108 results about "Empagliflozin" patented technology

The invention discloses a metformin empagliflozin tablet composition and a preparation method thereof. The metformin empagliflozin tablet composition is prepared from the following raw materials: metformin hydrochloride, empagliflozin, corn starch, copovidone, colloidal silicon dioxide, magnesium stearate and a gastric-soluble film coating premix. According to the metformin empagliflozin composition and the preparation method thereof, empagliflozin is dispersed in part of auxiliary materials, then mixing granulation is carried out through a wet granulator, empagliflozin and part of the auxiliary materials are premixed, and the particle size range of a metformin hydrochloride raw material is controlled, so that the problems of poor empagliflozin content uniformity and large inter-batch dissolution difference of the metformin empagliflozin composition prepared by a traditional process are solved; by controlling the mesh number of the wet granulation screen, the problems that materials adhere to the screen, discharging is difficult, and production efficiency is low in the wet granulation process are solved; compared with a fluidized bed production process, the equipment cost is low, the operation is simpler, and the production efficiency is higher; the pharmaceutical composition prepared by the preparation method disclosed by the invention is uniform in component mixing, simple to prepare, controllable in quality and consistent in in-vitro dissolution with an original preparation.

To provide a pharmaceutical composition containing empagliflozin while preserving its amorphous state.SOLUTION: The present invention provides an empagliflozin-containing pharmaceutical composition that comprises amorphous empagliflozin and an amorphous state-maintaining additive.SELECTED DRAWING: Figure 1

The invention provides a preparation method of metformin empagliflozin tablets, and relates to the technical field of pharmaceutical preparations. The metformin empagliflozin tablet is prepared from the following auxiliary materials in percentage by mass: 8-15% of a diluent, 2-5% of an adhesive and 0.5-2% of a lubricant, and the preparation method comprises the following steps: adding empagliflozin and the adhesive into water, and heating to obtain a clear solution; the preparation method comprises the following steps: crushing metformin hydrochloride, and mixing with a diluent to obtain mixed powder; atomizing and spraying the clarified solution into the mixed powder, performing wet granulation, drying, granulating, adding a lubricant, tabletting and coating to obtain the tablet. Compared with an original product, the tablet prepared from the granules obtained by adopting a wet granulation process and optimizing auxiliary materials and a preparation process has better intra-batch and inter-batch uniformity, is shorter in disintegration time limit and smaller in friability, and has more excellent stability under an acceleration condition.

The present invention relates to a process for the preparation of an oral pharmaceutical composition comprising empagliflozin, characterized in that empagliflozin is dissolved in a solution prepared with an organic solvent and a pH adjusting agent, and wet granulation or spray granulation technique is used in the process.

The present invention relates to a film coated tablet comprising Empagliflozin or a pharmaceutically acceptable salt thereof wherein the film coating comprising hydroxypropyl methylcellulose. Furthermore, the tablet is also obtained by using an effective process which is simple, rapid, cost effective, time-saving and industrially convenient process and is created to eliminate the disadvantages of active ingredient

The tablet comprises the following components in parts by mass: 5 parts of an active component empagliflozin, 20-30 parts of an auxiliary material, 45-75 parts of a filling agent, 5-8 parts of an adhesive, 1-3 parts of a disintegrating agent, 0.5-2 parts of a lubricant and 1-5 parts of a coating agent, the auxiliary material, the adhesive, the disintegrating agent and the lubricant are all compositions, the auxiliary material is a composition of Omega-3 fatty acid and cholecalciferol, and the coating agent is a composition of Cholecalciferol, Cholecalciferol, Cholecalciferol, Cholecalciferol, Cholecalciferol, Cholecalciferol and Cholecalciferol. And preparing the tablet by a wet method. The empagliflozin tablet has the beneficial effects that the prepared tablet product is good in stability and high in drug release control capability, the side effect of empagliflozin can be effectively reduced through cooperation of empagliflozin and auxiliary materials, and meanwhile, other complications of diabetes mellitus can be prevented and relieved to a certain extent.

The invention provides a method for improving mixing uniformity of a medicinal compound preparation of metformin and empagliflozin, and belongs to the technical field of medicines. The invention provides an ultrasonic uniform mixing method for dry granulation. The ultrasonic uniform mixing method adopts an air jet pulverization technology, an ultrasonic-assisted vertical shaft planetary stirrer mixing technology and a forced sieving technology, and adopts a strengthening means; by utilizing the synergistic effect of ultrasound and a mixer, the mixing time is shortened, the mixing effect is enhanced, the uniformity and dissolution rate of the preparation are remarkably improved, and the method is short in process route, simple in step operation, easy in condition control and suitable for large-scale production.

The present invention relates to an immediate release monolithic tablet comprising a) granules comprising Metformin or its pharmaceutically acceptable salt, hydroxypropyl cellulose and at least one more pharmaceutically acceptable excipient, and b) powder mixture consisting essentially of Empagliflozin or its pharmaceutically acceptable salts, low substituted hydroxypropyl cellulose and at least one diluent, wherein said immediate release monolithic tablet doesn't comprise copovidone. The said tablet has a desirable pharmacokinetic characteristic, favorable storage stability and comparative dissolution properties. The invention further relates to a process for the preparation of said pharmaceutical composition and use thereof as medicament in the treatment of diabetes.

The present invention relates to a film coated tablet comprising empagliflozin and metformin hydrochloride, wherein comprising at least one binder which is hydroxypropyl methyl cellulose or hydroxypropyl cellulose or mixtures thereof, the tablet provides pharmacotechnical properties and the desired dissolution profile. The present invention also relates to a simple, rapid, cost effective, time-saving and industrially convenient method of preparing the tablet.

The invention provides a purification method of empagliflozin. The method comprises the following steps: (1) extracting raw material liquid containing empagliflozin and impurities by using an extracting agent to obtain extract liquid containing empagliflozin; the impurities comprise one or more of an isomer, an ester and a hydrolysate of empagliflozin, the solvent in the raw material liquid is selected from a non-polar solvent and / or a weakly polar solvent, and the extraction agent comprises an ionic liquid or a mixture of the ionic liquid and a polar solvent; and (2) carrying out back extraction and concentration on the extract liquor containing empagliflozin to obtain empagliflozin. The method has the advantages of high separation efficiency, low solvent consumption, low production cost, safety, environment friendliness, easiness in industrial production and the like.

This application provides a method for improving the mixing uniformity of a compound preparation of metformin and empagliflozin, belonging to the field of pharmaceutical technology. The invention provides a dry granulation and ultrasonic mixing method, which utilizes airflow pulverization, ultrasonically assisted vertical axis planetary mixer mixing, and forced sieving technology to enhance the process. The method utilizes the synergistic effect of ultrasound and the mixer to shorten mixing time, enhance mixing efficiency, and significantly improve the uniformity and dissolution rate of the preparation. This process is short, simple to operate, and easily controllable, making it suitable for large-scale production.

The invention provides application of a sodium-glucose co-transporter 2 inhibitor in preparation of a medicine for preventing or treating senescence. In an aging animal model, it is found that the sodium-glucose co-transporter 2 inhibitor empagliflozin can improve heart aging, enhance heart functions caused by aging and increase the ejection fraction of left ventricle; meanwhile, the memory function caused by senescence can be improved, and the expression levels of senescence factors p16, p21 and p53 are improved. The sodium-glucose co-transporter 2 inhibitor empagliflozin has a prospect of being developed as an anti-aging drug.

The present application relates to a kind of asymmetric catalytic hydrogenation synthesis new method of (S)‑3‑(4‑(5‑bromo / iodine‑2 chlorobenzyl) phenoxy) tetrahydrofuran in engletin intermediate.This method is prepared by acylation, reduction from simple raw material, and formula a-1 compound is obtained.In which formula a-1 compound and formula a compound, through asymmetric catalytic hydrogenation process, and intramolecular dehydration ring-closing reaction synthesis (S)‑3‑(4‑(5‑bromo / iodine‑2 chlorobenzyl) phenoxy) tetrahydrofuran in engletin intermediate.The raw material of this synthesis method is easy to obtain, simple operation, suitable for industrial amplification.

The invention discloses a preparation process of empagliflozin, which comprises the following steps: by taking D-(+)-gluconic acid delta-lactone as a raw material, carrying out condensation reaction on D-(+)-gluconic acid delta-lactone and (R)-3-(4-(5-bromo-2-chlorobenzyl) phenoxy) tetrahydrofuran through a protective reagent under the action of a Grignard reagent; carrying out protonation reaction under the action of sulfuric acid to obtain an intermediate; and removing a protecting group through organic acid to obtain empagliflozin. The reaction route has the advantages of few steps, high selectivity, few byproducts, high product yield, easiness in product separation, convenience in operation, suitability for large-scale industrial production and the like, and is suitable for large-scale popularization and application.

The present invention relates to an immediate release monolithic tablet comprising a) granules comprising Metformin or its pharmaceutically acceptable salt, hydroxypropyl methylcellulose and at least one more pharmaceutically acceptable excipient, and b) powder mixture consisting essentially of Empagliflozin or its pharmaceutically acceptable salts, low substituted hydroxypropyl cellulose and at least one diluent, wherein said immediate release monolithic tablet doesn't comprise copovidone. The said tablet has a desirable pharmacokinetic characteristic, favorable storage stability and comparative dissolution properties. The invention further relates to a process for the preparation of said pharmaceutical composition and use thereof as medicament in the treatment of diabetes.

The present invention relates to a pharmaceutical composition for preventing or treating metabolic abnormality-related fatty liver diseases containing empagliflozin and telmisartan. The pharmaceutical composition has no issues of drug-drug interaction and exhibits a synergistic effect in the prevention or treatment of metabolic dysfunction-related fatty liver disease, thereby allowing effective application to patients with metabolic dysfunction-related fatty liver disease.

The present invention discloses a pharmaceutical combination formulation comprising sitagliptin and empagliflozin and a preparation method thereof.

The present invention belongs to the field of pharmaceutical synthesis technology and specifically relates to a method for preparing an empagliflozin intermediate compound. The method uses 2-chloro-5-iodobenzyl bromide and (S)-3-(4-bromophenoxy)tetrahydrofuran as starting materials, reacting them under the catalysis of magnesium and 2,2,6,6-tetramethylpiperidinyl oxide to produce the empagliflozin intermediate compound (S)-3-(4-(2-chloro-5-iodophenyl)phenoxy)tetrahydrofuran. This process eliminates the need for n-butyl lithium, has a short synthetic route, is simple to operate, and is more suitable for large-scale industrial production.

The present application relates to the biomedical field, specifically relates to a glucose-responsive empagliflozin microneedle delivery system and application thereof.The glucose-responsive empagliflozin microneedle delivery system of the present application is characterized in that the microneedle delivery system is a microneedle patch, comprising a substrate and a microneedle array arranged on the substrate; the microneedle in the microneedle array contains glucose-responsive empagliflozin nanoparticles CB@E or PCB@E.The present application has the following technical effects: the empagliflozin nanoparticles of the present application have precise glucose-responsive drug release performance.The microneedle drug delivery system of the present application has the effect of long-term control of blood glucose.In a T2DM rat model, MN@CB@E exhibits long-acting blood glucose control effect, can reduce blood glucose to normal level within 4h and maintain for 24h, and the hypoglycemic duration is significantly better than that of subcutaneous injection of free empagliflozin (only maintains for 6h), and there is no risk of hypoglycemia after administration to healthy rats.

The invention belongs to the field of pharmaceutical preparations, and particularly relates to a sustained release preparation containing empagliflozin and metformin hydrochloride and a preparation method of the sustained release preparation. The method comprises the following steps: (1) preparing a sustained-release bulk drug, a sustained-release skeleton auxiliary material A, a sustained-release skeleton auxiliary material B, a lubricant and purified water into a tablet core; (2) preparing a coating spacer fluid from a film-forming agent, a thickening agent, a plasticizer, an opacifying agent and purified water; (3) preparing a coating liquid medicine from the quick-release bulk drug, a film-forming agent, a thickening agent, a plasticizer, an opacifying agent and purified water; (4) preparing a sealing solution from a film-forming agent, a plasticizer, an opacifying agent, a color lake and purified water; and (5) sequentially treating the tablet core with a spacer fluid, a coating liquid medicine and a sealing fluid to prepare the empagliflozin and metformin hydrochloride sustained release tablet. Under the condition of ensuring similar dissolution curves, polyoxyethylene is replaced, and the risk of high-temperature burst release of a large amount of metformin hydrochloride is avoided; and the coating process and the process flow are simplified, and the material consumption is reduced.

The present invention belongs to the field of pharmaceutical synthesis technology, and specifically relates to a one-pot method for preparing empagliflozin. The preparation method comprises the following steps: using 4-(5-bromo-2-chlorobenzyl)phenol as a starting material, nucleophilic addition reaction with sugar occurs under the action of a Grignard reagent; then adding a methanolic solution of hydrogen chloride to undergo methyl etherification; then undergoing a nucleophilic substitution reaction with (R)-3-tetrahydrofuryl p-toluenesulfonate; and finally adding Et3SiH3 / AlCl3 to undergo a reduction reaction to obtain a crude product of empagliflozin. The one-pot method for preparing a crude product of empagliflozin provided by the present invention does not require the removal of intermediates during the reaction process, thus avoiding centrifugation and drying operations, and greatly shortening the production cycle. The preparation method is simple to operate, easy to operate in post-processing, and easy to recover the solvent; and it greatly improves production capacity. The purity of the refined finished product is above 99.5%, the total product yield can reach 40%, impurities are easy to control, and it is suitable for industrial production.

The invention provides a pharmaceutical composition. The pharmaceutical composition is prepared from amlodipine, empagliflozin, folic acid substances and a pharmaceutically acceptable carrier, wherein the amlodipine, the empagliflozin and the folic acid substances are in medicinal effective dose. The invention also provides application of the pharmaceutical composition in preparation of medicines for treating lower limb artery occlusion diseases.

The invention discloses a pharmaceutical composition for reducing blood sugar and application thereof, and belongs to the technical field of preparation of drugs for reducing blood sugar. The pharmaceutical composition is prepared from the following components in parts by weight: 5 to 7 parts of empagliflozin, 30 to 40 parts of cortex cinnamomi extract, 500 to 700 parts of metformin, 60 to 80 parts of microcrystalline cellulose, 10 to 15 parts of polyvinylpolypyrrolidone, 100 to 120 parts of HPMC K100M, 50 to 60 parts of ethyl cellulose, 40 to 50 parts of Eudragit FS30D, 40 to 50 parts of soybean phospholipid and 10 to 20 parts of poloxamer 188. The composition is applied to preparation of sustained-release tablets for reducing blood sugar, and can reduce loss of islet cells and protect kidney functions and gastric mucosa.

To provide methods for treating chronic heart failure, in particular in patients with HFrEF or HFpEF, with a good efficacy, with regard to disease modifying properties and with regard to reduction of risk of mortality or hospitalization while at the same time showing a good safety profile.SOLUTION: The present invention relates to methods for preventing or treating acute or chronic heart failure and for reducing the risk of cardiovascular death, hospitalization for heart failure and other conditions in patients with preserved or reduced ejection fraction by administering empagliflozin to the patient.SELECTED DRAWING: None

The present invention discloses a method for selectively synthesizing an empagliflozin intermediate. By selectively hydrogenating and reducing gluconolactone to chiral hemiacetal, and then directly performing a dehydroxy arylation coupling reaction with an aryl halide compound under the action of a catalyst to obtain an intermediate compound Ⅳ of empagliflozin. The beneficial effects of the present invention are as follows: Through the selective synthesis of chiral hemiacetal and the direct dehydroxy arylation coupling reaction, the selectivity of the gluconolactone connection reaction is effectively increased, the reaction steps of the overall route are reduced, and the generation of reaction by-products can be effectively reduced; in addition, the synthesis method of the present invention is simple to operate, the product is easy to process, the product yield and purity are relatively high, the raw materials are easily available, and it is suitable for industrial scale-up production.

The present invention relates to a pharmaceutical combination preparation, which comprises all of ezetimibe, rosuvastatin and empagliflozin as active ingredients, and thus can be administered as a single drug, and not through co-administration, in the simultaneous treatment of dyslipidemia and diabetes, thereby increasing patient dosing convenience, minimally affecting dissolution between drugs, ensuring biological equivalence, and providing excellent stability of the active ingredients.

1. The name of the design product: packaging box (empagliflozin tablets). 2. The use of the design product: for product packaging. 3. The design points of the design product: in the combination of shape and pattern. 4. The picture or photo that best indicates the design points: perspective view 1.

To provide a new pharmaceutical composition containing empagliflozin in which the solubility of empagliflozin in water is relatively high.SOLUTION: The present invention includes, for example, a pharmaceutical composition mainly comprising empagliflozin and a polymeric carrier, wherein the content ratio of empagliflozin to the polymeric carrier is within the range of 1:1 to 1:40 (empagliflozin: polymeric carrier) by mass, and empagliflozin is solid-dispersed in an amorphous state.SELECTED DRAWING: Figure 1

The invention discloses an empagliflozin metformin hydrochloride tablet. The tablet sequentially comprises a metformin hydrochloride quick-release tablet core, a quick-release isolating layer, an empagliflozin coating layer and a film coating layer from inside to outside, wherein the metformin hydrochloride quick-release tablet core comprises metformin hydrochloride, polyethylene glycol 4000, a water-soluble diluent, copovidone and an adhesive; the quick release isolation layer comprises hydroxypropyl methyl cellulose, potassium citrate and a plasticizer, and the empagliflozin coating layer comprises empagliflozin, a stabilizer, a film forming material and a plasticizer. The tablet provided by the invention can solve the release problem of empagliflozin and metformin hydrochloride, solves the problem that empagliflozin is easy to generate impurities, and realizes quick release and impurity controllability of the empagliflozin and metformin hydrochloride tablet.

The application discloses a chiral synthesis process of an empagliflozin intermediate, and the process comprises the following steps: dissolving a reactant I in an organic solvent to perform chiral oxidation to alcohol, adding a protecting agent to protect, further reducing a carbonyl in an ester group in a product, and then performing deprotection to obtain a target product, a chiral intermediate compound (S)-(+) 3-hydroxytetrahydrofuran. The application has the advantages that: the chiral alcohol compound is obtained through the oxidation reaction of the relatively cheap raw material under the action of the chiral reagent, the chiral product can be obtained at a high yield, the reaction selectivity is good, the yield is high, the loss of the raw material is reduced, the expensive chiral compound (S)-(+) 3-hydroxytetrahydrofuran is avoided to purchase, the production cost is effectively reduced, meanwhile, the steps are simple, the operation is easy, the raw material is easy to obtain, the product is easy to process, and the application is suitable for industrial large-scale production.