This disclosure relates to the treatment of ischemic stroke at risk of brain swelling using SUR1-TRPM4 channel inhibitors. In some embodiments, the methods include treating patients suffering from a large hemispheric infarction. In certain embodiments, patients have a baseline NIHSS of ≤20. In other embodiments, patients have lesion volume of less than 140 cm3 or less than 125 cm3 as measured by MRI DWI or CTP. The patient may have suffered a wake-up stroke. Some embodiments involve treating patients who also undergo treatment with a thrombolytic agent and/or decompressive therapy.
The invention relates to the treatment of ischemic stroke at risk of brain swelling using SUR1-TRPM4 channel inhibitors in combination with mechanical thrombectomy. In some embodiments, the methods include treating patients suffering from a large hemispheric infarction. In certain embodiments, patients have a lesion volume of less than 140 cm3 or less than 125 cm3 as measured by MRI DWI or CTP. The patient may have suffered a wake-up stroke. Some embodiments involve treating patients who also undergo decompressive therapy.
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61B 17/22 - Instruments pour comprimer les ulcères ou similaires placés sur les organes internes du corpsInstruments pour curer les cavités des organes du corps, p. ex. des osInstruments, dispositifs ou procédés chirurgicaux pour l'élimination ou la destruction invasives des calculs utilisant des vibrations mécaniquesInstruments, dispositifs ou procédés chirurgicaux pour l'élimination non prévue ailleurs des obstructions dans les vaisseaux sanguins
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
3.
METHODS OF TREATING ISCHEMIC STROKE AT RISK FOR CEREBRAL OR CEREBELLAR EDEMA
The invention relates to the treatment of ischemic stroke at risk of brain swelling using SUR1-TRPM4 channel inhibitors in combination with mechanical thrombectomy. In some embodiments, the methods include treating patients suffering from a large hemispheric infarction. In certain embodiments, patients have a lesion volume of less than 140 cm3 or less than 125 cm3 as measured by MRI DWI or CTP. The patient may have suffered a wake-up stroke. Some embodiments involve treating patients who also undergo decompressive therapy.
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61B 17/22 - Instruments pour comprimer les ulcères ou similaires placés sur les organes internes du corpsInstruments pour curer les cavités des organes du corps, p. ex. des osInstruments, dispositifs ou procédés chirurgicaux pour l'élimination ou la destruction invasives des calculs utilisant des vibrations mécaniquesInstruments, dispositifs ou procédés chirurgicaux pour l'élimination non prévue ailleurs des obstructions dans les vaisseaux sanguins
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
4.
METHODS OF TREATING ISCHEMIC STROKE AT RISK FOR CEREBRAL OR CEREBELLAR EDEMA
The invention relates to the treatment of ischemic stroke at risk of brain swelling using SUR1-TRPM4 channel inhibitors in combination with mechanical thrombectomy. In some embodiments, the methods include treating patients suffering from a large hemispheric infarction. In certain embodiments, patients have a lesion volume of less than 300 cm3 or less than 125 cm3 as measured by MRI DWI or CTP. In certain embodiments, patients have a lesion volume expanding at a rate of <25 mL/h. The patient may have suffered a wake-up stroke. Some embodiments involve treating patients who also undergo decompressive therapy.
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
5.
METHODS OF TREATING ISCHEMIC STROKE AT RISK FOR CEREBRAL OR CEREBELLAR EDEMA
The invention relates to the treatment of ischemic stroke at risk of brain swelling using SUR1-TRPM4 channel inhibitors in combination with mechanical thrombectomy. In some embodiments, the methods include treating patients suffering from a large hemispheric infarction. In certain embodiments, patients have a lesion volume of less than 300 cm3 or less than 125 cm3 as measured by MRI DWI or CTP. In certain embodiments, patients have a lesion volume expanding at a rate of <25 mL/h. The patient may have suffered a wake-up stroke. Some embodiments involve treating
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
A61P 25/00 - Médicaments pour le traitement des troubles du système nerveux
6.
METHODS OF TREATING ISCHEMIC STROKE AT RISK FOR CEREBRAL OR CEREBELLAR EDEMA USING A SUR1-TRPM4 CHANNEL INHIBITOR
The invention relates to the treatment of ischemic stroke at risk of brain swelling using SUR1-TRPM4 channel inhibitors. In some embodiments, the SUR1-TRPM4 channel inhibitor is used in combination with mechanical thrombectomy. In some embodiments, the methods include treating patients suffering from a large hemispheric infarction. In certain embodiments, patients have a baseline NIHSS of ≤ 20. In certain embodiments, patients have a lesion volume of less than 300 cm3, less than 140 cm3, or less than 125 cm3 as measured by MRI DWI or CTP. In certain embodiments, patients have a lesion volume expanding at a rate or < 25 mL/h. The patient may have suffered a wake-up stroke. Some embodiments involve treating patients who also undergo treatment with a thrombolytic agent and/or decompressive therapy.
A61B 17/22 - Instruments pour comprimer les ulcères ou similaires placés sur les organes internes du corpsInstruments pour curer les cavités des organes du corps, p. ex. des osInstruments, dispositifs ou procédés chirurgicaux pour l'élimination ou la destruction invasives des calculs utilisant des vibrations mécaniquesInstruments, dispositifs ou procédés chirurgicaux pour l'élimination non prévue ailleurs des obstructions dans les vaisseaux sanguins
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
7.
METHODS OF TREATING ISCHEMIC STROKE AT RISK FOR CEREBRAL OR CEREBELLAR EDEMA
The invention relates to the treatment of ischemic stroke at risk of brain swelling using SUR1-TRPM4 channel inhibitors. In some embodiments, the SUR1-TRPM4 channel inhibitor is used in combination with mechanical thrombectomy. In some embodiments, the methods include treating patients suffering from a large hemispheric infarction. In certain embodiments, patients have a baseline NIHSS of ≤ 20. In certain embodiments, patients have a lesion volume of less than 140 cm3or less than 125 cm3 as measured by MRI DWI or CTP. The patient may have suffered a wake-up stroke. Some embodiments involve treating patients who also undergo treatment with a thrombolytic agent and/or decompressive therapy.
