# US 7,611,730 B2 · Tramadol-based medicament > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,611,730 B2 - Document ID: US7611730B2 - Status: Granted - Kind: B2 - Application number: 10/641,779 - Filed: 2003-08-15 - Published: 2004-04-22 - Granted: 2009-11-03 - Earliest claimed: 2001-02-21 - Assignees: GrüNenthal GmbH - Inventors: Johannes Bartholomäus; Elmar Josef Friderichs - Web page: https://patentgrep.com/patent/US7611730B2 ## CPC - A61K 9/5084: {Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs (tablets containing such a mixture A61K9/2077)} - A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)} - A61K 9/209: {containing drug in at least two layers or in the core and in at least one outer layer} - A61K 9/5047: {Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose} - A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)} - A61P 1/12: Antidiarrhoeals - A61P 11/14: Antitussive agents - A61P 13/10: of the bladder - A61P 25/00: Drugs for disorders of the nervous system - A61P 25/04: Centrally acting analgesics, e.g. opioids - A61P 25/24: Antidepressants - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The invention relates to a medicament containing the racemate of tramadol in a retarded form and the (+)-enantiomer of tramadol in a non-retarded form. ## Claims ### Claim 1 A medicament comprising (a) the racemate of tramadol or a physiologically tolerated salt thereof in slow-release form and (b) the (+) enantiomer of tramadol or a physiologically tolerated salt thereof in immediate-release form. ### Claim 2 (depends on 1) The medicament as claimed in claim 1, wherein at least one of the racemate or (+) enantiomer is present in the form of a physiologically tolerated salt. ### Claim 3 (depends on 2) The medicament as claimed in claim 2, wherein the physiologically tolerated salt is selected from the group consisting of chloride, bromide, sulfate, sulfonate, phosphate, tartrate, teoclate, embonate, formate, acetate, propionate, benzoate, oxalate, succinate, citrate, diclofenacate, naproxenate, salicylate, acetyl-salicylate, glutamate, fumarate, aspartate, glutarate, stearate, butyrate, malonate, lactate, mesylate, saccharinate, cyclamate and acesulfamate. ### Claim 4 (depends on 1) The medicament as claimed in claim 1, which comprises from 10 to 75% by weight of (+)-tramadol and from 90 to 25% by weight of slow-release racemic tramadol, calculated as free active ingredient and based on the total amount of active ingredients. ### Claim 5 (depends on 1) The medicament as claimed in claim 1, which is in a form suitable for oral or parenteral administration. ### Claim 6 (depends on 1) The medicament as claimed in claim 1, which comprises the racemate and (+) enantiomer in separately formulated subunits. ### Claim 7 (depends on 6) The medicament as claimed in claim 6, wherein the subunits are different layers of a multilayer tablet. ### Claim 8 (depends on 6) The medicament as claimed in claim 6, wherein the subunits are present in multiparticulate form. ### Claim 9 (depends on 7) The medicament as claimed in claim 7, which comprises the racemate in slow-release subunits that are provided with a coating containing the (+) enantiomer. ### Claim 10 (depends on 1) The medicament as claimed in claim 1, wherein the slow release form comprises at least one of the racemate coated by a release-slowing coating, embedded in a release-slowing matrix, or attached to an ion-exchange resin. ### Claim 11 (depends on 10) The medicament as claimed in claim 10, which comprises a release-slowing coating based on one or more components selected from the group consisting of water-insoluble optionally modified natural or synthetic polymers and natural, semisynthetic or synthetic waxes or fats or fatty alcohols. ### Claim 12 (depends on 11) The medicament as claimed in claim 11, wherein the release-slowing coating is based on water-insoluble polymers, and the water-insoluble polymers are poly(meth)acrylates and/or copolymers thereof. ### Claim 13 (depends on 11) The medicament as claimed in claim 11, wherein the release-slowing coating is based on water-insoluble polymers, and the water-insoluble polymers are cellulose derivatives. ### Claim 14 (depends on 12) The medicament as claimed in claim 12, wherein the release-slowing coating is based on polymers that have been applied from aqueous medium. ### Claim 15 (depends on 11) The medicament as claimed in claim 11, wherein the release-slowing coating is based on a mixture of polyvinyl acetate and polyvinylpyrrolidone. ### Claim 16 (depends on 11) The medicament as claimed in claim 11, wherein the release-slowing coating is based on a wax, and the wax comprises one or more members selected from the group consisting of carnauba wax, beeswax, glycerol monostearate, glycerol monobehenate, glycerol ditripalmitostearate, and microcrystalline wax. ### Claim 17 (depends on 11) The medicament as claimed in claim 11, wherein the release-slowing coating comprises one or more polymers in combination with at least one plasticizer. ### Claim 18 (depends on 17) The medicament as claimed in claim 17, wherein the plasticizers are selected from the group consisting of lipophilic diesters of C6-40 aliphatic or aromatic dicarboxylic acids and C1-8 aliphatic alcohols, hydrophilic or lipophilic esters of citric acid, polyalkylene glycols, esters of glycerol, acetylated mono- and/or diglycerides, medium chain-length triglycerides, and oleic acid. ### Claim 19 (depends on 17) The medicament as claimed in claim 17, wherein the plasticizer is employed in an amount ranging from 5 to 50% by weight based on the weight of polymers in the release-slowing coating. ### Claim 20 (depends on 10) The medicament as claimed in claim 10, which comprises a release-slowing matrix based on a hydrophilic matrix material. ### Claim 21 (depends on 10) The medicament as claimed in claim 10, which comprises a release-slowing matrix based on a hydrophobic matrix material. ### Claim 22 (depends on 1) The medicament as claimed in claim 1, which comprises at least one protective coating. ### Claim 23 (depends on 22) The medicament as claimed in claim 22, wherein the protective coating improves the taste of the medicament. ### Claim 24 (depends on 22) The medicament as claimed in claim 22, wherein the protective coating is resistant to gastric fluid. ### Claim 25 (depends on 24) The medicament as claimed in claim 24, wherein the protective coating resistant to gastric fluid consists of one or more components selected from the group consisting of methacrylic acid/methyl methacrylate copolymers with a monomer molar ratio of 1:1, methacrylic acid/methyl methacrylate copolymers with a monomer molar ratio of 1:2, methacrylic acid/ethyl acrylate copolymers with a monomer molar ratio of 1:1,methacrylic acid/methyl acrylate/methyl methacrylate copolymers with a monomer molar ratio of 7:3:1, shellac, hydroxypropylmethylcellulose acetate succinate, and cellulose acetate phthalate, optionally in combination with poly(meth)acrylates. ### Claim 26 (depends on 1) A method of controlling pain comprising administering to a patient in need thereof an effective pain controlling amount of the medicament of claim 1. ### Claim 27 (depends on 26) The method of claim 26, where the pain is acute pain. ### Claim 28 (depends on 26) The method of claim 26, where the pain is chronic pain. ### Claim 29 (depends on 1) A method of treating urinary incontinence comprising administering to a patient in need thereof an effective amount therefor of the medicament of claim 1. ### Claim 30 (depends on 1) A method of treating cough comprising administering to a patient in need thereof an effective amount therefor of the medicament of claim 1. ### Claim 31 (depends on 1) A method of treating depression comprising administering to a patient in need thereof an effective amount therefor of the medicament of claim 1. ### Claim 32 (depends on 1) A method of treating diarrhea comprising administering to a patient in need thereof an effective amount therefor of the medicament of claim 1. ### Claim 33 (depends on 1) A method of treating mental disorders comprising administering to a patient in need thereof an effective amount therefor of the medicament of claim 1. ### Claim 34 (depends on 10) The medicament of claim 10, where the release-slowing coating is selected from water insoluble polymer, waxes or combinations thereof, where the water insoluble polymer is an ethyl acetate/methyl methacrylate copolymer with a monomer molar ratio of 2:1, and the wax is Carnuba wax. ### Claim 35 (depends on 34) The medicament of claim 34, where the water-insoluble polymer is plasticized by dibutyl sebacate plasticizer. ### Claim 36 (depends on 35) The medicament of claim 35, further comprising a non-slow release coating where the non-slow release coating is methacrylic acid/methyl methacrylate copolymer with a monomer molar ratio of 1:1. ### Claim 37 (depends on 3) The medicament of claim 3, where the physiologically tolerated salt is selected from the group consisting of chloride, sulfate, saccharinate, teoclate, embonate, diclofenacate, naproxenate and salicylate. ### Claim 38 (depends on 3) The medicament of claim 3, where the physiologically tolerated salt is chloride. ### Claim 39 (depends on 4) The medicament of claim 4, which comprises from 20 to 50% by weight of (+)-tramadol and from 80 to 50% by weight of slow-release racemic tramadol, calculated as free active ingredient and based on the total amount of active ingredients. ### Claim 40 (depends on 11) The medicament as claimed in claim 11, where the water-insoluble polymers are alkylcelluloses. ### Claim 41 (depends on 11) The medicament as claimed in claim 11, where the water-insoluble polymer is cellulose acetate. ### Claim 42 (depends on 17) The medicament as claimed in claim 17, where the plasticizer is present in amounts of from 10 to 30% by weight of the polymers in the release-slowing coating. ### Claim 43 (depends on 5) The medicament as claimed in claim 5, which is in a form suitable for oral administration. ### Claim 44 (depends on 7) The medicament as claimed in claim 7, wherein the subunits are different layers of a bilayer tablet. ### Claim 45 (depends on 8) The medicament as claimed in claim 8, wherein the subunits are present in a multiparticulate form selected from the group consisting of microtablets, microcapsules, granules, active ingredient crystals and pellets. ### Claim 46 (depends on 12) The medicament as claimed in claim 12, wherein the water-insoluble polymers are one or more members selected from the group consisting of poly(C1-4)-alkyl (meth)acrylates, poly(C1-4)dialkylamino-(C1-4)-alkyl (meth)acrylates and copolymers thereof. ### Claim 47 (depends on 46) The medicament as claimed in claim 46, wherein the water-insoluble polymers are one or more members selected from the group consisting of ethyl acrylate/methyl methacrylate copolymers with a monomer molar ratio of 2:1, and ethyl acrylate/methyl methacrylate/trimethylammoniumethyl methacrylate chloride copolymers with a monomer molar ratio of 1:2:0.1, ethyl acrylate/methyl methacrylate/trimethylammoniumethyl methacrylate chloride copolymers with a monomer molar ratio of 1:2:0.2. ### Claim 48 (depends on 14) The medicament as claimed in claim 14, wherein the polymers have been applied from aqueous latex or pseudolatex dispersions. ### Claim 49 (depends on 20) The medicament as claimed in claim 20, wherein the hydrophilic matrix material comprises one or more hydrophilic polymers. ### Claim 50 (depends on 49) The medicament as claimed in claim 49, wherein the one or more hydrophilic polymers are selected from the group consisting of cellulose ethers, cellulose esters and acrylic resins. ### Claim 51 (depends on 50) The medicament as claimed in claim 50, wherein the one or more hydrophilic polymers are selected from the group consisting of ethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydoxymethylcellulose cellulose and poly(meth)acrylic acid and salts, amides and esters thereof. ### Claim 52 (depends on 21) The medicament as claimed in claim 21, wherein the hydrophobic matrix material comprises one or more members selected from the group consisting of hydrophobic polymers, waxes, fats, long-chain fatty acids, fatty alcohols and esters, ethers and mixtures thereof. ### Claim 53 (depends on 52) The medicament as claimed in claim 52, wherein the hydrophobic matrix material comprises one or more members selected from the group consisting of mono- or diglycerides of C12-C30 fatty acids, C12-C30 fatty alcohols and waxes.