284 results about "ATPase" patented technology

Chemical syntheses and medical uses of novel inhibitors of the gastric H+, K+-ATPase for the treatment and / or management of duodenal ulcers, heartburn, acid reflux, other conditions mediated by gastric acid secretion and / or psoriasis are described.

An enteric coated pharmaceutical dosage form comprising an H+,K+-ATPase inhibitor is disclosed. The dosage form comprises at least two portions of the H+,K+- ATPase inhibitor to be released in at least two consecutive pulses. The dosage form has at least one fraction with a pulsed delayed release and another fraction with instant release of the H+,K+-ATPase inhibitor. The portions are released in time by from 0.5 and up to 12 hours interval, preferably by from 0.5 and up to 8 hours, and more preferably by from 0.5 and up to 4 hours interval. The dosage form is intended for once daily administration.

RNA interference is provided for inhibition of ocular hypertension target mRNA expression for lowering elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Ocular hypertension targets include carbonic anhydrase II, IV, and XII; β1- and β2 adrenergic receptors; acetylcholinesterase; Na+ / K+-ATPase; and Na—K-2Cl cotransporter. Ocular hypertension is treated by administering interfering RNAs of the present invention.

The reagent, pharmaceutical formulation, kit, and methods of the invention provides a new approach for treating hypoxia-related pathological conditions, such as Alzheimer's Disease, and those involving excessive angiogenesis, especially those non-cancer pathological conditions. The invention provides the use of Na+ / K+-ATPase inhibitors, such as cardiac glycosides (e.g. ouabain and proscillaridin, etc.), either alone or in combination with other standard therapeutic agents for treating such conditions. The invention also relates to the use of cardiac glycoside inhibitors / antagonists as reagents, pharmaceutical formulations, or in kits and methods for treating conditions arising from excessive amount of cardiac glycosides, including all symptoms of digitalis poisoning, depression, hypertension, etc. The pharmaceutical formulation of the invention may be delivered to a patient either systemically or locally, or both. The pharmaceutical formulations of the invention may be delivered either in one dose, or continuously over a sustained period of time using, for example, sustained drug delivery devices.

RNA interference is provided for inhibition of ocular hypertension target mRNA expression for lowering elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Ocular hypertension targets include carbonic anhydrase II, IV, and XII; β1- and β2 adrenergic receptors; acetylcholinesterase; Na+ / K+-ATPase; and Na—K-2Cl cotransporter. Ocular hypertension is treated by administering interfering RNAs of the present invention.

An enteric coated pharmaceutical extended release dosage form of a H+, K+-ATPase inhibitor giving an extended plasma concentration profile of a H+, K+-ATPase inhibitor. The extended plasma profile is obtained by a pharmaceutical composition which comprises a core material of a hydrophilic or hydrophobic matrix, and the H+, K+-ATPase inhibitor and optionally pharmaceutically acceptable excipients. The dosage form may be administered once daily.

The reagent, pharmaceutical formulation, kit, and methods of the invention provides a new approach to alleviate or eliminate certain negative effects associated with the use of certain cancer treatment agents (e.g. chemotherapy therapeutics, etc.) or regimens (e.g. radio therapies, etc.), including stimulation of the hypoxic stress response in tumor cells.

Methods and kits for detecting the presence of ATP, for measuring ATP concentrations, and for detecting viable cells using a composition comprising an ATP-dependent enzyme and one or more ATPase inhibitors.

