64 results about "Oseltamivir" patented technology

The present invention relates to a conjugate for inhibiting viral replication, a preparation method therefor, and use thereof. The conjugate comprises a dimer or trimer of a portion that inhibits influenza virus neuraminidase (e.g. zanamivir, peramivir, oseltamivir, or an analog thereof), the dimer or trimer being conjugated to an Fc domain monomer, an Fc domain, an Fc-binding peptide, an albumin, or an albumin-binding peptide. The conjugate can be used to treat viral infections (e.g., influenza virus infections).

According to the oseltamivir phosphate granules and the preparation method thereof, the granules are prepared by mixing the medicine-containing granules, the blank granules and the pharmaceutically acceptable auxiliary materials, and by selecting the specific auxiliary materials and the proportion of the auxiliary materials, the prepared granules maintain a high dissolution speed and achieve a good taste masking effect; according to the present invention, the traditional Chinese medicine composition has advantages of good taste, high content uniformity, high dissolution speed, good fluidity, low related substance content, good stability and the like, can meet different administration dosage requirements, and is suitable for children administration, and the pharmaceutical composition can be used for children, and can be used for preparing drugs for children, such that the pharmaceutical composition has characteristics of good taste, high content uniformity, high dissolution speed, good fluidity, low related substance content, and the like.

The invention belongs to the field of medicine, and relates to an oseltamivir phosphate taste-masking preparation and a preparation method thereof.The oseltamivir phosphate taste-masking preparation comprises a drug-loading pill, an isolation layer and a taste-masking layer, the drug-loading pill comprises oseltamivir phosphate and a blank pill core, the blank pellet core is selected from one of a sucrose pellet core, a microcrystalline cellulose pellet core, a starch pellet core, a lactose pellet core and a silicon dioxide pellet core; the isolation layer comprises an isolation material, the taste masking layer comprises a taste masking component, and the taste masking component is one or more of a methacrylic acid amine alkyl ester copolymer and polyacrylic resin IV. The taste of the active ingredients of the medicine is masked through a multi-layer coating technology, the taking taste is improved, the active ingredients of the medicine are endowed with good stability, the medicine can be rapidly released, meanwhile, the good taste is achieved, the taste masking effect is good, and meanwhile the stability of the medicine is guaranteed.

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.

Provided herein are oseltamivir analogs useful for the treatment and prevention of viral infections, pharmaceutical compositions comprising the same and methods preparation and use thereof.

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.

This application belongs to the field of pharmaceutical technology. More specifically, it relates to the use of sodium metatungstate in the preparation of drugs for treating or preventing influenza virus infection. Experiments have shown that sodium metatungstate has a broad-spectrum anti-influenza virus effect and can effectively inhibit influenza virus strains of different serotypes such as H1N1 and H3N2 on cell models. In addition, it also has an inhibitory effect on oseltamivir-resistant virus strains. The study on the anti-influenza virus mechanism of sodium metatungstate found that sodium metatungstate does not directly inactivate influenza virus; although it causes agglutination of the virus during the virus adsorption process, it does not affect the occurrence of adsorption, nor does it affect the process of the virus being endocytosed into the cytoplasm. However, sodium metatungstate will block the nuclear entry of influenza virus vRNP, thereby inhibiting virus replication.

1. The name of the product of this design: packaging box (oseltamivir phosphate dry suspension). 2. Purpose of this design product: used for the outer packaging of oseltamivir phosphate dry suspension medicine. 3. The design key point of this appearance 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 present invention relates to a method for detecting related substances in an oseltamivir phosphate starting material. The oseltamivir phosphate starting material is ethyl 5-(pentan-3-yloxy)-7-oxo-bicyclo[4.1.0]hept-3-ene-3-carboxylate. The detection method comprises the following steps: using reverse-phase high performance liquid chromatography (RP-HPLC) and acetonitrile-water as a mobile phase to detect ethyl 5-(pentan-3-yloxy)-7-oxo-bicyclo[4.1.0]hept-3-ene-3-carboxylate and seven related substance impurities thereof; wherein C10-SM1-ZZ9 is the process source of impurity C10-ZZF (impurity F in EP9.0) in an oseltamivir phosphate finished product; the detection method can quantitatively detect a content of C10-SM1-ZZ9 equivalent to 0.0084% of a test sample concentration, and can effectively control the content of impurity F in the finished product; the method is highly practical, and the detection process is simple and quick.

The present invention belongs to the technical field of antiviral drug preparations, and specifically relates to a composition containing oseltamivir phosphate and its use in preparing antiviral drugs. The composition containing oseltamivir phosphate of the present invention is composed of oseltamivir phosphate, pulegone, soybean lecithin or / and egg yolk lecithin, and cholesterol. Oseltamivir phosphate and pulegone are encapsulated by liposome technology, and the structural integrity of the liposome and the stability of the drug are maintained by dual regulation of glucose and pH, and the content of related substances is reduced. Animal experiments are also used to carry out drug efficacy verification, and the therapeutic effect is better than that of commercially available preparations.

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 utility model discloses an impurity removal device for oseltamivir intermediate production, which belongs to the technical field of medicine processing, and comprises a shell, a feeding component, a filtering component and a driving component, the shell comprises a shell, a sealing groove is formed in one side of the shell, a sealing plate is arranged in the sealing groove, the feeding component comprises a water pump, and the filtering component is arranged in the water pump. The water inlet end of the water pump is connected with the liquid inlet pipe, and the water outlet end of the water pump is connected with the guide pipe; according to the utility model, the intermediate body in the external liquid conveying pipeline can be sprayed on the surface of the filter screen from the plurality of liquid spraying pipes under the action of the working water pump, and the acting force between the intermediate body sprayed on the surface of the filter screen and the filter screen is increased, so that impurities in the intermediate body can be efficiently filtered by the filter screen; and then the cleaning tool is in contact with the filter screen and the filter screen is rotated, so that the filter screen can be cleaned, the operation is convenient, and the device can be conveniently maintained.

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 present invention discloses an oseltamivir azide derivative, the structure of which is shown as impurity 338 or impurity 340. The two impurities were first discovered during the preparation process of oseltamivir phosphate, and have relatively obvious toxicity. Therefore, it is necessary to control the content of these two impurities in oseltamivir phosphate to be no higher than 30 ppm to reduce the safety risks existing during the use of oseltamivir phosphate.

The present invention discloses a double-head granule filling device for preparing oseltamivir phosphate dry suspension, which relates to the field of processing oseltamivir phosphate dry suspension. A double-head granule filling device includes a workbench, a conveyor belt arranged on the workbench, and a double-head filling unit arranged on the top of the workbench. A detection unit is arranged at the bottom of the double-head filling unit, and a plurality of packaging cans are arranged on the conveyor belt. An installation box is fixedly installed on the top of the workbench, and a calibration mechanism is arranged on the installation box; for this double-head granule filling device for preparing oseltamivir phosphate dry suspension, the driving component drives the cross plate to rotate, so that the arc-shaped support plate arranged on the limiting baffle can clamp the packaging can and drive it to move upward to be separated from the conveyor belt, so that when the conveyor belt conveys the subsequent packaging cans forward, it will not affect the position of the current packaging can, enabling all packaging cans to be filled and then conveyed forward, thereby effectively reducing the probability of filling omission.

The invention discloses a preparation method of an oseltamivir phosphate crystal form B. The preparation method comprises the following steps: mixing oseltamivir, phosphoric acid and a first solvent at a first temperature to prepare a first solution; mixing the first solution with a second solvent at a first temperature, cooling to a third temperature, stirring, filtering, taking a filter cake, and drying to prepare an oseltamivir phosphate crystal form B; or mixing oseltamivir phosphate with a third solvent at a second temperature to prepare a second solution; mixing the second solution, a fourth solvent and the seed crystal at a second temperature, cooling to a third temperature, stirring, filtering, taking a filter cake, and drying to prepare an oseltamivir phosphate crystal form B; wherein the first solvent is an alcohol solvent; the second solvent is a ketone solvent; the third solvent is selected from one or more of an alcohol solvent and water; the fourth solvent is selected from one or more of a ketone solvent, an alkane solvent and an ester solvent. The preparation method can obviously improve the yield of the target crystal form, and is simple and convenient to operate.

The present invention provides an oseltamivir intermediate preparation method, which comprises: carrying out a tert-butyl removal reaction on a compound 1 under an acidic condition to obtain a compound 2, wherein the acidic condition is trichloroacetic acid, chloroacetic acid, dichloroacetic acid, acetic acid, methanesulfonic acid, benzenesulfonic acid, formic acid or a mixture thereof. The post-treatment step comprises the following steps: after the reaction is finished, dissolving by using an organic solvent to obtain a solution containing the compound shown in the formula 2, cooling the obtained solution of the compound shown in the formula 2, adjusting the pH value by using an inorganic alkali aqueous solution, extracting, layering and concentrating to obtain the compound shown in the formula 2. According to the preparation method of the oseltamivir intermediate provided by the invention, materials with lower cost are used for replacing original expensive reagents, the molecular availability is improved, the cost is greatly reduced, and post-treatment and purification methods are simple and convenient to optimize.

The invention relates to a conjugate for inhibiting virus replication and a preparation method and application thereof. The present invention relates to a conjugate comprising a dimer or trimer of a moiety that inhibits influenza virus neuraminidase (e.g., zanamivir, peramivir, oseltamivir, or an analog thereof) coupled to an Fc domain monomer, an Fc domain, an Fc binding peptide, an albumin, or an albumin binding peptide. The conjugates are useful in the treatment of viral infections (e.g., influenza virus infections).

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 invention discloses oseltamivir phosphate particles and a preparation method thereof, and particularly relates to the technical field of oseltamivir particle preparation, and the preparation method comprises the following steps: raw material preparation, raw material mixing, soft material preparation, drying and grinding, whole particle sieving, and filling and sub-packaging. The oseltamivir phosphate adopting erythritol, starch slurry and water as a diluent, an adhesive and a solvent can generate relatively low heat in a body, meanwhile, the starch slurry is dissolved in water, so that the preparation cost of the oseltamivir phosphate is reduced, the starch slurry can be decomposed into glucose in the body after being taken, the glucose is absorbed into blood circulation, and the blood circulation is promoted. The oseltamivir phosphate granules have the advantages that the oseltamivir phosphate granules prepared by the aid of the method are low in toxicity and low in harm to human bodies, the oseltamivir phosphate granules are dried at the temperature of 60 DEG C for 7.5 hours when the oseltamivir phosphate granules are dried after the oseltamivir phosphate granules are prepared, accordingly, the water content of the oseltamivir phosphate granules can be reduced, the oseltamivir phosphate granules can be conveniently crushed into powder, the brown scorch rate of the oseltamivir phosphate granules can be reduced, and the yield of the

The invention discloses a preparation method of an oseltamivir phosphate crystal form A. The preparation method comprises the following steps: mixing oseltamivir phosphate with a first solvent at a first temperature to prepare a first solution; mixing the first solution with a second solvent at a second temperature, cooling to a third temperature, stirring, filtering, taking a filter cake, and drying; wherein the first solvent is selected from one or more of an alcohol solvent and water; the second solvent is selected from one or more of a ketone solvent, an alkane solvent, an ester solvent and a nitrile solvent. The preparation method provided by the invention can obviously improve the yield of the target crystal form, and is easy to operate, mild in condition and relatively short in process and duration.