JP6832113B2 - Pharmaceutical composition - Google Patents
Pharmaceutical composition Download PDFInfo
- Publication number
- JP6832113B2 JP6832113B2 JP2016194937A JP2016194937A JP6832113B2 JP 6832113 B2 JP6832113 B2 JP 6832113B2 JP 2016194937 A JP2016194937 A JP 2016194937A JP 2016194937 A JP2016194937 A JP 2016194937A JP 6832113 B2 JP6832113 B2 JP 6832113B2
- Authority
- JP
- Japan
- Prior art keywords
- hesperidin
- pharmaceutical composition
- derivative
- nabumetone
- unpleasant odor
- 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.)
- Active
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 45
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 claims description 86
- 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 claims description 85
- 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 claims description 84
- 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 claims description 81
- 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 claims description 81
- 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 claims description 81
- 229940025878 hesperidin Drugs 0.000 claims description 81
- 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 claims description 81
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 claims description 36
- 229960004270 nabumetone Drugs 0.000 claims description 35
- -1 alkyl hesperidin Chemical compound 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- AIONOLUJZLIMTK-AWEZNQCLSA-N hesperetin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O)=CC(O)=C2C(=O)C1 AIONOLUJZLIMTK-AWEZNQCLSA-N 0.000 claims description 5
- 229960001587 hesperetin Drugs 0.000 claims description 5
- AIONOLUJZLIMTK-UHFFFAOYSA-N hesperetin Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(O)=CC(O)=C2C(=O)C1 AIONOLUJZLIMTK-UHFFFAOYSA-N 0.000 claims description 5
- 235000010209 hesperetin Nutrition 0.000 claims description 5
- FTODBIPDTXRIGS-UHFFFAOYSA-N homoeriodictyol Natural products C1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 FTODBIPDTXRIGS-UHFFFAOYSA-N 0.000 claims description 5
- FDHNLHLOJLLXDH-JIYHLSBYSA-N (e)-3-(3-hydroxy-4-methoxyphenyl)-1-[2-hydroxy-6-methoxy-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-[[(2r,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxymethyl]oxan-2-yl]oxyphenyl]prop-2-en-1-one Chemical compound C1=C(O)C(OC)=CC=C1\C=C\C(=O)C(C(=C1)OC)=C(O)C=C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)O1 FDHNLHLOJLLXDH-JIYHLSBYSA-N 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 229940076640 hesperidin methylchalcone Drugs 0.000 claims description 4
- ARGKVCXINMKCAZ-UZRWAPQLSA-N neohesperidin 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)O3)O[C@H]3[C@@H]([C@H](O)[C@@H](O)[C@H](C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UZRWAPQLSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 235000019645 odor Nutrition 0.000 claims 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims 2
- 239000003826 tablet Substances 0.000 description 15
- 239000002552 dosage form Substances 0.000 description 14
- 238000000034 method Methods 0.000 description 9
- 208000002193 Pain Diseases 0.000 description 7
- 239000000654 additive Substances 0.000 description 7
- GUMSHIGGVOJLBP-SLRPQMTOSA-N methyl hesperidin Chemical compound C1=C(OC)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 GUMSHIGGVOJLBP-SLRPQMTOSA-N 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 238000003860 storage Methods 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 150000008442 polyphenolic compounds Chemical class 0.000 description 3
- 235000013824 polyphenols Nutrition 0.000 description 3
- 241001672694 Citrus reticulata Species 0.000 description 2
- 208000001145 Metabolic Syndrome Diseases 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000000740 bleeding effect Effects 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
- 239000002775 capsule Substances 0.000 description 2
- 235000020971 citrus fruits Nutrition 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 238000005728 strengthening Methods 0.000 description 2
- 239000007940 sugar coated tablet Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940124549 vasodilator Drugs 0.000 description 2
- 239000003071 vasodilator agent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 239000004129 EU approved improving agent Substances 0.000 description 1
- 206010014020 Ear pain Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010072132 Fracture pain Diseases 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000004044 Hypesthesia Diseases 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
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 206010028391 Musculoskeletal Pain Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 206010068319 Oropharyngeal pain Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 239000004820 Pressure-sensitive adhesive Substances 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- OVVGHDNPYGTYIT-VHBGUFLRSA-N Robinobiose Natural products O(C[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)O1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](C)O1 OVVGHDNPYGTYIT-VHBGUFLRSA-N 0.000 description 1
- 208000007613 Shoulder Pain Diseases 0.000 description 1
- HIWPGCMGAMJNRG-ACCAVRKYSA-N Sophorose Natural products O([C@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HIWPGCMGAMJNRG-ACCAVRKYSA-N 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- 239000003434 antitussive agent Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 235000019606 astringent taste Nutrition 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- HIWPGCMGAMJNRG-UHFFFAOYSA-N beta-sophorose Natural products OC1C(O)C(CO)OC(O)C1OC1C(O)C(O)C(O)C(CO)O1 HIWPGCMGAMJNRG-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000000872 buffer Substances 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
- 230000003177 cardiotonic effect Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229940124568 digestive agent Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- 229940066493 expectorants Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000034783 hypoesthesia Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000008991 intestinal motility Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- OVVGHDNPYGTYIT-BNXXONSGSA-N rutinose Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)O1 OVVGHDNPYGTYIT-BNXXONSGSA-N 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000004799 sedative–hypnotic effect Effects 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- PZDOWFGHCNHPQD-VNNZMYODSA-N sophorose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](C=O)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O PZDOWFGHCNHPQD-VNNZMYODSA-N 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Description
本発明は、ヘスペリジン及び／又はその誘導体の不快臭を抑制できる医薬組成物に関する。 The present invention relates to a pharmaceutical composition capable of suppressing the unpleasant odor of hesperidin and / or its derivative.
