26 results about "Amethopterin" patented technology

The invention relates to the technical field of biological medicine, in particular to a multifunctional ternary complex based on cyclodextrin and a preparation method thereof. The invention provides a multifunctional curcumin / methotrexate ternary complex based on beta-cyclodextrin. The ternary complex can realize synergistic delivery and controlled-release release of natural polyphenol and synthetic drugs in a medication mode of'one dose with multiple effects'. Meanwhile, the problems that a traditional medicine is poor in water solubility and low in bioavailability, the treatment effect of a single medicine is limited, and an existing nano delivery system is complex in structure, tedious in preparation and the like are solved, and the technical requirements of modern medicine preparations are met.

This invention discloses a hyaluronic acid-phenylboronic acid-methotrexate antitumor conjugate and its preparation method in the field of drug preparation technology. First, hyaluronic acid is activated with carboxylic acid, then subjected to an amidation reaction with 3-aminophenylboronic acid to obtain a hyaluronic acid-phenylboronic acid conjugate. Next, methotrexate is activated and added to the hyaluronic acid-phenylboronic acid mixture, followed by stirring to obtain the hyaluronic acid-phenylboronic acid-methotrexate antitumor conjugate. The preparation method of this invention is simple. While the three drugs exert their respective effects, the introduction of phenylboronic acid enhances the targeted antitumor effect of the drug. The combined use of hyaluronic acid and phenylboronic acid further reduces the toxic side effects of methotrexate and improves the biocompatibility, bioavailability, and degradability of the resulting drug, making it suitable for application in the preparation of antitumor drugs.

The present application is a dry granulation method of methotrexate tablets, comprising: mixing methotrexate and excipients by geometric dilution method, and adopting roll pressing method and directly pressing to obtain methotrexate tablets. The excipients include anhydrous lactose, microcrystalline cellulose, pre-gelatinized starch and sodium carbonate. The content of methotrexate in each methotrexate tablet is 2-3%. The present application has the advantages that the components and method design are reasonable, the cost and energy can be effectively saved, the solvent contact in the granulation process is reduced, the time is saved, the stability of the pharmaceutical preparation components can be effectively improved, and the production efficiency is improved.

Provided herein are compositions comprising disodium levofolinate. Also provided are processes for preparing compositions comprising disodium levofolinate. Also provided are compositions comprising disodium levofolinate prepared by the processes provided herein. Also provided are methods of treating folic acid deficiency in a subject in need thereof, comprising administering a composition provided herein to the subject. Also provided are methods of treating cancer in a subject in need thereof, comprising administering 5-fluorouracil and a composition provided herein to the subject. Also provided are methods of reducing the immediate toxic effects of methotrexate overdose in a subject in need thereof, comprising administering a composition provided herein to the subject. Also provided are methods of treating cancer in a subject in need thereof, comprising administering high-dose methotrexate and a composition provided herein to the subject. Also provided are methods of treating megaloblastic anemia in a subject in need thereof, comprising administering a composition provided herein to the subject.

The application discloses a method for efficiently synthesizing methotrexate, and relates to the technical field of methotrexate preparation. The method comprises the following steps: preparing three intermediates, and then preparing methotrexate by using the three intermediates. In the process of preparing the intermediates, a step of improving the purity of tribromoacetone is added, so that the content of the tribromoacetone is increased from 89-90% to more than 98%, thereby reducing the separation difficulty of the product, reducing the generation of impurities, and improving the yield; in the step of preparing the methotrexate, a new catalyst is used, sodium acetate trihydrate and potassium dihydrogen phosphate are used as a composite catalyst, and the yield of the methotrexate is improved.

The invention discloses a method for determining related substances in methotrexate, which comprises the following steps: firstly preparing an impurity C positioning solution, a system applicability solution and a test solution, then respectively carrying out liquid chromatography detection on the impurity C positioning solution, the system applicability solution, a reference substance solution and the test solution, recording chromatograms, and determining the content of the related substances in methotrexate according to the chromatograms. And performing quantitative analysis on the impurity C and other impurities in the test solution by comparing the chromatograms. According to the method, a system applicable solution is prepared by destroying a main component reference substance solution, the solution is a mixed solution containing an impurity B, an impurity C and methotrexate, the impurity C can be positioned, and the separation degree between the impurity B and the impurity C is controlled to be not less than 1.5.

