JP2012021025A - Composition comprising meloxicam - Google Patents
Composition comprising meloxicam Download PDFInfo
- Publication number
- JP2012021025A JP2012021025A JP2011222068A JP2011222068A JP2012021025A JP 2012021025 A JP2012021025 A JP 2012021025A JP 2011222068 A JP2011222068 A JP 2011222068A JP 2011222068 A JP2011222068 A JP 2011222068A JP 2012021025 A JP2012021025 A JP 2012021025A
- Authority
- JP
- Japan
- Prior art keywords
- pain
- meloxicam
- pharmaceutical composition
- magnesium
- active compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 title claims abstract description 69
- 229960001929 meloxicam Drugs 0.000 title claims abstract description 67
- 239000000203 mixture Substances 0.000 title description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 41
- 239000000932 sedative agent Substances 0.000 claims abstract description 41
- 150000001875 compounds Chemical class 0.000 claims abstract description 36
- 229940069428 antacid Drugs 0.000 claims abstract description 33
- 239000003159 antacid agent Substances 0.000 claims abstract description 33
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 230000001754 anti-pyretic effect Effects 0.000 claims abstract description 12
- 229940125723 sedative agent Drugs 0.000 claims abstract description 12
- 239000002269 analeptic agent Substances 0.000 claims abstract description 10
- 230000000202 analgesic effect Effects 0.000 claims abstract description 10
- 208000002193 Pain Diseases 0.000 claims description 33
- 239000002552 dosage form Substances 0.000 claims description 33
- 230000001624 sedative effect Effects 0.000 claims description 29
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 21
- 230000001458 anti-acid effect Effects 0.000 claims description 18
- 208000006820 Arthralgia Diseases 0.000 claims description 15
- 206010019233 Headaches Diseases 0.000 claims description 15
- 206010068319 Oropharyngeal pain Diseases 0.000 claims description 15
- 201000007100 Pharyngitis Diseases 0.000 claims description 15
- 206010037660 Pyrexia Diseases 0.000 claims description 15
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims description 15
- 231100000869 headache Toxicity 0.000 claims description 15
- 208000000112 Myalgia Diseases 0.000 claims description 14
- 208000013465 muscle pain Diseases 0.000 claims description 14
- KSUUMAWCGDNLFK-UHFFFAOYSA-N apronal Chemical compound C=CCC(C(C)C)C(=O)NC(N)=O KSUUMAWCGDNLFK-UHFFFAOYSA-N 0.000 claims description 13
- 229960004459 apronal Drugs 0.000 claims description 13
- 208000024891 symptom Diseases 0.000 claims description 13
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 12
- 229960001948 caffeine Drugs 0.000 claims description 12
- 208000027866 inflammatory disease Diseases 0.000 claims description 12
- 239000000654 additive Substances 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 229940024546 aluminum hydroxide gel Drugs 0.000 claims description 10
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 claims description 9
- 208000008035 Back Pain Diseases 0.000 claims description 8
- 208000034656 Contusions Diseases 0.000 claims description 8
- 208000005171 Dysmenorrhea Diseases 0.000 claims description 8
- 206010014020 Ear pain Diseases 0.000 claims description 8
- 206010072132 Fracture pain Diseases 0.000 claims description 8
- 206010024453 Ligament sprain Diseases 0.000 claims description 8
- 208000010040 Sprains and Strains Diseases 0.000 claims description 8
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 230000009519 contusion Effects 0.000 claims description 8
- 238000000605 extraction Methods 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 208000004296 neuralgia Diseases 0.000 claims description 8
- 239000000021 stimulant Substances 0.000 claims description 8
- 208000004371 toothache Diseases 0.000 claims description 8
- 206010052904 Musculoskeletal stiffness Diseases 0.000 claims description 7
- 208000008930 Low Back Pain Diseases 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 claims description 6
- 229940023964 caffeine and sodium benzoate Drugs 0.000 claims description 6
- JAUGGEIKQIHSMF-UHFFFAOYSA-N dialuminum;dimagnesium;dioxido(oxo)silane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O JAUGGEIKQIHSMF-UHFFFAOYSA-N 0.000 claims description 6
- 229960002449 glycine Drugs 0.000 claims description 6
- 235000013905 glycine and its sodium salt Nutrition 0.000 claims description 6
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 6
- 239000000347 magnesium hydroxide Substances 0.000 claims description 6
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 6
- 239000000395 magnesium oxide Substances 0.000 claims description 6
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 6
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 6
- JWBPVFVNISJVEM-UHFFFAOYSA-M sodium caffeine benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1.CN1C(=O)N(C)C(=O)C2=C1N=CN2C JWBPVFVNISJVEM-UHFFFAOYSA-M 0.000 claims description 6
- CMCCHHWTTBEZNM-UHFFFAOYSA-N 2-bromo-N-carbamoyl-3-methylbutanamide Chemical compound CC(C)C(Br)C(=O)NC(N)=O CMCCHHWTTBEZNM-UHFFFAOYSA-N 0.000 claims description 5
- UTUUIUQHGDRVPU-UHFFFAOYSA-K aluminum;2-aminoacetate;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Al+3].NCC([O-])=O UTUUIUQHGDRVPU-UHFFFAOYSA-K 0.000 claims description 5
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 claims description 5
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 229960001545 hydrotalcite Drugs 0.000 claims description 5
- 229910001701 hydrotalcite Inorganic materials 0.000 claims description 5
- 208000014674 injury Diseases 0.000 claims description 5
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 5
- 239000001095 magnesium carbonate Substances 0.000 claims description 5
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 5
- 239000008203 oral pharmaceutical composition Substances 0.000 claims description 5
- 230000001603 reducing effect Effects 0.000 claims description 5
- 230000008733 trauma Effects 0.000 claims description 5
- PCRDIRUKXOTDNN-UHFFFAOYSA-K aluminum;sodium;carbonate;hydroxide Chemical compound [OH-].[Na+].[Al+3].[O-]C([O-])=O PCRDIRUKXOTDNN-UHFFFAOYSA-K 0.000 claims description 4
- 239000002221 antipyretic Substances 0.000 claims description 4
- 235000019739 Dicalciumphosphate Nutrition 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 3
- HZVVJJIYJKGMFL-UHFFFAOYSA-N almasilate Chemical compound O.[Mg+2].[Al+3].[Al+3].O[Si](O)=O.O[Si](O)=O HZVVJJIYJKGMFL-UHFFFAOYSA-N 0.000 claims description 3
- LFKUIHYBSGTRNF-UHFFFAOYSA-K aluminum magnesium potassium hydroxide sulfate Chemical compound [Al+3].S(=O)(=O)([O-])[O-].[K+].[OH-].[Mg+2] LFKUIHYBSGTRNF-UHFFFAOYSA-K 0.000 claims description 3
- LHPJBAIYHPWIOT-UHFFFAOYSA-K aluminum;magnesium;carbonate;hydroxide Chemical compound [OH-].[Mg+2].[Al+3].[O-]C([O-])=O LHPJBAIYHPWIOT-UHFFFAOYSA-K 0.000 claims description 3
- 239000001506 calcium phosphate Substances 0.000 claims description 3
- 229940038472 dicalcium phosphate Drugs 0.000 claims description 3
- 229910000390 dicalcium phosphate Inorganic materials 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- ZADYMNAVLSWLEQ-UHFFFAOYSA-N magnesium;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[Mg+2].[Si+4] ZADYMNAVLSWLEQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000008183 oral pharmaceutical preparation Substances 0.000 claims description 3
- 229940088417 precipitated calcium carbonate Drugs 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- 230000000472 traumatic effect Effects 0.000 claims description 3
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- CNYNTXVCKHBXHP-UHFFFAOYSA-I [OH-].[Mg+2].[Al+3].[Ca+2].[O-]C([O-])=O.[O-]C([O-])=O Chemical compound [OH-].[Mg+2].[Al+3].[Ca+2].[O-]C([O-])=O.[O-]C([O-])=O CNYNTXVCKHBXHP-UHFFFAOYSA-I 0.000 claims description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 2
- RJZNFXWQRHAVBP-UHFFFAOYSA-I aluminum;magnesium;pentahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Al+3] RJZNFXWQRHAVBP-UHFFFAOYSA-I 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 229960000816 magnesium hydroxide Drugs 0.000 claims description 2
- 235000012254 magnesium hydroxide Nutrition 0.000 claims description 2
- 210000003205 muscle Anatomy 0.000 claims description 2
- 239000002244 precipitate Substances 0.000 claims 3
- 230000033444 hydroxylation Effects 0.000 claims 1
- 238000005805 hydroxylation reaction Methods 0.000 claims 1
- 201000009240 nasopharyngitis Diseases 0.000 claims 1
- UNSYHJWOORERTF-UHFFFAOYSA-J sodium dicarboxyoxyalumanyl hydrogen carbonate hydrogen carbonate Chemical compound [Na+].[Al+3].OC([O-])=O.OC([O-])=O.OC([O-])=O.OC([O-])=O UNSYHJWOORERTF-UHFFFAOYSA-J 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 6
- 239000008187 granular material Substances 0.000 description 45
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 32
- 239000004615 ingredient Substances 0.000 description 30
- 239000003826 tablet Substances 0.000 description 26
- 239000010410 layer Substances 0.000 description 21
- 239000002245 particle Substances 0.000 description 21
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 20
- 239000008108 microcrystalline cellulose Substances 0.000 description 20
- 229940016286 microcrystalline cellulose Drugs 0.000 description 20
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 20
- 239000002775 capsule Substances 0.000 description 19
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 17
- 239000008101 lactose Substances 0.000 description 17
- 238000007796 conventional method Methods 0.000 description 16
- 235000019359 magnesium stearate Nutrition 0.000 description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 15
- 239000000454 talc Substances 0.000 description 15
- 229910052623 talc Inorganic materials 0.000 description 15
- 235000012222 talc Nutrition 0.000 description 15
- 239000011247 coating layer Substances 0.000 description 13
- 229920002261 Corn starch Polymers 0.000 description 11
- -1 analgesic Chemical compound 0.000 description 11
- 239000008120 corn starch Substances 0.000 description 11
- 229940099112 cornstarch Drugs 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 229940111134 coxibs Drugs 0.000 description 10
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 10
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 10
- 235000012239 silicon dioxide Nutrition 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 8
- 230000004054 inflammatory process Effects 0.000 description 8
- 239000011248 coating agent Substances 0.000 description 7
- 239000007941 film coated tablet Substances 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 6
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 6
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 6
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 239000000194 fatty acid Substances 0.000 description 6
- 229930195729 fatty acid Natural products 0.000 description 6
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 5
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 5
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 239000001530 fumaric acid Substances 0.000 description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 3
- 108010011485 Aspartame Proteins 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 239000001856 Ethyl cellulose Substances 0.000 description 3
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 3
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 3
- 235000010358 acesulfame potassium Nutrition 0.000 description 3
- 229960004998 acesulfame potassium Drugs 0.000 description 3
- 239000000619 acesulfame-K Substances 0.000 description 3
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 239000000605 aspartame Substances 0.000 description 3
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 3
- 235000010357 aspartame Nutrition 0.000 description 3
- 229960003438 aspartame Drugs 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 3
- 229950008138 carmellose Drugs 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 235000019325 ethyl cellulose Nutrition 0.000 description 3
- 229920001249 ethyl cellulose Polymers 0.000 description 3
