Hepatic targeting of acyclovir

용철순 전남대학교 약품개발연구소 1997 약품개발연구지 Vol.6 No.1

With the purpose of improving the therapeutic index of [³H] acyclovir (ACV) in the treatment of chronic hepatitis B infection, asialofetuin (AF) which after selective interaction with Ashwell's receptor specifically eaters into hepatocytes, was chosen as a carrier system for hepatic targeting. This drug was first converted to its monophosphate (ACVMP), which was subsequently activated by water soluble carbodiimide to conjugate with ε-NH₂ groups of lysine residues of AF. The molar ratio of ACVMP to AF in the conjugate was 3.9. In rats, elimination of ACVMP-AF conjugate after i.v. injection showed two phase elimination kinetics. Initial apparent elimination rate constant in rats was 0.191 min^(-1) which was greater than that of ACV. The elimination rate constant from terminal phase was 0.021 min^(-1). Area under the total radioactivities versus time curve was found to be several times larger in liver than in other organs (spleen, intestine, lung and kidney) after i.v, administration of the conjugate labelled in the drug moiety. The above results suggested that ACVM-AF conjugate was rapidly taken up by hepatocytes and could be a useful hepatic targeting system.

프레탈정 (실로스타졸 100mg)에 대한 실로스탄정 (한국유나이티드 제약)의 생물학적 동등성

용철순,이경희,최진석,박병주,정세현,김용일,박상만,유봉규,이종달,최한곤 한국병원약사회 2003 병원약사회지 Vol.20 No.2

Bioequivalence of one cilostazol tablets, the Pletaal^(R)(Korea Otsuka Pharmaceutical Co., Ltd.) and Cilostan^(R)(Korea united Pharmaceutical Co., Ltd.), was evaluated according to the guideline of KFDA. Sixteen normal male volunteers(age 20~30 years old)were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 100㎎ of cilostazol were orally administered, blood was taken at predetermined time intervals and the concentration of cilostazol in plasma was determined with an HPLC method using UV detector. The pharmacokinetic parameters(C_(max), T_(max) and AUC_(t)) were calculated and ANOVA was utilized for the statistical analysis of parameter. The results showed that the differences in C_(max), T_(max) and AUC_(t) between one tablet were 16.08%, 18.88% and 17.57%, respectively. The powers (1-β) for C_(max), T_(max) and AUC_(t) were 85.03%, 83.92% and 80.12%, respectively. Detectable differences(Δ) and confidence intervals were all less than 20%, and confidence interval of all the parameters were also less than 20% at the significance level(α) of 0.05. All of these parameters met the criteria of KFDA for bioequivalence, indicating that Cilostan^(R) tablet is bioequivalent to Pletaal^(R) tablet.

경피흡수에 영향을 미치는 인자

용철순,이종달,최한곤 영남대학교 약품개발연구소 2000 영남대학교 약품개발연구소 연구업적집 Vol.10 No.-

Transdermal drug delivey systems(TDDS) are known to have various adavantages over conventional dosage forms, such as simple dosage, prolonged and controlled action of drugs, avoidance of hepatic first-pass effect, and greater improved patient compliance. One of the main shortcomings of TDDS, however, is poor percutaneous absorption. Many biological and physicochemical factors influencing percutaneous absorption is described together with the corresponding experimental results and practical examples.

헬리코박터 파이로리 균 진단용 ¹³C-요소 캅셀의 개발

용철순,김용일,김지만,강성훈,권기철,이종달,김종국,사홍기,최한곤,Yong, Chul-Soon,Kim, Yong-Il,Kim, Chi-Man,Kang, Sung-Hoon,Quan, Qi-Zhe,Rhee, Jong-Dal,Kim, Chong-Kook,Sah, Hong-Kee,Choi, Han-Gon 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.1

The purpose of this study was to develop a new $^{l3}C-urea-containing$ capsule for diagnosis of H. pylori. The urea-containing capsules were prepared with various diluents such as polyethylene glycol (PEG), microcrystalline cellulose, sodium lauryl sulfate and citric acid. The dissolution test, $^{l3}C-urea$ breath test and stability test were then performed on the capsules. Microcrystalline cellulose and sodium lauryl sulfate retarded the initial dissolution rates of urea. However, PEG increased the initial dissolution rates of urea. Furthermore, two formulae composed of PEG, [$^{l3}C-urea/PEG$ (38/1.9 mg/cap)] and [$^{l3}C-urea/PEG/citric$ acid (38/1.9/1.9 mg/cap)] had the maximum DOB value, about 16 at 20 mim, while the formula composed of only 38 mg $^{l3}C-urea$ had the maximum DOB value at 30 min. The results indicated that PEG improved the, sensitivity of $^{l3}C-urea$ in the human volunteers. The capsule [$^{l3}C-urea/PEG$ (38/1.9 mg/cap)] was stable for at least six months in 25 and $37^{\circ}C$. Thus, a PEG-containing capsule, [$^{l3}C-urea/PEG$ (38/1.9 mg/cap)] would be a more economical, sensitive and stable preparation for diagnosis of H. pylori.

