49502 results about "Pharmaceutical Substances" patented technology

The present application relates to the technical field of medicines, and relates to a macrocyclic compound containing amide substitution, in particular to a compound as shown in formula (I) or a pharmaceutically acceptable salt thereof, and a preparation method therefor, a pharmaceutical composition containing the compound, and a use thereof in the treatment of disease.

Provided herein are polymorphs and crystalline forms of 2-fluoro-5-((5S,5aS,6S,9R)-1-fluoro-12-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-5-methyl-5a,6,7,8,9,10-hexahydro-5H-4-oxa-3,10a,11,13,14-pentaaza-6,9-methanonaphtho[1,8-ab]heptalen-2-yl)-3-methyl-4-(trifluoromethyl)aniline (Compound of Formula (I)), pharmaceutical compositions thereof, and methods of their use, for example, in the treatment of cancer. Also provided herein are synthetic processes for the manufacture of a compound of Formula (I) (i.e., 2-fluoro-5-((5S,5aS,6S,9R)-1-fluoro-12-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-5-methyl-5a,6,7,8,9,10-hexahydro-5H-4-oxa-3,10a,11,13,14-pentaaza-6,9-methanonaphtho[1,8-ab]heptalen-2-yl)-3-methyl-4-(trifluoromethyl)aniline). Also provided are compounds useful in its synthesis (e.g., those of Formulae (A), (B), (By), and (H)) and synthetic processes directed thereto.

The invention relates to the field of biological medicine, in particular to a stapled peptide targeting RAS-Raf protein interaction and application of the stapled peptide, the stapled peptide is obtained in the mode that Ac-SLHDCLMKALKVR-NH2 and Ac-SLHDCLMKALKVRGL-NH2 serve as peptide chain templates, amino acid at the i site and amino acid at the (i + 4) site are replaced with S5 and cyclized, and the nitrogen terminal is further modified with stearic acid. The stapled peptide can effectively inhibit proliferation and migration of tumor cells; the serum stability is high, and meanwhile, the cell transmembrane capability is excellent, so that target protein in cells can be better targeted, and the biological function of the target protein can be exerted. Therefore, the alphaH helical conformation of the RBD of the RAF can be stabilized through the stapled peptide and a nitrogen-terminal fatty acid modification strategy, the membrane permeability and stability of the RAF are improved, the binding force of the RAF and RAS is further improved, and proliferation and migration of various tumor cells are inhibited.

Disclosed herein are compositions comprising an NSAID such as meloxicam and / or rizatriptan in combination with a cyclodextrin and / or a carbonate or a bicarbonate. These compositions may be orally administered, for example, to improve the bioavailability or pharmacokinetics of the NSAID for the treatment of pain such as migraine, arthritis, and other conditions. Also disclosed herein are methods of treating pain, such as migraine, comprising administering meloxicam and rizatriptan to a human being suffering from pain, such as migraine. For migraine, these methods may be particularly useful when the meloxicam and rizatriptan are administered while the human being is suffering from an acute attack of migraine pain or migraine aura. In some embodiments, the combination of meloxicam and rizatriptan may be administered in a manner that results in a Tmax of meloxicam of 3 hours or less.

The invention relates to the field of biotechnology and medicine, and more particularly to a polypeptide having the amino acid sequence SEQ ID NO: 1 and being capable of inhibiting RAS-GTPase activity, to the use of said polypeptide to produce a drug for treating stomach cancer or rectal cancer in a dose of 0.81-3.00 mg / kg, as well as to a drug based on said polypeptide for the treatment of stomach cancer or rectal cancer, and to a method for treating stomach cancer or rectal cancer by intraperitoneally administering said drug to a subject in an amount of 150 ml twice at an interval of 7 days.

Provided are a pyrimidine polycyclic derivative inhibitor, a preparation method therefor and the use thereof. In particular, provided are a compound as shown in the general formula, a preparation method therefor, a pharmaceutical composition comprising the compound, and the use thereof in the treatment of cancers and other related diseases.

