Introduction of evidence-based practical medicine through safety classification for herbal medicine(1)

Yeong-Chul Park; Sundong Lee; Park, Yeong-Chul; Lee, Sundong

doi:10.13048/jkm.14011

JKM > Volume 35(1); 2014 > Article

Park and Lee: Introduction of evidence-based practical medicine through safety classification for herbal medicine(1)

Original Article

The Journal of Korean Oriental Medicine 2014; 35(1): 114-123.

Published online: March 30, 2014

DOI: https://doi.org/10.13048/jkm.14011

Introduction of evidence-based practical medicine through safety classification for herbal medicine(1)

Yeong-Chul Park¹, Sundong Lee^{, 2}

¹GLP Center, Catholic University of Daegu

²Dept. of Preventive Korean Medicine, School of Korean Medicine, Sangji University

Correspondence to: 이선동(Sundong Lee)상지대학교 한의과대학 예방의학교실, Tel: +82-33-730-0665, Fax: +82-33-738-7825, E-mail: sdlee@sangji.ac.kr

Received February 21, 2014 Revised March 25, 2014 Accepted March 25, 2014

Abstract

Objectives

Evidence-based medicine(EBM) advocates the use of up-to-date “best” scientific evidence from health care research as the basis for making medical decisions. EBM also has been applied to traditional Korean medicine(TKM), especially in the field of safety. Recently, the standard prescription for TKM by Korea Institute of Oriental Medicine was published based on toxic index from various toxicity tests. However, there are some limitations when the results from the study based on EBM are applied in clinics. To overcome these imitations, the term “evidence-based practical medicine” was developed and defined as clinically applicable results from the study based on EBM. And safety classification for TKM was suggested as an example of evidence-based practical medicine.

Methods:

For safety classification for TKM, the data for LD₅₀(50% lethal dose), which was transformed to theoretical LD₁(1% lethal dose), was analyzed as one of tools for EMB study and divided by maximum dose used in clinics.

Results and Conclusions:

As a result, human equivalent dose(HED)-based MOS(margin of safety) for korean traditional medicine was calculated and used for safety classification with 5 categories. These categories would be helpful for oriental medicine clinicians to decide the increase and decrease of dosage according to various factors such as patient’s sensitivity, potential toxicity of herbal medicines, clinician’s experience for better cure. Thus, this safety classification provides some evidences enough that evidence-based practical medicine should be not the same with EBM and defined differently from EBM.

Keywords: Herbal medicine, Safety classification, Evidence-based practical medicine

Table 1

Classification of Herbal-medicine based on HED-based MOS

등급	HED-based MOS	임상응용 특성
Class 1	< 1	효능용량과 치사용량이 겹치기 때문에 사용금지의 한약재 또는 기존 투여량의 1/10 –1/100 정도의 투여용량 감소가 필요한 한약재
Class 2	1–10	효능용량이 독성용량과 근접하여 소량의 투약으로 극도의 주의가 필요하며 장기 투약을 제한하는 한약재
Class 3	10–50	약물민감성을 가진 환자 및 노약자에게 독성을 유발할 가능성이 있는 한약재
Class 4	50–100	환자에 따라 임상용량의 3배 이하로 증가가 가능한 한약재
class 5	100–500	환자에 따라 임상용량의 5배 이하로 증가가 가능한 한약재
Class 6	> 500	식품과 같이 사용 가능

Table 2

Aristolochic acid containing herbal medicines

한약명	학명

방기	Radix Aristolochiae fangchi(광방기)
	Radix Stephaniae tetrandrae(분방기)
	Radix Aristolochiae heterophyllae(한중방기)
	Radix Cocculi trilobi(목방기)
	Fructus Aristolochia contort(마두령)^*
	Radix Aristolochia contort(청목향, 마두령근)^*
	Radix Aristolochia debilis(마령초)

목통	Caulis Aristolochiae manshuriensis(관목통)
	Caulis Clematidis armandii(천목통)
	Caulis Akebiae quinata(목통)

백모등	Herba Aristolochia mollissemae(백모등)

	Herba Solani lyrati (백영)

세신	Asarum sieboldii Miq.(화세신)
	Asarum heterotropoides(북세신)
	Asarum sieboldi Var.(한성세신)

* 사용 금지된 한약재

Table 3

LD⁵⁰ of Aristolochia debilis

한약재	동물 및 투여	LD₅₀(g/kg)
마령초의 뿌리	마우스 경구	146.5
수치된 마령초 뿌리	마우스 경구	846.1

Table 4

HED-based MOS and safety classification of Aristolochia debilis

한약재	투여	LD₅₀ (g/kg)	ALD 전환인자	추정 ALD (g/kg)	Km factor (animal/human)	ALD의 theoretical HED (g/60kg)	임상투여최고 용량(g)	HED-based MOS	Class
Aristolochia debilis의뿌리	경구	146.5	2	293	3/37	1425	9	158	4
수치된 마령초 뿌리	경구	846.1	2	1692	3/37	8231	9	914	5

Table 5

HED-based MOS and safety classification of Aristolochia fangchi

부자 종류	동물 및 투여	LD50 (g/kg)	ALD 전환인자	추정 ALD (g/kg)	Km factor (animal/human)	ALD의 theoretical HED (g/60kg)	임상투여최고용량(g)	HED-based MOS	Class
Aristolochia fangchi의전탕	마우스경구	7.76	2	15.52	3/37	75.5	9	8.3	2

Table 6

LD₅₀ of Aristolochiaceae

여러 종류의 세신	추출형태	동물 및 투여	LD50(/kg)
화세신(Asarum sieboldii Miq.)	전탕	마우스 경구	100.8 g
	분말	마우스 경구	7.5 g
	휘발성오일	마우스 경구	3.13 ml
한성세신(Asarum sieboldii var. Seoulense Nakai)	전탕	마우스경구	48.7 g
	분말	마우스 경구	31.2 g
	휘발성오일	마우스 경구	1.92 ml
북세신(Asarum heterotropoides Fr. Schmidt var. mandshuricum kitag)	전탕	마우스 경구	240 g
	분말	마우스 경구	4.8 g
	휘발성오일	마우스 경구	2.53 ml

Table 7

HED-based MOS and safety classification of Aristolochiaceae

세신 종류	추출형태	LD₅₀ (g/kg)	ALD 전환인자	추정 ALD (g/kg)	Km factor (animal/human)	ALD의 theoretical HED (g/60kg)	임상투여최고용량(g)	HED-based MOS	Class
화세신	전탕	100.8	2	50.4	3/37	245	3	81	4
	분말	7.5	2	3.75	3/37	18	1	18	3
	휘발성오일	3.13	2	1.56	3/37	7.6	1	7.6	2
한성세신	전탕	48.7	2	24.35	3/37	118	3	39	3
	분말	31.2	2	15.6	3/37	75	1	75	4
	휘발성오일	1.92	2	0.96	3/37	4.7	1	4.7	2
북세신	전탕	240	2	120	3/37	584	3	194	5
	분말	4.8	2	2.4	3/37	11.7	1	11.7	3
	휘발성오일	2.53	2	1.27	3/37	3	1	3	2

Table 8

Summarized HED-based MOS and safety classification for Aristolochiaceae

세신 종류	추출형태	HED-based MOS	Class
화세신	전탕	81	4
한성세신	전탕	39	3
북세신	전탕	194	5

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