27 results about "Atorvastatin" patented technology

The invention discloses an anti-tumor pharmaceutical composition with a synergistic effect and application thereof, the composition is composed of cis-platinum and atorvastatin, and the molar ratio of the cis-platinum to the atorvastatin is 1: 1.5; the invention provides a different drug concentration ratio scheme for treating cancer cells, inhibiting proliferation and activation of cancer cells and inducing apoptosis of the cancer cells by drug combination at low drug concentration, and compared with a traditional scheme, the scheme weakens drug resistance of the cells, and has the advantages of lower concentration, safer and more effective drug concentration ratio and higher safety. The toxic reaction of an organism caused by high-concentration drugs is weakened.

A method of treating a wound may include topically administering a statin composition including a statin selected from atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, or combination thereof. The statin composition may be administered in an ointment, powder, or liquid format. The method may also include topically administering one or more antimicrobial drugs.

The invention discloses a synthesis method of an atorvastatin intermediate. The method comprises the following steps of: catalyzing alpha-chlorophenylacetyl chloride and fluorobenzene to perform Friedel-Crafts acylation reaction by taking immobilized Bronsted-Lewis acidic ionic liquid as a catalyst, and performing condensation reaction on a product and isobutyryl acetanilide under the action of alkali and the assistance of microwaves, the preparation method comprises the following steps: adding 2-[2-(4-fluorophenyl)-2-oxo-1-phenylethyl]-4-methyl-3-oxo-N-phenyl pentanamide into an organic solvent to obtain the atorvastatin intermediate 2-[2-(4-fluorophenyl)-2-oxo-1- By utilizing the characteristics of large specific surface area and abundant active sites of graphite-like carbon nitride, the graphite-like carbon nitride is used as an ionic liquid immobilization carrier and a parent nucleus to participate in the ionic liquid preparation process, the catalytic activity of the ionic liquid is retained, the catalyst is simple to separate, the reaction rate and selectivity are improved, the steps are simple, and the method is suitable for industrial production. The method has the advantages of mild reaction conditions in each step, low cost, high yield and easily available reaction conditions, and improves the application prospect.

The invention discloses a system for monitoring the influence of atorvastatin on mitochondrial functions in real time, and the system comprises a biosensor module which is used for monitoring biomarkers related to the mitochondrial functions and glycometabolism in blood in real time; the micro-fluidic chip is used for rapidly separating and enriching cells or specific components in blood; the optical detection module monitors the active oxygen level of mitochondria in real time; the data processing and transmission module processes and analyzes the collected data in real time; the equipment terminal receives the processed data and displays the data on a user interface in real time; the analysis and early warning module analyzes the monitoring data in real time and provides early warning and personalized suggestions for diabetes mellitus; the database module is used for storing monitoring data and historical records; through a biosensor, optical detection, a micro-fluidic chip and the like, after a patient takes atorvastatin, indexes of blood sugar, insulin and the like in a blood sample, and mitochondrial functions and oxidative damage indexes of active oxygen level, mitochondrial membrane potential and the like are detected.

This invention discloses a synergistic antitumor drug composition and its application. The composition consists of cisplatin and atorvastatin, with a molar ratio of cisplatin to atorvastatin of 1:1.5. This invention provides a combination of drug concentrations at low concentrations to treat cancer cells, inhibit cancer cell proliferation, activate and induce apoptosis. Compared with traditional methods, this method reduces cellular drug resistance, has a lower concentration, is safer and more effective, and reduces the toxic reactions caused by high concentrations of drugs.

The invention discloses a transaminase mutant and application of the transaminase mutant in preparation of an atozepam intermediate compound I. The invention discloses a novel transaminase mutant which can convert 50g / L of a compound III into an atozepam intermediate compound I, the conversion rate is greater than 99%, the dr value is greater than 65: 1, and the novel transaminase mutant is more suitable for industrial application.

