22 results about "Sitagliptin Phosphate" patented technology

The present invention provides a method for determining the content of dimer impurities in sitagliptin phosphate, belongs to the technical field of drug analysis, and performs chromatographic analysis on a control solution, a test solution, and a test solution spiked with a sample. The control solution is a dimer impurity reference solution, the test sample is a sitagliptin phosphate test sample, and the test solution spiked with a sample is a mixed solution of the sitagliptin phosphate test sample and dimer impurities. The present invention establishes a method for determining the content of dimer impurities in sitagliptin phosphate by HPLC, and quantitatively detects dimer impurities that may exist in sitagliptin phosphate. The present invention has strong specificity, high sensitivity, good repeatability, and good durability, and is of great significance for the quality control of dimer impurities in sitagliptin phosphate, and provides a basis for the establishment of the quality standard of sitagliptin phosphate.

The invention provides a sitagliptin and metformin sustained-release pharmaceutical composition as well as a preparation method and application thereof, and relates to the technical field of sustained-release preparations. The pharmaceutical composition comprises a sustained-release tablet core and a quick-release coating layer, the sustained-release tablet core comprises an active ingredient metformin hydrochloride and a sustained-release framework material hydroxypropyl methylcellulose, and the sustained-release tablet core does not contain microcrystalline cellulose; the quick-release coating layer comprises an active component sitagliptin phosphate; the weight ratio of metformin hydrochloride to hydroxypropyl methylcellulose in the sustained release tablet core is 50: (24-27). The composition utilizes a double-layer structure to realize double-phase release of the medicine; the microcrystalline cellulose is removed, and the specific ratio of the active component to the framework material is limited, so that the moldability and ideal dissolution behavior of the preparation are ensured while the tablet weight is remarkably reduced to improve the swallowing compliance, and the technical problem that the slow-release framework function is difficult to maintain under the condition that the weight of a high-drug-loading-capacity compound preparation is greatly reduced is successfully solved.

The application provides a sitagliptin and metformin hydrochloride sustained-release pharmaceutical composition and a preparation method and application thereof, and relates to the technical field of sustained-release preparations. The pharmaceutical composition comprises a sustained-release tablet core and a quick-release coating layer; the sustained-release tablet core comprises active ingredients metformin hydrochloride and a sustained-release matrix material hydroxypropyl methyl cellulose, and the sustained-release tablet core does not contain microcrystalline cellulose; the quick-release coating layer comprises active ingredients sitagliptin phosphate; the weight ratio of metformin hydrochloride to hydroxypropyl methyl cellulose in the sustained-release tablet core is 50:(24-27). The composition realizes double-phase release of drugs by using a double-layer structure; by removing the microcrystalline cellulose and limiting the specific ratio of active ingredients to the matrix material, the forming property of the preparation and the ideal dissolution behavior are ensured while the tablet weight is significantly reduced to improve the swallowing compliance, and the technical problem that a high drug loading compound preparation is difficult to maintain the function of the sustained-release matrix under a large amount of weight reduction is successfully solved.

The utility model discloses a drying device for preparing sitagliptin phosphate, which belongs to the technical field of medicine production and comprises a base, a drying box is mounted on the base, a conveying belt is arranged in the drying box, a plurality of air holes are formed in the conveying belt, a plurality of rotating rollers are mounted in the conveying belt, and the rotating rollers are arranged on the drying box. The two ends of the rotating roller are connected with the interior of the drying box, and a rotating shaft is installed on the rotating roller at one end in the conveying belt. According to the drying device for sitagliptin phosphate preparation, the conveying belt is driven to rotate, meanwhile, the air bellow installed on the base works, air generated by the air bellow can move upwards through the air blowing opening, the air is heated through the electric heating wire to form hot air, and the hot air moves upwards to penetrate through air holes formed in the conveying belt so as to dry medicine on the conveying belt; and the conveyor belt rotates to move the dried medicines to the discharge port, and then the medicines slide down from the inclined plate, so that the subsequent collection work is facilitated, and the time and energy of workers are saved.

