35 results about "CYP2D6" patented technology

The invention relates to a preparation method, a detection method and application of a probe drug composition for determination of metabolic activity of cytochrome P450. The composition mainly comprises a preparation made with a specific probe with major isoforms of CYP450, i.e. CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4, as an active component. Cocktail probe drug solution is prepared, the probe drug composition is injected into an animal or liver microsomes for in vitro co-incubation, and the concentration of each probe drug is determined to assess the metabolic activity of the CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. In the early stage of research and development of new drugs, the effects of the drugs on the activity of each isoform of the cytochrome P450 are screened in a high-throughput way, and the interactions of the drugs can be predicted. In the stage of clinical research, the testing can be performed with the probe drug composition in an in-vivo probe method, and the effects of the drugs on the in-vivo metabolic activity of different isoforms of the human liver CYP450 can be examined.

The present invention relates, generally to a method of determining and assessing cytochrome P450 2D6 isoenzyme (CYP2D6)-related metabolic capacity in an individual mammalian subject via a breath assay, by determining the relative amount of 13CO2 exhaled by a the subject upon intravenous or oral administration of a 13C-labeled CYP2D6 substrate compound. The present invention is useful as an in vivo phenotype assay for evaluating CYP2D6-related activity using the metabolite 13CO2 in expired breath and to determine the optimal dosage and timing of administration of CYP2D6 substrate compound.

The present invention relates to htSNPs for determining a genotype of cytochrome P450 1A2 (CYP1A2), 2A6 (CYP2A6) and 2D6 (CYP2D6), PXR and UDP- glucuronosyltransf erase Ia (UGTlA) genes and a gene chip using the same, and more particularly, to a selection method of htSNPs for determining a haplotype of human CYP1A2, CYP2A6, CYP2D6, PXR and UGTlA genes, a method of determining a genotype of the genes by using the htSNPs and a gene chip therefor.

The invention discloses a kit and method for detecting the tamoxifen personalized medicine genetic polymorphism by use of the pyrosequencing technique. The genetic polymorphism specifically refers to the single nucleotide polymorphism of CYP2D6*10(rs1065852) and (SULT1A1*2) (rs9282861). The kit comprises the primer shown by SEQ ID NO.3-8. The kit disclosed by the invention can realize accurate, quick and high-flux detection on CYP2D6*10(rs1065852) and (SULT1A1*2) (rs9282861) so as to realize safe, reasonable and effective personalized administration of the tamoxifen medicine.

The present invention relates, generally to a method of determining and assessing cytochrome P450 2D6 isoenzyme (CYP2D6)-related metabolic capacity in an individual mammalian subject via a breath assay, by determining the relative amount of 13CO2 exhaled by a the subject upon intravenous or oral administration of a 13C-labeled CYP2D6 substrate compound. The present invention is useful as an in vivo phenotype assay for evaluating CYP2D6-related activity using the metabolite 13CO2 in expired breath and to determine the optimal dosage and timing of administration of CYP2D6 substrate compound.

The invention relates to the field of gene detection, in particular to a gene detection method, a primer probe combination and a kit for precise drug use of depression to overcome the shortcoming thatthe market is short of products for gene detection of the drug use of the depression, only detection of a drug metabolism gene is adopted clinically, and the drug therapeutic effect predication is inaccurate. 11 loci of 5 related genes of CYP2D6, CYP2C19, FKBP5, HTR2A and HTR1A of anti-depression drugs are detected to determine the relevant gene locus types, and the clinical drug use can be guided by analysis.

The invention belongs to the technical field of biology, and particularly relates to an individualized medication gene testing reagent kit for a beta-receptor blocker. The individualized gene testingreagent kit for the beta-receptor blocker mainly comprises: (1) two pairs of CYP2D6*10 and ADRBB1(1165 G) [C] locus amplification and sequencing primers, (2) PCR amplification reagents, (3) a PCR product purification reagent, and (4) a DNA sequencing reagent. The reagent kit is used for detecting the loci of the beta-receptor blocker drug metabolizing enzyme and the receptor CYP2D6*10 and ADRBB1 (1165 G) [C] of the hypertension patient, uses the key technology for Sanger sequencing (the accuracy rate is more than 99.9%). The genotypes of the two loci are proved to be closely associated with the curative effect of medication of the beta-receptor blocker, so that the gene testing reagent kit can be used for guiding the hypertension patient in using the beta-receptor blocker drug reasonably and safely according to the testing result of the gene testing reagent kit.

