27 results about "Dapoxetine-N-oxide" patented technology

1. Name of the product in this design: Drug Packaging Box (Dapoxetine Hydrochloride Tablets). 2. Purpose of this design: for product packaging. 3. The key design features of this product are the combination of pattern and color. 4. The image or photograph that best illustrates the design's key features: the front view. 5. The design for which protection is sought includes color.

The application relates to the technical field of biotechnology, in particular to a dopamine reuptake inhibitor intermediate synthesis enzyme mutant and application, and amino acid sequences are shown in SEQ ID NO: 7-SEQ ID NO: 12. The stereoselectivity of asymmetric reduction catalysis of the dopamine reuptake inhibitor intermediate precursor is improved, the R-type dopamine reuptake inhibitor intermediate with high chirality purity is obtained, and the synthesis efficiency of the dopamine reuptake inhibitor intermediate is improved.

Provided are a benzisothiazole compound and application thereof, and a pharmaceutical composition and application thereof, which relate to the technical field of medications, and specifically relate to a 2H-benzotriazole-substituted benzisothiazole compound having a novel structure shown in a formula (I), as well as a pharmaceutical composition including the compound, and use of the pharmaceutical composition for the manufacture of a medicament for treatment and / or prevention of premature ejaculation. The anti-premature ejaculation activity of the compound is significantly higher than that of a marketed drug, namely dapoxetine, as studied by in vivo activity tests.

The invention discloses a dapoxetine oral soluble film and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The oral soluble film of dapoxetine is prepared from the following raw materials and auxiliary materials: a dapoxetine resin compound, a film forming material, a plasticizer and a pH regulator, the dapoxetine resin compound is a compound formed by performing ion exchange on dapoxetine hydrochloride and cation exchange resin. Compared with the existing commercially available dapoxetine tablets, the dapoxetine hydrochloride oral soluble film provided by the invention has bioequivalence before meal and after meal and uniform quality, and can realize industrial production.

1.The name of the design product: dapoxetine hydrochloride packaging box (red, blue and black). 2.The use of the design product: for packaging products. 3.The design points of the design product: the combination of shape, pattern and color. 4.The picture or photo that best indicates the design points: design 1 front view. 5.The design for which protection is sought includes color. 6.Design 1 is designated as the basic design.

The application discloses a dapoxetine hydrochloride tablet and a preparation method thereof. The dapoxetine hydrochloride tablet comprises the following components in percentage by mass: 15-45% of dapoxetine hydrochloride, 45-75% of a filling agent, 0.1-2% of a solubilizing agent, 2-10% of a disintegrating agent and 0.5-3% of a lubricant. The dapoxetine hydrochloride tablet is prepared by optimizing the types and proportions of the components, thereby effectively improving the stability and dissolution rate during accelerated storage and long-term storage, and reducing the impurity content. Specifically, the impurity contents during accelerated storage for 6 months and long-term storage for 36 months are lower than 0.06% and 0.05% respectively; the 15min dissolution rate during accelerated storage for 6 months is 99-100%; and the 15min dissolution rate during long-term storage for 36 months is 99.2-100.2%.

The invention discloses a benzisothiazole compound as well as a pharmaceutical composition and application thereof, belongs to the technical field of medicines, and particularly relates to a 2H-benzotriazole substituted benzisothiazole compound with a novel structure as shown in a formula (I), a pharmaceutical composition containing the compound and application of the compound in preparation of medicines for treating and / or preventing premature ejaculation. Through in-vivo activity test research, the compound has obviously higher anti-premature ejaculation activity than the on-sale drug dapoxetine.

The invention discloses a dapoxetine hydrochloride tablet pharmaceutical composition and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The composition comprises dapoxetine hydrochloride, sodium bicarbonate, a filler, a disintegrating agent and a lubricant. Aiming at the problems of low dissolution rate, poor stability, complex preparation process and the like of dapoxetine hydrochloride tablets in the prior art, sodium bicarbonate is introduced as a key auxiliary material, a raw material pretreatment process is optimized, a traditional adhesive is omitted, and the dissolution rate and the preparation stability are remarkably improved. The preparation method comprises the following steps: pre-drying the filling agent (microcrystalline cellulose) until the water content is less than or equal to 2.0%, sieving sodium bicarbonate with a sieve of more than 100 meshes, mixing the sodium bicarbonate with dapoxetine hydrochloride and the lubricant, directly tabletting, and then coating. The preparation method is simple in process, low in cost and suitable for industrial production, and the obtained tablet is high in dissolution rate and excellent in stability under the conditions of high temperature, high humidity and illumination.