The application discloses a synthesis method of an atorvastatin intermediate. The method comprises the following steps: firstly, using a solidized Brønsted-Lewis acidic ionic liquid as a catalyst, catalyzing a Friedel-Crafts acylation reaction of alpha-chlorobenzene acyl chloride and fluorobenzene, then, under the action of alkali and microwave assistance, performing a condensation reaction of the product and isobutyryl acetanilide, and finally, obtaining the atorvastatin intermediate 2-[2-(4-fluorophenyl)-2-oxo-1-phenylethyl]-4-methyl-3-oxo-N-phenylpentanamide. The method uses the characteristics of a large specific surface area and rich active sites of graphite-like carbon nitride, simultaneously uses the graphite-like carbon nitride as an ionic liquid solid carrier and as a mother nucleus to participate in the preparation process of the ionic liquid, retains the catalytic activity of the ionic liquid, improves the reaction rate and selectivity through simple separation of the catalyst, and has the advantages of low cost, high yield, easy reaction conditions, and improved application prospect.

This invention belongs to the field of biomedicine and relates to a procoagulant polypeptide TPTX and its applications. The procoagulant polypeptide TPTX of this invention can exert its procoagulant and hemostatic effects by specifically inhibiting plasmin activity. Experiments have shown that TPTX exhibits significant dose-dependent procoagulant and hemostatic effects in ferric chloride-induced mouse carotid artery thrombosis models, mouse liver hemorrhage models, mouse tail hemorrhage models, and mouse saphenous vein hemorrhage models, with effects superior to the positive control drug 6-aminocaproic acid. Simultaneously, TPTX can reduce the area of ​​atorvastatin-induced cerebral hemorrhage in zebrafish and improve their motor dysfunction. Mechanistic studies show that TPTX has an inhibitory constant Ki of 17.76 nM on plasmin and has no significant effect on the activity of seven other key serine proteases in the coagulation system, demonstrating a clear target and high selectivity. The procoagulant polypeptide of this invention can be used to prepare hemostatic drugs, possessing the advantages of high efficiency, clear target, and high selectivity, with broad prospects for clinical application.

The application provides a comprehensive recycling method of atorvastatin M4 organic waste, which comprises the following steps: S1, mixing M4 crude mother liquor and M4 refined mother liquor high-boiling residues generated in the preparation of atorvastatin M4 by a linear method, and adjusting the water content of the system to obtain a mixed system; S2, cooling and standing the mixed system to crystallize, and centrifuging to obtain M4 crude products. The method of the application makes the M4 product be precipitated to the maximum extent by using the solvent and impurity system in the M4 crude mother liquor and M4 refined mother liquor high-boiling residues, significantly improves the yield of the M4 product, simultaneously comprehensively recycles the M4 crude mother liquor and M4 refined mother liquor high-boiling residues, greatly reduces the amount of organic solid waste generated in the production process of atorvastatin M4, improves the comprehensive utilization rate of resources and the level of clean production, reduces the cost of raw materials, and has good economic and social environmental benefits.

The invention discloses a coaxial electrostatic spinning stent coupled with electret electrical stimulation and an angiogenic drug, which utilizes the characteristic of sequential degradation (slow degradation of a core layer and relatively fast degradation of a shell layer) of a core-shell structure of a coaxial electrostatic spinning technology, and takes a PCL material which is slowly degraded as a matrix of the stent, thereby being beneficial to maintaining a space necessary for bone regeneration. AVT with a good angiogenesis promoting effect is loaded in a shell layer, the hydrophilicity of the PCL stent is improved, meanwhile, early-stage ordered release of the shell layer AVT is utilized to promote early-stage angiogenesis, SiO2 is loaded in a coaxial electrostatic spinning core layer, the influence of the surrounding body fluid environment is avoided, and electret electrical stimulation for promoting osteogenesis is continuously provided. The hydrophilic stent with the'electricity and medicine 'integrated core-shell fiber structure prepared by the invention is good in overall hydrophilicity and slow in degradation, continuous electrical stimulation promotes osteogenesis, early released AVT promotes early vascularization, and ultimately, skull critical bone defect vascularization bone regeneration is promoted.