The invention relates to the technical field of in vitro diagnosis, in particular to a kit for detecting polymorphism of human CYP2D6, CYP2C9, ADRB1, AGTR1, ACE genes by a multiple fluorescent PCR method. The kit is used to detect CYP2D6*10, CYP2C9*3, ADRB1 (1165G > C), AGTR1 (1166A > C), ACE (I / D) polymorphism sites. The primer and the probe have high sensitivity and high specificity, and can accurately detect genomic DNA as low as 0.1 ng / <mu>L. The kit is easy to operate, and can cooperate with an automated instrument for detection.

The present invention relates to htSNPs for determining a genotype of cytochrome P450 1A2 (CYP1A2), 2A6 (CYP2A6) and 2D6 (CYP2D6), PXR and UDP-glucuronosyltransferase Ia (UGT1A) genes and a gene chip using the same, and more particularly, to a selection method of htSNPs for determining a haplotype of human CYP1A2, CYP2A6, CYP2D6, PXR and UGT1A genes, a method of determining a genotype of the genes by using the htSNPs and a gene chip therefor.

The invention discloses a cytochrome P450 gene genetic variation detecting chip. It includes the probe fixed on the solid phase carrier to hybridize with the cytochrome P450 gene nucleotide sequence and / or complementation sequence. The invention also discloses the used chip detecting method. The detecting chip can effectively detect subtype genetic variation of CYP2C9, CYP2C19, CYP2D6, CYP3A5, forecast the therapeutic effectiveness of over 40% clinic common medicine to realize individualization medical treatment.

The present invention relates to htSNPs for determining a genotype of cytochrome P450 1A2 (CYP1A2), 2A6 (CYP2A6) and 2D6 (CYP2D6), PXR and UDP-glucuronosyltransferase Ia (UGT1A) genes and a gene chip using the same, and more particularly, to a selection method of htSNPs for determining a haplotype of human CYP1A2, CYP2A6, CYP2D6, PXR and UGT1A genes, a method of determining a genotype of the genes by using the htSNPs and a gene chip therefor.

The invention provides a primer probe combination, a kit and a method for detecting copy number variation and genotyping of human CYP2D6. The nucleotide sequences of the primer probe combination for detecting the copy number variation of the human CYP2D6 are as shown in SEQ ID No.1 to SEQ ID No.9, and the nucleotide sequences of the primer probe combination for detecting the genotyping of the human CYP2D6 are as shown in SEQ ID No.10 to SEQ ID No.17. The primer probe combination can be used for in-vitro qualitative detection of CYP2D6 copy number variation and * 10 and * 41 genotypes in human genome DNA, realizes simultaneous detection of * 10 and * 41 genotypes in a single tube on imported / domestic fluorescent quantitative PCR equipment without mutual interference, has the advantages of high accuracy, good stability and excellent detection limit, and has a wide application prospect. According to the detection result, clinical selection of antipsychotic drugs can be assisted to realize medication guidance for mental / depression patients, the curative effect is ensured, and toxic and side effects are reduced.

Compounds of Formula I, pharmaceutically acceptable salts thereof, enantiomers thereof, metabolites thereof, derivatives thereof, prodrugs thereof, acid addition salts thereof, pharmaceutically acceptable salts thereof, or N-oxides thereof; or a combination thereof; processes and intermediates for preparation thereof, compositions thereof, and uses thereof; are provided. Pharmaceutical compositions comprising a compound of Formula I, or enantiomers thereof, metabolites thereof, derivatives thereof, prodrugs thereof, acid addition salts thereof, pharmaceutically acceptable salts thereof, or N-oxides thereof; or a combination thereof; wherein the compound is a double and / or triple agent or ligand for CYP2D6, 5-HT2A, and / or 5HT2C receptors, and / or acetylcholinesterase are provided.

