33 results about "Dapagliflozin" patented technology

The present invention discloses modified-release bilayer tablets consisting of two layers, layer 1 consisting 500 mg sustained release metformin and layer 2 consisting 250 mg normal release metformin and 5mg / 10mg delayed-release dapagliflozin. This formulation is meticulously designed to regulate blood glucose levels effectively over an extended period. Immediate-release metformin swiftly addresses acute glucose spikes, while sustained-release metformin ensures prolonged glucose control, minimizing fluctuations throughout the day. The delayed-release dapagliflozin component allows for controlled and timed release, managing persistent hyperglycemia synergistically with metformin. By optimizing efficacy and minimizing glucose fluctuations, this innovative formulation offers a promising solution for stable glycemic control in individuals with diabetes. Present invention aims to improve patient outcomes and enhance overall quality of life by maintaining stable glucose levels and reducing the risk of complications associated with uncontrolled diabetes.

The application discloses a preparation method of a key intermediate of dapagliflozin, and belongs to the technical field of preparation of medical intermediates. The preparation method of the key intermediate of dapagliflozin comprises the following steps: 1, 1-ethoxy-4-methylbenzene is prepared by using p-cresol, sodium hydroxide and diethyl sulfate; 2, (4-ethoxybenzyl) phenyl sulfide is prepared by using 1-ethoxy-4-methylbenzene, thiophenol, a palladium catalyst, an alkali and an oxidant; 3, 1-benzyl-4-ethoxybenzene is prepared by using (4-ethoxybenzyl) phenyl sulfide under a hydrogen atmosphere; 4, 4-ethoxy-2'-chlorobenzhydrol is prepared by carrying out chlorination reaction on 1-benzyl-4-ethoxybenzene; and 5, 5-bromo-2-chloro-4'-ethoxybenzhydrol is prepared by carrying out bromination reaction on 4-ethoxy-2'-chlorobenzhydrol. The yield and purity of 5-bromo-2-chloro-4'-ethoxybenzhydrol prepared by the method are higher, the process is safer, and the production cost is reduced.

Disclosed is a method of treating patients with microvascular angina by using a combination of zibotentan and dapagliflozin.

The invention relates to a dapagliflozin impurity and a preparation method thereof, 5-bromo-2-chlorobenzoic acid (IV) is used as a raw material, (5-bromo-2-chlorphenyl) (4-ethyoxyl phenyl) ketone (III) is prepared through chlorination and Friedel-Crafts acylation, (5-bromo-2-chlorphenyl) (4-ethyoxyl phenyl) methanol (II) is obtained through reduction, and the benzhydryl ether impurity (I) is obtained through condensation under the catalysis of iodine. The preparation method has the advantages of simple operation, low cost, easily available raw materials and good product purity.

Methods for treating high proteinuria chronic kidney disease and / or at least one disease, disorder, or condition associated therewith in patients by the use of a fixed-dose combination of zibotentan and dapagliflozin are disclosed.

The utility model discloses a dapagliflozin preparation reaction device with a protection function, and relates to the technical field of chemical medicine production equipment. Comprising a reaction kettle body, a protection part is rotatably arranged in an inner cavity of the reaction kettle body, a main material enters the reaction kettle body through a main material pipe, an ingredient enters an ingredient barrel in the reaction kettle body through an ingredient pipe, and at the moment, a sealing disc is tightly attached to the bottom of an inner cavity of the ingredient barrel to seal the bottom of the ingredient barrel. The main material and the auxiliary material do not react immediately, so that the material and the auxiliary material are prevented from violently reacting to generate material flushing, and liquid medicine in the reaction kettle body is prevented from being sprayed out through the auxiliary material pipe and the main material pipe to injure personnel.

