Recent patents on cardiovascular drug discovery最新文献

Endothelial dysfunction represents an imbalance between vasodilatory and vasoconstrictory molecules secreted by endothelium. Oxidative stress is a major factor leading to endothelial dysfunction with significant prognostic implications for cardiovascular events. The generation of reactive oxygen species is strongly related to various oxidase enzymes such as xanthine oxidase, uncoupled endothelial nitric oxide synthase, cyclooxygenase, glucose oxidase, lipooxygenase, nicotinamide-adenine dinucleotide phosphate oxidase and to mitochondrial electron transport mechanisms. Several pharmaceutical agents exert effects beyond their principal role, such as anti-inflammatory and antioxidant, while the reports on antioxidant vitamins remain controversial especially those based on large scale studies. Moreover, there are studies on other agents already patented, but these are not well evaluated. Recently, there is growing interest in the role of dietary flavonoids and their potential to improve endothelial function by modifying oxidative stress status. Flavonoids are important components of 'functional foods', with beneficial effects on cardiovascular health, mainly due to their antioxidant activity. However, the vascular-protective role of flavonoids and especially their antioxidant properties are still under investigation.

HoFH is an autosomal co-dominant disease with a prevalence of one in 1,000,000. Mutations of LDL-R gene are responsible for this disease. HoFH needs to be distinguished from autosomal recessive hypercholesterolemia protein (ARH) that causes a similar clinical phenotype. HoFH induces aggressive cardiovascular disease that can develop from birth. These patients possess high LDL-C levels, cutaneous and tendon xanthomas, and accelerated atherosclerosis shown in the first 2 decades of life. Current treatment modalities include life-style modifications, lipid-lowering therapy and LDL-apheresis. However, the treatment goal cannot be achieved only by statin therapy. New therapeutic strategies to lower LDL-C have been developed over recent years. These include monoclonal antibodies binding to PCSK9, inhibition of ApoB production and MTP-inhibitors. This review is focused on new treatments for HoFH and their patents. It is known to be an important contribution in this rare disease, which is difficult to manage.

Valvular heart disease affects millions of Americans yearly and currently requires surgical intervention to repair or replace the defective valves. Through a close-knit collaboration between physicians, scientists and biomedical engineers, a vast degree of research and development has been aimed towards the optimization of prosthetic heart valves. Although various methods have made fantastic strides in producing durable prostheses, the therapeutic efficacy of prosthetic valves is inherently limited by a dependency upon lifelong anticoagulant regimens for recipients - a difficult challenge for many in clinical setting. Thus, biological tissue valves have been developed to circumvent vascular and immunemediated complications by incorporating biological materials to mimic native valves while still maintaining a necessary level of structural integrity. Over the past decade, a multitude of patents pertaining to the refinement of designs as well as the advancement in methodologies and technologies associated with biological tissue valves have been issued. This review seeks to chronicle and characterize such patents in an effort to track the past, present, and future progress as well as project the trajectory of tissue valves in the years to come.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in clinical practice associated with significant morbidity and mortality. With the growing number of the affected individuals, the development of safe and effective treatment options for AF has become a worldwide priority. Currently available antiarrhythmic medications for the restoration and maintenance of sinus rhythm have limitations due to the modest efficacy and a potential for adverseeffects. Although substantial progress has been made in AF-ablation techniques, broad application of these nonpharmacological treatment modalities is limited and antiarrhythmic drug treatment is still the cornerstone and the first-line therapy for the majority of AF patients. Improvements in the understanding of the principal pathophysiological mechanisms of AF obtained in the last several years have provided promising treatment opportunities. New therapeutic options are based on the more selective targeting of ion channels and intercellular connection proteins predominantly expressed in the atria, the restoration of intracellular Ca(2+) homeostasis and the prevention of AF-associated electrical and structural remodeling. In this review, we provide a highlight of the most important pathophysiological mechanisms in AF with a relation to the potential therapeutic interventions, and discuss novel findings regarding the current and future pharmacological AF management and recent patents.

The assessment of tissue contact is an area undergoing much research as a means of improving the outcomes of cardiac radiofrequency ablation. This review provides an overview of RF ablation with specific reference to the relevance of good tissue contact to adequate RF lesion formation. An up-to-date review of the clinical evidence is provided, and recent patents of novel contact-sensing technologies in the field of cardiac RF ablation are presented.

