65results about "Vasoactive intestinal peptide" patented technology

The invention relates to the technical field of preparation methods of polypeptide drugs, and provides a solid-phase preparation method of tirpotide, which comprises the following steps: by taking amino resin as initial resin, sequentially coupling amino acid and small-fragment peptide according to an amino acid sequence of the tirpotide by using a solid-phase synthesis method to synthesize tirpotide resin; and cracking and purifying the tilpotide resin to obtain a pure tilpotide product. Wherein the small fragment peptide is 1-4 tetrapeptide fragment Boc-Tyr (tBu)-Aib-Glu (OtBu)-G1y-OH, 5-6 dipeptide fragment Fmoc-Thr (tBu)-Phe-OH, 7-8 dipeptide fragment Fmoc-Thr (tBu)-Ser (tBu)-OH, 10-11 dipeptide fragment Fmoc-Tyr (tBu)-Ser (tBu)-OH, 12-13 dipeptide fragment Fmoc-Ile-Aib-OH, 17-18 dipeptide fragment Fmoc-Lys (AEEA-AEA-gamma-Glu (alpha-OtBu)-Ecosanoic acid (mon-tBu), 20 side chain peptide Fmoc The coupling agent coupling the amino acid and the small fragment peptide is selected from the group consisting of Oxyma and DIC, TPTU and TMP or COMU and DIEA. The crude product of the tirpotide prepared by the method disclosed by the invention is high in yield and high in purity.

The present invention is directed to antagonistic antibodies and antigen binding fragments thereof having binding specificity for PACAP. These antibodies inhibit, block or neutralize at least one biological effect associated with PACAP, e.g., vasodilation. In exemplary embodiments these antibodies and antigen binding fragments thereof may comprise specific VH, VL, and CDR polypeptides described herein. In some embodiments these antibodies and antigen binding fragments thereof bind to and / or compete for binding to specific epitope(s) on human PACAP. The invention is further directed to using these antagonistic anti-PACAP antibodies, and binding fragments thereof, for the diagnosis, assessment, and treatment of diseases and disorders associated with PACAP and conditions where antagonism of PACAP-related activities, such as vasodilation, mast cell degranulation, and / or neuronal activation, are therapeutically beneficial, e.g., headache and migraine indications.

The present disclosure relates to VIP antagonists for use in managing the treatment or prevention of cancer and viral infections. In certain embodiments, the present disclosure relates to chimeric variants of VIP antagonists as peptides disclosed herein and pharmaceutical compositions comprising the same. In certain embodiments, the present disclosure contemplates a method of targeting cancer by stimulating immune cells, combining the immune cells in vitro with the peptides disclosed herein, and administering an effective amount of the stimulated immune cells to a subject in need of cancer treatment.

This disclosure relates to VIP antagonist for uses in managing the treatment or prevention of cancer and viral infections. In certain embodiments, this disclosure relates to chimeric variants of VIP antagonists, as peptides disclosed herein, and pharmaceutical composition comprising the same. In certain embodiments, this disclosure contemplates methods of stimulating immune cells to target cancer by mixing immune cells in vitro with peptides disclosed herein and further administering an effective amount of stimulated immune cells to a subject in need of cancer treatment.

A Fusion Peptide for Activation of the APJ and / or GLP-1 Receptors This invention relates to a fusion peptide comprising a GLP-1 receptor agonist (GLP-1 RA) and an APJ receptor agonist; wherein the GLP-1 RA is covalently linked to the APJ receptor agonist by a link; and wherein the fusion peptide retains at least some activity of at least one of the GLP-1 RA and the APJ receptor agonist.

Methods and compositions are provided for extending the half-life of a therapeutic agent. A modified therapeutic agent (mTA) comprises a therapeutic agent, a staple, and a half-life extending molecule. The mTAs disclosed herein may be used to treat a disease or a condition in a subject in need thereof.

The present invention discloses a polypeptide compound and its application in preventing or treating diabetes or diabetic complications. The polypeptide compound shows good long-term hypoglycemic effect and therapeutic effect of diabetic nephropathy; at the same time, it has the effects of high enzymatic stability, high biological activity, no adverse reactions, etc., and can be used to prepare drugs for treating overeating, obesity and overweight, elevated cholesterol, diabetes and diabetic nephropathy.

