39 results about "Voriconazole" patented technology

The invention discloses a pharmaceutical composition, a preparation containing the pharmaceutical composition, a kit containing the pharmaceutical composition, and a preparation method and application of the pharmaceutical composition. The pharmaceutical composition comprises an active pharmaceutical ingredient and a hot melt adhesive, wherein the active pharmaceutical ingredient is voriconazole, and the hot-melt adhesive is selected from an A-type hot-melt adhesive, namely poloxamer P188 and / or poloxamer P407, and a B-type hot-melt adhesive, namely poloxamer P188 and / or poloxamer P407; or the B-type hot melt adhesive is polyethylene glycol 6000; the mass percent of the B-type hot melt adhesive in the pharmaceutical composition is 12%-25%; the pharmaceutical composition is a pharmaceutical composition in the form of hot-melt granulated particles. According to the pharmaceutical composition and the preparation and the kit containing the pharmaceutical composition, the stability of active pharmaceutical ingredients can be improved, swallowing of a patient can be further improved, and the medicine taking compliance of the patient during actual taking can be improved.

The invention belongs to the field of intelligent medical treatment, and particularly relates to an individualized administration method for treating a PID child patient by combining sirolimus with voriconazole. The method comprises the following steps: acquiring the age of a PID child patient; based on the age of the PID child patient, determining the dosage of sirolimus when the voriconam is combined, and if the age of the PID child patient is in a [1, 6] year interval, the dosage is [0.100, 0.330] mg / QD; if the age is in the interval of [6, 13], the dosage is [0.280, 0.540] mg / QD. According to the method, the PPK model is formulated for the first time when the PID child patient is combined with the VRC in the SRL mode, the optimal administration dosage is explored based on PPK when the PID child patient is combined with the VRC in the SRL mode, and simple medication dosage guidance is provided for child patients of different age groups; individualized and customized SRL medication guidance can be provided for individuals through a posterior Bayesian method.

The invention discloses a voriconazole dry suspension as well as a preparation process, medical application and a detection method thereof. The voriconazole dry suspension is prepared from voriconazole and cane sugar, wherein the particle size D10 of the sucrose is 1-8 [mu] m, the particle size D50 of the sucrose is 9-40 [mu] m, and the particle size D90 of the sucrose is 30-120 [mu] m; the particle size D10 of the voriconazole dry suspension is 10 to 70 [mu] m, the particle size D50 of the voriconazole dry suspension is 50 to 300 [mu] m, and the particle size D90 of the voriconazole dry suspension is 150 to 500 [mu] m. The voriconazole dry suspension provided by the invention has excellent stability, is still low in genotoxic impurities after long-term storage, can be suitable for normal-temperature transportation, storage and use, reduces the transportation and storage cost, and improves the use convenience of patients.

This invention belongs to the field of intelligent healthcare, specifically relating to a personalized dosing method for sirolimus combined with voriconazole in the treatment of PID in children. The method includes: obtaining the age of the PID child; determining the sirolimus dosage when combined with voriconazole based on the PID child's age; if the PID child's age is in the range of [1, 6) years, the dosage is [0.100, 0.330] mg / QD; if the age is in the range of [6, 13) years, the dosage is [0.280, 0.540] mg / QD. This application is the first to develop a PPK model for PID children using sirolimus combined with voriconazole (VRC), and based on the PPK, explores the optimal dosage for PID children using sirolimus combined with VRC, providing concise dosage guidance for children of different age groups; and through posterior Bayesian methods, it can provide individualized sirolimus medication guidance.

The invention discloses a voriconazole dispersible tablet and a preparation method thereof, relates to the technical field of pharmacy, and solves the technical problem of low bioavailability caused by low dissolution rate and slow disintegration speed of the conventional voriconazole dispersible tablet. The voriconazole dispersible tablet comprises 30-50 parts of voriconazole, 10-20 parts of a disintegrating agent, 15-25 parts of a sweetening agent, 3-8 parts of an adhesive, 1-2 parts of a lubricant and 8-16 parts of a pore forming agent, the pore-forming agent comprises beta-tricalcium phosphate and a polyethylene glycol-chitosan grafted copolymer, the pore-forming agent is prepared by performing ultrasonic treatment and freeze-drying on beta-tricalcium phosphate and a polyethylene glycol-chitosan grafted copolymer aqueous solution, and in the pore-forming agent, the polyethylene glycol-chitosan grafted copolymer is adsorbed in pores of beta-tricalcium phosphate; the voriconazole dispersible tablet provided by the invention can accelerate disintegration and dissolution of drugs, improves the dissolution rate and bioavailability of the drugs, and is high in drug stability and low in impurity content.