A composition for preventing or treating a TNF-α-related disease is disclosed. The composition includes hydroflumethiazide or a pharmaceutically acceptable salt thereof as an active ingredient. The composition can effectively inhibit the expression or activity of TNF-α and exhibits an excellent treatment effect compared to methotrexate (MTX) or hydroxychloroquine (HCQ), which are rheumatoid arthritis treatment agents currently on the market, and, thus, can be effectively used for prevention or treatment of a TNF-α-related disease.

The present application relates to a kind of diclofenac-methotrexate co-amorphous substance and its preparation method and application, in the diclofenac-methotrexate co-amorphous substance, the molar ratio of diclofenac and methotrexate is 1:2, its X-ray powder diffraction pattern has no sharp diffraction peak, indicating the formation of co-amorphous form.The present application is obtained by using rotary evaporation method to obtain co-amorphous substance, and the results of pharmacokinetics and in vitro and in vivo pharmacodynamics experiments show that the performance indicators such as DIC-MTX co-amorphous system are superior to physical mixture in bioavailability, anti-inflammatory effect, etc., which embodies its potential application value, and shows that there is positive effect between the two drugs for treating rheumatoid arthritis, which provides a research basis for realizing the combination of DIC and MTX.

The present application relates to the technical field of rheumatoid arthritis drugs, and particularly relates to methotrexate-baiji polysaccharide nanoparticles and a preparation method and application thereof.The present application provides methotrexate-baiji polysaccharide nanoparticles, which have a structure shown in formula 1.The nanoparticles are formed by connecting methotrexate and baiji polysaccharide through a disulfide bond, and in theory, can realize drug release in response to high active oxygen stimulation in the microenvironment of rheumatoid arthritis.In addition, the present application researches and proves that the nanoparticles can effectively inhibit the proliferation and migration of fibroblast-like synoviocytes, regulate the polarization of M1 macrophages to M2 macrophages, and reduce synovial inflammation.The methotrexate-baiji polysaccharide nanoparticles of the present application have simple preparation process operation, are convenient to use, and have a good development and utilization prospect.Formula 1

The present application belongs to the technical field of medicine, and particularly relates to a refining method of methotrexate intermediate (i.e. methotrexate disodium salt). The finished product of methotrexate contains stubborn impurity C (the limit of impurity C in European Pharmacopoeia EP9.0 is ≤0.5%), which is difficult to remove by ordinary refining method. The inventors surprisingly found that, by adding sodium chloride to the reaction solution of methotrexate disodium salt for crystallization, the content of stubborn impurity C precursor can be greatly reduced, the number and content of impurity peaks are reduced, the pigment in the methotrexate intermediate is removed, and then the content of stubborn impurity C in the methotrexate bulk drug is reduced, so that the purity meets the requirements of European Pharmacopoeia.

The invention relates to a diclofenac-methotrexate co-amorphous substance and a preparation method and application thereof, in the diclofenac-methotrexate co-amorphous substance, the molar ratio of diclofenac to methotrexate is 1: 2, and the X-ray powder diffraction pattern of the diclofenac-methotrexate co-amorphous substance has no sharp diffraction peak, indicating the formation of the co-amorphous state. The co-amorphous substance is obtained through a rotary evaporation method, pharmacokinetic and in-vivo and in-vitro pharmacodynamic experiment results show that the DIC-MTX co-amorphous system is superior to a physical mixture in bioavailability, anti-inflammatory effect and other performance indexes, the potential application value of the DIC-MTX co-amorphous system is embodied, and the DIC-MTX co-amorphous system has good application prospects. Moreover, the two medicines have a positive effect of treating rheumatoid arthritis, and a research basis is provided for realizing the drug combination of the DIC and the MTX.

The application discloses a method for determining related substances in methotrexate, which comprises the following steps: preparing an impurity C positioning solution, a system suitability solution and a test sample solution, and then respectively detecting the impurity C positioning solution, the system suitability solution, a reference substance solution and the test sample solution by using liquid chromatography, recording chromatograms, and quantitatively analyzing impurity C and other impurities in the test sample solution by comparing the chromatograms. The system suitability solution is prepared by destroying the main component reference substance solution, and the solution is a mixed solution containing impurity B, impurity C and methotrexate, so that impurity C can be positioned, and the separation degree between impurity B and impurity C should be not less than 1.5.

