This document provides information on the herbal medicine Crotonis Semen (Croton seed), including its common name, botanical name, toxicity level, indications for use, pharmacological actions, cautions, and major constituents. It states that Croton seed is very toxic and carcinogenic, especially in its oil form, which can promote radiation transformation in animal studies. While used topically for conditions like scabies and eczema, it requires pretreatment and caution against use in pregnancy due to its toxicity.

1. June-Seek Choi, M.D., PhD
Korean Motherisk Program
Div. of Maternal-Fetal Medicine,
Dept. of OB & GYN,
Cheil General Hospital & Women’s Healthcare Center

2.  Definition
 Herbal medicines relate to uterine contraction (in animal study vs human)
 Herbal medicines relate to spontaneous abortion (in animal study vs
human)
 Data of pregnancy outcomes of herbal medicine exposure in Korean
Motherisk Program
 Summary

3.  방제를 구성하고 있는 각각의 생약 혹은 생약에 함유되어 있는
여러 성분들에 대한 약리 작용을 확립하고 그것의 토대 위에 방
제의 약리를 완성 시키는 것이다 .

4.  한방 약물은 한약의 기본
 한약은 천연물 그대로 혹은 건조 등의 간단한 조작을 가한 후에 임
상에 사용
 다수의 생리활성을 가지는 물질로 구성된 매우 복잡한 복합체
 동일한 한약 중에 서로 상반된 약리작용을 가지는 물질이 공존

5.  한약에 함유되어 있는 개개 성분으로 그 효능을 파악하는 것이
아니라 임상적 경험에 비추어 인체와 약물과의 상호 작용에 의
해 표출되는 점으로 분류
 약성 이론 : 사기 , 오미 , 승강부침 , 귀경

6.  4 기 : 약물이 사용되는 질병이 어떤 상태에 놓여 있는지 또는
약물에 대한 환자의 반응이 어떠한지 등에 따라 분류
[ 한성 ( 寒性 ), 열성 ( 熱性 ), 온성 ( 溫性 ), 양성 ( 凉性 )]
 예 : 열성질환을 치료할 수 있는 약물은 한성의 약물로 분
류하고 ,
한성 질환을 치료할 수 있는 약물은 열성의 약물로 분류

7.  5 미 : 산미 ( 酸味 ), 고미 ( 苦味 ), 감미 ( 甘味 ), 신미 ( 辛味 ), 함미 ( 鹹味 )
다섯 종류의 맛은 한약 그 자체가 가지는 맛을 의미하는 것보다는 인체
에서 약물의 작용형태의 표출
 오미는 약물이 가지는 작용 또는 치료작용과 관련성이 매우 깊다 .
하나의 약물이 한가지 맛만 가지고 있는 것이 아니라 여러 가지 맛을 가
지고 있는 것이 대부분이다 .
 승강부침 : 질병의 위치가 위에 있거나 밖에 있는 경우는 승과 부의 성질
을 가지는 약물을 사용한다 .

8.  귀경 : 약물이 특정한 장부와 경락에 작용하여 질병을 치료
한다는 개념으로 약물의 치료작용이 나타나는 위치를 말함 .
예 : 한 ( 寒 ) 한 약물이 청열 ( 淸熱 ) 작용을 가지지만 약물의
작용부위가 서로 다르다는 것이다 . 즉 , 어떤 약물은 폐의 열
을 청열시키고 또 다른 약은 위의 열을 청열시킨다 .

9.  상수 (Synergism)
 상사 (Mutual enhancement): 황기와 방기가 비허가 있는 자의 부종 치료
 상외 (Mutual inhibition)
 상살 (Mutual detoxication): 생강이 반하의 독성을 감소 시킴
 상반 (Incompatibility)
 상오 (Mutual antagonism)
이로움보다는 해가 있는
것으로 배합에 금기

10.  양약과 한약의 동시 복용으로 작용이 증강되는 경우 :
Warfarin+ 은행엽 , 마늘 , 당귀 , 혹은 단삼
 항응고 작용이 증가
감초 +corticosteroid 제제 corticosteroid 제제의 작용 증가
 작용이 감소하는 경우 :
소시호탕 +prednisolone prednisolone 의 혈중 농도 감소

11.  한약은 단일제 또는 복합제의 형태 ( 방제 ) 로 액상 ( 액제 )
또는 산제로 투여되는 경우가 대부분 .
 한약은 함유되어 있는 주성분에 의한 약리작용에 의해 약효
가 발현되는 것이 아니라 이러한 성분이 1 차적으로 장내에
서 대사가 이루어진 다음 흡수됨
 한약은 경구 투여 시 효과가 발현되지만 정맥주사 등의
형태로 투여되는 경우 , 약효 발현에 문제가 있을 수 있다 .

12.  다 성분계의 한약의 경우 어떠한 성분이 태반을
통과하는지 또는 태반을 전혀 통과하지 않는지
등에 대한 연구는 거의 전무하다 .
 임신부에게 약물의 사용은 태반으로 약물의 이행
이 어느 정도 이루어질 지에 대한 것이 가장 큰
문제가 아닐 수 없다 .
 대부분의 약물은 정도의 차이는 있으나 모유로
분비되며 유아에게 부작용을 일으킬 수 있어 수
유 중인 경우는 다량의 약물 복용에 주의 하여야
하며 , 특히 Anthraguinone 의 경우 유아에게 중독
을 일으킬 수 있으므로 이를 함유하고 있는 처방
의 복용 시에는 주의 ( 노회 , 대황 )
C15H10O5

