43 results about "Trelagliptin succinate" patented technology

The invention provides a related substance detection method for trelagliptin succinate and preparation thereof. According to the related substance detection method for trelagliptin succinate and preparation thereof, a diode array detector is adopted, a chromatographic column adopted in the method is an octadecyl silane bonded silica gel chromatographic column, a mobile phase A is phosphate buffer solution, a mobile phase B is acetonitrile, the volume ratio of the phosphate buffer solution to acetonitrile is 60: 40 to 85: 15, the pH value of the phosphate buffer solution is 5.0 to 5.5, the concentration of the phosphate buffer solution is 0.05 to 0.1mol/L, and a detection wavelength is 278nm. The various ingredients in the analysed substances are thorough in separation and high in operability; the analysis method is high in specificity, high in accuracy and sensitivity, high in adaptability, and capable of providing a basis for the safety, effectiveness and controllability of medicines.

The invention discloses a trelagliptin and a preparation method of succinate thereof. The preparation method includes the following steps that a trelagliptin intermediate II and a trelagliptin intermediate III perform nucleophilic substitution reaction in an organic solvent in the presence of phosphate and a phase transfer catalyst to obtain trelagliptin I, and then trelagliptin I reacts with the succinate to produce salt. The operation process of the preparation method is simple and safe, special devices are not needed, the impurity contents of bis-substituted and primary amine substituted isomers can significantly reduced, only one-time recrystallization is needed, the purity of the obtained trelagliptin succinate I' can be above 99.5%, the impurity contents of the bis-substituted and primary amine substituted isomers are both below 0.05%, the contents of all the other impurities are all below 0.05%, the prepared trelagliptin succinate I' is high in purity, the production cost is low, and the trelagliptin and the preparation method are suitable for industrialized production.

The invention discloses a preparation method of trelagliptin succinate. The preparation method comprises four steps. The method for preparing the trelagliptin succinate is rapid and efficient. By adopting the method disclosed by the invention, reaction time is shortened and materials are saved.

The invention relates to the technical field of drug preparation, and discloses a preparation method of trelagliptin succinate. The preparation method comprises the following steps: performing a reaction on a compound represented by a formula (2), (R)-3-amino-piperidine dihydrochloride and a weak base in a molar ratio of 1: (1-2): (1.5-5) to obtain a coarse product represented by a formula (3); and then recrystallizing the coarse product represented by the formula (3) by using an organic solvent with medium polarity to remove main impurities close to the coarse product represented by the formula (3) in polarity. The preparation method solves the problems in an existing preparation method that the difficulty for separating and purifying a final product is great, the yield and purity are low, the amount of the organic solvent during separation and purification is large and green industrial scaled production is not facilitated. The preparation method disclosed by the invention is high in total yield, and the purity of trelagliptin succinate is 99.83%, so that safe medication of trelagliptin succinate is guaranteed, and the quality and safe medication of trelagliptin succinate are improved.

The invention discloses a method for separating and analyzing trelagliptin succinate and preparation related substances thereof. According to the method, the chromatographic conditions comprise that an octadecyl bonded silica gel is adopted as a stationary phase, a buffer liquid is adopted as a mobile phase A and an organic solvent is adopted as a mobile phase B to carry out gradient elution, and the gradient elution conditions comprise that the mobile phase A is 85-50 (V%) and the mobile phase B is 15-50 (V%) at the time of 0-10 min, the mobile phase A is 50 (V%) and the mobile phase B is 50 (V%) at the time of 25-30 min, and the mobile phase A is 85-50 (V%) and the mobile phase B is 15-50 (V%) at the time of 31-35 min; the sample solution preparation comprises that the sample to be detected is prepared into the sample solution by using the mobile phase A; and separating and analyzing are performed, wherein the sample solution is injected into a high performance liquid chromatography so as to complete the detection of the trelagliptin succinate and the preparation related substances thereof. With the method of the present invention, the trelagliptin and the related substances can be rapidly and effectively separated under the same chromatographic conditions. The detection method of the present invention has advantages of high specificity, high precision, strong accuracy, convenient operation, and effective control of drug quality.

