A modulator of glucosylceramide degradation and pharmaceutical compositions containing the same. Also, the use of the modulator of glucosylceramide degradation and pharmaceutical compositions containing the same in the treatment or the prevention of viral infections and disorders associated to the viral infections, such as Zika infection, dengue infection, influenza infection and coronavirus infection.

A modulator of glucosylceramide degradation and pharmaceutical compositions containing the same. Also, the use of the modulator of glucosylceramide degradation and pharmaceutical compositions containing the same in the treatment or the prevention of viral infections and disorders associated to the viral infections, such as Zika infection, dengue infection, influenza infection and coronavirus infection.

This invention is referred to the field of medicine, namely preventative treatment, and may be used as a means of synergetic minimization of negative impact of flights on human health (brain, stomach, lungs, blood vessels, heart etc.) with application of known substances and medicines with newly discovered pharmacological properties in new conditions. The ultimate technical solution of this invention would be synergetic minimization of negative impact of flying on human health without foot swelling, belching, jet-lag, tiredness and fatigue etc. The claimed technical result is achieved by the method of synergetic minimization of negative impact of air flights on human health, including consumption of substances that improve osmotic concentration of blood plasma, in the form of oral rehydration solution, split into two intakes as a minimum, first intake in the amount of at least 0.3 liters up to 1 liter before boarding and further during the flight from half an hour to 2 hours at least 0.3 liters to 1 liter and on as-needed basis.

This invention is referred to the field of medicine, namely preventative treatment, and may be used as a means of synergetic minimization of negative impact of flights on human health (brain, stomach, lungs, blood vessels, heart etc.) with application of known substances and medicines with newly discovered pharmacological properties in new conditions. The ultimate technical solution of this invention would be synergetic minimization of negative impact of flying on human health without foot swelling, belching, jet-lag, tiredness and fatigue etc. The claimed technical result is achieved by the method of synergetic minimization of negative impact of air flights on human health, including consumption of substances that improve osmotic concentration of blood plasma, in the form of oral rehydration solution, split into two intakes as a minimum, first intake in the amount of at least 0.3 liters up to 1 liter before boarding and further during the flight from half an hour to 2 hours at least 0.3 liters to 1 liter and on as-needed basis.

The disclosure relates to methods, compounds for use and medicaments for the treatment of cancer comprising administering to a subject in need thereof a first agent in a therapeutically effective amount and one or more second agents each in a therapeutically effective amount. In some embodiments, the first agent comprises an EZH2 inhibitor. In certain embodiments, the first agent is tazemetostat or a pharmaceutically acceptable salt thereof and the methods of the disclosure are used to treat lung cancer, e.g., non-small cell lung cancer.

The disclosure relates to methods, compounds for use and medicaments for the treatment of cancer comprising administering to a subject in need thereof a first agent in a therapeutically effective amount and one or more second agents each in a therapeutically effective amount. In some embodiments, the first agent comprises an EZH2 inhibitor. In certain embodiments, the first agent is tazemetostat or a pharmaceutically acceptable salt thereof and the methods of the disclosure are used to treat lung cancer, e.g., non-small cell lung cancer.

A scored tablet comprises Tapentadol or a physiologically acceptable salt thereof embedded in a prolonged release matrix material; wherein the scored tablet provides prolonged release of Tapentadol or the physiologically acceptable salt thereof; wherein the scored tablet has a site of mechanical weakness along which it can be manually broken into two separate halves preferably having essentially the same size, shape and weight; and wherein the in vitro release profile of the scored tablet essentially corresponds to the in vitro release profile of each of the two separate halves. Also disclosed is a process for the preparation of such a scored tablet.

A scored tablet comprises Tapentadol or a physiologically acceptable salt thereof embedded in a prolonged release matrix material; wherein the scored tablet provides prolonged release of Tapentadol or the physiologically acceptable salt thereof; wherein the scored tablet has a site of mechanical weakness along which it can be manually broken into two separate halves preferably having essentially the same size, shape and weight; and wherein the in vitro release profile of the scored tablet essentially corresponds to the in vitro release profile of each of the two separate halves. Also disclosed is a process for the preparation of such a scored tablet.

Described herein is a multiplexed and high content screening assay using primary neurons for identifying small molecule modulators of neuronal mitochondrial mitostasis (MnMs). Also described is a high throughput screening assay using primary neurons for identifying small molecules that increase mitochondrial function, identified by measuring the electrochemical potential across the inner mitochondrial membrane and ATP generation. Most MnMs that increased mitochondrial content, length and/or health also increased mitochondrial function without altering neurite outgrowth. Some MnMs protect mitochondria in primary neurons from Aβ(1-42) toxicity, glutamate toxicity, increased oxidative stress and the toxic cellular environment associated with Alzheimer's disease. Some MnMs target mitochondria directly. An MnM also increases the synaptic activity of hippocampal neurons and is potent in vivo, increasing the respiration rate of brain mitochondria after administering the compound to mice. The MnMs were demonstrated to protect the mitochondrial population in neurons in an in vivo model of Alzheimer's Disease. Also described is a method for treating a patient suffering from a disorder characterized by dysfunction of neuronal mitostasis, comprising administering to the patient a therapeutically effective amount of a compound (MnM), or a pharmaceutically acceptable salt thereof.

Described herein is a multiplexed and high content screening assay using primary neurons for identifying small molecule modulators of neuronal mitochondrial mitostasis (MnMs). Also described is a high throughput screening assay using primary neurons for identifying small molecules that increase mitochondrial function, identified by measuring the electrochemical potential across the inner mitochondrial membrane and ATP generation. Most MnMs that increased mitochondrial content, length and/or health also increased mitochondrial function without altering neurite outgrowth. Some MnMs protect mitochondria in primary neurons from Aβ(1-42) toxicity, glutamate toxicity, increased oxidative stress and the toxic cellular environment associated with Alzheimer's disease. Some MnMs target mitochondria directly. An MnM also increases the synaptic activity of hippocampal neurons and is potent in vivo, increasing the respiration rate of brain mitochondria after administering the compound to mice. The MnMs were demonstrated to protect the mitochondrial population in neurons in an in vivo model of Alzheimer's Disease. Also described is a method for treating a patient suffering from a disorder characterized by dysfunction of neuronal mitostasis, comprising administering to the patient a therapeutically effective amount of a compound (MnM), or a pharmaceutically acceptable salt thereof.