A clozapine individualized drug gene detection kit comprises the following components: CYP2D6*2 (886C) A, CYP2D6*41 (985+39G) A, CYP2D6*10 (100C) T and MC4R (57882787C) T; 4 pair of site amplificationand sequencing prim, 1 pair of CYP2D6Z large fragment PCR amplification primers, PCR amplification reagent, PCR product purification reagent and DNA sequencing reagent; as shown in Table 1 of that prim sequence. The invention has the following technical effects: a gene detection kit for individualized clozapine medication for Chinese people is provided, and the sensitivity is high and the accuracy is high. The kit is used for CYP2D6*2 (886C) A), CYP2D6*41(985+39G)A), CYP2D6*10 (100C) T) and MC4R (57882787C) T). The genetic difference between individuals can be found through the test of this item, and the drug constitution (slow metabolism or normal metabolism) can be defined, the relevant gene information can be interpreted, and the physiological status or drug reaction can be known in time, so that the drug efficacy can be improved, the toxic and side effects of drugs can be reduced, and the medical cost can be reduced.

The invention discloses a construction method of a humanized CYP2D6*10 transgenic mouse. According to the method, the homologous recombination principle is utilized, an ES targeting mode is adopted, an expression cassette of hCYP2D6*10 is knocked into an exon4-5 site of the Cyp2d22 gene in a fixed-point mode, and then a Cyp2d gene cluster is knocked out in a Crispr / Cas9 mode; firstly, a targeting vector is prepared, and ES cells are electrically transfected after the vector is linearized; through long-fragment PCR identification, positive clones of correct homologous recombination are obtained; and the positive ES cell clone is amplified to be injected into a blastocyst of a C57BL / 6J mouse to obtain a chimeric mouse. Compared with a non-transgenic mouse, the humanized CYP2D6*10 transgenic mouse bred by the invention can express a human CYP2D6*10 type gene (dominant proportion allele of Chinese population), and can replace human beings to be used for developing pharmacokinetic and pharmacodynamic related research of substrate drugs.

The invention discloses a gene detection kit used for [beta] receptor antagonist medication, and a detection method and application of the gene detection kit. The detection kit designs specific amplification primers and sequencing primers by aiming at the polymorphism and the CYP2D6 effective copy number of two genes, including CYP2D6C100T and ADRB1G1165C. The kit comprises the following ingredients: amplification reaction liquid, a CYP2D6C100T sequencing primer, an ADRB1G1165C sequencing primer, a CYP2D6 effective copy number sequencing primer and a positive control. The gene detection kit adopts asymmetric multiplex PCR one-tube amplification on CYP2D6(C100T), ADRB1(G1165C and the CYP2D6 effective copy number, a great quantity of biotin-labeled single-strand DNA is generated, in a single-strand amplification process, a CYP2D7-PNA blocking probe blocks binding of a biotin-labeled probe and a pseudogene CYP2D7 so as to prevent the pseudogene from disturbing a sequencing result, the biotin-labeled single-strand DNA carries out binding with streptavidin, after washing is carried out, the sequencing primers and a sequencing raw material are added, pyrophosphoric acid sequencing is carried out, injuries to an amplified fragment by a strong basicity reagent are reduced, sequencing procedures are simplified, and sequencing time is shortened.

The invention discloses a fluvoxamine clinical precise application virtual simulation experiment platform based on a CYP2D6 genotype, the platform is oriented to clinical problems, a complete knowledge system of laboratory research and pharmaceutical service is built, students' understanding of precise medication is cultivated, and specifically, according to the project, students are guided to understand and master gene sequencing and analysis according to the ideas of drug monitoring, drug enzyme gene detection, metabolic type judgment, guide searching and individualized drug administration scheme making of special crowds.

