127 results about "Citalopram" patented technology

Disclosed is an extended or controlled release dosage form of citalopram or its related forms and other newer antidepressants for oral administration to treat chronic patients suffering from depression and to minimize the side effects associated with the current drug treatment.

The invention provides a method, and dosage form therefor, of treating impaired motor function associated with Parkinson's disease, anti-Parkinson's drug treatment, e.g. L-Dopa therapy, and / or dementia associated with Parkinson's disease. The invention includes the combined administration of an NMDA receptor antagonist and an antidepressant, e.g., the combination of amantadine and citalopram or venlafaxine, or an NMDA receptor antagonist and an anxiolytic agent, e.g., amantadine and buspirone or trazodone, for the amelioration of undesired tremors, akinesia, dyskinesia, or bradykinesia associated with one or more different disorders or diseases. The drugs can be included in a single dosage form. One embodiment includes a combination dosage form containing each drug in controlled release forms. Another embodiment includes a combination dosage form providing a controlled release of an NMDA receptor antagonist and a rapid release of a neuroactive agent after administration to a subject.

The comprehensive pharmacologic therapy for treatment of obesity including Cysteine is a procedure which involves the administration of a desired therapeutic range of Diethylpropion and / or Phentermine in combination with a SSRI medication and nutritional supplementation for brief and long durations which may be 12 months or more. The preferred procedure involves the administration of drugs in combination which are identified as: Citalopram (Celexa) and Phentermine; Citalopram (Celexa) and Diethylpropion; Citalopram (Celexa), Phentermine, and Diethylpropion. In addition nutritional supplementation such as a multivitamin, 5-Hydroxytryptophan, Cysteine, vitamin B6, vitamin C, Tyrosine, Calcium, and Lysine may be used to enhance the performance of the weight loss treatment program.

The present invention provides a method for the treatment of depression, including treatment-resistant depression, and other mood disorders using a combination of an NMDA receptor antagonist and a SSRI that is citalopram or escitalopram. It has unexpectedly been shown that the combination has a synergistic and potentiated effect of either compound as monotherapy, resulting in an enhanced therapeutic effect at lower doses.

Provided is a skin irritation suppressant for transdermal preparations, having a sufficient reduction effect of skin irritation due to a drug. Also provided is a transdermal preparation comprising the skin irritation suppressant. One embodiment of the invention is a skin irritation suppressant for suppressing the skin irritation due to a drug and a pharmaceutical ingredient to be used in a transdermal preparation other than the drug, the skin irritation suppressant comprising a sterol compound selected from the group consisting of cholesterol, cholesterol derivatives and cholesterol analogs, and the drug is one or more basic drugs selected from the group consisting of tolterodine, asenapine, bisoprolol, risperidone, nicotine and citalopram, and their pharmaceutically acceptable salts.

The invention belongs to the field of drug detection, and particularly relates to a method and a kit for detecting five psychotropic drugs and main metabolites thereof in blood. The five psychotropicdrugs and the main metabolites thereof comprise: olanzapine and demethyl olanzapine, risperidone and 9-hydroxy risperidone, aripiprazole and dehydrogenated aripiprazole, Escitalopram and demethyl citalopram, sertraline and N-demethyl sertraline. Accoridng to the method provided by the invention, a pair of quantitative ion pairs is respectively selected for each detection substance, a relative retention time thereof is used as a qualitative basis, and a standard curve is made by using a standard product for quantification; furthermore, the accuracy and effectiveness of the method are evaluatedfrom quality control of three low, middle and high levels, thereby avoiding distortion of the detection result; and meanwhile, an internal standard working solution is applied to correction, so that matrix effects can be avoided, and accurate quantification is realized. The method provided by the invention has the advantages of simple and rapid operation, high flux and low cost, and can be appliedto the therapeutic drug monitoring of the psychotropic drugs in the clinical work of the psychiatry department.

