• Title/Summary/Keyword: 신약

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Development of Classification Model for hERG Ion Channel Inhibitors Using SVM Method (SVM 방법을 이용한 hERG 이온 채널 저해제 예측모델 개발)

  • Gang, Sin-Moon;Kim, Han-Jo;Oh, Won-Seok;Kim, Sun-Young;No, Kyoung-Tai;Nam, Ky-Youb
    • Journal of the Korean Chemical Society
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    • v.53 no.6
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    • pp.653-662
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    • 2009
  • Developing effective tools for predicting absorption, distribution, metabolism, excretion properties and toxicity (ADME/T) of new chemical entities in the early stage of drug design is one of the most important tasks in drug discovery and development today. As one of these attempts, support vector machines (SVM) has recently been exploited for the prediction of ADME/T related properties. However, two problems in SVM modeling, i.e. feature selection and parameters setting, are still far from solved. The two problems have been shown to be crucial to the efficiency and accuracy of SVM classification. In particular, the feature selection and optimal SVM parameters setting influence each other, which indicates that they should be dealt with simultaneously. In this account, we present an integrated practical solution, in which genetic-based algorithm (GA) is used for feature selection and grid search (GS) method for parameters optimization. hERG ion-channel inhibitor classification models of ADME/T related properties has been built for assessing and testing the proposed GA-GS-SVM. We generated 6 different models that are 3 different single models and 3 different ensemble models using training set - 1891 compounds and validated with external test set - 175 compounds. We compared single model with ensemble model to solve data imbalance problems. It was able to improve accuracy of prediction to use ensemble model.

A Comparison of Components and Biological Activities Between the Hot Water Extracts of Achyranthes japonica Nakai and Achyranthes bidentata Blume (토우슬과 회우슬의 열수 추출물의 성분 및 생리활성 비교)

  • Lee, Ye-Seul;Kim, Mi-Sun;Kwon, Ha-Young;Sohn, Ho-Yong
    • Journal of Life Science
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    • v.24 no.6
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    • pp.655-663
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    • 2014
  • Woosul (Achyranthis radix), a widely used material in food and oriental medicinal industry, has different origins of plant species in Korea, Japan and China. In Korea, woosul is designated as the radix of Achyranthes japonica Nakai (AJN) and Achyranthes bidentata Blume (ABB) in the regulation of The Korean Pharmacopoeia. However, the comparative study of hot water (HW) extracts between AJN and ABB is still rudimentary. In this study, HW extracts and its subsequent organic solvent fractions of AJB and ABB were prepared, and their in-vitro antimicrobial, antioxidant and anti-diabetes activities were evaluated. The HW extract of ABB has higher sugars and polyphenol compounds, and higher lightness and lower yellowness compared than those of AJN. Analysis of biological activities showed that the ethylacetate (EA) fraction of AJN and n-hexane fraction of ABB have antibacterial activities, and the EA fractions of AJN and ABB has strong antioxidation activities determined by radical scavenging activity and reducing power. In anti-diabetes activity assay, the EA fractions of AJN and ABB showed ${\alpha}$-amylase inhibitory activities, while the butanol fractions of AJN and ABB showed ${\alpha}$-glucosidase inhibitory activities. Our results suggest that the HW extracts of AJB and ABB have different components and extraction yields, and their subsequent fractions have different biological activity. Therefore it was concluded that the EA fraction of AJN is appropriate to develop as natural medicine, and the HW extract of AJN is suitable to woosul-tea or woosul-sikhye production.

Limits of Innovation in Korean Medicine Industry (한의학산업의 혁신 저해요인)

  • Ku, Nam-Pyong;Seol, Sung-Soo
    • Journal of Korea Technology Innovation Society
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    • v.18 no.4
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    • pp.667-692
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    • 2015
  • The study examined the Korean medicine industry from the perspective of the innovation system theory of each business, while it concentrated on the conflict between traditional Korean medicine and Western medicine, which have a major influence on the innovation system of Korean medicine industry, rather than the innovation system itself. The Korean healthcare system is a dual system of Western and Korean medicine, yet the definitions of Western medical practices and Korean medical practices are ambiguous. Thus the distinction of dual system depends on judicial precedents, and the innovation of Korean medicine has been inhibited due to the excessive emphasis placed on the Western medical practice in both healthcare system and pharmaceutical system. First of all, the usage of most medical devices derived from the development of modern medical engineering is not permitted in the Korean medicine industry, on the basis that most of the medical devices were originated from the Western medicine field. Secondly, new drugs using natural substances, once approved by the drug administration, cannot be prescribed by the Korean medicine industry although they are developed based on Korean medicine. Thirdly, the major safety issues on herbal medicine are about hazardous materials in medicinal herbs and liver toxicity of prescribed herbal medicine. The problem of hazardous materials can be solved by appropriate quality and safety tests in the cultivation and importation process. Whereas the Korean medicine circles points out that the liver toxicity issue is only a unilateral condemnation by the Western medicine circles.

