32 results about "Oseltamivir" 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 belongs to the field of medicines, and particularly relates to application of a cough relieving agent in preparation of an anti-influenza virus medicine. Through the synergistic effects of resisting viruses, resisting inflammation, regulating mucus secretion and inhibiting nerve sensitization, the antitussive agent relieves influenza symptoms and promotes recovery from the source, has the advantages of being stable in curative effect, small in toxic and side effect, not prone to generating drug resistance, not capable of promoting virus variation and the like, is wider in application stage and application crowd, and can intervene in the early stage of influenza infection. Due to the fact that the antitussive agent can treat influenza caused by exogenous cold and influenza viruses, the antitussive agent can be used in time to relieve symptoms when cough, excessive phlegm and other symptoms are found in the early stage of a patient, the antitussive agent can relieve the exogenous cold for a non-influenza patient, and the antitussive agent can prevent influenza from being converted into severe influenza from mild influenza for an influenza patient. And the reduction of the treatment effect caused by definite diagnosis delay and oseltamivir treatment delay is also avoided.

The application belongs to the technical field of pharmaceutical chemistry synthesis, and specifically discloses a preparation method of oseltamivir and a phosphate thereof and an intermediate thereof, which comprises the following steps: (1) a compound of formula VII is reacted with VIII under the action of a base in a solvent to obtain an intermediate of formula VI, and then the intermediate of formula VI is reacted under the action of a strong base at high temperature to obtain formula V; (2) formula V is subjected to ring-opening reaction with tert-butylamine in a solvent under the catalysis of a Lewis acid to obtain formula IV; (3) formula IV is reacted with an acetylating agent in a solvent under the action of a base to obtain formula III; (4) formula III is reacted under the action of an acid at a certain temperature to obtain formula II; and (5) formula II is subjected to salt formation with phosphoric acid in a solvent to obtain oseltamivir. The preparation method has the characteristics of simple operation, low cost, high yield, high optical purity of the product, stable process and the like, and is suitable for industrial production.

The invention belongs to the field of medicines, and particularly relates to application of oseltamivir in a medicine for inhibiting porphyromonas gingivalis infected esophageal squamous cell carcinoma. According to the application of oseltamivir in the medicine for inhibiting the porphyromonas gingivalis infection type esophageal squamous cell carcinoma, tumor cell proliferation, cell migration and cell invasion of the porphyromonas gingivalis infection type esophageal squamous cell carcinoma can be inhibited.

The application provides oseltamivir tablets and a preparation method, the oseltamivir tablets comprising, in terms of weight fractions, 230-250 parts of sustained-release granules, 45-65 parts of immediate-release granules, 10-20 parts of a glidant, and 20-30 parts of a binder, wherein the sustained-release granules contain 110-130 parts of oseltamivir free base, and the immediate-release granules contain 25-35 parts of oseltamivir free base.The oseltamivir tablets have a small single tablet weight and good sustained-release effect, and the patient's medication compliance is strong; by optimizing the particle size and preparation process of the immediate-release granules to reduce the deviation of the initial dissolution rate, the drug quality is controllable and the drug efficacy is stable.

The present application relates to a kind of oseltamivir compositions and its preparation method, belong to the field of pharmaceutical preparation.The composition oseltamivir or its pharmaceutically acceptable salt, taste masking agent and optionally other pharmaceutically acceptable auxiliary materials.The taste masking agent is a kind of water-insoluble material or a kind of enteric material.The composition is convenient to take, good taste masking, good taste, fast release, good stability.The preparation method is good in reproducibility, and preparation is simple.

The invention discloses a method for determining isomers in an oseltamivir phosphate product by using high performance liquid chromatography. The chromatographic condition is that a Waters Symmetry C8 chromatographic column is used, a mobile phase is phosphate buffer solution-methanol-acetonitrile, the volume ratio is 620: 245: 135-700: 245: 135, isocratic elution is performed, the concentration of the phosphate buffer solution is 0.040 mol / L to 0.075 mol / L, the pH value is 6.25 to 6.40, the column temperature is 43 to 47 DEG C, the flow velocity is 1.1 to 1.3 ml / min, the detection wavelength is 207 nm, and the sample size is 60 microliters. According to the method, the isomer in the oseltamivir phosphate product can be rapidly and accurately detected, the content of the isomer can be calculated, the operation is simple, the reproducibility is good, the quality control of an oseltamivir phosphate preparation and an intermediate product thereof can be well realized, and a guarantee is provided for synthesis and preparation process optimization.

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.

The utility model discloses an oseltamivir preparation reaction kettle with a quantitative feeding structure, which belongs to the technical field of medicine preparation devices and comprises a storage box, a storage box is arranged in the storage box, and a discharging box is arranged at the bottom of one end of the storage box; according to the reaction kettle, impurity particles in raw materials can be filtered through the filter screen at the bottom of the inner side of the discharging box, impurities are prevented from entering the reaction kettle to influence the reaction quality, the crushing blades connected with the bottom of the barrier can crush larger crystal blocks, and the crystal blocks and crystal powder are prevented from entering the reaction kettle through the filter screen to influence the metering of the raw materials. Raw materials are stirred through a stirring rod, so that the raw materials are kept in a uniform state in a storage box and a discharging box, crystallization caused by too high local concentration is prevented, a resistance wire in a cavity in a stirring roller can heat the raw materials under the action of a transformer, crystals can be dissolved through the synergistic effect of stirring and heating, and the crystallization effect is improved. And raw materials can smoothly enter the reaction kettle through the discharge pipe.

The invention provides a combined medicine composition for treating brain glioma and application. The medicine composition comprises a copper ion carrier and a targeted NEU1 anti-influenza medicine. According to the combined medicine composition, an effective medicine combination strategy is provided for treatment of the brain glioma, and the combined medicine composition comprises a copper ion carrier, namely the illicit and an anti-influenza medicine, namely the oseltamivir. According to the invention, the condition that the combination of the ilismos and the oseltamivir has a synergistic effect on the treatment of the brain glioma is found for the first time.

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.

The application discloses a Marburg virus-based micro-genome replication-defective system and application thereof, and belongs to the field of biological medicine. The system significantly improves the expression efficiency and signal-to-noise ratio of a model reporter gene through a codon optimization strategy. Experimental verification shows that the model can safely simulate the MARV genome replication and transcription process under a biosafety level 2 (BSL-2) condition, and has high specificity and sensitivity. Through parallel verification of positive drugs such as ribavirin, suramin sodium salt and negative controls such as oseltamivir, it is confirmed that the model can accurately and quantitatively evaluate the activity of small-molecule drugs targeting the replication link of the virus and calculate EC50. The model provides a safe and efficient platform for the study of the MARV replication mechanism and the high-throughput screening of antiviral drugs, breaks through the limitation of a biosafety level 4 laboratory, and has important scientific research and application value.

The application belongs to the technical field of medicine, and particularly relates to application of butaclamol in preparation of anti-influenza virus products. The application proves through in-vivo and in-vitro experiments that butaclamol can play an antiviral role by inhibiting replication of H1N1. The in-vitro antiviral effect of butaclamol is superior to that of positive drug oseltamivir, and intragastrically administered butaclamol can reduce the mortality of mice by reducing replication of H1N1 in vivo, and has good practical application value in development of anti-influenza virus drugs.

The utility model discloses a raw material screening device for oseltamivir intermediate production, which belongs to the technical field of medicine processing, and comprises a screening shell, two support frames, a transmission component, a screening component, a motor and a cleaning component, a first discharge port and a third discharge port are formed in one side of the shell, and a second discharge port and a fourth discharge port are formed in the front surface of the shell; according to the utility model, raw materials are poured into the feed port, large raw material particles slide into the first discharge port along the rotating belt, raw materials filtered by the second sieve pores slide into the second discharge port, and smaller raw material particles pass through the third sieve pores, move to the rotating belt at the bottom and slide into the fourth discharge port; according to the device, various raw material particles with different sizes can be screened out only by pouring the raw materials into the feeding opening, operation is easy, and the applicability of the device is improved.

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 present application relates to a kind of microcapsules of oseltamivir or its pharmaceutically acceptable salt and its preparation method, belong to the field of pharmaceutical preparations.The preparation method includes drying using centrifugal spray dryer, and using process parameters such as atomizer frequency 25Hz-50Hz, the microcapsule particle prepared using the preparation method is uniform, taste masking is good, yield is high, and stability is good.

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.

This invention relates to a method for determining the absolute configuration of oseltamivir. The method involves obtaining the NMR spectrum of the oseltamivir derivative after the reaction of oseltamivir with a chiral carboxylic acid using nuclear magnetic resonance spectroscopy (NMR spectroscopy). The absolute configuration of oseltamivir is then determined by resolving the NMR spectrum, primarily through the NOESY spectrum. This method is simple to operate, convenient to use, and can be widely applied in the pharmaceutical industry.

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 application discloses a neuraminidase inhibitor based on a hydrophobic tag technology and a preparation method, a derivative, a pharmaceutical composition and an application thereof, and the structure of the neuraminidase inhibitor is shown as formula (I). The neuraminidase inhibitor based on the hydrophobic tag technology has enhanced antiviral activity and effective oseltamivir resistance reversal activity, and provides a new drug for the treatment of influenza virus infection, especially oseltamivir-resistant virus infection.

The invention discloses application of akebia quinata phenylethanoid glycoside B in preparation of a product for preventing and treating influenza virus infection, and relates to the technical field of biological medicines. Through molecular docking screening, cytotoxicity experiments and antiviral activity verification, the application value of the akebia quinata phenylethanoid glycoside B in prevention and treatment of influenza virus infection is defined, and the technical effect is remarkable. In the aspect of safety, the akebia quinata phenylethanoid glycoside B has no obvious influence on the survival rate of MDCK cells under high concentration, is far higher than clinical potential medication concentration, has no obvious cytotoxicity and is good in biocompatibility. In the aspect of antiviral activity, the akebia quinata phenylethanoid glycoside B shows an efficient inhibition effect on influenza viruses, the IC50 value is as low as 28.5 mu M, and the inhibition effect is superior to that of part of natural components and oseltamivir. In an application scene, the akebia quinata phenylethanoid glycoside B can be prepared into various drug dosage forms and can also be used as an active ingredient of a disinfectant, and a novel safe, efficient and multifunctional influenza prevention and control scheme is provided for the field of biological medicine.

The utility model is applicable to the technical field of separation devices, and provides a separation device with adjustable screening aperture for oseltamivir preparation, which comprises a bottom frame and a separation box, the bottom frame is fixedly connected with the separation box, and the inner wall of the separation box is fixedly connected with a concentric-square-shaped plate. The inner wall of the concentric-square-shaped plate is slidably connected with a plurality of first U-shaped sieve plates and second U-shaped sieve plates which are evenly distributed, and the side walls of the two second U-shaped sieve plates and the side walls of the two first U-shaped sieve plates are fixedly connected with first supporting plates; threaded rotating rods are in threaded connection between the two first supporting plates connected with the first U-shaped sieve plate and between the two first supporting plates connected with the second U-shaped sieve plate correspondingly, one end of each threaded rotating rod is rotationally connected with a second supporting plate, and a linkage assembly is arranged between the two threaded rotating rods in a matched mode; and distance adjusting assemblies are arranged between the multiple second U-shaped sieve plates and between the multiple first U-shaped sieve plates in a matched mode correspondingly. The vibrating screen has the advantage that the screening aperture can be flexibly adjusted.

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 discloses a dynamic monitoring method for oseltamivir hydrolysis process based on surface enhanced Raman spectroscopy, which comprises the following steps: adding carboxylesterase into oseltamivir solution, taking graphene oxide alkyne quantum dot wrapped gold nanosphere as an SERS probe, performing Raman spectrum collection on the oseltamivir solution at different time points, and calculating the concentration of carboxylesterase in the oseltamivir hydrolysis process. And monitoring the hydrolysis kinetics process of oseltamivir in real time according to the intensity change of the Raman peak. The graphite oxide alkyne quantum dot wrapped gold nanosphere composite nanomaterial used in the invention is of a core-shell structure, the core is gold nanoparticles of 100 nm, the outer surface is wrapped by graphite oxide alkyne quantum dots to form a structure similar to a sesame ball, and the composite nanomaterial has a large specific surface area and can adsorb more target molecules. Meanwhile, chemical enhancement can be promoted through charge transfer between the graphene oxide alkyne quantum dot pi-pi structure and oseltamivir molecules, biocompatibility is good, and the graphene oxide alkyne quantum dot is suitable for analysis and detection of oseltamivir drug molecules.

The invention relates to the field of food detection, in particular to an analysis and detection method for antiviral drug residues in eggs, which comprises the following steps: S1, sample pretreatment: 1.1, sample preparation: shelling eggs, homogenizing, and storing at 4 DEG C; 1.2, extracting: weighing a homogenate sample, extracting twice by using 90% acetonitrile-1% formic acid solution, and merging supernate; 1.3, purifying and redissolving: purifying the supernate through an EMR-Lipid solid-phase extraction column, collecting eluent, blowing the eluent to be nearly dry at 40 DEG C by nitrogen, redissolving by using a formic acid-methanol solution, and filtering to obtain a matrix extracting solution; s2, preparing a standard solution; s3, instrument detection: performing chromatography-tandem mass spectrometry detection; s4, quantitative analysis: calculating the residual quantity of the eight antiviral drugs in the eggs according to the quantitative ion peak area by adopting a matrix matching standard curve external standard method. The precise detection of eight viruses, namely nevirapine, peramivir, famciclovir, rimantadine, amantadine, oseltamivir, imiquimod and memantine, is realized.