303 results about "Genotoxicity" patented technology

The invention discloses a preparation method of remdesivir, and belongs to the field of pharmaceutical chemicals; the preparation method comprises the steps: carrying out a reaction on a compound V with pentafluorophenol under the action of an alkali to obtain a compound IV; further splitting the compound IV to obtain a compound III; carrying out a reaction on the compound III with a compound II under the action of organic base with large steric hindrance, and carrying out acid hydrolysis to obtain a compound I. According to the method disclosed by the invention, the use of genotoxic nitro substitutes is avoided, the risk of genotoxic impurities is reduced, and the method is suitable for industrial large-scale production.

The invention discloses a method for measuring genotoxic impurities (or doubtful genotoxicity), namely phenylhydrazine compound residues, in crude drugs through the HPLC (high performance liquid chromatography). The detection is directly implemented by taking phenyl bonded silica gel as a chromatographic column of a solid phase and organic phase and buffer solution mixed solvent gradient elution as a mobile phase. The detection method is high in detection sensitivity, strong in specificity, high in precision, high in accuracy, convenient to operate and strong in adaptability and can be used for detecting phenylhydrazine compounds in various crude drugs, and the quality of the crude drugs can be effectively controlled.

The invention relates to an antitumor 3,5-diphenylmethylene-4-piperidone derivative and a preparation method thereof, and belongs to the technical fields of antitumor drugs and preparation methods thereof. The preparation method comprises the following steps: performing a Claisen-Schmidt condensation reaction on a 4-piperidone derivative having antitumor activity and 4-trifluoromethyl through 4-piperidone hydrochloride to obtain an intermediate a; and reacting the intermediate a with an acylation or sulfonylation reagent to obtain N-R-3,5-di(4-trifluoromethyl benzylidene)-4-piperidone b-5. The 3,5-diphenylmethylene-4-piperidone derivative is novel in structure, has the advantage of combination of a plurality of molecular targets, and has multidrug resistance activity; and the genotoxicity of currently-used antitumor drugs can be avoided. Compared with normal cells, the derivative has higher antitumor activity to tumor cells, so that the derivative has a great application prospect in the field of antitumor drugs.

The invention relates to a method for detecting nucleic acid alkali group with optical electric chemical technique, wherein said method comprises: a, contacting the tested sample and the material with optical electric chemical activity; b, evaluating the oxidization and reduction reaction between the nucleic acid alkali group and said optical electric chemical material, that using light to transform the optical electric chemical material into exciting state with existed electrode, and processing oxidization reduction reaction with nucleic acid alkali group when the excited material loses electrons, to evaluate the current generated in oxidization reduction reaction; c, based on said current, analyzing the sample qualitative or quantitatively. The invention can be used in biological detection, as nucleic acid cross detection, nucleic hurt detection and chemical material gene toxicity detection.

The present invention relates a method for the enumeration of eukaryotic cell micronuclei, while simultaneously acquiring cytotoxicity and mode of action information. The method utilizes differential labeling of chromatin from dead and dying cells to distinguish the chromatin from micronuclei, nuclei, and metaphase chromosomes, and differential labeling of metaphase events to provide additional information regarding cytotoxicity and genotoxic modes of action. Counting of micronuclei events relative to the number of nuclei and quantifying perturbations to the proportion of metaphase events can be used to assess the DNA-damaging potential of a chemical agent, the DNA-damaging potential of a physical agent, the effects of an agent which can modify endogenously-induced DNA damage, the effects of an agent which can modify exogenously-induced DNA damage, and genotoxic mode of action.

The invention relates to a method for detecting genotoxic impurities in an AL58805 bulk drug or medicinal preparation by using high-performance liquid chromatography. The method is directed at methyl p-toluenesulfonate (MPTS) and ethyl p-toluenesulfonate (EPTS); a sample undergoes pre-treatment at first; and then high-performance liquid chromatography is employed for determination, wherein a C18 chromatographic column is employed; detection wavelength is 225 nm; an aqueous acetonitrile-phosphoric acid solution is used as a mobile phase; flow velocity is 0.8 to 1.2 mL / min; column temperature is 30 to 40 DEG C; a sample size is 20 [mu]L; and elution time is 18 min. Results show that the detection limit of MPTS is 0.3 ppm and the limit of quantitation of MPTS is 1 ppm; and the detection limit of EPTS is 0.5 ppm and the limit of quantitation of EPTS is 1.4 ppm. The method has the advantages of good specificity, simple operation, high sensitivity and accurate results and is applicable to determination of MPTS and EPTS in AL58805.

The invention provides a linezolid injection and a preparation method thereof. The preparation method of the linezolid injection comprises the steps of weighing, preparation, filtration, encapsulationand sterilization, and nitrogen filling protection is carried out on liquid medicine in the steps of preparation and / or encapsulation. The content of 3-fluoro-4-(4-morpholinyl) aniline in the linezolid injection product can be obviously reduced by performing nitrogen charging protection on the liquid medicine in the steps of preparation and / or encapsulation, so that the product quality and the medication safety of the linezolid injection are favorably improved, and the medication risk of the variety is also obviously reduced by reducing the content of genotoxic impurities.

