• Journal of Pharmaceutical Investigation
• /
• v.28 no.4
• /
• pp.283-288
• /
• 1998

Lovastatin, one of the potent cholesterol-lowering agents, is an inactive lactone prodrug which is metabolized to its active open acid, lovastatin acid (LVA). Bioequivalence study of two lovastatin preparations, the test drug ($Mevacor^{\circledR}$: Chungwae Pharmaceutical Co., Ltd.) and the reference drug ($Lovaload^{\circledR}$: Chong Kun Dang Pharmaceutical Co., Ltd.), was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Fourteen healthy male volunteers, $23.9{\pm}3.9$ years old and $67.6{\pm}8.0$ kg of body weight in average, were divided randomly into two groups and administered the drug orally at the dose of 160 mg as lovastatin in a $2{\times}2$ crossover study. Plasma concentrations of lovastatin acid were analysed by HPLC method for 12 hr after administration. The extent of bioavailability was obtained from the plasma concentration-time profiles of total lovastatin acid after alkaline hydrolysis of the plasma samples. By alkaline hydrolysis, trace amounts of unmetabolized lovastatin were converted to lovastatin acid. The $AUC_{0-12hr}$ was calculated by the linear trapezoidal rule method. The $C_{max}$ and $T_{max}$ were compiled directly from the plasma drug concentration-time data. Student's t-test indicated no significant differences between the formulations in these parameters. Analysis of variance (ANOVA) revealed that there were no differences in AUC, $C_{max}$, and $T_{max}$ between the formulations. The apparent differences between the formulations were far less than 20% (e.g., 7.07, 5.77 and 1.18% for AUC, $C_{max}$, and $T_{max}$, respectively). Minimum detectable differences(%) between the formulations at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 17.2, 15.1, and 15.9% for AUC, Cmax, and Tmax, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (e.g.. $-5.20{\sim}19.3$, $-5.00{\sim}16.5$, and $-10.2{\sim}12.5%$ for AUC, $C_{max}$, and $T_{max}$, respectively). These results satisfied the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of lovastatin were bioequivalent.

• 한국유가공학회:학술대회논문집
• /
• 2004.06a
• /
• pp.21-39
• /
• 2004

Fermented milks have been recognized as healthy foods since ancient times, but those using intestinal bacteria such as Bifidobacterium and lactic acid bacteria (LAB) are even more valuable from the standpoint of view of maintaining health. They have also now come to be recognized as important in the field of preventive medicine. Although advances in the medical sciences in the last 50 years have significantly increased the human lift span, an unfortunate fact is that many of us are now living long enough to experience chronic disorders such as coronary heart disease, hypertension, osteoporosis, diabetes and cancer. In recent years there has been renewed interest in health promotion and disease prevention by incorporating probiotic bacteria into foods to counteract harmful bacteria in the intestinal tract. Therefore, there are now a wide variety of commercial products containing prospective probiotics that claim health-promoting effects, such reductions in large botvel carcinogens and mutagens, antitumor properties, cholesterol-lowering effects, increased lactose digestion, relief from con-stipation, stimulation of immunocomponent cells and enhancement of phagocytosis. Two well-known representative probiotic is LAB and Bifidobaclerium. Traditional probiotic dairy strains of LAB which have been designated as GRAS (Generally Recognized As Safe) bacteria have a long history of safe use and most strains are considered comestible microorganisms with no pathogenic potential. Accordingly, there is considerable interest in extending the range of foods containing probiotic organisms from dairy foods to infant formulas, baby foods, and pharmaceuticals. In addition, the ingestion of probiotics, prebiotics, and symbiotic as wll as combinations of pro- and prebiotics has recently aroused renewed interest as enhancing the beneficial relationship between the host and intestinal microflora in both healthy and diseased indivisuals. Non-communicable chronic diseases such as cancer, cerebral hemorrhage, is chemic heart disease, and diabetes mellitus has recently been recognized as adult diseases in Japan as well as other countries. and are considered to be inevitably associated with aging. These diseases occur as a result of individual life styles. The Japanes Government. Ministry of Health, Labor and Welfare has proposed substituting the term 'adult diseases' with 'lifestyle-related diseases'. It has emphasized the importance of prevention rather than treatment. since the well-known increase in the elderly population in Japan is predicted to result in a variety of socioeconomic problems. n this lecture on the Present status of fermented milk products in Japan, I will report a strategy for the development of fermented milk products in Japan from the standpoint of view of research in Japan on LAB and Bifidobacteria. They could play an important role in preserving human health by controlling intestinal microflora capable of producing toxic effects on the host.

