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Physostigmine 과 Procyclidine 으로 구성된 복합예방제의 유기인제 해독효능
허경행(Gyeung Haeng Hur),천기철(Ki Cheol Cheon),피택산(Taek San Phi),김지천(Jee Cheon Kim),홍대식(Dea Sik Hong),박훈(Hoon Park),정창희(Chang Hee Jung),이용한(Yong Han Lee),김윤배(Yun Bae Kim) 한국응용약물학회 2001 Biomolecules & Therapeutics(구 응용약물학회지) Vol.9 No.1
N/A Antidotal efficacy of combinational prophylactics composed of physostigmine plus procyclidine, alone or in combination with antidotes such as atropine plus 2-pralidoxime or atropine plus HI-6, was evaluated in rats. Physostigmine (0.1 mg/kg) plus procyclidine (3 mg/kg), pretreated subcutaneously 30 min prior to subcutaneous exposure to organophosphates of militarily importance, exerted protection ratios of 7.2, 6.5, 4.0, 2.9 and 8.0 fold for tabun, sarin, soman, cyclosarin and V-agent, respectively. In comparison, low effects (1.7 fold for soman and 1.3 fold for cyclosarin) were achieved with the traditional antidotes atropine (17.4 mg/ kg) plus 2-pralidoxime (30 mg/kg) administered intramuscularly immediately after organophosphate, in contrast to high effects (5.5 fold for soman and 160.0 fold for cyclosarin) with atropine (17.4 mg/kg) plus HI-6 (125 mg/kg), although the protection ratio markedly decreased when treatment of antidotes was delayed. Noteworthy, the combinational prophylactics markedly potentiated the effects of antidotes to higher than 5.0 fold in all cases. In addition, the combinational prophylactics fully prevented the seizures and excitotoxic brain injuries induced by a high dose (100 mg/kg, 1.3 LD_(50)) of soman. Taken together, it is suggested that the prophylactics composed of physostigmine and procyclidine, in combination with posttreatment antidotes, could be a promising regimen for the prevention of lethality, seizures and brain injuries induced by organophosphates possessing diverse properties.
유기인제 중독의 복합예방제로서의 physostigmine과 procyclidine이 랫드의 학습 및 기억에 미치는 염향
조순옥(Soon Ock Cho),박우규(Woo-Kyu Park),이선애(Sun Ae Lee),조영(Young Cho),허경행(Gyeung-Haeng Hur),김왕수(Wang-Soo Kim),천기철(Ki-Cheol Cheon),하연철(Yeon-Cheol Ha),연규백(Gyu-Baek Yeon),김지천(Jee-Cheol Kim),김형규(Hyong-Kyu Kim 한국실험동물학회 2004 Laboratory Animal Research Vol.20 No.4
The effects of physostigmine and procyclidine, as a combinational prophylactic regimen for organophosphate poisoning, on learning and memory process were examined in rats administering subcutaneously. Procyclidine at doses of 3 through 10 ㎎/㎏ produced significant impairment of learning and memory process in step-through passive avoidance test. However, this harmful effect of procyclidine (3 and 5 ㎎/㎏) was reversed by simultaneous injection of physostigmine (0.1 ㎎/㎏). Procyclidine at doses of 7 and 10 ㎎/㎏ produced reversible inhibition of learning and memory process in Morris water maze test. Physostigmine (0.1 ㎎/㎏) recovered the memorial impairment induced by procyclidine in this test. In conclusion, procyclidine can affect learning and memory process at the doses not less than 3 ㎎/㎏, and the dose of procyclidine to influence the learning and memory process in rats might be increased to more than 5 ㎎/㎏ by the simultaneous administration of physostigmine (0.1 ㎎/㎏).
Physostigmine과 procyclidine으로 구성된 유기인제 중독 예방용 패취제의 약물농도에 따른 피부자극성 및 재결정화 경향 연구
김윤배(Yun-Bae Kim),피택산(Taek-San Phi),김왕수(Wang-Soo Kim),조영(Young Cho),서원준(Won-Jun Seo),최승주(Seung-Ju Choi),천기철(Ki-Cheol Cheon),허경행(Gyeung-Haeng Hur),연규백(Gyu-Baek Yeon) 한국실험동물학회 2004 한국실험동물학회 학술발표대회 논문집 Vol.2004 No.-
Skin irritation potencies of novel combinational transdermal patches, composed of various concentrations of physostigmine and procyclidine for the prophylaxis of organophosphate poisoning, were investigated in rabbits and human volunteers. In rabbits, procyclidine, but not 25% physostigmine, induced skin erythema in concentration- and attachment duration-dependent manners, in which moderate to severe redness was produced by attachment with patches containing 8% 01' higher concentrations of procyclidine over 3 days, although skin lesions including edema was not induced by patches containing procyclidine up to 10%. Interestingly, the erythemata caused by procyclidine were reduced by combination with physostigmine, and further by hydrocortisone, and the reactions were rapidly disappeared following detachment of the patches. The skin reactions induced by combinational patches in men were much similar to those in rabbits, although slight and transient edema, itching and pain were induced by patches containing 10% procyclidine, Whereas, patches containing pmcyclidine up to 6% in combination with physostigmine (15%) in the presence of hydrocortisone induced negligible redness, leading to scores lower than 1.0. Separately, only patches with a high concentration (10%) of procyclidine recrystallized from 3 weeks of storage at 4℃ and 23℃, but not at 37℃, reaching 96% after 25 weeks, although the recrystallization rate was greatly lowered by addition of hydrocortisone, Based on the skin irritation and recrystallization profiles, in addition to previous skin penetration and blood concentration analyses, we selected a combinational patch containing 1.5% physostigmine +6% procyclidine +0.5% hydrocortisone as a transient composition for the follow-up non-clinical toxicity studies.