To provide a composition for preventing or treating neurotrophic keratitis.SOLUTION: It is found that a PACAP peptide exerts an inhibitory effect of cornea disorder in a neurotrophic keratitis model, and model axon extension is promoted in a cultured nerve cell. Furthermore, provided are a composition for preventing or treating neurotrophic keratitis which contains a PACAP peptide or a stabilized PACAP peptide in which stability significantly enhances by substituting a carboxyl group of aspartic acid at the 3- and / or 8-position in a sequence of PACAP with tetrazole, and an axon extension promoter.SELECTED DRAWING: Figure 4

VIP-R antagonists are disclosed for use in managing the treatment or prevention of cancer and viral infection. In certain embodiments, the disclosure relates to chimeric variants of VIP-R antagonists as peptides disclosed herein, and pharmaceutical compositions comprising same. In certain embodiments, the disclosure contemplates a method of treating a subject with cancer or infectious disease with VIP-R antagonists, or a method of stimulating immune cells that target cancer by mixing immune cells with peptides disclosed herein in vitro, and further administering an effective amount of stimulated immune cells to a subject in need of cancer treatment.

To provide a pharmaceutical composition for prevention or treatment of metabolic syndrome.SOLUTION: The present invention provides a composition comprising: a glucagon derivative; and a GLP-1 receptor and GIP receptor dual agonist, and use thereof.SELECTED DRAWING: None

The present invention is entitled Triple Agonists at the Glucagon / GLP-1 / GIP Receptor. The present invention relates to triple agonists that are active at all of the glucagon, GLP-1 and GIP receptors and uses thereof.

Provided is a fusion protein. The fusion protein simultaneously blocks a calcitonin gene-related peptide (CGRP) pathway and a pituitary adenylate cyclase-activating polypeptide (PACAP) pathway, wherein the fusion protein comprises at least one single-domain antibody, at least one Fc fragment, and at least one extracellular domain fragment of pituitary adenylate cyclase 1 (PAC1 ECD). The fusion protein can simultaneously block the CGRP and PACAP pathways, thereby improving the response rate of a drug for treatment of migraine.

Disclosed herein is a novel pharmaceutical composition for treating pain, wherein the pharmaceutical composition targets a transient receptor potential vanilloid 1 (TRPV1) receptor and acts as an antagonist.

The present disclosure provides a method for delivering a neuroprotective polypeptide to at least a portion of a central nervous system (CNS) of a subject. The method includes administering to the systemic blood circulation of the subject a therapeutically effective amount of a neuroprotective polypeptide by a controlled-release formulation or a device providing a sustained release of the neuroprotective polypeptide including at least one neuroprotective polypeptide selected from the group consisting of GLP-1, exendin-4, or a therapeutically effective GLP-1 or exendin-4 analogue; the neuroprotective polypeptide binds to and activates a receptor that binds at least one of GLP-1, exendin-4, or a combination thereof; and the controlled-release neuroprotective formulation or the sustained release of the neuroprotective polypeptide enhances the delivery of the neuroprotective polypeptide across a blood-brain barrier (BBB) of the subject to at least a portion of the CNS relative to a rapid release formulation of the neuroprotective polypeptide. Also disclosed is a method of treating a subject with a CNS-related disease or reducing at least one symptom of a CNS-related disease in a subject in need thereof.

Disclosed are VIP-R antagonists for uses in managing the treatment or prevention of cancer and viral infections. In certain embodiments, this disclosure relates to chimeric variants of VIP-R antagonists, as peptides disclosed herein, and pharmaceutical composition comprising the same. In certain embodiments, this disclosure contemplates methods of treating subjects with cancer or infection with VIP-R antagonists or stimulating immune cells to target cancer by mixing immune cells in vitro with peptides disclosed herein and further administering an effective amount of stimulated immune cells to a subject in need of cancer treatment.

