대한예방한의학회지 (Journal of Society of Preventive Korean Medicine)

대한예방한의학회 (Society of Preventive Korean Medicine)
권호 표지

독성대사체를 생성하는 다빈도사용 한약재의 안전성등급화 - 천궁, 당귀, 감초, 숙지황을 중심으로 -

Safety classification for frequently-used herbal medicines inducing toxic metabolites

  • 박영철 (대구가톨릭대학교 GLP센터) ;
  • 이선동 (상지대학교 한의과대학 예방의학교실)
  • Park, Yeong-Chul (GLP Center, Catholic University of Daegu) ;
  • Lee, Sundong (Dept. of Preventive Korean Medicine, School of Korean Medicine, Sangji University)
  • 투고 : 2015.08.05
  • 심사 : 2015.08.13
  • 발행 : 2015.08.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

The new formular for herbal medicine-safety classification in terms of evidence-based medicine was developed and applied to evaluate various herbal medicines in the previous study. This study is aimed to evaluate the frequently-used herbal medicines inducing toxic metabolites or reactive intermediates(RI), such as Ligusticum wallichii Franch, Angelica sinensis, Glycyrrhizae Radix, Rehmanniae Radix, based on 6 safety grades calculated from human equivalent dose(HED)-based MOS(margin of safety). HED-based MOS can be explained as the ratio of theoretical ALD(approximate lethal dose) of human as $LD_1$(lethal dose of 1%)/ clinical maximum dose as $ED_{99}$(Effective dose of 99%). The herbal medicine showing the ratio less than 1 belongs to Class 1, but the herbal medicine showing the ratio more than 500 belongs to Class 6 with the lowest toxicity. As a result, they were evaluated as class 2 for Angelica sinensis and Glycyrrhizae Radix, class 3 for Ligusticum wallichii Franch and Rehmanniae Radix. These resultant grades for 4 herbal medicines were lower than the grade expected under consideration that these herbal medicines are used very frequently in oriental clinics. These low grades would be due to their ingredients which is biotransformed to toxic metabolites.

키워드

참고문헌

  1. 중화인민공화국. 의료용 독성약품관리법. 1988.
  2. Kim, Ellie JY, Chen Y, Huang JQ, Li KM, Razmovski-Naumovski V, Poon J, Chan K, Roufogalis BD, McLachlan AJ, Moe SL, Yang D, Yao M, Liu Z, Li GQ. Evidence-based toxicity evaluation and scheduling of Chinese herbal medicines. Journal of Ethnopharmacology. 2013;146:40-61. https://doi.org/10.1016/j.jep.2012.12.027
  3. 식약처. 용역연구개발과제 식의약품 등 통합안전관리 기반연구 중 한약재 안전사용을 위한 등급별 차등관리 방안 연구. 2012.
  4. 박영철. 이선동. 한약의 안전성 등급화를 위한 evidence-based approach: Human equivalent dose-based the margin of safety. 대한예방한의학회지. 2013;17(3):1-12.
  5. 박영철, 이선동. 한약의 안전성 등급화를 통한 근거중심실용의학적 연구(1). J Korean Med. 2014;35(1):114-123. https://doi.org/10.13048/jkm.14011
  6. 박영철, 독성학의 분자-생화학적 원리, 한국학술정보(주), 2010. ISBN: 978-89-268-1259-4.
  7. 이선동, 박영철. 한약독성학 I. 한국학술정보(주). 2012. ISBN:978-89-268-3190-8.
  8. 이선동, 박영철. 한약독성학 II. 한국학술정보(주). 2013. ISBN. 978-89-268-4190-7
  9. Yan CC and Ryan J. Effects of Monocrotaline, a Pyrrolizidine Alkaloid, on glutathione Metabolism in the Rat. Huxtable Biochemical Pharmacology. 1996;51: 375-379. https://doi.org/10.1016/0006-2952(95)02189-2
  10. Jeffrey, AM, Williams GM. Risk assessment of DNA-reactive carcinogens in food. Toxicology and Applied Pharmacology. 2005;207:S628-S635. https://doi.org/10.1016/j.taap.2005.03.024
  11. Zhou S, Gao Y, Jiang W, Huang M, Xu A and Paxton JW. Interactions of Herbs with Cytochrome P450. Drug metabolism review. 2003;35(1):35-98. https://doi.org/10.1081/DMR-120018248
  12. Kim, Dong-Hyun Kim, Bok-Ryang Kim, Ji-Yeon Kim, Yo-Chan Jeong. Mechanism of covalent adduct formation of aucubin to proteins. Toxicology Letters. 2000;114:181-188. https://doi.org/10.1016/S0378-4274(99)00295-7
  13. Peter J. Vit. Approximate lethal dose versus median lethal dose in acute toxicity testing of pharmaceuticals. A retrospective study. Arch Toxicol. 1989;63(4):343-4. https://doi.org/10.1007/BF00278650
  14. Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. Journal of the Federation of American Societies for Experimental Biology. 2008;22:659-661. https://doi.org/10.1096/fj.07-9574LSF
  15. Beasley V. Introduction to Toxicology. International Veterinary Information Service, Ithaca, New York, USA. 1999.
  16. www.clearsynth.com/docs/MSD-CS-PH-0626
  17. Dietz BM. Bolton JL. Biological reactive intermediates(BRIs) formed from botanicaldietary supplements. Chemico-Biological Interactions. 2011;192:72-80. https://doi.org/10.1016/j.cbi.2010.10.007
  18. Makingcosmetics-MSDS. www.makingcosmetics.com
  19. US FDA. Safrole. 1989. PART 189-SUBSTANCES PROHIBITED FROM USE IN HUMAN FOOD, $\S$ 189.180.
  20. Johnson BM, van Breemen RB. In vitro formation of quinoid metabolites of the dietary supplement Cimicifuga racemosa (black cohosh). Chem. Res. Toxicol. 2003;16(7):838-884. https://doi.org/10.1021/tx020108n
  21. US FDA. FDA Poisonous Plant Database-Toxicity of medicinal herbal preparations. 2008.
  22. Editorial Committee of Chinese Materia Medica. State Drug Administration of China. Chinese Materia Medica. Shanghai: Science and Technology Press; 1998.
  23. Isbrucker RA, Burdock GA. Risk and safety assessment on the consumption of Licorice root (Glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin. Regulatory Toxicology and Pharmacology. 2006;46:167-192. https://doi.org/10.1016/j.yrtph.2006.06.002
  24. MAFCO WORLDWIDE CORPORATION, Product Data Sheet, www.in-cosmeticsasia.com
  25. Materia Medica Group. Medical Vacational College of Northern Henan. Pharmacy Bulletin. 1982;17(2):114.