• 약학회지
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• 제47권4호
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• pp.239-243
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• 2003

Metformin is an oral antihyperglycemic agent used in the therapy of noninsulin-dependent diabetes mellitus and does not cause hypoglycemia at the therapeutic dose. The purpose of the present study was to evaluate the bioequivalence of two metformin hydrochloride tablets, Glucophage tablet (DaeWoong Pharmaceutical Co., reference drug) and Dybis tablet (Shinpoong Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration(KFDA). Twenty-four normal volunteers, 26.6$\pm$4.01 years in age and 60.6$\pm$9.80 kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 500 mg of metformin hydrochloride was orally administered, blood was taken at predetermined time intervals and the concentrations of metformin hydrochloride in serum were determined using HPLC with UV detector. The pharmacokinetic parameters such as AUCt, Cmax and Tmax were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in AUCt, Cmax and Tmax between two products were -1.05％, -6.76％ and -4.51％, respectively, when calculated against the reference drug. The 90％ confidence intervals using logarithmically transformed data were within the acceptance range of log0.8$\leq$$\delta$$\leq$log1.25 (e.g., log0.9082$\leq$$\delta$$\leq$log1.0906 and log0.8188$\leq$$\delta$$\leq$log1.0392 for $AUC_{t}$ and $C_{max}$, respectively). The 90％ confidence intervals using untransformed data was within $\pm$20％ (e.g., -17.66％$\leq$$\delta$$\leq$8.63％ for $T_{max}$). All parameters met the criteria of KFDA for bioequivalence, indicating that Dybis tablets (Shinpoong Pharmaceutical Co.) is bioequivalent to Glucophage tablets (DaeWoong Pharmaceutical Co.).

• Journal of Ginseng Research
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• 제42권3호
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• pp.312-319
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• 2018

Background: Previous studies have shown that both ginseng root and ginseng berry exhibit antiobesity and antidiabetic effects. However, a direct comparison of the efficacy and mechanisms between the root and the berry after oral administration remains to be illuminated. Methods: In this study, we observed the effects of fermented ginseng root (FGR) and fermented ginseng berry (FGB) on obesity and lipid metabolism in high-fat diet induced obese mice. Results: FGR and FGB significantly inhibited the activity of pancreatic lipase in vitro. Both FGR and FGB significantly suppressed weight gain and excess food intake and improved hypercholesterolemia and fatty liver, while only FGR significantly attenuated hyperglycemia and insulin resistance. Both FGR and FGB significantly inhibited the mRNA expression of Ldlr and Acsl1 while FGR also significantly inhibited expression of Cebpa and Dgat2 in liver. FGR significantly decreased the epididymal fat weight of mice while FGB significantly inhibited the mRNA expression of genes Cebpa, Fas, Hsl, Il1b, and Il6 in adipose tissue. Conclusion: Saponin from both FGR and FGB had a beneficial effect on high-fat diet-induced obesity. Compared to FGB, FGR exhibited more potent antihyperglycemic and antiobesity effect. However, only FGB significantly inhibited mRNA expression of inflammatory markers such as interleukins $1{\beta}$ and 6 in adipose tissue.

• Archives of Pharmacal Research
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• 제27권7호
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• pp.806-810
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• 2004

