Myasoedova Veronika A, Ivashinnikova Galina A, Sobenin Igor A, Ivanova Ekaterina A, Orekhov Alexander N
Unit of Atherosclerosis Prevention, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138, Milan. Italy.
Pharmaceutical Research Associates, Moscow. Russian Federation.
Curr Pharm Des. 2017;23(8):1195-1206. doi: 10.2174/1381612823666170102121927.
Atherosclerosis is one of the main problems in modern medical practice. This multifactorial disease can remain asymptomatic for a long time before manifesting itself in cardiovascular disorders, causing ischemic heart disease, myocardial infarction and even sudden death. Many synthetic drugs have been developed to reduce the symptoms of atherosclerosis, however, their efficacy in terms of reduction of atherosclerotic lesions progression is a matter of debate. Adverse effects of the exiting therapy should also be taken into account. The development of cellular models and improved understanding of the mechanisms of atherogenesis at the vascular wall level helped establishing the "direct anti-atherosclerosis therapy" approach. In this approach, the decrease of intracellular lipid deposition and atherogenicity of human blood serum are considered primary (direct) antiatherosclerotic effects. Screening of synthetic and natural substances for anti-atherosclerotic activity revealed a number of botanicals that could be used for direct anti-atherosclerotic therapy to treat early-stage atherosclerosis. As a result, 3 novel non-pharmaceutical products were developed (Allicor, Inflaminat and Karinat). Studies on in vitro and ex vivo models of atherogenesis confirmed their anti-atherosclerotic and anti-atherogenic activities and safety in patients. Clinical studies of Allicor, Inflminat and Karinat were carried out in subjects with diagnosed early stage atherosclerosis, demonstrating a clinically significant anti-atherosclerotic effect of the drugs. In this overview, we will present the complete process of the development of novel non-pharmaceutical products and report the results obtained in the conducted pre-clinical and clinical studies of these medications.
动脉粥样硬化是现代医学实践中的主要问题之一。这种多因素疾病在心血管疾病表现出来之前可能长期无症状,会导致缺血性心脏病、心肌梗死甚至猝死。已经研发了许多合成药物来减轻动脉粥样硬化的症状,然而,它们在减缓动脉粥样硬化病变进展方面的疗效仍存在争议。现有疗法的不良反应也应予以考虑。细胞模型的发展以及对血管壁水平动脉粥样硬化发生机制的更好理解有助于确立“直接抗动脉粥样硬化疗法”。在这种疗法中,细胞内脂质沉积的减少以及人血清的致动脉粥样硬化性降低被视为主要(直接)抗动脉粥样硬化作用。对合成和天然物质的抗动脉粥样硬化活性进行筛选后发现了一些可用于直接抗动脉粥样硬化疗法以治疗早期动脉粥样硬化的植物药。结果,研发出了3种新型非药物产品(Allicor、Inflaminat和Karinat)。对动脉粥样硬化发生的体外和离体模型的研究证实了它们在患者中的抗动脉粥样硬化和抗动脉粥样硬化活性以及安全性。对Allicor、Inflminat和Karinat进行了针对已诊断为早期动脉粥样硬化患者的临床研究,证明了这些药物具有临床上显著的抗动脉粥样硬化作用。在本综述中,我们将介绍新型非药物产品的完整研发过程,并报告在这些药物的临床前和临床研究中所获得的结果。