The invention discloses a layered screening method for acute lymphocytic leukemia patients based on methotrexate medication and application thereof, and the layered screening method for acute lymphocytic leukemia is characterized in that the patients are divided into three types of GG, AG and AA by detecting the genotype of the rs1544105 site of an FPGS gene in an in-vitro sample. Based on Meta analysis data of 1760 patients in 11 studies, the GG type is judged as a methotrexate standard dose suitable crowd, the AG or AA type needs to be adjusted, and the AG type corresponds to gt; 20 mg / m < 2 > high-dose methotrexate preparation and AA type corresponding non-folic acid medicine preparation. The invention also includes monitoring somatic mutation in recurrent patients, and switching to a non-methotrexate regimen if GG type mutation is AG / AA type. According to the method, precise layering is achieved, the disease progress risk is reduced, and technical support is provided for pharmaceutical enterprises to prepare personalized drugs and clinical test layering.

Disclosed are methods of treating cancer by administering a first agent comprising an antibody or fragment thereof that binds CD206 present on tumor associated macrophages conjugate to a mutant of human carboxypeptidase A (hCPA), followed by administering second agent comprising 3-cyclopentyl-alpha-phenylalanine-methotrexate.

The invention discloses a layered screening method for acute lymphocytic leukemia patients based on methotrexate medication and application thereof, and the layered screening method for acute lymphocytic leukemia is characterized in that the patients are divided into three types of GG, AG and AA by detecting the genotype of the rs1544105 site of an FPGS gene in an in-vitro sample. Based on Meta analysis data of 1760 patients in 11 studies, the GG type is judged as a methotrexate standard dose suitable crowd, the AG or AA type needs to be adjusted, and the AG type corresponds to gt; 20 mg / m < 2 > high-dose methotrexate preparation and AA type corresponding non-folic acid medicine preparation. The invention also includes monitoring somatic mutation in recurrent patients, and switching to a non-methotrexate regimen if GG type mutation is AG / AA type. According to the method, precise layering is achieved, the disease progress risk is reduced, and technical support is provided for pharmaceutical enterprises to prepare personalized drugs and clinical test layering.

The invention aims to provide an acid response type rheumatoid arthritis targeted therapy nano preparation as well as a synthesis method and application thereof, and belongs to the technical field of preparation of nano biomedical materials. The preparation method comprises the following steps: synthesizing Zn / SiO nano-particles with a dandelion-shaped structure through an oil-water two-phase method, loading methotrexate by utilizing the large-aperture characteristic of the particles, and coating an M2 macrophage membrane on the outer layer to prepare the methotrexate-loaded Zn / SiO nano-particles. The nano preparation has good biocompatibility, stability and capability of targeting rheumatoid arthritis parts by virtue of inflammation chemotaxis and homologous targeting effects of M2 macrophage membranes. In an acidic microenvironment, the nanoparticles can respond to release zinc ions and drugs, so that safe and effective treatment of rheumatoid arthritis is realized.

The invention relates to a methotrexate immunodetection reagent as well as a preparation method and a detection method thereof, in particular to a methotrexate chemiluminescence immunodetection reagent as well as a preparation method and a detection method thereof, and the methotrexate chemiluminescence immunodetection reagent comprises an anti-methotrexate specific antibody and an indicating reagent for detecting an anti-methotrexate specific antibody-methotrexate conjugate, the anti-methotrexate specific antibody is obtained by immunizing an animal with methotrexate immunogen. The methotrexate immunogen has the beneficial effects that the methotrexate immunogen has strong specificity and high immunogenicity, and the prepared anti-methotrexate specific antibody has strong specificity and high titer; the chemiluminescence immunoassay reagent containing the anti-methotrexate specific antibody can conveniently, quickly and accurately determine the methotrexate content in a sample, can simultaneously determine a plurality of samples on a full-automatic chemiluminescence immunoassay instrument, realizes high-throughput quick determination of methotrexate, and has the advantages of high accuracy, strong specificity, high sensitivity, high sensitivity, high sensitivity and high sensitivity. And the accuracy and the detection efficiency are greatly improved.

