JP2013053134A - Oral preparation - Google Patents
Oral preparation Download PDFInfo
- Publication number
- JP2013053134A JP2013053134A JP2012166599A JP2012166599A JP2013053134A JP 2013053134 A JP2013053134 A JP 2013053134A JP 2012166599 A JP2012166599 A JP 2012166599A JP 2012166599 A JP2012166599 A JP 2012166599A JP 2013053134 A JP2013053134 A JP 2013053134A
- Authority
- JP
- Japan
- Prior art keywords
- domperidone
- iron
- preparation
- internal
- unpleasant taste
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 50
- FGXWKSZFVQUSTL-UHFFFAOYSA-N domperidone Chemical compound C12=CC=CC=C2NC(=O)N1CCCN(CC1)CCC1N1C2=CC=C(Cl)C=C2NC1=O FGXWKSZFVQUSTL-UHFFFAOYSA-N 0.000 claims abstract description 45
- 229960001253 domperidone Drugs 0.000 claims abstract description 45
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000006188 syrup Substances 0.000 claims abstract description 14
- 235000020357 syrup Nutrition 0.000 claims abstract description 14
- 229910052742 iron Inorganic materials 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 4
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 claims description 5
- 239000004222 ferrous gluconate Substances 0.000 claims description 5
- 235000013924 ferrous gluconate Nutrition 0.000 claims description 5
- 229960001645 ferrous gluconate Drugs 0.000 claims description 5
- VRIVJOXICYMTAG-IYEMJOQQSA-L iron(ii) gluconate Chemical compound [Fe+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O VRIVJOXICYMTAG-IYEMJOQQSA-L 0.000 claims description 5
- PMVSDNDAUGGCCE-TYYBGVCCSA-L Ferrous fumarate Chemical compound [Fe+2].[O-]C(=O)\C=C\C([O-])=O PMVSDNDAUGGCCE-TYYBGVCCSA-L 0.000 claims description 4
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 4
- 239000011640 ferrous citrate Substances 0.000 claims description 4
- 235000019850 ferrous citrate Nutrition 0.000 claims description 4
- 239000011773 ferrous fumarate Substances 0.000 claims description 4
- 235000002332 ferrous fumarate Nutrition 0.000 claims description 4
- 229960000225 ferrous fumarate Drugs 0.000 claims description 4
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 4
- APVZWAOKZPNDNR-UHFFFAOYSA-L iron(ii) citrate Chemical compound [Fe+2].OC(=O)CC(O)(C([O-])=O)CC([O-])=O APVZWAOKZPNDNR-UHFFFAOYSA-L 0.000 claims description 4
- AEQDJSLRWYMAQI-UHFFFAOYSA-N 2,3,9,10-tetramethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline Chemical compound C1CN2CC(C(=C(OC)C=C3)OC)=C3CC2C2=C1C=C(OC)C(OC)=C2 AEQDJSLRWYMAQI-UHFFFAOYSA-N 0.000 claims description 3
- 229960001781 ferrous sulfate Drugs 0.000 claims description 3
- 239000011790 ferrous sulphate Substances 0.000 claims description 3
- 235000003891 ferrous sulphate Nutrition 0.000 claims description 3
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims description 3
- 229910000359 iron(II) sulfate Inorganic materials 0.000 claims description 3
- 239000000176 sodium gluconate Substances 0.000 claims description 3
- 235000012207 sodium gluconate Nutrition 0.000 claims description 3
- 229940005574 sodium gluconate Drugs 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- CGVPYAREDIUBOY-UHFFFAOYSA-K 2-hydroxypropane-1,2,3-tricarboxylate;iron(2+) Chemical compound [Fe+2].[Fe+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O CGVPYAREDIUBOY-UHFFFAOYSA-K 0.000 claims 1
- 239000007788 liquid Substances 0.000 abstract description 11
- 230000002378 acidificating effect Effects 0.000 abstract description 4
- 238000004090 dissolution Methods 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 13
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000011156 evaluation Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- PLKYGPRDCKGEJH-UHFFFAOYSA-N azane;2-hydroxypropane-1,2,3-tricarboxylic acid;iron Chemical compound N.[Fe].OC(=O)CC(O)(C(O)=O)CC(O)=O PLKYGPRDCKGEJH-UHFFFAOYSA-N 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 235000015165 citric acid Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- -1 2-oxo-1-benzimidazolinyl Chemical group 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 238000013329 compounding Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002506 iron compounds Chemical class 0.000 description 2
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 2
- YOBAEOGBNPPUQV-UHFFFAOYSA-N iron;trihydrate Chemical compound O.O.O.[Fe].[Fe] YOBAEOGBNPPUQV-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- YNVZDODIHZTHOZ-UHFFFAOYSA-K 2-hydroxypropanoate;iron(3+) Chemical compound [Fe+3].CC(O)C([O-])=O.CC(O)C([O-])=O.CC(O)C([O-])=O YNVZDODIHZTHOZ-UHFFFAOYSA-K 0.000 description 1
- CAAMSDWKXXPUJR-UHFFFAOYSA-N 3,5-dihydro-4H-imidazol-4-one Chemical compound O=C1CNC=N1 CAAMSDWKXXPUJR-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- GLMQHZPGHAPYIO-UHFFFAOYSA-L azanium;2-hydroxypropane-1,2,3-tricarboxylate;iron(2+) Chemical compound [NH4+].[Fe+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O GLMQHZPGHAPYIO-UHFFFAOYSA-L 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229940067573 brown iron oxide Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 description 1
- 229940062672 calcium dihydrogen phosphate Drugs 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- WPUMTJGUQUYPIV-JIZZDEOASA-L disodium (S)-malate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](O)CC([O-])=O WPUMTJGUQUYPIV-JIZZDEOASA-L 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- CADNYOZXMIKYPR-UHFFFAOYSA-B ferric pyrophosphate Chemical compound [Fe+3].[Fe+3].[Fe+3].[Fe+3].[O-]P([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])([O-])=O CADNYOZXMIKYPR-UHFFFAOYSA-B 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000012676 herbal extract Substances 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000004313 iron ammonium citrate Substances 0.000 description 1
- 235000000011 iron ammonium citrate Nutrition 0.000 description 1
- WTFXARWRTYJXII-UHFFFAOYSA-N iron(2+);iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+2].[Fe+3].[Fe+3] WTFXARWRTYJXII-UHFFFAOYSA-N 0.000 description 1
- LDHBWEYLDHLIBQ-UHFFFAOYSA-M iron(3+);oxygen(2-);hydroxide;hydrate Chemical compound O.[OH-].[O-2].[Fe+3] LDHBWEYLDHLIBQ-UHFFFAOYSA-M 0.000 description 1
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000019691 monocalcium phosphate Nutrition 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- VRVKOZSIJXBAJG-TYYBGVCCSA-M monosodium fumarate Chemical compound [Na+].OC(=O)\C=C\C([O-])=O VRVKOZSIJXBAJG-TYYBGVCCSA-M 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940109850 royal jelly Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019265 sodium DL-malate Nutrition 0.000 description 1
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 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 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 239000001394 sodium malate Substances 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- KZQSXALQTHVPDQ-UHFFFAOYSA-M sodium;butanedioate;hydron Chemical compound [Na+].OC(=O)CCC([O-])=O KZQSXALQTHVPDQ-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
本発明は、ドンペリドンを含有する内服製剤に関する。 The present invention relates to an internal preparation containing domperidone.
ドンペリドンは優れた制吐作用を有する化合物であり、既に錠剤及び細粒剤が上市されている。これまでにドンペリドンを含有する製剤が特許文献で報告されている（特許文献１、特許文献２、特許文献３参照）が、内服製剤中でのドンペリドンの不快味について検討された報告はない。 Domperidone is an excellent antiemetic compound, and tablets and fine granules have already been marketed. So far, preparations containing domperidone have been reported in the patent literature (see Patent Literature 1, Patent Literature 2, and Patent Literature 3), but there has been no report on the unpleasant taste of domperidone in oral formulations. .
一方、内服液剤やドライシロップ剤は、嚥下能力が劣った老人、小児なども容易に服用することができる優れた剤型であり、生活者に広く求められている。 On the other hand, internal liquids and dry syrups are excellent dosage forms that can be easily taken by elderly people, children, and the like who have poor swallowing ability, and are widely demanded by consumers.
なお、ドンペリドンは塩基性薬物であるため、ｐＨが低い酸性域の方が溶解しやすいことが知られている。 In addition, since domperidone is a basic drug, it is known that an acidic region having a low pH is more easily dissolved.
そこで、本発明者らは、ドンペリドンを配合した内服製剤の提供にあたり、ドンペリドンの溶解性が高く、これを安定に配合しうる内服製剤の提供を試みた。 Therefore, the present inventors tried to provide an internal preparation that is highly soluble in domperidone and that can be stably mixed in providing an internal preparation containing domperidone.
しかしながら、特にドンペリドンが溶解しやすい酸性域では、ドンペリドンに起因する不快味が増強され、服用性の悪化を招来するという知見を得た。 However, in the acidic range where domperidone is easily dissolved, the unpleasant taste attributed to domperidone was enhanced, and it was found that ingestion deteriorates.
従って、本発明は、ドンペリドンを配合した際に生じる不快味を減殺し、服用性の良好なドンペリドン含有内服製剤を提供することを課題とする。 Accordingly, an object of the present invention is to provide a domperidone-containing internal preparation that can reduce the unpleasant taste that occurs when domperidone is blended and has good dosing properties.
本発明者らは、上記課題を解決するために鋭意検討を重ねた結果、ドンペリドン含有内服製剤に、鉄を配合することによりドンペリドンの不快味を抑えられることを見出し、本発明を完成するに至った。 As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that the unpleasant taste of domperidone can be suppressed by adding iron to the domperidone-containing internal preparation, thereby completing the present invention. It came to.
即ち本発明は、
（１）ａ）ドンペリドン及びｂ）鉄を含有することを特徴とする内服製剤、
（２）鉄が、クエン酸鉄アンモニウム、フマル酸第一鉄、塩化第二鉄、クエン酸第一鉄、グルコン酸第一鉄ナトリウム、グルコン酸第一鉄及び硫酸第一鉄からなる群から選ばれる少なくとも１種である請求項１に記載の内服製剤、
（３）内服製剤がｐＨ２．５〜７．０の内服液剤である、（１）又は（２）に記載の内服製剤、
（４）内服製剤がドライシロップ剤である、（１）又は（２）に記載の内服製剤、
（５）ドンペリドンを含有する内服製剤において、鉄を配合することにより、ドンペリドンに基因する不快味を抑制する方法、
である。
That is, the present invention
(1) an oral preparation characterized by containing a) domperidone and b) iron,
(2) Iron is selected from the group consisting of ammonium iron citrate, ferrous fumarate, ferric chloride, ferrous citrate, ferrous sodium gluconate, ferrous gluconate and ferrous sulfate The internal preparation according to claim 1, which is at least one selected from the group consisting of
(3) The internal preparation according to (1) or (2), wherein the internal preparation is an internal solution having a pH of 2.5 to 7.0,
(4) The internal preparation according to (1) or (2), wherein the internal preparation is a dry syrup preparation,
(5) A method for suppressing an unpleasant taste caused by domperidone by blending iron in an oral preparation containing domperidone,
It is.
本発明により、主に酸性域におけるドンペリドンの不快味を抑制することができ、服用性良好なドンペリドン含有内服製剤を提供することが可能となった。 According to the present invention, it is possible to suppress the unpleasant taste of domperidone mainly in the acidic region and to provide a domperidone-containing internal preparation with good dosing properties.
本発明の有効成分として用いられるドンペリドンは、化学名が５−クロロ−１−［１−［３−（２−オキソ−１−ベンズイミダゾリニル）プロピル］−４−ピペリジル］−２−ベンズイミダゾリノンで表される化合物である。 Domperidone used as an active ingredient of the present invention has a chemical name of 5-chloro-1- [1- [3- (2-oxo-1-benzimidazolinyl) propyl] -4-piperidyl] -2-benz. It is a compound represented by imidazolinone.
本発明におけるドンペリドンの配合量は目的に応じ適宜選択し使用できるが、例えば１日当たり１〜３０ｍｇ服用することが好ましい。内服製剤中に０．０００２〜１質量％配合することが好ましい。 The compounding amount of domperidone in the present invention can be appropriately selected and used according to the purpose, but it is preferable to take 1 to 30 mg per day, for example. It is preferable to add 0.0002 to 1% by mass in the internal preparation.
本発明の鉄は、クエン酸鉄アンモニウム、フマル酸第一鉄、塩化第二鉄、クエン酸第一鉄、グルコン酸第一鉄ナトリウム、グルコン酸第一鉄、乳酸鉄、ピロリン酸鉄、硫酸第一鉄、黄酸化鉄、黄色三二酸化鉄、褐色酸化鉄、黒酸化鉄又は三二酸化鉄が好ましい。 The iron of the present invention comprises ammonium iron citrate, ferrous fumarate, ferric chloride, ferrous citrate, sodium ferrous gluconate, ferrous gluconate, iron lactate, iron pyrophosphate, sulfuric acid ferrous Ferrous iron, yellow iron oxide, yellow iron sesquioxide, brown iron oxide, black iron oxide or iron sesquioxide are preferred.
本発明における「内服製剤」とは、好ましくは内服液剤とドライシロップ剤である。内服液剤は、内服することができる液体であれば特に制限はない。また、ドライシロップ剤は、用時に溶解または懸濁して服用する製剤である。 The “internal preparation” in the present invention is preferably an internal preparation and a dry syrup. The internal liquid preparation is not particularly limited as long as it is a liquid that can be taken internally. A dry syrup is a preparation to be taken after being dissolved or suspended at the time of use.
本発明の内服製剤において、ドンペリドンと鉄の配合比は、ドンペリドン１質量部に対して通常０．０１〜１００質量部であり、好ましくは０．０６〜８０質量部であり、より好ましくは１４〜８０質量部である。 In the internal preparation of the present invention, the compounding ratio of domperidone and iron is usually 0.01 to 100 parts by mass, preferably 0.06 to 80 parts by mass, more preferably 1 part by mass of domperidone. 14 to 80 parts by mass.
本発明にかかる内服液剤のｐＨは、ドンペリドン基因の不快味を抑制するという点から、７．０以下であり、２．５〜７．０が好ましく、２．５〜４．５がより好ましく、２．５〜４．０がさらに好ましい。ｐＨが４．５以下になるとドンペリドンの不快味は強くなるが、ドンペリドンの溶解性が向上するため、ｐＨ２．５〜４．５の範囲で本発明を実施する意義は大きい。また、ｐＨ２．５〜４．０の範囲では、内服液剤の防腐効果も大きく、もっとも好ましいといえる。 The pH of the internal liquid preparation according to the present invention is 7.0 or less, preferably 2.5 to 7.0, more preferably 2.5 to 4.5, from the viewpoint of suppressing the unpleasant taste caused by domperidone. 2.5 to 4.0 is more preferable. When the pH is 4.5 or less, the unpleasant taste of domperidone becomes strong, but the solubility of domperidone is improved. Therefore, the significance of carrying out the present invention in the range of pH 2.5 to 4.5 is great. Moreover, in the range of pH2.5-4.0, the antiseptic effect of an internal use liquid agent is also large, and it can be said that it is the most preferable.
本発明の内服液剤のｐＨを上記範囲に保つため、またドライシロップ剤においては水等に溶解または懸濁した際の液体のｐＨを上記範囲に保つために、ｐＨ調整剤を配合しても良い。ｐＨ調整剤としては、クエン酸、クエン酸ナトリウム、リンゴ酸、リンゴ酸ナトリウム、酒石酸、酒石酸ナトリウム、乳酸、乳酸カルシウム、コハク酸、コハク酸一ナトリウム、グルコン酸、酢酸、アジピン酸、フマル酸一ナトリウム、グリシン、リン酸、リン酸二水素カルシウム、リン酸二カリウム、リン酸二水素カリウム、塩酸、水酸化ナトリウム、水酸化カリウムまたは炭酸水素ナトリウムが好ましい。ただし、ドライシロップ剤においては、ドライシロップ剤を溶解または懸濁させる液体そのものが上記ｐＨ範囲内に該当する場合は、ｐＨ調製剤を配合しなくてもよい。 In order to keep the pH of the internal liquid preparation of the present invention in the above range, and in the dry syrup preparation, a pH adjusting agent may be blended in order to keep the pH of the liquid when dissolved or suspended in water or the like in the above range. pH adjusters include citric acid, sodium citrate, malic acid, sodium malate, tartaric acid, sodium tartrate, lactic acid, calcium lactate, succinic acid, monosodium succinate, gluconic acid, acetic acid, adipic acid, monosodium fumarate Glycine, phosphoric acid, calcium dihydrogen phosphate, dipotassium phosphate, potassium dihydrogen phosphate, hydrochloric acid, sodium hydroxide, potassium hydroxide or sodium bicarbonate are preferred. However, in the dry syrup preparation, when the liquid itself in which the dry syrup preparation is dissolved or suspended falls within the above pH range, the pH adjusting agent may not be blended.
本発明の内服製剤にはその他の成分としてビタミン類、ミネラル類、アミノ酸又はその塩類、生薬、生薬抽出物、カフェイン、ローヤルゼリーなどを本発明の効果を損なわない範囲で適宜に配合することができる。 In the internal preparation of the present invention, vitamins, minerals, amino acids or salts thereof, herbal medicines, herbal extracts, caffeine, royal jelly, etc. can be appropriately blended as other components within the range not impairing the effects of the present invention. .
さらに必要に応じて、抗酸化剤、着色剤、香料、矯味剤、界面活性剤、溶解補助剤、結合剤、滑沢剤、崩壊剤、コーティング剤、懸濁化剤、乳化剤、保存剤、甘味料、酸味料などの添加物を本発明の効果を損なわない範囲で適宜に配合することができる。 Furthermore, as necessary, antioxidants, coloring agents, fragrances, flavoring agents, surfactants, solubilizers, binders, lubricants, disintegrating agents, coating agents, suspending agents, emulsifiers, preservatives, sweeteners Additives such as additives and acidulants can be appropriately blended within a range that does not impair the effects of the present invention.
本発明の内服製剤は、常法により調製することができ、その方法は特に限定されるものではない。内服液剤の場合、通常、各成分をとり適量の精製水で溶解した後、ｐＨを所望の範囲に調整し、さらに精製水を加えて容量調製し、必要に応じてろ過、殺菌処理を施すことにより得られる。また、ドライシロップ剤の場合、通常、各成分をとり適切な造粒装置にて造粒、成形することにより得られる。 The internal preparation of the present invention can be prepared by a conventional method, and the method is not particularly limited. In the case of an internal solution, usually take each component and dissolve with an appropriate amount of purified water, then adjust the pH to the desired range, add purified water to adjust the volume, and filter and sterilize as necessary. Is obtained. In the case of a dry syrup agent, it is usually obtained by taking each component and granulating and molding with an appropriate granulator.
本発明の内服製剤は、シロップ剤やドリンク剤を始めとする内服液剤や、ドライシロップ剤を始めとする固形製剤などの医薬品や医薬部外品として提供することができる。 The internal preparation of the present invention can be provided as a pharmaceutical or quasi-drug such as a liquid preparation including syrup and drink and a solid preparation including dry syrup.
以下に実施例、比較例及び試験例を挙げ、本発明をさらに詳しく説明する。 Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples and Test Examples.
実施例１
ドンペリドン５ｍｇ、クエン酸鉄アンモニウム２００ｍｇ、塩化カリウム１４．９ｍｇ、酒石酸０．９ｍｇ、クエン酸１４０ｍｇを精製水に溶解し、塩酸及び水酸化ナトリウムを用いてｐＨを３．０に調整し、精製水を加えて全量を２０ｍＬとし、ガラス瓶に充填しキャップを施して内服液剤を得た。
Example 1
Domperidone 5 mg, ammonium iron citrate 200 mg, potassium chloride 14.9 mg, tartaric acid 0.9 mg, and citric acid 140 mg are dissolved in purified water, and the pH is adjusted to 3.0 using hydrochloric acid and sodium hydroxide. Was added to make a total volume of 20 mL, filled into a glass bottle and capped to obtain an internal solution.
以下の実施例２〜１１及び比較例１も実施例１と同様に調製した。それぞれの処方を表１、２に示す。 The following Examples 2 to 11 and Comparative Example 1 were also prepared in the same manner as Example 1. Each formulation is shown in Tables 1 and 2.
実施例１２
ドンペリドン５ｍｇ、クエン酸鉄アンモニウム２００ｍｇ、クエン酸１４０ｍｇをデンプン３５５ｍｇと混合し造粒、成形を施してドライシロップ剤を得た。
Example 12
Domperidone (5 mg), iron ammonium citrate (200 mg), and citric acid (140 mg) were mixed with starch (355 mg), granulated and molded to obtain a dry syrup preparation.
以下の比較例２も実施例１２と同様に調製した。それぞれの処方を表３に示す。 The following Comparative Example 2 was also prepared in the same manner as Example 12. Each formulation is shown in Table 3.
試験例１
専門パネル２名で、表１、２に示す実施例および比較例の内服液剤を約５ｍＬ服用し、調製直後のドンペリドンの不快味についてブラインドで評価した。なお、１つのサンプルを評価した後は、水で口中をすすぎ、十分経過してから次の試験液の評価を行った。評価は鉄化合物を配合していない比較例１（コントロール）との比較を行い、「比較例１（コントロール）に比べて非常に弱く不快味を感じる」を−３、「比較例１（コントロール）に比べて弱く不快味を感じる」を−２、「比較例１（コントロール）に比べてやや弱く不快味を感じる」を−１、「比較例１（コントロール）と同等に不快味を感じる」を０、「比較例１（コントロール）に比べてやや強く不快味を感じる」を１として５段階の評価で行った。専門パネル２名の評価結果の平均値を表４に評価点として示した。
Test example 1
About 5 mL of the internal liquid preparations of Examples and Comparative Examples shown in Tables 1 and 2 were taken by two specialized panels, and the unpleasant taste of domperidone immediately after preparation was evaluated blindly. In addition, after evaluating one sample, the inside of the mouth was rinsed with water, and the next test solution was evaluated after sufficient time had passed. The evaluation was made by comparing with Comparative Example 1 (control) in which no iron compound was blended. "I feel a little unpleasant taste compared to" -2 "," I feel a little unpleasant taste compared to Comparative Example 1 (control) "-1," I feel an unpleasant taste equivalent to Comparative Example 1 (control) " The evaluation was made on a five-point scale, with 0 being “feeling a slightly unpleasant taste compared to Comparative Example 1 (control)” as 1. The average value of the evaluation results of the two specialist panels is shown in Table 4 as evaluation points.
試験例２
表３に示す実施例および比較例のドライシロップ剤を２０ｍＬの精製水に懸濁した。専門パネル２名でこの液剤を約５ｍＬ服用し、調製直後のドンペリドンの不快味についてブラインドで評価した。なお、１つのサンプルを評価した後は、水で口中をすすぎ、十分経過してから次の試験液の評価を行った。評価は鉄化合物を配合していない比較例２（コントロール）との比較を行い、「比較例２（コントロール）に比べて非常に弱く不快味を感じる」を−３、「比較例２（コントロール）に比べて弱く不快味を感じる」を−２、「比較例２（コントロール）に比べてやや弱く不快味を感じる」を−１、「比較例２（コントロール）と同等に不快味を感じる」を０、「比較例２（コントロール）に比べてやや強く不快味を感じる」を１として５段階の評価で行った。専門パネル２名の評価結果の平均値を表５に評価点として示した。
Test example 2
The dry syrups of Examples and Comparative Examples shown in Table 3 were suspended in 20 mL of purified water. About 5 mL of this solution was taken by two specialist panels, and the unpleasant taste of domperidone immediately after preparation was evaluated blindly. In addition, after evaluating one sample, the inside of the mouth was rinsed with water, and the next test solution was evaluated after sufficient time had passed. Evaluation is made by comparing with Comparative Example 2 (control) in which no iron compound is blended. "I feel weak and unpleasant compared to 2", "I feel somewhat weak and unpleasant compared to Comparative Example 2 (Control)", -1 "I feel unpleasant taste equivalent to Comparative Example 2 (Control)" The evaluation was made on a five-point scale, with 0 being “feeling a slightly unpleasant taste compared to Comparative Example 2 (control)” as 1. The average value of the evaluation results of the two specialist panels is shown in Table 5 as evaluation points.
表４及び表５から明らかなように、クエン酸鉄アンモニウム、フマル酸第一鉄、塩化第二鉄、クエン酸第一鉄、グルコン酸第一鉄ナトリウム、グルコン酸第一鉄及び硫酸第一鉄のいずれかを含有するとドンペリドンを配合した際に生じる不快味が抑えられた。 As is apparent from Tables 4 and 5, ammonium iron citrate, ferrous fumarate, ferric chloride, ferrous citrate, ferrous sodium gluconate, ferrous gluconate and ferrous sulfate When any of these was contained, the unpleasant taste produced when domperidone was blended was suppressed.
本発明により、服用性良好なドンペリドン含有内服製剤の提供を通じて、患者の服薬コンプライアンスを改善し、健全な医薬品産業の発達に寄与することが期待される。 The present invention is expected to improve patient compliance and contribute to the development of a healthy pharmaceutical industry by providing domperidone-containing internal preparations with good dosing properties.
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2012166599A JP2013053134A (en) | 2011-08-09 | 2012-07-27 | Oral preparation |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2011173984 | 2011-08-09 | ||
| JP2011173984 | 2011-08-09 | ||
| JP2012166599A JP2013053134A (en) | 2011-08-09 | 2012-07-27 | Oral preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2013053134A true JP2013053134A (en) | 2013-03-21 |
Family
ID=48130455
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012166599A Pending JP2013053134A (en) | 2011-08-09 | 2012-07-27 | Oral preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2013053134A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10101580A (en) * | 1996-09-27 | 1998-04-21 | Eisai Co Ltd | Composition hiding unpleasant taste of medicine |
| JP2004337133A (en) * | 2003-05-19 | 2004-12-02 | Mitsui Norin Co Ltd | Agent for suppressing iron smell |
| JP2013035824A (en) * | 2011-07-14 | 2013-02-21 | Kyowa Hakko Kirin Co Ltd | Domperidone orally-disintegrating tablet |
-
2012
- 2012-07-27 JP JP2012166599A patent/JP2013053134A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10101580A (en) * | 1996-09-27 | 1998-04-21 | Eisai Co Ltd | Composition hiding unpleasant taste of medicine |
| JP2004337133A (en) * | 2003-05-19 | 2004-12-02 | Mitsui Norin Co Ltd | Agent for suppressing iron smell |
| JP2013035824A (en) * | 2011-07-14 | 2013-02-21 | Kyowa Hakko Kirin Co Ltd | Domperidone orally-disintegrating tablet |
Non-Patent Citations (1)
| Title |
|---|
| JPN6016016244; 'ドンペリドン' 医療用医薬品集（２００７年版） , 20060901, ｐ．１６０７-１６１０ * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4051717B2 (en) | Biotin-containing oral solution | |
| ITMI20092198A1 (en) | CHELATED BISGLYCINATED IRON FOR USE IN ORAL TREATMENT OF ANEMIA IN CELIAC PATIENTS. | |
| KR20080079644A (en) | Liquid medicine for internal use | |
| JPH07227256A (en) | Liquid agent for oral administration | |
| JP5151083B2 (en) | Oral composition | |
| JP2013053134A (en) | Oral preparation | |
| JP4940492B2 (en) | Iron compound combination oral solution | |
| JP4959864B2 (en) | Glutamate-containing solution | |
| JP5511183B2 (en) | Oral composition in which dissolution of tooth enamel by organic acid is inhibited | |
| ITMI20071979A1 (en) | PHARMACEUTICAL FORMULATIONS CONTAINING BISGLYCINATED CHELATED IRON | |
| JP2006306848A (en) | Copper compound-incorporated composition for liquid preparation for internal use | |
| JP6584777B2 (en) | Powder composition for beverages containing water electrolyte | |
| JP4403595B2 (en) | Iron compound-containing oral solution composition | |
| JPH04287660A (en) | Prophylactic composition against fluorosis and method for prevention thereof | |
| JP2013053135A (en) | Oral preparation | |
| JP2013053136A (en) | Oral liquid preparation | |
| JP2818892B2 (en) | Foam formulation | |
| JP5823131B2 (en) | A composition containing windproof tsushosan | |
| JP4789292B2 (en) | Oral solution with improved flavor | |
| JP2007246508A (en) | Oral composition compounded with zinc compound | |
| JP5924604B1 (en) | Oral care composition | |
| JP2000044469A (en) | Internal liquid medicine | |
| JP4013267B2 (en) | Oral solution | |
| JP5853462B2 (en) | Oral solution | |
| JPH11292769A (en) | Hyperpotassemia-improving agent composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150709 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20160425 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160510 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20161108 |