동의생리병리학회지 (Journal of Physiology & Pathology in Korean Medicine)

  • 제25권1호
  • /
  • Pages.122-131
  • /
  • 2011
  • /
  • 1738-7698(pISSN)
  • /
  • 2288-2529(eISSN)
대한동의생리학회·한의병리학회 ( The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine)
권호 표지

육미지황탕가미방(六味地黃湯加味方)의 마우스 경구 단회 투여 독성 평가

Single Oral Dose Toxicity Test of Yukmijihwangtanggamibang, a Polyherbal Formula in ICR Mice

  • 박미연 (대구한의대학교 한의과대학 폐계내과학교실)
  • Park, Mee-Yeon (Department of Internal Medicine, College of Oriental Medicine, Daegu Haany University)
  • 투고 : 2010.10.27
  • 심사 : 2011.12.14
  • 발행 : 2011.02.25
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

The object of this study was to evaluate the single dose toxicity of Yukmijihwangtanggamibang (YMJHTGMB), a polyherbal formula have been traditionally used as prevention or treatment agent for various lung diseases including chronic obstructive pulmonary disease (COPD), in male and female mice. Aqueous extracts of YMJHTGMB (Yield = 16.33%) wasadministered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, and changesin the body and organ weight except for soft feces restricted to YMJHTGMB 2,000 mg/kg treated two male mice (2/5; 40%) at 1 day after administration. In addition, no YMJHTGMB-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for some sporadic accidental findings. The results obtained in this study suggest that the 50% lethal dose and approximate lethal dose of YMJHTGMB aqueous extracts in both female and male mice were considered as over 2,000 mg/kg, the limited highest dosage recommended by KFDA Guidelines.

