24 results about "CGRP receptor" patented technology

The application discloses a method for preparing a CGRP receptor antagonistic intermediate, and belongs to the field of synthesis of medical intermediates. Compound 1 is used as a raw material, reacts with hydroxylamine hydrochloride in an organic solvent to generate an intermediate 2, and then reacts in the presence of a reducing agent to obtain a remikiren intermediate 3. The application is characterized in that a large steric hindrance silicon group is used as the R substituent in the compound 1, so that high stereoselectivity is ensured in the reduction reaction. The key intermediate obtained by using the method has high chiral purity, and the operation is simple, so that the industrial production of the product in the later stage can be realized.

The invention provides an application of a CGRP inhibitor in preparation of a medicine for treating myocardial infarction or heart failure, relates to the technical field of biomedicine, and has the technical key points that the invention provides the CGRP inhibitor Rimegepant and provides an effect of the CGRP inhibitor Rimegepant in myocardial infarction and heart failure, and the CGRP inhibitor Rimegepant can be used for preparing a medicine for treating myocardial infarction or heart failure. The myocardial infarction and / or heart failure model is constructed through left anterior descending branch coronary artery ligation. In-vitro experiments verify that the expression of the CGRP receptor protein in the heart of a mouse after heart failure is increased, and prove that the CGRP inhibitor Rimegeant can effectively inhibit the expression of the CGRP receptor protein, and further research is carried out, so that a potential treatment strategy is provided for drug research and development. The in-heart CGRP receptor inhibitor can obviously relieve the myocardial infarction and / or heart failure course of mice, and down-regulate the protein expression of the CGRP receptor at the same time.

Nausea and vomiting are unpleasant events caused by a variety of triggering factors. Wherein medicines often cause nausea and vomiting. An anti-tumor chemotherapeutic agent is one of the most emetic drugs, and often causes chemotherapy-induced nausea and vomiting (CINV). The latter seriously impairs the therapeutic effect and the quality of life of the patient. It is of great interest in determining agents capable of preventing and combating drug-induced nausea and vomiting, including CINV. A calcitonin gene-related peptide (CGRP) is a neuropeptide having various effects in a human body. However, neuropeptide effects in the brain are still to be clarified. CGRP receptor antagonists (named as gezepam) have been recently approved for use in the treatment of migraine. The use of gezepams for the direct treatment of nausea and vomiting, including CINV, is described.

Interoception is the mechanism by which an individual is informed about the status of its own body. When interoception becomes dysfunctional, it turns into a deleterious event for the health status of an individual. The use of calcitonin gene-related peptide (CGRP) receptor antagonists (gepants) for the treatment and 70 prevention of interoception disorders is described.

The application discloses application of a CGRP receptor small molecule antagonist in preparation of a medicine for treating chronic rhinosinusitis with nasal polyps. The medicine preparation is composed of an effective amount of the CGRP receptor small molecule antagonist and pharmaceutically acceptable adjuvants, and the dosage form is a nasal spray / drop / irrigation agent, and the administration route is simple and easy to operate, and is convenient for patients to use. The application can significantly reduce eosinophilic inflammation by inhibiting CGRP-mediated mast cell activation, and has a clear treatment advantage for eosinophilic nasal polyps. Compared with a biological preparation targeting type 2 cytokines, a small molecule compound is safer and simpler to obtain, can significantly reduce the treatment cost of patients, and provides a new efficient and economical choice for nasal polyp treatment.

The invention provides a conjugate comprising a peptide that binds to the Calcitonin Gene-Related Peptide Receptor that is linked to a therapeutic or a detectable radionuclide. The conjugates are useful for imaging the Calcitonin Gene-Related Peptide Receptor and for treating diseases wherein the activity of the Calcitonin Gene-Related Peptide Receptor is implicated.

The application provides an application of a hair follicle immune homeostasis regulation strategy in treating alopecia diseases. A group of pathological LAMP3 + CCR7 + IL4I1 + DC3 dendritic cell subpopulation. A DC3 dendritic cell subpopulation marker gene Il4i1 Drive conditionally knockout one of the CGRP receptor complexes Calcrl The constructed spontaneous alopecia areata animal model can well simulate the progressive and active hair loss of alopecia areata patients, form stable hair loss patches, and combine with pathological changes such as hair follicle immune cell infiltration, which indicates that the dendritic cell CGRP signal loss is an important inducement for mediating systemic alopecia areata. The application also discloses a pharmaceutical composition or kit for preparing a drug for relieving / treating hair loss, improving hair follicle homeostasis, or enhancing hair growth / black coloration (reducing white hair), which comprises: (a) a JAK kinase inhibitor, and (b) a neuropeptide CGRP or a receptor agonist thereof.

