41 results about "Enkephalinase" patented technology

This invention relates to novel compounds, compositions containing the compounds, that inhibit dipeptidyl peptidase (especially DPP-IV) and neprilysin (NEP, neutral endopeptidase) as well as dipeptidyl peptidase (especially DPP-IV) and angiotensin converting enzyme (ACE) and / or dipeptidyl Peptidase (especially DPP-IV) and vasopeptidases (especially ACE and NEP). These compounds and pharmaceutical compositions thereof are useful for the treatment as well as the prevention of type 2 diabetes mellitus.

Methods and compositions that can reduce the symptoms of autism in a human patient comprising administering a physiologically effective amount of one or both of a purified casomorphin inhibitor selected from the group consisting of a casomorphinase and a casomorphin ligand, and a physiologically effective amount of a purified gluteomorphin inhibitor selected from the group consisting of a gluteomorphinase and a gluteomorphin ligand, to a human patient in sufficient quantities to reduce the effects of the autism. In some embodiments, the compositions and methods further comprise a physiologically effective amount of an enkephalin inhibitor, preferably an enkephalinase, and a physiologically effective amount of an endorphin inhibitor, preferably an endorphinase.

Methods and compositions that can reduce the symptoms of autism in a human patient comprising administering a physiologically effective amount of one or both of a purified casomorphin inhibitor selected from the group consisting of a casomorphinase and a casomorphin ligand, and a physiologically effective amount of a purified gluteomorphin inhibitor selected from the group consisting of a gluteomorphinase and a gluteomorphin ligand, to a human patient in sufficient quantities to reduce the effects of the autism. In some embodiments, the compositions and methods further comprise a physiologically effective amount of an enkephalin inhibitor, preferably an enkephalinase, and a physiologically effective amount of an endorphin inhibitor, preferably an endorphinase.

The invention specifically relates to a preparation method for a dual inhibitor LCZ696 of angiotensin II receptor and neprilysin, which belongs to the technical field of drug synthesis. The preparation method comprises the following steps: preparing valsartan and AHU-377 or AHU-377 calcium salt at first; and then mixing valsartan with AHU-377 or AHU-377 calcium salt under stirring so as to prepare LCZ696. The LCZ696 prepared in the invention has good quality and high purity; and the preparation method has the advantages of simplicity, low energy consumption, low cost and suitability for large batch production.

The invention discloses a composition for treating diarrhea and a preparation thereof, relating to a medicinal composition for stopping the diarrhea. The invention also relates to a preparation of the medicinal composition for stopping the diarrhea. The medicinal composition is mainly prepared from the main raw materials of 1 part of Racecadotril and 0.25-25 parts of berberine hydrochloride as well as 0.01-250 parts of auxiliary materials in proportion. The medicinal composition has scientific and reasonable prescription, and can be used for inhibiting the rise of calcium ion concentration in colon smooth muscle cells and improving the motion functional coordination of the intestinal tract to realize the effect on stopping the diarrhea mainly by inhibiting the activity of enkephalinase and further inhibiting the excessive secretion of water and electrolyte via the Racecadotril, and simultaneously by the stronger bactericidal effect of the berberine hydrochloride on escherichia coli, Streptococcus hemolyticus, Diplococcus pneumoniae and the like.

The invention relates to novel compounds of formula (I): H2N-CH(R1)-CH2-S-S- CH2-CH(R2)-CONH-R5, wherein R1 is a hydrocarbon chain, phenyl or benzyl radical, methylene radical substituted by a 5 or 6 atom heterocycle; R2 is a phenyl or benzyl radical, a 5 or 6 atom aromatic heterocycle, methylene group substituted by a 5 or 6 atom heterocycle; R5 is a CH(R3)-COOR4 radical, wherein R3 is hydrogen, an OH or OR group, a saturated hydrocarbon group, a phenyl or benzyl radical and OR4 is hydrophile ester, or 5 or 6 membered heterocycle comprising several heteroatoms selected from a group consisting of nitrogen, sulphur and oxygen, with at least two nitrogene atoms, wherein said heterocycle is substitutable by an alkyl C1-C6, phenyl or benzyl radical.; The use of the inventive compounds in the form of drugs, a pharmaceutical composition comprising said compounds, a pharmaceutically acceptable excipient, the use in conjunction of at least one type of cannabinoid derivative for potentiating the analgesic and antidepressant effect of the novel compounds of formula (I) and / or morphine or the derivatives thereof are also disclosed.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a one or more assays configured to detect a kidney injury marker selected from the group consisting of Cathepsin B, Renin, Dipeptidyl Peptidase IV, Neprilysin, Beta-2-microglobulin, Carbonic anhydrase IX, and C-X-C motif chemokine 2 as diagnostic and prognostic biomarkers in renal injuries.

