JP2022168079A - oral solid composition - Google Patents
oral solid composition Download PDFInfo
- Publication number
- JP2022168079A JP2022168079A JP2022142007A JP2022142007A JP2022168079A JP 2022168079 A JP2022168079 A JP 2022168079A JP 2022142007 A JP2022142007 A JP 2022142007A JP 2022142007 A JP2022142007 A JP 2022142007A JP 2022168079 A JP2022168079 A JP 2022168079A
- Authority
- JP
- Japan
- Prior art keywords
- solid composition
- naproxen
- oral solid
- composition according
- manufactured
- 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.)
- Granted
Links
- 239000008247 solid mixture Substances 0.000 title claims abstract description 28
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims abstract description 64
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims abstract description 64
- 229960002009 naproxen Drugs 0.000 claims abstract description 64
- 150000007514 bases Chemical class 0.000 claims abstract description 28
- 229920000642 polymer Polymers 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 229920002678 cellulose Polymers 0.000 claims abstract description 14
- 239000001913 cellulose Substances 0.000 claims abstract description 14
- 239000008187 granular material Substances 0.000 claims description 58
- 239000000203 mixture Substances 0.000 claims description 57
- 238000009472 formulation Methods 0.000 claims description 28
- 239000000843 powder Substances 0.000 claims description 18
- -1 amine compounds Chemical class 0.000 claims description 17
- 239000003826 tablet Substances 0.000 claims description 15
- 235000010980 cellulose Nutrition 0.000 claims description 13
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 11
- 229910052751 metal Inorganic materials 0.000 claims description 11
- 239000002184 metal Substances 0.000 claims description 11
- 238000002156 mixing Methods 0.000 claims description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 10
- 230000001754 anti-pyretic effect Effects 0.000 claims description 9
- 150000002739 metals Chemical class 0.000 claims description 8
- 230000000202 analgesic effect Effects 0.000 claims description 7
- 239000002221 antipyretic Substances 0.000 claims description 6
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 5
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 5
- 239000001095 magnesium carbonate Substances 0.000 claims description 5
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 5
- 239000000395 magnesium oxide Substances 0.000 claims description 5
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 5
- 235000012245 magnesium oxide Nutrition 0.000 claims description 5
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 5
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 4
- 229940024546 aluminum hydroxide gel Drugs 0.000 claims description 4
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 claims description 4
- 239000000378 calcium silicate Substances 0.000 claims description 4
- 229910052918 calcium silicate Inorganic materials 0.000 claims description 4
- 235000012241 calcium silicate Nutrition 0.000 claims description 4
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 claims description 4
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 4
- 239000000347 magnesium hydroxide Substances 0.000 claims description 4
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 4
- 239000011736 potassium bicarbonate Substances 0.000 claims description 4
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 4
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 4
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 4
- 229940086066 potassium hydrogencarbonate Drugs 0.000 claims description 4
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 claims description 3
- AMZWNNKNOQSBOP-UHFFFAOYSA-M [n'-(2,5-dioxoimidazolidin-4-yl)carbamimidoyl]oxyaluminum;dihydrate Chemical compound O.O.NC(=O)NC1N=C(O[Al])NC1=O AMZWNNKNOQSBOP-UHFFFAOYSA-M 0.000 claims description 3
- 229940015825 aldioxa Drugs 0.000 claims description 3
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims 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 claims description 3
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 claims description 3
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 3
- 229960001545 hydrotalcite Drugs 0.000 claims description 3
- 229910001701 hydrotalcite Inorganic materials 0.000 claims description 3
- 235000014380 magnesium carbonate Nutrition 0.000 claims description 3
- 235000012254 magnesium hydroxide Nutrition 0.000 claims description 3
- ZADYMNAVLSWLEQ-UHFFFAOYSA-N magnesium;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[Mg+2].[Si+4] ZADYMNAVLSWLEQ-UHFFFAOYSA-N 0.000 claims description 3
- 210000000214 mouth Anatomy 0.000 claims description 3
- 229940088417 precipitated calcium carbonate Drugs 0.000 claims description 3
- 239000001509 sodium citrate Substances 0.000 claims description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 3
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 claims description 3
- 229960004291 sucralfate Drugs 0.000 claims description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 2
- 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 claims description 2
- 229920000881 Modified starch Polymers 0.000 claims description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 claims description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 claims description 2
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 claims description 2
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 229960001790 sodium citrate Drugs 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims 1
- 230000001741 anti-phlogistic effect Effects 0.000 claims 1
- 239000008108 microcrystalline cellulose Substances 0.000 claims 1
- 229940016286 microcrystalline cellulose Drugs 0.000 claims 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 239000008213 purified water Substances 0.000 description 16
- 238000009775 high-speed stirring Methods 0.000 description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
- 239000007788 liquid Substances 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 239000011812 mixed powder Substances 0.000 description 11
- 238000004090 dissolution Methods 0.000 description 10
- 238000010828 elution Methods 0.000 description 10
- 238000004898 kneading Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- 230000003110 anti-inflammatory effect Effects 0.000 description 8
- 239000011248 coating agent Substances 0.000 description 7
- 235000019359 magnesium stearate Nutrition 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 101100013145 Drosophila melanogaster Flo2 gene Proteins 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000007922 dissolution test Methods 0.000 description 6
- 238000011049 filling Methods 0.000 description 6
- 239000007888 film coating Substances 0.000 description 6
- 238000009501 film coating Methods 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 238000000576 coating method Methods 0.000 description 5
- 238000001125 extrusion Methods 0.000 description 5
- 239000007941 film coated tablet Substances 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 4
- 238000005469 granulation Methods 0.000 description 4
- 230000003179 granulation Effects 0.000 description 4
- 239000007902 hard capsule Substances 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 238000004806 packaging method and process Methods 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 description 3
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 229960003943 hypromellose Drugs 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000004570 mortar (masonry) Substances 0.000 description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 description 3
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 3
- 150000003722 vitamin derivatives Chemical class 0.000 description 3
- 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 2
- FLNXBVJLPJNOSI-UHFFFAOYSA-N 1-[2-[(4-chlorophenyl)-phenylmethoxy]ethyl]piperidine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)OCCN1CCCCC1 FLNXBVJLPJNOSI-UHFFFAOYSA-N 0.000 description 2
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 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
- 108010011485 Aspartame Proteins 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 244000131316 Panax pseudoginseng Species 0.000 description 2
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 2
- 235000003140 Panax quinquefolius Nutrition 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 235000010358 acesulfame potassium Nutrition 0.000 description 2
- 229960004998 acesulfame potassium Drugs 0.000 description 2
- 239000000619 acesulfame-K Substances 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- BWZOPYPOZJBVLQ-UHFFFAOYSA-K aluminium glycinate Chemical compound O[Al+]O.NCC([O-])=O BWZOPYPOZJBVLQ-UHFFFAOYSA-K 0.000 description 2
- 239000002269 analeptic agent Substances 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 230000000954 anitussive effect Effects 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 239000000043 antiallergic agent Substances 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 229940125715 antihistaminic agent Drugs 0.000 description 2
- 229940124584 antitussives Drugs 0.000 description 2
- 239000000605 aspartame Substances 0.000 description 2
- 235000010357 aspartame Nutrition 0.000 description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 2
- 229960003438 aspartame Drugs 0.000 description 2
- 229960002544 cloperastine Drugs 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003172 expectorant agent Substances 0.000 description 2
- 230000003419 expectorant effect Effects 0.000 description 2
- 229940066493 expectorants Drugs 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000008434 ginseng Nutrition 0.000 description 2
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 2
- 229960004949 glycyrrhizic acid Drugs 0.000 description 2
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 2
- 235000019410 glycyrrhizin Nutrition 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229960004708 noscapine Drugs 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229960003975 potassium Drugs 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 238000004513 sizing Methods 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- RVDUTAJUOSJFPW-XFNAGHOKSA-N (2S)-2-(6-methoxynaphthalen-2-yl)propanoic acid Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21.C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 RVDUTAJUOSJFPW-XFNAGHOKSA-N 0.000 description 1
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 description 1
- AJZJIYUOOJLBAU-CEAXSRTFSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;n,n,2-trimethyl-3-phenothiazin-10-ylpropan-1-amine Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1=CC=C2N(CC(CN(C)C)C)C3=CC=CC=C3SC2=C1.C1=CC=C2N(CC(CN(C)C)C)C3=CC=CC=C3SC2=C1 AJZJIYUOOJLBAU-CEAXSRTFSA-N 0.000 description 1
- YQSHYGCCYVPRDI-UHFFFAOYSA-N (4-propan-2-ylphenyl)methanamine Chemical compound CC(C)C1=CC=C(CN)C=C1 YQSHYGCCYVPRDI-UHFFFAOYSA-N 0.000 description 1
- DKSZLDSPXIWGFO-BLOJGBSASA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.OP(O)(O)=O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC DKSZLDSPXIWGFO-BLOJGBSASA-N 0.000 description 1
