제어방출형 Amoxicillin 제제의 제조 및 평가

지웅길,전운종,이계원,한건,정연복 충남대학교 약학대학 의약품개발연구소 1994 藥學論文集 Vol.10 No.-

The microcapsules of amoxicillin using stearyl alcohol and polyethyleneglycol 8000 (PEG 8000) were prepared by a emulsion melted-cooled process in water phase. The size distribution, dissolution test, observation with SEM and in vivo test were investigated. The microcapsules obtained were spherical, uniform and free flowing particles. The release of drug from microcapsule was increased in proportional to the content of PEG 8000. As the PEG 8000 content increased, the particle size of microcapsule was decreased. Sanning electron micrograph study revealed that microcapsules had comparatively rough surfaces as drug content was increased. The AUC_(o-12) after administration of amoxicillin microcapsules was more increased 40% as compared with the AUC after administration of amoxicillin powder in rabbits.

당뇨병 환자에서 혈장 Thrombin-Antithrombin Ⅲ 및 Plasmin-α_2-Plasmin Inhibitor 복합체의 임상적 의의

김경욱,김은숙,정상수,윤수지,박우일,이준희,남수연,안철우,문병수,김경래,차봉수,송영득,임승길,이현철,허갑범 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.5

연구배경:당뇨병 환자에서 혈액응고 및 섬유소용해 체계의 이상경향이 있어 그 결과로 여러 혈관합병증의 발생위험이 높다는 사실은 널리 알려져 있다. 그 기전은 아직 확실히 밝혀지지 않았으나, 고혈당으로 인한 혈장 단백질들의 비효소성 당화작용이나 산화성 스트레스로 인한 유리 라티칼 작용으로 응고항진이나 섬유소용해 활성의 저하를 유발하는 것으로 생각되고 있다. 최근 응고 및 용해인자와 그 억제자의 복합체들의 증가가 이 상태를 비교적 예민하게 반영한다고 알려져 있다. 방법:본 연구에서는 당뇨병 환자 101명과 정상 대조군 20명에서 혈장내 thrombin­antithrombin complex(TAT)와 plasmin­α₂­plasmin inhibitor complex(PIC)를 측정하여 비교하고, 당뇨병 환자에서 미세혈관 합병증과 대혈관합병증의 유무에 따른 차이와, 이미 혈관 질환의 위험인자로 알려져 있는 인자들간의 상관성을 알아보고자 하였다. 결과:1. 환자의 분포를 살펴보면 혈관합병증이 있는 군은 85명, 혈관합병증이 없는 군은 16명이었고, 평균연령은 각각 57.9±14.1세, 49.9±16.6세로 혈관 합병증이 있는 군에서 더 나이가 많았고, 체질량지수는 23.2±3.4㎏/㎡, 24.1±3.4㎏/㎡로 두 군간 유의한 차이는 없었다. 또 두 군간의 혈압 및 HbA1c, 공복혈당 및 인슐린과 C­peptide, 총 콜레스테롤, 중성지방, HDL­콜레스테롤, Lp⒜는 유의한 차이가 없었고, 미세혈관합병증이 있는 군에서 당뇨병의 유병기간이 길었다. 2. TAT 및 PIC의 농도는 정상 대조군에서는 2.8±1.2 ng/mL, 240.4±69.7 ng/mL이었고, 당뇨병 환자군에서는 9.5±22.6 ng/mL, 472.2±258.7 ng/mL이었다. TAT와 PIC 모두 당뇨병 환자군에서 정상 대조군에 비해 유의하게 증가되어 있었고(p<0.001), TAT/PIC ratio는 두 군간 차이가 없었다. 3. 당뇨병 환자의 혈관합병증에 따른 TAT 및 PIC, fibrinogen 농도는 합병증이 없는 군은 각각 4.1±2.4ng/mL, 362.2±272.0ng/mL, 322.7±102.4mg/mL으로 PIC와 fibrinogen의 증가를 보였으나, 연령을 보정한 후에는 통계학적 유의성은 없었다. 또 대혈관 합병증군에서는 각각 6.0±4.9 ng/mL, 507.4±321.6 ng/mL, 427.1±194.7 mg/dL이었으며 미세·대혈관 합병증군에서는 10.4±6.4 ng/mL, 484.8±269.7 ng/mL, 388.4±132.4 mg/dL으로 TAT의 증가를 보였으나 역시 연령을 보정한 후에는 통계학적 유의성은 없었다. 4. 미세혈관합병증군에서 HbA1c(>8%)가 높은 군의 PIC 농도가 유의하게 높았고(p=0.049), 대혈관합병증군에서 HbA1c(>8%)가 높은 군의 총 콜레스테롤 농도가 유의하게 높았다(p=0.042). 5. 총 당뇨병 환자군에서 PIC는 fibrinogen과 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며(r=0.47, 0.31,-0.25), 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다(r=0.67). 결론:이상의 결과에서 혈장 TAT 및 PIC 농도는 당뇨병 환자에서 정상 대조군에 비해 의미있게 증가되어 있었고, 당뇨병 환자군에서는 연령의 증가와 유병기간이 혈액응고항진 및 용해의 장애에 큰 역할을 함을 알 수 있었으며, 총 당뇨병 환자군에 PIC와 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다. 따라서 당뇨병 환자에서 혈액응고 및 용해의 장애가 동반되어 있다고 볼 수 있으며, 혈장 TAT 및 PIC는 혈관합병증으로의 진행을 예측하는 지표로서 유용하리라 생각된다. 