Motherisk round herbal medicine/최준식 교수


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Motherisk round herbal medicine/최준식 교수

  1. 1. Herbal Medicines in Pregnancy June-Seek Choi, M.D., PhDKorean Motherisk ProgramDiv. of Maternal-Fetal Medicine,Dept. of OB & GYN,Cheil General Hospital & Women’s Healthcare Center,School of Medicine, Kwan-dong University, Seoul, Korea
  2. 2. Contents • Definition • Introduction • 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. 3. Definition (1) • Herbal medicines: include herbs, herbal materials, herbal preparations and finished herbal products, that contain as active ingredients part of plants, or other plant materials, or combinations. WHO
  4. 4. Definition (2) • Herbs: crude plant materials such as leaves, flowers, fruit, seed, stems, wood, bark, roots, rhizomes or other plant parts, which may be entire, fragmented or powdered. • Herbal materials: in addition to herbs, fresh juices, gums, fixed oils, essential oils, resins and dry powders of herbs. WHO
  5. 5. Definition (3) • Herbal preparations: may include comminuted or powdered herbal materials, or extracts, tinctures and fatty oils of herbal materials. They are produced by extraction, fractionation, purification, concentration, or other physical or biological processes. • Finished herbal products: herbal preparations made from one or more herbs. WHO
  6. 6. Introduction (1) • It is estimated that about 25% of all modern medicines are directly or indirectly derived from higher plants. Farnsworth NR 1976, Shu YZ 1998 • Anticancer and antimicrobial drugs, about 60% of the medicines currently available on the Illicii Fructus market and most of those in the late stages of clinical trials are derived from natural products, mainly from higher plants. Gragg GM et al 1997
  7. 7. Introduction (2)• Representing an annual global market of US $60 billion every year, herbal medicines account for around 20% of the overall drug market.• Africa- 80% of population China- 30-50% of total medical consumption Europe, North America- over 50% of population have used complementary or alternative medicine at least once. WHO news 2004• Fee for herbal medical treatment was increased 57 times in Korea [ US $ 19 million (1990) US $ 1.1 billion (2006)] A study on the current status and prospect of CAM world market 2007
  8. 8. Important factors to growth of this worldwideIntroduction (3) complementary/alternative medicine(CAM) • Preference of consumers for natural therapies • Concern regarding undesirable side effects of modern medicines and the belief that herbal drugs are free from side effects • Great interest in alternative medicines • Herbal medicines might be of effective benefit in the treatment of certain diseases where conventional therapies and medicines have proven to be inadequate • High cost of synthetic medicines Grünwald J 1995
  9. 9. Compared with well-defined synthetic drugs,Introduction (4) herbal medicines exhibit some marked difference • Active principles are frequently unknown. • Standardization, stability and quality control are feasible but not easy • Availability and quality of raw materials are frequently problematic. • Well-controlled double-blind clinical and toxicological studies to prove their efficacy and safety are rare. • Wide range of therapeutic use and are suitable for chronic treatments. • Usually cost less than synthetic drugs Calixto J.B. 2000
