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새로운 플라보노이드 유도체인 DA-6034의 TNBS 유발성 염증성대장염 모델에서의 치료효과
손미원,고준일,김희기,장동경,유무희,김원배,이강춘,송인성 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1
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 30㎎ TNBS in 50% ethanol (0.5㎖) 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 DA-6034 (0.3∼30㎎/㎏) or sulfasalazine (50∼100㎎/㎏), prednisolone (0.3∼3㎎/㎏) after the induction of colitis until they were sacrificed. Oral treatment with DA-6034 resulted in significant reductions of macroscopic colonic damage, colonic inflammation. DA-6034 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 in 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.
새로운 플라보노이드 유도체인 DA-6034의 TNBS 유발성 염증성대장염 모델에서의 치료효과
손미원(Mi Won Son),고준일(Jun Il Ko),김희기(Hee Kee kim),장동경(Dong Kyung Jang),유무희(Moo Hi You),김원배(Won Bae Kim),이강춘(Kang Chun Lee),송인성(In Sung Song) 대한약학회 1998 약학회지 Vol.42 No.2
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 B4 (LTB4) 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 LTB4 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 LTB4 synthesis and MPO inhibition.
새로운 캅사이신 유도체 DA-5018 의 진통활성 기전연구 Opiate 수용체 및 Prostanoid 와의 상관성
손미원(Mi Won Son),손문호(Moon Ho Son),배은주(Eun Ju Bae),김순회(Soon Hoe Kim),김원배(Won Bae Kim),양중익(Junn Ick Yang) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.1
DA-5018, a new capsaicin derivative, showed potent analgesic effect comparable to that of morphine in various experimental acute pain models. In this study, whether the analgesic mechanism of DA-5018 is related to opiate receptors or prostanoids was investigated. The affinity of DA-5018 for opiate receptor was determined by receptor binding assay. The Ki values of DA-5018 for nonspecific and specific μ, k, δ-opiate receptor was 299±8.88, 735±215, 2930±163, 1550±813 nM, respectively and DA-5018 exhibited lower affinity than morphine. DA-5018 (10^(-9)∼3 x 10^(-5) M) inhibited electrically-evoked contractions of the guinea pig ileum and rat vas deferens, and these inhibition was not antagonized by naloxone(10 nM), an opiate receptor antagonist. Antagonism of analgesic effect of DA-5018 by naloxone was examined by tail pinch test. Analgesic action of DA-5018(0.1∼2 mg/kg, s.c.) was not antagonized by naloxone(1 mg/㎍, i.p.). These results indicate that pharmacological action of DA-5018 is not related with opiate receptor. Cyclooxygenase and 5-lipoxygenase activities in rat peritoneal neutrophil treated with A23187 and arachidonic acid were measured by radioimmunoassay. DA-5018 stimulated the cyclooxygenase activity and the concentration showing the two fold increase of activity was 124 μM. DA-5018 slightly inhibited 5-lipoxygenase activity and these results together indicate that analgesic action of DA-5018 is not mediated through inhibition of cyclooxygenase or lipoxygenase. These results suggest that the analgesic effect of DA-5018 is not due to blocking opiate receptor or to inhibiting the synthesis of prostanoids in the arachidonic acid metabolism pathway.
