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      • KCI등재

        토끼의 수종 점막 추출액중 로이신엔케팔린 및 [D-알라$^2]$-로이신엔케팔린아미드의 효소적 분해 특성

        전인구,박인숙,Chun, In-Koo,Park, In-Sook 대한약학회 1994 약학회지 Vol.38 No.5

        To study the feasibility of transmucosal delivery of leucine enkephalin (Leu-Enk) and $[D-ala^2]$-leucine enkephalinamide (YAGFL), their degradation extents and pathways in various rabbit mucosa extracts were investigated by high performance liquid chromatography. The degradation of Leu-Enk and YAGFL was observed to follow the first-order kinetics. The degradation half-lives of Leu-Enk in the nasal, rectal and vaginal mucosal extracts were 1.62, 0.37 and 1.12 hrs and those of YAGFL were 30.55, 9.70 and 6.82 hrs, respectively, indicating Leu-Enk was degraded in a more extensive and rapid manner than YAGFL. But the mucosal and serosal extracts of the same mucosa showed the similar degradation rates for both pentapeptides. The degradation was most rapid in the neutral pH and increasing concentrations of substrates retarded the degradation rates. The maior hydrolytic fragments of Leu-Enk were Des-Tyr-Leu-Enk and tyrosine, indicating the enzymatic hydrolysis by aminopeptidases. However, the data also suggested endopeptidases such as dipeptidyl carboxypeptidase and dipeptidyl aminopeptidase could play some role in the degradation of Leu-Enk. On the other hand, the hydrolytic fragments of YAGFL in all the mucosa extracts were mainly Tyr-D-Ala-Gly and Phe-Leu-Amide, demonstrating the hydrolytic breakdown by endopeptidases. The degradation pathways were further explored by concomitantly determining the formation of smaller metabolites of primary hydrolytic fragments of Leu-Enk and YAGFL in the mucosa extracts.

      • SCOPUSKCI등재

        수용성 폴리파라시클로판류와 약물과의 상호작용(제 2보) -수용액중 수용성 폴리파라시클로판류와 형광 소수 나프탈렌 유도체류와의 상호 작용-

        전인구,이민화,김신근,Chun, In-Koo,Lee, Min-Hwa,Kim, Shin-Keun 한국약제학회 1988 Journal of Pharmaceutical Investigation Vol.18 No.3

        A series of water-soluble polyparacyclophanes bearing two diphenylmethane or two diphenyl ether skeletons were investigated to develop useful host compounds by using 1-anilinonaphthalene-6-sulfonate (ANS) and 2-p-toluidinylnaphthalene-6-sulfonate (TNS) as fluorescent hydrophobic substrates in aqueous solution. It was noteworthy that remarkable fluorescent enhancements and blue shifts of ANS and TNS were observed only in the presence of 1,6,20,25-tetraaza[] paracyclophane (CPM 44) and 1,6,21,27-tetraaza [] paracyclophane (CPM 55) for diphenylmethane skeleton, and 1,7,21,27-tetraaza-14,34-dioxa [] paracyclophane (CPE 55) and 1,8,22,29-tetraaza-15,36-dioxa [] paracyclophane (CPE 66) for diphenyl ether skeleton, comparing with ${\alpha}-\;and\;{\beta}-cyclodextrins$. However, their acyclic analogues such as 4,4'-dimethylaminodiphenylmethane and 4,4'-dimethylaminodiphenyl ether, and paracyclophanes whose cavities were smaller showed only small effects under the same conditions. These facts suggested that hosts and substrates were in an intimate contact which would not occur without larger structures, and thus that guest molecules were strongly incorporated in the hydrophobic cavities of these larger paracyclophanes. The effects of pH on the fluorescent intensity of ANS-CPM 44, ANS-CPM 55, ANS-CPE 55, ANS-CPE 66, TNS-CPM 44, TNS-CPM 55, TNS-CPE 55 and TNS-CPE 66 systems were not significant below pH 2.0, but their fluorescent intensities were markedly reduced with increasing ionic strength.

