322 results about "Pharmacokinetics" patented technology

The present invention relates to a GLP-1- / GlP- / amylin-receptor tri-agonist having a balanced potency ratio across all three receptors and / or having improved pharmacokinetic properties. The invention also relates to pharmaceutical compositions comprising such a GLP-1- / GlP- / amylin-receptor tri-agonist as well as their use as a medicament for the treatment of subjects with overweight, obesity and associated co-morbidity.

The invention provides an isoxazoline compound and application thereof, the isoxazoline compound has a structure as shown in a formula I. The isoxazoline compound can be used for preventing and treating parasitic infection and killing agricultural pests, has a good prevention and treatment effect, and shows good pharmacokinetic properties in a mouse body.

The invention belongs to the technical field of medical data processing, and discloses a multi-drug combined dose dynamic optimization method, equipment and a medium. The method comprises the following steps: constructing a multi-drug time-varying structure causal diagram; based on historical clinical observation data, performing causal effect learning on the structural causal diagram; in response to the current state input of a patient to be treated, carrying out anti-factual reasoning on the structure causality graph; an optimal dose combination is calculated that maximizes the desired efficacy and minimizes the uncertainty. According to the method, the structural causal diagram is constructed, the physiological state of the patient, multi-drug dose intervention, the pharmacokinetic process and the clinical outcome are uniformly modeled in the same causal framework, and the causal influence of the drug dose on the clinical outcome and the non-causal association relationship can be distinguished under the condition that historical clinical observation data are mixed and biased; and on this basis, anti-factual reasoning is performed on different dose combinations, so that potential clinical outcome distribution under assumed intervention conditions is obtained.

The present invention belongs to the field of medical technology and specifically disclosed is a compound represented by formula (I′), or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, and each symbol therein is as defined in the claims. The compound of the present invention may be used as a drug for regulating RET kinase activity or treating RET-related diseases, and has better pharmacokinetic properties.

The invention discloses an NLRP3 inhibitor as well as a preparation method and application thereof. Specifically, the invention relates to a compound shown as a formula (NLRP3i-3) or a pharmaceutically acceptable salt thereof, the formula (I) is COCCNc1nc2c (c (= O) n (C) c (= O) n2C) n1Cc1cc (OC) ccc1N, and the chemical name is 8-((4-amino-2-methoxybenzyl)-7, 9-dimethyl-7, 9-dihydro-8H-purine-6, 8-diketone. The invention also provides a preparation method of the compound, a pharmaceutical composition containing the compound, and application of the compound in preparation of drugs for preventing and / or treating NLRP3-mediated diseases. The disease is preferably myocardial ischemia reperfusion injury. Experimental results show that the compound provided by the invention has excellent NLRP3 inhibitory activity (IC50lt, 100nM), and has high selectivity to NLRP3 inflammasomes; good pharmacokinetic characteristics are achieved in a rat body, and the bioavailability is high; in myocardial ischemia reperfusion injury models of mice and rats, the composition can significantly reduce myocardial infarction area, reduce myocardial enzyme level, alleviate inflammatory response and improve heart function; preliminary toxicological evaluation shows that the safety is good. Therefore, the compound disclosed by the invention is expected to be developed into a novel medicine for treating NLRP3 related diseases such as myocardial ischemia-reperfusion injury.

According to the salivation promoting beverage for treating diabetes and the preparation method and chemical and pharmacokinetic application of the salivation promoting beverage, eight medicinal and edible medicinal materials such as folium mori and radix rehmanniae are scientifically matched, and a material basis is laid for the blood glucose reducing effect of a compound through the design of a multi-component and multi-target synergistic effect. The absorption, distribution, metabolism and excretion processes of active ingredients in traditional Chinese medicinal materials in a living body can be systematically illuminated through pharmacokinetic research, meanwhile, strict methodology verification is carried out, a UHPLC-Q-TOF-MS high-resolution mass spectrometry technology and a modern pharmacokinetic application method are creatively integrated, and a set of systematic traditional Chinese medicine compound application strategy is constructed. Not only is the hypoglycemic action mechanism of the compound clarified, but also an innovative technical path and a reliable application normal form are provided for modern application of the traditional Chinese medicine compound, and organic combination of chemical characterization and efficacy evaluation is realized.

