33 results about "Febuxostat" patented technology

The invention relates to the technical field of biological medicines, in particular to a febuxostat and aloperine co-amorphous substance as well as a preparation method and application thereof. The molar ratio of the febuxostat to the aloperine in the co-amorphous substance of the febuxostat and the aloperine is (0.5-3): 1. The febuxostat and aloperine co-amorphous substance provided by the invention has excellent stability, not only can effectively improve the water solubility and bioavailability of febuxostat, but also can effectively improve the treatment effect on related diseases such as gout, gouty arthritis, hyperuricemia and the like, and has a wide application prospect.

The invention belongs to the technical field of preparation of febuxostat intermediates, and particularly relates to a preparation method of a febuxostat intermediate. The preparation method comprises the following steps: taking thiourea and ethyl 2-butanone acid ester as raw materials, and carrying out nucleophilic addition-cyclization reaction to prepare 2-amino-4-methylthiazole-5-carboxylic acid ethyl ester; then, the 2-amino-4-methyl thiazole-5-carboxylic acid ethyl ester is subjected to a diazotization reaction, and 4-methyl-5-ethoxy carbonyl thiazole-2-diazonium chloride is obtained; the method comprises the following steps: taking 5-bromosalicylaldehyde and 4-methyl-5-ethoxycarbonyl thiazole-2-diazonium chloride as raw materials, and carrying out coupling reaction under the catalytic action to prepare the febuxostat intermediate. The synthetic route provided by the invention is efficient, economical and environment-friendly, is suitable for industrial production, can meet the market demand, and overcomes the technical defects existing in the preparation of the febuxostat intermediate in the prior art.

The present invention provides a pharmaceutical composition comprising a therapeutically effective amount of allopurinol, febuxostat, or a pharmaceutically acceptable salt thereof as an active ingredient for preventing or treating cardiovascular disease, in which the composition is administered to a subject having a serum uric acid level of 6 mg / dl or higher to reduce the serum uric acid level of the subject to less than 6 mg / dl. Therefore, the pharmaceutical composition according to the present invention exhibits an excellent effect on xanthine oxidase inhibitor and is administered to selected subjects to effectively treat or prevent cardiovascular disease.

The invention relates to a preparation method of febuxostat tablets, which comprises the following steps: adding febuxostat, a filler and an adhesive into a wet granulation pot, and premixing; dissolving the solubilizer with absolute ethyl alcohol, and then adding purified water to form a solution; adding the solution formed in the step 2 into the premixed material, and granulating to obtain an intermediate; putting the intermediate into an oscillating granulator for wet granulation; drying the wet granules by using a fluidized bed; carrying out dry granulation on the dried granules by using a 24-mesh screen; placing the dried whole granules in a three-dimensional mixer, adding a corresponding amount of disintegrating agent and lubricant according to the yield, and carrying out total mixing to obtain a semi-finished product; and tabletting and coating the semi-finished product to finally obtain a finished product. The solubilizer is polyoxyethylene hydrogenated castor oil; the febuxostat tablet solves the problems of possible crystal transformation and poor dissolution rate in the preparation process of the existing febuxostat tablet through the steps.

This invention provides a method for preparing febuxostat. The route uses ethyl 2-(3-aldehyde-4-hydroxyphenyl)-4-methylthiazolium-5-carboxylate as the starting material, first alkylating the 4-hydroxyl group, then reducing the 3-aldehyde group to a cyano group, and finally hydrolyzing to generate febuxostat. This method is simple to operate, has mild reaction conditions, high yield, low cost, is environmentally friendly, and is suitable for large-scale industrial production of febuxostat.

The present invention belongs to the field of pharmaceutical technology, and discloses a febuxostat tetravalent platinum prodrug, a preparation method and a preparation. The present invention synthesizes two small molecule tetravalent platinum prodrugs of tetravalent platinum, febuxostat cisplatin and febuxostat oxaliplatin, for the first time, and prepares a febuxostat cisplatin nanoformulation. The nanoformulation solves the shortcomings of cisplatin such as poor water solubility, congenital or acquired drug resistance, and obvious toxic and side effects, and has many advantages such as passive targeting of tumor tissue. It is not only economical and practical, but also provides possibilities for industrial production. By using the idea of ​​"drug repositioning", the anti-tumor effect of febuxostat is further studied, and a combined anti-tumor effect with platinum drugs is achieved. At the same time, a carrier-free preparation method is adopted to avoid the unknown toxicity of the carrier, the preparation has good safety, and the tumor targeting of platinum drugs is achieved by nanoformulation, while enhancing the accumulation of tumor sites and reducing systemic toxic and side effects.

