3) 대한한방부인과학회지 pissn / eissn J Korean Obstet Gynecol. VOL.33 NO.1 : (2020) 비정

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1 3) 대한한방부인과학회지 pissn / eissn J Korean Obstet Gynecol. VOL.33 NO.1 : (2020) 1 동의대학교대학원한의학과, 2 동의대학교한의과대학부인과교실 김준희 1, 이인선 2 ABSTRACT A Literature Review on the Recent Tendency of the Treatment about Atypical Hyperplasia of Breast on the Chinese Herbal Medicine Jun-Hee Kim 1, In-Seon Lee 2 1 Dept. of Korean Medicine, Graduate School, Dong-Eui University 2 Dept. of OB & GY, College of Oriental Medicine, Dong-Eui University Objectives: We conducted a literature study on the treatment trends in China to find out the possibility of Oriental medicine treatment of atypical hyperplasia of breast (AHB). Methods: RCTs (randomized controlled trial) on AHB were collected from CNKI (China National Knowledge Infrastructure). The search words were 乳腺增生, 乳腺囊性增生, 乳癖, 中医, 中药 and 中西医结合. The search period was limited from July 2006 to May Finally, we selected 107 RCTs which were clinical studies to find out the effectiveness of Chinese herbal medicine in comparison with Western medicine. After reviewing, we investigated Chinese herbal medication guide, Chinese treatment method and prescriptions. And the correlation between the treatments and the medicinal herbs was investigated to be useful in the clinical practice. Results: 1. The administration of herbal medicine was 58.9 percent in 63 cases, followed by menstrual cycles, and 41.1 percent in 44 cases, regardless of menstrual cycles. 2. In the basic frequency analysis between the treatment and the medicinal herb, the frequency of dissipate binds ( 散結 ) was the highest. Next, there was a high frequency of therapies such as activating blood-activating ( 活血 ), relieve pain ( 止痛 ), soothe the liver ( 疏肝 ), regulate qi ( 理氣 ), resolve phlegm ( 化痰 ), soften hardness ( 軟堅 ), resolve depression ( 解鬱 ), move qi ( 行氣 ) of frequency was high. In herbal medicine, bupleuri radix ( 柴胡 ), cyperi rhizoma ( 香附子 ), angelicae gigantis radix ( 當歸 ), fritillaria thunbergii bulb ( 貝母 ), paeoniae radix alba ( 白芍藥 ), prunellae spica ( 夏枯草 ), corydalis rhizoma ( 玄胡索 ) showed high frequency. 3. We finded out the correlation between the frequent treatment methods and the medicinal herbs using Text Mining. Conclusions: These findings are thought to help implement Korean traditional medicine treatments for AHB. Key Words: Atypical Hyperplasia of Breast, TCM treatment, Chinese Herbal Medicine This Work was supported by Dong-eui University Foundation Grant ( ) Corresponding author(in-seon Lee) : Dept. of OB & GY, College of Korean Medicine, Dong-Eui University, Yangjeong-ro, Busanjin-gu, Busan, Republic of Korea Tel : inslee@deu.ac.kr 36

2 J Korean Obstet Gynecol Vol.33 No.1 February 2020 Ⅰ. 서론 비정형유방증식은유선도관과소엽의조직들이변화하여변형된유선조직들이서로엉기면서덩어리형태로된것을말하는데 1), 비종양성, 비염증성의유선상피증식성질환으로유방형성이상 (mammary dysplasia) 이라고도하며, 中醫에서 乳癖, 乳核 등의범주에속하는양성유선질환이다 2). 유방종괴와유방통증두가지증상이주가되고월경주기에나타나는가임기여성들에게가장흔한양성증식질병이다 3). 유선증식, 만성유선종, 유선소엽증식, 유방낭성증식증등의용어로표현되는유방의낭성증식증및섬유낭성변화등을포괄한다 1). 주로 30~50세의여성에서나타나며, 사춘기와폐경이후에는발병률이낮다 3-5). 하지만현대인들은정신적스트레스, 고에스트로겐함유음식의섭취및환경오염등여러외적 내적원인으로유방증식의발병률이해마다상승하는추세를보이고있다 6). 비정형유방증식은유방암의발병에상대적으로높은위험요소중하나로여겨지고있어 3,5,7-11) 유선병가족력이있는환자는더욱주의해야하며, 유선증식을시기적절하게치료하는것은임상적으로매우중요한의미를지닌다 12). 그러나한국에서는이에대한개념과치료가활성화되어있지않으며이에대한참고자료나임상연구를찾아보기어려운실정이다. 서양의학에서는비정형유방증식의치료를위해호르몬억제요법을주로사용하는데유효성은높지만부작용이비교적크다고하였으며 13), 타목시펜만복용하면치료과정이길고부작용도크다고하였 다 8,14). 기타내분비요법, 수술치료도사용하는데역시부작용이크고재발률도높다고한다 15). 따라서비정형유방증식의중의치료를위해중약이나중서의결합치료의효능에대한많은임상연구들이있으며, 이연구들을 Meta 분석한결과중약이나중서의결합치료의비정형유방증식에대한효과가단순양약의치료효과보다좋은것을확인할수있었다 16-8). 이에한국에비정형유방증식의치료를알리기위해중국에서시행된중의치료효과검증을위한임상연구들을검색하여치료동향을보고하는바이다. Ⅱ. 대상및방법 1. 대상본연구에서는중국학술정보사이트 CNKI (China National Knowledge Infrastructure, 中國知網 ) 을통해서비정형유방증식에관한임상연구자료를수집하였다. 연구자료를수집하기위한검색어는 乳腺增生, 乳腺囊性增生, 乳癖, 中醫, 中藥, 中西醫結合 을사용하였다. 검색기간은 2006년 7월부터자료수집일인 2017년 5월 31일까지로한정하였으며이러한조건을통해서 CNKI에서검색된연구는총 2,454편이다. 연구선택된기준에의해선택된연구는검색된 2,454편가운데중복연구 43편을제외하여 2,411편의연구가선택되었으며, 다시초록을검토하여주제와관련없는연구 1,194 편, 남성을대상으로한연구 141편, 유방의다른질환연구 16편, 문헌연구 7편등총 1,358편을제외한 1,053편이 1차로선택되었다. 다음전체연구를보고중약투여를통한치료법이아닌연구 487편, 변증 37

