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.
Fluid replacement and conductivity logging have been applied to three boreholes in coastal aquifer in order to identify permeable fractures and to estimate the origin of saline groundwater. Fluid replacement technique measures and monitors the change of borehole fluid conductivity with depth under ambient or pumping condition after replacing the original borehole fluid with different one (by pumping out original one and injecting simultaneously new one at the hole bottom). After the replacement of borehole fluid, the change of fluid conductivity can be the direct indicator of the intake flow of formation water through aquifer such as permeable fractures or porous formations. The conductivity profiles measured with times therefore indicate the locations of permeable zone or fractures within the open hole or the fully slotted casing hole. As a result of fluid conductivity logging for three boreholes at coastal area in Yeonggwang, Jeonam Province, it is interpreted that the seawater intrusion in this area is not by remnant saline groundwater after land reclamation but mainly by intrusion of saline water through fractured rock. This approach might be useful for assessing the characteristics of seawater intrusion, the design of optimal pumping, the mitigation of seawater intrusion using freshwater injection, and estimating the hydraulic characteristics in coastal aquifer.
This study was conducted to investigate of hepatoprotective effect of dandelion water extract (DWE) according to repeated administration of thioacetamide (TAA) induced hepatotoxicity in Spraque-Dawley rats. Thirty rats were randomly assigned to 5 groups; normal control, DWE-control, TAA-control (TAA injection during the feeding of normal diet), TAA&DWE600 (TAA repeated injection during the feeding of DWE 600 mg/kg BW), TAA&DWE1200 (TAA repeated injection during the feeding of DWE 1,200 mg/kg BW). Rats in DWE-control and TAA&DWE groups were treated with DWE (600 or 1,200 mg/kg BW daily) by gavage for 20 days (twice a day). All the rats in the TAA-control and TAA&DWE groups were repeated injection of TAA (100 mg/kg BW) into the abdominal cavity 3 days interval and 12 hrs later, all rats were sacrificed. At the same time, normal control and DWE-control groups were injected normal saline. In TAA&DWE groups, serum alanine and aspartate aminotransferase (ALT, AST) were significantly decreased and triglyceride (TG) synthesis was significantly increased compared to TAA group. As well as total billilubin and GGT were slightly decreased by the treatment of DWE. Lipid peroxidation (MDA) concentration was significantly decreased and hepatic GSH content was slightly or significantly increased in the TAA&DWE groups compared to TAA group. Hepatic anti-oxidative enzyme activities, such as GSH, GST, SOD and catalase were slightly or significantly elevated by the treatment of DWE. According to these results, When dandelion extract was long term supplied, it could be used as a potential protective material for a longer time liver damage by repeated adminstration of the TAA.
This study was carried out to investigate the preventive and therapeutic effect of Panax ginseng water extract (PG-WE) on the toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), one of the most notorious toxic environmental pollutants belonging to the group of polyhalogenated aromatic hydrocarbons. Normal control (NC) group guinea pigs (180~200 g) received vehicle and saline, and TCDD-treated (TT) group was given TCDD and saline. P100 and P200 group animals received PG-WE for 28 days since 1 week before TCDD exposure at daily doses of 100 mg/kg b.w. and/or 200 mg/kg b.w., respectively. C100 and C200 group received PG-WE for 14 days starting 1 week after TCDD-exposure. Toxicity was induced by a single intraperitoneal injection of TCDD (1 $\mu\textrm{g}$/kg b.w.). Abnormal increase in AST and ALT activities in TT group was significantly improved by the administration of PC-WE. Microscopically, there were mild to moderate swelling of hepatocytes, hyperchromatism of individual cells, acidophilic cytoplasm and cytoplasm vacuolation of some hepatocytes, slight to moderate variations of staining density, occasional single cell necrosis, variable size and shape of some hepatocytes, small groups of degenerating hepatocytes surrounded by mononuclear cells, dilated sinusoids of centrilobular zone and some loss of lobular architecture in TT group liver. From these results, we could find the protective and therapeutic role of PG-WE in TCDD-induced liver toxicity by examining the blood chemical parameters and histopathological observation.
