42 results about "Amisulpride" patented technology

A benzamide derivative, especially amisulpride, is used to prevent or treat bipolar depression of a patient suffering from bipolar disorder I or bipolar disorder II.

The invention concretely relates to R-amisulpride medicine salt, a preparation method, a crystal form and application thereof in preparing a medicine for treating diabetes. The preparation method comprises the following steps: by adopting 2-aminomethyl-N-ethyl pyrrolidine as a raw material, and adopting L-tartaric acid, for splitting to obtain (R)-2-aminomethyl-N-ethyl pyrrolidine; directly condensing amisulpride acid and the (R)-2-aminomethyl-N-ethyl pyrrolidine under the catalysis of isopropyl chlorocarbonate and triethylamine, thus obtaining R-amisulpride; reacting the R-amisulpride obtained in the step (2) and acid to obtain the R-amisulpride medicine salt. The preparation method has the advantages of simplicity in operation, high safety, good product quality, low cost and the like, and is convenient for scale production.

The present invention provides, inter alia, compositions containing enantiomerically pure (R)(+)-amisulpride or enantiomerically pure (R)(+)-sulpiride, optionally with dopamine receptor modulators. The present invention also provides compositions containing racemic (RS)-amisulpride or (RS)-sulpiride in combination with dopamine receptor modulators. Methods for preventing, treating, or ameliorating the effects of a metabolic disorder or key element thereof, for modulating blood glucose levels, and for preventing, treating, or ameliorating the effects of diabetes in a subject are also provided. Additionally, the present invention provides methods for counter-acting the dopamine antagonist activity of (S)-amisulpride in racemic (RS)-amisulpride, or the dopamine antagonist activity of (S)-sulpiride in racemic (RS)-sulpiride, administered to a subject to prevent, treat, or ameliorate the effects of a metabolic disorder.

The invention relates to a solid pharmaceutical composition for oral administration of amisulpride, which comprises at least one coated amisulpride particle and at least one pharmaceutically acceptable excipient suitable for an orodispersible administration of the composition.

The present invention is related to a novel process for the preparation of amisulpride (I) which involves: methylation of 4-amino-salicylic-acid (VI) with dimethyl sulphate and base, optionally in presence of TBAB to obtain 4-amino-2-methoxy methyl benzoate (VII) and (ii) oxidation of 4-amino-2-methoxy-5-ethyl thio benzoic acid (IX) or 4-amino-2-methoxy-5-ethyl thio methyl benzoate (X) with oxidizing agent in the presence of sodium tungstate or ammonium molybdate to give 2-methoxy-4-amino-5-ethyl-sulfonyl benzoic acid (IV) or 2-methoxy-4-amino-5-ethyl-sulfonyl methyl benzoate (XI) respectively.

The invention relates to a preparation method of (S)(-)-amisulpride. According to the preparation method, by introducing an R2 group which is selected from benzyl, p-methoxybenzyl, 2,4-dimethoxybenzyl, p-nitrobenzyl and p-methylbenzyl, on one hand, the steric hindrance is increased, the side reaction is avoided, on the other hand, amino is activated, the nucleophilicity of amino is increased, and the condensation reaction can be easily carried out at mild conditions. The preparation method has the characteristics that the raw materials are low in toxicity and easily available, and the reaction conditions are mild; the generation of chiral isomer dextroisomers is avoided; the preparation method is applicable to the industrial production.

The invention discloses an amisulpride tablet and a method for preparing the same. The amisulpride tablet comprises raw materials and excipients, and is characterized in that film coating is carried out on the surfaces of the amisulpride tablet by the aid of film coating premixes; the film coating premixes comprise opadry gastric-soluble coating powder and flavoring agents; the flavoring agents comprise sweeteners, taste masking agents and aromatizers; the sweeteners are selected from a type of aspartame and acesulfame potassium; each taste masking agent is sodium chloride; the aromatizers are selected from a type of cherry flavor essence, apple flavor essence, honey peach flavor essence, sweet orange flavor essence, strawberry flavor essence and mint flavor essence. The amisulpride tablet and the method have the advantages that film coating is carried out on the amisulpride tablet, accordingly, bitter taste of amisulpride can be masked to a certain extent while the stability of the amisulpride tablet which is a medicine is improved, the medication compliance of patients can be improved, and medicine taking pretending possibility of the patients can be reduced to a certain extent; usage of lubricants is controlled, accordingly, the dissolution of the medicine can be greatly improved, and the medicine can be stably and quickly released in bodies.