The present invention relates to a trelagliptin succinate crystal form A preparation method, and belongs to the technical field of the chemistry. The technical scheme comprises: preparing a trelagliptin fine product, and preparing a trelagliptin succinate bulk drug. The invention provides the trelagliptin succinate crystal form A preparation method suitable for industrial production, wherein the purity of the product prepared through the method is more than 99.95%; and the used single solvent anhydrous ethanol can be recovered and applied, is the optimal solvent for preparing the trelagliptin succinate crystal form A, is the bulk drug refining solvent recommended in ICH, and has characteristics of low prices and environmental protection.

The invention discloses a trelagliptin succinate rapid-release pellet preparation and a preparation method thereof, and relates to the field of pharmaceutic preparation technologies and application. The rapid-release pellet preparation is administrated orally; a core pellet is taken as a carrier, and a trelagliptin succinate aqueous solution containing a co-solvent and a bonding agent is taken as an administration solution. The trelagliptin succinate rapid-release pellet preparation has the characteristics of high administration rate, high content uniformity, rapid release, quick response of the analgesic activity and the like. Meanwhile, the rapid-release pellet preparation has high clinical use compliance, high security and the like.

The invention relates to a method for preparing an impurity C reference substance of Trelagliptin succinate. The technical scheme of the invention is as follows: the method comprises the steps: (1) carrying out refluxing on Trelagliptin succinate, which serves as a raw material, and a protonic solvent which serves as a solvent, so as to prepare an impurity C of the Trelagliptin succinate; (2) refining a crude product, thereby obtaining the qualified impurity C reference substance. The method for preparing the impurity C reference substance of the Trelagliptin succinate, provided by the invention, is easy and feasible and is used for providing the satisfactory impurity C reference substance for quality control on the Trelagliptin succinate.

The invention relates to a Trelagliptin succinate-related substance L which has not been reported in literature, a preparation, analysis and detection method and an application of the substance L. Theanalysis and detection method can detect 10 related substances including related substance L, and has good separation degree and high sensitivity.

The invention discloses a microporous membrane-coated controlled-release trelagliptin succinate pellet and a preparation method thereof. The microporous membrane-coated controlled-release trelagliptin succinate pellet sequentially comprises a drug-containing pellet core and a controlled-release coating layer from inside to outside, wherein the drug-containing pellet core is prepared from a primary material and an auxiliary material at the ratio of (5%-20%):(80%-95%). According to the microporous membrane-coated controlled-release trelagliptin succinate pellet, a bitter taste can be coated, the effective ingredients can be dissolved out, constant long-acting plasma concentration is ensured, and the defect that a drug is discharged along with excrement before not completely released is avoided.

The invention discloses a trelagliptin succinate solid preparation and a preparation method thereof. The method comprises the following steps that by mass, 50-80 parts of trelagliptin succinate, 5-20parts of a filling agent, 1-10 parts of an adhesive, 3-15 parts of a disintegrating agent and 0-5 parts of a lubricant are prepared; trelagliptin succinate, the filling agent and the adhesive are mixed proportionally, and pre-mixed powder is obtained; then, water is added into the pre-mixed powder for granulation to obtain medicated granules; the medicated granules are dried by a fluidized bed fordrying, and dried medicated granules are obtained; the disintegrating agent and the lubricant are added into the dried medicated granules, and uniform mixing is performed to obtain total mixed granules; then, pressing and tableting are performed to obtain trelagliptin tablet cores. The method is simple and feasible in technology, the dissolution of the obtained solid preparation meets the requirement of a quick release agent, the tablet wright difference is small, and stability is good.

The invention provides a method for analyzing and determining a genotoxic impurity 2-(dibromo methyl)-4-fluorobenzonitrile in trelagliptin succinate by utilizing HPLC (High Performance Liquid Chromatography). According to the method provided by the invention, an HPLC analysis method established by adopting octadecyl silane bonded silica gel as a stationary phase and a phosphoric acid water solution and an acetonitrile solution as moving phases and adopting a gradient eluting mode is capable of accurately determining the potential genotoxic impurity 2-(dibromo methyl)-4-fluorobenzonitrile in the trelagliptin succinate. An HPLC-UV (Ultraviolet) method is simple in operation, short in analysis time, high in accuracy degree and good in repeatability, the sensitivity can be up to 1.66ppm, a reliable detecting method is provided for quality standard of the trelagliptin succinate, safeguard is provided for health administration of a patient, and the method belongs to the technical field of medicine.

