SB-31ⓡ 의 일반약리작용 ( General Pharmacology of SB-31ⓡ )

공재양(Jae Yang Kong),박우규(Woo Kyu Park),천혜경(Hyae Gyeong Cheon),권경자(Kyoung Ja Kwon),윤여생(Yeo Saeng Yoon),신화섭(Hwa Sup Shin) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.4

General pharmacological effects of SB-31^R the extracts of Pulsatilla koreana, were investigated in mice, rats and guinea-pigs. Intravenous injection of SB-31 (3 and 6 ml/kg) produced almost no effect on central nervous system; no effects on the general symptom and behaviors of mice, spontaneous locomotor activity, pentobarbital-induced sleeping time, rotarod performance, electroshock and pentylenetetrazole-induced seizures, acetic acid-induced writhing and normal body temperature in mice. SB-31 showed little effects on the spontaneous movement of the isolated ileum and contraction induced by agonists in isolated ileum, suggesting no influence on autonomic nervous system. Administration of SB-31 also did not show any effect on blood pressure in conscious rats. However, a slight decrease in heart rate was observed at high doses (6 and 10 ml/kg) of SB-31 in conscious rats. Similarly, a slight increase in respiratory rate was observed at 6 ml/kg of SB-31 in anesthetized rats. SB-31 did not produce any effect at the dose of 3 ml/kg, but showed a tendency to increase the urinary volume at 6 ml/kg, and produced a decrease in urinary excretions of Na^+ and K^+ at 6 ml/kg. However, transport capacity within the gastrointestinal tract and the secretion of the gastric juice were not influenced by 6 ml/kg of SB-31. In conclusion, these results suggest that SB-31 did not produce any acute effects on the central nervous system, autonomic nervous system, respiratory and circulatory systems, digestive system and kidney function at the dose of below 3 ml/kg.

새로운 캅사이신유도체 DA-5018 의 피하주사 및 구소도포시 진통효과

김원배(Won Bae Kim),양중익(Junn Ick Yang),배은주(Eun Ju Bae),신명수(Myeong Soo Shin),손문호(Moon Ho Son),김희기(Hee Kee Kim),공재양(Jae Yang Kong) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.2

The analgesic effects of DA-5018, a new capsaicin derivative, were evaluated in various experimental pain models. Drugs were administered subcutaneously or topically. When drugs were administered subcutaneously, 1) the ED_(50) values of DA-5018, morphine ·HCl, capsaicin and acetaminophen were 0.091-2.0, 0.3-4.3, 1.4-26.5 and 45.4-643 mg/kg, respectively in various pain or inflammatory models including acetic acid writhing, formalin, tail flick, Randall-Selitto, hot plate and croton oil-induced ear edema test, 2) the AD₂ values (the dose for doubling of pain threshold of vehicle control) of DA-5018, capsaicin and ketoprofen were 1.07±0.18, 23.47±4.46 and 2.97±0.43 mg/kg in Freund`s complete adjuvant (FCA)-induced arthritic pain model. And by topical application, 1) neither DA-5018 0.3% cream nor Zostrio-HP (capsaicin 0.075%) were effective in formalin test, 2) although DA-5018 0.3% cream significantly inhibited the croton oil-induced ear edema being better than Zostrix-HP and Kenofen (ketoprofen 3%). 3) Ln FCA model, DA-5018 0.3% cream reversed the decreased pain threshold of arthritic rat from 136.4 g (day 0) to 289.0 g (day 5) and 250.1 g (day 10), which was similar to Zostrix-HP, These results suggest that DA-5018 administered subcutaneously has a potent and broad analgesic spectrum than nonsteroidal antiinflammatory drugs against acute and chronic pain, and by topical application it exerts comparable analgesic and antiinffammatory effects to capsaicin cream.

