• Title/Summary/Keyword: R&D of new drug

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Effects of Medicinal Herbal Drink on Alcohol Metabolic Enzyme in Drunken Rats (한약재 추출물 함유 음료가 알코올 투여 흰쥐의 알코올 대사 관련 효소에 미치는 영향)

  • Hwang, Su-Jung;Choi, Hye-Min;Park, Hyun-Jin;Lee, Jin-Sang;Heo, Dam;Kim, Mi-Ryeo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.4
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    • pp.610-615
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    • 2010
  • Alcohol is the most widely psychoactive drug and has known in almost all civilization since ancient time. Recently increase consuming alcoholic beverages, alcohol is on of the major public health problems in the world. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) play important roles in the metabolism of alcohols and aldehydes. The drink consists of medicinal herbs, Puerariae Radix, Phyllostachyos Folium, Citri Pericarpium, Polygonati Rhizoma, Rehmanniae Rhizoma (Vinegar), which have been widely used in oriental medicine. This study was designed to investigate effects of medicinal herbal drink (MHD) on alcohol metabolism in drunken SD rats subjects. In experiment, rats were treated to ethanol (EtOH, 3 g/kg, PO) at 60 min. after saline (CON) or MHD (1 ml/kg, PO) administration. The blood alcohol concentration (BAC), blood acetaldehyde concentration (BALC) activities of ADH, ALDH, AST and ALT were significantly decreased in MHD group than in control group as a time-dependent manner. And drinking water volume in MHD group with duplicate treatment, were significantly decreased than in CON group. These results suggested that MHD intake could give an influence upon the reduction in BAC and BALC may alleviate acute ethanol-induced hepatotoxicity by altering alcohol metabolic enzyme activities.

3D QSAR Studies of Mps1 (TTK) Kinase Inhibitors Based on CoMFA

  • Balasubramanian, Pavithra K.;Balupuri, Anand;Cho, Seung Joo
    • Journal of Integrative Natural Science
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    • v.9 no.2
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    • pp.113-120
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    • 2016
  • Monopolar spindle 1 (Mps1) is an attractive cancer target due to its high expression levels in a wide range of cancer cells. Mps1 is a dual specificity kinase. It plays an essential role in mitosis. The high expression od Mps1 was observed in various grades of breast cancers. In the current study, we have developed a CoMFA model of pyridazine derivatives as Mps1 kinase inhibitors. The developed CoMFA model ($q^2=0.797$; ONC=6; $r^2=0.992$) exhibited a good predictive ability. The model was then validated by Leave out five, progressive sampling and bootstrapping and found to be robust. The analysis of the CoMFA contour maps depicted favorable and unfavorable regions to enhance the activity. Bulky positive substitution at $R^3$ position and Negative substitution in $R^1$ position is favored could increase the activity. In contrast, bulky substitution in $R^1$ position is not favored. Our results can be used in designing a potent Mps1 (TTK) inhibitor.

A CoMFA Study of Phenoxypyridine-Based JNK3 Inhibitors Using Various Partial Charge Schemes

  • Balasubramanian, Pavithra K.;Balupuri, Anand;Cho, Seung Joo
    • Journal of Integrative Natural Science
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    • v.7 no.1
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    • pp.45-49
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    • 2014
  • The (c-Jun N-terminal kinase 3) JNK3 is a potential therapeutic target for various neurological disorders. Here, a three dimensional quantitative structure-activity relationship (3D-QSAR) study on phenoxypyridine as JNK3 inhibitors was performed to rationalize the structural requirements responsible for the inhibitory activity of these compounds. The comparative molecular field analysis (CoMFA) using different partial atomic charges, was employed to understand the structural factors affecting JNK3 inhibitory potency. The Gasteiger-Marsili yielded a CoMFA model with cross-validated correlation coefficient ($q^2$) of 0.54 and non-cross-validated correlation coefficient ($r^2$) of 0.93 with five components. Furthermore, contour maps suggested that bulky substitution with oxygen atom in $R^3$ position could enhance the activity considerably. The work suggests that further chemical modifications of the compounds could lead to enhanced activity and could assist in the design of novel JNK3 inhibitors.

System Dynamics Modeling for FDA Regulation Effect of Pharmaceutical Industry (제약산업에서 FDA규제 영향에 관한 시스템 다이내믹스 모델링: FDA규제가 R&D비용에 미치는 영향을 중심으로)

  • Ko, Seong-Pil;Choi, Jeong-Hwan;Nam, Dong-Wok;Lee, Jeong-Dong
    • Korean System Dynamics Review
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    • v.13 no.4
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    • pp.57-80
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    • 2012
  • This research studies effect of FDA regulations in pharmaceutical industry on new drug development. System dynamics is implemented to demonstrate dynamic relationship between FDA regulations and R&D costs, firm's profits, sales. This research is focused on clinical trials of new medical entity process 50~60% portion of total development cost. Simulation results say that firm's profit is more sensitive to increasing the regulation than alleviating the regulation and effect of regulation policy make different result depending on the intensity of regulation and policy direction. Our simulation model provides the instrumental means for the policy makers and strategic decision in pharmaceutical industry.

