26 results about "Linagliptin" patented technology

The present disclosure provides a pharmaceutical composition for the prevention or treatment of neurodegenerative disorders comprising a phosphodiesterase 5 inhibitor and a glucagon-like peptide 1 (GLP-1) receptor agonist or a dipeptidyl peptidase IV (DPP-4) inhibitor as active ingredients. The phosphodiesterase 5 inhibitor is selected from mirodenafil, sildenafil, vardenafil, tadalafil, udenafil, dasantafil, avanafil, and pharmaceutically acceptable salts, solvates and hydrates thereof. The GLP-1 receptor agonist is selected from semaglutide, exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, tirzepatide, cotadutide, and taspoglutide. The DPP-4 inhibitor is selected from sitagliptin, vildagliptin, saxagliptin, linagliptin, gemigliptin, teneligliptin, alogliptin, evogliptin, and anagliptin. The combination exhibits synergistic effects in reducing intracellular Aβ42, IL1β, and TNFα levels compared to the individual compounds alone.

The present invention relates to a stable pharmaceutical formulation comprising linagliptin or pharmaceutically acceptable forms or derivatives thereof and at least one pharmaceutically acceptable excipient is obtained wherein the manufacturing method is direct compression method, wherein the composition is free of any nitrosamine impurity.

The invention discloses a pharmaceutical composition for treating diabetes and a preparation method thereof.The pharmaceutical composition comprises a tablet core and a coating layer, the tablet core comprises metformin hydrochloride, linagliptin, an adhesive, a stabilizer, a diluent, a flow aid and a lubricant, the stabilizer is composed of sodium hydroxide and meglumine, and the diluent is composed of sodium hydroxide and meglumine. The pharmaceutical composition for treating diabetes mellitus has good dissolution and stability.

A single-layer tablet comprising linagliptin, or a pharmaceutically acceptable salt thereof, metformin hydrochloride, a diluent, a glidant and a lubricant, wherein the tablet is produced by direct compression.

The invention relates to the technical field of pharmacy, and discloses a linagliptin preparation method, which comprises: 1, reacting a compound a and a compound b under an alkaline condition, according to the preparation method of the linagliptin, the high-purity linagliptin is prepared through reaction steps of aromatic nucleophilic substitution reaction, substitution, deprotection and the like and screening reaction conditions of proper material proportion, reaction time, reaction temperature, post-treatment mode and the like, and the process reaction of the method is relatively mild in conditions in the preparation process of an intermediate g; the reaction time is greatly shortened, the mixed solvent is used for crystallization, effective solidification of the product can be realized, the product can be efficiently separated, the product purity is improved, in the process of removing tert-butyl carbonyl protection, efficient dissociation of impurities of a dimer can be realized under the alkaline condition, so that the high-purity linagliptin raw material is obtained, the new raw material is easy to obtain, the production cost is low, and the method is suitable for industrial production. The industrial production requirements of linagliptin can be met to the greatest extent.

The invention relates to a linagliptin and metformin sustained-release composition and a preparation method thereof, and relates to the technical field of pharmaceutical preparations, the linagliptin and metformin sustained-release composition comprises a metformin sustained-release tablet core and a linagliptin coating layer wrapping the metformin sustained-release tablet core; the linagliptin coating layer accounts for 2-3% of the total mass of the composition; the metformin sustained-release tablet core comprises a plain pellet core, a coating layer and a filling agent; wherein the plain pellet core comprises a large-particle-size pellet core of 1.10-1.25 mm, a medium-particle-size pellet core of 0.80-0.95 mm and a small-particle-size pellet core of 0.50-0.65 mm, and the mass ratio of the large-particle-size pellet core to the medium-particle-size pellet core to the small-particle-size pellet core is 15: 60: 25; through particle size grading, pore differentiation design and hydrophobic modification treatment, the drug release curve is optimized, the release uniformity is improved, and meanwhile, the production stability and the consistency of the preparation are improved.