The present invention relates to methods for diagnosis of chronic prostatitis / chronic pain pelvic syndrome (CP / CPPS). We have found specific biomarkers that are present in higher concentrations in patients that have chronic prostatitis / chronic pain pelvic syndrome (CP / CPPS) as compared to subjects that have no symptoms of CP / CPPS. In particular, uromodulin (THP), aminopeptidase N (AMPN), dipeptidylpeptidase IV (CD26), neprilysin (NEP), zinc-α-2-glycoprotein (ZA2G) and alkaline phosphatase (ALP) were found to be present at higher concentrations in CP / CPPS patient urine that is voided after prostatic message. Accordingly, the invention is directed to methods for diagnosis of CP / CPPS by monitoring the levels of at least one of these proteins in post-prostatic massage urine, as well as to diagnostic kits designed for diagnosis of CP / CPPS.

The invention is directed to compounds having the formula: (I) wherein: Ar, r, n, X, R2-3 and R5-7 are as defined in the specification, and pharmaceutically acceptable salts thereof. These compounds have AT1 receptor antagonist activity and neprilysin inhibition activity. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

This invention is directed to methods and compositions for increasing the expression or activity of neprilysin in, for example, the frontal cortex or the entorhinal cortex using a progranulin polypeptide or effector. The present invention is further directed to methods of reducing microglia in the brain of a patient with neurodegenerative disease using a progranulin polypeptide or effector.

The present invention relates to polypeptides comprising protease variants of wild type human neprilysin having an altered specificity and / or activity. In particular the present invention relates to polypeptides comprising protease variants derived from human neprilysin having an increased specificity and / or activity against certain substrates, in particular against amyloid beta.

Novel substrates for detection of activity of amyloid beta degrading enzyme, such as Neprilysin (NEP) and insulin degrading enzyme (IDE), associated with Alzheimer's disease, are provided. A quenched fluorogenic peptide substrate containing the first seven residues of the Aβpeptide plus a C-terminal Cys residue to detect neprilysin activity with a fluorophore attached to the C-terminal Cys and a quencher linked to the N-terminus of the peptide is disclosed. An assay system sensitive to endopeptidase activity of NEP and IDE, but insensitive to other Aβ-degrading enzymes is disclosed. Active compounds are identified by a cell-based assay system for high-throughput screening.

The present invention relates to a pharmaceutical composition for the prevention or treatment of neurological disorders, comprising an ICAM-1 (intercellular adhesion molecule-1) protein, or a fragment or a variant thereof as an active ingredient, which can increase the expression of neprilysin to remove amyloid-beta (Aβ), a cause of dementia, and is thus useful in preventing or treating a neurological disease including Alzheimer's disease.

The present invention relates to fusion proteins and their use in enzymatic treatment of Alzheimer's disease patients. Said fusion protein comprises a component that cleaves the amyloid beta (Ab) peptide e.g. neprilysin, insulin degrading enzyme (IDE), another component that modulates the half-life in plasma e.g. the Fc portion of IgG or PEG; and a third component that connects the first two components.

Disclosed is a method for the treatment of a neurodegenerative disorder by isolating a plurality of monocytic cells and introducing a vector containing a gene that expresses a protease capable of degrading amyloid peptide into the isolated monocytic cells. The modified cells are then administered to the patient. Preferably the introduced gene is selected from the group consisting of neprilysin, insulin degrading enzyme and endothelin converting enzyme. The protease capable of degrading amyloid peptide is secreted from the monocytic cells into the extracellular space thereof. According to one variant, the gene that expresses a protease capable of degrading amyloid peptide is the NEP gene with a deletion in the membrane binding domain and / or an appended signal peptide to drive secretion of the modified gene product. This invention contemplates the use of heterologous and autologos (the monocytic cells are obtained from the patient) transplants.

The present invention relates to a pharmaceutical composition for the prevention or treatment of neurological disorders, comprising an ICAM-1 (intercellular adhesion molecule-1) protein, or a fragment or a variant thereof as an active ingredient, which can increase the expression of neprilysin to remove amyloid-beta (Aβ), a cause of dementia, and is thus useful in preventing or treating a neurological disease including Alzheimer's disease.

The invention discloses a combining method for optogenetics and neprilysin (NEP) genes. The method comprises the following main steps: 1) by using mammalian expression plasmid VR1012 as a gene vector,recombining the neprilysin genes and light-activated neuronal channel protein ChR2 genes to a eukaryotic expression plasmid through PCR, digestion, connection and monoclonal picking, and adding a neural specific promoter of hSyn before ChR2 to obtain a recombinant plasmid capable of simultaneously expressing neprilysin and the light-activated neuronal channel protein ChR2 in vivo and in vitro; 2)connecting an EGFP green label after the neprilysin, and connecting an mCherry red label after the ChR2; and 3) performing gene sequencing on the obtained recombinant plasmid DNA, and verifying whether the neprilysin and ChR2 genes are inserted correctly into the VR1012 eukaryotic expression plasmid at the nucleic acid molecular level. The NEP is the most important enzyme for degrading Abeta protein in a brain, so that the NEP can be used to reduce risk.

Mixed inhibitors of aminopeptidase N and of neprilysine are described. Pharmaceutical compositions containing at least one of these compounds, used alone or in combination with morphine and derivatives thereof, endocannabinoids and inhibitors of the metabolism thereof, GABA derivatives such as gabapentin or pregabalin, duloxetine or methadone, can be used as an analgesic, anxiolytic, antidepressant or anti-inflammatory.