  10. 10. Side effects by Korean herbal medicines-drug interactions Western Medicine Drug interaction and results Angelicae Gigantis Radix(Dang gui), Warfarin, Aspirin Decreased International Normalized Ginseng Radix, Extract of Ginkgonis Ratio and anticoagulant effects Germen Glycyrrhizae Radix (Gam cho) Digoxin, Furosemide, Licorice and digoxin may result in Hydrochlorothiazide 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 (Ma Glyburide, Insulin, Metformin Severe Hypoglycemia due to increase hwang) , Zinberis Rhizoma Recens (Saeng insulin gang) Glycyrrhizae Radix (Gam cho) Metoprolol, Verapamil, Diltiazem Decrease drug effect and Hypertension Allii Bulbus (Ma neul) Isoniazid Decrease serum concentration of isoniazid Zinberis Rhizoma Recens (Saeng gang) Nifedipine, Verapamil, Diltiazem Severe Hypotension Extract of Ginkgonis Germen Thiazide Hypertension Extract of Ginkgonis Germen, Ephedrae Anticonvulsant Increase risk of seizure Herba (Ma hwang) Ginseng Radix Azathioprine, Cyclosporine, Decrease effect of immunosuppressant Corticosteroid Ephedrae Herba (Ma hwang) Pseudoephedrine, MAO inhibitor Hypertension Ephedrae Herba (Ma hwang) Amiodaron, Procainamide, Quinidine Prolongation of QT interval Park YC et al 2011
  11. 11. Introduction (5) • Some Chinese medical (CM) natural herbs listed in the official Chinese Pharmacopoeia (CP), CP are considered poisonous or toxic due to the presence of poisonous or toxic chemical constituents in the herb. • Of which about 50 of animal, plant and mineral natural materials are included in the CP. • In the CP the words “toxic, non-toxic, very-toxic or slightly toxic” are often used in describing Chinese Materia Medica. Chan K 2003
  12. 12. Herbs Toxicity Herbs ToxicityArtemisiae Argyi Folium (황해쑥) Slightly toxic 백화자 Toxic초오두 Slightly toxic 경대극 Toxic조휴 Slightly toxic Meliae Cortex (고련피) ToxicToosendan Fructus (천련자) Slightly toxic Sulphur (유황) ToxicCarpesii Fructus (학슬) Slightly toxic Agkistrodon (살모사) ToxicEuphorbiae Pekinesis Radix (대극) Slightly toxic Pharbitidis Semen (견우자) ToxicTribuli Fructus (백질려) Slightly toxic Calomelas (경분) Toxic금성자 Slightly toxic Scorpio (전갈) ToxicPicrasmae Lignum (고목) Slightly toxic Sophorae Subprostratae Radix (산두근) ToxicArmeniacae Semen (고행인) Slightly toxic Phytolaccae Radix (상륙) Toxic남학슬 Slightly toxic Hirudo (수질) ToxicCnidii Fructus (사상자) Slightly toxic Arisaematis Rhizoma (천남성) ToxicEupolyphaga (자충) Slightly toxic Scolopendra (오공) ToxicEvodiae Fructus (오수유) Slightly toxic 선모 Toxic소엽련 Slightly toxic 향가피 Toxic아담자 Slightly toxic Realgar (웅황) ToxicGleditsiae Fructus (조협) Slightly toxic 앵속각 ToxicTyphonii Rhizoma (백부자) Toxic Genkwa Flos (원화) ToxicGinkgo Semen (백과(은행)) Toxic Cinnabaris (주사) ToxicPinelliae Rhizoma (반하) Toxic Crotonis Semen (파두) Very toxicBufonis Venenum (섬수) Toxic 파두상 Very toxicDichroae Radix (상산) Toxic Mylabris (반묘) Very toxicAconiti Tuber Laterale (부자) Toxic Aconiti Ciliare Tuber (초오) Very toxicLacca Sinica Exsiccata (건칠) Toxic Aconiti Radix (천오) Very toxicKansui Radix (감수) Toxic Strychni Semen seu nux Vomicae Semen (마전자) Very toxic
