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

The present invention relates to a time-delayed sustained release pharmaceutical composition for oral administration, which comprises an immediate release phase and a prolonged sustained release phase, wherein said immediate release phase and prolonged sustained release phase respectively comprise dapoxetine therein as an active ingredient.; The pharmaceutical composition of the present invention comprises dapoxetine, which is an agent for treating premature ejaculation, in both the immediate release phase and the prolonged sustained release phase thereof, to thereby immediately exhibit the effectiveness of the pharmaceutical composition of the present invention in order to enable a patient to achieve sexual satisfaction during the early stage of administration, as well as to reduce side effects by means of the time-delayed sustained release of the prolonged sustained release phase during the early stage of administration and enable a continuous in vivo absorption of dapoxetines, to thereby lengthen the duration of the effectiveness of the pharmaceutical composition of the present invention.; Further, agents for treating erectile dysfunction, such as sildenafil, tadalifil or the like can be added to the immediate release phase so as to allow for a coincidence of the durations of the effectiveness of a premature ejaculation treatment agent and erectile dysfunction treatment agents, even though a half-life difference exists between the two types of treatment agents, thus maximizing patient satisfaction.

The invention discloses a dapoxetine detection method using a diode array detector and using a phosphate buffer solution (pH value is adjusted to 3.2 with phosphoric acid)-acetonitrile-methanol solution as a mobile phase. The dapoxetine detection method is as follows: taking proper amounts of dapoxetine and dapoxetine-containing relevant preparations, adding the mobile phase to prepare a solution containing 0.2mg of the dapoxetine every 1ml of the solution as a solution to be tested; diluting the solution to be tested with the mobile phase into a solution containing 0.2mug of the dapoxetine every 1ml of the solution as a contrast solution; and respectively injecting samples; wherein the sum of peak areas of impurities in a chromatogram map of the solution to be tested may not be greater than main peak area of the contrast solution. According to the detection method for the related substances in the dapoxetine and the dapoxetine-containing relevant preparations, the conditions of the impurities and degradation products of the dapoxetine can be quickly and accurately detected, and the detection method is simple in operation and high in sensitivity, and can be used to better control the quality of the product.

The invention discloses a method for preparing dapoxetine intermediate by using carbonyl reductase. In the method, a crushed mixed solution of wet cells obtained by induction culture of engineered bacteria containing the carbonyl reductase gene after ultrasonication is used as a catalyst, and 3-chlorophenylacetone is used as a substrate, and NADH and isopropanol are added, and a phosphate buffer with a pH of 6.5. -7.5 is used as a reaction medium to constitute a reaction system. The reaction system is complete with magnetic stirring at 30-40 DEG C. The reaction solution is separated and purified to obtain (R)-3-chlorophenylpropanol. The invention adopts a new type of carbonyl reductase to catalyze a reduction reaction, has the advantages of small amount of biocatalyst, mild reaction conditions (30-40 DEG C), short reaction time (6-12 hours), 95.2% of yield coefficient, and good optical purity (greater than 99), and the like.

The invention discloses a method for preparing a dapoxetine intermediate (S)-3-chloro-N, N-dimethyl-1-phenyl-1-propylamine, and preparation of dapoxetine hydrochloride by using the intermediate through condensation and salification. The preparation of dapoxetine hydrochloride is shortened in reaction steps, reduced in cost, simple in operation and is applicable to industrial production.

The invention relates to a crystal form A of dapoxetine hydrochlorate which is a drug for treating male premature ejaculation, and a preparation method thereof; the crystal form A is characterized in that the crystal form A has characteristic diffraction peaks corresponding to positions with 2theta values of about 8.9 degrees, 14.4 degrees, 15.1 degrees, 16.3 degrees, 16.6 degrees, 18.9 degrees, 20.7 degrees, 22.7 degrees, 23.8 degrees, 25.3 degrees, 29.0 degrees, and 29.5 degrees on an X-ray powder diffraction pattern, and the new crystal form has the characteristics of high purity, good stability, and the like.