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 present invention discloses crystalline particles of escitalopram oxalate which either have a broad particle size distribution or comprise at least 0.01% (w / w) of Z-4-(4-dimethylamino-1-(4-fluorophenyl)-but-1-enyl)-3-hydroxymethyl-benzonitrile, said particles being suitable for use in direct compression. Furthermore, the invention discloses a novel pharmaceutical unit dosage form containing such crystalline particles of escitalopram oxalate as well as methods for manufacture of such crystalline particles of escitalopram oxalate Finally, the invention provides a method for reduction of the amount of hydroxyl containing impurities in a solution of citalopram or escitalopram.

The invention provides a preparation method of a citalopram intermediate, and belongs to the technical field of pharmaceuticals. In the method, 2-methyltetrahydrofuran is taken as a reaction solvent. Under the protection of nitrogen, a 4-fluorophenylmagnesium bromide solution Grignard reagent, 5-cyanophthalein and a N,N-dimethylpropyl magnesium chloride Grignard reagent are taken as raw materials. A reaction is carried out to synthesize 4-(4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrilehydrobromide. The method is characterized by high yield and high purity, and is suitable for industrial production.

The comprehensive pharmacologic therapy for treatment of obesity is a procedure which involves the administration of a desired therapeutic range of Diethylpropion and / or Phentermine in combination with a SSRI medication and nutritional supplementation for brief and long durations which may be 12 months or more. The preferred procedure involves the administration of drugs in combination which are identified as: Citalopram (Celexa) and Phentermine; Citalopram (Celexa) and Diethylpropion; Citalopram (Celexa), Phentermine, and Diethylpropion. In addition nutritional supplementation such as a multivitamin, 5-Hydroxytryptophan, vitamin B6, vitamin C, Tyrosine, Calcium, and Lysine may be used to enhance the performance of the weight loss treatment program.

The comprehensive pharmacologic therapy for treatment of obesity including Cysteine is a procedure which involves the administration of a desired therapeutic range of Diethylpropion and / or Phentermine in combination with a SSRI medication and nutritional supplementation for brief and long durations which may be 12 months or more. The preferred procedure involves the administration of drugs in combination which are identified as: Citalopram (Celexa) and Phentermine; Citalopram (Celexa) and Diethylpropion; Citalopram (Celexa), Phentermine, and Diethylpropion. In addition nutritional supplementation such as a multivitamin, 5-Hydroxytryptophan, Cysteine, vitamin B6, vitamin C, Tyrosine, Calcium, and Lysine may be used to enhance the performance of the weight loss treatment program.

The present invention discloses crystalline particles of escitalopram oxalate which either have a broad particle size distribution or comprise at least 0.01% (w / w) of Z-4-(4-dimethylamino-1-(4-fluorophenyl)-but-1-enyl)-3-hydroxymethyl-benzonitrile, said particles being suitable for use in direct compression. Furthermore, the invention discloses a novel pharmaceutical unit dosage form containing such crystalline particles of escitalopram oxalate as well as methods for manufacture of such crystalline particles of escitalopram oxalate Finally, the invention provides a method for reduction of the amount of hydroxyl containing impurities in a solution of citalopram or escitalopram.

The invention relates to a method of preparing S-type diol that is a dextral citalopram intermediate product. Aiming at the disadvantages of high cost, low yield rate, fussy operation, high difficulty, and bad stability and repeatability in the existing method of preparing dextral citalopram that has single optical isomers, the invention provides a separation method of the S-type diol that is the dextral citalopram intermediate product which has low cost, convenient operation, and good stability and repeatability. The method is completed by the following way: racemic glycols (IV) are separated by adopting a separation method; resolving agent used for separation is organic acid that has the single optical isomers; resolving solvent used for separation is mixed solvent composed of halogenated hydrocarbon and absolute ethyl alcohol, or the mixed solvent composed of acetone and the absolute ethyl alcohol, or the acetone and isopropanol; when in separation, the racemic glycols (IV) are put in the mixed solution composed of the resolving agent and the resolving solvent, the salt of the S-type diol is crystallized and precipitated, and the S-type diol (I) which has single optical configurations is obtained through dissociation.