One aspect of the present invention relates to: a conjugate comprising a peptide of a novel sequence and glycyrrhizin; and a pharmaceutical composition for preventing or treating obesity, the composition comprising the conjugate. The conjugate and composition comprising same according to one aspect were found to inhibit hypertrophy of fat cells, increase the cell membrane expression level of ATP-binding cassette transporter A1 (ABCA1), and reduce the secretion of tumor necrosis factor-α (TNF-α). In addition, the conjugate and composition comprising same were found to remain in a greater amount in the blood and have better pharmacokinetic properties than glycyrrhizin used by itself, and thus can be used in the obesity prevention and / or treatment market / industry.

The present disclosure provides a compound having a specific chemical structure, which exhibits excellent androgen receptor (AR) degrading activity and has excellent pharmacokinetic and pharmacodynamic characteristics, or a pharmaceutically acceptable salt thereof. The present disclosure also provides a composition comprising the compound or a pharmaceutically acceptable salt thereof. In addition, the present disclosure provides a medical use of a compound according to the present disclosure, a salt thereof, or a composition containing the same for the treatment or prevention of an AR-related disease. In addition, the present disclosure provides a method for treating or preventing an AR-related disease by administering to a subject in need thereof an effective amount of a compound according to the present disclosure, a salt thereof, or a composition containing the same.

The present invention describes the synthesis and biological evaluation of new substituted pyridine derivatives as foxj1 activity enhancers. In embodiments, novel pyridine derivatives were synthesized and the ability thereof to enhance foxj1 activity was evaluated. The novel pyridine derivatives synthesized in the present invention not only exhibited excellent activity but also exhibited excellent metabolic safety and pharmacokinetic profile in a Tg (foxj1: egfp) transgenic zebrafish animal model. In addition, the novel pyridine derivatives synthesized in the present invention enhanced cilia-promoting capability in a motile ciliated cell differentiation experiment in which mouse tracheal epithelial cells (mTECs) were isolated from the airways of mice and cultured by ALI. As a result, a series of foxj1 activity enhancers with substituted pyridine skeleton has the potential to be developed as preventive and therapeutic agents for respiratory diseases.

The present invention provides a liposome preparation containing a population of liposomes containing a CD1d ligand compound, wherein the average particle size of the population of liposomes is 90 to 110 nm and the polydispersity index of particle size distribution is 0.2 or less. and the polydispersity index of the particle size distribution is 0.2 or less. The present invention also provides the use of the liposome preparation in the prevention or treatment of graft-versus-host disease and organ transplant rejection.

The invention relates to the field of waste liquid harmless treatment equipment, in particular to integrated pharmacokinetics experiment waste liquid harmless treatment equipment which comprises a sealing installation assembly, an operation box, a waste liquid recycling assembly, a waste liquid recycling assembly, a waste liquid recycling assembly, a waste liquid recycling assembly and a waste liquid recycling assembly, and the sealing installation assembly is used for supporting the whole equipment and comprises a protection box; the feeding assembly is used for collecting waste liquid and comprises a concave storage disc and a conical storage opening, and the conical storage opening is formed in the operation box; and the filtering and impurity removing module is arranged in the protection box, communicates with the feeding assembly, is used for filtering the waste liquid and comprises a filtering tank. Through cooperation of all built-in components, special process design, a multifunctional integrated sterilization structure and full-automatic closed operation, integrated harmless treatment of the pharmacokinetic experiment waste liquid is achieved, and the device has the advantages of being thorough in treatment, high in safety, free of cross contamination and capable of being matched with a small number of times in a laboratory; the problem that special, efficient and safe integrated processing equipment is lacked in the prior art is solved.

The present invention relates to compounds according to formula (I), which are prodrugs of the psychoactive compound phenethylamine or its derivatives. The prodrugs provided herein exhibit improved pharmacokinetic properties during uptake as compared to phenethylamine (or the respective phenethylamine derivative), as well as reduced side effects resulting from the metabolites thus formed. Due to the affinity of the active phenethylamine compound, inter alia, for the 5-HT2a-receptor, these prodrugs are particularly advantageous for use in therapy, e.g., in the treatment of depression, posttraumatic stress disorder (PTSD), Alzheimer's disease or dementia.