The invention provides an application of a fusarium verticillium transcription factor FVEG06682 in regulating the sensitivity of fusarium to azole drugs, and belongs to the technical field of drug resistance. The invention provides an application of a fusarium verticillium transcription factor FVEG06682 in regulating the sensitivity of fusarium to azole drugs or regulating the toxicity of fusarium to plants, and the FVEG06682 improves the sensitivity of fusarium to azole drugs and reduces the toxicity of fusarium to plants through negative regulation. Therefore, the transcription factor is identified and proved to be a key molecule for regulating and controlling the intrinsic resistance of the azole drugs in the fusarium verticillium for the first time, and the sensitivity of pathogenic bacteria to various clinical and agricultural azole drugs (such as ketoconazole, voriconazole, triazolone and tebuconazole) can be remarkably improved by knocking out the FVEG06682 gene; a brand-new and efficient molecular target is provided for overcoming the inherent drug resistance problem of fusarium.

The invention discloses a voriconazole tablet and a preparation method thereof, a tablet core is formed by pressing main drug particles, and the main drug particles comprise an active pellet core and a dissolution controlled release layer coating the active pellet core; the active pellet core comprises voriconazole, gelatin, anthocyanin, a filling agent and a lubricating agent; the dissolution controlled release layer comprises the following components in parts by mass: lactose, sodium hydrogen phosphate and ethyl cellulose. According to the voriconazole sustained-release pellet disclosed by the invention, the gelatin and the anthocyanin are added into the active pellet core, and the gelatin and the anthocyanin can be subjected to a cross-linking reaction to form a three-dimensional network structure, so that voriconazole is well coated, and meanwhile, the three-dimensional structure of the gelatin can also form constraint on the voriconazole, so that the aim of slowly releasing the voriconazole is fulfilled; meanwhile, the active pellet core is coated with the dissolution controlled release layer, and after the coating is dissolved, the voriconazole is also coated with a layer of auxiliary material, so that the active component can be prevented from being in direct full contact with a medium in the body, and the dissolution concentration is controlled during initial disintegration.

The invention discloses a nano-robot based on tear driving, a preparation method of the nano-robot and application of the nano-robot in eye drops. The preparation method comprises the following steps: step 1, loading ophthalmic disease treatment drugs such as amphotericin B, voriconazole and natamycin into nano-particles such as polylactic acid-glycolic acid copolymer, chitosan and sodium alginate; 2, coupling urease on the surfaces of the nano-particles to obtain a nano-robot with autonomous movement ability; step 3, performing morphology characterization on the obtained nanometer robot driven by the tear liquid; and step 4, dispersing the prepared tear-driven nano-robot in a buffer solution to prepare the eye drops. The tear-driven nano-robot can utilize urea in tears as fuel to generate cluster motion on the cornea surface, so that the retention time is remarkably prolonged, the drug retention amount is increased, and the treatment effect is improved. The nano-robot eye drops based on tear driving have biocompatibility and treatment safety, and have wide application prospects in the field of ophthalmic local administration.

This invention relates to the field of biomedical technology, specifically to an antifungal nanoparticle, a combination drug, and its application. The antifungal nanoparticle is prepared by covalently linking the aptamer AU1 to drug-loaded silk fibroin nanoparticles via amide bonds. The mass ratio of the drug-loaded silk fibroin nanoparticles to the aptamer AU1 is 20:0.5~2.0. The antifungal nanoparticles of this invention are prepared by a desolvation method using voriconazole-loaded silk fibroin nanoparticles, and the targeting aptamer AU1 is attached to their surface using a carbodiimide chemical cross-linking method. This allows for specific recognition of Candida albicans, increasing drug accumulation at the infection site. Further combination with methylene blue-mediated photodynamic therapy can disrupt biofilm structures, enhance nanoparticle penetration, achieve synergistic bactericidal activity, and reduce systemic toxicity, providing a novel, highly effective, and low-toxicity treatment strategy for fungal biofilm infections.

