• Archives of Pharmacal Research
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• 제22권3호
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• pp.279-287
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• 1999

Therapeutic use of anti-inflammatory steroids is limited due primarily to their systemic suppressive effects on pituitary function and the immune system.. To overcome the clinical limitation, a new approach toward the discovery of non-systemic anti-inflammatory steroids is based upon the antedrug concept introduced by this laboratory. The new concept describes locally active agents which are designed to undergo a predictable biotransformation to inactive metabolites upon entry into systemic circulation from the applied site. Thus, true antedrugs are devoid of systemic adverse effects. In a continuing effort, 16$\alpha$-carboxylate and isoxazoline derivatives of prednisolone have been synthesized and screened. In the croton oil-induced ear edema bioassay, the following relative potencies were obtained setting hydrocortisone=1.0; 3a, 1.5; 3b, 3.1; 4a, 4.0; 4b, 12.2; 5b, 8.2; 6b, 11.2; 7a, 1.9; 7b, 4.1; 8a, 3.3; 8b 6.8; 9a, 0.7; 9b 8.6; 10a 2.6; 10b, 7.4. Results of the five-day bioassay indicated that, in contrast to the parent compound, the novel steroidal antedrugs did not significantly alter body weight gain, thymus weights, adrenal weights or plasma corticosterone levels. Taken together, the antedrug concept appears to be a fundamentally sound strategy for the separation of local anti-inflammatory activity form systemic adverse effects.

• KSBB Journal
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• 제14권3호
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• pp.297-302
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• 1999

Poly(DL-lactide)로 피막된 고분자 매트릭스를 약물전달시스템에 이용하기 위해 키토산, 키토산 염산염 및 술폰화 키토산으로 제조되었다. 모델 약물로 프레드니솔론을 사용하는 본 약물방출에 관한 연구는 pH 1.2 염산 용액에서 실험을 하였다. 약물 방출 속도는 고분자 매트릭스의 함유량이 증가할 수록 감소하였다. 피막된 고분자 매트릭스의 종류에 따라 지연된 약물의 방출시간은 키토산의 경우가 가장 길었으며, 술폰화 키토산, 키토산 염산염의 순서였다. DL-PLA로 피막된 고분자 매트릭스가 피막되지 않는 고분자 매트릭스 보다 약물 방출시간이 2배 정도의 지연되었을 뿐만 아니라 초기에 약물 과잉방출 현상도 작아 피막된 경우가 방출 조절형 제재로서 더 바람직한 결과를 보였다. 따라서 DL-PLA로 피막된 고분자 매트릭스는 장시간의 약물 방출을 위한 약물전달체로써의 응용이 기대된다.

• 약학회지
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• 제42권2호
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• pp.205-213
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• 1998

The efficacy of DA-6034, a new flavonoid derivative, was investigated in comparison with sulfasalazine in a trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. Under light anaesthesia with ether, rats were subjected to intracolonic administration of 30mg TNBS in 50% ethanol (0.5ml) and were then sacrificed at 7 or 21 days after colitis induction. The TNBS control group (the saline treated colitic rat) exhibited ulceration and inflammation of the distal colon with formation of granuloma and pathologic connections. Moreover, an increase in colonic myeloperoxidase (MPO) activity (investigated as an index of leukocyte adhesion and accumulation) and an elevated colonic leukotriene $B_4$ ($LTB_4$) level were observed. The colitic rats received DA6034 (0.3-30mg/kg) or sulfasalazine (50-100mg/kg), prednisolone (0.3-3mg/kg) after the induction of colitis until they were sacrificed. Oral treatment with DA-6034 resulted in significant reductions of macroscopic colonic damage, colonic inflammation. DA6034 had a more potent effect than sulfasalazine and prednisolone on macroscopic colonic damage, while it has similar effect with prednisolone on the reduction of colonic $LTB_4$ synthesis and MPO activity. This study show, therefore, that DA-6034 is effective m attenuating the colonic lesion in an TNBS-induced colitis model. Furthermore, the results suggest that the effect of DA-6034 is partially related to its action on $LTB_4$ synthesis and MPO inhibition.