The present patent application relates to an improved process for the preparation of escitalopram, its salts and intermediates. It also relates to a novel crystalline form S of citalopram diol intermediate, process for preparation and its use in the preparation of citalopram, escitalopram and their salts.

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 present invention provides, inter alia, a novel process for the preparation of Citalopram, a known antidepressant.

The invention relates to a process for the preparation of racemic citalopram free base or an acid addition salt thereof and / or R- or S-citalopram as the free base or an acid addition salt thereof by separation of a mixture of R- and S-citalopram with more than 50% of one of the enantiomers into a fraction consisting of racemic citalopram and / or a fraction of S-citalopram or R-citalopram characterized in that i) citalopram is precipitated from a solvent as the free base or as an acid addition salt thereof; ii) the precipitate formed is separated from the mother liquor; iia) if the precipitate is crystalline it is optionally recrystallised one or more times to form racemic citalopram, and then optionally converted into an acid addition salt thereof; iib) if the precipitate is not crystalline, steps i) and ii) are optionally repeated until a crystalline precipitate is obtained and the crystalline precipitate is recrystallised one or more times to form racemic citalopram, and then optionally converted into an acid addition salt thereof; iii) the mother liquor is optionally subjected to further purification and S-citalopram or R-citalopram is isolated from the mother liquor and optionally converted into an addition salt thereof.

The invention provides a method for preparing citalopram and S-citalopram. In the method, 1-[2-(hydroxymethyl)-5-substituting group-]phenyl-4-(dimethylamino)-1-(4-fluorophenyl)-1- butyl alcohol undergoes a cyclization reaction with halogenated acylate in water and an organic solvent immiscible with water under the alkali condition to form a citalopram product. The method has high yield and high purity and is suitable for industrialized production.

Use of escitalopram (the S-(+)-enantiomer of citalopram) or a pharmaceutically acceptable salt thereof for the preparation of a medicament useful in the treatment of neurotic disorders is provided, including anxiety states, in particular generalised anxiety disorder and social anxiety disorder, post traumatic stress disorder, obsessive compulsive disorder and panic attacks.

The invention relates to novel synthetic methods for three impurities of escitalopram oxalate. The methods have great significance for synthesis of the escitalopram oxalate with high purity. The invention mainly study syntheses of a citalopram amide impurity 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-isobenzofuran-5-formamide (II), a citalopram lactone impurity 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (III) and a citalopram-N-oxide impurity 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-isobenzofuran-5-cyano-N-oxide (IV). Specific synthetic routes of the impurities are showed as follows.

The invention discloses an oxalic acid esmolol citalopram oral solid preparation and a preparation method. The oral solid preparation comprises raw materials of: 2-40 parts by weight of oxalic acid esmolol citalopram, 5-60 parts by weight of starch, 5-200 parts by weight of microcrystalline cellulose, 5-60 parts by weight of lactose, 0.05-5 parts by weight of binding agent and 0.05-3 parts by weight of lubricant; the binding agent is one or a plurality of mixed aqueous solutions or alcoholic solutions from the group consisting of polyvinyl pyrrolidone, hydroxyethyl methylcellulose, methylcellulose, hydroxypropyl cellulose and ethyl cellulose, the concentration of the binding agent is 0.1-10.0%; and the lubricant is stearic acid, magnesium stearate, calcium stearate, talcum or superfine silica gel powder.

Disclosed is a process for the preparation of racemic citalopram free base or an acid addition salt thereof and / or R- or S-citalopram as the free base or an acid addition salt thereof by separation of a mixture of R- and S- citalopram with more than 50% of one of the enantiomers into a fraction consisting of racemic citalopram and a fraction of S-citalopram or R-citalopram characterised in that: i) citalopram is precipitated from a solvent as the free base or as an acid addition salt thereof; ii) the precipitate formed is separated from the mother liquor; iia) if the precipitate is crystalline it is optionally recrystallised one or more times to form racemic citalopram, and then optionally converted into an acid addition salt thereof; or iib) if the precipitate is not crystalline, steps i) and ii) are optionally repeated until a crystalline precipitate is obtained and the crystalline precipitate is optionally recrystallised one or more times to form racemic citalopram, and then optionally converted to an acid addition salt thereof; and iii) the mother liquor is optionally subjected to further purification and S-citalopram or R-citalopram is isolated from the mother liquor and optionally converted to an acid addition salt thereof.

