• Archives of Pharmacal Research
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• v.27 no.8
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• pp.878-883
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• 2004

Tacrolimus (FK506), which is isolated from Streptomyces tsukubaensis, is a new potent immu-nosuppressant. Because of poor solubility in water, the conventional intravenous dosage forms of tacrolimus contain surfactants such as cremophor EL (BASF Wyandotte Co.) or hydroge-nated polyoxy 60 castor oil (HCO-60) which may cause adverse effects. This study relates to a polymer-tacrolimus conjugate, which can be dissolved in water, formed by chemically binding the sparingly soluble drug, tacrolimus, with the water soluble polymer, methoxypoly(ethylene glycol) (mPEG). Water soluble tacrolimus-mPEG conjugates have been synthesized and shown to be function in vitro as prodrugs. These conjugates are in the form of an ester wherein the 24-, 32- or 24,32-positions are esterified. The desired 24-, 32- or 24,32-esterified com-pounds were obtained by initially acylating of tacrolimus with iodoacetic acid at the 24-,32-, or 24,32-positions and then reacting the resulting acylated tacrolimus with a mPEG in the pres-ence of a base such as sodium bicarbonate. These conjugates were converted again into tac-rolimus by the action of enzymes in human liver homogenate, and the half-lives of the conjugates are approximately 10 min in the homogenate, indicating that the esterified tacroli-mus derivatives may be practically applicable as a prod rug for the immunosuppressant.

• Journal of Food Hygiene and Safety
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• v.11 no.2
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• pp.159-164
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• 1996

The antilipidperoxidative and hepatopreventive effects of Aloe water extract (30 mg, 50 mg, 100 mg) were investigated at the levels of liver-total homogenates and the sera of SDrats intoxicated with CCl4 (0.5 cc/100g) and 50% ethanol. We measured MDA (Malondialdehyde) in the liver homogenate, AST (L-Aspartate-2-oxoglutarate aminotransferase) and ALT(L-Alanine-2-oxo-glutraate aminotransferase) in the serum. The analysis of the measurement indicated that Aloe water extract reduced MDA, ALT and AST significantly and their reduction was in relation to dose dependence. In rat liver homogenate intoxicated with ethanol and CCl4, Aloe treatment group markedly inhibited lipidperoxidation by 30%∼70%. In rat serum intoxicated with ethanol and CCl4, Aloe treatment group inhibited AST, ALT by 40%∼90%. In these data Aloe may be used to inhibit or prevent the hapatic toxicity with results from the environmental and alcohlic factors through the further study of its exact antihepatotoxic mechanism.

• YAKHAK HOEJI
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• v.37 no.6
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• pp.638-646
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• 1993

A cepfialosporin with an aminothiazoiylmethoxyimino-type side chain at the 7 position and bicyclic quinolone dithicarbamate at the 3' position was synthesized. It has broad and potent antivacterial activity in vitro. The antibacterial spectrum reflects contributions of both the cephalosporin moiety and the quinolone moiety. Thus, this compound was named DACD implying a dualaction cephalosporin derivative. In this paper, the physicochemical proper-ties (lipid-water partition, pKa), stability and pharmacokinetics of DACD were determined and compared with cefotaxime 3'-norfloxacin dithiocarbamate (CENO). Stability tests were studied in pH 1.20, 6.80 and 8.00 buffers and in the presence of AB type human plasma, rat liver homogenate and its .betha.-lactamase. The pharmacokinetic parameters of DACD were evaluated in mice after a single intravenous dose of 40 mg/kg. The results are as follows. The lipid-water partition coefficient of DACD was higher than that of CENO. The calculated pKa values of CENO and DACD, were 6.82$\pm$0.03, 7.53$\pm$0.21, respectively. In the hydrolysis test, half-lives (t$^{1/2}$) of CENO and DACD was 66.0 hr and 80.0 hr in pH 6.80 buffer, 190 hr and 91.4 hr in pH 8.00 buffer. CENO and DACD were rapidly hydrolyzed in human plasma and in rat liver hornogenate. Half-lives (t$_{1/2}$ of CENO and DACD were 1.29 hr and 1.15 hr in hyman plasma, 0.62 hr and 0.71 hr rat liver homogenate. In $\beta$-lactamase stability test, CENO and DACD were very stable to the .betha.-lactamases obtained from three different strains. Half-life (t$_{1/2}$) and areas under the curve (AUC) in mice were 2.33 hr and 15.97 (mg.h/1), respectively.