      • SCOPUSKCI등재

        완충 수용액중 pH, 온도, 이온강도 및 금속이온이 Aucubin의 분해에 미치는 영향

        전인구,조영미,Chun, In-Koo,Cho, Young-Mee 한국약제학회 1995 Journal of Pharmaceutical Investigation Vol.25 No.3

        The physico-chemical stability of aucubin, a hepatoprotective iridoid glucoside, in buffered aqueous solutions was studied using a stability-indicating reversed-phase high performance liquid chromatography. The degradation of aucubin followed the pseudo-first-order kinetics. In strong acidic regions, aucubin was rapidly degraded by the specific acid catalysis, forming dark brown precipitates. From the rate-pH profiles, it was found that aucubin was most stable at the pH of about 10. From the temperature dependence of degradation, activation energies for aucubin at pH 2.1 and 4.9 were calculated to be 22.0 and 24.3 kcal/mole, respectively. The shelf-life $(t_{90%})$ for aucubin at pH 9.07 and $20^{\circ}C$ was predicted to be about 603 days. A higher ionic strength accelerated the degradation of aucubin at pH 4.01. The effect of metal ions on the degradation rate of aucubin at pH 7.16 was in the rank order of $Cu^{2+}\;>\;Fe^{3+}\;>\;Co^{2+}\;>\;Fe^{2+}\;>\;Mg^{2+}$. On the other hand, $Mn^{2+}\;and\;Ba^{2+}$ slowed the degradation rate.

      • SCOPUSKCI등재

        수용성 폴리파라시클로판류와 약물과의 상호작용(제 3보)-수용액 중 수용성 폴리파라시클로판류와 형광 소수 나프탈렌 유도체류와의 복합체 형성-

        전인구,이민화,Chun, In-Koo,Lee, Min-Hwa 한국약제학회 1989 Journal of Pharmaceutical Investigation Vol.19 No.2

        Complex formation of water-soluble polyparacyclophanes bearing two diphenylmethane or two diphenyl ether skeletons with l-anilinonaphthalene-8-sulfonate (ANS) and 2-p-toluidinylnaphthalene-6-sulfonate (TNS) was investigated quantitatively to develop useful host compounds comparing with ${\alpha}\;-\;and\;{\beta}-cyc1odextrins$$({\alpha}-\;and\;{\beta}-CyDs$) in aqueous solution. Benesi-Hildebrand type analysis of the fluorescent intensity showed that the dissociation constants (Kd) of paracyclophane-ANS complexes were $1.55\;{\times}\;10^{-4}M$ for 1,6,20,25-tetraaza[]paracyclophane(CPM 44) and $1.23\;{\times}\;10^{-4}M$ for 1,7,21,27-tetraaza[]paracyclophane (CPM 55), and those of paracyclophane-TNS complexes were $6.99\;{\times}\;10^{-6}M$ for CPM 44 and $6.23\;{\times}\;10^{-5}M$ for CPM 55, in 1:1 molar ratio. On the other hand, the Kd values of 1,7,21,27-tetraaza-14,34-dioxa[]paracyclophane (CPE 55)-ANS, 1,8,22,29-tetraaza-15,36-dioxa[]paracyclophane (CPE 66)-ANS, CPE 55-TNS, CPE 66-TNS complexes were $1.75\;{\times}\;10^{-3}M$, $3.07\;{\times}\;10^{-3}M$, $3.75\;{\times}\;10^{-3}M$ and $2.15\;{\times}\;10^{-3}M$, respectively. On the contrary, the Kd values of ${\alpha}-CyD-ANS$, ${\beta}-CyD-ANS$, ${\alpha}-CyD-TNS$ and ${\beta}-CyD-TNS$ complexes were found to be $3.98\;{\times}\;10^{-2}M$, $1.05\;{\times}\;10^{-2}M$, $1.38\;{\times}\;10^{-2}M$ and $3.52\;{\times}\;10^{-4}M$, respectively. These results mean that the complexation of CPMs with ANS or TNS is by 5.6-1,975 fold stronger than that for ${\alpha}-or\;{\beta}-CyDs$, and the complex formation of CPEs with ANS or TNS is nearly same as or somewhat stronger than that for ${\alpha}-or\;{\beta}-CyDs$. From the Kd values determined at different temperatures, thermodynamic parameters were calculated and the complexation was found to be a spontaneous exothermic reaction. The effects of pH on Kd values of CPM 44-ANS, and CPM 55-ANS complexes were negligible in the range of pH 1.2-1.8. However, the Kd values of these complexes increased significantly with increasing ionic strength.

