Recent patents on cardiovascular drug discovery最新文献

Obesity is a major public health concern associated with increased morbidity and mortality. Its prevalence is rising worldwide mainly due to modern lifestyle habits. Several mechanisms like inflammation, endothelial dysfunction, increased sympathetic tone, high leptin and insulin concentrations as well as enhanced thrombogenesis are implicated to the emergence and progress of cardiovascular disease. Although, changes in the lifestyle remain the cornerstone of antiobesity treatment, alone do not always provide the desired weight loss. Often, the addition of pharmacotherapy or bariatric surgery is considered the treating option for patients meeting eligibility criteria. Although, bariatric surgery is limited to patients with a high body mass index due to the risks of the procedures, the effects of anti-obesity medication on cardiovascular outcome are still unclear. Several anti-obesity drugs have been abandoned because of serious adverse events. Qsymia is a combination of phentermine and topiramate used for obesity treatment. Administration of this drug reduces body weight and has favorable effects in various metabolic and anthropometric parameters. However, there are concerns regarding cardiovascular safety of this drug. In this review, we are going to present the history of current antiobesity medication focusing on the combination of phentermine and topiramate and recent patents.

Dietary omega-3 polyunsaturated fatty acids (ω-3 PUFAs) benefits are not clearly defined in childhood although already well-defined in adults. Recent studies have demonstrated their positive effects on bronchial asthma, neuropsychiatric disorders and cognitive brain function in childhood. Furthermore, it has been demonstrated as a relationship between the increased incidence of childhood obesity and the role of ω-3 PUFAs in reducing the metabolic and vascular alterations induced by the fat accumulation since young age. Such relationship could be more important in prevention of future cardiovascular events. In fact, ω-3 PUFAs could improve endothelial function and structure since childhood. By considering endothelial dysfunction as a well-known early marker of atherosclerosis, its amelioration in the beginning years of individuals' life will certainly reduce the cardiovascular risk profile in adulthood. Nevertheless, their use is limited by several factors, such as the lack of studies in children and the awful taste of the products enriched with ω-3 PUFAs, although several patents have managed to overcome such defects and developed the use of these molecules. This paper is a literature study and patents analysis aiming to explore key issues regarding ω-3 PUFAs administration in childhood in order to take into account its routine intake daily. However, it is well-established that further studies are needed to endorse the promising results outlined by literature analysis.

Soy is the principal plant that produces phytoestrogens, named so because they bind to the estrogen receptors, however weakly compared to the estrogens. Recent reviews concluded that there is no convincing evidence in favor of alleviation of menopausal symptoms by phytoestrogens. However, some studies suggest their efficacy. The question is discussed here, whether vegetable analogues should be used for replacement therapy instead of physiological hormones, also because phytoestrogen preparations often contain a mixture of different components. There is a controversy: phytoestrogens are used to compensate for estrogen deficiency in menopause; but their estrogenic potential does not prevent from the use of soy in infant formulas and other foodstuffs. Feminizing effect of phytoestrogens and soy products may be subtle, detectable only in large populations. This matter should be clarified by independent research, which can be of importance for the future of soy in agriculture. Furthermore a tendency to present placebos and substances with unproven effects in the guise of evidence-based medications is discussed. In conclusion, research quality and possible influence by the industry should be taken into account defining inclusion criteria for studies into meta-analyses and reviews. The article presented patents discussion relevant to the article.

Cardiac surgery, especially if it involves cardiopulmonary bypass, is associated with a severe systemic inflammatory response. It is characterized by complement activation and initiation of coagulation, fibrinolysis and kallikrein cascades. Consecutive activation of immunoregulatory cells results in an extensive release of pro- and anti-inflammatory cytokines. This inflammatory storm is related to organ dysfunction or failure and correlates with postoperative morbidity. In order to attenuate this deleterious inflammatory response in the perioperative period alternative surgical techniques, novel extracorporeal circulation devices and immunomodulatory pharmacological strategies are in focus of contemporary research. Since decades corticosteroids have been used and studied in patients undergoing cardiac surgery. Although it could be shown that glucocorticoids seem to change the pro-inflammatory cytokine profile in a favourable manner, it still remains controversial if this effect translates into a better clinical outcome. Several clinical trials have proclaimed an association between this inflammatory response and the incidence of major complications i.e, myocardial infarction and pulmonary complications, but until now they have failed to show conclusive results. This article describes the different types and recommended dose schemes of corticosteroids in the perioperative period of cardiac surgery along with the discussion of few patents. It will comment on potential side effects and review the effect on the postoperative outcome.