13.  Chinese Herbal Nephropathy (CHN): 한약재 복용으로 인한
신부전 환자의 발생
 대만 독성 센터 : 총 273 건의 독성 관련 중 22 건이 사망 ,
이중 47% 가 한약에 함유되어 있는 독성에 기인함 .
 마황 심혈관 질환 ( 미국 , 호주 )
 단삼 출혈을 가중 시킴
 육두구 사망 ( 유럽 )

14. Western Medicine Drug interaction and results
Angelicae Gigantis Radix( 당귀 ), Ginseng
Radix, Extract of Ginkgonis Germen
Warfarin, Aspirin Decreased International Normalized Ratio
and anticoagulant effects
Glycyrrhizae Radix ( 감초 ) Digoxin, Furosemide,
Hydrochlorothiazide
Licorice and digoxin may result in
increased risk of digoxin toxicity. Licorice
and diuretics may result in increased risk
of hypokalemia and/or reduced
effectiveness of the diuretic.
Ginseng Radix, Ephedrae Herba ( 마황 ) ,
Zinberis Rhizoma Recens ( 생강 )
Glyburide, Insulin, Metformin Severe Hypoglycemia due to increase
insulin
Glycyrrhizae Radix ( 감초 ) Metoprolol, Verapamil, Diltiazem Decrease drug effect and Hypertension
Allii Bulbus ( 마늘 ) Isoniazid Decrease serum concentration of isoniazid
Zinberis Rhizoma Recens ( 생강 ) Nifedipine, Verapamil, Diltiazem Severe Hypotension
Extract of Ginkgonis Germen Thiazide Hypertension
Extract of Ginkgonis Germen, Ephedrae
Herba ( 마황 )
Anticonvulsant Increase risk of seizure
Ginseng Radix Azathioprine, Cyclosporine,
Corticosteroid
Decrease effect of immunosuppressant
Ephedrae Herba ( 마황 ) Pseudoephedrine, MAO inhibitor Hypertension
Ephedrae Herba ( 마황 ) Amiodaron, Procainamide, Quinidine Prolongation of QT interval
Park YC et al 2011

15. Herbs Toxicity Herbs Toxicity
Artemisiae Argyi Folium ( 황해쑥 ) Slightly toxic 백화자 Toxic
초오두 Slightly toxic 경대극 Toxic
조휴 Slightly toxic Meliae Cortex ( 고련피 ) Toxic
Toosendan Fructus ( 천련자 ) Slightly toxic Sulphur ( 유황 ) Toxic
Carpesii Fructus ( 학슬 ) Slightly toxic Agkistrodon ( 살모사 ) Toxic
Euphorbiae Pekinesis Radix ( 대극 ) Slightly toxic Pharbitidis Semen ( 견우자 ) Toxic
Tribuli Fructus ( 백질려 ) Slightly toxic Calomelas ( 경분 ) Toxic
금성자 Slightly toxic Scorpio ( 전갈 ) Toxic
Picrasmae Lignum ( 고목 ) Slightly toxic Sophorae Subprostratae Radix ( 산두근 ) Toxic
Armeniacae Semen ( 고행인 ) Slightly toxic Phytolaccae Radix ( 상륙 ) Toxic
남학슬 Slightly toxic Hirudo ( 수질 ) Toxic
Cnidii Fructus ( 사상자 ) Slightly toxic Arisaematis Rhizoma ( 천남성 ) Toxic
Eupolyphaga ( 자충 ) Slightly toxic Scolopendra ( 오공 ) Toxic
Evodiae Fructus ( 오수유 ) Slightly toxic 선모 Toxic
소엽련 Slightly toxic 향가피 Toxic
아담자 Slightly toxic Realgar ( 웅황 ) Toxic
Gleditsiae Fructus ( 조협 ) Slightly toxic 앵속각 Toxic
Typhonii Rhizoma ( 백부자 ) Toxic Genkwa Flos ( 원화 ) Toxic
Ginkgo Semen ( 백과 ( 은행 )) Toxic Cinnabaris ( 주사 ) Toxic
Pinelliae Rhizoma ( 반하 ) Toxic Crotonis Semen ( 파두 ) Very toxic
Bufonis Venenum ( 섬수 ) Toxic 파두상 Very toxic
Dichroae Radix ( 상산 ) Toxic Mylabris ( 반묘 ) Very toxic
Aconiti Tuber Laterale ( 부자 ) Toxic Aconiti Ciliare Tuber ( 초오 ) Very toxic
Lacca Sinica Exsiccata ( 건칠 ) Toxic Aconiti Radix ( 천오 ) Very toxic
Kansui Radix ( 감수 ) Toxic Strychni Semen seu nux Vomicae Semen ( 마전자 ) Very toxic

16. Herbal name Common name Korean common
name
Binominal name Toxicity
Crotonis Semen Croton seed 파두 Croton tiglium L. (Euphorbiaceae) Very toxic
Mylabris Mylabris 반묘 1. Mylabris cichorii Fabricius
(Meloidae)
2. Mylabris phalerata Pall.
(Meloidae)
3. Mylabris sidae Fabricius
(Meloidae)
Very toxic
Aconiti Ciliare Tuber Wild aconite (tuber) 초오 Aconitum ciliare DC.
(Ranunculaceae)
Very toxic
Aconiti Kusnezoffii
Radix
Wild aconite (tuber) 초오 Aconitum kusnezoffii Reichb.
(Ranunculaceae)
Very toxic
Aconiti Proliferum
Radix
Wild aconite (tuber) 초오 Aconitum proliferum Nakai
(Ranunculaceae)
Very toxic
Aconiti Radix Wild aconite (tuber) 초오 Aconitum triphyllum Nakai
(Ranunculaceae)
Very toxic
Aconiti Radix Aconite main tuber 천오 1. Aconitum carmichaeli Debx.
(Ranunculaceae)
2. Aconitum chinense Paxton
(Ranunculaceae)
Very toxic
Strychni Semen seu nux
Vomicae Semen
Nuxvomica 마전자 Strychnos nux-vomica L.
(Loganiaceae)
Very toxic
The Pharmacopoeia Commission of PRC, 2000