또 혈당조절정도와 상관성이 있으므로 혈당조절후에 추적검사를 시행하여 합병증의 예방이 가능한지 추후 연구가 필요하리라 생각된다. Background : Abnormality of coagulation and fibrinolystic system is known as a predisposing factor of vascular complication in diabetes. Although the pathogenesis is not well known, non-enzymatic glycation reaction and the increase in production of free radicals due to an increased oxidative stress may be linked to the hypercoagulibility and hypofibrinolytic activity. As indices of abnormality in coagulation and firinolysis in peripheral blood, plasma thrombin-antithrombin Ⅲ complex (TAT) and plasmin-α_2-plasmin inhibitor complex (PIC) were measured. The purpose of this study was to clarify whether hypercoagulability exists in diabetic patients with or without vascular complication. Methods : In our study, we measured plasma thrombin-antithrombin Ⅲ compelx (TAT) and plasmin-α_2-plasmin inhibit or complex (PIC) in 101 diabetic subjects and 20 controls. Comparing TAT and PIC levels in diabetic microvascular complication group, diabetic macrovascular complication group and controls, we examined correlation between risk factors associated with diabetic vascular complication. Results : 1. The group with diabetic vascular complication was older than group without complication. There was no significant difference in BMI, blood pressure, HbA_ic, blood sugar level, insulin, C-peptide, serum creatinine, total cholesterol, triglyceride, HDL-cholesterol, Lp (a) between two groups. The group with diabetic microvascular complication had longer duration of diabetes. 2. Concentration of TAT and PIC were 2.8±1.2 ng/ mL, 240.4±69.7 ng/ mL in controls and 9.5±22.6 ng/ mL, 472.2±258.7 ng/ mL in diabetic patients, respectively. TAT and PIC were significantly higher in diabetic patients than in control (p<0.001). But TAT/PIC ratio was no significant difference between two groups. 3. In diabetic patients, concentration of TAT and PIC and fibrinogen were respectively 4.1±2.4 ng/ mL, 362.2±272.0 ng/ mL, 322.7±102.4 mg/ dL in group without vascular complication and 5.3±4.1 ng/ mL, 529.5±258.7 ng/ mL, 374.9±106.2 mg/ dL in group with microvascular complication, which group had increase in PIC and Fibrinogen but no significance after correction of age. Concentration of TAT and PIC and Fibrinogen were 60.±4.9 ng/ mL, 507.4±321.6 ng/ mL, 427.1±194.7 mg/ dL in macrovascular complication, and 10.4±6.7 mg/ mL, 484.8±269.7 ng/ mL, 388.4±132.4 mg/ dL in combined vascular complication which group showed increase of TAT but also had no significant increase after correction of age. 4. In diabetic microvascular complication patients, group of high HbA_1c (>8%) (p=0.049) had significant high PIC concentration. In diabetic macrovascular complication patients, group of high HbA_1c (>8%) (p=0.042) had significant high total cholesterol concentration. 5. In all diabetic patients, PIC was positively correlated with fibrinogen and HbA_1c and negatively correlated BMI (r=0.47, 0.31, -0.25). Only in daibetic patients without angiopathy, TAT was positively correlated with HbA_1c (r=0.67). Conclusion : In this study, plasma TAT and PIC concentration significantly increased in diabetic patients compared with controls, and PIC was increased in group with microvascular complication, TAT were increased in group with combined micro macrovascular complication. However, there was no significance relationship existed when correctinf for age. PIC was correlated with HbA_1c. TAT was correlated with HbA_1c only in the group without angiopathy. Abnormality of coagulation and fibrinolysis were combined in diabetes, plasma TAT and PIC can be used as an index of vascular complication. Also we found the correlation with the degree of the blood glucose control. Therefore we need follow up study for the possibility of prevention of vascular complication after controlling the blood glucose to age-matched patients (J Kor Diaabetes Asso 25:354~363, 2001).