To provide voriconazole granules that are suitably usable for administration through a simple suspension technique.SOLUTION: The problem can be solved by voriconazole granules containing voriconazole and a mixture of fumaric acid, stearic acid, polyvinyl acetal diethylaminoacetate, and hydroxypropyl methylcellulose 2910. A preferable embodiment includes a coating layer containing the mixture of fumaric acid, stearic acid, polyvinyl acetal diethylaminoacetate, and hydroxypropyl methylcellulose 2910 on the exterior of a core particle containing voriconazole.SELECTED DRAWING: None

The invention relates to a voriconazole dry suspension. The voriconazole dry suspension comprises the following components: 2-4 parts of voriconazole; 36 to 41 parts of isomaltitol; 1-4 parts of a microcrystalline cellulose-sodium carboxymethyl cellulose compound; 0.1 to 0.5 part of colloidal silicon dioxide; 0.2 to 1.0 part of sodium lactate; 0.05 to 0.2 part of disodium hydrogen phosphate; 0.05 to 0.5 part of essence; 0.1-0.3 part of a preservative; the dry suspension disclosed by the invention has the characteristics of high settling volume ratio, excellent stability and remarkably improved dissolution rate.

This invention discloses the application of primer sets for identifying polymorphic site combinations in the preparation of a kit for predicting voriconazole metabolism, and the kit itself. The polymorphic site combinations include rs4244285, rs4986893, rs3740066, rs4149056, and rs4646437. This invention enables effective prediction of voriconazole blood concentrations, overcoming the lag and empirical limitations of traditional therapeutic drug monitoring.

The present invention relates to a process for preparing a voriconazole intermediate liquid for injection, which comprises weighing water for injection, adjusting the liquid preparation temperature to 40-55°C, then sequentially adding sulfobutyl-β-cyclodextrin sodium and voriconazole and stirring evenly, stirring until completely dissolved, cooling to 20-30°C, adding water for injection to the total amount, mixing evenly, filtering, filling, and semi-pressing. The present invention adjusts the liquid preparation steps and controls the selection of the auxiliary material sulfobutyl-β-cyclodextrin sodium to ultimately obtain a voriconazole intermediate liquid for injection with better stability, so as to obtain a voriconazole finished product for injection with higher stability, especially maintaining the specified standard under the condition of a high stability-high temperature of 55°C±2°C, so that the finished drug can cope with more stringent storage and transportation environments.

The invention relates to the field of pharmaceutical preparations, and discloses a voriconazole freeze-dried powder injection for injection and a preparation method of the voriconazole freeze-dried powder injection. The freeze-dried powder injection comprises voriconazole, sulfobutyl-beta-cyclodextrin, sorbitol, sodium chloride and methanesulfonic acid, and the solubility and stability of the medicine are remarkably improved by optimizing the ratio of auxiliary materials and the pH value (4.0-5.0). Experiments show that in an acceleration test (40 + / -2 DEG C, 75% RH) and a long-term stability test (25 + / -2 DEG C, 60% RH), the content decrease rate of the preparation is less than or equal to 3%, the total impurity content is less than or equal to 0.1%, the moisture content is less than or equal to 0.5%, and the validity period can reach 24 months. In addition, after redissolution, the compatibility with various clinical diluents (such as 0.9% sodium chloride and 5% glucose) is good, and precipitation or degradation is avoided. The problems that in the prior art, auxiliary materials are high in toxicity and poor in stability, and diluent is easy to separate out are solved, and the clinical application value is remarkable.

Disclosed in the present invention are antifungal compounds, a preparation method therefor, and the use thereof. The compounds have the following general formula I, wherein L represents a linking moiety, referring to a small molecule fragment, and Ar represents a heterocyclic ring or a substituted heterocyclic ring. The series of compounds of the present invention can better bind to an enzyme target by means of various interaction forces, thereby exhibiting good activity; and the compounds exhibit excellent activity in both in vitro experiments and animal experiments, the activity of most of the compounds against Candida albicans being better than that of fluconazole. In addition, the series of compounds have anti-inflammatory effects while eliminating fungal infections; and compared with voriconazole, the series of compounds of the present invention can remarkably down-regulate the expression of an inflammatory factor interleukin 6.

