JP2021054728A - Pharmaceutical - Google Patents
Pharmaceutical Download PDFInfo
- Publication number
- JP2021054728A JP2021054728A JP2019176879A JP2019176879A JP2021054728A JP 2021054728 A JP2021054728 A JP 2021054728A JP 2019176879 A JP2019176879 A JP 2019176879A JP 2019176879 A JP2019176879 A JP 2019176879A JP 2021054728 A JP2021054728 A JP 2021054728A
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- JP
- Japan
- Prior art keywords
- mass
- group
- component
- packaging
- meloxicam
- 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
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- 150000003839 salts Chemical class 0.000 claims abstract description 108
- 239000012453 solvate Substances 0.000 claims abstract description 93
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 73
- 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 claims abstract description 69
- 229960001929 meloxicam Drugs 0.000 claims abstract description 67
- 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 claims abstract description 26
- LSNWBKACGXCGAJ-UHFFFAOYSA-N ampiroxicam Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)OCC)=C1C(=O)NC1=CC=CC=N1 LSNWBKACGXCGAJ-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229950011249 ampiroxicam Drugs 0.000 claims abstract description 24
- 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 claims abstract description 24
- 229960002202 lornoxicam Drugs 0.000 claims abstract description 24
- 229960002702 piroxicam Drugs 0.000 claims abstract description 22
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000004806 packaging method and process Methods 0.000 claims description 79
- -1 proxanthine Chemical compound 0.000 claims description 54
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims description 40
- 229960001948 caffeine Drugs 0.000 claims description 27
- 239000003814 drug Substances 0.000 claims description 20
- 229940079593 drug Drugs 0.000 claims description 18
- 239000002552 dosage form Substances 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 15
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 claims description 15
- QUNWUDVFRNGTCO-UHFFFAOYSA-N 1,7-dimethylxanthine Chemical compound N1C(=O)N(C)C(=O)C2=C1N=CN2C QUNWUDVFRNGTCO-UHFFFAOYSA-N 0.000 claims description 14
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 14
- 229940127557 pharmaceutical product Drugs 0.000 claims description 14
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 claims description 14
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims description 13
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims description 13
- 239000008187 granular material Substances 0.000 claims description 13
- 239000007787 solid Substances 0.000 claims description 13
- 239000002775 capsule Substances 0.000 claims description 12
- 239000000843 powder Substances 0.000 claims description 11
- 229960002819 diprophylline Drugs 0.000 claims description 7
- KSCFJBIXMNOVSH-UHFFFAOYSA-N dyphylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1N(CC(O)CO)C=N2 KSCFJBIXMNOVSH-UHFFFAOYSA-N 0.000 claims description 7
- 239000006187 pill Substances 0.000 claims description 7
- 229960004559 theobromine Drugs 0.000 claims description 7
- 229960000278 theophylline Drugs 0.000 claims description 7
- 238000002845 discoloration Methods 0.000 abstract description 35
- 238000000034 method Methods 0.000 abstract description 34
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 29
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 29
- 239000000395 magnesium oxide Substances 0.000 description 26
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 26
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 26
- 239000003826 tablet Substances 0.000 description 25
- 239000011521 glass Substances 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 239000002244 precipitate Substances 0.000 description 17
- 239000000203 mixture Substances 0.000 description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 14
- 229910052782 aluminium Inorganic materials 0.000 description 14
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 14
- KSUUMAWCGDNLFK-UHFFFAOYSA-N apronal Chemical compound C=CCC(C(C)C)C(=O)NC(N)=O KSUUMAWCGDNLFK-UHFFFAOYSA-N 0.000 description 14
- 229960004459 apronal Drugs 0.000 description 14
- 229940008027 aluminum hydroxide / magnesium carbonate Drugs 0.000 description 13
- 150000007514 bases Chemical class 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 13
- 229910052751 metal Inorganic materials 0.000 description 13
- 239000002184 metal Chemical class 0.000 description 13
- 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 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 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 description 12
- 239000011888 foil Substances 0.000 description 11
- 239000004800 polyvinyl chloride Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 239000005022 packaging material Substances 0.000 description 10
- 229920000915 polyvinyl chloride Polymers 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 238000003860 storage Methods 0.000 description 10
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 9
- 239000000499 gel Substances 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 150000002894 organic compounds Chemical class 0.000 description 9
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 8
- 235000006886 Zingiber officinale Nutrition 0.000 description 8
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 8
- 229940024545 aluminum hydroxide Drugs 0.000 description 8
- 239000005025 cast polypropylene Substances 0.000 description 8
- 235000008397 ginger Nutrition 0.000 description 8
- 238000005469 granulation Methods 0.000 description 8
- 230000003179 granulation Effects 0.000 description 8
- 150000002484 inorganic compounds Chemical class 0.000 description 8
- 229910010272 inorganic material Inorganic materials 0.000 description 8
- 239000011777 magnesium Substances 0.000 description 8
- 229910052749 magnesium Inorganic materials 0.000 description 8
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 8
- 239000000347 magnesium hydroxide Substances 0.000 description 8
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 8
- KBJPBSNKRUDROY-UHFFFAOYSA-N n-carbamoyl-3-methylbutanamide Chemical class CC(C)CC(=O)NC(N)=O KBJPBSNKRUDROY-UHFFFAOYSA-N 0.000 description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 7
- BWZOPYPOZJBVLQ-UHFFFAOYSA-K aluminium glycinate Chemical compound O[Al+]O.NCC([O-])=O BWZOPYPOZJBVLQ-UHFFFAOYSA-K 0.000 description 7
- 229940043673 aluminum hydroxide / calcium carbonate Drugs 0.000 description 7
- 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 description 7
- 229940015826 dihydroxyaluminum aminoacetate Drugs 0.000 description 7
- 229960001545 hydrotalcite Drugs 0.000 description 7
- 229910001701 hydrotalcite Inorganic materials 0.000 description 7
- 239000011591 potassium Substances 0.000 description 7
- 229910052700 potassium Inorganic materials 0.000 description 7
- 229960003975 potassium Drugs 0.000 description 7
- GRLPQNLYRHEGIJ-UHFFFAOYSA-J potassium aluminium sulfate Chemical compound [Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRLPQNLYRHEGIJ-UHFFFAOYSA-J 0.000 description 7
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 6
- 235000016639 Syzygium aromaticum Nutrition 0.000 description 6
- 239000000654 additive Substances 0.000 description 6
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 6
- 150000001342 alkaline earth metals Chemical class 0.000 description 6
- 229910000019 calcium carbonate Inorganic materials 0.000 description 6
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 6
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 6
- 239000001095 magnesium carbonate Substances 0.000 description 6
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 6
- 235000014380 magnesium carbonate Nutrition 0.000 description 6
- 229960000869 magnesium oxide Drugs 0.000 description 6
- 229920005989 resin Polymers 0.000 description 6
- 235000015424 sodium Nutrition 0.000 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 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 229910001868 water Inorganic materials 0.000 description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- 239000004471 Glycine Substances 0.000 description 5
- 239000004698 Polyethylene Substances 0.000 description 5
- LCHGOKZNRDAXEK-UHFFFAOYSA-N caffeine monohydrate Chemical compound O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C LCHGOKZNRDAXEK-UHFFFAOYSA-N 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 239000007884 disintegrant Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 229960002449 glycine Drugs 0.000 description 5
- 229920001903 high density polyethylene Polymers 0.000 description 5
- 239000004700 high-density polyethylene Substances 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 229920001684 low density polyethylene Polymers 0.000 description 5
- 239000004702 low-density polyethylene Substances 0.000 description 5
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 5
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 244000061408 Eugenia caryophyllata Species 0.000 description 4
- GLZPCOQZEFWAFX-UHFFFAOYSA-N Geraniol Chemical compound CC(C)=CCCC(C)=CCO GLZPCOQZEFWAFX-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 208000002193 Pain Diseases 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 241000234314 Zingiber Species 0.000 description 4
- 244000273928 Zingiber officinale Species 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 150000001340 alkali metals Chemical class 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 4
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 4
- 239000010227 chenpi Substances 0.000 description 4
- 238000007906 compression Methods 0.000 description 4
- 230000006835 compression Effects 0.000 description 4
- 239000000470 constituent Substances 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 4
- FAHBNUUHRFUEAI-UHFFFAOYSA-M hydroxidooxidoaluminium Chemical compound O[Al]=O FAHBNUUHRFUEAI-UHFFFAOYSA-M 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 238000013112 stability test Methods 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- AKNNEGZIBPJZJG-MSOLQXFVSA-N (-)-noscapine Chemical compound CN1CCC2=CC=3OCOC=3C(OC)=C2[C@@H]1[C@@H]1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-MSOLQXFVSA-N 0.000 description 3
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 241000723346 Cinnamomum camphora Species 0.000 description 3
- 244000000626 Daucus carota Species 0.000 description 3
- 235000002767 Daucus carota Nutrition 0.000 description 3
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- 239000004793 Polystyrene Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 229920003144 amino alkyl methacrylate copolymer Polymers 0.000 description 3
- 239000003907 antipyretic analgesic agent Substances 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 229930008380 camphor Natural products 0.000 description 3
- 229960000846 camphor Drugs 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- 239000004359 castor oil Substances 0.000 description 3
- 235000019438 castor oil Nutrition 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 235000009508 confectionery Nutrition 0.000 description 3
- 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 description 3
- XLIDPNGFCHXNGX-UHFFFAOYSA-N dialuminum;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[O-2].[O-2].[Al+3].[Al+3].[Si+4] XLIDPNGFCHXNGX-UHFFFAOYSA-N 0.000 description 3
- 235000019700 dicalcium phosphate Nutrition 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 235000012054 meals Nutrition 0.000 description 3
- 150000002739 metals Chemical class 0.000 description 3
- GKRZNOGGALENQJ-UHFFFAOYSA-N n-carbamoylacetamide Chemical compound CC(=O)NC(N)=O GKRZNOGGALENQJ-UHFFFAOYSA-N 0.000 description 3
- 229960004708 noscapine Drugs 0.000 description 3
- 239000006191 orally-disintegrating tablet Substances 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 229920000728 polyester Polymers 0.000 description 3
- 229920000573 polyethylene Polymers 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 239000005033 polyvinylidene chloride Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 239000011877 solvent mixture Substances 0.000 description 3
- 239000004575 stone Substances 0.000 description 3
- 229940098465 tincture Drugs 0.000 description 3
- 229920002554 vinyl polymer Polymers 0.000 description 3
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 2
- 208000008035 Back Pain Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
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Landscapes
- Medicinal Preparation (AREA)
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Abstract
Description
本発明は、医薬品等に関する。 The present invention relates to pharmaceutical products and the like.
アンピロキシカム、ピロキシカム、メロキシカム、ロルノキシカム等のオキシカム系NSAIDsは優れた解熱鎮痛作用を示し、関節リウマチや変形性関節症、腰痛症、頸肩腕症候群、肩関節周囲炎などに効能効果を有する医薬品として利用されている(非特許文献1〜4)。
これらのオキシカム系NSAIDsのうち、アンピロキシカム(化学名:4−[1−(acetyloxy)ethoxy]−2−methyl−3−[(pyridin−2−yl)carbamoyl]−1,2−dihydro−1,2−benzothiazine−1,1−diium−1,1−bis(olate))は、下記式
Oxicam-based NSAIDs such as ampiroxicam, piroxicam, meloxicam, and lornoxicam show excellent antipyretic and analgesic effects, and are used as drugs with efficacy effects on rheumatoid arthritis, osteoarthritis, lumbar pain, cervicobrachial syndrome, and periarthritis shoulder. (Non-Patent Documents 1 to 4).
Among these oxicam-based NSAIDs, ampiroxicam (chemical name: 4- [1- (acetoxy) etoxy] -2-methyl-3-[(pyridin-2-yl) carbamoyl] -1,2-dihydro-1, 2-benzothiazine-1,1-diium-1,1-bis (late)) is expressed by the following formula.
で表される化合物である。また、ピロキシカム(化学名:4−hydroxy−2−methyl−3−[(pyridin−2−yl)carbamoyl]−1,2−dihydro−1,2−benzothiazine−1,1−diium−1,1−bis(olate))は、下記式 It is a compound represented by. In addition, piroxicam (chemical name: 4-hydroxy-2-methyl-3-[(pyridin-2-yl) carbamoyl] -1,2-dihydro-1,2-benzothiazine-1,1-diium-1,1- bis (late)) is the following formula
で表される化合物である。また、メロキシカム(化学名:4−hydroxy−2−methyl−3−[(5−methyl−1,3−thiazol−2−yl)carbamoyl]−1,2−dihydro−1,2−benzothiazine−1,1−diium−1,1−bis(olate))は、下記式 It is a compound represented by. In addition, meloxicam (chemical name: 4-hydroxy-2-methyl-3-[(5-methyl-1,3-thiazol-2-yl) carbamoyl] -1,2-dihydro-1,2-benzothiazine-1, 1-diium-1,1-bis (late)) is expressed by the following formula.
で表される化合物である。また、ロルノキシカム(化学名:6−chloro−4−hydroxy−2−methyl−N−(2−pyridyl)−2H−thieno [2, 3−e]−1, 2−thiazine−3−carboxamide 1, 1−dioxide)は、下記式 It is a compound represented by. In addition, lornoxicam (chemical name: 6-chloro-4-hydroxy-2-methyl-N- (2-pyridyl) -2H-thiono [2, 3-e] -1, 2-thiazine-3-carboxamide 1, 1 −dioxide) is the following formula
で表される化合物である。これらの化合物はいずれも含窒素複素環と環縮合チアジンジオキシドとがアミド結合した構造を有し、化学構造が相互に極めて類似している。 It is a compound represented by. All of these compounds have a structure in which a nitrogen-containing heterocycle and a ring-condensed thiazinedioxide are amide-bonded, and their chemical structures are very similar to each other.
上記の状況の下、本発明者が、オキシカム系NSAIDsを含む医薬を開発するため鋭意検討したところ、アンピロキシカム、ピロキシカム、メロキシカム、ロルノキシカム及びそれらの塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を高温条件下で長期間保存すると、意外にも、時間の経過に伴い変色が生じることが判明した。
従って、本発明は、アンピロキシカム、ピロキシカム、メロキシカム、ロルノキシカム及びそれらの塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を高温条件下で長期間保存した場合に生じ得る変色を抑制する技術を提供することを課題とする。
Under the above circumstances, the present inventor diligently studied to develop a drug containing oxicam-based NSAIDs, and the present invention was selected from the group consisting of ampiroxicam, piroxicam, meloxicam, lornoxicam, salts thereof, and solvates thereof. Surprisingly, it was found that discoloration occurs over time when one or more species are stored for a long period of time under high temperature conditions.
Therefore, the present invention suppresses discoloration that may occur when one or more selected from the group consisting of ampiroxicam, piroxicam, meloxicam, lornoxicam and salts thereof, and solvates thereof are stored for a long period of time under high temperature conditions. The challenge is to provide technology.
そこで、本発明者は、上記課題を解決すべく鋭意検討したところ、アンピロキシカム、ピロキシカム、メロキシカム、ロルノキシカム及びそれらの塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上(以下、本明細書において「成分(A)」と称することがある。)に、以下の成分1〜3のうちのいずれか(以下、本明細書において、成分1、2、3をそれぞれ「成分(B−1)」、「成分(B−2)」、「成分(B−3)」と称し、また、成分(B−1)、(B−2)及び(B−3)よりなる群から選ばれる1種以上を「成分(B)」と称することがある。):
1 無水カフェインなどの、キサンチン誘導体
2 酸化マグネシウム、水酸化アルミニウムゲルなどの、塩基性化合物
3 アリルイソプロピルアセチル尿素などの、イソバレリル尿素誘導体
Therefore, as a result of diligent studies to solve the above problems, the present inventor has made one or more selected from the group consisting of ampiroxicam, piroxicam, meloxicam, lornoxicam, salts thereof, and solvates thereof (hereinafter, the present specification). In the book, "component (A)" may be referred to as "component (A)"), and any one of the following components 1 to 3 (hereinafter, in the present specification, components 1, 2 and 3 are referred to as "component (B-1)", respectively. ) ”,“ Component (B-2) ”,“ Component (B-3) ”, and selected from the group consisting of components (B-1), (B-2) and (B-3) 1 Seeds and above may be referred to as "ingredient (B)") :.
1 Xanthine derivatives such as anhydrous caffeine 2 Basic compounds such as magnesium oxide and aluminum hydroxide gel 3 Isovaleryl urea derivatives such as allylisopropylacetylurea
を共存せしめ、かつ、ビン包装やPTP包装等の気密包装体に収容することによって、アンピロキシカム、ピロキシカム、メロキシカム、ロルノキシカム及びそれらの塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を高温条件下で長期間保存した場合に生じ得る変色が抑制され、これらの成分を安定化できることを見出し、本発明を完成した。 At least one selected from the group consisting of ampiroxicam, piroxicam, meloxicam, lornoxicam, salts thereof, and solvates thereof by coexisting with each other and housing in an airtight package such as bottle packaging or PTP packaging. We have found that discoloration that can occur when stored for a long period of time under high temperature conditions can be suppressed and these components can be stabilized, and the present invention has been completed.
すなわち、本発明は、次の成分(A)及び(B):
(A)アンピロキシカム、ピロキシカム、メロキシカム、ロルノキシカム及びそれらの塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上;
(B)次の成分(B−1)〜(B−3)よりなる群から選ばれる1種以上;
(B−1)キサンチン誘導体
(B−2)塩基性化合物
(B−3)イソバレリル尿素誘導体
を含有する医薬組成物が、気密包装体に収容されてなる医薬品を提供するものである。
That is, the present invention describes the following components (A) and (B):
(A) One or more selected from the group consisting of ampiroxicam, piroxicam, meloxicam, lornoxicam and salts thereof, and solvates thereof;
(B) One or more selected from the group consisting of the following components (B-1) to (B-3);
(B-1) Xanthine Derivative (B-2) Basic Compound (B-3) A pharmaceutical composition containing an isovaleryl urea derivative is provided in an airtight package.
本発明によれば、アンピロキシカム、ピロキシカム、メロキシカム、ロルノキシカム及びそれらの塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を高温条件下で長期間保存した場合の変色が抑制され、保存安定性に優れる医薬品を提供することができる。 According to the present invention, discoloration when one or more selected from the group consisting of ampiroxicam, piroxicam, meloxicam, lornoxicam and salts thereof, and solvates thereof is stored for a long period of time under high temperature conditions is suppressed and stored. It is possible to provide a drug having excellent stability.
<成分(A)>
本明細書において「アンピロキシカム、ピロキシカム、メロキシカム、ロルノキシカム及びそれらの塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上」には、アンピロキシカム、ピロキシカム、メロキシカム、ロルノキシカムそのもののほか、それらの薬学上許容される塩、さらにはアンピロキシカム、ピロキシカム、メロキシカム、ロルノキシカムそのものやそれらの薬学上許容される塩と、水やアルコール等との溶媒和物も含まれる。ここで、塩としては、薬学上許容される塩であれば特に限定されず、例えば、塩酸塩、硫酸塩、硝酸塩、フッ化水素酸塩、臭化水素酸塩等の無機酸塩;酢酸塩、酒石酸塩、乳酸塩、クエン酸塩、フマル酸塩、マレイン酸塩、コハク酸塩、メタンスルホン酸塩、エタンスルホン酸塩、ベンゼンスルホン酸塩、トルエンスルホン酸塩、ナフタレンスルホン酸塩、カンファースルホン酸塩等の有機酸塩;ナトリウム塩、カリウム塩、リチウム塩、カルシウム塩、マグネシウム塩等の金属塩;アンモニア、トリメチルアミン、トリエチルアミン、ピリジン、コリジン、ルチジン等のアミン塩;リシン、アルギニン等の有機塩基塩等が挙げられる。
なお、これらは1種単独で、又は2種以上を適宜組み合わせて使用できる。
<Ingredient (A)>
In the present specification, "one or more selected from the group consisting of ampiroxicam, piroxicam, meloxicam, lornoxicam and salts thereof, and their solvates" includes ampiroxicam, piroxicam, meloxicam, lornoxicam itself, and their respective substances. It also includes pharmaceutically acceptable salts, as well as ampiroxicam, piroxicam, meloxicam, lornoxicam itself, and pharmaceutically acceptable salts thereof, and a solvent mixture of water, alcohol, or the like. Here, the salt is not particularly limited as long as it is a pharmaceutically acceptable salt, and for example, an inorganic salt such as a hydrochloride, a sulfate, a nitrate, a hydrofluoride salt, or a hydrobromide; an acetate salt. , Tartrate, lactate, citrate, fumarate, maleate, succinate, methanesulfonate, ethanesulfonate, benzenesulfonate, toluenesulfonate, naphthalenesulfonate, camphorsulfone Organic acid salts such as acid salts; metal salts such as sodium salt, potassium salt, lithium salt, calcium salt, magnesium salt; amine salts such as ammonia, trimethylamine, triethylamine, pyridine, colidin, rutidin; organic bases such as lysine and arginine. Examples include salt.
It should be noted that these can be used alone or in combination of two or more.
成分(A)としては、アンピロキシカム、ピロキシカム、メロキシカム及びロルノキシカムよりなる群から選ばれる1種以上が好ましく、メロキシカムが特に好ましい。
なお、成分(A)は公知の成分であり、公知の方法により製造できるほか、市販のものを使用してもよい。市販品としては例えば、メロキシカム(Hwail Pharmaceutical Co., Ltd.)などが挙げられる。
As the component (A), one or more selected from the group consisting of ampiroxicam, piroxicam, meloxicam and lornoxicam is preferable, and meloxicam is particularly preferable.
The component (A) is a known component and can be produced by a known method, or a commercially available product may be used. Examples of commercially available products include meloxicam (Hwail Pharmaceutical Co., Ltd.) and the like.
医薬組成物における成分(A)の含有量は特に限定されず、服用者の性別、年齢、症状等に応じて適宜検討して決定すればよい。例えば、1日あたり、成分(A)をフリー体換算で1〜100mg、より好適には2〜75mg、特に好適には3〜50mg服用できる量を含有せしめることができる。
中でも、成分(A)としてアンピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、1日あたり、そのフリー体換算で合計して5〜75mg、より好適には10〜50mg、特に好適には15〜30mg服用できる量を含有せしめることができる。
また、成分(A)としてピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、1日あたり、そのフリー体換算で合計して2〜75mg、より好適には5〜50mg、特に好適には10〜30mg服用できる量を含有せしめることができる。
また、成分(A)としてメロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、1日あたり、そのフリー体換算で合計して1〜50mg、より好適には3〜30mg、特に好適には5〜15mg服用できる量を含有せしめることができる。
さらに、成分(A)としてロルノキシカム及びその塩ならびにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、1日あたり、そのフリー体換算で合計して1〜30mg、より好適には3〜20mg、特に好適には5〜10mg服用できる量を含有せしめることができる。
The content of the component (A) in the pharmaceutical composition is not particularly limited, and may be appropriately examined and determined according to the sex, age, symptoms, etc. of the user. For example, the component (A) can be contained in an amount that can be taken in an amount of 1 to 100 mg, more preferably 2 to 75 mg, and particularly preferably 3 to 50 mg per day in terms of free form.
Above all, when one or more selected from the group consisting of ampiroxicam, a salt thereof and a solvate thereof is used as the component (A), the total amount is 5 to 75 mg per day in terms of free form. It can contain an amount of 10 to 50 mg, particularly preferably 15 to 30 mg.
Further, when one or more selected from the group consisting of piroxicam, a salt thereof and a solvate thereof are used as the component (A), a total of 2 to 75 mg per day in terms of free form is more preferable. Can contain 5 to 50 mg, particularly preferably 10 to 30 mg.
Further, when one or more selected from the group consisting of meloxicam, a salt thereof, and a solvate thereof are used as the component (A), a total of 1 to 50 mg per day in terms of free form is more preferable. Can contain 3 to 30 mg, particularly preferably 5 to 15 mg.
Further, when one or more selected from the group consisting of lornoxicam, a salt thereof and a solvate thereof are used as the component (A), a total of 1 to 30 mg per day in terms of free form is more preferable. Can contain 3 to 20 mg, particularly preferably 5 to 10 mg.
本発明においては、成分(A)をフリー体換算で医薬組成物全質量に対して合計で0.05〜70質量%含有するのが好ましく、0.1〜60質量%含有するのがより好ましく、0.5〜50質量%含有するのが特に好ましい。
中でも、成分(A)としてアンピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、そのフリー体換算で医薬組成物全質量に対して合計で1〜75質量%含有するのが好ましく、2〜50質量%含有するのがより好ましく、4〜30質量%含有するのが特に好ましい。
また、成分(A)としてピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、そのフリー体換算で医薬組成物全質量に対して合計で0.5〜70質量%含有するのが好ましく、1〜50質量%含有するのがより好ましく、3〜30質量%含有するのが特に好ましい。
また、成分(A)としてメロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、そのフリー体換算で医薬組成物全質量に対して合計で0.5〜50質量%含有するのが好ましく、1〜30質量%含有するのがより好ましく、2〜10質量%含有するのが特に好ましい。
さらに、成分(A)としてロルノキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、そのフリー体換算で医薬組成物全質量に対して合計で0.1〜30質量%含有するのが好ましく、0.5〜20質量%含有するのがより好ましく、1〜10質量%含有するのが特に好ましい。
In the present invention, the component (A) is preferably contained in a total amount of 0.05 to 70% by mass, more preferably 0.1 to 60% by mass, based on the total mass of the pharmaceutical composition in terms of free form. , 0.5 to 50% by mass is particularly preferable.
Above all, when one or more selected from the group consisting of ampiroxicam, a salt thereof and a solvate thereof is used as the component (A), the total mass of the pharmaceutical composition is 1 to 1 in terms of its free form. It is preferably contained in an amount of 75% by mass, more preferably 2 to 50% by mass, and particularly preferably 4 to 30% by mass.
In addition, when one or more selected from the group consisting of piroxicam, a salt thereof, and a solvate thereof are used as the component (A), the total mass of the pharmaceutical composition is 0.5 in terms of its free form. It is preferably contained in an amount of ~ 70% by mass, more preferably 1 to 50% by mass, and particularly preferably 3 to 30% by mass.
In addition, when one or more selected from the group consisting of meloxicam, a salt thereof, and a solvate thereof are used as the component (A), the total mass of the pharmaceutical composition is 0.5 in terms of its free form. It is preferably contained in an amount of ~ 50% by mass, more preferably 1 to 30% by mass, and particularly preferably 2 to 10% by mass.
Furthermore, when one or more selected from the group consisting of lornoxicam, a salt thereof, and a solvate thereof are used as the component (A), the total mass of the pharmaceutical composition is 0.1 in terms of its free form. It is preferably contained in an amount of ~ 30% by mass, more preferably 0.5 to 20% by mass, and particularly preferably 1 to 10% by mass.
<成分(B−1)>
本明細書において「キサンチン誘導体」としては、下記一般式(1)で表される化合物及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上が好ましい。
<Ingredient (B-1)>
In the present specification, the "xanthine derivative" is preferably one or more selected from the group consisting of the compound represented by the following general formula (1), a salt thereof, and a solvate thereof.
[式(1)中、R1及びR2は各々独立して水素原子又はメチル基を示し、R3は水素原子、メチル基、モノヒドロキシプロピル基又はジヒドロキシプロピル基を示す。] [In formula (1), R 1 and R 2 each independently represent a hydrogen atom or a methyl group, and R 3 represents a hydrogen atom, a methyl group, a monohydroxypropyl group or a dihydroxypropyl group. ]
式(1)中、R3において、モノヒドロキシプロピル基としては、2−ヒドロキシプロピル基が好ましい。また、ジヒドロキシプロピル基としては、2,3−ジヒドロキシプロピル基が好ましい。 In formula (1), in R 3 , the monohydroxypropyl group is preferably a 2-hydroxypropyl group. The dihydroxypropyl group is preferably a 2,3-dihydroxypropyl group.
なお、上記一般式(1)において、
(1)R1がメチル基であり、R2がメチル基であり、R3がメチル基であるものは、カフェインを意味するものである。
(2)R1がメチル基であり、R2がメチル基であり、R3が水素原子であるものは、テオフィリンを意味するものである。
(3)R1が水素原子であり、R2がメチル基であり、R3がメチル基であるものは、テオブロミンを意味するものである。
(4)R1がメチル基であり、R2が水素原子であり、R3がメチル基であるものは、パラキサンチンを意味するものである。
(5)R1がメチル基であり、R2がメチル基であり、R3が2−ヒドロキシプロピル基であるものは、プロキシフィリンを意味するものである。
(6)R1がメチル基であり、R2がメチル基であり、R3が2,3−ジヒドロキシプロピル基であるものは、ジプロフィリンを意味するものである。
In the above general formula (1),
(1) When R 1 is a methyl group, R 2 is a methyl group, and R 3 is a methyl group, it means caffeine.
(2) When R 1 is a methyl group, R 2 is a methyl group, and R 3 is a hydrogen atom, it means theophylline.
(3) When R 1 is a hydrogen atom, R 2 is a methyl group, and R 3 is a methyl group, it means theobromine.
(4) When R 1 is a methyl group, R 2 is a hydrogen atom, and R 3 is a methyl group, it means paraxanthine.
(5) When R 1 is a methyl group, R 2 is a methyl group, and R 3 is a 2-hydroxypropyl group, it means proxiphyrin.
(6) When R 1 is a methyl group, R 2 is a methyl group, and R 3 is a 2,3-dihydroxypropyl group, it means diprophylline.
キサンチン誘導体としては、上記の一般式(1)で表される化合物そのもののほか、その薬学上許容される塩(例えば、複塩を形成したもの(安息香酸ナトリウムカフェイン(安息香酸ナトリウムとカフェインの複塩)、アミノフィリン(テオフィリンとエチレンジアミンとの複塩))等)、一般式(1)で表される化合物又はその塩と水やアルコール等との溶媒和物を用いることもでき、これらも「キサンチン誘導体」に包含され、上述の化合物(カフェイン、テオフィリン、テオブロミン、パラキサンチン、プロキシフィリン及びジプロフィリン)には、当該化合物、その塩やそれらの溶媒和物も包含される。なお、本発明においては、これらキサンチン誘導体のうち、1種又は2種以上を用いることができる。
なお、成分(B−1)は公知の成分であり、本発明においては、公知の方法により製造したもののほか、市販のものを用いることができる。市販品としては例えば、無水カフェイン((株)静岡カフェイン工業所)などが挙げられる。
As the xanthine derivative, in addition to the compound itself represented by the above general formula (1), a pharmaceutically acceptable salt thereof (for example, a compound salt formed (sodium benzoate caffeine (sodium benzoate and caffeine)) , Aminophylline (complex salt of theophylline and ethylenediamine), etc.), a compound represented by the general formula (1) or a solvent mixture of a salt thereof and water, alcohol, etc. can also be used. The above-mentioned compounds (caffeine, theophylline, theobromine, paraxanthine, proxanthine and diprophylline) included in the "xanthine derivative" also include the compound, a salt thereof and a solvent mixture thereof. In the present invention, one or more of these xanthine derivatives can be used.
The component (B-1) is a known component, and in the present invention, a commercially available product can be used in addition to the product produced by a known method. Examples of commercially available products include anhydrous caffeine (Shizuoka Caffeine Industry Co., Ltd.).
成分(B−1)としては、成分(A)の変色を抑制する観点から、カフェイン、テオフィリン、テオブロミン、パラキサンチン、プロキシフィリン、ジプロフィリン及びそれらの塩並びにそれらの溶媒和物よりなる群より選ばれる1種以上が好ましく、特に、カフェイン及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上が好ましい。当該カフェイン及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上としては、カフェイン水和物、無水カフェイン、安息香酸ナトリウムカフェイン及びクエン酸カフェインよりなる群から選ばれる1種以上が好ましく、カフェイン水和物、無水カフェイン及び安息香酸ナトリウムカフェインよりなる群から選ばれる1種以上が特に好ましい。 The component (B-1) is selected from the group consisting of caffeine, theophylline, theobromine, paraxanthine, proxanthine, diprophylline, salts thereof, and solvates thereof from the viewpoint of suppressing discoloration of the component (A). One or more of them are preferable, and one or more of them selected from the group consisting of caffeine, salts thereof, and solvates thereof are particularly preferable. One or more selected from the group consisting of the caffeine and its salts and their solvent products is selected from the group consisting of caffeine hydrate, anhydrous caffeine, sodium benzoate caffeine and caffeine citrate. One or more is preferable, and one or more selected from the group consisting of caffeine hydrate, anhydrous caffeine and sodium benzoate caffeine is particularly preferable.
医薬組成物における成分(B−1)の含有量は特に限定されず、適宜検討して決定すればよい。例えば、1日あたり、成分(B−1)をフリー体換算で10〜750mg、より好適には20〜500mg、特に好適には30〜300mg服用できる量を含有せしめることができる。
本発明においては、成分(A)の変色を抑制する観点から、成分(B−1)をフリー体換算で医薬組成物全質量に対して合計で2〜95質量%含有するのが好ましく、5〜90質量%含有するのがより好ましく、10〜85質量%含有するのが特に好ましい。
The content of the component (B-1) in the pharmaceutical composition is not particularly limited, and may be appropriately examined and determined. For example, the component (B-1) can be contained in an amount that can be taken in an amount of 10 to 750 mg, more preferably 20 to 500 mg, and particularly preferably 30 to 300 mg per day in terms of free form.
In the present invention, from the viewpoint of suppressing discoloration of the component (A), it is preferable that the component (B-1) is contained in a total amount of 2 to 95% by mass with respect to the total mass of the pharmaceutical composition in terms of free form. It is more preferably contained in an amount of ~ 90% by mass, and particularly preferably contained in an amount of 10 to 85% by mass.
医薬組成物における、成分(A)と成分(B−1)との含有質量比率は特に限定されないが、成分(A)の変色を抑制する観点から、成分(A)をそのフリー体換算で合計して1質量部に対し、成分(B−1)をそのフリー体換算で合計して0.1〜65質量部含有するのが好ましく、0.2〜50質量部含有するのがより好ましく、0.5〜40質量部含有するのが特に好ましい。
中でも、成分(A)としてアンピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、そのフリー体換算で合計して1質量部に対し、成分(B−1)をそのフリー体換算で合計して0.2〜40質量部含有するのが好ましく、0.5〜20質量部含有するのがより好ましく、1〜10質量部含有するのが特に好ましい。
また、成分(A)としてピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、そのフリー体換算で合計して1質量部に対し、成分(B−1)をそのフリー体換算で合計して0.5〜40質量部含有するのが好ましく、1〜30質量部含有するのがより好ましく、2〜20質量部含有するのが特に好ましい。
また、成分(A)としてメロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、そのフリー体換算で合計して1質量部に対し、成分(B−1)をそのフリー体換算で合計して1〜50質量部含有するのが好ましく、2〜40質量部含有するのがより好ましく、4〜30質量部含有するのが特に好ましい。
さらに、成分(A)としてロルノキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、そのフリー体換算で合計して1質量部に対し、成分(B−1)をそのフリー体換算で合計して2〜50質量部含有するのが好ましく、4〜40質量部含有するのがより好ましく、6〜35質量部含有するのが特に好ましい。
The mass ratio of the component (A) to the component (B-1) in the pharmaceutical composition is not particularly limited, but the component (A) is totaled in terms of its free form from the viewpoint of suppressing discoloration of the component (A). The total amount of the component (B-1) in terms of its free form is preferably 0.1 to 65 parts by mass, more preferably 0.2 to 50 parts by mass, based on 1 part by mass. It is particularly preferable to contain 0.5 to 40 parts by mass.
Above all, when one or more selected from the group consisting of ampiroxicam, a salt thereof and a solvate thereof is used as the component (A), the component (B) is based on 1 part by mass in total in terms of its free form. -1) is preferably contained in a total of 0.2 to 40 parts by mass, more preferably 0.5 to 20 parts by mass, and particularly preferably 1 to 10 parts by mass in terms of the free form. ..
When one or more selected from the group consisting of piroxicam, a salt thereof, and a solvate thereof are used as the component (A), the component (B-) is based on 1 part by mass in total in terms of its free form. 1) is preferably contained in a total of 0.5 to 40 parts by mass, more preferably 1 to 30 parts by mass, and particularly preferably 2 to 20 parts by mass in terms of the free form.
When one or more selected from the group consisting of meloxicam, a salt thereof, and a solvate thereof are used as the component (A), the component (B-) is based on 1 part by mass in total in terms of its free form. 1) is preferably contained in a total of 1 to 50 parts by mass, more preferably 2 to 40 parts by mass, and particularly preferably 4 to 30 parts by mass in terms of the free form.
Further, when one or more selected from the group consisting of lornoxicam, a salt thereof and a solvate thereof are used as the component (A), the component (B-) is based on 1 part by mass in total in terms of its free form. 1) is preferably contained in a total of 2 to 50 parts by mass, more preferably 4 to 40 parts by mass, and particularly preferably 6 to 35 parts by mass in terms of free form.
<成分(B−2)>
本明細書において「塩基性化合物」としては、例えば、マグネシウム、アルミニウム、カルシウム等のアルカリ土類金属及び/又は土類金属系塩基性無機化合物、ナトリウム、カリウム等のアルカリ金属系塩基性無機化合物、アミン系塩基性無機化合物等の塩基性無機化合物;マグネシウム、アルミニウム、カルシウム等のアルカリ土類金属及び/又は土類金属系塩基性有機化合物、ナトリウム、カリウム等のアルカリ金属系塩基性有機化合物、アミン系塩基性有機化合物等の塩基性有機化合物が挙げられる。
なお、これらは1種単独で、又は2種以上を適宜組み合わせて使用できる。
<Ingredient (B-2)>
In the present specification, the "basic compound" includes, for example, alkaline earth metals such as magnesium, aluminum and calcium and / or earth metal-based basic inorganic compounds, and alkali metal-based basic inorganic compounds such as sodium and potassium. Basic inorganic compounds such as amine-based basic inorganic compounds; alkaline earth metals such as magnesium, aluminum and calcium and / or earth metal-based basic organic compounds, alkali metal-based basic organic compounds such as sodium and potassium, amines Examples thereof include basic organic compounds such as system-based basic organic compounds.
It should be noted that these can be used alone or in combination of two or more.
上記塩基性無機化合物において、アルカリ土類金属及び/又は土類金属系塩基性無機化合物としては、例えば、ケイ酸マグネシウム、ケイ酸アルミン酸マグネシウム、ケイ酸マグネシウムアルミニウム、酸化マグネシウム、水酸化マグネシウム、水酸化マグネシウム・硫酸アルミニウムカリウムの共沈生成物、炭酸マグネシウム、合成ヒドロタルサイト、メタケイ酸アルミン酸マグネシウム、乾燥水酸化アルミニウムゲル、合成ケイ酸アルミニウム、合成ケイ酸アルミニウム・ヒドロキシプロピルスターチ・結晶セルロース、水酸化アルミナマグネシウム、水酸化アルミニウムゲル、水酸化アルミニウム・炭酸水素ナトリウム共沈生成物、水酸化アルミニウム・炭酸マグネシウム混合乾燥ゲル、水酸化アルミニウム・炭酸マグネシウム・炭酸カルシウム共沈生成物、ベントナイト、ケイ酸カルシウム、炭酸カルシウム、沈降炭酸カルシウム、リン酸水素カルシウム、無水リン酸水素カルシウム等のマグネシウム、アルミニウム及びカルシウムから選ばれる金属の無機塩等が挙げられる。
また、アルカリ金属系塩基性無機化合物としては、例えば、乾燥炭酸ナトリウム、水酸化ナトリウム、炭酸水素ナトリウム、炭酸ナトリウム水和物、ピロリン酸四ナトリウム、リン酸三ナトリウム、リン酸水素ナトリウム水和物、無水ピロリン酸ナトリウム、無水リン酸一水素ナトリウム、水酸化カリウム、炭酸水素カリウム、炭酸カリウム等のナトリウム及びカリウムから選ばれる金属の無機塩等が挙げられる。
Among the above-mentioned basic inorganic compounds, examples of the alkaline earth metal and / or the earth metal-based basic inorganic compound include magnesium silicate, magnesium silicate aluminumate, magnesium aluminum silicate, magnesium oxide, magnesium hydroxide, and water. Co-precipitated products of magnesium oxide and potassium aluminum sulfate, magnesium carbonate, synthetic hydrotalcite, magnesium aluminometasilicate, dry aluminum hydroxide gel, synthetic aluminum silicate, synthetic aluminum silicate, hydroxypropyl starch, crystalline cellulose, water Alumina oxide magnesium oxide, aluminum hydroxide gel, aluminum hydroxide / sodium hydrogen carbonate co-precipitated product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate co-precipitated product, bentonite, calcium silicate , Calcium carbonate, precipitated calcium carbonate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate and the like, and inorganic salts of metals selected from aluminum and calcium.
Examples of the alkali metal-based basic inorganic compound include dry sodium carbonate, sodium hydroxide, sodium hydrogen carbonate, sodium carbonate hydrate, tetrasodium pyrophosphate, trisodium phosphate, and sodium hydrogen phosphate hydrate. Examples thereof include anhydrous sodium pyrophosphate, anhydrous sodium monohydrogen phosphate, potassium hydroxide, potassium hydrogen carbonate, potassium carbonate and other sodiums, and inorganic salts of metals selected from potassium.
また、上記塩基性有機化合物において、アルカリ土類金属及び/又は土類金属系塩基性有機化合物としては、例えば、アルジオキサ、ジヒドロキシアルミニウムアミノアセテート、スクラルファート水和物、パントテン酸カルシウム等が挙げられる。
また、アルカリ金属系塩基性有機化合物としては、例えば、クエン酸ナトリウム水和物、コハク酸二ナトリウム六水和物、DL−酒石酸ナトリウム、L−酒石酸ナトリウム、銅クロロフィリンナトリウム、ポリアクリル酸ナトリウム、5´−リボヌクレオチド二ナトリウム、銅クロロフィリンカリウム等が挙げられる。
また、アミン系塩基性有機化合物としては、例えば、グリシン(アミノ酢酸)、L−アルギニン、メグルミン等が挙げられる。
なお、本発明においては、上記塩基性化合物として、烏賊骨、石決明、ボレイ(牡蠣)等の塩基性化合物を含有する生薬を用いてもよい。
In addition, among the above-mentioned basic organic compounds, examples of the alkaline earth metal and / or the earth metal-based basic organic compound include aldioxa, dihydroxyaluminum aminoacetate, scralfate hydrate, calcium pantothenate and the like.
Examples of the alkali metal-based basic organic compound include sodium citrate hydrate, disodium succinate hexahydrate, DL-sodium tartrate, L-sodium tartrate, sodium copper chlorophyllin, sodium polyacrylate, and 5, ´-ribonucleotide disodium, copper chlorophyllin potassium and the like can be mentioned.
Examples of the amine-based basic organic compound include glycine (aminoacetic acid), L-arginine, and meglumine.
In the present invention, as the basic compound, a crude drug containing a basic compound such as cuttlefish bone, stone determination, and volley (oyster) may be used.
なお、上記塩基性化合物は単独でもよく、2種以上を組み合わせてもよい。これらは公知の化合物であり、公知の方法により製造できるほか、市販のものを使用してもよい。市販品としては例えば、酸化マグネシウム(富田製薬(株))などが挙げられる。 The basic compound may be used alone or in combination of two or more. These are known compounds and can be produced by a known method, or commercially available compounds may be used. Examples of commercially available products include magnesium oxide (Tomita Pharmaceutical Co., Ltd.).
本発明において、成分(B−2)としては、成分(A)の変色を抑制する観点から、グリシン、ケイ酸アルミン酸マグネシウム、ケイ酸マグネシウム、合成ケイ酸アルミニウム、合成ヒドロタルサイト、酸化マグネシウム、ジヒドロキシアルミニウムアミノアセテート、水酸化アルミナマグネシウム、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・炭酸マグネシウム混合乾燥ゲル、水酸化アルミニウム・炭酸水素ナトリウム共沈物、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物、水酸化マグネシウム、水酸化マグネシウム・硫酸アルミニウムカリウムの共沈生成物、炭酸マグネシウム、炭酸水素ナトリウム、沈降炭酸カルシウム、メタケイ酸アルミン酸マグネシウム、無水リン酸水素カルシウム、リン酸水素カルシウム、烏賊骨、石決明、ボレイ等が好適な例として挙げられ、グリシン、ケイ酸マグネシウム、合成ケイ酸マグネシウム、合成ヒドロタルサイト、酸化マグネシウム、ジヒドロキシアルミニウムアミノアセテート、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・炭酸水素ナトリウム共沈物、水酸化アルミニウム・炭酸マグネシウム混合乾燥ゲル、水酸化アルミニウム・炭酸マグネシウム・炭酸カルシウム共沈物、水酸化マグネシウム・硫酸アルミニウムカリウムの共沈生成物、炭酸マグネシウム及びメタケイ酸アルミン酸マグネシウムよりなる群から選ばれる1種以上が好ましく、アルカリ土類金属及び/又は土類金属系塩基性無機化合物及びアルカリ土類金属及び/又は土類金属系塩基性有機化合物よりなる群から選ばれる1種以上がより好ましく、ケイ酸マグネシウム、合成ケイ酸アルミニウム、合成ヒドロタルサイト、酸化マグネシウム、ジヒドロキシアルミニウムアミノアセテート、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・炭酸水素ナトリウム共沈物、水酸化アルミニウム・炭酸マグネシウム混合乾燥ゲル、水酸化アルミニウム・炭酸マグネシウム・炭酸カルシウム共沈物、水酸化マグネシウム・硫酸アルミニウムカリウムの共沈生成物、炭酸マグネシウム及びメタケイ酸アルミン酸マグネシウムよりなる群から選ばれる1種以上がさらに好ましく、酸化マグネシウム及び水酸化アルミニウムゲルよりなる群から選ばれる1種以上が特に好ましい。 In the present invention, the component (B-2) includes glycine, magnesium aluminate silicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, from the viewpoint of suppressing discoloration of the component (A). Dihydroxyaluminum aminoacetate, aluminum hydroxide magnesium hydroxide, aluminum hydroxide gel, dry aluminum hydroxide gel, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / sodium hydrogencarbonate coprecipitate, aluminum hydroxide / calcium carbonate / carbonic acid Magnesium co-precipitate, magnesium hydroxide, co-precipitate product of magnesium hydroxide / aluminum potassium sulfate, magnesium carbonate, sodium hydrogen carbonate, precipitated calcium carbonate, magnesium aluminometasilicate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, Preferable examples include sardine bone, stone determination, volley, etc., such as glycine, magnesium silicate, synthetic magnesium silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate, aluminum hydroxide gel, and dry aluminum hydroxide. Gel, aluminum hydroxide / sodium hydrogen carbonate co-precipitate, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate co-precipitate, magnesium hydroxide / potassium aluminum sulfate co-precipitate, carbonic acid One or more selected from the group consisting of magnesium and magnesium aluminometasilicate is preferable, and alkaline earth metal and / or earth metal-based basic inorganic compound and alkaline earth metal and / or earth metal-based basic organic compound. One or more selected from the group consisting of magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate, aluminum hydroxide gel, dry aluminum hydroxide gel, aluminum hydroxide. Sodium hydrogen carbonate co-precipitate, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate co-precipitate, magnesium hydroxide / potassium aluminum sulfate co-precipitate, magnesium carbonate and aluminic acid metasilicate One or more selected from the group consisting of magnesium is more preferable, and one or more selected from the group consisting of magnesium oxide and aluminum hydroxide gel is particularly preferable.
医薬組成物における成分(B−2)の含有量は特に限定されず、適宜検討して決定すればよい。例えば、1日あたり、成分(B−2)を5〜1800mg、より好適には10〜1600mg、特に好適には20〜1300mg服用できる量を含有せしめることができる。
中でも、成分(B−2)として酸化マグネシウムを用いる場合においては、1日あたり25〜1000mg、より好適には50〜800mg、特に好適には80〜600mg服用できる量を含有せしめることができる。
また、成分(B−2)として水酸化アルミニウムゲルを用いる場合においては、1日あたり25〜1500mg、より好適には50〜1400mg、特に好適には100〜1200mg服用できる量を含有せしめることができる。
The content of the component (B-2) in the pharmaceutical composition is not particularly limited, and may be appropriately examined and determined. For example, the component (B-2) can be contained in an amount that can be taken in an amount of 5 to 1800 mg, more preferably 10 to 1600 mg, and particularly preferably 20 to 1300 mg per day.
Among them, when magnesium oxide is used as the component (B-2), it can contain 25 to 1000 mg per day, more preferably 50 to 800 mg, and particularly preferably 80 to 600 mg.
When aluminum hydroxide gel is used as the component (B-2), it can contain 25 to 1500 mg per day, more preferably 50 to 1400 mg, and particularly preferably 100 to 1200 mg. ..
本発明においては、成分(A)の変色を抑制する観点から、成分(B−2)を医薬組成物全質量に対して合計で12〜95質量%含有するのが好ましく、20〜94質量%含有するのがより好ましく、27〜93質量%含有するのが特に好ましい。
中でも、成分(B−2)として酸化マグネシウムを用いる場合においては、医薬組成物全質量に対して10〜95質量%含有するのが好ましく、15〜90質量%含有するのがより好ましく、30〜87質量%含有するのが特に好ましい。
また、成分(B−2)として水酸化アルミニウムゲルを用いる場合においては、医薬組成物全質量に対して25〜95質量%含有するのが好ましく、40〜92質量%含有するのがより好ましく、60〜90質量%含有するのが特に好ましい。
In the present invention, from the viewpoint of suppressing discoloration of the component (A), it is preferable to contain the component (B-2) in a total amount of 12 to 95% by mass with respect to the total mass of the pharmaceutical composition, which is 20 to 94% by mass. It is more preferable to contain it, and it is particularly preferable to contain it in an amount of 27 to 93% by mass.
Among them, when magnesium oxide is used as the component (B-2), it is preferably contained in an amount of 10 to 95% by mass, more preferably 15 to 90% by mass, and 30 to 90% by mass, based on the total mass of the pharmaceutical composition. It is particularly preferably contained in an amount of 87% by mass.
When an aluminum hydroxide gel is used as the component (B-2), it is preferably contained in an amount of 25 to 95% by mass, more preferably 40 to 92% by mass, based on the total mass of the pharmaceutical composition. It is particularly preferably contained in an amount of 60 to 90% by mass.
医薬組成物における、成分(A)と成分(B−2)との含有質量比率は特に限定されないが、成分(A)の変色を抑制する観点から、成分(A)をそのフリー体換算で合計して1質量部に対し、成分(B−2)を0.1〜180質量部含有するのが好ましく、1〜170質量部含有するのがより好ましく、2〜150質量部含有するのが特に好ましい。
中でも、成分(A)としてアンピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−2)として酸化マグネシウムを用いる場合においては、アンピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、酸化マグネシウムを1〜60質量部含有するのが好ましく、2〜40質量部含有するのがより好ましく、3〜20質量部含有するのが特に好ましい。
また、成分(A)としてアンピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−2)として水酸化アルミニウムゲルを用いる場合においては、アンピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、水酸化アルミニウムゲルを1〜60質量部含有するのが好ましく、2〜50質量部含有するのがより好ましく、5〜40質量部含有するのが特に好ましい。
また、成分(A)としてピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−2)として酸化マグネシウムを用いる場合においては、ピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、酸化マグネシウムを1〜50質量部含有するのが好ましく、2〜40質量部含有するのがより好ましく、4〜30質量部含有するのが特に好ましい。
また、成分(A)としてピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−2)として水酸化アルミニウムゲルを用いる場合においては、ピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、水酸化アルミニウムゲルを1〜90質量部含有するのが好ましく、2〜80質量部含有するのがより好ましく、5〜70質量部含有するのが特に好ましい。
また、成分(A)としてメロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−2)として酸化マグネシウムを用いる場合においては、メロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、酸化マグネシウムを2〜75質量部含有するのが好ましく、5〜65質量部含有するのがより好ましく、8〜55質量部含有するのが特に好ましい。
また、成分(A)としてメロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−2)として水酸化アルミニウムゲルを用いる場合においては、メロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、水酸化アルミニウムゲルを5〜175質量部含有するのが好ましく、10〜150質量部含有するのがより好ましく、15〜120質量部含有するのが特に好ましい。
また、成分(A)としてロルノキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−2)として酸化マグネシウムを用いる場合においては、ロルノキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、酸化マグネシウムを2〜85質量部含有するのが好ましく、5〜75質量部含有するのがより好ましく、10〜65質量部含有するのが特に好ましい。
さらに、成分(A)としてロルノキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−2)として水酸化アルミニウムゲルを用いる場合においては、ロルノキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、水酸化アルミニウムゲルを10〜170質量部含有するのが好ましく、15〜150質量部含有するのがより好ましく、20〜130質量部含有するのが特に好ましい。
The content mass ratio of the component (A) and the component (B-2) in the pharmaceutical composition is not particularly limited, but the component (A) is totaled in terms of its free form from the viewpoint of suppressing discoloration of the component (A). The component (B-2) is preferably contained in an amount of 0.1 to 180 parts by mass, more preferably 1 to 170 parts by mass, and particularly preferably 2 to 150 parts by mass with respect to 1 part by mass. preferable.
Among them, when one or more selected from the group consisting of ampyroxycam and its salt and a solvate thereof is used as the component (A) and magnesium oxide is used as the component (B-2), ampyroxycam and its salt are used. In addition, it is preferable that 1 to 60 parts by mass of magnesium oxide is contained with respect to 1 part by mass in total in terms of free form of one or more selected from the group consisting of those solvates, and 2 to 40 parts by mass is contained. It is more preferable to use 3 to 20 parts by mass, and it is particularly preferable to contain 3 to 20 parts by mass.
When one or more selected from the group consisting of ampyroxycam, a salt thereof and a solvate thereof are used as the component (A), and aluminum hydroxide gel is used as the component (B-2), ampyroxycam and It is preferable that 1 to 60 parts by mass of aluminum hydroxide gel is contained in 1 part by mass in total in terms of free form of one or more selected from the group consisting of the salt and solvates thereof. It is more preferably contained in an amount of 50 parts by mass, and particularly preferably contained in an amount of 5 to 40 parts by mass.
When one or more selected from the group consisting of pyroxycam and its salts and solvates thereof are used as the component (A), and magnesium oxide is used as the component (B-2), pyroxicum and its salts and their salts are used. It is preferable that 1 to 50 parts by mass of magnesium oxide is contained with respect to 1 part by mass in total in terms of a free form of one or more selected from the group consisting of the solvates of the above, and 2 to 40 parts by mass is contained. Is more preferable, and it is particularly preferable that the content is 4 to 30 parts by mass.
Further, when one or more selected from the group consisting of pyroxycam and its salt and a solvate thereof are used as the component (A) and aluminum hydroxide gel is used as the component (B-2), pyroxicum and its salt are used. In addition, it is preferable that 1 to 90 parts by mass of aluminum hydroxide gel is contained with respect to 1 part by mass in total in terms of free form of one or more selected from the group consisting of those solvates, and 2 to 80 parts by mass. It is more preferably contained in parts, and particularly preferably 5 to 70 parts by mass.
In addition, when one or more selected from the group consisting of meroxycam and its salts and solvates thereof is used as the component (A) and magnesium oxide is used as the component (B-2), meroxycam and its salts and them are used. It is preferable that magnesium oxide is contained in an amount of 2 to 75 parts by mass and 5 to 65 parts by mass based on 1 part by mass in total in terms of a free form of one or more selected from the group consisting of the solvates of the above. Is more preferable, and it is particularly preferable that the content is 8 to 55 parts by mass.
Further, when one or more selected from the group consisting of meroxycam and its salt and a solvate thereof is used as the component (A) and aluminum hydroxide gel is used as the component (B-2), meroxycam and its salt are used. In addition, it is preferable that 5 to 175 parts by mass of aluminum hydroxide gel is contained with respect to 1 part by mass in total in terms of free form of one or more selected from the group consisting of those solvates, and 10 to 150 parts by mass. It is more preferably contained in parts, and particularly preferably 15 to 120 parts by mass.
When one or more selected from the group consisting of lornoxicum and its salts and solvates thereof are used as the component (A), and magnesium oxide is used as the component (B-2), lornoxicum and its salts and their salts are used. It is preferable to contain 2 to 85 parts by mass of magnesium oxide, and 5 to 75 parts by mass, based on 1 part by mass in total in terms of free form of one or more selected from the group consisting of the solvates of. Is more preferable, and it is particularly preferable that the content is 10 to 65 parts by mass.
Further, when one or more selected from the group consisting of lornoxicum and a salt thereof and a solvate thereof are used as the component (A), and aluminum hydroxide gel is used as the component (B-2), lornoxicum and a salt thereof are used. In addition, it is preferable to contain 10 to 170 parts by mass of aluminum hydroxide gel with respect to 1 part by mass in total in terms of free form of one or more selected from the group consisting of those solvates, and 15 to 150 parts by mass. The content is more preferably 20 to 130 parts by mass, and particularly preferably 20 to 130 parts by mass.
<成分(B−3)>
本明細書において「イソバレリル尿素誘導体」とは、ブロムワレリル尿素、アリルイソプロピルアセチル尿素及びそれらの塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を意味する。このうち、ブロムワレリル尿素が好ましい。
なお、イソバレリル尿素誘導体には不斉炭素が存するため、種々の光学異性体が存するが、本発明においては、いずれの光学異性体をも含み、単一の光学異性体でもよく、各種光学異性体の混合物でもよい。これらは1種単独で、又は2種以上を適宜組み合わせて使用できる。
なお、イソバレリル尿素誘導体は公知の成分であり、公知の方法により製造できるほか、市販のものを使用してもよい。市販品としては例えば、アリルイソプロピルアセチル尿素(東京化成工業(株))などが挙げられる。
<Ingredient (B-3)>
As used herein, the term "isovaleryl urea derivative" means one or more selected from the group consisting of bromvalerylurea, allylisopropylacetylurea and salts thereof, and solvates thereof. Of these, bromvalerylurea is preferable.
Since the isovaleryl urea derivative has an asymmetric carbon, various optical isomers exist. However, in the present invention, any optical isomer may be contained and a single optical isomer may be used, and various optical isomers may be used. May be a mixture of. These can be used alone or in combination of two or more.
The isovaleryl-urea derivative is a known component and can be produced by a known method, or a commercially available product may be used. Examples of commercially available products include allyl isopropyl acetyl urea (Tokyo Chemical Industry Co., Ltd.).
医薬組成物における成分(B−3)の含有量は特に限定されず、適宜検討して決定すればよい。例えば、1日あたり、成分(B−3)をフリー体換算で合計5〜900mg、より好適には10〜850mg、特に好適には15〜800mg服用できる量を含有せしめることができる。
中でも、成分(B−3)としてアリルイソプロピルアセチル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、1日あたり、そのフリー体に換算して合計で5〜250mg、より好適には10〜220mg、特に好適には20〜200mg服用できる量を含有せしめることができる。
また、成分(B−3)としてブロムワレリル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、1日あたり、そのフリー体に換算して合計で25〜900mg、より好適には50〜800mg、特に好適には70〜700mg服用できる量を含有せしめることができる。
The content of the component (B-3) in the pharmaceutical composition is not particularly limited, and may be appropriately examined and determined. For example, the component (B-3) can be contained in a total amount of 5 to 900 mg, more preferably 10 to 850 mg, and particularly preferably 15 to 800 mg per day in terms of free form.
Above all, when one or more selected from the group consisting of allyl isopropyl acetyl urea and its salts and their solvates is used as the component (B-3), the total amount is converted to the free form per day. It can contain 5 to 250 mg, more preferably 10 to 220 mg, and particularly preferably 20 to 200 mg.
In addition, when one or more selected from the group consisting of bromvalerylurea, a salt thereof, and a solvate thereof are used as the component (B-3), a total of 25 to 25 to the free form per day is used. It can contain 900 mg, more preferably 50-800 mg, and particularly preferably 70-700 mg in an acceptable amount.
本発明においては、成分(A)の変色を抑制する観点から、成分(B−3)をフリー体換算で医薬組成物全質量に対して合計で0.1〜95質量%含有するのが好ましく、1〜94質量%含有するのがより好ましく、4〜93質量%含有するのが特に好ましい。
中でも、成分(B−3)としてアリルイソプロピルアセチル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、そのフリー体に換算して医薬組成物全質量に対して合計で1〜85質量%含有するのが好ましく、2〜80質量%含有するのがより好ましく、5〜75質量%含有するのが特に好ましい。
また、成分(B−3)としてブロムワレリル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、医薬組成物全質量に対して合計で10〜95質量%含有するのが好ましく、15〜94質量%含有するのがより好ましく、30〜92質量%含有するのが特に好ましい。
In the present invention, from the viewpoint of suppressing discoloration of the component (A), it is preferable that the component (B-3) is contained in a total of 0.1 to 95% by mass with respect to the total mass of the pharmaceutical composition in terms of free form. , 1 to 94% by mass is more preferable, and 4 to 93% by mass is particularly preferable.
Above all, when one or more selected from the group consisting of allyl isopropyl acetyl urea, a salt thereof and a solvate thereof is used as the component (B-3), it is converted into the free form thereof to the total mass of the pharmaceutical composition. On the other hand, the total content is preferably 1 to 85% by mass, more preferably 2 to 80% by mass, and particularly preferably 5 to 75% by mass.
When one or more selected from the group consisting of bromvalerylurea, a salt thereof, and a solvate thereof are used as the component (B-3), the total mass is 10 to 95% by mass with respect to the total mass of the pharmaceutical composition. It is preferably contained, more preferably 15 to 94% by mass, and particularly preferably 30 to 92% by mass.
医薬組成物における、成分(A)と成分(B−3)との含有質量比率は特に限定されないが、成分(A)の変色を抑制する観点から、成分(A)をそのフリー体換算で合計して1質量部に対し、成分(B−3)をそのフリー体換算で合計して0.001〜95質量部含有するのが好ましく、0.01〜90質量部含有するのがより好ましく、0.1〜85質量部含有するのが特に好ましい。
中でも、成分(A)としてアンピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−3)としてアリルイソプロピルアセチル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、アンピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、アリルイソプロピルアセチル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して0.01〜30質量部含有するのが好ましく、0.1〜20質量部含有するのがより好ましく、0.5〜10質量部含有するのが特に好ましい。
また、成分(A)としてアンピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−3)としてブロムワレリル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、アンピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、ブロムワレリル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して0.1〜75質量部含有するのが好ましく、1〜50質量部含有するのがより好ましく、2〜30質量部含有するのが特に好ましい。
また、成分(A)としてピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−3)としてアリルイソプロピルアセチル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、ピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、アリルイソプロピルアセチル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して0.01〜50質量部含有するのが好ましく、0.1〜30質量部含有するのがより好ましく、1〜15質量部含有するのが特に好ましい。
また、成分(A)としてピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−3)としてブロムワレリル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、ピロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、ブロムワレリル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して0.1〜85質量部含有するのが好ましく、1〜75質量部含有するのがより好ましく、2〜50質量部含有するのが特に好ましい。
また、成分(A)としてメロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−3)としてアリルイソプロピルアセチル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、メロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、アリルイソプロピルアセチル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して0.1〜50質量部含有するのが好ましく、1〜30質量部含有するのがより好ましく、2〜20質量部含有するのが特に好ましい。
また、成分(A)としてメロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−3)としてブロムワレリル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、メロキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、ブロムワレリル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1〜85質量部含有するのが好ましく、2〜80質量部含有するのがより好ましく、5〜75質量部含有するのが特に好ましい。
また、成分(A)としてロルノキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−3)としてアリルイソプロピルアセチル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、ロルノキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、アリルイソプロピルアセチル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1〜45質量部含有するのが好ましく、2〜30質量部含有するのがより好ましく、3〜25質量部含有するのが特に好ましい。
さらに、成分(A)としてロルノキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用い、成分(B−3)としてブロムワレリル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上を用いる場合においては、ロルノキシカム及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して1質量部に対し、ブロムワレリル尿素及びその塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上をそのフリー体換算で合計して2〜90質量部含有するのが好ましく、5〜85質量部含有するのがより好ましく、10〜80質量部含有するのが特に好ましい。
The mass ratio of the component (A) to the component (B-3) in the pharmaceutical composition is not particularly limited, but the component (A) is totaled in terms of its free form from the viewpoint of suppressing discoloration of the component (A). The total amount of the component (B-3) in terms of free form is preferably 0.001 to 95 parts by mass, more preferably 0.01 to 90 parts by mass, based on 1 part by mass. It is particularly preferably contained in an amount of 0.1 to 85 parts by mass.
Among them, one or more selected from the group consisting of ampyroxycam and its salts and their solvates are used as the component (A), and allylisopropylacetylurea and its salts and their solvates are used as the component (B-3). When one or more selected from the group consisting of ampyloxycam and its salts and their solvates are used, one or more selected from the group consisting of ampyloxycam and their solvates are totaled with respect to 1 part by mass in terms of free form. It is preferable that one or more selected from the group consisting of allylisopropylacetylurea and salts thereof and solvates thereof is contained in a total of 0.01 to 30 parts by mass in terms of free form thereof, and 0.1 to 20 parts by mass. It is more preferably contained in parts, and particularly preferably 0.5 to 10 parts by mass.
Further, as the component (A), one or more selected from the group consisting of ampyroxycam and a salt thereof and a solvate thereof is used, and as a component (B-3), bromvalerylurea and a salt thereof and a solvate thereof are used. When one or more selected from the group is used, one or more selected from the group consisting of ampyroxycam, a salt thereof, and a solvate thereof are totaled in terms of free form, and bromvalerylurea is added to 1 part by mass. And one or more selected from the group consisting of salts thereof and solvates thereof are preferably contained in an amount of 0.1 to 75 parts by mass in total in terms of free form, and more preferably contained in an amount of 1 to 50 parts by mass. It is preferably contained in an amount of 2 to 30 parts by mass, particularly preferably.
Further, as the component (A), one or more selected from the group consisting of pyroxicum and its salts and their solvates are used, and as the component (B-3), allylisopropylacetylurea and its salts and their solvates are used. When one or more selected from the group consisting of pyroxycam, a salt thereof, and a solvate thereof, one or more selected from the group consisting of pyroxycam and its solvate are totaled in terms of free form, and allyl isopropyl per part by mass. It is preferable that one or more selected from the group consisting of acetylurea, a salt thereof and a solvate thereof are contained in a total of 0.01 to 50 parts by mass in terms of free form, and 0.1 to 30 parts by mass is contained. It is more preferable, and it is particularly preferable to contain 1 to 15 parts by mass.
Further, as the component (A), one or more selected from the group consisting of pyroxicum and its salts and their solvates is used, and as the component (B-3), the group consisting of bromvalerylurea and its salts and their solvates. When one or more selected from the above is used, one or more selected from the group consisting of pyroxicum, a salt thereof, and a solvate thereof are totaled in terms of free form, and bromvalerylurea and its solvate are added to 1 part by mass. It is preferable that one or more selected from the group consisting of salts and their solvates is contained in a total of 0.1 to 85 parts by mass in terms of free form, and more preferably 1 to 75 parts by mass. It is particularly preferable to contain 2 to 50 parts by mass.
Further, as the component (A), one or more selected from the group consisting of meroxycam and its salts and their solvates is used, and as the component (B-3), allylisopropylacetylurea and its salts and their solvates are used. When one or more selected from the group consisting of meroxycam, a salt thereof, and a solvate thereof are used, one or more selected from the group consisting of meroxycam and its solvate are totaled in terms of free form, and allyl isopropyl per part by mass. It is preferable that one or more selected from the group consisting of acetylurea, a salt thereof and a solvate thereof are contained in a total of 0.1 to 50 parts by mass in terms of free form, and 1 to 30 parts by mass is contained. Is more preferable, and it is particularly preferable that the content is 2 to 20 parts by mass.
Further, as the component (A), one or more selected from the group consisting of meroxycam and its salts and their solvates is used, and as the component (B-3), the group consisting of bromvalerylurea and its salts and their solvates. When one or more selected from the above is used, one or more selected from the group consisting of meroxycam, a salt thereof, and a solvate thereof are totaled in terms of free form, and bromvalerylurea and its solvate are added to 1 part by mass. It is preferable that one or more selected from the group consisting of salts and their solvates are contained in a total of 1 to 85 parts by mass, more preferably 2 to 80 parts by mass, and 5 to 80 parts by mass in terms of free form. It is particularly preferable to contain 75 parts by mass.
Further, as the component (A), one or more selected from the group consisting of lornoxicum and its salt and their solvates are used, and as the component (B-3), allylisopropylacetylurea and its salts and their solvates are used. When one or more selected from the group consisting of lornoxicum, a salt thereof, and a solvate thereof are used, one or more selected from the group consisting of lornoxicum and a solvate thereof are totaled in terms of free form, and allyl isopropyl per part by mass. It is preferable that one or more selected from the group consisting of acetylurea, a salt thereof and a solvate thereof are contained in a total of 1 to 45 parts by mass in terms of free form, and more preferably 2 to 30 parts by mass. It is preferably contained in an amount of 3 to 25 parts by mass, and particularly preferably contained in an amount of 3 to 25 parts by mass.
Further, as the component (A), one or more selected from the group consisting of lornoxicum and its salt and its solvate is used, and as the component (B-3), the group consisting of bromvalerylurea and its salt and their solvate. When one or more selected from the above is used, one or more selected from the group consisting of lornoxicum, a salt thereof, and a solvate thereof are totaled in terms of free form, and bromvalerylurea and its solvate are added to 1 part by mass. It is preferable that one or more selected from the group consisting of salts and their solvates are contained in a total of 2 to 90 parts by mass, more preferably 5 to 85 parts by mass, and 10 to 10 parts by mass in terms of free form. It is particularly preferable to contain 80 parts by mass.
医薬組成物は、薬効成分として、上記以外の成分、例えば、解熱鎮痛剤、抗ヒスタミン剤、鎮咳剤、ノスカピン類、気管支拡張剤、去痰剤、催眠鎮静剤、ビタミン類、抗炎症剤、胃粘膜保護剤、制酸剤、抗コリン剤、生薬類、漢方処方等からなる群より選ばれる1種又は2種以上を含んでいても良い。 The pharmaceutical composition has other components as medicinal properties, such as antipyretic analgesic, anti-histamine, antitussive, noscapine, bronchodilator, sputum, hypnotic sedative, vitamins, anti-inflammatory agent, gastric mucosa protective agent, It may contain one or more selected from the group consisting of antacids, anticholiners, crude drugs, Chinese herbs and the like.
解熱鎮痛剤としては、具体的には例えば、アスピリン、アスピリンアルミニウム、アセトアミノフェン、イソプロピルアンチピリン、イブプロフェン、エテンザミド、サザピリン、サリチルアミド、サリチル酸ナトリウム、ラクチルフェネチジン、ロキソプロフェン等が挙げられる。
抗ヒスタミン剤としては、具体的には例えば、アゼラスチン塩酸塩、アリメマジン酒石酸塩、イソチペンジル塩酸塩、イプロヘプチン塩酸塩、エピナスチン塩酸塩、エメダスチンフマル酸塩、オキサトミド、オロパタジン塩酸塩、カルビノキサミンジフェニルジスルホン酸塩、カルビノキサミンマレイン酸塩、クレマスチンフマル酸塩、d−クロルフェニラミンマレイン酸塩、dl−クロルフェニラミンマレイン酸塩、ケトチフェンフマル酸塩、ジフェテロール塩酸塩、ジフェテロールリン酸塩、ジフェニルピラリン塩酸塩、ジフェニルピラリンテオクル酸塩、ジフェンヒドラミン塩酸塩、ジフェンヒドラミンサリチル酸塩、ジフェンヒドラミンタンニン酸塩、シプロへプタジン塩酸塩水和物、トリプロリジン塩酸塩、トリペレナミン塩酸塩、トンジルアミン塩酸塩、フェネタジン塩酸塩、プロメタジン塩酸塩、プロメタジンメチレン二サリチル酸塩、ホモクロルシクリジン塩酸塩、メキタジン、メトジラジン塩酸塩、メブヒドロリンナパジシル酸塩、ロラタジン等が挙げられる。
Specific examples of the antipyretic analgesic include aspirin, aspirin aluminum, acetaminophen, isopropylantipyrine, ibuprofen, ethenzamide, sazapyrine, salicylamide, sodium salicylate, lactylphenetidine, loxoprofen and the like.
Specific examples of the antihistamine include azerastin hydrochloride, alimemazine tartrate, isotipendyl hydrochloride, iproheptin hydrochloride, epinastine hydrochloride, emedastin fumarate, oxatomide, olopatazine hydrochloride, and carbinoxamine diphenyldisulfonate. , Carbinoxamine maleate, cremastine fumarate, d-chlorpheniramine maleate, dl-chlorpheniramine maleate, ketotiphen fumarate, difeterol hydrochloride, difeterol phosphate, diphenylpyraline hydrochloride Salt, diphenylpyraline theocrate, diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydraminetannate, cyproheptazine hydrochloride hydrate, triprolidine hydrochloride, tryperenamine hydrochloride, tonzilamine hydrochloride, phenetazine hydrochloride, promethazine hydrochloride , Promethazine methylene disalicylate, homochlorocyclidine hydrochloride, mequitazine, metodilazine hydrochloride, mebuhydrolin napadisylate, loratazine and the like.
鎮咳剤としては、具体的には例えば、コデイン、コデインリン酸塩水和物、ジヒドロコデイン、ジヒドロコデインリン酸塩等のコデイン類の他、アロクラミド塩酸塩、エプラジノン塩酸塩、カルベタペンタンクエン酸塩、クロペラスチン塩酸塩、クロペラスチンフェンジゾ酸塩、ジブナートナトリウム、ジメモルファンリン酸塩、チペピジンクエン酸塩、チペピジンヒベンズ酸塩、デキストロメトルファン、デキストロメトルファン臭化水素酸塩水和物、デキストロメトルファンフェノールフタリン塩等が挙げられる。 Specific examples of the antitussive agent include codeins such as codeine, codeine phosphate hydrate, dihydrocodein, and dihydrocodein phosphate, as well as allocramide hydrochloride, epradinone hydrochloride, carbetapentanecate, and cloperastine hydrochloride. Cloperastin fendizoate, dibunato sodium, dimemorphan phosphate, tipepidin citrate, tipepidin hibenzate, dextrometholphan, dextromethorphan hydrobromide hydrate, dextromethorphan phenol phthal Phosphate and the like can be mentioned.
ノスカピン類としては、具体的には例えば、ノスカピン塩酸塩、ノスカピン等が挙げられる。
気管支拡張剤としては、具体的には例えば、トリメトキノール塩酸塩等が挙げられる。
Specific examples of noscapines include noscapine hydrochloride, noscapine and the like.
Specific examples of the bronchodilator include trimetokinol hydrochloride and the like.
去痰剤としては、具体的には例えば、アンモニア・ウイキョウ精、エチルシステイン塩酸塩、塩化アンモニウム、カルボシステイン、グアイフェネシン、グアヤコールスルホン酸カリウム、クレゾールスルホン酸カリウム、メチルシステイン塩酸塩、l−メントール、リゾチーム塩酸塩等が挙げられる。 Specific examples of the expectorant include ammonia / uikyosei, ethyl cysteine hydrochloride, ammonium chloride, carbocysteine, guayphenesin, potassium guayacol sulfonate, potassium cresol sulfonate, methyl cysteine hydrochloride, l-menthol, and lysoteam hydrochloride. Examples include salt.
ビタミン類としては、具体的には例えば、ビタミンB1、ビタミンB2、ビタミンB5、ビタミンB6、ビタミンB12、ビタミンC、ヘスペリジン及びその誘導体並びにそれらの塩類等(具体的には例えば、チアミン、チアミン塩化物塩酸塩、チアミン硝化物、ジセチアミン塩酸塩、セトチアミン塩酸塩、フルスルチアミン、フルスルチアミン塩酸塩、オクトチアミン、シコチアミン、チアミンジスルフィド、ビスイブチアミン、ビスベンチアミン、プロスルチアミン、ベンフォチアミン、リボフラビン、リボフラビンリン酸エステル、リボフラビン酪酸エステル、リン酸リボフラビンナトリウム、パンテノール、パンテチン、パントテン酸ナトリウム、ピリドキシン塩酸塩、ピリドキサールリン酸エステル、シアノコバラミン、メコバラミン、アスコルビン酸、アスコルビン酸ナトリウム、アスコルビン酸カルシウム、ヘスペリジン等)が挙げられる。 Specific examples of vitamins include vitamin B1, vitamin B2, vitamin B5, vitamin B6, vitamin B12, vitamin C, hesperidin and derivatives thereof, and salts thereof (specifically, for example, thiamine, thiamine chloride). Hydrochloride, thiamine nitrate, disetiamine hydrochloride, setothiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octothiamine, sicothamine, thiamine disulfide, bisibuchiamine, bisbenchamine, prosultiamine, benfothamine, riboflavin , Riboflavin phosphate, Riboflavin butyrate, Sodium riboflavin phosphate, Pantenol, Pantetin, Sodium pantothenate, Pyridoxin hydrochloride, Pyridoxal phosphate, Cyanocobalamine, Mecobalamine, Ascorbic acid, Sodium ascorbate, Calcium ascorbate, Hesperidin, etc. ).
抗炎症剤としては、具体的には例えば、グリチルリチン酸及びその誘導体並びにそれらの塩類(例えば、グリチルリチン酸二カリウム、グリチルリチン酸モノアンモニウム等)、セアプローゼ、セミアルカリプロティナーゼ、セラペプターゼ、トラネキサム酸、プロクターゼ、プロナーゼ、ブロメライン等が挙げられる。 Specific examples of the anti-inflammatory agent include glycyrrhizic acid and its derivatives and salts thereof (for example, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, etc.), seaprose, semi-alkali proteinase, serratiopeptidase, tranexamic acid, proctase, and pronase. , Bromelain and the like.
胃粘膜保護剤としては、具体的には例えば、ゲファルナート、セトラキサート塩酸塩、ソファルコン、テプレノン、メチルメチオニンスルホニウムクロリド等が挙げられる。 Specific examples of the gastric mucosa protective agent include gefarnate, cetraxate hydrochloride, sofalcone, teprenone, methylmethionine sulfonium chloride and the like.
抗コリン剤としては、具体的には例えば、オキシフェンサイクリミン塩酸塩、ジサイクロミン塩酸塩、メチキセン塩酸塩、チペピジウム臭化物、メチルベナクチジウム臭化物、ピレンゼピン塩酸塩、ヨウ化イソプロパミド、ヨウ化ジフェニルピペリジノメチルジオキソラン等が挙げられる。 Specific examples of the anticholinergic agent include oxyphencyclimine hydrochloride, dicyclamine hydrochloride, methixene hydrochloride, tipepidium bromide, methylbenactidium bromide, pirenzepine hydrochloride, isopropamide iodide, and diphenylpiperidino iodide. Examples thereof include methyldioxolane.
生薬類としては、具体的には例えば、アカメガシワ(赤芽柏)、アセンヤク(阿仙薬)、インヨウカク(淫羊霍)、ウイキョウ(茴香)、エンゴサク(延胡索)、オウゴン(黄岑)、オウセイ(黄精)、オウバク(黄柏)、オウヒ(桜皮)、オウレン(黄連)、オンジ(遠志)、ガジュツ(我朮)、カノコソウ(鹿子草)、カミツレ、カロニン(か楼仁)、キキョウ(桔梗)、キョウニン(杏仁)、クコシ(枸杞子)、クコヨウ(枸杞葉)、ケイガイ(荊芥)、ケイヒ(桂皮)、ケツメイシ(決明子)、ゲンチアナ、ゲンノショウコ(現証拠)、コウブシ(香附子)、ゴオウ(牛黄)、ゴミシ(五味子)、サイシン(細辛)、サンショウ(山椒)、シオン(紫苑)、ジコッピ(地骨皮)、シャクヤク(芍薬)、ジャコウ(麝香)、シャジン(沙参)、シャゼンシ(車前子)、シャゼンソウ(車前草)、獣胆(ユウタン(熊胆)を含む)、ショウキョウ(生姜)、ジリュウ(地竜)、シンイ(辛夷)、セキサン(石蒜)、セネガ、センキュウ(川きゅう)、ゼンコ(前胡)、センブリ(千振)、ソウジュツ(蒼朮)、ソウハクヒ(桑白皮)、ソヨウ(蘇葉)、タイサン(大蒜)、チクセツニンジン(竹節人参)、チョウジ(丁子)、チンピ(陳皮)、トウキ(当帰)、トコン(吐根)、ナンテンジツ(南天実)、ニンジン(人参)、バイモ(貝母)、バクモンドウ(麦門冬)、ハンゲ(半夏)、バンコウカ(番紅花)、ハンピ(反鼻)、ビャクシ(白し)、ビャクジュツ(白朮)、ブクリョウ(茯苓)、ボタンピ(牡丹皮)、ロクジョウ(鹿茸)等の生薬及びこれらの抽出物(エキス、チンキ、乾燥エキス等)等が挙げられる。 Specific examples of crude drugs include red bud wrinkles (red buds), asenyaku (Asenyaku), inyokaku (innocent sheep), uikyo (ginger), engosaku (clove), ginger (yellow clove), and ausei (yellow spirit). Oubaku (yellow kashiwa), Ouhi (cherry bark), Ouren (yellow ream), Onji (distant soul), Gajutsu (selfish), Kanokosou (kagokusa), chamomile, caronin (karojin), kikyo (kikyo), kyonin (kikyo) Kyoujin), Kukoshi (Tincture), Kukoyo (Tincture leaf), Keigai (Clove), Keihi (Chenpi), Ketsumeishi (Chenpi), Gentiana, Gennoshoko (Current evidence), Kobushi (Kabushi), Goou (Clove yellow), Garbage (Gomiko), Saishin (Spicy), Sansho (Sansho), Zion (Shien), Jikoppi (Chenpi), Shakuyaku (Crude drug), Jakou (Tincture), Shajin (Sasan), Shazenshi (Car front child) , Shazensou (in front of the car), Beast ginger (including ginger), Ginger (Ginger), Jiryu (earth dragon), Shini (spicy), Sexan (stone), Senega, Senkyu (Kawakyu), Zenko (Maehu), Senburi (Senburi), Soujutsu (Soujou), Souhakuhi (Kuwashirohide), Soyo (Souha), Taisan (Daiban), Chikusetsu carrot (Takebushi carrot), Clove (Clove), Chinpi (Chenpi) , Touki (Toki), Tokon (Vomiting root), Nantenjitsu (Nantenmi), Carrot (Ginger), Baimo (Ginger), Bakumondou (Mugimon winter), Hange (Half-summer), Bankouka (Bankohana), Hampi (Anti-nose), Byakushi (white), Byakujutsu (white ginger), Bukuryo (茯 蓓), Buttonpi (peony skin), Rokujo (deer mushroom) and other crude drugs and their extracts (extracts, tinctures, dried extracts, etc.) Can be mentioned.
漢方処方としては、具体的には例えば、カッコントウ(葛根湯)、ケイシトウ(桂枝湯)、コウソサン(香蘇散)、サイコケイシトウ(柴胡桂枝湯)、ショウサイコトウ(小柴胡湯)、ショウセイリュウトウ(小青竜湯)、バクモンドウトウ(麦門冬湯)、ハンゲコウボクトウ(半夏厚朴湯)、マオウトウ(麻黄湯)等が挙げられる。 Specific examples of Chinese prescriptions include Kakkonto (Kakkonto), Keishito (Keishito), Kososan (Kososan), Saiko Keishito (Saiko Keishito), Shosaikoto (Shoseikoto), and Sho. Examples include Seiryuto (Shoseiryuto), Bakumondoto (Mai Men Dong Tang), Hangekobokuto (Hangekobokuto), Maoto (Maoto), and the like.
本明細書において「医薬組成物」の剤形は特に限定されず、固形状、半固形状、又は液状製剤のいずれであってもよく、その利用目的等に応じて選択することができる。医薬組成物の剤形としては、例えば、第十七改正日本薬局方 製剤総則等に記載の剤形が挙げられる。具体的には例えば、経口投与用の剤形としては、錠剤(例えば、通常錠、口腔内崩壊型錠剤、チュアブル錠、発泡錠、分散錠、溶解錠などを含む)、カプセル剤、顆粒剤(例えば、発泡顆粒剤などを含む)、散剤、丸剤等の固形製剤;経口ゼリー剤等の半固形状製剤;経口液剤(例えば、エリキシル剤、懸濁剤、乳剤、リモナーデ剤などを含む)等の液状製剤等が挙げられる。また、非経口投与用の剤形としては、注射剤、吸入剤、点眼剤、点耳剤、点鼻剤、座剤、外用固形剤、外用液剤、スプレー剤、軟膏剤、クリーム剤、ゲル剤、貼付剤等が挙げられる。 In the present specification, the dosage form of the "pharmaceutical composition" is not particularly limited, and may be a solid, semi-solid, or liquid preparation, and can be selected according to the purpose of use and the like. Examples of the dosage form of the pharmaceutical composition include the dosage forms described in the 17th revised Japanese Pharmacopoeia General Regulations for Formulation. Specifically, for example, the dosage form for oral administration includes tablets (including, for example, ordinary tablets, orally disintegrating tablets, chewable tablets, effervescent tablets, dispersion tablets, dissolving tablets, etc.), capsules, and granules (for example, For example, solid preparations such as effervescent granules), powders, pills, etc .; semi-solid preparations such as oral jelly preparations; oral liquid preparations (including, for example, elixirs, suspensions, emulsions, limonades, etc.), etc. Liquid preparations and the like. Dosage forms for parenteral administration include injections, inhalants, eye drops, ear drops, nasal drops, suppositories, external solids, external solutions, sprays, ointments, creams, and gels. , Patches and the like.
医薬組成物の剤形としては、服用のし易さ等の観点から、固形製剤であるのが好ましく、錠剤(例えば、通常錠、口腔内崩壊型錠剤、チュアブル錠、発泡錠、分散錠、溶解錠などを含む)、カプセル剤、顆粒剤(例えば、発泡顆粒剤などを含む)、散剤及び丸剤から選ばれる固形製剤であるのが特に好ましい。 The dosage form of the pharmaceutical composition is preferably a solid preparation from the viewpoint of ease of ingestion, and tablets (for example, ordinary tablets, orally disintegrating tablets, chewable tablets, effervescent tablets, dispersed tablets, dissolution tablets). It is particularly preferable that it is a solid preparation selected from tablets (including tablets and the like), capsules, granules (including effervescent granules and the like), powders and pills.
医薬組成物は、その剤形に応じ、例えば第十七改正日本薬局方 製剤総則等に記載の公知の方法により製造することができる。この場合において、医薬組成物には、製薬上許容される担体(製剤添加物)を加えてもよい。こうした製剤添加物としては、例えば、賦形剤、崩壊剤、結合剤、滑沢剤、可塑剤、フィルム形成剤、粉体、難水溶性高分子物質、抗酸化剤、矯味剤、甘味剤等が挙げられるが、これらに限定されるものではない。なお、これらの製剤添加物としては、具体的には例えば、医薬品添加物辞典2016(株式会社薬事日報社発行)、Handbook of Pharmaceutical Excipients, Seventh Edition(Pharmaceutical Press社発行)等に収載されたものが挙げられる。 The pharmaceutical composition can be produced, for example, by a known method described in the 17th revised Japanese Pharmacopoeia General Regulations for Formulation, etc., depending on the dosage form. In this case, a pharmaceutically acceptable carrier (formulation additive) may be added to the pharmaceutical composition. Examples of such preparation additives include excipients, disintegrants, binders, lubricants, plasticizers, film-forming agents, powders, poorly water-soluble polymer substances, antioxidants, flavoring agents, sweeteners and the like. However, the present invention is not limited to these. Specific examples of these additive additives include those listed in the Pharmaceutical Additives Dictionary 2016 (published by Yakuji Nippo Co., Ltd.), Handbook of Pharmaceutical Expicients, Seventh Edition (published by Pharmaceutical Press Co., Ltd.), and the like. Can be mentioned.
賦形剤としては、具体的には例えば、無水硫酸ナトリウム、塩化ナトリウム、軽質無水ケイ酸、重質無水ケイ酸、硫酸カルシウム等の無機系賦形剤;アメ粉、デンプン(コムギデンプン、コメデンプン、トウモロコシデンプン、部分アルファー化デンプン等)、果糖、カラメル、カンテン、キシリトール、パラフィン、結晶セルロース、ショ糖、麦芽糖、乳糖、乳糖水和物、白糖、ブドウ糖、プルラン、ポリオキシエチレン硬化ヒマシ油、マルチトール、還元麦芽糖水アメ、粉末還元麦芽糖水アメ、エリスリトール、ソルビトール、マンニトール、ラクチトール、トレハロース、還元パラチノース、アミノアルキルメタクリレートコポリマーE、ポリビニルアセタールジエチルアミノアセテート、クエン酸カルシウム等の有機系賦形剤等が挙げられる。これらは、1種又は2種以上を組み合わせて使用することができる。 Specific examples of the excipient include inorganic excipients such as anhydrous sodium sulfate, sodium chloride, light anhydrous silicic acid, heavy anhydrous silicic acid, and calcium sulfate; candy flour and starch (wheat starch, rice starch). , Corn starch, partially pregelatinized starch, etc.), fructose, caramel, canten, xylitol, paraffin, crystalline cellulose, sucrose, maltose, lactose, lactose hydrate, sucrose, glucose, purulan, polyoxyethylene hydrogenated castor oil, mulch Toll, reduced maltose water candy, powdered reduced maltose water candy, erythritol, sorbitol, mannitol, lactitol, trehalose, reduced palatinose, aminoalkyl methacrylate copolymer E, polyvinyl acetal diethylaminoacetate, organic excipients such as calcium citrate, etc. Be done. These can be used alone or in combination of two or more.
崩壊剤としては、具体的には例えば、カルボキシメチルスターチナトリウム、クロスカルメロースナトリウム、クロスポビドン等のスーパー崩壊剤やカルメロース、カルメロースカルシウム、デンプン、ショ糖脂肪酸エステル、ゼラチン、炭酸水素ナトリウム、デキストリン、デヒドロ酢酸及びその塩、ポビドン、ポリオキシエチレン硬化ヒマシ油60等が挙げられる。これらは、1種又は2種以上を組み合わせて使用することができる。 Specific examples of the disintegrant include super disintegrants such as sodium carboxymethyl starch, sodium croscarmellose, and crospovidone, carmellose, carmellose calcium, starch, sucrose fatty acid ester, gelatin, sodium hydrogencarbonate, dextrin, and the like. Examples thereof include dehydroacetic acid and salts thereof, povidone, and polyoxyethylene hydrogenated castor oil 60. These can be used alone or in combination of two or more.
結合剤としては、具体的には例えば、牛脂硬化油、硬化油、水素添加植物油、ダイズ硬化油、カルナウバロウ、サラシミツロウ、ミツロウ、モクロウ等の油脂類の他、メチルセルロース、ヒドロキシプロピルセルロース、ヒプロメロース、カルメロースナトリウム、デンプン(コムギデンプン、コメデンプン、トウモロコシデンプン、部分アルファー化デンプン等)、デキストリン、プルラン、アラビアゴム、カンテン、ゼラチン、トラガント、アルギン酸ナトリウム、ポビドン、ポリビニルアルコール、アミノアルキルメタクリレートコポリマーE、ポリビニルアセタールジエチルアミノアセテート等が挙げられる。これらは、1種又は2種以上を組み合わせて使用することができる。 Specific examples of the binder include fats and oils such as hydrogenated beef fat, hydrogenated oil, hydrogenated vegetable oil, hardened soybean oil, carnauba wax, sardine starch, beeswax, and mokuro, as well as methyl cellulose, hydroxypropyl cellulose, hypromellose, and carme. Sodium loin, starch (wheat starch, rice starch, corn starch, partially pregelatinized starch, etc.), dextrin, purulan, gum arabic, canten, gelatin, tragant, sodium alginate, povidone, polyvinyl alcohol, aminoalkyl methacrylate copolymer E, polyvinyl acetal Examples thereof include diethylaminoacetate. These can be used alone or in combination of two or more.
滑沢剤としては、具体的には例えば、ステアリン酸カルシウム、ステアリン酸マグネシウム、フマル酸ステアリルナトリウム、ショ糖脂肪酸エステル等が挙げられる。これらは、1種又は2種以上を組み合わせて使用することができる。 Specific examples of the lubricant include calcium stearate, magnesium stearate, stearyl fumarate, and sucrose fatty acid ester. These can be used alone or in combination of two or more.
可塑剤としては、具体的には例えば、クエン酸トリエチル、グリセリン、ゴマ油、ソルビトール、ヒマシ油、ポリソルベート80(ポリオキシエチレン(20)ソルビタンオレイン酸エステル)等が挙げられる。これらは、1種又は2種以上を組み合わせて使用することができる。 Specific examples of the plasticizer include triethyl citrate, glycerin, sesame oil, sorbitol, castor oil, and polysorbate 80 (polyoxyethylene (20) sorbitan oleic acid ester). These can be used alone or in combination of two or more.
フィルム形成剤としては、具体的には例えば、メチルセルロース、エチルセルロース等のアルキルセルロース;アルギン酸ナトリウム等のアルギン酸又はその塩;カラギーナン;カルボキシメチルセルロースナトリウム、カルボキシメチルセルロースカルシウム、カルボキシメチルセルロースカリウム、カルボキシメチルセルロース、カルボキシメチルエチルセルロース等のカルボキシアルキルセルロース;キサンタンガム;ヒドロキシメチルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、ヒプロメロース(ヒドロキシプロピルメチルセルロース)等のヒドロキシアルキルセルロース;ヒドロキシプロピルメチルセルロースフタレート等のヒドロキシアルキルセルロースフタレート;プルラン;ポリ酢酸ビニル;ポリ酢酸ビニルフタレート;ポリビニルピロリドン等が挙げられる。これらは、1種又は2種以上を組み合わせて使用することができる。 Specific examples of the film-forming agent include alkyl cellulose such as methyl cellulose and ethyl cellulose; alginic acid such as sodium alginate or a salt thereof; carrageenan; sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, potassium carboxymethyl cellulose, carboxymethyl cellulose, carboxymethyl ethyl cellulose and the like. Carboxymethyl cellulose; xanthan gum; hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyalkyl cellulose such as hypromellose (hydroxypropyl methyl cellulose); hydroxyalkyl cellulose phthalate such as hydroxypropyl methyl cellulose phthalate; purulan; vinyl acetate; polyvinyl acetate phthalate ; Polyvinylpyrrolidone and the like can be mentioned. These can be used alone or in combination of two or more.
粉体としては、タルク、酸化チタン、黄色三二酸化鉄、三二酸化鉄、法定色素等の有機粉体又は無機粉体が挙げられる。これらは、1種又は2種以上を組み合わせて使用することができる。 Examples of the powder include organic powders such as talc, titanium oxide, yellow iron sesquioxide, iron sesquioxide, and legal pigments, or inorganic powders. These can be used alone or in combination of two or more.
難水溶性高分子物質としては、具体的には例えば、カルボキシビニルポリマー、アミノアルキルメタクリレートコポリマー等が挙げられる。これらは、1種又は2種以上を組み合わせて使用することができる。
抗酸化剤としては、具体的には例えば、アスコルビン酸、亜硫酸水素ナトリウム、亜硫酸ナトリウム、エデト酸ナトリウム、エリソルビン酸、酢酸トコフェロール、ジブチルヒドロキシトルエン、天然ビタミンE、トコフェロール、ブチルヒドロキシアニソール等が挙げられる。これらは、1種又は2種以上を組み合わせて使用することができる。
Specific examples of the poorly water-soluble polymer substance include carboxyvinyl polymers and aminoalkyl methacrylate copolymers. These can be used alone or in combination of two or more.
Specific examples of the antioxidant include ascorbic acid, sodium hydrogen sulfite, sodium sulfite, sodium edetate, erythorbic acid, tocopherol acetate, dibutylhydroxytoluene, natural vitamin E, tocopherol, and butylhydroxyanisole. These can be used alone or in combination of two or more.
矯味剤としては、具体的には例えば、リモネン、ピネン、カンフェン、サイメン、シネオール、シトロネロール、ゲラニオール、ネロール、リナロール、メントール、テルピネオール、ロジノール、ボルネオール、イソボルネオール、メントン、カンフル、オイゲノール、シンゼイラノール等のテルペン;トウヒ油、オレンジ油、ハッカ油、樟脳白油、ユーカリ油、テレピン油、レモン油、ショウキョウ油、チョウジ油、ケイヒ油、ラベンダー油、ウイキョウ油、カミツレ油、シソ油、スペアミント油等のテルペンを含有する精油;アスコルビン酸、酒石酸、クエン酸、リンゴ酸及びこれらの塩等の酸味剤等が挙げられる。これらは、1種又は2種以上を組み合わせて使用することができる。 Specific examples of the flavoring agent include limonene, pinen, camphor, cymen, cineole, citronellol, geraniol, nerol, linalol, menthol, terpeneol, rosinol, borneol, isobornole, menthon, camphor, eugenol, syntheilanol and the like. Terpenes; Tohi oil, orange oil, peppermint oil, camphor white oil, eucalyptus oil, terepine oil, lemon oil, ginger oil, butterfly oil, kehi oil, lavender oil, uikyo oil, chamomile oil, perilla oil, spare mint oil, etc. Terpene-containing essential oils; ascorbic acid, tartrate acid, citric acid, orange acid, acidulants such as salts thereof and the like. These can be used alone or in combination of two or more.
甘味剤としては、具体的には例えば、アスパルテーム、ステビア、スクラロース、グリチルリチン酸、ソーマチン、アセスルファムカリウム、サッカリン、サッカリンナトリウム等が挙げられ、これらの1種又は2種以上を組み合わせて使用できる。 Specific examples of the sweetener include aspartame, stevia, sucralose, glycyrrhizic acid, thaumatin, acesulfame potassium, saccharin, sodium saccharin, and the like, and one or a combination of two or more of these can be used.
医薬組成物は、その剤形に応じて公知の方法により製造することができる。
例えば、医薬組成物が固形製剤である場合には、粉砕、混合、造粒、乾燥、整粒、分級、充填、打錠、コーティング等の単位操作を適宜組み合わせることにより製造することができる。
より具体的には例えば、医薬組成物の剤形が顆粒剤、散剤、丸剤等の粒状の製剤の場合、成分(A)、成分(B)に加え、必要に応じ賦形剤や結合剤、崩壊剤、滑沢剤等の製剤添加物を用い、これらの成分の全部又は一部を混合した後、押出造粒、転動造粒、攪拌造粒、流動層造粒、噴霧造粒、溶融造粒、破砕造粒等の公知の造粒方法により造粒して造粒物を得、さらに必要に応じて分級、整粒等することで製造することができる。なお、得られた造粒物は、公知の方法によりコーティング剤等で被覆することもできる。
また、医薬組成物の剤形が錠剤の場合、成分(A)、成分(B)に加え、必要に応じ賦形剤や結合剤、崩壊剤、滑沢剤等の適当な製剤添加物を用い、これらの成分の全部又は一部を混合して混合物を得、これを直接圧縮(打錠)すること(直接粉末圧縮法)や、上記の造粒物を必要に応じて分級、整粒等したあと圧縮(打錠)すること(半乾式顆粒圧縮法、乾式顆粒圧縮法、湿式顆粒圧縮法など)により製造することができる。なお、得られた圧縮物(錠剤)は、公知の方法によりコーティング剤等で被覆することもできる。
さらに、医薬組成物の剤形がカプセル剤の場合、上記の造粒物や圧縮物等を、カプセルに充填すればよい。
The pharmaceutical composition can be produced by a known method depending on the dosage form thereof.
For example, when the pharmaceutical composition is a solid preparation, it can be produced by appropriately combining unit operations such as pulverization, mixing, granulation, drying, sizing, classification, filling, tableting, and coating.
More specifically, for example, when the dosage form of the pharmaceutical composition is a granular preparation such as a granule, a powder, or a pill, in addition to the component (A) and the component (B), an excipient or a binder is required as necessary. After mixing all or part of these components using formulation additives such as disintegrants and lubricants, extrusion granulation, rolling granulation, stirring granulation, fluidized bed granulation, spray granulation, It can be produced by granulating by a known granulation method such as melt granulation or crushing granulation to obtain a granulated product, and further classifying, sizing, etc. as necessary. The obtained granulated product can also be coated with a coating agent or the like by a known method.
When the dosage form of the pharmaceutical composition is a tablet, in addition to the component (A) and the component (B), appropriate formulation additives such as excipients, binders, disintegrants, and lubricants are used as necessary. , All or part of these components are mixed to obtain a mixture, which is directly compressed (tablet) (direct powder compression method), and the above granules are classified, sized, etc. as necessary. After that, it can be produced by compression (tablet) (semi-dry granule compression method, dry granule compression method, wet granule compression method, etc.). The obtained compressed product (tablet) can also be coated with a coating agent or the like by a known method.
Further, when the dosage form of the pharmaceutical composition is a capsule, the above-mentioned granulated product, compressed product, or the like may be filled in the capsule.
本発明において、医薬組成物はさらに気密包装体に収容される(なお、以下、本明細書において、医薬組成物を気密包装体に収容してなるものを「医薬品」と称する。)。なお、本発明において、医薬品は気密包装体以外に、さらに下記「気密包装体」に該当しない包装を備えていてもよく、また、医薬組成物は、気密包装体に直接的あるいは間接的に収容されていればよい。
本明細書において「気密包装体」とは、通常の取扱い、運搬又は保存等の状態において、固形又は液状の異物の侵入を抑制し得る包装を意味し、第十七改正日本薬局方 通則に定義される「気密容器」及び「密封容器」を包含する概念である。気密包装体としては、定形、不定形のいずれのものも用いることができ、具体的には例えば、ビン包装、SP(Strip Package)包装、PTP(Press Through Package)包装、ピロー包装、スティック包装等が挙げられる。気密包装体としては、これらを複数組み合わせたものであってもよく、具体的には例えば、医薬組成物をまずPTP包装にて包装し、これをさらにピロー包装にて包装する態様等が挙げられる。
気密包装体としては、配合変化を抑制する観点から、ビン包装、SP包装、PTP包装、ピロー包装及びスティック包装よりなる群から選ばれる1種以上であるのが好ましく、少なくともPTP包装を備えるもの(PTP包装と、さらに必要に応じてビン包装、SP包装、ピロー包装、スティック包装等の他の包装を組み合わせたもの)、少なくともビン包装を備えるものであるのが特に好ましい。
In the present invention, the pharmaceutical composition is further contained in an airtight package (hereinafter, in the present specification, the pharmaceutical composition contained in the airtight package is referred to as a "pharmaceutical product"). In the present invention, the pharmaceutical product may further include a package that does not fall under the following "airtight packaging" in addition to the airtight packaging, and the pharmaceutical composition is directly or indirectly contained in the airtight packaging. It suffices if it is done.
As used herein, the term "airtight package" means a package that can suppress the intrusion of solid or liquid foreign matter under normal handling, transportation, storage, etc., and is defined in the 17th Amendment of the Japanese Pharmacy Regulations. It is a concept including "airtight container" and "sealed container". As the airtight package, either a fixed form or an amorphous package can be used. Specifically, for example, bottle packaging, SP (Strip Package) packaging, PTP (Press Through Package) packaging, pillow packaging, stick packaging, etc. Can be mentioned. The airtight package may be a combination of a plurality of these, and specific examples thereof include a mode in which the pharmaceutical composition is first packaged in PTP packaging and then packaged in pillow packaging. ..
The airtight packaging is preferably one or more selected from the group consisting of bottle packaging, SP packaging, PTP packaging, pillow packaging, and stick packaging from the viewpoint of suppressing changes in composition, and includes at least PTP packaging ( A combination of PTP packaging and, if necessary, other packaging such as bottle packaging, SP packaging, pillow packaging, stick packaging), at least bottle packaging is particularly preferred.
気密包装体の包装材料(素材)は特に限定されず、例えば、ガラス、プラスチック(ポリエチレンテレフタレート、ポリエチレンナフタレート等のポリエステル;ポリエチレン(低密度(LDPE)、中密度(MDPE)、高密度(HDPE)を含む)、ポリプロピレン等のポリオレフィン;ポリカーボネート;ポリスチレン等)、金属(アルミニウム等)などの、医薬品や食品等の分野で用いられる材料を、1種単独で又は2種以上を組み合わせて適宜用いることができる。 The packaging material (material) of the airtight packaging is not particularly limited, and for example, glass, plastic (polystyrene terephthalate, polyethylene naphthalate, etc.); polyethylene (low density (LDPE), medium density (MDPE), high density (HDPE)). , Polyethylene and other polyolefins; polycarbonate; polystyrene, etc.), metals (aluminum, etc.) and other materials used in the fields of pharmaceuticals, foods, etc., may be used alone or in combination of two or more. it can.
例えば、ビン包装に用いられる包装材料は特に限定されるものではなく、ガラス、プラスチック、金属などが挙げられ、これらの1種又は2種以上を適宜組み合わせることができる。ビン包装の材料としては、ガラス、ポリエチレン、ポリプロピレンが好ましく、ガラス、低密度ポリエチレン(LDPE)、高密度ポリエチレン(HDPE)がより好ましく、ガラス、高密度ポリエチレン(HDPE)が特に好ましい。
ビン包装するに際しては例えば、医薬組成物を、ビン内に適当な数量格納し、次いで、適当な栓や蓋で封をすればよい。なお、ビンは、格納する医薬組成物の数量等に応じた大きさのものを適宜選択すればよく、ビンの容量としては例えば、10〜500mL程度であり、14〜400mLが好ましく、24〜350mLがより好ましい。
For example, the packaging material used for bottle packaging is not particularly limited, and examples thereof include glass, plastic, and metal, and one or more of these can be appropriately combined. As the material for the bottle packaging, glass, polyethylene and polypropylene are preferable, glass, low density polyethylene (LDPE) and high density polyethylene (HDPE) are more preferable, and glass and high density polyethylene (HDPE) are particularly preferable.
When packaging in a bottle, for example, the pharmaceutical composition may be stored in an appropriate quantity in the bottle, and then sealed with an appropriate stopper or lid. The size of the bottle may be appropriately selected according to the quantity of the pharmaceutical composition to be stored, and the volume of the bottle is, for example, about 10 to 500 mL, preferably 14 to 400 mL, and 24 to 350 mL. Is more preferable.
また、SP包装、PTP包装、ピロー包装やスティック包装等に用いられる包装材料は特に限定されるものではなく、例えば、二軸延伸ポリプロピレン(OPP)、二軸延伸ポリエステル(PET)、グリコール変性PET(PET−G)、二軸延伸ナイロン(ONy、PA)、セロハン、紙、低密度ポリエチレン(LDPE)、直鎖状低密度ポリエチレン(L−LDPE)、エチレン−酢酸ビニル共重合体(EVA)、無延伸ポリプロピレン(CPP、IPP)、アイオノマー樹脂(IO)、エチレン−メタクリル酸共重合体(EMAA)、ポリアクリロニトリル(PAN)、二軸延伸ポリ塩化ビニリデン(PVDC)、エチレン−ビニルアルコール共重合樹脂(EVOH)、ポリ塩化ビニル(PVC)、環状ポリオレフィン(COC)、無延伸ナイロン(CNy)、ポリカーボネート(PC)、ポリスチレン(PS)、硬質塩化ビニル(VSC)等の樹脂や、アルミニウム箔(AL)のような金属箔等が挙げられ、これらの1種又は2種以上を適宜組み合わせることができる。 The packaging materials used for SP packaging, PTP packaging, pillow packaging, stick packaging and the like are not particularly limited, and for example, biaxially stretched polypropylene (OPP), biaxially stretched polyester (PET), glycol-modified PET ( PET-G), biaxially stretched nylon (ONy, PA), cellophane, paper, low density polyethylene (LDPE), linear low density polyethylene (L-LDPE), ethylene-vinyl acetate copolymer (EVA), none Stretched polypropylene (CPP, IPP), ionomer resin (IO), ethylene-methacrylic acid copolymer (EMAA), polyacrylonitrile (PAN), biaxially stretched polyvinylidene chloride (PVDC), ethylene-vinyl alcohol copolymer resin (EVOH) ), Polyvinyl chloride (PVC), cyclic polyolefin (COC), unstretched nylon (CNy), polycarbonate (PC), polystyrene (PS), hard vinyl chloride (VSC) and other resins, and aluminum foil (AL). Metal foil and the like can be mentioned, and one or more of these can be appropriately combined.
SP包装、PTP包装、ピロー包装やスティック包装等するに際しては、上記したような包装材料の1種以上を用いたシートを用いて、公知の方法で製造すればよく、この場合において、当該包装材料は適宜組合せた多層構造とすることもできる。シートとして、2種以上の包装材料を用いた多層構造とする方法としては、当該包装材料をラミネートして積層シートを製造する方法が挙げられる。積層シートは、押出しラミネート、ドライラミネート、共押出しラミネート、サーマルラミネート、ウェットラミネート、ノンソルベントラミネート、ヒートラミネート等の公知の方法で製造することができる。また、SP包装、PTP包装、ピロー包装やスティック包装用のシートは、公知の市販品を用いることもできる。 In the case of SP packaging, PTP packaging, pillow packaging, stick packaging, etc., it may be manufactured by a known method using a sheet using one or more of the above-mentioned packaging materials. In this case, the packaging material. Can also have a multi-layer structure that is appropriately combined. As a method of forming a multi-layer structure using two or more kinds of packaging materials as a sheet, a method of laminating the packaging materials to produce a laminated sheet can be mentioned. The laminated sheet can be produced by a known method such as extruded laminate, dry laminate, coextruded laminate, thermal laminate, wet laminate, non-solvent laminate, heat laminate and the like. Further, as the sheet for SP packaging, PTP packaging, pillow packaging and stick packaging, known commercially available products can also be used.
上記シートにおいて、1種の包装材料を用いた単層シートとしては、PVCシートやCPPシート等が挙げられ、また2種以上の包装材料を用いた積層シートとしては、そのシート構成が、例えば、PVCとPVDCを積層したもの(PVC/PVDC。以下、同様に略する。)、PVC/PVDC/PE/PVC、PVC/PVDC/PE/PVDC/PVC、CPP/COC/CPP、PVC/PCTFE、CPP/PCTFE、PVC/AL/PA、PVC/AL、CPP/AL、CPP/CPP/CPP(左記シートは、CPPとして、2種以上を用いるものである。)等が挙げられるが、これらのみに限定されるものではない。 In the above sheet, examples of the single-layer sheet using one kind of packaging material include a PVC sheet and a CPP sheet, and as a laminated sheet using two or more kinds of packaging materials, the sheet composition thereof is, for example, A stack of PVC and PVCC (PVC / PVCC; hereinafter abbreviated in the same manner), PVC / PVDC / PE / PVC, PVC / PVCC / PE / PVDC / PVC, CPP / COC / CPP, PVC / PCTFE, CPP. / PCTFE, PVC / AL / PA, PVC / AL, CPP / AL, CPP / CPP / CPP (the sheet on the left uses two or more types of CPP), but is limited to these. It is not something that is done.
PTP包装の形態としては、公知の方法で樹脂シート等に所望数形成したポケットに、医薬組成物を1個又は1投与単位ずつ格納し、次いでアルミニウム箔等の金属箔を構成材料とするシートをフタ材として用いて蓋をすることが挙げられる。なお、ポケットを形成するシートとしてもアルミニウム箔を構成材料とするシートを用いた、いわゆる両面アルミPTP包装としてもよい。本発明においては、配合変化を抑制する観点から、PTP包装をさらにピロー包装(例えば、アルミピロー包装など)により包装するのが好ましい。
SP包装やピロー包装、スティック包装の形態としては、公知の方法で樹脂シートやアルミニウム箔を構成材料とするシート等を用いて、医薬組成物を1個又は1投与単位ずつ包装することが挙げられる。本発明においては、配合変化を抑制する観点から、アルミニウム箔を構成材料とするシートを用いるのが好ましい。
As a form of PTP packaging, a sheet in which a desired number of pharmaceutical compositions are stored in a pocket formed on a resin sheet or the like by a known method, one or one administration unit at a time, and then a metal foil such as an aluminum foil is used as a constituent material. It can be used as a lid material to cover the lid. The sheet forming the pocket may be a so-called double-sided aluminum PTP packaging using a sheet made of aluminum foil as a constituent material. In the present invention, it is preferable to further wrap the PTP wrapping with pillow wrapping (for example, aluminum pillow wrapping) from the viewpoint of suppressing the change in composition.
Examples of the forms of SP packaging, pillow packaging, and stick packaging include packaging the pharmaceutical composition one by one or one administration unit at a time using a resin sheet, a sheet containing aluminum foil as a constituent material, or the like by a known method. .. In the present invention, it is preferable to use a sheet made of aluminum foil as a constituent material from the viewpoint of suppressing a change in composition.
なお、本明細書において、医薬品における医薬組成物の包装体内部での占有率(容積率)は、包装体がビン包装の場合、通常、25〜90%であり、28〜75%が好ましく、30〜50%がより好ましい。また、包装体がSP包装、PTP包装、ピロー包装、スティック包装の場合、通常、30〜98%であり、40〜95%が好ましく、45〜93%がより好ましく、50〜90%が特に好ましい。なお、この場合において、占有率とは、包装体内部の全容積に対する医薬組成物の占有率を意味するものであり、包装体内部に格納した医薬組成物の破損防止のための詰め物や中栓等は、空間占有率を算出するに際して考慮されるものではない。 In the present specification, the occupancy ratio (floor area ratio) of the pharmaceutical composition in the pharmaceutical product is usually 25 to 90%, preferably 28 to 75%, when the package is bottle-wrapped. More preferably, it is 30 to 50%. When the package is SP packaging, PTP packaging, pillow packaging, or stick packaging, it is usually 30 to 98%, preferably 40 to 95%, more preferably 45 to 93%, and particularly preferably 50 to 90%. .. In this case, the occupancy rate means the occupancy rate of the pharmaceutical composition with respect to the total volume inside the package, and the filling or inner plug for preventing damage to the pharmaceutical composition stored inside the package. Etc. are not taken into consideration when calculating the space occupancy rate.
気密包装体としては、市販の包装体をそのまま用いてもよく、また市販の包装材料を加工して用いてもよい。市販品のビン包装の包装体としては、例えば、ガラス瓶(磯矢硝子工業(株)製)、錠剤ビン(東京硝子(株)製)、Z−シリーズ(阪神化成工業(株)製)等が挙げられる。また、市販品のピロー包装の包装体としては、ラミジップ(登録商標)((株)生産日本社製)等が挙げられる。さらに、SP包装、PTP包装、ピロー包装やスティック包装用の包装材料としては、スミライトVSS、スミライトVSL、スミライトNS、スミライトFCL(以上、住友ベークライト(株)製)、TASシリーズ(大成化工(株)製)、PTP用ビニホイル、PTP用スーパーホイル(以上、三菱樹脂(株)製)、ニッパクアルミ箔(日本製箔(株)製)、アルミ箔銀無地(大和化学工業(株)製)等が挙げられる。 As the airtight package, a commercially available package may be used as it is, or a commercially available package material may be processed and used. Examples of commercially available bottle packaging include glass bottles (manufactured by Isoya Glass Industry Co., Ltd.), tablet bottles (manufactured by Tokyo Glass Co., Ltd.), Z-series (manufactured by Hanshin Kasei Kogyo Co., Ltd.), and the like. Be done. Examples of commercially available pillow packaging include Lamizip (registered trademark) (manufactured by Japan Co., Ltd.) and the like. Furthermore, as packaging materials for SP packaging, PTP packaging, pillow packaging and stick packaging, Sumilite VSS, Sumilite VSL, Sumilite NS, Sumilite FCL (all manufactured by Sumitomo Bakelite Co., Ltd.), TAS series (Taisei Kako Co., Ltd.) , PTP vinyl foil, PTP super foil (above, manufactured by Mitsubishi Resin Co., Ltd.), Nippaku aluminum foil (manufactured by Nippon Foil Co., Ltd.), aluminum foil silver plain (manufactured by Daiwa Chemical Industry Co., Ltd.), etc. Be done.
医薬組成物を気密包装体に収容する方法は特に限定されるものではなく、包装体内への医薬組成物の投入等の適当な手段により、医薬組成物を包装体内に配置することで達成できる。この場合において、包装体内に医薬組成物とともに乾燥剤(例えば、円柱状(錠剤型)のものやシート状のもの)を投入する手段を用いてもよい。 The method of accommodating the pharmaceutical composition in the airtight package is not particularly limited, and it can be achieved by arranging the pharmaceutical composition in the package by an appropriate means such as putting the pharmaceutical composition into the package. In this case, a means for charging a desiccant (for example, a columnar (tablet type) or sheet-shaped one) together with the pharmaceutical composition into the package may be used.
本発明において、医薬組成物あるいは医薬品は、オキシカム系NSAIDsであるアンピロキシカム、ピロキシカム、メロキシカムやロルノキシカムを含有することから、頭痛・歯痛・抜歯後の疼痛・咽頭痛・耳痛・関節痛・神経痛・腰痛・筋肉痛・肩こり痛・打撲痛・骨折痛・ねんざ痛・月経痛(生理痛)・外傷後の鎮痛、悪寒・発熱時の解熱、かぜの諸症状(のどの痛み、悪寒、発熱、頭痛、関節の痛み、筋肉の痛み)等に効能又は効果を有し、総合感冒薬(かぜ薬)や解熱鎮痛薬等として有用である。 In the present invention, since the pharmaceutical composition or pharmaceutical contains oxycam-based NSAIDs ampyroxycam, pyroxicum, meroxycam, and lornoxicum, headache, toothache, post-extraction pain, sore throat, ear pain, joint pain, nerve pain, and so on. Low back pain, muscle pain, stiff shoulder pain, bruising pain, fracture pain, numbness pain, menstrual pain (physiological pain), post-traumatic pain relief, cold / fever relief, cold symptoms (throat pain, bad cold, fever, headache) , Joint pain, muscle pain), etc., and is useful as a general sensation drug (cold drug), antipyretic analgesic, etc.
医薬組成物の服用経路は特に限定されず、適用する疾患、剤形の種類、服用者の性別、年齢、症状等に応じて適宜検討して決定することができるが、服用の容易性の観点から、経口投与が好ましい。また、医薬組成物は、1日につき、1〜4回程度に分けて、食前、食間、食後、就寝前等に服用することができる。 The route of administration of the pharmaceutical composition is not particularly limited, and it can be appropriately examined and determined according to the disease to be applied, the type of dosage form, the sex, age, symptoms, etc. of the user, but from the viewpoint of ease of administration. Therefore, oral administration is preferable. In addition, the pharmaceutical composition can be taken before meals, between meals, after meals, before bedtime, etc., in 1 to 4 divided doses per day.
なお、本明細書は、これらに何ら限定されるものでは無いが、例えば以下の態様を開示する。
[1A] 次の成分(A)及び(B):
(A)アンピロキシカム、ピロキシカム、メロキシカム、ロルノキシカム及びそれらの塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上;
(B)次の成分(B−1)〜(B−3)よりなる群から選ばれる1種以上;
(B−1)キサンチン誘導体
(B−2)塩基性化合物
(B−3)イソバレリル尿素誘導体
を含有する医薬組成物が、気密包装体に収容されてなる医薬品。
[2A] 医薬組成物が、固形製剤である、[1A]記載の医薬品。
[3A] 医薬組成物の剤形が、錠剤、カプセル剤、顆粒剤、散剤又は丸剤である、[1A]又は[2A]記載の医薬品。
[4A] 気密包装体が、ビン包装、SP包装、PTP包装、ピロー包装及びスティック包装よりなる群から選ばれる1種以上である、[1A]〜[3A]のいずれか記載の医薬品。
[5A] 気密包装体が、少なくともPTP包装を備えるものである、[1A]〜[4A]のいずれか記載の医薬品。
The present specification is not limited to these, but discloses, for example, the following aspects.
[1A] The following components (A) and (B):
(A) One or more selected from the group consisting of ampiroxicam, piroxicam, meloxicam, lornoxicam and salts thereof, and solvates thereof;
(B) One or more selected from the group consisting of the following components (B-1) to (B-3);
(B-1) Xanthine derivative (B-2) Basic compound (B-3) A pharmaceutical product containing a pharmaceutical composition containing an isovaleryl urea derivative contained in an airtight package.
[2A] The drug according to [1A], wherein the pharmaceutical composition is a solid preparation.
[3A] The drug according to [1A] or [2A], wherein the dosage form of the pharmaceutical composition is a tablet, a capsule, a granule, a powder or a pill.
[4A] The drug according to any one of [1A] to [3A], wherein the airtight package is one or more selected from the group consisting of bottle packaging, SP packaging, PTP packaging, pillow packaging and stick packaging.
[5A] The drug according to any one of [1A] to [4A], wherein the airtight package comprises at least a PTP package.
[6A] 成分(B−1)が、カフェイン、テオフィリン、テオブロミン、パラキサンチン、プロキシフィリン、ジプロフィリン及びそれらの塩並びにそれらの溶媒和物よりなる群より選ばれる1種以上である、[1A]〜[5A]のいずれか記載の医薬品。
[7A] 成分(B−1)が、カフェイン水和物、無水カフェイン及び安息香酸ナトリウムカフェインよりなる群から選ばれる1種以上である、[1A]〜[6A]のいずれか記載の医薬品。
[8A] 成分(B−2)が、グリシン、ケイ酸マグネシウム、合成ケイ酸マグネシウム、合成ヒドロタルサイト、酸化マグネシウム、ジヒドロキシアルミニウムアミノアセテート、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・炭酸水素ナトリウム共沈物、水酸化アルミニウム・炭酸マグネシウム混合乾燥ゲル、水酸化アルミニウム・炭酸マグネシウム・炭酸カルシウム共沈物、水酸化マグネシウム・硫酸アルミニウムカリウムの共沈生成物、炭酸マグネシウム及びメタケイ酸アルミン酸マグネシウムよりなる群から選ばれる1種以上である、[1A]〜[7A]のいずれか記載の医薬品。
[6A] The component (B-1) is at least one selected from the group consisting of caffeine, theophylline, theobromine, paraxanthine, proxanthine, diprophylline and salts thereof, and solvates thereof, [1A]. -The drug according to any one of [5A].
[7A] The above-mentioned any one of [1A] to [6A], wherein the component (B-1) is at least one selected from the group consisting of caffeine hydrate, anhydrous caffeine and sodium benzoate caffeine. Pharmaceuticals.
[8A] The component (B-2) is glycine, magnesium silicate, synthetic magnesium silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate, aluminum hydroxide gel, dry aluminum hydroxide gel, aluminum hydroxide. Sodium hydrogen carbonate co-precipitate, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate co-precipitate, magnesium hydroxide / potassium aluminum sulfate co-precipitate, magnesium carbonate and aluminic acid metasilicate The drug according to any one of [1A] to [7A], which is one or more selected from the group consisting of magnesium.
[1B] 気密包装体に収容するための、次の成分(A)及び(B):
(A)アンピロキシカム、ピロキシカム、メロキシカム、ロルノキシカム及びそれらの塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上;
(B)次の成分(B−1)〜(B−3)よりなる群から選ばれる1種以上;
(B−1)キサンチン誘導体
(B−2)塩基性化合物
(B−3)イソバレリル尿素誘導体
を含有する医薬組成物。
[2B] 固形製剤である、[1B]記載の医薬組成物。
[3B] 剤形が、錠剤、カプセル剤、顆粒剤、散剤又は丸剤である、[1B]又は[2B]記載の医薬組成物。
[4B] 気密包装体が、ビン包装、SP包装、PTP包装、ピロー包装及びスティック包装よりなる群から選ばれる1種以上である、[1B]〜[3B]のいずれか記載の医薬組成物。
[5B] 気密包装体が、少なくともPTP包装を備えるものである、[1B]〜[4B]のいずれか記載の医薬組成物。
[1B] The following components (A) and (B) for containing in an airtight package:
(A) One or more selected from the group consisting of ampiroxicam, piroxicam, meloxicam, lornoxicam and salts thereof, and solvates thereof;
(B) One or more selected from the group consisting of the following components (B-1) to (B-3);
(B-1) Xanthine derivative (B-2) Basic compound (B-3) A pharmaceutical composition containing an isovaleryl-urea derivative.
[2B] The pharmaceutical composition according to [1B], which is a solid preparation.
[3B] The pharmaceutical composition according to [1B] or [2B], wherein the dosage form is a tablet, a capsule, a granule, a powder or a pill.
[4B] The pharmaceutical composition according to any one of [1B] to [3B], wherein the airtight package is one or more selected from the group consisting of bottle packaging, SP packaging, PTP packaging, pillow packaging and stick packaging.
[5B] The pharmaceutical composition according to any one of [1B] to [4B], wherein the airtight package comprises at least a PTP package.
[6B] 成分(B−1)が、カフェイン、テオフィリン、テオブロミン、パラキサンチン、プロキシフィリン、ジプロフィリン及びそれらの塩並びにそれらの溶媒和物よりなる群より選ばれる1種以上である、[1B]〜[5B]のいずれか記載の医薬組成物。
[7B] 成分(B−1)が、カフェイン水和物、無水カフェイン及び安息香酸ナトリウムカフェインよりなる群から選ばれる1種以上である、[1B]〜[6B]のいずれか記載の医薬組成物。
[8B] 成分(B−2)が、グリシン、ケイ酸マグネシウム、合成ケイ酸マグネシウム、合成ヒドロタルサイト、酸化マグネシウム、ジヒドロキシアルミニウムアミノアセテート、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・炭酸水素ナトリウム共沈物、水酸化アルミニウム・炭酸マグネシウム混合乾燥ゲル、水酸化アルミニウム・炭酸マグネシウム・炭酸カルシウム共沈物、水酸化マグネシウム・硫酸アルミニウムカリウムの共沈生成物、炭酸マグネシウム及びメタケイ酸アルミン酸マグネシウムよりなる群から選ばれる1種以上である、[1B]〜[7B]のいずれか記載の医薬組成物。
[6B] The component (B-1) is at least one selected from the group consisting of caffeine, theophylline, theobromine, paraxanthine, proxanthine, diprophylline and salts thereof, and solvates thereof, [1B]. The pharmaceutical composition according to any one of [5B].
[7B] The above-mentioned any one of [1B] to [6B], wherein the component (B-1) is at least one selected from the group consisting of caffeine hydrate, anhydrous caffeine and sodium benzoate caffeine. Pharmaceutical composition.
[8B] The component (B-2) is glycine, magnesium silicate, synthetic magnesium silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate, aluminum hydroxide gel, dry aluminum hydroxide gel, aluminum hydroxide. Sodium hydrogen carbonate co-precipitate, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate co-precipitate, magnesium hydroxide / potassium aluminum sulfate co-precipitate, magnesium carbonate and aluminic acid metasilicate The pharmaceutical composition according to any one of [1B] to [7B], which is one or more selected from the group consisting of magnesium.
[1C] 次の成分(A)及び(B):
(A)アンピロキシカム、ピロキシカム、メロキシカム、ロルノキシカム及びそれらの塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上;
(B)次の成分(B−1)〜(B−3)よりなる群から選ばれる1種以上;
(B−1)キサンチン誘導体
(B−2)塩基性化合物
(B−3)イソバレリル尿素誘導体
を含有する医薬組成物を気密包装体に収容する工程を含む、医薬組成物の安定化方法(例えば、成分(A)の安定化方法。なお、「安定化方法」は、好適には「変色の抑制方法」である。)。
なお、本方法において、医薬組成物中に成分(A)、(B)を含有せしめる工程、並びに医薬組成物を気密包装体に収容する工程の順序は特に限定されず、例えば、成分(A)、(B)を任意の順序で医薬組成物に含有せしめた後、これを気密包装体に収容してもよく、また、成分(A)、(B)の一部を医薬組成物に含有せしめた後、これを気密包装体に収容し、その後さらに残りの成分を医薬組成物に含有せしめてもよい。
[2C] 医薬組成物が、固形製剤である、[1C]記載の方法。
[3C] 医薬組成物の剤形が、錠剤、カプセル剤、顆粒剤、散剤又は丸剤である、[1C]又は[2C]記載の方法。
[4C] 気密包装体が、ビン包装、SP包装、PTP包装、ピロー包装及びスティック包装よりなる群から選ばれる1種以上である、[1C]〜[3C]のいずれか記載の方法。
[5C] 気密包装体が、少なくともPTP包装を備えるものである、[1C]〜[4C]のいずれか記載の方法。
[1C] The following components (A) and (B):
(A) One or more selected from the group consisting of ampiroxicam, piroxicam, meloxicam, lornoxicam and salts thereof, and solvates thereof;
(B) One or more selected from the group consisting of the following components (B-1) to (B-3);
(B-1) Xanthine Derivative (B-2) Basic Compound (B-3) A method for stabilizing a pharmaceutical composition, which comprises a step of accommodating a pharmaceutical composition containing an isovaleryl urea derivative in an airtight package (for example,). A method for stabilizing the component (A). The "stabilization method" is preferably a "method for suppressing discoloration").
In this method, the order of the steps of incorporating the components (A) and (B) in the pharmaceutical composition and the steps of accommodating the pharmaceutical composition in the airtight package is not particularly limited, and for example, the component (A). , (B) may be contained in the pharmaceutical composition in any order and then contained in an airtight package, and some of the components (A) and (B) may be contained in the pharmaceutical composition. After that, this may be contained in an airtight package, and then the remaining components may be further contained in the pharmaceutical composition.
[2C] The method according to [1C], wherein the pharmaceutical composition is a solid preparation.
[3C] The method according to [1C] or [2C], wherein the dosage form of the pharmaceutical composition is a tablet, a capsule, a granule, a powder or a pill.
[4C] The method according to any one of [1C] to [3C], wherein the airtight package is one or more selected from the group consisting of bottle packaging, SP packaging, PTP packaging, pillow packaging and stick packaging.
[5C] The method according to any one of [1C] to [4C], wherein the airtight package comprises at least PTP packaging.
[6C] 成分(B−1)が、カフェイン、テオフィリン、テオブロミン、パラキサンチン、プロキシフィリン、ジプロフィリン及びそれらの塩並びにそれらの溶媒和物よりなる群より選ばれる1種以上である、[1C]〜[5C]のいずれか記載の方法。
[7C] 成分(B−1)が、カフェイン水和物、無水カフェイン及び安息香酸ナトリウムカフェインよりなる群から選ばれる1種以上である、[1C]〜[6C]のいずれか記載の方法。
[8C] 成分(B−2)が、グリシン、ケイ酸マグネシウム、合成ケイ酸マグネシウム、合成ヒドロタルサイト、酸化マグネシウム、ジヒドロキシアルミニウムアミノアセテート、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・炭酸水素ナトリウム共沈物、水酸化アルミニウム・炭酸マグネシウム混合乾燥ゲル、水酸化アルミニウム・炭酸マグネシウム・炭酸カルシウム共沈物、水酸化マグネシウム・硫酸アルミニウムカリウムの共沈生成物、炭酸マグネシウム及びメタケイ酸アルミン酸マグネシウムよりなる群から選ばれる1種以上である、[1C]〜[7C]のいずれか記載の方法。
[6C] The component (B-1) is at least one selected from the group consisting of caffeine, theophylline, theobromine, paraxanthine, proxanthine, diprophylline and salts thereof, and solvates thereof, [1C]. The method according to any one of ~ [5C].
[7C] The above-mentioned any one of [1C] to [6C], wherein the component (B-1) is at least one selected from the group consisting of caffeine hydrate, anhydrous caffeine and sodium benzoate caffeine. Method.
[8C] The component (B-2) is glycine, magnesium silicate, synthetic magnesium silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate, aluminum hydroxide gel, dry aluminum hydroxide gel, aluminum hydroxide. Sodium hydrogen carbonate co-precipitate, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate co-precipitate, magnesium hydroxide / potassium aluminum sulfate co-precipitate, magnesium carbonate and aluminic acid metasilicate The method according to any one of [1C] to [7C], which is one or more selected from the group consisting of magnesium.
以下、実施例により本発明をより具体的に説明するが、本発明はこれらにより何ら限定されるものではない。なお、以下の試験例において各成分の使用量は、換算量を特に断らない限り、表示した成分そのものの量を示す。 Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto. In the following test examples, the amount of each component used indicates the amount of the indicated component itself unless the conversion amount is specified.
[試験例1]安定性試験
以下に示すサンプル1−1〜1−4をそれぞれ調製後、40℃の条件下で2ヶ月間保存し、高温での長期間保存によるサンプルの変色を確認した。
なお、サンプルの変色は、保存前及び保存後の各サンプルの明度(L*)を分光測色計(CM−700d:コニカミノルタジャパン(株))を用いて測定し、保存前後による明度の変化(ΔL*)を算出して変色の指標とした。なお、ΔL*は絶対値として評価した。
[Test Example 1] Stability test After preparing each of the samples 1-1 to 1-4 shown below, they were stored under the condition of 40 ° C. for 2 months, and discoloration of the sample due to long-term storage at high temperature was confirmed.
To discolor the sample, measure the brightness (L * ) of each sample before and after storage using a spectrophotometer (CM-700d: Konica Minolta Japan Co., Ltd.), and change the brightness before and after storage. (ΔL * ) was calculated and used as an index of discoloration. In addition, ΔL * was evaluated as an absolute value.
〔サンプル1−1〕
メロキシカム(MELOXICAM:Hwail Pharmaceutical Co., Ltd.製)を、蓋を開けたガラス製の容器(2K規格瓶)にとり、サンプル1−1とした。
〔サンプル1−2〕
メロキシカム(MELOXICAM:Hwail Pharmaceutical Co., Ltd.製)を1質量部に対して無水カフェイン(無水カフェイン:(株)静岡カフェイン工業所製)を1質量部の割合で混合した。得られた混合物を、蓋を開けたガラス製の容器(2K規格瓶)にとり、サンプル1−2とした。
〔サンプル1−3〕
メロキシカム(MELOXICAM:Hwail Pharmaceutical Co., Ltd.製)を、ガラス製の容器(2K規格瓶)に入れて蓋をし、サンプル1−3とした。
[Sample 1-1]
Meloxicam (MELOXICAM: Hwheel Pharmaceutical Co., manufactured by Ltd.) was placed in a glass container (2K standard bottle) with an open lid and used as sample 1-1.
[Sample 1-2]
Meloxicam (MELOXICAM: Hwheel Pharmaceutical Co., manufactured by Ltd.) was mixed with 1 part by mass of anhydrous caffeine (anhydrous caffeine: manufactured by Shizuoka Caffeine Industry Co., Ltd.) at a ratio of 1 part by mass. The obtained mixture was placed in a glass container (2K standard bottle) with an open lid and used as sample 1-2.
[Sample 1-3]
Meloxicam (MELOXICAM: Hwheel Pharmaceutical Co., manufactured by Ltd.) was placed in a glass container (2K standard bottle) and covered with a lid to prepare Samples 1-3.
〔サンプル1−4〕
メロキシカム(MELOXICAM:Hwail Pharmaceutical Co., Ltd.製)を1質量部に対して無水カフェイン(無水カフェイン:(株)静岡カフェイン工業所製)を1質量部の割合で混合した。得られた混合物を、ガラス製の容器(2K規格瓶)に入れて蓋をし、サンプル1−4とした。
結果を表1に示す。
[Sample 1-4]
Meloxicam (MELOXICAM: Hwheel Pharmaceutical Co., manufactured by Ltd.) was mixed with 1 part by mass of anhydrous caffeine (anhydrous caffeine: manufactured by Shizuoka Caffeine Industry Co., Ltd.) at a ratio of 1 part by mass. The obtained mixture was placed in a glass container (2K standard bottle) and covered with a lid to prepare Samples 1-4.
The results are shown in Table 1.
表1に示す試験結果から、メロキシカムのみを蓋をせず保存した場合(サンプル1−1)には40℃2ヶ月間の保存により変色(ΔL*)が生じた。また、メロキシカムを無水カフェインと混合して蓋をせず保存した場合(サンプル1−2)には若干変色の程度が抑制されたものの、メロキシカムのみを蓋をして保存した場合(サンプル1−3)にはむしろ変色の度合いが大きくなった。 ところが、メロキシカムを無水カフェインと混合したうえで蓋をして保存した場合(サンプル1−4)には、変色が大きく抑制された。 From the test results shown in Table 1, when only meloxicam was stored without a lid (Sample 1-1), discoloration (ΔL * ) occurred after storage at 40 ° C. for 2 months. In addition, when meloxicam was mixed with anhydrous caffeine and stored without a lid (Sample 1-2), the degree of discoloration was slightly suppressed, but when only meloxicam was stored with a lid (Sample 1-). In 3), the degree of discoloration was rather large. However, when meloxicam was mixed with anhydrous caffeine and then stored with a lid (Sample 1-4), discoloration was greatly suppressed.
以上の試験結果から、メロキシカムに代表される成分(A)を高温条件下で長期間保存すると変色が生じる一方、成分(A)にさらに無水カフェインに代表される成分(B−1)を共存せしめ、これをガラス瓶に代表される気密包装体に収容することで、斯かる変色は抑制されることが明らかとなった。 From the above test results, when the component (A) represented by meloxicam is stored for a long period of time under high temperature conditions, discoloration occurs, while the component (A) further coexists with the component (B-1) represented by anhydrous caffeine. It has been clarified that such discoloration is suppressed by containing this in an airtight package represented by a glass bottle.
[試験例2]安定性試験 その2
サンプルとして以下に示すサンプル2−1〜2−3を用いたほかは試験例1と同様の方法により試験を実施した。
[Test Example 2] Stability test Part 2
The test was carried out in the same manner as in Test Example 1 except that Samples 2-1 to 2-3 shown below were used as samples.
〔サンプル2−1〕
メロキシカム(MELOXICAM:Hwail Pharmaceutical Co., Ltd.製)を、蓋を開けたガラス製の容器(2K規格瓶)にとり、サンプル2−1とした。
〔サンプル2−2〕
メロキシカム(MELOXICAM:Hwail Pharmaceutical Co., Ltd.製)を、ガラス製の容器(2K規格瓶)に入れて蓋をし、サンプル2−2とした。
[Sample 2-1]
Meloxicam (MELOXICAM: Hwheel Pharmaceutical Co., manufactured by Ltd.) was placed in a glass container (2K standard bottle) with an open lid and used as sample 2-1.
[Sample 2-2]
Meloxicam (MELOXICAM: Hwheel Pharmaceutical Co., manufactured by Ltd.) was placed in a glass container (2K standard bottle) and covered with a lid to prepare sample 2-2.
〔サンプル2−3〕
メロキシカム(MELOXICAM:Hwail Pharmaceutical Co., Ltd.製)を1質量部に対して水酸化アルミニウムゲル(乾燥水酸化アルミニウムゲル:協和化学工業(株)製)を1質量部の割合で混合した。得られた混合物を、ガラス製の容器(2K規格瓶)に入れて蓋をし、サンプル2−3とした。
結果を表2に示す。
[Sample 2-3]
Meloxicam (MELOXICAM: Hwheel Pharmaceutical Co., manufactured by Ltd.) was mixed with 1 part by mass of aluminum hydroxide gel (dry aluminum hydroxide gel: manufactured by Kyowa Kagaku Kogyo Co., Ltd.) at a ratio of 1 part by mass. The obtained mixture was placed in a glass container (2K standard bottle) and covered with a lid to prepare Samples 2-3.
The results are shown in Table 2.
表1に示す試験結果から、メロキシカムのみを蓋をせず保存した場合(サンプル2−1)には40℃2ヶ月間の保存により変色(ΔL*)が生じた。また、メロキシカムのみを蓋をして保存した場合(サンプル2−2)にはむしろ変色の度合いが大きくなった。
ところが、メロキシカムを水酸化アルミニウムゲルと混合したうえで蓋をして保存した場合(サンプル2−3)には、変色が大きく抑制された。
From the test results shown in Table 1, when only meloxicam was stored without a lid (Sample 2-1), discoloration (ΔL * ) occurred after storage at 40 ° C. for 2 months. In addition, when only meloxicam was stored with a lid (Sample 2-2), the degree of discoloration was rather large.
However, when meloxicam was mixed with aluminum hydroxide gel and then stored with a lid (Sample 2-3), discoloration was greatly suppressed.
[試験例3]安定性試験 その3
サンプルとして以下に示すサンプル3−1〜3−3を用い、保存温度を80℃に変更したほかは試験例1と同様の方法により試験を実施した。
[Test Example 3] Stability Test Part 3
Samples 3-1 to 3-3 shown below were used as samples, and the test was carried out by the same method as in Test Example 1 except that the storage temperature was changed to 80 ° C.
〔サンプル3−1〕
メロキシカム(MELOXICAM:Hwail Pharmaceutical Co., Ltd.製)を、蓋を開けたガラス製の容器(2K規格瓶)にとり、サンプル3−1とした。
〔サンプル3−2〕
メロキシカム(MELOXICAM:Hwail Pharmaceutical Co., Ltd.製)を、ガラス製の容器(2K規格瓶)に入れて蓋をし、サンプル3−2とした。
[Sample 3-1]
Meloxicam (MELOXICAM: Hwheel Pharmaceutical Co., manufactured by Ltd.) was placed in a glass container (2K standard bottle) with an open lid and used as sample 3-1.
[Sample 3-2]
Meloxicam (MELOXICAM: Hwheel Pharmaceutical Co., manufactured by Ltd.) was placed in a glass container (2K standard bottle) and covered with a lid to prepare sample 3-2.
〔サンプル3−3〕
メロキシカム(MELOXICAM:Hwail Pharmaceutical Co., Ltd.製)を1質量部に対して酸化マグネシウム(酸化マグネシウム:富田製薬(株)製)を1質量部の割合で混合した。得られた混合物を、ガラス製の容器(2K規格瓶)に入れて蓋をし、サンプル3−3とした。
結果を表3に示す。
[Sample 3-3]
Meloxicam (MELOXICAM: Hwheel Pharmaceutical Co., manufactured by Ltd.) was mixed with 1 part by mass of magnesium oxide (magnesium oxide: manufactured by Tomita Pharmaceutical Co., Ltd.) at a ratio of 1 part by mass. The obtained mixture was placed in a glass container (2K standard bottle) and covered with a lid to prepare sample 3-3.
The results are shown in Table 3.
表3に示す試験結果から、メロキシカムのみを蓋をせず保存した場合(サンプル3−1)には80℃2ヶ月間の保存により変色(ΔL*)が生じた。またメロキシカムのみを蓋をして保存した場合(サンプル3−2)にはむしろ変色の度合いが大きくなった。
ところが、メロキシカムを酸化マグネシウムと混合したうえで蓋をして保存した場合(サンプル3−3)には、変色が大きく抑制された。
From the test results shown in Table 3, when only meloxicam was stored without a lid (Sample 3-1), discoloration (ΔL * ) occurred after storage at 80 ° C. for 2 months. Further, when only meloxicam was stored with a lid (Sample 3-2), the degree of discoloration was rather large.
However, when meloxicam was mixed with magnesium oxide and stored with a lid (Sample 3-3), discoloration was greatly suppressed.
以上の試験例2、3の結果から、メロキシカムに代表される成分(A)を高温条件下で長期間保存すると変色が生じる一方、成分(A)にさらに水酸化アルミニウムゲル、酸化マグネシウムに代表される成分(B−2)を共存せしめ、これをガラス瓶に代表される気密包装体に収容することで、斯かる変色は抑制されることが明らかとなった。 From the results of Test Examples 2 and 3 above, discoloration occurs when the component (A) represented by meloxicam is stored for a long period of time under high temperature conditions, while the component (A) is further represented by aluminum hydroxide gel and magnesium oxide. It has been clarified that such discoloration is suppressed by coexisting the components (B-2) and storing them in an airtight package represented by a glass bottle.
[試験例4]安定性試験 その4
サンプルとして以下に示すサンプル4−1〜4−3を用いたほかは試験例3と同様の方法により試験を実施した。
[Test Example 4] Stability test No. 4
The test was carried out in the same manner as in Test Example 3 except that Samples 4-1 to 4-3 shown below were used as samples.
〔サンプル4−1〕
メロキシカム(MELOXICAM:Hwail Pharmaceutical Co., Ltd.製)を、蓋を開けたガラス製の容器(2K規格瓶)にとり、サンプル4−1とした。
〔サンプル4−2〕
メロキシカム(MELOXICAM:Hwail Pharmaceutical Co., Ltd.製)を、ガラス製の容器(2K規格瓶)に入れて蓋をし、サンプル4−2とした。
[Sample 4-1]
Meloxicam (MELOXICAM: Hwheel Pharmaceutical Co., manufactured by Ltd.) was placed in a glass container (2K standard bottle) with an open lid and used as a sample 4-1.
[Sample 4-2]
Meloxicam (MELOXICAM: Hwheel Pharmaceutical Co., manufactured by Ltd.) was placed in a glass container (2K standard bottle) and covered with a lid to prepare sample 4-2.
〔サンプル4−3〕
メロキシカム(MELOXICAM:Hwail Pharmaceutical Co., Ltd.製)を1質量部に対してアリルイソプロピルアセチル尿素(Apronal:東京化成工業(株)製)を1質量部の割合で混合した。得られた混合物を、ガラス製の容器(2K規格瓶)に入れて蓋をし、サンプル4−3とした。
結果を表4に示す。
[Sample 4-3]
Meloxicam (MELOXICAM: Hwheel Pharmaceutical Co., manufactured by Ltd.) was mixed with 1 part by mass of allyl isopropyl acetyl urea (Apronal: manufactured by Tokyo Chemical Industry Co., Ltd.) at a ratio of 1 part by mass. The obtained mixture was placed in a glass container (2K standard bottle) and covered with a lid to prepare sample 4-3.
The results are shown in Table 4.
表4に示す試験結果から、メロキシカムのみを蓋をせず保存した場合(サンプル4−1)には80℃2ヶ月間の保存により変色(ΔL*)が生じた。また、メロキシカムのみを蓋をして保存した場合(サンプル4−2)にはむしろ変色の度合いが大きくなった。
ところが、メロキシカムをアリルイソプロピルアセチル尿素と混合したうえで蓋をして保存した場合(サンプル4−3)には、変色が大きく抑制された。
From the test results shown in Table 4, when only meloxicam was stored without a lid (Sample 4-1), discoloration (ΔL * ) occurred after storage at 80 ° C. for 2 months. In addition, when only meloxicam was stored with a lid (Sample 4-2), the degree of discoloration was rather large.
However, when meloxicam was mixed with allyl isopropyl acetyl urea and then stored with a lid (Sample 4-3), discoloration was greatly suppressed.
以上の試験結果から、メロキシカムに代表される成分(A)を高温条件下で長期間保存すると変色が生じる一方、成分(A)にさらにアリルイソプロピルアセチル尿素に代表される成分(B−3)を共存せしめ、これをガラス瓶に代表される気密包装体に収容することで、斯かる変色は抑制されることが明らかとなった。 From the above test results, when the component (A) represented by meloxicam is stored for a long period of time under high temperature conditions, discoloration occurs, while the component (A) further contains a component (B-3) represented by allyl isopropyl acetyl urea. It was clarified that such discoloration was suppressed by coexisting and accommodating this in an airtight package represented by a glass bottle.
[製造例1〜6]
1錠当りに下記表5に記載の成分及び分量(mg)を含有する錠剤(製造例1〜5:フィルムコーティング錠剤、製造例6:口腔内崩壊型錠剤)を常法により製造した。得られた錠剤を、常法によりPTP包装し、次いでアルミピロー包装し、これをさらに紙箱に入れて製造例1〜6の医薬品を得た。なお、下記表において各成分の分量は、換算量を特に断らない限り、表示した成分そのものの量を示す。
[Manufacturing Examples 1 to 6]
Tablets (Production Examples 1 to 5: Film-coated tablets, Production Example 6: Orally disintegrating tablets) containing the components and amounts (mg) shown in Table 5 below were produced by a conventional method. The obtained tablets were PTP-wrapped by a conventional method, then aluminum pillow-wrapped, and further placed in a paper box to obtain the pharmaceutical products of Production Examples 1 to 6. In the table below, the amount of each component indicates the amount of the indicated component itself unless the conversion amount is specified.
[製造例7〜12]
アンピロキシカム27mgを、ピロキシカム20mgに置き換えたほかは製造例1〜6と同様にして、製造例7〜12の医薬品を常法により製造した。
[Manufacturing Examples 7 to 12]
The pharmaceutical products of Production Examples 7 to 12 were produced by a conventional method in the same manner as in Production Examples 1 to 6 except that 27 mg of ampiroxicam was replaced with 20 mg of piroxicam.
[製造例13〜18]
アンピロキシカム27mgを、メロキシカム10mgに置き換えたほかは製造例1〜6と同様にして、製造例13〜18の医薬品を常法により製造した。
[Manufacturing Examples 13 to 18]
The pharmaceutical products of Production Examples 13 to 18 were produced by a conventional method in the same manner as in Production Examples 1 to 6 except that 27 mg of ampiroxicam was replaced with 10 mg of meloxicam.
[製造例19〜24]
アンピロキシカム27mgを、ロルノキシカム4mgに置き換えたほかは製造例1〜6と同様にして、製造例19〜24の医薬品を常法により製造した。
[Manufacturing Examples 19 to 24]
The pharmaceutical products of Production Examples 19 to 24 were produced by a conventional method in the same manner as in Production Examples 1 to 6 except that 27 mg of ampiroxicam was replaced with 4 mg of lornoxicam.
本発明によれば、優れた薬理作用を有するオキシカム系NSAIDsを含有し、保存安定性に優れる医薬品を提供できるため、例えば医薬品産業等において利用できる。 According to the present invention, since it is possible to provide a drug containing oxicam-based NSAIDs having an excellent pharmacological action and having excellent storage stability, it can be used, for example, in the pharmaceutical industry.
Claims (6)
(A)アンピロキシカム、ピロキシカム、メロキシカム、ロルノキシカム及びそれらの塩並びにそれらの溶媒和物よりなる群から選ばれる1種以上;
(B)キサンチン誘導体;
を含有する医薬組成物が、気密包装体に収容されてなる医薬品。 The following components (A) and (B):
(A) One or more selected from the group consisting of ampiroxicam, piroxicam, meloxicam, lornoxicam and salts thereof, and solvates thereof;
(B) Xanthine derivative;
A pharmaceutical product in which a pharmaceutical composition containing the above is contained in an airtight package.
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JP2021091616A (en) * | 2019-12-06 | 2021-06-17 | ライオン株式会社 | Pharmaceutical preparation, solid pharmaceutical preparation and tablet |
JP7391639B2 (en) | 2019-12-06 | 2023-12-05 | ライオン株式会社 | pharmaceutical formulations |
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