β - Cyclodextrin 과의 복합체 형성에 의한 Tiaprofenic Acid 의 용출증가

전인구,박인숙 한국약제학회 1986 Journal of Pharmaceutical Investigation Vol.16 No.2

Inclusion complexation of tiaprofenic acid (TPA) with cyclodextrins (α-, β-, γ-CyDs) in aqueous solution and in solid phase was investigated by solubility method, measurement of partition coefficient, ultra-violet, circular dichroism, infrared spectroscopies, powder X-ray diffractometry and differential scanning calorimetry. Investigations were made to prepare inclusion complexes of TPA with β-CyD in solid powdered form by coprecipitation, freeze-drying, spray-drying and co-pulverization methods. The coprecipitation, freeze-drying and spray-drying methods were successful in obtaining inclusion complexes. The results showed that the latter two methods might be originally superior to the former in obtaining powdered inclusion complexes. Especially, it was shown by powder X-ray diffractometry that spray-dried β-CyD alone, TPA-spray-dried β-CyD physical mixture, and spray-dried TPA-β-CyD complex were amorphous. The dissolution behaviours of TPA-β-CyD systems prepared by above four methods were compared with those of TPA alone and TPA-β-CyD physical mixture, and the rates of dissolution of TPA in pH 1.2 buffer were greatly enhanced by inclusion complexation and copulverization.

케토프로펜 - β - 시클로덱스트린 고체분산체의 마이크로캅셀화 및 제어 방출

전인구,박정화 한국약제학회 1992 Journal of Pharmaceutical Investigation Vol.22 No.1

This study was aimed to control the release characteristics of ketoprofen by microencapsulating ketoprofen-β-cyclodextrin (KF-β-CyD) solid dispersion with Eudragit RS by the phase separation method using a nonaqueous vehicle. KF alone was also microencapsulated with Eudragit RS by the evaporation process in water phase. The results obtained showed that it was not possible to microencapsulate KF alone by phase separation in a chloroform-cyclohexane system while it was easy to microencapsulate KF-β-CyD solid dispersion system. For the microcapsules, the release test was performed in the first fluid (pH 1.2) and the second fluid (pH 6.8) of K.P.V disintegration medium at 37℃. The release of KF from KF-β-CyD solid dispersion microcapsules (1:1 core wall ratio) was more sustained than that from KF microcapsules, and followed zero-order kinetics. Especially, solid dispersion microcapsules showed pH-independent release patterns with higher wall to core ratio (1:1 w/w).

Intrathecal Lamotrigine Attenuates Antinociceptive Morphine Tolerance and Suppresses Spinal Glial Cell Activation in Morphine-Tolerant Rats

전인구,김성훈,윤영인,박종연 대한의학회 2013 Journal of Korean medical science Vol.28 No.2

Glial cells play a critical role in morphine tolerance, resulting from repeated administration of morphine. Both the development and the expression of tolerance are suppressed by the analgesic lamotrigine. This study investigated the relationship between the ability of lamotrigine to maintain the antinociceptive effect of morphine during tolerance development and glial cell activation in the spinal cord. In a rat model, morphine (15 μg)was intrathecally injected once daily for 7 days to induce morphine tolerance. Lamotrigine (200 μg) was co-administered with morphine either for 7 days or the first or last 3 days of this 7 day period. Thermal nociception was measured. OX-42 and GFAP immunoreactivity,indicating spinal microglial and astrocytic activation were evaluated on day 8. Tolerance developed after 7 days of intrathecal morphine administration; however, this was completely blocked and reversed by co-administration of lamotrigine. When lamotrigine was coinjected with morphine on days 5-7, the morphine effect was partially restored. Glial cell activation increased with the development of morphine tolerance but was clearly inhibited in the presence of lamotrigine. These results suggest that, in association with the suppression of spinal glial cell activity, intrathecally coadministered lamotrigine attenuates antinociceptive tolerance to morphine.