3 치료에관련된연구 21편, 메타분석연구 3편, 연구를찾을수없는 1편, 총 512편을제외한 541편이 2차선택되었다. 이가운데 RCT(randomized controlled trial) 가아닌연구 231편, 무작위배정을하지않은 59편을합한 290편을제외한 251편이 3차선택되었으며, 선택된 RCT 가운데중약끼리의효과를비교한연구 144편을제외한 107의연구가최종선택되었다 (Fig. 1). Fig. 1. Flow chart for literature selection. 2. 방법본연구에서는임상연구 107편의내용을검토하여중약복약법, 중의치법과처방의빈도, 처방내용을조사하였다. 그러나연구에사용된처방이문헌근거가있는경우가적고임의조제한경우가많아실제임상에서활용하는데도움이되기위해치법과약재간의상관관계를조사하였다. 또한시판되고있는제제약중처방내용을확인할수있는경우그내용을조사하였다. 3. 통계통계방법은텍스트마이닝 (textmining) 을사용하였다 19-23). 텍스트마이닝이란문서상의의미있는패턴과관계를찾고이를추출하는것으로써적절한알고리즘을이용하여비정형화된데이터를정형화데이터로변환시켜분석하는일련의과정이다. 텍스트마이닝에서행해지는일련의작업들을정리하면다음과같다. 1) 단어빈도분석 : 문서상에있는수많은텍스트들중에서유의한단어들을추출하고어떤단어들이빈번히나오는지분석하고추가적으로이를시각적으로표현하는것을워드클라우드 (wordcloud) 라함. 2) 연관성분석 : 하나의문서내에단어들간에어떤연관성이있는지분석하는것 38

4 J Korean Obstet Gynecol Vol.33 No.1 February ) 문서군집분석 (document clustering) : 단어와단어들간의유사성을이용하여문서들을몇개의집단으로군집화 Ⅲ. 결과 1. 중약투여방법중약의투여는월경주기에따라투약하는경우가 63건 58.9%, 월경주기와관계없이연속적으로투여한경우가 44건 41.1% 로많은연구에서월경주기에따 른치료법을사용하고있는것으로조사되었다. 투여시기는, 1 월경기에복용을중지하는경우, 2 황체기에투약하는경우, 3 난포기에이어서며칠간투여하는경우, 4 월경주기에따라다른약재를투여하는경우등으로조사되었으며, 5 기타월경의주기와관계없이일정기간만투여한경우도있었다. 연속투여한경우또는연속투여라는말은없지만월경기에휴약한다는언급이없는경우를연속투여로구분하였다 (Table 1). Table 1. Chinese Medicine Medication Guide Periodic therapy Administration guide Frequency RE (reference number) 3-5, 7, 11, 14, 24, 31-2, 35, 40, Non-Dose in menstrual period 44 45, 49, 54, 57, 59-62, 65, 71, 73-6, 78, 80, 82, 86, 90-91, Dose in ovulation period, luteal phase 11 15, 38-39, 41-2, 48, 55, 84-5, 88, 105 Dose for 15 days from the end of menstruation 3 63, 89, 106 Two different drugs to the ovaries and the luteal phase Dose for a certain period of time regardless of menstruation cycle Continuous administration 44 Total Amount , 13, 30, 33-4, 36-7, 43-4, 46-7, 50-3, 56 58, 64, 66-7, 68-70, 72, 77, 79, 81, 83, 87, 먼저, 한가지약을쓰면서월경기에투약을중단하는경우가 43편이었으며, 복약지침은 월경중약을중지, 20일또는 21일간투여, 월경 3-5일경과후투여, 월경 7일후투여 등으로기술하고있다. 이는월경주기가운데월경기를제외한난포기, 배란기, 황체기에중약을투여하는방법이다. 한편李등의 24) 연구에서는월경기에柴胡, 香附子, 茯苓, 芍藥, 丹參등으로구 성된중약을투여하고, 월경 5일후부터海藻, 蒲公英, 鹿角, 三七, 紅花, 雞血藤, 玄參, 天花粉, 昆布등으로구성된乳消顆粒을 21일간복용시켰는데비록월경기에복약을중지하지는않았지만疏肝解鬱, 化痰散結, 活血化瘀하는약물대신월경기에는疏肝活血시키는약재를사용하여월경기에解鬱散結의치법을중지하여여기에분류하였다. 다음은한가지약을쓰면서월경기와난 39

5 포기를제외한배란기부터황체기까지투약하는경우로 11편이었으며, 월경전 2주간또는 15일간투여, 월경중기 ( 배란기 ) 에시작해 14일간투여, 월경전 7일부터 10일간투여한다 등으로기술하고있다. 세번째로한가지약을쓰면서월경끝난후부터또는월경시작후 5일째, 즉난포기에시작하여 15일간투약하는경우가 3건이었다. 이방법은난포기, 배란기, 황체기초기까지투약하는방법이다. 네번째로난포기와황체기를구분하여두가지약을다르게투약한경우가 3건있었는데, 林등 25) 은난포기에六味地黃湯加減合二至丸을황체기에는柴胡舒肝散을투여하였고, 王등 26) 은월경후인월경 5일에康乳散結湯 6일투여하고 3일간복약을중지하였다가康乳散結湯에익모초를가하여 6일간투여하였으며, 楊은 27) 난포기에消癖散結湯 Ⅰ 號를황체기에消癖散結湯 Ⅱ 號를투여하였는데消癖散結湯 Ⅰ 號는六味地黃丸에活血化瘀, 行氣止痛 軟堅散結解鬱安神하는약을가하여補肝腎, 調沖任하는목적으로구성되었고, 消癖散結湯 Ⅱ 號는疏肝理氣, 活血散結을목적으로구성된중약이다. 기타한가지약을쓰되일주일중 6일은투약하고하루는휴약하는경우가 1건있었고 28), 한가지약을쓰되월경주기중어느시기에대한언급은없이단순히 12일연속투약하는경우도 1건있었다 29). 다음으로중약을연속복용시키지않고월경주기에따라투약하는이유를알아보기위해복용법에따른치법을조사하였다 (Table 2). 치법은유사한성격에따라몇가지로분류하여조사하였는데이는각연구마다 2~6가지정도의치법이사용되었으며치법의배합이조금씩다르기때문이다. 조사한치법은비정형유방증식치료의근본이되는疏肝과관련된치법과종괴를줄이기위한散結, 化痰, 軟堅, 活血祛瘀의치법과調理沖任, 補腎, 補腎陽등補法의세가지를조사하였다. Table 2. Chinese Medicine Treatment Frequency The period of dosage Continuous dosage Non-Dose in menstrual Dose in ovulation period, (total number of (127) period (134) lusteal phase (33) treatments) Frequency (ratio, %) Frequency (ratio, %) Frequency (ratio, %) 散結, 軟堅, 化痰 35 (27.6) 32 (23.9) 11 (33.3) 活血, 祛瘀, 破瘀 30 (23.6) 33 (24.6) 8 (24.2) 疏肝解鬱, 理氣行氣 20 (15.7) 26 (19.4) 5 (15.2) 補法 * 14 (11) 25 (18.6) 2 (6.1) Total 99 (78) 116 (86.6) 26 (80.8) * 補法 : 調理沖任, 益氣健脾, 補腎, 補肝腎補腎陽, 養血柔肝, 舒肝理氣 조사결과연속복용한 44편의연구에서조사된치법은 127개, 월경기복약을중지한 44편의연구에서조사된치법은 134개, 배란기황체기에복용한 11편의연구에서조사된치법은 33개가조사되었다. 복용방법에따른치법의차이는월경기 투약을중단하는경우와연속복용하는경우에軟堅散結, 活血祛瘀, 疏肝解鬱理氣하는치법빈도가유사하였으며다만월경기투약을중단하는경우에補法의빈도가다소높았다. 배란기와황체기에투약하는경우보법의비율은낮았지만散 40

6 J Korean Obstet Gynecol Vol.33 No.1 February 2020 結의치법빈도는다소높았다. 2. 중약사용빈도비정형유방증식의중약사용동향을알아보기위하여연구에사용된처방을조사하였다. 각각의연구에서사용된처방이다양하고, 처방명이같으면서처방구성이다른경우와제제약의경우동일한처방에대해서제조사별로다른명칭을쓰는경우가있어처방의특성과구성성분을확인하는작업을통해서최대한일괄되게정리하였다. 연구에사용된 107편연구중제제약에대한연구는 42편 39.3% 있었고, 탕제를 사용한연구가 68편 63.5% 있었다. 이가운데 3편은제제약과유명처방또는임의조제한처방을중복사용하였다. 제제약은 42편의연구에서 34개의처방이사용되었으며, 그중처방내용이기재된연구 15편의처방명및처방내용은다음과같았다 (Table 3). 탕제를사용한연구에서기존처방으로사용된것은逍遙散이 4회, 柴胡舒肝散과瓜蔞薤白半夏湯이 2회사용되었으며, 丹梔消遙散, 六味地黃湯加減合二至丸, 血府逐瘀湯, 黃連溫膽湯合佛手散加減, 定經湯加減이각각 1회사용되었으며나머지는임의조제한처방을사용하였다. Table 3. Name and Contents of Prescription RE* Prescription name Prescription contents 30) 李 1 鹿角, 蒲公英, 昆布, 夏枯草, 雞血藤, 三七, 赤藥, 海藻, 漏蘆, 1 乳癖消木香, 玄參等 2 逍遙丸 2 柴胡, 白藥, 當歸, 獲荃, 白朮等 31) 丁 1 乳生 Ⅰ 號 1 逍遙散加益母草, 夏枯草, 紫花地丁, 皂刺, 黃芪等 2 乳生 Ⅱ 號 2 乳生 Ⅰ 加菟絲子, 女貞子等 35) 李 消乳散結膠囊 柴胡 ( 醋炙 ), 白藥 ( 炒 ), 香附 ( 醋炙 ), 玄參, 昆布, 瓜蔞, 夏枯草, 牡蠣, 當歸, 貓爪草, 黃芩, 丹參, 土貝母, 山慈菇, 全蠍, 牡丹皮, 96) 劉 柴胡艾葉公英川楝子海藻天門冬全瓜蔞 119) 趙 坤乳寧顆粒柴胡 10 g, 艾葉 10 g, 蒲公英 10 g, 川楝子 10 g, 海藻 15 g, 天門冬 10 g, 全瓜蔞 30 g 97) 幸 乳增寧膠囊 三七, 紅花, 萊菔子, 鹿茸等 77) 鄭 乳癖舒 瓜蔞皮, 蒲公英, 丹參, 土貝母, 延胡索, 柴胡, 赤藥等 24) 李 乳消顆粒 海藻, 蒲公英, 鹿角, 三七, 紅花, 雞血藤, 玄參, 天花粉, 昆布等 15 味中藥制成 105) 張 乳癖消薄膜衣片鹿角, 蒲公英, 昆布, 雞血藤, 三七, 海藻, 玄參, 紅花等 98) 劉 乳痛消膠囊 香附, 鬱金, 青皮, 三棱, 莪朮, 浙貝, 山甲, 路路通, 制山甲, 黨參, 黃芪, 白芷 12 味中藥制成 112) 趙 消散乳塊膠囊 由當歸, 乳香, 丹參, 川芎, 荔核, 山茨菇, 王不留行, 穿山甲, 皂刺, 鬱金, 瓜蔞, 甘草共 13 味中藥組成 10) 張 血府逐瘀湯 桃仁 10 g, 紅花 10 g, 當歸 15 g, 生地 15 g, 赤藥 15 g, 柴胡 10 g, 川芎 15 g, 醋延胡索 10 g, 龜甲 20 g, 海藻 30 g, 昆布 30 g, 三棱 15 g, 莪朮 15 g, 甘草 6 g 115) 馬 乳癖散結膠囊 夏枯草, 川芎, 僵蠶, 鱉甲, 柴胡, 赤藥, 玫瑰花, 莪朮, 當歸, 延胡索, 牡蠣 44) 雷 乳痛核散顆粒 柴胡, 黃芪, 丹參, 白藥, 青皮, 當歸, 貓爪草, 延胡索, 香附, 全瓜蔞 3) 雷 柴胡, 鬱金, 青皮, 桔核, 生牡蠣, 皂角刺, 王不留行, 鹿角霜, 淫羊藿, 乳痛核散顆粒 3 號制半夏, 甘草等 *RE : reference number 41

7 3. 치료에사용된치법 107편에사용된치법과약재의빈도를조사하는과정에서저자에따라유사한치법에다른명칭을사용하고있어유사한치법을정리하여사용된치법을조사하였다 (Table 4). 표에표시되지않은치법으로, 滋陰, 益陰, 生津, 壯陽補陰, 補虛, 通乳活絡, 乳絡疏通, 安神寧心, 托毒生肌, 潤腸通便등의 치법이각 1회기재되어있었다. 비정형유방증식의치료에사용된치법은軟堅散結이 40회로가장높은사용빈도를보였으며, 다음으로는活血이 31회, 疏肝解鬱 26회, 疏肝理氣 25회, 調理沖任이 23회의순서로많았다. 다음으로化痰散結, 清熱散結, 活血止痛, 散結, 溫腎陽, 止痛散結등의치법이 5회이상사용되었다 (Table 5). Table 4. Terminology Theorem for Treatment Methods Treatment Similar treatment methods methods 氣行氣 ( 通氣, 通達氣機, 疏散鬱遏之氣, 走竄行散 ), 理氣 ( 利氣 ), 益氣 ( 補氣 ) 逐瘀, 破瘀 ( 破血, 消瘀 ), 祛瘀 ( 散瘀, 散瘀結, 消除瘀滯 ), 活血 ( 化瘀, 解瘀, 血行血 ), 養血 ( 補血 ) 滌痰, 祛痰 ( 消痰 ), 化痰 ( 止痰, 痰凝得化, 痰凝漸化 ), 除濕, 祛濕, 燥濕, 利濕痰濕 ( 滲濕, 利水 ) 清熱 ( 清熱瀉火, 瀉熱 ), 清肝火 ( 清肝, 清肝瀉火, 清肅肝熱, 淸熱疏肝, 達肝經淸熱鬱熱 ), 清肺降火寒祛寒 ( 散寒 ), 溫經通陽 ( 溫通血脈 ) 疏肝 ( 條達肝氣, 疏通肝經鬱滯, 調肝 ), 舒肝 ( 肝氣得舒, 肝氣漸舒, 柔肝 ), 平肝, 肝養肝 ( 補肝體, 顧護肝陰 ), 清肝火 ( 清肝瀉火, 清肝, 清肅肝熱, 達肝經鬱熱 ) 脾健脾 ( 健脾胃, 健脾和胃, 理脾調中, 理脾 ), 和胃補腎 ( 補先天之腎氣, 補益腎氣, 益腎 ), 溫腎陽 ( 溫補腎陽, 溫陽補腎, 壯腎陽, 腎補腎助陽, 補腎溫陽 ), 滋腎陰 ( 補腎填精, 補腎精 ) 補肝腎 ( 補益肝腎, 調補肝腎, 滋補肝腎, 滋補肝腎之陰 ), 滋養肺腎, 補益肝脾, 肝腎脾肺溫補脾腎 ( 溫腎健脾 ) 衝任調理沖任 ( 調攝沖任, 調沖任, 調和沖任, 調補沖任, 調節沖任, 調沖 ), 通行沖任調經 ( 通經 ), 活絡 ( 通絡, 舒經, 開通經絡, 暢通氣血 ), 溫經 ( 溫通經絡血脈 ) 解鬱行滯導滯, 行滯 ( 化滯 ), 消滯, 解鬱 ( 開鬱 ), 寬胸 ( 開胸 ) Others 消散軟堅消腫, 解毒 ( 消炎, 消癰 ), 軟堅散結 ( 消積, 化核, 消腫塊, 消塊, 消瘰, 消癖, 消癥, 解結, 消散凝塊 ), 散結消痞, 消脹止痛止痛 ( 消痛 ) Table 5. Frequency of Treatment Methods Treatment 清熱散結散結 / 溫腎陽, 軟堅散結活血疏肝解鬱疏肝理氣調理沖任化痰散結 methods 活血止痛止痛散結 Frequency

8 J Korean Obstet Gynecol Vol.33 No.1 February 통계를이용한치법에따른사용약물조사문헌조사결과치료에사용된처방에대한일관된정보를얻기어려워비정형유방증식의치료와약물사용에대한객관적결과도출을위해, 다빈도치법과이와상관있는사용약재사용을알아보기위해서본연구에서는텍스트마이닝 (textmining) 을사용하였다 19-23). 먼저빈도분석및워드클라우드 (wordcloud) 를사용하여중요도가높은치법이나약재를시각적으로살펴보고, 상관분석을통해유의한상관관계를가진치법들과약재를조사하였으며마지막으로클러스터 (Cluster) 분석을통해치법들과약재간에의미있는군집들을살펴보았다. 1) 치법과약재간의기초빈도분석치법과약재의기초분석으로빈도분석을실시하고워드클라우드를이용하여빈도수가높게나타난치법과약재를시각화하였다 (Fig 2). 워드클라우드는중요도가높을수록그래프의중심에위치하게되며글자크기및글자색이진하게표현된다 21). 분석결과가장빈도가높은散結은가장중심에위치하고있으며, 다음으로活血, 止痛, 疏肝, 理氣, 化痰, 軟堅, 解鬱, 行氣등의중요도가높게나타났다. 약재는柴胡, 香附子, 當歸, 貝母, 白藥藥, 夏枯草, 玄胡索등의중요도가높게나타났다. Fig. 2. Wordcloud between treatment methods and medicine. 2) 상관분석 치법들과약재간의상관분석결과를살 펴보면, 散結과상관관계가있는치법은 解毒과淸熱로나타났으며, 상관관계가있 는약재는牡蠣, 貝母, 海藻, 昆布, 瓜蔞, 夏枯草, 半夏였다. 이처럼각치법과상관관계가있는약 재를보면, 活血은치법調經과祛瘀, 약 재는川芎, 沒藥, 乳香, 紅花, 丹蔘, 雞血 藤, 蓬朮, 當歸, 赤藥藥, 桃仁이었으며, 止 痛은白藥藥, 三稜, 三七根이었고, 疏肝은 치법寬胸, 行氣, 通氣, 약재는香附子, 鬱金, 靑皮, 白藥藥, 枳殼이었다. 理氣는 치법行滯, 약재는香附子, 鬱金, 靑皮이 었고, 化痰은치법健脾, 燥濕, 약재는半 夏, 牡蠣, 貝母, 茯苓, 南星, 珍珠, 白芥子, 海藻였고, 軟堅은치법祛痰, 약재는牡 蠣, 海藻, 貝母, 昆布, 鱉甲, 生牡蠣, 穿山 甲이었으며, 解鬱은치법行滯, 약재는 枳殼, 香附子, 鬱金, 靑皮였다. 行氣는치 법寬胸, 通氣, 疏肝, 약재는枳殼이었고, 活絡은치법消脹, 祛瘀, 약재는絲瓜絡 漏蘆, 桃仁, 益母草, 麝香, 三稜이었다. 淸 熱은치법解毒, 益陰, 散結, 약재는蒲公 英, 連翹, 鬼箭羽, 金銀花, 紫花地丁, 雞 血藤, 白芷, 天花粉, 梔子, 玄蔘이었다. 養 血은치법舒肝, 益氣升陽, 生津, 益陰, 43

9 약재는白藥藥, 雞血藤, 益母草, 川椒이 었고, 消腫은치법除濕, 祛濕, 解毒, 약 재는路路通金銀花白芷, 土茯苓, 連翹, 地龍, 澤蘭으로나타났다 (Table 6). Table 6. Correlation with Frequent Treatment Methods and Medicinal Herbs Treatment methods 散結 活血 Correlation Herbs treatment 解毒 (0.27)* 牡蠣 (0.31), 貝母 (0.31), 海藻 (0.28), 昆布 (0.23), 瓜蔞 (0.23), 清熱 (0.21) 夏枯草 (0.21), 半夏 (0.20) 川芎 (0.34), 沒藥 (0.32), 乳香 (0.32), 紅花 (0.32), 丹蔘 (0.31), 調經 (0.30) 雞血藤 (0.30), 蓬朮 (0.28), 當歸 (0.27), 赤藥藥 (0.25), 桃仁祛瘀 (0.25) (0.23), 三稜 (0.21), 益母 (0.21) 止痛 白藥藥 (0.24), 三稜 (0.24), 三七根 (0.22) 疏肝 寬胸 (0.28) 行氣 (0.24) 通氣 (0.20) 香附子 (0.52), 鬱金 (0.41), 靑皮 (0.37), 白芍藥 (0.28), 枳殼 (0.21) 理氣 行滯 (0.29) 香附子 (0.40), 鬱金 (0.39), 靑皮 (0.38) 化痰 健脾 (0.31) 半夏 (0.38), 牡蠣 (0.31), 貝母 (0.30), 茯苓 (0.29), 南星 (0.24), 燥濕 (0.24) 珍珠 (0.23), 白芥子 (0.20), 海藻 (0.20) 軟堅 祛痰 (0.26) 牡蠣 (0.58), 海藻 (0.43), 貝母 (0.39), 昆布 (0.38), 鱉甲 (0.27), 生牡蠣 (0.26), 穿山甲 (0.23) 解鬱 行滯 (0.21) 枳殼 (0.32), 香附子 (0.32), 鬱金 (0.29), 靑皮 (0.25) 行氣 寬胸 (0.39) 通氣 (0.28) 疏肝 (0.24) 枳殼 (0.24) 活絡 消脹 (0.23) 絲瓜絡 (0.33), 雞血藤 (0.26), 漏蘆 (0.26), 桃仁 (0,26), 益母草祛瘀 (0.20) (0.26), 麝香 (0.23), 三稜 (0.20) 清熱 解毒 (0.54) 蒲公英 (0.54), 連翹 (0.35), 鬼箭羽 (0.24), 金銀花 (0.24), 白芷益陰 (0.24) (0.24), 雞血藤 (0.24), 天花粉 (0.24), 梔子 (0.24), 玄蔘 (0.24) 散結 (0.21) 養血 舒肝 (0.45) 白藥藥 (0.44), 雞血藤 (0.28), 益母草 (0.28), 川椒 (0.25), 生地黃益陰 (0.25) (0.23) 消腫 除濕 (0.37) 路路通 (0.37), 金銀花 (0.26), 白芷 (0.26), 土茯苓 (0.26), 連翹祛濕 (0.26) (0.26), 地龍 (0.26), 澤蘭 (0.26), 連翹 (0.24) 解毒 (0.21) *( ) : coefficient of correlation 3) 클러스터분석클러스터분석을실시한결과, 거리 10 을기준으로군집을구분하였을때 4개의군집이관찰되었다. 군집1(C1) 은理氣, 鬱金, 靑皮, 疏肝, 解鬱, 柴胡, 香附子로구성되어있고, 군집2 (C2) 는止痛과活血로구성되었다. 군집3 (C3) 은집단내에포함되는치법과약재가다수를차지하기때문에거리를좁혀재분류하기로하고, 마지막군집4(C4) 는散結, 化痰, 軟堅, 昆布, 海藻, 貝母, 牡蠣로구성되었다. 군집3(C3) 은거리 7을기준으로보면다시 5개의군집으로분류할수있다. C3-1 44

10 J Korean Obstet Gynecol Vol.33 No.1 February 2020 은舒肝, 養血, 當歸, 白藥藥, C3-2는淸熱, 解毒, 蒲公英, C3-3은健脾, 白朮, 茯苓, C3-5는行氣, 活絡과, 三稜, 蓬朮로구성된다. 구성이많은 C3-4를분석하면, C3-4군집의하부군집으로祛瘀, 沒藥, 乳香, 玄胡索, 赤藥藥, 川芎이한군집 (a) 을구성하였고, 消腫, 夏枯草, 橘核, 荔支核이 (b) 군집을형성하였으며, 마지막으로溫腎陽, 調理沖任調經, 丹蔘, 桃仁, 紅花, 寬胸, 半夏瓜蔞仁이 (c) 군집을형성하는것을알수있다 (Fig. 3). Fig. 3. Cluster analysis. Ⅳ. 고찰 비정형유방증식은변형된유선도관과소엽의조직들이서로엉기면서덩어리형태로된것을말하는데, 여성들에게가장흔한양성증식질병이다 114). 증상은월경전에유방통증이있으며, 감정변화가있을때는더욱심해진다. 특히월경 3-4일전에유방창통과종괴의증대가가장심해지면서단단해졌다가월경이시작되면완화되는주기성통증이있게된다 1). 간혹유두에서분비가있으며, 한쪽이나양쪽의유방을만지면여러개의크기가같지않은덩어 리모양이나줄무늬모양의불규칙한종양이있다. 이종양은경계가명확하지않고질이단단하지않으며이동성이있고초음파영상을보면유선소엽이나섬유조직의증식, 유선도관확장및유선낭종의형태가나타난다 4). 서양의학에서는주요원인을크게세가지로설명하고있는데첫째가여성호르몬대사장애로에스트로겐비율의불균형으로인해유선선체증식과섬유화이고둘째는고지방음식, 운동부족, 불규칙한생활습관으로인한호르몬장애, 셋째로는사회적심리적요인, 생활스트레스가많고정신적으로높은긴장감등 45

11 이유방증식의원인으로보고있다 10,58). 중의학에서유방증식은 肝氣가울체되어오래되면熱로바뀌어진액을소작하여痰이되고, 氣滯, 痰凝, 血瘀이되어유방에종괴가생긴다 고하였으며, 또, 혹肝腎의기운이부족하여충임맥이조화로움을잃고氣血이血瘀가되어막히거나, 혹脾腎의陽氣가허하여痰과濕의흐름이원활하지못하고정체되어經脈이막히면유방에종괴가생기고통증이유발되며월경이조화롭지못하다 하는등의원인으로유선증식이발병한다고하였다 10). 진단은이학적검사와진단기기를이용한검사가있는데이학적검사소견은 1 한쪽이나양쪽의유방에통증이있으며월경주기와관계가있고, 월경전에통증이심하지만월경이끝나면통증이감소하거나사라지거나, 2 유방을만지면여러개의크기가같지않은덩어리모양이나줄무늬모양의불규칙한종양이있으며, 질은질기지만단단하지않다. 서로유착되지않지만주위조직과경계가명확하지않으며, 3 병정이비교적길고발전이느리고중년여성들에게많이나타나고, 4 소수환자에서장액성또는혈성의유두분비물이있는데이와같은증상중 2가지이상이해당되면비정형유방증식이라고진단할수있다 4,65,78). 또한적외선, 초음파검사, 유방촬영술, 핵자기장등의영상검사나종양세포흡인검사, 국소생검사등통해서단순유방통증, 유선섬유종, 유선염, 유방암환자를제외하고진단한다 9,10,13,14,25,44,55,58,65,73,76,82,90,91,101,105). 중의에서는유선증식을치료하는주요원칙으로軟堅散結, 行氣活血, 疏肝理氣를들고있다 13). 즉, 한의학치료는整體관념 에서출발하여변증치료를하고, 주로肝을중심으로疏肝理氣, 化痰散結, 活血祛瘀의치료원칙하에脾腸과腎臟을고루돌보면서전체와국지를함께치료하고, 내치와외치의결합을중시한다 120). 본연구는비정형유방증식의중의치료동향을알아보기위한연구로 CNKI에서 2006년 7월부터 2017년 5월 31일까지기간에서검색된 2,454편을연구중중약의양약에대한효능을검증하고자시행된무작위임상연구결과유효한효과를보인 107편의 RCT 임상연구에대해치법과사용약재에대해알아보았다. 먼저치료에활용된중약의투여방법을살펴보았는데, 약 60% 의연구에서월경주기를따르고있었다. 이는이질환에서보이는통증과종괴등의증상이월경주기에따라증상의증감을보이는것과관계있는것으로생각된다. 투약의시기는배란기와황체기, 배란기이후황체기초기를포함하는일정기간에중약을복용하고월경기에는복약을중지하는양상을보였으며이중월경기에복약을중단하는경우가 43건, 배란기와황체기투여가 11건으로비교적많았다. 월경이끝난후난포기부터시작하여 15일간만복약하는경우가 3건, 난포기와황체기에다른중약을투여하는경우가 3건있었다. 이처럼월경주기에따라투약하는이유를알아보기위해복용법에따른치법을조사한결과, 월경기투약을중단하는경우와연속복용하는경우치법에큰차이를발견할수없었다. 그러나李등 24) 이월경기에는疏肝解鬱, 化痰散結, 活血化瘀하는약물대신疏肝活血시키는약재만사용한것과王이 36) 월경량이많으면 46

12 J Korean Obstet Gynecol Vol.33 No.1 February 2020 월경기에휴약하고그렇지않으면계속복약시킨것을볼때, 종괴를없애기위한散結의치료로월경과다를초래할우려가있을것을우려하여복약을중지할수있을것으로생각되었다. 또비록 3편의연구에불과하지만난포기와황체기를구분하여두가지약을다르게투약한경우는난포기에는六味地黃湯계열의처방으로補肝腎, 調沖任하는중약을투여하고황체기에柴胡舒肝散이나疏肝理氣, 活血散結을목적으로하는처방을투여하거나 25,27), 난포기에투여한약에익모초를가하여활혈을강조하고있다 26). 이에대해蘭등 95) 은월경주기에따라치료를하는경우疼痛완화, 消瘀散腫하거나補虛治本, 溫腎助陽, 調攝沖任할수있어중약투여로標本을兼治할수있다고하였다. 이상의중약투여방법을종합하면, 월경주기에따른중약의투여는연구자에따라달라월경기복약을중지하거나연속복약하는경우가많았는데, 종괴를없애기위한치료로월경과다를초래할우려가있을경우복약을중지할것을고려할수있을것으로생각되었으며, 난포기와황체기를나누어투약하는경우각각補肝腎, 調沖任하거나疏肝理氣, 活血散結하는등치법에차이를두는것을알수있었다. 치료에사용된중약의제형은제제약에대한연구가 42편 39.8% 있었고, 탕제를사용한연구가 68편 63.5% 있었다. 제제약은처방구성을알수없는경우가많았지만확인가능한연구에서살펴보면乳癖消, 散結의의미를가진약 (18회) 이주로사용되고있으며, 이밖에乳痛, 消, 散結, 乳增을사용하고있어주로증식 을消散하는것을목표로하는것을알수있었다. 탕제가운데기존처방으로가장많이사용된것은逍遙散계통이 5회로가장많았으며柴胡舒肝散이 2회사용되었다, 제제약에서도逍遙丸을기준으로한약은 8회이었던것을볼때肝을중심으로치료한疏肝의치법이주로활용되었을것으로생각되었다. 사용된처방을조사하려하였으나임의조제하거나구성을알수없는제제약을사용하는경우가많아치료에사용된치법과약재를조사분석하였으며, 분석된결과에대해텍스트마이닝기법을활용하여분석을진행하였다. 텍스트마이닝은탐색적통계기법으로문서자료에숨겨진패턴이나정보를발견하고자할때사용된다 20). 먼저연구마다사용된용어가달라유사용어를통합하여치법빈도를조사하였으며통계를활용하여치법과사용된약재간의상관관계를알아보았다. 치법빈도는軟堅散結이 40회로가장높은사용빈도를보였으며, 다음으로는活血이 31회, 疏肝解鬱 26회, 疏肝理氣 25회, 調理沖任이 23회의순서로나타났다. 이러한빈도분석결과를통계적으로확인하고관련된약재를알아보기위해먼저빈도분석및워드클라우드를사용하여중요도가높은치법이나약재를시각적으로살펴보고상관분석을통해유의한상관관계를가진치법들과약재를조사하였으며마지막으로클러스터분석을통해치법들과약재간에의미있는군집들을살펴본결과, 散結은빈도가가장높아중심에위치하고있으며, 다음으로活血, 止痛, 疏肝, 理氣, 化痰, 軟堅, 解鬱, 行氣등의치법이빈도가높게나타났으 47

13 며, 약재에있어서는柴胡, 香附子, 當歸, 貝母, 白藥藥, 夏枯草, 玄胡索의빈도가높았다. 이들빈도조사와통계분석결과를살펴보면, 빈도가가장높은散結은클러스터분석결과는치법化痰, 軟堅, 약재昆布, 海藻, 貝母, 生牡蠣와군집4를이루는것으로조사되었다. 이중치법化痰은상관분석에서치법健脾, 燥濕, 약재半夏, 生牡蠣, 貝母, 茯苓, 南星, 珍珠, 白芥子, 海藻와관계가있었으나이는비정형유방증식을치료하는목적과는거리가있는것으로생각되며, 치법軟堅은치법祛痰, 약재海藻, 貝母, 昆布, 鱉甲, 生牡蠣, 穿山甲과관계가있는것으로나타났는데이는상기약재에鱉甲, 穿山甲이추가된것을알수있다. 散結에대한상관분석에서는치법解毒, 清熱, 活血, 약재生牡蠣, 貝母, 海藻, 昆布, 瓜蔞, 夏枯草半夏등이관계가있는것으로나타났는데, 이는치법은다르지만군집4의약재에瓜蔞, 夏枯草, 半夏이추가된것이다. 이중치법解毒은상관분석에서상관관계가있는치법이나약재가조사되지않았으며, 치법清熱은치법解毒, 益陰, 散結, 약재蒲公英, 連翹, 鬼箭羽, 金銀花, 白芷, 雞血藤, 天花粉, 梔子, 玄蔘과관계있었고, 이가운데清熱, 解毒, 蒲公英은군집3-2를구성하였다. 결과적으로散結은化痰, 軟堅과한군집을이루나解毒, 清熱과도관계있으며이경우蒲公英으로대표되는관련약재를활용할수있는것으로생각되었다. 한편散結과관계있는또다른치법으로活血이있었는데이는치법調經, 祛瘀, 약재川芎, 沒藥, 乳香, 紅花, 丹蔘, 雞血藤, 蓬朮, 當歸, 赤藥藥, 桃仁와관계가있는것으로나타 났으며, 이가운데調經은丹蔘, 桃仁, 紅花와함께祛瘀는沒藥, 乳香, 玄胡索, 赤藥藥, 川芎과함께군집3-4를구성하고있다. 유방의비정형증식의증상이월경주기와관련하여호르몬의변화나이와관련한유방의통증과종괴증가등의증상을보이므로일반종괴의치료와달리活血, 調經, 祛瘀의치법과약재들이상관관계를보인것으로생각된다. 活血은빈도조사에서散結보다는止痛과더많이동반사용된것으로조사되었는데, 이두치법은네트워크분석에서비교적높은빈도를보이고있다. 클러스터분석에서도活血과止痛은함께군집2를이루고있다. 군집2에속한약재는없었으며, 상관분석에서活血의결과는散結에서서술하였고, 止痛은관계있는치법은없었으며, 약재白藥藥, 三稜, 三七根과관계가있는것으로나타났다. 이것을볼때비정형유방증식에서유방의통증을완화하기위해活血, 調經, 祛瘀의치법을주로사용하는것을알수있었으며, 丹蔘, 桃仁, 紅花, 沒藥, 乳香, 玄胡索, 赤藥藥, 川芎, 白藥藥, 三稜, 三七根등의약재를활용할수있을것으로생각된다. 疏肝, 理氣와解鬱은각각 26회 13회동반사용된치법으로클라우드분석에서군집1을구성하였으며군집1에속하는약재는鬱金, 靑皮, 柴胡, 香附子가있었다. 각치법의상관분석에서疏肝은寬胸, 行氣와관계가있으며약재는香附子, 鬱金, 靑皮, 白藥藥, 枳殼과관계가있었고, 이가운데寬胸은半夏, 瓜蔞仁과함께군집3-4를구성하였다. 解鬱은치법行滯, 약재香附子, 鬱金, 靑皮, 枳殼, 香附子, 鬱金, 靑皮와관계있었고, 行氣는치법寬 48

14 J Korean Obstet Gynecol Vol.33 No.1 February 2020 胸, 疏肝약재枳殼과상관관계가있었고군집3-5에서치법活絡, 약재三稜, 蓬朮등과한군집을이루었다. 중의학에서유방증식은肝의울체가주원인으로인식되고있다 11). 따라서理氣, 行氣를통한寬胸, 疏肝, 解鬱은중요한치법의하나이며이런이유로疏肝理氣, 疏肝解鬱의치법빈도가 26회로軟堅散結에이어 2번째를차지했으며통계분석에서도같은결과를보이는것으로생각되며鬱金, 靑皮, 柴胡, 香附子, 白藥藥, 枳殼, 半夏, 瓜蔞仁등의약재를사용할수있을것으로생각된다. 이에비해舒肝은빈도가 13회로疏肝에비해낮았으며상관관계가있는치법이나약재도조사되지않았다. 다만養血과관계있는치법과약재에대한상관분석에서치법舒肝, 益氣升陽, 生津, 益陰, 약재白藥藥, 雞血藤, 益母草, 川椒가관계있는것으로조사되었고, 養血과舒肝은當歸, 白藥藥과함께군집3-1을구성하는것으로조사되었다. 이는疏肝, 理氣, 行氣, 寬胸, 解鬱의방법에비해빈도는떨어지지만, 養血, 益氣升陽, 生津益陰과같은방법으로舒肝하여유방증식을치료하는방법이사용될수있으며白芍藥, 雞血藤, 益母草, 川椒등의약재를사용할수있는것으로생각되었다. 기타치법빈도가높았던調理沖任은상관관계가있는치법이나약재는없었으며溫腎陽과함께군집3-4를이루는것으로조사되었는데沖任의기능을회복시키기위해腎을溫陽하는것으로생각되었으며, 消腫은夏枯草, 橘核, 荔支核과함께군집3-4을이루며, 상관분석에서치법除濕, 祛濕, 解毒, 약재路路通, 金銀花, 白芷, 土茯苓, 連翹, 地龍, 澤蘭 과관계가있었다. 이상의결과를종합하면, 가장빈도가높았던散結의치법에관련하여散結, 化痰, 軟堅등의치법에昆布, 海藻, 貝母, 生牡蠣, 鱉甲, 穿山甲등의약재를사용하거나, 散結, 解毒, 清熱등의치법에蒲公英, 連翹, 金銀花, 白芷, 雞血藤, 天花粉, 梔子, 玄蔘등의약재를사용하거나, 散結, 活血, 調經, 祛瘀등의치법에丹蔘, 桃仁, 紅花, 沒藥, 乳香, 玄胡索, 赤藥藥, 川芎, 雞血藤, 蓬朮, 當歸, 赤藥藥등의약재를사용하는경우가있었다. 다음活血, 調經, 祛瘀, 止痛등의치법에丹蔘, 桃仁, 紅花, 沒藥, 乳香, 玄胡索, 赤藥藥, 川芎, 白藥藥, 三稜, 三七根등의약재를사용하는경우와, 疏肝, 理氣, 行氣, 寬胸, 解鬱등의치법에鬱金, 靑皮, 柴胡, 香附子, 白藥藥, 枳殼, 半夏, 瓜蔞仁등의약재를사용하는빈도가높았다. 기타養血, 舒肝의치법에白藥藥, 雞血藤, 益母草, 川椒등의약재를사용한경우와調理沖任을치료하기위해溫腎陽한경우, 消腫을위해夏枯草, 橘核, 荔支核, 路路通, 金銀花, 白芷, 土茯苓, 連翹, 地龍, 澤蘭등의약재를사용한경우가통계적으로유의한것으로조사되었다. Ⅴ. 결론 비정형유방증식의중의치료동향을알아보기위해 CNKI에서 2006년 7월부터 2017년 5월 31일의기간연구를검색하여무작위대조군임상연구결과중서의복합치료가양약단독치료에비해유효한효과를보인 107편의 RCT 임상연구에대해조사한결과는다음과같다. 49

15 1. 중약투여방법은월경주기에따르는경우가 63건 58.9%, 월경주기와상관없이투약하는경우가 44건 41.1% 이었다. 2. 치법과약재간의기초빈도분석결과, 散結은빈도가가장높았고, 다음으로活血, 止痛, 疏肝, 理氣, 化痰, 軟堅, 解鬱, 行氣등이높게나타났으며, 약재는柴胡, 香附子, 當歸, 貝母, 白芍藥, 夏枯草, 玄胡索의빈도가높았다. 3. 치법과약재의관계에대한상관분석과클러스터분석결과는다음과같다. 1) 散結, 化痰, 軟堅등의치법에昆布, 海藻, 貝母, 生牡蠣, 鱉甲, 穿山甲등의약재를사용 2) 散結, 解毒, 清熱등의치법에蒲公英, 連翹, 金銀花, 白芷, 雞血藤, 天花粉, 梔子, 玄蔘등의약재를사용 3) 散結, 活血, 調經, 祛瘀등의치법에丹蔘, 桃仁, 紅花, 沒藥, 乳香, 玄胡索, 赤藥藥, 川芎, 雞血藤, 蓬朮, 當歸, 赤藥藥등의약재를사용 4) 活血, 調經, 祛瘀, 止痛등의치법에丹蔘, 桃仁, 紅花, 沒藥, 乳香, 玄胡索, 赤藥藥, 川芎, 白藥藥, 三稜, 三七根등의약재를사용 5) 疏肝, 理氣, 行氣, 寬胸, 解鬱등의치법에鬱金, 靑皮, 柴胡, 香附子, 白芍藥, 枳殼, 半夏, 瓜蔞仁등의약재를사용 6) 養血, 舒肝의치법에白藥藥, 雞血藤, 益母草, 川椒등의약재를사용 7) 理沖任을치료하기위해溫腎陽을다용 8) 消腫을위해夏枯草, 橘核, 荔支核, 路路通, 金銀花, 白芷, 土茯苓, 連翹, 地龍, 澤蘭등의약재를사용 References Received : Jan 09, 2020 Revised : Jan 20, 2020 Accepted : Feb 28, Bae JG. The Breast of Oriental Medicine. Seoul:Jungdam. 2005: Liang XL, Wang L. Treatment of breast hyperplasia with traditional Chinese and Western Medicine. Chinese J. of Ethnomedicine and Ethnopharmacy. 2016;25(19): Lei QM, Hu YC. Clinical observation of Rūtonghesan granule No.3 in the Treatment of Breast hyperplasia of Chong Ren disorder type. Shanxi Traditional Chinese Medicine. 2010;26(10): Shi XC, Zhou SP. Clinical Research on Mammary Hyperplasia Treated with Integrated Chinese and Western Medicine, World J. of Integrated Traditional and Western Medicine. 2010;5(12): Du Yanni. 62 cases of Mammary hyperplasia treated by Chinese and Western Medicine. Chinese Medicine Modern Distance Education of China. 2011;9(18): Park SH. The Breast Cancer White Paper. Korea Breast Society. 2018: Wang GF. Experience in the treatment of mammary hyperplasia with the combination of Chinese and Western Medicine. J. of Practical Medical Techniques. 2007;14(33): Huang Q. A Clinical study of Rūpixiao 50

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