The application belongs to microneedle, and particularly relates to soluble microneedle based on metal-amino acid / peptide / drug coordination nanoparticles and a preparation method and application thereof. 2+ The coordination center ion of the nanoparticles is selected from Zn 2+ , the ligand is selected from a mixture of 9-fluorenylmethyl oxycarbonyl modified histidine (Fmoc-H) and macrophage targeting peptide (Fmoc-HTKPR) modified by 9-fluorenylmethyl oxycarbonyl modified histidine derivatives, and methotrexate (MTX), a rheumatoid arthritis treatment drug containing a carboxyl group, and the microneedle carrier material is selected from a soluble polymer PVP. The application provides a scheme for realizing metal-drug coordination at normal temperature, and the nanoparticles are released by the microneedle in vivo, the nanoparticles can be actively targeted to inflammatory sites through the targeting peptide, and high-load MTX and active oxygen scavenging drugs are responsively released, so that high-efficiency and safe rheumatoid arthritis treatment is realized based on the synergistic effect of eliminating inflammatory macrophages and converting the same into an anti-inflammatory phenotype.

The application discloses application of HLA-B*13 allele in preparation of a detection reagent for predicting liver injury caused by methotrexate. The application scheme firstly discovers and verifies that the HLA-B*13 allele is related to the risk of liver injury caused by methotrexate, and can be used as a marker gene for predicting the risk of liver injury caused by methotrexate, thereby providing a new evaluation method for avoiding or reducing the risk of liver injury adverse reactions in the clinical application of methotrexate.

The invention relates to the technical field of methotrexate blood concentration in-vitro detection, in particular to a methotrexate detection kit and a preparation method thereof. The invention provides a preparation method of a methotrexate detection kit, the preparation method comprises the four steps of S1 surface modified magnetic bead preparation, S2R1 reagent preparation, S3R2 reagent preparation and S4 combination, and a molecular imprinting technology and a bimetallic chelation strategy are combined and applied to magnetic bead modification. High-selectivity capture of methotrexate is realized through a synergistic effect of spatial configuration matching and multivalent chemical bonding. The methotrexate detection kit prepared by the preparation method has good detection selectivity, sensitivity and accuracy.

The invention discloses a fluorouracil methotrexate conjugate as well as a preparation method and application thereof. The present invention provides a compound represented by formula (I) or formula (II), or a pharmaceutically acceptable salt thereof. Compared with the methotrexate and fluorouracil which are physically mixed, the methotrexate and fluorouracil conjugate and the powder injection preparation have one or more of better anti-tumor activity, pharmacokinetic property, targeting property and toxic effect.

The invention belongs to the technical field of medical detection, and firstly provides a kit for screening high-risk people with liver injury caused by chemotherapeutic drug methotrexate, and a detection reagent for detecting linoleic acid and oxidative metabolite content of human body is arranged in the kit. The invention also provides an application of the detection reagent in preparation of a methotrexate liver injury prediction product, the detection reagent is a reagent for detecting the content of linoleic acid and oxidative metabolites of the linoleic acid of a human body, and the product is a detection kit. In the invention, when the content of the linoleic acid and the oxidative metabolite thereof is relatively high, high liver injury caused after the methotrexate is used by the human body is predicted. According to the method, high-risk people suffering from methotrexate liver injury can be quickly screened, and intervention can be performed in the early stage so as to reduce the risk of suffering from methotrexate liver injury.

Provided herein are compositions comprising disodium levofolinate. Also provided are processes for preparing compositions comprising disodium levofolinate. Also provided are compositions comprising disodium levofolinate prepared by the processes provided herein. Also provided are methods of treating folic acid deficiency in a subject in need thereof, comprising administering a composition provided herein to the subject. Also provided are methods of treating cancer in a subject in need thereof, comprising administering 5-fluorouracil and a composition provided herein to the subject. Also provided are methods of reducing the immediate toxic effects of methotrexate overdose in a subject in need thereof, comprising administering a composition provided herein to the subject. Also provided are methods of treating cancer in a subject in need thereof, comprising administering high-dose methotrexate and a composition provided herein to the subject. Also provided are methods of treating megaloblastic anemia in a subject in need thereof, comprising administering a composition provided herein to the subject.

The present invention provides a drug identifying method designed to evaluate specific candidate drugs for targeted diseases, identifying those most effective for treating the condition. And a new indication of the selected drugs methotrexate or metronidazole for the treatment of diseases mediated by neutrophilic inflammation targeting the aberrant CD177+ neutrophil subpopulation.

1. The name of the design product: packaging box (methotrexate injection). 2. The use of the design product: a kind of medicine packaging box. 3. The design points of the design product: the combination of shape, pattern and color. 4. The picture or photo that best shows the design points: design 1 front view. 5. The design protected contains color. 6. Design 1 is designated as the basic design.