The invention discloses a preparation method of a febuxostat intermediate, and relates to the technical field of chemical synthesis of medicines, cyanophenol and thioacetamide are catalyzed by polyphosphoric acid, zinc chloride and Bi (OTf), and a reaction solution is subjected to impurity removal and centrifugation to obtain a centrifugal wet product; 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester reacts with 2-chloroacetoacetic acid ethyl ester to obtain 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester, and finally 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester reacts with hexamethylenetetramine under the action of p-toluenesulfonic acid and concentrated sulfuric acid to obtain the febuxostat intermediate product. The reaction period is greatly shortened, the production cost is reduced, and the yield and the purity of the product are improved.

The invention discloses application of euglena and a product thereof to improvement of hyperuricemia. The euglena and the product thereof are used for improving the hyperuricemia. The euglena and the product thereof improve hyperuricemia by reducing uric acid and protecting the kidney from uric acid damage. The uric acid reducing effect of the euglena and the euglena product and the uric acid reducing effect of the medicine febuxostat have a superposed effect According to the euglena and the euglena product, intestinal flora is regulated by promoting probiotic flora in the intestinal tract and inhibiting growth of harmful flora in the intestinal tract, catabolism of purine and uric acid in the intestinal tract is promoted, and uric acid metabolism is regulated. The euglena and products thereof include euglena and euglena polysaccharides. The invention provides a new method for treating people with hyperuricemia. The euglena and the euglena polysaccharide improve hyperuricemia by reducing uric acid and protecting kidneys from being damaged by uric acid, regulate intestinal flora by promoting probiotic flora in intestinal tracts and inhibiting growth of harmful flora in the intestinal tracts, promote catabolism of purine and uric acid in the intestinal tracts and regulate uric acid metabolism.

The present invention discloses the use of luteolin, isoquercetin and febuxostat in the preparation of a medicament for preventing and / or treating hyperuricemia and gout. In the composition of luteolin and isoquercetin, the mass ratio of luteolin to isoquercetin is 1:5 to 100. In the solution of the present invention, it is found that luteolin and isoquercetin are used in combination with febuxostat in a specific ratio. On the one hand, it has the effects of inhibiting XOD oxidase and reducing uric acid, and on the other hand, it can antagonize the EP4 receptor to reduce inflammation. Therefore, the dosage of febuxostat can be reduced, the inflammatory factors during the occurrence of gouty arthritis can be inhibited, the acute attack of gouty arthritis can be relieved, and it has a significant effect on the treatment of gouty arthritis without obvious toxic and side effects.

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an LXH-2301 pharmaceutical composition and application of the LXH-2301 pharmaceutical composition in preparation of a medicine for treating gout with hyperuricemia. The LXH-2301 pharmaceutical composition disclosed by the invention comprises the following components: (a) LXH-2301 tablets with the specification of 0.5 g / tablet; (b) febuxostat tablets with the specification of 20 mg / tablet; wherein the LXH-2301 tablet is administered three times a day, two tablets are administered each time, the total dosage is 1.0 g, and the LXH-2301 tablet is combined with the febuxostat tablet for use. Patients suitable for the composition need to simultaneously meet the following screening standards: morning urine pHlt; and 6.0. The LXH-2301 pharmaceutical composition provided by the invention is applied to the preparation of medicines for treating gout with hyperuricemia, and the limitation of insufficient curative effect on patients with uric acid poor excretion type gout is solved; the problem of lack of prevention means for uric acid crystallization kidney injury is solved.

The present invention relates to the field of biomedicine technology, and more particularly to a kind of Febuxostat and alopecurine co-amorphous substance and its preparation method and application. The Febuxostat and alopecurine co-amorphous substance has a mol ratio of Febuxostat and alopecurine of (0.5-3): 1. The Febuxostat and alopecurine co-amorphous substance provided by the present invention has excellent stability, can effectively improve the water solubility and bioavailability of Febuxostat, and can effectively improve the therapeutic effect for related diseases such as gout, gouty arthritis and hyperuricemia, and has broad application prospects.

The present invention relates to a novel febuxostat derivative compound and a composition comprising same as an active ingredient for preventing or treating inflammatory or autoimmune diseases. The compounds of the present invention significantly reduce the expression of inflammatory cytokines in macrophages even at low doses, thereby effectively suppressing excessive inflammatory responses, and can thus be advantageously used for long-term administration in the treatment of inflammatory diseases, which are, for the most part, chronic.