In vivo Antitumor Activity and Acute, Subacute Toxicity of Keumsa (Phellinus linteus) Extracts (금사목질진흙버섯 자실체 추출물의 in vivo 항암활성 및 급성, 아 급성 독성 시험)

  • Kim, Jong-Myeung;Park, Jun-Duck;Park, Dong-Chan;Kim, Byung-Oh
    • Journal of Life Science
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    • v.23 no.11
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    • pp.1388-1396
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    • 2013
  • This study used an S-180 cell-injected mouse model to evaluate the antitumor effects of the acute and subacute toxicity of Keumsa (Phellinus linteus) extract intravenously administrated in ICR mice. When administered intravenously (31.3-250 mg/kg body weight), Keumsa (Phellinus linteus) extract significantly inhibited the growth of the solid tumor cell. The antitumor activity of Keumsa (Phellinus linteus) extract increased in a dose-dependent manner. The highest dose (250 mg/kg body weight) was highly effective, reducing tumor formation by 42.7% compared with the control group. In the acute toxicity test, $LD_{50}$ of the Keumsa (Phellinus linteus) extract showed 632.84 mg/kg (♂) and 814.48 mg/kg (♀) after intravenous administration. In addition, liver and spleen weight were increased in a dose-dependent manner. In the subacute toxicity test, the mice were intravenously administered over the course of 28 days. The $LD_{50}$ of the Keumsa (Phellinus linteus) extract showed 355.41 mg/kg (♂) and 383.53 mg/kg (♀) after intravenous administration. The liver and spleen weight also increased in a dose-dependent manner. In the case of the group that received more than 125 mg/kg of intravenous administration, exercise capacity, such as jumping ability and agility, were significantly increased. These results suggest that Keumsa (Phellinus linteus) extract can be regarded as a potent enhancer of the innate immune response, and it can be considered as a new natural product with low toxicity that may be used as a candidate for antitumor action.

Ernst Bloch and Jürgen Moltmann: The Hope for What? (블로흐와 몰트만: 무엇을 위한 희망인가?)

  • Kim, Jin
    • Journal of Korean Philosophical Society
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    • v.145
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    • pp.217-244
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    • 2018
  • This paper reviews how $J{\ddot{u}}rgen$ Moltmann embraces and transforms the philosophy of Ernst Bloch. For what are the hopes of the two thinkers who presuppose opposing worldviews? This question will provide a good opportunity to look at how different religious types, based on different worldviews in modern philosophy of religion, can understand and communicate with one another. Ernst Bloch was a philosopher who originally interpreted Judeo-Christian thought through Marxism and Persian Dualism and helped to carry out the intrinsic criticism of the doctrine of Christian eschatology by developing atheism of Christianity into a philosophy of hope. Bloch and Moltmann deal with the concepts of future, humanity, nation, and hope in the eschatological horizon, but their worldviews are so different. For example, the connection between the Beginning and Ending, Disjunction or Continuation, the Core of Existence and Resurrection, Messianism and Marxism, Atheism and Theism, Persian Dualism and Judeo-Christian Monotheism. Therefore, a one-sided interpretation that ignores worldview differences in the hopes of these two thinkers should be avoided. Moltmann actively embraced the Messianism of the Jewish thinker, Bloch, by excluding Marxism, made the spectrum of broad-minded horizons diminished in the union of Messianism and Marxism. Moltmann replaced the utopian possibilities of matter in the Ontology of Not-Yet-Being, with the resurrection of Christ, who was crucified, and with the God of Creation and the God of Exodus. By overthrowing the position of atheism in Christianity, which was very important for Bloch, with the system of Trinitarian Monotheism, it resulted in the disconnection and conflict between the Old Testament and the New Testament, especially the ignorance of the tension between God the Lord and Jesus Christ.