The invention discloses a targeted hepatic stellate cell conjugate as well as a preparation method and application thereof, and belongs to the technical field of biological medicine and medicinal chemistry. The conjugate disclosed by the invention is RRG-TK-Ato, and the molecular formula of the conjugate is C98H144FN27O14S2. According to the present invention, the atorvastatin is covalently linked with the targeting polypeptide RRGRLKRWY through the reactive oxygen species (ROS)-sensitive thioketal (TK) connexon to form the conjugate, such that the specific targeting of the aHSCs can be achieved, the atorvastatin can be intelligently released in the hepatic fibrosis oxidative stress microenvironment, the limitation of the drug is overcome, and the efficacy-enhancing and toxicity-reducing targeting treatment of the hepatic fibrosis is achieved; the apoptosis of the activated hepatic stellate cells can be more effectively induced, the specific inhibition effect on the proliferation of the activated hepatic stellate cells is obvious, and the migration ability of the activated hepatic stellate cells can be more effectively inhibited, so that the diffusion of fibrosis is limited, and the liver function of hepatic fibrosis is improved.

The invention discloses a benzisoselenazolone-statin bonding molecule as well as a preparation method and application of the benzisoselenazolone-statin bonding molecule. The bonding molecule is formed by chemically bonding a statin pharmacophore (3, 5-dihydroxyvaleric acid or a lactone structure thereof) and an ebbeselenium pharmacophore (benzisoselenazolone). The invention provides a plurality of synthesis paths including'first connection and then cyclization 'and'first parent nucleus construction and then coupling', and a plurality of specific compounds such as IA-6, IB-6, IIA-7, IIIB-5 and the like are efficiently prepared. In-vitro activity experiments show that the compounds can significantly reduce the content of triglyceride (TG) in hepatic cells induced by oleic acid and palmitic acid at the cellular level, the cytotoxicity is low, and the activity of part of the compounds is equivalent to that of atorvastatin. The invention provides a brand-new lead compound for developing a novel NASH treatment medicine with lipid-lowering and antioxidant / anti-inflammatory dual activities.

The invention provides a derivative based on atorvastatin structure modification, a preparation method of the derivative and application of the derivative in hyperlipidemia, and belongs to the field of medicinal chemistry. It is found that the atorvastatin structure modified derivative has good lipid lowering activity, the inhibition efficiency of the atorvastatin structure modified derivative on 3-hydroxy-3-methylglutaryl coenzyme A reductase is remarkably superior to that of atorvastatin, safety is higher, and the atorvastatin structure modified derivative can be used for preparing the medicine for preventing and / or treating hyperlipidemia and related metabolic diseases.

The invention belongs to the technical field of medicines, and particularly relates to application of atorvastatin in preparation of a medicine for preventing or treating heat stroke. Through observation of mouse anal temperature, blood biochemical and blood routine related indexes, heart function related indexes and the like, atorvastatin can reduce the level of anal temperature and creatine kinase isoenzyme after mouse HS injury; and the levels of white blood cells, lymphocytes and intermediate cells are increased, so that the application of the atorvastatin in preparing the medicine for preventing or treating the heat stroke is provided.

This invention belongs to the field of pharmaceutical technology, specifically relating to the application of atorvastatin in the preparation of drugs for the prevention or treatment of heatstroke. This invention establishes an in vivo animal model of heatstroke and its induced myocardial injury, and observes related indicators such as rectal temperature, blood biochemistry and routine blood tests, and cardiac function in mice. The findings reveal that atorvastatin can reduce the levels of rectal temperature and creatine kinase isoenzyme in mice after heatstroke injury, and increase the levels of white blood cells, lymphocytes, and intermediate cells. Therefore, the invention proposes the application of atorvastatin in the preparation of drugs for the prevention or treatment of heatstroke.

