• Title/Summary/Keyword: Development of New Drug

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A Study of the Implication of Clinical Trial Registration Information and its Application to Industry: Focused on 「COVID-19」 Registered in ICTRP (임상 시험등록정보의 산업적 활용과 시사점: ICTRP에 등록된 COVID-19 사례 중심으로)

  • Lee, Hwajung;Kim, Kyungmi
    • Journal of the Society of Disaster Information
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    • v.17 no.4
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    • pp.778-785
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    • 2021
  • Purpose: The study is to analyze the current status of international clinical trial information services related to COVID-19 and to find out the impact of disclosing activities of clinical trial registration on the medical and pharmaceutical industry. Method: To achieve the purpose of the study, this study analyzed the current status of 780 registered clinical trials for COVID-19 during March of 2020 by using regression analysis. Result: The analysis of clinical trial research registration information showed and proved its usefulness for the development of related new drugs, treatments, vaccines, predictive and prognostic diagnostic kits and treatments related to the COVID-19 (Corona 19) in the world. Conclusion: The study concludes and urges all medical and pharmaceutical companies to register their trials on CRIS and recommends utilizing this registered data to develop advanced drug to benefits all patients related to COVID-19.

Analysis on Research Trend of Studies Related with Scutellariae Radix in Korea (황금(黃芩)에 관한 국내 연구 동향에 관한 소고)

  • Kim, Kang-San;Kim, Lae-Hee;Rhee, Yun-Jin;Lee, Su-Hyoun;Choi, Ji-Hye;Ko, Ha-Neul
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.6
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    • pp.1095-1101
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    • 2011
  • Scutellariae Radix has been used as a traditional medicine for anti-oxidant, anti-inflammatory, anti-allergic function. But most study methods were restricted to in vitro and in vivo. Therefore to perform for clinical trials further for a new natural drug development is necessary and this study will be used as a basis for it. The studies selected from domestic academic database included the following key words; '황금', '黃芩', 'skullcap', 'Scutellariae Radix', 'scutellaria baicalensis' and considered were those published from 1990 to July, 2011. All 1080 studies were found to include the keywords related to the study subjects either in their title of contents or abstracts. and 298 studies were finally selected as subjects for this study. 243 studies among 293 studies were published between 2000 to 2011. Classification was proceeded according to study subjects as followed; anti-Inflammatory effect and antiallergic and antihistamin effect(66), antibacterial and antivirus effect(61), antioxidant effect(51), neuronal cell apoptosis and neuronal cell protective effect(22), liver cell protective effect(20). According to method type of study, 194 studies practicing in vitro, 60 studies practicing in vivo, 37 studies practicing in both. and 5 studies on documentary records. Most study methods were restricted in vitro and in vivo. For developmenting of function of anti-inflammatory effect and antiallergic, antihistamin effect & atopic dermatitis effect, antibacterial and antivirus effect, antioxidant effect, case report on various fields and multicenter clinical trials is necessary.

Optimization of Ferric Chloride Induced Carotid Artery Thrombosis Model in a Rat: Effect of Ginkgo biloba Extracts

  • Lee, In Sun;Choi, SeungGu;Jeon, Won Kyung
    • Korean Journal of Clinical Laboratory Science
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    • v.43 no.4
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    • pp.179-187
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    • 2011
  • Animal models are important tools in thrombosis research and preclinical drug development. In recent studies, ferric chloride ($FeCl_3$) has been widely used to induce arterial thrombosis in a variety of species. The purpose of this study was to find an optimal concentration of $FeCl_3$ and validate this model suited better for thrombosis research. A small piece of filter paper, soaked in $FeCl_3$ solution (10, 20 or 35%, v/v, in distilled water) was topically applied on the carotid artery of SD rats to measure the time to occlusion (TTO) and thrombus weight (TW) to ascertain 35%, as an optimal $FeCl_3$ concentration ($8.63{\pm}0.92min$; p =0.000, $0.79{\pm}0.03mg/mm$; p =0.000, respectively). To validate this experimental model, Ginkgo biloba special extract EGb761 (5, 10 or 30 mg/kg) as a reference agent administered by peritoneal route for 1h prior to the induction of thrombosis, showed significantly delayed TTO in a dose dependent manner ($18.50{\pm}2.17$, $29.17{\pm}1.83$, and $38.00{\pm}1.79min$, respectively) and significantly reduced TW and repaired collagen fibre in the injured vessel compare to vehicle group. Our results provide a simple, reproducible and well controlled in vivo screening system to induce thrombosis in rats by the topical application of 35% $FeCl_3$ to assess the efficacy of the new anti-thrombotic agents.