- PMGQWSIVQFOFOQ-BDUVBVHRSA-N (e)-but-2-enedioic acid;(2r)-2-[2-[1-(4-chlorophenyl)-1-phenylethoxy]ethyl]-1-methylpyrrolidine Chemical compound OC(=O)\C=C\C(O)=O.CN1CCC[C@@H]1CCOC(C)(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 PMGQWSIVQFOFOQ-BDUVBVHRSA-N 0.000 description 1
- FWLKKPKZQYVAFR-LVEZLNDCSA-N (e)-but-2-enedioic acid;1-(2-ethoxyethyl)-2-(4-methyl-1,4-diazepan-1-yl)benzimidazole Chemical compound OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.N=1C2=CC=CC=C2N(CCOCC)C=1N1CCCN(C)CC1 FWLKKPKZQYVAFR-LVEZLNDCSA-N 0.000 description 1
- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- ZKLPARSLTMPFCP-OAQYLSRUSA-N 2-[2-[4-[(R)-(4-chlorophenyl)-phenylmethyl]-1-piperazinyl]ethoxy]acetic acid Chemical compound C1CN(CCOCC(=O)O)CCN1[C@@H](C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-OAQYLSRUSA-N 0.000 description 1
- FSSICIQKZGUEAE-UHFFFAOYSA-N 2-[benzyl(pyridin-2-yl)amino]ethyl-dimethylazanium;chloride Chemical compound Cl.C=1C=CC=NC=1N(CCN(C)C)CC1=CC=CC=C1 FSSICIQKZGUEAE-UHFFFAOYSA-N 0.000 description 1
- SPCKHVPPRJWQRZ-UHFFFAOYSA-N 2-benzhydryloxy-n,n-dimethylethanamine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 SPCKHVPPRJWQRZ-UHFFFAOYSA-N 0.000 description 1
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
- WQOYJMWVNIGIQR-UHFFFAOYSA-N 3-(dithiophen-2-ylmethylidene)-1-methylpiperidine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1N(C)CCCC1=C(C=1SC=CC=1)C1=CC=CS1 WQOYJMWVNIGIQR-UHFFFAOYSA-N 0.000 description 1
- QNVKOSLOVOTXKF-UHFFFAOYSA-N 4-[(2-amino-3,5-dibromophenyl)methylamino]cyclohexan-1-ol;hydron;chloride Chemical compound Cl.NC1=C(Br)C=C(Br)C=C1CNC1CCC(O)CC1 QNVKOSLOVOTXKF-UHFFFAOYSA-N 0.000 description 1
- CDQGZJGHIVUWQA-UHFFFAOYSA-N 4-[2-(4-hydroxy-3,5-dimethylphenyl)butan-2-yl]-2,6-dimethylphenol Chemical compound C=1C(C)=C(O)C(C)=CC=1C(C)(CC)C1=CC(C)=C(O)C(C)=C1 CDQGZJGHIVUWQA-UHFFFAOYSA-N 0.000 description 1
- QOLHOCYZKJILAV-UHFFFAOYSA-N 5-[(3-carboxy-4-hydroxyphenyl)methyl]-2-hydroxybenzoic acid;n,n-dimethyl-1-phenothiazin-10-ylpropan-2-amine Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1.C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1.C1=C(O)C(C(=O)O)=CC(CC=2C=C(C(O)=CC=2)C(O)=O)=C1 QOLHOCYZKJILAV-UHFFFAOYSA-N 0.000 description 1
- PUHLHLQBIFRKRD-CSKARUKUSA-N 5-methyl-2-[(E)-2-phenylethenyl]-1,3-benzoxazole Chemical compound N=1C2=CC(C)=CC=C2OC=1\C=C\C1=CC=CC=C1 PUHLHLQBIFRKRD-CSKARUKUSA-N 0.000 description 1
- 241000332371 Abutilon x hybridum Species 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 1
- 235000007866 Chamaemelum nobile Nutrition 0.000 description 1
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 244000247747 Coptis groenlandica Species 0.000 description 1
- 235000002991 Coptis groenlandica Nutrition 0.000 description 1
- 240000001980 Cucurbita pepo Species 0.000 description 1
- 235000009852 Cucurbita pepo Nutrition 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- DBAKFASWICGISY-DASCVMRKSA-N Dexchlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C1([C@H](CCN(C)C)C=2N=CC=CC=2)=CC=C(Cl)C=C1 DBAKFASWICGISY-DASCVMRKSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 241000218671 Ephedra Species 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 240000006927 Foeniculum vulgare Species 0.000 description 1
- 235000004204 Foeniculum vulgare Nutrition 0.000 description 1
- 241000605372 Fritillaria Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000202807 Glycyrrhiza Species 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- BIVBRWYINDPWKA-VLQRKCJKSA-L Glycyrrhizinate dipotassium Chemical compound [K+].[K+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O BIVBRWYINDPWKA-VLQRKCJKSA-L 0.000 description 1
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- QUQPHWDTPGMPEX-UHFFFAOYSA-N Hesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC4C(C(O)C(O)C(C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- QYEORIIWGAAORG-UHFFFAOYSA-N Iproheptine hydrochloride Chemical compound [Cl-].CC(C)CCCC(C)[NH2+]C(C)C QYEORIIWGAAORG-UHFFFAOYSA-N 0.000 description 1
- BFSMWENDZZIWPW-UHFFFAOYSA-N Isopropamide iodide Chemical compound [I-].C=1C=CC=CC=1C(C(N)=O)(CC[N+](C)(C(C)C)C(C)C)C1=CC=CC=C1 BFSMWENDZZIWPW-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 244000042664 Matricaria chamomilla Species 0.000 description 1
- 235000007232 Matricaria chamomilla Nutrition 0.000 description 1
- HOKDBMAJZXIPGC-UHFFFAOYSA-N Mequitazine Chemical compound C12=CC=CC=C2SC2=CC=CC=C2N1CC1C(CC2)CCN2C1 HOKDBMAJZXIPGC-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 241000972673 Phellodendron amurense Species 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 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 1
- GBFLZEXEOZUWRN-VKHMYHEASA-N S-carboxymethyl-L-cysteine Chemical compound OC(=O)[C@@H](N)CSCC(O)=O GBFLZEXEOZUWRN-VKHMYHEASA-N 0.000 description 1
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000004902 Softening Agent Substances 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 244000223014 Syzygium aromaticum Species 0.000 description 1
- 235000016639 Syzygium aromaticum Nutrition 0.000 description 1
- 239000007983 Tris buffer Chemical class 0.000 description 1
- 229930003471 Vitamin B2 Natural products 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 244000273928 Zingiber officinale Species 0.000 description 1
- 235000006886 Zingiber officinale Nutrition 0.000 description 1
- NTCYWJCEOILKNG-ROLPUNSJSA-N [(1r,2s)-1-hydroxy-1-phenylpropan-2-yl]-dimethylazanium;chloride Chemical compound Cl.CN(C)[C@@H](C)[C@H](O)C1=CC=CC=C1 NTCYWJCEOILKNG-ROLPUNSJSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- MANKSFVECICGLK-UHFFFAOYSA-K aloxiprin Chemical compound [OH-].[Al+3].CC(=O)OC1=CC=CC=C1C([O-])=O.CC(=O)OC1=CC=CC=C1C([O-])=O MANKSFVECICGLK-UHFFFAOYSA-K 0.000 description 1
- AKNNEGZIBPJZJG-UHFFFAOYSA-N alpha-noscapine Natural products CN1CCC2=CC=3OCOC=3C(OC)=C2C1C1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-UHFFFAOYSA-N 0.000 description 1
- ZJAZXCAGLPZEKF-UHFFFAOYSA-K aluminum carbonic acid trihydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3].OC(O)=O ZJAZXCAGLPZEKF-UHFFFAOYSA-K 0.000 description 1
- 229940008027 aluminum hydroxide / magnesium carbonate Drugs 0.000 description 1
- 229940103272 aluminum potassium sulfate Drugs 0.000 description 1
- PCRDIRUKXOTDNN-UHFFFAOYSA-K aluminum;sodium;carbonate;hydroxide Chemical compound [OH-].[Na+].[Al+3].[O-]C([O-])=O PCRDIRUKXOTDNN-UHFFFAOYSA-K 0.000 description 1
- 229960000985 ambroxol hydrochloride Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000002216 antistatic agent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- QUQPHWDTPGMPEX-UTWYECKDSA-N aurantiamarin Natural products COc1ccc(cc1O)[C@H]1CC(=O)c2c(O)cc(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)cc2O1 QUQPHWDTPGMPEX-UTWYECKDSA-N 0.000 description 1
- 229960004335 azelastine hydrochloride Drugs 0.000 description 1
- YEJAJYAHJQIWNU-UHFFFAOYSA-N azelastine hydrochloride Chemical compound Cl.C1CN(C)CCCC1N1C(=O)C2=CC=CC=C2C(CC=2C=CC(Cl)=CC=2)=N1 YEJAJYAHJQIWNU-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 229940108858 belladonna total alkaloid Drugs 0.000 description 1
- UDGHXQPQKQPSBB-UHFFFAOYSA-N benzenesulfonic acid;4-[4-[(4-chlorophenyl)-pyridin-2-ylmethoxy]piperidin-1-yl]butanoic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1.C1CN(CCCC(=O)O)CCC1OC(C=1N=CC=CC=1)C1=CC=C(Cl)C=C1 UDGHXQPQKQPSBB-UHFFFAOYSA-N 0.000 description 1
- 229960001105 bepotastine besilate Drugs 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 238000005282 brightening Methods 0.000 description 1
- 229960002335 bromhexine hydrochloride Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- LCHGOKZNRDAXEK-UHFFFAOYSA-N caffeine monohydrate Chemical compound O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C LCHGOKZNRDAXEK-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- OJFSXZCBGQGRNV-UHFFFAOYSA-N carbinoxamine Chemical compound C=1C=CC=NC=1C(OCCN(C)C)C1=CC=C(Cl)C=C1 OJFSXZCBGQGRNV-UHFFFAOYSA-N 0.000 description 1
- 229960000428 carbinoxamine Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229960004342 cetirizine hydrochloride Drugs 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 1
- 229960002689 clemastine fumarate Drugs 0.000 description 1
- APSNPMVGBGZYAJ-GLOOOPAXSA-N clematine Natural products COc1cc(ccc1O)[C@@H]2CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2 APSNPMVGBGZYAJ-GLOOOPAXSA-N 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 229930003836 cresol Natural products 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 229960001985 dextromethorphan Drugs 0.000 description 1
- 229960003782 dextromethorphan hydrobromide Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229960000920 dihydrocodeine Drugs 0.000 description 1
- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 description 1
- 229940015826 dihydroxyaluminum aminoacetate Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229960001056 dimemorfan Drugs 0.000 description 1
- KBEZZLAAKIIPFK-NJAFHUGGSA-N dimemorfan Chemical compound C1C2=CC=C(C)C=C2[C@@]23CCN(C)[C@@H]1[C@H]2CCCC3 KBEZZLAAKIIPFK-NJAFHUGGSA-N 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 1
- 229960004646 diphenhydramine tannate Drugs 0.000 description 1
- OWQUZNMMYNAXSL-UHFFFAOYSA-N diphenylpyraline Chemical compound C1CN(C)CCC1OC(C=1C=CC=CC=1)C1=CC=CC=C1 OWQUZNMMYNAXSL-UHFFFAOYSA-N 0.000 description 1
- 229960000879 diphenylpyraline Drugs 0.000 description 1
- LPRLDRXGWKXRMQ-UHFFFAOYSA-N diphenylpyraline hydrochloride Chemical compound [Cl-].C1C[NH+](C)CCC1OC(C=1C=CC=CC=1)C1=CC=CC=C1 LPRLDRXGWKXRMQ-UHFFFAOYSA-N 0.000 description 1
- 229960002392 diphenylpyraline hydrochloride Drugs 0.000 description 1
- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229940005636 dl- methylephedrine Drugs 0.000 description 1
- 229940073563 dl- methylephedrine hydrochloride Drugs 0.000 description 1
- 229960001971 ebastine Drugs 0.000 description 1
- MJJALKDDGIKVBE-UHFFFAOYSA-N ebastine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)CCCN1CCC(OC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 MJJALKDDGIKVBE-UHFFFAOYSA-N 0.000 description 1
- 229960000325 emedastine Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- WHWZLSFABNNENI-UHFFFAOYSA-N epinastine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 WHWZLSFABNNENI-UHFFFAOYSA-N 0.000 description 1
- 229960002548 epinastine hydrochloride Drugs 0.000 description 1
- 229960002561 eprazinone Drugs 0.000 description 1
- BSHWLCACYCVCJE-UHFFFAOYSA-N eprazinone Chemical compound C=1C=CC=CC=1C(OCC)CN(CC1)CCN1CC(C)C(=O)C1=CC=CC=C1 BSHWLCACYCVCJE-UHFFFAOYSA-N 0.000 description 1
- 229960000514 ethenzamide Drugs 0.000 description 1
- SBNKFTQSBPKMBZ-UHFFFAOYSA-N ethenzamide Chemical compound CCOC1=CC=CC=C1C(N)=O SBNKFTQSBPKMBZ-UHFFFAOYSA-N 0.000 description 1
- YRSGDLIATOURQO-UHFFFAOYSA-N ethyl 4-acetyl-5-oxohexanoate Chemical compound CCOC(=O)CCC(C(C)=O)C(C)=O YRSGDLIATOURQO-UHFFFAOYSA-N 0.000 description 1
- 229940061262 ethyl cysteine hydrochloride Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- PFAXACNYGZVKMX-UHFFFAOYSA-N fenethazine Chemical compound C1=CC=C2N(CCN(C)C)C3=CC=CC=C3SC2=C1 PFAXACNYGZVKMX-UHFFFAOYSA-N 0.000 description 1
- 229950007454 fenethazine Drugs 0.000 description 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
- 229960003592 fexofenadine Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000008397 ginger Nutrition 0.000 description 1
- 239000001685 glycyrrhizic acid Substances 0.000 description 1