A prolonged-release pharmaceutical composition containing berberine and sitagliptin for the treatment of diabetes, the composition comprising: a) Berberine hydrochloride in an amount of 400 mg to 600 mg; b) Sitagliptin phosphate in an amount of 80 mg to 120 mg; c) hydroxypropylmethylcellulose (HPMC K100M) as a controlled release polymer in an amount of 100 mg to 200 mg; d) Microcrystalline cellulose (MCC) as diluent in an amount of 80 mg to 150 mg; e) polyvinylpyrrolidone (PVP K30) as a binder in an amount of 30 mg to 50 mg; f) Colloidal silicon dioxide as a lubricant in an amount of 5 mg to 15 mg; g) magnesium stearate as a lubricant in an amount of 3 mg to 10 mg; h) talc as a lubricant in an amount of 3 mg to 10 mg; and i) a film-coating polymer selected from HPMC-based coatings or Opadry in an amount of 10 mg to 30 mg; wherein the composition provides controlled release of berberine and sitagliptin over 24 hours, maintaining an effective plasma concentration suitable for glycemic control and reducing dosing frequency.

The utility model relates to the technical field of medicine production, in particular to screening equipment for producing sitagliptin phosphate tablets, which comprises a device box, a screening cylinder, a raking mechanism, a driving mechanism and a feeding hopper, the screening barrel is rotationally arranged in the device box, and one end of the screening barrel extends out of the device box; the material raking mechanism is rotationally arranged in the device box, and one end of the material raking mechanism extends into the screening barrel; the driving mechanism is arranged on the device box, and the output end of the driving mechanism is in transmission connection with the screening barrel and the raking mechanism; the feeding hopper is installed on the device box, and the discharging end of the feeding hopper extends into the screening barrel through the raking mechanism. According to the tablet screening device, the driving mechanism, the screening barrel and the raking mechanism are arranged in a matched mode, the driving mechanism drives the screening barrel and the raking mechanism to rotate, the tablet screening speed can be increased, bonded tablets can be separated, the possibility that the tablets are accumulated in the screening barrel is effectively reduced, and then the workload of operators is reduced.

The invention relates to a composition of a compound hypoglycemic drug and a preparation method of the composition, and relates to the technical field of pharmaceutical compositions. The composition of the compound hypoglycemic drug mainly comprises metformin hydrochloride and sitagliptin phosphate, a filling agent is microcrystalline cellulose and the like, a disintegrating agent is croscarmellose sodium and the like, a binding agent is povidone K30 and the like, a lubricating agent is sodium stearyl fumarate and the like, a wetting agent is lauryl sodium sulfate and the like, and a disintegrating agent is microcrystalline cellulose and the like. The sitagliptin metformin tablet is prepared by adopting a core-coated tablet preparation technology, firstly, sitagliptin is prepared into small tablets by adopting a powder direct compression process, metformin hydrochloride is prepared into particles by adopting a wet granulation process, then the small sitagliptin tablets are pressed into tablet cores to obtain finished tablets, and then the finished tablets are coated to obtain the sitagliptin metformin tablet. The preparation process can ensure the content uniformity of the product and improve the storage stability of the product.

The invention discloses an efficient catalytic synthesis preparation method of sitagliptin phosphate, and belongs to the technical field of medicine synthesis. According to the key points of the technical scheme, 2, 4, 5-trifluorophenylacetic acid is taken as a plurality of synthesis paths of an initial raw material, and the methods relate to key reaction steps of condensation, asymmetric hydrogenation, hydrolysis, catalytic hydrogenation and the like. By comparing and analyzing the advantages and disadvantages of different synthesis routes, the common problems of tedious reaction steps, high production cost, dependence on expensive catalysts and the like in the traditional synthesis method are found.

This invention provides a stable sitagliptin phosphate pharmaceutical composition comprising the following components: the active ingredient sitagliptin phosphate, a sulfite stabilizer, a filler, a disintegrant, and a lubricant. By adding a sulfite stabilizer to the sitagliptin phosphate pharmaceutical composition, this invention effectively controls the formation of nitrosamine impurities (NTTP) in the sitagliptin pharmaceutical composition, ensuring the quality stability of the sitagliptin phosphate pharmaceutical composition. The sitagliptin phosphate pharmaceutical composition of this invention has a dissolution effect comparable to a reference. The stable sitagliptin phosphate pharmaceutical composition of this invention is prepared using conventional preparation processes and is suitable for industrial production.

