• Journal of Society of Preventive Korean Medicine
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• v.17 no.3
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• pp.19-30
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• 2013

This study was aimed to develop a new formula for herbal medicine-safety classification in terms of evidence-based medicine. Recently, human equivalent dose(HED)-based therapeutic index was developed for herbal medicine-safety classification by transforming $LD_{50}$ to HED. However, the use of the $ED_{50}$ and $LD_{50}$ to derive the therapeutic index may be misleading as to safety, depending on the slope of the dose-response curves for therapeutic and lethal effects. To overcome this deficiency, HED-based MOS(Margin of Safety)was developed and suggested in this study. The HED-based MOS developed by using $LD_1$, changing to ALD(approximate lethal dose), and $ED_{99}$. The HED-based MOS seems to be more useful and safer than HED-based therapeutic index since its values for several herbal medicines are basically two times less than the values from HED-based therapeutic index. Thus, HED-based MOS can be a good example of Evidence-based approach for herbal medicine-safety classification.

• Journal of Society of Preventive Korean Medicine
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• v.19 no.2
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• pp.123-133
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• 2015

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.

• The Korea Journal of Herbology
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• v.33 no.4
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• pp.53-58
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• 2018

Objectives : Kaempferia parviflora Rhizome is black ginger indigenous to Laos and Thailand. It has been used as a folk medicine to improve blood flow and promote vitality and longevity with good health and well being. For these reasons, Kaempferia parviflora Rhizome has been focused on developing it as a food or food supplement. In addition, Kaempferia parviflora Rhizome could be under consideration of new prescription based on its characteristic compounds, polymethoxyflavonoids. However, it needs to be certified as safe before it can be used. Here, a single-oral toxicity test and safety classification was carried out to identity acute information of the toxicity of Kaempferia parviflora Rhizome powder and to make sure of its safety in clinical applications. Methods : Test substance was orally administered to male and female SD-rat at dose levels of 5000 mg/kg to estimate approximate lethal dose(ALD). Based on the acute information of the toxicity, the safety classification was estimated using the HED(human equivalent dose)-based MOS(margin of safety). Results : At 14 days after treatment with test substance. there were no of test substance related with mortalities and clinical signs. In addition, no changes in the body or organ weights and no gross or histopathological findings were observed. Thus, the ALD of Kaempferia parviflora Rhizome powder was considered over 5,000 mg/kg in both female and male mice. Conclusions : Based on the single oral toxicity test using the highest and limit dose, 5,000 mg/kg and the decision guideline for safety classification based on HED-based MOS, it was estimated that Kaempferia parviflora Rhizome powder is classified as "Specified class B" indicating that clinical dose is not limited to patients as safe as food.

• Journal of Society of Preventive Korean Medicine
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• v.20 no.1
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• pp.125-144
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• 2016

Objectives : About 13% of the medicines used by traditional korean medicines(TKM), are called animal medicines and are derived from non-herbal sources such as animals and insects. However, the clinical use of these preparations from animal medicines is often based on tradition and belief, rather than on evidence of toxicity and efficacy. As a result, animal medicines containing toxin have caused serious problems from injecting patients with venom. Here, various venoms frequently used as TKM were reviewed in terms of their instinct toxity and tried to estimate their safety classification. Methods : The estimation of safety classification was based on human equivalent dose(HED)-based MOS (margin of safety) and clinical dose applied for patients. Results and Conclusions : Except that of snake venom due to no clinical dose, they were evaluated as class 3 for bee venom, class 4 for cantharidin, toxin from blister beetle, and class 1 for venom from scolopendrid. In conclusion, animal medicines showed a wide range of safety classification from class 1 to class 4. This wide range is estimated to result from extremely limited applications of each venom for patients because of their strong toxicity. However, it should be cautious for application in clinics since animal medicines can produce anaphylactic reactions particularly after veinous administration even with a tiny amount of venom.

• The Journal of Korean Medicine
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• v.35 no.1
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• pp.114-123
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• 2014

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 $LD_{50}$(50% lethal dose), which was transformed to theoretical $LD_1$(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.

• The Korea Journal of Herbology
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• v.32 no.4
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• pp.33-38
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• 2017

Objectives : Termitomyces albuminosus (Berk.) Heim is one of the famous wild edible mushrooms in the southern part of China. It is known that Termitomyces albuminosus, like Aconitum koreanum used in Korean traditional medicine, contains a kind of cerebroside, termitomycesphin, causing a pharmacologic effect on the neuron system. The pharmacologic effect of Termitomyces albuminosus can be used to possibly replace Aconitum koreanum. However, It needs to be certified as safe before it can be used. Here, a single-oral toxicity test and safety classification was conducted to obtain acute information of the toxicity of dried-Termitomyces albuminosus powder and to secure its safety in clinical applications. Methods : In order to calculate approximate lethal dose(ALD), test substance was orally administered to male and female SD-rat at dose levels of 5,000 and 0 (vehicle control) mg/kg (body weight). Based on the result of this toxicity, also the estimation of safety classification was calculated using the HED-based (human equivalent dose) MOS (margin of safety). Results : There were no mortalities, test substances treatment-related clinical signs, no changes in the body or organ weights, and no gross or histopathological findings at 14 days after treatment with test substance. Thus, the approximate lethal dose of dried-Termitomyces albuminosus powder was considered over 5,000 mg/kg in both female and male mice. Conclusions : Based on the limit dose, 5000 mg/kg, it was estimated that dried-Termitomyces albuminosus powder is classified as "Specified class B" indicating that clinical dose is not limited to patients as safe as food.