The application relates to the field of biotechnology, in particular to a dapoxetine intermediate precursor reductase mutant, gene, engineering bacteria and application. The dapoxetine intermediate precursor reductase mutant, gene, engineering bacteria and application provided by the embodiment of the application, the amino acid sequence of the dapoxetine intermediate precursor reductase mutant is shown as SEQ ID NO: 16-SEQ ID NO: 19, the stereoselectivity of the asymmetric reduction catalysis of the dapoxetine intermediate precursor reductase mutant is improved, the R-type dapoxetine intermediate with high chirality purity is obtained, and the synthesis efficiency of the dapoxetine intermediate is improved.

The invention discloses a method for preparing dapoxetine hydrochloride process impurities, which has the advantages of mild reaction conditions, simple operation, high product purity, good and stable yield, no need of other harsh reaction conditions and high-pressure liquid phase preparation and complex separation and purification means, and can be used for preparing dapoxetine hydrochloride keto impurities and hydroxyl impurities of dapoxetine hydrochloride. The preparation method provides powerful support for quality research of dapoxetine hydrochloride and market supply of impurity reference substances, and also provides a method with improved value for large-scale preparation of the dapoxetine hydrochloride and the dapoxetine hydrochloride. The reaction general formula is shown in the specification.

The invention discloses a dapoxetine tablet and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The dapoxetine tablet comprises dapoxetine micelles, a filling agent, a composite disintegrating agent, a lubricant and a coating agent, dry granulation is adopted, and the stability problem caused by introduction of water is avoided. The dapoxetine hydrochloride is hermetically wrapped by the micelle (wrapped by the gastric-soluble coating), and the long-term stability of the drug is improved by matching with the antioxidant. Through the synergistic micellar effect of the composite disintegrating agent and the bicarbonate-doped coating, the prepared tablet has the technical effects of quick release and long-term stability.

The invention relates to the technical field of biology, in particular to a dapoxetine intermediate precursor reductase mutant, a gene, an engineering bacterium and application. According to the dapoxetine intermediate precursor reductase mutant, the gene, the engineering bacterium and the application provided by the embodiment of the invention, the amino acid sequence of the dapoxetine intermediate precursor reductase mutant is as shown in SEQ ID NO: 16-SEQ ID NO: 19, the stereoselectivity of asymmetric reduction catalysis on a dapoxetine intermediate precursor is improved, and the activity of the dapoxetine intermediate precursor reductase mutant is improved. The R-type dapoxetine intermediate with high chiral purity is obtained, and the synthesis efficiency of the dapoxetine intermediate is improved.

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an oral instant film agent containing dapoxetine or hydrochloride thereof and a preparation method of the oral instant film agent. The oral instant film provided by the invention is prepared from an active component, a film forming material, a taste masking agent and a pH (Potential of Hydrogen) regulator, the active component is dapoxetine or hydrochloride thereof; the film-forming material comprises 17-88 parts of polyvinyl alcohol, 5-88 parts of polyvinyl alcohol and hydroxypropyl methylcellulose E15. The invention provides the oral instant film agent of dapoxetine or hydrochloride thereof, which is good in taste, has good film-forming property and can take effect quickly. The film agent does not need to be taken with water, is convenient to take, good in taste, rapid in dissolution and very suitable for patients with premature ejaculation and poor ejaculation control ability, and the medication compliance and safety of the patients are improved.

The invention discloses a method for removing polymerization impurities of dapoxetine hydrochloride, which comprises the following operation steps of: (1) adding a dapoxetine hydrochloride crude product containing the polymerization impurities into a good solvent of dapoxetine hydrochloride, heating, stirring and dissolving; (2) adding an adsorbent into the clear solution obtained in the step (1), stirring for a certain time, and filtering; (3) dropwise adding a poor solvent of dapoxetine hydrochloride into the filtrate obtained in the step (2) while keeping the temperature; and (4) cooling and crystallizing the mixed system obtained in the step (3), and carrying out suction filtration to obtain a refined dapoxetine hydrochloride product. According to the dapoxetine hydrochloride obtained through the refining method of the dapoxetine hydrochloride polymeric impurities, the recovery rate can reach 90% or above, and the purity of the dapoxetine hydrochloride can reach 99.93% or above. The method has the characteristics of high yield, simple operation, mild conditions, less discharge of three wastes and the like, is suitable for industrial production, and has high practical value.