Metformin is a biguanide antihyperglycemic agent often used for the treatment of non-insulin dependent diabetics (NIDDM). In this study, the pharmacokinetics and pharmacodynamics of metformin were investigated in Korean healthy volunteers during a fasting state for over 10 h. In order to evaluate the amount of glucose-lowering effect of metformin, the plasma concentrations of glucose were measured for a period of 10 h followed by the administration of metformin (oral 500 mg) or placebo. In addition, the concentration of metformin in blood samples was determined by HPLC assay for the drug. All volunteers were consumed with 12 g of white sugar 10 minutes after drug intake to maintain initial plasma glucose concentration. The time courses of the plasma concentration of metformin and the glucose-lowering effect were analyzed by nonlinear regression analysis. The estimated $C_{max}$, $T_{max}$, $CL_{t}$/F (apparent clearance), V/F(apparent volume of distribution), and half-life of metformin were 1.42$\{pm}$0.07 $\mu\textrm{g}$/mL, 2.59$\{pm}$0.18h, 66.12$\{pm}$4.6 L/h, 26.63 L, and 1.54 h respectively. Since a significant counterclock-wise hysteresis was found for the metformin concentration in the plasma-effect relationship, indirect response model was used to evaluate pharmacodynamic parameters for metformin. The mean concentration at half-maximum inhibition $IC_{50}$, $k_{in}$, $k_{out}$ were 2.26 $\mu\textrm{g}$/mL, 83.26 $H^{-1}$, and 0.68 $H^{-1}$, respectively. Therefore, the pharmacokinetic-pharmacodynamic model may be useful in the description for the relationship between plasma concentration of metformin and its glucose-lowering effect.

• 한국잠사학회:학술대회논문집
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• 한국잠사학회 1997년도 Progress and Future Development of Sericultural Science and Technology 40th Anniversary Commemoration Symposium
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• pp.133-158
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• 1997

Since 1992, Sericulture & Entomology Research Institute(NSERI) and Kyung Hee University group screened an activity of lowering blood-glucose levels with silkworm related materials such as silkworm larvae powder, dried feces, pupae and silkworm moth in other to guide laymans to rational and educated utilization of silkworm-related materials for the treatment of diabetes mellitus. In experiments examining several silkworms in different stages and prepared in different conditions, a freeze dried silkworm powder of 5th instar 3rd day showed a higher glucose lowering activity about 20% than heat dried matured silkworm powder. Among the three dosage of 500mg, 830mg and 1,160mg in ate preliminary clinical trial, the 830mg exhibited a significant effect on postprandial blood glucose level and did and did not cause any hypoglycemic side effect. In the blood glucose lowering activity of mulberry and silkworm varieties, the Yongcheonppong and Samkwangjam showed the highest activity for lowering blood glucose levels. In experiments to see the difference in blood-glucose lowering activity between either male and female or larvae and pupae, activity of larvae was higher than that of pupae and the male was higher than female. The heating dry and artificial diet showed lower than mulberry diet and normal freeze dry of the 5th instar 3rd day. Among the sericultural products, larvae showed the highest activity. We find out the fact that effect of silkworm powder attributed to the inhibition of ${\alpha}$-glucohydrolase catalyzed reaction in the small intestine.

• 대한약침학회지
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• 제25권2호
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• pp.130-137
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• 2022

Objectives: Insulin resistance (IR) is major cause of type 2 diabetes (T2D), and adipokines (e.g., adiponectin, leptin, and resistin) play an important role in insulin sensitivity. Medicinal plants are frequently used for T2D treatment. This study investigates the effect of Artemisia annua L. (AA) extracts on adipokines in mice with high-fat-diet (HFD)/streptozotocin (STZ)-induced T2D. Methods: We divided 60 mice into 12 groups (n = 5 per group): control, untreated T2D, treated T2D, and 9 other groups. T2D was induced in all groups, except controls, by 8 weeks of HFD and STZ injection. The treated T2D group was administered 250 mg/kg of metformin (MTF), while the nine other groups were treated with 100, 200, and 400 mg/kg of hot-water extract (HWE), cold-water extract (CWE), and alcoholic extract (ALE) of AA (daily oral gavage) along with 250 mg/kg of MTF for 4 weeks. The intraperitoneal glucose tolerance test (IPGTT) was performed, and the homeostasis model assessment of adiponectin (HOMA-AD) index and blood glucose and serum insulin, leptin, adiponectin, and resistin levels were measured. Results: Similar to MTF, all three types of AA extracts (HWEs, CWEs, and ALEs) significantly (p < 0.0001) decreased the area under the curve (AUC) of glucose during the IPGTT, the HOMA-AD index, blood glucose levels, and serum insulin, leptin, and resistin levels and increased serum adiponectin levels in the MTF group compared to the T2D group (p < 0.0001). The HWEs affected adipokine release, while the CWEs and ALEs decreased leptin and resistin production. Conclusion: Water and alcoholic AA extracts have an antihyperglycemic and antihyperinsulinemic effect on HFD/STZ diabetic mice. In addition, they decrease IR by reducing leptin and resistin production and increasing adiponectin secretion from adipocytes.