ヘスペリジン及びその誘導体には、毛細血管の強化、出血予防、血圧調整、骨形成促進、メタボリックシンドロームの改善等の作用があり、様々な医薬品への応用が検討されている。例えば、特許文献１には、消化管粘膜傷害を呈する医薬活性成分とヘスペリジンを含む医薬組成物は、消化管粘膜傷害を軽減できることが開示されている。また、特許文献２には、α受容体刺激剤及びヘスペリジン及び／又はその誘導体を含む医薬組成物は、鼻づまり、咳、痰等のかぜの諸症状を効果的に改善又は解消できることが開示されている。 Hesperidin and its derivatives have actions such as strengthening capillaries, preventing bleeding, regulating blood pressure, promoting bone formation, and improving metabolic syndrome, and their application to various pharmaceuticals is being studied. For example, Patent Document 1 discloses that a pharmaceutical composition containing a pharmaceutically active ingredient exhibiting gastrointestinal mucosal injury and hesperidin can reduce gastrointestinal mucosal injury. Further, Patent Document 2 discloses that a pharmaceutical composition containing an α-receptor stimulant and hesperidin and / or a derivative thereof can effectively improve or eliminate various cold symptoms such as stuffy nose, cough and sputum. ing.
しかしながら、ヘスペリジン及びその誘導体には特有の不快臭があり、ヘスペリジン及びその誘導体を含む製剤は、ヘスペリジン及びその誘導体に起因する不快臭が経時的に増大するという欠点がある。このような不快臭は、服用感の悪化や服薬コンプライアンスの低下をもたらすため、ヘスペリジン及びその誘導体の不快臭を抑制するため製剤化技術の開発が求められている。 However, hesperidin and its derivatives have a peculiar unpleasant odor, and preparations containing hesperidin and its derivatives have a drawback that the unpleasant odor caused by hesperidin and its derivatives increases over time. Since such an unpleasant odor causes deterioration of the feeling of administration and deterioration of drug compliance, development of a formulation technique is required to suppress the unpleasant odor of hesperidin and its derivatives.
従来、不快臭を伴う成分については、コーティング錠や糖衣錠に製剤化することによって、不快臭をマスキングできることが知られている。しかしながら、コーティング錠や糖衣錠として製剤化する場合、製造時間やコストの増大を招くという欠点がある。 Conventionally, it is known that an unpleasant odor can be masked by formulating a component with an unpleasant odor into a coated tablet or a sugar-coated tablet. However, when formulated as a coated tablet or a sugar-coated tablet, there is a drawback that the production time and cost are increased.
一方、ナブメトンは、白色〜帯黄白色を呈する結晶又は結晶性の粉末であり、水には殆ど解けず、それ自体は味も示さない成分である。また、ナブメトンは、長時間作用型の鎮痛作用があり、繰り返す痛みをぶり返しなく鎮めるのに適していることが知られている。しかしながら、従来、ナブメトンをヘスペリジン及び／又はその誘導体と共に配合した製剤は報告されておらず、ナブメトンが、ヘスペリジン及び／又はその誘導体の不快臭に対して及ぼす影響については一切明らかにされていない。 On the other hand, nabumetone is a crystalline or crystalline powder exhibiting a white to yellowish white color, and is a component that is hardly soluble in water and does not show a taste by itself. In addition, nabumetone has a long-acting analgesic effect and is known to be suitable for relieving repeated pain without recurring. However, conventionally, a preparation in which nabumetone is blended with hesperidin and / or its derivative has not been reported, and the effect of nabumetone on the unpleasant odor of hesperidin and / or its derivative has not been clarified at all.
本発明の目的は、ヘスペリジン及び／又はその誘導体を含む医薬組成物において、ヘスペリジン及び／又はその誘導体の不快臭を抑制する製剤化技術を提供することである。 An object of the present invention is to provide a formulation technique for suppressing an unpleasant odor of hesperidin and / or a derivative thereof in a pharmaceutical composition containing hesperidin and / or a derivative thereof.