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3D QSAR Study on Pyrrolopyrimidines-Based Derivatives as LIM2 Kinase Inhibitors

  • Balasubramanian, Pavithra K.;Balupuri, Anand;Cho, Seung Joo
    • Journal of Integrative Natural Science
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    • v.8 no.4
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    • pp.285-292
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    • 2015
  • LIM kinases belong to the serine/Threonine kinase family. The members of the LIM kinase (LIMK) family include LIMK 1 and 2 which are involved in the regulation of actin polymerisation and microtubule disassembly. LIMK1 was shown to be involved in cancer metastasis, while LIMK2 activation promotes cells cycle progression. Since LIMK2 plays a vital role in many disease conditions such as pulmonary hypertension, cancer and viral diseases, and till date there are not much selective inhibitors been reported, LIMK2 becomes an interesting therapeutic target among the kinases. 3D QSAR study was carried out on a series of pyrrolopyrimidines based derivatives as LIMK2 inhibitors. A reasonable CoMFA ($q^2$=0.888; ONC=3; $r^2$=0.974) with good statistical values was developed. The developed model was validated using 1000 runs of boostrapping and was found to be predictable. The results of CoMFA contour map analysis suggested that the bulky substitution at $R_4$ and $R_5$ position are highly desirable to increase the activity. Similarly, positive substitution at $R_3$ position is also required to increase the activity. It is also noted that bulky substitution at $R_1$ position must be avoided. Our results could provide valuable information to enhance the activity of the LIMK2 inhibitors and to design potent pyrrolopyrimidines derivatives.

Effects of Hair Tonic and Food including Korean Medicinal Herbs on Hair Growth in an Alopecia Model of C57BL/6 Mice (한약재 함유 헤어토닉 및 식품이 C57BL/6 마우스의 탈모 모델에서 모발성장에 미치는 영향)

  • Choi, Hye-Min;Hwang, Su-Jung;Lee, Jin-Sang;Do, Eun-Ju;Kim, Mu-Young;Kim, Mi-Ryeo
    • The Korea Journal of Herbology
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    • v.26 no.1
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    • pp.119-124
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    • 2011
  • Objective : This study was carried out to investigate effect of korean medicinal herbs-included hair tonic (MHT) and food (MF) on hair growth in an alopecia model of C57BL/6 mice. Methods : Six-weeks old mice were given laboratory rodent chow diet for 1 week. Then, we used a depilatory for hair removal on mice. The next day, mice were randomized and separated in 3 groups of 6 mice; normal group (N, vehicle epidermal application+normal diet-treated group), positive control group (C, 3% minoxidil sulfate epidermal application+normal diet-treated group), and the treatment group (T, HT epidermal application+ MF diet-treated group). The hair regrowth was determined by photograph, which was taken at 7, 14 and 21 days. And scoring indices, hair density and hair thickness, were evaluated by Folliscope at same day. In addition, the hair regrowth was analyzed insulin-like growth factor (IGF-1) in the dorsal skin of mice. Results : As a result, not only external appearance but also hair density and hair thickness on dorsal skin were increased more in C, T groups than in N group at 21 days with mixed treatment. Therefore, distinct regrowth pattern is appeared by treatment of herbal tonic and natural food for 21 days. Also, the expressions of IGF-1 on dorsal skin were higher in C, T groups than in N group. Conclusion : These results suggested that this herbal hair tonic and natural food has hair growth promoting activities and may be useful for treatment of bald or alopecia.

Antioxidative Activities of Mixture of Schisandrae Fructus (SF) and Perilae Folium (PF) using Natural Color fixation technic (천연 색소 고정화 기술을 활용한 오미자와 자소엽 추출물 함유 음료의 항산화 활성 연구)

  • Shin, In-Soon;Hwang, Su-Jung;Kim, Sung-Ok;Heo, Dam;Kim, Mi-Ryeo
    • The Korea Journal of Herbology
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    • v.26 no.3
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    • pp.37-45
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    • 2011
  • Objectives : This study focused on Schisandrae Fructus (SF) and Perilae Folium (PF), traditional medicine herbs and health functional food in Korea, Japan and China. We investigated various pharmacological activities that include a potential source of free radical scavenging, anti-viral, anti-microbial, anti-allergy and anti-inflammatory activities. Methods : We conducted an investigation of total contents of phenolic and flavonoid compounds in these single herbal extraction with/without combined to mixture. We also measured antioxidant activities such as DPPH free radical scavenging, SOD-like scavenging, nitrite scavenging and hydroxyl radical scavenging activities, xanthine oxidase inhibition, linoleic acid peroxidation inhibition, and reducing power. Results : As the results, contents of total phenoilc compounds and flavonoids were higher in those of PF than those of SF. Those of SF+PF mixture showed the synergy effects compared with those of SF and PF single extractions. Activities of DPPH free radical and SOD-like scavenging in 1 mg/mL concentration increased in dose dependent manners. That of SF increased compared with that of PF. That of SF and PF mixture also increased compared with that of BHA as a positive control. The other antioxident activities also showed similar to patten of activity of DPPH free radical scavenging. When combined to SF and PF extractions, there was showed synergic effect compared with those of BHA, excepted activities of xanthine oxidase inhibition and reducing power. Taken together, SF and PF have high phenolic and flavonoid compounds content furthermore, antioxidant activities in SF and PF mixture showed more synergy effect compared with those of BHA. Conclusions : Therefore, these findings suggest that SF and PF mixture may offer functional materials potential for development of functional beverage. But further studies are needed for the identification of the active compounds.

