23 results about "Citalopram" patented technology

The invention relates to a method for preparing S-citalopram based on an R-diol intermediate. The method comprises the following steps: (1) carrying out SN2 configuration inversion on a citalopram R-diol intermediate under the action of a large-steric-hindrance acid and a large-steric-hindrance ligand to obtain a mixture containing S-citalopram and R-citalopram; and (2) obtaining the S-citalopram from the mixture in the step (1) under the action of a resolving agent. In addition, the invention also discloses a preparation method of the S-citalopram. The optical purity of the S-citalopram prepared by the method is greater than 95%, and the optical purity is greater than 99% after the S-citalopram is purified. In addition, the total yield of S-citalopram is increased to 82% from 31% in the prior art.

The invention discloses application of Cacumen biotae-derived extracellular vesicles in preparation of drugs for treating anxiety, depression or insomnia. The EVs are separated and purified from cacumen biotae through a specific differential ultracentrifugation method, the EVs have a typical double-layer membrane structure, the average particle size is about 100 nm, about 1012 EVs can be extracted from each gram of cacumen biotae, and 62 volatile components are contained. Cacumen biotae EVs can be taken by PC12 cells, and corticosterone-induced neuron damage can be relieved; for chronic constraint stress model mice, anxiety behaviors and spatial learning and memory disorders can be improved, and central nervous inflammation can be inhibited; for chronic unpredictable mild stress model mice, the weight, the sucrose preference rate and the cognitive ability can be recovered, and the levels of 5-hydroxytryptamine and gamma-aminobutyric acid are increased; and for 4-chloro-DL-phenylalanine induced insomnia model mice, the sleep condition can be improved, the neurotransmitter level can be recovered, and the effect is equivalent to that of positive drugs such as citalopram, fluoxetine, diazepam and the like.

The present invention provides an immediate release oral pharmaceutical composition comprising, by weight, greater than or equal to 60.1% of citalopram oxalate or escalopram oxalate or greater than or equal to 25.1% of citalopram oxalate or escalopram oxalate having a median diameter greater than 40 [mu] m, and 0% to 74.9% of an additional pharmaceutical excipient.

The invention provides the composite injection containing ketamine and citalopram, and when the composite injection is used for treating depressive disorder, the composite injection takes effect more quickly and responds more accurately, the effect delay period can be further shortened, and the anti-depression curative effect can be further improved. And the medicine is more convenient to take, and the medication compliance is greatly improved.

The present application relates to a method for purifying citalopram or S-citalopram or their salts. The method comprises treating citalopram or S-citalopram with a water-soluble solution containing sulfite or thiosulfate, and then taking the organic layer, and further separating to obtain citalopram or S-citalopram free base; or adding acid to form a salt, and separating to obtain citalopram or S-citalopram acid salt. The purification method provided by the present application is simple in operation and high in impurity removal rate.

Described herein are methods of treating fibromyalgia, comprising administering esreboxetine to a human being in need thereof. Esreboxetine may also be used in the manufacture of a medicament for the treatment of fibromyalgia.

This invention discloses a method for the etherification of 5-cyanodiol hydrochloride to citalopram bromate using a dehydration membrane. The method includes: adding 5-cyanodiol hydrochloride, toluene, and a strong acid resin catalyst to a round-bottom reaction flask equipped with a magnetic stirrer; placing a water separation membrane in the reaction flask; maintaining a high vacuum on the permeate side of the water separation membrane; and then heating the reaction on a magnetically stirred heater. In the toluene system, the water separation membrane removes the water generated in situ through vapor permeation, driving the reaction forward, breaking the thermodynamic equilibrium constraint, improving product yield and purity, and achieving coupling of reaction and separation. This invention uses a strong acid resin catalyst coupled with a water separation membrane, resulting in a simple reaction procedure and favorable reaction conditions; the catalyst is safe and stable, with a low risk factor, is a green catalyst, can be recycled, and is easily separated from the reaction liquid; the water separation membrane removes water in situ through vapor permeation, improving raw material conversion rate and product purity.

The invention belongs to the field of rapid detection of SSRIs series drugs, and particularly relates to a monoclonal antibody, a nucleic acid molecule, a carrier, a detection kit and a detection reagent of citalopram and application of the monoclonal antibody, the nucleic acid molecule, the carrier, the detection kit and the detection reagent. The citalopram monoclonal antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises a heavy chain CDR1, a heavy chain CDR2 and a heavy chain CDR3, the light chain variable region comprises a light chain CDR1, a light chain CDR2 and a light chain CDR3, the sequence of the heavy chain CDR1 is as shown in SEQ ID NO.1, the sequence of the heavy chain CDR2 is as shown in SEQ ID NO.2, and the sequence of the heavy chain CDR3 is as shown in SEQ ID NO.3. The invention further discloses a preparation method of the citalopram monoclonal antibody. The monoclonal antibody provided by the invention has high detection sensitivity on citalopram, the lowest detection limit is 0.06807 ng / mL, the quantitative detection range is 0.17567-4.49194 ng / mL, and the specificity is strong.