17.  Indications: Scabies ,Eczema, Abscess
 Pretreatment: Croton seed without husk, Croton seed plaster,
Croton seed frost-like powder
 Pharmacological action: increase GI movement (inhalation,
human), increase cell differentiation (in vitro)
Hanyak yangnihak 2001
 Toxicity: Croton oil has the ability to promote radiation
transformation. It is very toxic and carcinogenic (animal study).
Huang, K.C., The pharmacology of Chinese herbs II, CRC press, 1999.
 Caution: Not use in pregnancy
 Formula in Korea: 35/ OTC in Korea:1
www.tradimed.co.kr/www.kimsonline.co.kr
Constituents
4-alpha-Deoxy-5-hydroxy-20-acetoxy-12-O-(2-methyl-amino-benzoyl)phorbol
4-alpha-Deoxy-5-hydroxy-12-O-(N-deca-2,4,6-trienoyl)phorbol
4-alpha-Deoxy-12-O-(2-methylbutyryl)-phorbol-13-acetate
4-alpha-Deoxy-12-O-tiglyl-phorbol-13-acetate
4-alpha-Deoxy-12-O-tiglylphorbol-13-isobutyrate
4-alpha-Deoxy-phorbol-13-acetate
4-alpha-Phorbol
Angelic acid
Cocacinogen A1
Cocacinogen A2
Cocacinogen A3
Cocacinogen A4
Cocacinogen B1
Cocacinogen B2
Cocacinogen B3
Cocacinogen B4
Cocacinogen B6
Cocacinogen B7
Crotin I
Crotin tiglium lectin
Crotonoside
4-Deoxyphorbol tiglate acetate
4-Deoxy-5,13,20-triacetoxy-12-O-(n-deca-2,4,6-trienoyl)phorol
4,20-Dideoxy-5-hydroxy-12-O-(n-deca-2,4,6-trienoyl)-phorbol-13-acetate
12-O-Acetylphorbol-13-acetate
12-O-(alpha-Methyl-butyryl)-phorbol-13-decanoate
Octyl acetate
12-O-[2-Methyl-amino-benzoyl]-4-alpha-deoxy-5-Hydroxy-phorbol
12-O-[2-Methyl-amino-benzoyl]-4-alpha-deoxy-phorbol-5,13,20-triacetate
12-O-[2-Methyl-amino-benzoyl]-4-deoxy-5-hydroxy-phorbol-13-acetate
12-O-[2-Methyl-amino-benzoyl]-4,20-dideoxy-5-hydroxy-phorbol
12-O-[2-Methyl-amino-benzoyl]-4,20-dideoxy-5-hydroxy-phorbol-13-acetate
12-O-[2-Methyl-amino-benzoyl]-4,20-dideoxy-phorbol-5,13-diacetate
12-O-(2-Methyl-butyryl)-phorbol-13-acetate
12-O-(2-Methylbutyryl)-phorbol-13-isobutyrate
12-O-[n-Deca-2,4,6-trienoyl]-4-deoxy-5-hydroxy-phorbol-13-acetate
12-O-[n-Tetradecanoyl]-4,20-dideoxy-5-hydroxy-phorbol-13-acetate
12-O-Tigloylphorbol-13-(2-methyl)-butyrate
12-O-Tiglylphorbol 13-isobutyrate
12-O-Tiglylphorbol-13-acetate
Phorbol
Phorbol 13-butyrate 12-tiglate
Phorbol 13-caprylate 12-acetate
Phorbol 13-caprylate 12-tiglate
Phorbol 13-linoleate 12-acetate
Phorbol 13-myristate 12-acetate
Phorbol-13-acetate
Phorbol-12-tiglate
www.tradimed.co.kr

18.  Indications: Rabies, Scabies, Mercury intoxication, Hepatic
cirrhosis due to Clonorchiasis, Tuberculosis, Tuberculous
lymphadenitis, Eczema, Abscess, Atopic dermatitis, Fever and
chill
 Pretreatment: parched Mylabris with rice
 Pharmacological action: intoxication of snake venom,
increase urination, increase abortion Dong-Eui-Bo-Gam
 Caution: Not use in pregnancy
 Formula in Korea: 4 www.tradimed.co.kr
Cantharidin
• Phytochemical group: Monoterpenoid
• Molecular weight: 196.2
• Cantharidin may cause symptoms from dermal inflammation to
blisters. If ingested, it may cause irritation and burning of the
mouth, severe vesication of the upper GI tract, diarrhea, and
kidney and cardiovascular damage.
• Ii is a weak experimental animal carcinogen.
www.thomsonhc.com, www.tradimed.co.kr