本発明者は、前記課題を解決すべく鋭意検討を行ったところ、ヘスペリジン及び／又はその誘導体と共にナブメトンを配合した医薬組成物では、ヘスペリジン及び／又はその誘導体の不快臭を抑制できることを見出した。また、本発明者は、ヘスペリジン及び／又はその誘導体を製剤化して保存すると、ヘスペリジン及び／又はその誘導体の不快臭は経時的に増大するという新たな知見を得たが、ヘスペリジン及び／又はその誘導体と共に所定量のナブメトンを配合した場合には、経時的に増大する不快臭をより一層効果的に抑制できることをも見出した。本発明は、これらの知見に基づいて、更に検討を重ねることにより完成したものである。 As a result of diligent studies to solve the above problems, the present inventor has found that a pharmaceutical composition containing nabumetone together with hesperidin and / or its derivative can suppress the unpleasant odor of hesperidin and / or its derivative. In addition, the present inventor has obtained a new finding that when hesperidin and / or its derivative is formulated and stored, the unpleasant odor of hesperidin and / or its derivative increases with time, but hesperidin and / or its derivative thereof. It was also found that when a predetermined amount of nabumetone is blended together, the unpleasant odor that increases with time can be suppressed more effectively. The present invention has been completed by further studies based on these findings.
即ち、本発明は、下記に掲げる態様の発明を提供する。
項１． ヘスペリジン及び／又はその誘導体、並びにナブメトンを含有する、医薬組成物。
項２． ヘスペリジン及び／又はその誘導体の総量１００重量部当たり、ナブメトンを１００〜１７０００重量部含む、項１に記載の医薬組成物。
項３． ヘスペリジン及び／又はその誘導体を０．１〜１５重量％、ナブメトンを５〜９９．９重量％含む、項１又は２に記載の医薬組成物。
項４． ヘスペリジン及び／又はその誘導体がメチルヘスペリジンである、項１〜３のいずれかに記載の医薬組成物。
項５． 固体状製剤である、項１〜４のいずれかに記載の医薬組成物。
項６． ナブメトンを有効成分とする、ヘスペリジン及び／又はその誘導体の不快臭抑制剤。
項７． 医薬組成物に、ヘスペリジン及び／又はその誘導体と共にナブメトンを配合する、ヘスペリジン及び／又はその誘導体の不快臭低減方法。
That is, the present invention provides the inventions of the following aspects.
Item 1. A pharmaceutical composition containing hesperidin and / or a derivative thereof, and nabumetone.
Item 2. Item 2. The pharmaceutical composition according to Item 1, which contains 100 to 17,000 parts by weight of nabumetone per 100 parts by weight of hesperidin and / or a derivative thereof.
Item 3. Item 3. The pharmaceutical composition according to Item 1 or 2, which contains 0.1 to 15% by weight of hesperidin and / or a derivative thereof and 5 to 99.9% by weight of nabumetone.
Item 4. Item 8. The pharmaceutical composition according to any one of Items 1 to 3, wherein hesperidin and / or a derivative thereof is methyl hesperidin.
Item 5. Item 8. The pharmaceutical composition according to any one of Items 1 to 4, which is a solid preparation.
Item 6. An unpleasant odor suppressant of hesperidin and / or its derivative containing nabumetone as an active ingredient.
Item 7. A method for reducing an unpleasant odor of hesperidin and / or a derivative thereof, in which nabumetone is blended with hesperidin and / or a derivative thereof in a pharmaceutical composition.
本発明によれば、医薬組成物に含まれるヘスペリジン及び／又はその誘導体の不快臭を抑制できる。特に、本発明の好適な一態様では、経時的に増大するヘスペリジン及び／又はその誘導体の不快臭をより一層効果的に抑制することもできる。そのため、本発明によれば、ヘスペリジン及び／又はその誘導体を含む医薬組成物を服用し易くし、服薬コンプライアンスを高めることができる。 According to the present invention, the unpleasant odor of hesperidin and / or its derivative contained in the pharmaceutical composition can be suppressed. In particular, in a preferred embodiment of the present invention, the unpleasant odor of hesperidin and / or its derivative, which increases with time, can be suppressed even more effectively. Therefore, according to the present invention, it is possible to facilitate taking a pharmaceutical composition containing hesperidin and / or a derivative thereof, and to enhance medication compliance.
１．医薬組成物
本発明の医薬組成物は、ヘスペリジン及び／又はその誘導体、並びにナブメトンを含有することを特徴とする。以下、本発明の医薬組成物について詳述する。
1. 1. Pharmaceutical Composition The pharmaceutical composition of the present invention is characterized by containing hesperidin and / or a derivative thereof, and nabumetone. Hereinafter, the pharmaceutical composition of the present invention will be described in detail.
ヘスペリジン及び／又はその誘導体
本発明の医薬組成物はヘスペリジン及び／又はその誘導体を含有する。ヘスペリジン及び／又はその誘導体には、不快臭があり、製剤化すると経時的に不快臭が増大するという欠点があるが、本発明では、ナブメトンを使用することによって、かかる欠点を克服し、ヘスペリジン及び／又はその誘導体の不快臭を抑制することができる。
Hesperidin and / or its derivative The pharmaceutical composition of the present invention contains hesperidin and / or its derivative. Hesperidin and / or its derivatives have an unpleasant odor, and when formulated, the unpleasant odor increases over time. However, in the present invention, hesperidin and / or its derivatives can be overcome by using nabumetone. / Or the unpleasant odor of its derivative can be suppressed.
