24 results about "Agomelatine" patented technology

Disclosed in the present invention are a preparation method for a brain-targeting agomelatine nasal spray micelle and use thereof, which belong to the technical field of pharmaceutical formulations. According to the present invention, an injectable pharmaceutical excipient polyethylene glycol (15)-hydroxystearate (HS15) is taken as a carrier material, HS15 and agomelatine are dissolved in an organic solvent, and the resulting solution is subjected to rotary evaporation under reduced pressure to form a uniform film, which, upon hydration, forms an agomelatine micelle solution capable of being sprayed nasally for treating depression and insomnia. According to the present invention, the problem of low oral bioavailability of agomelatine due to poor solubility, serious first pass effect of hepar, difficulty in penetrating a blood-brain barrier, etc., is solved. The micelle structure constructed in the present invention is quickly delivered into the brain after nasal administration, and it is stable in cerebrospinal fluid and can achieve slow release of the drug, thereby improving the intracerebral bioavailability of the drug and achieving high brain targeting property and low systemic toxic and side effects. The micelle structure has good clinical application value and market prospects.

The present invention relates to the use of agomelatine (or its prodrugs or salts) in the treatment of major depressive disorder or bipolar disorder, including the selection of patients who would benefit most from agomelatine.

FIELD: psychiatry; narcology.SUBSTANCE: used to stabilize remission of alcohol dependence in patients with comorbid depression. After the withdrawal state with alcohol dependence syndrome and comorbid depressive disorder has been relieved, the patient takes agomelatine orally at a dosage of 25 mg once a day daily for 12 weeks.EFFECT: method is accessible and allows for stabilizing remission in patients with alcohol dependence syndrome and depressive disorder.1 cl

The present invention relates to a transmucosal treatment system for transmucosal administration of agomelatine, comprising a mucosal adhesion layer structure containing a therapeutically effective amount of agomelatine, the transmucosal treatment system for use in a treatment method, a treatment method including the application of the transmucosal treatment system of agomelatine, and a method of manufacturing the transmucosal treatment system.

The application provides a synthesis method of agomelatine. The starting material I is reacted with SOCl2 to obtain acyl chloride under the action of a solvent A, and then reacted with NH4OH to obtain intermediate I; the intermediate I is reacted with (CF3CO)2O under the action of a solvent B and triethylamine to obtain intermediate II through dehydration; the intermediate II is subjected to catalytic hydrogenation reaction with Raney Ni and H2 under the action of a solvent C to obtain intermediate III; the intermediate III is reacted with HCl under the action of a solvent D to obtain intermediate IV; and the intermediate IV is condensed with CH3COCl under the action of a solvent E and Cs2CO3 to obtain agomelatine. The method is simple in operation, mild in reaction condition, high in yield, low in cost, friendly to the environment, and suitable for industrial large-scale production of agomelatine.

The present invention relates to the use of agomelatine (or a prodrug or salt thereof) in the treatment of severe depression or bipolar affective disorder, comprising selecting a patient who will benefit most from agomelatine.

New co-crystal of agomelatine composed of: agomelatine, or N-[2-(7-methoxy-1naphthyl)ethyl]acetamide of formu1a (I)and - an organic acid, and a pharmaceutical composition comprising thereof for treating disorders of the melatoninergic system

This invention relates to an agomelatine microemulsion, a microemulsion gel, and a method for preparing the same, belonging to the field of pharmaceutical formulation. The agomelatine microemulsion comprises agomelatine and a drug carrier, the drug carrier including an emulsifier, a co-emulsifier, an oil phase, and an aqueous phase; the agomelatine microemulsion gel comprises an agomelatine microemulsion and a gel matrix. The agomelatine microemulsion and microemulsion gel of this invention exhibit good stability, high bioavailability, and good clinical safety, and the preparation process is simple and easily scaled up for industrial production.

The present invention relates to the technical field of pharmaceutical preparations, and discloses an agomelatine coating preparation and a processing technology thereof. The processing technology comprises the following steps: S1: taking agomelatine powder, distearoylphosphatidylethanolamine, soybean sterol, and a mixed solvent, stirring them evenly, and then removing the solvent under reduced pressure, adding a potassium dihydrogen phosphate-dipotassium hydrogen phosphate buffer solution, shaking, stirring evenly, homogenizing and emulsifying, filtering, and freeze-drying to obtain agomelatine liposomes; S2: mixing agomelatine powder, agomelatine liposomes, povidone K30, sodium starch glycolate, starch, and lactose evenly in equal amounts, adding water, stirring evenly, sieving, drying, adding silicon dioxide and magnesium stearate, and pressing with a die to obtain agomelatine granules; S3: coating the agomelatine granules with a coating solution, coating them again with a taste-masking coating agent, and cooling to obtain the agomelatine coating preparation.

