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The purpose of this research was to investigate the effect of reactionprecipitate from Coptidis Rhizoma and Glycyrrhizae Radix aqueous mixture(CGP; on the cytotoxicity. The effects of CGP on the growth of tumor cells, Balb/c 3T3 cell, mouse spleen cell and human lymphocyte were compared with those of berberine, glycyrrhizin and berberine glycyrrhizinate(BG), which were estimated by MTT colorimetric assay or cell counting. CGP, benberine and BG inhibited the growth of several tumor cells, such as Hep G2, A549, Raji, MCF-7, HeLa and KHOS-NP. Whereas, glycyrrhizin inhibited the growth of Raji and MCF-7, CGP did not affect on Balb/C 3T3 cells, mouse spleen cells and human lymphocyte at 10^(-6)∼10^(-5)g/㎖. CGP increased the number of leukocyte in mice. This results indicate that CGP have the inhibitory action of the growth of human tumor cells, and the side effect of CGP is less than berberine and BG.
To increase the bioavailability of berberine inclusion complex were prepared and studied in this experiment. Inclusion complexes of berberine(BER) and methanol extract of Coptis Rhizomia(MEX) with B-cyclodextrin were prepared. The solubilities of BER and MEX were 0.14% and 1.79%, while those of BECD and MECD were 0.36 and 3.22% respectively. The lipid-water partition coefficients of Ber-B-CD indlusion complex(BECD) and MEX-B-CD inclusion complex(MECD) were more increased than BER and MEX respectively. The absorption rates of BECD and MECD in stomach, duodenum, and jejunum of rats were compared with those of BER and MEX, which were more increased than BER and MEX respectively. The times required for the maximum serum concentration fo berberine from BER, MEX, BECD and MECD in mice were 30 minutes after oral administration. The maximum serum concentrations of berberine from BECD and MECD were higher than those from BER and MEX respectively. BECD was shown more increased antibacterial activity to all the gram positive bacteria, gram begative bacteria and mold than BER,MECD was shown more increased antibacterial activity to only S. epidermidis, K. pneumoniae, E. coli than MEX. The dissolutions of BECD and MECD were higher than BER and MEX respectiely. Therefore, it suggest that preparing of inclusion complex brings to prevention of coprecititated formation and improvement fo bioavailability of berberine.
Gardeniae Fructus is consisted of geniposide and its derivatives. For the purpose of treatment of skin disease, geniposide and hydrolyzed products (HP) of Gardeniae Fructus were studied on skin permeation and crosslinking with biological tissue. The hydrolyzed products (HP) and active ingredients of Gardeniae Fructus were identified and investigated about skin permeability. Genipin has provided low cytotoxic crosslinking reagents and formed stable and biocompatible crosslinked products. The permeation enhancing effects of geniposide and genipin under the hydrolyzed products of cream and hydrogel preparations were tested using Franz type diffusion cell and the skin of hairless mouse. The remaining pro-portions of geniposide and genipin were measured in the hydrolyzed products of cream and hydrogel preparations. The crosslinking of epidermic and endodermic tissue with genipin under the hydrolyzed prodcuts of cream and hydrogel preparation was observed using light microscopy. Increased absorption ratio of the skin of hairless mouse about genipin was higher than that of geniposide. Loads at break, tensile strengths and skin permeation rate of the hydrolyzed products (HP) of cream and hydrogel preparations were higher than the nonhydrolyzed products (NHP). The hydrolyzed products (HP) of cream and hydrogel of Gardeniae Fructus Extracts were proper preparations and crosslinking agents to increase the trans-dermal absorption with epidermic and endodermic tissue.
The inhibition rate of bacteria growth per molecular weight was higher according as the molecular weight increased, the rate was the highest at the molecular weight 200,000. Microcapsule of ionized calcium was able to be produced by molecular weight 15,000. 30,000, 50,000 and 200,000 of chitosan which was dried for 48 hours after melting it in 2% of acetic acid, adding ionized calcium and controlling pH 1.2. The size of ionized calcium microcapsule was between 200 and 300 μm, the solvency, concentration and the content showed big difference by the molecular weight of chitosan. The inhibition rate of bacteria growth of microcapsule designated high in Gram positive, which was high in S. aureus, S. epidermidis and Bacillus subtilis, low in S. mutans, high in C, albicans in fungi, low in A. niger. The inhibition rate of bacteria growth of chitosan was comparatively high in Gram positive, low in S. mutans and it showed high numerical value in C. albicans of fungi. The rate recorded good result at molecular weight 200,000 relatively, there was no difference according to the molecular weight. The inhibition rate of bacteria growth according to the concentration of the microcapsule increased differently between 1,000∼10.000㎍/㎖, it showed antibacterial activity close to the inhibition rate of growth of chitosan rather than ionized calcium. The minimum inhibitory concentration marked the highest in the mixture of chitosan and ionized calcium for all kind of bacteria generally, there was a little difference between yeast and fungi.
