103 results about "Paroxetine" patented technology

Described herein are silicone-containing acrylic polymers useful, for example, in transdermal drug delivery compositions, to methods of making and using them, to transdermal drug delivery compositions comprising them, and to methods of making and using such transdermal drug delivery compositions. The polymers are particular suitable for formulating amine drugs, such as amphetamine, methylphenidate, rivastigmine, paroxetine and clonidine.

A liquid paroxetine composition containing at least 5 mg/ml of paroxetine or a pharmaceutically acceptable salt thereof, a non-carbohydrate sweetener, and a solvent containing 60-100% of ethanol, polyol or mixtures and 0-40% of water, provides for good stability and taste.

The invention provides a kit for detecting anti-depressant drugs in serum and plasma by liquid chromatography tandem mass spectrometry. The kit comprises drug standard substances, drug internal standardization compounds, drug extraction compositions, negative plasma and a diluent. The drug standard substances comprise amfebutamone, oxybupropion, citalopram, Escitalopram, venlafaxine, O-desmethylvenlafaxine, duloxetine, fluoxetine, norfloxetine, fluvoxamine, mirtazapine, paroxetine, sertraline and trazodone. The drug internal standardization compounds comprise amfebutamone-d9, oxybupropion-d6,citalopram-d6, venlafaxine-d6, O-desmethylvenlafaxine-d6, duloxetine-d3, fluoxetine-d6, norfloxetine-d6, fluvoxamine-d4, mirtazapine-d3, paroxetine-d6, sertraline-d3 and trazodone-d6. The drug extraction compositions comprise, by volume, 60% of methanol solution, 20% of acetonitrile solution, 10% of isopropyl alcohol solution and 10% of purified water. The diluent comprises 50 % of methanol waterfluid. The kit can be used for simultaneous detection of the anti-depressant drugs and active metabolites, the detection time is short, and flux is high.

The invention belongs to the technical field of biocatalysis and discloses a method for preparing a paroxetine intermediate through enzymatic resolution in an ionic liquid, which comprises the following step of: preparing (3S,4R)-4-(4-fluorophenyl)-3-hydroxymethyl-1-R-piperidine by using the ionic liquid as a reaction medium and utilizing the transesterification reaction of racemic 4-(4-fluorophenyl)-3-hydroxymethyl-1-R-piperidine (II) as a lipase-catalyzed substrate and an acyl donor. The preparation method provided by the invention has the advantages of mild reaction conditions, simple operation and high conversion ratio, the highest optical purity can reach 98 percent, and the enzyme can be repeatedly utilized and is environmentally-friendly. The (3S,4R)-4-(4-fluorophenyl)-3-hydroxymethyl-1-R-piperidine is a key intermediate for preparing paroxetine as an antidepressant, and the invention supplies a feasible approach for the preparation of the paroxetine.

Embodiments of the invention describe compositions and methods for the administration of fast disintegrating atypical antipsychotics, metabolites of atypical antipsychotics, and antidepressants which reduce weight in patients previously taking conventional formulation of atypical antipsychotics and antidepressants. In a preferred embodiment said fast dissolving atypical antipsychotic is FAZACLO. In another preferred embodiment said fast dissolving metabolite of an atypical antipsychotic is desmethyl clozapine. In another preferred embodiment said fast dissolving antidepressant is paroxetine.

The pharmaceutical composition of the present invention comprises (1) a carbostyril derivative and (2) a serotonin reuptake inhibitor in a pharmaceutically acceptable carrier. The carbostyril derivative may be aripiprazole or a metabolite thereof, which is a dopamine-serotonin system stabilizer. The serotonin reuptake inhibitor may be fluoxetine, duloxetine, venlafaxine, milnacipran, citalopram, fluvoxamine, paroxetine, sertraline or escitalopram. The pharmaceutical composition of the present invention is useful for treating patients with mood disorders, particularly depression or major depressive disorder.