- 229940074774 glycyrrhizinate Drugs 0.000 description 1
- 229920000578 graft copolymer Polymers 0.000 description 1
- 229960002146 guaifenesin Drugs 0.000 description 1
- 229940025878 hesperidin Drugs 0.000 description 1
- VUYDGVRIQRPHFX-UHFFFAOYSA-N hesperidin Natural products COc1cc(ccc1O)C2CC(=O)c3c(O)cc(OC4OC(COC5OC(O)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 VUYDGVRIQRPHFX-UHFFFAOYSA-N 0.000 description 1
- QUQPHWDTPGMPEX-QJBIFVCTSA-N hesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-QJBIFVCTSA-N 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- LTINPJMVDKPJJI-UHFFFAOYSA-N iodinated glycerol Chemical compound CC(I)C1OCC(CO)O1 LTINPJMVDKPJJI-UHFFFAOYSA-N 0.000 description 1
- 229950000120 iproheptine Drugs 0.000 description 1
- 229960001543 isopropamide iodide Drugs 0.000 description 1
- 229960003517 isothipendyl Drugs 0.000 description 1
- OQJBSDFFQWMKBQ-UHFFFAOYSA-N isothipendyl Chemical compound C1=CN=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 OQJBSDFFQWMKBQ-UHFFFAOYSA-N 0.000 description 1
- 239000008863 koso-san Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001508 levocetirizine Drugs 0.000 description 1
- 229960002373 loxoprofen Drugs 0.000 description 1
- BAZQYVYVKYOAGO-UHFFFAOYSA-M loxoprofen sodium hydrate Chemical compound O.O.[Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 BAZQYVYVKYOAGO-UHFFFAOYSA-M 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- FQQIIPAOSKSOJM-UHFFFAOYSA-N mebhydrolin Chemical compound C1N(C)CCC2=C1C1=CC=CC=C1N2CC1=CC=CC=C1 FQQIIPAOSKSOJM-UHFFFAOYSA-N 0.000 description 1
- 229960004934 mebhydrolin Drugs 0.000 description 1
- 229960005042 mequitazine Drugs 0.000 description 1
- IEISBKIVLDXSMZ-UHFFFAOYSA-N methdilazine hydrochloride Chemical compound Cl.C1N(C)CCC1CN1C2=CC=CC=C2SC2=CC=CC=C21 IEISBKIVLDXSMZ-UHFFFAOYSA-N 0.000 description 1
- 229960001397 methdilazine hydrochloride Drugs 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 229950005216 napadisilate Drugs 0.000 description 1
- PLPRGLOFPNJOTN-UHFFFAOYSA-N narcotine Natural products COc1ccc2C(OC(=O)c2c1OC)C3Cc4c(CN3C)cc5OCOc5c4OC PLPRGLOFPNJOTN-UHFFFAOYSA-N 0.000 description 1
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229960002698 oxatomide Drugs 0.000 description 1
- BAINIUMDFURPJM-UHFFFAOYSA-N oxatomide Chemical compound O=C1NC2=CC=CC=C2N1CCCN(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 BAINIUMDFURPJM-UHFFFAOYSA-N 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- GHZNWXGYWUBLLI-UHFFFAOYSA-N p-Lactophenetide Chemical compound CCOC1=CC=C(NC(=O)C(C)O)C=C1 GHZNWXGYWUBLLI-UHFFFAOYSA-N 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- QFRKWSPTCBGLSU-UHFFFAOYSA-M potassium 4-hydroxy-3-methoxybenzene-1-sulfonate Chemical compound [K+].COC1=CC(S([O-])(=O)=O)=CC=C1O QFRKWSPTCBGLSU-UHFFFAOYSA-M 0.000 description 1
- 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 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical class [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229940069505 potassium guaiacolsulfonate Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- XXPDBLUZJRXNNZ-UHFFFAOYSA-N promethazine hydrochloride Chemical compound Cl.C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 XXPDBLUZJRXNNZ-UHFFFAOYSA-N 0.000 description 1
- 229960002244 promethazine hydrochloride Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- PXWLVJLKJGVOKE-UHFFFAOYSA-N propyphenazone Chemical compound O=C1C(C(C)C)=C(C)N(C)N1C1=CC=CC=C1 PXWLVJLKJGVOKE-UHFFFAOYSA-N 0.000 description 1
- 229960002189 propyphenazone Drugs 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 229960000581 salicylamide Drugs 0.000 description 1
- 229940048730 senega Drugs 0.000 description 1
- 239000011257 shell material Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000010243 sho-seiryu-to Substances 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 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 1
- XYEXKDCAGSHWSD-UHFFFAOYSA-M sodium dibunate Chemical compound [Na+].[O-]S(=O)(=O)C1=C(C(C)(C)C)C=CC2=CC(C(C)(C)C)=CC=C21 XYEXKDCAGSHWSD-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 229960000896 tipepidine Drugs 0.000 description 1
- 239000012929 tonicity agent Substances 0.000 description 1
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 1
- 229960000401 tranexamic acid Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229960000732 tripelennamine hydrochloride Drugs 0.000 description 1
- CUZMOIXUFHOLLN-UMVVUDSKSA-N triprolidine hydrochloride monohydrate Chemical compound O.Cl.C1=CC(C)=CC=C1C(\C=1N=CC=CC=1)=C/CN1CCCC1 CUZMOIXUFHOLLN-UMVVUDSKSA-N 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
Abstract
Description
本発明は、経口固形組成物に関し、更に詳細には、塩基性化合物を含有することでナプロキセンの効果発現を早めた経口固形組成物に関する。 TECHNICAL FIELD The present invention relates to an oral solid composition, and more particularly to an oral solid composition containing a basic compound to accelerate the effect expression of naproxen.
ナプロキセンは、プロピオン酸系の非ステロイド性消炎鎮痛剤であり、発熱や炎症を引き起こす原因となるプロスタグランジンの生合成を抑制することによって、消炎、鎮痛、解熱作用を有する。しかし、ナプロキセンを固形製剤とし、経口投与した場合、ナプロキセンは水に溶解し難い薬物であるため、服用してから解熱鎮痛等の効能が表れるまでに時間がかかることが知られている。 Naproxen is a propionic acid-based non-steroidal anti-inflammatory analgesic, and has anti-inflammatory, analgesic and antipyretic effects by inhibiting the biosynthesis of prostaglandins that cause fever and inflammation. However, when naproxen is made into a solid formulation and orally administered, it is known that it takes time for the effects of antipyretic analgesia and the like to appear after taking it, because naproxen is a drug that is difficult to dissolve in water.
このような、経口固形製剤でのナプロキセンの効果発現が遅いという欠点を解消するために、ナプロキセンの溶解を速めるための試みがなされており、例えば、ナプロキセンナトリウムに、スプレー乾燥した粒径75~300ミクロンのマンニトールを組み合わせる技術が報告されている(特許文献1)。しかしながら、この技術では、予めマンニトールをスプレー乾燥しなければならず、さらに、スプレー乾燥時にマンニトールを上記のような特定の粒径に調整する必要があるため、製造において複雑で手間がかかるという問題があった。 In order to overcome this drawback of slow onset of efficacy of naproxen in oral solid formulations, attempts have been made to accelerate the dissolution of naproxen. A technique of combining micron mannitol has been reported (Patent Document 1). However, in this technique, mannitol must be spray-dried in advance, and mannitol must be adjusted to a specific particle size as described above during spray-drying, so the manufacturing process is complicated and time-consuming. there were.
従って、本発明は、簡単な手段によってナプロキセンの難溶性を改善し、速やかな効果発現が期待できる経口固形組成物を提供することを課題とする。 Accordingly, an object of the present invention is to provide an oral solid composition which can improve the poor solubility of naproxen by a simple means and which can be expected to exhibit a rapid effect.
本発明者らは、上記課題を解決すべく鋭意研究を行っていたところ、ナプロキセンに塩基性化合物を組み合わせることにより、ナプロキセンが水に対して速やかに溶解するとの知見を得、この知見を利用すれば効果発現が速やかな経口固形組成物が得られることを見出した。特に、塩基性化合物として、1~3価の金属を含む塩基性化合物を使用した場合は、速やかに、かつ、持続的な溶解性が得られることを見出した。また、セルロース系水膨潤性高分子を更に配合させることにより、固形製剤とした場合であっても、崩壊性の良い即効性のある経口固形組成物が得られることを見出し、本発明を完成した。 The inventors of the present invention have conducted intensive research to solve the above problems, and obtained the knowledge that naproxen is rapidly dissolved in water by combining naproxen with a basic compound. It has been found that an oral solid composition with rapid effect expression can be obtained. In particular, when a basic compound containing a monovalent to trivalent metal is used as the basic compound, it has been found that rapid and sustained solubility can be obtained. In addition, the present inventors have found that an oral solid composition with good disintegration and immediate effect can be obtained by further blending a cellulose-based water-swellable polymer, even in the case of a solid preparation, and completed the present invention. .
すなわち、本発明は、ナプロキセンまたはその塩と塩基性化合物とを含有することを特徴とする経口固形組成物である。 That is, the present invention is an oral solid composition characterized by containing naproxen or a salt thereof and a basic compound.
また、本発明は、上記塩基性化合物が、1~3価の金属を含む塩基性化合物及びアミン系塩基性化合物から選ばれる一種以上である上記経口固形組成物である。 The present invention also provides the oral solid composition, wherein the basic compound is one or more selected from basic compounds containing monovalent to trivalent metals and amine-based basic compounds.
さらに、本発明は、セルロース系水膨潤性高分子をさらに含有する上記経口固形組成物である。 Furthermore, the present invention is the oral solid composition further comprising a cellulosic water-swellable polymer.
本発明の経口固形組成物によれば、ナプロキセンを速く溶解させることができるため、即効性に優れた消炎、鎮痛、解熱作用を有する経口固形組成物を提供することができる。また、塩基性物質として、1~3価の金属を含む塩基性化合物を使用した場合は、速やかに、かつ、持続的な溶解性に優れた経口固形組成物を提供することができる。さらに、セルロース系水膨潤性高分子をさらに配合することで、固形製剤とした場合であっても、経口摂取時の口腔内等での崩壊性が高まり、より速やかな薬効を得ることができる。 INDUSTRIAL APPLICABILITY According to the oral solid composition of the present invention, naproxen can be rapidly dissolved, so that an oral solid composition having excellent immediate anti-inflammatory, analgesic and antipyretic effects can be provided. In addition, when a basic compound containing a monovalent to trivalent metal is used as the basic substance, it is possible to provide an oral solid composition excellent in rapid and sustained solubility. Furthermore, by further blending a cellulose-based water-swellable polymer, even when it is made into a solid preparation, disintegration in the oral cavity or the like upon oral ingestion is enhanced, and more rapid efficacy can be obtained.
本発明の経口固形組成物は、ナプロキセンまたはその塩と塩基性化合物とを含有するもの(以下、「本発明組成物」という)である。 The oral solid composition of the present invention contains naproxen or a salt thereof and a basic compound (hereinafter referred to as "the composition of the present invention").
本発明組成物で用いられるナプロキセンは、消炎、鎮痛、解熱作用を有することが知られている化合物であり、化学名は(2S)-2-(6-メトキシナフタレン-2-イル)プロパン酸((2S)-2-(6-Methoxynaphthalen-2-yl)propanoic acid)、その分子式がC14H14O3で、分子量は230.26である。 Naproxen used in the composition of the present invention is a compound known to have anti-inflammatory, analgesic, and antipyretic effects, and its chemical name is (2S)-2-(6-methoxynaphthalen-2-yl)propanoic acid ( (2S)-2-(6-Methoxynaphthalen-2-yl)propanoic acid) , whose molecular formula is C14H14O3 and molecular weight is 230.26 .
本発明組成物で使用されるナプロキセンまたはその塩としては、フリーのナプロキセンおよび薬学的に許容されるその塩、例えば、ナトリウム塩、カリウム塩、アンモニウム塩、メグルミン塩、トリス塩、塩基性アミノ酸の塩等が挙げられる。本発明組成物で使用するナプロキセンまたはその塩としては、フリーのナプロキセンをそのまま用いることが好ましい。 Naproxen or a salt thereof used in the composition of the present invention includes free naproxen and pharmaceutically acceptable salts thereof such as sodium salt, potassium salt, ammonium salt, meglumine salt, tris salt and salts of basic amino acids. etc. As naproxen or a salt thereof used in the composition of the present invention, it is preferable to use free naproxen as it is.
本発明組成物におけるナプロキセンまたはその塩(以下、単に「ナプロキセン」という)の配合量は、服用者の性別、年齢、症状等によって適宜決定すればよい。例えば、成人1日当たりの服用量として、通常10~1200mg、好ましくは15~600mg、より好ましくは20~400mgとなるように本発明組成物中に配合することが好ましい。また、本発明組成物の全質量に対するナプロキセンの含有量は、例えば、1~99質量%(以下、「%」という)が好ましく、5~95%がより好ましい。 The amount of naproxen or a salt thereof (hereinafter simply referred to as "naproxen") in the composition of the present invention may be appropriately determined depending on the sex, age, symptoms, etc. of the recipient. For example, it is preferable that the composition of the present invention is formulated so that the daily dosage for an adult is usually 10-1200 mg, preferably 15-600 mg, more preferably 20-400 mg. The content of naproxen relative to the total mass of the composition of the present invention is, for example, preferably 1 to 99% by mass (hereinafter referred to as "%"), more preferably 5 to 95%.