19.  Indications: Beriberi edema, Cold limbs, Myalgia, Cold type
dysentery, Epigastric pain, Child epilepsy, Chronic osteomyelitis,
Hemiparalysis, Hemiplegia, Migratory arthropathy
 Pretreatment: processed Wild aconite tuber
 Pharmacological action: analgesics, anti-inflammation,
vasodilatation, and local anesthetic action in animal study
 Toxicity: Toxic symptoms include bradycardia and irregular
rhythm. Nausea and vomiting may occur, as well as spasm of
extremities and cardiac arrhythmias. The intestinal absorption of
the alkaloids is relatively fast. Because of this, gastric lavage is
recommended in case of overdose.
Huang, K.C., The pharmacology of Chinese herbs II, CRC press, 1999.
 Formula in Korea: 16 / OTC in Korea: 10
www.tradimed.co.kr/www.kimsonline.co.kr
Aconiti Ciliare Tuber
Aconiti Kusnezoffii Radix
Constituents of Aconiti Ciliare Tuber
& Aconiti Porliferum Radix
Aconitine
Hypaconitine
Mesaconitine
Constituents of Aconiti Kusnezoffii Radix
3-Acetylaconitine
Aconitine
Acontine
Beiwutine
Bullatine A(structure unknown){formula: C(21)H(31)NO(2)}
Bullatine C
Chasmanine; 6-Epimer
Denudatine
Hypaconitine
Lepenine
Mesaconitine
Neoline
Pendulin
Songorine
Aconitine
• Phytochemical group: Alkaloid
• Molecular weight: 645.75
• Bioactivity: bind to neurotoxin binding site 2 of α-subunit of
Na+
channel activation of Na+
channel , increase intracellular
Ca2+
 arrhythmia Hanbang Yangnihak 2010
• Toxicity: Very toxic if swallowed or by skin absorption.
Human systemic effects by ingestion. LD50 (mus, orl) 1 mg/kg, LD50
(mus, ivn) 0.175 mg/kg, exp. lethal doses by subcutaneous route reported. LD50 in
mice (mg/kg): 0.166 i.v.; 0.328 i.p.; approx 1 orally (Dybing); also reported as LD50
in mice (mg/kg): 1.8 orally, 0.270 s.c.; 0.380 i.p.; 0.12 i.v. (Sato).
www.tradimed.co.kr

20.  Indications: Beriberi edema, Myalgia, Cold type dysentery,
Paresthesia, Child epilepsy, Epigastric pain, Chronic
osteomyelitis, Vomiting and Diarrhea, Testiculitis
 Pretreatment: processed Aconite main tuber
 Pharmacological action: analgesics, anti-inflammation,
vasodilatation, and local anesthetic action in animal study
 Caution: not use in pregnancy
 Toxicity: headache, paralysis of tongue, paraplegia, pain on
upper extremity, nausea, vomiting, respiration difficulty, coma
Hanyak yangnihak 2001
 Formula in Korea: 1/ OTC in Korea: 5
www.tradimed.co.kr/www.kimsonline.co.kr
Constituents of Aconitum carmichaeli Debx.
14-Acetyltalatizamine
Aconine
Aconitan A
Aconitan B
Aconitan C
Aconitan D
Aconitine
Aldohypaconitine
Beiwutine
Benzoylaconine
Benzoylhypaconine
Benzoylmesaconine
Chuanfumine
Chuan-Wu base A (structure unknown)(Tertiary base with 20H, 20Me and one N-Et groups.)
Chuan-Wu base B(structure unknown){formula: C(32)H(35)NO(4)}
Coryeine
Coryneine
Fuzitine
Hokbusine A
Hokbusine B
Hypaconitine
Ignavine
Isodelphinine
Isotalatisamine
Isotalatizamine
Karakoline
Lipoaconitine (R = linoleoyl, palmitoyl, oleoyl, stearoyl, linolenoyl)
Lipodeoxyaconitine (R = linoleoyl, palmitoyl, oleoyl, stearoyl, linolenoyl)
Lipohypaconitine (R = linoleoyl, palmitoyl, oleoyl, stearoyl, linolenoyl)
Lipomesaconitine (R = linoleoyl, palmitoyl, oleoyl, stearoyl, linolenoyl)
Mesaconitine
Neojiangyouaconitine
Neoline
Salsolinol
Senbusine A
Senbusine B
Senbusine C
Songarine
Songorine
Talatizamine
www.tradimed.co.kr
Constituents of Aconitum chinense
Paxton
Violdelphin

23. Hanyak yangnihak 2001

24. Herbal name Common name Korean name Binominal name
Lycii Radicis Cortex Lycium root bark 지골피 1. Lycium chinense Mill. (Solanaceae)
2. Lycium barbarum L. (Solanaceae)
Dianthi Herba Dianthus 구맥 1. Dianthus chinensis L. (Caryophyllaceae)
2. Dianthus superbus L. (Caryophyllaceae)
Aurantii Fructus Immaturus Unripe bitter orange 지각 Citrus aurantium var. daidai Makino (Rutaceae)
Crataegi Fructus Crataegus fruit 산사육 Crataegus pinnatifida Bunge (Rosaceae)
Typhae Pollen Typha pollen 포황 Typha angustifolia L. (Typhaceae)
Cnidii Rhizoma Cnidium (root) 천궁 Cnidium officinale Makino (Umbelliferae)
Chuanxiong Rhizoma Cnidium rhizome 천궁 Ligusticum chuanxiong Hort. (Umbelliferae)
Ligustici Rhizoma Ligusticum rhizome 천궁 Ligusticum wallichii var. officinale Yook (Umbelliferae)
Corydalis Tuber Corydalis (tuber) 현호색 1. Corydalis ternata Nakai (Papaveraceae)
2. Corydalis ambigua Chamisso et Schlechtendal
(Papaveraceae)
3. Corydalis decumbens Pers. (Papaveraceae)
4. Corydalis nakaii Ishidoya (Papaveraceae)
Leonuri Herba 1. Chinese motherwort
2. Motherwort
익모초 1. Leonurus sibiricus L. (Labiatae)
2. Leonurus heterophyllus Sweet (Labiatae)
Carthami Flos Carthamus flower (safflower) 홍화 Carthamus tinctorius L. (Compositae)
Angelicae Gigantis Radix Dang gui root 당귀 Angelica gigas Nakai (Umbelliferae)
Angelicae Sinensis Radix Dang gui root 당귀 Angelica sinensis (Oliv.) Diels (Umbelliferae)
Angelicae Acutilobae Radix Dang gui root 당귀 Angelica acutiloba Kitagawa (Umbelliferae)
Cassiae Semen Feotid cassia (seed) 결명자 1. Cassia tora L. (Leguminosae)
2. Cassia obtusifolia L. (Leguminosae)

