• Archives of Pharmacal Research
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• 제18권1호
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• pp.22-26
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• 1995

The solubility and dissolution rate of naproxen (NPX) complexed with 2-hydroxypropyl-.betha.-cyc-lodextrin (2-HP.betha.CD) using coprecipitation, evaporation, freeze-drying and kneading method were investigated. Solubility of NPX linearly increased (correlation cefficient, 0.995) as $2-HP\betaCD$ concentraction increased, resutling in $A_l$ type phase solubility curve. Inclusion complexes prepared by four different methods were compared by different methods were compared by dfferential scanning calorimetry(DSC). The NPX showed sharp endothemic peak around $156^{\circ}C$ but inclusion complexes by evaporation, freeze-drying and kneading method showed very broad peak without distinct phase transtion temperature. In contrast, inclusion complex prepared by coprecipitation method resulted in detectable peak around $156^{\circ}C$ which is similar to NPX, suggesting incoplete formation of indusion co plex. Dissolution rate of inclusion complexes prepared by evaporation, frezz-drying and kneding except coprecipitation method was largely enhanced in the simultaed gastric and intestinal fluid when compared to NPX powder and commercial $NA-XEN^\registered$tablet. However, about 65% of NPX in gstric fluid. in case of inclusion complex prepared by coprecipitation method, formation of inclusion complex appeared to be incoplete, resulting in no marked enhancement of dissolution rate. From these findings, inclusion complexes of poorly water-soluble NPX with $2-HP\betaCD$ were useful to increase soubility and dissolution rate, resting in enhancement of bioavailability and minimization of gastrointestinal toxicity of drug upon oral administration of inclusion complex.

• Journal of Pharmaceutical Investigation
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• 제26권1호
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• pp.1-11
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• 1996

Biphenyldimethyldicarboxylate (PMC), which has been used to treat hepatitis, is insoluble in water, therefore it has low bioavailability after oral administration. For the purpose of increasing the dissolution rate of PMC, the physical mixtures and inclusion complexes of PMC and $dimethyl-{\beta}-cyclodextrin\;(DM\;{\beta}CD)\;or\;hydroxypropyl-{\beta}-cyclodextrin\;(HP{\beta}CD)$ in molar ratio of 1 : 1 and 1 : 2 were prepared by solvent evaporation method. Mixed micelles of PMC were prepared by reacting PMC with bile salts [sodium cholate(NaC), sodium glycocholate (NaGC)] and oleic acid (OA) or palmitoylcarnitine chloride(PCC). Chloroform/water partition coefficient (PC) of PMC was 36.14 in artificial gastric juice (AGJ) and 33.47 in artificial intestinal juice (AIJ), respectively, on the other hand octanol/water PC was 63.36. PMC formulation was prepared by reacting PMC with PEG400-glycerin system(95 : 5, 90 : 10, respectively) and PEG400-PEG4000-glycerin system (70 : 25 : 5, 65 : 25 : 10, respectively). Dissolution test was performed in AGJ and AIJ by paddle method at $37{\pm}0.5^{\circ}C$. The dissolution rates of PMC tablets on the market were 5.74% and 8.26% at AGJ and AIJ, respectively and marketed PMC capsules were 22.14% and 28.64% at AGJ and AIJ, respectively. The dissolution rates of inclusion complexes of PMC with $DM{\beta}CD$ and $HP{\beta}CD$ in a molar ratio of 1 : 1 were more fast than those of corresponding physical mixtures. The decreasing order of dissolution rates was as follows; PMC-PEG400-PEG4000-glycerin formulation > PMC-PEG400-glycerin formulation > mixed micelles > CD inclusion complexes. The dissolution rates of PMC-PEG400-glycerin and PMC-PEG400-PEG4000-glycerin formulation were most fast and the percentage of dissolution was almost 100% within 20 minutes. And their dissolution rates after 120 minutes were markedly increased as compared with capsules on the market (4.0-fold and 3.2-fold in PMC-PEG400-glycerin formulation at AGJ and AIJ, respectively, and 4.8-fold and 3.7-fold in PMC-PEG400-PEG4000-glycerin formulation at AGJ and AIJ, respectively).

• 대한화학회지
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• 제51권6호
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• pp.526-535
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• 2007

아다만탄 또는 β-cyclodextrin이 결합된 루테늄(II)-터피리딘 착화합물(8, 9, 11)을 합성하고 1H NMR, 13C NMR 및 질량분석스펙트럼으로 구조를 확인하였다. 아다만탄이 결합된 루테늄(II)-터피리딘 착화합물(8, 11) 은 물에 전혀 녹지 않으나, β-cyclodextrin 수용액에 혼합할 경우 β-cyclodextrin과의 초분자를 형성하여 물에 잘 녹아들어갔다. 비슷한 방법으로 수용액 중에서 루테늄(II)-터피리딘 착화합물(8, 11)을 각각 착화합물 9와 혼합 하였을 때, 착화합물(8, 11)의 아다만탄 부분이 루테늄 착화합물 9의 β-cyclodextrin 내부에 포접 됨으로써 안정 한 초분자를 형성하였다.