Expression of beta-catenin and its mechanism of delocalization in intestinal-type early gastric cancer based on mucin expression.

Lee, Soo Han,Kang, Hyun Jeong,Shin, Dong-Hun,Cho, Duk-Yeon,Song, Jin Mi,Lee, Han Cheol,Kim, Gwang Ha,Song, Geun Am,Sol, Mee Young,Kim, Jee Yeon,Choi, Kyung Un,Lee, Chang Hun,Huh, Gi Young,Park, Do You Gutenberg 2009 HISTOLOGY AND HISTOPATHOLOGY Vol.24 No.7

<P>The biological characteristics of intestinal-type early gastric cancers (ICs) differ based on mucin phenotypes. Beta-catenin delocalization is a predictive marker of aggressive biological behavior (submucosal invasion and lymph node metastasis) of ICs. The presumptive causative genetic alterations leading to delocalization of beta-catenin in ICs are still controversial, and there are only a few reports regarding beta-catenin expression in gastric cancer based on mucin phenotypes. Therefore, in the current study, the expression and mechanisms of delocalization of beta-catenin were elucidated on the basis of mucin phenotypes in 109 cases of ICs. There was increased cytoplasmic and nuclear beta-catenin expression (delocalization) in ICs with a predominant intestinal mucin phenotype (ICIP; 46.3% [25/54 cases]) compared to ICs with a predominant gastric mucin phenotype (ICGP; 20% [11/55 cases]). There were no beta-catenin or APC mutations in ICs. APC promoter hypermethylation was present in 49 of 105 (46.7%) cases of ICs. There was a significant relationship between APC promoter hypermethylation and beta-catenin delocalization in ICs, especially in ICIPs. There was no relationship between beta-catenin delocalization and APC gene loss of heterozygosity in ICs. In conclusion, we showed that beta-catenin delocalization was more evident in ICIPs, and APC promoter hypermethylation might play a role in delocalization of beta-catenin, especially in ICIPs.</P>

In Silico Screening of a Novel Inhibitor of β-Ketoacyl Acyl Carrier Protein Synthase I

Jee-Young Lee,Dong-Il Kang,Ju-Un Lee,정기웅,김양미 대한화학회 2011 Bulletin of the Korean Chemical Society Vol.32 No.5