25.  Indications: Secondary amenorrhea, Muscle spasm,
Hemiplegia, Seborrheic dermatitis, Persistent headache,
Metrorrhagia, Thoracoabdominal pain, Consumptive disease,
Abnormal menstruation, Syncope, Confusion, Pelvic mass,
Gingival bleeding, Gingivitis, Paresthesia, Pneumonia
 Pharmacologic action: vasodilatation, analgesics, anti
inflammation, and uterine contraction in animal
Hanyak yangnihak 2001

Formula in Korea: 25
www.tradimed.co.kr

OTC in Korea: 1,186
www.kimsonline.co.kr
Constituents of Cnidii Rhizoma
Adenosine
Apiol
Butylidenephthalide
Butylphthalide
Chlorogenic acid
Cnidilide
Coniferyl ferulate
Ferulic acid
Ligustilide
Ligustilidiol
Neocnidilide
Pregnenolone
Senkyunolide
Senkyunolide B
Senkyunolide C
Senkyunolide D
Senkyunolide F
Senkyunolide G
Senkyunolide H
Senkyunolide I
Senkyunolide J
Umbelliferose
Vanillin
Vitamin C
www.tradimed.co.kr

26. Korean Motherisk Program, unpublished
Number %
Spontaneous
abortion
2/80 2.5
IUFD 4/78 5.1
Preterm birth 8/78 10.3
LBW 3/78 3.8
Malformation 2*/78 2.6
* Mega-cysterna magna(11mm)
Left ventriculomegaly of cerebrum (11mm)
Median (Min.-Max)
Last exposure weeks 4.6 (0.6-12.4)
Duration of exposure (days) 2.0 (1.0-59.0)
Dosage (mg/day) (42/80) 1,250 (9.3-9,000)

27. June-Seek Choi1,2
, Jung-Yeol Han1,2
, Hyun-Kyong Ahn1,2
, Hyun-Mee Ryu2
, Moon-
Young Kim2
, E. Yadira Velazquez-Armenta,3
Alejandro A. Nava-Ocampo3,4
1
Korean Motherisk Program, 2
Obstetrics and Gynaecology, Cheil General Hospital & Women’s Healthcare
Centre, Kwandong University, Seoul, Republic of Korea
3
PharmaReasons, Toronto, Ontario, Canada
4
Dept. of Pharmacology & Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

28.  OBJECTIVE:
To prospectively evaluate the fetal and
neonatal outcome in women inadvertently
exposed to Cnidii Rhizoma during pregnancy.
 METHODS:
In a prospective cohort study design, 111
singleton pregnant women who were taking
Cnidii Rhizoma for various reasons, and 219
age-matched singleton pregnant women
not exposed to any potential teratogenic
agent, were followed up until delivery.

29. Cases
(n=111)
Controls
(n=219)
95% CI for the difference P-value
Age (years) 31.9 ± 4.0 31.6 ± 3.7 -1.3, 0.5 0.350
Gravidity (n) 2.2 ± 1.3 2.2 ± 1.3 -0.3, 0.3 0.797
Parity (n) 1.0 (0, 2.0) 1.0 (0, 3.0) -0.1, 0.2 0.867
Body mass index (kg/m2
) 20.8 ± 2.9 20.6 ± 3.8 -1.0, 0.6 0.662
Exposure to X-rays
a) n (%) 11 (9.9) 36 (16.4) OR= 0.6 (0.3, 1.1) 0.109
b) total dose (mSv) 0.01 (0.0006, 36.0) 0.005 (0.0006, 38.8) -7.6, 6.0 0.810
c) gestational age at exposure (weeks) 4.0 ± 2.6 3.7 ± 2.4 -2.0, 1.4 0.703
Exposure to alcohol (%)
a) n (%) 51 (45.9) 87 (39.7) OR= 1.3 (0.8, 2.0) 0.279
b) total dose (oz) 1.6 ± 1.3 1.4 ± 1.3 -0.8, 0.2 0.215
c) gestational age at exposure (weeks) 4.0 ± 2.8 4.7 ± 3.1 -0.3, 1.8 0.177
Smoking (%)
a) n (%) 9 (8.1) 23 (10.5) OR= 0.8 (0.3, 1.7) 0.487
b) cigarettes/day 5.9 ± 6.4 7.1 ± 5.4 -3.5, 6.0 0.594
c) gestational age at exposure (weeks) 3.0 ± 2.1 4.5 ± 2.9 -0.8, 3.8 0.203
Comorbidities [n (%)] 0.737
a) type 2 diabetes mellitus - 1 (0.5) -
b) hypertension 1 (0.9) - -
c) thyroid disease - 1 (0.5) -
Education level [n (%)] 0.359
a) post-secondary education 49 (44.1) 93 (42.5)
b) high school 6 (5.4) 22 (10.0)
c) not answered 56 (50.5) 104 (47.5)
Continuous data were summarized as mean ± SD or median (range), and compared between groups by either the Student t test or Wilcoxon rank sum test, respectively.
Dichotomous data were summarized as n (%) and compared by either a 2×2 chi-squared test, Fisher exact test (if n<5 in a 2×2 table), or 2×k chi-square test.

