Recent patents on cardiovascular drug discovery最新文献

The present review will discuss the technical aspects of a new patent invented in 1999 which allows cryoballoon ablation, an emerging technology used for the non pharmacological treatment of paroxysmal atrial fibrillation. A general evaluation of the safety and the reliability of the technique will be given together with an overview on its short and midterm outcome. Finally future directions of the technology and its possible implementation will be briefly treated.

MicroRNAs (miRNAs) are a broad class of small non-coding RNAs that control expression of complementary target messenger RNAs. Dysregulation of miRNAs has been described in various disease states including cancer and cardiac disease. A particular miRNA that was consistently reported to be upregulated in both cancer and various forms of cardiovascular diseases is miR-21. MiR-21 exerts oncogenic activity and therefore is considered as an oncomir. In the cardiovascular system miR-21 is enriched in fibroblasts and contributes to the development of fibrosis and heart failure. MiR-21 therefore emerges as an interesting candidate for the development of therapeutic strategies against many forms of cancer as well as heart diseases. Indeed, treatment with anti-miR-21 oligonucleotides reduced breast cancer growth. Inhibition of miR-21 by synthetic miRNA antagonists (antagomirs) improved heart function in a cardiac disease model. The same beneficial effects were observed in miR-21 knockout mice subjected to pressure-overload of the left ventricle underlining the key role of miR-21 as a therapeutic target. We here overview the current patent situation about the therapeutic use of miR-21 modulation in cancer and cardiovascular disease.

The need for safe and effective antiplatelet agents motivates scientists towards a non-ceasing research which has through the past few years provided patients suffering from coronary artery disease, submitted or not to percutaneous intervention or heart surgery with safe and life-saving pharmaca; after ticlopidine and clopidogrel and just recently, ticagrelor and prasugrel have been developed with the aim to provide adequate protection against thrombotic cardiovascular episodes and avoid significant bleeding events. Herein, we are presenting through an updated literature research and recent patents data the novel agents ticagrelor and prasugrel, which promise improved effectiveness combined with an increased level of safety.

Coronary heart disease (CHD) is the leading cause of morbidity and mortality across the entire world. In effect, reversion of angina or improvement of ECG remains an unrealistic therapeutic option for most patients. Unfortunately, most research clinical trials in these patients have focused on coronary atherosclerosis, even decades after the first observation that angina, and myocardial infarction may occur in the presence of normal coronary arteries. Further, there has been little attention from academic and pharmaceutical institutions on comparative therapeutic research as it has been recently addressed by the Institute of Medicine of the National Academies in USA, and by a similar statement from the World Medical Association in the year 2000. This review, thus, has tried to present the best of our knowledge on the pathophysiology and management of CHD, along with other striking relevant but neglected findings with some recent patents. Four sections were included from the physiological principles of myocardial oxygen delivery, with emphasis on RBC sensing O(2) demand and delivery in myocardial ischemia, up to the recent advances on approaches intended to reverse angina and the ECG alteration in coronary heart disease. Finally, this review presents the principles, design and results of the first New Drug Application to address improvement in RBC K uptake, and consequently the chain of simultaneous tissue H/K and O(2)/CO(2) exchanges, and NO-generation, along with their promising therapeutic effect on reversion of angina, and ST-T alterations in coronary artery disease patients.

Many researchers have until now united their efforts in the endeavor to discover new anticoagulants, which would be simpler to use and safer to administer, so that patients would avoid both thromboembolic events as well as life threatening episodes of bleeding. One of these agents, that is hereby presented along with patents, is dabigatran, which promises much for the future, despite the fact that time and the awaited results of ongoing trials will be necessary for its establishment as a first-line anticoagulant. More specifically, based on the major trials of RELY and RECOVER, we could state that dabigatran has presented satisfactory outcomes in terms of bleeding and prevention of venous thromboembolism.

Cardiac arrest remains one of the most common causes of death in developed countries. Those who survive may have significant neurologic morbidity. In the current decade, therapeutic medical hypothermia (TMH) has emerged as the only treatment that unequivocally improves neurologic outcomes in post ventricular fibrillation / ventricular tachycardia induced cardiac arrest. The role of TMH in other forms of cardiac arrest continues to evolve. We present the current status of medical hypothermia, recent patents and recent advances of this evolving therapy.

Contrast echocardiography is a safe, accurate, and reproducible method to assess left ventricular volumes and function. Based on current guidelines, ultrasound contrast is indicated for left ventricular opacification at rest in patients with suboptimal echocardiographic images, and in stress echocardiography when >or= 2 adjacent segments are poorly visualised. Adding contrast for assessment of regional myocardial perfusion expands the use of echocardiography in ischemic heart disease from detection of left ventricular dysfunction at rest or during stress to assessment of myocardial ischemia, extent of myocardial necrosis and re-flow after coronary revascularisation. Myocardial perfusion also adds prognostic information to that given by structural and functional assessment alone and may reduce the need for more time consuming, expensive cardiac imaging procedures associated with radiation as well as coronary angiography with the risk of vascular complications. This article gives an overview of ultrasound contrast agents and their impact on echocardiographic assessment of ischemic heart disease also discussing recent patents.