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Anti-hyperlipidemic Effects of Scutellariae Radix, Aucklandiae Radix and Bupleuri Radix (SAB) extract in FL83B cells (지방간 유도 세포모델에서 황금(黃芩), 목향(木香), 시호(柴胡) 복합 추출물의 이상지질혈증에 대한 효과)

  • Do, Hyun Ju;Kim, Kyungho;Oh, Tae Woo
    • The Korea Journal of Herbology
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    • v.35 no.5
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    • pp.23-31
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    • 2020
  • Objectives : This study was conducted to evaluate the anti-hyperlipidemia effect of Scutellariae Radix, Aucklandiae Radix and Bupleuri Radix(SAB). Methods : FL83B cells were mouse liver hepatocytes, and we used this cell line. FL83B cells were treated with 0.5 mM oleic acid(OA) for 24 h, SAB extract was treated. After OA treatment, intracellular triglyceride (TG) and free fatty acid contents were measured with AdiopoRed™ assay and Free Fatty Acid Quantitation assay kit, respectively. Further, we evaluated several lipogenesis and metabolic markers such as sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), 3-hydroxy3-methyl-glutaryl CoA reductase (HMGCR), hormone-sensitive lipase (HSL), carnitine palmitoyltransferase (CPT-1), peroxisome proliferator activated receptor alpha (PPARα), and cluster of differentiation (CD36) using RT-PCR and Western-blot analysis. Results : OA markedly increased intracellular TG and free fatty acid, which plays a key role in reducing hepatic lipid accumulation, in FL83B cells. These increases were alleviated by SAB extract. The mRNA and protein expression of Fatty acid(FA) oxidation factors (CPT-1, PPARα), lipolysis factor(HSL), FA transporter(CD36), cholesterol synthesis factors (HMGCoA) and Lipodenesis (SREBP-1c, FAS, and ACC-1) were significantly increased by treatment of SAB extract in the OA-induced fatty liver cell model. Conclusions : In summary, the treat of SAB extract showed a significant reduction of the influx of fatty acids into hepatocytes, promoted the oxidation of fatty acids, and regulated fat synthesis-related factors, thereby regulating the accumulation of TG and free fatty acids.

Breakthroughs in the Systemic Treatment of HER2-Positive Advanced/Metastatic Gastric Cancer: From Singlet Chemotherapy to Triple Combination

  • Sun Young Rha;Hyun Cheol Chung
    • Journal of Gastric Cancer
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    • v.23 no.1
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    • pp.224-249
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    • 2023
  • Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC; trastuzumab emtansine [T-DM1]), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone. Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents. HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.

Econazole Induces p53-Dependent Apoptosis and Decreases Metastasis Ability in Gastric Cancer Cells

  • Choi, Eun Kyoung;Park, Eun Jung;Phan, Tien Thuy;Kim, Hea Dong;Hoe, Kwang-Lae;Kim, Dong-Uk
    • Biomolecules & Therapeutics
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    • v.28 no.4
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    • pp.370-379
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    • 2020
  • Econazole, a potent broad-spectrum antifungal agent and a Ca2+ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.

Single cell heterogeneity in human pluripotent stem cells

  • Yang, Seungbok;Cho, Yoonjae;Jang, Jiwon
    • BMB Reports
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    • v.54 no.10
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    • pp.505-515
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    • 2021
  • Human pluripotent stem cells (hPSCs) include human embryonic stem cells (hESCs) derived from blastocysts and human induced pluripotent stem cells (hiPSCs) generated from somatic cell reprogramming. Due to their self-renewal ability and pluripotent differentiation potential, hPSCs serve as an excellent experimental platform for human development, disease modeling, drug screening, and cell therapy. Traditionally, hPSCs were considered to form a homogenous population. However, recent advances in single cell technologies revealed a high degree of variability between individual cells within a hPSC population. Different types of heterogeneity can arise by genetic and epigenetic abnormalities associated with long-term in vitro culture and somatic cell reprogramming. These variations initially appear in a rare population of cells. However, some cancer-related variations can confer growth advantages to the affected cells and alter cellular phenotypes, which raises significant concerns in hPSC applications. In contrast, other types of heterogeneity are related to intrinsic features of hPSCs such as asynchronous cell cycle and spatial asymmetry in cell adhesion. A growing body of evidence suggests that hPSCs exploit the intrinsic heterogeneity to produce multiple lineages during differentiation. This idea offers a new concept of pluripotency with single cell heterogeneity as an integral element. Collectively, single cell heterogeneity is Janus-faced in hPSC function and application. Harmful heterogeneity has to be minimized by improving culture conditions and screening methods. However, other heterogeneity that is integral for pluripotency can be utilized to control hPSC proliferation and differentiation.