The invention discloses application of atorvastatin in preparation of a medicine for treating retinal artery occlusion, and belongs to the technical field of medicines. The atorvastatin is found to be capable of effectively relieving retinal structure damage and retinal ganglion cell apoptosis caused by retinal artery occlusion, effectively inhibiting activation of retinal microglia cells and reducing polarization of the microglia cells to M1. The invention provides application of atorvastatin in preparation of a medicine for treating retinal artery occlusion, and provides a new medicine for treating the retinal artery occlusion.

This invention belongs to the fields of pharmaceutical formulation and biomedicine, and relates to an anti-atherosclerotic hybrid exosome, its preparation method, and its application. A hybrid composed of M2 macrophage exosomes and liposomes is used as a carrier, with the carrier loaded with a ferroptosis inhibitor and atorvastatin. The drug loading and encapsulation efficiency of the ferroptosis inhibitor are 1.55–2.57% and 11.99–49.86%, respectively; the drug loading and encapsulation efficiency of atorvastatin are 1.48–12.66% and 46.4–77.31%, respectively. The hybrid exosome provided by this invention has inflammatory targeting ability and higher stability, and can avoid the first-pass effect of the liver and the clearance of the circulatory system through intravenous injection. Simultaneously, this hybrid exosome has effects such as inhibiting ferroptosis, promoting cholesterol efflux, promoting cell burial, anti-inflammation, and regulating the immune microenvironment, enabling multi-faceted treatment of atherosclerosis, thus achieving better therapeutic effects.

This invention provides a method for synthesizing an atorgipam intermediate. The method uses compound I as a starting material, first undergoing a cyanation reaction, followed by cyanohydrolysis and detert-butylation to generate the target compound III. This method is low-cost, high-yield, simple to operate, and suitable for large-scale industrial production of compound III.

The invention discloses an antibody coupling medicine for targeting colorectal cancer cells and a preparation method of the antibody coupling medicine, and belongs to the technical field of biological medicine. The antibody coupling drug is formed by connecting cetuximab, atorvastatin or a derivative thereof and a specific connexon through covalent bonds and is constructed by adopting a site specific coupling technology, the average drug-antibody ratio is 3.13, and the monomer purity is greater than or equal to 97%. The connexon can be broken in response to acidity, high reducibility or high cathepsin expression conditions of a tumor microenvironment, so that accurate release of the effective load is realized. The invention also discloses a preparation method of the antibody coupling drug, which comprises the steps of antibody reduction, active intermediate preparation, coupling, quenching and purification, and the yield is greater than or equal to 85%. The antibody coupling drug can specifically target EGFR high-expression KRAS mutant colorectal cancer cells, reverses the drug resistance of tumors to an EGFR inhibitor by inhibiting a mevalonic acid pathway, remarkably reduces the systemic toxicity of atorvastatin, and has excellent curative effect and safety.

The invention relates to a preparation method of an atorvastatin degradation impurity epoxy diketone. The invention relates to the technical field of organic synthesis, in particular to a preparation method of 3-(4-fluoro-benzoyl)-2-isobutyl-3-phenyl oxide-2-carboxylic acid benzamide (hereinafter referred to as' epoxy diketone '), which comprises the following steps: step 1, preparing atorvastatin salt or atorvastatin lactone into a solution, and carrying out light degradation, step 2, collecting the degradation solution to separate out precipitate, and step 3, carrying out vacuum drying to obtain 3-(4-fluoro-benzoyl)-2-isobutyl-3-phenyl oxide-2-carboxylic acid benzamide (hereinafter referred to as' epoxy diketone '). And step 3, dissolving the epoxy impurity crude product in a proper organic solvent, filtering to remove insoluble impurities, and distilling to remove the organic solvent, thereby obtaining the epoxy diketone.

