al. The neuroprotective effect of modified Yeoldahansotang via autophagy enhancement in models of Parkinson's disease. J Ethnopharmacol. 2011;134(2):313-322. 29. Ma JY, Huang DS, Lee SW, Kim JY, Shin HK. Acute Toxicity Study on Yeoldahanso-tang in Mice. J Sasang Constitut Med. 2009;21(1):247-253. 30. Jin SE, Ha HK, Shin HK. Effects of Yuldahanso-tang and Chungsimyonja-tang on Cytochrome P450 Activities. J Sasang Constitut Med. 2012;24(4):84-91. 31. Kim MS, Park SS. Effects of Yuldahansotang on rat skin occured the Allergic Contact Dermatitis. J Sasang Constitut Med. 2002;14(3):97-113. 32. Choi JS, Kim KY, Kim HM, Ju JC. Studies on the Cytokine Production Regulation in Human Astrocytes by Yuldahansotang. J Sasang Constitut Med. 2001; 13(1):61-69. 33. Hong JA, Kim KY, Yu DG, Park HS, Kim HS. Effects of Yuldahansotang water extract on Cultured Spinal Sensory Neurons Damaged by Xanthine Oxidase/ Hypoxanthine. J Sasang Constitut Med. 2001;13(1): 88-96. 34. Park SJ, Kim HS, Bae YC, Lee SM, Kim KY, Won KS, et al. Influence of Yeoldahanso-tang on the Hypoxic Damage of Cultured Cerebral Neurons from mouse and SK-N-MC cells. J Sasang Constitut Med. 2003;15(1): 72-89. 35. Lee JH, Park HS, Kim KY, Kho KD, Kim IH. Effects of Yuldahansotang water extract on Cultured Primary Hippocampal Cell Culture Damaged by Hydrogen Peroxide. J Sasang Constitut Med. 2002;14(1):79-89. 36. Bae NY, Yang HO, Ahn TW. Protection effect of New-Yeolda-Hanso tang against β-amyloid Induced Cytotoxicity in NGF-differentiated PC12 Cells. J Sasang Constitut Med. 2009;21(3):138-153. 37. Han BS, Bae YC, Song SY, Park HS, Lee JH, Kim KY. Antioxidant effects and its mechanism of Cheongsimyeonjatang in Sasang Constitutional Medicine. J Sasang Constitut Med. 2004;16(1):130-147. 38. Yoo JS, Yang SM, Kim SH, Kim DR. A Case Report on the Ban-Chang-Byung of Taeumin. J Sasang Constitut Med. 2001;13(2):190-193. 39. Go WS, Kim KS, Lim EC. A Case Report on a patient diagnosed as Diabetic Foot. J Sasang Constitut Med. 2002;14(2):169-174. 40. Kim YJ, Kim BO, Kim HJ, Kwack JJ, Jeon SY, Hong S. A Clinical Report of CVA with Diabetic Foot. The Journal of Korean Oriental Internal Medicine. 2003;24(3):727-734. 41. Kim HS, Kim IH. Clinical Cases about Facial Palsy by Using Yeoldahanso-tang. J Sasang Constitut Med. 2004;16(3):133-138. 42. Han DY, Jung WK, Kim EY, Lee SM, Shin MR, Choi JW, et al. A Case of Taeumin Chorea originated after Cerebral infarction. J Sasang Constitut Med. 2005;17(3):128-134. 43. Kim YH, Kim SY, Hwang MW. A Case Study of Taeumin Patient with Gastro-esophageal reflux disease(gerd) who Treated Successfully with Yeoldahansotang. J Sasang Constitut Med. 2011;23(1):132-138. 44. Choi JS, Jang MH, Ahn TW. A Case Study of Parkinson's Disease Patient Treated with Yuldahanso-tang gagam. J Sasang Constitut Med. 2012;24(3):104-113. 45. Kim ST, Choi AR, Koo DM. A Case Report of Herpes Zoster in Tae-eumin Improved with Yeoldahanso-tang. J Sasang Constitut Med. 2012;24(2):71-77. 46. Kwon K, Park YH. Two case studies of Ramsay Hunt syndrome. The Journal of Korean Oriental Ophthalmology & Otorhinolaryngology & Dermatology. 2001;14(2): 183-193. 47. Burns JJ, Zhao L, Taylor EW, Spelman K. The influence of traditional herbal formulas on cytokine activity. Toxicology. 2010;278(1):140-159. (eng) 48. Choi JS, Jung SW, Ju JC, Lee SW, Kim KY, Kim
HW Oh et al. 109 HM. Cytokine Production Regulation in human astrocytes by a herbal combination(yuldahansotang). Immunopharmacology and immunotoxicology. 2002; 24(1):55-67. 49. Lee JA, Ha HK, Lee HY, Jung DY, Lee JK, Huang DS, et al. Anti-inflammatory Activities of Herbal Formulas for Sasang Constitutional Medicine. J Sasang Constitut Med. 2010;22(4):56-64. 50. Kim OS, Kim YJ, Shin HK. Anti-atherosclerotic Effects of Herbal Formulas for Sasang Constitutional Medicine J Sasang Constitut Med, 2012; 51-61. 51. Yoo SR, Jeong SJ, Shin HK. Effects of Yeoldahanso- tang, a Sasang Constitutional Herbal Prescription for Taeeumin, on the Adipogenesis in 3T3-L1 Cells. J Sasang Constitut Med. 2012;24(4):75-83. 52. Lee KR, Lee SG, Song JM. A Case Study of Chronic Cough of Taeumin through the Change Process of Sweating. J Sasang Constitut Med. 2004;16(3): 139-142. 53. Lim JH, Hwang MW, Ham TI, Lee SK, Koh BH, Song IB. A Case of Treatment of a Taeumin patient diagnosed to Adrenoleukodystrophy. J Sasang Constitut Med. 2004;16(1):155-161.