• Korean Journal of Clinical Pharmacy
• /
• v.8 no.2
• /
• pp.107-112
• /
• 1998

Lovastatin is a lipid lowering agent for the treatment of hypercholesterolemia and belongs to a new class of pharmacologic compounds called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. By competitively inhibiting HMG CoA reductase, lovastatin disrupts the biosynthesis of cholesterol in hepatic and peripheral cells and increases the synthesis of high-density-lipoprotein HDL) receptors. Following oral administration, the lactone ring of lovastatin is hydrolysed to the active inhibitor of HMG CoA reductase, lovastatin acid. Lovastatin is known to have poor oral absorption and wide individual variation. In this study, bioequivalence test of two lovastatin formulations, the test drug ($Lovaload^{TM}$, Chong Kun Dang Pharmaceutical Co.) and the reference drug ($Mevacor^{TM}$, Chung Wae Pharmaceutical Co.) were conducted according to the guidelines of Korea Food and Drug Administration (KFDA). A total of 18 healthy male volunteers, $31.90\pm3.60$ years old and $72.17\;7.88$ kg of body weight in average, were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of lovastatin acid in plasma were measured upto 12 hours following a single oral administration of eight tablets (20 mg of lovastatin per tablet) by high-performance liquid chromatography with UV detection at 238 nm. The area under the concentration-vs-time curve from 0 to 12 hours $(AUC_{0-12h})$ was calculated by the trapezoidal summation method. The statistical analysis showed that there are no significant differences in $AUC_{0-12h),\;C_{max}\;and\;T_{max}$ between the two formulations ($6.72\%,\;1.52\%,\;and\;0.88\$, respectively). The least significant differences between the formulations at $\alpha$=0.05 were less than $20\%\;(11.65\%,\;19.73\%,\;and\;14.81\%\;for\;AUC_{0-12h},\;C_{max}\;and\;T_{max}$, respectively). The $90\%$ confidence intervals for these parameters were also within $\pm20\%\;(-1.50{\leq}{\delta}{\leq}15.00$, $-12.50{\leq}{\delta}{\leq}15.50,\;and\;-9.64{\leq}{\delta]{\leq}11.40{\leq}\;for\;\;AUC_{0-12h}$ ,$C_{max}\;and\;T_{max}$, respectively). In conclusion, the new generic product $Lovaload^{TM}$ was proven to be bioequivalent with the reference drug.

• Korean Journal of Food Science and Technology
• /
• v.46 no.4
• /
• pp.477-482
• /
• 2014

This study was performed to evaluate the anti-obesity and lipid-lowering effects of phytoplant diets in rats fed with a high-fat/cholesterol diet (HFCD). Experimental diet formulae contained various phytoplants such as brown rice, barley, soybean, germinated brown rice, malt, black bean, sea tangle, and/or dietary fibers including polydextrose, garcinia combogia, glucomannan, ${\small}L$-carnitine, and chitosan. Male Sprague-Dawley rats were fed with a HFCD for 6 weeks and then fed with a HFCD with/without phytoplants for another 6 weeks. Rats fed with phytoplant diets showed lower body weights, liver weights, visceral fat levels, and blood lipid levels compared to those of rats fed with HFCD alone. In addition, rats administered phytoplant diets showed increased daily feces production during the second experimental phase. These results suggest that phytoplant diets improve body weight, feces production, adipose tissue weight, and lipid metabolism.

• Archives of Plastic Surgery
• /
• v.36 no.5
• /
• pp.525-530
• /
• 2009

Purpose: The hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are widely used in the treatment of dyslipidemia for the lowering of cholesterol. And studies about simvastatins have been shown to enhance bone formation in vitro and in vivo in rodents. But some other researchers have reported that there was no anabolic effect abouts simvastatins on bone. The peripheral distribution beyond the liver represents a small fraction of an orally administered dose. We hypothesize that this poor peripheral distribution is the likely reason that simvastatins, yield ambiguous results as anabolic agents. We therefore investigated whether the effects of simvastatins on bone may be enhanced by subcutaneous administration, providing better peripheral delivery of these drugs. Methods: 36 rat unilaterally mandible fractured models were prepared and divided into two groups. The simvastatin treated group where 1 mg/kg of simvastatin was daily injected subcutaneously. The same dose of normal saline was injected on the control group. And 3 rats in each group were sacrificed and taken bone samples in each week. Bone sample was evaluated with tensile strength and histological morphology after 1, 2, 3, 4, 5 and 6 weeks. Results: In simvastatin treated group, the fracture healing process, chondrocyte aggregation, collagen formation and trabecular bone formation was rapidly proceeded than the control group in histologically. The tensile strength of the simvastatin treated group was 1.02, 2.25, 3.95, 4.42, 5.49 and $6.00N/mm^2$ by weeks. The control group data was 0.60, 1.05, 2.17, 3.75, 4.15 and $5.17N/mm^2$ by weeks. The average tensile strength was higher by $1.04N/mm^2$ in simvastatin treated group. Conclusion: The currently available data on the effects of simvastatin on bone has done to confirm the finding that simvastatin helps fracture healing. And the potential for simvastatin to be used as anabolic agents for bone when delivered by the subcutaneous route.