  13. 13. Very Toxic Herbal MedicineHerbal name Common name Korean common Binominal name Toxicity nameCrotonis Semen Croton seed Pa doo Croton tiglium L. (Euphorbiaceae) Very toxicMylabris Mylabris Ban myo 1. Mylabris cichorii Fabricius Very toxic (Meloidae) 2. Mylabris phalerata Pall. (Meloidae) 3. Mylabris sidae Fabricius (Meloidae)Aconiti Ciliare Tuber Wild aconite (tuber) Cho o Aconitum ciliare DC. Very toxic (Ranunculaceae)Aconiti Kusnezoffii Wild aconite (tuber) Cho o Aconitum kusnezoffii Reichb. Very toxicRadix (Ranunculaceae)Aconiti Proliferum Wild aconite (tuber) Cho o Aconitum proliferum Nakai Very toxicRadix (Ranunculaceae)Aconiti Radix Wild aconite (tuber) Cho o Aconitum triphyllum Nakai Very toxic (Ranunculaceae)Aconiti Radix Aconite main tuber Chun o 1. Aconitum carmichaeli Debx. Very toxic (Ranunculaceae) 2. Aconitum chinense Paxton (Ranunculaceae)Strychni Semen seu nux Nuxvomica Ma jun ja Strychnos nux-vomica L. Very toxicVomicae Semen (Loganiaceae) The Pharmacopoeia Commission of PRC, 2000
  14. 14. Crotonis Semen (Pa Doo)• Indications: Scabies ,Eczema, Abscess 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• Pretreatment: Croton seed without husk, Croton seed plaster, 4-alpha-Deoxy-12-O-tiglylphorbol-13-isobutyrate 4-alpha-Deoxy-phorbol-13-acetate 4-alpha-Phorbol Angelic acid Croton seed frost-like powder Cocacinogen A1 Cocacinogen A2 Cocacinogen A3 Cocacinogen A4 Cocacinogen B1• Pharmacological action: increase GI movement (inhalation, Cocacinogen B2 Cocacinogen B3 Cocacinogen B4 Cocacinogen B6 Cocacinogen B7 human), increase cell differentiation (in vitro) 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 Hanyak yangnihak 2001 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• Toxicity: Croton oil has the ability to promote radiation 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 transformation. It is very toxic and carcinogenic (animal study). 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 Huang, K.C., The pharmacology of Chinese herbs II, CRC press, 1999. 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• Caution: Not use in pregnancy 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• Formula in Korea: 35/ OTC in Korea:1 Phorbol-13-acetate Phorbol-12-tiglate
  15. 15. Mylabris (Ban Myo)• Indications: Rabies, Scabies, Mercury intoxication, Hepatic Cantharidin cirrhosis due to Clonorchiasis, Tuberculosis, Tuberculous lymphadenitis, Eczema, Abscess, Atopic dermatitis, Fever and • Phytochemical group: Monoterpenoid chill • Molecular weight: 196.2• • Pretreatment: cause symptoms from dermal inflammation to Cantharidin may parched Mylabris with rice blisters. If ingested, it may cause irritation and burning of the• Pharmacological action: intoxication of snake venom, increase urination, increase abortion GI tract, diarrhea, and mouth, severe vesication of the upper Dong-Eui-Bo-Gam kidney and cardiovascular damage.• Caution: Not use in pregnancy • Ii is a weak experimental animal carcinogen.• Formula in Korea: 4,
  16. 16. Aconiti Ciliare Tuber, Aconiti Kusnezoffii Radix, AconitiProliferum Radix, Aconiti Radix (Cho O)• Indications: Beriberi Aconiti Ciliare Tuber Myalgia, Cold type Constituents of edema, Cold limbs, & Aconiti Porliferum Radix Aconitine Aconitine dysentery, Epigastric pain, Child epilepsy, Chronic osteomyelitis, Hypaconitine Mesaconitine • Phytochemical group: Alkaloid Hemiparalysis, Hemiplegia, Migratory arthropathy • Molecular weight: 645.75• Pretreatment: processedKusnezoffii Radix tuber Constituents of Aconiti Wild aconite • Bioactivity: bind to neurotoxin binding site 2 of α-subunit of 3-Acetylaconitine Aconitine• Pharmacological action:Na+ channel ,anti-inflammation, Acontine Na+ channel activation of analgesics, increase intracellular Beiwutine Bullatine A(structure unknown){formula: C(21)H(31)NO(2)} vasodilatation, and local anesthetic action in animal study 2010 Ca2+ arrhythmia Bullatine C Hanbang Yangnihak Chasmanine; 6-Epimer Denudatine• • Toxicity: Toxictoxic if swallowed orbradycardia and irregular Toxicity: Very symptoms include by skin absorption. Human Hypaconitine Lepenine Mesaconitine systemic effects by ingestion. LD50 (mus, orl) 1 well LD50 (mus, of rhythm. Nausea and vomiting may occur, asmg/kg, as spasm ivn) Neoline Pendulin 0.175 mg/kg, exp. lethal doses by subcutaneous route reported. LD50 in mice extremities and cardiac arrhythmias. The intestinal absorption of Songorine (mg/kg): 0.166 i.v.; 0.328 i.p.; approx 1 orally (Dybing); also reported as LD50 in the alkaloids 1.8 relatively s.c.; 0.380 i.p.; 0.12of this, gastric lavage is mice (mg/kg): is orally, 0.270 fast. Because i.v. (Sato). Aconiti Ciliare Tuber recommended in case of overdose. Huang, K.C., The pharmacology of Chinese herbs II, CRC press, 1999. Aconiti Kusnezoffii Radix• Formula in Korea: 16 / OTC in Korea: 10
  17. 17. Aconiti Radix (Chun O)• Indications: Beriberi edema, Myalgia, Cold type dysentery, Paxton Constituents of Aconitum carmichaeli Debx. Constituents of Aconitum chinense 14-Acetyltalatizamine Violdelphin Aconine Paresthesia, Child epilepsy, Epigastric pain, Chronic Aconitan A Aconitan B Aconitan C Aconitan D osteomyelitis, Vomiting and Diarrhea, Testiculitis Aconitine Aldohypaconitine Beiwutine Benzoylaconine Benzoylhypaconine• Pretreatment: processed Aconite main tuber 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• Pharmacological action: analgesics, anti-inflammation, Fuzitine Hokbusine A Hokbusine B Hypaconitine vasodilatation, and local anesthetic action in animal study Ignavine Isodelphinine Isotalatisamine Isotalatizamine Karakoline• Caution: not Lipoaconitine (R = linoleoyl, palmitoyl, oleoyl, stearoyl, linolenoyl) use in pregnancy Lipodeoxyaconitine (R = linoleoyl, palmitoyl, oleoyl, stearoyl, linolenoyl) Lipohypaconitine (R = linoleoyl, palmitoyl, oleoyl, stearoyl, linolenoyl) Lipomesaconitine (R = linoleoyl, palmitoyl, oleoyl, stearoyl, linolenoyl) Mesaconitine• Toxicity: headache, paralysis of tongue, paraplegia, pain on Neojiangyouaconitine Neoline Salsolinol upper extremity, nausea, vomiting, respiration difficulty, coma Senbusine A Senbusine B Senbusine C Songarine Hanyak yangnihak 2001 Songorine Talatizamine• Formula in Korea: 1/ OTC in Korea: 5
  18. 18. How to make herbal medicine in Korea
  19. 19. Korean women have a chance to be exposed to herbalmedicine from marriage to lactation Increase Decrease Increase Promote Decreased pregnancy nausea & breast Health lochia chance vomiting milk
  20. 20. Herbal Medicines relate to Uterine Contraction Animal study Hanyak yangnihak 2001