A61B 17/22 - Instruments pour comprimer les ulcères ou similaires placés sur les organes internes du corpsInstruments pour curer les cavités des organes du corps, p. ex. des osInstruments, dispositifs ou procédés chirurgicaux pour l'élimination ou la destruction invasives des calculs utilisant des vibrations mécaniquesInstruments, dispositifs ou procédés chirurgicaux pour l'élimination non prévue ailleurs des obstructions dans les vaisseaux sanguins
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
8.
METHODS OF TREATING ISCHEMIC STROKE WITH LARGE VESSEL OCCLUSION USING A SUR1-TRPM4 CHANNEL INHIBITOR
The invention relates to treating an ischemic stroke patient with a large vessel occlusion, comprising administering a therapeutically effect amount of a SUR1-TRPM4 inhibitor, wherein the patient has an ASPECTS score of 0-2. In certain embodiments, patients have a lesion volume of less than 140 cm3or less than 125 cm3 as measured by MRI DWI or CTP. The patient may have suffered a wake-up stroke. Some embodiments involve treating patients who also undergo decompressive therapy.
A61B 17/22 - Instruments pour comprimer les ulcères ou similaires placés sur les organes internes du corpsInstruments pour curer les cavités des organes du corps, p. ex. des osInstruments, dispositifs ou procédés chirurgicaux pour l'élimination ou la destruction invasives des calculs utilisant des vibrations mécaniquesInstruments, dispositifs ou procédés chirurgicaux pour l'élimination non prévue ailleurs des obstructions dans les vaisseaux sanguins
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
9.
METHODS OF TREATING ISCHEMIC STROKE AT RISK FOR CEREBRAL OR CEREBELLAR EDEMA USING A SUR1-TRPM4 CHANNEL INHIBITOR
The invention relates to the treatment of ischemic stroke at risk of brain swelling using SUR1-TRPM4 channel inhibitors. In some embodiments, the SUR1-TRPM4 channel inhibitor is used in combination with mechanical thrombectomy. In some embodiments, the methods include treating patients suffering from a large hemispheric infarction. In certain embodiments, patients have a baseline NIHSS of ≤ 20. In certain embodiments, patients have a lesion volume of less than 300 cm3, less than 140 cm3, or less than 125 cm3 as measured by MRI DWI or CTP. In certain embodiments, patients have a lesion volume expanding at a rate or < 25 mL/h. The patient may have suffered a wake-up stroke. Some embodiments involve treating patients who also undergo treatment with a thrombolytic agent and/or decompressive therapy.
A61B 17/22 - Instruments pour comprimer les ulcères ou similaires placés sur les organes internes du corpsInstruments pour curer les cavités des organes du corps, p. ex. des osInstruments, dispositifs ou procédés chirurgicaux pour l'élimination ou la destruction invasives des calculs utilisant des vibrations mécaniquesInstruments, dispositifs ou procédés chirurgicaux pour l'élimination non prévue ailleurs des obstructions dans les vaisseaux sanguins
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
Methods and formulations for minimizing or avoiding the sorption of glyburide to surfaces of delivery tubing, filters, bags, and other containers and materials, thereby storing and delivering a more stable product, delivering a predictable and accurate dose of glyburide, while minimizing impurities, avoiding drug waste, reducing cost, and significantly reducing the amount of dosing solution that must be infused into the patient.
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 9/19 - Préparations médicinales caractérisées par un aspect particulier à l'état particulaire, p. ex. poudres lyophilisées
A61K 47/18 - AminesAmidesUréesComposés d’ammonium quaternaireAcides aminésOligopeptides ayant jusqu’à cinq acides aminés
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
11.
METHODS OF INTRAVENOUS ADMINISTRATION OF GLYBURIDE
The present disclosure is drawn to a method of treating a patient in need of treatment, comprising identifying a patient in need of treatment for stroke, traumatic brain injury, spinal cord injury, myocardial infarction, shock, organ ischemia, ventricular arrhythmias, ischemic injury, or hypoxia/ischemia; administering a bolus of glyburide to the patient; and administering a continuous infusion of glyburide to the patient at from about 15 μg/hr and about 300 μg/hr, wherein the continuous infusion glyburide is administered for a period of time more than about 20 hours.
3 as measured by MRI DWI or CTP. The patient may have suffered a wake-up stroke. Some embodiments involve treating patients who also undergo decompressive therapy.
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61B 17/22 - Instruments pour comprimer les ulcères ou similaires placés sur les organes internes du corpsInstruments pour curer les cavités des organes du corps, p. ex. des osInstruments, dispositifs ou procédés chirurgicaux pour l'élimination ou la destruction invasives des calculs utilisant des vibrations mécaniquesInstruments, dispositifs ou procédés chirurgicaux pour l'élimination non prévue ailleurs des obstructions dans les vaisseaux sanguins
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
13.
LOW-SORBING GLYBURIDE KIT, FORMULATION AND METHODS
The disclosure relates to compositions and methods of using a pomalidomide derivative that exhibits improved pharmacological effects as compared to pomalidomide for treating brain diseases. The pomalidomide derivative exhibits excellent binding to cereblon, has almost no cytotoxicity, is unlikely to cause teratogenic adverse effects, can control TNF-α expression, exhibits excellent in vivo pharmacokinetic stability while suppressing oxidative stress, ameliorates a decrease in motor function which is a symptom of Parkinson's disease, and increases tyrosine hydroxylase expression which is reduced by Parkinson's disease, and thus can be used for preventing or treating brain diseases such as Parkinson's disease.
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.
A61K 31/4045 - Indole-alkylaminesLeurs amides, p. ex. sérotonine, mélatonine
A61K 31/7076 - Composés ayant des radicaux saccharide et des hétérocycles ayant l'azote comme hétéro-atome d'un cycle, p. ex. nucléosides, nucléotides contenant des cycles à six chaînons avec l'azote comme hétéro-atome d'un cycle contenant des pyrimidines condensées ou non-condensées contenant des purines, p. ex. adénosine, acide adénylique
A61K 38/48 - Hydrolases (3) agissant sur des liaisons peptidiques (3.4)
3 as measured by MRI DWI or CTP. The patient may have suffered a wake-up stroke. Some embodiments involve treating patients who also undergo treatment with a thrombolytic agent and/or decompressive therapy.
3 as measured by MRI DWI or CTP. The patient may have suffered a wake-up stroke. Some embodiments involve treating patients who also undergo decompressive therapy.