According to the application of the quinacrine and the linagliptin in treatment of glioma, the quinacrine can change the metabolic state of tumor cells, so that the sensitivity of the tumor cells to the linagliptin is increased, the treatment effect is enhanced, and the synergistic effect cannot be achieved by a single medicine. The treatment scheme of the quinacrine combined with the linagliptin is expected to become a new and effective treatment choice. The traditional Chinese medicine composition not only can improve the survival rate of a patient, but also can improve the life quality of the patient, and has important clinical application value and wide market prospect.

To provide a novel polymorph of linagliptin that is stable, and to provide a method for producing a novel polymorph of linagliptin by a safe and simple method that facilitates commercial mass production.SOLUTION: Provided is a novel polymorph of linagliptin that is a compound 1-[ (4-methyl-quinazolin-2- yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine having a peaks at 2θ(°)=6.9, 7.6, 9.2, 14.5, 17.7, 20.9±0.2θ in powder X-ray diffraction. The invention also relates to a method of producing the same.SELECTED DRAWING: Figure 1

To provide a linagliptin-containing pharmaceutical composition, particularly a linagliptin-containing film-coated tablet, and a method for producing the same, which can suppress the delayed disintegration, delayed dissolution, and increase of related substances that occur over time by simpler means. [Solution] The invention provides linagliptin as an active ingredient, along with excipients, disintegrants, binders, and lubricants. The binder used is a polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer or a polyvinyl alcohol / polyethylene glycol / graft copolymer. The uncoated tablets are prepared by a wet granulation method called fluid bed granulation drying. Hypromellose is used as the film coating agent, and the film coating layer does not contain polyethylene glycol, resulting in linagliptin-containing film-coated tablets.

The invention provides a linagliptin tablet which is stable in quality and does not need coating and double-aluminum packaging and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The linagliptin tablet is prepared from 50 parts of medicated pellets, 92 parts of mannitol, 18 parts of pregelatinized starch, 18 parts of corn starch and 2 parts of magnesium stearate, the medicated pellets are prepared from 5 parts of linagliptin, 29-37 parts of mannitol blank pellets, 2-4 parts of shellac and 6-12 parts of kaolin, and the linagliptin tablet is prepared through a fluidized bed bottom spraying technology.

The invention relates to solid pharmaceutical dosage forms comprising an extended release core comprising metformin hydrochloride and one or two immediate release coatings comprising linagliptin and / or empagliflozin.

The present invention provides an injectable depot composition comprising linagliptin and low-dose liraglutide. The combination therapy of linagliptin and low-dose liraglutide provides a synergistic effect in the treatment of obesity compared to the administration of each drug alone. In addition, the administration dose of liraglutide can be reduced compared to the administration of liraglutide alone, and thus the direct cause of side effects related to the gastrointestinal system and the cardiovascular system of liraglutide can be reduced. Furthermore, by the combination of linagliptin, it has the advantage of additionally providing an improvement effect on metabolic diseases and cardiovascular diseases related to blood sugar, blood lipids, blood pressure, fatty liver, etc. In addition, compared to the conventional liraglutide dosage form of once-daily subcutaneous injection, the depot composition of linagliptin and liraglutide of the present invention can significantly improve patient convenience and patient compliance by unifying the administration route and improving the administration cycle.

The present invention relates to pharmaceutical compositions of linagliptin, pharmaceutical dosage forms, their preparation, their use and methods for treating metabolic disorders.

The application discloses a key amino acid induced new crystal form of linagliptin based on protein-drug interaction structure mining and a preparation method thereof; and the technical scheme is that key amino acids are introduced into a solvent crystallization system of linagliptin to induce five new crystal forms of linagliptin; the preparation method does not need to use a large amount of organic solvents, has the characteristics of being simple, precise and efficient, has strong crystal form regulation capacity, is energy-saving, environment-friendly and safe, and is easy to realize green industrial production.

