• Archives of Pharmacal Research
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• 제27권8호
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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.

• 한국식품위생안전성학회지
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• 제11권2호
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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.

• 약학회지
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• 제37권6호
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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.

• 동아시아식생활학회지
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• 제12권4호
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• pp.318-325
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• 2002

감귤과피 물 균질액으로 코팅한 유색미의 취반 특성을 조사하였다. 유색미의 색상은 진노랑L＊; 63.6, a＊; -7.87, b＊; 46.35)으로 취반 후에도 유사한 색상을 나타내었다. Total carotenoids는 감귤과피에서는 10.74mg%, 과피의 물 균질액에는 0.46mg% 이었으며 유색미에는 0.l2mg%, 유색미 취반에는 0.05mg%를 나타내었다. Hesperidin은 과피, 물 균질액, 유색미 및 유색미 취반에서 각각 2173.l2mg%, 108.65mg%, 21.73mg% 및 8.67mg%이었으며, naringin은 각각 1468.40mg%, 73.38mg%, 14.62mg% 및 5.87mg%를 나타내었다. 감귤과피의 유리아미노산은 asparagine이 94.22mg%로 가장 높았으며, methionine이 24.88mg%, alanine이19.64mg%, ${\gamma}$-aminoisobutylic acid가 15.37mg%로 이들 4종의 아미노산이 전체 유리아미노산 함량의 70%를 나타내었다. 유색미 취반에는 백미 취반에 비하여 총 유리아미노산의 함량이 15%정도 증가되었으며, 그 중에서 glutamic acid는 2.5배가 증가되었다. 감귤과피의 주요 무기질은 K(652.60mg%)와 Ca(222.50mg%)로 전체 무기질 함량의 86%를 차지하였으며 유색미 취반은 백미 취반에 비하여 K는 2.3배, Mn는 76%, Ct P, Mg은 16~26%, Fe는 13%가 각각 증가되었다. 취반의 경도(harness), 점착성(gum-miness) 및 깨짐성(brittleness)은 유색미 취반과 백미 취반간에 차이가 없으나 응집성(cohesiveness)과 탄력성(springiness)은 유색미 취반에서 높았다. 색상에 대한 기호도, 구수한 맛 및 종합적인 기호도는 유색미 취반에서 높았으며 단맛, 쓴맛은 백미 취반과 차이를 보이지 않았다.경우와 비슷한 좋은 결과를 보여 활동성 심내막염의 조기 외과적 치료가 효과적으로 감염을 제거할 수 있다고 사료된다.N-화합물의 함량과 이들의 수량에 미치는 붕소의 시비효과는 초종, 단파와 혼파재배, 그러고 추비의 시비조건에 따라서 차이가 있었다.

• 동아시아식생활학회지
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• 제12권5호
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• pp.397-406
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• 2002

감귤과피 분말을 l~5% 함유하는 물 균질액을 첨가한 빵의 품질특성을 조사하였다. 반죽의 pH는 첨가량이 증가할수록 낮아졌으며 산도는 반대로 높아졌다. 반죽의 부피와 빵의 loaf volume은 첨가량이 높아질수록 감소하였다. 3% 첨가빵의 total carotenoids, hesperidin 및 naringin 함량은 각각 0.14 mg%, 38.4 mg% 및 25.3 mg%이었다. 빵의 hardness는 감귤과피 분말의 첨가량이 증가할수록 높았다. 1%를 첨가한 경우의 strength는 대조군과 차이가 없었으며 그 이상으로 첨가할수록 높아졌다. Cohesiveness는 1% 첨가는 대조구와 차이가 보이지 않았으나 3~5% 첨가구는 크게 감소하였다. Springiness는 0, 1 및 3% 첨가는 유의적 차이를 보이지 않았으나 5% 첨가군에서는 현저히 낮았다. 색상, 맛, 향, 씹힘성 및 종합적인 기호도로 평가한 결과 3% 첨가구가 가장 양호하였다.

• Archives of Pharmacal Research
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• 제27권6호
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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.

• 한국식품영양과학회지
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• 제24권5호
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• pp.707-712
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• 1995

돌산갓 중의 천연 항균활성 물질을 이용하여 식품의 보존 효과를 증진시킬 목적으로, 갓을 물로 전처리하여 항균활성과 allylisothiocyanate(AIT) 함량을 조사하였다. 갓을 마쇄하여 $30^{\circ}C$에서 72시간 까지 진탕하면서 전처리할 때, 휘발성 AIT 함량은 전처리 2시간에서 가장 많았고, 전처리한 농축물 추출물(WPE)의 항균활성은 21시간 이후 부터 나타나서 48~72시간에 가장 강하게 나타내었고, 농축하지 않은 것은 WPE와는 달리 2~3시간에서도 항균활성을 나타내었지만 20시간 이후 부터는 동일한 패턴의 항균활성을 나타내었다. Ethylacetate 분획물에서 항균활성이 높았으며, 갓의 WPE는 전처리하지 않은 것보다 1.2~1.4배 항균활성이 증가되었다. WPE는 S. typhimurium과 S. aureus에 강한 저해활성을 나타내었으며, $121^{\circ}C$, 30분간 열처리하여도 항균활성은 거의 그대로 유지되었고, 전처리하지 않은 것은 항균활성이 거의 없거나 약하게 나타났다.

• 한국축산식품학회지
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• 제25권2호
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• pp.189-195
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• 2005

본 연구는 모델시스템과 가열우육에서 옻나무 추출물의 항산화 효과를 구명함으로서 육제품에 이용 가능성을 검토하고자 실시하였다. DPPH에 대한 소거력$(\%)$은 옻나무 에탄올 추출물을 1, 10, 100, 1,000 ppm으로 증가시킴에 따라 14.79, 75.08, 82.02, $83.97\%$로 증가하였다(p<0.05). 옻나무 에탄올 추출물(10 ppm)을 liposome과 육균질물에 첨가하면 대조구보다 높은 항산화 효과를 나타냈으며, 단독 첨가보다 $\alpha-tocopherol$(2 ppm) 혼용 첨가가 억제율이 증가되었다. 육균질물은 pH 6.0에서, liposome은 pH $5.0\~6.0$에서 최대 산화 억제율을 보였다. 또한 옻나무 열수 추출물의 첨가로 인해 가열 우육의 냉장저장 중 TBARS와 POV가 대조구보다 낮은 수준으로 유지되었으며(p<0.05), 소금을 첨가하여 산화를 촉진시켰어도 강력한 항산화 효과를 나타내었다. 따라서 육제품 제조 시 옻나무 추출물이 천연 항산화제로서 이용 가능성이 있다고 판단된다.

• Journal of Pharmaceutical Investigation
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• 제31권2호
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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.

• 생약학회지
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• 제28권1호
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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.