• Journal of Pharmaceutical Investigation
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• v.34 no.5
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• pp.385-391
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• 2004

The purpose of the present study was to formulate the aqueous solution of $20-O-{\beta}-D-glucopyranosyl-20(S)-protopanaxadiol\;(IH-901)$, an intestinal bacterial metabolic derivative from Ginseng protopanaxadiol saponin. For this purpose, the effects of various solubilization agents such as cosolvents [ethanol, propylene glycol (PG), polyethylene glycol 300 (PEG 300), polyethylene glycol 400 (PEG 400), glycerin], surfactants $(Tween\;80,\;Cremophor^{\circledR}\;RH40,\;Cremophor^{\circledR}\;EL,\;Poloxamer\;407,\;Poloxamer\;188)$ and a complexation agent $[hydroxypropyl-{\beta}-cyclodextrin\;(HPBCD)]$, on the solubility of IH-90l in aqueous solution were evaluated. The solubility of IH-901 in water was under $1\;{\mu}g/ml\;at\;20^{\circ}C$. Cosolvents such as ethanol, PG, PEG 300, PEG 400 and glycerin did not enhance the solubility of IH-901 at the 0 - 40% concentration range. The solubility of IH-901 was significantly elevated by the addition of cosolvents over the 80% concentration range. On the other hand, tween 80, $Cremophor^{\circledR}\;EL,\;Cremophor^{\circledR}\;RH40$ and HPBCD showed enhanced effects on the solubility of IH-901. The enhanced effects of Poloxamer 407 or Poloxamer 188 on the IH-901 solubility were less pronounced compared with $Cremophor^{\circledR}\;EL\;or\;Cremophor^{\circledR}\;RH40$. As a results, $Cremophor^{\circledR}$ aqueous solution was selected as an optimum solvent system. The aqueous solutions containing 10% $Cremophor^{\circledR}\;EL$ and 7% $Cremophor^{\circledR}\;RH40$ were formulated as dosing solutions containing 5.0 mg/ml of IH-901 for its intravenous and oral administration, respectively. The formular showed physical stability after stored for 7 days at $4^{\circ}C$.

• YAKHAK HOEJI
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• v.38 no.4
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• pp.440-450
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• 1994

Due to the limited bioavailability of $[D-Ala^6]$LHRH from nonparenteral transmucosal sites of administration, enhancement of mucosal permeability by coadministration of several protease inhibitors and/or penetration enhancers were studied in rabbit mucosa. As a reliable bioassay method for $[D-Ala^6]$LHRH, ovulation-inducing effect were measured after vaginal administration in the rat. The permeation of $[D-Ala^6]$LHRH through the mucosal membrane of rabbit mounted on George-Grass diffusion cells were examined in the presence of polyoxyethylene 9-lauryl ether (POE), ${\beta}$-cyclodextrin$({\beta}-CyD)$ or ethylene diamine tetra acetate disodium salt(EDTA). The vaginal membrane showed higher permeability of $[D-Ala^6]$LHRH than the rectal and nasal membrane. POE and ${\beta}-CyD$ showed a small promoting effect on the membrane permeation of $[D-Ala^6]$LHRH, but EDTA showed significant enhancement. Ovaluation was enhanced by the coadministration of sodium laurate(0.5%), a protease inhibitor but was not enhanced by EDTA, a penetration enhancer. On the other hands, coadministration of sodium tauro 24,25 dihydrofusidate(1%) and EDTA(2%) enhanced the ovulation inducing-effect 2.8 times. These results suggest that the vaginal administration of $[D-Ala^6]$LHRH with STDHF or sodium laurate as a protease inhibitor, and EDTA as a penetration enhancer, may become an elective method for transmucosal delivery of $[D-Ala^6]$ LHRH.