인삼의 항스트레스 작용에 관한 연구

김낙두(Nak Doo Kim),한병훈(Byung Hoon Hahn),이은방(Eun Bang Lee),공재양(Jae Yang Kong),김명혜(Myoung Hae Kim),진창배(Chang Bae Jin) 한국생약학회 1979 생약학회지 Vol.10 No.2

Two pure saponin components, Panax saponin C (protopanaxatriol derivative, ginsenoside Re) and Panax saponin E (protopanaxadiol derivative, ginsenoside Rb_l) were isolated from Panax ginseng root and their acute toxicities in mice and antistress effects in rats were investigated. Average lethal doses (LD_(50)) of ginsenoside Re were 130㎎/㎏ (i.v.), more than 1,000㎎/㎏ (i.p.) and more than 1,500 ㎎/㎏ (s.c.), respectively. Average lethal dose of ginsenoside Rb₁ was 243㎎/㎏ intravenously. Adrenal ascorbic acid and cholesterol contents were significantly decreased when normal rats were exposed to heat (40℃) for 30 min. The reduction of the adrenal ascorbic acid and cholesterol contents in rats was partially prevented when the rats received the ginseng saponins prior to exposure to heat stress and most pronounced effects were observed in rats received ginsenoside Re. However, it was found that administration of ginseng alone, without stress, did not significantly change the ascorbic acid and cholesterol contents in adrenal glands. Eosinophil counts in the blood of the rats were elevated when the rats were exposed to the heat stress, and the elevation of the eosinophil counts were prevented with the ginseng saponins under the stress, but the changes were all insignificant statistically.

신규 플르오로퀴놀론계 항생물질인 DWP20373 의 흰쥐 및 개에서의 체내동태와 조직분포

심점순(Jeom Soon Shim),유영효(Young Hyo Yu),남권호(Kweon Ho Nam),박명환(Myung Hwan Park),공재양(Jae Yang Kong),조재열(Jae Youn Cho),한승희(Seung Hee Han),김병오(Byoung O Kim),김지연(Ji Yeon Kim),유은숙(Eun Sook Yoo),정대영(Dae Young 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.2

The pharmacokinetics and tissue distribution of DWP20373, a novel fluoroquinolone, were examined in rats and beagle dogs after a single intravenous and oral administration. Analysis of DWP20373 in plasma, tissue, and urine was performed by both HPLC and microbiological assay. The plasma drug concentration declined biexponentially both rats and beagle dogs. In the rats, the terminal drug elimination half-life (t_(½β)) was 64 min (IV) and 57 min (PO) by bioassay, and 76 min (IV) and 77 min (PO) by HPLC. Whereas, in beagle dogs, t_(½β) was 196 min (IV) and 350 min (PO). The volume of distribution at steady-state (Vd_(ss)) was 811 ml/kg (bioassay) and 2061 ml/kg (HPLC) in rats, and 2738 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl₁) of DWP20373 was 10 ml/min/kg (bioassay) and 7 ml/min/kg (HPLC) in rats, and 11 ml/min/kg (bioassay) in beagle dogs. The extent of bioavailability after oral administration was 49% (bioassay) and 67% (HPLC) in rats, and 84% (bioassay) in beagle dogs. The 24-h urinary recovery, measured by bioassay, was 2.7% after oral dosing and 5.5% after intravenous dosing in rats. Serum protein binding ratio determined at 2 ㎍/㎖ was 78%. This drug was also distributed in tissues in the decreasing order of liver, kidney, spleen, lung, heart, and muscle determined at 30 min after oral administration.

