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곽혜선(Hye Sun Gwak),전인구(In Koo Chun) 한국응용약물학회 2000 Biomolecules & Therapeutics(구 응용약물학회지) Vol.8 No.4
Physicochemical properties of aspalatone (acetylsalicylic acid maltol ester, AM), which has been recently found to have an antithrombotic effect, were studied in terms of solubility, dissolution, partition coefficient (Pc) and stability. The solubility of AM at 37℃ was about 1.2 mg/ml and the P_c value for n-octanol/ water and chloroform/water was 11.4 and 382.6, respectively. Dissolution rates of AM at pH 1.2 and 6.8 were more than 80% within 30 min. The degradation of AM followed apparent first-order kinetics, and was dependent on temperature, pH and ionic strength. From the pH-rate profile, the optimal pH was found to be at around 4.0. Half-lives at pH 1.2 and 6.8 were 33.5 and 44.4 hr, respectively. The degradation rate of AM at pH 1.2 was somewhat faster than that of aspirin, but at pH 7.0, the degradation rate of AM was slower than that of aspirin.
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한국 Streptomyces sp. 로 부터 분리한 방향족 화합물과 지질 화합물의 세포독성 연구
신석우(Suck Woo Shin),염곤(Kon Ryeom) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.2
In an effort to screen new selective antitumor agents from the broth of soil microorganism, cytotoxicity oriented screening was performed against tumor cells and 3 compounds (Compound 1, 2 and 3) were isolated from Streptomyces parvullus ISP 5048 and their chemical structures were determined. Among these compounds, Compound 2 showed the highest cytotoxicity against P388D1 and L1210. While the IC_(50) values of compound 2 against P388D1 and L1210 were 0.073 ㎍/㎖ and 0.07 ㎍/㎖, respectively, and the IC_(50) value of Compound 3 was 0.17 ㎍/㎖ against human lung cancer cells, A549, the cytotoxicity of Compound 2 and 3 against normal cell line, Vero E6 cell was about 4- and 8-fold lower than that of adriamycin. Based on the chemical analysis data, Compound 3 was octacosamicine A, a known antibiotic, which was reported by Dobasih et al. (1988). Taken together the results demonstrated that Compound 2 and Compound 3 has the possibility to be developed as antitumor agent because of its potent cytotoxicity as well as high selectivity against various cancer cell lines.
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김원배(Won Bae Kim),양중익(Jung Ick Yang),이상득(Sang Deuk Lee),강수형(Soo Hyung Kang),이응두(Eung Doo Lee),심현주(Hyun Joo Shim),이종진(Jong Jin Lee) 한국응용약물학회 1994 Biomolecules & Therapeutics(구 응용약물학회지) Vol.2 No.4
The pharmacokinetics and tissue distribution of DA-3030 (recombinant human granulocyte colony-stimulating factor, rhG-CSF, recently manufactured by Dong-A research laboratory of Dong-A Pharmaceutical Company) were compared with reported data in the literature. After intravenous(i.v.) administration of DA-3030, at dose of 5, 10 and 100 ㎍/㎏ to rats, some pharmacokinetic parameters, such as terminal half-lives(1.05, 1.19 and 1.83 hr, respectively) and clearance (84.0, 54.8 and 45.5 ㎖/hr/㎏, repectively), were dose-dependent. This could be due to the saturable metabolism of DA-3030 in rats. Similar results were also reported. After subcutaneous(s.c.) and intramuscular(i.m.) administrations of DA-3030, 10 ㎍/㎏ to rats, the extent of bioavailability(absolute bioavailability) were incomplete; the values were 23.3 and 18.2% after s.c. and i.m. injections, respectively, due to the degradation of DA-3030 by protease. After 7-consecutive day i.v. administrations of DA-3030, 10 ㎍/㎏/day, to rats, the plasma concentrations and pharmacokinetic parameters of DA-3030 were not significantly different from those in single administration. In mice and dogs at DA-3030 dose of 10 ㎍/㎏, the plasma concentrations of DA-3030 were also declined rapidly with terminal half-lives of 1.31 and 1.15 hr, respectively. DA-3030 was highly concentrated in the kidney after i.v. administration of DA-3030, 10 ㎍/㎏, to rats, and the results were similar to those obtained using radiolabelled rhG-CSF in the literature. Above data indicate that DA-3030 has similar properties to rhG-CSF manufactured by other companies in view of pharmacokinetics.
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랫트에서 한국형유산균인 Bifidobacterium breve K-110 , K-111 및 B. infantis K-525 균주제제의 경구투여 급성독성
이영경(Young Kyoung Rhee),한명주(Myung Joo Han),최응칠(Eung Chil Choi),김동현(Dong Hyun KIm) 한국응용약물학회 1998 Biomolecules & Therapeutics(구 응용약물학회지) Vol.6 No.4
Acute oral toxicity of Bifidobacterium breve K-110, Bifidobacterium breve K-111, Bifidobacterium infantis K-525 were studied in Sprague-Dawley rats of both sexes. In this study, we examined number of deaths, clinical signs, body weight and gross findings for 14 days after single oral administration of B. breve K-110, B. breve K-111 or B. infantis K-525 with different levels. They did not show any toxic effect in rats and oral LD_(50) value was over 5 g/㎏ in rats.
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32P-Postlabelling 방법의 응용 : Azo 색소 및 Flavonoid 화합물에의해 유도되는 DNA Adduct 의 검출에 관한 연구
김재현(Jae Hyun Kim),박창원(Chang Won Park),박정식(Jung Sik Park),홍연탁(Yonn Tack Hong) 한국응용약물학회 1993 Biomolecules & Therapeutics(구 응용약물학회지) Vol.1 No.1
DNA adducts induced by putative chemical related to carcinogenesis were detected and determined by (32)^P-Postlabelling assay after exposure of 4 compounds comprising two azo dyes (amaranth, new coccine) and two flavonoid compounds (rutin, quercetin) to ICR mouse. DNA was isolated from mouse liver and digested enzymatically to deoxyribonucleoside 3`-monophosphate. The postincubation of DNA digests with nuclease P1 before (32)^P-labelling enhanced the technique`s sensitivity. Nuclease P1 cleaves deoxyribonucleoside 3`-monophosphates of normal nucleotides to deoxyribonucleosides which do not serve as substrates for polynucleotide kinase, while most of adducts were found to be totally or partially resistant to the 3`-dephosphorylating action of nuclease Pl. The adducted deoxyribonucleoside 3`-monophosphate was converted to 5`-(32)^P-labelled deoxynucleoside 3`,5`-bisphosphate by T4 polynucleotide kinase. The nucleotides were separated by anion-exchange thin layer chromatography(TLC) on polyethyleneimine cellulose by 4-dimensional or 2-dimensional TLC then detected by autoradiography. The results show that DNA adducts were detected in liver DNA of ICR mouse after administration of amaranth and quercetin by 2-dimensional and/or 4-dimensional TLC.
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단현광(Hyun Kwang Tan),배준호(Joon Ho Bae),박은석(Eun Seok Park),지상철(Sang Cheol Chi) 한국응용약물학회 1998 Biomolecules & Therapeutics(구 응용약물학회지) Vol.6 No.1
The pharmacokinetic properties and antiinflammatory activity of 3% ketoprofen lotion (ID-lotion), formulated with poloxamer 407, were evaluated using rats. For the pharmacokinetic study, the lotion, at the dose of 4.5 mg/kg, was applied on the dorsal skin of rats and the drug concentration in plasma was determined using an HPLC method. As references, ketoprofen suspended in saline was administered orally, and Elotion, which is a 3% ketoprofen lotion in the Japanese market, was applied transdermally. Following the transdermal application of ID-lotion and E-lotion, C_(max) were 316±22.3 ng/ml and 163 ±12.2 ng/ml, respectively, at the same T_(max) of 2 hours postdose, while C_(max) and T_(max) after oral administration of the drug were 1,030 ±89.1 ng/ml and 0.25 hours, respectively. Relative bioavailabilities of ID-lotion and E-lotion were 69.3% and 34.2%, respectively. The antiinflammatory activity of the two 3% ketoprofen lotions was evaluated with carrageenen-induced edema method after 50 mg of the lotions was applied on the paw of rats. ID-lotion showed 67.6% inhibition of the edema formation, while E-lotion showed 34.7%. The calculated EDT after transdermal application of ID-lotion was 2.5 mg/kg, while that after oral administration was 7.0 mg/kg. Based on these results, the relative equiponderal availability of ID-lotion was 296% compared to the oral administration of ketoprofen.
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유전자 재조합 사람형 erythropoietin, GC-rhEPO의 약물동태 및 조직분포
김선돈 ( Sun Don Kim ),한성규 ( Seong Kyu Han ),이호성 ( Ho Sung Lee ),김성남 ( Seong Nam Kim ),정원휘 ( Wo Nee Chong ),백대현 ( Dae Hyun Baek ),조은성 ( Eun Sung Cho ),허재욱 ( Jae Wook Huh ),류판동 ( Pan Dong Ryu ) 한국응용약물학회 2000 Biomolecules & Therapeutics(구 응용약물학회지) Vol.8 No.2
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지상철(Sang Cheol Chi),박은석(Eun Seok Park),단현광(Hyun Kwang Tan),이윤석(Yun Seok Rhee) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.4
The effects of formulation variables of topical lotion on the skin permeation of ketoprofen were evaluated using excised rat skins. The formulation variables were the amounts of poloxamer 407, drug and ethanol, and penetration enhancers. The Keshary-Chien diffusion cells were used for the diffusion study. The flux of ketoprofen linearly decreased as the concentration of poloxamer increased from 5% to 15% in the preparation, and linearly increased as the amount of drug increased. Penetration enhancers such as fatty acids and fatty alcohols showed markedly enhancing effects at the level of 5%. Among them, the highest flux was shown in linolenic acid. From these results, optimum formula containing 3% ketoprofen, 5% poloxamer 407, 40% ethanol and 5% linolenic acid having the flux of 537.6 ㎍/㎠/hr were noted.
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