61 results about "Eszopiclone" patented technology

One aspect of the present invention relates to pharmaceutical compositions containing two or more active agents that when taken together can be used to treat, e.g., insomnia and / or depression. The first component of the pharmaceutical composition is a GABA receptor modulating compound. The second component of the pharmaceutical composition is a serotonin reuptake inhibitor, a norepinephrine reuptake inhibitor, a 5-HT2A modulator, or dopamine reuptake inhibitor. In certain embodiments, the pharmaceutical composition comprises eszopiclone. In a preferred embodiment, the pharmaceutical composition comprises eszopiclone and fluoxetine. The present invention also relates to a method of treating a sleep abnormality, treating insomnia, treating depression, augmenting antidepressant therapy, eliciting a dose-sparing effect, reducing depression relapse, improving the efficacy of antidepressant therapy or improving the tolerability of antidepressant therapy, comprising co-administering to a patient in need thereof a GABA-receptor-modulating compound; and a SRI, NRI, 5-HT2A modulator or DRI.

One aspect of the present invention relates to pharmaceutical compositions containing two or more active agents that when taken together can be used to treat, e.g., insomnia and / or depression. The first component of the pharmaceutical composition is a GABA receptor modulating compound. The second component of the pharmaceutical composition is a serotonin reuptake inhibitor, a norepinephrine reuptake inhibitor, a 5-HT2A modulator, or dopamine reuptake inhibitor. In certain embodiments, the pharmaceutical composition comprises eszopiclone. In a preferred embodiment, the pharmaceutical composition comprises eszopiclone and fluoxetine. The present invention also relates to a method of treating a sleep abnormality, treating insomnia, treating depression, augmenting antidepressant therapy, eliciting a dose-sparing effect, reducing depression relapse, improving the efficacy of antidepressant therapy or improving the tolerability of antidepressant therapy, comprising co-administering to a patient in need thereof a GABA-receptor-modulating compound; and a SRI, NRI, 5-HT2A modulator or DRI.

The invention relates to a process for making of 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo-[3,4-b] pyrazin-5-yl-4-methyl piperazine-1-carboxylate, also known as zopiclone. The invention further describes an effective method for resolving of zopiclone into its enantiomers (eszopiclone and (R)-zopiclone) and also provides a method of recycling of (R)-zopiclone.

This invention relates generally to methods and pharmaceutical formulations useful in treating patients suffering from obstructive sleep apnea syndrome (OSAS). Treatment of OSAS is effected by administering a carbonic anhydrase inhibitor to the patient in combination with at least one additional active agent. Examples of additional active agents include modafinil, eszopiclone, zolpidem, zaleplon, and phentermine.

Eszopiclone is prepared by reacting zopiclone with an enatiomerically pure di-p-toluoyl tartaric acid, recovering a solid salt, and reacting a solid salt with a base. Zopiclone is prepared by reacting 6-(5-chloropyrid-2-yl)-5-hydroxy-7-oxo-5,6-dihydropyrrolo[3,4-b]-pyrazine with 1-chlorocarbonyl-4-methylpiperazine hydrochloride.

The invention belongs to the field of a pharmaceutical preparation, and in particular relates to a dexzopiclone oral fast-dissolving film and a preparation method thereof. The film mainly consists of such ingredients as a dexzopiclone inclusion compound, a film-forming material, a filling agent, a plasticizer, a flavoring agent and an antioxidant. The preparation method comprises the following processes: (1) preparing the dexzopiclone inclusion compound; (2) preparing a blank glue solution; (3) preparing a dexzopiclone drug-containing glue solution; and (4) coating and drying the drug-containing glue solution. The oral fast-dissolving film is capable of masking the bitterness of the dexzopiclone, and the film is unnecessary to be taken with water and is suitable for children, old people and insomnia patients having difficulty in swallowing; and moreover, the oral fast-dissolving film is good in flexibility and not easy to become broken, and the film is capable of fast dissolving in an oral cavity and is high in bioavailability.

The invention relates to a sedative-hypnotic preparation, a compound preparation, a preparation method and a pharmaceutical composition thereof. The compound preparation of the sedative-hypnotic preparation includes zopiclone or eszopiclone and a pharmaceutically acceptable auxiliary material which includes a stabilizing agent with a dosage being, by mass, 0.1%-10% of the zopiclone or the eszopiclone. The stabilizing agent is one or more of a pharmaceutically acceptable organic acid salt, a pharmaceutically acceptable organic acid buffer pair and a pharmaceutical acceptable anti-oxidant. The pharmaceutical composition of the sedative-hypnotic preparation forms a compound preparation pharmaceutical composition with other pharmaceutical active substances. The preparation method of the sedative-hypnotic preparation or the compound preparation includes carrying out a wet granulation process to the pharmaceutical composition of the sedative-hypnotic preparation or the compound preparation pharmaceutical composition. The sedative-hypnotic preparation or the compound preparation is good in stability and is excellent in dissolution rate and content uniformity. Quality of the preparations can be ensured and the preparations are suitable for industrial production.