메칠메타크릴레이트 - 부틸메타크릴레이트 공중합체 필름의 평가 및 니트로푸라존 방출의 속도론적 연구

전인구 한국약제학회 1987 Journal of Pharmaceutical Investigation Vol.17 No.3

Methyl methacrylate-butyl methacrylate copolymer (MMBM)-dibutyl phthalate (DBP) films were investigated as a potential topical drug delivery system for the controlled release of nitrofurazone. The kinetic analysis of release data indicated that drug release followed a diffusion-controlled granular matrix model, where the quantity released per unit area is proportional to the square root of time. DBP of several hydrophobic plasticizers selected was found to give the highest release of nitrofurazone. However, hydrophilic plasticizers such as propylene glycol and polyethylene glycol 400 had no controlled release properties and acceptable film formation. The effects of changes in film composition, drug concentration, film thickness, pH of release medium, and temperature on the in vitro release of nitrofurazone were analyzed both theoretically and experimentally. The release rate constant(k') was found to be proportional to DBP content, pH, and the temperature of release medium, but independent of film thickness, and drug concentration in a range of 0.1-0.4% by weight. The linear relationship was found to exist between the log k' and DBP content. The release of nitrofurazone from MMBM-DBP (8:2) films was found to be an energy-linked process. Two energy terms were calculated; the activation energy for matrix diffusion was 13.45 ㎉/mole, and the heat of drug crystal solvation was 27.26-29.34 ㎉/mole. Observation of scanning electron micrographs and microscopic photographs showed that the incorporation of DBP in films increased markedly the particle size of nitrofurazone dispersed in the film matrix, comparing with the fine dispersion of nitrofurazone in pure MMBM film alone.

약무수행 전문인력 양성제도의 도입

전인구,권경희 한국에프디시규제과학회(구 한국에프디시법제학회) 2009 한국에프디시법제학회 학술대회 Vol.2009 No.1

강원(인제) 지역의 수해 피해 원인 및 대책방안

전인구,Jeon, In-Gu 한국관개배수위원회 2006 한국관개배수논문집 Vol.13 No.2

점막 추출액중 치로트로핀 유리호르몬의 효소적 분해 및 안정화

전인구,신동원 ( In Koo Chun,Dong Won Shin ) 한국약제학회 1997 Journal of Pharmaceutical Investigation Vol.27 No.2

N/A To evaluate the feasibility of mucosal delivery of thyrotropin releasing hormone (TRH) through various mucosae, enzymatic degradation and stabilization of TRH in the nasal, rectal and duodenal extracts of rabbits were studied. TRH in the extracts was assayed by HPLC and its degradation was found to follow apparent first-order kinetics. The residual concentrations of TRH in the mucosal extracts of nasal, rectal and duodenal segments after 24 hr of incubation were found to be 65.1(±1.1), 19.7(±2.7) and 0%, and in the serosal extracts. 65.6(±5.5), 75.2(±1.1) and 68.7(±1.4)%, respectively. This result suggests that there is a significant difference in the activity of TRH-degrading enzymes among the sites of administration. The inhibition of TRH degradation in the mucosa extracts was kinetically investigated using various additives such as thimerosal, benzalkonium chloride, disodium edetate, ο-phenanthroline, dithiothreitol and dithioerythritol, and IC_(50) values of inhibitors were calculated. The results obtained showed that thimerosal (0.5 mM) and benzalkonium chloride (0.141 mM) protected TRH from the enzymatic degradation in all the mucosa extracts more than 95% after 24 hr of incubation.

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[6.1.6.1]paracyclophane (7), 1,7,21,27-tetraaza-14,34-dioxa[7.1.7.1]paracyclophane (8) and 1,8,22,29-tetraaza-15,36-dioxa[8.1.8.1]paracyclophane (9). As the corresponding acyclic analogue, 4,4'-dimethylaminodiphenyl ether (11) was synthesized for the comparative study of further host-guest interaction.

Dissolution Characteristics of Hydrophobic Drug-Soluble Carrier Coprecipitates(III) -Dissolution Behaviour of Indomethacin from Several Fast Release Solid Dispersions of Indomethacin-

전인구,이민화,김신근,Jeon, In-Koo,Lee, Min-Hwa,Kim, Shin-Keun The Korean Society of Pharmaceutical Sciences and 1976 Journal of Pharmaceutical Investigation Vol.6 No.3