• Journal of KIISE:Databases
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• v.31 no.5
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• pp.468-478
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• 2004

It is essential in various application areas of data mining and bioinformatics to effectively retrieve the occurrences of interesting patterns from sequence databases. For example, let's consider a network event management system that records the types and timestamp values of events occurred in a specific network component(ex. router). The typical query to find out the temporal casual relationships among the network events is as fellows: 'Find all occurrences of CiscoDCDLinkUp that are fellowed by MLMStatusUP that are subsequently followed by TCPConnectionClose, under the constraint that the interval between the first two events is not larger than 20 seconds, and the interval between the first and third events is not larger than 40 secondsTCPConnectionClose. This paper proposes an indexing method that enables to efficiently answer such a query. Unlike the previous methods that rely on inefficient sequential scan methods or data structures not easily supported by DBMSs, the proposed method uses a multi-dimensional spatial index, which is proven to be efficient both in storage and search, to find the answers quickly without false dismissals. Given a sliding window W, the input to a multi-dimensional spatial index is a n-dimensional vector whose i-th element is the interval between the first event of W and the first occurrence of the event type Ei in W. Here, n is the number of event types that can be occurred in the system of interest. The problem of‘dimensionality curse’may happen when n is large. Therefore, we use the dimension selection or event type grouping to avoid this problem. The experimental results reveal that our proposed technique can be a few orders of magnitude faster than the sequential scan and ISO-Depth index methods.hods.

• Bulletin of the Korean Chemical Society
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• v.30 no.9
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• pp.2021-2026
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• 2009

Toluene, xylene and styrene are volatile organic solvents that are commonly used in mixtures in many industries. Because these solvents are metabolized and then excreted in urine, their urinary metabolites are thought to be biomarkers of occupational exposure to these solvents. Therefore, a simple, rapid, and yet reliable analytical method for determining the metabolites is required for accurate biological monitoring. In the present study, a simple and rapid HPLC-UV method was developed for the simultaneous determination of eight major metabolites of toluene, xylene and styrene: hippuric acid (HA), mandelic acid (MA), o-, m- and p-methylhippuric acids (o-, m- and p-MHAs), and o-, m- and p-cresols. A monolithic column was employed as the stationary phase and several conditions, including flow rate, composition of mobile phase and column temperature, were variables for the optimization of the chromatographic resolution. All eight metabolites were successfully resolved within 5 minutes in 10% aqueous ethanol containing 0.3% acetic acid and 1.6% $\beta$-cyclodextrin, using a flow rate gradient of 1.0 - 5.0 mL/min at 25 ${^{\circ}C}$. The performance of this method was validated by linearity, intra- and inter-day accuracy, and precision. The linearity was observed with correlation coefficients of 0.9998 for HA, 0.9999 for MA, 0.9989 for o-MHA, 0.9998 for m-MHA, 0.9991 for p-MHA, 0.9997 for o-cresol, 0.9998 for m-cresol, and 0.9986 for p-cresol. The intra- and inter-day precision of the method were less than 5.89% (CV) and the accuracy ranged from 92.95 to 106.62%. The validity was further confirmed by analysis of reference samples that were prepared by the inter-laboratory quality assurance program of the Korea Occupational Safety and Health Agency (KOSHA, Seoul, Korea). All measured concentrations of the analytes agreed with the certified values.

• Clean Technology
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• v.26 no.1
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• pp.1-6
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• 2020

Rapid expansion of supercritical solution (RESS) process was used to make molsidomine (MOL) loaded peracetyl-β-cyclodextrin (PAc-β-CD) nanoparticles, which were collected into the air. The effect of the concentration of the drug PAc-β-CD (0.5 and 1 wt%), extraction temperature (45 ~ 60 ℃), nozzle length (5 ~ 20 mm) and internal diameter (ID) (50 ~ 150 μm) of a capillary, and spray distance on the particle size and morphology of the resulting particles were investigated. The interaction of a drug and PAc-β-CD was confirmed by ¹H-NMR spectroscopy while the particle size was measured by means of a scanning electron microscope. It was found that increasing the temperature from 45 ℃ to 60 ℃ and decreasing the nozzle diameter from 150 μm to 50 μm had an increasing effect on the average particle size, while increasing the spray distance led to a decrease in the average particle size at a constant pressure of 34.5 MPa and temperature of 45 ℃. With 0.5 wt% of PAc-β-CD, the capillary nozzle of short length (5 mm) and small ID (50 μm) gave the smallest size (165 nm). The obtained nanoparticles showed increased dispersity and solubility in oil. The oil suspension of the inclusion complex showed increased sustainability, which can increase the in-vitro controlled release time of the drug.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.173-183
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• 1992

To study the feasibility of transmucosal delivery of $[D-ala^2]-methionine$ enkephalinamide (YAGFM), 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 resistent 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 $37^{\circ}C$. It was found from the results that mixed inhibitors such as TM (0.5 mM)/EDTA (5 mM) or AM $(50{\mu}M)/TM$ (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 $(50{\mu}M)$, AM 50 $(50{\mu}M)$ or TP$(50{\mu}M)$ alone did not reveal sufficient inhibition except TM (0.5 mM) or EDTA (5 mM). The adddition of $2-hydroxylpropyl-{\beta}-cyclodextrin$(10%) to the nasal mucosal extract, and $dimethyl-{\beta}-cyclodextrin$(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.