The disclosure belongs to the technical field of biomedicine, and specifically relates to an application of Akkermansia muciniphila (AKK) in the amelioration and treatment of cerebral malaria caused by Plasmodium berghei. The disclosure aims to evaluate the efficacy of AKK alone or in combination with adjuvant drugs (dihydroartemisinin, rapamycin, and atorvastatin) in ameliorating and treating experimental cerebral malaria in an experimental cerebral malaria model. The results indicate that AKK, whether used alone or in combination with drugs, can effectively ameliorate behavioral deficits and immunopathological damage of each organ, lower parasitemia levels, and prolong survival period of mice. Compared with the use of drug alone, the combination therapy can effectively treat the experimental cerebral malaria. The disclosure is the first to propose the concept of bacterial-drug synergy concept, and provides a solution to the treatment of human cerebral malaria on the basis of the concept.

The invention discloses a halohydrin dehalogenase directional modification method for synthesis of an atorvastatin intermediate, and belongs to the technical field of enzyme directional modification, and the method comprises the following steps: downloading an amino acid sequence of H halohydrin dehalogenase from an NCBI (National Center of Biotechnology Information) protein database, carrying out multi-sequence alignment by using CLUSTALW software, carrying out molecular dynamics simulation, then carrying out PEGylation modification, and carrying out enzyme directional modification. The directionally modified halohydrin dehalogenase is prepared. According to the immobilization method combining the directionally modified halohydrin dehalogenase and the functionalized magnetic porous carrier, the intrinsic activity and stability of the enzyme are improved through directional modification, and the functionalized carrier provides a suitable microenvironment for the enzyme and realizes firm immobilization; the invention not only solves the technical problems of large activity loss, poor stability and the like in the traditional enzyme immobilization process, but also provides an efficient, stable and reusable biocatalyst for industrial application.

Endogenous mechanisms leading to host protection and resolution of infections without immunosuppression are of wide interest. Here we elucidated the structures of four new host-protective molecules produced in neutrophil-endothelial co-cultures, and present in human and mouse tissues after sterile inflammation or infection. These bioactive molecules contained conjugated triene and diene double bonds with each carrying a 13-carbon position alcohol and were derived from n-3 docosapentaenoic acid (DPA, C22:5). These compounds, termed 13-series resolvins (RvT), demonstrated potent protective actions increasing mice survival during Escherichia coil infections. RvT also regulated human and mouse phagocyte responses stimulating bacterial phagocytosis and regulating inflammasome components. Their biosynthesis during neutrophil-endothelial cell interactions was initiated by endothelial cyclooxygenase-2 (COX-2) and increased by atorvastatin via S-nitrosylation of COX-2. The actions of atorvastatin and RvT were additive in E.coli infections in mice where they accelerated resolution of inflammation and increased survival >60%.

The invention provides an anti-atherosclerosis pharmaceutical composition and a preparation method thereof. The composition is prepared from a traditional Chinese medicine extracting solution, a western medicine active ingredient, a plant active polypeptide component and a prebiotic component, the traditional Chinese medicine extracting solution is prepared by mixing radix salviae miltiorrhizae, fructus crataegi, fructus hippophae and folium ginkgo and carrying out gradient alcohol extraction, water purification and freeze drying, the western medicine is atorvastatin and other statins, the plant active polypeptide is balsam pear polypeptide and seaweed polypeptide with the molecular weight smaller than 3000Da, and the prebiotics are fructo-oligosaccharide and oat beta-glucan. The preparation method comprises the steps of premixing, total mixing and preparation forming, and the antioxidant and the flow aid are added to guarantee the stability. Through cooperation of four components, multi-target intervention is achieved, the effective lipid-lowering and anti-inflammatory effects are achieved under the low statin dosage, the toxic and side effects of western medicines are reduced, and the pharmaceutical composition is suitable for atherosclerosis related diseases and meets clinical requirements.

The application relates to a preparation method of atorvastatin, and belongs to the field of pharmaceutical chemistry. The preparation method comprises a substitution reaction of raw materials under alkalinity to obtain atorvastatin. The preparation method provided by the application is high in product purity, mild in reaction condition, simple in operation and beneficial to industrial implementation.