39 results about "Paroxysmal AF" patented technology

The invention relates to a multi-feature-value multi-model fusion atrial fibrillation recognition method, and relates to the technical field of medical signal processing, and the method comprises the steps: obtaining an RR interval sequence; in parallel, extracting a multi-dimensional short-time feature set containing the RR interval fuzzy measure entropy from the RR interval sequence of the preset short time period, and generating a short-time recognition result through a short-time model; meanwhile, a multi-dimensional long-time feature set is extracted from the RR interval sequence of the preset long time period, and a long-time recognition result is generated through a long-time model; and the model result fusion module outputs a final atrial fibrillation recognition result based on the long-time recognition result by combining the proportion of the atrial fibrillation conclusions in the plurality of short-time recognition results and applying dual threshold judgment logic. According to the method, non-linear dynamic characteristics of different time scales are combined, and an intelligent fusion strategy of hierarchical decision is adopted, so that the detection sensitivity of paroxysmal atrial fibrillation and the suppression capability of interference noise can be effectively considered, and the comprehensive accuracy of automatic identification of atrial fibrillation is improved.

Methods of administering an anti-arrhythmic, such as dofetilide, to a patient in an amount effective for treating a cardiovascular condition are described. The drug can be administered intravenously for at least one hour. A loading dose of 0.1 to 12 μg / kg bodyweight over a duration of up to 60 minutes can be administered and / or a maintenance dose of 0.1 to 10 μg / kg / hr can be administered intravenously over a duration of at least 1 hour, optionally alternatively or in addition wherein the amount of the loading dose and / or the IV maintenance dose is in the range of about ±50% of a maintenance dofetilide dose. The cardiovascular condition can include atrial fibrillation or flutter, ventricular tachycardia, hemodynamically stable or unstable ventricular tachycardia, paroxysmal atrial fibrillation, ventricular fibrillation, paroxysmal supraventricular tachycardia, heart failure, coronary artery disease, or pulmonary artery hypertension. A patient's QT interval and / or a creatinine clearance can be measured, and the effective amount can be selected based on either or both of the QT interval or the creatinine clearance measurements.

This disclosure relates to RNAi agents capable of inhibiting complement factor B (CFB) gene expression. Pharmaceutical compositions containing CFB RNAi agents and methods of use thereof are also disclosed. The CFB RNAi agents disclosed herein may be conjugated to a targeted ligand containing an N-acetyl-galactosamine ligand to facilitate in vivo delivery to hepatocytes. RNAi agents can be used in methods of treating diseases, disorders, or conditions partially mediated by CFB gene expression, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membrane proliferative glomerulonephritis (IC-MPGN), lupus nephritis (LN), anti-glomerular basement membrane antibody disease (anti-GBM), ischemia-reperfusion injury and T-cell-mediated rejection in kidney transplantation (TCMR), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, age-related macular degeneration (AMD) including early and / or intermediate-stage AMD, geographic atrophy (GA), glaucoma, Doyne honeycomb retinal dystrophy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), pre-eclampsia, rheumatoid arthritis (RA), and / or other complement-mediated disorders.

The present invention relates to novel polymorphic forms of Iptacopan hydrochloride and preparation thereof. The invention also relates to pharmaceutical composition comprising novel polymorphic forms of Iptacopan hydrochloride and their use in the treatment of paroxysmal nocturnal hemoglobinuria and proteinuria.

Methods for treating paroxysmal nocturnal hemoglobinuria, complement factor 3 glomerulopathy, or idiopathic immune complex-mediated glomerulonephritis using MASP-3 serine protease inhibitors are provided. In some embodiments, the MASP-3 serine protease inhibitor is an anti-MASP-3 antibody. Use of MASP-3 serine protease inhibitors in the treatment of paroxysmal nocturnal hemoglobinuria, complement factor 3 glomerulopathy, or idiopathic immune complex-mediated glomerulonephritis, and for the manufacture of a medicament for treating paroxysmal nocturnal hemoglobinuria, complement factor 3 glomerulopathy, or idiopathic immune complex-mediated glomerulonephritis, is also provided. TIFF2025537131000011.tif104156

Methods and compositions are provided for inhibiting MASP-3-dependent complement activation in a subject suffering from paroxysmal nocturnal hemoglobinuria by administering to the subject a composition comprising an amount of a MASP-3 inhibitor in an amount effective to inhibit MASP-3-dependent complement activation. Methods and compositions for increasing red blood cell survival in a subject suffering from paroxysmal nocturnal hemoglobinuria are provided by administering to the subject a composition comprising an amount of at least one of a MASP-1 inhibitor and / or a MASP-3 inhibitor, the amount of the inhibitor being effective to increase red blood cell survival. A MASP-2 inhibitor and a MASP-1 inhibitor, a MASP-2 inhibitor and a MASP-3 inhibitor, a MASP-3 inhibitor and a MASP-1 inhibitor, or a MASP-1 inhibitor, a MASP-2 inhibitor and a MASP-3 inhibitor may be administered to the subject.