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61B 17/22 - Instruments pour comprimer les ulcères ou similaires placés sur les organes internes du corpsInstruments pour curer les cavités des organes du corps, p. ex. des osInstruments, dispositifs ou procédés chirurgicaux pour l'élimination ou la destruction invasives des calculs utilisant des vibrations mécaniquesInstruments, dispositifs ou procédés chirurgicaux pour l'élimination non prévue ailleurs des obstructions dans les vaisseaux sanguins
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
17.
METHODS OF TREATING INJURIES OR CONDITIONS RELATED TO CNS EDEMA
The present technology is related to reducing or treating neurological swelling and related conditions with SUR1-TRPM4 channel inhibitors. In some embodiments, the methods include: reducing late neurological deterioration or preventing death, reducing cerebral midline shift, reducing the degree of disability in a subject, counteracting blood glucose levels in a subject receiving a SUR1-TRPM4 channel inhibitor, preventing brain swelling, monitoring liver enzyme activity along with treating injury or conditions related to CNS edema, or monitoring cardiac activity along with treating injury or conditions related to CNS edema.
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/166 - Amides, p. ex. acides hydroxamiques ayant des cycles aromatiques, p. ex. colchicine, aténolol, progabide ayant l'atome de carbone d'un groupe carboxamide lié directement au cycle aromatique, p. ex. procaïnamide, procarbazine, métoclopramide, labétalol
A61K 31/451 - Pipéridines non condensées, p. ex. pipérocaïne ayant un carbocycle lié directement à l'hétérocycle, p. ex. glutéthimide, mépéridine, lopéramide, phencyclidine, piminodine
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
Methods and formulations for minimizing or avoiding the sorption of glyburide to surfaces of delivery tubing, filters, bags, and other containers and materials, thereby storing and delivering a more stable product, delivering a predictable and accurate dose of glyburide, while minimizing impurities, avoiding drug waste, reducing cost, and significantly reducing the amount of dosing solution that must be infused into the patient.
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 9/19 - Préparations médicinales caractérisées par un aspect particulier à l'état particulaire, p. ex. poudres lyophilisées
A61K 47/18 - AminesAmidesUréesComposés d’ammonium quaternaireAcides aminésOligopeptides ayant jusqu’à cinq acides aminés
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
19.
METHODS OF TREATING INJURIES OR CONDITIONS RELATED TO CNS EDEMA
The present technology is related to reducing or treating neurological swelling and related conditions with SUR1-TRPM4 channel inhibitors. In some embodiments, the methods include: reducing late neurological deterioration or preventing death, reducing cerebral midline shift, reducing the degree of disability in a subject, counteracting blood glucose levels in a subject receiving a SUR1-TRPM4 channel inhibitor, preventing brain swelling, monitoring liver enzyme activity along with treating injury or conditions related to CNS edema, or monitoring cardiac activity along with treating injury or conditions related to CNS edema.
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/166 - Amides, p. ex. acides hydroxamiques ayant des cycles aromatiques, p. ex. colchicine, aténolol, progabide ayant l'atome de carbone d'un groupe carboxamide lié directement au cycle aromatique, p. ex. procaïnamide, procarbazine, métoclopramide, labétalol
A61K 31/451 - Pipéridines non condensées, p. ex. pipérocaïne ayant un carbocycle lié directement à l'hétérocycle, p. ex. glutéthimide, mépéridine, lopéramide, phencyclidine, piminodine
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
20.
Methods of intravenous administration of glyburide
The present disclosure is drawn to a method of treating a patient in need of treatment, comprising identifying a patient in need of treatment for stroke, traumatic brain injury, spinal cord injury, myocardial infarction, shock, organ ischemia, ventricular arrhythmias, ischemic injury, or hypoxia/ischemia; administering a bolus of glyburide to the patient; and administering a continuous infusion of glyburide to the patient at from about 15 μg/hr and about 300 μg/hr, wherein the continuous infusion glyburide is administered for a period of time more than about 20 hours.
Methods and formulations for minimizing or avoiding the sorption of glyburide to surfaces of delivery tubing, filters, bags, and other containers and materials, thereby storing and delivering a more stable product, delivering a predictable and accurate dose of glyburide, while minimizing impurities, avoiding drug waste, reducing cost, and significantly reducing the amount of dosing solution that must be infused into the patient.
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61K 9/19 - Préparations médicinales caractérisées par un aspect particulier à l'état particulaire, p. ex. poudres lyophilisées
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
A61K 47/18 - AminesAmidesUréesComposés d’ammonium quaternaireAcides aminésOligopeptides ayant jusqu’à cinq acides aminés
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
22.
METHOD FOR TREATING SUBJECTS SUFFERING FROM CENTRAL NERVOUS SYSTEM CONTUSIONS
Methods of inhibiting expansion of cerebral contusion, inhibiting secondary hemorrhage and capillary fragmentation in the brain, reducing pericontusional edema and hemorrhage size in the brain, decreasing water content in a CNS tissue, inhibiting disruption of the blood-brain barrier, inhibiting CNS contusion progression and improving post-contusion motor function, inhibiting microvascular impairment caused by endothelial cell swelling and fragmentation, inhibiting extravasation of blood into the brain parenchyma of a subject, inhibiting endothelial cell breakdown in a brain tissue, inhibiting extravasation of endovascular fluids into the brain's interstitium, decreasing vasogenic edema as measured by T2 flair magnetic resonance imaging, and decreasing matrix metalloprotease concentration in a CNS tissue, by administering a SUR1-TRPM4 channel inhibitor alone or in combination with one or more drugs or agents.
The present technology is related to reducing or treating neurological swelling and related conditions with SUR1-TRPM4 channel inhibitors. In some embodiments, the methods include: reducing late neurological deterioration or preventing death, reducing cerebral midline shift, reducing the degree of disability in a subject, counteracting blood glucose levels in a subject receiving a SUR1-TRPM4 channel inhibitor, preventing brain swelling, monitoring liver enzyme activity along with treating injury or conditions related to CNS edema, or monitoring cardiac activity along with treating injury or conditions related to CNS edema.
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/166 - Amides, p. ex. acides hydroxamiques ayant des cycles aromatiques, p. ex. colchicine, aténolol, progabide ayant l'atome de carbone d'un groupe carboxamide lié directement au cycle aromatique, p. ex. procaïnamide, procarbazine, métoclopramide, labétalol
A61K 31/451 - Pipéridines non condensées, p. ex. pipérocaïne ayant un carbocycle lié directement à l'hétérocycle, p. ex. glutéthimide, mépéridine, lopéramide, phencyclidine, piminodine
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
24.