The invention discloses a preparation process of a trelagliptin succinate tablet, which comprises the following steps of: mixing a carrier with an API raw material according to a preferable ratio, and granulating by using spray drying equipment under preferable parameters, so that the granule has better granule property and regular appearance property compared with an original grinding fluidized bed, and has smaller bulk volume and good flowability and compressibility compared with pure API; the risk of tablet cracking caused by difficulty in discharging air in gaps of materials in tablets and poor compressibility due to physical properties of fluidization granulation and API is avoided, so that the design range of technological parameters is wider, the technological process is more controllable and stable, various process feasibility problems caused by poor physical attributes of API, fluffy particles after fluidization granulation, poor compressibility and the like can be solved, process control is easy to realize, product quality attributes are guaranteed, meanwhile, the production process can be simplified, the production efficiency can be improved, and the production cost can be saved.

The invention provides a method for analyzing and determining 2-cyano-5-fluorobenzyl bromide in trelagliptin succinate. According to the method, octadecylsilane chemically bonded silica is adopted asa stationary phase, a phosphoric acid aqueous solution and an acetonitrile solution are adopted as mobile phases, a gradient elution mode is adopted, and an established high performance liquid chromatography method can accurately determine the potential genotoxic impurity 2-cyano-5-fluorobenzyl bromide in trelagliptin succinate. The HPLC-UV method is simple to operate, short in analysis time, highin accuracy and good in repeatability; the sensitivity of the method can reach 3.0 ppm; a reliable detection method is provided for the quality standard of trelagliptin succinate; a guarantee is provided for the healthy medication of patients; and the HPLC-UV method belongs to the technical field of medicines.

The invention provides a preparation method of composite trelagliptin succinate tablets. Preparation of trelagliptin succinate raw materials comprises the step of separately sieving 50 g-230 g of trelagliptin succinate raw materials, 300 g-1380 g of apocynum venetum plaster powder, 30 g-86 g of mannitol, 2 g-58 g of microcrystalline celluloses, 1.8 g-37 g of croscarmellose sodium and 3.2 g-54 g ofsodium stearyl fumarate by using a sieve with meshes of 60, wherein the trelagliptin succinate raw materials and the apocynum venetum plaster powder are added according to the ratio of 1: (5-7), theuse amount of drugs and the toxic and side effects of the drugs are reduced obviously, and an effect of treating diabetes is remarkable.

The present invention discloses a trelagliptin succinate synthesis process, and relates to the technical field of pharmaceutical chemical synthesis. In the process, 2-cyano-5-fluorobenzyl bromide and 6-chloro-3-methyl uracil are adopted as starting raw materials, and condensation reaction is performed under the action of cuprous acetylacetonate and an acid-binding agent I to prepare an intermediate 1; then the intermediate 1 and (R)-3-aminopiperidine dihydrochloride are subjected to a condensation reaction under the action of dibutyltin dichloride and an acid-binding agent II to prepare an intermediate 2, and the intermediate 2 and succinic acid are subjected to a salt forming reaction to prepare trelagliptin succinate. Herein, the acid-binding agent and the catalyst are matched to improve the yield of the intermediate 1 and the intermediate 2, so that the total yield of the trelagliptin succinate is improved, the total yield reaches 80% or above, and the purity of the trelagliptin succinate reaches 99.5% or above.

The invention belongs to the field of medicines, and particularly relates to a preparation method of a trelagliptin succinate dimer and an applicationthereof, and the method comprises the following steps: preparing a reaction raw material trelagliptin succinate; and preparing trelagliptin succinate dimer by thermally melting trelagliptin succinate under a solvent-free condition. According to the technical scheme provided by the invention, the route is simple, the reaction conditions are easy to control, the process is simple, the purity of the obtained product is relatively high, and the method can be applied to qualitative and quantitative research and detection of trelagliptin succinate related substances, and has important significance for effectively controlling the quality of trelagliptin succinate.