The invention provides a conjugate comprising a peptide that binds to the Calcitonin Gene-Related Peptide Receptor that is linked to a therapeutic or a detectable radionuclide. The conjugates are useful for imaging the Calcitonin Gene-Related Peptide Receptor and for treating diseases wherein the activity of the Calcitonin Gene-Related Peptide Receptor is implicated.

The present application relates to a substituted piperidine carboxamide azaindane derivative, a method for preparing same, and use of a pharmaceutical composition containing the derivative or a deuterated derivative in medicine. Specifically, the present application relates to a substituted piperidine carboxamide azaindane derivative represented by general formula (I), a method for preparing same, a pharmaceutically acceptable salt thereof, and use thereof as a CGRP receptor antagonist in preventing and / or treating CORP-related diseases, in particular the field of migraine. The definition of each substituent in general formula (I) is the same as that in the specification.

The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition for treating headache and a preparation method thereof. The pharmaceutical composition comprises the following raw materials in parts by weight: 30-40 parts of a pharmaceutical active component, 2-4 parts of a disintegrating agent, 6-11 parts of a filler and 0.2-0.5 part of a lubricant, the active pharmaceutical ingredient consists of porphyridium polysaccharide and manganese gluconate in a mass ratio of 1: (0.5-1). The action mechanisms of the two active components in the pharmaceutical composition are clear and complementary: porphyridium polysaccharide reduces the expression of a proinflammatory factor by inhibiting an NF-kappa B signal channel so as to relieve the stimulation to trigeminal nerve endings, and the porphyridium polysaccharide is mild in action and can avoid the potential influence of strong immunosuppression on the immune system of children; manganese gluconate blocks a CGRP receptor in a targeting manner, directly inhibits nerve ending sensitization and central pain signal transduction mediated by the pain-inducing peptide, and intervenes migraine attack from a key path.

The invention relates to the technical field of biological medicines, in particular to application of a CGRP inhibitor remegapam and a PD-1 inhibitor in combined preparation of a medicine for treating colorectal cancer liver metastasis. Experimental results show that remegapam effectively reverses a liver immunosuppression microenvironment by blocking a CGRP receptor, and generates a remarkable synergistic anti-tumor effect with a PD-1 inhibitor, so that a brand new effective strategy is provided for overcoming immunotherapy drug resistance of colorectal cancer liver metastasis.

A method in which gepants (antagonists of calcitonin gene related peptide (CGRP) receptor) are used for direct treatment of nausea and vomiting including chemotherapy-induced nausea and vomiting (CINV). Among them, drugs frequently prompt nausea and vomiting, such as antitumor chemotherapeutics which often cause CINV which in turn can severely compromise efficacy of therapy, as well as patient quality of life. The method uses antagonists of the CGRP receptor recently approved for migraine treatment to target calcitonin gene related peptide (CGRP), a neuropeptide with pleiotypic effects in the human body to prevent and counteract drug-induced nausea and vomiting including CINV.

The invention discloses a CGRP receptor antagonist and application thereof. The CGRP receptor antagonist has a structure as shown in a formula I, or pharmaceutically acceptable salt of the structure as shown in the formula I, and an isomer thereof. The invention also provides application of the compound shown in the formula I in preparation of medicines for preventing and / or treating related respiratory diseases such as asthma.

The invention discloses an application of a CGRP receptor small molecule antagonist in preparation of a medicine for treating eosinophilic chronic sinusitis with nasal polyp. The pharmaceutical preparation is composed of an effective amount of a CGRP receptor small molecule antagonist and pharmaceutically acceptable auxiliary materials, the dosage form is nasal spray / nose drop / irrigation, and the pharmaceutical preparation is simple and convenient in administration route, easy to operate and convenient for patients to use. According to the invention, by inhibiting CGRP-mediated mast cell activation, eosinophilic granulocyte inflammation is significantly relieved, and especially, the traditional Chinese medicine composition has a definite treatment advantage on eosinophilic granulocyte nasal polyp; and compared with a biological agent of a targeted type 2 cytokine, the small molecule compound is safer, simpler and more convenient to obtain, the treatment cost of a patient can be remarkably reduced, and a new efficient and economic choice is provided for nasal polyp treatment.