一方、本発明組成物で用いられる塩基性化合物としては、1~3価の金属を含む塩基性化合物やアミン系塩基性化合物等が挙げられる。1~3価の金属を含む塩基性化合物としては、特に限定されないが、例えば、炭酸水素カリウム、炭酸水素ナトリウム、ケイ酸カルシウム、沈降炭酸カルシウム、無水リン酸水素カルシウム、炭酸マグネシウム、水酸化マグネシウム、酸化マグネシウム、ケイ酸マグネシウム、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、合成ケイ酸アルミニウム、乾燥水酸化アルミニウムゲル、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等の1~3価の金属を含む塩基性無機化合物や、クエン酸ナトリウム、アルジオキサ、スクラルファート、ジヒドロキシアルミニウムアミノアセテート等の1~3価の金属を含む塩基性有機化合物を挙げることができる。 On the other hand, examples of the basic compound used in the composition of the present invention include basic compounds containing monovalent to trivalent metals, amine-based basic compounds, and the like. Basic compounds containing monovalent to trivalent metals are not particularly limited, but examples include potassium hydrogen carbonate, sodium hydrogen carbonate, calcium silicate, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate, magnesium carbonate, magnesium hydroxide, Magnesium oxide, magnesium silicate, synthetic hydrotalcite, magnesium aluminometasilicate, synthetic aluminum silicate, dried aluminum hydroxide gel, aluminum hydroxide gel, aluminum hydroxide-sodium bicarbonate coprecipitate, aluminum hydroxide-carbonic acid Basic inorganic compounds containing monovalent to trivalent metals such as magnesium mixed dried gel, aluminum hydroxide/magnesium carbonate/calcium carbonate coprecipitate, magnesium hydroxide/aluminum potassium sulfate coprecipitate, sodium citrate, Basic organic compounds containing monovalent to trivalent metals such as aldioxa, sucralfate, and dihydroxyaluminum aminoacetate can be mentioned.
また、上記アミン系塩基性化合物としては、特に限定されないが、例えば、グリシナール、アルギニン等が挙げられる。 The amine-based basic compound is not particularly limited, and examples thereof include glycinal and arginine.
本発明組成物における塩基性化合物は単独または二種以上を組み合わせて本発明組成物に使用することができ、その好ましいものとしては、炭酸水素カリウム、炭酸水素ナトリウム、ケイ酸カルシウム、沈降炭酸カルシウム、無水リン酸水素カルシウム、炭酸マグネシウム、水酸化マグネシウム、酸化マグネシウム、ケイ酸マグネシウム、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、合成ケイ酸アルミニウム、乾燥水酸化アルミニウムゲル、水酸化アルミニウムゲル、クエン酸ナトリウム、アルジオキサ、スクラルファート等の1~3価の金属を含む塩基性化合物を挙げることができる。1~3価の金属を含む塩基性化合物を用いることにより、速やかで持続的な溶解性を得ることができる。 The basic compound in the composition of the present invention can be used singly or in combination of two or more kinds, and preferable examples thereof include potassium hydrogen carbonate, sodium hydrogen carbonate, calcium silicate, precipitated calcium carbonate, Anhydrous calcium hydrogen phosphate, magnesium carbonate, magnesium hydroxide, magnesium oxide, magnesium silicate, synthetic hydrotalcite, magnesium aluminometasilicate, synthetic aluminum silicate, dry aluminum hydroxide gel, aluminum hydroxide gel, sodium citrate , aldioxa, and basic compounds containing monovalent to trivalent metals such as sucralfate. Rapid and sustained solubility can be obtained by using a basic compound containing a monovalent to trivalent metal.
本発明組成物におけるナプロキセンと塩基性化合物の含有比は、特に限定されず、ナプロキセンの配合量に応じて適宜検討して決定すればよいが、ナプロキセン1質量部に対し、塩基性物質を0.001~100質量部含有することが好ましく、0.01~50質量部含有することがより好ましく、0.1~30質量部含有することがさらに好ましい。 The content ratio of naproxen and the basic compound in the composition of the present invention is not particularly limited, and may be determined according to the blending amount of naproxen. 001 to 100 parts by mass, more preferably 0.01 to 50 parts by mass, and even more preferably 0.1 to 30 parts by mass.
また、本発明組成物は、更に、セルロース系水膨潤性高分子を配合することが望ましい。セルロース系水膨潤性高分子を配合することで、経口投与した際の口腔内等での崩壊性が良くなり、ナプロキセンの溶解性をさらに高めることができる。 Moreover, it is desirable that the composition of the present invention further contains a cellulose-based water-swellable polymer. By blending the cellulose-based water-swellable polymer, the disintegration property in the oral cavity or the like when orally administered is improved, and the solubility of naproxen can be further increased.
上記セルロース系水膨潤性高分子としては、例えば、低置換度ヒドロキシプロピルセルロース、クロスカルメロースナトリウム、カル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、結晶セルロース、アルファー化デンプン、カルボキシメチルスターチナトリウム等が挙げられる。このうち好ましいものとしては、低置換度ヒドロキシプロピルセルロースが挙げられる。 Examples of the cellulose-based water-swellable polymer include low-substituted hydroxypropylcellulose, croscarmellose sodium, carboxymethylcellulose sodium, carboxymethylcellulose calcium, carboxymethylcellulose, crystalline cellulose, pregelatinized starch, sodium carboxymethylstarch, and the like. be done. Among these, low-substituted hydroxypropyl cellulose is preferred.
セルロース系水膨潤性高分子として低置換度ヒドロキシプロピルセルロースを用いる場合は、優れた形状および粒子径の経口固形組成物に加工しやすいという製造性の面からヒドロキシプロポキシ基が5.0~16.0質量%であるものが好ましく、さらに7.0~13.0質量%であるものが好ましい。このような低置換度ヒドロキシプロピルセルロースとしては、例えば信越化学(株)製、LH-11(ヒドロキシプロポキシ基10.0~12.9質量%)、LH-21(ヒドロキシプロポキシ基10.0~12.9質量%)LH-22(ヒドロキシプロポキシ基7.0~9.9質量%)LH-31(ヒドロキシプロポキシ基10.0~12.9質量%)、LH-32(ヒドロキシプロポキシ基7.0~9.9質量%)、LH-B1(ヒドロキシプロポキシ基10.0~12.9質量%)、NBD-020(ヒドロキシプロポキシ基13.0~15.9質量%)、NBD-021(ヒドロキシプロポキシ基10.0~12.9質量%)NBD-022(ヒドロキシプロポキシ基7.0~9.9質量%)などが挙げられる。さらに、低置換度ヒドロキシプロピルセルロースの平均粒径はおよそ60μm以下が好ましく、55μm以下がより好ましい。 When low-substituted hydroxypropyl cellulose is used as the cellulosic water-swellable polymer, the hydroxypropoxy group content is 5.0 to 16.0 from the standpoint of ease of processing into an oral solid composition with excellent shape and particle size. It is preferably 0% by mass, more preferably 7.0 to 13.0% by mass. Examples of such low-substituted hydroxypropyl cellulose include LH-11 (10.0 to 12.9% by mass of hydroxypropoxy groups) and LH-21 (10.0 to 12% by mass of hydroxypropoxy groups) manufactured by Shin-Etsu Chemical Co., Ltd. .9% by mass) LH-22 (7.0 to 9.9% by mass of hydroxypropoxy group) LH-31 (10.0 to 12.9% by mass of hydroxypropoxy group), LH-32 (7.0% by mass of hydroxypropoxy group ~9.9% by mass), LH-B1 (hydroxypropoxy group 10.0 to 12.9% by mass), NBD-020 (hydroxypropoxy group 13.0 to 15.9% by mass), NBD-021 (hydroxypropoxy 10.0 to 12.9% by mass of groups) and NBD-022 (7.0 to 9.9% by mass of hydroxypropoxy groups). Furthermore, the average particle size of the low-substituted hydroxypropyl cellulose is preferably about 60 µm or less, more preferably 55 µm or less.
本発明組成物において、セルロース系水膨潤性高分子を配合する場合の配合量は、特に限定されないが、例えば、本発明組成物中1~99%が好ましく、5~95%がより好ましい。 In the composition of the present invention, the blending amount of the cellulose-based water-swellable polymer is not particularly limited.
本発明組成物には、上記した各成分の他、その他の活性医薬成分として、例えば、ナプロキセン以外の抗炎症・解熱鎮痛薬、抗ヒスタミン薬、抗アレルギー薬、鎮咳去痰薬、中枢神経興奮薬、ビタミン及び生薬等を添加してもよい。 In addition to the above ingredients, the composition of the present invention may include other active pharmaceutical ingredients, such as anti-inflammatory/antipyretic analgesics other than naproxen, antihistamines, antiallergics, antitussive expectorants, central nervous system stimulants, Vitamins, crude drugs, etc. may be added.
上記ナプロキセン以外の抗炎症・解熱鎮痛薬としては、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、エテンザミド、サザピリン、サリチルアミド、ロキソプロフェン、ラクチルフェネチジン、イソプロピルアンチピリン、グリチルリチン、グリチルリチン酸アンモニウム、グリチルリチン酸カリウム、グリチルリチン酸二カリウム等のグリチルリチン酸及びその類縁物質若しくはその塩、トラネキサム酸等が挙げられる。これらは、1種または2種以上を使用しても良い。 Examples of anti-inflammatory/antipyretic analgesics other than naproxen include aspirin, aspirin aluminum, acetaminophen, ethenzamide, sazapyrin, salicylamide, loxoprofen, lactylphenetidine, isopropylantipyrine, glycyrrhizin, ammonium glycyrrhizinate, potassium glycyrrhizinate, Examples thereof include glycyrrhizic acid such as dipotassium glycyrrhizinate, analogues thereof or salts thereof, and tranexamic acid. These may use 1 type(s) or 2 or more types.
また、上記抗ヒスタミン薬及び抗アレルギー薬としては、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、エバスチン、エメダスチンフマル酸塩、オキサトミド、カルビノキサミンジフェニルジスルホン酸塩、カルピノキサミンマレイン酸塩、クレマスチンフマル酸塩、クロルフェニラミンマレイン酸塩、d-クロルフェニラミンマレイン酸塩、ジフェテロール塩酸塩、ジフェテロールリン酸塩、ジフェニルジスルホン酸カルビノキサミン、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、セチリジン塩酸塩、トリプロリジン塩酸塩水和物、トリペレナミン塩酸塩、トンジルアミン塩酸塩、フェキソフェナジン、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、ベポタスチンベシル酸塩、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、レボセチリジン塩酸塩等が挙げられる。これらは、1種または2種以上を使用しても良い。 Examples of antihistamines and antiallergic agents include azelastine hydrochloride, alimemazine tartrate, isothipendyl hydrochloride, iproheptine hydrochloride, epinastine hydrochloride, ebastine, emedastine fumarate, oxatomide, and carbinoxamin diphenyl. Disulfonate, carpinoxamine maleate, clemastine fumarate, chlorpheniramine maleate, d-chlorpheniramine maleate, difererol hydrochloride, difererol phosphate, carbinoxamine diphenyldisulfonate, diphenylpyraline hydrochloride, diphenylpyraline teocrate, diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, cetirizine hydrochloride, triprolidine hydrochloride hydrate, tripelennamine hydrochloride, tonjilamine hydrochloride, fexofenadine, phenetazine hydrochloride, promethazine hydrochloride, promethazine methylene disalicylate, bepotastine besilate, homochlorcyclidine hydrochloride, mequitazine, methdilazine hydrochloride, mebhydroline napadisilate, levocetirizine hydrochloride and the like. These may use 1 type(s) or 2 or more types.
