42 results about "Oseltamivir Phosphate" patented technology

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.

1. Name of the designed product: medicine packing box (8 pieces of Oseltamivir Phosphate Capsules of Sensaijue brand). 2. Use of the designed product: the designed product is used for packing medicine. 3. Design points of the designed product: combination of shape and pattern. 4. Picture or photo best indicating the design points: front view.

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 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 provides a compound preparation containing macarovir, a preparation method and application of the compound preparation in anti-influenza treatment, the multi-layer pellet compound preparation sequentially comprises a pellet core layer containing macarovir, an isolating layer, an active layer and an enteric layer from inside to outside, the pellet core layer containing macarovir and a sustained-release material, the isolating layer comprises an adhesive and an anti-sticking agent, the active layer comprises a hydrophobic layer and a hydrophobic layer, and the enteric layer comprises a hydrophobic layer and a hydrophobic layer. The active layer comprises oseltamivir phosphate and an adhesive, and the enteric-coated layer is made of synthetic polymer materials. The multi-layer pellet provided by the invention has good compressibility, disintegrability and lubricity. The compound preparation solves the problems of drug resistance, drug interaction and children medication compliance. The preparation is suitable for single-drug or combined treatment of influenza A / B viruses, and is especially suitable for children and drug-resistant influenza patients.

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.

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 invention discloses a high performance liquid chromatography method for detecting related substances in an oseltamivir phosphate product, and the chromatographic conditions are as follows: an octyl silane bonded silica gel column is used as a chromatographic column, 0.05 mol / L monopotassium phosphate buffer solution-methanol-acetonitrile is used as a mobile phase, the volume ratio is 620: 245: 135-700: 245: 135, the pH value of the 0.05 mol / L monopotassium phosphate buffer solution is regulated to 5.5-5.9 by using a 1mol / L potassium hydroxide solution, and the column temperature is controlled to be 30-60 DEG C; the flow velocity is 1.1-1.3 ml / min, the column temperature is 48-52 DEG C, the detection wavelength is 207 nm, and the sample injection volume is 15-30 [mu] l. The chromatographic method provided by the invention can effectively separate and detect oseltamivir phosphate and related substances in an oseltamivir phosphate product, is not interfered by auxiliary material peaks, can fully meet the requirements of detection of related substances and determination of decomposed products, well controls specific impurities and non-specific impurities in a sample, and improves the detection accuracy of oseltamivir phosphate. Therefore, the product quality of the oseltamivir phosphate capsule is controlled, and a guarantee is provided for synthesis and preparation process optimization.

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 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.

1. Name of the product of this design: Pharmaceutical packaging box (Gansage Oseltamivir Phosphate Capsule Series). 2. Purpose of this design product: This 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 key points of the design: Main view of Design 1. 5. Designate Design 1 as the base design.

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 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.

This invention proposes a high-efficacy oseltamivir phosphate capsule and its preparation method. The oseltamivir phosphate capsule comprises the following components: 120-130 parts of oseltamivir phosphate, 30-45 parts of pregelatinized starch, 5-10 parts of sodium stearate, 5-10 parts of drug-loaded material, 5-10 parts of talc, and 20-25 parts of povidone K30; the drug-loaded material is microcrystalline cellulose and poloxamer. The oseltamivir phosphate capsule prepared by this invention achieves an average cumulative dissolution rate of over 90% within 15 minutes in dissolution media of water and pH 6.8 phosphate buffer solution, exhibiting excellent dissolution. In an accelerated 6-month test, the dissolution rate still reaches over 85%, demonstrating good stability, drug stability, and high efficacy.

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.

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 provides for a flow synthesis process for producing Oseltamivir and pharmaceutically acceptable salts thereof from shikimic acid in particular but not exclusively to a flow synthesis process for producing Oseltamivir phosphate from shikimic acid in a nine-step flow synthesis that provides for superior reaction times and product yields compared to known methods.

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 provides a plumeria rubra extract, a preparation method thereof and application of the plumeria rubra extract in preparation of a medicine with a neuraminidase inhibition effect, and relates to the technical field of natural medicine extraction and application. The preparation method of the plumeria rubra extract comprises the following steps: firstly, performing alcohol extraction on plumeria rubra powder by using ethanol to obtain a plumeria rubra alcohol extract; and performing chromatographic elution, concentration and drying on the plumeria rubra alcohol extract by using a composite resin chromatographic column to obtain the plumeria rubra extract. Through verification, the plumeria rubra extract prepared by the method has an inhibition effect on neuraminidase, and the inhibition effect is obviously higher than that of oseltamivir phosphate. In addition, when the prepared plumeria rubra extract is combined with oseltamivir phosphate for use, the inhibition effect of oseltamivir phosphate on oseltamivir drug-resistant neuraminidase can be effectively improved. Therefore, the plumeria rubra extract disclosed by the invention, as an effective component, can be widely applied to a preparation process of a medicine with a neuraminidase inhibiting effect.

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.

1. Name of the product of this design: Medicine box (oseltamivir phosphate dry suspension). 2. Purpose of this design product: used for outer packaging of medicines. 3. The key design points of this design product lie in the shape, pattern and their combination. 4. The picture or photo that best illustrates the key points of the design: main view.

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.