• Journal of the East Asian Society of Dietary Life
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• v.12 no.4
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• pp.318-325
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• 2002

Cooking characteristics of coated rice with water homogenate of citrus fruit peels (1% for rice) were investigated. The color of the coated rice both before and after cooking was dark yellow. The total content of carotenoids, hesperidin and naringin were 10.74, 2173.12 and 1468.40 mg% for citrus fruit peels, 0.46, 108.65 and 73.35 % for its water homogenate, 0.12, 21.73 and 14.62 mg% for coated rin, and 0.05, 8.67 and 5.87 mg% fur cooked coated rice, respectively. Citrus fruits peel contained 94.22 mg% of asparagine, 24.88 mg% of methionine, 19.64 mg% of alanine, and 15.37 mg% of ${\gamma}$-aminoisobutyric acid as the majority free amino acids, accounting for 70% of the total free amino acids present. Total free amino acid content of the cooked coated rice increased by 15% compared to those of cooked uncoated rice. The majority of minerals in the citrus fruit peels were K and Ca, accounting for 56% of total minerals present. The mineral content of cooked coated rice was generally higher than that of the cooked uncoated rice. The cooked coated rice showed comparable hardness, gumminess and brittleness, but higher cohesiveness and springiness than the cooked uncoated rice. There were no differences in sweet and bitter taste between the cooked uncoated and coated rice. However, the cooked coated rice showed higher sensory scores fur color acceptability, savory taste and overall acceptability than the cooked uncoated rice.

• Journal of the East Asian Society of Dietary Life
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• v.12 no.5
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• pp.397-406
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• 2002

Quality characteristics of bread added with water homogenate of citrus peel powder(WHCP, 1~5% of wheat flour) were investigated. The pH, the volume of dough, and the loaf volume index of bread added with WHCP were lower than those of the control. The contents of total carotenoids, hesperidin and naringin in the bread with 3% of WHCP were 0.14, 38.4 and 25.3 mg%, respectively. The bread with WHCP(3%) showed comparable cohesiveness and springiness, but higher hardness than the control product. The bread with WHCP(3%) showed the best quality evaluated by color and overall acceptability, taste, flavor and texture.

• Archives of Pharmacal Research
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• v.27 no.6
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• pp.662-669
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• 2004

The highly water-soluble monomethoxypoly(ethyleneglycol) (mPEG) prod rugs of cyciosporin A(CsA) were synthesized. These prod rugs were prepared by initially preparing intermediate in the form of carbonate at the 3'-positions of CsA with chloromethyl chloroformate, in the pres-ence of a base to provide a 3'-carbonated CsA intermediate. Reaction of the CsA intermediate with mPEG derivative in the presence of a base provides the desired water-soluble prod rugs. As a model, we chose molecular weight 5 kDa mPEG in the reaction with CsA to give water soluble prodrugs. To prove that the prod rug is decomposed in the body to produce CsA, the enzymatic hydrolysis test was conducted using human liver homogenate at $37^{\circ}C$. The prodrug was decomposed in human liver homogenate to produce the active material, CsA, and the hydrolysis half-life ($t_{1/2}$) of the prodrug, KI-306 was 2.2 minutes at $37^{\circ}C$. However, a demon-stration of non-enzymatic conversion in pH 7.4 phosphate buffer was provided by the fact that the half-life ($t_{1/2}$) is 21 hours at 37$^{\circ}C$. The hydrolysis test in rat whole blood was also conducted. The hydrolysis was seen with half-life ($t_{1/2}$) of about 9.9, 65.0, 14.2, 3.4, 2.1 9.5, and 1.6 minutes for KI-306, 309, 312, 313, 315, 316, and 317, respectively. This is the ideal for CsA prodrug. The pharmacokinetic study of the prodrug, KI-306, in comparison to the commer-cial product (Sandimmune Neoral Solution) was also carried out after single oral dose. Each rat received 7 mg／kg of CsA equivalent dose. Especially, the prodrug KI-306 exhibits higher AUC and $C_{max}$ than the conventional Neoral. The AUC and $C_{max}$ were increased nearly 1.5 fold. The kinetic value was also seen with $T_{max}$ of about 1.43 and 2.44 hours for KI-306 and Neoral, respectively.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.5
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• pp.707-712
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• 1995

