http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Norfloxacin과 ${\beta}-Cyclodextrin$간의 Inclusion Complex에 관한 약제학적 연구
지웅길,박목순,권중무,Jee, Ung-Kil,Park, Mork-Soon,Kwon, Joong-Moo 한국약제학회 1987 Journal of Pharmaceutical Investigation Vol.17 No.1
To increase the bioavailability of norfloxacin, inclusion complex of antimicrobial agent norfloxacin with ${\beta}-Cyclodextrin$ was prepared and studied by the solubility method, spectrophotometric methods(UV, IR, $^1H-NMR$), differential thermal analysis, powder X-ray diffractometry, the physical properties, the antimicrobial activity, DNA binding and in situ recirculation technique. The conclusions are summerized as following; 1) The inclusion complexation was identified by means of solubility, spectrophotometry(UV, IR, NMR), DTA and X-ray diffraction. 2) The molar ratio of $norfloxacin-{\beta}-cyclodextrin$ complex was 1 : 1. 3) The stability constant of $norfloxacin-{\beta}-cyclodextrin$ complex was $21.5\;M^{-1}$, and both true and apparent partition coefficients of the inclusion complex were larger than those of norfloxacin. 4) The time required to dissolve 60% $(T_{60}%)$ of the inclusion complex was 120 min. in distilled water and in the artificial intestinal juice, while norfloxacin did not reach to 60% dissolution within 120 min. 5) The antimicrobial activity of the inclusion complex against Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus showed no significant difference compared to that of norfloxacin alone. 6) Studies on binding properties between the inclusion complex and norfloxacin alone to DNA according to equilibrium dialysis showed no significant differency. 7) In situ absorption rates (Ka) of inclusion complex and norfloxacin alone were 0.229 and $0.102hr^{-1}$, respectively.
5-플루오로우라실 프로드럭의 제조, 물리화학적 성질 및 항암효과
지웅길(Ung Kil Jee),이계원(Gye Won Lee) 대한약학회 1996 약학회지 Vol.40 No.3
To assess their stability as a prodrug of 5-fluorouracil (5-FU), four N-acyloxycarbonyl derivatives (1-(N-tert-butyloxycarbonyl)glycyloxymethyl-5-FU :BGFU, 1-(N-tert-butyloxycarbonyl)-leucyloxymethyl-5-FU:BLFU, 1-(N-tert-carbobenzyloxymethyl) glycyloxymethyl-5-FU:CGFU and 1-(N-tert-carbobenzlyoxymethyl)leucyloxymethyl-5-FU:CLFU) possessing differently protected amino acids, and two acetic acid derivatives (5FU-1-acetylpentane:FUAP and 5-FU-1-acetylhexane:FUAH) were synthesized and their physicochemical properties, hydrolysis kinetics, acute toxicity and antitumor activity were evaluated. The lipid-water partition coefficients of six 5-FU prodrugs were higher than that of 5-FU and their aqueous solubilities were in the following rank order; BGFU>FUAP>CGFU>BLFU>CLFU=FUAH. The hydrolysis of N-acyloxycarboyl derivatives, greater at higher pH, was enhanced in presence of liver homogenate or human plasma. Meanwhile, acetic acid ester derivatives, very stable, were hydrolyzed by liver homogenate. Absorption rate constants were 0.181, 0.121, 0.111, 0.168, 0.168, 0.116 and 0.125 hr-1 for 5-FU, BGFU, BLFU, CGFU, CLFU, FUAP and FUAH, respectively. The cytotoxicity of N-acyloxycarbonyl derivatives was 4 to 5 times lower than that of 5-FU, but that of acetic acid ester derivatives was negligeble. The LD50 values were 204, 325.97 (133.59, amount as 5-FU), 708.16 (262.13), 663.50 (211.77), 382.33 (192.54) and 272.33 (130.09) mg/kg for 5-FU, BGFU, CGFU, CLFU, FUAP and FUAH, respectively. While N-acyloxycarbonyl derivatives showed enhanced antitumor activity and therapeutic ratio (3.30, 3.06, 4.19, 3.11 and 1.81 for BGFU, BLFU, CGFU, CLFU and 5-FU, respectively), FUAH and FUAP showed a smaller therapeutic ratio (0.79 and 0.83).
새로운 경구용 세팔로스포린류의 물리화학적 성질 및 분해특성
나성범,김완주,지웅길,La, Sung-Bum,Kim, Wan-Joo,Jee, Ung-Kil 대한약학회 1994 약학회지 Vol.38 No.2
Physicochemical properties and hydrolysis kinetics of new some oral cephalosporins were examined in buttered solution and human plasma or rat liver homogenate. The test cephalosporins were 7-[(Z)-2-(2-aminothiazole-4-yl)-2- methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl] thiocarbonylthhiomethyl-3-cephem-4-carboxylic acid (CEN1), 7-[(Z)-2-(2-aminoth iazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyrimidyl)piperazinyl]th iocarbonylthiomethyl-3-cephem-4-carboxylic acid (CEN2), pivaloyloxymethyl-7-[ (Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazi nyl]thiocarbonylthiomethy1-3-cephem-4-carboxylate (CEN1P), and pivaloyloxymethyl-7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[ 4-(2-pyrimidyl)piperazinyl]thiocarbonyl-thiomethyl-3-cephem-4-carboxylate (CEN2P). The partition coefficient(Ko/w) of CEN1P, CEN2P were higher than those of CEN1, CEN2. The calculated pKa values of CEN1, CEN2, CEN1P, and CEN2P were 7.09, 7.75, 4.92, and 5.39, respectively. The hydrolysis of CEN1P and CEN2P were not depend on the composition of pH of the test medium except weak alkaline buffered solution (pH 8.00). CEN1 and CEN2 were very stable in pH 6.80 and 8.00 buffer solutions. CEN1P and CEN2P were rapidly deesterified to CEN1 and CEN2 in human plasma and in rat liver homogenate. Half-lives$(t_{1/2})$ of CEN1 and CEN2 were 3.49 and 4.93 hr in human plasma, 1.47 and 1.26 hr in rat liver homogenate, respectively.