52 results about "Atorvastatin" patented technology

The invention provides a carbonyl reductase mutant. The carbonyl reductase mutant is obtained by performing single-point mutation or multi-point combined mutation on the 17th site, the 40th site and the 64th site of an amino acid sequence as shown in SEQ ID NO.1. The invention also provides a coding gene, a recombinant vector containing the coding gene, a co-expression engineering bacterium and an application of the co-expression engineering bacterium. Compared with a wild type enzyme, the carbonyl reductase mutant has high activity and high stereoselectivity, the enzyme activity can reach more than two times that of the wild type enzyme, the catalytic efficiency on a substrate precursor ketone is remarkably improved, the yield of a statin drug intermediate and chiral alcohol synthesized by an enzyme method of the carbonyl reductase mutant is remarkably improved, and the yield of a rosuvastatin intermediate (3R, 3R, 3R, 3R, 3R, 3R, 3R, 3R, 3R, 3R, 3R, 3R, 3R, 3R, 3R, 3R, 3R, 3R, 3R, 3R, 3R) is remarkably improved. The highest yields of the (3R, 5R)-6-chloro-3, 5-dihydroxyhexanoic acid tert-butyl ester and the atorvastatin intermediate (3R, 5R)-6-cyano-3, 5-dihydroxyhexanoic acid tert-butyl ester reach 99% and 97.6% respectively, e.e. Is larger than 99%, and the method has high industrial application value.

The invention belongs to the technical field of nano medicine, and particularly relates to a targeted nano drug delivery system based on bionic composite membrane modification and application of the targeted nano drug delivery system. The preparation method comprises the following steps: firstly, loading hydrophobic drugs astragaloside and atorvastatin in a phospholipid bilayer of a liposome to obtain a drug-loaded liposome, then mixing an erythrocyte membrane with a macrophage membrane to obtain a hybrid composite membrane, coating the drug-loaded liposome with the hybrid composite membrane to obtain a liposome-composite membrane, and preparing the drug-loaded liposome-composite membrane. Finally, hyaluronic acid is inserted into the outer layer of the liposome-composite membrane, and the targeted nano drug delivery system is obtained. Compared with treatment by singly using drugs, the targeted nano drug delivery system provided by the invention has a remarkable combined synergistic effect, and a feasible treatment strategy is provided for effectively treating atherosclerosis.

The invention provides a pharmaceutical composition. The pharmaceutical composition is prepared from aspirin, atorvastatin, valsartan, hydrochlorothiazide, folic acid substances and pharmaceutically acceptable auxiliary materials. The pharmaceutical composition provided by the invention has the advantages that the pharmaceutical composition provided by the invention has a multi-target synergistic prevention effect on vascular diseases, especially cerebral embolism, that is, the composition not only can reduce blood pressure, blood fat and blood homocysteine level, but also has an effect of preventing thrombosis, and reduces the risk of cerebral apoplexy. In addition, the form of the pharmaceutical composition is beneficial to improving the medication compliance of patients.

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.

The present invention belongs to the field of biomedical technology and specifically relates to the use of Akkermansia muciniphila in ameliorating and treating cerebral malaria caused by Plasmodium berghei. This study evaluated the efficacy of Akkermansia muciniphila alone or in combination with adjuvant drugs (dihydroartemisinin, rapamycin, and atorvastatin) in ameliorating and treating cerebral malaria in a mouse cerebral malaria model. The results suggest that the bacteria, whether used alone or in combination with other drugs, effectively improved mouse behavior, immune pathological damage to various organs, reduced parasitemia, and prolonged mouse survival, demonstrating its effectiveness in treating cerebral malaria in mice compared to using the drugs alone. Because Akkermansia muciniphila is a common probiotic in the human gut, the three drugs used in this study (dihydroartemisinin, rapamycin, and atorvastatin) are all currently in clinical use. Clinical translation for the treatment of human cerebral malaria caused by Plasmodium falciparum is highly feasible and can also shorten the conversion time. This study proposes for the first time the concept of bacterial-drug synergy, whereby probiotics can complement drug treatments, and provides a solution for the treatment of human cerebral malaria based on this concept.