According to the present invention there is provided a pharmaceutically acceptable composition in the form of a solid amorphous single particulate powder comprising a mixture of: (a) a pharmacologically effective dose of a small molecule CGRP receptor antagonist or a pharmaceutically acceptable salt thereof; and (b) a pharmaceutically acceptable carrier material comprising maltodextrin having a glucose equivalent (DE) of greater than 15. The compositions are suitable for, for example, transmucosal drug delivery, including transnasal delivery, which compositions are loadable into single use transnasal applicators by transnasal delivery. The composition is preferably made by spray drying, and may further include a disaccharide, such as lactose or trehalose, which may be spray dried in combination with the active ingredient and maltodextrin. The composition may further comprise one or more alkyl saccharides. Preferred alkyl saccharides include sucrose esters, such as sucrose monolaurate. Preferred CGRP receptor antagonists include a gezepam, such as ubugepam, atogepam, remegepam, and zalvigepam. Thus, the composition is particularly useful in the treatment of migraine-related conditions.

The present invention relates to a calcitonin gene-related peptide (CGRP) receptor antagonist of formula (I) or a or equivalent net peptide weight of a pharmaceutically active salt thereof, namely AXN-001, which is also known as FE 205030 A pharmaceutical composition comprising AXN-001 can be used in the treatment of acute migraine.

The present invention provides an antibody molecule or antigen-binding fragment that specifically binds to a calcitonin gene-related peptide (CGRP) receptor, a fusion protein comprising two antibody molecules or antigen-binding fragments of the CGRP receptor, and a fusion protein further comprising a binding domain that specifically binds to a human HSA protein. The present invention also provides a nucleic acid encoding the antibody molecule or antigen-binding fragment and the fusion proteins thereof, a vector, a cell, a kit and pharmaceutical composition containing same, a use in the preparation of a drug for diseases related to CGRP over-activation, and the like.

The present disclosure relates to productive tissue repair and regeneration, and in particular fusion proteins and polypeptides, compositions including said fusion proteins and polypeptides, and methods of using said polypeptides or compositions for productive tissue repair and regeneration. In one aspect, there is provided a fusion protein comprising (i) a calcitonin gene-related peptide (CGRP) receptor agonist polypeptide; and (ii) an extracellular matrix (ECM) binding polypeptide. In another aspect, there is provided a fusion protein comprising: (a) a first polypeptide; and (b) a second polypeptide, wherein the first and second polypeptide are joined by a linker that comprises, consists essentially of or consists of the amino acid sequence KGYR (SEQ ID NO: 70).

The application relates to a substituted piperidylcarboxamide azaindane derivative, a preparation method thereof and medical application of a pharmaceutical composition containing the derivative or a deuterated derivative. Specifically, the application relates to a substituted piperidylcarboxamide azaindane derivative shown in a general formula (I), a preparation method thereof and a pharmaceutically acceptable salt, and purposes of the substituted piperidylcarboxamide azaindane derivative as a CGRP receptor antagonist in prevention and / or treatment of CGRP related diseases, especially in the field of migraine. Wherein definitions of the substituents in the general formula (I) are the same as those in the specification.

Provided are Calcitonin gene-related peptide (CGRP) analogues which are potent CGRP receptor agonists.

The present disclosure provides methods for the treatment of migraine, such as the acute treatment of migraine, in particular during the prodrome stage of a migraine attack, comprising administering a CGRP receptor antagonist. In particular, the present disclosure provides methods for administering ubrogepant during the prodrome or premonitory phase for the acute treatment of migraine.

The invention provides a conjugate comprising a peptide that binds to the Calcitonin Gene-Related Peptide Receptor that is linked to a therapeutic or a detectable radionuclide. The conjugates are useful for imaging the Calcitonin Gene-Related Peptide Receptor and for treating diseases wherein the activity of the Calcitonin Gene-Related Peptide Receptor is implicated.

The present invention relates to the use of an antibody in the preparation of a medicament for treating or preventing migraine. The present invention relates to a method for preventing migraine using an anti-CGRP receptor antibody or binding fragment. Specifically, the present invention discloses a method for preventing or reducing the occurrence of migraine in a patient in need thereof, the method comprising administering to the patient an anti-CGRP receptor or binding fragment according to a specific dosage regimen. The present invention also describes a pharmaceutical composition and an administration device comprising an anti-CGRP receptor antibody or binding fragment for use in the method.