455 results about "Pharmacometrics" patented technology

A computer-implemented system for personalized health optimization constructs a confidence-weighted personal health knowledge graph (PHKG) from heterogeneous data, including wearable sensors, medical devices, lab results, medication logs, and conversational inputs. A multi-stage causal-inference stack identifies modifiable drivers of outcomes using layered methods (e.g., MI, GAM, Neural Granger, DAG-GNN), and simulates candidate interventions. A recommendation engine ranks lifestyle or pharmacologic actions using a benefit-to-friction score, selecting a personalized intervention aligned with user readiness and clinical safety constraints. Interventions may include a minimum effective dose (MED), optimal level, adaptive low-dose, or behavioral challenge. Optional modules include reinforcement learning for timing adaptation and privacy-preserving on-device inference. The system operates across domains including metabolic, cardiovascular, renal, sleep, stress, and medication response, enabling cross-condition synergy evaluation. The architecture is modular, supports runtime plug-in targets, and adapts in real time with or without continuous clinical oversight, depending on deployment.

Veterinary pharmaceutical compositions for direct systemic introduction, also known as DSI pharmaceutical compositions. One veterinary pharmaceutical composition for direct systemic introduction includes about 10-17 dry mass % bovine gelatin; about 10-17 dry mass % mannitol; about 0-1 dry mass % of a surfactant; and about 65-80 dry mass % of the active pharmaceutical ingredient which is a proton pump inhibitor. A method of manufacturing a veterinary pharmaceutical composition for direct systemic introduction includes combining one or more pharmacologically inactive compounds to form a first solution; using one or more surfactants to form a second solution; adding an active pharmaceutical ingredient to the second solution to form a first mixture; adding the first solution to the first mixture to form a pre-formulation; freezing the pre-formulation; and lyophilizing the pre-formulation.

The invention discloses a pseudomonas aeruginosa InA protein and application thereof, and relates to the technical field of biological detection, the InA protein is InAS2, InAAP41 or InAS8, the amino acid sequences of the InA protein are respectively shown as SEQ ID NO.1-3, and the nucleotide sequences for coding the InAS2, the InAAP41 and the InAS8 are shown as SEQ ID NO.4-6. Compared with the prior art, the InA protein can improve the solubility of target protein, in addition, the InA protein and pseudomonas aeruginosa immune protein also have ultrahigh affinity, a biosensing chip with regeneration reversibility is developed based on the InA protein, the chip can capture fusion protein with the InA protein, and the biosensing chip has the advantages that the biosensing chip can be used as a biosensing chip with regeneration reversibility, so that the biosensing chip can be applied to biosensing of pseudomonas aeruginosa. The chip can be used for detecting the affinity between the fusion protein with the InA tag and a candidate drug, drug screening is realized, and meanwhile, the protein-drug affinity kinetics detected by the chip can also be used for pharmacological research of drugs.

The invention relates to the technical field of traditional Chinese medicines, and discloses application of an active ingredient of shiny-leaved yellowhorn leaves in preparation of a medicine for treating hyperuricemia. The xanthoceras sorbifolia leaf active ingredients comprise quercitrin, rutin and myricetin; the content of quercitrin is 0.2508 mg / g to 0.6719 mg / g, the content of rutin is 0.6707 mg / g to 1.5831 mg / g, and the content of myricetin is 0.8002 mg / g to 3.4858 mg / g. According to the invention, myricetin, quercitrin and rutin are determined as core effective substances of shiny-leaved yellowhorn leaves for treating hyperuricemia for the first time; the multi-target and multi-channel action mechanism is disclosed; meanwhile, network pharmacological analysis shows that the three components have high connectivity in a network and jointly act on key targets such as XOD, ACE, AKR1B1 and TNF, it is prompted that the three components do not act singly, but play a treatment role through multi-target and multi-channel cooperation, the traditional'single target-single drug 'thinking is changed into a'multi-component-multi-target-multi-channel' system regulation mode, and the treatment effect is improved. A new thought is provided for comprehensive treatment of the hyperuricemia.