The invention provides an application of agomelatine in preparation of a medicine for treating systemic lupus erythematosus, relates to the technical field of biomedicine, and has the technical key points that the application shows the application of agomelatine in treatment of systemic lupus erythematosus for the first time, specifically, agomelatine is used for intragastric administration of two systemic lupus erythematosus model mice, and the application of agomelatine in treatment of systemic lupus erythematosus in treatment of systemic lupus erythematosus in treatment of systemic lupus erythematosus in treatment of systemic lupus erythematosus is realized. Agomelatine can relieve spleen swelling and reduce spleen indexes, and urine protein is quantified in 24 hours; the degree of kidney damage is reduced, and serum autoantibodies and kidney function indexes are reduced; the symptoms of facial skin injury or abdominal granuloma nodules are improved; the proportion of M1 macrophages, Tfh cells, Th17 cells and plasma cells of the spleen is reduced. Mechanism research shows that the agomelatine reduces release of macrophage inflammatory factors, interferon and interferon stimulating genes, which indicates that the agomelatine improves the condition of systemic lupus erythematosus by reversing the functional disorder of macrophages of systemic lupus erythematosus mice, and provides a new way for treating systemic lupus erythematosus.

The application relates to the technical field of pharmaceutical preparations, and discloses an agomelatine inhalant as well as a preparation method and application thereof. The agomelatine inhalant provided by the application comprises agomelatine or a pharmaceutically acceptable salt thereof in a form capable of being inhaled or capable of being changed into a form capable of being inhaled after being excited. From the aspect of synergism, the inhalant can avoid first-pass metabolism by changing a drug administration route, significantly improve bioavailability, and realize rapid effect by directly entering blood from the lung; from the aspect of attenuation, the inhalant can greatly reduce a drug usage amount to achieve a same treatment effect as a tablet, significantly reduce occurrence of drug toxic and side reactions, and significantly reduce liver toxicity by avoiding liver metabolism.

The present application provides a transdermal patch of agomelatine and a preparation method thereof. Specifically, the transdermal patch of agomelatine comprises (a) a backing layer, (b) an adhesive matrix layer and (c) a protective layer, wherein the adhesive matrix layer contains agomelatine and an adhesive matrix, and optionally further comprises a penetration enhancer. The transdermal patch of agomelatine prepared by the method has a fast transdermal absorption rate, a high transdermal absorption amount, and the characteristics of stability, high efficiency, good uniformity and low irritation, and the preparation method is simple.

The invention discloses a preparation method of a deuterated alkyl (hetero) aryl ether compound (deuterated medicine), and belongs to the technical field of deuterated compound synthesis. The preparation method comprises the following steps: adding a (hetero) aryl halide, deuterated alcohol, a nickel catalyst, organic alkali and a silane reagent into an organic solvent, and reacting in an inert gas atmosphere to obtain the deuterated alkyl (hetero) aryl ether compound and the deuterated drug. The compound can be applied to later modification of drug molecules and synthesis of deuterated drugs such as agomelatine and phenacetin. The method has the advantages of mild reaction conditions, simple operation and low cost, and has good application prospects in the field of deuterated drug synthesis.

This invention belongs to the field of pharmaceutical formulation technology, specifically relating to a transdermal absorption patch for agomelatine and its preparation method. The patch is a pressure-sensitive adhesive dispersion type patch, consisting of a backing layer, a drug-loaded pressure-sensitive adhesive layer, and an anti-adhesion layer. The drug-loaded pressure-sensitive adhesive layer comprises an agomelatine-organic acid eutectic mixture, a non-functionalized polyacrylate pressure-sensitive adhesive containing hexyl acrylate, and a transdermal absorption enhancer. The agomelatine-organic acid eutectic mixture accounts for 5.0-20 wt% of the total weight, the pressure-sensitive adhesive accounts for 70-94 wt%, and the transdermal absorption enhancer accounts for 0.5-10 wt%. The transdermal absorption patch for agomelatine provided by this invention enables 12-hour drug delivery, improves the low bioavailability and poor compliance of existing oral formulations, provides good mechanical adhesion, and enhances medication safety, accuracy, and patient compliance.

The invention provides an agomelatine tablet composition as well as a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations. The preparation method of the agomelatine tablet composition comprises the following steps: pre-mixing agomelatine with the filler, the adhesive and the disintegrating agent according to the weight percentage by using a high-shear wet type granulator; adding purified water into the high-shear wet type granulator for granulating, and stirring and shearing at the same time; the wet particles are transferred into a fluidized bed to be dried after being finished, and dry particles are obtained; finishing the dry particles, adding a lubricant, and blending to obtain total mixed particles; and adding the total mixed particles into a high-speed tablet press for tabletting. According to the invention, glyceryl behenate is adopted to replace stearic acid, so that the sticking problem caused by lower melting point of stearic acid in the tabletting process is avoided, the tablet pushing force can be reduced, and the compressibility in tablet and capsule production is improved; and the temperature control range of the sheet bed can be expanded to 35-50 DEG C.

The present invention relates to a transmucosal therapeutic system for transmucosal administration of agomelatine comprising a mucoadhesive layer structure containing a therapeutically effective amount of agomelatine, to such an agomelatine transmucosal therapeutic system for use in a method of treatment, to a method of treatment comprising the administration of such an agomelatine transmucosal therapeutic system and to a method of manufacturing such a transmucosal therapeutic system.

