244 results about "Blockade" patented technology

The invention relates to devices and methods for nanopore sequencing. The invention includes compositions and methods of nucleic acid sequencing using a single polymerase enzyme complex comprising a polymerase enzyme and a template nucleic acid attached proximal to a nanopore, and nucleotide analogs in solution comprising charge blockade label that are attached to the polyphosphate portion of the nucleotide analog such that the charge blockade labels are cleaved when the nucleotide analog is incorporated into a growing nucleic acid and the charge blockade label is detected by the nanopore to determine the presence and identity of the incorporated nucleotide and thereby determine the sequence of a template nucleic acid.

The invention relates to devices and methods for nanopore sequencing. The invention includes compositions and methods of nucleic acid sequencing using a single polymerase enzyme complex comprising a polymerase enzyme and a template nucleic acid attached proximal to a nanopore, and nucleotide analogs in solution comprising charge blockade label that are attached to the polyphosphate portion of the nucleotide analog such that the charge blockade labels are cleaved when the nucleotide analog is incorporated into a growing nucleic acid and the charge blockade label is detected by the nanopore to determine the presence and identity of the incorporated nucleotide and thereby determine the sequence of a template nucleic acid.

The present disclosure provides substituted piperidines or pyrrolidines having Formula IA:and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2a, R2b, R6, A, X, m and n are defined as set forth in the specification. In certain embodiments, Compounds of the present disclosure are useful for treating pain. The present disclosure is also directed to the use of Compounds of the present disclosure to treat a disorder responsive to blockade of one or more sodium channels.

The invention relates to substituted pyridine compounds of Formula I: (I) and the pharmaceutically acceptable salts, prodrugs, and solvates thereof, wherein R1a, R1b, R2a, R2b, R2c, A1, A2, and X are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain.

The invention provides compounds that are useful as sodium channel blockers. In one aspect, the invention provides compounds of Formula I:and pharmaceutically acceptable salts, solvates, hydrates, or diastereomers thereof, wherein W1, W2, W3, W4, U, G, m, R1, and R2 are defined in the disclosure. In certain embodiments, the invention provides compounds of Formulae II to V as set forth supra. The invention also provides the use of compounds of any of the above discussed formulae to treat a disorder responsive to blockade of sodium channels. In one embodiment, Compounds of the Invention are useful for treating pain.

The present disclosure provides substituted pyridine and pyrimidine compounds of Formula (I): A1-X-A2-Z-R1 (I) and the pharmaceutically acceptable salts, solvates and prodrugs thereof, wherein A, X, A, Z, and R are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.

The present invention relates to the use of cannabinoid-containing plant extracts in the prevention or treatment of diseases or conditions that are alleviated by blockade of one or more types of TRP channel. Preferably the subset of TRP channel that is blockaded is the TRPA channel. More preferably the TRPA channel is the TRPA1 channel. Preferably the diseases or conditions to be prevented or treated include: neuropathic pain, inflammation or vasoconstriction. Alternatively the TRP channel that is blockaded is the TRPM channel. More preferably the TRPM channel is the TRPM8 channel. Preferably the diseases or conditions to be prevented or treated are cancer. More preferably the cancers to be treated include: cancer of the prostate, cancer of the breast, cancer of the colon, cancer of the lung or cancer of the skin. Alternatively the TRP channel that is blockaded is the TRPV channel. More preferably the TRPV channel is the TRPV1 channel. Preferably the diseases or conditions to be prevented or treated include neuropathic pain, inflammation or vasoconstriction.

The invention relates to aryl and heteroaryl substituted compounds of Formula (I), and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein G, R1, and Z1-Z5 are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain.

The Invention provides indole derivatives of Formula I:and pharmaceutically acceptable salts and solvates thereof, wherein R1e, R1f, A, X, Y, Z, and W4 are defined as set forth in the specification. The Invention also provides the use of compounds of Formula I and the pharmaceutically acceptable salts and solvates thereof to treat pain. In certain embodiments, the Compounds of the Invention are effective in treating a disorder responsive to blockade of one or more sodium channels.

The present disclosure provides substituted pyridyl-, pyrimidinyl-, pyrazinyl-, pyridazinyl-, and triazinyl-based carboxamides of Formula I-A: R10 Z-HET-E I-A and the pharmaceutically acceptable salts and solvates thereof, wherein Z, HET, R10 and E are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I-A to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.