Despite significant effects on macroscopic migration and distribution of CO2 injected during geological sequestration, only limited information is available on wettability in microscopic scCO2-brine-mineral systems due to difficulties in pore-scale observation. In this study, a micromodel had been developed to improve our understanding of how scCO2 flooding and residual characteristics of porewater are affected by the wettability in scCO2-water-glass bead systems. The micromodel (a transparent pore structure made of glass beads and glass plates) in a pressurized chamber provided the opportunity to visualize scCO2 spreading and porewater displacement. CO2 flooding followed by fingering migration and dewatering followed by formation of residual water were observed through an imaging system. Measurement of contact angles of residual porewater in micromodels were conducted to estimate wettability in a scCO2-water-glass bead system. The measurement revealed that the brine-3M NaCl solution-is a wetting fluid and the surface of glass beads is water-wet. It is also found that the contact angle at equilibrium decreases as the pressure decreases, whereas it increases as the salinity increases. Such changes in wettability may significantly affect the patterns of scCO2 migration and porewater residence during the process of CO2 injection into a saline aquifer at high pressures.
Journal of the Korean Society for Marine Environment & Energy
/
v.18
no.2
/
pp.94-101
/
2015
To mitigate the greenhouse gas emission, many carbon capture and storage projects are underway all over the world. In Korea, many studies focus on the storage of $CO_2$ in the offshore sediment. Assurance of safety is one of the most important issues in the geological storage of $CO_2$. Especially, the assessment of possibility of leakage and amount of leaked $CO_2$ is very crucial to analyze the safety of marine geological storage of $CO_2$. In this study, the leakage of injected $CO_2$ through fault was numerically studied. TOUGH2-MP ECO2N was used to simulate the subsurface behavior of injected $CO_2$. The storage site was 150 m thick saline aquifer located 825 m under the continental shelf. It was assumed that $CO_2$ leak was happened through the fault located 1,000 m away from the injection well. The injected $CO_2$ could migrate through the aquifer by both pressure difference driven by injection and buoyancy force. The enough pressure differences made it possible the $CO_2$ to migrate to the bottom of the fault. The $CO_2$ could be leaked to seabed through the fault due to the buoyancy force. Prior to leakage of the injected $CO_2$, the formation water leaked to seabed. When $CO_2$ reached the seabed, leakage of formation water stopped but the same amount of sea water starts to flow into the underground as the amount of leaked $CO_2$. To analyze the effect of injection rate on the leakage behavior, the injection rate of $CO_2$ was varied as 0.5, 0.75, and $1MtCO_2/year$. The starting times of leakage at 1, 0.75 and $0.5MtCO_2/year$ injection rates are 11.3, 15.6 and 23.2 years after the injection, respectively. The leakage of $CO_2$ to the seabed continued for a period time after the end of $CO_2$ injection. The ratios of total leaked $CO_2$ to total injected $CO_2$ at 1, 0.75 and $0.5MtCO_2/year$ injection rates are 19.5%, 11.5% and 2.8%, respectively.
Journal of the Korean Society of Food Science and Nutrition
/
v.22
no.4
/
pp.374-380
/
1993
Effect of green tea extract, on duodenal ulceration was studied in male Sprague Dawley rats treated with cysteamine, a drug, which causes duodenal ulcers in experimental animal. As a result, in the proximal duodenum, a significant decrease of ulceration was detected twenty four hours after cysteamine injection in rats raised in green tea extract for 63days. Special reference to duodenal alkaline phosphatase activity was measured in mucosal homogenates. In control rats raised in tap water Riven saline, significant decrease was observed in proximal duodenal alkaline phosphataes activity. The decrease effect seems site specific, since the enzyme in the distal duodenum remains. Moreover the effect cysteamine in control rats alkaline phosphatase is specific, because, in rats raised in green tea extracts did not show significant change in activity. It is suggested that green tea extract acts in ideal properties as an anti-duodenal ulcer agent.