- 229960002202 lornoxicam Drugs 0.000 description 3
- OXROWJKCGCOJDO-JLHYYAGUSA-N lornoxicam Chemical compound O=C1C=2SC(Cl)=CC=2S(=O)(=O)N(C)\C1=C(\O)NC1=CC=CC=N1 OXROWJKCGCOJDO-JLHYYAGUSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000006186 oral dosage form Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000002831 pharmacologic agent Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 206010000087 Abdominal pain upper Diseases 0.000 description 2
- 229940124638 COX inhibitor Drugs 0.000 description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 2
- 108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 229940125716 antipyretic agent Drugs 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
- 239000007894 caplet Substances 0.000 description 2
- 230000001079 digestive effect Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 210000004211 gastric acid Anatomy 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 229940031702 hydroxypropyl methylcellulose 2208 Drugs 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 2
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 239000000820 nonprescription drug Substances 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 2
- 229960002702 piroxicam Drugs 0.000 description 2
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 208000018556 stomach disease Diseases 0.000 description 2
- 229960002871 tenoxicam Drugs 0.000 description 2
- LZNWYQJJBLGYLT-UHFFFAOYSA-N tenoxicam Chemical compound OC=1C=2SC=CC=2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 LZNWYQJJBLGYLT-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- PSIREIZGKQBEEO-UHFFFAOYSA-N 2-(1h-benzimidazol-2-ylsulfinylmethyl)-n-methyl-n-(2-methylpropyl)aniline Chemical compound CC(C)CN(C)C1=CC=CC=C1CS(=O)C1=NC2=CC=CC=C2N1 PSIREIZGKQBEEO-UHFFFAOYSA-N 0.000 description 1
- ZGDLVKWIZHHWIR-UHFFFAOYSA-N 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]morpholine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N2CCOCC2)N=C1 ZGDLVKWIZHHWIR-UHFFFAOYSA-N 0.000 description 1
- 229940124125 5 Lipoxygenase inhibitor Drugs 0.000 description 1
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- LCXSRQGYOFKPSF-UHFFFAOYSA-N BrC(C(=O)NC(=O)N)C(C)C.BrCCCCC(=O)NC(=O)N Chemical compound BrC(C(=O)NC(=O)N)C(C)C.BrCCCCC(=O)NC(=O)N LCXSRQGYOFKPSF-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229940122957 Histamine H2 receptor antagonist Drugs 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- KMZQAVXSMUKBPD-DJWKRKHSSA-N Lafutidine Chemical compound C=1C=COC=1C[S+]([O-])CC(=O)NC\C=C/COC(N=CC=1)=CC=1CN1CCCCC1 KMZQAVXSMUKBPD-DJWKRKHSSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 229940123921 Nitric oxide synthase inhibitor Drugs 0.000 description 1
- AQLLBJAXUCIJSR-UHFFFAOYSA-N OC(=O)C[Na] Chemical compound OC(=O)C[Na] AQLLBJAXUCIJSR-UHFFFAOYSA-N 0.000 description 1
- IQPSEEYGBUAQFF-UHFFFAOYSA-N Pantoprazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-UHFFFAOYSA-N 0.000 description 1
- DYWNLSQWJMTVGJ-KUSKTZOESA-N Phenylpropanolamine hydrochloride Chemical compound Cl.C[C@H](N)[C@H](O)C1=CC=CC=C1 DYWNLSQWJMTVGJ-KUSKTZOESA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Chemical class 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- QJLYKBIVMWMIDH-UHFFFAOYSA-N [Ca].CN1C(=O)N(C)C(=O)C2=C1N=CN2C Chemical compound [Ca].CN1C(=O)N(C)C(=O)C2=C1N=CN2C QJLYKBIVMWMIDH-UHFFFAOYSA-N 0.000 description 1
- 239000003082 abrasive agent Substances 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- WJGAPUXHSQQWQF-UHFFFAOYSA-N acetic acid;hydrochloride Chemical compound Cl.CC(O)=O WJGAPUXHSQQWQF-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229940024545 aluminum hydroxide Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000002216 antistatic agent Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- LCHGOKZNRDAXEK-UHFFFAOYSA-N caffeine monohydrate Chemical compound O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C LCHGOKZNRDAXEK-UHFFFAOYSA-N 0.000 description 1
- HHSPVTKDOHQBKF-UHFFFAOYSA-J calcium;magnesium;dicarbonate Chemical compound [Mg+2].[Ca+2].[O-]C([O-])=O.[O-]C([O-])=O HHSPVTKDOHQBKF-UHFFFAOYSA-J 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 239000007931 coated granule Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- WHWZLSFABNNENI-UHFFFAOYSA-N epinastine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 WHWZLSFABNNENI-UHFFFAOYSA-N 0.000 description 1
- 229960002548 epinastine hydrochloride Drugs 0.000 description 1
- 229960004667 ethyl cellulose Drugs 0.000 description 1
- 229960001596 famotidine Drugs 0.000 description 1
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 229960003303 lafutidine Drugs 0.000 description 1
- 229960003174 lansoprazole Drugs 0.000 description 1
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 description 1
- 229950007395 leminoprazole Drugs 0.000 description 1
- 229940126065 leukotriene A4 hydrolase inhibitor Drugs 0.000 description 1
- 239000003913 leukotriene B4 receptor antagonist Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000000236 nitric oxide synthase inhibitor Substances 0.000 description 1
- 229960004872 nizatidine Drugs 0.000 description 1
- SGXXNSQHWDMGGP-IZZDOVSWSA-N nizatidine Chemical compound [O-][N+](=O)\C=C(/NC)NCCSCC1=CSC(CN(C)C)=N1 SGXXNSQHWDMGGP-IZZDOVSWSA-N 0.000 description 1
- 229960000381 omeprazole Drugs 0.000 description 1
- 239000000014 opioid analgesic Substances 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229960004048 pantoprazole sodium Drugs 0.000 description 1
- 229960002305 phenylpropanolamine hydrochloride Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- FFNMBRCFFADNAO-UHFFFAOYSA-N pirenzepine hydrochloride Chemical compound [H+].[H+].[Cl-].[Cl-].C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 FFNMBRCFFADNAO-UHFFFAOYSA-N 0.000 description 1
- 229960000293 pirenzepine hydrochloride Drugs 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical class [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 229960001778 rabeprazole sodium Drugs 0.000 description 1
- 229960001520 ranitidine hydrochloride Drugs 0.000 description 1
- GGWBHVILAJZWKJ-KJEVSKRMSA-N ranitidine hydrochloride Chemical compound [H+].[Cl-].[O-][N+](=O)\C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 GGWBHVILAJZWKJ-KJEVSKRMSA-N 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/541—Non-condensed thiazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/08—Oxides; Hydroxides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/10—Carbonates; Bicarbonates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/12—Magnesium silicate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/04—Drugs for disorders of the respiratory system for throat disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Inorganic Chemistry (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pulmonology (AREA)
- Psychiatry (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Otolaryngology (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
本発明は、メロキシカム又はその医薬的に許容される塩、及び制酸薬、鎮静薬及び中枢神経興奮薬からなる群から選択される少なくとも第二の医薬活性化合物に関する。さらに本発明は、そのような組成物を含む経口医薬製剤形態に関する。本発明のさらなる目的は、この組成物及びこの経口医薬製剤形態の使用に関する。さらに本発明は、そのような経口医薬製剤形態を製造するための、メロキシカム、及び制酸薬、鎮静薬及び中枢神経興奮薬からなる群から選択される少なくとも第二の医薬活性化合物の使用に関する。さらに本発明は、炎症性疾患、炎症性疾患の症状、頭痛、歯痛、抜歯後の痛み、咽頭痛、耳痛、関節痛、神経痛、腰痛、筋肉痛、肩の筋肉の凝り、挫傷の痛み、骨折の痛み、捻挫の痛み、月経痛、外傷痛、悪寒、発熱反応、及び/又は風邪、及び咽頭痛、悪寒、発熱、頭痛、関節痛及び筋肉痛などの風邪の種々の症状を治療又は軽減する方法に関する。 The present invention relates to meloxicam or a pharmaceutically acceptable salt thereof and at least a second pharmaceutically active compound selected from the group consisting of antacids, sedatives and central nervous stimulants. The present invention further relates to oral pharmaceutical dosage forms comprising such compositions. A further object of the present invention relates to the use of this composition and this oral pharmaceutical dosage form. The invention further relates to the use of meloxicam and at least a second pharmaceutically active compound selected from the group consisting of antacids, sedatives and central nervous stimulants for the manufacture of such oral pharmaceutical dosage forms. Furthermore, the present invention is an inflammatory disease, a symptom of inflammatory disease, headache, toothache, pain after extraction, sore throat, ear pain, joint pain, neuralgia, back pain, muscle pain, shoulder muscle stiffness, contusion pain, Treat or treat various symptoms of cold such as fracture pain, sprain pain, menstrual pain, trauma pain, chills, fever reaction, and / or cold, and sore throat, chills, fever, headache, joint pain and muscle pain It relates to the mitigation method.
非ステロイド系抗炎症薬（NSAIDs）は、種々の疾患を有する多くの患者を治療するために、古くから広い範囲の治療に用いられている薬剤種である。既存のNSAIDsは、非特異的にシクロオキシゲナーゼ（COX）を阻害するCOX阻害薬であり、プロスタグランジン（PG）をアラキドン酸から生合成するための律速酵素である。COXの阻害は、PGE2の製造を阻害することにより、抗炎症性、鎮痛性及び解熱性効果を与えるが、他方で、消化疾患及び腎疾患などの薬剤副作用も引き起こす。ちなみに、COXは2種類の異性体、すなわちCOX-1及びCOX-2を含む。COX-1は、胃及び腎臓などほとんどの臓器で恒常的に生成されている（ある量の蛋白質は、増殖又は環境変化に関わらず生成されている）。さらに、COX-2は、炎症部における種々の炎症媒介物又は内毒素によって誘導されることが明らかとなった。 Non-steroidal anti-inflammatory drugs (NSAIDs) are a type of drug that has long been used for a wide range of treatments to treat many patients with various diseases. Existing NSAIDs are COX inhibitors that non-specifically inhibit cyclooxygenase (COX), and are rate-limiting enzymes for biosynthesis of prostaglandins (PG) from arachidonic acid. Inhibition of COX provides anti-inflammatory, analgesic and antipyretic effects by inhibiting the production of PGE 2 , while also causing drug side effects such as digestive and renal diseases. Incidentally, COX contains two types of isomers, namely COX-1 and COX-2. COX-1 is constitutively produced in most organs such as the stomach and kidney (a certain amount of protein is produced regardless of proliferation or environmental changes). Furthermore, COX-2 was found to be induced by various inflammatory mediators or endotoxins in the inflamed area.
最近開発された選択的COX-2阻害薬であるメロキシカムは、消化管で起こる望ましくない薬剤副作用の危険性を減らし、且つ優れた抗炎症性、鎮痛性及び解熱性効果を有するため、使用が増加している。しかし、選択的COX-2阻害薬は、経口投薬によるいくつかの消化系副作用、例えば胃病及び胃痛をなおも引き起こし得る。従って、抗炎症性、鎮痛性及び解熱性効果を増強し、胃腸疾患などの副作用を軽減することにより、強力な効力発現及び優れた安全性を有する経口医薬組成物が望まれる。 Meloxicam, a recently developed selective COX-2 inhibitor, increases use because it reduces the risk of undesirable drug side effects that occur in the gastrointestinal tract and has excellent anti-inflammatory, analgesic and antipyretic effects is doing. However, selective COX-2 inhibitors can still cause some digestive side effects from oral dosing, such as stomach disease and stomach pain. Therefore, an oral pharmaceutical composition having strong efficacy and excellent safety by enhancing anti-inflammatory, analgesic and antipyretic effects and reducing side effects such as gastrointestinal diseases is desired.
メロキシカムの効力発現を増強する方法として、COX-2阻害薬及びオピオイド鎮痛薬を含む医薬組成物が、国際出願WO 99/13799号明細書に開示されている。モルホリン及びメロキシカムを1:10の割合で組み合せて含む医薬組成物が、その中に開示されている。しかし、オピオイドは望ましくない副作用を引き起こし得るため、そのような組成物は安全性の理由上好ましくない。
偏頭痛の治療及び/又は予防に有効であるとして、選択的COX-2阻害薬及び5HT1B/1D受容体拮抗薬を含む医薬組成物が、国際出願WO 00/25779号明細書に開示されている。
炎症関連疾患の治療に有効であるとして、炎症及び炎症性疾患の治療を誘導する一酸化窒素シンターゼ阻害薬及びCOX-2阻害薬の組み合せが、国際出願WO 99/18960号明細書に開示されている。
炎症及び炎症関連疾患の治療に有効であるとして、COX-2阻害薬及びロイコトリエンB4受容体拮抗薬の組み合せが、国際出願WO 96/41645号明細書に開示されている。
炎症及び炎症関連疾患の治療に有効であるとして、COX-2阻害薬及び5-リポキシゲナーゼ阻害薬の組み合せが、国際出願WO 96/41626号明細書に開示されている。
炎症及び炎症関連疾患の治療に有効であるとして、COX-2阻害薬及びロイコトリエンA4ヒドロラーゼ阻害薬の組み合せを含む組成物が、国際出願WO 96/41625号明細書に開示されている。
鼻炎の治療に有効であるとして、選択的COX-2阻害NSAIDs、及び抗アレルギー薬又は抗ヒスタミン薬を含む医薬組成物が、日本特許出願2001-247481A号明細書の公開公報に開示されている。この出願の例2において、メロキシカム、エピナスチン塩酸塩、フェニルプロパノールアミン塩酸塩、及びリゾチーム塩化物を含む錠剤形態の組成物が開示されている。しかし、その組成物には制酸薬が含まれていない。
制酸薬と組み合せることにより吸収性が促進されたクロルテノキシカム、テノキシカム又はピロキシカムから選択されるオキシカム群の抗炎症薬剤の内服用固形医薬製剤が、日本特許出願2-906528A号明細書に開示されている。しかし、この特許出願で挙げられているクロルテノキシカム（ロルノキシカム）、テノキシカム及びピロキシカムは、全て非特異的にシクロオキシゲナーゼ（COX）を阻害するCOX阻害薬である。選択的COX-2阻害薬であるメロキシカムは、その中に例示されていない。
As a method for enhancing the efficacy of meloxicam, a pharmaceutical composition containing a COX-2 inhibitor and an opioid analgesic is disclosed in International Application WO 99/13799. A pharmaceutical composition comprising morpholine and meloxicam in a 1:10 combination is disclosed therein. However, such compositions are not preferred for safety reasons because opioids can cause undesirable side effects.
A pharmaceutical composition comprising a selective COX-2 inhibitor and a 5HT 1B / 1D receptor antagonist is disclosed in International Application WO 00/25779 as effective for the treatment and / or prevention of migraine. Yes.
A combination of a nitric oxide synthase inhibitor and a COX-2 inhibitor that induces treatment of inflammation and inflammatory diseases as being effective in the treatment of inflammation-related diseases is disclosed in international application WO 99/18960. Yes.
A combination of a COX-2 inhibitor and a leukotriene B4 receptor antagonist is disclosed in International Application WO 96/41645 as being effective in treating inflammation and inflammation-related diseases.
A combination of a COX-2 inhibitor and a 5-lipoxygenase inhibitor is disclosed in International Application WO 96/41626 as being effective for the treatment of inflammation and inflammation-related diseases.
A composition comprising a combination of a COX-2 inhibitor and a leukotriene A4 hydrolase inhibitor as being effective in the treatment of inflammation and inflammation-related diseases is disclosed in international application WO 96/41625.
A pharmaceutical composition containing selective COX-2 inhibitory NSAIDs and an antiallergic agent or antihistamine as disclosed in Japanese Patent Application No. 2001-247481A has been disclosed as effective for treating rhinitis. In Example 2 of this application, a composition in tablet form is disclosed comprising meloxicam, epinastine hydrochloride, phenylpropanolamine hydrochloride, and lysozyme chloride. However, the composition does not contain an antacid.
A solid pharmaceutical preparation for internal use of an anti-inflammatory drug of the oxicam group selected from chlortenoxicam, tenoxicam or piroxicam, whose absorption is promoted by combination with an antacid, is disclosed in Japanese Patent Application No. 2-906528A. ing. However, chlortenoxicam (lornoxicam), tenoxicam and piroxicam listed in this patent application are all COX inhibitors that non-specifically inhibit cyclooxygenase (COX). Meloxicam, a selective COX-2 inhibitor, is not exemplified therein.
本発明の目的は、起こり得る副作用に関するメロキシカムの安全面をさらに改善することである。
本発明の別の目的は、それぞれがメロキシカムを含み且つ改善された抗炎症性、鎮痛性及び解熱性効果を有する医薬組成物及び経口医薬製剤形態を提供することである。
本発明はさらに、改善された有効性及び安全性を有する医薬組成物及び経口医薬製剤形態を提供することを目的とする。
本発明のさらなる目的は、炎症性疾患、頭痛、歯痛、抜歯後の痛み、咽頭痛、耳痛、関節痛、神経痛、腰痛、筋肉痛、肩の筋肉の凝り、挫傷の痛み、骨折の痛み、捻挫の痛み、月経痛、外傷痛、悪寒、発熱反応などの治療又は軽減方法を提供することである。
The object of the present invention is to further improve the safety aspects of meloxicam with respect to possible side effects.
Another object of the present invention is to provide pharmaceutical compositions and oral pharmaceutical dosage forms each comprising meloxicam and having improved anti-inflammatory, analgesic and antipyretic effects.
The present invention further aims to provide pharmaceutical compositions and oral pharmaceutical dosage forms having improved efficacy and safety.
Further objects of the present invention are inflammatory diseases, headache, toothache, post-extraction pain, sore throat, ear pain, joint pain, neuralgia, low back pain, muscle pain, shoulder muscle stiffness, contusion pain, fracture pain, It is to provide a method for treating or alleviating sprain pain, menstrual pain, trauma pain, chills, fever reaction and the like.
本発明は、メロキシカム又はその医薬的に許容される塩、及び制酸薬、鎮静薬及び中枢神経興奮薬からなる群から選択される少なくとも第二の医薬活性化合物を含む新しい医薬組成物に関する。好ましくは、メロキシカム又はその塩は、それ自体で抗炎症性、鎮痛性及び解熱性効果を発揮することのできる有効量で存在する。
本発明の組成物は、メロキシカムの治療効果、例えば鎮痛性、抗炎症性及び解熱性効果を強め、良好な生物学的利用能を提供する。
特に、第二の医薬活性化合物として制酸薬を選ぶことにより、胃病及び胃痛などの経口投薬による消化系副作用の可能性を減らすことができる。本発明の組成物は、優れた安全性を有するため、非処方薬の製造に都合よく好適である。
第二の医薬活性化合物として鎮静薬及び/又は中枢神経興奮薬を選択するときの本発明の利点は、本発明の組成物が、メロキシカムの投薬量を増やす必要なく、鎮痛性、抗炎症性及び解熱性効果などの治療効果を強められることである。従って、改良された有効性及び安全性を有する医薬組成物及び経口医薬製剤形態を提供することができる。従って、本発明の組成物は非処方薬の製造に特に好適である。
The present invention relates to a new pharmaceutical composition comprising meloxicam or a pharmaceutically acceptable salt thereof and at least a second pharmaceutically active compound selected from the group consisting of antacids, sedatives and central nervous stimulants. Preferably, meloxicam or a salt thereof is present in an effective amount capable of exerting anti-inflammatory, analgesic and antipyretic effects by itself.
The compositions of the present invention enhance the therapeutic effects of meloxicam, such as analgesic, anti-inflammatory and antipyretic effects and provide good bioavailability.
In particular, by selecting an antacid as the second pharmaceutically active compound, it is possible to reduce the possibility of digestive system side effects due to oral medication such as stomach disease and stomach pain. Since the composition of the present invention has excellent safety, it is conveniently suitable for the production of non-prescription drugs.
The advantage of the present invention when selecting a sedative and / or central nervous stimulant as the second pharmaceutically active compound is that the composition of the present invention provides analgesic, anti-inflammatory and anti-inflammatory properties without the need to increase meloxicam dosage. The therapeutic effect such as antipyretic effect can be strengthened. Accordingly, pharmaceutical compositions and oral pharmaceutical dosage forms having improved efficacy and safety can be provided. Therefore, the composition of the present invention is particularly suitable for the production of non-prescription drugs.
メロキシカムは、非ステロイド系抗炎症薬（NSAIDs）の酸性エノールカルボキサミド（オキシカム）型に属する既知の選択的COX-2阻害薬である。化合物(4-ヒドロキシ-2-メチル-N-(5-メチル-2-チアゾリル)-2H-1,2-ベンゾチアジン3-カルボキサミド1,1-ジオキサイド)は、欧州特許第0,002,482B1号明細書及び米国特許第4,233,299号明細書に記載されている。
本発明は、メロキシカムそのもの、又はその医薬的に許容される塩のいずれを用いてもよい。メロキシカムの医薬的に許容される塩は、ナトリウム塩、カリウム塩、アンモニウム塩、メグルミン塩、トリス塩、及び例えば塩基性アミノ酸とのメロキシカムの塩を含む。メロキシカムの種々の塩が、欧州特許第0,002,482B1号明細書、米国特許第4,233,299号明細書及び国際出願WO 99/49867号明細書に記載されている。
Meloxicam is a known selective COX-2 inhibitor that belongs to the acidic enol carboxamide (oxicam) form of non-steroidal anti-inflammatory drugs (NSAIDs). The compound (4-hydroxy-2-methyl-N- (5-methyl-2-thiazolyl) -2H-1,2-benzothiazine 3-carboxamide 1,1-dioxide) is described in EP 0,002,482B1 and U.S. Pat. No. 4,233,299.
In the present invention, either meloxicam itself or a pharmaceutically acceptable salt thereof may be used. Pharmaceutically acceptable salts of meloxicam include sodium salt, potassium salt, ammonium salt, meglumine salt, tris salt, and meloxicam salt with, for example, basic amino acids. Various salts of meloxicam are described in EP 0,002,482B1, US 4,233,299 and international application WO 99/49867.
本発明の第一実施態様では、医薬組成物が、メロキシカム又はその医薬的に許容される塩、及び少なくとも1種の制酸薬を含む。
本発明の第二実施態様では、医薬組成物が、メロキシカム又はその医薬的に許容される塩、及び少なくとも1種の鎮静薬を含む。
上記のメロキシカム及び鎮静薬に加え、本発明の第二実施態様の組成物は、さらに制酸薬などの他の薬理学的有効成分を含んでいてもよい。
本発明の第三実施態様では、医薬組成物が、メロキシカム又はその医薬的に許容される塩、及び少なくとも1種の中枢神経興奮薬を含む。
上記のメロキシカム及び中枢神経興奮薬に加え、本発明の第三実施態様の組成物は、さらに他の薬理学的有効成分、例えば制酸薬及び/又は鎮静薬を含んでいてもよい。本発明のこの実施態様の好ましい改良は、医薬組成物が、メロキシカム又はその医薬的に許容される塩及び少なくとも1種の中枢神経興奮薬、及び少なくとも1種の鎮静薬を含む。上記のようなメロキシカム及び中枢神経興奮薬、及び任意成分としての鎮静薬に加え、本発明の前記医薬組成物は、さらに制酸薬など他の薬理学的有効成分を含んでいてもよい。
In a first embodiment of the invention, the pharmaceutical composition comprises meloxicam or a pharmaceutically acceptable salt thereof and at least one antacid.
In a second embodiment of the invention, the pharmaceutical composition comprises meloxicam or a pharmaceutically acceptable salt thereof and at least one sedative.
In addition to the above meloxicam and sedatives, the composition of the second embodiment of the present invention may further contain other pharmacologically active ingredients such as antacids.
In a third embodiment of the invention, the pharmaceutical composition comprises meloxicam or a pharmaceutically acceptable salt thereof and at least one central nervous system stimulant.
In addition to the above meloxicam and central nervous stimulant, the composition of the third embodiment of the present invention may further contain other pharmacologically active ingredients such as antacids and / or sedatives. In a preferred improvement of this embodiment of the invention, the pharmaceutical composition comprises meloxicam or a pharmaceutically acceptable salt thereof and at least one central nervous stimulant and at least one sedative. In addition to meloxicam and central nervous stimulant as described above and sedative as an optional ingredient, the pharmaceutical composition of the present invention may further contain other pharmacologically active ingredients such as antacids.
本発明の制酸薬の用語は、2つの型を包含する。第一の型は、胃酸を中和する。第二の型は、胃酸分泌を制御する。本発明では、胃酸中和効果を有する第一の型が好ましい。
好ましくは、制酸薬は、アミノ酢酸、ケイ酸マグネシウム、合成ケイ酸アルミニウム、ハイドロタルサイト、酸化マグネシウム、ジヒドロキシアルミニウムアミノ酢酸、水酸化アルミニウムゲル、乾燥水酸化アルミニウムゲル、水酸化アルミニウム-炭酸マグネシウム共乾燥ゲル、水酸化アルミニウム-重炭酸ナトリウム共沈殿物、水酸化アルミニウム-炭酸カルシウム-炭酸マグネシウム共沈殿物、水酸化マグネシウム-硫酸アルミニウムカリウム共沈殿物、炭酸マグネシウム、アルミノメタケイ酸マグネシウム、アルミノケイ酸マグネシウム、水酸化マグネシウムアルミニウム、水酸化マグネシウム、炭酸水素ナトリウム、沈殿炭酸カルシウム、無水第二リン酸カルシウム、及びリン酸水素カルシウムからなる群から選択される。
最も好ましい制酸薬の例は、アミノ酢酸、合成ケイ酸アルミニウム、ハイドロタルサイト、酸化マグネシウム、ジヒドロキシアルミニウムアミノ酢酸、水酸化アルミニウムゲル、乾燥水酸化アルミニウムゲル、水酸化アルミニウム-重炭酸ナトリウム共沈殿物、炭酸マグネシウム、アルミノメタケイ酸マグネシウム、水酸化マグネシウム、炭酸水素ナトリウム及びリン酸水素カルシウムからなる群から選択される。
好ましくはないが、本発明の組成物は、さらに胃酸分泌を制御する制酸薬を含んでいてもよい。そのような制酸薬の例は、ヒスタミンH2受容体拮抗薬、例えばシメチジン、ファモチジン、ラニチジン塩酸塩、ロキサチジン塩酸酢酸塩、ニザチジン及びラフチジン、プロトンポンプ阻害薬、例えばオメプラゾール、ランソプラゾール、レミノプラゾール、パントプラゾール及びラベプラゾールナトリウム、選択的ムスカリン受容体拮抗薬、例えば臭化チキジウム及び塩酸ピレンゼピンである。
The term antacid of the present invention encompasses two types. The first type neutralizes gastric acid. The second type controls gastric acid secretion. In the present invention, the first mold having a gastric acid neutralizing effect is preferred.
Preferably, the antacid is aminoacetic acid, magnesium silicate, synthetic aluminum silicate, hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetic acid, aluminum hydroxide gel, dry aluminum hydroxide gel, aluminum hydroxide-magnesium carbonate Dry gel, aluminum hydroxide-sodium bicarbonate coprecipitate, aluminum hydroxide-calcium carbonate-magnesium carbonate coprecipitate, magnesium hydroxide-aluminum potassium sulfate coprecipitate, magnesium carbonate, magnesium aluminometasilicate, magnesium aluminosilicate, Selected from the group consisting of magnesium aluminum hydroxide, magnesium hydroxide, sodium bicarbonate, precipitated calcium carbonate, anhydrous dicalcium phosphate, and calcium hydrogen phosphate.
Examples of most preferred antacids are aminoacetic acid, synthetic aluminum silicate, hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetic acid, aluminum hydroxide gel, dry aluminum hydroxide gel, aluminum hydroxide-sodium bicarbonate coprecipitate , Magnesium carbonate, magnesium aluminometasilicate, magnesium hydroxide, sodium bicarbonate and calcium hydrogen phosphate.
Although not preferred, the compositions of the present invention may further comprise an antacid that controls gastric acid secretion. Examples of such antacids are histamine H2 receptor antagonists such as cimetidine, famotidine, ranitidine hydrochloride, loxatidine hydrochloride acetate, nizatidine and lafutidine, proton pump inhibitors such as omeprazole, lansoprazole, leminoprazole, panto Prazole and rabeprazole sodium, selective muscarinic receptor antagonists such as tiquidium bromide and pirenzepine hydrochloride.
好ましくは、鎮静薬は、アリルイソプロピルアセチル尿素（(2-イソプロピル-4-ペンテノイル)尿素）、及びブロムワレリル尿素（(2-ブロモ-3-メチルブチリル)尿素）からなる群から選択される。
好ましくは、中枢神経興奮薬は、カフェイン（3,7-ジヒドロ-1,3,7-トリメチル-1H-プリン-2,6-ジオン一水和物）、無水カフェイン（3,7-ジヒドロ-1,3,7-トリメチル-1H-プリン-2,6-ジオン）、及びカフェインと安息香酸ナトリウムとの錯塩（カフェイン及び安息香酸ナトリウム）からなる群から選択される。2種以上の中枢神経興奮薬の組み合せを用いてもよい。
Preferably, the sedative is selected from the group consisting of allyl isopropyl acetyl urea ((2-isopropyl-4-pentenoyl) urea) and bromovalerylurea ((2-bromo-3-methylbutyryl) urea).
Preferably, the central nervous stimulant is caffeine (3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione monohydrate), anhydrous caffeine (3,7-dihydro -1,3,7-trimethyl-1H-purine-2,6-dione) and a complex salt of caffeine and sodium benzoate (caffeine and sodium benzoate). A combination of two or more central nervous stimulants may be used.
好ましい実施態様では、本発明の医薬組成物は、さらに少なくとも1種の医薬的に許容されるキャリア及び/又は添加剤を含む。好適なキャリア及び添加剤は当業者にとって既知であり、例えば日本医薬品添加剤辞典2000（日本医薬品添加剤協会編集、薬事日報出版）に記載されている。好適なキャリア及び/又は添加剤の例は、ラクトース、スクロース、グルコース、マンニトール、キシリトール、コーンスターチ、ポテトスターチ、小麦スターチ、ライススターチ、タピオカスターチ、カルボキシメチルナトリウムスターチ、微結晶性セルロース、エチルセルロース、ヒドロキシプロピルメチルセルロース、低置換ヒドロキシプロピルセルロース、ヒドロキシプロピルセルロース、クロスカルメロースナトリウム、カルメロース、カルメロースカリウム、カルメロースカルシウム、カルメロースナトリウム、ポリビニルピロリドン、プロピレングリコール、ポリエチレングリコール、グリセロール、植物油、ワックス、クロスポビドン、寒天、軽質無水ケイ酸、ステアリン酸マグネシウム、タルク、酸化チタン、アカシア、アルギン酸ナトリウム、エタノール及び精製水である。 In a preferred embodiment, the pharmaceutical composition of the invention further comprises at least one pharmaceutically acceptable carrier and / or additive. Suitable carriers and additives are known to those skilled in the art and are described, for example, in Japanese Pharmaceutical Additives Dictionary 2000 (edited by Japan Pharmaceutical Additives Association, published by Yakuji Nippo). Examples of suitable carriers and / or additives are lactose, sucrose, glucose, mannitol, xylitol, corn starch, potato starch, wheat starch, rice starch, tapioca starch, carboxymethyl sodium starch, microcrystalline cellulose, ethyl cellulose, hydroxypropyl Methylcellulose, low substituted hydroxypropylcellulose, hydroxypropylcellulose, croscarmellose sodium, carmellose, carmellose potassium, carmellose calcium, carmellose sodium, polyvinylpyrrolidone, propylene glycol, polyethylene glycol, glycerol, vegetable oil, wax, crospovidone, agar , Light anhydrous silicic acid, magnesium stearate, talc, titanium oxide, acacia, Sodium lginate, ethanol and purified water.
さらに本発明は、本発明の医薬組成物を含む医薬製剤形態に関する。
本発明に記載の経口医薬製剤形態に用いられるメロキシカムの量は、好ましくは1〜30mgの範囲、さらに好ましくは2.5〜15mgの範囲、及び最も好ましくは5〜10mgの範囲である。これらの量は、成人の1日当たり1回の投薬における好ましい投薬量範囲に相当する。
本発明の第一実施態様では、少なくとも1種の第二の医薬活性化合物が制酸薬からなる群から選択される。本発明の経口医薬製剤形態における制酸薬の量は、その制酸薬の型によって変動し得るが、好ましくは10〜7,000mgの範囲、さらに好ましくは16〜4,000mgの範囲である。これらの量は、成人に1日当たりに与えられる好ましい投薬量に相当する。
好ましい制酸薬に関して、本発明の経口医薬製剤形態における各制酸薬の量は、好ましくは、アミノ酢酸及び水酸化アルミニウム-重炭酸ナトリウム共沈殿物では30〜900mgの範囲、ケイ酸マグネシウム、合成ケイ酸アルミニウム、及び水酸化アルミニウム-炭酸マグネシウム共乾燥ゲルでは100〜3,000mgの範囲、ハイドロタルサイトでは133〜4,000mgの範囲、酸化マグネシウムでは16〜500mgの範囲、ジヒドロキシアルミニウムアミノ酢酸、水酸化アルミニウム-炭酸カルシウム-炭酸マグネシウム共沈殿物、アルミノメタケイ酸マグネシウム、沈殿炭酸カルシウム、及びリン酸水素カルシウムでは50〜1,500mgの範囲、水酸化アルミニウムゲル及び乾燥水酸化アルミニウムゲルでは33〜1,000mgの範囲、水酸化マグネシウム-硫酸アルミニウムカリウム共沈殿物では60〜1,800mgの範囲、炭酸マグネシウム、アルミノケイ酸マグネシウム、及び水酸化マグネシウムアルミニウムでは66〜2,000mgの範囲、水酸化マグネシウム及び無水第二リン酸カルシウムでは40〜1,200mgの範囲、及び炭酸水素ナトリウムでは83〜2,500mgである。これらの量は、本発明において成人に1日当たりに与えられる各制酸薬の好ましい投薬量に相当する。
Furthermore, this invention relates to the pharmaceutical formulation form containing the pharmaceutical composition of this invention.
The amount of meloxicam used in the oral pharmaceutical formulation described in the present invention is preferably in the range of 1-30 mg, more preferably in the range of 2.5-15 mg, and most preferably in the range of 5-10 mg. These amounts correspond to the preferred dosage range in a single daily dose for an adult.
In a first embodiment of the invention, the at least one second pharmaceutically active compound is selected from the group consisting of antacids. The amount of the antacid in the oral pharmaceutical preparation form of the present invention may vary depending on the type of the antacid, but is preferably in the range of 10 to 7,000 mg, more preferably in the range of 16 to 4,000 mg. These amounts correspond to the preferred dosage given to an adult per day.
For preferred antacids, the amount of each antacid in the oral pharmaceutical dosage form of the present invention is preferably in the range of 30-900 mg for aminoacetic acid and aluminum hydroxide-sodium bicarbonate coprecipitate, magnesium silicate, synthetic 100-3,000 mg for aluminum silicate and aluminum hydroxide-magnesium carbonate co-dried gel, 133-4,000 mg for hydrotalcite, 16-500 mg for magnesium oxide, dihydroxyaluminum aminoacetic acid, aluminum hydroxide -In the range of 50 to 1,500 mg for calcium carbonate-magnesium carbonate coprecipitate, magnesium aluminometasilicate, precipitated calcium carbonate, and calcium hydrogen phosphate, in the range of 33 to 1,000 mg for aluminum hydroxide gel and dry aluminum hydroxide gel, 60 for magnesium hydroxide-potassium aluminum sulfate coprecipitate 1,800 mg range, magnesium carbonate, magnesium aluminosilicate, and magnesium hydroxide in the range 66-2,000 mg, magnesium hydroxide and anhydrous dicalcium phosphate in the range 40-1,200 mg, and sodium bicarbonate 83-2,500 mg It is. These amounts correspond to the preferred dosage of each antacid given to an adult per day in the present invention.
本発明の第二実施態様では、少なくとも1種の第二の医薬活性化合物が鎮静薬からなる群から選択される。本発明の経口医薬製剤形態における鎮静薬の量は、その鎮静薬の型によって変動し得るが、好ましくは15〜1,200mgの範囲、さらに好ましくは30〜600mgの範囲である。これらの量は、成人に1日当たりに与えられる好ましい投薬量に相当する。
好ましい鎮静薬に関して、本発明の経口医薬製剤形態における各鎮静薬の量は、好ましくは、アリルイソプロピルアセチル尿素では30〜180mgの範囲、及びブロムワレリル尿素では100〜600mgの範囲である。これらの量は、本発明において成人に1日当たりに与えられる各鎮静薬の好ましい投薬量に相当する。
In a second embodiment of the invention, the at least one second pharmaceutically active compound is selected from the group consisting of sedatives. The amount of sedative in the oral pharmaceutical dosage form of the present invention may vary depending on the type of sedative, but is preferably in the range of 15 to 1,200 mg, more preferably in the range of 30 to 600 mg. These amounts correspond to the preferred dosage given to an adult per day.
For preferred sedatives, the amount of each sedative in the oral pharmaceutical dosage form of the present invention is preferably in the range of 30-180 mg for allylisopropylacetylurea and in the range of 100-600 mg for bromvalerylurea. These amounts correspond to the preferred dosage of each sedative given to an adult per day in the present invention.
本発明の第三実施態様では、少なくとも1種の第二の医薬的活性化合物が中枢神経興奮薬からなる群から選択される。本発明の経口医薬製剤形態における中枢神経興奮薬の量は、その中枢神経興奮薬の型によって変動し得るが、好ましくは15〜1,200mgの範囲、さらに好ましくは30〜300mgの範囲である。これらの量は、成人に1日当たりに与えられる好ましい投薬量に相当する。
好ましい中枢神経興奮薬に関して、本発明の経口医薬製剤形態における各中枢神経興奮薬の量は、好ましくは、カフェイン及び安息香酸ナトリウムでは60〜300mgの範囲、及びカフェイン及び/又は無水カフェインでは30〜250mgの範囲である。これらの量は、本発明において成人に1日当たりに与えられる各中枢神経興奮薬の好ましい投薬量に相当する。
In a third embodiment of the invention, the at least one second pharmaceutically active compound is selected from the group consisting of central nervous system stimulants. The amount of the central nervous stimulant in the oral pharmaceutical dosage form of the present invention may vary depending on the type of the central nervous stimulant, but is preferably in the range of 15 to 1,200 mg, more preferably in the range of 30 to 300 mg. These amounts correspond to the preferred dosage given to an adult per day.
With respect to preferred central nervous stimulants, the amount of each central nervous stimulant in the oral pharmaceutical dosage form of the present invention is preferably in the range of 60-300 mg for caffeine and sodium benzoate, and for caffeine and / or anhydrous caffeine. It is in the range of 30-250 mg. These amounts correspond to the preferred dosage of each central nervous stimulant given to an adult per day in the present invention.
第三実施態様の経口医薬製剤形態がさらに鎮静薬を含む場合、この経口医薬製剤形態の鎮静薬の量は、その鎮静薬の型によって変動し得る。好ましくは、15〜1,200mgの範囲、及びさらに好ましくは30〜600mgの範囲である。これらの量は、成人に1日当たりに与えられる好ましい投薬量に相当する。
好ましい鎮静薬に関して、そのような経口医薬製剤形態における各鎮静薬の量は、好ましくは、アリルイソプロピルアセチル尿素では30〜180mgの範囲、及びブロムワレリル尿素では100〜600mgの範囲である。これらの量は、本発明において成人に1日当たりに与えられる各鎮静薬の好ましい投薬量に相当する。
When the oral pharmaceutical dosage form of the third embodiment further comprises a sedative, the amount of sedative in this oral pharmaceutical dosage form can vary depending on the type of sedative. Preferably, it is in the range of 15 to 1,200 mg, and more preferably in the range of 30 to 600 mg. These amounts correspond to the preferred dosage given to an adult per day.