The present disclosure is directed to methods of treating patients with heart failure with reduced ejection fraction (HFrEF), with and without Type 2 diabetes, with an SGLT2 inhibitor, such as dapagliflozin. The methods disclosed herein can reduce the risk of a composite outcome of a first episode of worsening heart failure (hospitalization for heart failure or an urgent heart failure visit) or death from cardiovascular causes. Each of the three components of this composite outcome can also be reduced, as well as the total number of heart failure hospitalizations and deaths from cardiovascular causes. SGLT2 inhibitors, such as dapagliflozin, can also reduce a worsening of heart failure symptoms. The methods disclosed herein can also improve heart failure symptoms, health status, and quality of life.

The present disclosure relates to the endothelin receptor antagonist (ERA) zibotentan in combination with the sodium-dependent glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin for use in the treatment of certain endothelin related diseases.

The invention relates to the technical field of biological medicine, in particular to application of tripterine or medicinal salt thereof in preparation of medicine for treating ketoacidosis or symptoms caused by ketoacidosis. The invention provides application of tripterine or medicinal salt thereof in preparation of a medicine for treating ketoacidosis or symptoms caused by ketoacidosis. The result of the specific embodiment of the invention shows that the tripterine can obviously reduce the mouse serum beta-hydroxybutyric acid level caused by hunger; the tripterine can be used for remarkably reducing the expression of HMGCS2 in the liver of a mouse; the dapagliflozin remarkably promotes the level of beta-hydroxybutyric acid, and the tripterine remarkably reduces the level of mouse serum beta-hydroxybutyric acid caused by treatment of the dapagliflozin. Therefore, tripterine can be used for treating or improving ketoacidosis or symptoms caused by ketoacidosis. The invention provides a new technical scheme for treatment and improvement of ketoacidosis or symptoms caused by ketoacidosis.

The present disclosure provides methods of preparing pharmaceutical formulations containing dapagliflozin and uses thereof. The method for preparing the dapagliflozin-containing pharmaceutical preparation comprises the following steps: dissolving dapagliflozin and / or a hydrate thereof and lactose in an aqueous solution of alcohol and / or ketone to ensure that the mass ratio of the dissolved lactose to the dapagliflozin is (1-9.4): 1 to obtain a coating solution; and preparing an upper drug coating layer by using the coating liquid. Therefore, the dissolution stability of dapagliflozin in the pharmaceutical preparation in the storage process can be improved.

Provided herein are compositions and methods for reducing or preventing ovarian aging comprising: administering to a subject in need of a reduction or prevention of ovarian aging an effective amount of an SGLT2 antagonist. Examples of SGLT2 antagonists include canagliflozin, bexagliflozin, dapagliflozin, empagliflozin, ertugliflozin, sotagliflozin, phlorizin, or combinations thereof.

The invention relates to the field of medicines, and particularly discloses application of dapagliflozin to preparation of a medicine for preventing and / or treating obesity-related salt-sensitive hypertension. According to the application, the new application of dapagliflozin in prevention and treatment of a specific and high-risk disease subtype of obesity-related salt-sensitive hypertension is defined for the first time. Experiments prove that dapagliflozin can improve the sodium treatment function of the kidney and promote urine sodium excretion by inhibiting abnormal continuous coupling of a Na / K-ATPase / c-Src signal axis in the kidney. The discovery reveals a new kidney protection mechanism of dapagliflozin independent of the hypoglycemic effect, and provides a new drug use and a treatment scheme for clinical prevention and treatment of obesity-related renal sodium metabolism disorders and salt-sensitive hypertension.

The application discloses a compound sustained-release tablet for treating diabetes and a preparation method thereof. The compound sustained-release tablet for treating diabetes comprises a dapagliflozin layer, a metformin sustained-release layer and a coating layer. The metformin sustained-release layer comprises a release modifier which is composed of hydroxypropyl methyl cellulose K4M and hydroxypropyl methyl cellulose K35M. Through screening and optimization of the selection and proportioning of a drug source, sustained-release materials and auxiliary agents, the two active components in the compound sustained-release tablet are released gently and durably, and the absorption of the drug is good.

