96 results about "Lacosamide" patented technology

Therapeutic methods, therapeutic combinations and pharmaceutical compositions provided herein are useful for inhibiting demyelination, for delaying the clinical onset of a demylination condition, for inhibiting progression and / or reducing frequency of relapse of a demylination condition, and / or enhancing physical ability of a human subject having a demylination condition. Lacosamide is one of the active compounds.

A therapeutic combination, useful in a co-therapy method for prevention, alleviation or treatment of psychosis, comprises a first agent and a second agent, wherein the first agent comprises at least one psychosis-treating compound and the second agent comprises at least one compound according to Formula (III): or a pharmaceutically acceptable salt thereof, wherein R4 is one or more substituents independently selected from the group consisting of hydrogen, halo, alkyl, alkenyl, alkynyl, nitro, carboxy, formyl, carboxyamido, aryl, quaternary ammonium, haloalkyl, aryl alkanoyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, aryloxy, mercapto, alkylthio, alkylmercapto, and disulfide; R3 is selected from the group consisting of hydrogen, alkyl, alkoxy, alkoxyalkyl, aryl, N-alkoxy-N-alkylamino, and N-alkoxyamino; and R1 is alkyl.

The invention provides a synthetizing method of lacosamide. The method comprises the steps of: based on D-serine as a raw material, performing an acylation reaction with acetic anhydride and then performing a condensation reaction with benzylamine; and finally, performing a methylation reaction with dimethyl sulfate, thereby obtaining lacosamide, wherein N,N' dicyclohexylcarbodiimide (DCC) or N,N' carbonyl diimidazole (CDI) is used as a catalyst in the condensation reaction; and a phase transfer catalyst including triethyl benzyl ammonium chloride (TEBA), tetrabutylammonium chloride (TBAC), tetrabutylammonium bromide (TBAB) or tetrabutylammonium hydrogen sulfate (TBAHS) is adopted in the methylation reaction. The method has the advantages of being simple in synthetizing process, moderate in reaction condition, simple in after-treatment, high in yield and high in product purity.

The invention relates to a synthetic intermediate of lacosamide and a preparation method and application thereof. In the method, a compound shown as a formula I is prepared by condensing a compound 6; the compound shown as the formula I is a novel intermediate compound for synthesizing the lacosamide; (R)-2-(amino-Boc)-N-benzyl-3-methoxyl propionamide (compound 4) can be conveniently prepared from the compound shown as the formula I through alkylation reaction; and the (R)-2-(amino-Boc)-N-benzyl-3-methoxyl propionamide is another important intermediate for synthesizing the lacosamide. The related chemical reaction formulas are shown in the specifications.

The present invention provides a modified release formulation of lacosamide. The modified release formulation of the present invention comprising lacosamide and modified release polymer provides modified release of lacosamide with minimal Cmax to Cmin peak to trough variation over a period of at least 12 hrs.

A preparing process of lacosamide is disclosed. D-serine is adopted as an initial raw material. The method includes: performing amino protection, performing methylation, condensing with benzylamine under a condition of existence of a carboxyl activator, removing an amino protection group, and performing amidation to obtain the lacosamide. The total yield is higher than 66%. The method is high in yield, simple and convenient to operate, high in product purity and especially suitable for industrial production.

The invention provides a new compound, which can be used for preparing lacosamide, and provides a new method for preparing the lacosamide. In the reaction process, precious methyl iodide and silver oxide are not used, a Pd-c catalyst is not used, the production cost is low, raw materials and auxiliary materials are cheap and readily available, the process is easy to operate, and the industrial production is easy to realize; and the yield is high and the economic benefit is high.

The invention relates to a tablet for treating epilepsy and a preparation method for the tablet, in particular to a lacosamide tablet for treating epilepsy and a preparation method for the lacosamide tablet. The lacosamide tablet comprises lacosamide, an inclusion material, filler, disintegrant, lubricant and / or wetting agent, adhesive and a coating material. The main medicine lacosamide is coated by the inclusion material, and other auxiliary materials are added into the lacosamide, so that a tablet core is obtained, and a finished product is obtained after the tablet core is coated by the coating material. The obtained lacosamide tablet is relatively high in dissolution rate, medicine stability is greatly improved, and medicine-using risks are reduced.

The invention provides a preparation method for lacosamide. According to the invention, easily available Boc-serine (a compound I) is used as a starting material for preparation of lacosamide, and the quality of prepared lacosamide is identical to the quality of an original drug. The preparation method provided by the invention uses easily available raw materials, does not need expensive iodomethane or severely toxic dimethyl sulfate, and is high in product purity and yield and low in toxicity and pollution, and requirements of reaction conditions on equipment are not high; thus, the method is suitable for industrial production.

The invention discloses a lacosamide solid preparation and a preparation method thereof. The lacosamide solid preparation comprises lacosamide, an internally added disintegrating agent, an externally added disintegrating agent, an internally added attenuant, an externally added attenuant, an adhesive, a glidant and a lubricant. Through adoption of the preparation method, the defects, of the conventional lacosamide fast-release tablet, that raw materials are loose and light to cause high layering possibility after mixing, the conventional preparation is high in fine powder content and low in flowability, the dissolution rate of the conventional preparation is relatively low, special equipment is required due to adoption of the inclusion technology, the process is cumbersome, and commercialized production is inconvenient are overcome.

The invention discloses a preparation method of (R)-2-acetamido-N-benzyl-3-methoxypropionamide (lacosamide). The method provided by the invention increases the purity and yield of lacosamide through controlling the temperature condition of each step and has the advantages of rational route, simple process operation and definite condition control.