30. INDICATIONSa
n (%)
Analgesics 4 (3.6)
Anti-inflammatory enzymes 2 (1.8)
Anti-obesity preparations 4 (3.6)
Cough and cold preparations 60 (54.1)
Dermatological preparations 2 (1.8)
Functional gastrointestinal disorders 19 (17.1)
Gynecological antiinfectives and antiseptics 1 (0.9)
Psycholeptics 3 (2.7)
Others 16 (14.4)
Median (range)
Dose (mg/day)b
1250.0 (1.0 – 12000.0)
Cumulative dose (mg/kg)b
25.5 (0.03 – 5117.7)
Duration of exposure (days)c
2.0 (1.0 -366.0)
Gestational age at last dosec
4.4 weeks (1 day - 12.4 weeks)
a
According to the pharmacological/therapeutic subgroups of the ATC classification system (World Health Organization Collaborating Centre for Drug
Statistics Methodology 2011)
b
n= 59
c
n= 111

31. Cases (n= 108) Controls (n= 204) 95% CI for the difference P value
Gestational age at birth (weeks) 38.9 ± 2.4 39.4 ± 1.6 0.1, 0.9 0.044
Birth weight (g) 3,227.6 ± 506.2 3,308.8 ± 452.1 -29.2, 191.6 0.149
Birth length (cm) 49.3 ± 2.0 49.7 ± 1.8 -0.0, 0.9 0.052
Head circumference at birth (cm) 34.4 ± 1.3 34.7 ± 1.2 0.1, 0.7 0.013
Apgar score, 1 min 8.2 ± 1.4 8.3 ± 0.8 -0.2, 0.3 0.504
Apgar score, 5 min 8.9 ± 1.4 9.1 ± 0.7 -0.1,0.4 0.186
IUFD (%) 3 (2.8) 1 (0.5) OR= 5.8 (0.6, 56.4) 0.121
Major malformationsa
(%) 3 (2.8) 12 (5.9) OR= 0.5 (0.1, 1.7) 0.174
Minor malformations (%) 6 (5.6) 19 (9.3) OR=0.6 (0.2, 1.5) 0.245
NICU admission (%) 14 (13.1) 23(11.3) OR= 1.2 (0.6, 2.4) 0.651
Duration of NICU admission (days) 11.3 ± 4.1 9.8 ± 5.0 -4.7, 1.8 0.369
Breathing difficulty at birth (%) 27 (25.2) 45 (22.2) OR= 1.2 (0.7, 2.0) 0.543
Neonatal jaundice (%) 10 (9.3) 19 (9.4) OR= 1.0 (0.5, 2.2) 0.997
•a
In the case group: a baby born with megacisterna magna(13.6mm), second one with VSD, third one with bilat.inguinal hernia. In the
control group: a baby born with PDA with ASD, second one with Lt. MCDK, third one with Lt. cryptochidism and segmental cystic
dysplastic change of Rt. kidney, fourth one with ASD, fifth one with bilat. cryptochidism, sixth one with cleft palate, seventh one with
Rt. microtia, eighth one with VSD, ninth one with VSD and aortic valve prolapse, tenth one with VSD, eleventh one with Lt. microtia,
and twelfth one with bowel obstruction.
•Dichotomous data are summarized as n (%) and compared between groups by the Fisher’s exact test. Continuous data are
summarized as mean ± SD and comparisons between groups were performed by the Student t test.

32.  Our study suggests that Cnidii Rhizoma is not a major human teratogen.
 Whether the reduced gestational age at birth, birth length and head
circumference are of any clinical relevance in the neurological development of
in-utero exposed babies, remains to be elucidated in further studies.

33.  Indications: Metrorrhagia, Nasal bleeding, Postpartum faint ,
Chest pain, Bruise, Abnormal menstruation, Back and knee
pain, Peptic ulcer, Pancreatitis, Hyperhidrosis, Postpartum
lochiorrhea, Pelvic mass, Spontaneous abortion, Multiple
arthritis, Rheumatoid arthritis, Dysentery and Diarrhea
 Pretreatment: processed Corydalis tuber with vinegar
 Pharmacological action: muscle relaxation, hypotension,
anti-inflammatory action, decrease secretion of gastric acid,
anti-ulcer action , and increase contraction of extract uterus in
animal Hanyak yangnihak 2001
 Toxicity: Over dosage intoxication leads to CNS depression
and muscle relaxation.
 Caution: Not recommend in pregnancy
 Formula in Korea: 10/ OTC: 77
www.tradimed.co.kr/www.kimsonline.co.kr
Tetrahydropalmatine
•Phytochemical group: Alkaloid
•Molecular weight: 355.44
•Bioactivity: hypnotic activity exceeds that of
morphine
www.tredimed.co.kr

34. Korean Motherisk Program, unpublished
Number %
Spontaneous
abortion
1/25 4.0
IUFD - 0
Preterm birth 1/24 4.2
LBW - 0
Malformation 1*
/24 4.0
* Post axial polydactyly of left foot
Median (Min.-Max)
Last exposure weeks 5.4 (0.4-13.0)
Duration of exposure (days) 3.0 (1.0-38.0)
Dosage (mg/day) (16/25) 180 (75.0-7,200)

