20 results about "Rotigotine" patented technology

The invention belongs to the technical field of biology and medicinal chemistry, and discloses a transaminase mutant, a method and application of the transaminase mutant in preparation of a key chiral intermediate of rotigotine, and the preparation method of the key chiral intermediate of rotigotine is a biological conversion method using the transaminase mutant as a main enzyme. The amino acid sequence of the transaminase mutant is an amino acid sequence obtained by mutating the amino acid sequence of wild type transaminase as shown in SEQ ID NO.1, the amino acid sequence of the transaminase mutant has a mutation site in the mutated amino acid sequence, and the amino acid sequence of the transaminase mutant has more than 90% of homology with the mutated amino acid sequence. When 5-methoxy-2-tetralone (a compound shown in a formula III) is catalyzed by an enzymatic reaction method to prepare a key chiral intermediate (S)-5-methoxy-1, 2, 3, 4-tetrahydronaphthalene-2-amine (a compound shown in a formula II) of rotigotine, the product is chiral purity gt, and the purity gt of the key chiral intermediate (S)-5-methoxy-1, 2, 3, 4-tetrahydronaphthalene-2-amine is gt. The yield of the biological catalysis step is gt; 95%.

This rotigotine-containing adhesive patch comprises a support layer and an adhesive layer, wherein the adhesive layer contains: at least one selected from the group consisting of rotigotine and pharmaceutically acceptable salts of rotigotine; a rubber-based adhesive base; and an antioxidant. The antioxidant includes propyl gallate, ascorbyl palmitate, and sodium pyrosulfite.

A rotigotine-containing patch which is provided with a support layer and an adhesive layer, and wherein the adhesive layer contains an adhesive base and propyl gallate, and at least one substance selected from the group consisting of rotigotine and a pharmaceutically acceptable salt of rotigotine.

The invention discloses an application of rotigotine microspheres in preparation of a medicine for preventing or treating multiple sclerosis. The rotigotine microspheres can improve spinal cord demyelination and infiltration of spinal cord inflammatory cells, can also improve the weight problem, can be administrated once every 14 days as a microsphere preparation, greatly improves the use compliance of patients, and provides a new thought for treating multiple sclerosis.

The invention discloses a high-efficiency rotigotine preparation process which comprises the following steps: dissolving sodium triacetoxyborohydride in a reaction solvent, adding 2-thiopheneethylamine while stirring, dropwise adding a dichloromethane solution of 5-methoxy-2-tetralone, continuously reacting, and carrying out post-treatment to obtain N-(1, 2, 3, 4-tetramethyl-4-piperidine)-1, 2, 3, 4-tetramethyl-4-piperidine. The preparation method comprises the following steps: adding 2, 2, 4-tetrahydro-5-methoxy-2-naphthyl)-2-thiophene ethylamine; dissolving L-DTTA and L-DBTA in ethanol and a water solvent, adding into the product, carrying out a reflux reaction, and recrystallizing to obtain a single-configuration resolution salt; the preparation method comprises the following steps: adding sodium triacetoxyborohydride into a reaction kettle, carrying out product alkalization, carrying out methyl tertiary ether extraction, concentrating an organic layer until the organic layer is dry, dissolving with dichloromethane, adding sodium triacetoxyborohydride, dropwise adding propionaldehyde, continuously carrying out stirring reaction after dropwise adding, after the reaction is finished, concentrating until no liquid drop exists, and carrying out post-treatment to obtain (S)-5-methoxyrotigotine; and dropwise adding HBr, and recrystallizing with n-hexane to obtain rotigotine. According to the present invention, the STAB-mediated continuous reductive amination is adopted to replace the high pressure hydrogenation, and the L-DTTA / L-DBTA composite resolution system is designed to improve the chiral selectivity, such that the process is simplified, and the cost is reduced.

The present invention relates to a transdermal therapeutic system (TTS) for administering rotigotine as an active ingredient, comprising a matrix layer containing rotigotine, the matrix layer further comprising one or more non-amine-resistant silicone adhesives in an amount of more than 50% by weight, based on the total weight of the pressure-sensitive adhesives contained in the matrix layer, and paraffin, and to a method for preparing the same. The transdermal therapeutic system of the present invention is particularly suitable for the treatment of Parkinson's disease.