Precipitation was formed during the preparation of decoction from a mixture of Scutellariae Radix and Coptidis Rhizoma or Phellodendri Cortex according to the prescription of Hwang-ryean-hae-dog-tang. Baicalin and berberine were identified in coprecipitated product and these components were the active ingredients of two herbal medicine. The coprecipitated product was very slightly soluble in water and sparingly soluble in ethanol. The stoichiometric ratio of baicalin and berberine was found to be 1:1. The lipid-water partition coefficients of coprecipitated product were increased more than baicalin and berberine in chloroform, but were decreased in other organic solvents. The content of baicalin and berberine in coprecipitated product, determined by HPLC, were 23.08% and 26.75%, but the content of active ingredients in supernatant were 0.66% and 0.26%, respectively. The dissolution profile of baicalin of coprecipitated product was increased more than extract of Scutellariae Radix in artificial gastric juice, but was decreased in artificial intestinal juice. The dissolution rate of berberine of coprecipitated product was lower than extract of Coptidis Rhizoma in artificial gastric juice and intestinal juice commonly.
Ketorolac tromethamine gel (KT gel) and ketorolac tromethamine gel containing genipin (KTG gel) were prepared and their therapeutic effects on periodontitis were evaluated. The skin permeation rate of ketorolac from the KT gel and KTG gel was 5.75±0.53 and 5.82 ± 0.74 µg/cm2/ h, respectively. The skin permeation rate of genipin from the KTG gel was 10.13 ± 1.47 µg/ cm2/h. The tensile strength of the KTG gel was larger than the KT gel. After 4 weeks, the periodontal pocket depth of the KTG gel group (3.22 ± 0.20 mm) significantly decreased compared with the non-treated group (4.50 ± 0.25 mm) and the KT group (3.84 ± 00.26 mm). The KTG gel did not induce separation of the stratum corneum and subcutaneous tissue, and the collagen layers of the corium were closer, more fibrous, and showed longer connections than in the other groups. The KTG gel appears to be effective against gingivitis in the periodontal pocket through its increased anti-inflammatory activity and the crosslinking of genipin with the biological tissue.
Triamcinolone acetonide (TA) is a corticosteroid that is used in the systemic and topical treatment of many inflammatory diseases. In this study, a phonophoretic drug delivery system was designed to enhance the TA permeability and the influence of ultrasound was examined. In order to establish the transdermal delivery system for TA, a hydrophilic carbopol gel containing TA was prepared after adopting phonophoresis. A permeation study through mouse skin was performed at 37oC using a Franz diffusion cell, and the ultrasound treatment was carried out for 10 h. The level of TA permeation through the skin was evaluated under various ultrasound conditions including the frequency (1.0, 3.0 MHz), intensity (1.0, 2.5 W/cm2), and duty cycle (continuous, pulse mode) using a 0.5% TA gel. The highest permeation was observed under the ultrasound treatment conditions of low frequency, high intensity, and in continuous mode.
The tests of dissolution and bioavailability of six formulas of lorazepam tablet under various binders were performed. Lorazepam can be seperated in pharmaceutical preparation and biological plasma by high performance liquid chromatograph. Dissolution process of lorazepam tablet was largely influenced by binder and the dissolution rate was increased by sodium starch glycolate and microcrystalline cellulose, the slower dissolution rate in starch. Bioavailability of lorazepam tablet got relationship with dissolution rate, because tablets containing sodium starch glycolate and microcrystalline cellulose as binder maintained higher plasma level than other binders.
These experiments were conducted to investigate the anti inflammatory and analgesic action of Solanum lyratum extract(SL). The results were summarized as follows : The inhibitory effect of the leakage of evans blue into peritoneal cavity was significantly increased to be 46.4%, The paper disk granuloma formation displayed more potent effect than the control group. Mouse pew edema induced by histamine was significantly decreased. SL(75㎎/pouch)inhibited the protein exudation and did not the leucocyte migration in rats. But SL(25㎎/pouch) inhibited the leucocyte migration. The analgesic activity on 0.7% acetic acid induced writhing syndrome was significantly shown.
This study examined the effects of ketorolac tromethamine (KT) and baicalein (BE) on the levels of inflammatory factors in human synoviocytes. The fibroblast-like synoviocytes (FLS) cells were used to determine the possible regulatory effects of KT and BE (KTBE) on the levels of inflammatory factors in FLS cells. In addition, the levels of TNF-α, IL-6, and IL-1β mRNA expression in FLS cells induced by a TNF-α and IL-1β co-treatment were largely inhibited by a KTBE treatment. The level of FLS cells proliferation was increased by IL-1β and TNF-α, and strongly inhibited by KTBE treatment. The production of oxygen species (ROS) was inhibited by KTBE in FLS cells. KTBE appears to regulate the levels of mRNA that are important for regulating RA progression.