53 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 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 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.

Provided are a composite tablet comprising a first layer containing dry granules containing sitagliptin, or a pharmaceutically acceptable salt thereof, or a hydrate thereof, and dapagliflozin, or a pharmaceutically acceptable salt thereof, or a hydrate thereof, and a second layer containing wet granules containing metformin, or a pharmaceutically acceptable salt thereof, and colloidal silicon dioxide, and a method for producing the same.

The invention discloses a preparation method of a dapagliflozin intermediate 5-bromine-2-chlorine-4 '-ethyoxyl diphenylmethane, which comprises the following steps: carrying out nucleophilic substitution reaction on 4-bromine-1-chlorine-2-fluorobenzene and 4-ethyoxyl phenylacetate, and then hydrolyzing and decarboxylating to obtain the dapagliflozin intermediate 5-bromine-2-chlorine-4'-ethyoxyl diphenylmethane. By optimizing the preparation route, the reaction utilization rate, the product yield and the product purity of the raw materials are improved, high-risk and high-pollution chemicals are prevented from being used, and the method is convenient to operate, safe, environmentally friendly, efficient in reaction and beneficial to industrial implementation.

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.

The invention relates to a dapagliflozin and metformin sustained-release tablet and a preparation method thereof, corresponding anti-spallation stabilizers are respectively added into dapagliflozin and metformin layer materials in a prescription, and the problems of temperature, humidity and spallation generated in the storage process can be reduced.

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 invention discloses a method for preparing dapagliflozin based on a microchannel reaction technology, which comprises the following reaction steps: (1) reacting a 5-bromo-2-chloro-4 '-ethoxydiphenylmethane solution, a 2, 3, 4, 6-tetraacetoxy-alpha-D-glucopyranose bromide solution and an organic metal reagent solution in a microchannel reactor 1 to obtain a compound as shown in a formula IV; and (2) reacting the compound solution as shown in the formula IV and the deacetylation reagent solution in a micro-channel reactor 2 to obtain dapagliflozin. According to the method, acetyl-protected bromoglucose is adopted as a reaction material, multiple derivatization of hydroxyl in a traditional process and a reduction reaction step in the traditional process are avoided, the dapagliflozin is prepared by adopting a micro-channel reaction technology, the synthesis steps are simple, the yield is high, and the method is suitable for industrial production. A target product can continuously flow out while reaction raw materials are continuously pumped, the operation is convenient, and the reaction safety is high.

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.

Provided is a preparation method for a dual sustained-release dapagliflozin tablet. The dapagliflozin tablet consists of an enteric-soluble inner core, a gastric-soluble middle core, and a coating. The gastric-soluble middle core consists of the following raw and auxiliary materials, in percentage by weight: 5-7% of dapagliflozin, 10% of voglibose, 69-73% of a microcrystalline cellulose complex, 2-4% of a disintegrating agent, and 10% of an HPMC coating solution; and the enteric-soluble inner core consists of the following raw and auxiliary materials, in percentage by weight: 5-7% of dapagliflozin, 8% of Yuanzhen sugar, 63-77% of a microcrystalline cellulose complex, 4-8% of a disintegrating agent, 8% of an HPMC coating solution, and 6% of alginic acid. The prepared dapagliflozin tablet has the advantages of high dissolution rates of the pharmaceutical ingredients, good release effect, and low pressure on the kidneys.

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.

Disclosed are methods for treating high proteinuria chronic kidney disease and / or at least one disease, disorder or condition associated therewith in a patient by using a fixed dose combination of zipotentan and dapagliflozin.

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.

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.

The invention discloses a method for rapidly preparing a dapagliflozin crude product based on a microchannel continuous flow technology, which comprises the following steps: by taking 2-chloro-5-(1-methoxy-D-glucopyranose-1-yl)-4 '-ethyoxyl diphenylmethane and a reducing agent as raw materials, carrying out liquid-liquid two-phase reduction reaction in a microreactor to generate the dapagliflozin crude product, according to the present invention, the traditional kettle type reaction is changed into the continuous process, the reaction selectivity is substantially improved, the generation of the isomer is reduced, the amplification effect is inhibited to the maximum extent, the yield of the obtained product is more than 90%, the purity is more than 90%, and the safe, green and efficient method is provided for the synthesis of the dapagliflozin crude product.

The invention discloses a single crystal of a dapagliflozin intermediate as well as a preparation method and application of the single crystal. The single crystal has a monoclinic system and a P21 space group; the cell parameters are as follows: alpha = 90 degrees, beta = 93.900 (6) degrees and gamma = 90 degrees, and are consistent with the spatial configuration of dapagliflozin. The single crystal can be used for confirming the spatial configuration of dapagliflozin intermediates and bulk drugs and researching the chiral purity of dapagliflozin; the preparation method is good in reproducibility, the crystal is colorless acicular crystal at normal temperature, the morphology is good, and the purity is up to 99.9%.

The invention belongs to the technical field of biological medicine, and particularly relates to an experimental method for regulating immune infiltration of a breast cancer mouse model, an immunomodulator for inhibiting breast cancer and application of the immunomodulator. The experimental method for regulating immune infiltration of the breast cancer mouse model comprises the following steps: applying dapagliflozin to the breast cancer mouse model; the experimental method is used for non-disease diagnosis and treatment purposes. According to the experimental method for regulating immune infiltration of the breast cancer mouse model, a new way for carrying out immune regulation on the breast cancer mouse model can be provided for researchers, so that the researchers can regulate the immune condition of the breast cancer mouse model as required, and further, deeper research on treatment of breast cancer is facilitated.

Disclosed is a method of treating or preventing skeletal sequelae of coronavirus infection in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an endothelin receptor antagonist, with the proviso that the endothelin receptor antagonist is not co-administered with dapagliflozin or niclosamide. The skeletal sequelae may include one or more of arthralgia, viral arthritis, osteopenia, osteochondral injury, and osteoporosis.

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.