Amisulpride is used in the therapy of nausea, vomiting or retches. The therapy may utilize a novel injectable formulation, in unit dosage form, comprising less than 50 mg amisulpride.

The invention relates to a synthesis method for amisulpride. The method comprises the following steps: a, esterifying 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid (I) and low alcohol (II) under the catalysis of thionyl chloride to obtain low alcohol ester (III), b, performing condensation on the low alcohol ester (III) obtained in the step a and N-ethyl-2-aminomethylpyrrolidine (IV) to obtain the amisulpride (V). The synthesis method is short in synthesis route (a target compound can be obtained by two steps), high in yield and atom utilization rate and easy to operate, reaction conditions are mild, a product purification post-treatment process is simple, the use of a catalyst harmful to the environment during the reaction is avoided, and a common recyclable solvent can be used as a reaction solvent.

The invention discloses a method for preparing a key intermediate of amisulpride. 2- methoxyl-4-amino-5-diethyl sulfide benzoic acid is oxidized in an alkaline condition so as to obtain the amisulpride acid (key intermediate of amisulpride). Compared with the existing methods, the method can produce products with higher quality, the yield is improved remarkably, the operation is simpler, safer, and has environment-friendly effect, and the method is especially suitable for industrial production.

The R enantiomer of amisulpride and amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for antagonizing serotonin (e.g., 5-HT2a, 5-HT7) receptor in a subject, either individually or in combination with one or more other CNS active agents. The R enantiomer of amisulpride and amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for treating one or more conditions responsive to modulation of serotonin (e.g., 5-HT2a, 5-HT7) receptor in a subject, either individually or in combination with one or more other CNS active agents. The R enantiomer of amisulpride and amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for treating one or more disorders associated with an abnormality in levels of serotonin in the brain, either individually or in combination with one or more other CNS active agents.

The invention discloses an intermediate in amisulpride and a method for preparing amisulpride by using an intermediate. The method comprises the following steps: reacting 4-amino-2-methoxy group-5-ethylsulfonyl benzoic acid and di-tert-butyl dicarbonate ester so as to obtain the intermediate (4-(N-tert-tert-butoxycarbonyl)amino-2-methoxy group-5-ethylsulfonyl benzoic acid) of the amisulpride; and carrying out condensation reaction on the intermediate (4-(N-tert-butoxycarbonyl)amino-2-methoxy group-5-ethylsulfonyl benzoic acid) of the amisulpride and N-ethyl-2-aminomethyl pyrrolidine so as to obtain 4-(N-tert-tert-butoxycarbonyl)amino-N-((1-ethyl-2-pyrrolidyl)methyl)-5-ethylsulfonyl-2-methoxy benzamide, and carrying out deprotection of tert-butoxycarbonyl group (BOC) so as to obtain the amisulpride. According to the method, the process processing is simple, impurities which are hard to remove are avoided, the reaction yield is high and can be up to 76%, the purity of the obtained amisulpride is high, and the medical quality of the amisulpride is greatly improved.

The invention provides a drug solution applicable to oral dosing. The drug solution comprises Amisulpride, cyclodextrin or derivatives thereof, an appropriate medicinal solvent system and other adjuvants. The cyclodextrin or derivatives thereof and a drug cosolvent system can be used for remarkably improving the solubility of the Amisulpride in the solvent system, promoting drug absorption and enhancing a treatment effect. The Amisulpride oral liquid preparation provided by the invention is high in absorption rate, convenient to take and easy in divided dose, can rapidly exert a drug effect and can simultaneously meet various requirements such as clinical medication, sufferer compliance and industrialized mass production.