35.  Indications: Secondary amenorrhea, Nausea, Laceration,
Headache, Abdominal pain, Metrorrhagia, Hyperventilation,
Severe palpitation, Arrhythmia, Carbuncle, Influenza,
Abnormal menstruation, Hemorrhage without trauma, Nasal
bleeding, Syncope, Confusion, Acute pulpitis, Toothache,
Multiple arthritis, Skin tumor, Skin ulcer or Skin abscess,
Cerebrovascular accident, Dysentery and Diarrhea, Fever and
chill, Tuberculosis, Anemia, Paresthesia
 Pretreatment: parched dang gui with soil, charred dang gui,
parched dang gui with liquor, ginger processed dang gui
 Pharmacologic action: Increase blood flow to heart,
hypotension, anti ulcer effect, analgesic, anti-inflammatory
effect, and uterine contraction (aqueous extracts) in animal
Hanbang Yangnihak 2010
 Formula in Korea: 120 www.tradimed.co.kr
 OTC in Korea: 1,401 www.kimsonline.co.kr
Constituents of Angelicae Gigantis Radix
Aegelinol
alpha-Pinene(+,-)
Choline
Coumarin
Decursidin
Decursin
Decursinol
Decursinol angelate
Decusinol angelate
Gigasol
Imperatorin
Isoimperatorin
Marmesin
Nodakenetin
Nodakenin
p-Cymene
Prenyletin
Umbelliferone
www.tradimed.co.kr

36. Korean Motherisk Program, unpublished
Median (Min.-Max)
Last exposure weeks 4.6 (0.6-12.6)
Duration of exposure (days) 3.0 (1.0-59.0)
Dosage (mg/day) (34/74) 1,250 (13.5-9,000)
Number %
Spontaneous
abortion
3/74 4.1
IUFD 2/71 2.8
Preterm birth 6/71 8.5
LBW 1/71 1.4
Malformation 1*
/71 1.4
* Mega-cysterna magna(11mm)

37. Hanyak yangnihak 2001

38. Herbal name Common name Korean name Binominal name
Menthae Herba Mint 박하 1. Mentha arvensis var. piperascens Malinv. (Labiatae)
2. Mentha haplocalyx Briq. (Labiatae)
Trichosanthis Radix Trichosanthes root 천화분 Trichosanthes kirilowii Maxim. (Cucurbitaceae)
Moutan Radicis Cortex Moutan root bark 목단피 Paeonia suffruticosa Andr. (Paeoniaceae)
Lonicerae Flos Lonicera flowers 금은화 1. Lonicera japonica Thunb. (Caprifoliaceae)
2. Lonicera confusa DC. (Caprifoliaceae)
Kansui Radix Kansui root 감수 Euphorbia kansui Liou ex Wang (Euphorbiaceae)
Clematidis Radix Clematis (root) 위령선 1. Clematis mandshurica Rupr. (Ranunculaceae)
2. Clematis chinensis Osbeck (Ranunculaceae)
3. Clematis hexapetala Pall. (Ranunculaceae)
Sulphur Sulphur 유황 Sulphur
Curcumae Longae Tuber Common turmeric 강황 Curcuma longa L. (Zingiberaceae)
Curcumae Rhizoma Zedoary 아출 1. Curcuma phaeocaulis Val. (Zingiberaceae)
2. Curcuma kwangsiensis S. G. Lee et C. F. Liang
(Zingiberaceae)
Achyranthis Radix Achyranthes root 우설 1. Achyranthes japonica Nakai (Amaranthaceae)
2. Achyranthes bidentata Bl. (Amaranthaceae)
3. Achyranthes fauriei Leville et Vaniot (Amaranthaceae)
Pinelliae Rhizoma Pinellia rhizome 반하 Pinellia ternata (Thunb.) Breit (Araceae)
Aristolochiae Fructus Aristolochia fruit 마두령 1. Aristolochia contorta Bunge (Aristolochiaceae)
2. Aristolochia debilis Sieb.et Zucc. (Aristolochiaceae)
Albizziae Cortex Silk tree bark 합환피 Albizia julibrissin Durazz. (Leguminosae)
Moschus Musk 사향 1. Moschus moschiferus L. (Moschidae)
2. Moschus berezovskii Flerov (Moschidae)
3. Moschus sifanicus Przewalski (Moschidae)

39.  Indications: Common cold, Frozen shoulder, Fever
accompanied with fear, Cholera, Acute gastric cramp, Aphthous
stomatitis, Tuberculous lymphadenitis, Persistent headache,
Measles, Nasal bleeding, Snake bite, Liver cirrhosis, Ascites,
Urticaria, Palpebral conjunctivitis, Laryngitis or Laryngeal
abscess, Suppurative otitis media, Aphasia in Stroke , Contact
dermatitis, Burn , Headache, Rubella, Bloody dysentery,
Pharyngitis
 Pharmacologic action: anti-inflammatory effects, anti-
pyretic , vasodilatation, decrease secretion of bronchus (high
conc.), and necrosis of placenta in animal.
Hanbang Yangnihak 2010, Hanyak yangnihak 2001
 Formula in Korea: 225 www.tradimed.co.kr
 OTC in Korea: 311 www.kimsonline.co.kr

40. Median (Min.-Max)
Last exposure weeks 4.3 (0.4-12.6)
Duration of exposure (days) 3.0 (1.0-46.0)
Dosage (mg/day) (25/48) 852 (20.0-2,256)
Number %
Spontaneous
abortion
1/48 2.1
IUFD - 0
Preterm birth 3/47 6.4
LBW 2/47 4.3
Malformation - 0
Korean Motherisk Program, unpublished