The application discloses an agomelatine self-microemulsion preparation which comprises an oil phase, an emulsifier and a co-emulsifier, and the agomelatine is distributed in the oil phase. The agomelatine self-microemulsion preparation prepared by the application has the advantages of simple preparation process, good stability, high bioavailability and good clinical safety.

This invention relates to a method for preparing agomelatine, belonging to the field of pharmaceutical synthesis technology. To address the problems of long, unsafe, and low-yield existing routes, this invention provides a method for preparing agomelatine, comprising: reacting a compound of formula 8 with acetic anhydride to obtain the final product, compound 1 (agomelatine); further comprising reacting a compound of formula 4 with dimethyl sulfate in a mixed solvent of alcohol and water in the presence of an alkali metal hydroxide to obtain compound 5; subjecting compound 5 to hydrogenation reduction under the catalysis of borohydride to obtain compound 6; reacting compound 6 with benzylamine under the action of potassium tert-butoxide to obtain compound 7; and subjecting compound 7 to catalytic hydrogenation reduction under the catalysis of a palladium-containing catalyst to obtain compound 8. This invention features simple post-processing, easier recovery of the palladium catalyst, and high product yield, effectively improving reaction efficiency and safety.

The present invention relates to the field of pharmaceutical technology, and particularly relates to an agomelatine pharmaceutical composition, a preparation method thereof and an application thereof. The agomelatine pharmaceutical composition comprises inner layer microparticles, a coating layer and outer layer excipients; the inner layer microparticles comprise the following raw materials: agomelatine, hypromellose, mannitol and colloidal silicon dioxide; the coating layer is obtained by coating a chitosan-sodium carboxymethyl starch suspension on the surface of the inner layer microparticles; the outer layer excipients comprise the following raw materials: glyceryl behenate, sucrose, polyvinylpyrrolidone, sodium carboxymethyl starch and magnesium stearate. The agomelatine pharmaceutical composition provided by the present invention has stable dissolution, extremely low impurities, controllable quality and excellent stability, and can be used for treating depression and related diseases.

The present invention belongs to the technical field of organic synthesis, and specifically relates to a method for synthesizing agomelatine. In the present invention, a compound having the structure shown in Formula 1 and a compound having the structure shown in Formula 2 are mixed for a condensation reaction, and the organic solution of the compound having the structure shown in Formula 3 obtained by solid-liquid separation is mixed with an acid solution for a decarboxylation reaction to obtain a compound having the structure shown in Formula 4; an ammonia methanol solution, the compound having the structure shown in Formula 4, an aromatization auxiliary agent, a palladium catalyst and a nickel catalyst are mixed for an aromatization reaction, and the obtained aromatization reaction solution is continued to carry out a reduction reaction in a hydrogen atmosphere to obtain a compound having the structure shown in Formula 5; the compound having the structure shown in Formula 5, an organic solvent, a second base reagent and an amidation reagent are mixed for an acetylation reaction to obtain the agomelatine. The present invention simplifies the operation, improves the yield and purity of the reaction target product, reduces the three wastes, and is suitable for industrial production.

The invention discloses a transdermal patch containing agomelatine as well as a preparation method and application of the transdermal patch. The transdermal patch comprises a polymer matrix layer, the polymer matrix layer comprises agomelatine as an active component, a water-insoluble crystallization inhibitor and a silicone pressure-sensitive adhesive, preferably, based on the weight of the polymer matrix layer, the weight content of agomelatine is 0.5-9%, the weight content of non-water-soluble crystallization inhibitor is 0.5-9%, and the weight content of silicone pressure-sensitive adhesive is 0.5-9%. The weight content of the water-insoluble crystallization inhibitor is 0.5%-50%, and the weight content of the silicone pressure-sensitive adhesive is 20%-99%. The transdermal patch disclosed by the invention is good in medicine permeability and colloid application performance, good in stability and high in safety, and can be used for treating depression patients.

This invention relates to the use of a reduced number of electroencephalogram (EEG) channels for predicting those who would benefit from drug treatment (such as with agomelatine) in patients with a psychiatric disorder (such as depression), as well as to an electroencephalogram (EEG) device for recording EEG data at these EEG channels.

The present invention discloses an agomelatine film for oral mucosal administration and a preparation method thereof, and provides a pharmaceutical preparation for administering agomelatine via the oral mucosa. The film is a double-layer film preparation consisting of a drug-containing adhesive layer and a drug-free backing layer. The double-layer film structure ensures good bioavailability and a good mouthfeel of the drug. The drug-containing adhesive layer of the agomelatine film prepared by the present invention comprises 0.1-40% (w / w) of the active ingredient agomelatine or a pharmaceutically acceptable salt thereof, 50-98% (w / w) of one or more film-forming materials, 0.5-20% (w / w) of one or more oil phases, and 0.5-17% (w / w) of one or more surfactants. The backing layer contains 60-100% (w / w) of one or more film-forming materials.