534 results about "Pharmacokinetics" patented technology

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 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 belongs to the technical field of nuclear medicine molecular diagnosis and treatment, and discloses a modified CAIX targeting cyclic peptide, a nuclide marker and application of the modified CAIX targeting cyclic peptide in tumor diagnosis and treatment. According to the CAIX targeted cyclic peptide, a rigid bifunctional chelating agent RESCA is introduced to replace a traditional chelating agent, and a sulfonated or alkylated amino acid connector is combined, so that the enzymolysis resistance and in-vivo stability of the probe are remarkably improved. By optimizing the structure of the connector, the lipophilicity is reduced, liver and gall metabolism and non-specific uptake are reduced, and the high uptake rate of tumor target tissues is maintained. The therapeutic nuclide marker of the cyclopeptide can be used for intratumoral irradiation therapy using DOTA or NOTA in combination with an alkylated amino acid linker or an albumin ligand. Experiments show that the marker has high radiochemical purity, excellent pharmacokinetic characteristics and low kidney retention, and is suitable for precise diagnosis and targeted therapy of CAIX high expression tumors such as kidney cancer, colorectal cancer and brain glioma.

Disclosed herein are dosage forms comprising a combination of: 1) an active pharmaceutical ingredient (API), 2) a cyclodextrin, and 3) a bicarbonate. These compositions may be orally administered, for example, to improve the bioavailability or pharmacokinetics of the drug for the treatment of conditions such as pain.

The invention discloses an alpha nuclide drug in-vitro cellular response prediction method and system based on multi-module mathematical modeling and a medium, and the method comprises the steps: constructing a basic parameter input module, a pharmacokinetic prediction module, a cell absorbed dose calculation module and a biological effect prediction module which are connected in sequence; a three-compartment dynamical model and a micro-dose learning point kernel convolution and DNA damage repair dynamical model are integrated, and full-chain and quantitative simulation from drug distribution, microscopic energy deposition to cell survival is achieved. The method overcomes the defects that an existing empirical model cannot accurately reflect the high LET characteristic of alpha particles, neglects the bystander effect and repair dynamics and the like, and the prediction precision is remarkably improved. According to the method, the curative effects of different drugs, cell lines and dosage schemes can be quickly simulated on a computer, the research and development cost and period are greatly reduced, and an efficient theoretical tool is provided for new drug screening and dosage optimization.

The invention belongs to the field of medicines, and relates to a heterocyclic compound as shown in formula (I), which can be used as a voltage-gated sodium channel inhibitor, especially has an excellent inhibition effect on Nav1.8, has excellent selectivity and pharmacokinetic properties, and can be applied to prevention, alleviation and / or treatment of voltage-gated sodium channel related diseases.

The invention discloses a sedation depth monitoring method based on a graph convolutional neural network, and relates to the technical field of sedation monitoring, and the method comprises the steps: collecting a multi-source biomarker of a patient, carrying out the filtering and artifact removal of an electroencephalogram signal, and generating preprocessed electroencephalogram data; performing attention pooling processing on the node-level feature tensor, calculating a sedation depth index, and generating a pain interference factor according to a connection edge weight of the dynamic function connection graph; and when the pain interference factor exceeds a preset pain threshold value and the sedation depth index meets a preset condition, generating a sedation optimization instruction, and when the virtual pharmacokinetic node displays metabolic abnormality, generating an infusion rate adjustment instruction. According to the method, through a dynamic function connection diagram construction link, the time-varying intensity of the skin conductance reaction signal and the rugosa electromyographic signal is used as a dynamic weight, and accurate quantification of the pain-sedation coupling effect is achieved.

Provided herein are novel cyclic peptides, their synthetic process, compositions, properties including stability and pharmacokinetic profiles, and applications for treating solid tumor cancers.

The disclosed device, system and method manages medication delivery failures. An effective therapeutic range of a patient physiological property is determined based on a pharmacokinetic profile of a medication. During an administration of the medication to the patient, an expected trend in the measured physiological property is determined based on sensor data, the pharmacokinetic profile of the medication, a dose of the medication provided to the patient, and the at least one physical property of the patient, and an infusion device is caused to adjust the dose of the medication to cause the physiological property to follow the expected trend. Responsive to determining that a current trend in the physiological property has deviated from the expected trend, and will fall outside the effective therapeutic range within a predetermined time period, a delivery failure is determined and an alarm is provided.