This invention belongs to the field of pharmaceutical preparation technology, specifically relating to a compound preparation of dapagliflozin and metformin hydrochloride and its preparation method. The compound preparation includes dapagliflozin granules and metformin hydrochloride granules; the dapagliflozin granules include dapagliflozin technical, β-cyclodextrin, filler, disintegrant, and lubricant; the metformin hydrochloride granules include metformin hydrochloride technical, sustained-release material, filler, binder, and lubricant; wherein the particle size D of the dapagliflozin raw material is... (90) The concentration ranges from 5μm to 50μm. This invention addresses the problem of inconsistent dosages of dapagliflozin and metformin hydrochloride, making it difficult to control content uniformity. Simultaneously, it effectively overcomes the low melting point and poor solubility of dapagliflozin, achieving dissolution curves for both dapagliflozin and metformin hydrochloride consistent with the original marketed products.

The invention belongs to the technical field of medicines, and particularly relates to application of radix achyranthis bidentatae in preparation of an anti-fibrosis medicine for treating myocardial infarction and the medicine. The medicine for treating fibrosis after myocardial infarction comprises a carrier and dapagliflozin, the carrier is radix achyranthis bidentatae, and the dapagliflozin is loaded on the radix achyranthis bidentatae. The invention discloses the application of radix achyranthis bidentatae in preparation of the anti-fibrosis medicine for treating myocardial infarction for the first time, and it is found in anti-myocardial fibroblast fibrosis experiments that expression of alpha-SMA and Col-I / III in TGF-beta + radix achyranthis bidentatae-DAPA group cells is obviously reduced, so that the medicine prepared by the invention can be used for treating anti-fibrosis after myocardial infarction.

The invention relates to the technical field of medicines, in particular to application of dapagliflozin to preparation of a medicine for preventing or treating uveitis. The invention discloses the key regulation effect of RanBP2 on CD4 + T cell proliferation, immature CD4 + T cell post-translational modification and differentiation bias in uveitis and other autoimmune diseases for the first time, and researches find that dapagliflozin can relieve the inflammatory response of EAU mice and refractory non-infectious uveitis patients, correct T cell imbalance, inhibit the apoptosis of the EAU mice and inhibit the apoptosis of the EAU mice and inhibit the apoptosis of the EAU mice. The uveitis disease symptoms of animal models and human beings can be effectively improved, so that a brand new molecular mechanism and a treatment target are provided for immunotherapy of autoimmune diseases.

The present disclosure is directed to methods of treating patients with chronic kidney disease (CKD), with and without Type 2 diabetes, with an SGLT2 inhibitor, such as dapagliflozin.

Methods for treating chronic kidney disease and liver fibrosis in patients using a fixed-dose combination of zibotentan and dapagliflozin are disclosed.

The invention discloses a method for detecting related substances of dapagliflozin tablets, and belongs to the technical field of medicine detection. The related substances comprise an impurity 383-1D, an impurity 383-1E, an impurity 383-1F and an impurity 383-1G, and the detection method comprises the following detection conditions: adopting a high performance liquid chromatography method, taking octadecyl silica gel as a chromatographic column, taking potassium hydrogen phosphate as a buffer solution, taking acetonitrile as a diluted solution, taking a methanol-water solution as a mobile phase A, taking an acetonitrile-water solution as a mobile phase B, carrying out gradient elution, and carrying out gradient elution to obtain the impurity 383-1D, impurity 383-1E, impurity 383-1F and impurity 383-1G. And separating the related substances of the dapagliflozin tablet, and detecting to obtain the amount of the related substances. By detecting the amount of related substances, the production of the related substances in the production process is controlled, so that the product quality of the medicine is guaranteed.

The present invention relates to pharmaceutical compositions in multi-layer tablet form comprising dapagliflozin or a pharmaceutically acceptable salt thereof and metformin or a pharmaceutically acceptable salt thereof as active substances.

