의약용(醫藥用) Bi(III) 화합물(化合物)에 관(關)하여

이계주,Rhee, Gye-Ju 한국약제학회 1985 Journal of Pharmaceutical Investigation Vol.15 No.4

합성규산알루미늄의 최적 제조조건에 관한 연구

이계주,Rhee, Gye-Ju 대한약학회 1989 약학회지 Vol.33 No.2

The optimum reaction conditions for the acid consuming capacity of aluminum silicate synthesized from the reaction of sodium silicate solution and potassium aluminum sulfate solution were investigated by Box-Wilson experimental design, and the micromeritic properties were examined by the means of BET $N_2$ adsorption, Hg penetrometer and methylen blue adsorption. The chemical composition of the samples were analyzed by gravitic method. The results were found to be as follows: optimum reaction temperature $54.7^{\circ}C$, both concentrations of reactant soln 15.7%, reactants molar ratio (Al/Si) 0.5 and drying temperature $65.0^{\circ}C$. The acid consuming capacity of the sample prepared by above optimum conditions was 68 ml and the chemical composition was $Al_2O_3{\cdot}3.6SiO_2{\cdot}3H_2O$. The relationship between acid consuming capacity and micromeritic properties could not found in the range of experiments. Therefore, it is assumed that the acid consuming mechanism of aluminum silicate depends on the neutralization of $Al_2O_3$ and buffer action of $SiO_2$ in sample.

Carbamide Peroxide 용액(溶液)의 안정성(安定性)

이계주,유병설,Rhee, Gye-Ju,Yu, Byung-Sul 대한약학회 1984 약학회지 Vol.28 No.6

In order to eluciate the effect of humidity and organic solvent on the decomposition of carbamide peroxide, the kinetic study was carried out. The carbamide peroxide was prepared from urea and 30%-hydrogen peroxide. The accelerated stability analysis for carbamide peroxide crystal in various relative humidity, and for 10%-carbamide peroxide solution of organic solvents were investigated. Both humidity and temperature were important factors influencing the decomposition rate of carbamide peroxide crystal. The higher the humidity and temperature, the greater was the reaction rate. The breakdown rate of crystal was observed as an apparent zero-order, and was faster than the rate of decomposition in dilute propylene glycol, glycerine or sorbitol solutioos which were measured as an apparent first-order reaction. The more dilute to 10% the organic solvents of 10%-carbamide peroxide, the slower was breakdown rate. It is, therefore, useful in the aspects of stability and economics to substitute solvent of carbamide peroxide topical solution (USP XXI) with 10%-propylene glycol or glycerine instead of anhydrous glycerine.

국산카올린의 흡착성에 관한 연구(III) 고체-액체 계면 흡착

이계주(Gye Ju Rhee) 대한약학회 1985 약학회지 Vol.29 No.6

The adsorption of quinine, atropine and methylrozaniline chloride from aqueous phase by different kaolins was studied to innovated utilization of Korean kaolins as pharmaceutical agents. The adsorption isotherms were determined at 27 +/- 1oC and the results were plotted according to the Langmuir equation. The Langmuir constants were calculated from adsorption isotherms of quinine and methylrozaniline chloride; a=1.46, 1.34 b=5.7, 9.3 and slope=O.175, 0.108, respectively. The kaolins gave the same type of curves with the two alkaloids and methylrozaniline chloride. The white colored premium grade kaolins were better adsorbent for the alkaloids and methylrozaniline chloride than the lower grade ones. The results indicate that the premium grade kaolins could be utilized as an ingredients in intestinal preparations. The condition of activation for the better adsorption was under the cases with the higher temperature and the lower pressure. The smaller particle size, the greater was adsorption power and the activated kaolins had superior adsorptive properties at higher pH value than at higher hydrogen-concentrations.