A method of treating gastric acid disorders by administering to a patient a pharmaceutical composition comprising a proton pump inhibitor (PPI) in a pharmaceutically acceptable carrier. The present invention provides an oral solution / suspension comprising a proton pump inhibitor and at least one buffering agent. The PPI can be any substituted benzimidazole compound having H+,K+-ATPase inhibiting activity and being unstable to acid. Omeprazole and lansoprazole are the preferred PPIs for use in oral suspensions in concentrations of at least greater than 1.2 mg / ml and 0.3 mg, respectively. The liquid oral compositions can be further comprised of parietal cell activators, anti-foaming agents and / or flavoring agents. The inventive compositions can alternatively be formulated as a powder, tablet, suspension tablet, chewable tablet, capsule, effervescent powder, effervescent tablet, pellets and granules. Such dosage forms are advantageously devoid of any enteric coating or delayed or sustained-release delivery mechanisms, and comprise a PPI and at least one buffering agent to protect the PPI against acid degradation. Similar to the liquid dosage form, the dry forms can further include anti-foaming agents, parietal cell activators and flavoring agents. Kits utilizing the inventive dry dosage forms are also disclosed herein to provide for the easy preparation of a liquid composition from the dry forms. In accordance with the present invention, there is further provided a method of treating gastric acid disorders by administering to a patient a pharmaceutical composition comprising a proton pump inhibitor in a pharmaceutically acceptable carrier and at least one buffering agent wherein the administering step comprises providing a patient with a single dose of the composition without requiring further administering of the buffering agent. Additionally, the present invention relates to a method for enhancing the pharmacological activity of an intravenously administered proton pump inhibitor in which at least one parietal cell activator is orally administered to the patient before, during or after the intravenous administration of the proton pump inhibitor.

Provided are previously uncharacterised markers of cancers, for example colorectal cancers, and uses of these as diagnostic and prognostic markers of cancers, and in particular colorectal cancers. The markers are SEQ ID NO: 1—hnRNP-K; SEQ ID NO:2—HMG-1; SEQ ID NO:3—proteasome subunit alpha type 1; SEQ ID NO:4—bifunctional purine biosynthesis protein; SEQ ID NO:5—ST11; SEQ ID NO:6—annex in IV; SEQ ID NO:7—60 kDa heat shock protein; SEQ ID NO:8—T complex protein 1 beta subunit; SEQ ID NO:9—T complex protein 1 epsilon subunit; SEQ ID NO: 10—mortalin; and SEQ ID NO: 11—TER-ATPase. The invention further provides related methods and materials for the use of the markers in therapeutic intervention in colorectal and other cancers e.g. to specifically target neoplastic cells without causing significant toxicity in healthy tissues, and to provide methods for the evaluation of the ability of candidate therapeutic compounds to modulate the biological activity of cancerous cells from the colon, rectum and other tissues.

The present invention is related to oral compositions comprising an irreversible gastric H+ / K+-ATPase proton pump inhibitor (PPI) as a gastric acid secretion inhibitor and succinc acid as a parietal cell activator in the gastric lumen. The compositions of the present invention are capable of enhancing the anti-acid activity of PPI in the stomach. The present invention further relates to a method of using such compositions to reduce gastric acid secretion in a mammal.

RNA interference is provided for inhibition of ocular hypertension target mRNA expression for lowering elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Ocular hypertension targets include carbonic anhydrase II, IV, and XII; β1- and β2 adrenergic receptors; acetylcholinesterase; Na+ / K+-ATPase; and Na—K-2Cl cotransporter. Ocular hypertension is treated by administering interfering RNAs of the present invention.

A class of compounds which are (H+ / K+)ATPase inhibitors can be used for the treatment of viral infections. Compounds of particular interest are defined by Formula III: [0001]wherein D is N or CH; wherein R7 is one or more radicals selected from hydrido, alkoxy, amino, cyano, nitro, hydroxyl, alkyl, halo, haloalkyl, carboxyl, alkanoyl, nitro, amino, alkylamino, amide, alkylamide, alkoxycarbonyl, alkylthio, alkylsulfinyl and alkylsulfonyl; wherein R9 is one or more radicals selected from hydrido, alkoxy, amino, alkyl, halo, cyano, nitro, hydroxyl, haloalkyl, carboxyl, alkanoyl, nitro, amine, alkylamine, dialkylamine, amide, alkylamide, alkoxycarbonyl, alkylthio, alkylsulfinyl and alkylsulfonyl; and wherein R10 and R11 are independently selected from hydrido and alkyl; or a pharmaceutically acceptable salt thereof.