The invention relates to the technical field of medicine analysis, and discloses an analysis method for measuring NTTP in sitagliptin phosphate, which comprises the following steps: S110: preparation of a test solution: taking a proper amount of sample, adding a first solvent for dissolving and diluting, filtering with a 0.25 [mu] m filter membrane, and taking the subsequent filtrate as the test solution; s120, preparing a reference substance solution: weighing a proper amount of NTTP reference substance, and adding a second solvent for dissolving to prepare a reference substance stock solution; precisely measuring a proper amount of reference substance stock solution, and diluting with a second solvent to prepare a reference substance solution; and S130, respectively injecting the test solution and the reference solution into an ultra-high performance liquid chromatograph-mass spectrometer, recording a chromatogram, and calculating the content of NTTP by peak area according to an external standard method. The method for analyzing the NTTP in the sitagliptin phosphate, established by the invention, is strong in specificity, high in stability, high in accuracy, high in precision and strong in durability, and can be used as a method for detecting the content of the NTTP in the sitagliptin phosphate.

The invention belongs to the technical field of medicines, and relates to a preparation method and application of sitagliptin phosphate resin sustained-release microcapsules. The sitagliptin phosphate resin sustained-release microcapsule is prepared from sitagliptin phosphate, cation exchange resin, an impregnant and a capsule wall material, the sitagliptin phosphate resin sustained-release microcapsule is prepared by the following steps: statically or dynamically loading sitagliptin phosphate and cation exchange resin to obtain sitagliptin phosphate drug resin, impregnating the sitagliptin phosphate drug resin with an impregnant to obtain impregnated drug resin, and coating the impregnated drug resin with a capsule wall material to obtain the sitagliptin phosphate resin sustained-release microcapsule. The weight ratio of the sitagliptin phosphate to the cation exchange resin is (1: 4)-(9: 4); the cation exchange resin is sulfonic acid type strong acid cation exchange resin; the capsule wall material is poly (ammonium methacrylate) or ethyl cellulose; the impregnant is polyethylene glycol. The sitagliptin phosphate resin sustained-release microcapsule disclosed by the invention has a release rate of about 75% in 10h, has an obvious sustained-release effect, and can stabilize the blood concentration level.

This invention relates to a method for preparing sitagliptin phosphate to extend the lifespan of immobilized transaminases, belonging to the field of pharmaceutical synthesis technology. To address the problem of short lifespan of existing immobilized enzymes, this invention provides a method for preparing sitagliptin phosphate to extend the lifespan of immobilized transaminases. The method includes, in the presence of immobilized transaminases, carrying out an enzymatic reaction of sitagliptin precursor ketone and isopropylamine in a non-water-soluble organic solvent. The reaction is terminated after the raw material conversion rate is detected to be ≥75%, the immobilized transaminases are recovered, the filtrate is washed with water to remove acetone, and an aqueous phosphate solution is added to the filtrate for extraction. The aqueous phase is separated to obtain an aqueous sitagliptin phosphate solution, and the solvent is removed. The organic phase is washed with water and directly reused. This invention can significantly shorten the reaction time, reduce the contact time of the immobilized transaminases in a high-concentration acetone system, and avoid excessive soaking time, thereby extending the overall lifespan of the immobilized transaminases.

The utility model discloses material mixing equipment for preparing sitagliptin phosphate tablets, which comprises a reinforcing bottom plate, a fixing frame body fixedly connected onto the reinforcing bottom plate, a mixing box body fixedly connected onto the fixing frame body, a plurality of fifth reinforcing frames fixedly connected onto the mixing box body, and measurement storage cylinders fixedly connected onto the fifth reinforcing frames. A discharging pipe is fixedly connected to the measuring storage cylinder, a second electric valve is installed on the discharging pipe of the measuring storage cylinder, a weight sensor is installed on the measuring storage cylinder, and a buzzer is installed on the fifth reinforcing frame. The measurement value of the weight sensor is set in advance, then raw materials needing to be mixed are placed in the measurement storage barrel, the weight sensor can detect the raw materials in real time, when the weight of the raw materials reaches a preset threshold value of the weight sensor, the buzzer can be controlled to sound for a period of time, and therefore the use amount of different kinds of raw materials can be controlled, and the mixing efficiency is improved. And the phenomenon of mixing failure caused by a wrong dosage proportion is prevented.