The invention provides a fusion protein for treating metabolic diseases, and a preparation method and use thereof. The fusion protein has a general formula of R1-L-R2 or R2-L-R1, wherein R1 is FGF21 protein, an FGF21 protein analog, or a similar peptide with the biological function of FGF21 protein; R2 is GIP, mutant GIP or a similar peptide with the biological function of GIP; and L is a linker peptide. The fusion protein of the present invention is used as a therapeutic agent or a pharmaceutical composition in the treatment of diseases associated with hyperglycemia and hyperlipidemia, including diabetes, obesity, steatohepatitis or cardiovascular diseases,

The present invention relates to glucose-dependent insulinotropic peptide (GIP) receptor (GIPR) antagonist GIP peptides in combination with glucagon-like peptide-1 (GLP-1) receptor agonists, such as GLP-1 peptides, for use in the treatment of obesity and obesity-related disorders, and GIPR antagonist GIP peptides for treating a subset of obesity-related disorders.

To provide a composition for preventing or treating neurotrophic keratitis.SOLUTION: It is found that a PACAP peptide exerts an inhibitory effect of cornea disorder in a neurotrophic keratitis model, and model axon extension is promoted in a cultured nerve cell. Furthermore, provided are a composition for preventing or treating neurotrophic keratitis which contains a PACAP peptide or a stabilized PACAP peptide in which stability significantly enhances by substituting a carboxyl group of aspartic acid at the 3- and / or 8-position in a sequence of PACAP with tetrazole, and an axon extension promoter.SELECTED DRAWING: Figure 4

Provided are a recombinant microorganism expressing a vasoactive intestinal peptide (VIP) gene, and a composition including the microorganism for preventing or treating a disease causing damage to the gastrointestinal tract.

The present invention relates to a novel brain disease therapeutic agent and a use thereof. The peptide or the pharmaceutical composition according to the present invention can improve the delivery level to a target site (particularly an inflamed region of the brain) due to having a high blood-brain barrier penetration level, can have an improved half-life in the blood flow, and can exhibit anti-inflammatory activity and treat or prevent brain diseases by reducing the level of inflammation.

The invention provides a novel oral blood sugar reducing polypeptide. The polypeptide is an improved derivative based on Exendin-4. According to the present invention, the Exendin-4 is analyzed so as to obtain the core sequence of 28 amino acids, wherein the core sequence is HGEGTFTSDLSKQMEEEAVRLFIEWLKN; in order to improve the stability and bioavailability, four key sites are subjected to amino acid substitution (K12H, R20H, F22A and K27H), AF and FK are respectively added at the N end and the C end, and finally a complete sequence with 32 amino acids is formed. The structural modifications significantly improve the oral absorption efficiency of the polypeptide. Compared with an Exendin-4 prototype, the antihyperglycemic polypeptide Ex32 disclosed by the invention has the advantages that the enzymolysis resistance is obviously improved, and the obtained Ex32-containing polypeptide has good physical and chemical stability and bioavailability and can be directly used for preparing various dosage forms, for example, the Ex32-containing polypeptide can be used for treating type II diabetes mellitus.

To provide a VIP antagonist for uses in managing the treatment or prevention of cancer and viral infections.SOLUTION: In certain embodiments, this disclosure relates to chimeric variants of VIP antagonists, as peptides disclosed herein, and pharmaceutical composition comprising the same. In certain embodiments, this disclosure contemplates methods of stimulating immune cells to target cancer by mixing immune cells in vitro with peptides disclosed herein and further administering an effective amount of stimulated immune cells to a subject in need of cancer treatment.SELECTED DRAWING: None

A fusion protein is provided that blocks both a calcitonin gene related peptide (CGRP) pathway and a pituitary adenylate cyclase activated peptide (PACAP) pathway, where the fusion protein comprises at least one single domain antibody, at least one Fc fragment, and at least one extracellular domain fragment of pituitary adenylate cyclase 1 (PAC1 ECD). The fusion protein can block CGRP and PACAP pathways at the same time, and the response rate of drugs for treating migraine is improved.