The utility model relates to the technical field of production filtering equipment, in particular to febuxostat production filtering equipment which comprises a base, a stock bin assembly, a filtering assembly, a scraper blade, a power rod, a motor, a collecting assembly and a discharging assembly, a stock bin assembly is arranged above the base, a filtering assembly is arranged in the stock bin assembly, a scraping plate is arranged above the filtering assembly, a power rod is arranged above the scraping plate, a motor is arranged at one end of the power rod, a collecting assembly is arranged on one side of the stock bin assembly, and a discharging assembly is arranged at the bottom of the stock bin assembly. By adding the self-cleaning structure, the device can automatically clean the filter screen in the production process, the filtering speed is guaranteed, dregs generated by cleaning are collected, the cleanness of the production environment is guaranteed, production stock solution contained in the dregs is recycled, waste in production is reduced, and the production cost is reduced. And secondary filtration is carried out in the recovery process, so that the filtration effect is guaranteed, and the practical value of the device is enhanced.

The invention discloses a febuxostat solid dispersion tablet as well as a preparation method and application thereof. The tablet comprises a solid dispersion consisting of an active component febuxostat, sucrose stearate and pullulan, and pharmaceutic adjuvants. The preparation method comprises the following steps: preparing a solid dispersion from febuxostat, sucrose stearate and Pulullan by a hot melt extrusion method or a solvent method, crushing, sieving, mixing with other auxiliary materials, and tabletting to obtain the febuxostat tablet. According to the invention, sucrose stearate and pullulan are innovatively combined, and the sucrose stearate and pullulan have a remarkable synergistic effect in the aspects of inhibiting drug crystallization and stabilizing an amorphous state. The prepared tablet is excellent in dissolution performance, the bioavailability of the tablet is far higher than that of a reference preparation, more importantly, the tablet has excellent physical stability, medicine recrystallization in the storage process can be effectively prevented, and the technical problem that a traditional solid dispersion is poor in stability is solved. The method is mature in process and suitable for industrial production.

The invention discloses a compound medicine composition for treating hyperuricemia, the compound medicine composition comprises a quick-release layer medicine and a slow-release layer medicine, the quick-release layer medicine comprises 0.5-2 parts by mass of dotenorad, and the slow-release layer medicine comprises 20-40 parts by mass of febuxostat; the quick-release layer medicine is quick-release layer particles obtained by dry granulation, the slow-release layer medicine is slow-release layer particles obtained by fluidized bed granulation, and the composite medicine composition is a double-layer tablet prepared by performing double-layer tabletting and film coating on the quick-release layer medicine and the slow-release layer medicine. According to the invention, the selected compound main components are dotenorad and febuxostat which are relatively small in side effect and excellent in curative effect in two channels for reducing uric acid, so that the relative dosage of febuxostat is reduced, and the incidence rate of damage of febuxostat to cardiovascular and liver is reduced in a slow release manner; through mechanism synergy, the curative effect is enhanced, and the traditional Chinese medicine composition has remarkable clinical advantages in treatment of hyperuricemia.

The invention provides a febuxostat-cytisine eutectic crystal as well as a preparation method and application thereof, and belongs to the technical field of medicines. The febuxostat-cytisine eutectic crystal provided by the invention is stable in property, the solubility of the febuxostat-cytisine eutectic crystal in water at 37 DEG C is 414 times that of a febuxostat raw material medicine in terms of febuxostat, the bioavailability of febuxostat can be remarkably improved, meanwhile, the febuxostat-cytisine eutectic crystal also has the effects of febuxostat and cytisine, and the febuxostat-cytisine eutectic crystal has a good application prospect.

The application belongs to the technical field of medicine detection, and particularly relates to a detection method of impurities in 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester. The method uses high performance liquid chromatography to detect related substances in 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester, and the content of each impurity is calculated by a principal component self-control method with a correction factor. Methodology verification shows that the detection method provided by the application is good in specificity, high in accuracy and sensitivity, and can be used for quality control of related substances in 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester, so that the product quality can be effectively controlled, and the medication safety of febuxostat medicine is improved.

The application belongs to the technical field of drug use, and particularly relates to an application of febuxostat in preparation of an antifungal drug and an antifungal composition. The application expands the application range and indications of febuxostat, improves the selection range of the antifungal drug, improves the antifungal effect, and has an inhibiting effect on a ketoconazole-resistant strain.