With respect to preferred sedatives, the amount of each sedative in such oral pharmaceutical dosage forms is preferably in the range of 30-180 mg for allylisopropylacetylurea and in the range of 100-600 mg for bromvalerylurea. These amounts correspond to the preferred dosage of each sedative given to an adult per day in the present invention.
本発明の経口医薬製剤形態は、分割された投薬量で経口的に与えられてもよいが、1日に1回経口的に与えられるのが好ましい。メロキシカム及び少なくとも1種の第二の医薬的活性化合物の投薬量の調整は、年齢、体重、及び顕在性疾患を反映し得る。
本発明に記載の経口医薬製剤形態は、錠剤、顆粒、細粒、粉末、カプセル、キャプレッツ、ソフトカプセル、丸薬、経口溶液、シロップ、乾燥シロップ、チュアブル錠、トローチ、成形錠剤、ドロップ、懸濁液及び速溶解性錠剤を含む。これらの製剤の全ては、通常の方法を用いて調製されてもよく、上記の成分に加え、一般的に使用される任意の添加物を必要に応じてこれらの製剤の調製に用いてもよい。加えて、マイクロカプセル、ナノカプセル、ミクロスフィア、ナノスフィア、及びリポソームなどの微粒子に形成された製剤も上記の製剤に含まれ得る。
加えて、経口医薬製剤形態のさらなる成分及び製剤の全ての成分は、好ましくは所望の機械的、化学的及び生物学的安定性、放出速度、味覚遮蔽、外観などを考慮して選択される。
The oral pharmaceutical dosage form of the present invention may be given orally in divided dosages, but is preferably given orally once a day. Adjustment of the dosage of meloxicam and at least one second pharmaceutically active compound may reflect age, weight, and overt disease.
The oral pharmaceutical preparation forms described in the present invention are tablets, granules, fine granules, powders, capsules, caplets, soft capsules, pills, oral solutions, syrups, dry syrups, chewable tablets, troches, molded tablets, drops, suspensions And fast dissolving tablets. All of these formulations may be prepared using conventional methods, and in addition to the above ingredients, any commonly used additives may be used to prepare these formulations as needed. . In addition, preparations formed into microparticles such as microcapsules, nanocapsules, microspheres, nanospheres, and liposomes can also be included in the above preparations.
In addition, the further components of the oral pharmaceutical formulation and all components of the formulation are preferably selected taking into account the desired mechanical, chemical and biological stability, release rate, taste masking, appearance, etc.
例えば、医薬的有効成分、すなわちメロキシカム又はその医薬的に許容される塩及び第二の医薬活性化合物は、別々の顆粒、多層顆粒、多層錠剤又は乾燥被覆錠剤、分離された顆粒の錠剤、マイクロカプセルなどに調剤することができる。糖衣錠剤などの被覆製剤、フィルム被覆錠剤、被覆顆粒、発泡医薬製剤は、咀嚼製剤、速溶解性製剤、マトリックス製剤と同様に、粉砕、固溶体などで用いることができる。これらの方法を組み合せることもできる。
好ましい実施態様では、経口製剤形態は、メロキシカム又はその医薬的に許容される塩を含む第一製剤形態、及び少なくとも第二の医薬的活性化合物を含む第二製剤形態の組み合せである。好ましくは、第一製剤形態は、有効成分を第二製剤形態よりも速く放出する。第一製剤形態は、さらに第二の医薬活性化合物、及び任意成分としてのさらなる有効成分を含んでいてもよい。第二製剤形態は、さらなる有効成分を含んでいてもよい。好ましくは、第二製剤形態はメロキシカムを含まない。
例えば、製剤形態は2層の錠剤であり、第一層は、メロキシカム又はその医薬的に許容される塩及び任意成分としての第二の医薬活性化合物、例えば鎮静薬又は中枢神経興奮薬、及び任意成分としてのさらなる有効成分及び医薬的に許容されるキャリア及び/又は添加剤を含む。第二層は、第二の医薬活性化合物、例えば鎮静薬又は中枢神経興奮薬、及び任意成分としてのさらなる有効成分及び医薬的に許容されるキャリア及び/又は添加剤を含み、それによって第二層は第一層と比べて遅い放出特性を有する。
For example, the pharmaceutically active ingredient, i.e. meloxicam or a pharmaceutically acceptable salt thereof and the second pharmaceutically active compound can be separated granules, multilayer granules, multilayer tablets or dry-coated tablets, isolated granules tablets, microcapsules Can be dispensed. Coated preparations such as sugar-coated tablets, film-coated tablets, coated granules, and foamed pharmaceutical preparations can be used in the form of pulverized, solid solution, etc., as with chewable preparations, fast-dissolving preparations, and matrix preparations. These methods can also be combined.
In a preferred embodiment, the oral dosage form is a combination of a first dosage form comprising meloxicam or a pharmaceutically acceptable salt thereof and a second dosage form comprising at least a second pharmaceutically active compound. Preferably, the first formulation form releases the active ingredient faster than the second formulation form. The first preparation form may further contain a second pharmaceutically active compound and an additional active ingredient as an optional ingredient. The second formulation form may contain further active ingredients. Preferably, the second formulation form does not contain meloxicam.
For example, the dosage form is a two-layer tablet where the first layer is meloxicam or a pharmaceutically acceptable salt thereof and a second pharmaceutically active compound as an optional ingredient, such as a sedative or central stimulant, and optional Further active ingredients as ingredients and pharmaceutically acceptable carriers and / or additives. The second layer comprises a second pharmaceutically active compound, such as a sedative or central nervous stimulant, and further active ingredients as optional ingredients and pharmaceutically acceptable carriers and / or additives, whereby the second layer Has slow release characteristics compared to the first layer.
さらなる例では、製剤形態は、2種類の顆粒を含むカプセルである。1種類目の顆粒は、メロキシカム又はその医薬的に許容される塩、及び任意成分としての第二の医薬活性化合物、例えば鎮静薬又は中枢神経興奮薬、及び任意成分としてのさらなる有効成分及び医薬的に許容されるキャリア及び/又は添加剤を含む。2種類目の顆粒は、第二の医薬活性化合物、例えば鎮静薬又は中枢神経興奮薬、及び任意成分としての有効成分及び医薬的に許容されるキャリア及び/又は添加剤を含み、それによって2種類目の顆粒は1種類目の顆粒と比べて遅い放出特性を有する。
これらの製剤は、一般的に入手できる医薬添加剤、例えば添加剤、結合剤、崩壊剤、潤滑剤、被覆剤、糖衣剤、可塑剤、消泡剤、研磨剤、発泡剤、帯電防止剤、乾燥剤、界面活性剤、溶解剤、緩衝剤、溶剤、可溶化剤、溶媒、希釈剤、安定剤、乳化剤、懸濁液、懸濁剤、分散剤、等張化剤、吸収剤、還元剤、抗酸化剤、湿潤剤、湿性条件剤、充填剤、拡張剤、接着剤、粘性剤、軟化剤、pH調節剤、防腐剤、保存剤、甘味剤、矯味剤、清涼剤、香料添加剤、香料、芳香剤、及び着色剤を薬理学的活性化合物に加えることによる通常の方法を用いて調製されてもよい。
そのような添加剤の例は、日本医薬品添加剤辞典2000（日本医薬品添加剤協会編集、薬事日報出版）に記載されている。
これらの製剤は、好ましくは医薬添加剤を薬理学的活性化合物に加えることにより製造される。
本発明の第一実施態様の医薬組成物及び製剤形態は、鎮痛薬、解熱薬及び/又は制酸薬として都合よく有用である。
本発明の第二実施態様の医薬組成物及び製剤形態は、鎮痛薬、解熱薬及び/又は鎮静薬として都合よく有用である。
本発明の第三実施態様の医薬組成物及び製剤形態は、鎮痛薬、解熱薬及び/又は中枢神経興奮薬として都合よく有用である。
In a further example, the dosage form is a capsule containing two types of granules. The first type of granule contains meloxicam or a pharmaceutically acceptable salt thereof, and a second pharmaceutically active compound as an optional ingredient, such as a sedative or central stimulant, and an additional active ingredient and pharmaceutically acceptable ingredient as an optional ingredient. Containing acceptable carriers and / or additives. The second type of granule comprises a second pharmaceutically active compound, such as a sedative or central nervous system stimulant, and an active ingredient as an optional ingredient and a pharmaceutically acceptable carrier and / or additive, whereby two types The eye granules have slow release characteristics compared to the first type of granules.
These preparations are generally available pharmaceutical additives such as additives, binders, disintegrants, lubricants, coating agents, sugar coatings, plasticizers, antifoaming agents, abrasives, foaming agents, antistatic agents, Desiccant, surfactant, solubilizer, buffer, solvent, solubilizer, solvent, diluent, stabilizer, emulsifier, suspension, suspension, dispersant, isotonic agent, absorbent, reducing agent , Antioxidants, wetting agents, wet condition agents, fillers, extenders, adhesives, viscosity agents, softeners, pH regulators, preservatives, preservatives, sweeteners, flavoring agents, refreshing agents, flavoring agents, It may be prepared using conventional methods by adding fragrances, fragrances, and colorants to the pharmacologically active compound.
Examples of such additives are described in the Japanese Pharmaceutical Additives Dictionary 2000 (edited by the Japan Pharmaceutical Additives Association, published by the Pharmaceutical Affairs Daily).
These formulations are preferably prepared by adding pharmaceutical additives to the pharmacologically active compound.
The pharmaceutical compositions and dosage forms of the first embodiment of the present invention are conveniently useful as analgesics, antipyretics and / or antacids.
The pharmaceutical composition and dosage form of the second embodiment of the present invention are conveniently useful as an analgesic, antipyretic and / or sedative.
The pharmaceutical compositions and dosage forms of the third embodiment of the present invention are conveniently useful as analgesics, antipyretics and / or central nervous stimulants.
本発明は、共に上記されている医薬組成物及び経口医薬製剤形態の、種々の症状を含む炎症性疾患を治療及び軽減するための使用に関する。
本発明の医薬組成物及び製剤形態は、頭痛、歯痛、抜歯後の痛み、咽頭痛、耳痛、関節痛、神経痛、腰痛、筋肉痛、肩の筋肉の凝り、挫傷の痛み、骨折の痛み、捻挫の痛み、月経痛、外傷痛、悪寒、発熱反応などを治療及び軽減するのに有効である。
さらに、本発明の医薬組成物及び製剤形態は、咽頭痛、悪寒、発熱、頭痛、関節痛及び筋肉痛などの風邪の種々の症状を軽減するのにも有効である。
The present invention relates to the use of the pharmaceutical compositions and oral pharmaceutical dosage forms both mentioned above for the treatment and alleviation of inflammatory diseases including various symptoms.
The pharmaceutical composition and preparation form of the present invention includes headache, toothache, pain after extraction, sore throat, ear pain, joint pain, neuralgia, low back pain, muscle pain, shoulder muscle stiffness, contusion pain, fracture pain, It is effective in treating and reducing sprain pain, menstrual pain, trauma pain, chills, and fever reactions.
Furthermore, the pharmaceutical composition and formulation of the present invention are also effective in reducing various symptoms of cold such as sore throat, chills, fever, headache, joint pain and muscle pain.
さらに本発明は、種々の症状を含む炎症性疾患、及び/又は頭痛、歯痛、抜歯後の痛み、咽頭痛、耳痛、関節痛、神経痛、腰痛、筋肉痛、肩の筋肉の凝り、挫傷の痛み、骨折の痛み、捻挫の痛み、月経痛、外傷痛、悪寒、発熱反応、及び/又は風邪、及び咽頭痛、悪寒、発熱、頭痛、関節痛及び筋肉痛などの風邪の種々の症状を予防又は軽減する薬剤を製造するための、上記の医薬組成物の使用に関する。
加えて、本発明は、本発明の経口医薬製剤形態を製造するための、メロキシカム又はその医薬的に許容される塩の使用に関する。
従って、本発明はさらに、本発明の経口医薬製剤形態を製造するための、制酸薬、鎮静薬及び中枢神経興奮薬からなる群から選択される医薬活性化合物の使用に関する。
Furthermore, the present invention provides inflammatory diseases including various symptoms and / or headache, toothache, post-extraction pain, sore throat, ear pain, joint pain, neuralgia, back pain, muscle pain, shoulder muscle stiffness, contusion. Various symptoms of cold such as pain, fracture pain, sprain pain, menstrual pain, traumatic pain, chills, fever reaction, and / or cold, and sore throat, chills, fever, headache, joint pain and muscle pain It relates to the use of a pharmaceutical composition as described above for the manufacture of a medicament for prevention or alleviation.
In addition, the present invention relates to the use of meloxicam or a pharmaceutically acceptable salt thereof for producing the oral pharmaceutical dosage form of the present invention.
Accordingly, the present invention further relates to the use of a pharmaceutically active compound selected from the group consisting of antacids, sedatives and central nervous stimulants for the manufacture of the oral pharmaceutical dosage forms of the present invention.
結果的に、本発明はさらに、炎症性疾患、その種々の症状を含む炎症性疾患、及び/又は頭痛、歯痛、抜歯後の痛み、咽頭痛、耳痛、関節痛、神経痛、腰痛、筋肉痛、肩の筋肉の凝り、挫傷の痛み、骨折の痛み、捻挫の痛み、月経痛、外傷痛、悪寒、発熱反応、及び/又は風邪、及び咽頭痛、悪寒、発熱、頭痛、関節痛及び筋肉痛などの風邪の種々の症状の治療を必要としている患者における治療又は軽減方法に関し、この方法は、患者に対して本発明の医薬組成物を経口投薬することを含む。
本発明によって治療される患者は、哺乳類、好ましくは人間である。
As a result, the present invention further includes inflammatory diseases, inflammatory diseases including various symptoms thereof, and / or headache, toothache, pain after extraction, sore throat, ear pain, joint pain, neuralgia, low back pain, muscle pain. , Shoulder muscle stiffness, contusion pain, fracture pain, sprain pain, menstrual pain, traumatic pain, chills, fever reaction, and / or cold, and sore throat, chills, fever, headache, joint pain and muscles With respect to a method of treatment or alleviation in a patient in need of treatment of various symptoms of a cold such as pain, the method comprises orally administering the pharmaceutical composition of the present invention to the patient.
The patient to be treated according to the present invention is a mammal, preferably a human.
本発明の患者に対して経口投薬される好ましい1日当たりの投薬量は、1〜30mg、さらに好ましくは2.5〜15mgの範囲のメロキシカム又はその塩、及び
a）第二の医薬活性化合物が制酸薬の場合は、10〜7,000mg、さらに好ましくは16〜4,000mgの量の制酸薬、
b)第二の医薬活性化合物が鎮静薬の場合は、15〜1,200mg、さらに好ましくは30〜600mgの量の鎮静薬、
c)第二の医薬活性化合物が中枢神経興奮薬の場合は、15〜1,200mg、さらに好ましくは30〜300mgの量の中枢神経興奮薬、
である。鎮静薬がさらなる有効成分として選択される場合は、本発明の患者に対して経口投薬される好ましい1日当たりの投薬量では、鎮静薬が15〜1,200mg、さらに好ましくは30〜600mgの範囲である。
種々の第二の医薬活性化合物に関する好ましい投薬量を、上記に特定した。従って、1日当たりに患者によって摂取される製剤形態の量、すなわち、錠剤、カプセル、キャプレッツ、トローチなどの数、又はグラム又はミリリットルなどで測定される顆粒、シロップ、溶剤、懸濁液などの量は、上記に特定された好ましい1日当たりの投薬量が達成されるようなものである。
A preferred daily dosage to be orally administered to a patient of the present invention is 1-30 mg, more preferably 2.5-15 mg in the range of meloxicam or a salt thereof, and
a) when the second pharmaceutically active compound is an antacid, 10 to 7,000 mg, more preferably 16 to 4,000 mg,
b) if the second pharmaceutically active compound is a sedative, sedative in an amount of 15-1,200 mg, more preferably 30-600 mg,
c) if the second pharmaceutically active compound is a central nervous system stimulant, a central nervous system stimulant in an amount of 15 to 1,200 mg, more preferably 30 to 300 mg,
It is. When a sedative is selected as a further active ingredient, the preferred daily dosage to be orally administered to the patient of the present invention ranges from 15 to 1,200 mg, more preferably 30 to 600 mg of sedative .
Preferred dosages for the various second pharmaceutically active compounds are specified above. Therefore, the amount of formulation taken by the patient per day, ie the number of tablets, capsules, caplets, troches, etc., or the amount of granules, syrups, solvents, suspensions, etc. measured in grams or milliliters Is such that the preferred daily dosages specified above are achieved.
メロキシカム又はその医薬的に許容される塩、及び少なくとも1種の医薬活性化合物は、好ましくは、上記の1つの経口製剤形態に組み合わされる。メロキシカム又はその塩、及び第二の医薬活性化合物は共に、1つがメロキシカム又はその塩を含み、もう1つが第二の医薬活性化合物を含む2つの別々の経口製剤形態で同時に投薬されてもよい。
本発明の組成物又は製剤形態を、以下の例によって説明するが、本発明の範囲を限定するものではない。例1.1〜1.6は本発明の第一実施態様を説明し、例2.1〜2.7は本発明の第二実施態様を説明し、及び例3.1〜3.7は本発明の第三実施態様を説明する。
Meloxicam or a pharmaceutically acceptable salt thereof and at least one pharmaceutically active compound are preferably combined in one oral dosage form as described above. Both meloxicam or a salt thereof and the second pharmaceutically active compound may be administered simultaneously in two separate oral dosage forms, one containing meloxicam or a salt thereof and the other containing the second pharmaceutically active compound.
The composition or formulation form of the present invention is illustrated by the following examples, but is not intended to limit the scope of the present invention. Examples 1.1-1.6 illustrate the first embodiment of the present invention, Examples 2.1-2.7 illustrate the second embodiment of the present invention, and Examples 3.1-3.7 illustrate the third embodiment of the present invention.
例1.1
錠剤
以下の成分を均一に混合する。得られた混合粒子を鋳型で圧縮し、各300mgの錠剤を調製する。
メロキシカム 15g
アミノ酢酸 600g
ラクトース 585g
微結晶性セルロース 564g
軽質無水ケイ酸 18g
ステアリン酸マグネシウム 10g
タルク 8g
Example 1.1
Tablet Mix the following ingredients uniformly. The obtained mixed particles are compressed with a mold to prepare tablets of 300 mg each.
Meloxicam 15g
Aminoacetic acid 600g
Lactose 585g
Microcrystalline cellulose 564g
Light anhydrous silicic acid 18g
Magnesium stearate 10g
Talc 8g
例1.2
粉末
以下の成分を均一に混合する。得られた混合粒子を800mgずつに分け、粉末組成物を調製する。
メロキシカム 15g
乾燥水酸化アルミニウムゲル 600g
コーンスターチ 469g
ラクトース 500g
ステアリン酸マグネシウム 16g
Example 1.2
Powder The following ingredients are mixed uniformly. The obtained mixed particles are divided into 800 mg portions to prepare a powder composition.
Meloxicam 15g
600g of dry aluminum hydroxide gel
Cornstarch 469g
Lactose 500g
Magnesium stearate 16g
例1.3
2層錠剤
層A及び層Bの以下の成分を通常の方法によって加工して、それぞれの混合粒子を提供し、及びそれらの粒子を圧縮して各250mg（層Aは100mg、層Bは150mg）の2層錠剤を形成する。
層A
メロキシカム 45g
ラクトース 273g
微結晶性セルロース 270g
軽質無水ケイ酸 6g
タルク 3g
ステアリン酸マグネシウム 3g
層B
酸化マグネシウム 300g
ラクトース 282g
微結晶性セルロース 300g
軽質無水ケイ酸 9g
タルク 3g
ステアリン酸マグネシウム 6g
Example 1.3
Two-layer tablet The following ingredients of layer A and layer B are processed by conventional methods to provide respective mixed particles, and the particles are compressed into 250 mg each (layer A is 100 mg, layer B is 150 mg) To form a two-layer tablet.
Tier A
Meloxicam 45g
Lactose 273g
Microcrystalline cellulose 270g
Light anhydrous silicic acid 6g
Talc 3g
Magnesium stearate 3g
Layer B
Magnesium oxide 300g
Lactose 282g
300g microcrystalline cellulose
Light anhydrous silica 9g
Talc 3g
Magnesium stearate 6g
例1.4
顆粒
以下の成分を、通常の方法によって顆粒として調製して混合粒子を調製し、及び包装し、1パック当たり1,400mgの量の顆粒を得る。
メロキシカム 15g
ジヒドロキシアルミニウムアミノ酢酸 200g
炭酸マグネシウム 400g
カルシウムカルボキシメチルセルロース 400g
マンニトール 1,100g
ラウリル硫酸ナトリウム 10g
コーンスターチ 649g
アスパルテーム 12g
アセスルファメカリウム 12g
芳香性材料 2g
Example 1.4
Granules The following ingredients are prepared as granules by conventional methods to prepare mixed particles and packaged to obtain granules in an amount of 1,400 mg per pack.
Meloxicam 15g
200g dihydroxyaluminum aminoacetic acid
Magnesium carbonate 400g
Calcium carboxymethyl cellulose 400g
Mannitol 1,100g
Sodium lauryl sulfate 10g
Cornstarch 649g
Aspartame 12g
Acesulfame potassium 12g
Aromatic material 2g
例1.5
フィルム被覆錠剤
以下の成分を、通常の方法によって加工して混合粒子を提供し、及びそれらの粒子を圧縮して各240mgの錠剤を形成する。
メロキシカム 45g
合成ケイ酸アルミニウム 720g
ラクトース 1,320g
微結晶性セルロース 900g
コーンスターチ 753g
低置換ヒドロキシプロピルセルロース 270g
ヒドロキシプロピルセルロース 180g
軽質無水ケイ酸 90g
タルク 24g
ステアリン酸マグネシウム 18g
その後、その錠剤を被覆用容器に移し、5%質量/体積のヒドロキシプロピルメチルセルロースを含むエチルアルコールと精製水との同体積混合物を含む被覆性溶液を用いて被覆し、1つの錠剤当たり10mg質量/体積増やす。このようにして、フィルム被覆錠剤を調製する。
Example 1.5
Film coated tablets The following ingredients are processed by conventional methods to provide mixed particles, and the particles are compressed to form 240 mg tablets each.
Meloxicam 45g
Synthetic aluminum silicate 720g
Lactose 1,320g
900g microcrystalline cellulose
Cornstarch 753g
Low-substituted hydroxypropylcellulose 270g
Hydroxypropylcellulose 180g
Light silicic acid 90g
Talc 24g
Magnesium stearate 18g
The tablets are then transferred to a coating container and coated with a coating solution containing an equal volume mixture of ethyl alcohol and purified water containing 5% mass / volume of hydroxypropyl methylcellulose, 10 mg mass / Increase the volume. In this way, film-coated tablets are prepared.
例1.6
カプセル
以下の成分を、通常の方法によって顆粒として調製し、及びカプセルに充填し、1つ当たり150mgの量のカプセルを得る。
メロキシカム 60g
アルミノメタケイ酸マグネシウム 1,280g
微結晶性セルロース 400g
ラクトース 260g
低置換ヒドロキシプロピルセルロース 200g
コーンスターチ 200g
Example 1.6
Capsules The following ingredients are prepared as granules by conventional methods and filled into capsules to obtain capsules in an amount of 150 mg per capsule.
Meloxicam 60g
Magnesium aluminometasilicate 1,280g
400g microcrystalline cellulose
Lactose 260g
Low substituted hydroxypropylcellulose 200g
Cornstarch 200g
例2.1
錠剤
以下の成分を、均一に混合する。得られた混合粒子を鋳型で圧縮し、各240mgの錠剤を調製する。
メロキシカム 15g
アリルイソプロピルアセチル尿素 120g
ラクトース 409g
微結晶性セルロース 388g
軽質無水ケイ酸 14g
ステアリン酸マグネシウム 8g
タルク 6g
Example 2.1
Tablet The following ingredients are mixed uniformly. The obtained mixed particles are compressed with a mold to prepare 240 mg tablets.
Meloxicam 15g
Allyl isopropyl acetyl urea 120g
Lactose 409g
Microcrystalline cellulose 388g
Light anhydrous silicic acid 14g
Magnesium stearate 8g
Talc 6g
例2.2
粉末
以下の成分を、均一に混合する。得られた混合粒子を800mgずつに分け、粉末組成物を調製する。
メロキシカム 15g
ブロムワレリル尿素 400g
コーンスターチ 569g
ラクトース 576g
ステアリン酸マグネシウム 40g
Example 2.2
Powder The following ingredients are mixed uniformly. The obtained mixed particles are divided into 800 mg portions to prepare a powder composition.