METHODS OF MEDICAL TREATMENT WITH SUR1-TRPM4 CHANNEL INHIBITORS
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.
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61P 25/00 - Médicaments pour le traitement des troubles du système nerveux
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61K 31/7076 - Composés ayant des radicaux saccharide et des hétérocycles ayant l'azote comme hétéro-atome d'un cycle, p. ex. nucléosides, nucléotides contenant des cycles à six chaînons avec l'azote comme hétéro-atome d'un cycle contenant des pyrimidines condensées ou non-condensées contenant des purines, p. ex. adénosine, acide adénylique
The present disclosure is drawn to a method of treating a patient in need of treatment, comprising identifying a patient in need of treatment for stroke, traumatic brain injury, spinal cord injury, myocardial infarction, shock, organ ischemia, ventricular arrhythmias, ischemic injury, or hypoxia/ischemia; administering a bolus of glyburide to the patient; and administering a continuous infusion of glyburide to the patient at from about 15 μg/hr and about 300 μg/hr, wherein the continuous infusion glyburide is administered for a period of time more than about 20 hours.
The present invention provides compositions, methods for lyophilizing compounds and making pharmaceutical compositions, and kits providing solutions and lyophilized formulations of compounds. The compositions, methods, and kits are particularly useful in pharmaceutical applications involving therapeutic agents that have low solubility at low and medium pH values. Certain embodiments provide methods for lyophilizing compounds in liquid solutions, which include the steps of: a) preparing aqueous solutions of a compound of interest in the absence of buffer; b) adjusting the pH to high values of pH in order to increase the solubility of the compound of interest; and c) freeze-drying the solution to provide a lyophilized solid composition. Aqueous solutions including buffer are also disclosed. Lyophilized formulations, including micronized and non-micronized powders, are provided.
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/175 - Amides, p. ex. acides hydroxamiques ayant le groupe N-C(O)-N ou N-C(S)-N, p. ex. urée, thiourée, carmustine ayant le groupe , N-C(O)-N=N- ou , p. ex. carbonohydrazides, carbazones, semicarbazides, semicarbazonesLeurs thio-analogues
A61K 31/451 - Pipéridines non condensées, p. ex. pipérocaïne ayant un carbocycle lié directement à l'hétérocycle, p. ex. glutéthimide, mépéridine, lopéramide, phencyclidine, piminodine
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
NSC antagonists are disclosed as useful in the treatment of dementia, in delaying the onset of dementia, and in the prevention of dementia. Dementia so treated may be, for example, Alzheimer's Disease (AD). NSC antagonists for treating dementia such as AD may be administered alone, a) in combination with other drugs used for treating dementia, b) in combination with drugs that stabilize or increase blood plasma glucose levels, or with both a) and b). Pharmaceutical compositions, dosage forms, and methods for using the same are disclosed, which include NSC antagonists, NSC antagonists combined with dementia drugs, NSC antagonists combined with glucose-level stabilizing or enhancing drugs, or combinations of these. Dosage forms may be designed to provide stable plasma levels for extended periods of time. Exemplary pharmaceutical compositions include compositions including glibenclamide and memantine; glibenclamide and donepezil; tolbutamide and memantine; tolbutamide and donepezil; and these compositions further including glucagon and/or glucose.
A61K 31/175 - Amides, p. ex. acides hydroxamiques ayant le groupe N-C(O)-N ou N-C(S)-N, p. ex. urée, thiourée, carmustine ayant le groupe , N-C(O)-N=N- ou , p. ex. carbonohydrazides, carbazones, semicarbazides, semicarbazonesLeurs thio-analogues
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
28.
Methods of intravenous administration of glyburide
The present disclosure is drawn to a method of treating a patient in need of treatment, comprising identifying a patient in need of treatment for stroke, traumatic brain injury, spinal cord injury, myocardial infarction, shock, organ ischemia, ventricular arrhythmias, ischemic injury, or hypoxia/ischemia; administering a bolus of glyburide to the patient; and administering a continuous infusion of glyburide to the patient at from about 15 μg/hr and about 300 μg/hr, wherein the continuous infusion glyburide is administered for a period of time more than about 20 hours.
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.
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61P 25/00 - Médicaments pour le traitement des troubles du système nerveux
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61K 31/7076 - Composés ayant des radicaux saccharide et des hétérocycles ayant l'azote comme hétéro-atome d'un cycle, p. ex. nucléosides, nucléotides contenant des cycles à six chaînons avec l'azote comme hétéro-atome d'un cycle contenant des pyrimidines condensées ou non-condensées contenant des purines, p. ex. adénosine, acide adénylique
The present invention provides compositions, methods for lyophilizing compounds and making pharmaceutical compositions, and kits providing solutions and lyophilized formulations of compounds. The compositions, methods, and kits are particularly useful in pharmaceutical applications involving therapeutic agents that have low solubility at low pH and medium pH values. Certain embodiments provide methods for lyophilizing compounds in liquid solutions, which include the steps of: a) preparing aqueous solutions of a compound of interest in the absence of buffer; b) adjusting the pH to high values of pH in order to increase the solubility of the compound of interest; and c) freeze-drying the solution to provide a lyophilized solid composition. Aqueous solutions including buffer are also disclosed. Lyophilized formulations, including micronized and non-micronized powders, are provided.
A61K 31/341 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à cinq chaînons avec un oxygène comme seul hétéro-atome d'un cycle, p. ex. isosorbide non condensés avec un autre cycle, p. ex. ranitidine, furosémide, bufétolol, muscarine
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 9/19 - Préparations médicinales caractérisées par un aspect particulier à l'état particulaire, p. ex. poudres lyophilisées
A61K 31/175 - Amides, p. ex. acides hydroxamiques ayant le groupe N-C(O)-N ou N-C(S)-N, p. ex. urée, thiourée, carmustine ayant le groupe , N-C(O)-N=N- ou , p. ex. carbonohydrazides, carbazones, semicarbazides, semicarbazonesLeurs thio-analogues
A61K 31/451 - Pipéridines non condensées, p. ex. pipérocaïne ayant un carbocycle lié directement à l'hétérocycle, p. ex. glutéthimide, mépéridine, lopéramide, phencyclidine, piminodine
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
NSC antagonists are disclosed as useful in the treatment of dementia, in delaying the onset of dementia, and in the prevention of dementia. Dementia so treated may be, for example, Alzheimer's Disease (AD). NSC antagonists for treating dementia such as AD may be administered alone, a) in combination with other drugs used for treating dementia, b) in combination with drugs that stabilize or increase blood plasma glucose levels, or with both a) and b). Pharmaceutical compositions, dosage forms, and methods for using the same are disclosed, which include NSC antagonists, NSC antagonists combined with dementia drugs, NSC antagonists combined with glucose-level stabilizing or enhancing drugs, or combinations of these. Dosage forms may be designed to provide stable plasma levels for extended periods of time. Exemplary pharmaceutical compositions include compositions including glibenclamide and memantine; glibenclamide and donepezil; tolbutamide and memantine; tolbutamide and donepezil; and these compositions further including glucagon and/or glucose.