The application discloses an antibody glycosylation modification regulation method, device and application, relates to the technical field of biopharmaceuticals and protein engineering, and realizes directional regulation of modification types, modification sites and modification proportions of N-glycan and O-glycan of the antibody through three core processes of constructing a glycosyltransferase engineering strain, optimizing a fermentation culture system and precisely regulating modification reaction conditions; solves the technical problems of low modification efficiency, poor specificity and insufficient product uniformity in the existing modification method, can improve the target glycan modification proportion to more than 90%, the modification product purity is greater than or equal to 98%, is suitable for glycosylation modification optimization of therapeutic monoclonal antibodies, bispecific antibodies and antibody drug conjugates, significantly improves the biological activity and pharmacokinetic performance of the antibody, wherein the ADCC activity is improved by 3-5 times, and the CDC activity is improved by 2-4 times, and has the advantages of strong controllability, good adaptability to large-scale production and high cost-effectiveness.

The application discloses an O-desmethylvenlafaxine prodrug and a preparation method and application thereof, relates to the technical field of drug synthesis, and the structural formula of the O-desmethylvenlafaxine prodrug is shown in the following formula: The phenolic hydroxyl in the structure of the O-desmethylvenlafaxine is etherified or carbonated through a substitution reaction, O-desmethylvenlafaxine prodrug is synthesized, the bioavailability of the O-desmethylvenlafaxine can be remarkably improved, and a compound with the prodrug property is screened through a pharmacokinetics test.

A compound represented by formula (I). The compound has good agonistic activity on an APJ receptor, can effectively inhibit the production of cAMP, has weak ability to recruit β-arrestin, and has good pharmacokinetic properties.

Extracellular protein degraders and compositions with improved pharmacokinetic properties are provided that have a potent asialoglycoprotein receptor (ASGPR) Binding Ligand bound to an Extracellular Protein Targeting Ligand for the selective degradation of the Target Extracellular Protein, for example immunoglobulin in vivo to treat disorders mediated by the extracellular protein.

This invention belongs to the field of biochemistry, specifically relating to the preparation and application of a cyclic peptide. The structure of the cyclic peptide CYP9 is Lys-Gly-Val-dGlu-Gly-Pro-Asp-CONH2, wherein lysine at position 1 and aspartic acid at position 7 are cyclically linked by an amide bond. This invention investigates the biological activity of the cyclic peptide CYP9, including constructing in vitro cell models and in vivo animal models of pulmonary fibrosis to evaluate its in vitro antifibrotic activity and in vivo therapeutic effects, as well as studying its cytotoxicity, serum stability, and pharmacokinetics. The results show that, compared with the parent peptide YD, the cyclic peptide CYP9 obtained in this invention exhibits superior activity and stability in all aspects, and can be used to prepare drugs for the prevention of pulmonary fibrosis.

The present invention relates to a pharmaceutical composition comprising a) nanosuspension comprising Canagliflozin or its pharmaceutically acceptable salts, b) silicified microcrystalline cellulose, and c) at least one pharmaceutically acceptable excipient. The said composition has a desirable pharmacokinetic characteristic and better dissolution properties. The invention further relates to a process for the preparation of said composition and use thereof as medicament in the treatment of type 2 diabetes mellitus.

The invention belongs to the technical field of medicines, and particularly relates to a beta-elemene tryptophan methyl ester derivative and application thereof in preparation of antitumor drugs. According to the beta-elemene tryptophan methyl ester derivative with the structure as shown in the formula (I), on the basis of maintaining a beta-elemene structural framework, a tryptophan methyl ester group is introduced to the 13th site of beta-elemene, and unsubstituted C3-7 heterocycloalkyl, substituted C3-7 heterocycloalkyl, unsubstituted C5-11 hetero-spirocycloalkyl or substituted C5-11 hetero-spirocycloalkyl is introduced to the 14th site of beta-elemene, so that the beta-elemene tryptophan methyl ester derivative with the structure as shown in the formula (I) is obtained. The water solubility and the pharmacokinetic property of the compound are effectively improved. Experimental results show that the anti-tumor activity of the beta-elemene tryptophan methyl ester derivative with the structure as shown in the formula (I) provided by the invention is obviously enhanced compared with that of beta-elemene. Formula (I).

Bacterial strains are provided having at least one of a reduced size, a sialic acid coat, inducibly altered surface antigens, and expression of PD-L1 or CTLA-4 antagonists and / or tryptophanase. The bacteria may have improved serum half-life, increased penetration into tumors, increased tumor targeting and increased antitumor activity. The bacteria are useful for delivery of therapeutic agents that treat neoplastic diseases including solid tumors and lymphomas.