This invention relates to a traditional Chinese medicine composition for improving cancer-related fatigue, its preparation method, and its application. Belonging to the field of traditional Chinese medicine technology, it solves the technical problems of the lack of modern traditional Chinese medicine preparations for cancer-related fatigue and the lack of a systematic explanation of the pharmacological mechanism. The solution is: a traditional Chinese medicine composition for improving cancer-related fatigue, its preparation method, and its application, formulated according to the principles of principal, assistant, adjuvant, and guide herbs. The principal herbs are Astragalus membranaceus and Codonopsis pilosula; the assistant herbs are Angelica sinensis and Rehmannia glutinosa; the adjuvant herbs are Poria cocos, Citrus reticulata peel, and Ophiopogon japonicus; and the guide herb is Glycyrrhiza uralensis. By weight fraction, the principal herb is 10-18 parts, the assistant herbs are 8-14 parts, the adjuvant herbs are 8-14 parts, and the guide herb is 1-3 parts. The preparation method of the traditional Chinese medicine composition for improving cancer-related fatigue includes the following steps: 1) water extraction; 2) concentration; 3) spray drying; 4) sieving and mixing; 5) granulation; and 6) drying and packaging. Compared with the prior art, this invention has the advantages of convenient administration, stable efficacy, and a systematic explanation of the pharmacological mechanism.

The application belongs to the field of neuropharmacology and medicine, and particularly relates to application of taurine cholic acid in preparation of a drug for preventing or treating Alzheimer's disease. Through animal model experiment verification, the A beta lateral ventricle injection is used to prepare an AD mouse model, and after oral administration of TCA for 2 weeks, cognitive behavior and pathological indexes are significantly improved.

The invention provides a traditional Chinese medicine composition, a traditional Chinese medicine preparation, a preparation method and application, and particularly belongs to the technical field of traditional Chinese medicine. The invention provides a traditional Chinese medicine composition. The traditional Chinese medicine composition comprises the following components in parts by weight: 20-50 parts of parched white peony root, 8-15 parts of pawpaw, 10-20 parts of radix clematidis, 20-40 parts of caulis spatholobi, 5-12 parts of honey-fried licorice root, 10-20 parts of fructus broussonetiae, 10-20 parts of radix cyathulae and 5-12 parts of cassia twig. The traditional Chinese medicine composition has great potential in the aspects of treating kOA and inhibiting osteophyte formation, and can be used for improving kOA cartilage injury. Through in-vitro experiments, network pharmacology and in-vivo experiments, the curative effect of XBD in treating kOA and the effect of XBD in inhibiting osteophyte formation are verified, it is proved that XBD has a regulation effect on cartilage degeneration and osteophyte formation, and an important thought is provided for developing innovative drugs with cartilage protection and abnormal osteophyte formation inhibition functions.

The invention relates to the fields of pharmacology and molecular biology, and discloses an autophagy inhibitory polypeptide competitively combined with an LIR docking site of an autophagy-related protein LC3 and application of the autophagy inhibitory polypeptide. Through molecular docking simulation, through LIR docking sites of targeted LC3 protein, 794 bioactive polypeptides which can be combined are screened out. Functional result analysis shows that peptide 3 #, peptide 4 # and peptide 5 # are competitively combined with LIR docking sites of the LC3 protein, so that formation of autophagy vesicles is inhibited in a targeted manner, and proliferation and survival of autophagy-dependent pancreatic cancer cells are effectively inhibited; the strategy is combined with chemotherapeutic drugs to show a synergistic effect, and the pancreatic cancer resisting curative effect is remarkably enhanced.

The present invention refers to compounds of formula (I). The present invention also relates to compounds of formula (I) for use as G Protein coupled Receptor 139 (GPR139) antagonists in methods of medical treatment of e.g. depression, Alzheimer's disease, schizophrenia, drug addiction, sleep disorders, pain, and attention deficit hyperactivity disorder. Exemplary compounds are e.g. 3-((1H-pyrazol-4-yl)methyl)-6′-(phenyl)-2H-(1,2′-bipyridin)-2-one derivatives and related compounds. The present description discloses the synthesis and characterisation of exemplary compounds, pharmacological data thereof, as well as exemplary tablet formulations comprising the compounds of the invention (e.g. page 83 to page 110; examples 1 to 33; reference example 1; test examples 1 and 2; tables 1 to 4).

The present invention addresses the problem of providing a medicine that, despite of being a non-ergot dopamine agonist (DA), reduces the risk of the drowsiness side effect, and exhibits an excellent therapeutic effect on neurodegenerative disorders such as Parkinson's disease (PD). The present invention relates to a pharmaceutical composition for treating neurodegenerative diseases such as Parkinson's disease, the pharmaceutical composition comprising 1-{[(4aR,6R,8aR)-2-amino-3-cyano-8-methyl-4,4a,5,6,7,8,8a,9-octahydrothieno[3,2-g]quinolin-6-yl]carbonyl}-3-[2-(dimethylamino)ethyl]-1-propylurea or a pharmacologically acceptable salt thereof. The pharmaceutical composition is characterized by being orally administered at a daily dose of 0.25 mg to 2 mg in terms of free form.

