• Journal of Pharmaceutical Investigation
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• 제31권4호
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• pp.281-287
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• 2001

Rebamipide is a novel anti-gastric ulcer agent that has been reported to increase the synthesis of mucus, to increase the mucosal concentration of prostaglandin, and to promote rapid ulcer healing. The purpose of the present study was to evaluate the bioequivalence of two rebamipide tablets, $Mucosta^{TM}$ (Otsuka Korea Pharmaceutical Co., Ltd.) and $Rebamide^{TM}$ (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The rebamipide release from the two rebamipide tablets in vitro was tested using KP VII Apparatus II method at pH 6.8 dissolution media. Twenty normal male volunteers, $24.20{\pm}2.26$ years in age and $66.19{\pm}9.41\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 100 mg of rebamipide was orally administered, blood was taken at predetermined time intervals and the concentrations of rebamipide in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two rebamipide tablets were very similar at pH 6.8 dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets based on the $Mucosta^{TM}$ were -2.57%, 5.77% and -1.47%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 12.62% and 17.63% for $AUC_t,\;and\;C_{max}$, respectively). The powers $(1-{\beta})$ at ${\alpha}=0.05$, ${\Delta}=0.2$ for $AUC_t\;and\;C_{max}$ were above 99.00% and 88.56%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-9.96{\sim}4.82$ and $-4.54{\sim}16.09$ for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Rebamide^{TM}$ tablet is bioequivalent to $Mucosta^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• 제40권2호
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• pp.117-123
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• 2010

Ibudilast, 3-isobutyryl-2-isopropyrazolo[1,5-a]pyridine, is a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It preferentially inhibits PDE 3A, PDE4, PDE10 and PDE11 as well as a number of the other PDE families, albeit to a lesser extent. Ibudilast is used clinically to treat bronchial asthma and cerebrovascular disorders. Thes e clinical uses are based on the ability of ibudilast to inhibit platelet aggregation, improve cerebral blood flow and attenuate allergic reactions. The purpose of the present study was to evaluate the bioequivalence of two ibudilast capsules, Ketas capsule (Handok Pharmaceuticals Co., Ltd.) and Pinatos capsule (Sam Chun Dang Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of ibudilast from the two ibudilast formulations was tested using KP Apparatus method with various dissolution media. Twenty six healthy male subjects, 23.31${\pm}$1.09 years in age and 70.45${\pm}$8.51 kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single capsule containing 10 mg as ibudilast was orally administered, blood samples were taken at predetermined time intervals and the concentrations of ibudilast in serum were determined using HPLC/UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and computer programs (Equiv Test and K-BE Test 2002) were utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Ketas, were 6.99%, -2.48% and 9.93% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations 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 0.8791~log 1.1861 and log 0.8347~log 1.1199 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Pinatos capsule was bioequivalent to Ketas capsule.

• 한국식품과학회지
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• 제46권2호
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• pp.231-236
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• 2014

본 연구에서는 자귀결명자추출혼합물 첨가사료의 혈청 콜레스테롤 저하효과를 확인하기 위하여 3주령된 SD계 수컷흰쥐를 실험군당 12마리씩 배치하여 10주 동안 동물실험을 수행하였다. 흰쥐용 사료(AIN-93G diet, 조지방 함량 7%)를 기본식이로 하여 돈지와 콜레스테롤을 각각 중량비로 7%, 1% 첨가하여 총지방함량이 15%가 되도록 고지방식이를 제조하였다. 흰쥐에게 실험 1기 (first phase) 5주 동안 고지방식이(high-fat diet)를 급여하여 고지혈증을 유발시켰다. 실험 2기(second phase)에는 고지방식이군을 대조군으로 하고, 자귀결명자추출혼합물 분말을 1.0, 2.5, 5.0, 10% 첨가군으로 하여 5주 동안 급여하였다. 자귀결명자추출혼합물 첨가사료(1.0, 2.5, 5.0%)는 고지방식이를 급여한 흰쥐의 배변량을 유의하게 증가시켰고, 체지방중 EFP 무게는 시료 첨가군(10%)에서 유의하게 감소하였다. 혈청 지질중 총콜레스테롤 농도는 시료첨가군(5.0, 10%)이 유의하게 낮았고, HDL-콜레스테롤 농도는 시료 첨가군(1.0%)이 가장 높았다. 중성지방농도는 고지방식이 대조군에 비해 시료 첨가군(2.5% 5.0, 10%)에서 낮은 경향인 것으로 나타났다. 간조직의 효소활성에서 G6PDH 활성은 고지방식이 대조군보다 모든 시료 첨가군에서 유의하게 감소한(p<0.05), 반면 malic enzyme 활성은 고지방식이 대조군에 비하여 시료 첨가군(1.0, 10%)이 유의하게 감소하였다. 이 결과들을 종합해보면, 고지혈증 흰쥐에서의 자귀결명자추출혼합물 분말은 전반적인 지질대사 개선에 긍정적인 효과를 나타냄으로써 앞으로 고콜레스테롤혈증 예방 등의 혈관 순환기 계통 질병을 예방하기 위한 식품으로서의 활용이 기대된다.

• 한국식품위생안전성학회지
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• 제33권5호
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• pp.389-398
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• 2018

본 연구는 고려엉겅퀴 주정추출물을 가지고 제작된 임상시험용제품(CNTM)이 3T3-L1 지방세포 및 고지방식이로 유도된 비만 쥐에 미치는 항비만 효능 관찰을 통하여 체지방 개선 기능성식품을 개발하기위하여 인체적용시험 시료를 제작한 후, 인체적용시험전에 그 효력이 유지됨을 확인하기위해 수행되었다. 본 연구에 사용된 시료 CNTM은 $80{\sim}320{\mu}g/mL$ 농도에서 세포독성이 관찰되지 않았으며, 지방 축적억제 효능 및 지방세포 분화, 지질대사 관련 유전인자들을 유의적으로 변화시키는 것으로 확인되었다. 또한 동물실험에서 CNTM 처리에 의하여 체중의 감소를 확인하였으며 혈중지질 성분 가운데 HDL-C/TC의 비율은 유의적으로 증가하며 LDL-cholesterol (LDL-C)과 non-esterified fatty acid (NEFA)의 비율은 유의적으로 감소하여 혈중 유리지방산 농도를 감소시키며 혈중 콜레스테롤 상승을 억제시키고 혈당을 감소시키는 효과가 있는 것으로 평가되었다. 따라서 고려엉겅퀴 주정추출물이 함유된 인체적용시험시료(CNTM)는 체지방 개선에 우수한 효과가 있는 것으로 확인되었다.

• Asian-Australasian Journal of Animal Sciences
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• 제31권8호
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• pp.1275-1284
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• 2018

Objective: A 28-d trial was conducted to evaluate the effect of diets with different energy and lipase levels on performance, nutrient digestibility, serum profiles, gut health, and carcass quality in broilers. Methods: A total of 720 one-day-old male Ross 308 broilers ($45.4{\pm}0.5g$) were randomly assigned to one of the following four treatments: i) RET, reduced energy treatment (metabolizable energy = 2,950 and 3,100 kcal/kg for starter and finisher diet), ii) BDT, basal diet treatment (metabolizable energy = 3,050 and 3,200 kcal/kg for starter and finisher diet, iii) RET015, RET+0.15 g/kg lipase, and iv) RET03, RET+0.3 g/kg lipase. There were 10 replications (cages) per treatment with 18 birds per cage. Results: During d 1 to 14, broilers fed BDT, RET015, and RET03 diets had higher (p<0.05) body weight gain than those fed RET diet. During d 1 to 14, 15 to 28 and the overall experiment, feed conversion ratio in RET03 treatment was lower (p<0.05) compared with RET treatment. On d 14, the apparent total tract digestibility (ATTD) of dry matter (DM), ether extract (EE), and gross energy in RET03 treatment was higher (p<0.05) than those in RET treatment, while the ATTD of N was increased (p<0.05) by RET03 treatment. On d 28, broilers fed RET03 diet had higher (p<0.05) ATTD of DM than those fed RET and RET015 diets, while the ATTD of EE in BDT and RET03 treatments was increased (p<0.05) compared with RET and RET015 treatments. Broilers fed RET03 diet had higher villus height (VH) and VH:crypt depth (CD) ratio than those fed RET and BDT diets. The activity of pancreatic lipase in BDT and RET03 treatments was higher (p<0.05) than that in RET treatment. Conclusion: Taken together, lipase supplementation (3,000 U/kg feed) increased growth performance, nutrient digestibility, VH, VH:CD ratio and lipase activity, but decreased triglyceride, low-density lipoprotein cholesterol and the abdominal fat percentage in broilers fed reduced energy diet.

• 한국자원식물학회지
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• 제27권4호
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• pp.271-278
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• 2014

고지혈증은 체내 지질대사에 이상이 생겨 혈중의 지질이 비정상적으로 높아진 상태로서, 지질이 필요 이상으로 혈액내 존재하게 되면 혈관벽에 쌓이고 굳어지게 되면서 동맥경화증, 고혈압, 뇌졸중 등의 심혈관계 질환을 일으키기도 한다. 본 연구에서는 고콜레스테롤 식이로 고지혈증을 유도한 생쥐의 동물모델에서 복분자 추출물의 유효성분인 protocatechuic acid(PCA)를 경구 투여하여 PCA의 간손상 보호 효과와 지질 대사함량 변화를 분석함으로써 PCA의 고지혈증 치료에 대한 유의적인 임상 효과를 제시하였다. PCA의 투여는 고콜레스테롤 식이에 의한 간무게 증가, 비장무게의 증가, 흉선의 위축, 신장의 위축 등 장기무게변화에 대하여 회복 효과를 보였고, 혈청 내 간세포 손상 마커 GPT 및 GOT의 회복 효과를 나타내었으며, 혈청 내 총콜레스테롤, 중성지방, HDL, LDL의 지질대사산물의 profile에서도 유의적인 회복효과를 보였다. 특히, PCA의 투여군에서는 혈중 HDL의 농도를 정상식이군 수준으로 높이고, LDL의 농도를 크게 낮추는 효과를 나타냄으로써 HDL/LDL의 균형유지에 역할을 나타내는 것으로 보이며 이러한 효과는 simvastatin의 HDL/LDL 조절 효과와는 다른 패턴을 보이고 있다. 따라서 PCA는 단독으로 고지혈증 치료의 기능성 소재로써의 개발 가능성뿐만 아니라, 합성의약품 simvastatin 등의 스타틴계 약물의 보조제로써의 개발 가능성을 제시한다.

• Journal of Pharmaceutical Investigation
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• 제38권6호
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• pp.413-419
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• 2008

Carvedilol, is a nonselective $\beta$-blocking agent and it also has vasodilating properties that are attributed mainly to its blocking activity at ${\alpha}_1$-receptors. The purpose of the present study was to evaluate the bioequivalence of two carvedilol tablets, $Dilatrend^{(R)}$ tablet 12.5 mg (Chong Kun Dang Pharmaceutical Co., Ltd.) and Cadilan tablet 12.5 mg (KyungDong Pharmaceutical. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of carvedilol from the two carvedilol formulations in vitro was tested using KP VIII Apparatus II method with pH 4.5 dissolution medium. Thirty two healthy male subjects, $25.00{\pm}3.09$ years in age and $70.71{\pm}11.35\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 12.5 mg as carvedilol was orally administered, blood samples were taken at predetermined time intervals and the concentrations of carvedilol in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution medium. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Dilatrend^{(R)}$ tablet 12.5 mg, were 4.66%, 8.33% and -7.45% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations 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., $\log\;0.9823{\sim}\log\;1.1042$ and $\log\;1.0132{\sim}\log\;1.1875$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Cadilan tablet 12.5 mg was bioequivalent to $Dilatrend^{(R)}$ tablet 12.5 mg.

• 한국임상약학회지
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• 제18권1호
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• pp.38-44
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• 2008

Rebamipide, ($\pm$)-2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. It works by enhancing mucosal defense, scavenging free radicals and temporarily activating genes encoding cyclooxygenase-2. The purpose of the present study was to evaluate the bioequivalence of two rebamipide tablets, $Mucosta^{(R)}$ (Korea Otsuca Pharmaceuticals Co., Ltd.) and Mustar (Korean Drug Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of rebamipide from the two rebamipide formulations in vitro was tested using KP VIII Apparatus II method with pH 6.8 dissolution medium. Twenty six healthy male subjects, $23.46{\pm}2.63$ years in age and $66.62{\pm}8.97\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 100 mg as rebamipide was orally administered, blood samples were taken at predetermined time intervals and the concentrations of rebamipide in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution medium. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Mucosta^{(R)}$ were -5.08, 3.52 and -9.71 % for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations 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 0.84$\sim$log 1.07 and log 0.90$\sim$log 1.17 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Mustar tablet was bioequivalent to $Mucosta^{(R)}$ tablet.

• 농업과학연구
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• 제44권3호
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• pp.409-415
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• 2017

This study was conducted to investigate the effect of supplementation of fermented wheat bran (FWB) on growth and blood characteristics in weaned pig. A total of 36 weaned pigs ($Landrace{\times}Yorkshire{\times}Duroc$; BW, $7.78{\pm}0.04kg$) were randomly allocated to three dietary treatments with different FWB concentrations (0, 0.5, and 1.0%), and each treatment had 3 replicate pens with 4 pigs per pen. The FWB was obtained from a mixture of wheat bran and two microbes (Lactobacillus plantarum M10 and Saccaromyces cerevisiae) and was determined to contain $10.19{\pm}0.27log\;CFU/g$ of L. plantarum and $7.73{\pm}0.38log\;CFU/g$ of S. cerevisiae. Experimental diets were prepared by mixing 0 (control), 0.5, or 1.0% of the FWB to the basal diet, and fed to the weaned pigs for 7 weeks. During the experimental period, the pigs had access to the diet and water ad libitum. Feed intake increased significantly in the 1.0% FWB group compared to the control and 0.5% FWB groups (p < 0.05), whereas the other growth parameters were not different among the treatment groups. White blood cells and lymphocytes were significantly decreased in the FWB treatment groups compared to the control group, but other blood corpuscles were not different among the treatment groups (p < 0.05). The pigs fed 0.5% FWB showed greater serum IgG than the control and 1.0% FWB groups (p < 0.05). In conclusion, the FWB fed to weaned pigs did not negatively affect their growth performance, but rather reduced mortality by fortifying immunity.

• 동아시아식생활학회지
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• 제18권5호
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• pp.725-731
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• 2008

The principal objective of this study was to assess the effects of low-calorie diets(LCD) for 8 weeks of medical nutrition therapy in individuals with BMI in excess of $23\;kg/m^2$. 41 over-weight or obese individuals (male=14, female=27, age $28.6{\pm}8.9\;yrs$), none of whom were diagnosed with a medical disease, were administered MNT 4 times over the study period. Approximately $1,100{\sim}1,300\;kcal/day$ were prescribed by a dietitian, via individualized counseling. Anthropometric parameters, daily nutrient intake, and blood levels of leptin, insulin, and lipid profiles were measured prior to and after the 8 weeks of the intervention period. We noted significant reductions in body weight, body mass index (BMI), fat mass (FM), visceral adipose tissue (VAT), abdominal skin-fold thickness, and waist circumference in both men and women. The mean body weight losses in men and women were $3.2{\pm}0.6\;kg$/8 weeks and $2.8{\pm}0.6\;kg$/8 weeks, respectively. However, the % of lean body mass (LBM) in men and women was shown to increase significantly (p<0.05). The daily intake of calorie, fat, protein, vitamin E, folate, and iron were significantly reduced during the LCD period. Blood levels of lipids and glucose were in normal range, and evidenced no changes after LCD. However, the serum levels of leptin in female subjects were significantly reduced (p<0.00l) from $8.9{\pm}4.8\;ng/mL$ to $6.9{\pm}4.8\;ng/mL$. In conclusion, 8 weeks of LCD with individualized counseling by a dietitian effectively reduced body fat and visceral fat in both men and women with BMI in excess of $23\;kg/m^2$.