90 results about "Medetomidine" patented technology

The invention provides an improved, highly efficient method for preparing Medetomidine, and its salts, in particular its pharmaceutically acceptable salts. The method utilizes the high reactivity of halogenated imidazoles towards transmetalation with Grignard reagents and the subsequent reaction with 2,3-dimethylbenzaldehyde.

The invention provides a new method for preparing dexmedetomidine hydrochloride. According to the method, Lewis acid is used as a catalyst, and racemized medetomidine is prepared by a Friedel-Crafts reaction; and the racemized medetomidine is resolved by (+)-di-p-toluoyl-tartaric acid [(+)-DDTA] to obtain dexmedetomidine. The dexmedetomidine is salified in hydrochloric acid to obtain dexmedetomidine hydrochloride.

A sympatholytic cardiovascular agent delivered by a drug delivery pump to a central nervous system site to alleviate symptoms of acute or chronic cardiac insult or impaired cardiac performance. The drug delivery pump can be external or implantable infusion pump (IIP) coupled with a drug infusion catheter extending to the site. A patient activator can command delivery of a dosage and/or an implantable heart monitor (IHM) coupled with a sensor can detect physiologic parameters associated with cardiac insult or impaired cardiac performance and trigger dosage delivery. The IIP and IHM can be combined into a single implantable medical device (IMD) or can constitute separate IMDs that communicate by any of known communication mechanisms. The sympatholytic cardiovascular agent is one of the group consisting of an alpha-adrenergic agonist and an alpha2-adrenergic agonist (e.g., clonidine, p-aminoclonidine, guanabenz, lidamidine, tizanidine, moxonidine, methyldopa, xylazine, guanfacine, detomidine, medetomidine, and dexmedetomidine).

The invention discloses a method for obtaining levorotatory enantiomer and dexiotropic enantiomer by separation from medetomidine (chemical name: 4-(1-(2,3-dimethylphenyl)-ethyl)-1H-imidazole) of racemate, which comprises the steps of reacting medetomidine racemate with optically active acid so that medetomidine racemate can be converted into salts of diastereoisomer, and then separating the saltsof the diastereoisomer by using a half-dose resolution method so as to obtain single enantiomer with particular optical purity.

The invention relates to a method for preparing dexmedetomidine hydroch. The method particularly includes the following steps that 1, dispinner medetomidine is dissolved in methyl alcohol and mixed with a right-handed resolving agent according to the molar ratio of 1:0.4-0.6, stirring is conducted for 2-3 hours at the heating temperature of 60-80 DEG C, diethyl ether is added, cooling, still standing, crystallization and filtering are conducted, a mother solution and a left-handed resolving agent are mixed according to the molar ratio of 1:0.4-0.6, stirring and crystallization are conducted for 24 hours, and dexmedetomidine is obtained after filtering is completed; 2, obtained dexmedetomidine is placed in HCl/diethyl ether, and the end product dexmedetomidine hydroch is formed. Compared with the prior art, dexmedetomidine hydroch is prepared at low cost; the synthetic route is short, dexmedetomidine hydroch with high purity can be prepared, isomers are not detected, quality meets the newest standard of the pharmacopeia, and industrial production is facilitated. Adopted raw materials are low in cost, reaction conditions are moderate, and the method can be applied to actual production.

The invention discloses a medetomidine industrial splitting method which takes L-(-) camphorsulfonic acid as a chiral reagent and C1-C5 alcohol as a chiral auxiliary. According to the method disclosed by the invention, the splitting yield reaches up to over 40% and the splitting optical purity reaches over 99.5%. The method is simple in industrialized operation and can be used for industrialized and commercialized production.

The invention provides a method of measuring the content of related substance in dexmedetomidine hydrochloride active ingredient. The method comprises the following steps: analyzing the dexmedetomidine hydrochloride active ingredient by means of liquid chromatography to obtain a chromatogram conveniently; and determining the content of related substance in the dexmedetomidine hydrochloride active ingredient based on the chromatogram. The method can effectively measure impurities, initial materials and intermediates probably introduced in a synthetic process of dexmedetomidine hydrochloride and effectively control the quality of a dexmedetomidine hydrochloride drug. The method has the characteristics of effectiveness, sensitivity, specificity and accuracy.

The invention provides a method for preparing dexmedetomidine and an intermediate thereof. Specifically speaking, the method comprises the steps that a compound shown as a formula II (please see the formula in the description) reacts with metal magnesium to prepare a metal magnesium Grignard reagent, and then the metal magnesium Grignard reagent reacts with a compound shown as a formula III (please see the formula in the description). The process has the advantages of being few in step, high in yield, easy to operate, high in product purity and the like and is quite suitable for large-scale industrialized production.

The invention discloses a preparation method for 2,3-dimethylphenyl-1-triphenylmethyl-imidazole-4-one. The method comprises the following steps: with imidazole-4-ethyl formate as a raw material, carrying out amino protection by using triphenylchloromethane and then carrying out basic hydrolysis so as to obtain 1-triphenylmethyl-1H-imidazole-4-formic acid; subjecting 1-triphenylmethyl-1H-imidazole-4-formic acid and N,O-dimethyl hydroxylamine hydrochloride so as to obtain N-methoxy-N-methyl-1-triphenylmethyl-1H-imidazole-4-methanamide; and subjecting N-methoxy-N-methyl-1-triphenylmethyl-1H-imidazole-4-methanamide and a Grignard reagent prepared through a reaction of 2,3-dimethylbromobenzene with magnesium metal to a Grignard reaction so as to produce the target product 2,3-dimethylphenyl-1-triphenylmethyl-imidazole-4-one. Compared with reported preparation methods in the prior art, the preparation method provided by the invention is easier and more convenient to operate and is beneficial for industrial production.

The present invention provides intranasal formulations comprising dexmedetomidine, or a pharmaceutically acceptable salt thereof, and uses thereof.

The present invention discloses a method of treating agitation or the signs of agitation in a subject comprising the sublingual administration of an effective amount of an alpha-2 adrenergic agonist, more particularly Dexmedetomidine, or a pharmaceutically acceptable salt thereof. The method is particularly suitable for the treatment of agitation associated with neurodegenerative and/or neuropsychiatric diseases. The present invention also discloses the sublingual administration of an alpha-2 adrenergic agonist, more particularly Dexmedetomidine or a pharmaceutically acceptable salt thereof at a dose that is effective to treat agitation or the signs of agitation in a subject, but does not cause significant sedation.

Non-domesticated mammalian animals are anesthetized and immobilized by injecting an effective amount of an anesthetizing and immobilizing drug comprising pharmaceutically active ingredients of butorphanol tartrate, azaperone tartrate and medetomidine hydrochloride (BAM) into the animal from a dart. The BAM combination is preferably initially formed as lyophilized powder of the pharmaceutically active ingredients, and then reconstituted before injection as an injectable liquid in the environment of the animal.

The present disclosure relates to the treatment of agitation or signs of agitation in certain human subjects, including subjects with a neurodegenerative, neuropsychiatric or opioid withdrawal disorder, by administering dexmedetomidine hydrochloride by the intravenous route.

The invention relates to a method of treating separation anxiety in companion animals, particularly dogs, comprising administering to a subject in need thereof an effective amount of dexmedetomidine, medetomidine or a pharmaceutically acceptable salt thereof as the active ingredient. The active ingredient is preferably administered oromucosally, e.g. in the form of an oromucosal gel.

The invention relates to a premixed preparation for dexmedetomidine. Specifically, the invention relates to a ready-to-use premixed preparation of dexmedetomidine packaged in a container containing plastic or a pharmaceutically acceptable salt thereof. The ready-to-use premixed preparation can be used for sedation of patients in an intensive care unit or procedural sedation.

The present invention provides stable, ready-to-use pharmaceutical compositions, comprising dexmedetomidine or a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable excipients, and a pharmaceutically acceptable liquid vehicle, where the composition is provided in a sealed container that comprises a cyclic olefin polymer. The present invention also provides ready-to-use pharmaceutical compositions comprising dexmedetomidine or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable liquid vehicle and an antioxidant and/or stabilizer, such as L-methionine. These solutions were found to be stable over the shelf life of the product. Other aspects of the invention relate to methods for making such compositions, as well as methods of using such compositions for perioperative care of a patient or for sedation.

The invention discloses an industrial preparation method of dexmedetomidine hydrochloride, and belongs to the field of medicines. The method comprises the following steps: directly carrying out a Friedel-Crafts alkylation reaction on initial raw materials comprising 1-(2,3-dimethylphenyl)ethanol not subjected to a chlorination (thionyl chloride) reaction and protected imidazole under the catalysis of a Lewis acid to obtain racemic dexmedetomidine, carrying out pre-resolution purification on the racemic dexmedetomidine through a chiral acid, carrying out chiral acid resolution and alkali dissociation, and adding a hydrochloric acid organic solvent to form a salt in order to obtain the dexmedetomidine hydrochloride. The method avoids use of the toxic and corrosive regent thionyl chloride, allows the above product with high chiral and chemical purity to be obtained and the yield to be high, and is suitable for industrial production.

Medetomidine or a salt thereof for use in controlling parasitic crustaceans, such as sea lice, on fish, e.g. salmon. A method of improving water flow into and out of a cage or net for fish farming, by providing said cage or net with a surface coating containing medetomidine or a salt thereof in an amount effective to reduce biofouling of said cage or net. The coating is capable of releasing medetomidine or the salt thereof into the water in the cage or net in an amount effective to reduce or prevent parasitic infestation of the fish in the cage or net.

The invention discloses a method for the preparation of medetomidine starting from 1-bromo 2,3-dimethylbenzene and chloroacetone.