A novel method is provided for the manufacture of escitalopram. The method comprises chromatographic separation of the enantiomers of citalopram or an intermediate in the production of citalopram using a chiral stationary phase such as Chiralpak™ or Chiralcel™ OD. Novel chiral intermediates for the synthesis of Escitalopram made by said method are also provided.

A method for preparing citalopram of general formula (I), wherein the compound of general formula (II), wherein Z is iodo, bromo, chloro or CF3-(CF2)n-SO2-O-, wherein n is 0, 1, 2, 3, 4, 5, 6, 7 or 8, a cyanide exchange reaction occurs. In the reaction, the group Z realizes the exchange with cyanide by reacting with the cyanide source; the crude citalopram produced The product is optionally subjected to some preliminary purification, and the crude citalopram base is then subjected to a liquid membrane distillation process; the citalopram product obtained is then optionally further purified, then worked up and converted to the base or a pharmaceutically acceptable salt thereof. seperate.

The invention is directed to methods of crystallizing pharmaceutically acceptable salts of citalopram, the resulting crystals, and pharmaceutical compositions comprising the crystals.

The invention belongs to the technical field of medicine and relates to an escitalopram percutaneous patch and a preparation method thereof. The escitalopram percutaneous patch is composed of a backing layer, a medicine-carrying pressure-sensitive adhesive layer and an anti-sticking layer, the medicine-carrying pressure-sensitive adhesive layer comprises escitalopram free alkali or organic acid ion pair compound thereof, pressure-sensitive adhesive and percutaneous absorption promoter, the escitalopram free alkali or organic acid ion pair compound thereof accounts for 2.0-20wt% of total weight of the medicine-carrying pressure-sensitive adhesive layer, pressure-sensitive adhesive accounts for 77-97wt% of the total weight, the percutaneous absorption promoter accounts for 0-6.8wt% of the total weight, and in the escitalopram organic acid ion pair compound, a ratio of escitalopram free alkali and different organic acids is 0.5:1-2:1. Compared with an escitalopram organic acid ion pair compound percutaneous absorption patch and an escitalopram free alkali percutaneous absorption patch, the escitalopram percutaneous patch has the advantages that medicine release up to seven days and similar to constant rate can be provided, so that medication compliance of a patient is improved greatly.

The present invention relates to the diol intermediate of citalopram useful for treatment of depression, that is to say, the crystal of free alkali of 3-hydroxylmethyl-4-[1-(4-fluorophenyl)-1-hydroxyl-4-(dimethylamino)] butylbenzonitrile and the method of crystallization thereof. The present invention has disclosed the method to prepare pure citalopram and its purified salts through crystallization of the described alkali;the optical resolution method of citalopram diol intermediate, the method to prepare S-citalopram and its purified salts by crystals mentioned above. The present invention has also disclosed the method to prepare citalopram and its purified salts, S-citalopram and its purified salts, as well as pharmaceutical formulation thereof obtained. Using methods of the present invention, the quality and yield of the product can be signally improved, and the production cost of the medicinal material can be decreased.

The comprehensive pharmacologic therapy for treatment of obesity is a procedure which involves the administration of a desired therapeutic range of Diethylpropion and / or Phentermine in combination with a SSRI medication and nutritional supplementation for brief and long durations which may be 12 months or more. The preferred procedure involves the administration of drugs in combination which are identified as: Citalopram (Celexa) and Phentermine; Citalopram (Celexa) and Diethylpropion; Citalopram (Celexa), Phentermine, and Diethylpropion. In addition nutritional supplementation such as a multivitamin, 5-Hydroxytryptophan, vitamin B6, vitamin C, Tyrosine, Calcium, and Lysine may be used to enhance the performance of the weight loss treatment program.