β-Ketoacyl acyl carrier protein synthase I (KAS I) is involved in the elongation of unsaturated fatty acids in bacterial fatty acid synthesis and a therapeutic target of designing novel antibiotics. In this study, we performed receptor-oriented pharmacophore-based in silico screening of E. coli KAS I (ecKAS I) with the aim of identifying novel inhibitors. We determined one pharmacophore map and selected 8 compounds as candidates ecKAS I inhibitors. We discovered one antimicrobial compound, YKAe1008, N-(3-pyridinyl) hexanamide,displaying minimal inhibitory concentration (MIC) values in the range of 128-256 μg/mL against MRSA and VREF. YKAe1008 was subsequently assessed for binding to ecKAS I using saturation-transfer difference NMR spectroscopy. Further optimization of this compound will be carried out to improve its antimicrobial activity and membrane permeability against bacterial cell membrane.

Research article Black ginseng activates Akt signaling, thereby enhancing myoblast differentiation and myotube growth

Lee, Soo-Yeon,Go, Ga-Yeon,Vuong, Tuan Anh,Kim, Jee Won,Lee, Sullim,Jo, Ayoung,An, Jun Min,Kim, Su-Nam,Seo, Dong-Wan,Kim, Jin-Seok,Kim, Yong Kee,Kang, Jong-Sun,Lee, Sang-Jin,Bae, Gyu-Un The Korean Society of Ginseng 2018 Journal of Ginseng Research Vol.42 No.1

Background: Black ginseng (BG) has greatly enhanced pharmacological activities relative to white or red ginseng. However, the effect and molecular mechanism of BG on muscle growth has not yet been examined. In this study, we investigated whether BG could regulate myoblast differentiation and myotube hypertrophy. Methods: BG-treated C2C12 myoblasts were differentiated, followed by immunoblotting for myogenic regulators, immunostaining for a muscle marker, myosin heavy chain or immunoprecipitation analysis for myogenic transcription factors. Results: BG treatment of C2C12 cells resulted in the activation of Akt, thereby enhancing hetero-dimerization of MyoD and E proteins, which in turn promoted muscle-specific gene expression and myoblast differentiation. BG-treated myoblasts formed larger multinucleated myotubes with increased diameter and thickness, accompanied by enhanced Akt/mTOR/p70S6K activation. Furthermore, the BG treatment of human rhabdomyosarcoma cells restored myogenic differentiation. Conclusion: BG enhances myoblast differentiation and myotube hypertrophy by activating Akt/mTOR/p70S6k axis. Thus, our study demonstrates that BG has promising potential to treat or prevent muscle loss related to aging or other pathological conditions, such as diabetes.

Neutralizing Interaction of Therapeutic Antibodies against TNF Superfamily

Jee Un Lee,Ji Young Son,Woori Shin,Ki-Young Yoo,Yong-Seok Heo 한국구조생물학회 2014 Biodesign Vol.2 No.2

The binding of the tumor necrosis factor superfamilies (TNFSF) to their receptors (TNFRSF) initiates many pro-inflammatory immune responses. TNFSF are inflammatory cytokines mediating a diverse range of signaling events within cells that trigger necrosis and apoptosis. Cytokines plays central roles in the communication of the immune systems, and thus selective disrupting of cytokine pathway by specific antibody can alter ongoing inflammation. Monoclonal antibody drugs have been developed for a long time to treat TNFSF-related diseases. Antibody drugs targeting TNFSF have shown dramatic improvement in patients of autoimmune diseases. The essential mechanism of these antibody-based drugs is antagonism of the interaction between TNFSF and TNFRSF. In this review, we describe the interactions of ligand-receptor interaction of TNFSF and structural basis for the neutralizing interactions of the FDA-approved antibody drugs directed to TNFSF.