  21. 21. Herbal name Common name Korean name Binominal nameLycii Radicis Cortex Lycium root bark Ji gol pi 1. Lycium chinense Mill. (Solanaceae) 2. Lycium barbarum L. (Solanaceae)Dianthi Herba Dianthus Gu mac 1. Dianthus chinensis L. (Caryophyllaceae) 2. Dianthus superbus L. (Caryophyllaceae)Aurantii Fructus Immaturus Unripe bitter orange Ji gac Citrus aurantium var. daidai Makino (Rutaceae)Crataegi Fructus Crataegus fruit San sa yug Crataegus pinnatifida Bunge (Rosaceae)Typhae Pollen Typha pollen Po hwang Typha angustifolia L. (Typhaceae)Cnidii Rhizoma Cnidium (root) Chun gung Cnidium officinale Makino (Umbelliferae)Chuanxiong Rhizoma Cnidium rhizome Chun gung Ligusticum chuanxiong Hort. (Umbelliferae)Ligustici Rhizoma Ligusticum rhizome Chun gung Ligusticum wallichii var. officinale Yook (Umbelliferae)Corydalis Tuber Corydalis (tuber) Hyun ho sac 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 Ik mo cho 1. Leonurus sibiricus L. (Labiatae) 2. Motherwort 2. Leonurus heterophyllus Sweet (Labiatae)Carthami Flos Carthamus flower (safflower) Hong hwa Carthamus tinctorius L. (Compositae)Angelicae Gigantis Radix Dang gui root Dang gui Angelica gigas Nakai (Umbelliferae)Angelicae Sinensis Radix Dang gui root Dang gui Angelica sinensis (Oliv.) Diels (Umbelliferae)Angelicae Acutilobae Radix Dang gui root Dang gui Angelica acutiloba Kitagawa (Umbelliferae)Cassiae Semen Feotid cassia (seed) Gyul myoung ja 1. Cassia tora L. (Leguminosae) 2. Cassia obtusifolia L. (Leguminosae)
  22. 22. Cnidii Rhizoma (Chun gung) (1)• Indications: Secondary amenorrhea, Muscle spasm, Constituents of Cnidii Rhizoma Adenosine Hemiplegia, Seborrheic dermatitis, Persistent headache, Apiol Butylidenephthalide Metrorrhagia, Thoracoabdominal pain, Consumptive disease, Butylphthalide Chlorogenic acid Cnidilide Abnormal menstruation, Syncope, Confusion, Pelvic mass, Coniferyl ferulate Ferulic acid Gingival bleeding, Gingivitis, Paresthesia, Pneumonia Ligustilide Ligustilidiol Neocnidilide• Pharmacologic action: vasodilatation, analgesics, anti Pregnenolone Senkyunolide Senkyunolide B inflammation, and uterine contraction in animal Senkyunolide C Senkyunolide D Senkyunolide F Senkyunolide G Hanyak yangnihak 2001 Senkyunolide H Senkyunolide I Senkyunolide J• Formula in Korea: 25 Umbelliferose Vanillin• OTC in Korea: 1,186 Vitamin C
  23. 23. Cnidii Rhizoma (Chun gung) (2) (80cases) 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) Number %Spontaneous 2/80 2.5abortionIUFD 4/78 5.1Preterm birth 8/78 10.3LBW 3/78 3.8Malformation 2*/78 2.6* Mega-cysterna magna(11mm) Left ventriculomegaly of cerebrum (11mm) Korean Motherisk Program, unpublished
  24. 24. Corydalis Tuber (Hyun ho sac) (1)• 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 Tetrahydropalmatine Dysentery and Diarrhea arthritis, Rheumatoid arthritis,• Pretreatment: processed Corydalis tuber with vinegar• Pharmacological action: muscle relaxation, hypotension, •Phytochemical group: Alkaloid anti-inflammatory action, decrease secretion of gastric acid, •Molecular weight: 355.44 anti-ulcer action , and increase contraction of extract uterus in •Bioactivity: hypnotic activity exceedsHanyak yangnihak 2001 animal that of• morphine Over dosage intoxication leads to CNS depression Toxicity: and muscle relaxation.• Caution: Not recommend in pregnancy• Formula in Korea: 10/ OTC: 77
  25. 25. Corydalis Tuber (Hyun ho sac) (2) (25 cases) 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) Number %Spontaneous 1/25 4.0abortionIUFD - 0Preterm birth 1/24 4.2LBW - 0Malformation 1*/24 4.0* Post axial polydactyly of left foot Korean Motherisk Program, unpublished