A61K 31/175 - Amides, p. ex. acides hydroxamiques ayant le groupe N-C(O)-N ou N-C(S)-N, p. ex. urée, thiourée, carmustine ayant le groupe , N-C(O)-N=N- ou , p. ex. carbonohydrazides, carbazones, semicarbazides, semicarbazonesLeurs thio-analogues
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
32.
Methods of reducing or preventing intimal damage caused by mechanical stimulation of endothelial cells
Embodiments of the disclosure encompass methods and/or compositions for ameliorating or preventing intimal damage caused by mechanical stimulation of endothelial cells. The damage may be caused by use of a device within an artery, vein, or capillary of an individual, such as to remove a thrombus, an embolus or an atherosclerotic plaque in the vessel. Treatment and prevention embodiments concern therapeutically effective amounts of one or more antagonists of the SUR1-TRPM4 channel that is upregulated upon the mechanical stimulation.
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 31/196 - Acides carboxyliques, p. ex. acide valproïque ayant un groupe amino le groupe amino étant lié directement à un cycle, p. ex. acide anthranilique, acide méfénamique, diclofénac, chlorambucil
A61K 31/132 - Amines, p. ex. amantadine ayant plusieurs groupes amino, p. ex. spermidine, putrescine
The present disclosure is drawn to a method of treating a patient in need of treatment, comprising identifying a patient in need of treatment for stroke, traumatic brain injury, spinal cord injury, myocardial infarction, shock, organ ischemia, ventricular arrhythmias, ischemic injury, or hypoxia/ischemia; administering a bolus of glyburide to the patient; and administering a continuous infusion of glyburide to the patient at from about 15 μg/hr and about 300 μg/hr, wherein the continuous infusion glyburide is administered for a period of time more than about 20 hours.
The present disclosure is drawn to a method of treating a patient in need of treatment, comprising identifying a patient in need of treatment for stroke, traumatic brain injury, spinal cord injury, myocardial infarction, shock, organ ischemia, ventricular arrhythmias, ischemic injury, or hypoxia/ischemia; administering a bolus of glyburide to the patient; and administering a continuous infusion of glyburide to the patient at from about 15 μg/hr and about 300 μg/hr, wherein the continuous infusion glyburide is administered for a period of time more than about 20 hours.
The invention provides liquid formulations of compounds that act at sulfonylurea receptors that are suitable for intravenous and intra-arterial infusion. Compounds active at a sulfonylurea receptor include glibenclamide, tolbutamide, repaglinide, nateglinide, meglitinide, midaglizole, LY397364, LY389382, glyclazide, and glimepiride. Liquid formulations may be concentrated solutions suitable for storage; may be diluted (e.g., dilution of 1:1 or 1:1.2) suitable for bolus injections, and may be further diluted (e.g., dilution of 1:10 or 1:20 or more) for intravenous and intra-arterial infusion over an extended period of time. For example, a liquid formulation may include at least about 0.05 mg/ml glibenclamide in a water-based solution including 40% polyethylene glycol 300, 10% Ethanol, 50% water, at about pH 9. The solution may include a buffer, and is suitable for storage in refrigerator or at room temperature. This solution may be diluted 1:1, or more (e.g., 1:20) without precipitation of the glibenclamide.
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
A61K 47/10 - AlcoolsPhénolsLeurs sels, p. ex. glycérolPolyéthylène glycols [PEG]PoloxamèresAlkyléthers de PEG/POE
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
36.
Methods of intravenous administration of glyburide
The present disclosure is drawn to a method of treating a patient in need of treatment, comprising identifying a patient in need of treatment for stroke, traumatic brain injury, spinal cord injury, myocardial infarction, shock, organ ischemia, ventricular arrhythmias, ischemic injury, or hypoxia/ischemia; administering a bolus of glyburide to the patient; and administering a continuous infusion of glyburide to the patient at from about 15 μg/hr and about 300 μg/hr, wherein the continuous infusion glyburide is administered for a period of time more than about 20 hours.
The present disclosure is drawn to a method of administering glyburide intravenously to a subject over a period of time as a first bolus administration of glyburide; a second bolus administration of glyburide, after the first bolus; and a first continuous infusion administration of glyburide, wherein the first continuous infusion is administered at a first rate of administration for a first period of time, after the second bolus administration of glyburide.
A61K 31/175 - Amides, p. ex. acides hydroxamiques ayant le groupe N-C(O)-N ou N-C(S)-N, p. ex. urée, thiourée, carmustine ayant le groupe , N-C(O)-N=N- ou , p. ex. carbonohydrazides, carbazones, semicarbazides, semicarbazonesLeurs thio-analogues
A01N 47/34 - Urées ou thiourées contenant les groupes N—CO—N ou N—CS—N contenant les groupes p. ex. biuretLeurs thio-analoguesProduits de condensation urée-aldéhyde
The present invention provides compositions, methods for lyophilizing compounds and making pharmaceutical compositions, and kits providing solutions and lyophilized formulations of compounds. The compositions, methods, and kits are particularly useful in pharmaceutical applications involving therapeutic agents that have low solubility at low pH and medium pH values. Certain embodiments provide methods for lyophilizing compounds in liquid solutions, which include the steps of: a) preparing aqueous solutions of a compound of interest in the absence of buffer; b) adjusting the pH to high values of pH in order to increase the solubility of the compound of interest; and c) freeze-drying the solution to provide a lyophilized solid composition. Aqueous solutions including buffer are also disclosed. Lyophilized formulations, including micronized and non-micronized powders, are provided.
