429 results about "Drug metabolism" patented technology

The invention provides population models, methods, and algorithms for targeting a dosing regimen or compound selection to an individual patient. The methods and algorithms of the invention utilize population models that incorporate genotype information for genes encoding drug metabolizing enzymes for one or more compounds of interest. The methods allow integration of genotype information for one or more genes encoding a drug metabolizing enzyme, particularly a cytochrome P450 gene with patient data. The methods allow integration of genotype information and the effect of one or more compounds on one or more drug metabolizing enzymes. The methods allow iterative feedback of drug metabolizing data obtained from a patient into the process of generating a dosage regimen recommendation for a compound of interest for an individual patient.

The present invention relates to a method capable of using natural and artificial synthetic isosulfocyanate compound or its derivative to prevent and cure prostatic diseases and skin carcinoma. The internal tests show that various isosulfocyanate compounds or their derivatives can induce prostatic cell II phase drug metabolic detoxication enzyme-glutathione transferase so as to can inhibit the hyperplasia of prostate and inflammation, and can prevent and cure prostatic carcinoma and skin carcinoma.

The present invention relates to methods for detecting polymorphisms in enzymes related to drug metabolizm (Drug Metabolizing Enzymes or DMEs) such as uridine diphosphate glucuronosyl transferase (UGT) gene promoter, cytochrome p450, with a non-amplified oligonucleotide detection assays. The present invention also relates to pharmacogenetic DME detection assay kits.

The invention provides a cultivation method of Cyp gene knocked-out rats, and a preparation method of liver microsome of the rats. The Cyp gene knock-out herein includes Cyp single gene knock-out and Cyp multiple gene knock-out. In the method, firstly a Cyp gene knocked-out rat is constructed by means of a CRISPR/Cas system, which includes selection of a knocked-out target site, in-vitro synthesis and transcription of sg RNA and Cas9m RNA, preparation of a pseudopregnant female rat, in-vitro micro-injection and transplanting of a single-cell embryo, and cultivation of the rat, and finally, a homozygote Cyp gene knocked-out rat can be cultured. Furthermore, the liver of the Cyp gene knocked-out rat is extracted and is subjected to homogenization and differential centrifugation to prepare the liver microsome of the rat in Cyp gene deletion. The invention also provides an application of the Cyp gene knocked-out rats and the liver microsome thereof in study on drug metabolism.

A method for intracellular metabolic flux analysis comprising (a) culturing cells in a medium not containing any isotope-labeled substrate to a target phase of the metabolic flux analysis, (b) adding an isotope-labeled substrate to the medium, and continuing culture and collecting samples from the medium in time course, (c) measuring isotope distribution in an intracellular metabolite contained in the samples collected in time course, (d) performing a regression analysis for measured data and calculating an isotope distribution ratio in a steady state, and (e) analyzing a metabolic flux of the cultured cells by using the calculated isotope distribution ratio.

A method of treating, preventing or ameliorating one or more symptoms of hepatitis C, or inhibiting cathepsin activity, in a subject is provided, in which at least one compound (e.g., a HCV protease inhibitor) is administered in one or more discrete dosages over a twenty-four hour time interval in an asymmetric pattern as to dosage amount and/or timing of dosage, wherein the at least one compound is selected from the group consisting of compounds of Formulae I-XXVI, described herein. Methods of modulating the activity of hepatitis C virus protease in a subject are also provided. Asymmetric dosing as to amount of dose and/or timing of dose permits adjustment of dosing to accommodate variations in drug metabolism and/or viral activity caused by viral cell division or a patient's circadian rhythms, thus delivering the maximum amount of dose at the time or times it is most effective.

The present invention identifies and quantifies changes in gene expression associated with non-small cell lung cancer NSCLC by examining gene expression in tissue from normal lung and diseased lung. The present invention also identifies and quantifies expression profiles which serve as useful diagnostic markers as well as markers that are useful to monitor disease states, disease progression, drug toxicity, drug efficacy and drug metabolism.

The present invention provides methods, pharmaceutical compositions, medicaments, and pharmaceutical kits that employ the use of boceprevir as a CYP3A4/5 inhibitor to improve the pharmacokinetics of therapeutic compounds metabolized by cytochrome P450 3A4/5 (CYP3A4/5) enzymes.

