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A New Format for Agarose Solid-Phase Enzyme Immunoassay
김학주,양중익,민신홍,변시명,Kim, Hack-Joo,Yang, Jung-Ick,Min, Shin-Hong,Byun, Si-Myung 생화학분자생물학회 1989 한국생화학회지 Vol.22 No.1
B형 간염 표면항원의 모노크로날 항체를 CNBr로 활성화시킨 agarose에 결합시켜 만든 고상 agarose-anti-HBs를 사용하여 측정하고자 하는 시료, 효소결합체, 효소반응을 1회용 플라스틱 주사기에서 이루어지도록 하는 진단방법을 연구하였다. 이 방법으로 실온에서 3시간 이내에 간단한 조작으로 측정이 완료될 수 있었으며 민감도는 기존의 상품화 되어 있는 진단시약과 동일수준을 보여주었고 B형 간염 표면항원 1 ng/ml의 농도를 측정할 수 있었다. A new format for agarose solid-phase enzyme immunosassay (ASEIA) has been developed in which a monoclonal antibody-coupled agarose, packed into a 1-ml disposable plastic syringe, regulates the sample and the enzyme reaction. The assay can be completed in less time at room temperature and in a simpler maner by use of this single-syringe system. The sensitivity of the technique is equivalent to a commercially available enzyme immunoassay kit and was able to detect $1{\mu}g/L$ of hepatitis B surface antigen in this study.
고상 Agarose - anti - HBs 결합체를 이용한 B형 간염 표면항원 진단시약
김학주,양중익,민신홍,변시명 ( Hack Joo Kim,Jung Ick Yang,Shin Hong Min,Si Myung Byun ) 생화학분자생물학회 1989 BMB Reports Vol.22 No.1
A new format for agarose solid-phase enzyme immunosassay (ASEIA) has been developed in which a monoclonal antibody-coupled agarose, packed into a 1-ml disposable plastic syringe, regulates the sample and the enzyme reaction. The assay can be completed in less time at room temperature and in a simpler maner by use of this single-syringe system. The sensitivity of the technique is equivalent to a commercially available enzyme immunoassav kit and was able to detect 1 ㎍/L of hepatitis B surface antigen in this study.
김원배(Won Bae Kim),양중익(Jung Ick Yang),이상득(Sang Deuk Lee),강수형(Soo Hyung Kang),이응두(Eung Doo Lee),심현주(Hyun Joo Shim),이종진(Jong Jin Lee) 한국응용약물학회 1994 Biomolecules & Therapeutics(구 응용약물학회지) Vol.2 No.4
The pharmacokinetics and tissue distribution of DA-3030 (recombinant human granulocyte colony-stimulating factor, rhG-CSF, recently manufactured by Dong-A research laboratory of Dong-A Pharmaceutical Company) were compared with reported data in the literature. After intravenous(i.v.) administration of DA-3030, at dose of 5, 10 and 100 ㎍/㎏ to rats, some pharmacokinetic parameters, such as terminal half-lives(1.05, 1.19 and 1.83 hr, respectively) and clearance (84.0, 54.8 and 45.5 ㎖/hr/㎏, repectively), were dose-dependent. This could be due to the saturable metabolism of DA-3030 in rats. Similar results were also reported. After subcutaneous(s.c.) and intramuscular(i.m.) administrations of DA-3030, 10 ㎍/㎏ to rats, the extent of bioavailability(absolute bioavailability) were incomplete; the values were 23.3 and 18.2% after s.c. and i.m. injections, respectively, due to the degradation of DA-3030 by protease. After 7-consecutive day i.v. administrations of DA-3030, 10 ㎍/㎏/day, to rats, the plasma concentrations and pharmacokinetic parameters of DA-3030 were not significantly different from those in single administration. In mice and dogs at DA-3030 dose of 10 ㎍/㎏, the plasma concentrations of DA-3030 were also declined rapidly with terminal half-lives of 1.31 and 1.15 hr, respectively. DA-3030 was highly concentrated in the kidney after i.v. administration of DA-3030, 10 ㎍/㎏, to rats, and the results were similar to those obtained using radiolabelled rhG-CSF in the literature. Above data indicate that DA-3030 has similar properties to rhG-CSF manufactured by other companies in view of pharmacokinetics.
당부분에서 4'-플루오린 또는 4'-아자이드로 치환된 3'-히드록시다우노루비신과 3'-히드록시독소루비신 유도체의 합성과 항암활성
옥광대,박정배,김문성,정동윤,양중익,Ok, Kwang-Dae,Park, Jeong-Bae,Kim, Moon-Sung,Jung, Dong-Yoon,Yang, Junn-Ick 대한약학회 1996 약학회지 Vol.40 No.2
3'-Deamino-3-hydroxy-4'-fluoro- or 3'-deamino-3'-hydroxy-4'-azido-daunorubicin(6,8) and -doxorubicin(7,9) have been synthesized, respectively. Compounds 7,8 and 9 were mo re cytotoxic than daunorubicin(1) and doxorubicin(2) against L1210 murine leukemic cell in vitro. When administered intraperitoneally for 9 days starting 1 day after tumor inoculation, compounds 7(T/C 605%) and 9(T/C 488%) showed significant antitumor activity for ip-inoculuated L1210 murine leukemia at wide range of doses.