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 9/19 - Préparations médicinales caractérisées par un aspect particulier à l'état particulaire, p. ex. poudres lyophilisées
A61K 31/175 - Amides, p. ex. acides hydroxamiques ayant le groupe N-C(O)-N ou N-C(S)-N, p. ex. urée, thiourée, carmustine ayant le groupe , N-C(O)-N=N- ou , p. ex. carbonohydrazides, carbazones, semicarbazides, semicarbazonesLeurs thio-analogues
A61K 31/451 - Pipéridines non condensées, p. ex. pipérocaïne ayant un carbocycle lié directement à l'hétérocycle, p. ex. glutéthimide, mépéridine, lopéramide, phencyclidine, piminodine
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
39.
++ activated ATP-sensitive cation channels regulated by SUR1 channels
NSC antagonists are disclosed as useful in the treatment of dementia, in delaying the onset of dementia, and in the prevention of dementia. Dementia so treated may be, for example, Alzheimer's Disease (AD). NSC antagonists for treating dementia such as AD may be administered alone, a) in combination with other drugs used for treating dementia, b) in combination with drugs that stabilize or increase blood plasma glucose levels, or with both a) and b). Pharmaceutical compositions, dosage forms, and methods for using the same are disclosed, which include NSC antagonists, NSC antagonists combined with dementia drugs, NSC antagonists combined with glucose-level stabilizing or enhancing drugs, or combinations of these. Dosage forms may be designed to provide stable plasma levels for extended periods of time. Exemplary pharmaceutical compositions include compositions including glibenclamide and memantine; glibenclamide and donepezil; tolbutamide and memantine; tolbutamide and donepezil; and these compositions further including glucagon and/or glucose.
The present invention provides compositions, methods for lyophilizing compounds and making pharmaceutical compositions, and kits providing solutions and lyophilized formulations of compounds. The compositions, methods, and kits are particularly useful in pharmaceutical applications involving therapeutic agents that have low solubility at low pH and medium pH values. Certain embodiments provide methods for lyophilizing compounds in liquid solutions, which include the steps of: a) preparing aqueous solutions of a compound of interest in the absence of buffer; b) adjusting the pH to high values of pH in order to increase the solubility of the compound of interest; and c) freeze-drying the solution to provide a lyophilized solid composition. Aqueous solutions including buffer are also disclosed. Lyophilized formulations, including micronized and non-micronized powders, are provided.
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61K 31/451 - Pipéridines non condensées, p. ex. pipérocaïne ayant un carbocycle lié directement à l'hétérocycle, p. ex. glutéthimide, mépéridine, lopéramide, phencyclidine, piminodine
A61K 31/175 - Amides, p. ex. acides hydroxamiques ayant le groupe N-C(O)-N ou N-C(S)-N, p. ex. urée, thiourée, carmustine ayant le groupe , N-C(O)-N=N- ou , p. ex. carbonohydrazides, carbazones, semicarbazides, semicarbazonesLeurs thio-analogues
A61K 9/19 - Préparations médicinales caractérisées par un aspect particulier à l'état particulaire, p. ex. poudres lyophilisées
41.
Methods of intravenous administration of glyburide and other drugs
Methods of administering glyburide, or other drug, are disclosed. The novel methods disclosed herein include intravenous methods of administering glyburide, or other drug, over periods of more than an hour, preferably over periods of about 72 hours. The novel methods include administering a bolus of glyburide, or other drug, followed by a first continuous infusion administration of glyburide, or other drug; and optionally a second or further bolus administration of glyburide, or other drug, and/or a second or further continuous infusion administration of glyburide, or other drug. These methods are effective to rapidly achieve a desired level of glyburide, or other drug, and to provide a substantially steady level of glyburide, or other drug, over a desired period of time. The methods disclosed herein may be useful for treating a subject in need of treatment for, e.g., acute stroke (ischemic and hemorrhagic), traumatic brain injury (TBI), spinal cord injury (SCI), myocardial infarction (MI), shock (including hemorrhagic shock), organ ischemia, and ventricular arrhythmias. These methods provide for the rapid achievement and maintenance of therapeutic glyburide, or other drug, plasma levels over an extended period of time, and further avoid excessive levels of drug and so avoid possible drug side-effects.
A61K 31/175 - Amides, p. ex. acides hydroxamiques ayant le groupe N-C(O)-N ou N-C(S)-N, p. ex. urée, thiourée, carmustine ayant le groupe , N-C(O)-N=N- ou , p. ex. carbonohydrazides, carbazones, semicarbazides, semicarbazonesLeurs thio-analogues
A01N 47/34 - Urées ou thiourées contenant les groupes N—CO—N ou N—CS—N contenant les groupes p. ex. biuretLeurs thio-analoguesProduits de condensation urée-aldéhyde
Methods of administering glyburide, or other drug, are disclosed. The novel methods disclosed herein include intravenous methods of administering glyburide, or other drug, over periods of more than an hour, preferably over periods of about 72 hours. The novel methods include administering a bolus of glyburide, or other drug, followed by a first continuous infusion administration of glyburide, or other drug; and optionally a second or further bolus administration of glyburide, or other drug, and/or a second or further continuous infusion administration of glyburide, or other drug. These methods are effective to rapidly achieve a desired level of glyburide, or other drug, and to provide a substantially steady level of glyburide, or other drug, over a desired period of time. The methods disclosed herein may be useful for treating a subject in need of treatment for, e.g., acute stroke (ischemic and hemorrhagic), traumatic brain injury (TBI), spinal cord injury (SCI), myocardial infarction (MI), shock (including hemorrhagic shock), organ ischemia, and ventricular arrhythmias. These methods provide for the rapid achievement and maintenance of therapeutic glyburide, or other drug, plasma levels over an extended period of time, and further avoid excessive levels of drug and so avoid possible drug side-effects.
The present invention provides compositions, methods for lyophilizing compounds and making pharmaceutical compositions, and kits providing solutions and lyophilized formulations of compounds. The compositions, methods, and kits are particularly useful in pharmaceutical applications involving therapeutic agents that have low solubility at low pH and medium pH values. Certain embodiments provide methods for lyophilizing compounds in liquid solutions, which include the steps of: a) preparing aqueous solutions of a compound of interest in the absence of buffer; b) adjusting the pH to high values of pH in order to increase the solubility of the compound of interest; and c) freeze-drying the solution to provide a lyophilized solid composition. Aqueous solutions including buffer are also disclosed. Lyophilized formulations, including micronized and non-micronized powders, are provided.