According to the asymmetric preparation method of dapoxetine hydrochloride, provided by the invention, the dapoxetine hydrochloride is obtained by taking 3-halogenated propiophenone as a raw material and carrying out asymmetric reduction, coupling etherification, amination and salification, a chiral center is prepared by adopting asymmetric reduction, a subsequent resolution process is avoided, the route economy is improved, and the method is suitable for industrial production. The method is of great significance to cost reduction of enterprises.

1. The name of the design product: packaging box (dapoxetine hydrochloride tablet small box 2). 2. The use of the design product: for packaging box. 3. The design features of the design product: the combination of shape and pattern. 4. The picture or photo that best indicates the design features: front view.

1. The name of the design product: packaging box (dapoxetine hydrochloride tablet 1). 2. The use of the design product: for packaging box. 3. The design points of the design product: in the combination of shape and pattern. 4. The picture or photo that best indicates the design points: front view.

This application relates to the field of biotechnology, and in particular to a method for the biological preparation of dapoxetine intermediates. The method uses a recombinant engineered bacterium containing a dapoxetine intermediate precursor reductase mutant, the amino acid sequence of which is shown in SEQ ID NO: 19. This bacterium exhibits improved stereoselectivity in asymmetric reduction catalysis of the dapoxetine intermediate precursor, yielding a highly chiral and pure R-type dapoxetine intermediate, which is beneficial for improving the synthesis efficiency of dapoxetine intermediates.

The invention discloses a dapoxetine hydrochloride tablet coating thickness detection device, which comprises a bottom plate, and is characterized in that the lower end of the bottom plate is symmetrically and fixedly connected with two support frames; the thickness detection mechanism comprises an L-shaped frame fixedly connected to the upper end of the bottom plate, a first shading box is fixedly connected to the lower end of the horizontal portion of the L-shaped frame, a second near-infrared detection head is installed on the inner top of the first shading box, and a second shading box is fixedly connected to the upper end of the bottom plate; a first near-infrared detection head is mounted at the inner bottom of the second shading box; and the medicine putting-in mechanism comprises a rotating shaft rotationally connected to the upper end of the bottom plate, the upper end of the rotating shaft is fixedly connected with a rotating disc, and three rectangular medicine putting openings are vertically formed in the rotating disc in a penetrating mode. The invention also discloses a dapoxetine hydrochloride tablet coating thickness detection method. When the detection device is used, the detection continuity is high, two-side detection is achieved at the same time, and the detection efficiency is effectively improved.

The main object of the present application is to provide a dapoxetine hydrochloride oral fast dissolving film and a method for preparing the same, the oral fast dissolving film comprising the following components: a combination of a dapoxetine hydrochloride resin complex and one or more of pharmaceutically acceptable oral preparation adjuvants, wherein the dapoxetine hydrochloride resin complex is a complex formed by dapoxetine hydrochloride and a taste masking ion exchange resin, and the mass ratio of dapoxetine hydrochloride to the taste masking ion exchange resin is 0.5:1-5:1, the oral fast dissolving film prepared by the method has no irritating taste, fast disintegration speed, fast absorption, and improves the medication privacy and compliance of patients.

The present invention relates to a process improvement method for dapoxetine hydrochloride. The synthesis process of the present invention uses 3-nitro-5-trifluoromethyl salicylaldehyde as a racemization catalyst, can achieve crystallization-induced asymmetric transformation, and compared with the prior art, which simply splits the isomers (theoretically, the maximum yield that can be achieved is only 50%), the product purity is high, the yield is high, and the cost is saved. At the same time, the synthesis process of the present invention is simple to operate and easy to realize industrialization.

The invention discloses a preparation method of dapoxetine hydrochloride, which adopts acetonitrile as a reaction solvent, is easy to recycle and reuse, and avoids the generation of a large amount of nitrogen-containing wastewater; sodium hydroxide or potassium hydroxide is used as an acid-binding agent which is cheap and easy to obtain; isopropyl ether is adopted as a crystallization solvent, heating is carried out until reflux is achieved, filtering is carried out while the solution is hot, insoluble impurities with large polarity can be filtered out, filtrate is cooled to-10-10 DEG C for crystallization, solid-liquid separation is carried out, impurities with small polarity can be removed, and the obtained dapoxetine base is good in crystallization performance. And the defect that the hydrochloride is prepared by introducing hydrogen chloride gas in the prior art is avoided. According to the dapoxetine hydrochloride, methylbenzene is adopted as a reaction solvent, concentrated hydrochloric acid is adopted as acid, after charging is completed, heating is conducted till backflow and water separation are conducted, after water separation is completed, a large amount of white crystalline solid dapoxetine hydrochloride can be separated out, and the dapoxetine hydrochloride prepared through the method and the intermediate of the dapoxetine hydrochloride are high in yield and purity.

The invention provides a preparation method of a dapoxetine hydrochloride intermediate (R)-3-chlorophenylpropanol. The preparation method is good in safety, convenient to operate, low in cost, good in product quality, high in yield and easier to industrialize. According to the method, the N, N-diethyl aniline hydrochloride is subjected to post-treatment in a vacuum concentration manner, so that the water content in the N, N-diethyl aniline hydrochloride can be remarkably reduced, and further, the hydration loss of (R)-3-chlorophenylpropanol caused by the water content in the N, N-diethyl aniline hydrochloride is avoided; the vacuum concentration mode is simple and convenient to operate, and the product is high in yield and quality.

The invention relates to the technical field of drug synthesis, and discloses a dapoxetine hydrochloride preparation method, which comprises: a catalytic reaction step: providing 3-chloropropiophenone and naphthol as reactants, and carrying out a condensation reaction by using a catalyst to generate a reaction intermediate; a reduction step: carrying out a reduction reaction on the reaction intermediate and a reducing agent to form a reduction precursor; methylation: carrying out methylation reaction on the reduction precursor and a methylation reagent to introduce a methyl group; and a hydrochloric acid acidification step: carrying out a hydrochloric acid acidification reaction on the methylation product and hydrogen chloride to generate dapoxetine hydrochloride. By adopting the supercritical carbon dioxide, the lipase or the metal organic framework catalyst, hydrogen reduction and the process of dropwise adding the methylation reagent, the reaction efficiency, the selectivity and the product purity are improved, the generation of by-products is reduced, the reaction conditions are optimized, and the environmental pollution is reduced.

The application relates to the field of biotechnology, in particular to a reductase mutant for synthesizing a dapoxetine intermediate and application, the amino acid sequence of the reductase mutant for synthesizing the dapoxetine intermediate is shown in SEQ ID NO: 13-SEQ ID NO: 15, the stereoselectivity of asymmetric reduction catalysis of the reductase mutant for a dapoxetine intermediate precursor is improved, the R-type dapoxetine intermediate with high chiral purity is obtained, and the synthesis efficiency of the dapoxetine intermediate is improved.

The invention provides a method for preparing a high-purity R-(+)-3-chlorobenzene propanol monospin. The method specifically comprises the following steps: dissolving NaBH4 in ethylene glycol dimethyl ether, sequentially adding N, N-diethylaniline hydrochloride, S-diphenyl amino prolinol and 3-chloropropiophenone, stirring for reaction, adding water for quenching, filtering, and concentrating filtrate under reduced pressure; adding methylbenzene and hydrochloric acid into the concentrated solution, extracting and separating liquid, washing an organic layer with water and a saturated saline solution, drying, filtering, evaporating under reduced pressure to remove a solvent, adding a solvent A and a solvent B into the obtained viscous substance, heating for dissolving, and cooling for crystallization to obtain the product. Wherein the solvent A is one or more of chloroform, dichloroethane, n-heptane, cyclohexane, petroleum ether, acetone and the like; and the solvent B is one or more of methanol, ethanol and isopropanol. The preparation method of R-(+)-3-chlorobenzene propanol provided by the invention is simple in process, the obtained product has high purity while keeping high yield, and a key and stable chiral intermediate is provided for preparing high-quality dapoxetine hydrochloride.