The invention discloses application of jellyfish and snow rabbits in inhibition of ERK phosphorylation level and MAPK pathway and an evaluation method of the jellyfish and snow rabbits, and relates to the technical field of biological medicines.The method comprises the following steps that 1, a treated jellyfish and snow rabbits breast cancer cell group and a control breast cancer cell group are established; and step 2, respectively dividing the two groups of samples in the step 1 into two parts, fixing one part in paraformaldehyde with the mass concentration of 10%, treating, embedding in paraffin for immunohistochemical analysis, and quickly freezing the other part for transcriptomics analysis and the like. According to the invention, UPLC-MS is adopted to determine the main components of SMM, the influence of SMM on breast cancer (BC) is evaluated through in-vivo experiments, in order to deeply clarify the mechanism, network pharmacology and transcriptomics analysis are integrated, finally, immunohistochemistry (IHC) is adopted to verify and explore the exact breast cancer resisting mechanism of SMM, and a scientific basis is provided for potential clinical application of SMM.

The group of inventions relates to the field of medicine, pharmacology and the chemical and pharmaceutical industry and includes an improved method for producing (10S, 13S, 16R, 17R)-17-hydroxy-10,13,16-trimethyl-17-propanoyl-7,8,12,14,15,16-hexahydro-6H-cyclopenta[a]phenanthrene-3-one (compound of formula (I)) and the use thereof for industrial batch, semi-continuous and continuous chemical production. Also described is a method for producing an intermediate compound, Vamorolone Acetate. The method for producing the compound of formula (I) is carried out according to the schema depicted. The production method makes it possible to produce the compound of formula (I) with a purity suitable for the use thereof in a finished dosage form for subjects requiring treatment for Duchenne muscular dystrophy. Thus, the technical results of the present invention consist in an improved production method which results in: a high yield and chemical purity, including stereoisomeric purity, of the compound of formula (I) and intermediate products in the synthesis of the compound of formula (I), which are suitable for use in a finished dosage form for subjects requiring treatment for Duchenne muscular dystrophy; the adaptability of the synthesis of the compound of formula (I) to industrial production; environmentally-friendly production; and a decrease in the formation of undesirable by-products.

FIELD: pharmacology.SUBSTANCE invention can be used to determine the concentration of an anti-tuberculosis drug in blood serum. The method for determining the concentration of bedaquiline in the blood serum in patients with tuberculosis or mycobacteriosis is that whole blood samples are centrifuged at 3000 rpm for 20 minutes, then the blood plasma is collected in sterile 1.5 mL Eppendorf tubes, then 900 mcL of acetonitrile are added to 300 mcL of plasma and centrifuged at 13500g for 15 minutes, then 1 mL of the supernatant is transferred to a chromatographic vial and make the assay by UHPLC MS / MS using an Athena UHPLC C18, 1.8 mcM, 120A, 2.1×100 mm chromatography column, when using an aqueous solution containing 5 g / L of ammonium acetate, 25 ml / L of concentrated acetic acid, 2 ml / L trifluoroacetic acid as mobile phase A and 100% acetonitrile as mobile phase B, the concentration of bedaquiline is determined using a pre-plotted calibration curve.EFFECT: determination of bedaquiline in human blood plasma in a time not exceeding 6 minutes.1 cl, 9 dwg, 6 tbl

The present invention provides a solid dispersion comprising a compound represented by a general formula (I) or (II), or a pharmacologically acceptable salt thereof: or

The present invention relates to a compound represented by the following general formula (I) or pharmacologically acceptable salt thereof. The present compound has an excellent adrenergic α1A receptor agonistic action, and is useful as a preventive or therapeutic drug for orthostatic hypotension, essential hypotension, acute hypotension associated with various diseases or conditions, and urinary incontinence.[In the formula, R1 represents a hydrogen atom or a C1-C3 alkyl group; and Z is selected from the group consisting of a substituted phenylamino group, a substituted phenyloxy group, a substituted phenylthio group, a substituted thienylamino group, and the like.]