The invention provides liquid formulations of compounds that act at sulfonylurea receptors that are suitable for intravenous and intra-arterial infusion. Compounds active at a sulfonylurea receptor include glibenclamide, tolbutamide, repaglinide, nateglinide, meglitinide, midaglizole, LY397364, LY389382, glyclazide, and glimepiride. Liquid formulations may be concentrated solutions suitable for storage; may be diluted (e.g., dilution of 1 : 1 or 1 : 1.2) suitable for bolus injections, and may be further diluted (e.g., dilution of 1 : 10 or 1 : 20 or more) for intravenous and intra-arterial infusion over an extended period of time. For example, a liquid formulation may include at least about 0.05 mg/ml glibenclamide in a water-based solution including 40% polyethylene glycol 300, 10% Ethanol, 50% water, at about pH 9. The solution may include a buffer, and is suitable for storage in refrigerator or at room temperature. This solution may be diluted 1 : 1, or more (e.g., 1 :20) without precipitation of the glibenclamide.
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61K 47/10 - AlcoolsPhénolsLeurs sels, p. ex. glycérolPolyéthylène glycols [PEG]PoloxamèresAlkyléthers de PEG/POE
A61K 47/34 - Composés macromoléculaires obtenus par des réactions autres que celles faisant intervenir uniquement des liaisons non saturées carbone-carbone, p. ex. polyesters, acides polyaminés, polysiloxanes, polyphosphazines, copolymères de polyalkylène glycol ou de poloxamères
A61P 3/10 - Médicaments pour le traitement des troubles du métabolisme de l'homéostase du glucose de l'hyperglycémie, p. ex. antidiabétiques
45.
IMPROVED FORMULATIONS AND METHODS FOR LYOPHILIZATION AND LYOPHILATES PROVIDED THEREBY
The present invention provides compositions, methods for lyophilizing compounds and making pharmaceutical compositions, and kits providing solutions and lyophilized formulations of compounds. The compositions, methods, and kits are particularly useful in pharmaceutical applications involving therapeutic agents that have low solubility at low pH and medium pll values. Certain embodiments provide methods for lyophilizing compounds in liquid solutions, which include the steps of: a) preparing aqueous solutions of a compound of interest in the absence of buffer; b) adjusting the pH to high values of pH in order to increase the solubility of the compound of interest; and c) frecze-drying the solution to provide a lyophilized solid composition. Aqueous solutions including buffer are also disclosed. Lyophilized formulations, including micronized and non-micronized powders, are provided.
A61K 31/175 - Amides, p. ex. acides hydroxamiques ayant le groupe N-C(O)-N ou N-C(S)-N, p. ex. urée, thiourée, carmustine ayant le groupe , N-C(O)-N=N- ou , p. ex. carbonohydrazides, carbazones, semicarbazides, semicarbazonesLeurs thio-analogues
46.
TREATMENT OF ALZHEIMER'S DISEASE USING COMPOUNDS THAT REDUCE THE ACTIVITY OF NON-SELECTIVE CA++- ACTIVATED ATP-SENSITIVE CATION CHANNELS REGULATED BY SUR1 RECEPTORS
NSC antagonists are disclosed as useful in the treatment of dementia, in delaying the onset of dementia, and in the prevention of dementia. Dementia so treated may be, for example, Alzheimer's Disease (AD). NSC antagonists for treating dementia such as AD may be administered alone, a) in combination with other drugs used for treating dementia, b) in combination with drugs that stabilize or increase blood plasma glucose levels, or with both a) and b). Pharmaceutical compositions, dosage forms, and methods for using the same are disclosed, which include NSC antagonists, NSC antagonists combined with dementia drugs, NSC antagonists combined with glucose-level stabilizing or enhancing drugs, or combinations of these. Dosage forms may be designed to provide stable plasma levels for extended periods of time. Exemplary pharmaceutical compositions include compositions including glibenclamide and memantine; glibenclamide and donepezil; tolbutamide and memantine; tolbutamide and donepezil; and these compositions further including glucagon and/or glucose.
A01N 47/34 - Urées ou thiourées contenant les groupes N—CO—N ou N—CS—N contenant les groupes p. ex. biuretLeurs thio-analoguesProduits de condensation urée-aldéhyde
A61K 31/175 - Amides, p. ex. acides hydroxamiques ayant le groupe N-C(O)-N ou N-C(S)-N, p. ex. urée, thiourée, carmustine ayant le groupe , N-C(O)-N=N- ou , p. ex. carbonohydrazides, carbazones, semicarbazides, semicarbazonesLeurs thio-analogues
47.
METHODS OF MEDICAL TREATMENT WITH SUR1-TRPM4 CHANNEL INHIBITORS
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 SURI -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 SURI-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 SURI -TRPM4 channel inhibitor is administered prior the onset of the cerebral edema-related side effects.
Abstract of the disclosure The invention provides a use of glyburide for treating acute stroke and other conditions, to provide a substantially steady level of glyburide in a patient's blood. The use provides use of a bolus of glyburide followed by first continuous infusion of glyburide at a first rate for a first period of time, followed by a second continuous infusion of glyburide at a second rate for a second period of time. The use optionally includes use of a third continuous infusion of glyburide or a second bolus of glyburide. Date Recue/Date Received 2020-12-03
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
A61P 25/00 - Médicaments pour le traitement des troubles du système nerveux
49.
IMPROVED FORMULATIONS AND METHODS FOR LYOPHILIZATION AND LYOPHILATES PROVIDED THEREBY
The present invention provides compositions, methods for lyophilizing compounds and making pharmaceutical compositions, and kits providing solutions and lyophilized formulations of compounds. The compositions, methods, and kits are particularly useful in pharmaceutical applications involving therapeutic agents that have low solubility at low pH and medium pll values. Certain embodiments provide methods for lyophilizing compounds in liquid solutions, which include the steps of: a) preparing aqueous solutions of a compound of interest in the absence of buffer; b) adjusting the pH to high values of pH in order to increase the solubility of the compound of interest; and c) frecze-drying the solution to provide a lyophilized solid composition. Aqueous solutions including buffer are also disclosed. Lyophilized formulations, including micronized and non-micronized powders, are provided.