The invention relates to a fused ring compound, a preparation method thereof and application of the fused ring compound in medicine. Specifically, the invention relates to a fused ring compound as shown in a general formula (IN), a preparation method thereof, a pharmaceutical composition containing the compound and application of the fused ring compound as a therapeutic agent, in particular to application of the fused ring compound in preparation of drugs for inhibiting KRAS G12D. Wherein each group in the general formula (IN) is as defined in the specification. # imgabs0 #

Disclosed herein are compositions comprising an NSAID such as meloxicam and / or rizatriptan in combination with a cyclodextrin and / or a carbonate or a bicarbonate. These compositions may be orally administered, for example, to improve the bioavailability or pharmacokinetics of the NSAID for the treatment of pain such as migraine, arthritis, and other conditions. Also disclosed herein are methods of treating pain, such as migraine, comprising administering meloxicam and rizatriptan to a human being suffering from pain, such as migraine. For migraine, these methods may be particularly useful when the meloxicam and rizatriptan are administered while the human being is suffering from an acute attack of migraine pain or migraine aura. In some embodiments, the combination of meloxicam and rizatriptan may be administered in a manner that results in a Tmax of meloxicam of 3 hours or less.

Related to macrocyclic compounds and therapeutic uses thereof. Disclosed a compound of formula (I), or a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of the pharmaceutically acceptable salt, and their use for the preparation of a medicament of treatment of cancer. Provided herein are useful compounds for the inhibition of RAS mutant and the compound shows good inhibitory activity against RAS.

A pharmaceutical composition comprising a protein arginine methyltransferase 5 (PRMT5) inhibitor and a KRASG12C (Kirsten rat sarcoma viral oncogene homolog glycine-to-cysteine) inhibitor. The pharmaceutical composition can be used for treating various cancers, comprising solid tumors. The combined product can be used for treating any number of diseases associated with PRMT5 and / or KRASG12C.

The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-freeze drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry 10 powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

Drug products adapted for nasal delivery comprising formulations with epinephrine and devices comprising such formulations are provided. Methods of treating anaphylaxis with epinephrine products are also provided.

The present invention relates to a compound as shown in formula (A) having a pan-RAS inhibitory effect, or an isotopic derivative or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing the compound, and the use of the compound of formula (A) in the prevention and / or treatment of cancers, tumors, inflammatory diseases, autoimmune diseases or immune-mediated diseases.

The present invention relates to the use of a FAK inhibitor in preparing a drug to be jointly used with a KRAS G12C inhibitor to treat a tumor.

Provided are a crystal form of a pyridopyrimidine derivative, a preparation method therefor, a pharmaceutical composition thereof and the use thereof. Specifically disclosed are a crystal form of a compound of formula (I), a preparation method therefor, a pharmaceutical composition thereof and the use thereof.

Dosage forms, drug delivery systems, and methods related to sustained release of dextromethorphan or improved therapeutic effects are disclosed. Typically, bupropion or a related compound is orally administered to a human being to be treated with, or being treated with, dextromethorphan.

Provided is a compound useful as an active ingredient in a pharmaceutical composition for treating cancer.　The present inventors have examined a compound useful as an active ingredient in a pharmaceutical composition for cancer treatment, and have completed the present invention by finding that: a heterocyclic compound represented by formula (I) and formula (I-I) has excellent an action of inducing degradation of a mutant KRAS protein and a wild-type KRAS protein, and in particular, an action of inducing degradation of a KRAS protein having a G12C mutation, G12D mutation, G12V mutation, or G13D mutation; and said heterocyclic compound has mutant KRAS inhibition and the inhibitory activity of KRAS amplified by a wild-type KRAS gene, and in particular, inhibitory activity of KRAS having a G12C mutation, G12D mutation, G12V mutation, or G13D mutation. The heterocyclic compound according to the present invention or a salt thereof can be used as a therapeutic agent for cancer.

A tricyclic compound as a VHL ligand, a preparation method therefor, and a use of the compound or a pharmaceutical composition thereof for preventing and / or treating a series of diseases, disorders, and conditions.

Dosage forms, drug delivery systems, and methods related to sustained release of dextromethorphan or improved therapeutic effects are disclosed. Typically, bupropion or a related compound is orally administered to a human being to be treated with, or being treated with, dextromethorphan.