The present invention relates to in vitro sialylated human factor H protein or biologically active sialylated fragments or biologically active sialylated variants thereof for use in treating paroxysmal nocturnal hemoglobinuria, for treating thromboinflammation, for treating pathological platelet aggregate formation for treating microangiopathy, and / or for treating Long COVID. Combination with a C5 inhibitor, e.g. eculizumab, is also envisaged.

The invention belongs to the technical field of medical ultrasonic remote monitoring, and discloses an echocardiogram remote monitoring system for a heart failure patient, which can capture acute cardiac function deterioration corresponding to paroxysmal dyspnea and postural chest distress at night in real time through a symptom pre-recognition module, an emergency level data transmission mechanism and continuous cardiac function parameter calculation; the system no longer only transmits static images, but generates a continuous cardiac function dynamic curve, and combines a causal reasoning algorithm to help doctors to clearly distinguish physiological and pathological attributes of parameter fluctuation, so that intervention delay caused by monitoring lag is avoided, a precious treatment window is won for acute cardiac function deterioration, and the risk of acute exacerbation of heart failure is reduced; based on the integrated data, the causal reasoning algorithm can quickly locate the heart failure deterioration pathogenesis, such as association between EF value decrease and anemia and renal injury, a physician does not need to manually integrate data across platforms, the time consumed for pathogenesis investigation is reduced, timely adjustment of a treatment scheme is ensured, and blind medication caused by unknown pathogenesis is avoided.

An electrocardiogram analysis apparatus includes a machine learning part that has a machine learning model realized by machine learning that uses training electrocardiogram data of a patient with paroxysmal arrhythmia during a non-paroxysmal period during which no episode of paroxysmal arrhythmia occurs; an input processing part that inputs electrocardiogram data of a person to be analyzed, which is a subject of analysis, into the machine learning model; and an output control part that outputs, to an information terminal, abnormality information which is to be output from the machine learning model and is about whether the person to be analyzed has paroxysmal arrhythmia.

The present disclosure relates to compositions and methods, including prodrugs of (S)-sec-butyl 2-(3-(4-(2- (diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate that find use in the treatment of diseases and disorders, such as therapies for cardiovascular disease, including cardiac arrhythmias, including, without limitations, atrial fibrillation, paroxysmal atrial fibrillation, atrial flutter, ventricular arrhythmias, or ventricular fibrillation.

The present invention includes surprisingly water-soluble salts of a phenylalkylamine compound that are potent antagonists of L-type calcium channels. Aqueous solutions including salts of the instant invention are formulated for nasal administration and provide a novel therapeutic platform for the treatment of stable angina, migraine, and cardiac arrhythmia, such as paroxysmal supraventricular tachycardia.

Methods of treating paroxysmal nocturnal hemoglobinuria using MASP-3 serine protease inhibitors are provided. In some embodiments, the MASP-3 serine protease inhibitors are anti-MASP-3 antibodies. Also provided are uses of MASP-3 serine protease inhibitors in treatment of paroxysmal nocturnal hemoglobinuria, and for manufacture of a medicament for treatment of paroxysmal nocturnal hemoglobinuria.

Provided are systems and methods that may be employed to detect the presence or absence of paroxysmal nocturnal hemoglobinuria (PNH) in a subject that includes a leukocyte including GPI-anchors the leukocyte incubated with one or more blocking agents each independently specific to one or more GPI-anchored proteins, the leukocyte further incubated with a pro-aerolysin or derivative thereof, and optionally a second leukocyte including GPI-anchors not incubated with one or more of the blocking agents. The systems may be used as a positive control in assays detecting the presence or absence of PNH.