Sestamibi 의 신규합성과 제제화에 따른 안정성 비교
손미원(Mi Won Son),임중인(Joong In Lim),장영수(Young Soo Chang),정미영(Mi Young Jung),정낙신(Lak Shin Jeong),김순회(Soon Hoe Kim),김원배(Won Bae Kim),정재민(Jae Min Jeong) 대한핵의학회 2001 핵의학 분자영상 Vol.35 No.5
N/A Purpose: Ascorbic acid is known to act as an antioxidant. Therefore, it can be used in increasing the efficiency of radiochemical labeling of Technetium-99m setamibi by inhibition of oxidation of Sn2+ at low concentration. We intended to estimate the efficiency of radiochemical labeling and the stability of the newly formed formulation when ascorbic acid was added to a commercial kit. Materials and Methods: Synthesis of sestamibi was performed according to Dong-A`s patent procedure (No.10-2001-0012877). First, we undertook a study to evaluate the efficiency of radiochemical labeling of sestamibi containing ascorbic acid. The stability of the vials was assessed using either 7.5 ㎍ or 75 ㎍ of ascorbic acid, added to commercial vials under the accelerated condition(Temp: 40℃, +2℃, Relative humidity: 75±5%). Results: Sestamibi was synthesized in overall 35-40% yield over 5 steps from a commercially available methallyl chloride as a starting material. When ascorbic acid was added, the efficiency of radiochemical labeling was maintained compared to the vial with no ascorbic acid. The accelerated test showed that the addition of ascorbic acid inhibited the oxidation of Sn2+ ion by antioxidation mechanism. Also, the efficiency of radiochemical labeling of this vial after 9 months was nearly the same as the starting point. Therefore, the storage period of the kit is likely to be extended. Taken together, it suggests that the addition of ascorbic acid as a stabilizer is desirable. Conclusion: To increase the stability of a sestamibi cold kit, it is desirable to add ascorbic acid as a stabilizer to the commercial fomulation. (Korean J Nucl Med 2001:35:334-341)
새로운 캅사이신 유도체 DA-5018 의 진통활성 기전연구 Substance P 관련성
손미원(Mi Won Son),손문호(Moon Ho Son),배은주(Eun Ju Bae),김순회(Soon Hoe Kim),김원배(Won Bae Kim),양중익(Junn Ick Yang) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.1
Capsaicin is known to be an analgesic agent, affecting the synthesis, storage, transport and release of substance P, the principal neurotransmitter of pain from periphery to the central nervous system(CNS). DA-5018, a newly synthesized capsaicin derivative has shown potent analgesic effect comparable to that of morphine in various rat models of experimentally induced acute pain. In this study the mechanism of analgesic activity of DA-5018 was examined. First, the electrically-evoked contraction of guinea pig trachea was inhibited by DA-5018 and these inhibition was recovered by incubation with capsazepine(3 ,μM), capsaicin receptor antagonist and this result suggested that DA-5018 has affinity on capsaicin receptor. The correlation between the norciceptive threshold and the release of substance P was evaluated. In vitro perfusion of slices of the rat spinal cord with DA-5018(10, 100 μM) produced a significant increase of the release of substance P and this increase was less than that of capsaicin(10 μM). The norciceptive threshold of rat treated with DA-5018(1 mg/ kg, p.o) in tail pinch test increased from 2.9±0.3 to 23.5±6.61. Tail pinch latency increased to a maximun at 15 min after DA-5018 treatment and then declined to control values by 120 min. The capsaicin-evoked release of substance P from the spinal cord slices of rat treated with DA-5018 reduced from 2.38±0.79 to 0.69±0.26 pg/mg wet weight. This reduction reached to a minium at 15 min after DA-5018 treatment and then recovered to control value by 120 min. These results mean that analgesic activity of DA-5018 is due to release of substance P. The effect of DA-5018 cream on electrically-evoked neurogenic inflammation of rat saphenous nerve was compared with capsaicin (zostrix-HP). DA-5018 showed 34% inhibition of the neurogenic extravasation while capsaicin showed significant 67% inhibition. This result indicates that the potency of DA5018 in the release of substance P is less than that of capsaicin. These results suggest that the release of substance P is partially involved in the mechanism of analgesic action of DA-5018.
기능성 소화불량증 환자에 대한 한약복합제형간의 비교 임상시험: 대조군 연구
이재진,손미원,홍권의,Lee, Jae-Jin,Son, Mi-Won,Hong, Kwon-Eui 대한약침학회 2009 Journal of pharmacopuncture Vol.12 No.2
Objective : Functional dyspepsia is a prevalent disease. It impedes subjective quality of life. The purpose of this research is to examine the equivalent effect of herb drug medicine treatment(H-D)and Over the Counter(OTC) for functional dyspepsia. Method : In this controlled study, we compared herb drug medicine(H-D) with Over the Counter(OTC) of functional dyspepsia. 30 volunteers who satisfied the requirements were enrolled in study. Severity of dyspepsia was measured by Nepean Dyspepsia Index(NDI-K) before and after treatments. Result : The results are summarized as follows. 1. In Herb drug medicine and Over the Counter groups, total key symptoms score of after treatment were significantly decreased and improve rate of key symptoms was higher than before treatment, but there were no statistical significance between two groups. 2. In Herb drug medicine and Over the Counter groups, each symptoms score of after treatment were significantly decreased and improve rate of key symptoms was higher than before treatment, but there were no statistical significance between two groups. 3. In Herb drug medicine and Over the Counter groups, quality of life score of after treatment were significantly decreased and improve rate of key symptoms was higher than before treatment, but there were no statistical significance between two groups. Conclusion : Herb drug medicine treatment(H-D) is effective to improve the symptoms and quality of life in patients with functional dyspepsia.