Meloxicam 15g
Bromvalerylurea 400g
Cornstarch 569g
Lactose 576g
Magnesium stearate 40g
例2.3
2層錠剤
層A及び層Bの以下の成分を通常の方法によって加工し、それぞれの混合粒子を提供し、及びそれらの粒子を圧縮して各200mg（層Aは100mg、層Bは100mg）の2層錠剤を形成する。
層A
メロキシカム 45g
アリルイソプロピルアセチル尿素 360g
ラクトース 381g
微結晶性セルロース 390g
軽質無水ケイ酸 12g
タルク 6g
ステアリン酸マグネシウム 6g
層B
アリルイソプロピルアセチル尿素 720g
ラクトース 228g
ヒドロキシプロピルメチルセルロース2208 60g
硬化油 60g
ステアリン酸 60g
脂肪酸のグリセロールエステル 60g
ステアリン酸マグネシウム 12g
Example 2.3
Two-layer tablet The following ingredients of layer A and layer B are processed by conventional methods to provide respective mixed particles, and the particles are compressed to 200 mg each (layer A is 100 mg, layer B is 100 mg) A bilayer tablet is formed.
Tier A
Meloxicam 45g
Allylisopropylacetylurea 360g
Lactose 381g
Microcrystalline cellulose 390g
Light anhydrous silicic acid 12g
Talc 6g
Magnesium stearate 6g
Layer B
720 g of allyl isopropyl acetyl urea
Lactose 228g
Hydroxypropyl methylcellulose 2208 60g
Hardened oil 60g
Stearic acid 60g
Fatty acid glycerol ester 60g
Magnesium stearate 12g
例2.4
顆粒
以下の成分を、通常の方法によって顆粒として調製して混合粒子を調製し、及び包装し、1パック当たり1,000mgの量の顆粒を得る。
メロキシカム 15g
ブロムワレリル尿素 400g
カルシウムカルボキシメチルセルロース 120g
マンニトール 1,100g
コーンスターチ 343g
アスパルテーム 10g
アセスルファメカリウム 10g
芳香性材料 2g
Example 2.4
Granules The following ingredients are prepared as granules by conventional methods to prepare mixed particles and packaged to obtain granules in an amount of 1,000 mg per pack.
Meloxicam 15g
Bromvalerylurea 400g
Calcium carboxymethyl cellulose 120g
Mannitol 1,100g
Corn Starch 343g
Aspartame 10g
Acesulfame potassium 10g
Aromatic material 2g
例2.5
フィルム被覆錠剤
以下の成分を、通常の方法によって加工して混合粒子を提供し、及びそれらの粒子を圧縮して各240mgの錠剤を形成する。
メロキシカム 45g
アリルイソプロピルアセチル尿素 540g
ラクトース 1,314g
微結晶性セルロース 1,080g
コーンスターチ 747g
低置換ヒドロキシプロピルセルロース 270g
ヒドロキシプロピルセルロース 180g
軽質無水ケイ酸 90g
タルク 36g
ステアリン酸マグネシウム 18g
その後、その錠剤を被覆用容器に移し、5%質量/体積のヒドロキシプロピルメチルセルロースを含むエチルアルコールと精製水との同体積混合物を含む被覆性溶液を用いて被覆し、1つの錠剤当たり10mg質量/体積増やす。このようにして、フィルム被覆錠剤を調製する。
Example 2.5
Film coated tablets The following ingredients are processed by conventional methods to provide mixed particles, and the particles are compressed to form 240 mg tablets each.
Meloxicam 45g
Allyl isopropyl acetyl urea 540g
Lactose 1,314g
Microcrystalline cellulose 1,080 g
Cornstarch 747g
Low-substituted hydroxypropylcellulose 270g
Hydroxypropylcellulose 180g
Light silicic acid 90g
Talc 36g
Magnesium stearate 18g
The tablets are then transferred to a coating container and coated with a coating solution containing an equal volume mixture of ethyl alcohol and purified water containing 5% mass / volume of hydroxypropyl methylcellulose, 10 mg mass / Increase the volume. In this way, film-coated tablets are prepared.
例2.6
カプセル
以下の成分を、通常の方法によって速放出顆粒及び遅放出顆粒として調製し、及びカプセルに充填し、1つ当たり225mgの量（速放出顆粒は75mg、遅放出顆粒は150mg）のカプセルを得る。
速放出顆粒
メロキシカム 60g
アリルイソプロピルアセチル尿素 480g
微結晶性セルロース 660g
遅放出顆粒
アリルイソプロピルアセチル尿素 960g
フマル酸 240g
硬化油 240g
微結晶性セルロース 744g
エチルセルロース（被覆層） 160g
脂肪酸のグリセロールエステル（被覆層） 44g
タルク（被覆層） 12g
Example 2.6
Capsules The following ingredients are prepared by conventional methods as fast release granules and slow release granules, and filled into capsules to obtain capsules in an amount of 225 mg each (75 mg for fast release granules and 150 mg for slow release granules) .
Fast release granules
Meloxicam 60g
480 g of allyl isopropyl acetyl urea
Microcrystalline cellulose 660g
Slow release granules
960 g allylisopropylacetylurea
240g fumaric acid
Hardened oil 240g
744g microcrystalline cellulose
Ethylcellulose (coating layer) 160g
Fatty acid glycerol ester (coating layer) 44g
Talc (coating layer) 12g
例2.7
カプセル
以下の成分を、通常の方法によって速放出顆粒及び遅放出顆粒として調製し、及びカプセルに充填し、1つ当たり225mgの量（速放出顆粒は75mg、遅放出顆粒は150mg）のカプセルを得る。
速放出顆粒
メロキシカム 60g
アリルイソプロピルアセチル尿素 480g
微結晶性セルロース 660g
遅放出顆粒
アリルイソプロピルアセチル尿素 960g
フマル酸 240g
微結晶性セルロース 720g
メタクリル酸コポリマーS（被覆層） 432g
脂肪酸のグリセロールエステル（被覆層） 32g
タルク（被覆層） 16g
Example 2.7
Capsules The following ingredients are prepared by conventional methods as fast release granules and slow release granules, and filled into capsules to obtain capsules in an amount of 225 mg each (75 mg for fast release granules and 150 mg for slow release granules) .
Fast release granules
Meloxicam 60g
480 g of allyl isopropyl acetyl urea
Microcrystalline cellulose 660g
Slow release granules
960 g allylisopropylacetylurea
240g fumaric acid
Microcrystalline cellulose 720g
Methacrylic acid copolymer S (coating layer) 432g
Fatty acid glycerol ester (coating layer) 32g
Talc (coating layer) 16g
例3.1
錠剤
以下の成分を、均一に混合する。得られた混合粒子を鋳型で圧縮し、各240mgの錠剤を調製する。
メロキシカム 15g
無水カフェイン 240g
アリルイソプロピルアセチル尿素 120g
ラクトース 289g
微結晶性セルロース 268g
軽質無水ケイ酸 14g
ステアリン酸マグネシウム 8g
タルク 6g
Example 3.1
Tablet The following ingredients are mixed uniformly. The obtained mixed particles are compressed with a mold to prepare 240 mg tablets.
Meloxicam 15g
240g anhydrous caffeine
Allyl isopropyl acetyl urea 120g
Lactose 289g
Microcrystalline cellulose 268g
Light anhydrous silicic acid 14g
Magnesium stearate 8g
Talc 6g
例3.2
粉末
以下の成分を、均一に混合する。得られた混合粒子を800mgずつに分け、粉末組成物を調製する。
メロキシカム 15g
カフェイン及び安息香酸ナトリウム 300g
コーンスターチ 617g
ラクトース 628g
ステアリン酸マグネシウム 40g
Example 3.2
Powder The following ingredients are mixed uniformly. The obtained mixed particles are divided into 800 mg portions to prepare a powder composition.
Meloxicam 15g
Caffeine and sodium benzoate 300g
Cornstarch 617g
Lactose 628g
Magnesium stearate 40g
例3.3
2層錠剤
層A及び層Bの以下の成分を通常の方法によって加工し、それぞれの混合粒子を提供し、及びそれらの粒子を圧縮して各220mg（層Aは100mg、層Bは120mg）の2層錠剤を形成する。
層A
メロキシカム 45g
無水カフェイン 480g
ラクトース 309g
微結晶性セルロース 330g
軽質無水ケイ酸 12g
ラウリル硫酸ナトリウム 12g
タルク 6g
ステアリン酸マグネシウム 6g
層B
無水カフェイン 1,020g
ラクトース 168g
ヒドロキシプロピルメチルセルロース2208 60g
硬化油 60g
ステアリン酸 60g
脂肪酸のグリセロールエステル 60g
ステアリン酸マグネシウム 12g
Example 3.3
Two-layer tablets The following ingredients of layer A and layer B are processed by conventional methods to provide respective mixed particles, and the particles are compressed to 220 mg each (layer A is 100 mg, layer B is 120 mg) A bilayer tablet is formed.
Tier A
Meloxicam 45g
Anhydrous caffeine 480g
Lactose 309g
330g microcrystalline cellulose
Light anhydrous silicic acid 12g
Sodium lauryl sulfate 12g
Talc 6g
Magnesium stearate 6g
Layer B
Anhydrous caffeine 1,020 g
Lactose 168g
Hydroxypropyl methylcellulose 2208 60g
Hardened oil 60g
Stearic acid 60g
Fatty acid glycerol ester 60g
Magnesium stearate 12g
例3.4
顆粒
以下の成分を、通常の方法によって顆粒として調製して混合粒子を調製し、及び包装し、1パック当たり1,000mgの量の顆粒を得る。
メロキシカム 15g
カフェイン 240g
カルシウムカルボキシメチルセルロース 120g
マンニトール 1,260g
コーンスターチ 343g
アスパルテーム 10g
アセスルファメカリウム 10g
芳香性材料 2g
Example 3.4
Granules The following ingredients are prepared as granules by conventional methods to prepare mixed particles and packaged to obtain granules in an amount of 1,000 mg per pack.
Meloxicam 15g
240g caffeine
Calcium carboxymethyl cellulose 120g
Mannitol 1,260g
Corn Starch 343g
Aspartame 10g
Acesulfame potassium 10g
Aromatic material 2g
例3.5
フィルム被覆錠剤
以下の成分を、通常の方法によって加工して混合粒子を提供し、及びそれらの粒子を圧縮して各240mgの錠剤を形成する。
メロキシカム 45g
カフェイン及び安息香酸ナトリウム 1,350g
ラクトース 504g
微結晶性セルロース 1,080g
コーンスターチ 747g
低置換ヒドロキシプロピルセルロース 270g
ヒドロキシプロピルセルロース 180g
軽質無水ケイ酸 90g
タルク 36g
ステアリン酸マグネシウム 18g
その後、その錠剤を被覆用容器に移し、5%質量/体積のヒドロキシプロピルメチルセルロースを含むエチルアルコールと精製水との同体積混合物を含む被覆性溶液を用いて被覆し、1つの錠剤当たり10mg質量/体積増やす。このようにして、フィルム被覆錠剤を調製する。
Example 3.5
Film coated tablets The following ingredients are processed by conventional methods to provide mixed particles, and the particles are compressed to form 240 mg tablets each.
Meloxicam 45g
Caffeine and sodium benzoate 1,350 g
Lactose 504g
Microcrystalline cellulose 1,080 g
Cornstarch 747g
Low-substituted hydroxypropylcellulose 270g
Hydroxypropylcellulose 180g
Light silicic acid 90g
Talc 36g
Magnesium stearate 18g
The tablets are then transferred to a coating container and coated with a coating solution containing an equal volume mixture of ethyl alcohol and purified water containing 5% mass / volume of hydroxypropyl methylcellulose, 10 mg mass / Increase the volume. In this way, film-coated tablets are prepared.
例3.6
カプセル
以下の成分を、通常の方法によって速放出顆粒及び遅放出顆粒として調製し、及びカプセルに充填し、1つ当たり225mgの量（速放出顆粒は75mg、遅放出顆粒は150mg）のカプセルを得る。
速放出顆粒
メロキシカム 60g
無水カフェイン 640g
微結晶性セルロース 500g
遅放出顆粒
無水カフェイン 1,280g
フマル酸 320g
微結晶性セルロース 584g
エチルセルロース（被覆層） 128g
ヒドロキシプロピルメチルセルロース（被覆層） 32g
脂肪酸のグリセロールエステル（被覆層） 44g
タルク（被覆層） 12g
Example 3.6
Capsules The following ingredients are prepared by conventional methods as fast release granules and slow release granules, and filled into capsules to obtain capsules in an amount of 225 mg each (75 mg for fast release granules and 150 mg for slow release granules) .
Fast release granules
Meloxicam 60g
Anhydrous caffeine 640g
500g microcrystalline cellulose
Slow release granules
Anhydrous caffeine 1,280g
320 g of fumaric acid
Microcrystalline cellulose 584g
Ethylcellulose (coating layer) 128g
Hydroxypropyl methylcellulose (coating layer) 32g
Fatty acid glycerol ester (coating layer) 44g
Talc (coating layer) 12g
例3.7
カプセル
以下の成分を、通常の方法によって速放出顆粒及び遅放出顆粒として調製し、及びカプセルに充填し、1つ当たり225mgの量（速放出顆粒は75mg、遅放出顆粒は150mg）のカプセルを得る。
速放出顆粒
メロキシカム 60g
無水カフェイン 640g
微結晶性セルロース 500g
遅放出顆粒
無水カフェイン 1,280g
フマル酸 240g
微結晶性セルロース 400g
メタクリル酸コポリマーS（被覆層） 432g
脂肪酸のグリセロールエステル（被覆層） 32g
タルク（被覆層） 16g
Example 3.7
Capsules The following ingredients are prepared by conventional methods as fast release granules and slow release granules, and filled into capsules to obtain capsules in an amount of 225 mg each (75 mg for fast release granules and 150 mg for slow release granules) .
Fast release granules
Meloxicam 60g
Anhydrous caffeine 640g
500g microcrystalline cellulose
Slow release granules
Anhydrous caffeine 1,280g
240g fumaric acid
400g microcrystalline cellulose
Methacrylic acid copolymer S (coating layer) 432g
Fatty acid glycerol ester (coating layer) 32g
Talc (coating layer) 16g
Claims (23)
a）第二の医薬活性化合物が制酸薬の場合は、10〜7,000mgの範囲、
b）第二の医薬活性化合物が鎮静薬又は中枢神経興奮薬の場合は、15〜1,200mgの範囲
である、経口医薬製剤形態。 14. The oral pharmaceutical dosage form according to any one of claims 12 or 13, wherein the amount of the second pharmaceutically active compound is
a) if the second pharmaceutically active compound is an antacid, in the range of 10-7,000 mg,
b) An oral pharmaceutical dosage form in the range of 15 to 1,200 mg when the second pharmaceutically active compound is a sedative or central nervous stimulant.
a）第二の医薬活性化合物が制酸薬の場合は、10〜7,000mgの量の制酸剤、
b）第二の医薬活性化合物が鎮静薬の場合は、15〜1,200mgの量の鎮静薬、
c）第二の医薬活性化合物が中枢神経興奮薬の場合は、15〜1,200mgの量の中枢神経興奮薬、
を患者に対して経口投薬する、請求項２０記載の方法。 Meloxicam or a pharmaceutically acceptable salt thereof in an amount of 1-30 mg and
a) if the second pharmaceutically active compound is an antacid, an antacid in an amount of 10 to 7,000 mg,
b) if the second pharmaceutically active compound is a sedative, an amount of sedative of 15 to 1,200 mg,
c) if the second pharmaceutically active compound is a central nervous system stimulant, an amount of 15 to 1,200 mg of central nervous system stimulant,
21. The method of claim 20, wherein the is orally administered to the patient.
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03015436.3 | 2003-07-09 | ||
| EP03015436 | 2003-07-09 | ||
| EP03015435 | 2003-07-09 | ||
| EP03015435.5 | 2003-07-09 | ||
| EP03015741.6 | 2003-07-10 | ||
| EP03015741 | 2003-07-10 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006518101A Division JP2009513512A (en) | 2003-07-09 | 2004-07-03 | Composition comprising meloxicam |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2012021025A true JP2012021025A (en) | 2012-02-02 |
Family
ID=34068724
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006518101A Pending JP2009513512A (en) | 2003-07-09 | 2004-07-03 | Composition comprising meloxicam |
| JP2011222068A Pending JP2012021025A (en) | 2003-07-09 | 2011-10-06 | Composition comprising meloxicam |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006518101A Pending JP2009513512A (en) | 2003-07-09 | 2004-07-03 | Composition comprising meloxicam |
Country Status (2)
| Country | Link |
|---|---|
| JP (2) | JP2009513512A (en) |
| WO (1) | WO2005004915A2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020262618A1 (en) | 2019-06-28 | 2020-12-30 | Ssp Co., Ltd. | Meloxicam-containing granulated product |
| JP2021054728A (en) * | 2019-09-27 | 2021-04-08 | 興和株式会社 | Pharmaceutical |
| JP2021107337A (en) * | 2019-12-27 | 2021-07-29 | ライオン株式会社 | Oral pharmaceutical formulation and solid pharmaceutical formulation |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020035107A1 (en) | 2000-06-20 | 2002-03-21 | Stefan Henke | Highly concentrated stable meloxicam solutions |
| DE10161077A1 (en) | 2001-12-12 | 2003-06-18 | Boehringer Ingelheim Vetmed | Highly concentrated stable meloxicam solutions for needleless injection |
| US8992980B2 (en) | 2002-10-25 | 2015-03-31 | Boehringer Ingelheim Vetmedica Gmbh | Water-soluble meloxicam granules |
| EP1568369A1 (en) | 2004-02-23 | 2005-08-31 | Boehringer Ingelheim Vetmedica Gmbh | Use of meloxicam for the treatment of respiratory diseases in pigs |
| EP1744757A4 (en) * | 2004-05-04 | 2009-04-22 | Equitech Corp | Improved nsaid composition |
| DK4378443T3 (en) | 2009-10-12 | 2025-08-18 | Boehringer Ingelheim Vetmedica Gmbh | CONTAINERS FOR COMPOSITIONS COMPRISING MELOXICAM |
| SG183846A1 (en) | 2010-03-03 | 2012-10-30 | Boehringer Ingelheim Vetmed | Use of meloxicam for the long-term treatment of musculoskeletal disorders in cats |
| US9795568B2 (en) | 2010-05-05 | 2017-10-24 | Boehringer Ingelheim Vetmedica Gmbh | Low concentration meloxicam tablets |
| CN103842330B (en) * | 2011-09-02 | 2016-10-19 | 诺华股份有限公司 | Choline salts of anti-inflammatory substituted cyclobutenediones |
| WO2014021455A1 (en) * | 2012-08-03 | 2014-02-06 | 国立大学法人愛媛大学 | Immune cell activation inhibitor and use thereof |
| JP2016535027A (en) * | 2013-10-22 | 2016-11-10 | エドワード タク ウェイＷＥＩ， Ｅｄｗａｒｄ Ｔａｋ | 1-di (sec-butyl) -phosphinoyl-pentane (DAPA-2-5) as a topical agent for the treatment of unkeratinized stratified epithelial (NKSE) tissue discomfort |
| US9526734B2 (en) | 2014-06-09 | 2016-12-27 | Iceutica Pty Ltd. | Formulation of meloxicam |
| JP7209537B2 (en) * | 2018-02-23 | 2023-01-20 | ライオン株式会社 | Solid pharmaceutical formulation |
| JP7391639B2 (en) * | 2019-12-06 | 2023-12-05 | ライオン株式会社 | pharmaceutical formulations |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04230330A (en) * | 1990-07-03 | 1992-08-19 | Mcneil Ppc Inc | Combination drug and method for relieving gastroenteric symptom arising from nonsteroidal anti inflammatory drug |
| JP2000095682A (en) * | 1998-07-22 | 2000-04-04 | Yamanouchi Pharmaceut Co Ltd | Solid preparation containing slightly soluble nsaids |
| JP2001247481A (en) * | 2000-03-06 | 2001-09-11 | Taisho Pharmaceut Co Ltd | Pharmaceutical composition |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1212778B (en) * | 1983-10-07 | 1989-11-30 | Lisapharma Spa | PHARMACEUTICAL COMPOSITIONS ANTI-INFLAMMATORY AND / OR ANALGESIC ADAPTERITY, NON ULCEROGENE. |
| JP2906528B2 (en) * | 1990-02-14 | 1999-06-21 | 大正製薬株式会社 | Solid preparation for internal use with enhanced absorption |
| WO1999012524A1 (en) * | 1997-09-11 | 1999-03-18 | Nycomed Danmark A/S | MODIFIED RELEASE MULTIPLE-UNITS COMPOSITIONS OF NON-STEROID ANTI-INFLAMMATORY DRUG SUBSTANCES (NSAIDs) |
| PT1109534E (en) * | 1998-09-10 | 2003-06-30 | Nycomed Danmark As | PHARMACEUTICAL COMPOUNDS FOR QUICK RELEASE PHARMACOSES |
-
2004
- 2004-07-03 WO PCT/EP2004/007264 patent/WO2005004915A2/en not_active Ceased
- 2004-07-03 JP JP2006518101A patent/JP2009513512A/en active Pending
-
2011
- 2011-10-06 JP JP2011222068A patent/JP2012021025A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04230330A (en) * | 1990-07-03 | 1992-08-19 | Mcneil Ppc Inc | Combination drug and method for relieving gastroenteric symptom arising from nonsteroidal anti inflammatory drug |
| JP2000095682A (en) * | 1998-07-22 | 2000-04-04 | Yamanouchi Pharmaceut Co Ltd | Solid preparation containing slightly soluble nsaids |
| JP2001247481A (en) * | 2000-03-06 | 2001-09-11 | Taisho Pharmaceut Co Ltd | Pharmaceutical composition |
Non-Patent Citations (1)
| Title |
|---|
| JPN6013041330; Ｃｌｉｎａｒｄ，Ｆ． ｅｔ ａｌ: 'Ｎｏｎ-ｓｔｅｒｏｉｄａｌ ａｎｔｉ-ｉｎｆｌａｍｍａｔｏｒｙ ａｎｄ ｃｙｔｏｐｒｏｔｅｃｔｉｖｅ ｄｒｕｇ ｃｏ-ｐｒｅｓｃｒｉｐｔｉｏｎ ｉｎ ｇｅｎｅｒａｌ ｐｒａｃｔｉｃｅ' Ｅｕｒ Ｊ Ｃｌｉｎ Ｐｈａｒｍａｃｏｌ Ｖｏｌ．５７, 2001, ｐ．７３７-７４３ * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020262618A1 (en) | 2019-06-28 | 2020-12-30 | Ssp Co., Ltd. | Meloxicam-containing granulated product |
| JP2021008412A (en) * | 2019-06-28 | 2021-01-28 | エスエス製薬株式会社 | Granulated product containing meloxicam |
| JP7348703B2 (en) | 2019-06-28 | 2023-09-21 | エスエス製薬株式会社 | Meloxicam-containing granules |
| JP2021054728A (en) * | 2019-09-27 | 2021-04-08 | 興和株式会社 | Pharmaceutical |
| JP2021107337A (en) * | 2019-12-27 | 2021-07-29 | ライオン株式会社 | Oral pharmaceutical formulation and solid pharmaceutical formulation |
| JP7515253B2 (en) | 2019-12-27 | 2024-07-12 | ライオン株式会社 | Solid pharmaceutical preparations |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005004915A3 (en) | 2005-03-17 |
| JP2009513512A (en) | 2009-04-02 |
| WO2005004915A2 (en) | 2005-01-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2012021025A (en) | Composition comprising meloxicam | |
| EP1755561B1 (en) | Multi-layer tablet comprising non-steroidal anti-inflammatory drugs decongestants and non-sedating antihistamines | |
| JP6226916B2 (en) | Pharmaceutical composition | |
| KR100490075B1 (en) | Oral Pharmaceutical Dosage Forms Comprising a Proton Pump Inhibitor and an Antacid Agent or Alginate | |
| RU2423975C2 (en) | Solid medication of olmesartan medoxomil and amlodipine | |
| CA2527368A1 (en) | Pharmaceutical composition | |
| EP0550083B1 (en) | Medicaments for treating inflammatory conditions or for analgesia containing a NSAID and ranitidine bismuth citrate | |
| KR20030045035A (en) | Oral fast-melt formulation of a cyclooxygenase-2 inhibitor | |
| US20050038018A1 (en) | Meloxicam compositions | |
| AU7397194A (en) | H2 antagonist-gastrointestinal motility agent combinations | |
| WO2005094832A1 (en) | Compositions comprising meloxicam | |
| JPS6241646B2 (en) | ||
| ZA200504908B (en) | Compositions of non-steroidal anti-inflammatory drugs decongestants and anti-histamines | |
| JP2008501655A (en) | Meloxicam-containing composition | |
| AU2004283047B2 (en) | Pharmaceutical composition comprising a selective I1 imidazoline receptor agonist and an angiotensin II receptor blocker | |
| JP5241510B2 (en) | Solid preparation | |
| AU2018347990A1 (en) | Bi-layer pharmaceutical tablet formulation | |
| WO1995001780A1 (en) | H2 antagonist-alginate combinations | |
| WO1995001792A1 (en) | H2 antagonist-antihistamine combinations | |
| JP4913359B2 (en) | Ibuprofen-containing pharmaceutical composition | |
| CN117999069A (en) | Pediatric formulations of ferric citrate | |
| CA2684171C (en) | Use of 4-cyclopropylmethoxy-n-(3,5-dichloro-1-oxidopyridin-4-yl)-5-(methoxy)pyridine-2-carboxamide for the treatment of cranial traumas | |
| JP2001247481A (en) | Pharmaceutical composition | |
| WO2006006577A1 (en) | Loxoprofen-containing composition for oral administration | |
| RU2707286C1 (en) | Pharmaceutical antifungal composition based on a chlorophenylbutanedione derivative and a method for production thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111104 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20111104 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130826 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20131113 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131118 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140226 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140421 |