Cardiomyopathies are heart muscle disorders which represent a heterogeneous group of diseases that often lead to progressive heart failure with significant morbidity and mortality. Here, the inventors show that neutralization of acyl CoA binding protein (ACBP) / diazepam binding inhibitor (DBI) reduces the deleterious effect of the Vehicle anthracycline doxombicin on cardiac function. Since anthracycline-induced heart failure and anthracycline-induced senescence are models of accelerated cardiac aging, it is also plausible to use ACBP / DBI inhibition or neutralization as a method to prevent or treat aging of the cardiovascular system. The inventors also found that genetic and pharmacological interventions to deplete ACBP / DBI efficiently improves cardiac dysfunction associated with experimental HFpEF, a condition associated with aging, hypertension and obesity. Accordingly, the present disclosure relates to methods for the treatment of cardiac dysfunction comprising neutralization of ACBP / DBI.

The invention discloses an mGluR5 small-molecule allosteric modulator and application thereof in inhibition of neuroinflammation, and belongs to the technical field of neuropharmacology and anti-inflammatory drug research, two mGluR5 small-molecule allosteric modulators are obtained by virtual screening through an allosteric pocket targeting mGluR5, the structural formulas of the two mGluR5 small-molecule allosteric modulators are shown in the specification, and the structural formula of the mGluR5 small-molecule allosteric modulators is shown in the specification. The mGluR5 micromolecule allosteric modulator can be used for inhibiting microglial cell inflammation, and can effectively relieve LPS-induced microglial cell NO release.

The invention discloses a traditional Chinese medicine composition and application thereof in medicine for improving non-alcoholic fatty liver, and the traditional Chinese medicine composition comprises pulvis fellis suis, pericarpium citri reticulatae, hawthorn and clostridium butyricum. On one hand, potential targets and pathways of drug diseases are determined in network pharmacological analysis, and on the other hand, in an in-vivo experiment, the drug provided by the invention improves obesity and impaired glucose tolerance caused by HFD, reduces the blood fat level, alleviates inflammation, protects the liver, alleviates liver fat vacuole deposition and fatty degeneration, and has a good application prospect. It is proved that the bile acid-hawthorn and pericarpium citri reticulatae-clostridium butyricum combination has prevention and treatment and protection effects on the HFD-induced non-alcoholic fatty liver disease.

The present invention pertains to an aqueous composition which contains (A) 4-phenylbutyric acid or an ester thereof, or a pharmacologically acceptable salt thereof, and which has a pH of 6.0-9.0 inclusive, the aqueous composition being housed in a discharge container having a filter containing a hydrophilic material.

The invention discloses a collagen peptide composition with a function of increasing muscle strength and application of the collagen peptide composition. The collagen peptide composition comprises fish collagen peptide and beef tendon collagen peptide. A mouse senescence sarcopenia model is constructed, then a collagen peptide composition is used for intragastric intervention, and the improvement effect is evaluated through behavioral testing, body component analysis and HE staining. The potential target and regulatory pathway of the collagen peptide composition are explored by combining network pharmacology and molecular docking. Results show that the four-limb grip strength, treadmill exhaustion time and movement distance of a model mouse can be remarkably improved, quadriceps femoris muscle and gastrocnemius muscle indexes are recovered, and muscle fiber atrophy and collagen deposition are relieved. And it is found that TNF, IL1B, AKT1, mTOR and MAPK1 may be core targets of the TNF, IL1B, AKT1, mTOR and MAPK1. The polypeptide plays a role by regulating and controlling biological processes such as MAPK cascade, protein processing and inflammatory reaction, cell apoptosis, a cAMP pathway and a calcium signal pathway.

The present invention provides an effective pharmacological therapy for pathological repetitive behaviours.

Provided herein are pharmacological response activation signatures for use in methods and compositions for predicting the response of a subject suffering from cancer to treatment with select inhibitors.

The invention relates to application of lentinan in preparation of a medicine for enhancing Kukuzhou cell immune function, and belongs to the technical field of immunopharmacology. The invention discloses a mechanism and application of lentinan LNT (Lentinan) based on a TLR2 (Toll-Liver Receptor 2) signal channel for enhancing the immune function of liver cumness cells and promoting lysosome maturation. By constructing an LNT fluorescence labeling system, a Kuptake cell in-vivo tracing model and a TLR2 function intervention model, it is proved that LNT can be directly combined with TLR2 and activate a TLR2 / MyD88 / NF-kappa B signal axis, and therefore the phagocytosis and immune response capacity of Kuptake cells is enhanced. Meanwhile, TLR2 signal-induced reactive oxygen species (ROS) up-regulation can promote TFEB dephosphorylation and nuclear translocation, lysosome maturation is driven, and degradation metabolism of LNT is accelerated. The invention provides a TLR2-based immune enhancement mechanism of the LNT, and provides a theoretical basis and an application basis for developing immunomodulatory targeted drugs.