The reagent, pharmaceutical formulation, kit, and methods of the invention provides a new approach for treating pancreatic cancers. The invention provides the use of Na+e / K+-ATPase inhibitors, such as cardiac glycosides (e.g. ouabain and proscillaridin, etc.), either alone or in combination with other standard therapeutic agents (chemo- or radio-therapies, etc.) for treating pancreatic cancers. The subject Na+ / K+-ATPase inhibitors, such as cardiac glycosides, including bufadieneolides or their corresponding aglycones (e.g., proscillaridin, scillaren, and scillarenin, etc.), especially in oral formulations and / or solid dosage forms containing more than 1 mg of active ingredients.

The present invention relates to stable liquid formulations that comprise a water free or almost water free, polyethylene glycol solution of sodium or potassium salt of a H<+>, K<+>-ATPase inhibitor of Formula I or a sodium or potassium salt of one single enantiomer thereof. Alternatively, the sodium or potassium salt of the H<+>, K<+>-ATPase inhibitor may be formed in situ in the polyethylene glycol solution by adding sodium or potassium hydroxide together and the active compound. The invention is also directed to the preparation of the claimed formulation, use of the stable liquid formulations in medicine and in the treatment of gastrointestinal diseases.

The present invention is related to novel oral compositions comprising an irreversible gastric H+ / K+-ATPase proton pump inhibitor (PPI) as a gastric acid secretion inhibitor, pentagastrin (PG) or a PG analogue as an activator of parietal cells in the gastric lumen. In a preferred embodiment, the composition further comprises at least one agent that preserves the availability of PG in the gastric fluids, thus enabling PG to act locally in the stomach. Unexpectedly, the compositions of the present invention exhibit anti-acid activity locally in the stomach that is meal-independent, exhibit fast onset and prolonged inhibition of acid secretion.

A method for identifying a Na+ channel blocker, including providing a cell containing a Na+ channel, demonstrating both a transient and a persistent current. The cell includes a potassium (K+) channel and a Na / K ATPase (Na+ pump). A fluorescent dye is disposed into the well. The fluorescent dye is sensitive to change in cell membrane potential in order to enable optical measurement of cell membrane potential. A Na+ channel blocker, to be identified, is added to the well and a stimulating current is passed through the cell in an amount sufficient to generate an action potential before and after the addition of the Na+ channel blocker. Thereafter, a change in cell membrane potential is optically measured.

The present invention provides methods of producing libraries of compounds with enhanced desirable properties and diminished side effects as well as the compounds produced by the methods. In preferred embodiments, methods of the present invention use a universal chemical glycosylation method that employs reducing sugars and requires no protection or activation. In a preferred embodiment, the invention provides a library of neoglycoside digitoxin analogs that includes compounds with significantly enhanced cytotoxic potency toward human cancer cells and tumor-specificity, but are less potent Na+ / K+-ATPase inhibitors in a human cell line than digitoxin.

The reagent, pharmaceutical formulation, kit, and methods of the invention provides a new approach to treat refractory cancers using Na+ / K+-ATPase inhibitors, such as cardiac glycosides, including bufadienolides or their corresponding aglycones (e.g., proscillaridin, scillaren, and scillarenin, etc.), especially in oral formulations and / or solid dosage forms containing more than 1 mg of active ingredients.

The reagent, pharmaceutical formulation, kit, and methods of the invention provides a new approach to treat refractory cancers using Na+ / K+-ATPase inhibitors, such as cardiac glycosides (e.g. ouabain or proscillaridin, etc.).