  26. 26. Angelicae Gigantis Radix (Dang gui) (1)• Indications: Secondary amenorrhea, Nausea, Laceration, Constituents of Angelicae Gigantis Radix Headache, Aegelinol Abdominal pain, Metrorrhagia, Hyperventilation, Severe palpitation, Arrhythmia, Carbuncle, Influenza, alpha-Pinene(+,-) Abnormal menstruation, Hemorrhage without trauma, Nasal Choline bleeding, Syncope, Confusion, Acute pulpitis, Toothache, Coumarin Multiple arthritis, Skin tumor, Skin ulcer or Skin abscess, Decursidin Decursin Cerebrovascular accident, Dysentery and Diarrhea, Fever and Decursinol chill, Tuberculosis, Anemia, Paresthesia Decursinol angelate• Pretreatment:angelate Decusinol parched dang gui with soil, charred dang gui, Gigasol parched dang gui with liquor, ginger processed dang gui Imperatorin Isoimperatorin• Pharmacologic action: Increase blood flow to heart, Marmesin Nodakenetin hypotension, anti ulcer effect, analgesic, anti-inflammatory Nodakenin effect, and p-Cymene contraction (aqueous extracts) in animal uterine Prenyletin Hanbang Yangnihak 2010 Umbelliferone• Formula in Korea: 120• OTC in Korea: 1,401
  27. 27. Angelicae Gigantis Radix (Dang gui) (2) (74 cases) 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 3/74 4.1 abortion 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) Korean Motherisk Program, unpublished
  28. 28. Herbal Medicines relate to Spontaneous Abortion Animal study Hanyak yangnihak 2001
  29. 29. Herbal name Common name Korean name Binominal nameMenthae Herba Mint Bak ha 1. Mentha arvensis var. piperascens Malinv. (Labiatae) 2. Mentha haplocalyx Briq. (Labiatae)Trichosanthis Radix Trichosanthes root Chun Hwa Boon Trichosanthes kirilowii Maxim. (Cucurbitaceae)Moutan Radicis Cortex Moutan root bark Mok dan pi Paeonia suffruticosa Andr. (Paeoniaceae)Lonicerae Flos Lonicera flowers Geum un hwa 1. Lonicera japonica Thunb. (Caprifoliaceae) 2. Lonicera confusa DC. (Caprifoliaceae)Kansui Radix Kansui root Gam su Euphorbia kansui Liou ex Wang (Euphorbiaceae)Clematidis Radix Clematis (root) Wi ryung sun 1. Clematis mandshurica Rupr. (Ranunculaceae) 2. Clematis chinensis Osbeck (Ranunculaceae) 3. Clematis hexapetala Pall. (Ranunculaceae)Sulphur Sulphur Yu hwang SulphurCurcumae Longae Tuber Common turmeric Gang hwang Curcuma longa L. (Zingiberaceae)Curcumae Rhizoma Zedoary A chool 1. Curcuma phaeocaulis Val. (Zingiberaceae) 2. Curcuma kwangsiensis S. G. Lee et C. F. Liang (Zingiberaceae)Achyranthis Radix Achyranthes root Oo seol 1. Achyranthes japonica Nakai (Amaranthaceae) 2. Achyranthes bidentata Bl. (Amaranthaceae) 3. Achyranthes fauriei Leville et Vaniot (Amaranthaceae)Pinelliae Rhizoma Pinellia rhizome Ban ha Pinellia ternata (Thunb.) Breit (Araceae)Aristolochiae Fructus Aristolochia fruit Ma doo ryung 1. Aristolochia contorta Bunge (Aristolochiaceae) 2. Aristolochia debilis Zucc. (Aristolochiaceae)Albizziae Cortex Silk tree bark Hab han pi Albizia julibrissin Durazz. (Leguminosae)Moschus Musk Sa hyang 1. Moschus moschiferus L. (Moschidae) 2. Moschus berezovskii Flerov (Moschidae) 3. Moschus sifanicus Przewalski (Moschidae)
  30. 30. Menthae Herba (Bak ha) (1)• 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• OTC in Korea: 311
  31. 31. Menthae Herba (Bak ha) (2) (48 cases) 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 1/48 2.1abortionIUFD - 0Preterm birth 3/47 6.4LBW 2/47 4.3Malformation - 0 Korean Motherisk Program, unpublished