The invention relates to an oral paroxetine solid preparation capable of being rapidly disintegrated and dissolved and a preparation process thereof. The solid preparation has the characteristics of maintaining favorable taste in the condition of using a covering process and a taste masking agent, and rapidly expanding and dispersing in water to dissolve the paroxetine out, thus the dissolution rate and biological availability of the preparation are greatly enhanced, and the therapeutic effect can be more efficiently and rapidly achieved.

The invention provides an oxa-spiral diphosphine ligand. The oxa-spiral diphosphine ligand has a structure shown by a general formula (I) as shown in description, wherein R1, R2, R3 and R4 in the general formula (I) are same and are alkyl, alkoxy, aryl, aroxyl, or hydrogen atoms; R1, R2, R3 and R4 comprise forms of ring formation, non-ring formation, any two ring formation or multiple-ring formation between pairs; R5 and R6 are alkyl, aryl or hydrogen atoms; and R7 and R8 are alkyl or benzyl or aryl. The invention further provides application of the oxa-spiral diphosphine ligand O-SDP in the alpha, beta-unsaturated carboxylic acid asymmetric hydrogenation. A complex of the oxa-spiral diphosphine ligand O-SDP and ruthenium has excellent activity and enantioselectivity in the asymmetric hydrogenation of the alpha, beta-unsaturated carboxylic acid in multiple types, and a chiral carboxylic acid product is obtained with the enantioselectivity being up to 99%. The synthesis method can be applied to the construction of a core skeleton of chemical molecules with important activity, wherein the chemical molecules comprise Paroxetine, Femoxetine, nipecotic acid and Sacubitril.

A process for the production of paroxetine is described, wherein N-substituted derivatives of 4-(p-fluorophenyl)-3-hydroxymethyl-1,2,3,6-tetrahydropyridine are treated according to the following sequence of reactions: (a) hydrogenation catalyzed by transition metal complexes with chiral diphosphinic ligands; (b) -OH derivatisation and nucleophilic substitution, the substituent being sesamol; (c) N-dealkylation. The process is highly stereospecific and brings about the formation of intermediates enriched with the desired isomeric components, which are converted into paroxetine in quantitative yields.

The invention relates to a paroxetine enteric-coated and sustained-release tablet, which comprises a single-layer tablet core, a sustained-release coating film and an enteric coating film, wherein the single-layer tablet core contains paroxetine or pharmaceutically acceptable salt and a sustained-release skeleton material; and the invention further provides a preparation method of the paroxetine enteric-coated and sustained-release tablet. The paroxetine enteric-coated and sustained-release tablet is simple in production technology and stable in quality.

The present invention discloses a hydrobromide paroxetine-sec-butyl alcohol compound and a preparation method thereof. The present invention provides the hydrobromide paroxetine-sec-butyl alcohol compound as shown in formula I. The present invention further provides the preparation method of the hydrobromide paroxetine-sec-butyl alcohol compound. The preparation method comprises the following steps: mixing hydrobromide paroxetine and sec-butyl alcohol, dissolving, and carrying out crystallization to obtain the hydrobromide paroxetine-sec-butyl alcohol compound. The hydrobromide paroxetine-sec-butyl alcohol compound can be used for preparing Alpha crystalline of the hydrobromide paroxetine, the desolvation temperature is low and the energy resources are saved during preparation, and the Alpha crystalline of the hydrobromide paroxetine is high in purity and appropriate in granularity, and is suitable for industrial production. The formula I is as shown in the specification.