The invention discloses the preparation method of eszopiclone solid preparation, which comprises the following steps of dissolving eszopiclone into acidic solution containing an acidifying agent to obtain medicine-containing acidic solution; and uniformly mixing alkalinizing agent, accessories and the medicine-containing acidic solution to granulate by a wet method, wherein the alkalinizing agentis agent by which the acidity of mixed solution of the alkalinizing agent and the medicine-containing acidic solution is reduced relative to the acidity of the medicine-containing acidic solution. The invention also discloses eszopiclone solid preparation prepared by the method. According to the method disclosed by the invention, the defects of the serious pollution, high loss and serous potential safety hazards brought by mechanical crushing treatment are avoided; and the method is simple, convenient and feasible for operation and easy for industrial production and has high safety coefficient. The eszopiclone solid preparation prepared by the method has the advantages of excellent dissolution property, stability, and content uniformity.

The invention relates to a process for making 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo-[3,4-b]pyrazin-5-yl-4-methyl piperazine-1-carboxylate, also known as zopiclone. The invention further describes an effective method for resolving zopiclone into its enantiomers (eszopiclone and (R)-zopiclone) and also provides a method of recycling of (R)-zopiclone. The process for making (S)-6(S)-6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo-[3,4-b]pyrazin-5-yl-4-methyl piperazine-1-carboxylate (eszopiclone), comprises reacting 2-amino 5-chloropyridine with pyrazine 2,3,dicarboxylic acid anhydride at room temperature to obtain 3-(5-chloropyrid-2-yl)carbamoyl-2-pyrazine-2-carboxylic acid; cyclizing the 3-(5-chloropyrid-2-yl)carbamoyl-2-pyrazine-2-carboxylic acid in a second inert organic solvent to obtain 6-(5-chloropyrid-2-yl)5,7-dioxo-5,6-dihydropyrrolo[3,4-b]-pyrazine; reducing the 6-(5-chloropyrid-2-yl)5,7-dioxo-5,6-dihydropyrrolo[3,4-b]-pyrazine to obtain 6-(5-chloropyrid-2-yl)-5-hydroxy-7-oxo-5,6-dihydropyrrolo-[3,4-b]pyrazine; pyrazine with 1-chlorocarbonyl-4-methylpiperazine hydrochloride in a third organic solvent in presence of triethyl amine along with a catalytic amount of an acylation catalyst to obtain racemic zopiclone; e) recrystallizing the zopiclone from an alkyl ester solvent followed by purifying in suitable alcohols or mixtures thereof; and resolving the racemic zopiclone by treating with (+)-O—O′ dibenzoyl tartaric acid to obtain eszopiclone.

The invention relates to an eszopiclone preparation method comprising main steps that: zopiclone is subjected to a reaction with D-dibenzoyltartaric acid or a hydrate thereof, such that dextral zopiclone-D-dibenzoyltartrate is produced; and the salt is dissociated, such that eszopiclone is obtained. According to the method, D-dibenzoyltartaric acid with a substance amount of a quarter to a half of that of zopiclone is adopted. The reaction conditions are mild, operation is convenient, product yield is high, and product purity is high. The method is suitable for large-scale industrialized productions.

One aspect of the present invention relates to pharmaceutical compositions containing two or more active agents that when taken together can be used to treat, e.g., menopause, mood disorders, anxiety disorders, or cognitive disorders. The first component of the pharmaceutical composition is a sedative eszopiclone. The second component of the pharmaceutical composition is O-desmethylvenlafaxine. The present invention also relates to a method of treating menopause, perimenopause, mood disorders, anxiety disorders, and cognitive disorders.

The present invention discloses a crystalline form of S-zopiclone having a powder X-Ray diffraction spectrum excited by Cu-Ka radiation with characteristic peaks expressed in terms of 28 at about 11.08°, about 12.38°, about 15.86°, about 17.88°, about 19.98° and about 20.58°; a DSC thermogram with a peak at about 207.7° C. and an infrared absorption spectrum (IR) with characteristic peaks at about 3078 cm−1, about 2942-2838 cm−1, about 2790 cm−1, about 1716 cm−1, about 1463 cm−1, about 1372 cm−1 and about 757 cm−1. The present invention also discloses a method for preparing the crystalline form of eszopiclone, its pharmaceutical composition and its use in preparing a medicament for treating sleep disorders.

The invention provides a method for synthesizing eszopiclone. According to the method, chiral imidazo thiazole is taken as a catalyst to catalyze a racemic hemiacetal intermediate and chloro-formic ester to produce kinetic resolution reaction, and (S)-hemiacetal carbonic ester with good yield and enantioselectivity is obtained. The (S)-hemiacetal carbonic ester is reacted with N-methyl piperazine, so that eszopiclone can be obtained. The method has the advantages that the chiral imidazo thiazole which is low in cost and easy to obtain is used as the catalyst, operation procedures are simple, the production cost is low, and the method has very high application value for the industrial preparation of eszopiclone.