1.The name of the design product: packaging box (febuxostat tablet). 2.The use of the design product: packaging medicine. 3.The design points of the design product: the combination of shape, pattern and color. 4.The picture or photo that best shows the design points: the unfolded state diagram. 5.The design contains colors.

The present invention relates to the technical field of pharmaceutical crystallization, and particularly relates to a febuxostat polymorph S and a preparation method thereof. The polymorph of the present invention does not contain crystal water or other crystallization solvents, and is characterized in that the X-ray powder diffraction pattern has the following characteristic peaks at 2θ±0.2°: 6.78, 7.25, 10.00, 10.97, 11.87, 12.86, 13.51, 14.53, 15.74, 16.24, 16.58, 17.59, 19.06, 19.65. The present invention provides a new febuxostat polymorph with moderate solubility, which is more conducive to formulation processing, has a simple preparation process and is easy to industrialize, and a preparation method thereof.

The utility model relates to the technical field of stirring devices for medicines, in particular to a stirring device for producing and transferring febuxostat. Comprising a mounting plate, a mounting bracket, a containing barrel, a driving assembly, a stirring paddle, a scraping plate, a supporting assembly, a sealing assembly and a moving assembly, compared with an existing stirring device for febuxostat production and transfer, the stirring device for febuxostat production and transfer has the advantages that raw materials are prone to remaining on the inner wall of the containing barrel to cause waste, and the interior of the containing barrel is difficult to clean; the scraping plate rotating along with the stirring paddle is arranged to clean the inner wall of the containing barrel, raw materials in the containing barrel are prevented from adhering to and remaining on the inner wall of the containing barrel to cause waste of the materials, meanwhile, the containing barrel is convenient to clean subsequently, the containing barrel is supported through the lifting supporting assembly, the containing barrel can be taken and placed, and the use is convenient. And the containing barrel is convenient to clean after being used.

The invention discloses a preparation method of febuxostat tablets, and belongs to the technical field of febuxostat tablet preparation.The preparation method comprises the steps that febuxostat, lactose hydrate, pregelatinized starch and an adhesive are mixed for fluidization granulation, and wet particles are obtained; drying the wet granules, and finishing the granules; mixing a disintegrating agent and a lubricating agent after granulating, and tabletting to obtain the febuxostat tablet. The disintegrating agent accounts for 2% of the febuxostat tablet in percentage by mass; a sample is prepared by controlling the dosage of a disintegrating agent, the model of an adhesive and the particle size of raw materials in a one-step granulation mode. According to the method, the process steps are simplified, the process continuity is optimized, the process amplification stability and reliability are effectively improved, meanwhile, the product release degree is guaranteed, the production efficiency is effectively improved, and the production cost is remarkably reduced.

The invention discloses a febuxostat oral instant film preparation which comprises the following components in percentage by mass: 0.1-10.0% of febuxostat, 20-60% of an oil phase, 10-40% of a polymer film-forming agent, 5.0-20% of a plasticizer, 5.0-20% of a filler and 5-20% of a disintegrating agent, and the oil phase is isopropyl myristate and Tween 80 or glyceryl triacetate and Tween 80. The oral instant film preparation prepared from the specific oil phase can improve the solubility of the febuxostat, meanwhile, the dissolution rate and the accumulative dissolution amount of the oral instant film preparation in an acid medium are both superior to those of tablets, the exposure amount of the febuxostat is improved, and then the bioavailability of the febuxostat is improved. The invention also discloses a preparation method of the febuxostat oral instant film preparation, the method adopts a phosphate buffer solution to prepare an aqueous solution required by a nano-emulsion system, and the uniform, clear and stable nano-emulsion system can be formed. The invention also discloses an application of the febuxostat oral instant film preparation in preparation of drugs for treating hyperuricemia or gout.

The present invention relates to a novel febuxostat derivative compound and to a composition for preventing or treating a nontuberculous mycobacterial infection, comprising same as an active ingredient. The compound of the present invention efficiently kills nontuberculous mycobacteria, including Mycobacterium shinjukuense and Mycobacterium kansasii, which exhibit low responsiveness to conventional standard therapies and a high frequency of resistance mutation occurrence, via host-directed therapy mediated by host macrophages, and thus can be effectively used as a fundamental therapeutic composition for various complications caused by nontuberculous mycobacteria infections.

The application provides a non-busheite-optimine co-crystal as well as a preparation method and application thereof, and belongs to the technical field of medicines. The non-busheite-optimine co-crystal provided by the application is stable in property, and the solubility of the non-busheite-optimine co-crystal in water at 37 DEG C is 414 times that of non-busheite raw medicine, so that the bioavailability of non-busheite can be significantly improved, and the non-busheite-optimine co-crystal also has the effects of non-busheite and optimine, and has a good application prospect.

The invention relates to a method for measuring an in-vitro dissolution curve of a febuxostat tablet, which comprises the following steps: taking the febuxostat tablet, taking a hydrochloric acid solution as a dissolution medium with the pH value of 1.2, carrying out dissolution according to a dissolution instrument paddle method, taking out a proper amount of dissolution liquid at different sampling time points, carrying out two-step dilution by using a phosphate buffer solution, and uniformly shaking to obtain a test solution; the method comprises the following steps: taking a febuxostat reference substance, placing the febuxostat reference substance in a measuring flask, dissolving the febuxostat reference substance with a phosphate buffer solution, diluting the febuxostat reference substance to a scale, uniformly shaking the febuxostat reference substance, precisely measuring the febuxostat reference substance, placing the febuxostat reference substance in the measuring flask, adding the phosphate buffer solution, diluting the febuxostat reference substance to the scale, and uniformly shaking the febuxostat reference substance to serve as a reference substance solution, respectively injecting the test solution and the reference solution into a high performance liquid chromatography by using the high performance liquid chromatography, recording a chromatogram, and calculating the dissolution amount; according to the dissolution rate result of the raw material medicine, a hydrochloric acid solution with the pH value of 1.2 is selected as a dissolution medium, the obtained curve distinguishing capacity is very excellent, the dissolution behaviors of febuxostat tablets from different sources can be obtained, and the inherent quality of the product is distinguished.

The invention belongs to the technical field of chemical synthesis, and in particular relates to an N-(1, 3-dioxo-2-aryl octahydrocyclopenta [c] pyrrole-4-yl) benzamide derivative and a synthesis method of the N-(1, 3-dioxo-2-aryl octahydrocyclopenta [c] pyrrole-4-yl) benzamide derivative. The invention successfully develops a [3 + 2] cycloaddition reaction of a photocatalytic cyclopropanamide compound and an N-substituted maleimide derivative, the N-(1, 3-dioxo-2-aryl octahydrocyclopenta [c] pyrrole-4-yl) benzamide derivative can be prepared according to the synthetic method disclosed by the invention, the yield can reach 34-92%, and the preparation method is simple and easy to operate. A convenient, mild-condition and efficient synthesis path is provided for constructing the functional five-membered carbocyclic compound, and a reaction system shows excellent functional group compatibility and substrate universality. Besides, through successful derivatization with complex drug molecules such as febuxostat and adapalene, the application potential of the synthesis method is highlighted, and the compound is expected to be widely applied to drug development and research.

The invention discloses application of febuxostat in preparation of a preparation for improving reproductive performance of rams, and relates to the technical field of animal reproduction. The invention discloses a novel application of febuxostat in improving the reproductive performance of rams, and discloses a method for treating febuxostat to be beneficial to keeping the normal form of testis curvilinear seminiferous ducts and providing a good histological environment for spermatogenesis. Febuxostat disclosed by the invention can obviously improve the spermatogenesis function, reduce abnormal sperms and improve the sperm quality; the invention also discloses febuxostat capable of effectively reducing the oxidative stress level and lipid peroxidation level in testicular tissues by regulating an inoxanthine metabolic pathway, and regulating the expression of ferroptosis related genes so as to regulate a ferroptosis pathway. The febuxostat has a positive promoting effect on the development and metabolism of the ram testis through the comprehensive effects, and finally the reproductive performance is improved. The invention provides a new thought for improving the reproductive capacity of the rams, and has important application value and wide development prospect.

The present invention discloses a highly stable tablet and its preparation method and application. The tablet comprises the following raw materials in parts by weight: febuxostat 20 - 30 parts, spray-dried lactose 15 - 25 parts, pregelatinized starch 12 - 18 parts, disintegrant 6 - 10 parts, glidant 1 - 3 parts, lubricant 1 - 3 parts, and phenylalanine 2 - 4 parts. After mixing febuxostat, spray-dried lactose, pregelatinized starch, disintegrant, glidant, lubricant, and phenylalanine, the tablet is prepared by granulation. Due to the use of spray-dried lactose and pregelatinized starch as fillers and mixing with a certain proportion of disintegrant, glidant, and lubricant, it has a relatively fast dissolution rate. Moreover, febuxostat and phenylalanine have a synergistic effect, and the prepared tablet will not undergo crystal form transformation during long-term storage, and the stability is significantly improved.