• Childhood Kidney Diseases
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• 제20권2호
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• pp.97-100
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• 2016

Toxic epidermal necrolysis (TEN) is a rare, acute, serious, and potentially fatal skin disease, in which cell death causes the epidermis to separate from the dermis. It is thought to be a hypersensitivity complex that affects the skin and mucous membranes, and is caused by certain medications, infections, genetic factors, underlying immunologic disease, or more rarely, cancers. We report two cases of TEN associated with deflazacort (DFZ), a derivative of prednisolone, used in the first episode of nephrotic syndrome (NS). The skin eruption appeared on the $4^{th}$ and $5^{th}$ weeks after DFZ administration, while NS was in remission. The widespread lesions were managed by intensive supportive treatment, discontinuation of DFZ, and oral administration of cyclosporine. Both patients showed a rapid improvement in symptoms of TEN without any complications or relapse of NS.

• Archives of Pharmacal Research
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• 제22권4호
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• pp.354-360
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• 1999

Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. DA-6034,$ 7-carboxymethyloxy-3^{l}, 4^{l},$ 5-trimethoxy flavone, is a synthetic flavonoid known to possess anti-inflammatory activity. This study was performed to evaluate the oral therapeutic effect of DA-6034 in three experimental animal models of IBD : two chemical-induced IBD models of rats and the human leukocyte antigen (HLA)-B27 transgenic rat model known to develop spontaneous colitis without the use of exogenous agents. Acute chemical colitis was induced by intracolonic instillation of 1.2 ml of 4% acetic acid solution. Prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (0.3~3 mg/kg) were orally administered twice daily for 6 days in these rats. In addition, chronic chemical colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) 30 mg in 50% ethanol and agents were orally administered for 6 or 20 days. In chemical-induced IBD models, all of these agents reduced the severity of colitis and specially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score. In HLA-B27 transgenic rats, DA-6034 (3 mg/kg) and prednisolone (0.5 gm/kg) were treated orally twice daily for 6 weeks. The HLA-B27 transgenic rats showed only mild colitis, compared with the chemical-induced colitis models. DA-6034 ameliorated the loose stool and decreased microscopic damage, which is the important indicator of this model. In conclusion, oral therapy of DA-6034 attenuated the macroscopic and histologic damages of the colon in all three experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD.

• 한국임상약학회지
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• 제10권2호
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• pp.51-56
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• 2000

Deflazacort, an oxazoline derivative of prednisolone, has been claimed to have anti-inflammatory effects with fewer side effects compared to prednisone. The objectives of the study were to evaluate efficacy and safety of deflazacort in children with nephrotic syndrome. Eligible Patients were the children with nephrotic syndrome who were treated with deflazacort from October. 1994 to April. 1999. Nephrotic syndrome was defined as having albumin level of less than 2.5 mg/dL and 24-hour urinary protein excretion of greater than $40\;mg/m^2/hr$. The primary parameters evaluating the efficacy of deflazacort were response rate, time to respond and relapse frequency. The safety profiles were the impact on children's growth, calcium sparing effect, glucose metabolism, lipid profile and adverse drug reactions. As results, total of 60 children were evaluated (47 boys, 13 girls). Response rate was $95\%$ (57/60) for initial and late responders. Median time to respond was 12 days (range 7-110 days) and median relapse frequency was one time (range 0-6). Weight/height ratio increased from $22.05\pm3.47\;to\23.20\pm3.44\;kg/m$ (p<0.001) and plasma calcium level, from $7.55\pm3.86\;to\;9.98\pm3.77\;mg/dL$ after treatment (p<0.001). Change of fasting glucose level was not statistically significant $(91.92\pm3.53\;vs.\;98.19\pm4.78\;mg/dL,\;p=0.072)$, while change of total cholesterol was significant $(362.3\pm12.0\;vs\;251.4\pm11.5\;mg/dL$, p<0.001). In conclusion, patients on deflazacort showed similar efficacy in treatment of nephrotic syndrome as reported for prednisone with less impact on growth inhibition and metabolic side effects of hyperglycemia and hyperlipidemia.