편자 고형엘릭실제의 분체 특성에 미치는 부형제의 영향

용철순,이종달,김종국,최한곤 영남대학교 약품개발연구소 2001 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

The purpose of this study was to investigate the effect of additives on the powder characteristicsof peonja dry elixir. Peonja dry elixirs were prepared with various amounts of dextrin using a spray-dryer, and their powder characteristics such as flow, cohesion and compressibility were evaluated as an angle of repose, cohesion index and compressibility indes, respectively. Their powder characteristics were not significantly different from one another, indicating that the hydrophilic dexrtin, = base of dry elixir hardly affected their powder characteristics. Peonja dry clixirs were prepared with 10% dextrin and various amounts of additives such as mannitol (hydrophilic excipieat), sodium lauryl sulfate (sur factant), colloidal silica (hydrophobic excipient) and HPMC ( polymer), respectively, and their angle of repose, cohesion index and compressibility index were measured. The powder characteristics of peonja dry elixirs prepared with mannitol were not significantly different from one another, indicating that the mannitol scarcely improved the powder characteristics of peonja dry elixirs. The angle of repose and cohesion index of peonja dry elixirs significantly decreased with increasing amount of sodium lauryl sulfate to 0.3% followed by no significant changes in them. The cohesion index of peonja dry elixir significantly decreased with increasing amount of colloidal silica. The angle of repose and cohesion index of peonja dry elixir significantly decreased with increasing amount of HPMC to 0.3% followed by an abrupt increase in them. However, the compressibility index of peonja dry elixir significantly increased with increasing amount of HPMC to 0.3% followed by an abrupt decrease in them. Our results suggested that a small amount of sodium lauryl sulfate, colloidal silica and HPMC improved markedly the powder characteristics of peonja dry elixirs due to forming stronger and less hygroscopic shell of peonja dry clixirs. Among the peonja dry elixirs studied, the peonja dry elixir prepared with 0.3% sodium lauryl sulfate and 0.3% HPMC had the lowest angle of repose of 27° and cohesion index of 37.8%, and the highest compressibility index of 38.7%, respectively. Thus, sodium lauryl sulfate and HPMC appear to be promising additives for peonja dry elixir, if used in adequate amounts.

원보 ; 항산화제인 Cu(Ⅱ)-DIPS 와 재조합 인간 수퍼옥사이드 디스뮤타제의 비교

용철순,남두현,허근 ( Chul Soon Yong,Doo Hyun Nam,Keun Huh ) 한국약제학회 1995 Journal of Pharmaceutical Investigation Vol.25 No.2

The superoxide dismutase (SOD) mimetic activity of copper complex of 3, 5-disopropylsalicylic acid (Cu(II)-DIPS) was tested and compared to those of human recombinant SOD (hrSOD) and its conjugate form with polyethyleneglycol (PEG) using fer-ricytochrome c reduction assay. Stability constant of Cu(II)-DIPS was measured po-tentiometrically using SCOGS2 program. In the presence of 10 g/L albumin. Cu(II)-DIPS lost most of its SOD mimetic activity. HrSOD was modified with polyethylene glycol (PEG) of M.W. 5000. These conjugates have markedly prolonged plasma half-lives of enzymatic activity (15.5 hr) compared to native hrSOD (5 min). In summary, efficient SOD mimetics should be stable enough not to dissociate in blood by serum protein. HrSOD could have longer half-life by conjugation with inert PEG for sustained SOD effect.

원보 ; HrSOD - 폴리에칠렌 접합체의 아세트아미노펜 간독성에 미치는 영향

용철순,박경아 오두만 ( Chul Soon Yong,Kyong Ah Park,Doo Man Oh ) 한국약제학회 1995 Journal of Pharmaceutical Investigation Vol.25 No.4

The covalent conjugation of human recombinant superoxide dismutase (hrSOD) with trichloros-triazine activated polyethylene glycol (PEG) 5000 formed soluble conjugates with molecular weight of 92KD, which retained 90∼98% of original activity with a markedly prolonged plasma half-life of enzyme activity. The effect of hrSOD-PEG conjugates on acetaminophen (ACP)-induced hepatotoxicity was tested in male rats which were pretreated with 3-methylcholanthrene. HrSOD-PEG conjugates inhibited the hepatotoxicity produced by ACP, on the other hand, native hrSOD had no protective effect. The above results indicated that oxygen radicals might participate in the mechanism of the ACP-induced hepatotoxicity and that polymer conjugated-protein drugs with prolonged half-lives could be employed as an effective therapeutic agent.

노인환자에 대한 약사의 복약지도

용철순,김정애,최한곤,유봉규 한국임상약학회 2004 한국임상약학회지 Vol.14 No.2

헬리코박터 파이로리 균 집당용 13C-요소 캅셀의 개발

용철순,이종달,김종국,최한곤,김용일,김지만,강성훈,권기철,사홍기 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.1

면역독소 연구의 최근 진보

용철순 영남대학교 약품개발연구소 1992 영남대학교 약품개발연구소 연구업적집 Vol.2 No.-