• Journal of Life Science
• /
• v.29 no.10
• /
• pp.1144-1151
• /
• 2019

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with various metabolic syndromes, such as obesity, dyslipidemia, hypertension, and diabetes. Cudrania tricuspidata is a medicinal plant distributed widely in Asia and has been used in clinical practice to treat various diseases. The aim of this study is to determine the lipid-lowering effects of C. tricuspidata fruit extract (CTE) using a cell model induced by free fatty acids (FFAs). HepG2 cells were exposed to 1mM FFAs (palmitic acid:oleic acid = 2:1) for 24 hr to simulate the conditions of NAFLD in vitro. CTE attenuated the increases of lipid accumulation, intracellular triglyceride, and cholesterol content and inhibited 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) activity in the HepG2 cells in a dose-dependent manner. Also, CTE inhibited the protein expression of lipogenesis-related genes, such as sterol regulatory element-binding protein-1/-2 (SREBP-1/-2), fatty acid synthase (FAS), and stearoyl CoA desaturase-1 (SCD-1) in FFAs-induced lipid accumulation in HepG2 cells. In addition, CTE-induced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in HepG2 cells. These results suggest that CTE attenuates hepatic lipid accumulation by inhibiting lipogenesis through the modulation of the AMPK signaling pathway on FFAs-induced lipogenesis in HepG2 cells and may potentially prevent NAFLD.

• Korean Journal of Agricultural Science
• /
• v.36 no.2
• /
• pp.185-197
• /
• 2009

For utilizing Cattail pollen as a raw material for functional foods, the nutrients such as free sugar, free amino acid, fatty acid composition, flavonoid content, and the biological activity within Cattail pollen were measured. The results of proximate analysis within Cattail pollen included the following readings: 12.7-13.2% of moisture, 15.7-17.8% of crude protein, 1.3% of crude fat, 7.5-7.7% of free sugar, 13.7-18.6% of crude fiber, 3.4-4.9% of ash, and 49.7-55.9% of nitrogen free extracts. The composition of free amino acids consisted of 1.923% of T. orientalis, 0.907% of T. angustata, and 0.333% of T. latifolia, which were measurements that varied significantly among different species. However, all species showed considerable portions of GABA alanine, glutamic acid, and proline. Specifically, it was shown that the GABA composition, which is known for increasing immunity while simultaneously lowering blood pressure, exceeded 50%. Therefore, this result implies that Cattail pollens have potential as a powerful utilization for functional foods. The composition of the fatty acids mainly consisted of linoeic, palmitic acid, oleic acid, and linolenic acid, and didn't show many variances across different species. Also, the total contents of unsaturated fatty acid were particularly high with a measured ratio of 67.2-76.0% value. Mineral in Cattail pollen was composed of 0.354-0.492% of K, 0.0516-0.0546% of Mg, 0.045-0.0486% of Ca, and 0.0101-0.0204% of Na. Among the Cattail pollens known as anti-oxidants, flavonoid contains 0.169-0.186% of quercetin, and therefore is the largest constituent followed by rutin making up a measurement of 0.0094-0.0147%. For the purpose of the study, the Cattail pollen and its extracts were fed to SC class rats for a span of 4 weeks. Then, the DPPH radical scavenging activity was measured from the tested rats'serums and the results showed significant variances. Also, the results indicated that the cholesterol and glucose levels in the blood were decreased which in turn led to the conclusion that the cattail pollen can help hyperlipidemia and diabetic treatments.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.40 no.11
• /
• pp.1548-1555
• /
• 2011