The invention relates to substituted pyridine compounds of Formula I: (I) or a pharmaceutically acceptable salt, prodrug, or solvate thereof wherein A1, X, A2, R1a, R1b, R1c, G, and z are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain.

The invention provides compounds that are useful as sodium channel blockers. In one aspect, the invention provides compounds of Formula I:or pharmaceutically acceptable salts, solvates, hydrates, or diastereomers thereof, wherein R1, R4, X, G, n, p, W1, W2, W3, W4, and the E ring are defined in the disclosure. In certain embodiments, the invention provides compounds of Formulae II-XIII as set forth supra. The invention also provides the use of compounds of any of the above discussed formulae to treat a disorder responsive to blockade of sodium channels. In one embodiment, Compounds of the Invention are useful for treating pain.

The instant application relates to morphinan derivatives of formula I with enhanced oral bioavailability for the treatment of diseases associated with opioid receptor activity or blockade including alcohol and opiate addiction.

The invention provides methods for treating autoimmunity and for reestablishing tolerance. The methods involve the coadministration of anti-CD3 antibodies and self-antigens. The coadministration has the potential to provide a synergistic effect of protecting or reducing autoaggressive immune processes and / or of reestablishing tolerance towards self-antigens. An underlying rationale behind the methods is that the administration of self-antigens together with anti-CD3 antibodies can alter the response to those self-antigens and prevent progression of autoimmunity. By rechallenging with the autoantigens and stimulating the non-pathogenic response, the blockade of the autoimmune process can be maintained. Preclinical evidence provided herein shows that the combination of anti-CD3 and autoantigen is synergistic in reversing autoimmune diabetes, and therefore, suggests that combination therapy of anti-CD3 and self-antigen may provide synergistic protection in reversing other autoimmune disorders.

It is an object of the present invention to provide a method and apparatus for enhanced bladder voidance which would have the advantages of a rhizotomy yet be temporary and reversible by combining low and high-frequency sacral nerve stimulation. Applicants propose a new sacral neurostimulation strategy based on a combination of nerve conduction blockade using high frequency signals and nerve stimulation using low-frequency signals. The method and apparatus enhances micturition in paraplegics by sacral neurostimulation involving a combination of a low-frequency electrical stimulation applied to one or more sacral nerves to induce bladder contraction and a high frequency electrical stimulation applied to at least one sacral nerve to cause nerve conduction blockade that prevents urethral sphincter dyssynergic contraction.

The invention relates to aryl substituted compounds of Formula (I): and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein Het, G, A, R, and n are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain.

The invention relates to devices and methods for nanopore sequencing. The invention includes compositions and methods of nucleic acid sequencing using a single polymerase enzyme complex comprising a polymerase enzyme and a template nucleic acid attached proximal to a nanopore, and nucleotide analogs in solution comprising charge blockade label that are attached to the polyphosphate portion of the nucleotide analog such that the charge blockade labels are cleaved when the nucleotide analog is incorporated into a growing nucleic acid and the charge blockade label is detected by the nanopore to determine the presence and identity of the incorporated nucleotide and thereby determine the sequence of a template nucleic acid.

The present disclosure provides pyrimidine diol amides of Formula (I), and the pharmaceutically acceptable solvates and prodrugs thereof, wherein A1, X, A2, W1, W2, W3, R1, R2, and R4 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.

The present disclosure provides cyclic sulfonamides of Formula (I), and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3a, R3b, and n are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. For example, compounds of the present disclosure are useful for treating pain.

The invention relates to substituted pyridine and pyrimidine compounds of Formula (I) and the pharmaceutically acceptable salts, prodrugs, and solvates thereof, wherein R1, R2a, R2b, A1, A2, X, and Z are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain.