The invention relates to the technical field of biological medicines, and discloses a polypeptide for treating osteoarthritis by aiming at AHR (Aryl Hydrocarbon Receptor), the amino acid sequence of the polypeptide is GFQQSDVIHQSVYELISINHTEDRA, and the amino acid sequence of the polypeptide is GFQQSDVIHQSVYELISINHTEDRA, and the amino acid sequence of the polypeptide is GFQQSDVIHQSVYELISINHTEDRA. The polypeptide is prepared by a solid-phase polypeptide synthesis method; the solid-phase polypeptide synthesis method specifically comprises the following steps: synthesizing from a C end to an N end, connecting a carboxyl group of a first amino acid to insoluble resin, then adding other amino acids one by one to form a peptide chain, and carrying out protection and deprotection reactions of a side chain in each step. The polypeptide is composed of natural amino acids and has good biocompatibility and degradability, and experimental results show that no obvious toxic reaction occurs in the cell level and the animal level, so that the polypeptide has conditions for further development of pharmacokinetic research and preclinical tests, and a feasible basis is provided for conversion to clinical application.

The invention belongs to the technical field of nuclear medicine, and relates to a CAIX-targeted cyclic peptide and a preparation method and application thereof, the CAIX-targeted cyclic peptide structure is shown as a formula 1, Linker is a cyclization connexon, and Chenator is a nuclide chelating group. The CAIX-targeted cyclic peptide provided by the invention has high affinity with CAIX, and has low affinity with isoenzyme CAII of CAIX, so that the CAIX-targeted cyclic peptide has high selective affinity with CAIX; the nuclide-labeled radioactive probe has high labeling rate and excellent in-vitro stability, has excellent pharmacokinetic characteristics in tumor-bearing model mice of human renal clear cell carcinoma, and has extremely high tumor uptake, tumor-muscle ratio and tumor-kidney ratio which can meet diagnosis requirements; due to the long-time retention characteristic in tumors, the polymer has a relatively high tumor treatment application value.

The present invention relates to a compound binding to an endogenous receptor, said compound comprising (i) an oligopeptide comprising a dipeptide with Trp being the C-terminal amino acid of said dipeptide, wherein said Trp is replaced with an α-amino acid Xaa2, whereby the stability in serum or plasma of the peptide bond connecting Xaa2 to the N-terminally adjacent amino acid is increased as compared to the peptide bond connecting Trp to the N-terminally adjacent amino acid in an otherwise identical compound; and (ii) a moiety capable of generating therapeutically effective radiation, said moiety being covalently bound to said oligopeptide.

The invention discloses a small animal in-vivo multi-parameter dynamic monitoring method based on photoacoustic imaging, and relates to the technical field of biomedical imaging, and the method comprises the steps: obtaining a photoacoustic signal generated by a small animal under the excitation of pulse laser output by an optical excitation module through an acoustic detection module; reconstructing a photoacoustic image of the photoacoustic signal through a filtering back projection algorithm; calculating the similarity between adjacent images in the photoacoustic image, identifying the image of which the similarity is lower than a set frame threshold value as a cross section slice polluted by respiratory motion artifacts and removing the cross section slice, and replacing the removed image frame by using the interpolation of an adjacent artifact-free image so as to obtain an updated photoacoustic image; selecting a region of interest in the photoacoustic image, and carrying out oxygenation kinetics monitoring, pharmacokinetics monitoring, perfusion kinetics monitoring or nanoparticle in-vivo kinetics monitoring; according to the monitoring method, motion artifacts caused by breathing of the small animals are effectively inhibited, and in-vivo multi-parameter dynamics monitoring of the small animals is achieved.

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 discloses a thiazole compound and medical application thereof, the structure of the thiazole compound is shown as a formula I. The compound shown as the formula I is a potent STING inhibitor and has good pharmacokinetic properties, and the compound shown as the formula I or pharmaceutically acceptable salt thereof can be used for preparing drugs for preventing or treating STING-mediated diseases.

Disclosed are a deuterated camptothecin compound represented by formula II and a pharmaceutically acceptable salt thereof, a preparation method thereof, a pharmaceutical composition containing the deuterated camptothecin compound or the pharmaceutically acceptable salt thereof, and uses thereof in the treatment of tumor-related diseases. The deuterated camptothecin compound has excellent pharmaceutical activity and pharmacokinetic characteristics, and has reduced in-vivo toxicity and improved in-vivo safety.

Provided are an isoxazoline compound and a use thereof. The isoxazoline compound has a structure as shown in formula I. The compound can be used for preventing and treating parasitic infections and killing agricultural pests, has a good prevention and treatment effect, and shows good pharmacokinetic properties in mice.

The invention relates to cyclic heptapeptide as well as a preparation method and application thereof. Specifically, the invention provides a cyclic peptide, and the cyclic peptide is characterized in that the cyclic heptapeptide is a cyclic peptide composed of an amino acid sequence as shown in SEQ ID NO. 1: Thr-Tyr-Val-Pro-Lys-Ala-Phe. The cyclic heptapeptide disclosed by the invention has the characteristics of stable structure, high biological activity, good pharmacokinetic characteristics, strong targeting specificity and the like, so that the cyclic heptapeptide has more remarkable advantages in drug development and biomedical application.

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 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 application belongs to the technical field of cosmetic and pharmaceutical chemistry, and discloses a 2,4-dihydroxyphenyl thiazole derivative and application thereof. The 2,4-dihydroxyphenyl thiazole derivative has the structure shown in the following formula: wherein n1 and n2 are each independently 1, 2, 3 or 4; and R is methyl or ethyl. Compared with existing peptide amido compounds, the 2,4-dihydroxyphenyl thiazole derivative of the application, while maintaining the active structure of the parent nucleus, significantly improves the solubility and physicochemical stability through molecular modification, and optimizes the pharmacokinetic characteristics. The derivative can effectively inhibit the activity of tyrosinase, and can be used as an active ingredient to prepare a novel tyrosinase inhibitor, related whitening and freckle-removing cosmetics and a drug for tyrosinase-related diseases.

Provided are long-acting atrial natriuretic peptide (ANP) polypeptides that bind to natriuretic peptide receptors, such as NPR-A, thereby functioning as NPR-A agonists and that exhibit improved stability. The present invention provides atrial natriuretic peptides with specific structural features that result in polypeptides with sufficient activity at NPR-A and also possess a number of other beneficial attributes related to their potential development as therapeutic treatments, including improved solubility of the analogs in aqueous solution, improved chemical and physical formulation stability, an enhanced pharmacokinetic profile, and minimized potential immunogenicity.

The application provides use of a compound A or a pharmaceutically acceptable salt thereof as a Bruton's tyrosine kinase (BTK) inhibitor in preparation of a drug for treating a BTK-related tumor disease. In vitro and in vivo test results show that the compound A has good inhibitory activity on BTK kinase, good inhibitory activity on human B-cell lymphoma cells with high BTK expression, and good in vivo anti-tumor activity. In addition, the compound A has good pharmacokinetic properties and metabolic stability, and can be used for developing a drug preparation for treating a BTK-related tumor disease, and has important clinical application value.

The invention belongs to the field of radioactive chemical synthesis, and particularly relates to carbon-14 labeled tetrahydroprogesterone as well as a preparation method and application thereof. The carbon-14 labeled tetrahydroprogesterone provided by the invention has a structure as shown in a formula I; the carbon-14 labeled tetrahydroprogesterone provided by the invention has the advantages that the labeled sites are determined, the radiochemical purity and the chemical purity are relatively high, the nuclide carbon-14 is firmly labeled in tetrahydroprogesterone molecules and is not easy to fall off, and the requirements of tracer experiments in pharmacokinetics can be met.

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 invention belongs to the technical field of crystal form drug molecules, and particularly relates to a baricitinib-trimesic acid eutectic crystal and a preparation method thereof. The baricitinib-trimesic acid eutectic crystal provided by the invention is good in stability and high in solubility, and has improved pharmacokinetics, so that subsequent development requirements of drugs are met; the preparation method is simple to operate, easy to control the crystallization process, good in reproducibility and suitable for industrial production.