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( TBMA ) Macromer 를 그라프트시킨 음이온성 아크릴 공중합체의 합성과 물성
김형욱,노시태,강신춘 ( Hyoung Ook Kim,Si Tae Noh,Shin Chun Kang ) 한국공업화학회 1993 공업화학 Vol.4 No.3
마크로머를 이용한 음이온성 아크릴 수지를 제조하기 위하여 음이온 리빙 중합법으로 TBMA를 합성하였고 이들을 다시 MMA와 공중합시켜 아크릴계 그라프트 공중합체를 제조하였다. 그라프트 공중합체의 음이온 site 함량을 제어하기 위하여 (TBMA)마크로머와 MMA의 weight 비율을 7/93, 10/90, 15/85, 20/80, 30/70, 40/60, 50/50까지 변화시켜 합성하였다. (TBMA)마크로머의 음이온 리빙 중합과정에서는 반응온도를 -78℃로 유지하면서 n-butyllithium-diphenylethylene계 개시제 시스템을 사용하였으며 정지반응 단계에서는 말단에 이중결합을 도입하기 위하여 capping material로 benzaldehyde를 사용한 후, methacryloyl chloride와 반응시켰으나, 넓은 분자량 분포(1.4∼1.5)가 나타났다. 또한 그라프트 공중합체 내의 TBMA는 p-toluenesufonic acid 촉매로 가수분해하였고 중화제로 triethylamine을 사용한 중화반응은 아크릴 수지의 음이온성을 부여하였다. (TBMA)마크로머의 분자량과 분자량 분포에 대한 측정은 GPC를 이용하였으며 TBMA의 가수분해 반응과 더불어 아크릴 수지의 이온화 반응을 IR과 NMR을 이용하여 분석하였다. (TBMA)수분산성 및 분산 안정성의 관점에서 그라프트 공중합체내의 (TBMA)마크로머 분자량에 대한 가지(branch)의 길이와 TBMA 함량을 관련지어 검토한 결과 분자량이 작은(TBMA) 마크로머에서는 적은 TBMA 함량으로도 안정된 수분산화 현상이 일어남을 알았다. Anionic acrylic resin utilizing macromer(TBMA-g-MMA) copolymer was synthesized by preparing(TBMA) macromer using anionic living polymerization, followed by graft copolymerization with MMA macromer. To control the anionic site content in graft copolymer, the relative composition((TBMA) macromer/MMA ratio) of the graft copolymer was controlled at 7/3, 10/90, 15/85, 20/80, 30/70, 40/60, 50/50 in weight content. In the course of anionic living polymerization of(TBMA) macromer, broad molecular weight distribution (1.4∼1.5) was obtained by using n-butyllithium-diphenyethylene initiatior system at -78℃. To introduce the double bond at the end of chain in termination step, methacryloyl chloride was reacted after insertion of benzaldehyde as capping material. Moreover, TBMA parts in graft copolymer were hydrolyzed in the presence of p-toluenesulfonic acid catalyst, and neutralization of graft copolymer with triethylamine was granted acrylic resin to anionic site. Molecular weight and molecular weight distribution of (TBMA) macromer were determined by GPC, and the hydrolysis of TBMA with neutralization of acrylic resin were determined by IR and NMR. From water dispersion and stability point of view, stable dispersion state appeared at low molecular weight(TBMA) macromer with a small TBMA content as a result of scrutiny about the relation to TBMA content and branch length for(TBMA) macromer molecular weight in graft copolymer.
김형욱,강경선,신동진,조재진,김배환,서광원,남기환,이영순,Kim, Hyoung-Ook,Kang, Kyung-Sun,Shin, Dong-Jin,Cho, Jae-Jin,Kim, Bae-Hwan,Seo, Kwang-Won,Nam, Ki-Hoan,Lee, Yong-Soon 한국독성학회 1992 Toxicological Research Vol.8 No.2
This study was performed to determine the toxic effects of graded dose levels of SKI 2053R after repeated administration. Three groups of Sprague-Dawley rats(10M and 10F per group) were given a total of 25 i.v. injections of SKI 2053R (1.50,3.75,9.38mg/kg/day). In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group of Sprague-Dawley rats (10M and 10F per group) were given a total of 25 i.v.injections of cisplatin (1.70mg/kg/day). The dosing schedule was divided into five courses of 5 consecutive days with 16-day dose-free intervals between each course. No drug-related toxicity occurred in low dose level group (1.50mg/kg/day) of SKI2053R. From the results of hematological examination, peripheral WBC counts, RBC counts and hemoglobin of high dose level group(9.38mg/kg/day)of SKI 2053R were significantly lower than those of no-treated group. Other toxicities including reduced final body weight, proteinuria and hematuria were observed in high dose level group of SKI 2053R. But, no change was detected in serum biochemical values of SKI 2053R treated groups. All of the rats in cisplatin treated group were died between 3 and 13 weeks, while rats treated with SKI2053R survived to the end except one rat of middle dose level group(3.75mg/kg/day). In histopathological examinations, rats that received cisplatin manifested severe tubular damage in kidney and hemosiderosis in spleen, but no critical pathological lesion was observed in rats of other groups. Considering the results of this study, it was concluded that non-toxic dose of SKI 2053R in this treatment schedule was estimated to be 3.75 mg/kg/day and the maximum tolerated dose was to be higher than 9.38mg/kg/day. The toxic profiles fo SKI 2053R were different from those of cisplatin, and its toxicity was considerably lower than that of cisplatin.