오메프라졸과 gamma-시클로덱스트린과의 복합체 형성 및 제제학적 특성

이계주(Gye Ju Rhee),김은영(Eun Young Kim) 대한약학회 1995 약학회지 Vol.39 No.2

The interaction of omeprazole(OMP) with gamma-cyclodextrin(gamma-CyD) was investigated by solubility study and the complexation was confirmed by means of UV/VIS spectrophotometer, circular dichroism, differential scanning calorimeter, and 1H nuclear magnetic resonance spectra. The stability, dissolution rate, and partition coefficient of the complex were measured. The results present that the benzimidazole moiety and a part of pyridine ring containing sulfur atom of OMP might be included into the cavity of gamma-CyD and the formation type of inclusion complex appeared to be Bs. The stoichiometric ratio of OMP to gamma-CyD in the complex was found to be 1 : 1 and the stability constant of the complex was found to be 97.1M-1. And the dissolution rate of OMP was markedly increased by inclusion complex formation with gammer-CyD, and so it was above 90% in 5 min, from solid complex. Oil to water partition coefficient of OMP-gamma-CyD complex was 60, which is significantly higher than that of OMP itself, 36.4. The degradation rate constant of OMP were greater than OMP-gamma-CyD complex in aqueous solutions of various pHs, and the half lives of OMP and OMP-gamma-CyD at pH 9 were 279.2 and 509.9 days, respectively, showing that the complex was more stable than OMP, therefore it was thought that OMP was stabilized by inclusion formation with gamma-CyD.

수용성 염산슈도에페드린과 난용성 테르페나단의 구형정석조립법과 액중미립구법을 이용한 서방성펠렛 복합제제의 개발

이계주(Gye Ju Rhee),도기찬(Ki Chan Do),김은희(Eun Hee Kim),박종범(Jong Bum Park),황성주(Sung Joo Whang) 대한약학회 1997 약학회지 Vol.41 No.3

Sustained release-microspheres and immediate release-pellets were prepared to develop a controlled release multiparticulate system containing both water soluble and insoluble drug. Pseudoephedrin.HCl (EPD) and terfenadine (TRF) were used as model drugs, respectively. Sustained release-EPD microspheres were prepared by solvent evaporation method using Eudragit RL or RS as a matrix combined with pH-insensitive film coating. Smaller EPD microspheres were obtained when smaller amount of Eudragit as a matrix material or larger amount of magnesium stearate as a dispersing agent was used. However the obtained microspheres did not show syfficient sustained release characteristics. About 97% of EPD was released after 1 hr irrespective of matrix material used. Subsequent coating of the microspheres with pH-insensitive polymer such as Eudragit RS or ethylcelulose (EC) resulted good sustained in 37.5, 73.3 and 92.0% release of encapsulated EPD in distilled water after 1, 3 abd 7 hr, respectively. It corresponds to mean dissolution time (MDT) of 2.3 hr, which is much larger than that of un-coated EPD microspheres (0.0048 hr). Immediate release TRF pellets were prepared by spherically agglomerated crystallization using Eudragit E as an inert matrix and methylene chloride as a liquid binder. Using Eudragit E alone as a matrix resulted in satisfactory physical properties of the pellets such as sphericity, surface texture and flowability, but led to slower release of TRF from pellets than un-modified TRF powder (MDT of 1.70 vs 1.43 hr in pH 1.2 dissolution medium). Introducing propylene glycol or sodium lauryl sulfate as an emulsifier brought about faster release of TRF from pellets (MDT of 1.14 and 0.95 hr, respectively). In conclusion, microencapsulation by solvent evaporation combined with film coating and spherically agglomerated crystallization were successfully utilized to prepare controlled release multiparticulate system composed of sustained release EPD-microspheres and immediate release TRF pellets.

설린닥의 경구용 지속성 제제설계 및 생체이용율

이계주(Gye Ju Rhee),박선희(Sun Hee Park),황성주(Sung Joo Whang) 대한약학회 1997 약학회지 Vol.41 No.1

In order to design a 24 hr sustained release preparation of sulindac for oral administration, fast release pellet (FR), slow release pellet (SR) and two combined formulation (1 : 1 and 1 : 2) were prepared. The pharmacokinetic effect of such preparations has been evaluated using rabbits as a suitable in vivo model, and tested in man. Dose determination was carried out using curve fitting according to RSTPJP II program. In bioavailability test using rabbit, AUCs of sulindac in a few designed formulations were similar to each other. Cmax- of RF and SR were 1.8 times and 1.2 times higher, respectively, compared to that of combined formulation (FR:SR=1:1). While plasma concentration of FR and SR decreased rapidly, that of combined formulation (FR:SR 1:1) lasted at the level close to Cmax for 24 hrs. Plasma concentration of sulfide form from the combined pellet(FR:SR=1:1) lasted for 24 hrs, and its AUC value was 1.4-fold, 2.7-fold. and 1.2-fold greater than FR pellet, SR pellet and combined pellet (FR:SR 1 : 2). Thus, the combined pellet of 1:1 ratio was found to be the most effective for oral sustained release formulation. Bioavailability test in human showed that AUC of sulfide from TSRP (1 : 1) was approximately 1.5 times greater than total AUC of Immbaron(R) administered twice in a day. While Tmax of sulfide from lmmbaron(R) was 4.33 +/- 1.37 hr (lst administration) and 3.33 +/- 0.82 hr (2nd administration), respectively, that of sulfide from TSRP increased to 7.17 +/- 2.86 hr. Plasma concentration of sulfide from TSRP was sustained at more, than 1.0mcg.hr/ml until 24 hrs after one dose administration. In addition, TSRP may decrease local adverse reaction in the stomach, since plasma concentration of sulfide from the combined pellet was low within 2hrs in the stomach. In conclusion, it is suggested that TSRP formulation may be effective for oral 24 hr sustained release formulation of sulindac dosing 300 ~ 350mg once a day.