강경구(Kyung Koo Kang),백남기(Nam Gi Baik),김원배(Won Bae Kim),양중익(Jung Ick Yang) 한국응용약물학회 1995 Biomolecules & Therapeutics(구 응용약물학회지) Vol.3 No.4
DA-3002 is a genuine human growth hormone produced by Dong-A Pharm. Co. Ltd. research laboratory using recombinant DNA technic. In this study, antigenic potential of DA-3002 was examined by active systemic anaphyaxis(ASA) in guinea pigs, mouse-rat passive cutaneous anaphylaxis(PCA) and passive hemagglutination(PHA) test as a part of safety research. DA-3002 induced anaphylactic shock in ASA test using guinea pigs immunized with DA-3002 alone or DA-3002 incoporated into Freund`s complete adjuvant(FCA) when challenged with 10 times higher dose of anticipated clinical dose of DA-3002, In the mouse-rat PCA and PHA test, DA-3002 also showed positive results. DA-3002, therfore, was considered to produce IgE, IgG and/or IgM in mice. The results of this study were similar to those of the other human growth hormones and these positive results were thought to be caused due to the fact that both DA-3002 and the other human growth hormones were heterogenous proteins to guinea pigs and mice. Considering the fact that DA-3002 is a genuine human growth hormone of which structure is identical with indigenous human growth hormone, DA-3002 is thought not to cause immunological problems in clinical use.
새로운 안트라사이클린계 항암제 DA-125 의 생식독성연구 (1) 랫트 최기형시험
정문구(Moon Koo Chung),한상섭(Sang Seop Han),양중익(Jung Ick Yang),노정구(Jung Koo Rho) 한국응용약물학회 1994 Biomolecules & Therapeutics(구 응용약물학회지) Vol.2 No.1
DA-125, a new anthracycline antitumor antibiotic, was at dose levels of 0, 0.1, 0.3 and 1.0 mg/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. Two-third of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development of F1 fetuses, as well as growth, behaviour and mating performance of F1 offspring were examined. 1. At 1 mg/kg, one out of the 10 dams showed difficult delivery. A decrease in food consumption, a loss in body weight and a decrease of spleen weight were found in this dose level group. At 0.3 mg/kg, difficult deliverys were observed in two out of the 10 dams. 2. At 1 mg/kg, an increased resorption rate and a decreased fetal weight were found. In addition, various types of external, visceral and skeletal malformations occurred at an incidence of 11.9, 41.8 and 14.5%, respectively. 3. At 1 mg/kg, body weight reduction, small eyeball, hydrocephalus and atrophy of sexual organs were observed in F1 offspring. One male pup receiving 0.3 mg/kg died on day 2 of lactation. The results show that the no-effect dose levels (NOELs) for dams and F1 offspring are 0.1 mg/kg/day and NOEL for F1 fetuses is 0.3 mg/kg/day.
Anthracycline 계 항암성 항생물질 DA-125 의 Beagle dog 에 대한 26 주 반복정맥투여독성시험
정태천(Tae Cheon Jeong),한상섭(Sang Seop Han),양중익(Jung Ick Yang),차신우(Shin Woo Cha),하창수(Chang Su Ha),노정구(Jung Koo Roh),박종일(Jong Il Park),신호철(Ho Chul Shin),김형진(Hyoung Chin Kim) 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.2
This study was performed to investigate the toxicity of DA-125 in beagle dogs, an anthracycline antitumor antibiotic. The dogs were administered DA-125 i.v. at 0.0023, 0.0375, 0.15 and 0.6 ㎎/㎏/day, 6 days/week for 26 weeks. At 0.6 ㎎/㎏, all male and female dogs were either sacrificed moribundly or dead during the 26-week treatment. The dogs revealed inactivity, salivation, dark bloody discharge, swelling of the subcutaneous injection site, abscess, and ulceration in the abdominal wall and legs. At 0.15 ㎎/㎏, anorexia, salivation, and swelling of the injection site were observed. The food consumption was decreased with a statistical significance at 6 and 12 weeks treatment in males of 0.6 ㎎/㎏. At 0.0375, 0.15 and 0.6 ㎎/㎏, body weights were decreased significantly in a dose-related fashion after 17 weeks treatment. Total white blood cell counts for male dogs at 0.6 ㎎/㎏ were lower than those of control dogs after 13 weeks treatment, which appeared mainly due to decreased neutrophils. At 0.15 ㎎/㎏, testicular atrophy was found in all males by gross pathology and the testicular weights were significantly decreased when compared to those of control males. Microscopically, the testis showed moderate atrophy of the seminiferous tubules and marked decrease in number of spermatozoa in the epididymal tubules. At 0.6 ㎎/㎏, petechia or echymotic hemorrhage was observed in gastrointestinal tract, heart, lungs, and other organs at the necropsy. Marked atrophy of thymus were observed in both males and females. In addition, severe testicular atrophy was noted in all males. Microscopically, gastrointestinal tract showed hemorrhage, epithelial denudation, hypermucus secretion, and atrophy of intestinal villi. Seminiferous tubules of the atrophic testis were lined with Sertoli cells only and devoid of germ cells. Severe oligospermia or aspermia was present in the epididymal tubules. Bone marrow showed marked depletion of hemopoietic cells. In addition, marked atrophy was found in the lymphoid tissue of gastrointestinal tract, various lymph nodes, and thymus. Injection sites showed marked inflammatory response with necrosis, necrotizing vasculitis, thrombus formation, and ulceration in the skin. According to the present results, no observed effect level appeared to be 0.0375 ㎎/㎏. At 0.15 ㎎/㎏, testis was a target organ, while at 0.6 ㎎/㎏ hemopoietic tissue, gastrointestinal tract, and testis were considered to be target organs. At 0.6 ㎎/㎏ the test compound seems to inflict a damage on the blood vessels causing hemorrhage in the various organs and tissues.