It is well established that dissolution is freruently the rate limiting step in the gastrointestinal absorpton of a drug from a solid dosage from. The relationship between the dissolution rate and absorption is particularly distinct when considering drugs of low solubility. Consequently, numerous attempts have been made to modify the dissolution characteristics of poorly water soluble drugs. Since dissolution rate is directly proportional to surface area, one may increase the rate by decreasing the particle size of the drug. Levy has considered a number of methods by which a drug may be presented to the GI fludids in finely divided from. The direct method is the utilization of microcrystalline or micronized particles. A second method involves the administration of solutions from which, upon dilution with gastric fluids, the dissolved drug will precipitate in the form of very fine particles. A more unique way of obtaining microcrystalline dispersions of a drug has been ercently suggested by Sekiguchi et al. They have first proposed the formation of a eutectic mixture of a poorly water soruble drug with a physiologically inert, easily soluble carrier. When such systems are exposed to water or GI fluids, the soluble carrier will dissolve rapidly and the finely dispersed drug particles will then be released. It has been suggested by Shefter and Higuchi that the formation of crystalline solvate could be a powerful tool in affecting rapid disslution of highly insoluble substances. Goldberg et al. have noted that the formation of solid solution could reduce the particle size to a minimum and increase the dissolution rate as well as the solubility of the durgs. It has also been shown that the rates of solution of drugs were appreciably increased by coprectipitating the drug with soluble polymers. The increase was found to be sensitive to the method of preparation, the molecular weight of polymer and the particular ratio of drugs to polymer. Although several investigations have demontrated that the solubility and/or dissolution rates of drugs can be increased in this manner, little information is available in the literature related to the in vivo absorption pattern of drugs orally administered as PVP coprecipitates. Recently, however, it was demonstrated that both the rate and extent of absorption of the insoluble drug could be markedly enhanced when orally administered to rats in the form of a coprecipitate with PVP. The purpose of the present investigation was to ascertain the general appility of soluble polymer coprectation technique as a method for enhancing the in vitro dissolution rate of hydrophobic indomethacin. To accomplish this aim, the dissolution characteristics of pure indomethacin, indomethcin-polymer physical mixtures and indomethacin-polymer coprecipitates were quantitatively studied by comparing their relative dissolution rates. The solubility and dissolution behavior of these systems were also examined.

토끼의 수종 점막 추출액중 [ D - Ala2 ] - Methionine Enkephalinamide 의 분해 및 안정화

전인구,양윤정 한국약제학회 1992 Journal of Pharmaceutical Investigation Vol.22 No.3

To study the feasibility of transmucosal delivery of [D-ala²]-methionine enkephalinamide (YA-GFM), its enzymatic degradation and stabilization in various rabbit mucosal extracts were investigated by HPLC method. The degradation of YAGFM was observed to follow the first-order kinetics and the half-lives of YAGFM in the nasal, rectal and vaginal mucosal extracts were found to be 25.7, 3.0 and 7.8 hr, respectively. However, there was no significant difference in degradation rates of YAGFM between the mucosal and serosal extracts obtained from the same mucosal membrane. This finding suggests that even a synthetic enkephalin analog, which is designed to be resistant to aminopeptidases, needs to be fully protected from the enzymatic degradation in mucosal sites for the delivery of the analog through mucosal routes. To inhibit the degradation of YAGFM in various mucosal extracts, effects of enzyme inhibitors such as bestatin (BS), amastatin (AM), thiorphan (TP), thimerosal (TM) and EDTA, alone or in combination, and modified cyclodextrins were observed by assaying YAGFM staying intact during 24 hr-incubation at 37℃. It was found from the results that mixed inhibitors such as TM (0.5 mM)/EDTA (5 mM) or AM (50 μM)/TM (0.5 mM)/EDTA (5 mM) provided very useful means for the stabilization in various mucosal extracts. The latter was found to protect YAGFM from the degradation in the nasal, rectal, and vaginal mucosal extracts by 90.9, 90.4 and 91.3%, respectively, after 24 hr-incubation, suggesting almost complete inhibition of YAGFM-degrading enzymes present in the incubation mixture. However, BS (50 μM), AM 50 (50 μM) or TP (50 μM) alone did not reveal sufficient inhibition except TM (0.5 mM) or EDTA (5 mM). The addition of 2-hydroxylpropyl-β-cyclodextrin (10%) to the nasal mucosal extract, and dimethyl-β-cyclodextrin (10%) to the rectal and vaginal mucosal extracts reduced the first-order rate constants for the degradation of YAGFM by 5.8, 17.3 and 8.9 times, respectively, compared to those with no additive.