The application belongs to the technical field of drug synthesis, and more particularly relates to a preparation method of a high-purity citalopram S-diol intermediate. The preparation method comprises the following steps: generating a racemic citalopram diol intermediate; adding an acid to quench the racemic citalopram diol intermediate, centrifuging, and concentrating the evaporation substrate by evaporation under reduced pressure to obtain an evaporation substrate; mixing the evaporation substrate with a mixed solvent, adding a chiral resolving agent, and performing chiral resolution; after the reaction is completed, cooling, incubation crystallization, washing and drying are performed to obtain the citalopram S-diol intermediate. Through optimization of the chiral resolution process, the racemic citalopram diol intermediate can be directly subjected to chiral resolution after simple post-treatment, and high-purity and high-optical-purity compound 1b can be directly prepared; meanwhile, a plurality of recrystallization processes can be omitted, the operation is simple, the production efficiency is high, and the cost is low.

The present application belongs to the field of analytical chemistry, and particularly relates to a method for determining related substances in citalopram or its salt and preparation thereof, which adopts HPLC to detect citalopram; wherein, mobile phase A is phosphate buffer with mass-volume ratio of 0.6-0.7% and pH of 6.0-7.0; mobile phase B is a mixed solution of methanol and acetonitrile with volume ratio of 30-50:70-50. The method can detect at least 12 known impurities in citalopram, and even 3 unknown impurities, with good peak shape, good separation degree, good reproducibility, and can realize effective separation and quantitative determination of citalopram.

This invention relates to a purification method for a key intermediate of citalopram, namely 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile or a salt thereof. The method includes treating a mixed solution of 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile and a water-insoluble organic solvent with a washing solution, then taking the organic layer for further separation to obtain the free base of 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile; or adding acid to form a salt, separating the acidic salt of 4-[4-(dimethylamino)-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile. The method provided by this invention can effectively remove aldehyde impurities from the intermediate.

This invention relates to a purification method for a key intermediate of citalopram, namely 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile and its salts. The method includes dissolving crude 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile (containing formaldehyde impurities, compound I) in an organic solvent, adding a washing solution, controlling the temperature, stirring, allowing the mixture to stand and separate into layers, and removing the aqueous layer to obtain a purified organic solution of 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile. The method provided by this invention can effectively remove the aldehyde impurities from the intermediate. This method is simple to operate, uses inexpensive raw materials, and operates under mild conditions, making it suitable for large-scale industrial production.

The application discloses a method for simultaneously detecting the concentration of six drugs in blood, comprising the following steps: S1, taking a blood sample, centrifuging, and adding methanol to precipitate protein; S2, preparing a series of concentration calibration solution, quality control sample and internal standard working solution; S3, adding the internal standard working solution to the supernatant 1 prepared in S1, vortex mixing, centrifuging, and taking the supernatant 2; S4, using high performance liquid chromatography-tandem mass spectrometry to detect the supernatant 2 obtained in S3 for the selected drugs, and performing mass spectrometry screening analysis on the basis of the retention time of the compound, two pairs or three pairs of parent ions / daughter ions; the drugs include one, multiple or all of fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and escitalopram; the detection method provided by the application has the characteristics of simple and convenient sample pretreatment, small required sample volume, high sensitivity, high accuracy and high throughput.

The present invention provides a method for purifying citalopram or S-citalopram or their salts, comprising the following steps: treating a solution composed of citalopram and a water-immiscible organic solvent with a washing solution, and separating to obtain an organic layer containing citalopram; or treating a solution composed of S-citalopram and a water-immiscible organic solvent with a washing solution, and separating to obtain an organic layer containing S-citalopram; then taking the organic layer and further separating to obtain citalopram or S-citalopram; or further adding an acid to form a salt, and separating to obtain an acid salt of citalopram or S-citalopram. The purification method provided by the present invention is simple to operate and has a high impurity removal rate.

The present invention provides an immediate release oral pharmaceutical composition comprising, by weight, 60.1% or more citalopram oxalate or escitalopram oxalate, or 25.1% or more citalopram oxalate or escitalopram oxalate with a median particle size greater than 40 μm, and 0% to 74.9% additional pharmaceutical excipients.