The invention relates to a preparation method of amisulpride, which comprises the steps of carrying out condensation reaction on 4-amino-2-methoxy-5-ethyl sulfonyl methyl benzoate, N-ethyl-2-aminomethylpyrrolidine and a solvent at the temperature of 50-100 DEG C under the condition of taking organic alkali as a catalyst, and after the reaction is finished, concentrating the reaction liquid to remove the solvent, and filtering and drying to obtain the amisulpride. The organic alkali is sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium isopropoxide, potassium isopropoxide, potassium tert-butoxide or sodium tert-butoxide, and the specific synthetic route is shown in the description. By adopting the preparation method disclosed by the invention, a catalyst harmful to the environment is not used in the reaction process, the post-treatment is simple, the solvent is a common recyclable solvent, the yield reaches 90% or above, the purity can reach 99.7%, the single impurity content is less than 0.1%, the requirements of medicinal preparations are met, and the preparation method is suitable for industrial production.

The invention provides a preparation method of amisulpride. The preparation method comprises the following steps: with 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid and thionyl chloride as raw materials, carrying out an acylation reaction to obtain 2-methoxy-4-amino-5-ethylsulfonyl benzoyl chloride; and then, subjecting 2-methoxy-4-amino-5-ethylsulfonyl benzoyl chloride and N-ethyl-2-aminomethylpyrrolidine to an amidation reaction on to obtain amisulpride. The preparation method has the following advantages: raw materials are easy to obtain; highly toxic products are not used; the preparation method is simple; preparation period is short; side reactions are few; the yield and purity of the target product are high; and the target product has market competitiveness.

Novel amisulpride derivatives and pharmaceutical compositions thereof are disclosed. The amisulpride derivative disclosed herein or a pharmaceutical composition thereof may have better membrane permeability compared to amisulpride. The amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for antagonizing dopamine and / or serotonin (e.g., 5-HT2a) and / or α2 receptor in a subject, either individually or in combination with other CNS active agents. The amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for treating one or more conditions responsive to modulation of dopamine and / or serotonin (e.g., 5-HT2a) and / or α2 receptor in a subject, either individually or in combination with other CNS active agents. The amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for treating one or more disorders associated with an abnormality in levels of dopamine and / or serotonin in the brain, either individually or in combination with other CNS active agents.

A fundamental shortcoming in the current treatment of schizophrenia is the lack of valid criteria to predict who will respond to antipsychotic treatment. The identification of blood-based biological markers of the therapeutic response would enable clinicians to identify the subgroup of patients in whom conventional antipsychotic treatment is ineffective and offer alternative treatments. As part of the Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE) programme, the inventors conducted a transcriptome analysis on 188 subjects with first episode psychosis, all of whom were subsequently treated with amisulpride for 4 weeks. They identify 32 genes for which the expression changed after treatment in good responders only. Among these genes, the expression of ALPL, a gene involved in vitamin B6 metabolism, as well as CA4, DGTA2, DHRS13, HOMER3 and WLS showed a significant difference in expression level between good and poor responders before starting treatment, allowing to predict treatment outcome with a predictive value of 93.8% when combined with clinical features Collectively, these findings identified new mechanisms to explain symptom improvement after amisulpride medication and highlight the potential of combining gene-expression profiling with clinical data to predict treatment response in first episode psychoses.

The R enantiomer of amisulpride and amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for antagonizing serotonin (e.g., 5-HT2a, 5-HT7) receptor in a subject, either individually or in combination with one or more other CNS active agents. The R enantiomer of amisulpride and amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for treating one or more conditions responsive to modulation of serotonin (e.g., 5-HT2a, 5-HT7) receptor in a subject, either individually or in combination with one or more other CNS active agents. The R enantiomer of amisulpride and amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for treating one or more disorders associated with an abnormality in levels of serotonin in the brain, either individually or in combination with one or more other CNS active agents.