• Food Engineering Progress
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• v.14 no.4
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• pp.359-366
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• 2010

Large-scale preparation steps of antithrombotic materials from wood ear mushroom (Auricularia auricular-judae) were established as follows. Grounded dry wood ear mushroom was extracted with 75% ethanol and its precipitate was extracted with $76^{\circ}C$ water for 2 hr followed by filter pressing. The filtrate was then concentrated by vacuum and extracted with 80% ethanol, and the resulting precipitate was then freeze-dried. The formula of the product was determined using consumer susceptibility tests as follows; mushroom extract 90.5%, high fructose corn syrup 2.0%, $\beta$-cyclodextrin 1.5%, fructo-oligosaccharide 2.0%, pear puree 4.0%. When the packed products were stored at 25, 37, or $45^{\circ}C$ for 8 weeks, there were no noticeable changes in water activity, moisture content, pH, and acidity. The viable cell number of total bacteria was slightly increased during the storage period at 25 and $37^{\circ}C$, The total bacteria were not detected in the product when stored at $45^{\circ}C$. When the product was injected intravenously into rat at the level of 1,000 mg/kg, antithrombotic activities such as activated partial thromboplastin time, thrombin time, prothrombin time, and FIB were increased when compared with the control group. When the product was administrated orally into rat at the level of 500 mg/kg, it showed the same antiplatelet activity to aspirin.

• Food Engineering Progress
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• v.13 no.1
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• pp.1-7
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• 2009

Fermented functional onion juice was developed using lactic acid bacteria as a fermentation starter of onion. From the preliminary studies, we selected the bacterium KC-007 (named as Pediococcus pentosaceus based on morphological and physiological characteristics, carbon utilization pattern, and molecular genetic characteristics) as a fermentation starter. The optimum recipe of functional fermented onion juice based on manufacturing process and sensory evaluation were determined as 27% of fermentation liquer, 27% of apple juice, 3.7% of HFCS, 1.86% of $\beta$-cyclodextrin, 0.9% of oligosaccharide, 0.2% of apple flavor, 0.09% of citric acid, and 39.25% of water.

• Journal of the Korean Society of Food Culture
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• v.23 no.1
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• pp.55-61
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• 2008

Non processed onion (Allium cepa L.) powder or onion powder processed with ${\beta}-cyclodextrin+1%$ calcium chloride+1% soluble starch solution was added to the diet of 16 week old Wistar and spontaneously hypertensive rats (SHR) for 5 weeks. 36 SHR and Wistar rats were randomly divided into 3 diet groups, each of six. They were named control, NPO (non processed onion), PO (processed onion). The rats of the control group were fed diet without onion powder. To NPO and PO groups were added 5% of non processed onion and processed onion, respectively. Body weight gain, food efficiency ratio (FER), blood pressure, angiotensin converting enzyme (ACE) activity and Na excretion of urine and feces were analyzed. The processed onion and non processed onion diet reduced body weight gain without affeting the total food intake in Wistar rats (p<0.05). The body weight gain was lowest in Wistar rats fed with a diet with processed onion powder. The rats fed with diet containing PO or NPO had lower blood systolic blood pressure in SHR (p<0.05). The effect of onion powder on decreasing the blood pressure was not significant in Wistar rats. The ACE activity in lung was lowered in the SHR fed with either PO or NPO (p<0.05) compared to those fed with control diet. The urinary Na excretion was significantly lower in SHR than Wistar rats. The effects of PO and NPO on increasing the urinary and fecal excretion of Na were significant (p<0.05). These results suggest that onion processed with ${\beta}-cyclodextrin+1%$+1% calcium chloride+1% soluble starch solution to reduce volatile flavor, browning and caking preserves an antihypertensive effect of non processed onion.

• Journal of Pharmaceutical Investigation
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• v.31 no.3
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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.