さらに、上記鎮咳去痰薬としては、アンブロキソール塩酸塩、塩酸アロクラミド、クエン酸チペピジン、クロペラスチン塩酸塩、クロペラスチンフェンジゾ酸塩、コデインリン酸塩水和物、ジヒドロコデインリン酸塩水和物、ジブナートナトリウム、チペピジンヒベンズ酸塩、デキストロメトルファン臭化水素酸塩、デキストロメトルファン・フェノールフタリン塩、ペントキシベリンクエン酸塩、ジメモルファンリン酸塩、ノスカピン、ノスカピン塩酸塩水和物、dl-メチルエフェドリン塩酸塩、dl-メチルエフェドリンサッカリン塩、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、ブロムヘキシン塩酸塩、L-カルボシステイン、L-エチルシステイン塩酸、ベラドンナ総アルカロイド、ヨウ化イソプロパミド、エプラジノン塩酸塩等が挙げられる。これらは、1種または2種以上を使用しても良い。 Furthermore, the above antitussive expectorants include ambroxol hydrochloride, aloclamide hydrochloride, tipepidine citrate, cloperastine hydrochloride, cloperastine fendizoate, codeine phosphate hydrate, dihydrocodeine phosphate hydrate, dibunate Sodium, Tipepidine Hibenzate, Dextromethorphan Hydrobromide, Dextromethorphan Phenolphthalate, Pentoxyberic Citrate, Dimemorphan Phosphate, Noscapine, Noscapine Hydrochloride Hydrate, dl-Methyl Ephedrine hydrochloride, dl-methylephedrine saccharin salt, guaifenesin, potassium guaiacol sulfonate, potassium cresol sulfonate, bromhexine hydrochloride, L-carbocysteine, L-ethylcysteine hydrochloride, belladonna total alkaloids, isopropamide iodide, eprazinone hydrochloride, etc. is mentioned. These may use 1 type(s) or 2 or more types.
さらにまた、上記中枢神経興奮薬としては、安息香酸ナトリウムカフェイン、無水カフェイン、カフェイン水和物が挙げられる。これらは、1種または2種以上を混合して添加しても良い。 Furthermore, the central nervous system stimulants include sodium caffeine benzoate, anhydrous caffeine, and caffeine hydrate. These may be added singly or in combination of two or more.
前記ビタミンとしては、例えば、ビタミンB1及びその誘導体並びにそれらの塩類、ビタミンB2及びその誘導体並びにそれらの塩類、ビタミンC及びその誘導体並びにそれらの塩類、ヘスペリジン及びその誘導体並びにそれらの塩類等が挙げられ、また、上記生薬としては、例えば、マオウ、ナンテンジツ、オウヒ、オンジ、カンゾウ、キキョウ、シャゼンシ、シャゼンソウ、セキサン、セネガ、バイモ、ウイキョウ、オウバク、オウレン、カジュツ、カミツレ、ケイヒ、ゲンチアナ、ゴオウ、獣胆、シャジン、ショウキョウ、ソウジュツ、チョウジ、チンピ、ビャクジュツ、ジリュウ、チクセツニンジン、ニンジン、葛根湯、葛根湯加桔梗、桂枝湯、香蘇散、柴胡桂枝湯、小柴胡湯、小青竜湯、麦門冬湯、半夏厚朴湯、麻黄湯等を挙げることができる。これらは、1種または2種以上を混合して添加しても良い。 Examples of the vitamins include vitamin B1 and derivatives thereof and salts thereof, vitamin B2 and derivatives thereof and salts thereof, vitamin C and derivatives thereof and salts thereof, hesperidin and derivatives thereof and salts thereof, and the like. In addition, the above crude drugs include, for example, Ephedra, Nantenjitsu, Touhi, Onji, Glycyrrhiza, Bellflower, Shazenshii, Shazensou, Sekisan, Senega, Fritillaria, Fennel, Phellodendron bark, Japanese coptis, Kajutsu, Chamomile, Cinnamon, Gentian, Chinese gourd, beast Bile, Shajin, Ginger, Sojutsu, Clove, Chimpi, Byakujutsu, Jiryu, Chikusetsu Ginseng, Ginseng, Kakkonto, Kakkonto Kakikyo, Keishito, Kososan, Saikokeishito, Shosaikoto, Shoseiryuto , Bakumondoto, Hangekobokuto, and Maoto. These may be added singly or in combination of two or more.
また、本発明組成物には、必要に応じて通常の経口固形組成物に含有させることのできる製剤添加剤を添加してもよい。 In addition, the composition of the present invention may optionally contain formulation additives that can be contained in ordinary oral solid compositions.
製剤添加剤としては、一般的に使用され得る賦形剤、結合剤、崩壊剤、滑沢剤の他、各種担体、安定(化)剤、界面活性剤、可塑剤、滑沢化剤、可溶(化)剤、還元剤、緩衝剤、甘味剤、基剤、吸着剤、矯味剤、懸濁(化)剤、抗酸化剤、光沢化剤、コーティング剤、剤皮、湿潤剤、湿潤調整剤、充填剤、消泡剤、清涼化剤、着色剤、着香剤、香料、糖衣剤、等張化剤、軟化剤、乳化剤、粘稠化剤、粘稠剤、発泡剤、pH調整剤、稀釈剤、分散剤、崩壊補助剤、崩壊延長剤、芳香剤、防湿剤、防腐剤、保存剤、流動化剤、帯電防止剤、増量剤、保湿剤、付湿剤等を挙げることができる。これら添加剤の例は、薬食発1204第1号(薬事行政法令)、医薬品添加物事典2007(日本医薬品添加剤協会編集、薬事日報社)及び第8版食品添加物公定書(日本食品添加物協会)に記載されている。 Formulation additives include commonly used excipients, binders, disintegrants, and lubricants, as well as various carriers, stabilizers, surfactants, plasticizers, lubricants, and softeners. Solubilizing agent, reducing agent, buffering agent, sweetening agent, base, adsorbent, flavoring agent, suspending agent, antioxidant, brightening agent, coating agent, shell, wetting agent, moisture control agent, filler, antifoaming agent, cooling agent, coloring agent, flavoring agent, fragrance, sugar coating agent, tonicity agent, softening agent, emulsifier, thickening agent, thickening agent, foaming agent, pH adjuster , diluents, dispersants, disintegration aids, disintegration extenders, fragrances, moisture-proof agents, preservatives, preservatives, fluidizers, antistatic agents, bulking agents, moisturizing agents, wetting agents, etc. . Examples of these additives include the PFSB Notification No. 1204 No. 1 (Pharmaceutical Affairs Administrative Law), Pharmaceutical Excipients Dictionary 2007 (edited by the Japan Pharmaceutical Excipients Association, Yakuji Nippo), and the 8th Edition Food Additives Official Code (Japan Food Additives Association).
上記製剤添加剤のうち賦形剤としては、例えば、乳糖、糖アルコール類、軽質無水ケイ酸、酸化チタン等が挙げられる。これらの賦形剤は1種または2種以上を使用することができる。 Excipients among the pharmaceutical additives include, for example, lactose, sugar alcohols, light anhydrous silicic acid, and titanium oxide. One or more of these excipients can be used.
上記結合剤としては、例えば、ゼラチン、アラビアゴム末、ヒプロメロース、ポリビニルピロリドン、ポリビニルアルコール、ポリビニルアルコール・アクリル酸・メタクリル酸メチル共重合体、ポリビニルアルコール・ポリエチレングリコール・グラフトコポリマー、プルラン、デキストリン、メタクリル酸コポリマー等のアクリル酸誘導体、セラック、カルボキシビニルポリマー等が挙げられる。これらの結合剤は1種または2種以上を使用することができる。 Examples of the binder include gelatin, gum arabic powder, hypromellose, polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl alcohol/acrylic acid/methyl methacrylate copolymer, polyvinyl alcohol/polyethylene glycol/graft copolymer, pullulan, dextrin, and methacrylic acid. Examples thereof include acrylic acid derivatives such as copolymers, shellac, and carboxyvinyl polymers. One or more of these binders can be used.
また崩壊剤としては、例えば、クロスポビドン、クロスリンクドインソルブルポリビニルピロリドン等が挙げられる。これらの崩壊剤は1種または2種以上を使用することができる。 Examples of disintegrants include crospovidone, cross-linked insoluble polyvinylpyrrolidone, and the like. One or more of these disintegrants can be used.
上記滑沢剤としては、例えば、タルク、ステアリン酸、ステアリン酸マグネシウム、ショ糖脂肪酸エステル類、ポリエチレングリコール等が挙げられる。これらの滑沢剤は1種または2種以上を使用することができる。 Examples of the lubricant include talc, stearic acid, magnesium stearate, sucrose fatty acid esters, polyethylene glycol and the like. One or more of these lubricants can be used.
本発明組成物は、ナプロキセンと塩基性化合物、あるいはこれらとセルロース系水膨潤性高分子に、必要に応じて上記した他の活性医薬成分や製剤添加剤を常法に従って配合し、これを適宜固形製剤とすることによって調製される。この固形製剤の例としては、粉末製剤、顆粒剤、錠剤等の内服固形製剤を挙げることができ、また、必要に応じてフィルムコーティングや糖衣を施し、コーティング製剤とすることも、また徐放性製剤等とすることもできる。 The composition of the present invention can be prepared by blending naproxen and a basic compound, or these and a cellulose-based water-swellable polymer with other active pharmaceutical ingredients and formulation additives according to a conventional method, if necessary. It is prepared by making a formulation. Examples of this solid preparation include internal solid preparations such as powder preparations, granules, and tablets. It can also be used as a formulation or the like.
本発明組成物の製造にあたり、各成分を混合する方法としては、例えば、乳鉢やメカノミル(MM-20N型、岡田精工社製)、高速撹拌造粒機(パウレック社製)等の装置を使用して混合する方法を挙げることができる。混合の条件としては、均一に混合することができれば特に制限はなく、混合に用いられる成分の種類や量により適宜選択することができる。 In the production of the composition of the present invention, as a method of mixing each component, for example, a mortar, a mechanomill (MM-20N type, manufactured by Okada Seiko Co., Ltd.), a high-speed stirring granulator (manufactured by Powrex Co., Ltd.), or the like is used. and mixing method. The mixing conditions are not particularly limited as long as they can be uniformly mixed, and can be appropriately selected according to the types and amounts of the components used for mixing.
また、本発明組成物は、さらに上記混合末に、練合液を添加して練合、造粒することができる。この際の練合液の添加量は、混合末の質量に対して、0.05~10倍量程度が好ましい。また、練合液としては、精製水、エタノール等を用いることができ、この中でも、精製水が好ましい。練合のために使用する装置としては、例えば、乳鉢、メカノミル(MM-20N型、岡田精工社製)、高速撹拌造粒機(パウレック社製)等が挙げられる。練合の条件としては、均一に練合することができれば特に制限はなく、練合に用いられる成分の種類や量により適宜選択することができる。 In addition, the composition of the present invention can be further kneaded and granulated by adding a kneading liquid to the above mixed powder. The amount of the kneading liquid added at this time is preferably about 0.05 to 10 times the mass of the mixed powder. Purified water, ethanol, or the like can be used as the kneading liquid, and among these, purified water is preferable. Equipment used for kneading includes, for example, a mortar, a mechanomill (MM-20N type, manufactured by Okada Seiko Co., Ltd.), a high-speed stirring granulator (manufactured by Powrex Co., Ltd.), and the like. The kneading conditions are not particularly limited as long as uniform kneading can be achieved, and can be appropriately selected depending on the types and amounts of the components used for kneading.