ヘスペリジンとは、ミカン等の柑橘類の皮に多く含まれているポリフェノールの一種であり、ヘスペレチンの配糖体として公知の成分である。 Hesperidin is a kind of polyphenol contained in a large amount in the skin of citrus fruits such as mandarin oranges, and is a known component as a glycoside of hesperetin.
また、ヘスペリジンの誘導体についても、ミカン等の柑橘類の皮に多く含まれているポリフェノールの一種であり、公知の化合物である。本発明で使用されるヘスペリジンの誘導体については、薬学的に許容されることを限度として特に制限されないが、例えば、ヘスペレチン、ネオヘスペリジン、ヘスペリジンメチルカルコン、アルキルヘスペリジン、糖転移ヘスペリジン、ヘスペリジンの硫酸エステル等が挙げられる。アルキルヘスペリジンとは、ヘスペリジン、メチル基、エチル基等のアルキル基を付加したヘスペリジン誘導体であり、具体的にはメチルヘスペリジンが挙げられる。糖転移ヘスペリジンとは、ヘスペリジンの水酸基に、グルコース、アラビノース、ガラクトース、ルチノース、ソホロース、グルクロン酸等の単糖又はオリゴ糖を転移させたヘスペリジン誘導体であり、具体的には、α−モノグルコシルヘスペリジン、α−ジグルコシルヘスペリジン、α−トリグルコシルヘスペリジン、α−テトラグルコシルヘスペリジン及びα−ペンタグルコシルヘスペリジン等が挙げられる。 A derivative of hesperidin is also a kind of polyphenol contained in a large amount in the skin of citrus fruits such as mandarin oranges, and is a known compound. The derivative of hesperidin used in the present invention is not particularly limited as long as it is pharmaceutically acceptable, and for example, hesperetin, neohesperidin, hesperidin methyl chalcone, alkyl hesperidin, glycosylated hesperidin, sulfate ester of hesperidin, etc. Can be mentioned. The alkyl hesperidin is a hesperidin derivative to which an alkyl group such as a hesperidin, a methyl group, or an ethyl group is added, and specific examples thereof include methyl hesperidin. Glycotransfer hesperidin is a hesperidin derivative obtained by transferring a monosaccharide or oligosaccharide such as glucose, arabinose, galactose, rutinose, sophorose, glucuronic acid to the hydroxyl group of hesperidin, and specifically, α-monoglucosyl hesperidin, Examples thereof include α-diglucosyl hesperidin, α-triglucosyl hesperidin, α-tetraglucosyl hesperidin and α-pentaglucosyl hesperidin.
本発明において、ヘスペリジン及びその誘導体の中から、１種を選択して単独で使用してもよく、また２種以上を組み合わせて使用してもよい。 In the present invention, one type may be selected from hesperidin and its derivatives and used alone, or two or more types may be used in combination.
これらのヘスペリジン及びその誘導体の中でも、好ましくはアルキルヘスペリジン、及びヘスペリジン、特に好ましくはメチルヘスペリジン及びヘスペリジンが挙げられる。 Among these hesperidins and derivatives thereof, preferred are alkyl hesperidins and hesperidins, and particularly preferably methyl hesperidin and hesperidin.
本発明の医薬組成物において、ヘスペリジン及び／又はその誘導体の含有量については、使用するヘスペリジン及び／又はその誘導体の種類、剤型、用途、一日当たりの投与量等に応じて適宜設定すればよいが、例えば、０．１〜１５重量％、好ましくは０．５〜１０重量％、更に好ましくは０．８〜８重量％が挙げられる。 In the pharmaceutical composition of the present invention, the content of hesperidin and / or its derivative may be appropriately set according to the type, dosage form, use, daily dose and the like of hesperidin and / or its derivative to be used. However, for example, 0.1 to 15% by weight, preferably 0.5 to 10% by weight, and more preferably 0.8 to 8% by weight can be mentioned.
本発明の医薬組成物において、ヘスペリジン及び／又はその誘導体の一日当たりの投与量については、使用するヘスペリジン及び／又はその誘導体の種類、剤型、用途、投与形態等に応じて適宜設定すればよいが、例えば、６〜１００ｍｇ／日、好ましくは１０〜９０ｍｇ／日、更に好ましくは１５〜６０ｍｇ／日が挙げられる。 In the pharmaceutical composition of the present invention, the daily dose of hesperidin and / or its derivative may be appropriately set according to the type, dosage form, use, administration form, etc. of hesperidin and / or its derivative to be used. However, for example, 6 to 100 mg / day, preferably 10 to 90 mg / day, and more preferably 15 to 60 mg / day can be mentioned.