Growth Characteristics of Artemisia argyi according to Harvest Count (황해쑥 수집계통의 수확횟수 별 생육특성)

  • Jeong, Jin Tae;Lee, Jeong Hoon;Lee, Yun Ji;Oh, Myeong Won;Chang, Jae Ki;Park, Chun Geon
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.10a
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    • pp.82-82
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    • 2019
  • 황해쑥(Artemisia argyi Lev. et. Vnt)은 국화과의 다년생 초본 식물로서 쑥, 산쑥과 함께 건조한 것이 애엽이라는 생약재로 쓰이며 2016년 기준 전국적으로 81 ha에서 871톤이 생산되고 있다. 주요 유효성분으로 Eupatilin, Jaceosidin 등이 있으며 위궤양에 효과가 있다고 알려져 있어 최근에는 스티렌정 등 신약원료로 각광 받고 있다. 황해쑥은 종자번식 뿐만 아니라 포복경을 이용한 영양번식이 가능하며 현재까지 '섬애' 등 1품종이 개발되어 있으나 농가와 산업체가 요구하고 있는 수량성 또는 Eupatilin 등 성분함량이 높은 품종개발이 필요하다. 국내 연구 결과를 보면 대부분 년 1회 수확을 기준으로 연구되어 왔으나 실제로는 년 2회 수확하는 경우가 더 많다. 따라서 본 실험에서는 년 1회 뿐만 아니라 년 2회로도 수확하여 조사하였다. 시험재료는 AA1801 등 7계통 이며, 시비량은 10 a 당 질소 15.3 kg 인산 20 kg 가리 5 kg이고, 흑색 비닐을 피복한 후 조간 30 cm 주간 15 cm로 하였다. 시험구배치는 난괴법 3반복으로 하였으며 포복경을 5 cm로 잘라 4월 19일에 정식하였다. 1회 수확 시에는 8월 12일, 2회 수확 시에는 6월 17일, 9월 19일에 수확 하였다. 년 1회 수확 시 계통 별 생육특성을 보면, 초장은 202.4~231.5 cm로 평균 213.6 cm 였으며 경경은 10~12.14 mm로 평균 10.9 mm 였다. 분지수는 32.6~37.3개로 평균 35.2개 였으며 엽병장, 엽장, 엽폭은 2.4~4.2 cm, 9.3~12 cm 9.2~12.2 cm로 평균 3.3 cm, 10.7 cm 그리고 10.9 cm 였다. 전초의 생중량과 건중량은 각각 4.9~6.9 kg, 1.8~2.7 kg로 평균 5.5 kg, 2.1 kg 이였다. 특히 AA1902는 다른 계통에 비해 분지수는 적었으나 초장이 크고 경경이 굵었으며 생중량과 건중량도 가장 무거웠다. 년 2회 수확 시 전초의 생중량과 건중량은 각각 5.1~6.2 kg, 1.7~2.0 kg로 평균 5.6 kg, 1.8 kg 이였다. 수량성으로 봤을때는 AA1902는 1회 수확에 적합하며 AA1801, AA1802는 2회 수확 시 생중량과 건중량이 무거웠다. 또한 AA1903의 경우 수확 회수와 상관없이 수량성이 높은 계통으로 판단되었다. 본 자료는 황해쑥 품종육성의 기초자료로 활용하고자 한다.

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Development of PLGA Nanoparticles for Astrocyte-specific Delivery of Gene Therapy: A Review (별아교세포 선택적 유전자 치료전달을 위한 PLGA 나노입자 개발)

  • Shin, Hyo Jung;Lee, Ka Young;Kwon, Kisang;Kwon, O-Yu;Kim, Dong Woon
    • Journal of Life Science
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    • v.31 no.9
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    • pp.849-855
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    • 2021
  • Recently, as nanotechnology has been introduced and used in various fields, the development of new drugs has been accelerating. Nanoparticles have maintained blood drug concentration for extended periods of time with a single administration of the drug. The drug can then be selectively released only at the pathological site, thereby reducing side effects to other non-pathological sites. In addition, nanoparticles can be modified for selective target sites delivery for other specific diseases, with polymers being widely used in the manufacture of these nanoparticles. Poly (D,L-lactic-co-glycolic acid ) (PLGA) is one of the most extensively developed biodegradable polymers. PLGA is widely used in drug delivery for a variety of applications. It has also been approved by the FDA as a drug delivery system and is widely applied in controlled release formulations, such as in gene therapy treatments. PLGA nanoparticles have been developed as delivery systems with high efficiency to specific cell types by using passive and active targeting methods. After the development of a drug delivery system using PLGA nanoparticles, the drug is selectively delivered to the target site, and the effective blood concentration for extended periods of time is optimized according to the disease. In this review paper, we focus on ways to improve cell-specific treatment outcomes by examining the development of astrocyte selective nanoparticles based on PLGA nanomaterials for gene therapy.