The present invention relates to a method for preparing S-citalopram on the basis of an R-diol intermediate. The method comprises the following steps: (1) under the action of a sterically hindered acid and a sterically hindered ligand, subjecting a citalopram R-diol intermediate to SN2 configuration inversion to obtain a mixture containing S-citalopram and R-citalopram; and (2) subjecting the mixture in step (1) to a resolving agent to obtain S-citalopram. In addition, further disclosed in the present invention is a method for preparing S-citalopram. The optical purity of the S-citalopram prepared by the method of the present invention is greater than 95% and is greater than 99% after purification. In addition, the overall yield of the S-citalopram is increased from 31% in a conventional process to up to 82%.

The invention relates to a chiral resolution method of an escitalopram intermediate. The synthesis method comprises the following steps: (1) adding citalopram diol, a novel chiral resolving agent and a solvent into a reaction flask, stirring and heating, and after the solution is clarified, keeping the temperature and stirring for 3 hours; (2) after the heat preservation is finished, slowly cooling, and stirring and crystallizing for 10 hours; filtering, pulping a filter cake with iced ethanol for 30 minutes, filtering, and leaching the filter cake with a small amount of iced ethanol; (3) adding methylbenzene, water and tetramethylammonium hydroxide into the filter cake, and stirring at room temperature for 4 hours; and washing an organic layer with water and a saturated saline solution in sequence, and drying by distillation under reduced pressure to obtain an oily substance S-diol.

The application belongs to the field of rapid detection of SSRIs drugs, and particularly relates to a monoclonal antibody of citalopram, a nucleic acid molecule, a carrier, a detection kit, a detection reagent and application thereof. The monoclonal antibody of citalopram comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises a heavy chain CDR1, a heavy chain CDR2 and a heavy chain CDR3, the light chain variable region comprises a light chain CDR1, a light chain CDR2 and a light chain CDR3, the sequence of the heavy chain CDR1 is shown as SEQ ID NO. 1, the sequence of the heavy chain CDR2 is shown as SEQ ID NO. 2, and the sequence of the heavy chain CDR3 is shown as SEQ ID NO. 3. The monoclonal antibody of the application has high sensitivity for citalopram detection, the minimum detection limit is 0.06807 ng / mL, the quantitative detection range is 0.17567-4.49194 ng / mL, and the specificity is strong.

The invention discloses a method for preparing citalopram bromate by applying a dehydration membrane to enhance etherification of 5-cyanodiol hydrochloride, which comprises the following steps of: adding a raw material 5-cyanodiol hydrochloride, a solvent methylbenzene and a strong acid resin catalyst into a round-bottom reaction flask filled with a stirring magneton, arranging a water separation membrane in the reaction flask, the permeation side of the water separation membrane is kept at a high vacuum degree, and then heating reaction is performed on a magnetic stirring heater. In a toluene system, the water separation membrane performs in-situ removal on water generated by the reaction through steam permeation, so that the reaction is performed in a forward direction, thermodynamic equilibrium limitation is broken, the yield and purity of the product are improved, and coupling of the reaction and separation is realized. According to the invention, the strong acidic resin catalyst is coupled with the water separation membrane, the reaction steps are simple, and the reaction conditions are friendly; the catalyst is safe, stable, low in danger coefficient, green in catalysis, recyclable and easy to separate from reaction liquid; the water separation membrane can remove water in situ through steam permeation, and the raw material conversion rate and the product purity are improved.

The invention belongs to the technical field of in-vitro detection, and particularly relates to escitalopram hapten, antigen and antibody as well as a preparation method and application thereof. The hapten disclosed by the invention is shown as a formula I. The invention also provides an antigen prepared from the hapten and a corresponding antibody. The invention also provides preparation methods of the hapten, the antigen and the antibody. By utilizing the antigen and the antibody provided by the invention, a detection kit with good sensitivity and specificity on escitalopram in blood can be prepared, and immunological detection of escitalopram is realized. Therefore, the method has a good application prospect. # imgabs0 #

The invention provides a pharmaceutical composition containing dextromethorphan. The pharmaceutical composition further comprises citalopram or escitalopram in the form of free alkali or a pharmaceutically acceptable salt. According to the pharmaceutical composition provided by the invention, the dextromethorphan or the salt thereof and the citalopram or the salt thereof are combined according to a specific proportion, so that the pharmaceutical composition has an excellent synergistic effect. The invention also provides application of the pharmaceutical composition in preparation of drugs for treating cough and psychiatric and neurological disorders, especially depression.

The present invention relates to a method for purifying key intermediates of Citalopram, i.e. 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile and a salt thereof. The method comprises dissolving crude 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile (compound of formula I containing formaldehyde impurity) with an organic solvent, adding a washing solution, controlling the temperature, stirring, leaving to stand for layering, and removing the aqueous layer, so as to obtain a purified organic solution of 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile. The method provided by the present invention can effectively remove aldehyde group-containing impurities in the intermediate. The method of the present invention has the advantages of simple operation, cheap raw materials and mild conditions, and is suitable for large-scale industrial production.