• 한국식품영양과학회지
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• 제40권2호
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• pp.321-326
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• 2011

본 연구는 제2형 당뇨모델 쥐에서 조각자 추출물의 항당뇨 효과를 알아보기 위해 SD계 수컷 흰쥐에 streptozotocin (STZ)을 복강주사 15분 후 nicotineamide(NA)로 복강에 재주사하여 제2형 당뇨를 유발시켰다. 그리고 당뇨대조군(DC), 당뇨 유발군+acarbose 4 mg/kg(AC), 당뇨유발군+조각자 추출물(Gleditschiae Spina ethanol extract) 50 mg/kg (GSE), 그리고 정상군(NC)으로 나누어 10주간 식이와 함께 물을 자유 급여하였다. 10주 동안 매일 식이 섭취량과 음료섭취량 및 매주 체중과 공복혈당을 측정하고, 마지막 주에 경구포도당 부하검사(OGTT)를 실시하였으며, 부검 시 혈액을 채취하여 혈장 TRAP 수준을 측정하였다. 정상군에 비해 당뇨그룹(DC, AC, GSE)의 체중 증가는 유의적으로 감소하였고, 당뇨 유발군들 간에는 유의적 차이가 없었다. 식이섭취량, 음료섭취량 및 식이이용효율은 정상군에 비해 당뇨그룹 DC, AC, GSE에서 유의적으로 높게 나타났으나, 음료섭취량은 DC에 비해 AC, GSE군에서 유의적으로 감소하였다. 정상군은 10주 동안 정상 수준 공복혈당을 나타내었고, acarbose는 8주부터 공복혈당이 유의적으로 감소하였으며, 9주까지 GSE군은 DC군보다 공복혈당은 낮았지만 유의적 차이는 보이지 않다가 마지막 10주에서는 DC군보다 공복혈당이 유의적으로 감소하였다. 경구 당부하 검사 결과에서는 포도당 투여 30분 후부터 혈당이 상승되기 시작하여 정상군보다 당뇨군들에서 유의적으로 상승하였고, 당뇨군들에서는 DC군에 비해 AC와 GSE군에서 유의적으로 혈당상승이 억제되었다. 10주간의 GSE 보충은 DC군에 비해 혈장 내총항산화(TRAP) 수준을 유의적으로 증가시키는 것으로 나타났다. 따라서 제2형 당뇨병에서 조각자 추출물을 장기간 투여한다면 혈당증가 억제에 있어 확연한 효과를 보일 것으로 생각된다. 이는 조각자 추출물의 항산화 활성과도 연관이 있을 것으로 추측되며, 향후 조각자 추출물의 혈당강하작용 효과를 가지는 물질의 분리 및 정제에 대한 연구가 이루어져야 할 것으로 사료된다.

