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세팔로스포린계 유도체 CKD-604 의 물성연구 수용액중에서의 안정화 및 가용화
권수연(Soo Yeon Kwon),신희종(Hee Jong Shin),김종국(Chong Kook Kim) 한국약제학회 1999 Journal of Pharmaceutical Investigation Vol.29 No.3
To formulate the parenteral delivery of a new cephalosporin derivative, 7-β-[(2)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[(2,3-cyclopenteno-4-carbamoyl-1-pyridinium)methyl]-3-cephem-4-carboxylate sulfate(CKD-604), the stability and solubility of CKD-604 in various aqueous media were investigated. The degradation kinetics of CKD-604 in aqueous solutions (ionic strength 0.1, pH 1-8) were studied at 37℃. The observed degradation rates followed pseudo-first order kinetics. The pH-rate profile exhibited a minimum degradation rate at pH 5. The Arrhenius activation energy was 14.2 ㎉/mol in pH 5 buffer solution. Excellent agreement between the cephalosporins` theoretical pH-rate profile and the experimental data indicated that the degradation pathway of CKD-604 could be predicted according to the general pathway of cephalosporins. The solubility of CKD-604 was 8.16 ㎎/㎖ at 25℃. To enhance the solubility and adjust the suitable pH, CKD-604 was solubilized by using sodium ascorbate, ascorbic acid and urea. The compositions were obtained to satisfy optimum pH and concentration, and the total amount of additives was several times of the active ingredient, CKD-604.
김종국,김경미,권수연 ( Chong Kook Kim,Kyoung Mi Kim,Soo Yeon Kwon ) 한국약제학회 1997 Journal of Pharmaceutical Investigation Vol.27 No.2
N/A Epidermal growth factor (EGF) is a mitogen which activate the proliferation of basal cells in skin, which implicate the wound healing in severe skin damage such as burn. To carry out the preclinical test for the pharmacological action of EGF, EGF in transdermal delivery system must be stable. Since EGF is a protein susceptible to proteolysis and unstable in aqueous solution, in vitro stabilization of EGF is prerequisite for the formulation. In this study, effect of additives on the stability of EGF is investigated in vitro. The stability of EGF in aqueous solution was enhanced with the various water-soluble polysaccharides such as HPMC, sorbitol. mannitol and dextrin. EGF was successfully extracted from the ointment with 5% HPMC solution, and EGF in aqueous solution and ointment was also successfully stabilized with 5% HPMC. The ointments prepared with different amount of EGF were applied on the damaged dorsal skin of rats for the determination of optimal concentration of EGF. The ointment with EGF (10 ㎍/g) showed good wound healing action on the damaged skin of rats.