ナブメトン
本発明の医薬組成物では、ヘスペリジン及び／又はその誘導体の不快臭を抑制するために、ナブメトンを含有する。
Nabumetone The pharmaceutical composition of the present invention contains nabumetone in order to suppress the unpleasant odor of hesperidin and / or its derivatives.
ナブメトンとは、４−（６−メトキシナフタレン−２−イル）−２−ブタノンとも称される公知の化合物である。 Nabumetone is a known compound also called 4- (6-methoxynaphthalene-2-yl) -2-butanone.
また、本発明の医薬組成物において、ナブメトンの含有量については、剤型等に応じて適宜設定すればよいが、例えば、５〜９９．９重量％、好ましくは１０〜９５重量％、更に好ましくは２０〜９０重量％が挙げられる。また、後記する試験例に示すようにヘスペリジン及び／又はその誘導体の不快臭は経時的に増大することが確認されているが、ナブメトンの含有量が、３０〜８５重量％（特に、４０〜８５重量％、５０〜８５重量％、又は６０〜８５重量％）の場合には、経時的に増大するヘスペリジン及び／又はその誘導体の不快臭をより一層効果的に抑制することが可能になる。それ故、本発明の医薬組成物におけるナブメトンの含有量の特に好適な範囲として、より好ましくは３０〜８５重量％、より一層好ましくは４０〜８５重量％、特に好ましくは５０〜８５重量％、最も好ましくは６０〜８５重量％が挙げられる。 Further, in the pharmaceutical composition of the present invention, the content of nabumetone may be appropriately set according to the dosage form and the like, and is, for example, 5 to 99.9% by weight, preferably 10 to 95% by weight, more preferably. Is 20 to 90% by weight. Further, as shown in the test example described later, it has been confirmed that the unpleasant odor of hesperidin and / or its derivative increases with time, but the content of nabumetone is 30 to 85% by weight (particularly 40 to 85). In the case of% by weight, 50 to 85% by weight, or 60 to 85% by weight), the unpleasant odor of hesperidin and / or its derivative, which increases with time, can be suppressed more effectively. Therefore, a particularly preferred range of nabumetone content in the pharmaceutical composition of the present invention is more preferably 30-85% by weight, even more preferably 40-85% by weight, particularly preferably 50-85% by weight, most preferably. Preferably, it is 60 to 85% by weight.
本発明の医薬組成物において、ヘスペリジン及び／又はその誘導体に対するナブメトンの比率については、両成分の含有量に応じて定まるが、ヘスペリジン及び／又はその誘導体の不快臭をより一層効果的に抑制するという観点から、ヘスペリジン及び／又はその誘導体の総量１００重量部当たり、ナブメトンが１００〜１７０００重量部、好ましくは１１０〜１００００重量部、更に好ましくは１５０〜７０００重量部、特に好ましくは５００〜４５００重量部、最も好ましくは１５００〜４５００重量部となる比率が挙げられる。 In the pharmaceutical composition of the present invention, the ratio of nabumetone to hesperidin and / or its derivative is determined according to the content of both components, but it is said that the unpleasant odor of hesperidin and / or its derivative is suppressed more effectively. From the viewpoint, nabumetone is 100 to 17,000 parts by weight, preferably 110 to 10,000 parts by weight, more preferably 150 to 7,000 parts by weight, and particularly preferably 500 to 4,500 parts by weight, per 100 parts by weight of the total amount of hesperidin and / or a derivative thereof. Most preferably, the ratio is 1500 to 4500 parts by weight.
本発明の医薬組成物において、ナブメトンの一日当たりの投与量については、特に制限されないが、例えば、１００〜１０００ｍｇ／日、好ましくは２００〜９００ｍｇ／日、更に好ましくは４００〜９００ｍｇ／日、特に好ましくは６００〜８００ｍｇ／日が挙げられる。 In the pharmaceutical composition of the present invention, the daily dose of nabumetone is not particularly limited, but is, for example, 100 to 1000 mg / day, preferably 200 to 900 mg / day, more preferably 400 to 900 mg / day, and particularly preferably. Is 600 to 800 mg / day.