• 한국식품영양과학회지
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• 제36권6호
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• pp.696-702
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• 2007

녹차 추출물이 당뇨병의 고혈당에 미치는 영향을 알아보기 위하여 1형 당뇨병 모델인 alloxan 당뇨쥐와 2형 당뇨병모델인 OLETF 쥐에 녹차 추출물을 4주간 투여하면서 혈당을 측정하여 관찰하였다. 녹차 추출물 투여 후 1주, 2주, 3주 및 4주째에 꼬리 정맥에서 혈당을 측정한 결과 alloxan 당뇨쥐는 대조군에 비하여 각각 혈당이 161, 176, 177 및 181 mg/dL가 감소되었고, OLETF 쥐는 녹차 추출물 투여군이 대조군에 비하여 각각 28, 33, 38 및 28 mg/dL가 감소되어, 녹차 추출물 투여로 1형 당뇨병인 alloxan 당뇨쥐와 2형 당뇨병인 OLETF 쥐에서 모두 투여 1주일째부터 혈당의 증가 둔화가 나타나서 4주째까지 지속되었다. 녹차 추출물이 당뇨쥐의 식이섭취량 및 체중에 미치는 영향을 알아보기 위하여 실험동물에 녹차 추출물을 투여한 후 1주일 간격으로 식이소모량과 체중을 4주까지 측정한 결과, 식이소모량은 alloxan당뇨쥐와 OLETF 쥐에서 모두 대조군과 녹차 추출물 투여군 사이에 변화가 없었다. 녹차 추출물 투여 당뇨쥐에서혈청 중성지질량의 변화를 관찰한 결과 alloxan 당뇨쥐와 OLETF 쥐에서 모두 녹차 추출물 투여로 중성지질량의 변화가 없었다. 녹차 추출물 투여로 인한 조직세포 손상정도를 측정하기 위하여 alloxan 당뇨쥐와 OLETF 쥐를 대조군과 녹차 추출물 투여군으로 나누어 4주간 사육한 후 혈청 AST 활성도를 측정한 결과 녹차 추출물 투여로 혈청 AST 활성도 변화는 관찰되지 않았다. 이상의 실험 결과로 녹차 추출물을 당뇨병 쥐에 경구투여하면 혈당증가 억제효과가 나타나는데, 녹차 추출물의 혈당증가 억제효과는 1형이나 2형당뇨병 등 당뇨병의 형태와 상관없이 작용할 수 있는 것으로생각된다. 따라서 녹차 추출물은 당뇨병 치료를 위한 우수한 식사요법 보조제로 개발될 수 있을 것으로 기대된다. 또한 녹차 추출물에 함유된 혈당강하작용 물질의 검색과 작용 기전, 특성에 대한 연구가 계속된다면 우수한 혈당강하작용을 가진 물질이 개발될 수 있을 것으로 추측된다.

• Journal of Pharmaceutical Investigation
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• 제32권3호
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• pp.223-229
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• 2002

Metformin is an oral antihyperglycemic agent used in the therapy of noninsulin-dependent diabetes mellitus and does not cause hypoglycemia at the therapeutic dose. Its mechanism of action may involve an increased binding of insulin to its receptors and glucose uptake at the post-receptor level. The purpose of the present study was to evaluate the bioequivalence of two metformin tablets, Glucophage (Daewoong Pharmaceutical Co., Ltd.) and Glycomin (Ilsung Pharmaceuticals Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The metformin release from the two metformin tablets in vitro was tested using KP VII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty four normal male volunteers, $23.75{\pm}1.96$ years in age and $68.77{\pm}10.41\;kg$ in body weight, were divided into two groups with a randomized $2{\times}2$ cross-over study. After one tablet containing 500 mg as metformin was orally administered, blood was taken at predetermined time intervals and the concentrations of metformin in serum were determined using HPLC with UV detector. Besides, the dissolution profiles of two metformin tablets were very similar at 떠1 dissolution media. The pharmacokinetic parameters such as $AVC_t,\;C_{max}\;and\;T_{max}$ were calculated. The ANOVA test was performed for the statistical analysis of the logarithmically transformed $AVC_t\;and\;C_{max}$, untransformed $T_{max}$. The results showed that the differences in $AVC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the Glucophage were 0.09%, 6.09% and -8.22%, respectively. There were no sequence effects between two tablets in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(0.94){\sim}log(1.09)\;and \;log(1.01){\sim}log(1.15)$\;for\;AVC_t\;and\;C_{max},\;respectively)$, indicating that Glycomin tablet is bioequivalent to Glucophage tablet.