The invention discloses a method for preparing a paroxetine intermediate by enzymatic selective hydrolysis in ionic liquid, and relates to a method for preparing a chiral medicament intermediate based on bio-enzyme catalysis, in particular to a method for preparing (4R,5S)-5-ethyl formate-4-(4-fluorophenyl)-1-R-2,6-dioxypiperidine-3-carboxylic acid (I) through biocatalysis. In the method, 4-(4-fluorophenyl)-1-R-2,6-dioxypiperidine-3,5-diethyl phthalate (II) is taken as a raw material, a bio-enzyme in a cosolvent-containing buffer solution system is taken as a catalyst, and the (4R, 5S)-5-ethyl formate-4-(4-fluorophenyl)-1-R-2,6-dioxypiperidine-3-carboxylic acid (I) is prepared at the temperature of between 15 and 60 DEG C and the rotating speed of 100-250 revolutions per minute of a table concentrator. The provided preparation method has mild reaction condition, the maximum conversion rate of 98 percent, the highest purity of 96 percent and high atom utilization rate, meets the requirements of green chemistry and greatly reduces the production cost. The compound in the formula (I) can be prepare into an important paroxetine intermediate through decarboxylation, reduction and other steps, namely (3R,4S)-4-(4-fluorophenyl)-3-hydroxymethyl-1-R-piperidine (III).

The present invention relates to an enteric, sustained-release tablet comprising paroxetine or a hydrates or anhydrides of a pharmaceutically acceptable salt thereof as active substance, more particularly to a tablet prepared by coating a sustained-release tablet core containing paroxetine with an enteric polymer, wherein the interaction between the tablet core and the enteric coating layer is minimized to enable constant drug release without regard to the residence time of the tablet in the stomach.

The invention belongs to the technical field of drug detection, and particularly relates to a method and a kit for detecting 19 drugs and metabolites thereof in blood through liquid chromatography-tandem mass spectrometry. The substances to be detected comprise sulpiride, pentafluridol, mianserin, buspirone, tandospirone, hydroxyazine, diazepam, venlafaxine, moclobemide, imipramine, paroxetine, reboxetine, amitriptyline, sertraline, digoxin, clonazepam, clopidogrel, toluenesulfobutyl urea, glimepiride, 1-pyrimidinepiperazine, desmethylvenlafaxine, 6-hydroxy buspirone and normipramine, and the substances to be detected are selected from the group consisting of sulpiride, pentafluridol, mianserin, venlafaxine, metandospirone, metandospirone, hydroxazine, diazepam, venlafaxine, moclobemide, the pharmaceutical composition is prepared from noramitriptyline, nordiazepam and clopidogrel metabolite; the detection method comprises the following steps: calibrating a standard solution, treating a to-be-detected sample, and detecting the to-be-detected sample by adopting high performance liquid chromatography-mass spectrometry. The embodiment of the invention can quickly and accurately measure the content, and the sample treatment method is simple and easy to implement, high in sensitivity and accurate in quantification.

The present invention relates to a method for treating a patient suffering from a thermoregulatory dysfunction, especially hot flashes and flushes associated with hormonal changes due to naturally occurring menopause (whether male or female) or due to chemically or surgically induced menopause. The method is also applicable to treating the hot flashes, hot flushes, or night sweats associated with disease states that disrupt normal hormonal regulation of body temperature.

The invention discloses a method for synthesizing a paroxetine chiral intermediate, which comprises the following steps: reacting N-methyl malonic ester and a chiral fluorine cinnamate derivative under alkaline condition, after reaction is finished, post-treatment is carried out to obtain the paroxetine chiral intermediate. The method has the advantage that a chiral aminoalcohol compound is taken for synthesizing fluorine cinnamate as a chiral substrate, then an additive cyclization reaction is carried out with N-methyl malonic ester to obtain the chiral dioxopiperidine, the chiral aminoalcohol is simultaneously recovered, an useless enantiomer can be fully used during a paroxetine production process, environment pressure is reduced, reaction yield is high, operation is simple, raw material is easily available, reaction condition is mild, and post-treatment is simple. The reaction condition of the present invention can be used for massive preparation, the method is suitable for industrial production, and has high utility value and social economic benefit.