その他の含有成分
本発明の医薬組成物には、ヘスペリジン及び／又はその誘導体、並びにナブメトン以外に、必要に応じて、他の薬理成分を含んでいてもよい。このような薬理成分の種類については、特に制限されないが、例えば、ナブメトン以外の鎮痛剤、腸管運動改善剤、制酸剤、健胃剤、消化剤、整腸剤、鎮痙剤、粘膜修復剤、抗炎症剤、収れん剤、鎮吐剤、鎮咳剤、去痰剤、消炎酵素剤、鎮静催眠剤、抗ヒスタミン剤、強心利尿剤、抗菌剤、血管収縮剤、血管拡張剤、局所麻酔剤、生薬、生薬エキス末、ビタミン類、カフェイン類、メントール類、ヘスペリジン及び／又はその誘導体以外のポリフェノール等が挙げられる。これらの薬理成分は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。また、これらの薬理成分の含有量については、使用する薬理成分の種類や医薬組成物の剤型等に応じて適宜設定すればよい。
Other Ingredients In addition to hesperidin and / or its derivatives and nabumetone, the pharmaceutical composition of the present invention may contain other pharmacological ingredients, if necessary. The types of such pharmacological components are not particularly limited, but for example, analgesics other than nabumetone, intestinal motility improving agents, antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, and astringency. Agents, antiemetics, antitussives, expectorants, anti-inflammatory enzyme agents, sedative hypnotics, antihistamines, cardiotonic diuretics, antibacterial agents, vasodilators, vasodilators, local anesthetics, crude drugs, crude drug extract powders, vitamins, caffeine , Mentors, polyphenols other than hesperidin and / or derivatives thereof and the like. These pharmacological components may be used alone or in combination of two or more. In addition, the content of these pharmacological components may be appropriately set according to the type of the pharmacological component used, the dosage form of the pharmaceutical composition, and the like.
本発明の医薬組成物には、所望の剤型に調製するために、必要に応じて、薬学的に許容される基剤や添加剤等が含まれていてもよい。このような基剤及び添加剤としては、例えば、賦形剤、結合剤、崩壊剤、滑沢剤、等張化剤、可塑剤、分散剤、乳化剤、溶解補助剤、湿潤化剤、安定化剤、懸濁化剤、粘着剤、コーティング剤、光沢化剤、水、油脂類、ロウ類、炭化水素類、脂肪酸類、高級アルコール類、エステル類、水溶性高分子、界面活性剤、金属石鹸、低級アルコール類、多価アルコール、ｐＨ調整剤、緩衝剤、酸化防止剤、紫外線防止剤、防腐剤、矯味剤、香料、粉体、増粘剤、色素、キレート剤、等が挙げられる。これらの基剤や添加剤は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。また、これらの基剤や添加剤の含有量については、使用する添加成分の種類や医薬組成物の剤型等に応じて適宜設定すればよい。 The pharmaceutical composition of the present invention may contain a pharmaceutically acceptable base, additive, or the like, if necessary, in order to prepare a desired dosage form. Such bases and additives include, for example, excipients, binders, disintegrants, lubricants, isotonic agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers. Agents, suspending agents, pressure-sensitive adhesives, coating agents, brighteners, water, fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps. , Lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, flavoring agents, fragrances, powders, thickeners, pigments, chelating agents, etc. These bases and additives may be used alone or in combination of two or more. The content of these bases and additives may be appropriately set according to the type of additive component to be used, the dosage form of the pharmaceutical composition, and the like.
剤型・投与形態
本発明の医薬組成物の剤型については、固体状、半固体状、又は液体状のいずれであってもよい。
Dosage Form / Dosage Form The dosage form of the pharmaceutical composition of the present invention may be solid, semi-solid, or liquid.
本発明の医薬組成物の剤型として、具体的には、錠剤、丸剤、カプセル剤（軟カプセル剤、硬カプセル剤）、散剤、顆粒剤（ドライシロップを含む）等の固体状製剤；ゼリー剤、フォーム剤、軟膏剤、クリーム剤、ゲル剤等の半固体状製剤；液剤、懸濁剤、シロップ剤、ローション剤、スプレー剤、エアゾール剤、乳液剤等の液体状製剤が挙げられる。これらの剤型の中でも、固体状製剤は、ヘスペリジン及び／又はその誘導体の不快臭が顕著に感じられ易く、その抑制が強く求められる剤型であり、本発明の医薬組成物の剤型として好適である。 Specific examples of the dosage form of the pharmaceutical composition of the present invention include solid preparations such as tablets, pills, capsules (soft capsules and hard capsules), powders and granules (including dry syrup); jelly agents. , Foams, ointments, creams, gels and the like; liquid preparations such as liquids, capsules, syrups, lotions, sprays, aerosols, emulsions and the like. Among these dosage forms, the solid formulation is a dosage form in which the unpleasant odor of hesperidin and / or its derivative is easily perceived and its suppression is strongly required, and is suitable as the dosage form of the pharmaceutical composition of the present invention. Is.
本発明の医薬組成物を前記剤型に調製するには、ヘスペリジン及び／又はその誘導体、ナブメトン、並びに必要に応じて添加される他の薬理成分、基剤、及び添加剤を用いて、医薬分野で採用されている通常の製剤化手法に従って製剤化すればよい。 In order to prepare the pharmaceutical composition of the present invention in the above dosage form, hesperidin and / or its derivative, nabumetone, and other pharmacological components, bases, and additives added as needed are used in the pharmaceutical field. It may be formulated according to the usual formulation method adopted in.
本発明の医薬組成物の投与形態については、特に制限されず、経口投与、経皮投与、経腸投与、経粘膜投与、血管内（動脈内又は静脈内）投与等のいずれであってもよいが、好ましくは経口投与が挙げられる。 The administration form of the pharmaceutical composition of the present invention is not particularly limited, and may be oral administration, transdermal administration, enteral administration, transmucosal administration, intravascular (arterial or intravenous) administration, or the like. However, oral administration is preferable.