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 process of an atorvastatin side chain intermediate, which comprises the following synthesis steps: 1, dissolving a compound II in an organic solvent, adding a compound I, adding an alkali reagent, adding a catalyst, heating to react for 2-4 hours, and cooling to room temperature to obtain a mixed solution of a compound III; and 2, slowly introducing hydrogen into the solution of the reaction compound III in the first step, synchronously heating and pressurizing to react for 2-4 hours, and after the reaction is finished, separating a product to obtain a compound V. The preparation method has the beneficial effects that the atorvastatin intermediate A9 is prepared from the rosuvastatin intermediate, so that the synthesis steps of atorvastatin and rosuvastatin are partially combined, the reaction process is more efficient, the efficiency of the whole synthesis route is improved, expensive or scarce raw materials can be saved, and the cost is reduced. By using the existing rosuvastatin intermediate as the starting point, it is possible to avoid the complicated steps required in the conventional synthesis route of the atorvastatin intermediate A9.

The invention discloses a carbonyl reductase directional modification method for synthesis of atorvastatin intermediates, which belongs to the technical field of enzyme gene engineering, and is characterized in that carbonyl reductase genes are used as templates, mutation primer pairs are designed, double-site mutation is carried out by adopting an overlapping extension PCR (polymerase chain reaction) method, escherichia coli is transformed, IPTG (isopropyl-beta-d-thiogalactoside) is used for inducing expression, and mutant carbonyl reductase is prepared. The K205D / R237W double mutation modified carbonyl reductase improves the enzyme activity, combines the synergistic effect of the thiophene pyridine coenzyme analogue, improves the conversion rate of the atorvastatin intermediate and the product purity, is significantly superior to the traditional chemical reduction method, avoids the low-temperature and high-pressure conditions of the traditional chemical method, reduces the energy consumption, and is suitable for industrial production. The use amount of an organic solvent and the generation amount of byproducts are reduced, and the generation amount of wastewater is reduced.

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.

To provide therapeutic approaches for treating epileptogenesis associated with a brain insult, e.g., traumatic brain injury (TBI), stroke, or brain infection.SOLUTION: Provided are liquid pharmaceutical compositions including topiramate or a pharmaceutically acceptable salt thereof, meglumine, and a pharmaceutically acceptable excipient, the liquid pharmaceutical compositions optionally further including, e.g., levetiracetam or brivaracetam and / or atorvastatin or a pharmaceutically acceptable salt thereof (e.g., atorvastatin sodium).SELECTED DRAWING: Figure 1

The invention relates to application of an activating agent in promotion of uranium element discharge. Specifically, the activating agent is prepared from rifampicin, erythromycin, progesterone, aldosterone, bilirubin, cholate vinblastine, doxomicin, adriamycin, paclitaxel, bosentan, ambrisentan, digoxin, verapamil, tonavir, amprenavir, indinavir, hypericum perforatum juice, curcumin, atorvastatin beclomethasone, budesonide, divaricasone carbamazepine and caffeine. And phenytoin. The use dosage of the activating agent is 10 to 60 mg / kg. According to the method, the accumulation amount of uranium in important organs such as bones and kidneys can be remarkably reduced, so that the potential toxic influence on the key organs is reduced.

The application discloses a kind of traditional Chinese medicine preparation for treating hyperlipidemia, which is prepared from the following raw medicinal materials: radix codonopsis 10-20 g, astragalus 25-35 g, gynostemma pentaphyllum 10-20 g, atractylodes 10-20 g, zanthoxylum 3-8 g, monascus 10-15 g, and galangal 10-20 g. When treating, it is orally taken, one dose per day, taken twice, taken half an hour after breakfast and dinner, and continuously taken for 4 weeks as a treatment course. The traditional Chinese medicine preparation for treating hyperlipidemia has the advantages that it is helpful to improve hyperlipidemia, and the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and other indicators of patients after treatment are obviously better than those of the control group (oral atorvastatin), with statistical significance (P<0.05). The traditional Chinese medicine preparation for treating hyperlipidemia has the advantages of remarkable curative effect, good safety, low price and simple prescription, and has high clinical popularization value.

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 present invention relates to a modified metal, a preparation method thereof and an application. The modified metal comprises a metal and a film layer located on the surface of the metal. Among them, the metal comprises one or more of titanium, tantalum, and magnesium, and the film layer comprises a statin compound, and the statin compound comprises one or more of simvastatin, pravastatin, atorvastatin, and rosuvastatin. The modified metal of the present invention has good antibacterial properties and can effectively avoid the infection of the orthopedic implants produced.

Disclosed are pharmaceutical compositions comprising atorvastatin or a salt thereof and a liquid carrier. Also provided are methods of administering the compositions, and methods of treating a subject in need thereof with the compositions.

The invention discloses a rosuvastatin intermediate side chain connection process which comprises the following steps: dissolving a compound I and a compound II in an organic solvent, adding a catalyst, reacting at 55-60 DEG C for 3-5 hours, and after the reaction is finished, separating a product to obtain a compound III; and dissolving the compound III in an organic solvent, introducing hydrogen, adding a catalyst, heating to 30-40 DEG C at 2-5atm, reacting for 4-6 hours, and separating a product after the reaction is finished to obtain a compound IV. The method has the beneficial effects that the reaction route is short, the operation is less, the operation is simple, the product yield and selectivity are high, the post-treatment of the product is convenient, and the industrial expanded-scale production is convenient; the reaction route provided by the invention provides a new synthesis direction for a rosuvastatin synthesis process; the reaction raw materials are easy to obtain, expensive reagents are not used, the product yield is high, the production cost is reduced, and a new research direction is provided for atorvastatin parent nucleus synthesis.

The invention belongs to the technical field of biological medicine, and particularly relates to a HA / CS / dECM-AD hydrogel medicine and application thereof in treatment of osteoarthritis, the hydrogel medicine is composed of a three-dimensional network composed of hyaluronic acid (HA), chitosan (CS) and a decellularized extracellular matrix (dECM), and two active ingredients of atorvastatin (Ato) and docosapentaenoic acid (DPA) are loaded in the three-dimensional network. The hydrogel has the following characteristics: a dual slow-release mechanism is adopted, Ato is quickly released within 2 hours, and DPA is accumulatively released by 70-90% within 7 days through PDA nanoparticles; according to biological activity induction, the dECM derived from hiPSCs retains cartilage specific components such as type II collagen (COL2) and aggregation protein glycan (ACAN), and cartilage cell proliferation is promoted; and the retention time in the articular cavity exceeds 6 weeks. Animal experiments show that the hydrogel can remarkably repair cartilage defects, inhibit M1 type macrophage infiltration and reduce expression of proinflammatory factors such as IL-1beta and TNF-alpha.

The invention discloses a modeling research management device for atorvastatin in atherosclerosis, and relates to the technical field of medical instruments, the device comprises a cage body, the top of the cage body is clamped with a cover plate, the top of the cover plate is fixedly connected with a storage tank, and the outer side wall of the cage body is provided with a display screen for recording data; the feeding mechanism comprises an electric telescopic rod fixedly connected to the bottom of the cover plate and a feeding disc fixedly connected to the output end of the electric telescopic rod; the feeding mechanism and the receiving mechanism comprise a heat insulation plate fixedly connected to the inner side wall of the storage tank, an isolation cylinder fixedly connected to the top of the heat insulation plate and used for dividing an upper half cavity of the storage tank into a storage bin and a water storage cavity, and a refrigeration piece penetrating through the heat insulation plate and used for refrigerating the water storage cavity. According to the modeling research management device for atorvastatin in atherosclerosis, the refrigeration sheet is started, so that the feed in the storage cavity is kept fresh.

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.