The present invention relates to a method for detecting related substances of sitagliptin phosphate, wherein the column temperature is 30°C, the flow rate of the mobile phase is 1.0 ml / min, the detection wavelength is 205 nm, the stationary phase is cyanosilane bonded silica gel, the mobile phase is mobile phase A and B; mobile phase A is an ion pair reagent added to a phosphate buffer solution, and the pH value is adjusted with acid; mobile phase B is acetonitrile, and gradient elution is performed; diluent; mixed impurity stock solution: impurities B, C, D, E, F, and G are weighed and diluted, and 1.0 ml of the obtained mixed solution is taken for dilution; system suitability solution: dilution of sitagliptin phosphate and mixed impurity stock solution; sample solution: dilution of sitagliptin phosphate sample; sample solution is injected into a high performance liquid chromatograph, and the content of related substances in sitagliptin phosphate is calculated by the main component self-comparison method. Related substances in sitagliptin phosphate can be efficiently separated under the same chromatographic conditions, the quality of the raw material drug can be effectively controlled, the specificity is good, the accuracy is strong, the precision is high, and the operation is performed at room temperature.

The invention discloses a sitagliptin phosphate pharmaceutical composition as well as a preparation, a preparation method and application thereof. The pharmaceutical composition comprises sitagliptin phosphate, HP-beta-CD and mesoporous silica. According to the invention, a synergistic effect is generated by utilizing a molecular-level clathration effect of HP-beta-CD and a nano-level confinement adsorption effect of mesoporous silica, so that chemical degradation of sitagliptin phosphate, especially generation of a genotoxic impurity NTTP, is remarkably inhibited from molecular and physical double levels, and the stability of a product is greatly improved. Meanwhile, the mesoporous silica effectively solves the technical problems that HP-beta-CD is strong in hygroscopicity and not easy to directly tablet, and the content uniformity of low-dose drugs is fundamentally ensured by forming uniform composite particles. The process is simple, granulation is not needed, the tablet is suitable for industrial production, the prepared tablet is excellent in stability and high in safety, and animal experiments show that the bioavailability of the tablet is superior to that of a commercially available reference preparation.

The invention belongs to the field of pharmaceutical preparations, and particularly relates to sitagliptin phosphate tablets as well as a preparation method and application thereof. According to the specific technical scheme, the sitagliptin phosphate tablet comprises sitagliptin phosphate, a filling agent, a disintegrating agent and a lubricating agent, the filling agent comprises microcrystalline cellulose, and the moisture content of the microcrystalline cellulose is smaller than 5%. When the lubricant is selected, the use of the lubricant sodium stearyl fumarate commonly used in the industry is avoided, so that the generation of impurities is effectively reduced. Meanwhile, the moisture content of microcrystalline cellulose in the filling agent is controlled, and the generation of impurities in the sitagliptin phosphate tablet is further reduced. Finally, the sitagliptin phosphate tablet which is high in purity, low in impurity content and stable in character is provided.

The utility model relates to the technical field of mixing, in particular to a sitagliptin phosphate metformin compound preparation mixing device. The mixing device comprises a rack, a stirring assembly and a vibration assembly, the rack is of an L-shaped structure, a mixing tank is movably arranged above the horizontal section of the rack, a limiting supporting assembly matched with the rack is arranged at the bottom of the mixing tank, the stirring assembly used for mixing raw materials is arranged in the mixing tank, and the vibration assembly is arranged on one side of the vertical section of the rack. The mixing tank is movably arranged on the rack through the limiting and supporting assembly, and the stirring assembly, the output assembly and the oscillation assembly are matched, so that when the motor drives the transverse shaft and the stirring blades to stir and mix raw materials inside, the output mechanism can transmit stirring force to the oscillation assembly, and the stirring force is transmitted to the vibration assembly; the mixing tank is driven by the oscillation assembly to perform reciprocating translation on the rack under the cooperation of the limiting and supporting assembly, so that the uniformity and the mixing efficiency of the whole mixed material are improved.

1. Name of the product of this design: Packaging box (Sitagliptin Phosphate Tablets). 2. Purpose of this design product: The design product is used for packaging of medicines. 3. The key design point of this design product lies in the combination of shape and pattern. 4. The picture or photo that best illustrates the design points: three-dimensional picture.