用途
本発明の医薬組成物は、ヘスペリジン及び／又はその誘導体による毛細血管の強化、出血予防、血圧調整、骨形成促進、メタボリックシンドロームの改善等の作用を発揮すると共に、ナブメトンによる鎮痛作用を発揮できるので、例えば、頭痛・月経痛（生理痛）・歯痛・抜歯後の疼痛・咽喉痛・腰痛・関節痛・神経痛・筋肉痛・肩こり痛・耳痛・打撲痛・骨折痛・ねんざ痛・外傷痛の鎮痛；悪寒・発熱時の解熱等の目的で使用することができる。
Uses The pharmaceutical composition of the present invention can exert actions such as strengthening of capillaries by hesperidin and / or a derivative thereof, prevention of bleeding, regulation of blood pressure, promotion of bone formation, improvement of metabolic syndrome, and pain relief by nabmeton. So, for example, headache, menstrual pain (physiological pain), toothache, pain after tooth extraction, sore throat, lower back pain, joint pain, nerve pain, muscle pain, stiff shoulder pain, ear pain, bruising pain, fracture pain, numbness pain, trauma. Pain relief; It can be used for the purpose of relieving fever during bad cold and fever.
２．ヘスペリジン及び／又はその誘導体、の不快臭抑制剤、及びヘスペリジン及び／又はその誘導体、の不快臭低減方法
前述するように、ナブメトンは、ヘスペリジン及び／又はその誘導体の不快臭を抑制することができる。従って、本発明は、更に、ナブメトンを有効成分とするヘスペリジン及び／又はその誘導体の不快臭抑制剤を提供する。また、本発明は、医薬組成物に、ヘスペリジン及び／又はその誘導体と共にナブメトンを配合する、ヘスペリジン及び／又はその誘導体の不快臭低減方法を提供する。
2. 2. An unpleasant odor suppressant for hesperidin and / or a derivative thereof, and a method for reducing an unpleasant odor of hesperidin and / or a derivative thereof As described above, nabumetone can suppress an unpleasant odor of hesperidin and / or its derivative. Therefore, the present invention further provides an unpleasant odor suppressant for hesperidin and / or a derivative thereof containing nabumetone as an active ingredient. The present invention also provides a method for reducing an unpleasant odor of hesperidin and / or a derivative thereof, in which nabumetone is blended with hesperidin and / or a derivative thereof in a pharmaceutical composition.
前記不快臭抑制剤はナブメトンの添加剤としての用途であり、また、前記不快臭低減方法は、ナブメトンを利用して、ヘスペリジン及び／又はその誘導体を含む医薬組成物の不快臭を抑制する方法である。 The unpleasant odor suppressant is used as an additive for nabumetone, and the unpleasant odor reducing method is a method for suppressing unpleasant odor of a pharmaceutical composition containing hesperidin and / or a derivative thereof by utilizing nabumetone. is there.
前記不快臭抑制剤及び不快臭低減方法において、使用する成分の種類や使用量、医薬組成物の形態等については、前記「１．医薬組成物」の欄に示す通りである。 The types and amounts of the components used in the unpleasant odor suppressant and the unpleasant odor reducing method, the form of the pharmaceutical composition, and the like are as shown in the column of "1. Pharmaceutical composition".
以下に実施例を示して本発明をより具体的に説明するが、本発明はこれらに限定されるものではない。 The present invention will be described in more detail with reference to Examples below, but the present invention is not limited thereto.
試験例１
表１に示す組成の錠剤（１錠当たり３００ｍｇ、１日当たりの投与量４錠）を常法に従って調製した。製造直後に各錠剤１０錠をアルミラミネート袋に入れて、ヒートシールにより密封し、６０℃で２週間保管した。
Test Example 1
Tablets having the compositions shown in Table 1 (300 mg per tablet, 4 tablets per day) were prepared according to a conventional method. Immediately after production, 10 tablets of each were placed in an aluminum laminated bag, sealed by heat sealing, and stored at 60 ° C. for 2 weeks.
保管前にアルミラミネート袋を開封し、無臭の場合を０点、強い臭いを感じる場合を１５点として、臭いの強さに応じて段階的に評点化することにより、不快臭の評価を行った。更に、保管後に、品温が常温になるまで戻した後に、アルミラミネート袋を開封し、同様に不快臭の評価を行った。なお、本評価法において、評点が９点以下と判断される場合には、服用感の点では問題ないレベルの臭いであることを示している。 The aluminum laminated bag was opened before storage, and the unpleasant odor was evaluated by gradually scoring according to the strength of the odor, with 0 points for odorless and 15 points for strong odor. .. Further, after storage, the product temperature was returned to room temperature, the aluminum laminated bag was opened, and the unpleasant odor was evaluated in the same manner. In addition, in this evaluation method, when it is judged that the score is 9 points or less, it indicates that the odor has a level that does not cause any problem in terms of the feeling of taking.