The present invention relates to a method for resolving the enantiomeric pair B of voriconazole. A method for preparing a resolving salt from the enantiomeric pair B of voriconazole, which comprises dissolving L-di-p-toluoyl tartaric acid (L-DTTA) and the enantiomeric pair B of voriconazole in a mixed solvent of ethyl acetate and acetone, heating to 60-65 °C to obtain a clear solution, and stepwise cooling and crystallizing to obtain the resolving salt. The resolving reagent of the present invention is inexpensive and easily available, the resolving method is simple to operate, and only one resolution is required to make the enantiomeric impurity (2S,3R) of voriconazole meet the quality requirements, and the product yield is as high as over 45%, with good optical purity, and has great industrial production value.

This invention provides an electrospun gastric perforation patch based on Ag / Zn bimetallic MOF and its preparation method. The gastric perforation patch comprises a tissue integration layer, an antibacterial drug-loaded core layer, and an anti-adhesion layer integrally formed by electrospinning. The antibacterial drug-loaded core layer is composed of Ag / Zn bimetallic MOF loaded with antifungal drugs and a biodegradable polymer material. In the Ag / Zn bimetallic MOF, the molar ratio of zinc to silver is (8:1) to (12:1), and the antifungal drug is voriconazole or amphotericin B. This invention combines the broad-spectrum antimicrobial properties of Ag / Zn bimetallic MOF with a three-layer functional gradient design, enabling the patch to adhere firmly to tissue without sutures. It can actively prevent infection, inhibit adhesion, promote tissue regeneration, and gradually degrade and absorb postoperatively, significantly reducing the risk of foreign body reaction, infection, and recurrence, demonstrating excellent biocompatibility and broad clinical application prospects.

The invention relates to the technical field of medical artificial intelligence, and discloses an artificial intelligence-based voriconazole hepatotoxicity occurrence risk prediction method, which comprises the following steps of: firstly, obtaining a medical record data set containing basic information of a patient, medicine information, inspection information and a research end point index, and performing cleaning and conversion treatment to obtain a medical record data set; a random forest, a naive Bayes algorithm and a limit gradient lifting algorithm are respectively adopted to construct a model, the performance of the model is evaluated through 5-fold cross validation in combination with multiple indexes, and an optimal liver injury endpoint index and a corresponding prediction model are determined; identifying a core risk factor by using the feature importance and an SHAP method; and finally, inputting medical record data of a patient to take medicine to obtain a risk assessment result, and automatically generating a medicine adjustment suggestion in combination with a risk threshold. According to the method, voriconazole hepatotoxicity risk accurate prediction and medication guidance are realized, and medication safety is improved.

The invention relates to the field of medicines, in particular to a compound and application thereof. The compound is shown as a formula I, and also comprises pharmaceutically acceptable salts, prodrugs, tautomers, stereoisomers, isotope derivatives or solvates of the compound. The compound disclosed by the invention has good antifungal activity, particularly has exact and excellent inhibition and antibacterial activity on candida, cryptococcus and rhizopus arrhizus, and also has excellent antibacterial activity on voriconazole drug-resistant bacteria. The compound can be used for preventing and / or treating various diseases caused by fungal infection.

The application adopts a gene knockout method of homologous recombination to knockout a gene sequence of an ABC transport protein coding gene Af-ABC in Aspergillus fumigatus, and has very important scientific significance and application value for studying growth, virulence and sensitivity to voriconazole of Aspergillus fumigatus, and researching new targeted drugs for the gene and the coded protein, and screening aspergillosis treatment drugs.