The application discloses a method for separating and detecting material A in rotigotine or a composition thereof, a rotigotine pharmaceutical salt or a composition thereof, a composition containing rotigotine or a pharmaceutical salt thereof, a pharmaceutical preparation and application. The separating and detecting method comprises the following steps: taking the rotigotine or the composition thereof, the rotigotine pharmaceutical salt or the composition thereof, and separating by using high performance liquid chromatography. The mobile phase in the high performance liquid chromatography comprises an aqueous phase and an organic phase, and the pH value of the aqueous phase is 6.0-8.0. The separating and detecting method has the advantages of good separating degree, symmetrical peak shape, high sensitivity and accurate quantification of the material A, and can make up for the defects of rotigotine quality control, and can be used for quality inspection or quality control of the rotigotine or the composition thereof, the rotigotine pharmaceutical salt or the composition thereof.

The application belongs to the technical field of biology and pharmaceutical chemistry, and discloses a transaminase mutant, a method and application of the transaminase mutant in preparation of a key chiral intermediate of rotigotine, and a preparation method of the key intermediate of rotigotine is a biological conversion method with the transaminase mutant as a main enzyme, an amino acid sequence of the transaminase mutant is an amino acid sequence mutated from an amino acid sequence of a wild-type transaminase shown in SEQ ID NO. 1, the amino acid sequence of the transaminase mutant has a mutation site in the mutated amino acid sequence, and has more than 90% homology with the mutated amino acid sequence. When 5-methoxy-2-naphtalone (a compound of formula III) is catalyzed to prepare a key chiral intermediate (S)-5-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine (a compound of formula II) of rotigotine through an enzymatic reaction method, the chiral purity of the product is greater than 99.9%, and the yield of the biological catalysis step is greater than 95%.

The invention discloses an application of rotigotine microspheres in preparation of medicines for preventing or treating rheumatic arthritis, the rotigotine microspheres can directly act on joint parts, joint synovial hyperplasia, joint injury and bone erosion are effectively reduced, and the curative effect of the rotigotine microspheres is improved. The rotigotine microspheres can be independently used or matched with other known medicines, compounds or carriers to be prepared into various forms of medicaments or pharmaceutical compositions for prevention or treatment, and the dopamine receptor can be continuously excited for 4-8 weeks by injecting once during administration, so that the'on-off 'phenomenon caused by fluctuation of blood concentration is remarkably improved, and the bioavailability of the rotigotine microspheres is improved. Therefore, the curative effect can be effectively improved, and the compliance of a patient is greatly improved.

In the transdermal absorption preparation according to the present invention and a method for preparing the same, the transdermal absorption preparation comprises a drug-containing adhesive layer comprising rotigotine or a pharmaceutically acceptable salt thereof as an active ingredient, hydroxy propyl cellulose (HPC) as a crystallization inhibitor, and a silicone-based polymer binder.

The present invention belongs to the technical field of pharmaceutical synthesis, and particularly relates to a rotigotine intermediate, a preparation method thereof and an application. The rotigotine intermediate has a structure shown in Formula 1 and / or a pharmaceutically acceptable salt thereof:. The preparation method provided by the present invention uses inexpensive and easily available synthetic raw materials, innovatively uses chiral 2-amino-2-aryl acetate as a starting material, and prepares a rotigotine intermediate with high optical purity by means of chiral induction. Rotigotine is prepared from the intermediate, the reaction conditions are mild, the optical purity of the target compound is high, the experimental operation is simple and safe, the environmental pollution is small, and it is more suitable for industrial production.

A rotigotine-containing patch comprising a support layer and an adhesive layer, wherein the adhesive layer contains at least one selected from the group consisting of rotigotine and pharmaceutically acceptable salts of rotigotine, a rubber-based adhesive base, and an antioxidant, wherein the antioxidant comprises propyl gallate, ascorbyl palmitate, and sodium pyrosulfite.

This invention relates to a transdermal therapeutic system (TTS) for the administration of the active ingredient rotigotine and its preparation method. The transdermal therapeutic system (TTS) comprises a matrix layer containing: rotigotine; one or more non-amine-resistant silicone adhesives in an amount greater than 50% by weight, based on the total weight of the pressure-sensitive adhesives in the matrix layer; and paraffin. The transdermal therapeutic system according to the invention is particularly suitable for the treatment of Parkinson's disease.

The invention discloses a rotigotine lyotropic liquid crystal precursor solution as well as a preparation method and application thereof, and belongs to the field of pharmaceutical preparations, the rotigotine lyotropic liquid crystal precursor solution comprises the following components: phospholipid, grease, a release regulator, an organic solvent and rotigotine or pharmaceutically acceptable salt thereof, the organic solvent accounts for 10-40% of the mass of the precursor, and the rotigotine or pharmaceutically acceptable salt thereof accounts for 1-30% of the mass of the precursor. The rotigotine lyotropic liquid crystal precursor solution is low in viscosity and easy to inject, lyotropic liquid crystal gel can be formed when the rotigotine lyotropic liquid crystal precursor solution encounters body fluid after injection, and the gel wraps a medicine to be slowly released, so that the rotigotine lyotropic liquid crystal precursor solution has a good slow-release effect, the medication frequency can be reduced, and the compliance of a patient is improved; the auxiliary materials are good in biocompatibility, and do not easily cause inflammatory response of the organism; the production cost is low, and the preparation method is simple and easy to industrialize. The invention can be used for auxiliary treatment of early primary Parkinson's disease and late primary Parkinson's disease.

The invention discloses a method for synthesizing rotigotine hydrochloride, which is characterized in that (S)-2-amino-5-methoxyl tetrahydronaphthalene hydrochloride is used as a raw material, and the rotigotine hydrochloride is obtained through a one-pot acylation reaction, a reduction reaction and a demethylation reaction. The synthetic route is as follows: # imgabs0 #. The synthetic method comprises the following steps: step 1, taking (S)-2-amino-5-methoxy tetrahydronaphthalene hydrochloride as a raw material, and carrying out one-pot acylation reaction to obtain an intermediate I; step 2, carrying out reduction reaction on the intermediate I to obtain an intermediate II; 3, the intermediate II is subjected to a demethylation reaction, and the rotigotine hydrochloride is obtained. The method is mild in reaction condition, simple and convenient to operate, high in yield, high in product purity (greater than 99.8%) and suitable for industrial production.

In the transdermal preparation and its manufacturing method according to the present invention, the transdermal preparation comprises a drug-containing adhesive layer containing rotigotine or a pharmaceutically acceptable salt thereof as an active ingredient; hydroxypropyl cellulose (HPC) as a crystallization inhibitor; and a silicone polymer adhesive.

The present application provides the anti-multiple myeloma activity and application of rotigotine. Experimental results show that rotigotine is relocated to the Tudor domain of the polycomb-like protein family PHF19 protein, and PHF19 is a significant marker of multiple myeloma. Rotigotine has good selectivity to non-polycomb-like proteins, effectively inhibits the viability of multiple myeloma cells MM1.S, and inhibits tumor growth in tumor-bearing mice, showing that rotigotine can become an anti-multiple myeloma drug.

The preparation method comprises the following steps: (1) mixing citric acid-L-carnitine ionic liquid, acrylic acid, methacrylic acid N, N-dimethylaminoethyl ester and a photoinitiator to obtain a pre-polymerized mixed solution, and then adding rotigotine medicine powder to obtain a medicine-carrying ionic gel pre-polymerized solution; and (2) injecting the drug-loaded ionic gel prepolymerization liquid into a microneedle mold, covering the surface of the drug-loaded ionic gel prepolymerization liquid with a PDMS friction layer subjected to oxygen plasma treatment, and performing curing demolding to obtain a PDMS upper layer and a rotigotine-loaded ionic gel microneedle lower layer, thereby obtaining the rotigotine-loaded triboelectric microneedle patch. The patch prepared by the preparation method disclosed by the invention has good flexible fitting property and biological safety, self-powered driving can be realized by virtue of self tremor of a Parkinson's disease patient, controllable transdermal delivery of rotigotine is promoted, and the treatment effect of the Parkinson's disease is improved.

The invention relates to a stable rotigotine transdermal drug delivery kit. More specifically, the present invention relates to a transdermal drug delivery kit containing rotigotine or a pharmaceutically acceptable salt thereof, and a preparation method and use thereof, and the transdermal drug delivery kit maintains the content of related substances such as oxide impurities in a transdermal patch at an extremely low level.

The present invention relates to a method for stabilizing rotigotine, comprising stabilizing rotigotine and / or a pharmaceutically acceptable salt thereof in a rotigotine-containing patch comprising a support layer and an adhesive layer, wherein the adhesive layer contains rotigotine and / or a pharmaceutically acceptable salt thereof and a styrene-based thermoplastic elastomer, wherein the adhesive layer further contains cross-linked polyvinyl pyrrolidone so that the content in the adhesive layer is 3 to 25% by mass.