• Bulletin of the Korean Chemical Society
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• 제33권12호
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• pp.4141-4144
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• 2012

This paper introduces a technique for resolving amino acids that combines the advantages of the conventional CSP (chiral stationary phase) method with the CMPA (chiral mobile phase additive) method. A commercially available chiral crown ether column, CROWNPAK CR(+), was used as the CSP and three cyclodextrins (${\beta}$-CD, ${\gamma}$-CD, HP-${\beta}$-CD) were used as the mobile phase additives. Chromatographic resolution was performed at $25^{\circ}C$ and $50^{\circ}C$ with or without sonication. A comparison of the chromatographic results under ultrasonic conditions with those under non-ultrasonic conditions showed that ultrasound decreased the elution time and enantioselectivity at all temperatures. In the case of the ${\beta}$-CD mobile phase additive, the elution time and enantioselectivity under ultrasonic condition were significantly higher than under non-sonic condition at all temperatures. Commercially available Chiralpak AD, Whelk-O2 and Pirkle 1-J columns were used as CSPs to examine more meticulously the effects of ultrasonication and temperature on the optical resolution. The optical resolution of some chiral samples analyzed at $25^{\circ}C$ and $50^{\circ}C$ with or without sonication was compared. As in the previous case, the enantioselectivity was lower at $25^{\circ}C$ but similar enantioselectivity was observed at $50^{\circ}C$.

• 한국어업기술학회:학술대회논문집
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• 한국어업기술학회 2001년도 춘계 수산관련학회 공동학술대회발표요지집
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• pp.193-194
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• 2001

Cyclodextrin(CD)의 산업화에 필요한 응용기술의 개발에 대해서는 주로 식품과 의약품 관련 산업에서 활발히 진행되고 있다. 실 예로 밀감 쥬스 시럽의 경우, 밀감 성분중 hesperidin이라는 flavonoid 배당체가 석출되어 시럽을 혼탁 시키는 원인이 된다. 시럽 혼탁을 방지하기 위해 $\beta$-CD를 첨가하여 난용성물질인 hesperidin을 포집하여 용해도를 증가시키므로 제품의 질을 개량하고 있다. (중략)

• Journal of Microbiology and Biotechnology
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• 제17권5호
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• pp.792-799
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• 2007

A gene encoding a putative glycogen-debranching enzyme in Sulfolobus shibatae(abbreviated as SSGDE) was cloned and expressed in Escherichia coli. The recombinant enzyme was purified to homogeneity by heat treatment and Ni-NTA affinity chromatography. The recombinant SSGDE was extremely thermostable, with an optimal temperature at $85^{\circ}C$. The enzyme had an optimum pH of 5.5 and was highly stable from pH 4.5 to 6.5. The substrate specificity of SSGDE suggested that it possesses characteristics of both amylo-1,6-glucosidase and $\alpha$-1,4-glucanotransferase. SSGDE clearly hydrolyzed pullulan to maltotriose, and $6-O-\alpha-maltosyl-\beta-cyclodextrin(G2-\beta-CD)$ to maltose and $\beta$-cyclodextrin. At the same time, SSGDE transferred maltooligosyl residues to the maltooligosaccharides employed, and maltosyl residues to $G2-\beta-CD$. The enzyme preferentially hydrolyzed amylopectin, followed in a decreasing order by glycogen, pullulan, and amylose. Therefore, the present results suggest that the glycogen-debranching enzyme from S. shibatae may have industrial application for the efficient debranching and modification of starch to dextrins at a high temperature.

• Journal of Pharmaceutical Investigation
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• 제31권3호
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• pp.151-160
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• 2001