Provided are systems and methods that may be employed to detect the presence or absence of paroxysmal nocturnal hemoglobinuria (PNH) in a subject that includes a leukocyte including GPI-anchors the leukocyte incubated with one or more blocking agents each independently specific to one or more GPI-anchored proteins, the leukocyte further incubated with a pro-aerolysin or derivative thereof, and optionally a second leukocyte including GPI-anchors not incubated with one or more of the blocking agents. The systems may be used as a positive control in assays detecting the presence or absence of PNH.

The present disclosure relates to stable aqueous solutions comprising high concentrations of an anti-C5 antibody (e.g., ravulizumab) and methods of making the solutions. The present disclosure also provides methods of using the solutions to treat or prevent complement-associated disorders, such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Therapeutic kits containing one or more of the solutions, and means for administering the solutions to a patient in need of such treatment, are also contemplated.

The present invention provides a paroxysmal hemoglobinuria indication drug ipropam key intermediate synthesis method, and relates to the technical field of ipropam, the method comprises: taking p-bromobenzaldehyde as an initial raw material, adopting an organic catalyst to obtain an intermediate 03, carrying out protection group removal on the intermediate 03, carrying out automatic ring closing to obtain an intermediate 04, and carrying out post-treatment to obtain the paroxysmal hemoglobinuria indication drug ipropam key intermediate. Reducing the intermediate 04 with sodium borohydride to obtain a single cis-configuration intermediate 05, then carrying out a chiral flip reaction and hydrolysis to remove p-nitrobenzoic acid, then carrying out an etherification reaction with diethyl sulfate to obtain an intermediate 08, reducing amide of the intermediate 08 with sodium borohydride and boron trifluoride diethyl etherate to obtain an intermediate 09, then carrying out an acetylation reaction to protect amino, and finally carrying out a reaction to obtain the chiral cis-configuration intermediate 03. Cuprous cyanide is subjected to a cyanation reaction and a hydrolytic esterification reaction to obtain the ipropam key intermediate TM. The method is low in raw material price, high in chiral control selectivity, easy in reaction condition control and low in equipment requirement, avoids column chromatography and other operations, and is more suitable for industrial production.

The present disclosure relates to RNAi agents able to inhibit Complement Factor B (CFB) gene expression. Also disclosed are pharmaceutical compositions that include CFB RNAi agents and methods of use thereof. The CFB RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosamine, to facilitate the in vivo delivery to hepatocyte cells. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by CFB gene expression, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN), lupus nephritis (LN), Anti-Glomerular Basement Membrane disease (anti-GBM), ischemia reperfusion injury and T-cell mediated rejection (TCMR) in kidney transplantation, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, age-related macular degeneration (AMD), including early and / or intermediate AMD, geographic atrophy (GA), glaucoma, Doyne honeycomb retinal dystrophy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), pre-eclampsia, rheumatoid arthritis (RA), and / or other complement-mediated diseases.

Described herein are methods of treating paroxysmal nocturnal hemoglobinuria (PNH) with the Factor B inhibitor LNP023 or a pharmaceutically acceptable salt thereof, e.g. LNP023 hydrochloride.

For paroxysmal or persistent AFib patients, if its untreated AFib level exceeds a threshold level of AFib, treatment is eligible with a drug (e.g., Bronidalon) capable of controlling the patient's heart rhythm. A qualified patient is subjected to drug treatment while monitoring its heart rate using a wearable device. If it is considered that the administered dose of medicament is invalid, adjusting the dose until an effective dose is determined for the patient; if the patient is confirmed to be non-reactive to the drug, the treatment is withdrawn.

Disclosed are methods for cardioversion using bundanolol or a pharmaceutical composition comprising bundanolol for cardioversion of patients with paroxysmal or persistent AFib.

The invention further discloses application of a pharmaceutical composition containing the novel compound containing the diaza subunit sulfonyl structure in preparation of drugs for treating anemia-related diseases. The anemia-related diseases may relate to myelodysplastic syndrome (MDS), hemoglobinopathy, sickle-type cell anemia (SCD), beta-thalassemia, hereditary non-spherical cell hemolytic anemia, hemolytic anemia, hereditary spherical polycythemia, hereditary elliptical polycythemia, non-beta lipoproteinemia, paroxysmal nocturnal hemoglobinuria, and the like. Acquired hemolytic anemia or congenital anemia or chronic anemia.

The invention relates to iRNA, e.g., double-stranded ribonucleic acid (dsRNA), compositions targeting the complement component C5 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.

The invention relates to iRNA, e.g., double stranded ribonucleic acid (dsRNA), compositions targeting the complement component C5 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.