The present application provides a PSMA-targeting ligand compound and chelate thereof and use thereof. The structure of the PSMA-targeting ligand compound is shown in formula I, wherein R1, R2 and R4 are each independently selected from H and optionally substituted C1-C5 linear or branched alkyl; R3 is selected from optionally substituted aryl ring group and optionally substituted aromatic heterocyclic group; X is a sulfur or oxygen atom; Y is selected from a chemical bond and -NH-(CH2)m-, wherein m is an integer selected from 0-18; and Z is a radioactive metal ion chelating group. The pharmacokinetic characteristics of the PSMA-targeting ligand compound are obviously improved, which can be more effectively absorbed by the human body, stably exist in the body, and be taken up and internalized by cancer cells, so that the coupling of the radioactive nuclide can obtain cancer treatment drugs and diagnostic reagents with obviously improved therapeutic effect.

The invention relates to the field of pharmacokinetics research, in particular to an experimental apparatus for preventing sample residues from precipitating and adhering to the wall, which comprises an experimental apparatus bottle body, a sealing cover is sleeved above the experimental apparatus bottle body, a first micro motor is fixedly mounted above the sealing cover, a stirring rod is fixedly mounted at the output end of the first micro motor, and the stirring rod is fixedly mounted at the output end of the first micro motor. And connecting pull rods are hinged to the exteriors of the stirring rods correspondingly, and fixing bolts penetrate through the front ends of the connecting pull rods in a threaded mode. According to the invention, the rotating disc rotates to drive the fluctuating rod to slide up and down, the fluctuating rod drives the protective bottle holder to slide up and down, an experimental apparatus bottle body placed in the protective bottle holder shakes up and down, then the rotating disc rotates to link the knocking rod to do intermittent motion, and the experimental apparatus bottle body is knocked through the soft cushion bottle sleeve to form resonance; and meanwhile, a rotary inner wall scraper in the bottle body of the experimental apparatus is matched, so that the experimental apparatus has the capability of preventing sample residues from precipitating and adhering to the wall.

Disclosed are a pharmaceutical composition comprising a compound of formula (I) as an active ingredient for inhibiting JAK, or treating JAK-mediated disease or disorder, a process for preparing the same and use of the same. The pharmaceutical composition has an advantage of high dissolution, and further has one or more advantages such as extended release, good pharmacokinetic properties.

The application discloses a heterocyclic compound, a pharmaceutical composition thereof, intermediates thereof, and a preparation method and application of the heterocyclic compound. Specifically provided is a compound shown in formula (A) or a pharmaceutically acceptable salt thereof. The compound of the application has one or more of the following effects: (1) the compound has inhibitory activity on Nav1.8; (2) the compound has good solubility; (3) the compound has good analgesic effect; (4) the compound has good pharmacokinetic characteristics; (5) the compound has fast onset; (6) the compound is rapidly absorbed orally; and (7) the compound meets the requirements of injection administration.

The present application belongs to the field of pharmaceutical chemistry, and relates to the use of a compound shown in formula (I) or a solvate thereof and a pharmaceutically acceptable salt thereof for preparing a drug for treating breast cancer. The compound has the characteristics of significantly improving the stability, solubility and dissolution of the drug and the metabolizability in vivo, has ideal pharmacokinetic characteristics and a good drug development prospect.

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.

Disclosed herein are salts and solid forms of MDMA, (R)-MDMA, (S)-MDMA, MDE, S-MDE, R-MDE, MDAI, MBDB, S-MBDB, R-MBDB, MEAI, and 5,6-Dimethoxy-2-aminoindane, including salts, solid forms of the compound and salts thereof, as well as polymorphs of solid forms. The solid forms disclosed herein may have improved properties, such as improved physical, chemical, and / or pharmacokinetic properties. Also disclosed are methods for making the salts and solid forms and methods for administering the same. The disclosed salt and solid forms of MDMA, (R)-MDMA, (S)-MDMA, MDE, S-MDE, R-MDE, MDAI, MBDB, S-MBDB, R-MBDB, MEAI, and 5,6-Dimethoxy-2-aminoindane may be useful for treating neurological disease and / or a psychiatric disorder in a subject.

The present application provides a kind of isoxazoline thiofene compound and its application, the isoxazoline compound has the structure as shown in formula I, the compound of the present application can be used to prevent and treat parasitic infection, has good prevention and treatment effect, shows good pharmacokinetic properties in mouse in vivo.