18 results about "Oseltamivir Phosphate" patented technology

The invention discloses a chemical-enzymatic coupling synthesis method of oseltamivir phosphate, which comprises the following steps: by taking monasic acid OS-01 as a substrate, sequentially carrying out S1 esterification, S2 ketalation, S3 selective ring opening, S4 TEMPO oxidation, S5 primary transaminase reaction, S6 acetylation, S7 secondary transaminase reaction and S8 phosphorylation reaction to obtain the final product oseltamivir phosphate OS-09. According to the method, the step of sodium azide required by a traditional route is avoided, the production safety and the industrialization possibility are enhanced, two different transaminases are used for respectively constructing different chiral centers, the steps of protecting groups and deprotecting groups on the traditional route are not needed, the overall route is short, the used chemical reagents are few, the yield is high, and the method is suitable for industrial production. The industrial requirements of environmental protection and low cost are met.

The invention relates to an oseltamivir phosphate freeze-dried tablet and a preparation method thereof. The oseltamivir phosphate freeze-dried tablet comprises oseltamivir phosphate serving as an active ingredient and water-soluble starch serving as a skeleton forming agent. According to the oseltamivir phosphate freeze-dried tablet and the preparation method thereof, the water-soluble starch is applied to skeleton construction of the oseltamivir phosphate freeze-dried tablet, and the water-soluble starch is derived from natural plants and has good biocompatibility and extremely high safety; the freeze-dried tablet can be quickly disintegrated in the oral cavity within 5 seconds, so that the medication compliance of a patient is improved; the water-soluble starch is odorless and natural and soft in taste, and meanwhile, a compact and porous structure formed in the preparation can wrap active ingredients and cover bitter taste to a certain extent, so that the taste is effectively improved; the water-soluble starch has moderate and good viscosity, forms a three-dimensional net-shaped framework with uniform and firm pores in the freeze-drying process, endows the freeze-dried tablet with good taste and mechanical strength, and is convenient for a patient to take and use; the water-soluble starch can be quickly dissolved in cold water, so that the process flow is simpler, more convenient and more efficient and suitable for large-scale production

The invention discloses a transaminase mutant and application thereof in oseltamivir synthesis, transaminase with an amino acid sequence as shown in SEQ ID NO.2 is taken as a parent and mutated through one or more sites, and the transaminase mutant is selected from one of the following mutants: a mutant TA-I17A, a mutant TA-I17A, a mutant TA-I17A, a mutant TA-I17B, a mutant TA-I17A, a mutant TA-I17B, a mutant TA-I17C A mutant TA-S56G; a mutant TA-L89M; the invention discloses a mutant TA-I17A-S56G and a mutant A mutant TA-S56G-L89M, and a mutant A mutant TA-I17A-L89M, and a mutant The mutant of TA-I17A-L89M-V147L has the following structural formula shown in the specification, the invention relates to a mutant TA-I17A-L89M-V147L-L182F, which has the following structural formula shown in the description The invention relates to a mutant TA-I17A-L89M-V147L-L182F-N245E, and the mutant has a structural formula shown in the specification. Compared with parent transaminase, the oseltamivir phosphate has higher catalytic activity, the production efficiency can be improved, the production cost is reduced, and the oseltamivir phosphate has a good application prospect in industrial production of oseltamivir phosphate.

1. Name of the product in this design: Packaging Box (Oseltamivir Phosphate Dry Suspension). 2. Purpose of this design: For packaging pharmaceuticals. 3. The key design features of this product are the combination of shape and pattern. 4. The image or photograph that best illustrates the key design points: unfolded diagram. 5. Other situations requiring explanation: The red and yellow border lines in the expanded diagram are to make the boundaries of each view clearer and are not within the scope of product protection.

1. Name of the product in this design: Oseltamivir Phosphate Dry Suspension. 2. Purpose of this design: This design is used for the packaging and protection of pharmaceuticals. 3. The key design feature of this product is its pattern. 4. The image or photograph that best illustrates the design's key points: a 3D model.

The invention discloses a transaminase mutant with improved enzymatic activity and application of the transaminase mutant, and the transaminase mutant is formed by mutation of one or more sites by taking transaminase with an amino acid sequence as shown in SEQ ID NO.2 as a parent. Compared with parent transaminase, the oseltamivir phosphate has higher catalytic activity, the production efficiency can be improved, the production cost is reduced, and the oseltamivir phosphate has a good application prospect in industrial production of oseltamivir phosphate.

The invention discloses a crystal form DCI of a compound I, a preparation method and application thereof, a pharmaceutical composition containing the crystal form, and application of the crystal form in preparation of drugs for treating hyperproliferative diseases. The crystal form DCI of the compound I provided by the invention has a certain purification effect, higher yield, good physical and chemical stability, good humidity stability and good mechanical stability, provides guarantee for subsequent production and development of drugs, and has higher industrial development value. Compound I.

