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Preclinical Study of DA-5018, a Non-narcotic Analgesic Agent

  • Kim, Soon-Hoe
    • Proceedings of the PSK Conference
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    • 2000.04a
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    • pp.70-81
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    • 2000
  • DA-5018 is a synthetic capsaicin derivative under development as a non-narcotic a analgesic ag$\varepsilon$nt. DA-50 18 showed a potent analgesic activity against acute and chronic pain m model(Tablel, 2.), but it had a narrow margin of safety. DA-5018 did not bind to opioid(${\kappa}, {\delta}, {\mu}$), NKl, CGRP receptors in vitro and its analgesic effect was not antagonized by naloxone, a and it did not develop analgesic tolerance. In addition DA-5018 had no inhibitory effects against c cyclooxygenase and 5-lipooxygenase activities. DA-5018 significantly increased the relcase of substance P from the slices of the rat spinal cord. These results suggest that DA-50 18 is not a narcotic nor aspirin-like analgesic and the release of substance P is one of analgesic mechanism of action of DA-5018. We found that DA-5018 was almost ten times more potent and was at l least IOO-times less irritable compared to capsaicin. Accordingly development of topical formula was adopted. Topical formula was desiged and screened by flux test of DA-5018 using hairless mouse skin and several formulas were selected. With these topical formulas we a assessed the analgesic efficacy and carried out the toxicity, skin irritation and pharmacokinetic studies. In streptozotocin-induced hyperalgesic rat and 50 % galactose-fed hyperalgesic rat as diabetic pain models, DA-5018 cream increased the pain thresh이ds up to 77.0% and 24.4% respectively, while Zostrix-HP(capsaicin cream) incr$\varepsilon$as cd by 65.9% and 21.0%. DA-5018 c cream showed a good analgesic effect as welI in FCA-induced arthritic rat. DA-5018 cream did not show any toxicological signs in acute and chronic toxicity test and had little skin irritation in car swclIing and scratching t$\varepsilon$st. Pharmacokinetics of DA-50 18 were studied after topical application of ${14}^C$-Iabelled or unlabelIed DA-5018 cream. Plasma and skin concentrations c except applied skin wcre below the dctection limit and after 7-day cummulative application, plasma concentrations were also below detection limit DA-50 18 may have an advantag$\varepsilon$ ov$\varepsilon$r c capsaicin and is now being developed as a topical agent for the treatment of pains. DA-50 18 cream was approved for Korean IND and is now under a Phase II clinical study for arthritic pain a after finising Phase I study. DA-50 18 was also liscensed out to Stiefel Company in America in

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The Gains To Bidding Firms' Stock Returns From Merger (기업합병의 성과에 영향을 주는 요인에 대한 실증적 연구)

  • Kim, Yong-Kap
    • Management & Information Systems Review
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    • v.23
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    • pp.41-74
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    • 2007
  • In Korea, corporate merger activities were activated since 1980, and nowadays(particuarly since 1986) the changes in domestic and international economic circumstances have made corporate managers have strong interests in merger. Korea and America have different business environments and it is easily conceivable that there exists many differences in motives, methods, and effects of mergers between the two countries. According to recent studies on takeover bids in America, takeover bids have information effects, tax implications, and co-insurance effects, and the form of payment(cash versus securities), the relative size of target and bidder, the leverage effect, Tobin's q, number of bidders(single versus multiple bidder), the time period (before 1968, 1968-1980, 1981 and later), and the target firm reaction (hostile versus friendly) are important determinants of the magnitude of takeover gains and their distribution between targets and bidders at the announcement of takeover bids. This study examines the theory of takeover bids, the status quo and problems of merger in Korea, and then investigates how the announcement of merger are reflected in common stock returns of bidding firms, finally explores empirically the factors influencing abnormal returns of bidding firms' stock price. The hypotheses of this study are as follows ; Shareholders of bidding firms benefit from mergers. And common stock returns of bidding firms at the announcement of takeover bids, shows significant differences according to the condition of the ratio of target size relative to bidding firm, whether the target being a member of the conglomerate to which bidding firm belongs, whether the target being a listed company, the time period(before 1986, 1986, and later), the number of bidding firm's stock in exchange for a stock of the target, whether the merger being a horizontal and vertical merger or a conglomerate merger, and the ratios of debt to equity capital of target and bidding firm. The data analyzed in this study were drawn from public announcements of proposals to acquire a target firm by means of merger. The sample contains all bidding firms which were listed in the stock market and also engaged in successful mergers in the period 1980 through 1992 for which there are daily stock returns. A merger bid was considered successful if it resulted in a completed merger and the target firm disappeared as a separate entity. The final sample contains 113 acquiring firms. The research hypotheses examined in this study are tested by applying an event-type methodology similar to that described in Dodd and Warner. The ordinary-least-squares coefficients of the market-model regression were estimated over the period t=-135 to t=-16 relative to the date of the proposal's initial announcement, t=0. Daily abnormal common stock returns were calculated for each firm i over the interval t=-15 to t=+15. A daily average abnormal return(AR) for each day t was computed. Average cumulative abnormal returns($CART_{T_1,T_2}$) were also derived by summing the $AR_t's$ over various intervals. The expected values of $AR_t$ and $CART_{T_1,T_2}$ are zero in the absence of abnormal performance. The test statistics of $AR_t$ and $CAR_{T_1,T_2}$ are based on the average standardized abnormal return($ASAR_t$) and the average standardized cumulative abnormal return ($ASCAR_{T_1,T_2}$), respectively. Assuming that the individual abnormal returns are normal and independent across t and across securities, the statistics $Z_t$ and $Z_{T_1,T_2}$ which follow a unit-normal distribution(Dodd and Warner), are used to test the hypotheses that the average standardized abnormal returns and the average cumulative standardized abnormal returns equal zero.

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