さらに、造粒は上記練合した練合物を、例えば、円筒造粒機、ロータリー型造粒機、スクリュー押し出し造粒機、ペレットミル型造粒機等の押し出し造粒装置等を利用し行うことができる。得られた造粒物は、そのまま、又はマルメライザー(不二パウダル社製)等の球形整粒機により球形にした後、乾燥することができる。乾燥に使用する装置としては、例えば、箱型乾燥機(エスペック社製)、流動層乾燥機(フロイント産業社製)等の乾燥機を使用し、40~90℃の条件で乾燥するのがよい。なお、乾燥を終える目安としては、例えば、赤外線水分計FD-800(ケツト科学研究所社製)を使用して、水分率が2%以下になるまで乾燥を行えばよい。造粒物を乾燥後、必要に応じて、ステンレススクリーン等を用いて整粒してもよい。 Furthermore, granulation is carried out by using an extrusion granulator such as a cylindrical granulator, a rotary granulator, a screw extrusion granulator, a pellet mill type granulator, etc. be able to. The obtained granules can be dried as they are or after being spheroidized by a spheronizer such as Marumerizer (manufactured by Fuji Paudal Co., Ltd.). As the apparatus used for drying, for example, a box type dryer (manufactured by Espec Co., Ltd.), a fluidized bed dryer (manufactured by Freund Sangyo Co., Ltd.) or the like is used, and drying is preferably performed under conditions of 40 to 90 ° C. . As a guideline for completing the drying, for example, an infrared moisture meter FD-800 (manufactured by Ketsuto Kagaku Kenkyusho Co., Ltd.) may be used to dry until the moisture content reaches 2% or less. After drying the granules, if necessary, the granules may be sized using a stainless screen or the like.
斯くして得られる本発明組成物は、ナプロキセンの溶解性が速いため、ナプロキセンを服用後、直ちにナプロキセン効果が表れるというものである。そのため、本発明組成物は、例えば、解熱剤、鎮痛剤、消炎剤等の用途、特に速やかにナプロキセンの消炎鎮痛効果が求められる用途に用いることができる。 Since naproxen is rapidly dissolved in the composition of the present invention thus obtained, the effect of naproxen appears immediately after administration of naproxen. Therefore, the composition of the present invention can be used, for example, as an antipyretic, an analgesic, an anti-inflammatory agent, and particularly for applications where rapid anti-inflammatory and analgesic effects of naproxen are required.
次に、実施例を挙げ、本発明を更に詳細に説明するが、本発明はこれら実施例に何ら制約されるものではない。 EXAMPLES Next, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples.
実 施 例 1
溶解性試験:
粉末製剤(1)
ナプロキセン1gと表1に記載の塩基性物質1gを乳鉢で混合し、粉末製剤を製造した。得られた粉末製剤について、下記の溶出試験方法によりナプロキセンの溶出率を測定した。なお、比較品として同じ粒度のナプロキセンについても溶出率を測定した。これらの結果を併せて表1に示す。
Example 1
Solubility test:
Powder formulation (1)
1 g of naproxen and 1 g of the basic substance listed in Table 1 were mixed in a mortar to prepare a powder formulation. The dissolution rate of naproxen in the resulting powder formulation was measured by the following dissolution test method. The dissolution rate was also measured for naproxen having the same particle size as a comparative product. These results are shown in Table 1 together.
上記結果より、ナプロキセン単独(比較品)よりも、ナプロキセンに表1に記載された塩基性物質を組み合わせたものの方が、ナプロキセンが速く溶解することが確認された。また、塩基性物質として、特に炭酸マグネシウムや酸化マグネシウム使用した場合は、ナプロキセンの30分後の溶出率が極めて高いことが確認された。 From the above results, it was confirmed that naproxen dissolved faster in the combination of naproxen and the basic substance listed in Table 1 than in naproxen alone (comparative product). It was also confirmed that when magnesium carbonate or magnesium oxide was used as the basic substance, the elution rate of naproxen after 30 minutes was extremely high.
<溶出試験方法>
日本薬局方溶出試験法第2法に従い、精製水900mLにナプロキセンとして20mg含有量の各粉末製剤を入れ、パドル回転数50rpm、温度37±0.5℃の条件下で溶出試験を行った。ナプロキセンの溶出量は、液体クロマトグラフ法により測定し、この溶出量から溶出率を算出した。
<Elution test method>
According to Japanese Pharmacopoeia Dissolution Test Method 2, each powder formulation containing 20 mg of naproxen was added to 900 mL of purified water, and a dissolution test was performed under the conditions of a paddle rotation speed of 50 rpm and a temperature of 37±0.5°C. The elution amount of naproxen was measured by liquid chromatography, and the elution rate was calculated from this elution amount.
実 施 例 2
溶解性試験:
粉末製剤(2)
ナプロキセン15g、表2に記載の塩基性物質15g及び低置換度ヒドロキシプロピルセルロース(ヒドロキシプロポキシ基11.1質量%のもの;信越化学工業社製;以下同じ)15gを、メカノミル(MM-20N型、岡田精工社製)を用い、主軸回転数900rpmで、3分間混合して粉末製剤を製造した。この粉末製剤について、上記同様の方法により溶出率を測定した。なお、比較品としては、実施例1と同様のナプロキセン粉末を使用した。結果を併せて表2に示す。
Example 2
Solubility test:
Powder formulation (2)
15 g of naproxen, 15 g of the basic substance listed in Table 2, and 15 g of low-substituted hydroxypropyl cellulose (11.1% by mass of hydroxypropoxy group; manufactured by Shin-Etsu Chemical Co., Ltd.; the same applies hereinafter) were added to Mechanomil (MM-20N type, manufactured by Okada Seiko Co., Ltd.), and mixed for 3 minutes at a spindle rotation speed of 900 rpm to produce a powder formulation. The dissolution rate of this powder formulation was measured by the same method as above. As a comparative product, the same naproxen powder as in Example 1 was used. The results are also shown in Table 2.
上記結果より、低置換度ヒドロキシプロピルセルロースを配合する場合において、ケイ酸カルシウムを使用すると、30分後のナプロキセンの溶出率が、実施例1の低置換度ヒドロキシプロピルセルロースを配合しない場合より高くなることが確認された。また、酸化マグネシウムと炭酸マグネシウムを使用する場合、5分後のナプロキセンの溶出率が極めて高いことが確認された。 From the above results, when calcium silicate is used when low-substituted hydroxypropyl cellulose is blended, the elution rate of naproxen after 30 minutes is higher than when low-substituted hydroxypropyl cellulose of Example 1 is not blended. was confirmed. It was also confirmed that when magnesium oxide and magnesium carbonate were used, the dissolution rate of naproxen after 5 minutes was extremely high.
実 施 例 3
溶解性試験:
顆粒剤(1)
ナプロキセン14.0g、表3に記載の塩基性物質14.0g及び低置換度ヒドロキシプロピルセルロース 14.0gをメカノミル(MM-20N型、岡田精工社製)を用いて、主軸回転数900rpmで、3分間混合した。この混合末に、練合液として精製水を56g加え、メカノミルで3分間、主軸回転数900rpmで練合した。この練合物をステンレススクリーンで押し出した後、箱型乾燥機(エスペック社製)で、水分率2%以下になるまで乾燥させて造粒物を得た(造粒物の水分量は、赤外線水分計FD-800(ケット科学研究所社製、60℃、10分)により測定した;以下同じ)。
Example 3
Solubility test:
Granules (1)
14.0 g of naproxen, 14.0 g of the basic substances listed in Table 3, and 14.0 g of low-substituted hydroxypropyl cellulose were treated with Mechanomill (MM-20N type, manufactured by Okada Seiko Co., Ltd.) at a spindle speed of 900 rpm for 3 Mix for a minute. To this mixed powder, 56 g of purified water was added as a kneading liquid, and the mixture was kneaded for 3 minutes with a Mechanomill at a spindle speed of 900 rpm. After extruding this kneaded product with a stainless screen, it was dried with a box dryer (manufactured by Espec Co., Ltd.) until the moisture content was 2% or less to obtain a granulated product (the moisture content of the granulated product was measured by infrared Measured with a moisture meter FD-800 (manufactured by Kett Science Laboratory Co., Ltd., 60° C., 10 minutes; hereinafter the same).
得られた造粒物を、26メッシュのステンレススクリーンで篩分し、それを通過した造粒物を、さらに150メッシュのステンレススクリーンで篩分し、スクリーン上に残ったものを回収し、100~600μmの整粒顆粒を得た。この整粒顆粒について、上記同様の方法により溶出率を測定した。結果を併せて表3に示す。 The resulting granules are sieved through a 26-mesh stainless screen, and the granules that have passed through it are further sieved through a 150-mesh stainless screen. A 600 μm sized granule was obtained. The dissolution rate of the sized granules was measured by the same method as above. The results are also shown in Table 3.
上記結果より、顆粒製剤とした場合、塩基性物質として、特に炭酸水素カリウムや炭酸水素ナトリウムを使用すると、5分後の溶出率が極めて高く、15分後及び30分後においても高い溶出率が維持されることが確認された。 From the above results, in the case of granule preparation, when potassium hydrogen carbonate or sodium hydrogen carbonate is used as a basic substance, the dissolution rate after 5 minutes is extremely high, and the dissolution rate is also high after 15 minutes and 30 minutes. confirmed to be maintained.
実 施 例 4
フィルムコーティング錠(1):
表4に記載の処方に従い、秤量した各成分を高速撹拌造粒機(VG-10型、パウレック社製)に投入し、3分間混合した。次いで、処方1から処方5に対応する各混合末に適量の精製水をそれぞれ添加し、高速撹拌造粒機(VG-10型、パウレック社製)にて、3分間練合した。次に、その練合物を押出造粒機(TDG-80型、ダルトン社製)を用いて造粒した。更に、得られた押出造粒物を流動層乾燥機(FLO-2型、フロイント産業社製)に投入し、造粒物中の水分が2%以下になるまで乾燥したのち、コーミルにて整粒を行い、顆粒を得た。
Example 4
Film-coated tablet (1):
According to the formulation shown in Table 4, each weighed component was put into a high-speed stirring granulator (VG-10 type, manufactured by Powrex) and mixed for 3 minutes. Next, an appropriate amount of purified water was added to each of the mixed powders corresponding to Formulations 1 to 5, and the mixture was kneaded for 3 minutes with a high-speed stirring granulator (VG-10 type, manufactured by Powrex Corporation). Next, the kneaded product was granulated using an extrusion granulator (Model TDG-80, manufactured by Dalton). Further, the obtained extruded granules are put into a fluidized bed dryer (FLO-2 type, manufactured by Freund Corporation), dried until the water content in the granules becomes 2% or less, and then comiled to align. Granulation was performed to obtain granules.
次いで、得られた各顆粒900gに結晶セルロース140g、ステアリン酸マグネシウム10gを各々添加し、V型混合機(TCV-5型、徳寿工作所社製)にて混合し、打錠末1050gを得た。次に、ロータリー打錠機(VIRG0512型、菊水製作所社製)にて打錠を行い、ナプロキセン含量100mgの直径9.5mm、錠剤質量350mgの素錠を製造した。 Next, 140 g of crystalline cellulose and 10 g of magnesium stearate were added to 900 g of each of the obtained granules and mixed with a V-type mixer (TCV-5 type, manufactured by Tokuju Kosakusho Co., Ltd.) to obtain 1050 g of tableting powder. . Next, tableting was performed using a rotary tableting machine (Model VIRG0512, manufactured by Kikusui Seisakusho) to produce uncoated tablets with a naproxen content of 100 mg, a diameter of 9.5 mm and a tablet weight of 350 mg.
次に、ヒプロメロース120g、ポリエチレングリコール 20gを精製水に溶解した後、タルク10g及び酸化チタン10gを分散して固形分濃度8%のフィルムコーティング液2000gを調製した。次いで、素錠500gをコーティング機(HC-LABO型、フロイント産業社製)に投入し、調製したフィルムコーティング液を噴霧してコーティングを行い、錠剤質量360mgの白色のフィルムコーティング錠を得た。 Next, after dissolving 120 g of hypromellose and 20 g of polyethylene glycol in purified water, 10 g of talc and 10 g of titanium oxide were dispersed to prepare 2000 g of a film coating liquid having a solid concentration of 8%. Then, 500 g of the uncoated tablet was put into a coating machine (HC-LABO type, manufactured by Freund Corporation) and coated by spraying the prepared film coating liquid to obtain a white film-coated tablet with a tablet weight of 360 mg.