The invention discloses a pharmaceutical composition containing linagliptin and metformin hydrochloride and a preparation method thereof.According to the composition, a small amount of meglumine (0.01%-1.0% w / w) is added, a linagliptin mixture and a metformin hydrochloride mixture are separately granulated, the growth of an impurity A, an impurity B and total impurities in an obtained linagliptin and metformin hydrochloride tablet is slow, the content of impurities in the linagliptin and metformin hydrochloride tablet is low, and the content of impurities in the linagliptin and metformin hydrochloride tablet is high. The stability of the composition is obviously improved, and the dissolution effect is not influenced. According to the preparation method of the composition, auxiliary materials in the preparation process are easy to obtain, the price is low, and the composition is suitable for commercial production.

The present application relates to the field of medicine, in particular to the use of POU2F2 gene or protein in screening products for preventing or treating atherosclerosis. The present application first discloses that POU2F2 can be used as a key pathogenic target of atherosclerosis, and on this basis, a candidate drug linagliptin is screened. The experimental results show that in the in vitro atherosclerosis model, linagliptin can significantly inhibit the expression of POU2F2 and down-regulate the levels of inflammatory factors and adhesion molecules. The findings clarify the mechanism of linagliptin in regulating POU2F2 related signal pathways, inhibiting vascular inflammatory response and reducing vascular endothelial damage, and fully show that it has a good clinical application prospect in preparing drugs for preventing or treating atherosclerosis and its related cardiovascular and cerebrovascular diseases.

A monolayer tablet comprising metformin granules and linagliptin granules, wherein the linagliptin granules are coated with a basic butylated methacrylate copolymer and the process of its preparation.

The present invention provides an obesity treatment regimen for reducing side effects by low-dose combination administration of linagliptin and liraglutide. The combination therapy of linagliptin and low-dose liraglutide provides a synergistic effect in obesity treatment compared to administration of each drug alone. Furthermore, the administration dose of liraglutide can be reduced compared to administration of liraglutide alone, and thus the direct cause of side effects related to the gastrointestinal system and the cardiovascular system of liraglutide can be reduced. Furthermore, by the combination of linagliptin, it has the advantage of additionally providing an improvement effect on metabolic diseases and cardiovascular diseases related to blood sugar, blood lipids, blood pressure, fatty liver, etc.

The invention belongs to the technical field of medicine oral solid preparations, and particularly relates to a linagliptin tablet and a preparation method thereof. The linagliptin tablet adopts a preparation process of a powder direct compression method, and raw materials and auxiliary materials comprise linagliptin, a filling agent, a disintegrating agent, a flow aid, a lubricating agent and a film coating premix. The filler is composed of one or two of microcrystalline cellulose, spray-dried lactose and pregelatinized starch; the disintegrating agent is prepared from one or two of polyvinylpolypyrrolidone, sodium carboxymethyl starch and low-substituted hydroxy propyl cellulose; the flow aid is prepared from one of silicon dioxide or superfine silica powder; the lubricant is magnesium stearate; and the film coating agent is a gastric-soluble film coating premix. The preparation method adopts a powder direct compression process, is simple and easy to implement, saves energy, reduces consumption, optimizes the composition and dosage of auxiliary materials, is high in yield, solves the problem of low content in a granulation process, optimizes the disintegration and dissolution behaviors of the preparation, and is suitable for industrial production.

The present invention relates to a parenteral composition of Linagliptin or its salt and one or more pharmaceutically acceptable excipient. The parenteral composition of Linagliptin or its salt and one or more pharmaceutically acceptable excipient provide immediate response, minimization of side effect, improving bioavailability and achieving the desired drug blood level rapidly and provide better patient compliance in the treatment of type 2 diabetes mellitus.