Provided are a fusion protein of an exenatide precursor and a use thereof. The fusion protein comprises an exenatide precursor and a tag protein fused at an N terminus of the exenatide precursor. The exenatide precursor has an amino acid sequence as shown in SEQ ID NO: 1. The tag protein is selected from any one of Fh8 tag protein, Ffu209 tag protein, CBM tag protein, Sumo tag protein, or Trx tag protein. The exenatide precursor is fused with the tag protein, and the exenatide precursor carrying the tag protein exhibits a high expression level, enabling the preparation of large quantities of high-purity exenatide precursors, thereby facilitating industrial-scale production and use of exenatide.

Disclosed are VIP-R antagonists for uses in managing the treatment or prevention of cancer and viral infections. In certain embodiments, this disclosure relates to chimeric variants of VIP-R antagonists, as peptides disclosed herein, and pharmaceutical composition comprising the same. In certain embodiments, this disclosure contemplates methods of treating subjects with cancer or infection with VIP-R antagonists or stimulating immune cells to target cancer by mixing immune cells in vitro with peptides disclosed herein and further administering an effective amount of stimulated immune cells to a subject in need of cancer treatment.

The present disclosure provides a method for delivering a neuroprotective polypeptide to at least a portion of a subject's central nervous system (CNS). The method includes administering a therapeutically effective amount of a neuroprotective polypeptide to the subject's systemic circulatory bloodstream using a controlled-release preparation or device that provides sustained release of the neuroprotective polypeptide, wherein the neuroprotective polypeptide comprises at least one neuroprotective polypeptide selected from the group consisting of GLP-1, exendin-4, or a therapeutically effective GLP-1 or exendin-4 analog, wherein the neuroprotective polypeptide binds to and activates a receptor that binds to at least one of GLP-1, exendin-4, or a combination thereof, and the controlled-release neuroprotective preparation or sustained release of the neuroprotective polypeptide increases delivery of the neuroprotective polypeptide across the subject's blood-brain barrier (BBB) ​​to at least a portion of the CNS compared to an immediate-release preparation of the neuroprotective polypeptide. The present disclosure also discloses a method for treating a subject with a CNS-related disorder or reducing at least one symptom of a CNS-related disorder in a subject in need thereof.

The present invention relates to the technical field of polypeptide drug preparation methods. Provided is a solid-phase preparation method for high-yield and high-purity tirzepatide. An amino resin is used as a starting resin; amino acids and small-fragment peptides are sequentially coupled according to the amino acid sequence of tirzepatide using a solid-phase synthesis method to synthesize a tirzepatide resin; and the tirzepatide resin is cleaved and purified to obtain a pure tirzepatide product. The small-fragment peptides include a 1-4 tetrapeptide fragment Boc-Tyr(tBu)-Aib-Glu(OtBu)-Gly-OH, a 5-6 dipeptide fragment Fmoc-Thr(tBu)-Phe-OH, a 7-8 dipeptide fragment Fmoc-Thr(tBu)-Ser(tBu)-OH, a 10-11 dipeptide fragment Fmoc-Tyr(tBu)-Ser(tBu)-OH, a 12-13 dipeptide fragment Fmoc-Ile-Aib-OH, a 17-18 dipeptide fragment Fmoc-Ile-Ala-OH, a 20-side-chain peptide Fmoc-Lys(AEEA-AEEA-γ-Glu(α-OtBu)-Eicosanedioic acid(mon-tBu))-OH, a 28-30 tripeptide fragment Fmoc-Ala-Gly-Gly-OH, a 32-34 tripeptide fragment Fmoc-Ser(tBu)-Ser(tBu)-Gly-OH, and a 36-38 tripeptide fragment Fmoc-Pro-Pro-Pro-OH. A coupling agent for coupling the amino acid and the small-fragment peptide is selected from Oxyma and DIC, TPTU and TMP, or COMU and DIEA.

Methods for increasing auditory cortex interneuron excitability and improving auditory perception, in particular pitch-discrimination acuity, are provided, which include the use of a Vasoactive Intestinal Peptide Receptor 1 (VIPR1) inhibitor.

The invention title of the present invention is a long-acting conjugate of a glucagon / GLP-1 / GIP receptor triple agonist. The present invention relates to a long-acting conjugate of a triple agonist that is active against all of the glucagon, GLP-1, and GIP receptors and its uses.