41.  Indications: Headache due to Brain tumor, Bronchial asthma,
Dizziness, Stomach cancer, Pyloric stenosis, Gastric gaseous
distension
 Pretreatment: purified Pinellia tuber, processed Pinellia
tuber, processed Pinellia tuber with ginger
 Pharmacologic action: antitussive effect, decrease
vomiting, decrease gastric ulcer, decrease ocular pressure, and
increase abortion in animal Hanyak yangnihak 2001
 Formula in Korea: 90 www.tradimed.co.kr
 OTC in Korea: 587 www.kimsonline.co.kr

42. Korean Motherisk Program, unpublished
Median (Min.-Max)
Last exposure weeks 4.5 (0.4-12.4)
Duration of exposure (days) 2.0 (1.0-53.0)
Dosage (mg/day) (18/43) 625.5 (2.67-3,340)
Number %
Spontaneous
abortion
- 0
IUFD 2/43 4.7
Preterm birth 4/43 9.3
LBW 3/43 7.1
Malformation 1*/43 2.3
* Mega cysterna magna (11mm)

43. Unpublished data

44. Age (years) 32.0 ± 3.6
Gravidity (n) 2.2 ± 1.3
Parity (n) 1.0 (0, 3.0)
Body mass index (kg/m2
) 20.8 ± 3.2
Exposure to X-rays
a) n (%) 54 (16.8)
b) total dose (mSv) 0.005 (0.0005, 28.8)
c) gestational age at exposure (weeks) 4.8 ± 3.2
Exposure to alcohol (%)
a) n (%) 128 (39.9)
b) total dose (oz) 1.6 ± 1.4
c) gestational age at exposure (weeks) 4.6 ± 2.3
Smoking (%)
a) n (%) 23 (7.2)
b) cigarettes/day 5.4 ± 4.4
c) gestational age at exposure (weeks) 6.3 ± 4.6
Comorbidities [n (%)]
a) type 2 diabetes mellitus 1 (0.3)
b) hypertension 2 (0.6)
c) thyroid disease 2 (0.6)
d) cancer 1 (0.3)
e) renal disease 1 (0.3)
Education level [n (%)]
a) post-secondary education 130 (40.5)
b) high school 20 (6.2)
c) not answered 171(53.3)
Occupation
a) professional, technical and related
occupations
54 (16.8)
b) executive, administrative, managerial and
sales
occupations
136 (42.4)
c) construction workers 124 (38.6)
d) unemployed 7 (2.2)
Korean Motherisk Program, unpublished

45. INDICATIONS a
n (%)
Analgesics 8 (2.5)
Anti-acne preparations 2 (0.6)
Anti-emetics & anti-nauseants 1 (0.3)
Anti-inflammatory enzymes 8 (2.5)
Anti-inflammatory & anti-rheumatic products 7 (2.2)
Anti-obesity preparations 21 (6.5)
Anti-thrombotic agents 2 (0.6)
Cough and cold preparations 129 (40.2)
Dermatological preparations 3 (0.9)
Drugs for acid related disorder 1 (0.3)
Functional gastrointestinal disorders 93 (29.0)
Gynecological anti infectives and antiseptics 11 (3.4)
Psycholeptics 2 (0.6)
Sex hormones & modulators the genital system 7 (2.2)
Others 26 (8.1)
a
According to the pharmacological/therapeutic subgroups of the ATC classification system (World Health Organization
Collaborating Centre for Drug Statistics Methodology 2011)
Korean Motherisk Program, unpublished
21 cases: Tonic
medicine

46. Median (range)
Numbers of herbal medicine including
one prescription
7.0 (1.0 - 40.0)
Duration of exposure (days) 3.0 (1.0 – 365.0)
Gestational age at last dose (weeks) 4.7 (0.1 - 25.0)
197 kinds of herbal medicines
Korean Motherisk Program, unpublished

47. Korean Motherisk Program, unpublished

48. Cases (n= 307)
Gestational age at birth (weeks) 38.9 ± 2.4
Birth weight (g) 3,294.2 ± 511.8
Birth length (cm) 49.7 ± 2.2
Head circumference at birth (cm) 34.6 ± 1.4
Apgar score, 1 min 8.3 ± 0.9
Apgar score, 5 min 9.0 ± 0.7
IUFD (%) 6 (2.0)
Malformationsa
(%) 7 (2.3)
NICU admission (%) 12 (3.9)
Duration of NICU admission (days) 12.5 ± 9.2
Neonatal jaundice (%) 10 (3.3)
a
A baby born with megacisterna magna, second one with dysplastic change of left kidney, left ectopic ureteral
insertion, third one with small pulmonary artery, fourth one with polydactyly of 5th
toe of left foot and cleft palate and
patent ductus arteriosus, fifth one with small echogenic foci of anterior papillary muclse of left ventricle heart, sixth
one with borderline left ventriculomegaly of cerebrum, and seventh one with patent ductus arteriosus
Korean Motherisk Program, unpublished

51.  Although herbal medicines have been used in
clinical practice for thousands of years, basic
research on herbal substances should be focused on
the toxicity and efficacy relationship for those potent
and poisonous herbal substances according to
composite formula.
 Most traditional medical herbs are used in the form
of an aqueous decoction. Therefore research
projects should be centered on development of
analytical and biological procedures for use to give
quality assurance, control, and clinical assessment of
efficacy, and safety of products.

52.  Herbal medications should be regulated for safety,
quality and for appropriate evidence of efficacy.
 Dosage and indications for treatment should be
standardized. And contraindications should be
clearly identified.
 Language problem is another aspect as herbal
ingredients are supplied with similarly names
substitutes that could be toxic.