A method of treating or preventing adverse outcomes associated with tissue plasminogen activator (tPA) administration, cerebral edema-related side effects, cerebral edema associated with radiation therapy, or migraine headaches by administering an effective amount of a SUR1-TRPM4 channel inhibitor, such as glyburide, and optionally the co-administration of a second therapeutically active agent, to a subject in need thereof. Adverse outcomes associated with tPA include cerebral hemorrhage, cerebral edema, physical impairment or death. The administration of the SUR1-TRPM4 channel inhibitors occurs prior to the radiation therapy, during the radiation therapy, after the radiation therapy, or combinations thereof. The SUR1-TRPM4 channel inhibitor is administered prior to surgical excision of a brain tumor, CAR-T therapy, or administration of flutarabine. Alternatively, or in addition, the SUR1-TRPM4 channel inhibitor is administered prior the onset of the cerebral edema-related side effects.

A method of treating or preventing adverse outcomes associated with tissue plasminogen activator (tPA) administration, cerebral edema-related side effects, cerebral edema associated with radiation therapy, or migraine headaches by administering an effective amount of a SUR1-TRPM4 channel inhibitor, such as glyburide, and optionally the co-administration of a second therapeutically active agent, to a subject in need thereof. Adverse outcomes associated with tPA include cerebral hemorrhage, cerebral edema, physical impairment or death. The administration of the SUR1-TRPM4 channel inhibitors occurs prior to the radiation therapy, during the radiation therapy, after the radiation therapy, or combinations thereof. The SUR1-TRPM4 channel inhibitor is administered prior to surgical excision of a brain tumor, CAR-T therapy, or administration of flutarabine. Alternatively, or in addition, the SUR1-TRPM4 channel inhibitor is administered prior the onset of the cerebral edema-related side effects.

A method of treating or preventing adverse outcomes associated with tissue plasminogen activator (tPA) administration, cerebral edema-related side effects, cerebral edema associated with radiation therapy, or migraine headaches by administering an effective amount of a SUR1-TRPM4 channel inhibitor, such as glyburide, and optionally the co-administration of a second therapeutically active agent, to a subject in need thereof. Adverse outcomes associated with tPA include cerebral hemorrhage, cerebral edema, physical impairment or death. The administration of the SUR1-TRPM4 channel inhibitors occurs prior to the radiation therapy, during the radiation therapy, after the radiation therapy, or combinations thereof. The SUR1-TRPM4 channel inhibitor is administered prior to surgical excision of a brain tumor, CAR-T therapy, or administration of flutarabine. Alternatively, or in addition, the SUR1-TRPM4 channel inhibitor is administered prior the onset of the cerebral edema-related side effects.

The inventors herein show that purinergic receptors regulate the conversion of macrophage pro-inflammatory reprogramming into anti-inflammatory phenotype in patients suffering from COVID-19 disease. Moreover, they show that P2Y receptor agonists repress NLRP3 inflammasome-dependent IL-1b secretion, but also impair the replication and the cytopathogenic effects of SARS-CoV-2. These results therefore suggest that some purinergic receptors agonists can treat acute lung injury and respiratory disease that are associated with SARS-CoV-2 infection. In addition, their results show that antagonists of the purinergic receptors P2X impair the replication of said virus. The present invention therefore proposes to use purinergic receptors modulators and NLR3-P2Y2R immune checkpoint modulators to treat patients suffering from a virus-induced acute respiratory distress syndrome.

The inventors herein show that purinergic receptors regulate the conversion of macrophage pro-inflammatory reprogramming into anti-inflammatory phenotype in patients suffering from COVID-19 disease. Moreover, they show that P2Y receptor agonists repress NLRP3 inflammasome-dependent IL-1b secretion, but also impair the replication and the cytopathogenic effects of SARS-CoV-2. These results therefore suggest that some purinergic receptors agonists can treat acute lung injury and respiratory disease that are associated with SARS-CoV-2 infection. In addition, their results show that antagonists of the purinergic receptors P2X impair the replication of said virus. The present invention therefore proposes to use purinergic receptors modulators and NLR3-P2Y2R immune checkpoint modulators to treat patients suffering from a virus-induced acute respiratory distress syndrome.

Described herein are methods for treating transthyretin (TTR) amyloidosis in a subject. The methods include specific dosing regimens that have great efficacy in treating the subjects and that are well tolerated in subjects

Described herein are methods for treating transthyretin (TTR) amyloidosis in a subject. The methods include specific dosing regimens that have great efficacy in treating the subjects and that are well tolerated in subjects

The invention relates to process for the preparation of grapiprant and its intermediates thereof. The invention also relates to grapiprant having a purity 98% or more and compounds of Formula (A), (B), (C) and (D) in an amount of 0.5 or less, relative to grapiprant, by area percentage of HPLC. The invention also relates to an amorphous form of grapiprant and process for preparation thereof.

The invention relates to process for the preparation of grapiprant and its intermediates thereof. The invention also relates to grapiprant having a purity 98% or more and compounds of Formula (A), (B), (C) and (D) in an amount of 0.5 or less, relative to grapiprant, by area percentage of HPLC. The invention also relates to an amorphous form of grapiprant and process for preparation thereof.

The present invention describes bioactive vitamin combinations that can be used in combination with other bioactive compounds, such as active drug ingredients or active vaccine components, to increase their therapeutic effects. The bioactive vitamin combinations comprise therapeutically effective amounts of L-Methylfolate, Adenosylcobalamin and Methylcobalamin.