The invention relates to a method for carrying out enzyme-linked immunoadsorption detection on an integral zebra fish and application of the method in drugs for identifying genotoxic compounds, screening anti-tumor drugs and repairing DNA damage. On one hand, the invention can be used for evaluating the genotoxicity of the compounds including environmental compounds, drugs, cosmetics, food additives and the like, and on the other hand, the invention can be used for screening new drugs, such as the anti-tumor drugs, antioxidants, anti-aging drugs, anti-neurodegenerative disease drugs and the like. The invention has very important guiding significance on diagnosing and treating certain diseases and novel drug research and development and compound toxicity screening. By applying the zebra fish to evaluate the compound toxicity and screen the novel drugs, the advantages of low cost, low use level of samples, automatic operation and the like can be achieved, and an in vivo physiological environment of a live animal can be provided, therefore, the goals of simple and convenient evaluating and screening works, rapidness, economy, high efficiency and high flux can be achieved.

The invention provides a rapid high throughput screening process to identify genotoxic compounds. This is accomplished by using a set of biomarker predictor genes that selectively screen for genotoxic or non-genotoxic compounds.

The present invention provides methods for determining the presence of immobilized nucleic acid employing unsymmetrical cyanine dyes that are derivatives of thiazole orange, a staining solution and select fluorogenic compounds that are characterized as being essentially non-genotoxic. The methods comprise immobilizing nucleic acid, single or double stranded DNA, RNA or a combination thereof, on a solid or semi solid support, contacting the immobilized nucleic acid with an unsymmetrical cyanine dye compound and then illuminating the immobilized nucleic acid with an appropriate wavelength whereby the presence of the nucleic acid is determined. The cyanine dye compounds are typically present in an aqueous staining solution comprising the dye compound and a tris acetate or tris borate buffer wherein the solution facilitates the contact of the dye compound and the immobilized nucleic acid. Typically the solid or semi-solid support is selected from the group consisting of a polymeric gel, a membrane, an array, a glass bead, a glass slide, and a polymeric microparticle. Preferably, the polymeric gel is agarose or polyacrylamide. The methods employing the non-genotoxic compounds represent an improvement over commonly used methods employing ethidium bromide wherein the present methods retain the advantages of ethidium bromide, ease of use and low cost, but without the disadvantageous, known mutagen requiring special handling and waste procedures.

The invention provides a method for detection of inflammatory disease in a subject that comprises assaying a test sample of peripheral blood from the subject for a marker of DNA damage. An elevated amount of marker present in the test sample compared to control sample is indicative of inflammatory disease activity, including sub-clinical inflammation. The method can be adapted for quantitatively monitoring the efficacy of treatment of inflammatory disease in a subject. Markers of DNA damage include single- and / or double-stranded breaks in leukocytes, oxidative DNA damage in leukocytes, or a marker of nitric oxide oxidative activity (protein nitrosylation in leukocytes). The inflammatory disease can be inflammatory bowel disease (ulcerative colitis or Crohn's disease). The invention may also be used for detection of other types of inflammatory disease, such as non-immune intestinal inflammatory disease (diverticulitis, pseudomembranous colitis), autoimmune diseases (rheumatoid arthritis, lupus, multiple sclerosis, psoriasis, uveitis, vasculitis), or non-immune lung diseases (asthma, chronic obstructive lung disease, and interstitial pneumonitis). This unexpected discovery of markers of genotoxicity present in circulating leukocytes enables detection of inflammation occurring at a localized site with a relatively simple and minimally invasive assay using peripheral blood.

The invention discloses a preparation method for free-state edoxaban.The synthetic route is shown in the description.According to the preparation method, the charging sequence is changed, and a curing problem caused by a traditional method is reduced; according to an existing method, a starting material A and triethylamine are added at first, a starting material B is added, a large amount of solid will appear in the temperature increasing process, and the stirring uniformity is greatly affected, so that the yield is greatly lowered, and the method is adopted for greatly solving the problem and improving the yield; when the compound free-state edoxaban is synthetized, a first amount of a saturated sodium bicarbonate water solution is added at first, the phenomenon that a product is rapidly separated out and impurities are included due to the fact that the added saturated sodium bicarbonate water solution is excessive is avoided, and meanwhile introduction of genotoxicity impurity methanesulfonate is effectively avoided; after the impurities are completely hydrolyzed, a second amount of the saturated sodium bicarbonate water solution is added so that the product can be separated out thoroughly; the method improves the crystallization way, the yield is improved, and generation of impurities is reduced.

The disclosure includes methods for the identification of chemotherapeutic agents that selectively reduce the growth or the survival of genotoxically stressed DNA damage checkpoint deficient tissue, such as irradiated cancerous tissue. The methods involve the use of genotoxically-stressed tissue(s) that are deficient in one or more DNA damage checkpoints. The disclosure also provides kits for performing the disclosed methods. The disclosure also includes chemotherapeutic agents that selectively reduce the growth or the survival of genotoxically stressed DNA damage checkpoint deficient tissue, such as irradiated cancerous tissue. The disclosure also includes methods of treatment or management of cancer, tumor formation, other conditions involving abnormal proliferation, or cell-cycle diseases or disorders.