The invention provides a pharmaceutical composition for intranasal administration comprising a salt of sumatriptan or a physiologically acceptable solvate thereof, an alkyl glycoside or saccharide alkyl ester and optionally at least one pharmaceutically acceptable excipient, wherein the said composition provides Tmax value of less than 30 minutes upon said administration. Other aspects and embodiments are contemplated and described.The invention also provides a pharmaceutical composition for intranasal administration comprising a triptan, a pharmaceutically acceptable vehicle and a mucosal permeation enhancer, wherein upon said administration said composition provides a Tmax substantially equivalent to subcutaneous administration of said triptan. Other aspects and embodiments are contemplated and described.

The invention discloses a drug combination risk prediction method and device based on multi-source feature fusion and comparative learning, equipment and a medium, and relates to the technical field of drug combination prediction. The drug combination risk prediction method comprises the following steps: acquiring a drug data set; and obtaining a feature map according to the drug data set. And according to the feature map, carrying out adaptive feature extraction on the molecular map structure to obtain molecular map features of the medicine. And defining molecular map features as structural features. And inputting the molecular graph features into a multi-layer cascaded graph convolutional network, extracting high-order topological features in a drug network, and obtaining relation features. According to the drug data set, similarity features are calculated, and interactive embedding features are extracted; according to the structural features and the similarity features, potential correlation and differences between the features are mined through a comparative learning mechanism, and structural comparative learning features and similarity comparative learning features are obtained; and performing feature fusion and feature alignment on the features to obtain fused features. And predicting the drug combination risk according to the fusion features.

Disclosed herein are compositions comprising an NSAID such as meloxicam and / or rizatriptan in combination with a cyclodextrin and / or a carbonate or a bicarbonate. These compositions may be orally administered, for example, to improve the bioavailability or pharmacokinetics of the NSAID for the treatment of pain such as migraine, arthritis, and other conditions. Also disclosed herein are methods of treating pain, such as migraine, comprising administering meloxicam and rizatriptan to a human being suffering from pain, such as migraine. For migraine, these methods may be particularly useful when the meloxicam and rizatriptan are administered while the human being is suffering from an acute attack of migraine pain or migraine aura. In some embodiments, the combination of meloxicam and rizatriptan may be administered in a manner that results in a Tmax of meloxicam of 3 hours or less.

A spiro compound, and a preparation method therefor and a use thereof. Specifically, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, metabolite, or prodrug thereof, a pharmaceutical composition comprising the compound, a preparation method therefor, and a use thereof in preparation of a drug for preventing or treating KRAS-mediated related diseases.

Dosage forms, drug delivery systems, and methods related to sustained release of dextromethorphan or improved therapeutic effects are disclosed. Typically, an antidepressant, such as bupropion or a related compound is orally administered to a human being to be treated with, or being treated with, dextromethorphan.

This disclosure relates to a method of treating a neurological disorder, comprising administering a bupropion, or a combination of a bupropion and a dextromethorphan, to a human being in need thereof, monitoring the human being for Brugada pattern / syndrome, drug reaction with eosinophilia and systemic symptoms, or acute generalized exanthematous pustulosis, and reducing or discontinuing use of the bupropion, or the combination of the bupropion and the dextromethorphan, if the human being develops Brugada pattern / syndrome, subcutaneous tissue disorder, drug reaction with eosinophilia and systemic symptoms (DRESS), or acute generalized exanthematous pustulosis.

Disclosed in the present invention are a quinazoline compound, and a pharmaceutical composition thereof and the use thereof. Provided in the present invention is a compound as represented by formula I, a stereoisomer thereof or a pharmaceutically acceptable salt thereof. The compounds of the present invention have a good degradation effect on the KRAS protein with a G12D mutation, have a good inhibitory activity against the proliferation of tumor cells with a KRAS G12D mutation, and exhibit good pharmacokinetic properties.

Disclosed herein are compositions comprising an NSAID such as meloxicam and / or rizatriptan in combination with a cyclodextrin and / or a carbonate or a bicarbonate. These compositions may be orally administered, for example, to improve the bioavailability or pharmacokinetics of the NSAID for the treatment of pain such as migraine, arthritis, and other conditions. Also disclosed herein are methods of treating pain, such as migraine, comprising administering meloxicam and rizatriptan to a human being suffering from pain, such as migraine. For migraine, these methods may be particularly useful when the meloxicam and rizatriptan are administered while the human being is suffering from an acute attack of migraine pain or migraine aura. In some embodiments, the combination of meloxicam and rizatriptan may be administered in a manner that results in a Tmax of meloxicam of 3 hours or less.