34 results about "Varenicline" patented technology

A composition for nasal administration comprising varenicline or its pharmaceutically acceptable salt and at least one excipient. The invention also provides a composition for buccal administration comprising varenicline or its pharmaceutically acceptable salt and at least one excipient to form a solid dosage form, wherein the solid dosage form disintegrates in an oral cavity at body temperature and may adhere to body tissue of the oral cavity; a composition for pulmonary administration comprising varenicline or its pharmaceutically acceptable salt and at least one excipient; and, a method for reducing nicotine addiction, aiding in the cessation of, or lessening of tobacco use in a subject.

Provided herein is an improved, convenient, commercially viable and environmentally friendly process for the preparation of varenicline or a pharmaceutically acceptable salt thereof comprising reacting 1-(4,5-diamino-10-aza-tricyclo[6.3.1.02 7]dodeca-2(7),3,5-trien-10-yl)-2,2,2-trifluoro-ethanone with chloroacetaldehyde in the presence of an oxygen source. Provided further herein is an improved and industrially advantageous process for the preparation of 1-(4,5-diamino-10-aza-tricyclo[6.3.1.02 7]dodeca-2(7),3,5-trien-10-yl)-2,2,2-trifluoro-ethanone.

The invention provides transdermal compositions comprising varenicline or its pharmaceutically acceptable salt or prodrug form.

The invention relates to a method for synthesizing Varenicline intermediate 2, 3, 4, 5-tetralin-1, 5-methylene-hydrogen-benzoazepine. The method includes the following steps: under the action of catalyst, mixing amyl nitrite with o-aminobenzoic acid solution to generate diazonium salt, then mixing the diazonium salt with cyclopentadiene, and heating to react to generate compound 1; feeding ozone into the solution of compound 1, after complete conversion, adding reducing agent to generate compound 2, then dripping the compound 2 to the mixed solution of triacetoxy sodium borohydride and benzylamine to generate compound 3 by loop closing; and hydrogenating the compound 3 under the action of palladium and carbon for debenzylation and reduction to obtain M intermediate 2, 3, 4, 5-tetralin-1, 5-methylene-hydrogen-benzoazepine. The method has the advantages of greatly simplifying the method for preparing Varenicline intermediate, being simple in production process and safe in operation, well ensuring no harm to the environment and control on production cost, increasing yield and being capable of becoming a process in great industrial production.

Provided is a medicated patch containing a medicinal agent and an adhesive base material and having an acid value of no greater than 28, where the medicinal agent is varenicline or a pharmaceutically acceptable salt of varenicline.

A chewing gum composition including a water insoluble base portion; a water soluble portion; and a therapeutically effective amount of varenicline or its pharmaceutical acceptable salt thereof. A method for reducing nicotine addiction and aiding in the cessation or lessening of tobacco use in an individual by administering to an oral cavity of an individual a chewing gum composition including an effective amount of varenicline or its pharmaceutical acceptable salt thereof; and chewing the gum composition to cause the varenicline or its pharmaceutical acceptable salt thereof to be released from the chewing gum composition into the oral cavity of the individual. A method of manufacturing a chewing gum composition.

The invention discloses preparation methods of a varenicline intermediate, varenicline and its salt. The invention provides a preparation method of a compound shown in a formula I. The preparation method comprises the following steps: carrying out a cyclization reaction on the compound 2 and glyoxal in the presence of a solvent and alkaline acid salt by using or not using inert gas protection to generate the compound as shown in the formula I, wherein R is an amino protecting group. The method can greatly shorten the reaction time of the cyclization reaction under the condition of ensuring the product yield and the product purity, obviously improve the production efficiency of the cyclization product, and greatly reduce the production cost and the time cost of the unit product; and meanwhile, the content of the impurity I in the varenicline intermediate product can be controlled within a relatively low level range, so that the product quality of the drug intermediate and the crude drug can be better guaranteed.

The invention relates to varenicline hemitartrate and a preparing method thereof. The salt has a structure shown as the formula II. The varenicline hemitartrate is good in stability, low in moisture adsorption and high in safety. The preparing method is simple in operation and good in reproducibility.

The invention provides an improved process for the preparation and purification of Varenicline and intermediates for the preparation of Varenicline.

The invention relates to varenicline hemitartrate and a preparing method thereof. The salt has a structure shown as the formula II. The varenicline hemitartrate is good in stability, low in moisture adsorption and high in safety. The preparing method is simple in operation and good in reproducibility.

The present invention provides an improved process for preparing a compound of formula (IIIA), an intermediate of the synthesis of varenicline. Also, the present invention provides an improved process for preparing varenicline, or a pharmaceutically acceptable salt or solvate thereof. Furthermore, the present invention provides a process for decolorizing varenicline, or a salt or solvate thereof. Still further, the present invention provides a process of preparing varenicline L-tartrate with improved yield. Still further, the present invention relates to the use of compound of formula (V), or a salt or solvate thereof, as a reference marker and reference standard for assessing the purity of varenicline, or a salt or solvate thereof.

The present invention generally relates to methods for predicting the safety of a nicotinic cholinergic receptor agonist drug-based pharmacological treatment, such as one based on varenicline, based on determining at least one allele of one or more of single-nucleotide polymorphisms (SNPs) rs9479757, rs7930792, rs12423809, rs4251417, rs7146, rs477292, rs495491, rs3778151, rs763132, rs4474069 and rs1183035, or of any SNP of the corresponding linkage groups thereof, in a biological sample of a subject.

A pharmaceutical long acting depot composition is provided as an aid to smoking cessation treatment. The formulation comprises a therapeutically effective amount of varenicline or its pharmaceutically acceptable derivative and pharmaceutically acceptable excipients. The process of preparation of the formulation is also provided.

It is disclosed a process for the preparation of a compound of formula (I) or a salt thereof, comprising:nitrating a compound of formula (II) or a salt thereof,to obtain a compound of formula (IV) or a salt thereof,reducing it, to obtain a compound of formula (V) or a salt thereof, andsubsequently cyclizing it to obtain a compound of formula (I) or a salt thereof and, if desired, converting a compound of formula (I) to a salt thereof, or vice versa, characterized in that:the nitration of a compound of formula (II) or a salt thereof is carried out with concentrated nitric acid in the presence of a strong inorganic acid and that the amino group in the compound of formula (II) is not protected.

The invention discloses a preparation method of a varenicline intermediate and nitroreduction impurity thereof. The preparation method of the varenicline intermediate and nitroreduction impurity thereof comprises the following steps: nitrifying 2,3,4,5-tetrahydro-3-(trifluoroacetyl)-1,5-methano-1H-3-benazepine, hydrogenating Pd / C, and selectively reducing nitryl, thus obtaining a target compound shown in a formula (I). The preparation method of the varenicline intermediate and nitroreduction impurity thereof has the advantages that no pollution is produced to the environment, column chromatography operation is avoided, and yield and purity of a product are improved. The formula (I) is described in the specification.

The invention provides a preparation method for an N-nitrosamine genotoxic impurity of varenicline tartrate. The preparation method comprises the following steps: with ammonium formate as a hydrogen donor, carrying out reduction reaction on dinitrate under the catalysis of palladium carbon to obtain a diamino compound, carrying out a cyclization reaction on the diamino compound and an aqueous glyoxal solution to obtain a cyclization product, carrying out a hydrolysis reaction on the cyclization product under the action of sodium hydroxide, removing trifluoroacetyl to obtain free alkali, and finally, subjecting the free alkali to reacting with sodium nitrite under the catalysis of protonic acid to obtain the N-nitrosamine impurity. According to the invention, the technical vacancy of preparation methods for the impurity at present is filled in, the prepared high-purity impurity can be applied as a control sample to the drug impurity research and production quality control process of varenicline tartrate, and a guarantee is provided for the genotoxicity research and comprehensive quality control of a varenicline tartrate bulk drug.

The invention discloses a varenicline pharmaceutical composition capable of reducing generation of nitrosamine impurities, and preparation and application of the varenicline pharmaceutical composition. According to the pharmaceutical composition disclosed by the invention, pharmaceutically acceptable acid is added into a secondary amine compound or the composition thereof, the generation of nitrosamine impurities can be effectively inhibited and reduced, the stability of the secondary amine compound or the composition thereof is improved, the content of nitrosamine genotoxic impurities is controlled at a relatively low level, and the safety requirement is met.

A pharmaceutical long acting depot composition is provided as an aid to smoking cessation treatment. The formulation comprises a therapeutically effective amount of varenicline or its pharmaceutically acceptable derivative and pharmaceutically acceptable excipients. The process of preparation of the formulation is also provided.

The subject invention provides a varenicline composition that comprises varenicline, or a pharmaceutically acceptable salt thereof, and an amount of a compound selected from one or more of several mononitro, monoamine mixed aminonitro, diamino or dinitro intermediates, and the concentration of said compound is greater than 0 ppm and not greater than about 500 ppm, not greater than about 100 ppm or not greater than about 10 ppm. Methods for synthesizing and using such varenicline compositions are also provided.

The preparation method comprises the following steps: reacting an initial raw material with trifluoroacetic anhydride in dichloromethane under the catalysis of triethylamine to obtain an intermediate 1, carrying out nitration reaction on the intermediate 1 and fuming nitric acid under the catalysis of concentrated sulfuric acid, extracting and concentrating dichloromethane to obtain an intermediate 2, and purifying the intermediate 2 to obtain the varenicline tartrate intermediate impurity. Carrying out reduction reaction on the intermediate 2 under the catalysis of palladium carbon to obtain an intermediate 3; and carrying out cyclization reaction on the intermediate 3 and triethyl orthoformate under the catalysis of sulfamic acid to obtain the varenicline tartrate intermediate impurity. The preparation method of the impurity is provided for the first time and can be better applied to the existing preparation process of the varenicline tartrate key intermediate, the impurity identification and separation degree is improved, and the product quality is improved.

The invention provides a varenicline tartrate composition and a preparation method thereof. In the composition, the weight percentage of sorbitol and microcrystalline cellulose is 5:1 to 10:1, and includes a disintegrant, a binder agents and lubricants. This product adopts the powder direct pressing process, the preparation process is simple, easy to operate, good reproducibility, and suitable for large-scale industrial production. Moreover, the varenicline tartrate composition prepared by the present invention not only does not need to control the particle size, but also has small friability, good fluidity, high dissolution rate, good stability and low probability of adverse reactions.

The present invention relates to a process for the preparation of varenicline or a pharmaceutically acceptable salt thereof. The invention also relates to an intermediate compound useful in the process and the preparation of such intermediate compound.

The invention provides a method for detecting nitrosamine genotoxic impurities in a varenicline intermediate. The method comprises the step of determining the content of the nitrosamine genotoxic impurities by adopting a high-resolution liquid chromatography and mass spectrometry technology, and the nitrosamine genotoxic impurities are compounds A, B and C with the chemical structural formulas shown in the specification, and the structure of the varenicline intermediate is shown in the specification. according to the method, the effective separation of the varenicline intermediate and the related genotoxic impurities can be achieved, and the quantitative detection of the micro-content can be achieved so as to effectively control the content of the genotoxic impurities in the bulk drug and ensure the medication safety; and the detection method provided by the invention adopts common reagents, and is simple and convenient to operate, good in separation degree, high in sensitivity and good in reproducibility.

The invention relates to a preparation method for a varenicline intermediate. The method includes: subjecting 1, 4-dihydro-1, 4-methanonaphthalene to an oxidation reaction under the action of an oxidizing agent so as to generate the varenicline intermediate. The oxidizing agent is an osmic acid salt or its hydrate, the oxidation reaction undergoes in a solvent in the presence of N-methyl-N-morpholine oxide, and the solvent is a mixed solvent of water and any one or more of the following organic solvents: C1-C6 alcohol solvents, ketone solvents, ether solvents and nitrile solvents. For the mixed solvent, water and the organic solvent are in a volume ratio of 1:0.1-9. The method provided by the invention has the advantages of low production cost, simple operation, mild reaction conditions and environmental friendliness, and can prepare the product that is easy to purify and has purity up to over 99%. With high yield, the method is suitable for both small-scale preparation in laboratories and large-scale industrialized production.

The present invention is directed to a combination of varenicline and bupropion for use in treating alcohol use disorder (AUD) and / or treating alcohol risk consumption in a subject in need thereof. Corresponding compositions, uses and methods of treatment are also provided.

The present invention relates to a varenicline transdermal solution. The transdermal solution comprises varenicline or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier is selected from any one or a combination of a penetration enhancer, a humectant, a preservative and a solvent, and the solvent is selected from any one or a combination of glycerol, propylene glycol, ethanol and water. The solution is absorbed through skin, has the advantages of being long-acting, high in bioavailability, good in patient compliance, convenient to carry and use, flexible in medication position, capable of achieving postaural targeted administration, free of skin irritation and the like, and the effectiveness and safety of the medicine and the medication compliance of the patient are remarkably improved.

The invention belongs to the field of medicine preparations, and particularly relates to a varenicline orally disintegrating tablet and a preparation method thereof. By aiming at the problems that varenicline has a bitter taste and has poor oral administration compliance, varenicline, a carrier and a solvent are prepared into a solid dispersion so as to cover the poor taste of a medicine; and the solid dispersion is adopted for preparing the orally disintegrating tablet, and the orally disintegrating tablet can be quickly disintegrated within 30 seconds, has a good taste, and remarkably improves the oral administration compliance.