Design of Transdermal Delivery System Using New Film-Forming Agents (신규 필름형성제를 이용한 경피흡수제제의 설계)

  • Choi, Yang-Gyu;Kim, Young-So;Kim, Jung-Ju;Sim, Young-Chul
    • Journal of Pharmaceutical Investigation
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    • v.33 no.3
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    • pp.163-169
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    • 2003
  • In order to develop a film-forming transdermal drug delivery system, polyurethane (PU) based on poly(ethylene glycol) and poly(tetramethylene oxide) was synthesized and characterized. The synthesized PU was blended with Gantrez ES 225 (GT) to improve the adhesion property of film-forming agent to the skin. When film-forming gel formulation containing 3% ketoprofen (KP) was applied, transparent thin film was obtained within 5 minutes and adhered to the skin for 8 hours. In vitro percutaneous absortion studies were performed to determine the rate of ketoprofen absorption through guinea pig skin. A prominent effect of limonene on the skin permeability of ketoprofen was observed among the various skin permeation enhancers investigated. Considering mechanica properties of film and skin permeability of ketoprofen, 2% of limonene was optimal content in the film forming transdermal formulation.

Development of the 3rd Generation Anticancer Platinum Complex as New Drug

  • Cho, Yong-Baik;Ph. D.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2002.07a
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    • pp.97-102
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    • 2002
  • Life Science Research Center of SK Chemicals has developed a 3rd-generation anticancer platinum drug for the first time in the nation′s 100-year-old pharmaceutical industry. The Korea Food and Drug Administration (KFDA) approved the sale of "Sunpla" (code name SKI 2053R, general name : Heptaplatin) on July 14, 1999 for the treatment of advance, metastatic gastric cancer. Cisplatin, the 1 st-generation anticancer drug, which was developed by Bristol-Myers of the United States in 1976, is one of the most potent anticancer drugs and is a major component of combination chemotherapy for a variety of human cancers. However its clinical usefulness has frequently been limited not only by undesirable side effects such as severe renal toxicity, nausea, vomiting, ototoxicity, and neurotoxicity but also by the development of resistance. Carboplatin, the 2nd-generation anticancer platinum drug, which was also developed by Bristol-Myers in 1986, has modified the problems of the renal and gastrointestinal toxicities of cisplatin. Carboplatin, however, has no enhanced therapeutic efficacy over cisplatin and does not possess the property to overcome cross-resistance to cisplatin.

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Case Study on the Effect of IPO on the Technology Commercialization Performance of the New Drug Development Bio Venture Company (증권시장 상장이 신약개발 바이오벤처기업의 기술사업화 성과에 미치는 사례연구)

  • Kim, Ju Young;Ha, Kyu Soo
    • Asia-Pacific Journal of Business Venturing and Entrepreneurship
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    • v.14 no.1
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    • pp.151-166
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    • 2019
  • New drug development requires 10 to 15 years of long time and more than $ 1 billion in funding, ranging from basic research${\rightarrow}$preclinical medicine${\rightarrow}$clinical medicine${\rightarrow}$product approval${\rightarrow}$sales. Many new drug development bio-venture companies will continue to pursue new drug development with funds secured through listing on the securities market. This study focuses on the impact of the listing on the market of bio-venture companies in the development of new drugs. It is necessary to determine whether the increase in registered patent, preclinical, clinical and technology transfer contracts at the time of listing (D) The results of this study are as follows. We also analyzed whether the registered patent, preclinical, and clinical effects had significant effect on technology transfer contracts at two years after listing and listing. The results of the analysis are as follows. First, Korea's new drug development bio-venture firms increased their registered patents but did not increase their pre-clinical, clinical and technology transfer contracts. Second, at the time of listing and two years after listing, pre-employment has a significant effect on Korea's technology transfer contracts and has a significant effect on overseas technology transfer contracts. However, registered patents and clinics have significant influence on technology transfer contracts. Korea 's new drug development bio-venture firms showed patent increase despite the stock market listing, but pre-clinical, clinical and technology transfer contracts did not increase. In order to strengthen technological commercialization of new drug development bio-venture companies in the future, it is required to establish R & D strategy for efficient use of IPO subscription funds, open innovation through strengthening industry-academia-partnerships, and more sophisticated preclinical and clinical strategy establishment.