This invention discloses an oseltamivir phosphate capsule and its preparation method, relating to the field of pharmaceutical formulation technology, including the following steps: (1) placing oseltamivir phosphate, filler, disintegrant, and binder in a wet granulation mixer and mixing them evenly; (2) dispersing mannitol and mesoporous polydopamine nanoparticles in purified water to form a mixed dispersion; (3) adding the mixed dispersion obtained in step (2) to a wet granulation mixer for wet granulation and drying to obtain a premix; (4) mixing the premix obtained in step (3) with a lubricant evenly to obtain a mixture; (5) filling the mixture obtained in step (4) into a soft capsule shell to obtain an oseltamivir phosphate capsule; This invention, by using mesoporous polydopamine nanoparticles and mannitol to synergistically prepare a wetting solution for wet granulation, can effectively improve the dissolution stability of oseltamivir phosphate capsules, maintaining high dissolution even after long-term storage, thus improving the stability of the drug.

The invention relates to a synthesis method of oseltamivir phosphate, which comprises the following steps: by taking (1R, 5R, 6R)-trans-5-(1-ethyl propoxy)-7-oxobicyclo [4.1. 0] hept-3-ene-3-carboxylic acid ethyl ester as a starting raw material, reacting with acetonitrile under the catalysis of indium chloride to synthesize (3aR, 4R, 7aR)-2-methyl-4-(pent-3-alcohol oxy)-3a, 4, 7, 7a-tetrahydrocyclohexene [2, 1-d] [1, 3] oxazole-6-ethyl formate; the preparation method comprises the following steps: synthesizing (3R, 4R, 5S)-4-(acetamido)-5-[(diphenylmethylene) amino]-3-(pent-3-oxyl) cyclohexene-1-ethyl formate by using ethyl acetate as a raw material, performing ring-opening reaction with benzophenonimine under the catalysis of cuprous iodide and cesium carbonate to synthesize (3R, 4R, 5S)-4-(acetamido)-5-[(diphenylmethylene) amino]-3-(pent-3-oxyl) cyclohexene-1-ethyl formate, hydrolyzing benzophenone to synthesize oseltamivir, and reacting with phosphoric acid to synthesize oseltamivir phosphate. The method has the advantages of short synthetic route, low cost, easily available initial raw materials, simple operation, few and controllable reaction impurities, and suitableness for industrial production.

The utility model discloses a raw material crusher for preparing oseltamivir phosphate dry suspension, which comprises a crushing box body, a third reinforcing frame fixedly connected to the crushing box body, a second driving motor fixedly mounted on the third reinforcing frame, a second rotating shaft rotatably connected to a first crushing chamber, a first gear connected to the second rotating shaft, and a second gear connected to the second rotating shaft. A third rotating shaft is rotationally connected to the first crushing chamber, a second gear is connected to the third rotating shaft, the first gear is meshed with the second gear, and grinding and crushing wheels are connected to the second rotating shaft and the third rotating shaft. Raw materials with large sizes are blocked through the filter screen plate, so that the raw materials are screened, the first rotating shaft and the filter screen plate are driven by the first driving motor to rotate and incline, the screened raw materials slide into the first crushing chamber, the raw materials are pre-crushed by the grinding and crushing wheel, and the crushing efficiency of the raw materials is improved.

The utility model discloses a raw material screening machine for preparing oseltamivir phosphate dry suspension, which comprises a support frame, a controller arranged on the support frame, a screening box body fixedly connected on the support frame, a fixed disc fixedly connected inside the screening box body, a first reinforcing frame body fixedly connected on the screening box body, and a second reinforcing frame body fixedly connected on the first reinforcing frame body. A driving motor is fixedly installed on the first reinforcing frame body, a rotating shaft is connected to the top end of an output shaft of the driving motor, a centrifugal screening box is connected to the top end of the rotating shaft, the centrifugal screening box is rotationally connected with the fixing disc and the rotating shaft, a discharging pipe is connected to the centrifugal screening box, and an electric valve is installed on the discharging pipe; a humidity sensor is installed in the screening box body, and a dehumidifier is fixedly installed on the screening box body. According to the utility model, humid gas in the screening box body is removed through the dehumidification machine, so that raw materials are kept dry, and numerical values detected by the humidity sensor are displayed through the display screen of the controller, so that the numerical value condition of humidity can be conveniently observed.

The present application relates to oseltamivir phosphate single crystal and its preparation method. The present application selects specific mixed solvent to slowly evaporate to obtain needle-like crystal, which is the first successful preparation of oseltamivir phosphate single crystal in the world. The oseltamivir phosphate single crystal prepared by the present application has the chemical formula of C 16 H 31 N2O8P, a molecular weight of 410.40, and a crystal structure belonging to orthorhombic system, a space group of P21212, a=23.9002(6)Å, b=24.4812(6)Å, c=7.4191(2)Å, α=90°, β=90°, γ=90°, V=4340.96(19)Å 3 , Z=8. The preparation and determination of the single crystal have important significance and application value for the structure-activity relationship study of oseltamivir phosphate drug and new drug development.

The application discloses a human rhubarb extract with anti-influenza A virus activity and a preparation method thereof. The preparation method comprises the following steps: preparing the human rhubarb by fermenting licorice with an artificial synthetic flora (15 kinds of probiotics are mixed according to a specific ratio), and then performing ultrasonic extraction with water as a solvent; and the optimized extraction conditions are as follows: a solid-liquid ratio of 1:30 g / mL, an ultrasonic power of 500 W, an ultrasonic temperature of 50 DEG C, an ultrasonic time of 35 min, and an extraction frequency of 2 times. Compared with traditional extraction and decoction methods, the extract yield is higher, the inhibitory effect on H1N1 influenza A virus is significantly enhanced, the blood clotting titer of mouse lung tissue is reduced to 0.6+ / -0.4, and is equivalent to that of the positive drug oseltamivir phosphate. The application avoids the risk of pathogenic microorganism pollution in traditional pit fermentation, simplifies the medication mode, realizes the reduction and efficiency increase, the process is stable and controllable, is suitable for industrial production, and provides technical support for modern anti-influenza application of the human rhubarb.

The invention discloses a synthesis method of an oseltamivir phosphate impurity, and belongs to the technical field of medicine synthesis. The synthesis method of the oseltamivir phosphate impurity comprises the following steps: S1, mixing 3-hydroxy-4-amino-benzoic acid with acetic acid, heating, keeping a reflux state for reaction, continuously separating water, cooling after the reaction is ended, then recovering acetic acid, and then purifying to obtain 3-hydroxy-4-acetamido-benzoic acid; s2, dissolving 3-hydroxy-4-acetamido-benzoic acid in a solvent, gradually adding concentrated hydrochloric acid, heating and refluxing the mixture, and after the reaction is finished and the solvent is evaporated, purifying to obtain a target product. Acetic acid is adopted for amidation, acetic anhydride is avoided, and industrial production is facilitated.

1. The name of the design product: packaging box (oseltamivir phosphate capsules 2). 2. The use of the design product: the design product is used for the packaging and protection of medicines. 3. The design points of the design product: in the pattern. 4. The picture or photo that best indicates the design points: perspective view.

The invention discloses an oseltamivir azido derivative. The structure of the oseltamivir azido derivative is shown as an impurity 338 or an impurity 340. The two impurities are found for the first time in the oseltamivir phosphate preparation process and have obvious toxicity, so that it is necessary to control the content of the two impurities in the oseltamivir phosphate to be not higher than 30 ppm so as to reduce the safety risk existing in the oseltamivir phosphate use process.

The invention belongs to the technical field of oseltamivir phosphate dry suspension detection methods, and particularly relates to a detection method for a glucose adduct in an oseltamivir phosphate dry suspension. The method for detecting the glucose adduct in the oseltamivir phosphate dry suspension comprises the following steps: preparing a system applicability solution, a test solution, a reference solution and a blank auxiliary solution, carrying out liquid chromatography detection on the solutions, recording a chromatogram, and obtaining the content of an impurity V and an impurity VI in the test solution according to a main component external standard method. According to the method for detecting the glucose adduct in the oseltamivir phosphate dry suspension, high performance liquid chromatography is adopted for detecting impurities V and VI, primary degradation products and secondary degradation products can be accurately and effectively detected and calculated, the content of the degradation products can be monitored in real time, meanwhile, an isocratic elution method is adopted, and the content of the glucose adduct in the oseltamivir phosphate dry suspension can be accurately and effectively detected. The load of a high performance liquid chromatograph is reduced, the instrument loss is reduced, and the inspection cost is saved.

The utility model discloses a granule filling device for preparing an oseltamivir phosphate dry suspension, which comprises a reinforcing bottom plate, a transportation frame body fixedly connected onto the reinforcing bottom plate, a plurality of electric rotating rollers mounted on the transportation frame body, a conveying belt sleeved among the plurality of electric rotating rollers, a plurality of placement frame bodies connected onto the conveying belt, and a plurality of conveying belts connected onto the placement frame bodies, a first electric push rod is fixedly installed on the first fixing frame, a telescopic rod of the first electric push rod is connected with a first connecting rod, the first connecting rod is connected with the placing frame body in a sliding mode, the first connecting rod is connected with a push plate, a groove is formed in the push plate, and a first weight sensor is installed at the position of the groove of the push plate. The weight of the medicament particles in the medicament bottle is detected through the first weight sensor, so that quantitative filling of the medicament particles is realized, the phenomenon that the medicament particles are too many or too few during filling is reduced, and the processing efficiency is improved.