The invention belongs to the technical field of therapeutic drug monitoring, and particularly relates to a voriconazole valley concentration substandard risk prediction model and a construction method thereof, and the method comprises the following steps: collecting clinical data of a patient treated by voriconazole and subjected to TDM; randomly dividing the data set into a training set and a verification set according to a ratio of 7: 3; carrying out single factor analysis and binary Logistic regression analysis on the training set to screen independent risk factors of which the voriconazole valley concentration does not reach the standard; carrying out correlation analysis on the screened independent risk factors, incorporating the independent risk factors with low correlation and constructing a Nomogram model; for the Nomogram model, the model distinction degree is evaluated by drawing an ROC curve, the calibration degree of the model is evaluated by drawing a calibration curve, the clinical net profit of the model is evaluated by drawing a decision analysis curve, and model internal verification is carried out by a Bootstrap method; and performing external verification on the model by using the verification set. The independent risk factors comprise LA, administration dosage, AST, severe pneumonia and tumors.

The present application relates to the field of pharmaceutical preparations, and discloses a voriconazole freeze-dried powder injection and a preparation method thereof.The freeze-dried powder injection comprises voriconazole, sulfobutyl betacyclodextrin, sorbitol, sodium chloride and methanesulfonic acid, and the solubility and stability of the drug are significantly improved by optimizing the proportion of the excipients and the pH value (4.0-5.0). Experiments show that in the accelerated test (40℃±2℃, 75%RH) and the long-term stability test (25℃±2℃, 60%RH), the content decrease rate is ≤3%, the total impurities are ≤0.1%, the moisture is ≤0.5%, and the effective period can reach 24 months. In addition, after reconstitution, the compatibility with various clinical diluents (such as 0.9% sodium chloride and 5% glucose) is good, without precipitation or degradation. The present application solves the problems of high toxicity of excipients, poor stability and easy precipitation of diluents in the prior art, and has significant clinical application value.

The present invention relates to a preparation method of voriconazole for injection, which comprises subliming and drying a mixed solution formed by injection water, sulfobutyl-β-cyclodextrin sodium and voriconazole after pre-freezing, and then drying by analytical drying to obtain voriconazole for injection, wherein the temperature is first lowered to below 50°C in the sublimation step, and then raised to above 10°C within 3 to 8 hours, the vacuum degree of the sublimation step is 0 to 10 Pa, the analytical drying time is 1 to 3 hours, the temperature is 55 to 70°C, and the vacuum is maintained for 3 to 10 hours. The present invention adjusts the steps and parameters of sublimation drying and analytical drying to make the prepared medicine have better stability to cope with more stringent high-temperature storage and transportation environments, and has fewer impurities and a shorter analytical drying time.

The present invention discloses a voriconazole and multivitamin compound freeze-dried powder injection, and relates to the technical field of pharmaceutical preparations, the voriconazole and multivitamin compound freeze-dried powder injection comprises: an active component comprising voriconazole or a pharmaceutically acceptable salt thereof, and a multivitamin system composed of at least one water-soluble vitamin and at least one fat-soluble vitamin; the stable system comprises a microenvironment regulating agent containing fat-soluble vitamins and an antioxidant synergist for the whole system; and freeze-drying the skeleton agent. According to the voriconazole freeze-dried powder injection disclosed by the invention, fat-soluble vitamins are clathrated by adopting a microenvironment regulating agent to form a water dispersible compound, and a specific antioxidant synergist and a freeze-dried skeleton agent system are combined, so that voriconazole, water-soluble vitamins and fat-soluble vitamins with different chemical properties can stably and uniformly coexist in the same freeze-dried powder injection.

The invention belongs to the field of detection, and particularly discloses a method for simultaneously detecting concentrations of six drugs in blood, and the method comprises the following steps: detecting a sample to be detected by using liquid chromatography-mass spectrometry, and determining the content of the drugs in the sample to be detected according to a detection result and a standard curve, the medicine is prepared from meropenem, vancomycin, voriconazole, linezolid, tacrolimus and cyclosporine A. The invention further discloses a preparation method of the medicine. According to the invention, LC-MS / MS is adopted to simultaneously detect the blood concentration of six drugs in blood, and the method has the advantages of high separation degree, high sensitivity, high accuracy, fast detection speed and the like, provides a reliable basis for clinical precise medication, and improves the safety and effectiveness of immunosuppressor combined antibacterial drug treatment.