Natural products including botanicals for both therapy of clinical manifestations of atherosclerosis and reduction of atherosclerosis risk factors are topics of recent patents. Only a few recent patents are relevant to the direct antiatherosclerotic therapy leading to regression of atherosclerotic lesions. Earlier, using a cellular model we have developed and patented several anti-atherosclerotic drugs. The AMAR (Atherosclerosis Monitoring and Atherogenicity Reduction) study was designed to estimate the effect of two-year treatment with time-released garlic-based drug Allicor on the progression of carotid atherosclerosis in 196 asymptomatic men aged 40-74 in double-blinded placebo-controlled randomized clinical study. The primary outcome was the rate of atherosclerosis progression, measured by high-resolution B-mode ultrasonography as the increase in carotid intima-media thickness (IMT) of the far wall of common carotid arteries. The mean rate of IMT changes in Allicor-treated group (-0.022±0.007 mm per year) was significantly different (P = 0.002) from the placebo group in which there was a moderate progression of 0.015±0.008 mm at the overall mean baseline IMT of 0.931±0.009 mm. A significant correlation was found between the changes in blood serum atherogenicity (the ability of serum to induce cholesterol accumulation in cultured cells) during the study and the changes in intima-media thickness of common carotid arteries (r = 0.144, P = 0.045). Thus, the results of AMAR study demonstrate that long-term treatment with Allicor has a direct anti-atherosclerotic effect on carotid atherosclerosis and this effect is likely to be due to serum atherogenicity inhibition. The beneficial effects of other botanicals including Inflaminat (calendula, elder and violet), phytoestrogen- rich Karinat (garlic powder, extract of grape seeds, green tea leafs, hop cones, β-carotene, α-tocopherol and ascorbic acid) on atherosclerosis have also been revealed in clinical studies which enforces a view that botanicals might represent promising drugs for anti-atherosclerotic therapy.

Radiofrequency catheter ablation without active cooling of the catheter tip is associated with significantly increased risk of thrombus formation and thromboembolism, especially when multiple and high-energy deliveries are considered. Therefore, irrigation of the distal electrode has become obligatory for catheter ablation of complex cardiac arrhythmias. The advancement in the cooling catheter technology is aimed to further reduce the risk of steam pop as well as coagulum formation on both electrode and tissue, and to maximize energy transfer to the tissue. Whether novel catheter designs will translate into better success rates of catheter ablation and lower risk of complications remains to be evaluated by upcoming studies. In future, a combination with novel sensors that enable online monitoring of lesion creation is expected. Such technology should allow optimization of radiofrequency delivery without risk of deep tissue overheating and steam pop creation. Recent patents in the field of irrigated ablation catheter focus mainly on novel porous materials that would enable diffuse irrigation around the catheter tip and alternative layout of irrigation holes. Additionally, some patents deal with combination of irrigation fluid tubing and different sensors located within the catheter tip.

Novel oral anticoagulants (NOACs) have been associated with multiple safety benefits compared with vitamin K antagonists in patients with diseases at high thromboembolic potential, including nonvalvular atrial fibrillation. Although these agents have several distinct advantages, they are limited by the lack of a proven antidote, which may represent a major concern in case of life-threatening bleeding. Several different drugs and compounds are currently under investigation as reversing agents of NOACs. This article provides an overview of potential NOACs antidotes, including recent patents of emerging compounds.

Valvular heart disease, inherited or acquired, affects more than 5 million Americans yearly. Whereas medical treatment is beneficial in the initial stages of valvular heart disease, surgical correction provides symptomatic relief and long-term survival benefits. Surgical options include either repair or replacement using mechanical or bio-prosthetic valves. Patient age and the post-operative need for anticoagulation therapy are major determinants of the choice between use of mechanical or bio-prosthetic valves. Since the first mechanical valves were made available several decades ago, the incorporation of increasingly sophisticated materials and methodologies has led to substantial improvements in the valve design, and has catalyzed a parallel increase in the amount of patents issued for these emerging technologies. In this paper, we have chronologically reviewed such patents, briefly discussed various challenges that mechanical heart valve implementation is faced with and finally reviewed some of the strategies employed to overcome such obstacles. An ideal prosthetic heart valve would comprehensively mimic the natural hemodynamics and physiology of the native heart valve. Additionally, such a valve would be easily implantable, associated with a minimal risk of thrombosis and thus need for anti-coagulation, and with a proven long-term durability. With cutting edge technological advancements in the recent times, the ongoing innovative and collaborative efforts of physicians, scientists, and engineers will not seize until an ideal mechanical heart valve becomes a reality.