The invention discloses a synthesis process of dapagliflozin. The method comprises the following steps: (1) preparing a Grignard reagent THF solution of 1-chloro-2-(4-ethoxybenzyl)-4 iodobenzene; (2) preparing 2, 3, 4, 6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide; (3) in the presence of a catalyst containing anhydrous cerium chloride and titanium tetraisopropoxide, carrying out coupled reaction on the Grignard reagent THF solution obtained in the step (1) and the 2, 3, 4, 6-tetra-O-acetyl-alpha-D-glucopyranose bromide obtained in the step (2) at the temperature of-15 to-10 DEG C to obtain an acetylated dapagliflozin intermediate; and (4) carrying out deprotection reaction on the acetylated dapagliflozin intermediate obtained in the step (3) to obtain the dapagliflozin. Under a composite catalytic system, the reaction shows excellent stereoselectivity, the required beta-configuration C-glycoside product is specifically generated, and the generation of by-products such as alpha-isomers and the like is effectively inhibited.

Methods for treating chronic kidney disease and liver fibrosis in patients using a fixed-dose combination of zibotentan and dapagliflozin are disclosed.

The present disclosure relates to the endothelin receptor antagonist (ERA) zibotentan in combination with the sodium-dependent glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin for use in the treatment of certain endothelin-related diseases.

The invention relates to a method for preparing a dapagliflozin impurity by catalysis of ferric iron, which comprises the following steps of: preparing 4-chloro-3-[(4-ethyoxyl phenyl) methyl] phenyl magnesium bromide (II) from 5-bromo-2-chloro-4 '-ethyoxyl diphenylmethane (III) serving as a raw material, and coupling under the catalysis of ferric trichloride to obtain a coupled impurity (I). The preparation method has the advantages of simple operation, low cost, easily available raw materials and good product purity.

The invention relates to the technical field of pharmaceutical preparations, in particular to a dapagliflozin tablet and a preparation method thereof. The dapagliflozin tablet comprises the following raw materials in parts by mass: 1-5 parts of dapagliflozin, 50-80 parts of a filler, 5-15 parts of a disintegrating agent, 1-5 parts of an adhesive, 0.5-3 parts of a stabilizer and 0.5-2 parts of a lubricant, according to the dapagliflozin tablet and the preparation method thereof, raw materials and the preparation method are improved, the in-vitro dissolution of the prepared dapagliflozin tablet can be consistent with that of an original drug, the dissolution uniformity is superior to that of the original drug, related substances of the preparation are not remarkably increased, the stability is good, the preparation process is simple, and the preparation method is suitable for industrial production. The method is suitable for large-scale low-cost production and application.

The invention discloses a specific quantitative detection method for 2-epimer and alpha-isomer in dapagliflozin, which adopts high performance liquid chromatography and uses a chiral chromatographic column as a separation unit. A filling agent of the chiral chromatographic column is [N-(R)-(+)-1-(1-naphthyl) ethyl] methacrylamide bonded silica gel; the mobile phase is obtained by compounding a disodium hydrogen phosphate solution and acetonitrile; the dapagliflozin 2-epimer and the dapagliflozin alpha-isomer are quantitatively determined by isocratic elution, the flow velocity of a mobile phase is 0.5-1.5 ml / min, the column temperature is 20-40 DEG C, efficient separation and quantitative detection of the dapagliflozin 2-epimer and the dapagliflozin alpha-isomer can be realized, the separation degree is greater than 1.5, quantitative detection of the 2-epimer can be carried out, and the method is suitable for industrial production. And the method has good sensitivity, specificity, precision, linearity, accuracy, solution stability and durability.

The present disclosure provides methods of preparing pharmaceutical formulations containing dapagliflozin and uses thereof. The method for preparing the dapagliflozin-containing pharmaceutical preparation comprises the following steps: dissolving dapagliflozin and / or a hydrate thereof and lactose in an aqueous solution of alcohol and / or ketone until the mass ratio of the dissolved lactose to the dapagliflozin is (0.1-0.5): 1 to obtain a binder; and mixing the binder with other auxiliary materials to prepare the tablet core. Therefore, the dissolution stability of dapagliflozin in the pharmaceutical preparation in the storage process can be improved.