7-O-(alpha-L-람노피라노실) 또는 7-O-(4''-아미노-alpha-L-람노피라노실)-다우노마이시논과 -아드리아마이시논 유도체의 합성과 항암활성
옥광대(Kwang Dae Ok),박정배(Jeong Bae Park),김문성(Moon Sung Kim),정동윤(Dong Yoon Jung),안상용(Sang Yong An),배중석(Chung Seok Bae),양중익(Junn Ick Yang) 대한약학회 1996 약학회지 Vol.40 No.1
Daunirubicin and doxorubicin analogues (5,7,8,9,) in which the natural amino sugar, daunosamine, is replaced by rhamnopyranosyl or 4''-amino rhamnopyranosyl residues have been prepared. The in vitro cytotoxicity of compound 5 or 7 was similar to that of doxorubicin for P388 murine leukemic cell line. But compound 8 or 9 was less cytotoxic than doxorubicin. When administered intravenously on day 1, compound 9 showed antitumor activity comparable to that of doxorubicin against ip-inoculated L1210 murine leukemia and found to be less toxic than doxorubicin. But the in vivo antitumor activity of compound 7 or 8 was inferior to that of doxorubicin.
토끼에 대한 천연형인성장호르몬 DA-3002 의 국소작극성
김옥진(Ok Jin Kim),안병옥(Byoung Ok Ahn),이순복(Soon Bok Lee),김원배(Won Bae Kim),양중익(Jung Ick Yang) 한국응용약물학회 1995 Biomolecules & Therapeutics(구 응용약물학회지) Vol.3 No.1
The local irritation studies of DA-3002, an authentic recombinant human growth hormone (rhGH), were carried out in rabbits after the following treatment ; application into the conjunctival sac of the eye (single), single subcutaneous and intramuscular injection, 7-day repeated subcutaneous and intramuscular injection. The results obtained were as follows. In the result of ocular irritation test, 0.16% solution of DA-3002 could be considered as a non-irritating material. In single subcutaneous and intramuscular irritation test, the irritancy of 0.16% DA-3002 solution was not so much different from that of saline. The local irritation of DA-3002 by 7-day repeated injection was negligible and similar to that of saline by both subcutaneous and intramuscular routes. These results suggest that DA-3002 has no irritating activity when injected through subcutaneous or intramuscular route for clinical practice as 0.16% solution.
새로운 괴립구 콜로니 자극인자 ( rhG-CSF ) DA-3030 의 국소자극성에 관한 연구
김옥진(Ok Jin Kim),안병옥(Byoung Ok Ahn),이순복(Soon Bok Lee),김원배(Won Bae Kim),양중익(Jung Ick Yang) 한국응용약물학회 1994 Biomolecules & Therapeutics(구 응용약물학회지) Vol.2 No.3
As a series of safety studies of DA-3030, a new rhG-CSF, its local irritancy was examined in the rabbits after the following treatment; application into the conjunctival sac of the eye(singie), subcutaneous injection(single), intramuscular injection(single), and intravenous injection(8-day repeated). In addition, paravenous irritation of DA-3030 was investigated in mice. The results obtained were as follows. 1. In the result of ocular irritation test, 0.03% solution of DA-3030 could be considered as a non-irritating material. 2. The local irritation of DA-3030 by an injection of 0.5 ml of its solution subcutaneously or intramuscularly was negligible and not so much different from that of saline. 3. In the vascular irritancy test, macro- and microscopic observations revealed that the irritating activity of DA-3030 in blood vessels was not different from that of saline when they were injected once a day into vein retroauricularis of rabbits for 8 days. 4. The paravenous administration of DA-3030 did not induce any abnormal changes at injection sites except mild swelling in 1 mouse at 3 hours after injection which was thought to be due to slow absorption. The above-mentioned results suggest that DA-3030 has no irritating activity when injected through intravenous or subcutaneous route for clinical practice as 0.03% solution.