신규 플루오로퀴놀론계 DWP20367 의 흰쥐 및 개에서의 체내동태와 조직분포

심점순(Jeom Soon Shim),유영효(Young Hyo Yu),남권호(Kweon Ho Nam),박명환(Myung Hwan Park),공재양(Jae Yang Kong),조재열(Jae Youl Cho),한승희(Seung Hee Han),김병오(Byoung O Kim),정대영(Dae Young Jeong),이재욱(Jae Wook Lee),손호정(Ho Jun 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.3

The pharmacokinetics and tissue distribution of DWP20367 (1-cyclopropyl-6-fluoro-8-chloro-7-(2,7-diazabicyclo[3,3,0]oct-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone, were examined in rats and beagle dogs after a single intravenous and oral administration. Analysis of DWP20367 in plasma, tissue, and urine was determined by both HPLC and microbiological assay (bioassay). The plasma concentration-time curves of the drug in rats and beagle dogs were biexponentially declined. The terminal halflife (t_(½β)) of the drug in rats was about 60.1 ±7.3 min (i.v.) and 61.3 ±12.4 min (p.o.) in bioassay, and 86.3 ±19.8 min (i.v.) and 50.9±14.9 min (p.o.) in HPLC. In beagle dogs, half-life of the drug determined by bioassay was about 121.8±6.2 min (i.v.) and 111.0±7.6 min (p.o.). The volume of distribution at steady-state (Vd_(ss)) was 243.8±74.1 ml/kg (bioassay) and 339.2±84.3 ml/kg (HPLC) in rats, and 1587.5±536.9 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl₁,) of DWP20367 was 3.4±0.4 ml/min/kg (bioassay) and 2.4±0.4 ml/min/kg (HPLC) in rats, and 12.3±1.0 ml/min/kg (bioassay) in beagle dogs, respectively. The extent of bioavailability after oral administration was 89.1 %(bioassay) and 79.9% (HPLC) in rats, and 78.7% (bioassay) in beagle dogs. Urinary recovery (24-h) assayed by bioassay was 0.7% (p.o.) and 1.2% (i.v.) in rats, and 0.8% (p.o.) and 1.0% (i.v.) in beagle dogs. In rats, 24-h fecal recovery determined by bioassay was 11.2% (p.o.) and 0.1% (i.v.). Rat and human serum protein binding ratios at 2 ㎍/ml were about 90∼91%. This drug determined by bioassay was also distributed by the order of liver, kidney, lung, heart, spleen and muscle 30 min after oral administration.

세팔로스포린 3′-퀴놀론의 물리화학적 성질, 안정성 및 체내약물동태

나성범,공재양,김완주,지웅길 충남대학교 약학대학 의약품개발연구소 1993 藥學論文集 Vol.9 No.-

A cephalosporin with an aminothiazolylmethoxyimino-type side chain at the 7 position and bicyclic quinolone dithicarbamate at the 3' position was synthesized. It has broad and potent antivacterial activity in vitro. The antibacterial spectrum reflects contributions of both the cephalosporin moiety and the quinolone moiety. Thus, this compound was named DACD implying a dual-action cephalosporin derivative. In this paper, the physicochemical properties (lipid-water partition, pKa), stability and pharmacokinetics of DACD were determined and compared with cefotaxime 3'-norfloxacin dithiocarbamate (CENO). Stability tests were studied in pH 1.20, 6.80 and 8.00 buffers and in the presence of AB type human plasma, rat liver homogenate and its β-lactamase. The pharmacokinetic paramaters of DACD were evaluated in mice after a single intravenous dose of 40 ㎎/㎏. The results are as follows. The lipid-water partition coefficient of DACD was higher than that of CENO. The calculated pKa values of CENO and DACD, were 6.82±0.03, 7.53±0.21, respectively. In the hydrolysis test, half-lives (t^1/2) of CENO and DACD was 66.0 hr and 80.0 hr in pH 6.80 buffer, 190 hr and 91.4 hr in pH 8.00 buffer. CENO and DACD were rapidly hydrolyzed in human plasma and in rat liver homogenate. Half-lives (t_1/2) of CENO and DACD were 1.29 hr and 1.15 hr in human plasma, 0.62 hr and 0.71 hr rat liver homogenate. In β-lactamase stability test, CENO and DACD were very stable to the β-lactamase obtained from three different strains. Half-life (t_1/2) and areas under the curve (AUC) in mice were 2.33 hr and 15.97 (㎎·h/I), respectively.