Leptospermum Scoparium 수증기 추출물인 마누카 기름의 항균효과

이계주(Gye Ju Rhee),정경수(Kyeong Soo Chung),김은희(Eun Hee Kim),서현주(Hyun Joo Suh),홍남두(Nam Doo Hong) 대한약학회 1997 약학회지 Vol.41 No.1

The antimicrobial activity of Manuka oil, a steam distillate from Leptospermum scoparium, was investigated, and it''s MIC against ten kinds of microorganisms was determined. MICs against bacteria and fungi were measured by means of both two-fold dliution method and agar plate two-fold dilution method, respectively. MICs of Manuka oil against Staphylococcus aureus KCTC 1916 and Micrococcus luteus KCTC 1915, gram-positive microrganisms, were identical as 3.05 mcg/ml, while it''s antibacterial activity against gram-negative microrganisms such as Pseudomonas aeruginosa KCTC 2513, Escherichia coli KCFC 1682, Klebsiella pneunioniae KCTC 2001 or Proteus vulgaris KCTC 2433 was negligible(MIC: > or = 1000 mcg/ml), suggesting a high susceptibility of gram-positive bacteria to Manuka oil. In addition, MIC against Aspergillus niger KCTC 6077 was 24 mcg/ml. and that against the other fungi, Tricophyton mentagrophytes KCTC 1374 and Candida albicans KCTC 1940 was > or + 1000 mcg/ml. When Manuka oil ointment was used in combination with other drugs. i.e.. gentamycin sulfate, chlotrimazol and hydrocortisone acetate, and diphenhydramine HCl and hydrocortisone acetate. it''s antibacterial activity against Staphylococcus aureus KCTC 1916 was higher than Manuka oil ointment or other drugs alone. In conclusion, Manuka oil possesses a selective antibacterial activity against Staphylococcus aureus KCTC 1916, and can be used as a potent antibacterial agent against it.

이온교환수지를 이용한 새로운 오메프라졸 복합체 개발

이계주(Gye Ju Rhee),이기명(Ki Myung Lee),김은영(Eun Young Kim),이창현(Chang Hyun Lee),황성주(Sung Ju Hwang) 대한약학회 1994 약학회지 Vol.38 No.3

Omeprazole(OMZ)-cholestyramine(CHL) and various OMZ-Dowex resin complexes were prepared by reaction between OMZ and activated resins in O.lN NaOH solution. And their physical properties were tested by means of infrared(IR), differential scaning caloimeter(DSC), X-ray diffraction. Chemical stability of OMZ-CHL was increased markedly compared with OMZ and the decomposition of OMZ-CHL followed the pseudo first-order kinetics and the rate constants were 2.743 X 10-4/day at 20oC, 7.83 X 10-3/day under 80% RH and 1.68 X 10-2/day 1 under UV radiation, respectively. On the other hand, the rate constants of OMZ were 2.996 X 10-4/day at 20oC, 1.17 X 10-2/day under 85% RH, and 4.07 X 10-2/day under UV radiation, respectively. The rates of dissolution of OMZ-CHL bulk and OMZ-CHL tablet were 100% and more than 85% in 15 minutes, respectively, which ere increased than OMZ base and OMZ-tablet. In the acute toxicological test, the value of oral LD50(mouse) was 4.608g/kg. OMZ-CHL was pelletized using lactose, polyethyleneglycol(PEG), D-sorbitol, Avicel PH 101, sodium laurylsulfate and polyvinylpyrrolidone(PVP) K-30, and enteric coated with HPMCP, Myvacet, acetone, ethanol and cetanol, of which dissolution rate was found to be more than 85% in 10 minutes. From the above results, it was found that OMZ-CHL is a useful means for development of new oral dosage forms of OMZ.

Zirconium - Pyrithione Complex 에 관한 연구 (Ⅰ)

이계주(Gye - Ju Rhee),권중무(Chung - Moo Kwon) 한국약제학회 1987 Journal of Pharmaceutical Investigation Vol.17 No.4

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