• The Korean Chronic Disease News
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• no.292
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• pp.5.1-5.1
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• 2005

• Clean Technology
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• v.13 no.4
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• pp.237-243
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• 2007

Phase behavior of the ternary systems of water-insoluble simvastatin drug, which is well known to be effective drugs for hypercholesterolemia therapy, in solvent mixtures of dimethyl ether (DME) and supercritical carbon dioxide was investigated to present a guideline of establishing operating conditions in the particle formation of the drugs by a supercritical anti-solvent recrystallization process utilizing DME as a solvent and carbon dioxide as an anti-solvent. The solubilities of simvastatin in the mixtures of DME and carbon dioxide were determined as functions of temperature, pressure and solvent composition by measuring the cloud points of the ternary mixtures at various conditions using a high-pressure phase equilibrium apparatus equipped with a variable-volume view cell. The solubility of the drug increased as the DME composition in solution and the system pressure increases at a fixed temperature. A lower solubility of the drug was obtained at a higher temperature.

• Korean Journal of Clinical Pharmacy
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• v.15 no.1
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• pp.41-45
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• 2005

심바스타틴은 cholesterol 생합성 과정에서 속도 조절 효소인 HMG-CoA reductase의 강력한 상경적 길항약으로서 고지혈증 치료에 널리 쓰이는 약물이다. 심바스타틴 제제인 MSD 사의 조코 20 mg정을 대조약으로 하여 시험약인 유영 제약의 엘바스타 20mg정의 생물학적 동등성 평가를 하기 위해 22명의 건강한 지원자를 모집하였다. 지원자를 두 군으로 나누어 2정씩 투여하였고 $2{\times}2$ 교차시험을 실시하였다. 심바스타틴의 혈장 중의 농도를 정량하기 위하여 발리데이션된 LC/MS/MS를 사용하였다. 채혈 시간은 투약 전 및 투약 후 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 시간에 걸쳐 총 12시점에 걸쳐 시행하였다. 생물학적 동등성을 판정하기 위한 파라미터로 12시간까지의 혈장 중 농도곡선 하 면적 ($AUC_{12hr}$)과 최고 혈중 농도($C_{max}$)를 사용하였다. 12시간 까지의 혈중 농도 곡선 하 면적의 기하 평균은 $17.30ng{\cdot}ml/hr$(시험약)과 $17.35ng{\cdot}ml/hr$(대조약)으로 나타났다. 최고 혈중 농도의 경우 각 각 5.08 ng/ml(시험약)과 5.20 ng/ml(대조약)으로 관찰 되었다. $AUC_{12hr}$의 경우 로그변환한 평균치 차의 $90{\%}$ 신뢰구간이 log0.8510 - log1.1694이었고, $C_{max}$의 경우 log0.8176 - log1.1649로 계산되어 두 항목 모두 log0.8-log1.25이어야 한다는 식품의약품 안전청과 FDA의 기준을 모두 만족시켰다. 이상의 결과를 종합하면 시험약 엘바스타 정 20mg은 대조약 조코정 20 mg에 대하여 생물학적 동등한 것으로 판정되었다.트리머 전기비저항 탐사를 수행하였다. 이를 통해 하저에 케이블을 설치하는 방식에 비해 매우 신속하고 경제적으로 하저에 분포하는 이상대의 분포범위와 발달방향을 규명할 수 있었다.대에 대해 가장 효과적이다. 모델과 현장 적용 결과들을 통해 GRM SSM 방법을 이용하여 불규칙한 굴절면을 가진 지층들에 대해 좀 더 신뢰할 수 있는 정밀한 탄성파 속도를 산출할 수 있음을 보여주고 있다.별한 주의를 기울여야 한다.EX>$\alpha/\beta$=10인 경우 $62.0\~121.9\;Gy_{10}$ (중앙값: $93.0\;Gy_{10}$)의 분포를, ${\alpha/\beta}=3$인 경우 $93.6\~187.3\;Gy_3$ (중앙값=$137.6\;Gy_3$ )의 분포를 보였다. MD-BED $Gy_3$는 직장합병증 발생과의 관계는 통계적으로 유의하였고, 방광합병증과는 유의하지 않았다. 직장합병증과의 연관성은 MD-BED $Gy_3$보다 개별 환자의 직장전벽 총 선량 BED값인 R-BED $Gy_3$가 훨씬 더 높았다. 요도카테터 풍선의 후방지점이 대변하는 방광의 총 선량 BED값인 V-BED $Gy_3$도 방광합병증과 경향성 테스트에서 통계적 유의성을 보였다. 하지만, 어떠한 방사선선량도 골반제어율과 의미 있는 상관관계를 보이지 않았다. 본 기관에서 주치의의 선호도에 따라 강내근접치료가 외부방사선치료의 중간에 시행되는 형태인 샌드위치기법과 외부방사선치료 후반부에 시행되는 순차적 기법으로 구분하였을 때, 두 방식간 치료성적 및 합병증의 차이는 없었다. 총 치료기간에 대한 분석에서는 치료기간이 길어질수록 재발 위험이 커지는 경향을 보였으나, 나이 및 병기, 종양의 크기, MD-BED $Gy_{10}$

• Clean Technology
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• v.13 no.1 s.36
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• pp.34-45
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• 2007

Phase behavior of the ternary systems of water-insoluble simvastatin drug, which is well known to be effective drugs for hypercholesterolemia therapy, in solvent mixtures of dichloromethane and supercritical carbon dioxide was investigated to present a guideline of establishing operating conditions in the particle formation of the drugs by a supercritical anti-solvent recrystallization process utilizing dichloromethane as a solvent and carbon dioxide as an anti-solvent. The solubilities of simvastatin in the mixtures of dichloromethane and carbon dioxide were determined as functions of temperature, pressure and solvent composition by measuring the cloud points of the ternary mixtures at various conditions using a high-pressure phase equilibrium apparatus equipped with a variable-volume view cell. The solubility of the drug increased as the dichloromethane composition in solution and the system pressure increases at a fixed temperature. A lower solubility of the drug was obtained at a higher temperature. The second half of this work is focused on the particle formation of the simvastatin drug by a supercritical anti-solvent recrystallization process in a cylindrical high-pressure vessel equipped with an impeller. Microparticles of the simvastatin drug were prepared as functions of pressure (8 MPa to 12 MPa), temperature (303.15 K, 313,15 K), feed flow rate of carbon dioxide, and stirring speed (up to 3000 rpm), in order to observe the effect of those process parameters on the size and shape of the drug microparticles recrystallized.

• Journal of Pharmaceutical Investigation
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• v.33 no.2
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• pp.121-127
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• 2003

The objective of this study was to solidify the simvastatin self-microemulsifying drug delivery system (SMEDDS) and to improve the encapsulation efficiency of solidified alginate beads using sodium alginate. Typical simvastatin SMEDDS was composed of various oils, surfactants and cosurfactants. Also solidified-alginate beads was prepared by crosslinking liquid emulsion mixtures containing sodium alginate and other excipients (cetylpyridinum chloride (CP-Cl), hydroxypropyl methylcellulose, starch and so on). in $CaCl_2$ solution, it has been investigated that the drug release pattern and encapsulation efficiency were varied with the ratio of cationic lipid (CP-Cl). Solidified sodium alginate beads containing simvastatin SMEDDS were redispersed into media without re-aggregation. Oil droplet size of redispersed solidified-beads in media produced smaller than the initial size. The density of beads and drug loading amount were increased with increasing cationic lipid content. These systems have advantages of storage stability and predictability of drug release rate.

• Journal of Life Science
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• v.33 no.12
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• pp.967-977
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• 2023

Rubus crataegifolius (RC) is a traditional Asian medicinal plant belonging to the Rosaceae family. The fruits of RC are known to prevent adult diseases through antioxidants. In this study, the effects of RC extract (RCex) on obesity and nonalcoholic fatty liver disease (NAFLD) were evaluated in animal models. Twenty-eight male C57BL/6J mice were induced to become obese for 8 weeks and then the extract was orally administered for 8 weeks. RCex reduced body weight, adipose tissue, liver weight. RCex improved biochemical biomarkers including lipid metabolism (alanine aminotransferase (ALT), aspartate aminotransferase (AST), plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol). The activation of AMP-activated protein kinase (AMPK) reduced the expression of adipogenesis genes (liver × receptor (LXR), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthesis (FAS), acetyl-CoA carboxylase 1 (ACC1) and the effect of enhancing carnitine palmitoyltransferase (CPT) activity by RCex was verified. RCex also influence on plasma production of hormones (adiponectin & leptin) related on energy expenditure and metabolism. In addition, we confirmed that RCex improved glucose intolerance in HFD-induced obese rats. RCex was first demonstrated to have anti-obesity as well as anti-NAFLD effects by regulating fatty acid oxidation and fatty acid synthesis by phosphorylation of AMPK. This suggests that RCex could be a good supplement for the prevention of obesity and related NAFLD.