  32. 32. Pinelliae Rhizoma (Ban ha) (1)• 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• OTC in Korea: 587
  33. 33. Pinelliae Rhizoma (Ban ha) (2) (43 cases) 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 - 0abortionIUFD 2/43 4.7Preterm birth 4/43 9.3LBW 3/43 7.1Malformation 1*/43 2.3* Mega cysterna magna (11mm) Korean Motherisk Program, unpublished
  34. 34. Pregnancy Outcomes Korean Motherisk Program Unpublished data
  35. 35. Demographic characteristics of participants(n=321)Age (years) 32.0 ± 3.6 Comorbidities [n (%)]Gravidity (n) 2.2 ± 1.3 a) type 2 diabetes mellitus 1 (0.3)Parity (n) 1.0 (0, 3.0) b) hypertension 2 (0.6)Body mass index (kg/m2) 20.8 ± 3.2 c) thyroid disease 2 (0.6) d) cancer 1 (0.3)Exposure to X-rays e) renal disease 1 (0.3) a) n (%) 54 (16.8) Education level [n (%)] b) total dose (mSv) 0.005 (0.0005, 28.8) a) post-secondary education 130 (40.5) c) gestational age at exposure (weeks) 4.8 ± 3.2 b) high school 20 (6.2)Exposure to alcohol (%) c) not answered 171(53.3) a) n (%) 128 (39.9) Occupation b) total dose (oz) 1.6 ± 1.4 a) professional, technical and related occupatio 54 (16.8) c) gestational age at exposure (weeks) 4.6 ± 2.3 nsSmoking (%) b) executive, administrative, managerial and sal 136 (42.4) a) n (%) 23 (7.2) es occupations b) cigarettes/day 5.4 ± 4.4 c) construction workers 124 (38.6) c) gestational age at exposure (weeks) 6.3 ± 4.6 d) unemployed 7 (2.2) Korean Motherisk Program, unpublished
  36. 36. Indications of herbal exposure (n=321) 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) 21 cases: Tonic Drugs for acid related disorder 1 (0.3) medicine 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)aAccording to the pharmacological/therapeutic subgroups of the ATC classification system (World Health Organization Korean Motherisk Program, unpublishedCollaborating Centre for Drug Statistics Methodology 2011)
  37. 37. Exposure to herbal medicine in pregnant women (n=321) Median (range) Numbers of herbal medicine including 7.0 (1.0 - 40.0) one prescription 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
  38. 38. Frequencies of Herbal medicine (>10%) n 188 200 150 100 75 91 81 71 103 50 46 65 71 57 57 48 43 45 0 43 45 41 40 33 Korean Motherisk Program, unpublished
  39. 39. Fetal outcomes Cases (n= 307)Gestational age at birth (weeks) 38.9 ± 2.4Birth weight (g) 3,294.2 ± 511.8Birth length (cm) 49.7 ± 2.2Head circumference at birth (cm) 34.6 ± 1.4Apgar score, 1 min 8.3 ± 0.9Apgar score, 5 min 9.0 ± 0.7IUFD (%) 6 (2.0)Malformationsa (%) 7 (2.3)NICU admission (%) 12 (3.9)Duration of NICU admission (days) 12.5 ± 9.2Neonatal jaundice (%) 10 (3.3)a A baby born with megacisterna magna, second one with dysplastic change of left kidney, left ectopic ureteralinsertion, third one with small pulmonary artery, fourth one with polydactyly of 5th toe of left foot and cleft palate andpatent ductus arteriosus, fifth one with small echogenic foci of anterior papillary muclse of left ventricle heart, sixthone with borderline left ventriculomegaly of cerebrum, and seventh one with patent ductus arteriosus Korean Motherisk Program, unpublished
  40. 40. Summary (1)• 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.
  41. 41. Summary (2)• 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.
  42. 42. Thank you for your attention