Application of Molecular Diagnostics Technology in the Development of a Companion Diagnostics for Malignant Solid Tumors (악성 고형암의 항암제 동반진단 기술에서 분자진단기술의 적용)

  • Kim, Jin-Hee
    • The Journal of the Korea Contents Association
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    • v.19 no.3
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    • pp.365-374
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    • 2019
  • Unlike benign tumors, malignant tumors are capable of metastasis, easy to relapse, poor survival, and low quality of life. In Korea, here is a tendency to treat the tumors collectively according to the General Principles of Cancer Chemotherapy(GPCC) of the Health Insurance Review & Assessment Service (HIRA). But recently, companion diagnostics(CDx) is recommended rather than unilateral medication because biomarker-based molecular diagnostics is possible to predict the drug response of patients before drug treatment. Not only domestic but also overseas Food and Drug Administratio (FDA) recommends the development of the CDx system at the stage of drug development to ensure the responsiveness and safety of medicines. In this study, I focused on the necessity of CDx development direction as well as CDx development status through literature review. Furthermore I also discussed CDx types according to the molecular diagnostic technology such as immunohistochemistry (IHC), polymerase chain reaction (PCR), in situ hybridization (ISH), and next-generation sequencing (NGS) not only in the approved CDx but also in the developing one by US FDA. And I suggested the technology issue of CDx development process such as a selection of molecular diagnostics at the time of release, a clear understanding of the CDx mechanism, and a convergence of drug with CDx development. The necessity of social insurance system also was proposed for CDx development.

A Study on forecasting the long-run path of the Korean bioindustry based on the experiences of the U.S. BT and the Korean ICT industries (미국 BT와 한국 ICT 산업 연구를 통한 한국 바이오산업 장기전망에 관한 연구)

  • Moon, Sunung;Kim, Minseong;Jeon, Yongil
    • International Area Studies Review
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    • v.13 no.3
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    • pp.331-359
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    • 2009
  • We forecast the performance of the Korean biotechnology industry by adopting similar development paths taken by the U.S. biotechnology and Korean ICT industries. Our long-term forecasting techniques predict that Korean BT market size will increase from 3.7 billion to 10.8 billion U.S. dollars by year 2030. The pharmaceutical industry, one of major bio-subindustries, is expected to dominate Korean BT market in the long-run. Also, the relative portion of the exports in the Korean BT industry will be larger and thus the export-oriented government policy is required for the long-run growth of the Korean BT industry. Since the Korean ICT industry has already slowed down in the development, Korean BT industry is likely to catch up with ICT industry in the near future.

Generation of a transgenic pig expressing human dipeptidylpeptidase-4 (DPP-4) (Human dipeptidylpeptidase-4(DPP-4) 발현 형질전환 돼지의 생산)

  • Chung, Hak Jae;Sa, Soo Jin;Baek, Sun Young;Cho, Eun Suek;Kim, Young Shin;Hong, Jun Ki;Cho, Kyu Ho;Kim, Ji Youn;Park, Mi Ryung;Kim, Kyung Woon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.20 no.9
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    • pp.306-314
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    • 2019
  • As dipeptidyl peptidase-4(DPP-4) inhibitors are used widely as a secondary treatment for type 2 diabetes because they tend to be well tolerated with minimal side effects, the human DPP-4(hDPP-4) gene was injected into a pig zygote through micro-injection, and 1-cell stage fertilized embryos were then transplanted surgically into the oviduct. Three pigs were fertilized with hDPP-4 genes and produced sixteen piglets, in which one male piglet was identified to be transgenic. Finally, transgenic pigs showing hDPP-4 gene expression in the tail were produced. Western blot and RT-PCR analysis confirmed that the hDPP-4 is expressed strongly in the membrane cells of the transgenic pig, and that the hDPP-4 gene appears in various tissues and tails. This suggests that the expression vector is normally expressed in transgenic pigs. These results are anticipated to be a model animal to check the endocrine function for insulin resistance that occurs in a hDPP-4 transgenic pig and to increase its value for use as a material in newly developed medicines.