25 results about "Hypoparathyroidism" patented technology

The invention relates to the field of biological medicine, and discloses a pTH long-acting polypeptide compound as well as preparation and application thereof. According to the polypeptide, at least one amino acid residue of the 13th, 26th and 27th amino acid residues of a pTH (1-34) parent peptide sequence is connected with octadecanedioic acid or eicosanoic acid and a derivative modification group of octadecanedioic acid or eicosanoic acid, and the polypeptide is covalently combined with a polypeptide skeleton through an AEA-AEA-gamma-Glu connecting unit. The binding capacity of the polypeptide and serum albumin is remarkably enhanced by utilizing a fatty acid side chain modification means, and meanwhile, the half-life period is prolonged. The pTH long-acting polypeptide compound disclosed by the invention has remarkable osteogenic activity promoting effect, can promote proliferation of MC3T3-E1 cells and generate osteogenic markers and calcium nodules under osteogenic induction conditions, and the binding capacity of the pTH long-acting polypeptide compound and serum albumin is improved by 2-6 times. The invention further provides a solid-phase synthesis method of the polypeptide compound and a pharmaceutical composition containing the polypeptide compound, the polypeptide compound can be used for treating osteoporosis and parathyroid hypofunction, and the compliance problem that an existing medicine needs to be injected every day is effectively solved.

Disclosed are compounds that are parathyroid hormone receptor 1 agonists, and methods useful for preventing or treating osteoporosis, fracture, osteomalacia, arthritis, thrombocytopenia, hypoparathyroidism, hyperphosphatemia or tumoral calcinosis.

Disclosed are compounds that are parathyroid hormone receptor 1 agonists, and methods for the prevention or treatment of osteoporosis, bone fractures, osteomalacia, arthritis, thrombocytopenia, parathyroid hypofunction, hyperphosphatemia, or neoplastic calcaremia.

The invention provides a method of treating or controlling hypoparathyroidism in a human patient by administering to the human patient a pharmaceutical composition comprising a controlled-release PTH compound or a pharmaceutically acceptable salt thereof. The controlled-release PTH compound comprises a PTH moiety reversibly conjugated to a branched polyethylene glycol carrier. The composition is administered by subcutaneous injection no more frequently than once every 24 hours with a dosage of the controlled-release PTH compound that corresponds to no more than 70% of the molar equivalent dose of PTH 1-84 administered by subcutaneous injection at the same dosing frequency required to maintain a serum albumin-adjusted calcium level in serum of above 8.5 mg / dL over a 24 hour period.

Disclosed are compounds that are parathyroid hormone receptor 1 agonists, and methods useful for preventing or treating osteoporosis, fracture, osteomalacia, arthritis, thrombocytopenia, hypoparathyroidism, hyperphosphatemia or tumoral calcinosis.

The invention provides a PTH1R agonist compound, a pharmaceutical composition and application of the PTH1R agonist compound. The compound has good PTH1R agonist activity and is used for treating diseases and / or diseases related to parathyroid hypofunction and / or osteoporosis and preparing drugs for the diseases and / or diseases.

The invention relates to parathyroid hormone (PTH) variants and pharmaceutical compositions comprising same. The invention further relates to PTH compositions with improved serum half-life and peak-trough ratios, and methods of controlling serum calcium levels with the PTH variants and compositions of the invention. The invention further relates to methods of treating hypoparathyroidism and / or hypocalcemia due to hypoparathyroidism with the PTH variants and compositions of the invention.

Disclosed are compounds that are parathyroid hormone receptor 1 agonists, and methods useful for preventing or treating osteoporosis, fracture, osteomalacia, arthritis, thrombocytopenia, hypoparathyroidism, hyperphosphatemia or tumoral calcinosis. Also disclosed are agonists of GLP-1R, GCGR, and / or GIPR, and methods of treating various therapeutic indications by administering an effective amount of an agonist of GLP-1R, GCGR, and / or GIPR.