The purpose of this study is to investigate the interaction of progesterone with various cyclodextrins (CDs) in the aqueous solution and in solid state, and finally to formulate a parenteral aqueous formulation. CDs used were ${\alpha}-$, ${\beta}-$, and ${\gamma}-CD$, $2-hydroxypropyl-{\beta}-CD$ (HPCD), sulfobutyl $ether-{\beta}-CD$ (SBCD), $dimethyl-{\beta}-CD$ (DMCD) and $trimethyl-{\beta}-CD$ (TMCD). The solubility studies of progesterone were performed in the presence of various CDs as a function of concentration or temperature. The solubility of progesterone increased in the rank order of ${\alpha}-CD$ < ${\beta}-CD$ < ${\gamma}-CD$ < TMCD$ < HPCD < DMCD < SBCD. Addition of SBCD (200 mg/ml) in water increased the aqueous solubility $(9.36\;{\mu}g/ml)$ about 3,200 times, and lowering the temperature facilitated the solubilization of progesterone. However, the addition of HPCD and SBCD in 20:80 (v/v) polyethylene glycol 300-water and propylene glycol-water cosolvents markedly decreased the solubility of progesterone, compared with solubilizing effects in water. Physical mixtures and solid dispersions of progesterone with HPCD or SBCD were prepared, and evaluated by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), near IR spectroscopy and dissolution studies. By DSC and IR studies, it was found that progesterone was dispersed in HPCD in monotectic state and dissolved rapidly from both solid dispersions. Based on solubility studies, new aqueous progesterone fonnulations (5 mg/ml) containing SBCD (200 mg/ml) could be prepared and did not form precipitates even after 2 months at $4^{\circ}C$. The solution was transparent when mixed with normal saline and 5% dextrose injection at 1: 1, 1:10 and 1:20 (v/v) even after 7 days. Permeation rates of progesterone through a cellulose membrane from 20% PEG 300 solution $(50\;{\mu}g/ml)$ containing HPCD or SBCD were compared with oily formulation. Permeation of progesterone from oily formulation did not occur up to 8 hr, but aqueous formulations showed fast permeation rates from early stage of permeation study. The addition of HPCD or SBCD retarded the permeation rates of progesterone with the increase of CD concentrations, suggesting the possibility of a controlled absorption from the site administered intramuscularly. These results demonstrate that it is feasible to develop a new progesterone parenteral aqueous injection (5 mg/ml) using SBCD.

• Applied Biological Chemistry
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• 제38권1호
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• pp.42-48
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• 1995

Bacillus megaterium이 생산하는 ${\gamma}-cyclodextrinase({\gamma}-CDase)$ 염석, DEAE-trisacryl, Ultrogel AcA 24 및 Ultrogel HA column chromatography 등의 방법으로 부분정제한 결과 specific activity는 120.4 units/mg protein으로 조효소액에 비하여 125.4배 정제되었다. 부분정제한 ${\gamma}-CDase$는 SDS-ployacrylamide gel 전기영동에 의해 2개의 band로 나타났으며 band I과 band II의 분자량은 각각 64,000과 50,000이었다. ${\gamma}-CDase$의 최적 pH는 6.0, 최적 온도는 $60^{\circ}C$이었고, $45^{\circ}C$ 이하의 온도와 pH $6.0{\sim}9.0$에서 안정하였으며, ${\gamma}-CD$에 대한 Km값은 0.903 mM이었다. $Mg^{2+}$와 $Mn^{2+}$ 이온에 의해 활성이 증가한 반면, $Hg^{2+}$와 $Cu^{2+}$에 의해서는 활성이 현저하게 감소되었다. ${\gamma}-CDase$는 ${\alpha}-CD$와 ${\beta}-CD$에는 거의 활성이 없었고, ${\gamma}-CD$에는 매우 높은 활성이 나타내었으며, 이의 분해 생성물은 주로 glucose와 maltose이었다.

• Bulletin of the Korean Chemical Society
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• 제25권3호
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• pp.377-381
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• 2004

Chiral separation of aryalcohols such as 1-phenyl-propanol, 1-phenyl-2-proanol, and 2-phenyl-1-propanol by capillary electrophoresis has been optimized using the overlapping resolution mapping (ORM) scheme. Three critical parameters of the electrophoretic media, i.e. phosphate concentration, sulfated ${\beta}$-cyclodextrin (CD) concentration and pH, were chosen for optimization. The working ranges were initially presumed by 7 preexperiments. Further optimization was carried out by another seven experiments within the narrow working ranges. From the final overlapping resolution mapping all peak pairs, the area of maximum separations were located. Using the conditions of a point in this area, we found that the target compounds were a baseline separated within 30 min. The maximum separation conditions of arylalcohols were a chiral selector concentration of 5.4%, a phosphate concentration of 28 mM, and a pH of 5.0.

• KSBB Journal
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• 제21권2호
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• pp.151-156
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• 2006

본 연구에서는 용매증발법을 이용하여 대표적 생리활성 물질인 Vitamin-C의 불안정성을 극복하기 위하여 HP-${\beta}$-CD와의 포접복합체를 제조하고 수용액상에서의 안정성을 분석하였다. Vitamin-C와 HP-${\beta}$-CD 간의 몰비를 변화시켜 제조한 포접복합체의 안정성 시험 결과 포접 몰비는 1:1로 추정되며, 포접복합체 제조에 사용된 용매의 유전상수가 커질수록 Vitamin-C의 안정성이 향상되는 것을 확인할 수 있었다. 3차 증류수를 용매로 하여 제조된 포접복합체의 경우 순수한 Vitamin-C보다 Vitamin-C의 겉보기 1차 분해속도 상수 값이 감소하는 것을 확인하였는데 이는 결과적으로 Vitamin-C의 안정성이 향상되었음을 의미한다. 따라서 HP-${\beta}$-CD와의 포접복합체 형성은 Vitamin-C의 안정성을 향상시켜 생체이용률을 향상시킬 수 있음을 확인하였으며 불안정한 여러 생리활성물질에 적용할 수 있을 것으로 기대된다.