3) 대한한방부인과학회지 pissn 1229-4292 / eissn 2508-3619 J Korean Obstet Gynecol. VOL.29 NO.4 : 024-033 (2016) http://dx.doi.org/10.15204/jkobgy.2016.29.4.024 조산방지및자궁수축관리의한의학적치료 유앤그린한의원 1, 대전대학교대학원한방부인과 2 김은섭 1, 장은하 1, 김남형 1, 장새별 2 ABSTRACT Prevention of Preterm Birth and Management of Uterine Contraction with Traditional Korean Medicine Eun-Seop Kim 1, Eun-Ha Jang 1, Nam-Hyoung Kim 1, Sae-Byul Jang 2 1 You and Green Korean Medical Clinic 2 Dept of Oriental Gynecology, College of Oriental Medicine, Graduate School of Dae-Jeon University Objectives: The aim of this study was to demonstrate the benefit of Traditional Korean Medicine as an adjuvant therapy in management of early uterine contractions and the prevention of Preterm Birth (PTB). Methods: It is a case report of a 38 year-old-woman hospitalized for irregular uterine contractions and cervical change at 33 +3/7 weeks of gestation. After 7 trials of IVF and artificial insemination, conception was successful via IVF with help of traditional Korean medicines. 2 TKMs were prescribed: Gami-danggui-san, and Antae-eum. 120 ml of Gami-danggui-san was given twice a day morning and evening along with same amount of Antae-eum once a day from 31 August 2013 to 28 November 2013. Tocolytics (Ritodrine) was administered as a first aid for maintenance of pregnancy. Information regarding progress until the delivery was collected during the patient s visit. Results: As of 34 +2/7 weeks of gestation, intermittent uterine contractions appeared (5-12 min) on cardiotocography and vaginal bleeding was also smeared at 34 +3/7 weeks. However, enhanced tocolytics and continuous administration of herbal medicine sustained the pregnancy to term. At 37 +2/7 weeks, no sign of labor with restored cervical length was confirmed. The woman gave a term birth to a healthy infant via vaginal delivery at 39 +3/7 gestational weeks. Conclusions: Our report implies the potential of herbal medicine as a adjuvant therapy for preterm labor treatment. Further studies are needed to assess the safety and efficacy of TKM herbal medicine as a therapeutic alternative for curing preterm birth. Key Words: Preterm Birth, Uterine Contraction, Gami-danggui-san, Antae-eum, Korean Medicine 본연구는 2016 년 8 월 9 일 Venice 에서개최된 ICCAIMH 에서구술발표내용을토대로작성되었었습니다. Corresponding author(eun-seop Kim) : You and Green Korean Medical Clinic, 70, Munjeong-ro, 48 Beon-gil, Seo-gu, Daejeon, Korea Tel : 042-471-4777 Fax : 042-471-4775 E-mail : greenmiz@naver.com 24
J Korean Obstet Gynecol Vol.29 No.4 November 2016 Ⅰ. 서론 Ⅱ. 증례및임상경과 조산은영아사망원인의절반을차지할뿐아니라생존아의신경계발달장애, 호흡기계합병증등의이환의주요원인이되며이로인한경제적부담도매우큰문제가되고있다. 최근기계식인공호흡기 (assisted ventilation) 와표면활성제치료 (surfactant therapy), 산전스테로이드사용의증가등으로조산아생존율이증가하였으나이환율에서는호전을보이지않으며만성폐질환, 패혈증, 출생후성장지연이여전히높게나타나고있다 1). 또한최근임신 34-36주에해당하는후기조기분만이매우중요하게다루어지고있는데. 후기조기분만아는정상분만아에비해신생아유병률이 7배높고호흡기계유병률, 불리한발달장애및학습능력장애, 그리고행동장애및 6세에서의낮은지능지수, 주의력결핍과연관이있다 1). 또한임신기간 34-39 주사이에임신기간이증가할수록신생아이환율이크게감소하는것으로보고되었다. 그러므로장기적예후를고려한다면조기진통이조산으로이어지지않도록하고만산 (full term delivery) 을목표로치료를하는것이바람직하다. 그러나다수의약물치료와약물이외의치료를사용하여조기진통을억제하려는시도를하였지만어떤것도완벽히효과적인것은없었으며 1) 미국산부인과학회는 2012년에자궁수축억제제는임신기간을현저히증가시키는것이아니라 48시간정도만분만을지연시킬수있다고결론지었다 2). 1. 이름 : 양 (F/39) 2. 초진일 : 2011년 2월 3. 주소증 : 조기진통, 자궁경부무력 4. 발병일 : 2013년 9월 5. 과거력 : 자궁내막증으로복강경수술 1회 6. 월경력 : LMP-3월 25일 7. 출산예정일 : 2013년 12월 8. 산과력 : Para 0-0-6-0( 인공수정후화학적유산, 임신 7주차의유산등을포함 ) 9. 현병력 1) 2013 년 4월시험관아기시술 IVF-ET (In Vitro Fertilization-Embryo Transfer) 2) 4월말임신확인후산부인과및본원에서임신중건강유지를위한침, 뜸, 한약 ( 가미당귀산1, 안태음 ) 을비롯한치료유지함. 3) 2013년 9월초, 임신 23주차에자궁수축및복통나타나산부인과외래에서수액처치후일시적으로증상호전되다재발되어 9월 6일본원내원 10. 치료내용및경과기록임신 23주차부터간헐적인아랫배뭉침및복통이나타나가미당귀산1(G1) 복용횟수를하루두번 ( 아침, 저녁식후 30분경 ) 에서매식후 30분경으로증량하였고, 안태음 (At) 은취침전처방으로투여하였다. 임신 26주경배우자전근발령으로원거리이주를준비하는환자가심신의부담가중을호소하여용안육을증량하고익지인을추가한처방 (G2) 을 At와함께기존과동일한방식으로투여하였다. 재태주수 28주 1일차에환자는점액상질분비물의증가와규칙적인자궁수축 25
조산방지및자궁수축관리의한의학적치료 을보여거주지인근산부인과외래수진하였고당시조기양막파열이의심되었으나 Actim test 상음성으로확인되어안정가료와경과관찰을권고받았다. 이에익지인을증량한처방 (G3) 과 At의취침전복용을지속하였다. 임신 30주차에이르러환자의자궁경부의길이가 14 mm로단축되고, 임신 33주경에는태동이감소하고자궁경부가 50% 가량소실되며숙화된소견을보여연고지근처의대학병원에입원하여자궁수축억제치료를병행하였다. 입원당시환자는 Ritodrine 정맥주사치료와한약투여를병행하며 4일간자궁수축증상을보이지않아입원 5일차에 Ritodrine 경구용약물로전환하고퇴원예정이었다. 그러나 Ritodrine 경구처방당일부터자궁수축이재현되어정맥주사치료로전환하고 한약복용 (G3, At) 과입원을지속하였다. 임신 34주 3일차에소량의갈색질출혈이보여예방적항생제가투여되고 Ritodrine 의용량을일시적으로증량하였으나출혈은재현되지않았다. Ritodrine 증량과정에서환자가가슴답답함을호소하여하루만에투여량을줄였고, 한약복용은기존의방식대로유지하였다. 임신 36주까지일중간헐적인조기자궁수축이관찰되어 Ritodrine 정맥주사와한약복용을지속하였고, 임신 37주 1일차에이르러자궁경부변화및조기진통이관찰되지않아산모는한약복용을마치고퇴원하였으며, 이후대학병원외래를통해경과를관찰하다 39(+3) 주에정상자연분만하였다. 처방된한약의자세한구성은아래표에제시하였다 (Table 1-4). Table 1. Components of Gami-danggui-san 1 (G1) Components of herb preparation Amount (g) 白朮 Atractylodes macrocephala Koidzumi 8.0 白芍藥 Paeoniae Radix Alba 6.0 當歸 Angelicae Gigantis Radix 6.0 川芎 Cnidium Officinale Makino 6.0 黃芩 Scutellaria baicalensis 4.0 黃耆 Astragalus membranaceus 6.0 人蔘 Ginseng Radix 4.0 白茯苓 Poria cocas Wolf 4.0 甘草 Glycyrrhiza uralensis 4.0 杜仲 Eucommia ulmoides Oliver 4.0 續斷 Dipsaci Radix 4.0 枸杞子 Lycium Chinense Miller 4.0 陳皮 Citri Unshii Pericarpium 8.0 貢砂仁 Amomum villosum 4.0 香附子 Cyperi Rhizoma 8.0 熟地黃 Rehmanniae Radix Preparata 4.0 升麻 Cimicifugae Rhizoma 2.0 烏藥 Linderae Radix 8.0 龍眼肉 Longanae Arillus 6.0 木香 Aucklandiae Radix 4.0 阿膠 Anisi Corii Colla 50.0 26
J Korean Obstet Gynecol Vol.29 No.4 November 2016 Table 2. Components of Gami-danggui-san 2 (G2) Components of herb preparation Amount (g) 白朮 Atractylodes macrocephala Koidzumi 8.0 白芍藥 Paeoniae Radix Alba 6.0 當歸 Angelicae Gigantis Radix 6.0 川芎 Cnidium Officinale Makino 6.0 黃芩 Scutellaria baicalensis 4.0 黃耆 Astragalus membranaceus 6.0 人蔘 Ginseng Radix 4.0 白茯苓 Poria cocas Wolf 4.0 甘草 Glycyrrhiza uralensis 4.0 杜仲 Eucommia ulmoides Oliver 4.0 續斷 Dipsaci Radix 4.0 枸杞子 Lycium Chinense Miller 4.0 陳皮 Citri Unshii Pericarpium 8.0 貢砂仁 Amomum villosum 4.0 香附子 Cyperi Rhizoma 8.0 熟地黃 Rehmanniae Radix Preparata 4.0 升麻 Cimicifugae Rhizoma 2.0 烏藥 Linderae Radix 8.0 龍眼肉 Longanae Arillus 6.0 木香 Aucklandiae Radix 4.0 阿膠 Anisi Corii Colla 50.0 益智仁 Alpinia Oxyphylla 2.0 Table 3. Components of Gami-danggui-san 3 (G3) Components of herb preparation Amount (g) 白朮 Atractylodes macrocephala Koidzumi 8.0 白芍藥 Paeoniae Radix Alba 6.0 當歸 Angelicae Gigantis Radix 6.0 川芎 Cnidium Officinale Makino 6.0 黃芩 Scutellaria baicalensis 4.0 黃耆 Astragalus membranaceus 6.0 人蔘 Ginseng Radix 4.0 白茯苓 Poria cocas Wolf 4.0 甘草 Glycyrrhiza uralensis 4.0 杜仲 Eucommia ulmoides Oliver 4.0 續斷 Dipsaci Radix 4.0 枸杞子 Lycium Chinense Miller 4.0 陳皮 Citri Unshii Pericarpium 8.0 貢砂仁 Amomum villosum 4.0 香附子 Cyperi Rhizoma 8.0 熟地黃 Rehmanniae Radix Preparata 4.0 升麻 Cimicifugae Rhizoma 2.0 烏藥 Linderae Radix 8.0 龍眼肉 Longanae Arillus 8.0 木香 Aucklandiae Radix 4.0 阿膠 Anisi Corii Colla 50.0 益智仁 Alpinia Oxyphylla 4.0 27
조산방지및자궁수축관리의한의학적치료 Table 4. Components of Antae-eum (At) Components of herb preparation Amount (g) 黃耆 Astragalus membranaceus 8.0 白朮 Atractylodes macrocephala Koidzumi 8.0 當歸 Angelicae Gigantis Radix 6.0 川芎 Cnidium Officinale Makino 6.0 白芍藥 Paeoniae Radix Alba 6.0 黃芩 Scutellaria baicalensis 6.0 人蔘 Ginseng Radix 4.0 白茯苓 Poria cocas Wolf 4.0 甘草 Glycyrrhiza uralensis 4.0 熟地黃 Rehmanniae Radix Preparata 4.0 杜沖 Eucommia ulmoides Oliver 4.0 續斷 Dipsaci Radix 4.0 香附子 Cyperi Rhizoma 4.0 陳皮 Citri Unshii Pericarpium 4.0 砂仁 Amomum villosum 4.0 白荳蔲 Amomum kravanh Pierre ex Gagnep. 4.0 蘇葉 Perilla frutescens Britton var. acuta 3.0 升麻 Cimicifugae Rhizoma 2.0 Ⅲ. 고찰 2012년미국산부인과학회 (ACOG) 에서는조기진통에대해 임신 37주이전에자궁경부의변화를동반하는규칙적인자궁수축 으로정의하였으며 3) 임상적으로는규칙적인자궁수축과함께자궁경부의상태변화 (effacement of dilation) 가있는경우, 혹은규칙적인자궁수축과함께자궁경부가최소 2 cm 이상개대되었을때조기진통이라고진단할수있다 4). 또한조산은임신기간을기준으로하여완료된 37주이전의분만으로정의된다 5). 자궁수축억제제에는 β-agonist(ritodrine, terbutaline), MgSO 4, Calcium channel blocker, NSAID(COX inhibitor), Oxitocin receptor antagonist(atosiban), NO 등의약제등이있는데대부분부작용의잠재 적인위험을가지고있으며, 다수의약물치료와약물이외의치료를사용하여조기진통을억제하려는시도를하였지만어떤것도완벽히효과적인것은없었다. 이러한불확실성때문에미국산부인과학회는규칙적인진통과명확한자궁경부의변화혹은상당한정도의자궁경부확장이나소실이동반된경우에만자궁수축억제를고려해야한다고하였으며 1), Gyetvai K 등은자궁수축억제제사용이단기간의임신기간연장에는효과적이지만임신 30주미만, 32주미만, 37주미만의조산과주산기사망률을감소시키지못하였으며각각의약제마다부작용이있으므로자궁수축억제제의사용의일차적목적은조산의예방이아닌태아폐성숙을위한스테로이드사용및산모의 3차기관의이송을위한일정시간의확보에있다고하였다 6). 28
J Korean Obstet Gynecol Vol.29 No.4 November 2016 본증례에사용된 ritodrine 은 β-agonist 로서자궁수축을억제하는효과를가지는데, 대표적인부작용은심박수증가, 일시적고혈당증, 저칼슘혈증, 심장부정맥, 폐부종, 심근허혈등이있다 7). 미국에서는안정성의문제가제기되어 ritodrine 을더이상조산의치료목적으로사용하지않으며 1) 유럽의약품청 (European Medicine Agency) 에서는정주제의사용기한을 22-37 주임신주수에서 48시간동안사용하는것으로제한하였으며 8) 국내에서는식약처에서 EMA의평과결과에따라산모및태아에미치는심혈관계부작용으로경구용은더이상산과적응증에사용되지말아야하며 Ritodrine 정맥주사는임신 22-37 주사이최대 48시간동안조기진통억제의목적으로만사용가능함을권고하였다 9). 한의학적으로조기진통과조산은姙娠腹痛, 胎動不安, 胎漏, 小産, 胞阻, 胎衣早破등의범주에속하고원인으로는모체의腎虛, 氣血虛弱, 血熱, 부모의先天精氣不足에의해氣血不調하여衝任에손상을미치거나跌打損傷, 독약독물의섭취, 임신중질환에이환되는등胞宮병변이모체기혈에영향을미치고胎元이손상되면胎元不固가유발된다고하였다. 치료원칙은반드시胎元을고려하는安胎法이요구되는데, 養血淸熱安胎, 理脾安胎, 開鬱順氣安胎, 固腎安胎의네가지안태방법을중심으로임신부의체질과병정을참고하여합리적으로적용하여야한다 10). 주단계는淸熱하는황금과健脾燥濕하는백출을安胎의聖藥이라칭하였고 11) 金匱要略 에기원한養血淸熱健脾하는당귀산과健脾溫中養胎하는백출산은 임신중대표적인상복약이며 10) 안태음또한임신관련질환을치료하는주요처방이다 12). 본연구의환자는 39세의불임기왕력과 6번의유산기왕력이있는여성으로임신을준비하는과정부터본원외래수진지속하다로컬산부인과에서 IVF 시술을통해 2013년 4월말임신을확인하였다. 이후환자는유산예방및임신중건강관리를위해본원내원지속하였고, 저자들은침구치료와함께난임과유산의기왕력을고려하여가미당귀산 (G1) 과안태음 (At) 를투여 (G1 아침, 저녁식후 30분, At 점심식후 30분 ) 하며경과를관찰하였다. 임신 23주차부터환자는간헐적인아랫배뭉침및복통이빈번히발생하여기존처방의복용횟수를증량 (G1 매식후 30분 3회, At 취침전복용 ) 하였고, 임신 26주경에는배우자전근발령으로원거리이주를준비하며심신의부담가중을호소하여養血安神작용의용안육을증량하고溫腎益氣효능의익지인을추가한처방 (G2 매식후 30분 3회, At 취침전복용 ) 하였다. 재태주수 28주 1일차에환자는점액상질분비물의증가와규칙적인자궁수축을주소로산부인과수진과정에서조기양막파열이의심되었으나 Actim test 상음성확인되어안정가료와경과관찰을권고받았다. 이에溫腎固胎작용이강화될필요가있다는판단으로익지인을증량한처방 (G3, 매식후 30분 3회 ) 과안태음의취침전복용을지속하였다. 임신 30주차에이르러자궁경부의길이가 14 mm로단축되었는데이러한자궁경부무력은모든분만의 0.05-2% 에서 29
조산방지및자궁수축관리의한의학적치료 발생하며조산의 10%, 임신중반기태아손실의약 15% 의원인이된다. 정상적인자궁경부의길이가 24-28 주사이는평균 35 mm, 만삭이되면대략 30 mm 정도를유지하는것을고려해볼때 1) 자궁경부무력이환자가호소한조기진통의원인으로작용하였을것이라추정된다. 임신 33주경태동이감소하고자궁경부가 50% 가량소실되며숙화된양상으로환자는연고지인근대학병원에입원하였고자궁수축억제치료과정에서한약복용 (G3, At) 을병행하였다. 환자는임신 34주 3일차에소량의갈색질출혈을보였고, 그에따른 ritodrine 증량과항생제처치를병행하며일시적인흉민증상을호소하였으나출혈은재현되지않았고 ritodrine 투여량을낮추어흉부불편감역시소실되었다. 36주차까지일중간헐적인자궁수축이보고되었으나임신 37 주차에이르러자궁경부개대및진통을수반한자궁수축관찰되지않아한약복용및입원치료를종결하였다. 이후대학병원외래를통해경과를관찰하다 39(+3) 주에정상자연분만하였다. 본증례의주요처방으로활용된가미당귀산 13) 은장중경의 金匱要略 14) 에기원한금궤당귀산을모체로한다. 금궤당귀산은당귀천궁작약황금백출로구성된방제로서 婦人姙娠宜常服當歸散主之 姙娠常服卽易産胎無苦疾 라하여임신전반의모자건강유지를도와만기분만을도모하는처방으로알려져있다. 백출과황금은健脾, 淸陽하여安胎의主藥이되고, 당귀와천궁은血滯를소통시키며작약은血脈의열을내려습관성유산, 胎動不安, 胎漏, 下血등의병증에통용한다 15. 실험적으로는박 16) 이금 궤당귀산을투여한백서의자궁근에서자궁수축력과자발운동빈도가저하되었음을보고하였으며, 문 17) 은금궤당귀산전탕액이백서의임신율과출산율을증가시키며자궁근수축과자발운동을억제하고혈액순환을촉진, total ATPase 활성화로자궁의신진대사를촉진하고 phosphatase 활성을촉진하여자궁근의이완을유발하고태반기능을촉진시킨다고보고한바있다. 가미당귀산은금궤당귀산의방제를토대로인삼, 백복령, 감초, 황기를가하여補氣固胎하고, 숙지황, 두충, 속단, 구기자의補肝腎작용과진피, 공사인, 소엽의調氣安胎작용을더해功效를강화하였다. 여기에맥문동과오미자를가하여滋陰潤燥, 收斂固澁하고, 承擧하는효능의승마를가하여胎氣不安을개선한다. 또한開鬱順氣하는향부자와오약이散鬱行氣하는목향과배합되어下焦의기를순행시켜지통하는효능을더하고, 養血安神하는용안육과滋陰止血하는아교를가해胎漏를예방하며, 안태작용을강화하였다. 요컨대가미당귀산은금궤당귀산보다補氣養血, 健脾安胎의효능을높인처방으로임상에서脾胃虛弱, 陰虛內熱, 血熱등으로변증된胎動不安을치료하고유산을예방하고태아의발육을양호하게한다 12. 여기에저자들은溫脾暖腎固氣澁精하는익지인을가해固胎효능강화를도모하였다 18. 또한보조적으로사용한안태음 15,19) 은補血의기본방인사물탕에安胎의주약인백출황금을위주로, 調氣安胎작용의사인, 진피, 諸藥을조화하는감초로구성되어태기불안, 태동복통, 임신중의 30
J Korean Obstet Gynecol Vol.29 No.4 November 2016 하혈, 임신중감모등임신중질환의통용방으로꼽힌다 20). 본연구는비록단일증례로서그유효성의보편적해석에한계가분명하나, 한양방병용치료가장기적으로지속된조기자궁수축및조산징후를개선하고, 태아의정상적인발육을도와만기분만을이루는데기여할수있음을보여주었다는점에서임상적가치가크다. 조기진통에상용되는 ritodrine 이 48시간내의분만과 7일이내분만수는감소시키나 37주이전의조산율을감소시키지못한다는기존의연구결과 21) 를참작할때한약의병용이자궁수축억제및만기임신의유지에일정부분기여하였을것으로추측된다. 또한, 본증례를통해난임과다수의유산의기왕력을가진여성에대한장기적인한약투여및양약병행이부작용이나합병증없이만기자연분만을이루어냄을확인할수있었다. 본연구에앞서조등 22) 은한양방병행치료로조산고위험군의조기진통을개선한 1례를보고하였는데, 조산의과거력이있으면서자궁경부가 2 cm 정도로짧아진환자에 19주부터 34주까지 progesterone 질정을매일투여하며안태음을병용한결과산모와아기에부작용이나합병증없이 38주차분만을하였음을보고하였다. 조기진통을관리하고조산을예방하는한의학적임상연구는이처럼극히부족한실정으로, 지속적인증례집적과약리학적기전연구를통해유효성과안전성을입증할필요가있다. 난임인구증가와고령임신율이늘어나는사회적흐름상임신중건강관리와질환중재에있어한의학적치료가직간접적으로기 여할수있는근거를밝히고확보하는노력이경주되어야할것이다. Ⅳ. 결론 저자들은난임의기왕력을가진 39세임산부에대하여재태주수 23주경발생한조기자궁수축및복통의관리를목적으로가미당귀산과안태음을투여하였다. 자궁경부변화와조기진통에대한산부인과입원치료과정에서한약복용을병행한결과, 주요증상이개선되어 39주 3일차에환자는자연분만에성공하였다. 본증례는조기진통을비롯한조산의징후에대해자궁수축억제제와한약의병용으로증상을개선하고만기분만에기여할수있음을시사한다. 향후, 조기진통을관리하고조산을예방하는보조요법내지단독치료로서한약의안전성과효능을입증할수있는임상증례및연구의집적이필요하다. Received : Oct 13, 2016 Revised : Nov 11, 2016 Accepted : Nov 16, 2016 Reference 1. Beckmann CR, et al. Obstetrics and Gynecology. 7 th ed. New York:Wolters Kluwer. 2013:546-7, 561-87. 2. The American College of Obstetricians and Gynecologists. Practice bulletin no. 130: Prediction and prevention of Preterm Birth. Obstetrics & Gynecology. 2012; 120(4):964-73. 31
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