The invention discloses a network pharmacology and Mendel randomization analysis method for resisting lithangiuria by chlorogenic acid, and belongs to the technical field of biomedical engineering, and the method comprises the following steps: taking an intersection of a potential action target of chlorogenic acid and a lithangiuria target as a candidate target; performing pathway enrichment analysis and screening on each candidate target spot to determine a plurality of first pathways; for each first path, calculating a target importance score of each candidate target and performing screening according to the target importance score, and obtaining the screened candidate target as a key target; respectively performing Mendel stochastic analysis on each key target spot to obtain a causal effect estimated value of each key target spot and the urinary calculus risk, screening all the first pathways according to the causal effect estimated value, taking the screened first pathways as target pathways, and taking the key target spots in the target pathways as target targets. The method can be used for efficiently and accurately screening and determining the core regulatory pathway playing the anti-lithangiuria role and the real key target to which the core regulatory pathway belongs.

The present invention provides: a compound which is an antisense oligonucleotide capable of regulating the expression of a RasGRP4 gene and treating myositis and rheumatoid arthritis, and which has a nucleic acid base sequence consisting of 8-80 linked nucleosides and comprising at least 8 consecutive nucleic acid bases complementary to a transcript of RasGRP4; or a pharmacologically acceptable salt thereof.

The invention belongs to the technical field of biological medicine, and particularly relates to application of LRRFIP1 serving as a bilberry extract to improvement of a target spot of insulin resistance of gestational diabetes mellitus. The insulin resistance of gestational diabetes mellitus is improved by specifically regulating and controlling a PI3K-AKT signal channel and a GLUT4 glucose transporter function in skeletal muscle based on the bilberry extract. The bilberry extract used in the invention is a natural plant source, is high in safety, and is suitable for pregnancy. PI3K-AKT signal channels can be activated at the same time, and insulin resistance and lipid metabolism disorder can be synergistically improved. The action mechanism is systematically illuminated through technical means such as proteomics, network pharmacology, molecular docking and the like. Glucose tolerance, insulin sensitivity and blood fat level of GDM rats can be remarkably improved, and no remarkable side effect exists.

Compositions and methods relating to a pharmacological therapy for a human genetic disease, specifically mitochondrial DNA depletion-deletions syndromes, and more specifically, those related to mutations in the GUK1 gene. The pharmacological therapy involves the administration of deoxyguanosine (dG), a purine nucleoside phosphorylase (PNP) inhibitor, including but not limited to forodesine, or both.

The disclosure provides the structure of an MFSD2A-SYNC2 complex together with functional data that revealed important molecular aspects of MFSD2A transport cycle, receptor-mediated cell-cell fusion, and pharmacology and resulted in the identification of two novel allosteric modulators of MFSD2A, which are two soluble fragments of SYNC2, namely SYNC2su-co and SYNC2su-co-2, representing first-in-class molecules to inhibit MFSD2A LPCs uptake and increase transcytosis rate.

Provided for are prodrugs of riluzole and pharmaceutical compositions and methods of use thereof. The prodrugs have advantageous pharmacological properties for use in methods for treating glutamate-associated diseases or disorders, or other diseases or disorders, against which riluzole is known or expected to be effective, including central nervous system (CNS) disorders, neuropsychiatric disorders, and neurodegenerative disorders.

The invention provides a screening method and application of external traditional Chinese medicine anti-psoriasis active ingredients, and relates to the technical field of modern research of traditional Chinese medicines. According to the screening method disclosed by the invention, components with transdermal ability and anti-psoriasis activity are systematically excavated and screened from a traditional Chinese medicine complex system through preparation of a traditional Chinese medicine transdermal sample solution, UPLC-Q-TOF-MS component identification, network pharmacological analysis, molecular docking prediction and HaCaT psoriasis cell model verification in sequence. The method solves the problems that the traditional Chinese medicine transdermal components are unclear in pharmacodynamic material basis and low in screening efficiency, and has the advantages of being high in systematicness, high in accuracy and good in pertinence. According to the method, a plurality of effective components such as dictamnine and limonin are successfully screened from the cortex dictamni, and a clear pharmacological basis is provided for research and development of the cortex dictamni externally applied anti-psoriasis medicine.