The present contribution reviews recent progress in bioengineering approaches used to mimic arterial hemodynamic conditions in vascular grafts and vessel substitutes used in vascular surgery. While implantation of vascular bypasses is still the primary option for cardiac and vascular surgeons to recover blood perfusion in cardiac and peripheral ischemic tissues, effective techniques to reduce the impact of post-grafting vascular remodeling are insufficient. In our view, the design of specific bioreactors to perform vascular conditioning with complex stimulation patterns will provide valuable tools for comprehensive molecular analysis of vessel arterialization process. In addition, this approach will allow the future design of refined protocols to perform pre-conditioning of natural vessels, reseeding of human or animalderived decellularized vascular grafts or, finally, derivation of fully engineered arterial-compliant substitutes, with a reduced remodeling impact.

Aortic stenosis (AS) is a serious condition in the aging US and European populations. Management of a stenotic valve is crucial as it can become symptomatic quickly leading to ventricular deterioration and overall poor quality of life. Considering that AS is a disease of the elderly patient population, surgical intervention may not be well tolerated by some patients. Transcatheter aortic valve implantation (TAVI) has emerged as an alternative approach for patients who are unsuitable surgical candidates. Since the first balloon-expandable Edwards SAPIEN valve (Edwards Lifesciences, Irvine, CA) was implanted by Dr. Cribier, many other valves have been introduced into clinical practice. Self-expanding valves such as the CoreValve ReValving system (Medtronic, Minneapolis, MN) for retrograde implantation and Symetis TX for antegrade and transapical implantation are the most frequently used self-expanding valves. The SAPIEN valve, on the other hand can be implanted both antegrade as well as retrograde. Overall, the most widely used valves are the Edwards SAPIEN and the CoreValve, which have been implanted in more than 40,000 patients worldwide. The Symetis valve has shown promising results in small series in Europe and may be introduced to the US market in the near future. This manuscript will review these 3 recently patented valves and discuss some of the clinical results that are available.

The off-label use of recombinant human coagulation factor VIIa has been increasing to a number of different treatment areas since its original approval in 1999. Several US patents describe claims for FVIIa utilization in nonhemophilia patients, treatment of bleeding due to trauma, as a means to reverse major bleeding, including intracranial bleeding, induced from fibrinolytic therapy as well as a patent for using FVIIa in the treatment of bleeding for patients with bleeding disorders not caused by hemophilia, but rather bleeding disorders due to thrombocytopenia, platelet disorders, and von Willebrand's disease. Bleeding after cardiac surgery remains a serious complication that can increase both morbidity and mortality. We review the off-label usage of recombinant factor VIIa as a hemostatic agent that may help control bleeding following cardiac surgery.

Cardiac surgery with cardiopulmonary induces a systemic inflammatory response (SIRS). SIRS is broadly defined as an inflammatory state of the whole body without a proven source of infection. Many pre and postoperative variables have been defined that have a negative impact on SIRS. Although many strategies have been developed, targeting given biomarkers very few of these proved to be effective in a clinical setting. In order to better understand why this happened a new approach for defining SIRS was proposed. This review describes this new concept and the recent patents involved.

Systemic inflammation response is a complex physiopathological host response following aggression. This phenomenon is well described during cardiac surgery under cardiopulmonary bypass but also in the context of off-pump cardiac surhery. The goal of this article is to review the different mechanisms involved in the systemic inflammation response, abusively called "systemic inflammatory response syndrome". The article will describe the different component of this response with a clear definition of different pathways found in this process. The possible relation between systemic inflammation and postoperative outcome will be described. The different therapeutic and prophylactic options evaluated to decrease the systemic inflammation reaction will be summarized.

Aortic valve stenosis is becoming a burden to society due to the constantly aging population. After the onset of the first symptoms it usually follows an ominous route with high mortality levels even at two years without any medical intervention. The gold standard for treating aortic valve stenosis is surgical replacement; nonetheless, 30% of patients are left untreated due to increased risk of surgery. A less invasive method has been developed in the past decade, transcatheter aortic valve implantation (TAVI), which allows implantation of prosthesis in the native stenosed aortic valve position, using a catheter that enters the body in a transvascular way or through a minimal surgical cut down. In this review, we briefly discuss where the TAVI field begun, focus on the recent valves that are being used and finally look at what lies ahead. The review of the patents will assist in the understanding of how this field evolved, how it became established and what is to be expected in the future.