      • SCOPUSKCI등재

        수용성 폴리파라시클로판류와 약물과의 상호작용 (제1보) -디페닐에텔을 골격으로 하는 수용성 폴리파라시클로판류의 설계 및 합성-

        전인구,이민화,김신근,Chun, In-Koo,Lee, Min-Hwa,Kim, Shin-Keun 한국약제학회 1988 Journal of Pharmaceutical Investigation Vol.18 No.2

        A series of novel water-soluble paracyclophanes containing two diphenyl ether skeletons and two bridging aliphatic chains of various length were designed and prepared to develop artificial host compounds which might provide efficient hydrophobic field. They were 1,5,19,23-tetraaza-12,30-dioxa[5,1.5.1] paracyclophane (6), 1,6,20,25-tetraaza-13,32-dioxa[]paracyclophane (7), 1,7,21,27-tetraaza-14,34-dioxa[]paracyclophane (8) and 1,8,22,29-tetraaza-15,36-dioxa[]paracyclophane (9). As the corresponding acyclic analogue, 4,4'-dimethylaminodiphenyl ether (11) was synthesized for the comparative study of further host-guest interaction.

      • KCI등재

        Eudragit RS(R)를 이용한 지속 방출형 아스피린 마이크로캅셀의 제조 및 평가

        전인구(In Koo Chun),신동원(Dong Won Shin) 대한약학회 1988 약학회지 Vol.32 No.1

        '스콜라' 이용 시 소속기관이 구독 중이 아닌 경우, 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

        Eudragit RS(R) polymer was used as a wall material for the microencapsulation of aspirin by a phase separation method from chloroform-cyclohexane system with 5% polyisobutylene (PIB) in cyclohexane, and microcapsules obtained were evaluated by particle size analysis, scanning electron microscopy (SEM), drug release and drug stability test. With PIB as a coacervation inducing agent, smooth and tight microcapsules with less aggregation were obtained. Below 1 : 0.3 core-wall ratio, it was possible to coat individual particle. Variation of production conditions showed that increasing the proportion of wall material, particle size and wall thickness of microcapsules and the concentration of paraffin wax in cyclohexane as a sealant sustained drug release rates effectively. SEM confirmed that larger microcapsules after drug release did not rupture into smaller particles but contained a few small pores on the surface. Aspirin release from Eudragit RS(R) coated microcapsules was independent of the pH of medium, and the mechanism of drug release from non-sealed and sealed microcapsules appeared to fit Higuchi matrix model kinetics. Aspirin in the mixture of aspirin microcapsules and sodium bicarbonate was by far more stable than that in the mixture of pure aspirin and sodium bicarbonate.

      • KCI등재

        퀘르세틴의 가용화, 퀘르세틴 및 루틴의 토끼 십이지장 점막 투과성

        전인구(In Koo Chun),서은하(Eun Ha Seo) 대한약학회 1998 약학회지 Vol.42 No.1

        '스콜라' 이용 시 소속기관이 구독 중이 아닌 경우, 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

        To increase the solubility of quercetin, which is a practically insoluble flavonoid of Ginkgo biloba leaf, the effects of nonaqueous vehicles. Their cosolvents, water-soluble polymers and modified cyclodextrins (CDs) were observed. Polyethylene glycols, diethyleneglycol monoethyl ether, and their cosolvents with water showed a good solvency toward quercetin. Also the aqueous solutions of povidone, copolyvidone and Cremophor RH 40 was effective in solubilizing quercetin. Complex formation of quercetin with beta-cyclodextrin (beta-CD), dimethyl-beta-cyclodextiin (DMCD), 2-hydroxypropyl-beta-cyclodextrin (HPCD) and beta-cyclodextrin sulfobutyl ether (SBCD) in water was investigated by solubility method at 37oC. The addition of CDs in water markedly increased the solubility of quercetin with increasing the concentration. AL type phase solubility diagrams were obtained with CDs studied. Solubilizaton efficiency by CDs was in the order of SBCD >> DMCD > HPCD > beta-CD. The dissolution rates of quercetin from solid dispersions with copolyvidone, povidone and HPCD were much faster than those of drug alone and corresponding physical mixtures, and exceeded the equilibrium solubility (3.03+/-1.72mcg/ml). The permeation of quercetin through duodenal mucosa did not occur even in the presence of enhancers such as bile salts, but the permeation was observed when the mucus layer was scraped off. This was due to the fact that quercetin had a strong binding to mucin (58.5mcg/mg mucin). However rutin was permeable to the duodenal mucosa. The addition of enhancer significantly increased the permeation of rutin in the order of sodium glycocholate