Expression, purification, crystallization, and preliminary crystallographic analysis of the Fab fragment of golimumab, a therapeutic antibody against TNFα

Jee Un Lee,Ji Young Son,Woori Shin,Ki-Young Yoo,Heejin Lim,Ju Yeon Lee,Hyun Tae Lee,Yong-Seok Heo 한국구조생물학회 2017 Biodesign Vol.5 No.2

TNFα is an inflammatory cytokine required for immune responses, playing a crucial role in the pathogenesis of inflammatory autoimmune diseases via interactions with its cognate receptors, TNFR1 and TNFR2. Therapeutic antibodies targeting TNFα, including infliximab, adalimumab, certolizumab pegol, and golimumab, are clinically used for the treatment of the inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis, Crohn’s disease, and inflammatory bowel disease. Here, the Fab fragment of golimumab was overexpressed in the periplasmic region of Escherichia coli and purified by affinity and gel-filtration chromatography. The purified protein was crystallized by hanging-drop vapor diffusion in the presence of 100 mM Tris, pH 8.5, 0.1 M ammonium phosphate, and 12% (w/v) PEG 6,000 at 20°C. The crystal diffracted X-ray to 2.60 Å resolution and belonged to the orthogonal space group P2 1 2 1 2, with unit cell parameters a = 72.74, b = 130.29, and c = 93.35 Å. An asymmetric unit of the crystal contains two molecules of the Fab fragment of golimumab with a V M of 2.14 Å 3 Da -1 and a solvent content of 42.48%.

In Silico Screening of a Novel Inhibitor of β-Ketoacyl Acyl Carrier Protein Synthase I

Lee, Jee-Young,Jeong, Ki-Woong,Lee, Ju-Un,Kang, Dong-Il,Kim, Yang-Mee Korean Chemical Society 2011 Bulletin of the Korean Chemical Society Vol.32 No.5

[ ${\beta}$ ]Ketoacyl acyl carrier protein synthase I (KAS I) is involved in the elongation of unsaturated fatty acids in bacterial fatty acid synthesis and a therapeutic target of designing novel antibiotics. In this study, we performed receptor-oriented pharmacophore-based in silico screening of E. coli KAS I (ecKAS I) with the aim of identifying novel inhibitors. We determined one pharmacophore map and selected 8 compounds as candidates ecKAS I inhibitors. We discovered one antimicrobial compound, YKAe1008, N-(3-pyridinyl) hexanamide, displaying minimal inhibitory concentration (MIC) values in the range of 128-256 ${\mu}g/mL$ against MRSA and VREF. YKAe1008 was subsequently assessed for binding to ecKAS I using saturation-transfer difference NMR spectroscopy. Further optimization of this compound will be carried out to improve its antimicrobial activity and membrane permeability against bacterial cell membrane.

Improvement of cancer bleeding in rectal cancer patient with a herbal decoction, Inhyungtang

Jee Young Lee,SeongHeon Choi,Sora Park,Sung Un Lee,Soomin Lee,Yeehong Jung 대한한의학회 2014 대한한의학회지 Vol.35 No.4

Improvement of cancer bleeding in rectal cancer patient with a herbal decoction, Inhyungtang : A case report

Lee, Jee Young,Choi, SeongHeon,Park, Sora,Lee, Sung Un,Lee, Soomin,Jung, Yeehong The Society of Korean Medicine 2014 대한한의학회지 Vol.35 No.4

Objectives: Rectal cancer bleeding occurs approximately 20% of overall rectal cancer patients. The current standard treatments cannot cover minor bleeding enough. Failures of the local or systemic approaches to stop bleeding are frequently reported. Methods: we reported a case of male rectal cancer patient who was treated with herbal decoction and significantly improved on symptoms, such as, loose stools and rectal bleeding. Previous to first visiting to our clinic, he was prescribed to use oral tranexamic acids, which failed to relieve his symptoms. He was administered with an herbal decoction, Inhyungtang, clinically known to have hemostastic effect in hematochezia. Results & Conclusion: The prescription showed significant improvement on his symptom, in particular, his bleeding. Thus, we report his case and we expect further experiences and experimental studies to support efficacy of Inhyungtang.