実 施 例 5
フィルムコーティング錠(2):
表5に記載の処方に従い、秤量した各成分を高速撹拌造粒機(VG-10型、パウレック社製)に投入し、3分間混合した。次いで、処方6から処方10に対応する各混合末に適量の精製水をそれぞれ添加し、高速撹拌造粒機(VG-10型、パウレック社製)にて、3分間練合、造粒した。次に、得られた造粒物を流動層乾燥機(FLO-2型、フロイント産業社製)に投入し、水分が2%以下になるまで乾燥したのち、コーミルにて整粒を行い、顆粒を得た。
Example 5
Film-coated tablet (2):
According to the formulation shown in Table 5, each weighed component was put into a high-speed stirring granulator (VG-10 type, manufactured by Powrex) and mixed for 3 minutes. Next, an appropriate amount of purified water was added to each of the mixed powders corresponding to Formulations 6 to 10, and kneaded and granulated for 3 minutes with a high-speed stirring granulator (VG-10 type, manufactured by Powrex). Next, the obtained granules are put into a fluidized bed dryer (FLO-2 type, manufactured by Freund Corporation) and dried until the water content is 2% or less, and then sieved with a combil to obtain granules. got
次いで、得られた各顆粒900gに結晶セルロース140g、ステアリン酸マグネシウム10gを各々添加し、V型混合機(TCV-5型、徳寿工作所社製)にて混合し、打錠末1050gを得た。次に、ロータリー打錠機(VIRG0512型、菊水製作所社製)にて打錠を行い、ナプロキセン含量100mgの直径9.5mm、錠剤質量350mgの素錠を製造した。 Next, 140 g of crystalline cellulose and 10 g of magnesium stearate were added to 900 g of each of the obtained granules and mixed with a V-type mixer (TCV-5 type, manufactured by Tokuju Kosakusho Co., Ltd.) to obtain 1050 g of tableting powder. . Next, tableting was performed using a rotary tableting machine (Model VIRG0512, manufactured by Kikusui Seisakusho) to produce uncoated tablets with a naproxen content of 100 mg, a diameter of 9.5 mm and a tablet weight of 350 mg.
次に、ヒプロメロース120g、ポリエチレングリコール20gを精製水に溶解した後、タルク10g及び酸化チタン10gを分散して固形分濃度8%のフィルムコーティング液2000gを調製した。次いで、素錠500gをコーティング機(HC-LABO型、フロイント産業社製)に投入し、調製したフィルムコーティング液を噴霧してコーティングを行い、錠剤質量360mgの白色のフィルムコーティング錠を得た。 Next, after dissolving 120 g of hypromellose and 20 g of polyethylene glycol in purified water, 10 g of talc and 10 g of titanium oxide were dispersed to prepare 2000 g of a film coating liquid having a solid concentration of 8%. Then, 500 g of the uncoated tablet was put into a coating machine (HC-LABO type, manufactured by Freund Corporation) and coated by spraying the prepared film coating liquid to obtain a white film-coated tablet with a tablet weight of 360 mg.
実 施 例 6
顆粒剤(2):
表6に記載の処方に従い、秤量した各成分を高速撹拌造粒機(VG-10型、パウレック社製)に投入し、3分間混合した。次いで、処方11から処方15に対応する各混合末に適量の精製水をそれぞれ添加し、高速撹拌造粒機(VG-10型、パウレック社製)にて、3分間練合した。次に、その練合物を押出造粒機(TDG-80型、ダルトン社製)を用いて造粒した。更に、得られた押出造粒物を流動層乾燥機(FLO-2型、フロイント産業社製)に投入し、造粒物中の水分が2%以下になるまで乾燥したのち、コーミルにて整粒を行い、顆粒を得た。
Example 6
Granules (2):
According to the formulation shown in Table 6, each weighed component was put into a high-speed stirring granulator (VG-10 type, manufactured by Powrex) and mixed for 3 minutes. Next, an appropriate amount of purified water was added to each of the mixed powders corresponding to Formulations 11 to 15, and the mixture was kneaded for 3 minutes with a high-speed stirring granulator (VG-10 model, manufactured by Powrex Corporation). Next, the kneaded product was granulated using an extrusion granulator (Model TDG-80, manufactured by Dalton). Further, the obtained extruded granules are put into a fluidized bed dryer (FLO-2 type, manufactured by Freund Corporation), dried until the water content in the granules becomes 2% or less, and then comiled to align. Granulation was performed to obtain granules.
次いで、得られた各顆粒800gにアスパルテーム10g、アセスルファムカリウム10g及びステアリン酸マグネシウム4gを各々添加し、V型混合機(TCV-5型、徳寿工作所社製)にて混合し、充填用顆粒末824gを得た。次に、アルミヒートシール包装を行い、ナプロキセン含量100mgで1包質量が1236mgの顆粒剤を得た。 Next, 10 g of aspartame, 10 g of acesulfame potassium, and 4 g of magnesium stearate were added to 800 g of each of the obtained granules, and mixed with a V-type mixer (TCV-5 type, manufactured by Tokuju Kosakusho Co., Ltd.) to obtain granule powder for filling. 824 g was obtained. Next, aluminum heat-seal packaging was performed to obtain granules with a naproxen content of 100 mg and a packaging weight of 1236 mg.
実 施 例 7
顆粒剤(3):
表7に記載の処方に従い、秤量した各成分を高速撹拌造粒機(VG-10型、パウレック社製)に投入し、3分間混合した。次いで、処方16から処方20に対応する各混合末に適量の精製水をそれぞれ添加し、高速撹拌造粒機(VG-10型、パウレック社製)にて、3分間練合した。次に、得られた練合造粒物を流動層乾燥機(FLO-2型、フロイント産業社製)に投入し、造粒物中の水分が2%以下になるまで乾燥したのち、コーミルにて整粒を行い、顆粒を得た。
Example 7
Granules (3):
According to the formulation shown in Table 7, each weighed component was added to a high-speed stirring granulator (VG-10 type, manufactured by Powrex) and mixed for 3 minutes. Next, an appropriate amount of purified water was added to each of the mixed powders corresponding to Formulations 16 to 20, and the mixture was kneaded for 3 minutes with a high-speed stirring granulator (VG-10 type, manufactured by Powrex Corporation). Next, the obtained kneaded granules are put into a fluidized bed dryer (FLO-2 type, manufactured by Freund Corporation) and dried until the water content in the granules becomes 2% or less. The granules were obtained by sizing.
次いで、得られた各顆粒800gにアスパルテーム10g、アセスルファムカリウム10g及びステアリン酸マグネシウム4gを各々添加し、V型混合機(TCV-5型、徳寿工作所社製)にて混合し、充填用顆粒末824gを得た。次に、アルミヒートシール包装を行い、ナプロキセン含量100mgで1包質量が1236mgの顆粒剤を得た。 Next, 10 g of aspartame, 10 g of acesulfame potassium, and 4 g of magnesium stearate were added to 800 g of each of the obtained granules, and mixed with a V-type mixer (TCV-5 type, manufactured by Tokuju Kosakusho Co., Ltd.) to obtain granule powder for filling. 824 g was obtained. Next, aluminum heat-seal packaging was performed to obtain granules with a naproxen content of 100 mg and a packaging weight of 1236 mg.
実 施 例 8
硬カプセル剤(1):
表8に記載の処方に従い、秤量した各成分を高速撹拌造粒機(VG-10型、パウレック社製)に投入し、3分間混合した。次いで、処方21から処方26に対応する各混合末に適量の精製水をそれぞれ添加し、高速撹拌造粒機(VG-10型、パウレック社製)にて、3分間練合した。次に、その練合物を押出造粒機(TDG-80型、ダルトン社製)を用いて造粒した。更に、得られた押出造粒物を流動層乾燥機(FLO-2型、フロイント産業社製)に投入し、造粒物中の水分が2%以下になるまで乾燥したのち、コーミルにて整粒を行い、顆粒を得た。
Example 8
Hard capsule (1):
According to the formulation shown in Table 8, each weighed component was put into a high-speed stirring granulator (VG-10 type, manufactured by Powrex) and mixed for 3 minutes. Next, an appropriate amount of purified water was added to each of the mixed powders corresponding to Formulations 21 to 26, and the mixture was kneaded for 3 minutes with a high-speed stirring granulator (VG-10 model, manufactured by Powrex Corporation). Next, the kneaded product was granulated using an extrusion granulator (Model TDG-80, manufactured by Dalton). Further, the obtained extruded granules are put into a fluidized bed dryer (FLO-2 type, manufactured by Freund Corporation), dried until the water content in the granules becomes 2% or less, and then comiled to align. Granulation was performed to obtain granules.
次いで、得られた各顆粒840gにステアリン酸マグネシウム8.4gを各々添加し、V型混合機(TCV-5型、徳寿工作所社製)にて混合し、充填用顆粒末848.4gを得た。次に、カプセル充填機(Liqufil-5型、クオリカプス社製)を用いて1号ゼラチンカプセルにカプセル充填を行い、ナプロキセン含量100mgで1カプセル内容物質量が303mgの硬カプセル剤を得た。 Next, 840 g of each granule obtained was added with 8.4 g of magnesium stearate and mixed with a V-type mixer (Type TCV-5, manufactured by Tokuju Kosakusho Co., Ltd.) to obtain 848.4 g of granule powder for filling. rice field. Next, No. 1 gelatin capsules were filled using a capsule filling machine (Liqufil-5 type, manufactured by Qualicaps) to obtain hard capsules containing 100 mg of naproxen and 303 mg of substance per capsule.
実 施 例 9
硬カプセル剤(2):
表9に記載の処方に従い、秤量した各成分を高速撹拌造粒機(VG-10型、パウレック社製)に投入し、3分間混合した。次いで、処方27から処方32に対応する各混合末に適量の精製水をそれぞれ添加し、高速撹拌造粒機(VG-10型、パウレック社製)にて、3分間練合した。次に、得られた練合造粒物を流動層乾燥機(FLO-2型、フロイント産業社製)に投入し、造粒物中の水分が2%以下になるまで乾燥したのち、コーミルにて整粒を行い、顆粒を得た。
Example 9
Hard capsule (2):
According to the formulation shown in Table 9, each weighed component was put into a high-speed stirring granulator (VG-10 type, manufactured by Powrex) and mixed for 3 minutes. Next, an appropriate amount of purified water was added to each of the mixed powders corresponding to formulations 27 to 32, and the mixture was kneaded for 3 minutes with a high-speed stirring granulator (VG-10 model, manufactured by Powrex Corporation). Next, the obtained kneaded granules are put into a fluidized bed dryer (FLO-2 type, manufactured by Freund Corporation) and dried until the water content in the granules becomes 2% or less. The granules were obtained by sizing.
次いで、得られた各顆粒840gにステアリン酸マグネシウム8.4gを各々添加し、V型混合機(TCV-5型、徳寿工作所社製)にて混合し、充填用顆粒末848.4gを得た。次に、カプセル充填機(Liqufil-5型、クオリカプス社製)を用いて1号ゼラチンカプセルにカプセル充填を行い、ナプロキセン含量100mgで1カプセル内容物質量が303mgの硬カプセル剤を得た。 Next, 840 g of each granule obtained was added with 8.4 g of magnesium stearate and mixed with a V-type mixer (Type TCV-5, manufactured by Tokuju Kosakusho Co., Ltd.) to obtain 848.4 g of granule powder for filling. rice field. Next, No. 1 gelatin capsules were filled using a capsule filling machine (Liqufil-5 type, manufactured by Qualicaps) to obtain hard capsules containing 100 mg of naproxen and 303 mg of substance per capsule.