Disclosed are compounds that are parathyroid hormone receptor 1 agonists, and methods useful for preventing or treating osteoporosis, fracture, osteomalacia, arthritis, thrombocytopenia, hypoparathyroidism, hyperphosphatemia or tumoral calcinosis. Also disclosed are agonists of GLP-1R, GCGR, and / or GIPR, and methods of treating various therapeutic indications by administering an effective amount of an agonist of GLP-1R, GCGR, and / or GIPR.

Disclosed are a compound that is a parathyroid hormone receptor 1 agonist and a method useful for preventing or treating osteoporosis, fractures, osteomalacia, arthritis, thrombocytopenia, hypoparathyroidism, hyperphosphatemia, or neoplastic calcification.

Disclosed are peptide-fatty acid conjugates, pharmaceutical compositions containing them, and methods of their medical use in the treatment of, e.g., a disease or condition associated with the PTHR1 signaling overactivity (e.g., hypercalcemia, hypophosphatemia, hyperparathyroidism, or Jansen's metaphyseal chondrodysplasia) or deficiency (e.g., hypoparathyroidism, hyperphosphatemia, osteoporosis, fracture repair, osteomalacia, arthritis, thrombocytopenia, or chronic kidney disease).

Disclosed are compounds that are parathyroid hormone receptor 1 agonists, and methods of using them for preventing or treating osteoporosis, fracture, osteomalacia, arthritis, thrombocytopenia, hypoparathyroidism, hyperphosphatemia or tumoral calcinosis.

This invention relates to the field of biomedicine, disclosing a long-acting pTH polypeptide compound and its preparation and application. The polypeptide has an octadecanoic acid or eicosanoic acid and its derivatives modified by at least one amino acid residue at the 13th, 26th, and 27th amino acid residues of the pTH (1-34) parent peptide sequence, and is covalently bound to the polypeptide backbone via an AEEA-AEEA-γ-Glu linker. This invention significantly enhances the binding ability of the polypeptide to serum albumin and prolongs its half-life by utilizing fatty acid side chain modification. The long-acting pTH polypeptide compound of this invention exhibits significant osteogenic activity, promoting the proliferation of MC3T3-E1 cells and generating osteogenic markers and calcium nodules under osteogenic induction conditions, with a 2-6 fold increase in binding ability to serum albumin. This invention also provides a solid-phase synthesis method for this polypeptide compound and a pharmaceutical composition containing it, which can be used to treat osteoporosis and hypoparathyroidism, effectively solving the compliance problem of existing drugs requiring daily injections.

The invention belongs to the technical field of biology, and particularly relates to a human parathyroid hormone 1-34 peptide analogue and a preparation method and application of the human parathyroid hormone 1-34 peptide analogue, and the human parathyroid hormone 1-34 peptide analogue is formed by peptide fragments shown in SEQ ID No.1-SEQ ID No.8 or homologous peptide fragments of the peptide fragments. The human parathyroid hormone 1-34 peptide analogue has osteoporosis treatment activity, is used for relieving parathyroid hypofunction and related symptoms after parathyroid gland resection or extirpation, and also has an erection promoting function, and the preparation method is economical and environment-friendly, is suitable for industrial development and has a wide prospect.

The invention relates to parathyroid hormone (PTH) variants and pharmaceutical compositions comprising same. The invention further relates to PTH compositions with improved serum half-life and peak-trough ratios, and methods of controlling serum calcium levels with the PTH variants and compositions of the invention. The invention further relates to methods of treating hypoparathyroidism and / or hypocalcemia due to hypoparathyroidism with the PTH variants and compositions of the invention.

Disclosed are peptide-fatty acid conjugates, pharmaceutical compositions containing them, and methods of their medical use in the treatment of, e.g., a disease or condition associated with the PTHR1 signaling overactivity (e.g., hypercalcemia, hypophosphatemia, hyperparathyroidism, or Jansen's metaphyseal chondrodysplasia) or deficiency (e.g., hypoparathyroidism, hyperphosphatemia, osteoporosis, fracture repair, osteomalacia, arthritis, thrombocytopenia, or chronic kidney disease).

A recombinant PTH fusion protein, a construction method therefor, and an application thereof. The recombinant PTH fusion protein comprises: A1) at least one signaling domain molecule capable of activating a PTHR1 intracellular pathway; A2) a molecule having one or more ECDs capable of binding to the PTHR1; A3) a human serum albumin nanobody, wherein an amino acid sequence of the human serum albumin nanobody is as shown in SEQ ID NO: 7. The recombinant PTH fusion protein is capable of effectively improving the duration and magnitude of pharmacodynamic action, increasing blood calcium levels within 24-48 hours, and returning to normal levels within 48-72 hours. Said protein has excellent temperature stability and freeze-thaw stability, and can be used for treating and / or preventing hypoparathyroidism. In addition, the preparation method for the recombinant PTH fusion protein is simple and can be used for industrial production.

The present invention relates to a PTH compound for use in the treatment of chronic hypoparathyroidism, wherein the treatment comprises the step of administering to a patient having chronic hypoparathyroidism a once weekly dose of a PTH compound and wherein prior to initiation of the treatment the patient is clinically determined as being no longer dependent on active vitamin D and calcium supplement to maintain serum within normal range; and related aspects.

Disclosed are compounds that are parathyroid hormone receptor 1 agonists, and methods useful for preventing or treating osteoporosis, fracture, osteomalacia, arthritis, thrombocytopenia, hypoparathyroidism, hyperphosphatemia or tumoral calcinosis. Also disclosed are agonists of GLP-1R, GCGR, and / or GIPR, and methods of treating various therapeutic indications by administering an effective amount of an agonist of GLP-1R, GCGR, and / or GIPR.

Disclosed are compounds that are parathyroid hormone receptor 1 agonists, and methods useful for preventing or treating osteoporosis, fracture, osteomalacia, arthritis, thrombocytopenia, hypoparathyroidism, hyperphosphatemia or tumoral calcinosis. Also disclosed are agonists of GLP-1R, GCGR, and / or GIPR, and methods of treating various therapeutic indications by administering an effective amount of an agonist of GLP-1R, GCGR, and / or GIPR.

Disclosed are compounds that are parathyroid hormone receptor 1 agonists, and methods useful for preventing or treating osteoporosis, fracture, osteomalacia, arthritis, thrombocytopenia, hypoparathyroidism, hyperphosphatemia or tumoral calcinosis. Also disclosed are agonists of GLP-1R, GCGR, and / or GIPR, and methods of treating various therapeutic indications by administering an effective amount of an agonist of GLP-1R, GCGR, and / or GIPR.

Compositions and methods for treating hypoparathyroidism in a subject are provided. A viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding a PTH fusion protein and regulatory sequences which direct expression thereof.

Disclosed are compounds that are parathyroid hormone receptor 1 agonists, and methods useful for preventing or treating osteoporosis, fracture, osteomalacia, arthritis, thrombocytopenia, hypoparathyroidism, hyperphosphatemia or tumoral calcinosis. Also disclosed are agonists of GLP-1R, GCGR, and / or GIPR, and methods of treating various therapeutic indications by administering an effective amount of an agonist of GLP-1R, GCGR, and / or GIPR.

To provide a more convenient and safer treatment of hypoparathyroidism with reduced side-effects.SOLUTION: The present invention provides a pharmaceutical composition comprising at least one controlled-release PTH compound or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the treatment, control, delay or prevention of a condition that can be treated, controlled, delayed or prevented with PTH. The pharmaceutical composition is administered at a frequency of at most once every 24 hours with a dosage of the controlled-release PTH compound that corresponds to 70% or less of the molar equivalent dose of PTH 1-84 administered every 24 hours required to maintain serum calcium within normal levels over the 24 hours in humans.SELECTED DRAWING: None

The present application relates to the use of a PTH compound for the treatment of chronic parathyroidism wherein said treatment comprises the step of administering a weekly dose of a PTH compound per week to a patient suffering from chronic parathyroidism, and wherein before the start of the treatment, the PTH compound is added to the patient. Patients are clinically determined to no longer rely on active vitamin D and calcium supplements to maintain serum within a normal range; and related aspects.