得られた結果を表１に示す。メチルヘスペリジンを単独で含む錠剤（比較例１及び２）は、保管前に不快臭が強く感じられ、保管後には不快臭が増大していた。これに対して、メチルヘスペリジン及びナブメトンを含む錠剤（実施例１〜６）では、比較例の錠剤に比べて保管前後で不快臭を効果的に低減できていた。特に、メチルヘスペリジンと共にナブメトンを６７重量％含んでいる錠剤（実施例１〜３）では、保管後でも、保管前に認められた不快臭の抑制効果を十分に維持できていた。 The results obtained are shown in Table 1. The tablets containing methyl hesperidin alone (Comparative Examples 1 and 2) had a strong unpleasant odor before storage, and the unpleasant odor increased after storage. On the other hand, the tablets containing methyl hesperidin and nabumetone (Examples 1 to 6) were able to effectively reduce the unpleasant odor before and after storage as compared with the tablets of Comparative Examples. In particular, the tablets containing 67% by weight of nabumetone together with methyl hesperidin (Examples 1 to 3) were able to sufficiently maintain the effect of suppressing the unpleasant odor observed before storage even after storage.
処方例
表２〜７に示す組成の錠剤（１錠当たり３００ｍｇ、１日当たりの投与量４錠）を調製した。得られた錠剤は、いずれも、ヘスペリジン又はメチルヘスペリジンの不快臭を抑制できていた。
Formulation Examples Tablets having the compositions shown in Tables 2 to 7 (300 mg per tablet, daily dose of 4 tablets) were prepared. All of the obtained tablets were able to suppress the unpleasant odor of hesperidin or methyl hesperidin.
Claims (7)
The hesperidins, wherein the pharmaceutical composition comprises nabmethone with at least one hesperidin selected from the group consisting of hesperidin, hesperetin, neohesperidin, hesperidin methyl chalcone, alkyl hesperidin, glycosylated hesperidin, and sulfate esters of hesperidin. How to reduce unpleasant odors.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2016194937A JP6832113B2 (en) | 2016-09-30 | 2016-09-30 | Pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2016194937A JP6832113B2 (en) | 2016-09-30 | 2016-09-30 | Pharmaceutical composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2018058769A JP2018058769A (en) | 2018-04-12 |
| JP6832113B2 true JP6832113B2 (en) | 2021-02-24 |
Family
ID=61909623
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016194937A Active JP6832113B2 (en) | 2016-09-30 | 2016-09-30 | Pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP6832113B2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20230355646A1 (en) * | 2020-09-17 | 2023-11-09 | Resonac Corporation | Autophagy activator |
| WO2024010035A1 (en) * | 2022-07-06 | 2024-01-11 | 株式会社レゾナック | Viral infection preventing agent |
-
2016
- 2016-09-30 JP JP2016194937A patent/JP6832113B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2018058769A (en) | 2018-04-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2000086510A (en) | Histamine release inhibitor | |
| JP6832113B2 (en) | Pharmaceutical composition | |
| JP2011148727A (en) | Beauty set for improving wrinkle and beauty method using the same | |
| US20230165920A1 (en) | Composition for increasing sexual desire or pleasure | |
| JPWO2014010658A1 (en) | Hihitsu formulation | |
| JP7037903B2 (en) | Pharmaceutical composition | |
| JP2007031302A (en) | Adiponectin production accelerator and metabolic syndrome preventive | |
| JP6949645B2 (en) | Pharmaceutical composition | |
| JP5876103B2 (en) | Skin preparation | |
| JP2012131760A (en) | Fatty acid absorption inhibitor | |
| JP6940265B2 (en) | Antidiarrheal composition | |
| JP4756223B2 (en) | Skin improvement additive and beverage, cosmetic cream, lotion and lotion using the same | |
| JP6929339B2 (en) | Topical composition | |
| JP5164407B2 (en) | Peripheral circulation improving drug | |
| JPWO2018124258A1 (en) | Treatment for chronic fatigue syndrome | |
| JP2007230989A (en) | Endurance enhancing and anti-fatigue agent | |
| JP2012051811A (en) | Immunoenhancing agent | |
| JP2007291011A (en) | Preventive or therapeutic agent of inflammatory intestinal disease | |
| JP2006169192A (en) | Lipolysis promoter, skin care composition, and food and beverage composition | |
| WO2003074040A1 (en) | Compositions for ameliorating fecal properties | |
| JP2021107330A (en) | Oral pharmaceutical composition | |
| JP2021107332A (en) | Oral pharmaceutical composition | |
| JP2021161038A (en) | Premenstrual hyperphagia inhibitor | |
| JP2021161041A (en) | Heart frequency increment inhibitor for inhibiting increment of heart frequency in drinking | |
| JP2022178149A (en) | external composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20170208 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190819 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200630 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20200626 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200821 |
|
| 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: 20210105 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210201 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6832113 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |