药物的物理化学再利用。它在俄罗斯的形成历史

Aleksandr L. Urakov, Petr D. Shabanov
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引用次数: 0

摘要

据报道,传统的发现和开发一种新药并进行整个临床前研究的方案需要数千种化合物,数亿美元和12年以上的工作。物化药理学诞生于20世纪末的俄罗斯,在我们的时代已经转变为对已知药物的物化再利用。第一个成功改造用途的已知药物是一种含有4%氯化钾的溶液,这种药物以前传统上属于常量和微量元素,通过静脉注射来调节酸碱平衡和心脏节律性活动。1983年,有人指出,这种药液加热到3942℃,局部冲洗出血表面,可归类为血管收缩剂和止血药物。热疗作为一种理化重构因子,根据阿伦尼乌斯定律,热疗一方面加速和加强了K+阳离子对张开的血管的痉挛作用(血管壁平滑肌形成高钾挛缩),另一方面加速和加强了伤口中的血液凝固过程。在随后的几年里,以水、过氧化氢、氯化钠和碳酸氢钠为例,通过有目的地改变它们的温度、酸度、渗透活性以及气体含量(通过)的数量和质量,表明了对已知药物进行物理化学再利用的希望。描述了已知药物溶液和片剂的物理化学重新利用的年表,并给出了诸如瘀伤和溶血剂等新药物组的本质。研究表明,这两组药物都是在俄罗斯发现的,用于当地漂白瘀伤(血迹),溶解粘稠的粘液、痰、脓、血块、胎粪和其他含有过氧化氢酶的致密生物组织。指出根据该方案重新利用的已知药物的优点同时也存在局限性,因为它们的新药理活性主要是由作用的物理和化学原理引起的,表现为与患者机体选定区域的局部相互作用。
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Physical-chemical repurposing of drugs. History of its formation in Russia
It is reported that the traditional scheme of finding and developing a new drug and conducting the whole complex of preclinical studies requires several thousand chemical compounds, hundreds of millions of US dollars and more than 12 years of work. It is shown that physicochemical pharmacology was born in Russia at the end of the 20th century, which in our days has been transformed into physicochemical repurposing of known medicines. The first successfully repurposed known drug was a solution of 4% potassium chloride, which had previously traditionally belonged to the group of macro- and microelements, used by intravenous injections to regulate acid-base balance and rhythmic activity of the heart. In 1983, it was stated that this medicinal solution, when heated to 3942C and applied topically by irrigation of the bleeding surface, could be classified as a vasoconstrictor and hemostatic drug. Hyperthermia was used as a physico-chemical reprofiling factor, which, according to the Arrhenius law, accelerated and intensified, on the one hand, the spastic action of K+ cations on the gaping blood vessels (formation of hyperkalium contracture in the smooth muscles of the vascular wall) and, on the other hand, the blood clotting process in the wound. In subsequent years, the promise of physicochemical repurposing of known drugs was shown on the example of water, hydrogen peroxide, sodium chloride and sodium bicarbonate by purposefully changing their temperature, acid, osmotic activity, as well as the amount and quality of gas content (passing). A chronology of the physicochemical repurposing of known drug solutions and tablets is described and the essence of such new groups of drugs as bleachers of bruises and pyolytics is given. It is shown that both groups of drugs were discovered in Russia and are intended for local use to bleach bruises (blood stains) and dissolve thick mucus, sputum, pus, blood clots, meconium and other dense biological tissues containing the enzyme catalase. It is pointed out that the advantage and at the same time the limitation of the known drugs repurposed according to this scheme is their local application, since their new pharmacological activity is caused mainly by the physical and chemical principle of action, which is manifested by local interaction with the selected area of the patients organism.
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