The invention provides an amisulpride injection and a preparation method thereof, the particle size of the used bulk drug amisulpride is not less than 20 [mu] m; preferably not less than 74 [mu] m; further, preferably, the particle size is 74-450 [mu] m; furthermore, the particle size of the particles is preferably 125-450 [mu] m. According to the amisulpride injection and the preparation method thereof provided by the invention, the preparation efficiency can be improved, and the content of a finished product is more stable.

The amisulpride transdermal patch comprises a medicine carrying layer, a backing layer and an anti-sticking layer, and the medicine carrying layer is composed of amisulpride, a penetration enhancer and a pressure-sensitive adhesive matrix. The weight percentage content of amisulpride in the medicine carrying layer is 3%-5%. The weight percentage content of the penetration enhancer in the medicine carrying layer is 4-6%, and the penetration enhancer is propylene glycol, oleic acid and menthol in a weight ratio of 10: (1-3): (0.1-0.2). The pressure-sensitive adhesive matrix is a hot-melt pressure-sensitive adhesive matrix.

The invention belongs to the field of pharmaceutical chemicals, and relates to a synthesis method of an amisulpride impurity H. According to the invention, N-ethyl-2-methylaminomethylpyrrolidine is prepared by using a one-step method, and an impurity H is prepared by constructing an amido bond by using chloroformate and an acid-binding agent system. The method is mild in reaction condition and high in product purity, and the prepared impurity H can be used for impurity research of amisulpride.

The invention belongs to the technical field of medicines, particularly relates to the field of pharmacy, and more particularly relates to an amisulpride tablet and a preparation method thereof. The amisulpride tablet is prepared from the following components in percentage by mass: 39.6 to 43.8 percent of amisulpride, 0.1 to 2.0 percent of a surfactant and the balance of pharmaceutically acceptable auxiliary materials. By adding the surfactant, the in-vivo release rate of the amisulpride during use can be remarkably increased, and drug absorption is guaranteed. Meanwhile, according to the preparation method disclosed by the invention, a dry granulation process is taken as a basis, and the problem of poor raw material fluidity of the amisulpride tablet is effectively solved through materialadding sequence design; and the problems of bitter taste and the like of the amisulpride are effectively solved in a preparation process, and the medication compliance of a patient is remarkably improved.

Novel amisulpride derivatives and pharmaceutical compositions thereof are disclosed. The amisulpride derivative disclosed herein or a pharmaceutical composition thereof may have better membrane permeability compared to amisulpride. The amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for antagonizing dopamine and / or serotonin (e.g., 5-HT2a) and / or α2 receptor in a subject, either individually or in combination with other CNS active agents. The amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for treating one or more conditions responsive to modulation of dopamine and / or serotonin (e.g., 5-HT2a) and / or α2 receptor in a subject, either individually or in combination with other CNS active agents. The amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for treating one or more disorders associated with an abnormality in levels of dopamine and / or serotonin in the brain, either individually or in combination with other CNS active agents.

The invention reports a preparation method for a pharmacopoeia impurity of amisulpride, and particularly relates to a preparation method for the pharmacopoeia impurity D of amisulpride. The method is simple and easy to operate, mild in condition, high in yield, low in energy consumption and pollution and suitable for laboratory-level standard substance preparation.

The invention provides a preparation method of amisulpride. The preparation method comprises the following steps: with 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid and thionyl chloride as raw materials, carrying out an acylation reaction to obtain 2-methoxy-4-amino-5-ethylsulfonyl benzoyl chloride; and then, subjecting 2-methoxy-4-amino-5-ethylsulfonyl benzoyl chloride and N-ethyl-2-aminomethylpyrrolidine to an amidation reaction on to obtain amisulpride. The preparation method has the following advantages: raw materials are easy to obtain; highly toxic products are not used; the preparation method is simple; preparation period is short; side reactions are few; the yield and purity of the target product are high; and the target product has market competitiveness.