      • KCI등재

        시클로덱스트린류와의 복합체 형성에 의한 벤즈이미다졸계 구충 약물의 용해성 및 용출 증가

        전인구(In Koo Chun),박인숙(In Sook Park) 대한약학회 1993 약학회지 Vol.37 No.3

        '스콜라' 이용 시 소속기관이 구독 중이 아닌 경우, 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

        Complex formations of practically insoluble antelmintic drugs such as mebendazole (MBZ), albendazole (ABZ) and flubendazole (FBZ) with dimethyl-beta-cyclodextrin (DM-beta-CyD) and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) together with alpha-, beta- and gammar-cyclodextrins (CyDs) in buffered solutions were investigated by solubility method. AL type phase solubility diagrams were obtained in all cases except for the complexation (BS type) of FBZ with gammar-CyD. The highest stability constants were obtained with DM-P-CyD, followed by allpha-CyD > beta-CYD > HP-beta-CyD > gammar-CyD for ABZ, and HP-beta-CyD > gammar-CyD > beta-CyD > alpha-CyD for FBZ at pH 1.2. On the other hand, solid dispersion systems of ABZ and FBZ with beta- and DM-beta-CyDs were prepared by solvent evaporation method and evaluated by dissolution, differential thermal analysis and powder x-ray diffractometry. The dissolution rates of ABZ- and FBZ-DM-P-CyD solid dispersions were much faster than those of drugs alone, corresponding physical mixtures and tablets on market both at pH 1.2 and 6.8. Although dissolution rates of all samples at pH 6.8 were by far lower than those obtained at pH 1.2, as explained by pH-solubility profiles for ABZ and FBZ, the dissolution rates at pH 6.8 of ABZ from beta- and DM-beta-CyD solid dispersions exceeded the respective equilibrium solubility (23.9mcg/ml). Fast dissolution of ABZ from solid dispersions with CyDs was attributed to the reduction of drug crystallinity and particle size which was supported by DTA and powder x-ray diffractometry. Consequently these results suggest that solid dispersion systems with CyDs may provide useful means to markedly enhance the solubility and dissolution of benzimidazole antelmintic drugs.

      • KCI등재

        비페닐디메칠디카르복실레이트 주사제의 설계 및 평가

        김혜진(Hye Jin Kim),전인구(In Koo Chun) 대한약학회 2000 약학회지 Vol.44 No.3

        '스콜라' 이용 시 소속기관이 구독 중이 아닌 경우, 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

        In an attempt to develop an injectable form of practically insoluble biphenyl dimethyl dicarboxylate (DDB), the effect of various vehicles, cosolvents and hydrotropic agents was investigated. It was found that polyethylene glycol (PEG) 400 revealed the best solvency toward DDB (17.7mg/ml at 370C), and decreasing order of the solubility was as follows: PEG 400 > PEG 300 > diethylene glycol monoethyl ether (DGME) > PEG-8 glyceryl caprylate/caprate. Among the hydrotropes used, sodium salicylate, sodium benzoate and nicotinamide were effective in increasing the solubility in water. The solubility of DDB in 2M sodium salicylate, sodium benzoate and cotinamide solutions was increased 44.3, 23.5 and 44.0 times than that in water, respectively. The addition of sodium salicylate and sodium benzoate to PEG 300-water, PEG 400-water and DGME-water cosolvents remarkably increased the solubility of DDB, and significantly retarded precipitate formation when mixed with water. Hemolytic properties of DDB injections (2mg/4~10ml) in PEG 300-water or DGME-water (60:40 v/v) cosolvents containing sodium benzoate (0.14~0.35M) were very low. It was concluded from the results that these solutions would be applied to the design of new DDB injections.

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