The present invention relates to a novel hepatocyte-like cell population derived from hBS cells and to the potential use of such heopatocyte-like cells in e.g. medical treatment, drug screening and toxicity testing. Furthermore, the invention relates to hepatoblast-like cells that may have suitable characteristics so that they can be used for the same applications as the hepatocyte-like cells and that furthermore may be used in in vitro studies of hepatogenesis such as early hepatogenesis or hepato-regenerative disorders. Both the hepatocyte-like and the hepatoblast-like cells according to the invention express drug transporter and/or drug metabolising characteristics either at the gene or protein expression level.

The invention provides a specific fluorescence probe substrates of human carboxylesterase 2 (CES2) and application thereof. The specific probe substrate is a benzoateb compound of a C4 hydroxyl naphthalimide, and is applicable to determine the enzyme activity of CES2 in a biological system. The CES2 enzyme activity determination flow comprises: selecting a hydrolysis benzoyl-removal reaction of the benzoate compound of the C4 hydroxyl naphthalimide as a probe reaction, and quantitatively determining the generation amount of a hydrolysis metabolite of the compound in a unit time, so as to determine the enzyme activity of CES2 in all biological samples, cells, bodies and integral organs. The probe is applicable to quantitative assessment of CES2 enzyme activity in biological samples of different species and different individual sources, and quantitative determination on CES2 enzyme activity in different sources of animal tissue cell culture fluids and cell preparation substances, so that the probe is expected to help to realize assessment on medicine disposal capability of important drug metablic enzyme CES2. Additionally, the probe also is applicable as an inhibitor for rapidly screening CES2 in vitro by means of the probe reaction.

The present invention relates to methods for detecting polymorphisms in enzymes related to drug metabolizm (Drug Metabolizing Enzymes or DMEs) such as uridine diphosphate glucuronosyl transferase (UGT) gene promoter, with nucleic acid detection assays. The present invention also relates to detection assay kits.

The invention relates to a modified zebra fish drug metabolism modeling method, which specifically comprises the steps of (1) enriching metabolites by virtue of a zebra fish metabolism model; (2) separating and analyzing the enriched metabolic components of the zebra fish in the last step by using modern chromatography or the hyphenated technique thereof, capturing or knocking out target components or metabolites; (3) collecting zebra fish germ cells; (4) putting zebra fish embryos in three days after fertilization in a culture plate which holds an embryo culture medium and administrating a drug; (5) dyeing the bones of the zebra fish; and (6) detecting and analyzing the dyed bones of the zebra fish. According to the invention, an adolescent zebra fish osteoporosis model is applicable to in-vivo effective evaluation of anti-osteoporosis activity of Chinese herbal medicinal ingredients such as trace ingredients; an adult zebra fish metabolism model is simple in metabolites and efficient in enrichment; the modern chromatography or the hyphenated technique thereof provide powerful guarantee for the separation and analysis of the complex Chinese herbal medicinal system and the metabolic components. The model obtained by the method has the outstanding advantage that the separation and analysis of Chinese herbal medicinal original-form ingredients and the metabolic components are integrated with the in-vivo anti-osteoporosis activity evaluation, and simple and efficient.

The invention discloses a PEG grafted polysulphone or polyether sulphone hollow fibrous membrane, a preparation method and application thereof. PEG grafted polysulphone (or polyether sulphone) and polysulphone (or polyether sulphone) are mixed according to a proportion of 1:3-9, and then dissolved in a solvent such as N-methylpyrrolidone and the like by a weight ratio of 15 to 30 percent for 10 to 12 hours under stirring; and after bubbles are removed, a spinning solution is obtained. The spinning solution is extruded by adopting two concentric circular hollow fibrous spinning nozzles at a speed of 5 to 20 milliliters per minute. Nascent fibers are spun with 10 to 30 centimeters in an environment and then solidified and molded in water bath at a temperature between 50 and 80 DEG C, and the fluid line speed is 5 to 40 meters per minute. The hollow fibrous membrane has the beneficial effect of resisting blood platelet, protein and small molecule adsorption, and can be used as a hemodialysis device, or used for researches on biological artificial organs of organization culture of various human or animal cells, drug metabolism, toxicity and pathology.