Novel crystalline Forms of trisodium [3-((1S,3R)-1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butyl carbamoyl) propionate-(S)-3′-methyl-T-(pentanoyl{2″-(tetrazol-5-ylate)biphenyl-4′-ylmethyl}amino)butyrate] hydrate, methods for their preparation, pharmaceutical compositions comprising these new forms, and use of them for treating or delaying progression or onset of diseases or disorders related to activity of angiotensin receptor 1 (AT1) blockage and neprilysin (NEP) inhibition, such as heart failure, are disclosed.

The present invention relates to agonists of Neprilysin and their use in preventing and treating pulmonary vascular remodeling. Also described are diagnostic and screening applications stemming from the inventor's discovery that Neprilysin is expressed at reduced levels in disease tissues.

The present invention relates to agonists of Neprilysin and their use in preventing and treating pulmonary vascular remodeling. Also described are diagnostic and screening applications stemming from the inventor's discovery that Neprilysin is expressed at reduced levels in disease tissues.

The present disclosure provides a therapeutic method of treating cancer metastasis by inducing clearance of EVs using a binding agent specific to an EV protein. The method utilizes one or more binding agents specific to EV proteins, where the EV proteins are selected from prostaglandin F2 receptor negative regulator (PTGFRN); basigin (BSG); immunoglobulin superfamily member 2 (IGSF2); immunoglobulin superfamily member 3 (IGSF3); immunoglobulin superfamily member 8 (IGSF8); integrin beta-1 (ITGB1); integrin alpha-4 (ITGA4); 4F2 cell-surface antigen heavy chain (SLC3A2); a class of ATP transporter proteins (ATP1A1, ATP1A2, ATP1A3, ATP1A4, ATP1B3, ATP2B1, ATP2B2, ATP2B3, ATP2B4); CD13 (aminopeptidase N); MME (neprilysin), ENPP1 (ectonucleotide pyrophosphatase / phosphodiesterase family member 1); and NRP1 (neuropilin-1). Further provided herein includes a pharmaceutical composition for the treatment of cancer metastasis.

Compounds for treating reward deficiency syndrome (RDS) behaviors and methods of use and administration of such compounds to induce dopamine homeostasis. These compounds synergistically combine two or more of (a) DP A, (b) NAC, and (c) kyotorphin (or arginine and tyrosine, the precursors of kyotorphin). These work together to enhance dopamine release by employing mechanisms tied to GABA regulation on Dorsal Raphe VGlut3 neurons via the Substania Nigra and increasing enkephalins (by increasing the release of enkepahlins and by the inhibition of enkephalinase). The resulting compound can induce dopamine homeostatis (and thus induce anti-stress states and diminish stress induced addictive behaviors). In embodiments of the present invention, the compound further includes nano-sized particles that enable the compound to be water- or powder-based even though DP A, NAC, and kyotorphin are not soluble in water.

The present invention relates to a solid unit oral dosage form comprising sacubitril and valsartan in a 1:1 molar ratio, preferably in the form of the so-called angiotensin receptor neprilysin inhibitor (ARNI) LCZ696, which is a complex salt hydrate of sacubitril, valsartan, and sodium ions, appropriate for use in pediatrics or other patients where low and individual dosing is required or who encounter problems with swallowing e.g. as a result of a disease or because of age, to the manufacture of said solid dosage form and to invention embodiments relating to therapy using said dosage form.

The invention relates to methods of diagnosing risk of amyloid β deposition following traumatic brain injury. The invention further relates to the discovery of a specific single nucleotide polymorphism in the neprilysin gene that is linked to an increased risk of amyloid β deposition after traumatic brain injury.

The composition for predicting Alzheimer's disease prognosis comprising a detection reagent that specifically binds to any one or more genes selected from the group consisting of (Nitric oxide synthase 1), Aph1B (Anterior pharynx defective 1 homolog B), Ryr3 (Ryanodine receptor 3), Atf6 (Activating transcriptional factor 6), Ip3r (Inositol trisphosphate receptor), Nep (Neprilysin), Cdk5 (cyclin dependent kinase 5) and Abad (Amyloid beta-binding alcohol dehydrogenase), a kit, and a method for providing information on Alzheimer's disease prognosis of the present invention can rapidly and accurately predict the prognosis of Alzheimer's disease, and can determine the prognosis for a drug by comparing the expression level before and after drug administration, so that an appropriate treatment direction can be determined according to the predicted prognosis. Therefore, they have an effect that can greatly contribute to the reduction of mortality due to Alzheimer's disease.

The invention relates to methods of diagnosing risk of amyloid β deposition following traumatic brain injury. More particularly, the invention relates to the discovery of a specific single nucleotide polymorphism in the neprilysin gene that is linked to an increased risk of amyloid β deposition after traumatic brain injury

The invention is directed to compounds having the formula: wherein: Ar, r, n, X, R2-3 and R5-7 are as defined in the specification, and pharmaceutically acceptable salts thereof. These compounds have AT1 receptor antagonist activity and neprilysin inhibition activity. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.