동맥경화증의 실험동물 모델화와 식이섬유의 동맥경화 방어기전에 관한 연구
김형욱,이영순,이흥식,신광순,임창형,Kim, Hyoung-ook,Lee, Yong-soon,Lee, Heung-shik S,Shin, Kwang-soon,Lim, Chang-hyeong 대한수의학회 1993 大韓獸醫學會誌 Vol.33 No.3
mechanisms for the hypocholesterolemic effects of $\beta$-glucan remain unclear. Rats were divided into 3 groups ; normal control group, atherogenic group(oral administration of cholesterol 40 mg/kg/day plus vit. $D_2$ 320,000 IU/kg/day), $\beta$-glucan treatment group(atherogenic treatment plus $\beta$-glucan 0.135 g/kg/day). The $\beta$-glucan treatment group showed moderate increases of serum lipids concentration compared with atherogenic group. In histopathological examination, aortas showed no critical lesions. The total fecal neutral sterols and bile acids excreted for 6 days was increased compared with both normal and atherogenic group. To compare effects of soluble fiber and insoluble fiber extracted from barley on postprandial lipemia, 5 healthy male adults ingested on separate days a low-fiber(total dietary fiber 2.61g) control meal or dietary fiber-enriched(12.61g) meals. Fasting and postprandial blood samples were obtained for 6.5h and serum lipids were analyzed. The serum total lipids, total cholesterols, LDL & VLDL-cholesterol were markedly reduced with soluble fiber-enriched meals, but no decrease with insoluble fiber-enriched meals. These results suggest that mechanisms for the hypocholesterolemic effect of $\beta$-glucan on rats were due to the inhibition of cholesterol absorption in the intestinal lumen and acceleration of cholesterol catabolism in the liver. And the soluble dietary fiber($\beta$-glucan) has the hypocholesterolemic effect by dropping serum LDL & VLDL-cholesterol in the clinical study.
Occurrence of Hairless Piglets with Congenital Goiter
김재훈,손현주,김형욱,진영화,Kim, Jae-hoon,Sohn, Hyun-joo,Kim, Hyoung-ook,Jean, Young-hwa The Korean Society of Veterinary Science 2003 大韓獸醫學會誌 Vol.43 No.3
A diagnosis of iodine-deficient goiter was confirmed in newborn piglets that were born hairless edematous, and with markedly enlarged thyroid gland. Clinically, most of the piglets were born dead, extreme weakness or dying within a few hours of birth. Gestation periods were prolonged for 3-7 days. Histopathologically, hair follicles were scarce and reduced in size, contained slender hairs, and revealed a shallow penetration into the hypodermis that showed severe diffuse edema. Thyroid glands had severely hyperplastic follicles and poorly staining colloid. The follicles were irregular in size and shape depending on varying amounts of lightly eosinophilic and granular colloid in the lumen. The iodine content of the diet fed to the sows and plasma total thyroxine and triiodothyronine concentration of sows were very low. This is a first report for iodine-deficient goiter in newborn piglets in Korea.
강경선,신동진,조재진,김형욱,김배환,이영순,Kang, Kyung-Sun,Shin, Dong-Jin,Cho, Jae-Jin,Kim, Hyoung-Ook,Kim, Bae-Hwan,Lee, Yong-Soon 한국독성학회 1992 Toxicological Research Vol.8 No.2
cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R), an antitumor platinum complex, was selected for clinical evaluation on the basis of its experimental antitumor and toxicologic profiles in preclinical studies. These studies were performed to obtain information on its toxic signs, orgnas which are mainly affected, and to estimate its lethality in mice and rats given SKI 2053R through two routes of administration. In male and female rats given a single intragastrical dose of SKI 2053R, we estimated that $LD_{50}$ values were over 3.00g/kg, respectively. In male and female mice given a signle intragastrical dose of SKI 2053R, we estimated that $LD_{50}$ values were 2.44g/kg and 1.59g/kg, respectively, In a single intraperitoneal dose of SKI 2053R, we determined that $LD_{50}$ values of male and female rats were 227mg/kg and 182mg/kg, and those of male and female mice were 198mg/kg and 207mg/kg, respectively. In gross and histopathological examinations on dead animals, we found that kidney and liver were mainly affected.
이영순,강경선,신동진,김형욱,조재진,김배환,남기환,서광원,Lee, Yong-Soon,Kang, Kyung-Sun,Shin, Dong-Jin,Kim, Hyoung-Ook,Cho, Jae-Jin,Kim, Bae-Hwan,Nam, Ki-Hoan,Seo, Kwang-Won 한국독성학회 1992 Toxicological Research Vol.8 No.2
SKI 2053R and SKI 2053R-human serum albumin(HSA) mixture were examined for their antigenicity in Hartley guinea pigs as well as C57BL/6 mice in comparison with distilled water (DW), HSA and DW-HSA conjugate. Several antigenicity tests, including acitive systemic anaphylaxis(ASA), passive systemic anaphylaxis (PSA), passive cutaneous anaphylaxis (PCA) and indirect hamagglutination test (IHA), were performed according to the Established Regulations of National Institute of Safety Research. The results were as follows: 1. When guinea pigs were sensitized with SKI2053R or SKI2053R-HSA emulsified with complete Freund's adjuvant(CFA), these animals showed negative reactions in ASA and PSA. 2.No blue spot was observed on the back skin of guinea pigs in the PCA test. 3. Sera from guinea pigs revealed a negative reaction in IHA. 4.Guinea pigs were sensitized by HSA emulsified with CFA as a positive control, and these animals showed positive reactions in ASA, PSA, PCA, and IHA. As shown above, SKI2053R was considered to possess neither antigenic, nor haptenic properties, and confirmed not to have the haemagglutinating activity.