The invention discloses a synthesis process of sitagliptin phosphate, which comprises the following steps: fully mixing (R)-3-(benzyloxy amino)-1-(3-(trifluorophenyl)-5, 6-dihydro-[1, 2, 4] triazolo [4, 3-a] pyrazine-7 (8H)-yl)-4-(2, 4, 5-trifluorophenyl) butane-1-one, trifluorophosphoric acid, a catalyst Cu (OAc) 2. H2O and a mixed solvent, reacting for 1-2 hours at the temperature of 5-10 DEG C, and after the reaction is finished, separating and purifying to obtain the sitagliptin phosphate. Sitagliptin phosphate is obtained through solvent evaporation and recrystallization. The synthesis process provided by the invention depends on green chemistry principles, such as ultraviolet light catalysis, microwave heating, an optimized solvent system and mild reaction conditions. The methods not only are beneficial to improving the reaction efficiency, but also can reduce the use of harmful solvents and reduce the risk of environmental pollution, and conform to the current trend of green chemistry and sustainable development.

The invention relates to the technical field of extraction, in particular to a sitagliptin phosphate intermediate supercritical fluid extraction device which comprises a separation mechanism and a guide mechanism, the guide mechanism is arranged on the inner side of the separation mechanism, and the separation mechanism comprises a transmission assembly, a reaction assembly, a discharge assembly and a buffer assembly. The reaction assembly is fixedly connected to the top of the transmission assembly, the discharge assembly is rotatably connected to the inner side of the transmission assembly, and the buffer assembly is fixedly connected to the bottom of the transmission assembly. The invention provides a supercritical fluid extraction device for a sitagliptin phosphate intermediate, which is provided with a structure for centrally guiding residues everywhere in the device in the extraction process, so that the residues can be centrally treated, the efficiency in the extraction process of the sitagliptin phosphate intermediate is improved, and a structure for separating the residues from finished products is arranged, so that the extraction efficiency is improved. Therefore, the residue can be quickly separated from the finished product, and the recovery stability of the sitagliptin phosphate intermediate finished product after extraction is improved.

This invention relates to the field of sitagliptin phosphate preparation technology, specifically disclosing a cyclic enzymatic catalytic synthesis process for sitagliptin phosphate. This process uses a diketone compound as a substrate and transaminase as a catalyst, innovatively combining an immobilized enzyme column to achieve a cyclic catalytic reaction. Engineered bacteria are cultured in a fermenter, and after cell disruption, impurity removal, and ultrafiltration concentration, a concentrated transaminase solution is prepared. This solution is then cross-linked with epoxy resin HFA001 to form an immobilized enzyme packing material, which is then packed into an enzyme column. Under optimized reaction conditions, the substrate solution and a catalytic solution containing pyridoxal phosphate are cyclically catalyzed through the enzyme column. The reaction solution is purified through acidification, extraction, washing, vacuum concentration, crystallization, and drying to obtain the sitagliptin product. This invention enables continuous production scale-up of more than 10 batches, with a catalytic yield of 80%-85% and a substrate conversion rate ≥95%, significantly reducing reaction costs and experimental risks, and improving production efficiency and product stability.

The present invention pertains to the technical field of pharmaceuticals and relates to a preparation method for a sitagliptin phosphate resin sustained-release microcapsule and use thereof. The sitagliptin phosphate resin sustained-release microcapsule comprises sitagliptin phosphate, a cation exchange resin, an impregnant, and a capsule material. The sitagliptin phosphate resin sustained-release microcapsule is obtained by performing static or dynamic drug loading of sitagliptin phosphate on the cation exchange resin to obtain a sitagliptin phosphate drug resin, then impregnating the resin with the impregnant to obtain an impregnated drug resin, and then coating the impregnated drug resin with the capsule material. The weight ratio of sitagliptin phosphate to the cation exchange resin is 1:4-9:4. The cation exchange resin is a sulfonic acid-type strongly acidic cation exchange resin. The capsule material is ammonium polymethacrylate or ethyl cellulose. The impregnant is polyethylene glycol. The sitagliptin phosphate resin sustained-release microcapsule of the present invention exhibits a release degree of about 75% at 10 h, indicating a significant sustained-release effect. The microcapsule can stabilize the plasma concentration level.