Medical compositions and methods of treating or preventing neurodegeneration in a human suffering from or that is at risk of or susceptible to neurodegeneration or cellular dysfunction associated with expression or impaired cellular function of a neuronal protein encoded by one or more genes that code for alpha-synuclein (SNCA), Parkin RBR E3 ubiquitin protein ligase, (PARK2), Leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase / (PINK1), Daisuke-Junko 1, (DJ-1) and ATPase type 13A2 (ATP13A2), are disclosed. Methods of treatment for these disorders is also provided, comprising administering a vector into a cell, wherein the vector facilitates expression of a molecular component that alters one of the aforementioned genes in the cell or expression of the gene in the cell, the gene being implicated in an etiology of the neurological deficit.

Protein targets for disease intervention through inhibition of nucleic acid metabolism are disclosed. Novel polypeptides for one such target, DNA-dependent ATPase A, and novel polynucleotides encoding DNA-dependent ATPase A are disclosed. Phosphoaminoglycoside compounds which act on such protein targets to inhibit nucleic acid metabolism. In addition, screening assays for identifying compounds that inhibit nucleic acid-dependent ATPase activity, including, but not limited to, DNA-dependent ATPase A, are disclosed. Such compounds are useful in the treatment of diseases, including but not limited to cancer and infectious disease, through disruption of nucleic acid metabolism and induction of apoptosis. Moreover, methods for prevention and treatment of diseases including, but not limited to cancer and infectious disease are disclosed.

The invention discloses a yeast fermentation small-molecular recombinant fibronectin protein peptide comprising at least one sodium-potassium ATPase beta subunit binding domain, and the sodium-potassium ATPase beta subunit binding domain has the amino acid sequence shown in SEQ ID NO:2. The invention also discloses a preparation method of the yeast fermentation small-molecular recombinant fibronectin protein peptide and an application of the yeast fermentation small-molecular recombinant fibronectin protein peptide. The yeast fermentation small-molecular recombinant fibronectin protein peptidecan be effectively absorbed by skin and has excellent healing and repairing effects on traumatic skin lesions or subcutaneous lesions with intact keratin.

A method for regulating Src and its downstream signaling pathway which includes binding between Src and Na+ / K+-ATPase is disclosed. The Na+ / K+-ATPase / Src complex is a functional receptor for cardiotonic steroids such as ouabain. Also disclosed are Src inhibitors or activators which include either Na+ / K+-ATPase or Src that interfere with the interaction between the Na / K-ATPase and Src, act via a different mechanism from ATP analogues, and is pathway (Na+ / K+-ATPase) specific.

A novel mammalian dihydroouabain-like factor is disclosed which substantially fails to cross-react with mammalian ouabain-like factor (OLF) for binding to anti-OLF antibody, but cross-reacts with plant-related dihydroouabain (dho) for binding to anti-dho antibody, has maximal u.v. absorbance at 196 nm, has a non-peptidic, non-lipidic chemical structure and a fully hydrogenated lactone ring, has a concentration-dependent Na<+>,K<+>-ATPase (sodium pump) catalytic inhibitory activity which is 10-fold lower than OLF and 3-fold higher than plant-related dihydroouabain, and a high pressure liquid chromatography elution time about the same as dho. This factor is useful for therapy for congestive heart failure. An antibody and antibody fragments having affinity for mammalian Dh-OLF but not for OLF, and diagnostic and therapeutic methods comprise the antibody and means for quantifying the antibody and are useful for treating a condition caused by high level of OLF or Dh-OLF. Two isomers of plant-related dihydroouabain have been isolated. These compositions and methods are suitable for characterizing a variety of diseases and conditions associated with reduced sodium pump activity.

A method and composition for treating viral infections using a combination of naturally occurring compounds is provided. The method includes administering to a patient at risk of or diagnosed with a viral infection a composition including therapeutically effective amounts of a helicase ATPase inhibitor, a sialidase enzyme inhibitor, and ICAM-1 inhibitor which each also down regulate the immune response. The composition may further include a permeation enhancer.