The invention provides a novel synthesis, gradient separation-purification, and salt forming method of dapoxetine. Easily available and cheap benzaldehyde is taken as the primary raw material of the synthesis route. The whole reaction conditions are mild. The synthesis route is short. No highly toxic or explosive raw material is used. The problem of chiral separation is well solved in the route. During the separation process, the product is purified. Finally, chlorinated hydromethyl tert-butyl ether which does not have any side or toxic effect is used to carry out salt forming. A large amount of labor, material, and time is saved. The production cost is reduced. The synthesis does not need any special equipment. The operation is simple and convenient. The method has a good industrial application prospect.

The invention discloses a dapoxetine intermediate and a preparation method thereof and provides a preparation method for the compound represented in the formula (2). The preparation method includes a step of performing a nucleophilic substitution reaction to the compound represented in the formula (3) with 1-naphthol in a solvent in the presence of alkali to prepare the compound represented in the formula (2). The R1 and the R2 are independently C1-C4 alkyl groups, or that the R1, the R2, oxygen atoms connected thereto respectively and carbon atoms connected to the oxygen atoms form a five-membered saturated ring structure or six-membered saturated ring structure, wherein X is Cl, Br or I. The raw materials are low in cost and easy to obtain. The preparation method is mild in reaction conditions, is high in conversion rate, is high in yield, is simple in after treatment, is low in production cost, is high in chemical purity of product, and is suitable for industrial production.

The invention discloses a preparation process for preparing a dapoxetine hydrochloride beta-isomer impurity shown as formula I and an enantiomer shown as formula II. The method comprises the following steps: taking optically pure Boc-(S) or (R)-3-amino-3-phenylpropanol as a raw material, performing condensation reaction with 2-fluoronaphthalene or 1-fluoronaphthalene, performing methylation reaction with formic acid-formaldehyde, and performing HCl salification reaction to obtain a target product dapoxetine hydrochloride beta-isomer or enantiomer impurity. Meanwhile, a detection method of isomer impurities is developed.

The invention discloses a biosynthesis method of a dapoxetine intermediate and an intermediate thereof. The method uses compound (2) and compound (3) as starting materials, and prepares compound (4) through a phase transfer catalytic substitution reaction , the compound (4) finally obtains the dapoxetine intermediate compound (1) through a biological enzyme conversion reaction, and its reaction formula is as follows: The biosynthesis method of the dapoxetine intermediate of the present invention has a novel synthetic route, Simple and easy to implement, low cost, high synthetic yield, high yield, good product purity, good product quality, cheap and easy-to-get raw materials, and suitable for industrial production. The preparation of poxetine provides a new intermediate raw material.

The invention discloses a preparation method of a dapoxetine impurity reference substance, which comprises the following steps: (1) reacting 3-(naphthalene-1-yloxy)-1-phenylpropan-1-ol with a p-methoxybenzyl reagent to obtain a compound 7; (2) reacting the compound 7 with 3-chloro-1-phenylpropyl-1-ketone to obtain a compound 8; (3) removing a p-methoxybenzyl protecting group in the compound 8 by using an oxidizing agent to obtain a compound 4; (4) reacting the compound 4 with alkyl sulfonyl chloride, and then reacting the compound with dimethylamine to obtain the dapoxetine impurity reference substance as shown in a formula 6. The dapoxetine impurity reference substance shown in the formula 6 is prepared for the first time.

The invention belongs to the field of pharmaceutical preparations. The dapoxetine hydrochloride tablet is composed of 33.6 mg of dapoxetine hydrochloride, less than 18 mg of microcrystalline cellulose, 40-45% of a filler, 2-8% of a disintegrating agent, 1-5% of a flow aid, 0.5-3% of a lubricant, 1-5% of coating powder and a special packaging material. The key composition auxiliary materials and the packaging material can greatly improve the stability of the medicine as well as the rate and degree of in-vivo absorption into blood, so that the curative effect is influenced.

The invention discloses a dapoxetine hydrochloride monohydrate and a preparation method thereof, a composition containing the dapoxetine hydrochloride monohydrate, and uses of the composition in preparation of drugs for treatment of sexual dysfunction, wherein the dapoxetine hydrochloride monohydrate is represented by a formula I. According to the present invention, the dapoxetine hydrochloride monohydrate overcomes the disadvantages of easy moisture absorption, poor stability, high requirements on storage conditions and difficult long-term preservation of the existing crystal form or the amorphous form of dapoxetine hydrochloride, and is suitable for industrial scale-up and preparation production. The formula I is defined in the specification.