Heparin, low molecular weight heparin (LMWH) and warfarin are well-established anticoagulants still in widespread use despite their well known drawbacks. Heparin requires continuous monitoring, has serious side-effects such as haemorrhage, thrombosis and osteoporosis, and lacks an oral route of administration. LMWH is a safer, more convenient anticoagulant to use but it cannot be given orally, does not have an antidote and may be difficult to administer in patients with renal failure. Warfarin has a narrow therapeutic window, interacts with other drugs and foods and requires monitoring like heparin. The limitations of all three of these established anticoagulants have prompted the search for better more convenient agents. The major examples of these newer anticoagulants are the direct and indirect factor Xa inhibitors and the direct thrombin inhibitors. These new agents tend to have more predictable pharmacokinetic properties, superior efficacy and safety and some can be administered orally. In this review, we summarise the advantages and disadvantages of three established anticoagulants (heparin, LMWH and warfarin) and the most promising new anticoagulants (fondaparinux, idraparinux, rivaroxaban, apixaban, dabigatran and ximelagatran) by discussing their pharmacodynamics and pharmacokinetics. We also discuss recent patents in the field of anticoagulation, which aim to improve the safety and effectiveness of antithrombotic agents currently in use or offer alternative ways for anticoagulation.

Lipid profiles were evaluated for 281 dyslipidemia patients treated with HMG-CoA reductase inhibitors (statins) for 2 years. The efficacy and safety of ezetimibe 10 mg/day one-year add-on therapy were also retrospectively evaluated. The results show that in 281 dyslipidemia patients with a mean low-density lipoprotein-cholesterol (LDL-C) level of 120 mg/dl or greater, ezetimibe 10 mg/day administration reduced LDL-C levels to 90 mg/dl or below. Patients who had been treated with one of six statins (pravastatin, simvastatin, fluvastatin, pitavastatin, atorvastatin, and rosuvastatin) for one year were given ezetimibe add-on therapy for one year, which reduced their LDL-C levels by 18% (pravastatin), 25% (simvastatin), 27% (fluvastatin), 30% (pitavastatin), 29% (atorvastatin), and 31% (rosuvastatin). Also, during the one-year add-on therapy, no severe adverse event was detected. An analysis of associations among lipids during a two-year lipid-lowering pharmacotherapy revealed correlations in a single patient. The correlation was between LDL-C and small, dense LDL as well as mid-band lipoprotein cholesterol. In conclusion, ezetimibe 10mg/day add-on therapy may be safe and effective for treating dislipidemia patients who have been treated with a statin. Moreover, this article discusses the disappearance thresholds for small, dense LDL and intermediate-density lipoprotein (IDL) by using the quantitative analysis of densitometric pattern based on genetic algorithm, which indicated that the major eight subspecies of lipoprotein (VLDL1, VLDL2, IDL1, IDL2, LDL1, LDL2, LDL3, HDL). The thershold for small dense LDL indicates the IDL1 plus IDL2 when LDL2 and LDL3 were not detectable, while the thershold for IDL indicates the LDL1 when IDL1, IDL2 and LDL3 were not detectable.

Cardiovascular diseases account for more deaths worldwide than any other illness. Myocardial ischemia, a common finding in cardiovascular diseases, lowers cellular energy levels, which affects a cell's integrity and function. Pre-clinical animal studies have reported lower cellular energy levels with an associated decreased function following myocardial ischemia. Recently, scientists have reported that the failing heart is energy starved and yet no pharmaceuticals have been able to address this issue with satisfactory results. Over decades, researchers have explored the use of various metabolites to replenish deficient cellular energy levels following induced ischemia with mixed results. However, D-ribose, a natural occurring carbohydrate, has demonstrated significant enhancing abilities in replenishing deficient cellular energy levels following myocardial ischemia, as well as improving depressed function in numerous animal investigations. Subsequent clinical trials have further substantiated these benefits of D-ribose in patients afflicted with ischemic cardiovascular disease and those carrying the diagnosis of congestive heart failure. The future of effective therapies for ischemic heart disease and congestive heart failure must strongly consider novel pharmaceuticals directed at replenishing cellular energy levels. Intellectual property and the represented patents in this paper emphasize the use of D-ribose for its cellular energy enhancing potential, reflected in both objective and subjective clinical improvements; therefore, substantiating its value in patients with ischemic cardiovascular diseases.