Persimmons are shown to contain high levels of phenolics. The present study was designed to investigate if a sweet persimmon wine (SPW) would affect the development of alcoholic fatty liver in rats. Initially, male Sprague-Dawley rats were housed singly in stainless steel wire-bottomed cages in a room of controlled temperature and lighting. The rats had free access to a nutritionally adequate AIN-93G diet and deionized water. After the acclimatization period, rats were weight-matched and assigned to the following three groups: two groups were fed 6.7% ethanol or the caloric equivalent of maltose-dextrin in a Lieber-DeCarli diet and the other group was fed the isocaloric Lieber-DeCarli diet containing SPW at the same ethanol level. All three groups were fed their respective diets for 6 weeks. Serum transaminase, cholesterol, and triglyceride levels were measured. Liver lipids and histology were assessed at 6 weeks. The total phenolic content and the antioxidant and free radical scavenging activities of SPW were determined. SPW significantly increased antioxidant and free radical scavenging activities. As markers of liver injury, serum alanine and aspartate transminases were markedly lowered by SPW at 6 weeks. SPW significantly reduced the serum levels of serum cholesterol and triglyceride compared to ethanol treatment. SPW delayed the development of an alcoholic fatty liver by reversing fat accumulation in the liver, as evidenced in histological observations. Taken together, SPW seems to protect the liver from becoming fatty by alleviating fatty liver symptoms and lowering hepatic and serum lipid levels. Such a protective effect of SPW appears to be in part due to its phenolics.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.39 no.4
• /
• pp.511-517
• /
• 2010

This study was performed to estimate the prevalence and the risk factors of metabolic syndrome in Andong rural area. A total of 1,431 people (533 males, 898 females) aged over 45 years participated in this study in 2003. The prevalence of metabolic syndrome was 38.2% (male 23.5%, female 46.9%, p<0.001). As age increased, the prevalence of the metabolic syndrome increased in female, but not in male. The major underlying components of metabolic syndrome were high blood pressure (67.1%), low HDL-cholesterol (60.6%), and abdominal obesity (39.9%). The distinctive component for male was high blood pressure (70.1%), and for female, low HDL-cholesterol (73.6%), high blood pressure (65.3%), and abdominal obesity (54.5%). Subjects having more than one component were 94.7%. The risk factors for metabolic syndrome were analyzed using the multiple logistic regression method according to gender and expressed as age-adjusted odds ratio (OR). The results of comparing female to male (OR=2.953), and of comparing obese by % body fat (M: OR=5.786, F: OR=13.498) or BMI (M: OR=3.782, F: OR=13.301) to normal body weight showed significantly higher risk for metabolic syndrome (p<0.001). Health related habits, such as smoking, alcohol drinking, and exercise, didn't show any effect on metabolic syndrome. This study revealed that the prevalence of metabolic syndrome was significantly higher in female subjects compared to both male and female, and high blood pressure was the main cause of metabolic syndrome. We suggest that the strategy for prevention or reducing the prevalence of metabolic syndrome in this area should be concentrated on reducing high blood pressure through lowering obesity and abdominal obesity.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.36 no.12
• /
• pp.1537-1543
• /
• 2007

This study was investigate the effect of grape seed water extract (GSW) on lipid profiles, lipid metabolism and erythrocyte antioxidant defense system in high-fat diet-induced obese mice. Three groups of male C57BL/6 mice were fed different diets for 6 weeks: normal diet (Normal), high-fat diet (HF control; 37% calorie from fat) and high-fat diet supplemented with GSW (HF-GSW; 1% wt/wt). Supplementation of GSW did not affect the body weight, food intake, daily energy intake, white adipose tissue weights and plasma leptin level in high-fat fed mice. Plasma and hepatic cholesterol and triglyceride contents were significantly higher in the HF control group than in the Normal group; however, GSW supplement significantly lowered plasma triglyceride and hepatic cholesterol concentrations compared to the HF control group. GSW supplement significantly increased fecal excretion of triglyceride in high-fat fed mice. Hepatic carnitine palmitoyl transferase activity was significantly higher in the HF-GSW group than in the HF control group, while fatty acid ${\beta}$-oxidation tended to be lowered by GSW supplement. Erythrocyte superoxide dismutase activity was also significantly higher in the HF-GSW group than in the HF control group and glutathione peroxidase activity tended to be lowered in HF-GSW group. The GSW supplement significantly lowered erythrocyte lipid peroxidation level compared to the HF control group. Accordingly, these results suggest that GSW can be considered as a lipid-lowering agent and as being effective for enhancing erythrocyte antioxidant defense system in high-fat diet-induced obese mice.