The invention discloses a novel method for synthesizing lacosamide. The novel method comprises that based on a one-step reaction, a compound shown in the formula I undergoes O-methylation to form a compound shown in the formula II, and the O-methylation is realized through a process that dimethyl carbonate is added into N-protective serine in the presence of an organometallic compound. The novel method adopts nontoxic and environmentally friendly dimethyl carbonate as a methylation reagent thus has no harm to human bodies and processing equipment and realizes a high yield.

The invention discloses a lacosamide oral solution and a preparation method of the lacosamide oral solution and belongs to the field of pharmaceutical preparations. The lacosamide oral solution comprises lacosamide, an appropriate medicine solvent system, one or more flavoring agents, one or more preservatives, one or more acid-base modifiers, one or more solubilizers and one or more thickeners. The lacosamide oral solution is stable in performance, good in taste, rapid in absorption, capable of acting rapidly and good in curative effect.

The present invention relates to an improved process for the preparation of Lacosamide of Formula (I), comprising: O-methylating a compound of Formula (V) or a compound of Formula (XX) or a compound of Formula XXII; in the presence of a methylating agent and a base to produce Lacosamide of Formula (I).

The invention mainly discloses a methylation method in lacosamide synthesis process. According to the method, a nontoxic and non-carcinogenic and cheap methylating agent, such as methyl p-methyltoluenesulfonate, etc. is used as an alkylating agent, and cheap alkali such as potassium hydroxide is used for the methylation. According to the invention, generation of N-methyl impurity can be effectively avoided. In addition, yield is high, and no racemization will be caused. The method has good selectivity to hydroxyl and is more suitable for industrial production.

Compositions and methods are provided for administering a pharmaceutical composition to a human patient. Compositions are administered to a human patient orally, once daily, at a therapeutically effective dose. The pharmaceutical compositions comprise a drug selected from the group consisting of brivaracetam, divalproex, lacosamide, levetiracetam, oxcarbazepine, vigabatrin, and pharmaceutically acceptable salts of any of the foregoing, and at least one excipient. At least one of said at least one excipients modifies the release of said drug to provide an extended release form. The pharmaceutical composition have pharmacokinetic properties recited in the claims.

The invention relates to solid forms of the anti-epileptic agent lacosamide (I). The invention also relates to mixtures of solid forms of lacosamide. The invention further relates to mixtures of lacosamide enantiomers crystallized in a conglomerate Form and the use thereof in providing enantiomerically enriched lacosamide, preferably lacosamide enriched with the (R)-enantiomer of lacosamide.

The present invention relates to a method for producing (R)-2-acetamido-N-benzyl-3-methoxypropionamide (lacosamide), by methylation of (R)-2-acetamino-2-N-benzyl-3-hydroxy-propionamide (V), in which the methylation is carried out at a temperature below 20° C.

The invention provides a preparation method of lacosamide, which comprises following steps: (A) performing a reaction between D-serine and acetic anhydride to generate an intermediate product N,O-diacetyl-D-serine; (B) performing methylation to the N,O-diacetyl-D-serine to obtain N-acetyl-D-serine methyl ether; (C) carrying out a reaction to the N-acetyl-D-serine methyl ether with benzylamine to obtain (R)-2-acetamido-N-benzyl-3-methoxyl propionamide. The preparation method is short in reaction route, can avoid racemization, and is high in yield and purity of a reaction product.

The invention relates to a lacosamide oral solution. The lacosamide oral solution comprises lacosamide, a solubilizer, a thickener, a corrigent, an acidity regulator and a preservative, wherein the mass concentration of the lacosamide is 10mg / mL, the mass concentration of the solubilizer is 100-150mg / mL, the mass concentration of the thickener is 0.5-1.5 mg / mL, the mass concentration of the corrigent is 180-300mg / mL, the mass concentration of the acidity regulator is 1.9-4 mg / mL, the mass concentration of the preservative is 2-3mg / mL, and the balance is water. The pH value of the oral solutionis controlled to be 3.5-6.0 by adding the acidity regulator, the solubility of the lacosamide is improved by adding the solubilizer, and the stability of the oral solution is improved by adding the thickener, so that the lacosamide can be uniformly dispersed in the oral solution. The preparation method is simple and efficient.

The invention discloses a lacosamide synthesis method. According to the method, D-serine, tertiary amine and alkyl chloroformate react with benzylamine to generate R-2-isobutoxy carbonyl-N-benzyl-3-hydroxy propanamide; then R-2-isobutoxy carbonyl-N-benzyl-3-hydroxy propionamide reacts with diazomethane to generate R-2-isobutoxy carbonyl-N-benzyl-3-methoxyl propanamide, and then reduction and acetylization are conducted, so that lacosamide is obtained. The purity of lacosamide prepared through the method reaches 99.95% and above, and the chiral purity reaches 99.90%.

The present application relates to a fixed dose combination comprising lacosamide and levetiracetam, as well as to dosage regimens including such fixed dose combinations. The fixed dose combinations are suitable for the oral or parenteral treatment of various diseases, including in particular epilepsy and / or epileptic seizures.

The invention discloses a high-efficiency racemic lacosamide preparation method. The preparation method is characterized in that N-acetyl serine shown in a formula (II) is utilized as a raw material and completely reacts with methyl bromide under the action of sodium hydride to obtain 2-acetamido-3-methoxy methyl propionate shown in a formula (III), and then the 2-acetamido-3-methoxy methyl propionate generates ester exchange reaction with benzylamine under the catalyst of trifluoromethanesulfonate to obtain a product namely racemic lacosamide. The suspended lacosamide preparation method disclosed by the invention has an industrial process route which has the advantages of short reaction line, high yield, high atom utilization rate, simpleness in aftertreatment and low cost.