The invention discloses a method for detecting the concentration of antidepressant drugs in serum by an ultra-high performance liquid chromatography-tandem mass spectrometry technology. The antidepressant drugs comprise bupropion, agomelatine, hydroxybupropion, nortriptyline, o-desmethylvenlafaxine, mianserin, mirtazapine, venlafaxine, amitriptyline, doxepin, norfluoxetine hydrochloride, duloxetine, fluoxetine, fluvoxamine, citalopram, paroxetine, trazodone and vortioxetine. After a serum sample is pretreated, a to-be-detected substance is separated from a serum matrix by utilizing ultra-highperformance liquid chromatography, a calibration curve is established by utilizing a mass spectrum isotope internal standard quantitative method and taking a concentration ratio of the standard substance to an internal standard substance as an X axis and a peak area ratio of the standard substance to the internal standard substance as a Y axis, and the content of the drugs in serum is calculated.The method is high in sensitivity, high in specificity, accurate and simple in pretreatment process, separation and detection can be completed within 4.5 min, and the accuracy degree and precision basically meet the requirements.

The invention relates to the technical field of crushing devices, and discloses a paroxetine processing raw material crushing device. The paroxetine processing raw material crushing device comprises astirring tank, wherein supporting plates are arranged below the stirring tank, and a supporting moving assembly is arranged between the supporting plates; vibration motors are fixedly installed on the two sides of the bottom of the stirring tank, and a material receiving hopper is fixedly installed inside the stirring tank; and a filter plate is slidably connected to the interior of the stirringtank, hydraulic cylinders are fixedly installed on the two sides of the bottom of the stirring tank in a sleeving mode, and the end parts of the telescopic ends of the hydraulic cylinders penetrate through the material receiving hopper, are fixedly connected with the bottom of the filter plate and are slidably connected with the material receiving hopper. According to the paroxetine processing rawmaterial crushing device, the vibration motors are matched with the supporting moving assembly, so that the stirring tank is vibrated during crushing, mixing of raw materials and falling of the raw materials on the wall of the stirring tank are facilitated, and waste is reduced; and a stirring crushing assembly is arranged, the crushed raw materials are crushed and sorted, the qualified raw materials are automatically selected out from the filter plate, and the production efficiency is improved.

The invention discloses an enteric-coated sustained release preparation and a preparation method thereof. The preparation is in form of a double-layer enteric-coated sustained release tablet containing paroxetine or pharmaceutically applicative salt thereof. According to the preparation, Acryl-EZE is used as the material of an enteric coating, so that the stability of the sustained release tablet in releasing can be improved.

Oral pharmaceutical compositions or functional foods with a mechanism of multi-target receptor retroaction for treating depression comprising ginseng saponin (Rg1+Rb1), glycyrrhizic acid and jujuba cAMP. Experiments demonstrate that as compared with the preferred drug for treating depression Paroxetine in the art, the present invention has significant anti-depression efficacy.

The invention discloses an oral medicament or health care food for treating melancholia with acting mechanism after being made into multiple-target drone receptor with raw materials of ginsenoside (Rg1+Rb1), glycyrrhizic acid and Chinese date cAMP. According to the experiment to prove, the medicament composition of the invention can obviously reduce the small mouse suspension tail dead time and body temperature descend induced by reserpine; obviously improve the rat horizontal and vertical movement increase and rat learning and memory function abatement caused by buibus olfactorius damage; meanwhile can improve saccharose drinking water amount decrease and body weight descend caused by unpredictable long term stress stimulus, can improve the rat horizontal and vertical movement decrease and obvious increase of the NE and 5-HT content in the rat cerebral cortex caused by unpredictable long term stress stimulus. The experiment result proves that the medicament has remarkable anti-melancholia efficacy, comparing to the current medicament Paroxetine for treating the melancholia in prior art.

A P2X₄ receptor antagonist such as paroxetine, a diazepinedione derivative having the following formula (IX) is used as an agent for preventing or treating neuropathic pain associated with Guillain-Barré syndrome:

wherein R¹ is hydrogen, a C_1-8 alkyl group, or the like;

• • each of R² and R³ is hydrogen, a C_1-8 alkyl group, or the like;
  • each of R⁴ and R⁵ is hydrogen or the like; and
  • W is a five-membered or six-membered heterocyclic ring optionally having one or more substituents and comprising one to four nitrogen atoms as the members of the ring.