Reference controls for use with pharmacogenomic testing, and methods for their identification, preparation, and use, are disclosed. The reference controls can confirm that pharmacogenomic testing correctly identifies individuals that do or do not have the mutation of interest, in both clinical trial and patient treatment settings. The reference controls can be selected to include one or more mutations to be identified, and prescreened to confirm that they bind to one or more of the primers used in the pharmacogenomic testing. The reference controls are human genomic DNA that includes certain identified polymorphisms (mutations) of interest, ideally derived from individuals, pre-selected and optionally properly consented, which have one or more of the polymorphism(s) of interest. The reference controls can be prepared by targeted pre-screening of human patients, by examining the genotype or genetic profile of the patients, isolating cells with the desired mutation, optionally immortalizing the cells, and obtaining DNA from the cells. The prescreening of prospective donors can be targeted based on any of a number of factors, such as genes of interest, mutations within the genes of interest, and membership in a specific ethnic or disease state population. The genomic DNA can be pre-screened for its ability to be detected, using a standard pharmacogenomic test, as including a specific mutation. Examples of mutations of interest include those present in a Phase I or Phase II metabolic enzyme such as CYP2D6, CYP2C19, CYP2C9, CYP2C8, and CYP3A5, CYP3A4, CYP2A6, CYP2B6, UGT1A1, DPD, ERCC1, MDR1, ADH2, NAT1 and NAT2 or any other metabolic or disease gene.

The invention discloses a CYP2D6*10 genetic polymorphism detection kit capable of distinguishing CYP2D7P and CYP2D8P, and belongs to the technical field of molecular medicine. The kit can utilize a highly specific primer pair CYP2D6 (rs1065852) to realize accurate target amplification; and through the combination of the advantages of a Taqman probe of being high in specificity, fast and simple, the genotyping of the CYP2D6 (rs1065852) can be realized.

A method of dosing LSD in treating patients, by assessing genetic characteristics in the patient by identifying polymorphisms of CYP2D6 before use of a composition chosen from the group consisting of LSD, analogs thereof, derivatives thereof, and salts thereof, administering the composition to the patient based on the patient genetics, wherein a 50% dose is administered in a patient with non-functional CYP2D6 compared to a dose in functional CYP2D6 individuals, and producing maximum positive subjective acute effects in the patient and / or reducing anxiety and negative effects. A method of determining a preferred dose of LSD.

The invention provides a drug tamoxifen treatment effect-related gene (CYP2D6, CYP3A5 and RRAS2) polymorphism detection kit and a drug tamoxifen treatment effect-related gene (CYP2D6, CYP3A5 and RRAS2) polymorphism detection method, wherein the kit comprises a PCR buffer solution, specific ARMS detection primers and quality control primers. The present invention further provides the tamoxifen treatment effect-related gene (CYP2D6, CYP3A5 and RRAS2) polymorphism detection method. According to the present invention, with the method, the tamoxifen treatment effect-related gene (CYP2D6, CYP3A5 andRRAS2) polymorphism can be rapidly and accurately detected; and the kit has characteristics of high sensitivity, strong specificity, simple method, accurate result and the like.

The invention belongs to the field of biological technology, relates to a genetic test reagent kit, in particular to an individual genetic test reagent kit of medicines for relieving fever and alleviating pain. The reagent kit comprises the main components of: (1) 4 pairs of CYP2D6*10, CYP2C9*3 and CYP2C19*2 / *3 gene PCR amplification and sequencing primers; (2) preparing a PCR amplification reagent; (3) preparing a PCR product purifying reagent; and (4) preparing a DNA sequencing reagent. The reagent kit can be used for detecting the metabolic capability of the medicines for relieving fever and alleviating pain, and understanding the metabolic capability of the medicines in bodies of children, can effectively and objectively assess the treatment effect and adverse reactions of the medicines to the children, and is favorable for reduction of damage of the medicines to the children, so that the treatment effect is maximized.

The invention discloses a detection kit for metabolic markers of ondansetron and tropisetron, a detection method of the detection kit and application of the detection kit and the detection method. The detection kit is used for detecting gene polymorphism of the metabolic markers CYP2D6C100T, CYP2D6G1846A and CYP2D6*5 of the ondansetron and the tropisetron. According to the kit, specific amplification primers and sequencing primers are designed according to the polymorphism of the three genes CYP2D6C100T, CYP2D6G1846A and CYP2D6*5. The kit comprises the following components of an amplification reaction solution, the CYP2D6C100T sequencing primer, the CYP2D6G1846A sequencing primer, the CYP2D6*5 sequencing primer and a positive control. According to the invention, blood direct expansion, rapid amplification and optimized pyrosequencing technologies are combined to detect gene polymorphism related to prediction of drug effects and adverse reactions of the ondansetron and the tropisetron, and suggestions from the gene perspective are provided for clinical use of the ondansetron and the tropisetron.