The present disclosure relates to RNAi agents, such as double-stranded RNAi agents or siRNAs, that can inhibit expression of the complement component C3 (C3) gene. Also disclosed are pharmaceutical compositions containing the C3 RNAi agents and methods of using them. The C3 RNAi agents disclosed herein can be conjugated to targeting ligands, including N-acetylgalactosamine-containing ligands, to facilitate delivery to liver cells. Delivery of the C3 RNAi agents in vivo provides inhibition of C3 gene expression. The RNAi agents can be used in methods for treating diseases, disorders, or conditions mediated in part by C3 gene expression, including IgA nephropathy, C3 glomerulopathy, paroxysmal nocturnal hemoglobinuria, and / or other complement-mediated kidney diseases.

In one aspect, the invention provides methods and compositions for inhibiting MASP-3-dependent complement activation in a subject suffering from or at risk for developing, a disease or disorder selected from the group consisting of paroxysmal nocturnal hemoglobinuria, age-related macular degeneration, arthritis, disseminated intravascular coagulation, thrombotic microangiopathy, asthma, dense deposit disease, pauci-immune necrotizing crescentic glomerulonephritis, traumatic brain injury, aspiration pneumonia, endophthalmitis, neuromyelitis optica and Behcet's disease by administering to the subject a composition comprising an amount of a MASP-3 inhibitory agent in an amount effective to inhibit MASP-3-dependent complement activation. In some embodiments, the subject is administered a MASP-2 inhibitory agent and a MASP-1 inhibitory agent, a MASP-2 inhibitory agent and a MASP-3 inhibitory agent administered, a MASP-3 inhibitory agent and a MASP-1 inhibitory agent, or a MASP-1 inhibitory agent, a MASP-2 inhibitory agent and a MASP-3 inhibitory agent.

The present disclosure relates to the use of a Factor B inhibitor in the treatment of paroxysmal nocturnal hemoglobinuria. Specifically, the present disclosure relates to the use of the Factor B inhibitor or a pharmaceutically acceptable salt thereof in the preparation of a formulation for treating paroxysmal nocturnal hemoglobinuria (PNH) previously using a C5 complement inhibitor, wherein the Factor B inhibitor is represented by formula (I), (II) or (III).

In one aspect, the invention provides methods and compositions for inhibiting MASP-3-dependent complement activation in a subject suffering from or at risk for developing, a disease or disorder selected from the group consisting of paroxysmal nocturnal hemoglobinuria, age-related macular degeneration, arthritis, disseminated intravascular coagulation, thrombotic microangiopathy, asthma, dense deposit disease, pauci-immune necrotizing crescentic glomerulonephritis, traumatic brain injury, aspiration pneumonia, endophthalmitis, neuromyelitis optica and Behcet's disease by administering to the subject a composition comprising an amount of a MASP-3 inhibitory agent in an amount effective to inhibit MASP-3-dependent complement activation. In some embodiments, the subject is administered a MASP-2 inhibitory agent and a MASP-1 inhibitory agent, a MASP-2 inhibitory agent and a MASP-3 inhibitory agent administered, a MASP-3 inhibitory agent and a MASP-1 inhibitory agent, or a MASP-1 inhibitory agent, a MASP-2 inhibitory agent and a MASP-3 inhibitory agent.

The present invention belongs to the field of biotechnology. Disclosed is use of a complement factor B inhibitor in the preparation of a drug for treating or preventing a disease or condition related to paroxysmal nocturnal hemoglobinuria. Specifically, the present invention provides use of a compound represented by formula A or a pharmaceutically acceptable salt thereof or a hydrate thereof in the preparation of a drug for treating or preventing a disease or condition related to paroxysmal nocturnal hemoglobinuria. The present invention can effectively inhibit the incidence of hemolysis in paroxysmal nocturnal hemoglobinuria, providing an effective and safe new option for the treatment of paroxysmal nocturnal hemoglobinuria.

Patients with paroxysmal or persistent atrial fibrillation whose untreated atrial fibrillation exceeds the threshold level are eligible for treatment with a drug that can control the patient's heart rhythm (e.g., budiodarone). Eligible patients are treated with the drug while their heart rate is monitored using a wearable device, and if a given drug dose is deemed ineffective, the dose is adjusted until an effective dose is determined for the patient or the patient is deemed unresponsive to the drug and is discontinued from treatment.