키워드

참고문헌

  1. Pauwels, R.A., Buist, A.S., Calverley, P.M., Jenkins, C.R., Hurd, S.S. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am. J. Respir. Crit. Care Med., 163: 1256-1276, 2001. https://doi.org/10.1164/ajrccm.163.5.2101039
  2. National Collaborating Centre for Chronic Conditions. Chronic obstructive pulmonary disease. National clinical guideline on management of chronic obstructive pulmonary disease in adults in primary and secondary care. Thorax, 59: 1-232, 2004.
  3. 박명재, 최천웅, 김승준, 김영균, 이승룡, 강경호, 신경철, 이 관호, 이진화, 김유일, 임성철, 박용범, 정기석, 김채형, 신동호, 유지홍. 우리나라 일차 진료의사의 만성폐쇄성폐질환 (COPD) 진료실태조사. 결핵 및 호흡기질환, 64: 109-124, 2008.
  4. Chan, W.Y., Ng, T.B. Adverse effect of Tripterygium wilfordii extract on mouse embryonic development. Contraception 51: 65-71, 1995. https://doi.org/10.1016/0010-7824(94)00001-D
  5. Tanira, M.O., Wasfi, I.A., Homsi, M.A., Bashir, A.K. Toxicological effects of Teucrium stocksianum after acute and chronic administration in rats. J. Pharm. Pharmacol., 48: 1098-1102, 1996. https://doi.org/10.1111/j.2042-7158.1996.tb05907.x
  6. Hsu, H.Y., Lin, C.C., Chen, J.Y., Yang, J.J., Zhang, R. Toxic effects of Erycibe obtusifolia, a Chinese medicinal herb, in mice. J. Ethnopharmacol., 62: 101-105, 1998. https://doi.org/10.1016/S0378-8741(98)00005-1
  7. Chen, J., Tong, Y., Zhang, X., Tian, H., Chang, Z. Acute toxicity of Stephania cepharantha. Zhong Yao Cai, 22: 468-469, 1999.
  8. Lee, J.E., Kim, H.J., Choi, E.K., Chai, H.Y., Yun, Y.W., Kim, D.J., Nam, S.Y., Lee, B.J., Ahn, B.W., Kang, H.G., Kim, Y.B. Four-week repeated-dose toxicity study on Pinellia Extract. Korean J. Lab. Anim. Sci., 19: 127-141, 2003.
  9. 정우식, 전귀옥, 서영호, 박미연, 최해윤, 김종대. 麻黃潤肺湯 추출물의 ICR 마우스에서 경구단회투여 독성 평가. 대한동의생리병리학회지 20: 442-448, 2006.
  10. Park, M.Y., Cho, H.Y., Kim, J.D., Lee, H.S., Ku, S.K. Single dose toxicity test of Kong-Jin-Dan, a polyherbal formula in ICR mice. J. Appl. Phramcol., 15: 245-251, 2007. https://doi.org/10.4062/biomolther.2007.15.4.245
  11. 박용주. 한방정책의 현재와 미래. 한국한의학연구원 국제학술심포지움, 1998.
  12. 허 준. 동의보감, 서울, 법인문화사, p 830, 871, 2005.
  13. 金榮權, 柳逢夏, 朴東源, 柳基遠. 六味地黃湯이 生理活性指標와 淋巴球細胞數에 미치는 影響. 대한한방종양학회지 4: 89-110, 1998.
  14. 문성식, 김병수, 강정수. 六味地黃湯의 항산화작용에 관한 연구. 동의병리학회지 17: 436-442, 2003.
  15. 서영은, 이은아, 배현수, 신민규, 홍무창. 六味地黃湯 구성약물이 PC12 세포의 酸化抑制에 미치는 영향. 동의병리학회지 17: 203-208, 2003.
  16. 金雨植, 李東熙. 六味地黃湯煎湯液이 家兎血壓및 白鼠肝 TBA値에 미치는 影響에 대한 硏究. 慶熙韓醫大論文集, 2: 145-152, 1979.
  17. 김경호, 윤종화, 조위제. 육미지황탕 (六味地黃湯) 약침자극이 Cyclosporin A 로 유발된 흰쥐의 신독성 (腎毒性)에 미치는 영향. 大韓鍼灸學會誌 13: 212-225, 1996.
  18. 박은혜, 정명숙, 박창범, 지상은, 이영혁, 배현수, 신민규, 김현택, 홍무창. 六味地黃湯加減方-1,2가 학습과 기억능력에 미치는 영향에 관한 임상연구. 동의병리학회지 16: 976-988, 2002.
  19. 郭桂豪, 宋孝貞, 金聖勳. 六味地黃湯加山藥이 Alloxan 糖尿 白鼠의 血黨및 血淸變化에 미치는 影響. 동의병리학회지 8: 137-156, 1993.
  20. 鄭鉉雨, 白榮贊, 金貞相. 六味地黃湯加味方이 局所腦血流量 및 血壓에 미치는 實驗的效果. 동의병리학회지 14: 245-255, 2000.
  21. 한국식품의약품안전청. 의약품 등의 독성시험기준. 한국식품의약품 안전청 고시 제 2005-60호. 2005.
  22. Irwin, S. Comprehensive observational assessment: Ia. A systemic, quantitative procedure for assessing the behavioral and physiological state of the mouse. Psychopharmacology, 13: 222-257, 1968. https://doi.org/10.1007/BF00401402
  23. Dourish, C.T. Effects of drugs on spontaneous motor activity. In Experimental Psychopharmacology (A.J. Greenshaw and C.T. Dourish, Ed.), Humana Press, Clifton, pp 325-334, 1987.
  24. Plata, E.J., Murphy, W.H. Growth and haematologic properties of the BALB/wm strain of inbred mice. Lab. Anim. Sci., 22: 712-720, 1972.
  25. Yamaguchi, C., Fujita, S., Obara, T., Ueda, T.. Effects of room temperature on reproduction, body weight and organ weights, food and water intakes, and hematology in mice. Exp. Anim., 32: 1-11, 1983.
  26. Lee, J.H, Yang, K.J., Shin, H.D., Park, B.R., Son, C.W., Jang, H.J., Park, D.C., Lee, H.S., Ku, S.K. Single subcutaneous dose toxicity of $Polycan^{circledR}$, a $\beta$-glucan originated from Aureobasidium in mice. Lab. Anim. Res., 21: 299-305, 2005.
  27. Lee, H.S., Lee, I.G., Ku, S.K. Single oral dose toxicity study of water extracts of Picrorrhiza Rhizoma in mice. J. Toxicol. Pub. Health, 22: 117-126, 2006.
  28. Banks, W.J. Female reproductive system. In: Banks WJ (Ed). Applied veterinary histology, 2nd ed., Williams & Wilkins: Baltimore, pp 506-526, 1986.
  29. Pineda, M.H. Female reproductive system. In: McDonald LE and Pineda MH (Eds). Veterinary endocrinology and reproduction, Lea & Febiger: Philadelphia, pp 303-354, 1989.
  30. U.S. Environmental Protection Agency. Health Effects Test Guidelines OPPTS 870.100, Acute Toxicity Testing Background. US EPA August, Washington, USA, 1998.