The present invention relates to a pharmaceutical formulation containing three drugs: linagliptin, dapagliflozin, and metformin, and being prepared as a bilayered tablet comprising: an immediate-release layer comprising dapagliflozin and linagliptin as active ingredients; and a sustained-release layer comprising metformin as an active ingredient, wherein the immediate-release layer includes a lipophilic polyphenolic antioxidant as a stabilizer, and the sustained-release layer uses carboxymethylcellulose sodium and hypromellose 2208 together as sustained-release agents. In the pharmaceutical formulation according to the present invention, delamination of the formulation is suppressed, thus enabling the preparation of a high-quality formulation, and the formation of related substances of the active ingredients is suppressed, thus enabling long-term storage. Thus, the pharmaceutical formulation can increase medication compliance as a pharmaceutical composition for improving glycemic control in patients with insufficient glycemic control.

The present invention relates to methods for preventing or treating of metabolic disorders and related conditions, such as in certain patient groups. The present invention relates to treatment of genotyped diabetic patients with DPP-IV inhibitors such as linagliptin. In addition, the present invention relates to pharmaceutical compounds, compositions or combinations, methods of preventing or treating a metabolic disorder in a patient, improving glycemic control, preventing, slowing progression of, delaying or reversing progression to type 2 diabetes mellitus, reducing body weight or preventing an increase in body weight, preventing or treating the degeneration and / or functionality decline of pancreatic beta cells, and uses of the pharmaceutical compositions for preparing pharmaceuticals.

The application provides linagliptin tablets with stable quality, without coating and double aluminum packaging and a preparation method, and belongs to the technical field of pharmaceutical preparations. The linagliptin tablet is composed of drug-containing pellets 50 parts, mannitol 92 parts, pregelatinized starch 18 parts, corn starch 18 parts and magnesium stearate 2 parts. The drug-containing pellets are composed of linagliptin 5 parts, mannitol blank pellet core 29-37 parts, shellac 2-4 parts and kaolin 6-12 parts, and are prepared through a fluidized bed bottom spraying process.

The invention relates to the technical field of drug detection, and discloses a linagliptin tablet in-vitro dissolution curve determination method, which comprises: 1, preparing a test solution: taking linagliptin tablets, taking 900ml of a 0.1 mol / L hydrochloric acid solution as a dissolution medium, and carrying out dissolution according to a dissolution instrument basket method, taking out a proper amount of the dissolved solution at different sampling time points, filtering, and taking a subsequent filtrate as a test solution; step 2, preparation of a reference substance solution: taking a proper amount of a linagliptin reference substance, precisely weighing the linagliptin reference substance, dissolving the linagliptin reference substance with a dissolution medium, and diluting the linagliptin reference substance to prepare a solution containing 5.6 micrograms per 1ml of the linagliptin reference substance; the method for determining the in-vitro dissolution curve of the linagliptin tablet has the characteristics of good dissolution property, strong specificity, good stability and the like on the linagliptin tablet. The method can effectively distinguish the difference between the self-made preparation and the reference preparation, has universality and practicability, and is simpler, more convenient and more efficient to operate.

The present invention relates to the technical field of medicine, particularly to a linagliptin synthesis and purification process, which comprises: 1, reacting a compound 1 with 1-bromo-2-butyne in an organic solvent under the condition of sodium bicarbonate at a preset temperature, and carrying out separation and purification to obtain a compound 2; 2, reacting the compound 2 with 2-chloromethyl-4-methylquinazoline in an organic solvent under alkaline conditions, and separating and purifying to obtain a compound 3; 3, the compound 3 and an acidified amino compound react in an organic solvent under the alkaline condition, and a linagliptin product is obtained through separation and purification. In the step 1, sodium bicarbonate is used as alkali, so that generation of a disubstituted impurity A is avoided, and the yield and the purity of the compound 2 are further improved. 30-40% of water is added in the reaction in the step 3, the reaction rate is increased, the position isomer impurity C is controlled to be smaller than or equal to 0.1%, and the purity of 99.9% can be achieved only through one-time crystallization in aftertreatment.