Compounds of Formula I, pharmaceutically acceptable salts thereof, enantiomers thereof, metabolites thereof, derivatives thereof, prodrugs thereof, acid addition salts thereof, pharmaceutically acceptable salts thereof, or N-oxides thereof; or a combination thereof, processes and intermediates for preparation thereof, compositions thereof, and uses thereof, are provided. Pharmaceutical compositions comprising a compound of Formula I, or enantiomers thereof, metabolites thereof, derivatives thereof, prodrugs thereof, acid addition salts thereof, pharmaceutically acceptable salts thereof, or N-oxides thereof; or a combination thereof, wherein the compound is double and / or triple agent or ligand for CYP2D6, 5-HT2A, and / or 5HT2C receptors, and / or acetylcholinesterase are provided.

The invention relates to a detection system for detecting CYP2D6*10 gene mutation and a kit of the detection system. The detection system comprises digital PCR (polymerase chain reaction) premixed solution and primer probe mixed solution, the primer probe mixed solution comprises an upstream primer, a downstream primer and a peptide nucleic acid probe which are used for detecting CYP2D6*10 sites of CYP2D6 genes, a nucleotide sequence of the upstream primer is as shown in SEQ ID No.1, a nucleotide sequence of the downstream primer is as shown in SEQ ID No.2, a nucleotide sequence of the peptidenucleic acid probe and CYP2D6*10 mutant gene sites are completely complemented, the nucleotide sequence of the peptide nucleic acid probe is as shown in SEQ ID No.3, and the 5' end of the peptide nucleic acid probe is connected with a strong chelation group formed by four amino acids. According to the detection system for detecting CYP2D6*10 gene mutation and the kit of the detection system, sensitivity and specificity are high, needed samples are less, and quantitative PCR detection can be performed rapidly, conveniently and accurately.

A method of dosing LSD in treating patients, by assessing genetic characteristics in the patient before LSD use, administering LSD to the patient based on the patient genetics, and producing maximum positive subjective acute effects in the subject and / or reducing anxiety and negative effects. A method of determining a preferred dose of LSD, by determining metabolic and genetic markers in a patient (such as by assessing CYP2D6 activity and / or assessing 5HTR1A rs6295 and 5HTR2A rs6313 genotypes in a patient), adjusting a dose of LSD based on the metabolic activity and genetic profile, administering the dose of LSD to the patient, and producing maximum positive subjective acute effects in the subject and / or reducing anxiety and negative effects. A method of determining a dose of LSD based on an assessment of the presence of CYP2D6 inhibitors.

The invention provides an SYBR Green I detection primer of a CYP2D6 * 10 gene, a kit and a detection method. Wherein the detection primer comprises a CYP2D6*10 wild type upstream primer, a CYP2D6*10 mutant type upstream primer, a CYP2D6*10 wild type universal downstream primer and a CYP2D6*10 mutant type universal downstream primer; the nucleotide sequence of the CYP2D6*10 wild type upstream primer is shown as SEQ ID NO: 1, the nucleotide sequence of the CYP2D6*10 mutant type upstream primer is shown as SEQ ID NO: 2, and the nucleotide sequence of the universal downstream primer is shown as SEQ ID NO: 3. According to the application, the detection primers and the kit containing the primers are used; a fluorescence signal value in the PCR process is directly explored, so that the detectionresult is obtained, PCR post-treatment or electrophoresis detection is not needed, the technical problems of easy pollution and false positive of the conventional PCR technology are solved, the problem of non-specific amplification can be effectively avoided, and the method is suitable for detection of large-batch samples. The method has the advantages of high sensitivity and strong specificity, and can guide patients with various diseases to realize individualized medication according to individual genome information.