The invention discloses an alpha conus polypeptide derivative, amino acid residues of which are shown in sequence 1 in a sequence table. To effectively resist the degradation digestion of partial protease in a human body, and improve the bioavailability and the drug metabolism performance, an N end of the alpha conus polypeptide derivative can be connected with a benzoyl group. The alpha conus polypeptide derivative can also be subjected to cyclization, fattening or PEG modification to strengthen the treatment effect of the alpha conus polypeptide derivative. A big mouse experiment shows that the alpha conus polypeptide derivative shows strong analgesic activity in a neuropathic pain model of a big mouse, and the analgesic activity is remarkably higher than that of control peptide Vc1.1 and shows dose-dependent relation.

Diagnostic devices and methods involve comparison of relative levels of first and second components and/or characteristics of a fluid sample (e.g., saliva), preferably using antibodies arranged to interact with selected components, and colorimetric indicators that are bound or released in proportion to relative concentration or amount of the components or characteristics, as indicative of a health condition such as dehydration state, shock state, stress state, disease state, drug consumption, and drug metabolization. Amylase and IgA may be selected as specific salivary components of interest.

The invention discloses a tanshinone IIA-polyactic acid/hydroxyacetic acid microsphere and a preparation method thereof. The microsphere is prepared by drying oil-in-water type emulsion, wherein the oil phase is dichloromethane solution of a polyactic acid/hydroxyacetic acid copolymer and the water phase is the water solution of polyvinyl alcohol. The drug content of tanshinone IIA in the microsphere is 1-10% and the entrapment efficiency is 60-90%. The particle size range of the microsphere is 30-200mm. The tanshinone IIA-polyactic acid/hydroxyacetic acid microsphere provided by the invention is suitable for interventional therapy of liver cancers, has a good liver tumor peripheral vascular thrombosis function, has an effective thrombosis time of 7-60 days, can be distributed in tumor tissues in a targeted manner, slowly release drugs, increase the local concentrations of the drugs, prolong the drug metabolism time, obviously inhibit animal liver tumor growth and prolong the animal lifetime and can inhibit expressions of a human hypoxia inducible factor 1alpha and a vascular endothelial growth factor and reduce the tumor tissue microvessel density after thrombosis.

The invention provides a primer set, application, a product and a method for detecting SNP sites related to drug metabolism in children, and relates to the field of biotechnology. The primer set of the SNP sites related to drug metabolism in children provided by the invention can be used to detect the metabolism capacity of thermoanalgesics, metabolism capacity of respiratory system drugs, metabolism capacity of neurological and psychiatric drugs, metabolism capacity of cardiovascular and cerebrovascular drugs, metabolism capacity of anti-infective drugs, metabolism capacity of endocrine drugs, metabolism capacity of digestion system drugs, metabolism capacity of anesthetic drugs and metabolism capacity of chemotherapy and immunosuppressant. Specific detection of site mutation related to common drug metabolism in children can be realized by the primer set, the accuracy is high, the detection cycle can be tremendously shortened, and the detection cost is reduced at the same time. Moreover, the needs of a drug metabolism can be predicted by the detection results, the metabolism capacity of a variety of drugs can also be comprehensively evaluated, and scientific reference is providedfor the individualized medication of children.

The invention discloses a relevant gene combination, a primer, a probe and application used for detecting a chemotherapeutic effect on acute myelogenous leukemia. The gene combination comprises four gene combinations closely relevant to pharmacotherapy of the acute myelogenous leukemia: medicament metabolism phase I enzyme gene CYP3A5, medicament metabolism phase II enzyme genes NAT2 and GSTO2, and medicament transport protein gene OATP1B1; and the gene combination comprises the following SNP loci: the locus rs776746 of the gene CYP3A5, the locus rs1799931 of the gene NAT2, the locus rs156697 of the gene GSTO2, and the locus rs4149056 of the gene OATP1B1. A method is performed by hybridizing a specific primer and probes which are subjected to fluorescence marks of different colors with target gene fragments in a nucleic acid sample after PCR amplification. The treatment effect of a leukemia medicament is detected and analyzed by mononucleotide extension technology so as to direct clinical medicament application, reduce a toxic or side effect of the medicament application for a patient, and increase a curative effect.