49 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 provides a synthesis method of voriconazole, and belongs to the field of medicine synthesis. The method comprises the following steps: taking an intermediate A as a raw material, and carrying out continuous flow on the intermediate A and hydrogen under the catalysis of palladium-carbon to obtain the voriconazole raceme. According to the synthesis method, hydrogen is used as a hydrogen source, palladium-carbon is used as a catalyst, chlorine atoms on a pyrimidine ring of an intermediate A are removed, and the raceme of voriconazole is obtained. The synthesis method has the advantages of few by-products, high product quality, mild reaction conditions, low cost and high process safety, and is suitable for industrial mass production.

The invention belongs to the field of pharmaceutical preparations, and particularly relates to a cyclodextrin inclusion compound and a preparation method thereof.The cyclodextrin inclusion compound comprises voriconazole, a cosolvent and sulfobutyl-beta-cyclodextrin, by increasing use of the cosolvent polysorbate 80 (II), the use amount of sulfobutyl ether-beta-cyclodextrin in voriconazole for injection is reduced, and the content of the sulfobutyl ether-beta-cyclodextrin in voriconazole for injection is reduced; the invention aims at remarkably reducing cyclodextrin accumulation in the body and provides guarantee for medication safety of patients with moderate to severe renal function impairment. Meanwhile, the preparation process is simple, industrial production is facilitated, and the inclusion effect of the inclusion compound and the stability of the product can be guaranteed.

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.

The invention discloses a method for synchronously determining multiple drug components in a biological sample based on an LC-MS / MS. The multiple drugs are phenytoin sodium, paliperidone, voriconazole, theophylline, fluvoxamine and lidocaine, and the method comprises the following steps: obtaining the biological sample, and pre-treating the biological sample; according to the method, phenytoin sodium, paliperidone, voriconazole, theophylline, fluvoxamine and lidocaine in a sample are synchronously detected by adopting a liquid chromatography-mass spectrometry technology. The method provided by the invention can realize rapid and synchronous determination of phenytoin sodium, paliperidone, voriconazole, theophylline, fluvoxamine and lidocaine, and has high sensitivity and accuracy.

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 present invention generally encompasses compositions and methods comprising inhalable voriconazole or a pharma- ceutically acceptable salt thereof produced in an amorphous form using thin film freezing. In various embodiments, the present invention includes dry powder voriconazole formulations that can be inhaled, for example, using a dry powder inhaler, and are well tolerated as a daily regimen for treating or preventing fungal infections. The compositions and methods of the present invention avoid or reduce systemic circulation of voriconazole, thus overcoming adverse events associated with circulating voriconazole.

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.

The invention belongs to the technical field of bulk drug production, and particularly relates to a voriconazole bulk drug production method which comprises the steps of voriconazole intermediate preparation, crude product preparation and refining. Crystallizing the voriconazole intermediate in an unwinding agent, and separating an isomer with pharmaceutical activity, namely a voriconazole crude product; the unwinding agent comprises an L-camphorsulfonic acid solution prepared from a voriconazole intermediate and L-camphorsulfonic acid which are fed according to a molar ratio of 1: 1.15. The production process provided by the invention is high in controllability and low in impurity content, the quality and yield of the product meet the specified requirements, and meanwhile, the voriconazole production process is reasonable and effective, has good reproducibility and reliability, and can ensure that the produced product meets the quality requirements.

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 invention relates to the technical field of voriconazole detection, in particular to a voriconazole structure identification method based on multi-dimensional nuclear magnetic resonance, and the voriconazole structure is analyzed through ultraviolet absorption spectrum (UV), infrared absorption spectrum (IR), ultrahigh resolution mass spectrum (FT-MS), 1D / 2D nuclear magnetic resonance (NMR), thermal analysis (TGA, DSC) and X-ray powder diffraction (XRD). According to the method, information of a nuclear magnetic HMBC spectrum is fully utilized, the configuration of a sample is reasonably analyzed, the result is consistent with the chemical structure of the sample, each spectrum is reasonable in attribution, the crystallinity of the voriconazole is verified through X-ray powder diffraction, the melting point and the thermal stability of the voriconazole are represented through thermal analysis, the voriconazole is detected through multiple dimensions, detection is more comprehensive, and the method is suitable for large-scale popularization and application. And accurate data support can be provided, in order to fully utilize information of the nuclear magnetic HMBC spectrum, the configuration of the sample is reasonably analyzed, the result is consistent with the chemical structure of the sample, the crystallinity of the sample is verified by X-ray powder diffraction, and the melting point and the thermal stability of the sample are represented by thermal analysis.

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.

The invention particularly relates to a method for preparing a voriconazole intermediate. The method comprises the following steps: carrying out bromination reaction on a first initiator to obtain a first intermediate; the synthesis method comprises the following steps: activating zinc powder to obtain an organic zinc reagent intermediate state, and carrying out Reformatsky reaction on a tetrahydrofuran solution containing the organic zinc reagent intermediate state, a first intermediate and a second initiator; the Reformatsky reaction product is sequentially subjected to concentration, quenching, tetrahydrofuran removal and extraction, and an organic phase obtained after extraction is washed, concentrated under reduced pressure and stirred for crystallization; finally, washing and drying the separated crystal to obtain a second intermediate; dechlorinating the second intermediate under a palladium-carbon catalysis condition to obtain a third intermediate; the quality and the yield of the voriconazole bulk drug produced by the method meet the specified requirements, the production process is reasonable and effective, good reproducibility and reliability are achieved, and it can be ensured that the produced product meets the quality requirements. The process disclosed by the invention is suitable for large-scale daily production under factory production conditions.

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 belongs to the technical field of pharmaceutical analysis, particularly relates to a method for detecting 4-(1, 1-dibromoethyl)-6-chloro-5-fluoropyrimidine in voriconazole, and provides a convenient, efficient and accurate detection method for solving the problem of detection of 4-(1, 1-dibromoethyl)-6-chloro-5-fluoropyrimidine in voriconazole. The content of 4-(1, 1-dibromoethyl)-6-chloro-5-fluoropyrimidine in voriconazole can be detected, so that the medication safety is effectively guaranteed, the quality control of voriconazole is facilitated, the method is convenient, efficient and accurate, the system applicability, repeatability, specificity and accuracy completely conform to the guidance principle verified by methods in Chinese Pharmacopoeia, and the method is suitable for popularization and application. The method can be used for quality control of voriconazole.

The invention relates to a voriconazole intermediate liquid medicine preparation process, which comprises: weighing water for injection, adjusting the liquid preparation temperature to 40-55 DEG C, sequentially adding sodium sulfobutyl-beta-cyclodextrin and voriconazole, uniformly stirring, stirring until completely dissolving, cooling to 20-30 DEG C, adding the water for injection to the total amount, uniformly stirring, cooling to 20-30 DEG C, and uniformly stirring to obtain the voriconazole intermediate liquid medicine. And after uniform mixing, filtering, filling and semi-plugging are carried out. The voriconazole intermediate liquid medicine for injection with better stability is finally obtained by adjusting the liquid preparation step and controlling the selection of the auxiliary material sulfobutyl-beta-cyclodextrin sodium, so that the finished product of voriconazole for injection with higher stability is prepared, and particularly, the specified standard is still kept under the condition of stability-high temperature of 55 DEG C + / -2 DEG C; and the finished product medicine can cope with harsh storage and transportation environments.

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.