The MFSmt gene reveals the role of voriconazole in treating Aspergillus fumigatus under the condition of pathogenicity: the deletion of MFSmt gene leads to the increase of amphotericin B resistance and the increase of voriconazole sensitivity in Aspergillus fumigatus. This finding suggests that if the drug that makes the MFSmt gene deletion or reduces the amount of expressed protein is used in clinical treatment, it can be combined with voriconazole to have a more effective bactericidal effect, and at the same time, the use of amphotericin B should be avoided to prevent drug resistance. This has important clinical value for determining the treatment plan for effective treatment of clinical Aspergillus fumigatus infection and controlling drug-resistant strains.

The invention relates to the technical field of freeze-drying devices, and discloses a freeze-drying device for voriconazole preparation and a method thereof.The freeze-drying device comprises a drying box internally provided with a cavity, a cabinet door is further arranged on the drying box, a plurality of movable storage plates are arranged in the cavity, mounting grooves are formed in the storage plates, and a plurality of placement grooves are formed in the lower side faces of the mounting grooves; notches are formed in the upper end faces of the storage plates, and clamping assemblies are arranged in the mounting grooves; a limiting assembly is further arranged in the mounting groove; a positioning assembly is further arranged in the mounting groove; a fixing groove is formed in the cabinet door, and a supporting assembly is arranged in the fixing groove; a drying assembly is further arranged in the cavity. By means of the structure, positioning of the positioning assembly on the storage plate is removed or removed, the storage plate can slide and ascend and descend in the cavity, the descended storage plate can bring convenience to a worker to take and place a container containing voriconazole on the storage plate, and therefore the worker can conveniently use the storage plate.

The invention discloses an iridium catalyst, a preparation method thereof and application of the iridium catalyst in preparation of deuterium-labeled voriconazole, and belongs to the technical field of catalysts. The structure of the iridium catalyst is innovatively improved, that is, large-steric-hindrance 1, 2, 4-tri (2, 6-diisopropylphenyl)-1, 2, 3-triazole carbene is used as a ligand, and meanwhile, traditional monodentate coordinated chloride ions of anions are changed into bidentate coordinated acetate, so that the obtained catalyst can catalyze voriconazole to carry out hydrogen-deuterium exchange reaction. When the catalyst disclosed by the invention catalyzes a hydrogen-deuterium exchange reaction, only heterocycle of the reaction is obviously different from the hydrogen-deuterium exchange reaction of an iridium catalyst reported in the prior art, which mainly occurs on a benzene ring, four deuterium atoms can be simultaneously introduced into the heterocycle of voriconazole, and meanwhile, the deuteration rate exceeds 98%, so that the requirement of quantitative analysis is met.

The present invention relates to antifungal drug preparations, and particularly to voriconazole topical preparations and their preparation methods. The voriconazole topical preparation at least comprises voriconazole, a matrix material and a solubilizer, wherein the solubilizer is an isopropyl ester or a hydrocarbon solvent. The voriconazole topical preparation of the present invention can more effectively target the affected area, and solves the problem of poor stability of voriconazole during the preparation of the voriconazole topical preparation. Especially in the presence of water, voriconazole is prone to hydrolysis and the products are recombined through the retro-aldol reaction to generate inactive isomeric impurities.

The invention discloses a method for simultaneously determining the concentrations of Venoclarias, Selanisol, voriconazole and fluconazole in human plasma, and belongs to the technical field of drug analysis and treatment drug monitoring. The invention aims to solve the problem that the prior art is lack of a method for synchronously monitoring the blood concentration of four drugs of'vinca + Sanisole 'double-targeted chemotherapy and'voriconazole + fluconazole' antifungal scheme. The method is characterized by comprising the following steps: taking a plasma sample, precipitating protein through an internal standard solution and an organic solvent, and taking supernatant as a test solution; carrying out gradient elution by adopting a C18 chromatographic column and taking an aqueous solution containing formic acid and an organic solvent as mobile phases; detecting elution components by adopting an electrospray ionization source positive ion mode and a multi-reaction monitoring mode; and finally calculating the concentrations of the four drugs according to a detection result by an internal standard method. The method is mainly used for rapid and synchronous treatment drug monitoring when a clinical patient jointly uses the four drugs, and a basis is provided for accurate dose adjustment.