43 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 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 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 discloses febuxostat tablet detection equipment and a detection method, and belongs to the technical field of medicine sampling detection equipment. The febuxostat tablet detection sampling device solves the problem that the detection result after sampling each time is affected due to the fact that the detection sampling mode after tabletting of febuxostat tablets at present is generally a manual sampling mode and the manual sampling has certain uncertainty. A tablet press is connected with a discharging mechanism and a discharging mechanism, bearing seats are symmetrically arranged on a base of a sampling inspection mechanism, a transmission shaft is rotationally installed on the bearing seats, a left-hand thread is machined on the left half portion of the transmission shaft, a right-hand thread is machined on the right half portion of the transmission shaft, and sliding blocks are connected to the left-hand thread and the right-hand thread. Each sliding block is connected with a sliding rail in a sliding manner, the sliding rails are symmetrically mounted on the base, a connecting seat is arranged on the base, a swing arm is hinged to each connecting seat, the swing arms are connected with guide blocks of the sliding blocks in a sliding manner, and the sampling hopper is hinged to the upper ends of the swing arms. According to the febuxostat tablet detection equipment, the accuracy degree of medicine detection and the medicine quality are improved.

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 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 a key intermediate 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-ethyl formate of a new generation of a xanthine oxidase inhibitor Febuxostat (Febuxostat), and particularly relates to a preparation method of the key intermediate 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-ethyl formate of the xanthine oxidase inhibitor Febuxostat. According to the method, 2-(3-formyl-4-isobutoxyphenyl)-4-methylthiazole-5-ethyl formate is taken as a raw material, ammonium acetate / hydroxylamine hydrochloride is taken as a nitrogen source, copper acetate / copper chloride / copper oxide is taken as a catalyst, cyanation reaction of aldehyde group is carried out, and the 2-(3-formyl-4-isobutoxyphenyl)-4-methylthiazole-5-ethyl formate is obtained. And the 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-ethyl formate is prepared by using the 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-ethyl formate as a solvent. The purity of the 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-ethyl formate prepared by the preparation method disclosed by the invention reaches 99% or above, and the yield of the 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-ethyl formate can reach 94%; the solvent used in the invention is wide in source, easy to prepare, mild in reaction condition, easy to operate, low in production cost and suitable for industrial production.

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 provides a method for preparing febuxostat tablets by dry granulation and tabletting, which not only avoids the adverse effects of moisture and high temperature on product quality in the traditional granulation and drying process, but also solves the problem of poor content uniformity caused by the adoption of a powder direct compression process due to poor powder flowability. The quality of the product is effectively ensured, the in-vitro dissolution is consistent with the reference, and the clinical bioequivalence test result is equivalent to the in-vivo bioequivalence test result.

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 a novel febuxostat derivative compound and a composition for the prevention or treatment of tuberculosis, comprising same as an active ingredient. The compound of the present invention can directly kill Mycobacterium tuberculosis, which is difficult to treat due to multidrug resistance (MDR) and extensive drug resistance (XDR), or can efficiently inhibit infected Mycobacterium tuberculosis through host-directed therapy mediated by macrophages of a host. Therefore, the compound of the present invention can be used alone as a therapeutic composition, and can also be administered in combination with a conventional anti-tuberculosis agent, thereby exhibiting a synergistic effect, and thus can be effectively used to improve a therapeutic effect while minimizing the dose and administration period of the anti-tuberculosis agent.

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 invention relates to a preparation method of a small-particle-size febuxostat crystal form C, and belongs to the field of medicine and pharmacy. The method comprises the following steps: dissolving febuxostat in a low-molecular alcohol or ketone solvent, dissolving, filtering, adding purified water into the obtained filtrate, controlling the feeding speed in the feeding process, cooling the system to 5 DEG C at a constant speed, growing grains for a certain time, finally filtering, leaching a filter cake with purified water, and drying for 5 hours. And the crystal form C product with ideal granularity is directly obtained through crystallization control, so that the use of crushing equipment is avoided, and the cost is reduced. The process is stable, strong in controllability, good in batch stability, low in cost and suitable for industrial production, and the yield can reach 90-95%. Meanwhile, the crystal form obtained by the process is complete, the particle size distribution curve is in normal distribution, and the crystal is easy to disperse and can be directly used for preparation products.

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 discloses a febuxostat preparation process, belongs to the technical field of medicine synthesis, and particularly relates to a preparation method and application of febuxostat. The method comprises the following steps: carrying out etherification reaction on 2-(3-aldehyde-4-isobutoxyphenyl)-4-methylthiazole-5-ethyl formate, carrying out cyanidation reaction, and carrying out ester hydrolysis reaction, so as to prepare the febuxostat bulk drug. According to the method, potassium trimethylsilanolate or sodium trimethylsilanolate is used for replacing sodium hydroxide in a traditional process in the ester hydrolysis step, so that side reaction of ester hydrolysis is avoided, production steps are reduced, and the production cycle and cost are greatly reduced. The purity of the prepared febuxostat finished product is greater than 99.9%, and the prepared febuxostat finished product has great market competitive advantages and is green and environment-friendly.

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 present invention belongs to the field of medical technology, and specifically provides a method for detecting genotoxic impurities in Febuxostat, wherein the method adopts liquid chromatography. The method for detecting genotoxic impurities in Febuxostat provided by the present invention adopts high performance liquid chromatography to realize rapid and accurate determination of three genotoxic impurities, has high sensitivity and specificity, and is simple to operate. The present invention can be used for the preparation process of Febuxostat and the quality control of the final product.

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 invention provides a pharmaceutical composition for reducing uric acid as well as a preparation method, application and a product thereof, and belongs to the field of medicines. The pharmaceutical composition for reducing uric acid is composed of a component A and a component B. The component A is composed of 5 parts of pseudobulbus cremastrae seu pleiones, 30 parts of rhizoma smilacis glabrae, 15 parts of herba taxilli, 15 parts of radix astragali, 15 parts of radix salviae miltiorrhizae, 30 parts of semen coicis and 10 parts of radix gentianae macrophyllae. The component B is a xanthine oxidase inhibitor, and the xanthine oxidase inhibitor is allopurinol or febuxostat. The xanthine oxidase inhibitor and the traditional Chinese medicine components including the pseudobulbus cremastrae seu pleiones, the rhizoma smilacis glabrae, the herba taxilli, the radix astragali seu hedysari, the radix salviae miltiorrhizae, the semen coicis and the radix gentianae macrophyllae act together and cooperate with one another, so that the blood uric acid level can be remarkably reduced, and the traditional Chinese medicine composition can be used for treating hyperuricemia, improving kidney functions and pathology and a basis is provided for clinical medication of combination of the traditional Chinese medicine composition and the xanthine oxidase inhibitor.

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.