The invention provides a use of glyburide for treating acute stroke and other conditions, to provide a substantially steady level of glyburide in a patient's blood. The use provides use of a bolus of glyburide followed by first continuous infusion of glyburide at a first rate for a first period of time, followed by a second continuous infusion of glyburide at a second rate for a second period of time. The use optionally includes use of a third continuous infusion of glyburide or a second bolus of glyburide.
The invention provides a use of glyburide for treating acute stroke and other conditions, to provide a substantially steady level of glyburide in a patient's blood.
Methods and formulations for minimizing or avoiding the sorption of glyburide to surfaces of delivery tubing, filters, bags, and other containers and materials, thereby storing and delivering a more stable product, delivering a predictable and accurate dose of glyburide, while minimizing impurities, avoiding drug waste, reducing cost, and significantly reducing the amount of dosing solution that must be infused into the patient.
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 9/19 - Préparations médicinales caractérisées par un aspect particulier à l'état particulaire, p. ex. poudres lyophilisées
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61K 47/18 - AminesAmidesUréesComposés d’ammonium quaternaireAcides aminésOligopeptides ayant jusqu’à cinq acides aminés
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
53.
METHODS OF MEDICAL TREATMENT WITH SUR1-TRPM4 CHANNEL INHIBITORS
Disclosed herein are methods 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.
A61K 31/045 - Composés hydroxylés, p. ex. alcoolsLeurs sels, p. ex. alcoolates
A61K 31/132 - Amines, p. ex. amantadine ayant plusieurs groupes amino, p. ex. spermidine, putrescine
A61K 31/166 - Amides, p. ex. acides hydroxamiques ayant des cycles aromatiques, p. ex. colchicine, aténolol, progabide ayant l'atome de carbone d'un groupe carboxamide lié directement au cycle aromatique, p. ex. procaïnamide, procarbazine, métoclopramide, labétalol
A61K 31/196 - Acides carboxyliques, p. ex. acide valproïque ayant un groupe amino le groupe amino étant lié directement à un cycle, p. ex. acide anthranilique, acide méfénamique, diclofénac, chlorambucil
A61K 31/325 - Acides carbamiquesAcides thiocarbamiquesLeurs anhydrides ou sels
A61K 31/428 - Thiazoles condensés avec des carbocycles
A61K 31/435 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à six chaînons avec un azote comme seul hétéro-atome d'un cycle
A61K 31/4439 - Pyridines non condenséesLeurs dérivés hydrogénés contenant d'autres systèmes hétérocycliques contenant un cycle à cinq chaînons avec l'azote comme hétéro-atome du cycle, p. ex. oméprazole
A61K 31/451 - Pipéridines non condensées, p. ex. pipérocaïne ayant un carbocycle lié directement à l'hétérocycle, p. ex. glutéthimide, mépéridine, lopéramide, phencyclidine, piminodine
A61K 31/49 - Dérivés du cinchonane, p. ex. quinine
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61K 31/7076 - Composés ayant des radicaux saccharide et des hétérocycles ayant l'azote comme hétéro-atome d'un cycle, p. ex. nucléosides, nucléotides contenant des cycles à six chaînons avec l'azote comme hétéro-atome d'un cycle contenant des pyrimidines condensées ou non-condensées contenant des purines, p. ex. adénosine, acide adénylique
A61K 38/10 - Peptides ayant de 12 à 20 amino-acides
A61P 25/00 - Médicaments pour le traitement des troubles du système nerveux
Methods and formulations for minimizing or avoiding the sorption of glyburide to surfaces of delivery tubing, filters, bags, and other containers and materials, thereby storing and delivering a more stable product, delivering a predictable and accurate dose of glyburide, while minimizing impurities, avoiding drug waste, reducing cost, and significantly reducing the amount of dosing solution that must be infused into the patient.
The present invention provides compositions, methods for lyophilizing compounds and making phamiaceutical compositions, and kits providing solutions and lyophilized fommlations of compounds. The compositions, methods, and kits are particularly useful in phamiaceutical applications involving therapeutic agents that have low solubility at low pH and medium pH values. Certain embodiments provide methods for lyophilizing compounds in liquid solutions, which include the steps of: a) preparing aqueous solutions of a compound of interest in the absence of buffer; b) adjusting the pH to high values of pH in order to increase the solubility of the compound of interest; and c) freeze-drying the solution to provide a lyophilized solid composition. Aqueous solutions including buffer are also disclosed. Lyophilized formulations, including micronized and non-micronized powders, are provided.
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
56.
METHODS OF TREATING INJURIES OR CONDITIONS RELATED TO CNS EDEMA
The present technology is related to reducing or treating neurological swelling and related conditions with SUR1-TRPM4 channel inhibitors. In some embodiments, the methods include: reducing late neurological deterioration or preventing death, reducing cerebral midline shift, reducing the degree of disability in a subject, counteracting blood glucose levels in a subject receiving a SUR1-TRPM4 channel inhibitor, preventing brain swelling, monitoring liver enzyme activity along with treating injury or conditions related to CNS edema, or monitoring cardiac activity along with treating injury or conditions related to CNS edema.
A method of treating or preventing amyloid related imaging abnormalities (ARIA) in patients receiving one or more course of medical treatment for Alzheimer's Disease includes administrating a SUR1-TRPM4 channel inhibitor, such as glyburide, in an amount effective to prevent the formation or reduce the size of one or more ARIAs in the brain.
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
The present disclosure provides compositions, methods for lyophilizing compounds and making pharmaceutical compositions, and kits providing solutions and lyophilized formulations of compounds. The compositions, methods, and kits are particularly useful in pharmaceutical applications involving therapeutic agents that have low solubility at low pH and medium pH values. For example, certain embodiments provide methods for preparing a pharmaceutically acceptable injection solution having increased solubility of glibenclamide or a pharmaceutically acceptable salt thereof therein by lyophilizing glibenclamide in a liquid solution.
A61J 3/02 - Dispositifs ou procédés spécialement conçus pour donner à des produits pharmaceutiques une forme physique déterminée ou une forme propre à leur administration la forme de poudres
A61K 9/19 - Préparations médicinales caractérisées par un aspect particulier à l'état particulaire, p. ex. poudres lyophilisées
A61K 31/64 - Sulfonylurées, p. ex. glibenclamide, tolbutamide, chlorpropamide
A61K 47/10 - AlcoolsPhénolsLeurs sels, p. ex. glycérolPolyéthylène glycols [PEG]PoloxamèresAlkyléthers de PEG/POE
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
brevets