Fatty acid amide hydrolase inhibitors of the Formula:are provided wherein X is NH, CH2, O, or S; Q is O or S; Z is O or N; R is an aromatic moiety selected from the group consisting of substituted or unsubstituted aryl; substituted or unsubstituted biphenylyl, substituted or unsubstituted naphthyl, and substituted or unsubstituted phenyl; substituted or unsubstituted terphenylyl; substituted or unsubstituted cycloalkyl, heteroaryl, or alkyl; and R1 and R2 are independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, and substituted or unsubstituted phenyl, substituted or unsubstituted biphenylyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; with the proviso that if Z is O, one of R1 and R2 is absent, and that if Z is N, optionally R1 and R2 may optionally be taken together to form a substituted or unsubstituted N-heterocycle or substituted or unsubstituted heteroaryl with the N atom to which they are each attached. Pharmaceutical compositions comprising the compounds of Formula I and methods of using them to inhibit FAAH and / or treat appetite disorders, glaucoma, pain, insomnia, and neurological and psychological disorders including anxiety disorders, epilepsy, and depression are provided.

The present disclosure provides substituted triazine carboxamides of Formula I:and the pharmaceutically acceptable salts and solvates thereof, wherein A1, X, A2, E, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.

The present invention relates to a peptide and analogs thereof that selectively inhibit the Nav1.7 sodium channel. The present invention also relates to pharmaceutical compositions useful for treating or preventing a disorder responsive to the blockade of sodium ion channels, especially Nav1.7 sodium ion channels. The present invention further provides methods of treating a disorder responsive to the blockade of sodium channels, and particularly Nav1.7 sodium channels, in a mammal suffering from excess activity of said channels, compositions and methods for providing analgesia by administering a peptide of the invention.

The invention discloses a cycloolefin copolymer with a structure shown in the formula (I), wherein m and n are polymerization degrees, m:n>=1.5, and R1 and R2 are independently selected from hydrogen or C1-C10 saturated aliphatic hydrocarbon. According to the invention, a cycloolefin monomer with a structure shown in the formula (II) and alpha-alkene are adopted as polymerization monomers; the copolymerization monomers are subjected to a polymerization reaction under the existence of a catalyst and in an inert solvent, such that the cycloolefin copolymer with the structure shown in the formula (I) is obtained. According to the invention, the cycloolefin monomer with the structure shown in the formula (II) is large-volume cycloolefin. Because of a stereospecific blockade effect, under the condition of a low insertion rate, the cycloolefin copolymer with high glass transition temperature and with the structure of the formula (I) is obtained. The flexible alpha-alkene units in the copolymer are increased, such that the rigidity of the cycloolefin copolymer chains is reduced, the entanglement among the chains is enhanced, such that the anti-tearing performance of the cycloolefin copolymer is improved, and the brittleness of the copolymer is ameliorated.

This invention provides methods, compositions and articles of manufacture for inhibiting the onset of and treating glomerular injury. The instant invention is based on the blockade of RAGE and / or RAGE G82S function.

A computer-implemented method for quantitatively determining a person's neuro-muscular blockade (NMB) level in real-time using at least one sensor attached to the person is provided. The method includes receiving a first input signal from the sensor, wherein the first input signal includes a measurement of a first muscular response, the first muscular response resulting from a baseline stimulus current delivered to the person before administration of NMB agents to the person, and establishing a baseline chronaxie based on the first input signal. The method also includes delivering one or more stimulus currents to the person after the administration of NMB agents to the person, receiving a second input signal from the sensor, wherein the second input signal includes a measurement of one or more muscular responses resulting from the one or more stimulus currents, and determining the person's NMB level based on the second input signal.

The present invention provides novel methods for classifying, diagnosing and / or treating a group of human and veterinary ailments involving endogenous opioid concentrations. Also provided is a novel use for an existing class of compounds, the opioids, to treat opiopathic ailments, particularly paresis / paralysis, pseudo-atrophy and / or opiopathic pain, and in the manufacture of pharmaceutical and veterinary formulations therefor. The invention also relates to neuropathic, polyneuropathic, neurologic and neurogenic ailments typically characterized by paresis / paralysis. These ailments can involve an abnormal concentration of one or more endogenous opioids, or the blockade, underexpression or overexpression of one or more opioid receptors. In that regard, the invention encompasses therapeutic uses, methods and compositions employing opiates and / or their receptors. In particular, the invention relates to certain laboratory testing methods, clinical testing methods, research and development methods, business methods, methods of treatment, novel therapeutic uses, and human and veterinary pharmaceutical dosage forms, dosing regimens and formulations, especially those pertaining to opiopathy (particularly hypo-opiopathy).