• Journal of Nutrition and Health
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• 제44권4호
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• pp.275-283
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• 2011

본 실험은 주요 phytoestrogen에 속하는 genistein, coumestrol, enterolactone의 식이보충이 제2형 당뇨동물모델에서 당질대사 개선에 미치는 효과를 알아보고자 C57BL/KsOlaHsd-db/db 마우스를 이용하여 내당능, 당화헤모글로빈 농도, 당대사 관련 효소활성, 조직 중 글리코겐과 최종당화산물 수준 등을 측정하였다. 그 결과, phytoestrogen의 보충(3.75 mg/100 g diet)이 당뇨동물의 체중변화, 식이 및 수분 섭취량 그리고 장기무게에는 유의적인 영향을 미치지 않았으나, 모든 phytoestrogen의 보충은 당뇨동물의 공복 혈당, 경구 내당능 검사 시 혈당반응곡선 아래면적 및 혈중 HbA1c 수준을 유의적으로 낮추었다. 또한 모든 phytoestrogen의 보충은 당뇨동물의 혈장 글루카곤 수준을 유의적으로 낮추었으며, coumestrol과 enterolactone의 보충은 간 조직 중 글리코겐 수준을 유의적으로 증가시켰다. 이상의 결과들은 genistein, coumestrol, enterolactone의 3종 phytoestrogen의 식이보충이 제2형 당뇨동물에서 내당능을 개선시킬 수 있음을 시사하였으나 그 기전에 대해서는 향후 추가 연구가 필요하다고 본다.

• 한국식품과학회지
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• 제31권4호
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• pp.1057-1064
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• 1999

8주령의 C57BL/KsJ db/db마우스에 상백피 냉침추출물을 투여하면서 5주간 사육하여 식이섭취량, 체중변화, 혈중 포도당 농도를 관찰하고, 소장내 ${\alpha}-glycosidase$ 활성변화와 혈중 당화헤모글로빈 농도, 중성지방 농도, 인슐린 농도를 측정하였다. 상백피추출물 500 mg/kg을 공급하는 Rad 500군과 1000 mg/kg을 공급하는 Rad 1000군, db/db 대조군과 lean군으로 나누고 대조약물로는 acarbose 5 mg/kg을 투여하였다. Rad 1000군은 식이섭취량에서 db/db 대조군보다 낮은 수준이었으며 그에 따라 체중증가량도 유의적으로 낮았다. 또한 공복시 혈중포도당 농도는 Rad 500, Rad 1000, acarbose군 모두 db/db 대조군보다 낮았다. 혈중 당화헤모글로빈 농도와 중성지방 함량 측정결과는 농도의존적으로 시료투여군이 db/db대조군보다 낮게 측정되었다. 혈중 인슐린 농도 측정결과 lean군을 제외한 나머지군간에 유의적인 차이는 없었고 Rad 500군에서 약간 높은 수준이 관찰되었다. 소장을 proximal, middle, distal 세부위로 나누어 각각에 대해 maltase, sucrase, lactase의 활성을 측정해본 결과 db/db군은 lean군에 비해 세효소의 활성이 매우 높은 활성을 나타내었으며, 시료투여군은 sucrase의 경우 proximal, middle 부위는 db/db군 보다 낮고 distal 부위는 활성이 높았다. Maltase, lactase의 활성은 모든부위에서 시료투여군이 db/db군 보다 낮아 lean군 수준이었다. 이상의 결과들로 미루어 상백피는 db/db마우스에서 식이섭취량을 줄여주어 체중증가를 억제시키고 소장내 glycosidase활성을 전반적으로 낮춰 혈중포도당 농도를 낮춰주고 혈중 당화헤모글로빈 농도와 중성지방 농도를 낮춰주는 등의 항당뇨효과가 있음을 알 수 있었다.