Evaluation for Long-term Stability of EGCG Rich Green Tea Extract (EGTE) (신규 건강기능식품소재 'EGCG 고함유 녹차추출물(EGTE)'의 장기안정성 평가)

  • Cheon, Se In;Heo, Eun Ji;Yoon, Min Ji;Choi, Sang Un;Ryu, Geon-Seek;Ryu, Shi Yong
    • Korean Journal of Pharmacognosy
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    • v.49 no.4
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    • pp.328-335
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    • 2018
  • 'EGCG(epigallocatechin gallate) rich Green Tea extract(EGTE)' was prepared by a convenient chromatographical manner using water and alcohol which was regarded as the most suitable and appropriate process for food manufacturing. The EGCG content in EGTE was estimated above 97%. Analysis of polyphenol components in green tea, i.e., catechin(C), epigallocatechin(EGC), epicatechin(EC), epigallocatechin gallate(EGCG), epicatechin gallate(ECG) and caffeine was performed by HPLC. The optimized HPLC method exhibited a good linearity of calibration curve, accuracy and precision. The long-term stability evaluation of EGTE was carried out with a powdered formulation and solution formulation by estimating the color change and measuring the EGCG content by HPLC analysis for one year. The EGCG content of the powdered EGTE stored in a transparent bottle at room temperature was retained over 97% at the end of the experimental period. The EGCG content of 0.1% water solution of EGTE stored in a transparent bottle at RT were observed to decrease below 30%, whereas that stored at $2^{\circ}C$ retained over 70%, respectively. These results suggested that a powdered formulation could be recommended for the commercialized nutraceutical product of EGTE rather than a solution formulation.

The Health Promotion Programme and Quality of Life in the 21 Century (21세기 삶의 질 향상을 위한 건강증진방안)

  • Nam Chul-Hyun;Kim Gi-Yoel
    • Journal of Society of Preventive Korean Medicine
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    • v.2 no.1
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    • pp.31-43
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    • 1998
  • The ultimate goal of national health promotion services is the improvement of quality of life and health longevity through the implementation of health promotion services. The approach strategy for national health promotion summariged as follows: 1) A model for health promotion should be developed by the level of government. 2) Roles and functions between central government and autonomous local governments should be defined to carry out the health promotion services effectively. 3) New manpower for health promotion such as health educator should be trained and activated at hospitals, health centers, industries, school, and related community agencies. 4) School health education should be strengthened in order to teach: various health subject(smoking & alcohol, drug abuse, accident and safe, nutrition, environmental pollution and preservation, population & family planning, personnel hygiene, physical growth, stress, sex education, communicable disease, physical exercise etc) students through appointing health teachers at school base. 5) Health promotion services in industries should be activated using manpower such as health educator, exercise instructor, dietist and counsellor, 6) Health promotion services for the elderly should be activated. 7) Health screening services in the medical insurance and his/her family should be activated for health promotion services. 8) Health education material development center for health promotion should be established and the materials should be made to distribute to related groups, agencies and institutions (health conte.5, hospitals, schools, pharmacies, industries etc). 9) The pilot health promotion center in each automous local governments(large cities, provinces, Guns and Gu level) should be established and operated for community people. 10) The mass media such as TV, radio, newspapers and magazines should be used effectively. 11) Periodic evaluation of health promotion services should be carried out in order to help effective and successful planning for community health promotion in the future.

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Implementation of Z-Factor Statistics for Performance Evaluation of Quality Innovation in the High Throughput Process (High Throughput 프로세스에서 품질혁신의 성능평가를 위한 Z-Factor의 적용방안)

  • Choi, Sung-Woon
    • Journal of the Korea Safety Management & Science
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    • v.15 no.1
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    • pp.293-301
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    • 2013
  • The purpose of this study is to introduce the limit of previously used six sigma quality process evaluation metrics, $Z_{st}$ and $P_{pk}$, and a solution to overcome this drawback by using a metric based on performance evaluation of Z-factor quality innovation. Case analysis on projects from national six sigma contest from 2011 to 2012 is performed and literature review on new drug development HTS (High Throughput Screening) is used to propose innovative performance evaluation metrics. This research shows that experimental study on six sigma evaluation metric, $Z_{st}$ and $P_{pk}$, have no significance difference between industrial type (Manufacturing, Semi-Public Institute, Public Institute) and CTQ type (Product Technology Type CTQ, Process Technology Type CTQ). Following discovery characterize this quality improvement as fixed target type project. As newly developed moving target type of quality innovation performance metric Z-Factor is used for evaluating experimental study, hypothetical analysis suggests that $Z_{st}$ and $P_{pk}$ share different relationship or even show reciprocal relationship. Constraints of the study are relatively small sample size of only 37 projects from past 2 years and conflict on having interview and communication with six sigma quality practitioner for qualitative experimental study. Both moving target type six sigma innovation project and fixed target type improvement project or quality circle enables efficient ways for a better understanding and quality practitioner use by applying quality innovation performance metric. Downside of fixed target type quality performance evaluation metric, $Z_{st}$ and $P_{pk}$, is presented through experimental study. In contrast, advantage of this study is that high throughput requiring product technology, process technology and quantum leap typed innovation effect is evaluated based on precision and accuracy and Z-Factor that enables relative comparison between enterprises is proposed and implemented.