The purpose of the present study was to examine the in vivo activity of oxytocin antagonist I (AI)in the nonpregnant estrous rat. Cannulas were placed in the jugular vein for infusing compounds and a water-filled balloon-tipped cannula placed in one uterine horn for assessing uterine activity. Uterine contractions were monitored with a Grass Polygraph and contractile activity determined as the integrated area for 10 minutes. Five minutes after infusing 5 ${\mu}\textrm{g}$ of AI, 100mU of oxytocin was given as an in bolus injection and repeated every hour for 5 hours. At five minutes, 1 and 2 hours after injection AI the uterine contractile response to 100 mU of oxytocin was significantly inhibited compared to controls(p<0.05). At 3, 4 and 5 hours no differences in response were detected compared to controls(p>0.05). These results in conjunction with other reports from our laboratory suggest that AI has the potential of being a potent and specific tocolytic for prevention of preterm labor in humans.
Zinc oxide nanoparticles (ZnONPs) are widely used in a variety of products and cosmetic products including paper, paints, plastics and sunscreen. However, information on the safety of ZnONPs are not enough and many publications suggest possible toxic effects on environmental and human health. Furthermore, physico-chemical characteristics of nanoparticles makes it hard to test toxicity using the test guidelines of chemicals adopted by regulatory bodies. In this study, stability of ZnONPs was investigated using different types of isotonic solution, which is important in the toxicity study of intravenous route. Precipitation, aggregation, size, zeta potential and morphology of ZnONPs were evaluated with different times and concentrations. Precipitation of ZnONPs were observed in ionic isotonic solution including phosphate-buffered saline, Kreb's-Ringer solution, physiological salt solution and cell culture media of DMEM (Dulbecco's Modified Eagle's Medium) with 10% fetal bovine serum. On the other hand, they were stable without precipitation in non-ionic isotonic solution such as 5% glucose and 2% glycerol, respectively, which are biocompatible for intravenous injection. The average size of ZnONPs in 5% glucose and 2% glycerol was stably maintained, which is less than 30 nm and very similar as that in water dispersion of ZnONPs, provided by the manufacturer. The stability was maintained during the experimental period of 5 days and diluted state up to 15,000 ppm. These data suggest that 5% glucose and 2% glycerol solution can be used for the vehicles of ZnONPs in the toxicity study of intravenous injection route.
Anemia, the condition of the diminished concentration of hemoglobin per erythrocyte is common in patients with cancer and is a frequent complication of myelosuppressive chemotherapy. Cham-Dang-Gui (Angelicae Gigantis Radix) has been used in traditional Korean medicine to treat hematologic deficiencies. In this study, Cyclophosphamide (CYP), an alkylating agent that has a broad spectrum of anti-cancer activities, was intraperitoneally injected into the experimental animals to suppress the bone marrow thereafter, causing anemia. The hemopoietic effects of Cham-Dang-Gui were examined using anemic rat model. Rats were divided into five groups: CON (control group), ANS (CYP-injected + normal diet), AND (CYP-injected + normal diet + Cham-Dang-Gui), ALS (CYP-injected + low iron diet), and ALD (CYP-injected + low iron diet + Cham- Dang-Gui) groups. CYP (30 mg/kg) was intraperitoneally injected to rats for 3 days to induce anemic condition. Saline or Cham-Dang-Gui was administrated orally during the entire experimental period. CYP injection decreased body weight gain and food consumption in comparison with CON group. Oral administration of Cham-Dang-Gui extract with normal iron diet significantly prevented the lower body weight gain. The blood level of hemoglobin, iron status (serum iron, transferrin, ferritin and TIBC) and blood level of vitamin B-12 in Cham-Dang-Gui treated groups were significantly higher than those of Cham-Dang-Gui untreated groups regardless of amount of iron in the diet. Taken together, it could be concluded that the Cham-Dang-Gui extract could improve anemic condition induced by CYP injection by improving hematological value, iron status and vitamin B12 status in rats.
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