Natural antimicrobial activities in leaf mustard Dolsan(Brassica juncea) were evaluated for food preservation. Antimicrobial activities and changes in volatile allylisothiocyanate(AIT) concentration were examined during incubation of leaf mustard homogenate for 72 hours at $30^{\circ}C$. The concentration of volatile AIT was highest at 2 hours of incubation. Antimicrobial activities, which were insignificant in raw homogenate without incubation, were occurred at 21 hours and were showed highest at 48~72 hours of incubation. Water-pretreated extract(WPE) showed the antimicrobial activity by 1.2~1.4 times higher than the water extract. Ethylacetate fraction of leaf mustard showed high antimicrobial activities. The WPE had strong antimicrobial activities against Salmonella typhimurium and Staphylococcus aureus. Heat treatment of the WPE for 30 min at $121^{\circ}C$ did not lose the antimicrobial activities.

• Food Science of Animal Resources
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• v.25 no.2
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• pp.189-195
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• 2005

This study was carried out to investigate the antioxidant effect of Rhus verniciflua Stokes (RVS) extracts. The antioxidant activity of ethanol and water extract from RVS was examined on model systems and cooked beef, respectively. As concentration of RVS ethanol extract increased (1, 10, 100, and 1,000 ppm), the reductive activity of DPPH (2, 2-diphenyl-1-picrylhydrazyl) was significantly increased (14.79, 75.08, 82.02, and $83.97\%$ respectively) (p<0.05). The RVS ethanol extract (10 ppm) was showed higher antioxidant activity than control in liposome and meat homogenate (p<0.05). It had more antioxidative effect in 10 ppm RVS ethanol extract with 2 ppm $\alpha-tocopherol$ treatment The maximum antioxidant activity appeared at pH 6.0 in meat homogenate and at pH $5.0\~6.0$ in liposome. Cooked beef mixed with Rhus verniciflua Stokes water extract showed significantly lower TBARS value, POV during storage for 4 days at $4^{\circ}C$ (p<0.05). And the RVS water extract also showed strong antioxidant activity in cooked beef which accelerated NaCl-catalyzed oxidation. Therefore, the results suggest that RVS extract may be used in commercial meat products as natural antioxidant in the near future.

• Journal of Pharmaceutical Investigation
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• v.31 no.2
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• pp.95-100
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• 2001

Various alkyl ester prodrugs of diclofenac were synthesized in order to investigate the relationship between their skin permeation characteristics and physicochemical properties. Solubility in various vehicles was measured at room temperature. 1-Octanol/water partition coefficients (Log P) and capacity factors (k') were measured to determine the lipophilicity of the prodrugs. Stability of prodrugs in the skin extract and homogenate was also investigated before conducting the skin permeation studies. Increases in the Log P and capacity factor values were observed when alkyl esters of diclofenac were prepared. Since the aqueous solubility of the prodrugs was not high enough, they were saturated in propylene glycol (PG) for skin permeation studies. Prodrugs were rapidly metabolized to diclofenac, both in skin homogenate and in dermal extract of skin. The skin permeation rate of alkyl ester prodrugs was significantly higher than diclofenac with shorter lag time. Moreover, a parabolic relationship was observed between the permeation rate and the log P values of prodrugs, and the maximum flux was achieved at a log P value of around 4.0.

• Korean Journal of Pharmacognosy
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• v.28 no.1
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• pp.48-53
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• 1997

This study was performed to elucidate the possible antioxidative effects of several wild plant extracts. Wild plants were extracted with methanol or water using general method. In first experiments, antioxidative effects were measured by lipid peroxidation using rat brain homogenate. Coptis japonica extract showed the highest antioxidative activity among the 15 wild plant extracts. In second experiments, rats were fed on the semipurified diets with or without Coptis japonica extracts at the level of 0.5% for 4 weeks. MDA production of liver homogenate were significantly lower in the rats fed Coptis japonica extracts (P<0.05). Cytosolic catalase. GPX, and SOD activities were not changed, whereas the activities of GST and glutathione level were significantly higher in rats fed Coptis japonica extracts (P<0.05). These results suggest that Coptis japonica extract has an antioxidative effect through increasing GST activity and glutathione level and decreasing MDA production.