67 results about "Tapentadol" patented technology

Prodrugs of tapentadol with amino acids or short peptides, pharmaceutical compositions containing such prodrugs and a method for providing pain relief with the tapentadol prodrugs are provided herein. Prodrugs having side chains of valine, leucine, isoleucine and glycine amino acids and mono-, di- and tripeptides thereof are preferred. Additionally, methods for avoiding or minimizing the adverse gastrointestinal side effects associated with tapentadol administration, as well as increasing the oral bioavailability of tapentadol are provided herein.

A once daily controlled release pharmaceutical compositions comprising tapentadol, wherein preferably the mean Tmax of tapentadol is reached after 10 hours of administration of the composition. The composition comprises tapentadol, such that it maintains serum concentration of tapentadol of at least about 20 ng / ml for at least about 17 hours after oral administration of the composition. According to one embodiment the controlled release pharmaceutical composition comprises tapentadol, which is gastroretentive.

The use of tapentadol for the manufacture of a medicament comprising at least one administration unit A containing dose a of tapentadol and at least one administration unit B containing dose b of tapentadol, where dose a<dose b, for the treatment of pain.

An aqueous pharmaceutical composition adapted for parenteral administration of tapentadol or a physiologically acceptable salt thereof having a pH value of at least 5.4.

The present invention provides a dosage form comprising at least one form of tapentadol, with or without a second analgesic, and at least one opioid antagonist, wherein tapentadol is present in an optimal or suboptimal amount and the said antagonist is present in an amount effective to improve the efficacy and or reduce the side effects of tapentadol. The present invention further provides a method of treating pain and pain related conditions by administering to a patient in need thereof, a dosage form comprising at least one form of tapentadol, with or without a second analgesic, and at least one opioid antagonist, wherein tapentadol is present in an optimal or suboptimal amount and the said antagonist is present in an amount effective to improve the efficacy and or reduce the side effects of tapentadol.

The use of tapentadol for treating pain due to osteoarthritis.

A semisolid aqueous pharmaceutical composition containing tapentadol or a physiologically acceptable salt thereof.

An aqueous pharmaceutical composition containing tapentadol or a physiologically acceptable salt thereof and being adapted for oral administration. The composition has excellent storage stability without relying on the presence of high amounts of preservatives.

The invention relates to the field of drug synthesis, in particular to a method for preparing an analgesic tapentadol intermediate (2R,3R)-3-(3-methoxyl phenyl)-N,N,2-trimethyl amylamine hydrochloride. The method is characterized by comprising the following steps of: chlorinating optically active (2S,3R)-1-dimethylamino-3-(3-methoxyl phenyl)-2-methyl amyl-3-ol and phosphorus pentachloride and salifying with hydrogen chloride to obtain hydrochloride, and then carrying out stereoselective hydrogenolysis in the presence of a catalyst, and salifying with the hydrogen chloride to obtain the analgesic tapentadol intermediate. The method provided by the invention has the advantages of cleanness, safety, convenience for after treatment and lower production cost. Compared with a method in a literature, the method has reaction time shortened by nearly 80 hours.

The present invention relates to a pharmaceutical composition of tapentadol for nasal administration. Present invention also relates to the process of preparation of pharmaceutical composition of tapentadol for nasal administration and its use in the treatment of pain.

The invention provides methods for preparing substituted phenylalkanes. In particular, the processes comprise reacting a phenyl boronic compound with an α-β unsaturated carbonyl-containing compound via an asymmetric 1,4-addition reaction. The processes may be useful in the synthesis of tapentadol.

A process for the synthesis of a salt of tapentadol.

The invention discloses a preparation method of a key intermediate (1R,2R)-1-ethyl-2-methylphenylethane compound of tapentadol and a method for preparing tapentadol and derivatives thereof from the key intermediate.

The present invention discloses processes for the preparation of 3-[(1R,2R)-3-(dimethyl-amino)-1-ethyl-2-methyl-propyl]phenol (Tapentadol), salts thereof and related compounds of formula (A), including stereoisomers and pharmaceutically acceptable salts thereof, and to certain intermediates used in such process.

The use of tapentadol in the treatment of pain and / or pain chronification in a subject suffering from pain chronification and / or in the treatment of pain and inhibition of pain chronification in a subject suffering from pain and at risk of pain chronification, as well as the use of tapentadol for the treatment or inhibition of migraine.

A method of treating irritable bowel syndrome in a patient in need thereof by administering to said patient a pharmaceutically effective amount of tapentadol.

The present invention relates to methods of treating and managing Parkinson's disease and related disorders. The methods especially find use in managing motor symptoms, including gait problems, particularly during advanced stages when effectiveness of standard medications wear off or side effects become problematic, as seen in Parkinson's disease, other disorders treated with dopaminergic agents, and other conditions associated with motor problems, such as aging or stroke. The treatment also may include disease-modifying effects, neuroprotection of, or neurorescue effects on neuronal cells in patients with Parkinson's disease and other neurodegenerative disorders. In particular, the invention relates to method of administering pharmaceutical compositions comprising effective amounts of tapentadol or a pharmaceutically acceptable salt or derivative thereof or, in other embodiments, stavudine or nabumetone, or a derivative thereof, for treating symptoms associated with Parkinson's disease, either as individual active agents, in combination with each other, or in combination with agents known to treat Parkinson's disease, such as the dopaminergic agent levodopa. The invention also relates to methods of preparing pharmaceutical compositions comprising effective amounts of tapentadol, stavudine, or nabumetone, or a derivative thereof, or further in combination with a dopaminergic agent, or derivative thereof, as well as to methods of using the pharmaceutical compositions in treating Parkinson's disease, related disorders, other conditions treated with dopaminergic agents, and other conditions with gait problems, for example by oral administration of the compositions.

A semisolid aqueous pharmaceutical composition containing tapentadol or a physiologically acceptable salt thereof.

The invention discloses a novel intermediate for preparing tapentadol and analogues thereof, wherein the structural formula is shown as formula I or II, and the groups are defined as the specification. The invention further discloses a method for preparing the novel intermediate and use of the intermediate for preparing tapentadol and analogues thereof. The invention can remarkably improve the product yield and quality of tapentadol, reduce the production cost, and simplify the production procedure. The preparation process is environment friendly, thus more suitable for the requirements of industrial production.

The invention belongs to the field of pharmacy, in particular to a tapentadol carbamate derivative with a general formula I, pharmaceutically acceptable salts, a preparation method and an application thereof. In the invention, the structure of phenolic hydroxyl groups in tapentadol molecules is improved by a chemical synthesis method, and proper carrier groups are introduced in the position to synthesize carbamate type prodrug. All amines adopted by the carbamate are fatty amines, wherein dimethylamine or methylamine fragments can generate demethylation metabolism easily in vivo, thereby being convenient for releasing raw tapentadol. Meanwhile, the existence of the carbamate structure increases the chemical stability of the prodrug and can obviously improve the oral bioavailability, reduce the administration dosage and lower the toxic side effect, and the tapentadol carbamate derivative can be further developed into novel tapentadol analgesics.

The invention provides methods for preparing substituted phenylalkanes. In particular, the processes comprise reacting a phenyl boronic compound with an α-β unsaturated carbonyl-containing compound via an asymmetric 1,4-addition reaction. The processes may be useful in the synthesis of tapentadol.

Disclosed herein is an improved process for the preparation of 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol of Formula-I and its pharmaceutically acceptable salt which comprises the reaction of (S)-1-(dimethylamino)-2-methylpentan-3-one of formula VIII with 3-bromo anisole of formula II under Grignard conditions to get the compound (2S,3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methyl pentan-3-ol of formula V followed by activation of the —OH group of the formula V to convert into sulfonate esters of formula IX, which are on reductive deoxygenation to yield (2R,3R)-3-(3-methoxyphenyl)-N,N,2-trimethylpentan-1-amine of formula VII and demethylation of formula VII to obtain the compound 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol of Formula-1.

The invention discloses a synthetic method of tapentadol. The method comprises the following steps: reacting meta-substitution cinnamic acid serving as a starting material with a chiral adjuvant to obtain amide; reacting the amide with a nucleophilic reagent and an electrophilic reagent, and introducing two chiral centers to obtain a chiral product; performing reduction and deprotection on the chiral product to obtain chiral alcohol; performing an amination reaction and a substitution reaction on the chiral alcohol to obtain the tapentadol. The tapentadol is synthesized by taking cheap and readily-available (1R,2R)-psedo-ephedrine as the chiral adjuvant, forming two chiral centers by using a one-pot method and performing simper deprotection and subsequent transformation. By adopting the synthetic method, the reaction route can be simplified, post-treatment steps can be reduced, and the production cost is reduced. The synthetic method is more suitable for industrial application.

Disclosed herein is an improved process for the preparation of 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol of Formula-I and its pharmaceutically acceptable salt which comprises the reaction of (S)-1-(dimethylamino)-2-methylpentan-3-one of formula VIII with 3-bromo anisole of formula II under Grignard conditions to get the compound (2S, 3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methyl pentan-3-ol of formula V followed by activation of the —OH group of the formula V to convert into sulfonate esters of formula IX, which are on reductive deoxygenation to yield (2R,3R)-3-(3-methoxyphenyl)-N,N,2-trimethylpentan-1-amine of formula VII and demethylation of formula VII to obtain the compound 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol of Formula-1.

The present invention refers to a new process for the synthesis of tapentadol comprising the quantitative resolution of the racemic mixture (V) to obtain the stereoisomer of (S)-3-(dimethylamino)-2-methyl-1-(3-nitrophenyl)-propan-1-one (VII) according to the Scheme 2 belowusing the (2R,3R)—O,O′-dibenzoyltartaric chiral acid wherein said resolution is quantitative.The present invention also refers to some intermediate compounds of the new synthesis process of tapentadol.