実 施 例 10
顆 粒 剤(4)
ナプロキセン15.0g、炭酸水素ナトリウム15.0g及び表10に示す各種の水膨潤性ポリマー15.0gを、メカノミル(MM-20N型、岡田精工社製)に入れ、主軸回転数900rpmで3分間混合した。この混合末に、練合液として精製水60gを加え、メカノミルで3分間、主軸回転数900rpmで練合した。この練合物をステンレススクリーンで押し出した後、箱型乾燥機(エスペック社製)で水分率2%以下になるまで乾燥させて造粒物を得た。
Example 10
Granules (4)
15.0 g of naproxen, 15.0 g of sodium bicarbonate, and 15.0 g of various water-swellable polymers shown in Table 10 are placed in Mechanomill (MM-20N type, manufactured by Okada Seiko Co., Ltd.) and mixed for 3 minutes at a spindle speed of 900 rpm. did. To this mixed powder, 60 g of purified water was added as a kneading liquid, and the mixture was kneaded for 3 minutes with a Mechanomill at a spindle speed of 900 rpm. This kneaded material was extruded through a stainless screen, and then dried with a box-type dryer (manufactured by Espec Co., Ltd.) until the moisture content became 2% or less to obtain a granulated material.
得られた造粒物を、26メッシュのステンレススクリーンで篩分し、それを通過した造粒物を、さらに150メッシュのステンレススクリーンで篩分し、スクリーン上に残ったものを回収し、100~600μmの整粒顆粒を得た。この整粒顆粒について、下記の方法により30分までの溶出率を測定した。結果を表11に示す。 The resulting granules are sieved through a 26-mesh stainless screen, and the granules that have passed through it are further sieved through a 150-mesh stainless screen. A 600 μm sized granule was obtained. The sieved granules were measured for dissolution rate up to 30 minutes by the following method. Table 11 shows the results.
< 溶出試験 >
日本薬局方溶出試験法第2法に従い、pH4.0の緩衝液900mLに、ナプロキセンとして100mg含有の各顆粒製剤を入れ、パドル回転数50rpm、温度37.0±0.5℃の条件下で溶出試験を行った。ナプロキセンの溶出量は、液体クロマトグラフ法により測定し、この溶出量から溶出率を算出した。
< Elution test >
According to Japanese Pharmacopoeia Dissolution Test Method 2, put each granule preparation containing 100 mg of naproxen in 900 mL of pH 4.0 buffer, and dissolve under the conditions of paddle rotation speed of 50 rpm and temperature of 37.0 ± 0.5°C. did the test. The elution amount of naproxen was measured by liquid chromatography, and the elution rate was calculated from this elution amount.
実 施 例 11
顆粒剤(5):
ナプロキセン15.0g、表12に記載の量の炭酸水素ナトリウム及び低置換度ヒドロキシプロピルセルロースをメカノミル(MM-20N型、岡田精工社製)に取り、これを主軸回転数900rpmで3分間混合した。この混合末に、練合液として精製水を50~60gを加え、メカノミルで3分間、主軸回転数900rpmで練合した。
Example 11
Granules (5):
15.0 g of naproxen, the amounts of sodium hydrogencarbonate and low-substituted hydroxypropyl cellulose shown in Table 12 were placed in Mechanomill (Model MM-20N, manufactured by Okada Seiko Co., Ltd.) and mixed at a spindle speed of 900 rpm for 3 minutes. To this mixed powder, 50 to 60 g of purified water was added as a kneading liquid, and the mixture was kneaded for 3 minutes with a Mechanomill at a spindle speed of 900 rpm.
この練合物をステンレススクリーンで押し出した後、箱型乾燥機(エスペック社製)で水分率2%以下になるまで乾燥させて造粒物を得た。得られた造粒物を、26メッシュのステンレススクリーンで篩分し、それを通過した造粒物を、さらに150メッシュのステンレススクリーンで篩分し、スクリーン上に残ったものを回収し、100~600μmの整粒顆粒を得た。この整粒顆粒について、実施例12の溶出試験により30分までの溶出率を測定した。この結果を表13に示す。 This kneaded material was extruded through a stainless screen, and then dried with a box-type dryer (manufactured by Espec Co., Ltd.) until the moisture content became 2% or less to obtain a granulated material. The resulting granules are sieved through a 26-mesh stainless screen, and the granules that have passed through it are further sieved through a 150-mesh stainless screen. A 600 μm sized granule was obtained. About this sized granule, the dissolution rate up to 30 minutes was measured by the dissolution test of Example 12. The results are shown in Table 13.
実 施 例 12
フィルムコーティング錠:
常法に従い、表14中の顆粒部に記載の配合成分と適量の精製水を使用して顆粒を得た。次いでこの顆粒に、錠剤添加部に記載の配合成分を加え、常法に従って、1錠360mgの素錠を打錠した。
Example 12
Film-coated tablets:
According to a conventional method, granules were obtained using the ingredients described in the granule section in Table 14 and an appropriate amount of purified water. Next, the compounding ingredients described in the tablet addition section were added to the granules, and tablets of 360 mg per tablet were compressed according to a conventional method.
一方、表14の被覆部に記載の各固形成分を、適量の精製水中に分散・懸濁させてコーティング液を調製した。このコーティング液を用い、常法に従って前記素錠をコーティングし、乾燥させて、1錠370mgのフィルムコーティング剤を得た。 On the other hand, each solid component described in the coating part of Table 14 was dispersed/suspended in an appropriate amount of purified water to prepare a coating liquid. Using this coating liquid, the uncoated tablets were coated according to a conventional method and dried to obtain a film coating agent of 370 mg per tablet.
得られたフィルムコーティング剤(ナプロキセンとして100mg含有)を、pH4.0の緩衝液900mlに入れ、日本薬局方溶出試験法第2法に準じて溶解性試験を行った(37℃、50rpm)。対照としては同量のナプロキセン原末を用いた。この結果を表15に示す。 The obtained film coating agent (containing 100 mg of naproxen) was placed in 900 ml of pH 4.0 buffer solution, and a solubility test was conducted according to Method 2 of Dissolution Test Method of Japanese Pharmacopoeia (37° C., 50 rpm). As a control, the same amount of naproxen bulk powder was used. The results are shown in Table 15.
本発明組成物は、ナプロキセンと塩基性化合物とを組み合わせて使用することにより、ナプロキセンの難溶性を改善したものである。さらに、これにセルロース系水膨潤性高分子を配合した場合は、製剤の崩壊性をも高めることができるものである。従って本発明は、即効性のある消炎解熱鎮痛等の作用を有する経口固形組成物を提供することができるものであり、製薬の分野において広く利用しうるものである。 The composition of the present invention uses a combination of naproxen and a basic compound to improve the sparing solubility of naproxen. Furthermore, when a cellulose-based water-swellable polymer is added to this, the disintegration of the formulation can also be enhanced. Therefore, the present invention can provide an oral solid composition having immediate anti-inflammatory, antipyretic, and analgesic effects, and can be widely used in the field of pharmaceuticals.
Claims (9)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2016213326 | 2016-10-31 | ||
JP2016213326 | 2016-10-31 | ||
JP2017210212A JP7163015B2 (en) | 2016-10-31 | 2017-10-31 | oral solid composition |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017210212A Division JP7163015B2 (en) | 2016-10-31 | 2017-10-31 | oral solid composition |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2022168079A true JP2022168079A (en) | 2022-11-04 |
JP7419462B2 JP7419462B2 (en) | 2024-01-22 |
Family
ID=62150007
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017210212A Active JP7163015B2 (en) | 2016-10-31 | 2017-10-31 | oral solid composition |
JP2022142007A Active JP7419462B2 (en) | 2016-10-31 | 2022-09-07 | Oral solid composition |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017210212A Active JP7163015B2 (en) | 2016-10-31 | 2017-10-31 | oral solid composition |
Country Status (1)
Country | Link |
---|---|
JP (2) | JP7163015B2 (en) |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1200178B (en) * | 1986-07-23 | 1989-01-05 | Alfa Farmaceutici Spa | GALENIC FORMULATIONS WITH SCHEDULED SALE CONTAINING DRUGS WITH ANTI-FLOGISTIC ACTIVITY |
IT1226549B (en) * | 1988-07-12 | 1991-01-24 | Resa Farma | PHARMACEUTICAL COMPOSITIONS WITH ANALGESIC AND ANTI-INFLAMMATORY ACTIVITY FOR ORAL USE, EQUIPPED WITH EXCELLENT PALATABILITY AND FREE FROM IRRITATING EFFECTS ON MUCOSES. |
PT96229B (en) * | 1989-12-22 | 1998-06-30 | Syntex Pharma Int | METHOD FOR PREPARING PHARMACEUTICAL COMPOSITIONS IN PO, DRIED BY SPRAY, DIRECTLY COMPRESSIVE IN TABLETS CONTAINING NAPROXEN OR NAPROXENE SODIUM |
IT1272149B (en) * | 1993-03-26 | 1997-06-11 | Zambon Spa | PHARMECEUTICAL COMPOSITION WITH ANALGESIC ACTIVITY |
EP1605916A4 (en) | 2003-02-12 | 2012-02-22 | R & P Korea Co Ltd | Solvent system of hardly soluble drug with improved elution rate |
PE20050445A1 (en) | 2003-10-30 | 2005-06-18 | Bayer Consumer Care Ag | PRESENTATION FORM OF SODIUM NAPROXEN |
CN102438592B (en) | 2009-04-24 | 2016-09-14 | 伊休蒂卡有限公司 | The dosage form of naproxen |
JP2010270019A (en) | 2009-05-19 | 2010-12-02 | Lion Corp | Solid internal medicine composition |
JP5974469B2 (en) | 2010-12-24 | 2016-08-23 | ライオン株式会社 | Tablet manufacturing method |
JP6031756B2 (en) | 2010-12-24 | 2016-11-24 | ライオン株式会社 | Granular pharmaceutical preparation and production method |
-
2017
- 2017-10-31 JP JP2017210212A patent/JP7163015B2/en active Active
-
2022
- 2022-09-07 JP JP2022142007A patent/JP7419462B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
JP7419462B2 (en) | 2024-01-22 |
JP2018076310A (en) | 2018-05-17 |
JP7163015B2 (en) | 2022-10-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11413295B2 (en) | Oral preparation of obeticholic acid | |
ES2642788T3 (en) | Manufacture of granules without active substance and tablets comprising the same | |
EP2099433A2 (en) | Modified release ibuprofen solid oral dosage form | |
BRPI0919466B1 (en) | ORAL PHARMACEUTICAL COMPOSITION FOR MODIFIED RELEASE AND PROCESS FOR MANUFACTURING AN ORAL PHARMACEUTICAL COMPOSITION FOR MODIFIED RELEASE | |
BR112012028035B1 (en) | immediate release formulation | |
WO2017028660A1 (en) | Pharmaceutical composition containing quinoline derivative or salt thereof | |
JP6580897B2 (en) | Pharmaceutical composition for cold | |
JP2013087061A (en) | Laminate tablet | |
JP2020128429A (en) | Pharmaceutical tablets containing levocarnitine | |
JP4926495B2 (en) | Coated granules containing ibuprofen | |
JP2009235020A (en) | Solid preparation containing ibuprofen and tranexamic acid | |
JP2007119453A (en) | Method for preventing lowering of bromhexine hydrochloride content | |
JP6015116B2 (en) | Tablet and production method thereof | |
JP4702763B2 (en) | Stable tablets containing crystalline cellulose | |
JP7163015B2 (en) | oral solid composition | |
JP6654426B2 (en) | Pharmaceutical composition | |
EP3880171B1 (en) | Ibuprofen-containing oral pharmaceutical formulation | |
JP2022113667A (en) | Edoxaban-containing pharmaceutical composition | |
JP5054966B2 (en) | Solid preparation | |
WO2017115764A1 (en) | Compression-molded preparation | |
JP2009167110A (en) | Sarpogrelate hydrochloride-containing oral preparation excellent in stability in unpacked state | |
JP2022167880A (en) | Solid preparation | |
JP4393119B2 (en) | Preparation containing iodopropamide | |
JP2015224228A (en) | Tablet and coated tablet | |
BR112015018952B1 (en) | PHARMACEUTICAL COMPOSITIONS CONTAINING DEXKETOPROFENE AND TRAMADOL, THEIR MANUFACTURING METHOD AND THEIR USE |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221006 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20221006 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230830 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230929 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20231220 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20240110 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7419462 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |