JP6088151B2 - Pharmaceutical composition - Google Patents
Pharmaceutical composition Download PDFInfo
- Publication number
- JP6088151B2 JP6088151B2 JP2012090158A JP2012090158A JP6088151B2 JP 6088151 B2 JP6088151 B2 JP 6088151B2 JP 2012090158 A JP2012090158 A JP 2012090158A JP 2012090158 A JP2012090158 A JP 2012090158A JP 6088151 B2 JP6088151 B2 JP 6088151B2
- Authority
- JP
- Japan
- Prior art keywords
- pharmaceutical composition
- scopolamine
- component
- group
- magnesium
- 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
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 37
- 235000019658 bitter taste Nutrition 0.000 claims description 51
- 229960002646 scopolamine Drugs 0.000 claims description 30
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 claims description 29
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 claims description 29
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 25
- 229940069428 antacid Drugs 0.000 claims description 23
- 239000003159 antacid agent Substances 0.000 claims description 23
- 239000000739 antihistaminic agent Substances 0.000 claims description 22
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 17
- 239000001095 magnesium carbonate Substances 0.000 claims description 17
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 17
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 16
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims description 16
- 230000001387 anti-histamine Effects 0.000 claims description 16
- LZCOQTDXKCNBEE-IKIFYQGPSA-N methscopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)C)=CC=CC=C1 LZCOQTDXKCNBEE-IKIFYQGPSA-N 0.000 claims description 13
- 229960001383 methylscopolamine Drugs 0.000 claims description 13
- 230000001458 anti-acid effect Effects 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000011777 magnesium Substances 0.000 claims description 7
- 229910052749 magnesium Inorganic materials 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-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
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 4
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 4
- 230000000116 mitigating effect Effects 0.000 claims description 4
- 108010011485 Aspartame Proteins 0.000 claims description 3
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 3
- 229940008027 aluminum hydroxide / magnesium carbonate Drugs 0.000 claims description 3
- 239000000605 aspartame Substances 0.000 claims description 3
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 3
- 235000010357 aspartame Nutrition 0.000 claims description 3
- 229960003438 aspartame Drugs 0.000 claims description 3
- 238000000975 co-precipitation Methods 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
- 239000000796 flavoring agent Substances 0.000 claims description 3
- 235000013355 food flavoring agent Nutrition 0.000 claims description 3
- 229960001545 hydrotalcite Drugs 0.000 claims description 3
- 229910001701 hydrotalcite Inorganic materials 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 claims description 2
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims description 2
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 claims description 2
- 244000228451 Stevia rebaudiana Species 0.000 claims description 2
- 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 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 2
- 229940024545 aluminum hydroxide Drugs 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 210000000988 bone and bone Anatomy 0.000 claims description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- 239000000287 crude extract Substances 0.000 claims description 2
- 229940010454 licorice Drugs 0.000 claims description 2
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 2
- 229940041616 menthol Drugs 0.000 claims description 2
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 claims description 2
- 235000020374 simple syrup Nutrition 0.000 claims description 2
- 239000004575 stone Substances 0.000 claims description 2
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 claims 3
- 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 claims 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims 1
- 240000004670 Glycyrrhiza echinata Species 0.000 claims 1
- 239000004376 Sucralose Substances 0.000 claims 1
- 150000001242 acetic acid derivatives Chemical class 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 235000010355 mannitol Nutrition 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 claims 1
- 229960004172 pyridoxine hydrochloride Drugs 0.000 claims 1
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 claims 1
- 239000011764 pyridoxine hydrochloride Substances 0.000 claims 1
- 235000019408 sucralose Nutrition 0.000 claims 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims 1
- STECJAGHUSJQJN-VJQRDGCPSA-N chembl3084722 Chemical compound C1([C@@H](CO)C(=O)O[C@@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-VJQRDGCPSA-N 0.000 description 27
- -1 magnesium carbonate Chemical class 0.000 description 16
- OCJYIGYOJCODJL-UHFFFAOYSA-N Meclizine Chemical compound CC1=CC=CC(CN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC(Cl)=CC=2)=C1 OCJYIGYOJCODJL-UHFFFAOYSA-N 0.000 description 11
- 230000000052 comparative effect Effects 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 239000007910 chewable tablet Substances 0.000 description 10
- 235000019640 taste Nutrition 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000003908 antipruritic agent Substances 0.000 description 7
- 235000003599 food sweetener Nutrition 0.000 description 7
- 229960004499 scopolamine hydrobromide Drugs 0.000 description 7
- WTGQALLALWYDJH-MOUKNHLCSA-N scopolamine hydrobromide (anhydrous) Chemical compound Br.C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 WTGQALLALWYDJH-MOUKNHLCSA-N 0.000 description 7
- 239000003765 sweetening agent Substances 0.000 description 7
- 229940125715 antihistaminic agent Drugs 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 6
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 229960001474 meclozine Drugs 0.000 description 6
- 235000010980 cellulose Nutrition 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 229960000520 diphenhydramine Drugs 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 229940018415 meclizine hydrochloride Drugs 0.000 description 5
- 229920001592 potato starch Polymers 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 230000001629 suppression Effects 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
- 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 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 229940068682 chewable tablet Drugs 0.000 description 4
- SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 description 4
- 229960003291 chlorphenamine Drugs 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 229960000879 diphenylpyraline Drugs 0.000 description 4
- OWQUZNMMYNAXSL-UHFFFAOYSA-N diphenylpyraline Chemical compound C1CN(C)CCC1OC(C=1C=CC=CC=1)C1=CC=CC=C1 OWQUZNMMYNAXSL-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 235000012054 meals Nutrition 0.000 description 4
- 229920000609 methyl cellulose Polymers 0.000 description 4
- 239000001923 methylcellulose Substances 0.000 description 4
- 235000010981 methylcellulose Nutrition 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 3
- 241000416162 Astragalus gummifer Species 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 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 3
- 229920002472 Starch Polymers 0.000 description 3
- 229920001615 Tragacanth Polymers 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 230000001139 anti-pruritic effect Effects 0.000 description 3
- 239000002518 antifoaming agent Substances 0.000 description 3
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 3
- 229960000541 cetyl alcohol Drugs 0.000 description 3
- 239000000812 cholinergic antagonist Substances 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 229960004993 dimenhydrinate Drugs 0.000 description 3
- MZDOIJOUFRQXHC-UHFFFAOYSA-N dimenhydrinate Chemical compound O=C1N(C)C(=O)N(C)C2=NC(Cl)=N[C]21.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 MZDOIJOUFRQXHC-UHFFFAOYSA-N 0.000 description 3
- PFAXACNYGZVKMX-UHFFFAOYSA-N fenethazine Chemical compound C1=CC=C2N(CCN(C)C)C3=CC=CC=C3SC2=C1 PFAXACNYGZVKMX-UHFFFAOYSA-N 0.000 description 3
- 229950007454 fenethazine Drugs 0.000 description 3
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 201000003152 motion sickness Diseases 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 3
- 235000012239 silicon dioxide Nutrition 0.000 description 3
- 150000005846 sugar alcohols Chemical class 0.000 description 3
- 235000010487 tragacanth Nutrition 0.000 description 3
- 239000000196 tragacanth Substances 0.000 description 3
- 229940116362 tragacanth Drugs 0.000 description 3
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical compound CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 235000006679 Mentha X verticillata Nutrition 0.000 description 2
- 235000002899 Mentha suaveolens Nutrition 0.000 description 2
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- IJHNSHDBIRRJRN-UHFFFAOYSA-N N,N-dimethyl-3-phenyl-3-(2-pyridinyl)-1-propanamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=CC=C1 IJHNSHDBIRRJRN-UHFFFAOYSA-N 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 2
- 230000003474 anti-emetic effect Effects 0.000 description 2
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- 239000003963 antioxidant agent Substances 0.000 description 2
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- 235000013871 bee wax Nutrition 0.000 description 2
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- 239000011230 binding agent Substances 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 229960001948 caffeine Drugs 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 229950008138 carmellose Drugs 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000004205 dimethyl polysiloxane Substances 0.000 description 2
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 2
- OGAKLTJNUQRZJU-UHFFFAOYSA-N diphenidol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)CCCN1CCCCC1 OGAKLTJNUQRZJU-UHFFFAOYSA-N 0.000 description 2
- 229960003520 diphenidol Drugs 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 229940030606 diuretics Drugs 0.000 description 2
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 2
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- 239000000284 extract Substances 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
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- 238000009472 formulation Methods 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
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- 231100000869 headache Toxicity 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
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- NFLGAXVYCFJBMK-UHFFFAOYSA-N isomenthone Natural products CC(C)C1CCC(C)CC1=O NFLGAXVYCFJBMK-UHFFFAOYSA-N 0.000 description 1
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- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
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Images
Description
本発明は、有効成分としてスコポラミンもしくはその誘導体、及び制酸剤を含む医薬組成物であり、詳しくは、スコポラミン、メチルスコポラミン及びそれらの塩からなる群から選ばれる１種又は２種以上、及び炭酸マグネシウム等の制酸剤を含み、適宜抗ヒスタミン剤を含有する医薬組成物であり、スコポラミンの苦味を炭酸マグネシウムで抑制することで経口で服用可能な医薬組成物に関する。 The present invention is a pharmaceutical composition comprising scopolamine or a derivative thereof as an active ingredient and an antacid, specifically, one or more selected from the group consisting of scopolamine, methyl scopolamine and salts thereof, and carbonic acid The present invention relates to a pharmaceutical composition comprising an antacid such as magnesium and optionally containing an antihistamine, which can be taken orally by suppressing the bitter taste of scopolamine with magnesium carbonate.
スコポラミン類は、乗り物酔い止め薬、すなわち鎮暈剤の有効成分として使用される成分であり、また高い鎮暈作用を得るために、スコポラミンと抗ヒスタミン剤であるメクリジン等を組み合わせて配合される例も多い。
一方、スコポラミンや種々の抗ヒスタミン剤は不快な味を有するため、経口固形製剤として使用するためには、コーティングを施したりカプセル剤とする等の製剤設計に基づく方法（特許文献１など）や、甘味剤を配合する方法（特許文献２、特許文献３など）など、苦味成分を物理的にマスキングすることが多い。しかしながら、コーティングやカプセル化などは煩雑な工程が必要でコストもかかり、また、スコポラミン等に糖アルコール、多価アルコール等甘味剤を配合してもその効果は十分とは言えなかった。
Scopolamines are components used as an active ingredient in motion sickness medicine, that is, an antipruritic agent, and in order to obtain a high antipruritic action, scopolamine is often combined with meclizine which is an antihistamine.
On the other hand, since scopolamine and various antihistamines have an unpleasant taste, in order to use them as oral solid preparations, methods based on formulation design such as coating or capsules (Patent Document 1 etc.), sweeteners, etc. In many cases, a bitter component is physically masked, such as a method of blending (Patent Document 2, Patent Document 3, etc.). However, coating and encapsulation require complicated steps and are expensive, and even if a sweetener such as sugar alcohol or polyhydric alcohol is added to scopolamine or the like, the effect is not sufficient.
また、鎮暈剤を服用するにあたっては、車中であるなどのため水などの飲み物を用意できない場合も多く、水なしで服用可能なチュアブル錠などが望ましい。しかし、チュアブル錠は口内で咀嚼して服用するため、製剤の味を感知しやすく、苦味など不快な味の強い製剤は使用者への負担が大きくなる。特に、乗り物酔い状態やそれに近い状態で服用すると、却って吐き気を催すことなどもあり、これらの課題を克服した鎮暈剤の開発が望まれていた。 In addition, when taking antipruritics, drinks such as water cannot be prepared because they are in the car, and chewable tablets that can be taken without water are desirable. However, since chewable tablets are chewed in the mouth and taken, it is easy to sense the taste of the preparation, and preparations with a strong unpleasant taste such as a bitter taste increase the burden on the user. In particular, if taken in a motion sickness state or a state close thereto, it may cause nausea on the contrary, and development of an antitussive that overcomes these problems has been desired.
一方、制酸剤を含有するチュアブル錠として、特許文献４、特許文献５などが知られているが、いずれにおいても、苦味をマスキングする作用については、記載も示唆もない。 On the other hand, Patent Document 4, Patent Document 5 and the like are known as chewable tablets containing an antacid, but none of them describes or suggests the action of masking bitterness.
本発明は、有効成分として不快な味を有するスコポラミン類を含む医薬組成物であって、不快な味をマスキングした経口固形製剤を完成させることを目的とする。具体的には、有効成分としてスコポラミンもしくはその誘導体、またはスコポラミンもしくはその誘導体および抗ヒスタミン剤の組み合わせを含む経口用組成物であって、不快な味をマスキングできる経口用組成物を提供することを目的とするものである。 An object of the present invention is to complete an oral solid preparation masking an unpleasant taste, which is a pharmaceutical composition containing scopolamines having an unpleasant taste as an active ingredient. Specifically, an object of the present invention is to provide an oral composition containing scopolamine or a derivative thereof, or a combination of scopolamine or a derivative thereof and an antihistamine as an active ingredient, which can mask an unpleasant taste. Is.
本発明者らは、上記課題を解決すべく鋭意検討したところ、スコポラミンもしくはその誘導体に、炭酸マグネシウム等の制酸剤を含有させることで、スコポラミン等の不快な味をマスキングできることを見出した。具体的には、スコポラミン、メチルスコポラミン及びそれらの塩からなる群から選ばれる１種又は２種以上、及び炭酸マグネシウム等の制酸剤を含有する医薬組成物であって、スコポラミン等の不快な味をマスキングできる経口用組成物を見出した。また、これら医薬用組成物においては、更にメクリジン等の抗ヒスタミン剤を含んでいてもよく、またこれらの抗ヒスタミン剤を含むことで更にそのマスキング作用が強まることを見出した。本発明は、これらの知見に基づいて完成したものである。 The present inventors diligently studied to solve the above problems, and found that unpleasant tastes such as scopolamine can be masked by adding antacids such as magnesium carbonate to scopolamine or its derivatives. Specifically, it is a pharmaceutical composition containing one or more selected from the group consisting of scopolamine, methyl scopolamine and salts thereof, and an antacid such as magnesium carbonate, and has an unpleasant taste such as scopolamine. The composition for oral use which can mask is found. Further, it has been found that these pharmaceutical compositions may further contain an antihistamine such as meclizine, and that the masking action is further enhanced by including these antihistamines. The present invention has been completed based on these findings.
本発明は、以下の組成物を提供するものである。
［項１］（ａ）スコポラミン、メチルスコポラミン及びそれらの塩からなる群から選ばれる１種又は２種以上、及び（ｂ）炭酸マグネシウムを含有する医薬組成物。
The present invention provides the following compositions.
[Item 1] A pharmaceutical composition comprising (a) one or more selected from the group consisting of scopolamine, methylscopolamine and salts thereof, and (b) magnesium carbonate.
［項２］（ａ）スコポラミン、メチルスコポラミン及びそれらの塩からなる群より選ばれる１種又は２種以上、（ｂ）制酸剤、及び（ｃ）抗ヒスタミン剤を含有する医薬組成物。 [Item 2] A pharmaceutical composition comprising (a) one or more selected from the group consisting of scopolamine, methylscopolamine and salts thereof, (b) an antacid, and (c) an antihistamine.
［項３］（ｂ）制酸剤が無機系制酸剤のマグネシウム、アルミニウム、ナトリウム、カルシウムの塩、並びに、合成ヒドロタルサイトからなる群より選ばれる１種又は２種以上である［項２］の医薬組成物。
［項４］（ｂ）制酸剤が炭酸マグネシウムである［項２］の医薬組成物。
[Item 3] (b) The antacid is one or more selected from the group consisting of magnesium, aluminum, sodium, calcium salts of inorganic antacids and synthetic hydrotalcite [Item 2 ] Pharmaceutical composition.
[Item 4] (b) The pharmaceutical composition of [Item 2], wherein the antacid is magnesium carbonate.
［項５］（ｃ）抗ヒスタミン剤が、メクリジン、クロルフェニラミン、ジフェンヒドラミン、ジフェニルピラリン、ジメンヒドリナート、フェネタジン、プロメタジン、ジフェニドール、フェニラミン、ジフェニルピラリン及びそれらの塩からなる群より選ばれる１種又は２種以上である［項２］〜［項４］のいずれかの医薬組成物。
［項６］（ｃ）抗ヒスタミン剤がメクリジン又はその塩である［項２］〜［項４］のいずれかの医薬組成物。
[Claim 5] (c) One or two antihistamines selected from the group consisting of meclizine, chlorpheniramine, diphenhydramine, diphenylpyralin, dimenhydrinate, phenetazine, promethazine, diphenidol, pheniramine, diphenylpyraline and salts thereof The pharmaceutical composition according to any one of [Item 2] to [Item 4].
[Claim 6] (c) The pharmaceutical composition according to any one of [Claim 2] to [Claim 4], wherein the antihistamine is meclizine or a salt thereof.
［項７］（ａ）成分が臭化水素酸スコポラミンである［項１］〜［項６］のいずれかの医薬組成物。 [Item 7] The pharmaceutical composition according to any one of [Item 1] to [Item 6], wherein the component (a) is scopolamine hydrobromide.
［項８］（ａ）成分１重量部に対し、（ｂ）成分が１重量部〜３０００重量部で含有する［項１］〜［項７］のいずれかの医薬組成物。
［項９］（ａ）成分１重量部に対し、（ｃ）成分が１重量部〜５００重量部で含有する［項２］〜［項８］のいずれかの医薬組成物。
［項１０］成人 １日あたりの配合量が、（ａ）成分 ０．０１〜０．５０ｍｇ、（ｂ）成分 ０．０１〜１５００ｍｇ、（ｃ）成分 ０．０１〜２５０ｍｇである［項２］〜［項９］のいずれかの医薬組成物。
[Item 8] The pharmaceutical composition according to any one of items [1] to [7], wherein the component (b) is contained in an amount of 1 part by weight to 3000 parts by weight with respect to 1 part by weight of the component (a).
[Item 9] The pharmaceutical composition according to any one of [Item 2] to [Item 8], wherein the component (c) is contained in an amount of 1 part by weight to 500 parts by weight with respect to 1 part by weight of the component (a).
[Item 10] Adult The compounding amount per day is (a) component 0.01 to 0.50 mg, (b) component 0.01 to 1500 mg, and (c) component 0.01 to 250 mg. -Pharmaceutical composition in any one of [Item 9].
［項１１］［項１］〜［項１０］のいずれかの医薬組成物を含む鎮暈剤。
［項１２］固形剤である［項１１］の鎮暈剤。
［項１３］チュアブル錠である［項１２］の鎮暈剤。
[Item 11] An antipruritic agent comprising the pharmaceutical composition according to any one of items [1] to [10].
[Item 12] The antipruritic agent of [Item 11], which is a solid agent.
[Item 13] The antipruritic agent of [Item 12], which is a chewable tablet.
［項１４］炭酸マグネシウムを含有する、スコポラミンもしくはその塩またはメチルスコポラミンもしくはその塩の苦味緩和剤。
［項１５］さらに抗ヒスタミン剤を含有する、項１４の苦味緩和剤。
［項１６］抗ヒスタミン剤がメグリジン又はその塩である、項１５の苦味緩和剤。
[Item 14] A bitterness alleviating agent for scopolamine or a salt thereof or methyl scopolamine or a salt thereof containing magnesium carbonate.
[Item 15] The bitterness reducing agent of Item 14, further comprising an antihistamine.
[Item 16] The bitterness alleviating agent of Item 15, wherein the antihistamine is megridin or a salt thereof.
［項１７］スコポラミンもしくはその塩またはメチルスコポラミンもしくはその塩の苦味を緩和するための炭酸マグネシウムの使用。
［項１８］スコポラミンもしくはその塩またはメチルスコポラミンもしくはその塩の苦味を緩和するための炭酸マグネシウム及び抗ヒスタミン剤の組み合わせの使用。
［項１９］抗ヒスタミン剤がメグリジン又はその塩である、項１８の使用。
[Item 17] Use of magnesium carbonate for alleviating the bitter taste of scopolamine or a salt thereof or methyl scopolamine or a salt thereof.
[Item 18] Use of a combination of magnesium carbonate and an antihistamine for alleviating the bitter taste of scopolamine or a salt thereof or methyl scopolamine or a salt thereof.
[Item 19] The use of Item 18, wherein the antihistamine is megridin or a salt thereof.
本発明により、医薬成分として有用なスコポラミン類を含有する医薬組成物において、その不快な苦味を、コーティング等することなく、また甘味剤等を配合しなくても緩和することが可能である。特に、スコポラミン類の有する鎮暈作用を利用した鎮暈剤として、車中など水など飲み物を用意できない場合でも水なしで服用可能なチュアブル錠としての製剤化が可能となる。但し、本発明の苦み抑制方法は、コーティングや甘味剤の配合等、従来の苦み抑制方法と組み合わせても用いられ得る。 According to the present invention, in a pharmaceutical composition containing scopolamines useful as a pharmaceutical ingredient, the unpleasant bitter taste can be alleviated without coating or without adding a sweetener or the like. In particular, as an antipruritic agent using the antipruritic action possessed by scopolamines, it is possible to formulate a chewable tablet that can be taken without water even when a drink such as water cannot be prepared. However, the bitterness suppression method of the present invention can also be used in combination with conventional bitterness suppression methods such as coating and blending of sweeteners.
本発明で用いられるスコポラミン、メチルスコポラミン、及びそれらの塩としては（以下、（ａ）成分と記すことがある）、スコポラミン及びその塩として、スコポラミン、臭化水素酸スコポラミン、塩酸スコポラミンなどが、メチルスコポラミン又はその塩として、メチルスコポラミン、臭化メチルスコポラミン、硝酸メチルスコポラミンなどが具体例として挙げられる。本発明においてはこれら（ａ）成分の２種以上を含有していてもよい。
スコポラミン類のヒトへの投与量としては、成人の場合、０．０１〜０．５ｍｇ／１日で、１日１〜３回に分けて投与され得る。スコポラミン類を鎮暈剤として用いる場合、１投与単位あたりのスコポラミン類の含有量は０．０１〜０．２５ｍｇ、好ましくは０．１〜０．２５ｍｇである。
本発明における（ａ）成分の１製剤単位あたりの濃度は、通常、０．００１５Ｗ／Ｗ％〜１．０Ｗ／Ｗ％であり、好ましくは、０．０１Ｗ／Ｗ％〜０．６Ｗ／Ｗ％である。（ａ）成分を２種以上組み合わせる場合は、その総量の含有量である。
As scopolamine, methyl scopolamine, and salts thereof used in the present invention (hereinafter sometimes referred to as component (a)), scopolamine and its salts include scopolamine, scopolamine hydrobromide, scopolamine hydrochloride, and the like. Specific examples of scopolamine or salts thereof include methyl scopolamine, methyl scopolamine bromide, and methyl scopolamine nitrate. In this invention, you may contain 2 or more types of these (a) components.
As for the dosage of scopolamines to humans, in the case of adults, it can be administered in an amount of 0.01 to 0.5 mg / day and divided into 1 to 3 times a day. When using scopolamines as an antipruritic agent, the content of scopolamines per dosage unit is 0.01 to 0.25 mg, preferably 0.1 to 0.25 mg.
The concentration of the component (a) in the present invention per one preparation unit is usually 0.0015 W / W% to 1.0 W / W%, preferably 0.01 W / W% to 0.6 W / W%. It is. (A) When combining 2 or more types of component, it is content of the total amount.
本発明で用いられる制酸剤（以下、（ｂ）成分と記すことがある）としては、炭酸マグネシウム、ケイ酸マグネシウム、酸化マグネシウム、水酸化マグネシウム、ケイ酸アルミン酸マグネシウム、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、水酸化アルミナマグネシウム、炭酸水素ナトリウム、沈降炭酸カルシウム、無水リン酸水素カルシウム、リン酸水素カルシウム、乾燥水酸化アルミニウムゲル、水酸化アルミニウムゲル、合成ヒドロタルサイト、水酸化アルミニウム・炭酸水素ナトリウム共沈生成物、水酸化アルミニウム・炭酸マグネシウム混合物乾燥ゲル、水酸化アルミニウム・炭酸マグネシウム・炭酸カルシウム共沈生成物、烏賊骨、石決明、ボレイ、アミノ酢酸、ジヒドロキシアルミニウムアミノアセテートなどが挙げられる。好ましくは、無機化合物系制酸剤が挙げられ、マグネシウム、アルミニウム、ナトリウム、カルシウムの塩、並びに、合成ヒドロタルサイトであり、その中でも炭酸マグネシウム、ケイ酸アルミン酸マグネシウム、メタケイ酸アルミン酸マグネシウムが特に好ましい。本発明においてはこれらの制酸剤の２種以上を含有していてもよい。
本発明における（ｂ）成分：制酸剤の含有量は、（ａ）成分 １重量部に対し、１重量部〜３０００重量部であり、好ましくは、１重量部〜１０００重量部である。
（ａ）成分もしくは（ｂ）成分を２種以上組み合わせる場合は、（ａ）成分の総量 １重量部に対し、（ｂ）成分の総量は１重量部〜３０００重量部であり、好ましくは、１重量部〜１０００重量部である。
本発明における制酸剤の含有量は、（ａ）成分 ０．０１〜０．５０ｍｇに対し、０．０１〜１５００ｍｇであり、好ましくは０．０１〜１０００ｍｇである。
（ａ）成分もしくは（ｂ）成分を２種以上組み合わせる場合は、（ａ）成分の総量 ０．０１〜０．５０ｍｇに対し、（ｂ）成分の総量は０．０１〜１５００ｍｇであり、好ましくは０．０１〜１０００ｍｇである。
本発明における（ｂ）成分の１製剤単位あたりの濃度は、通常、０．００１５Ｗ／Ｗ％〜８２．５Ｗ／Ｗ％であり、好ましくは、０．００５Ｗ／Ｗ％〜６０Ｗ／Ｗ％である。（ｂ）成分を２種以上組み合わせる場合は、その総量の含有量である。
Examples of the antacid used in the present invention (hereinafter sometimes referred to as the component (b)) include magnesium carbonate, magnesium silicate, magnesium oxide, magnesium hydroxide, magnesium silicate aluminate, magnesium metasilicate aluminate, Synthetic aluminum silicate, magnesium alumina hydroxide, sodium hydrogen carbonate, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, dry aluminum hydroxide gel, aluminum hydroxide gel, synthetic hydrotalcite, aluminum hydroxide / carbonic acid Sodium hydrogen coprecipitation product, aluminum hydroxide / magnesium carbonate mixture dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitation product, bandit bone, stone decision, volley, aminoacetic acid, dihydroxyaluminum aminoacetate Etc., and the like. Preferably, inorganic compound-based antacids are mentioned, such as magnesium, aluminum, sodium, calcium salts, and synthetic hydrotalcites, among which magnesium carbonate, magnesium aluminate, and magnesium aluminate metasilicate are particularly preferred. preferable. In the present invention, two or more of these antacids may be contained.
Component (b) in the present invention: The content of the antacid is 1 to 3000 parts by weight, preferably 1 to 1000 parts by weight, per 1 part by weight of component (a).
When combining two or more types of component (a) or component (b), the total amount of component (b) is 1 part by weight to 3000 parts by weight with respect to 1 part by weight of component (a), preferably 1 Parts by weight to 1000 parts by weight.
Content of the antacid in this invention is 0.01-1500 mg with respect to (a) component 0.01-0.50 mg, Preferably it is 0.01-1000 mg.
When combining two or more types of component (a) or component (b), the total amount of component (b) is 0.01 to 1500 mg, preferably 0.01 to 0.50 mg, 0.01 to 1000 mg.
In the present invention, the concentration of component (b) per preparation unit is usually 0.0015 W / W% to 82.5 W / W%, preferably 0.005 W / W% to 60 W / W%. . (B) When combining 2 or more types of component, it is the content of the total amount.
本発明で用いられる抗ヒスタミン剤（以下、(ｃ)成分と記すことがある）としては、例えば、メクリジン、クロルフェニラミン、ジフェンヒドラミン、ジフェニルピラリン、ジメンヒドリナート、フェネタジン、プロメタジン、ジフェニドール、フェニラミン、ジフェニルピラリン、又はそれらの塩が挙げられ、それらの抗ヒスタミン剤の２種以上を含有していてもよい。好ましくは、メクリジンおよびその塩、ジフェンヒドラミンおよびその塩、並びに、クロルフェニラミンおよびその塩が挙げられ、その中でも具体的には、塩酸メクリジン、ｄｌ‐マレイン酸クロルフェニラミン、ｄ‐マレイン酸クロルフェニラミン、マレイン酸フェニラミン、塩酸ジフェンヒドラミン、サリチル酸ジフェンヒドラミン、タンニン酸ジフェンヒドラミン、フマル酸ジフェンヒドラミン、塩酸ジフェニルピラリン、タンニン酸フェネタジン、テオクル酸ジフェニルピラリン、塩酸プロメタジン、プロメタジンメチレンジサリチル酸塩、ジメンヒドリナートなどが特に好ましい。また、（ａ）成分：スコポラミン類の苦味緩和効果の点からは、特に塩酸メクリジンが好ましい。
本発明における（ｃ）成分：抗ヒスタミン剤の含有量は、スコポラミン類１重量部に対し、１重量部〜５００重量部であり、好ましくは、１０重量部〜３５０重量部である。
（ａ）成分もしくは（ｃ）成分を２種以上組み合わせる場合は、（ａ）成分の総量 １重量部に対し、（ｃ）成分の総量は１重量部〜５００重量部であり、好ましくは、１０重量部〜３５０重量部である。
本発明における（ｃ）成分の含有量は、（ａ）成分：スコポラミン類 ０．０１〜０．５０ｍｇに対し、０．０１〜２５０ｍｇであり、好ましくは０．０１〜１８０ｍｇである。
（ａ）成分もしくは（ｃ）成分を２種以上組み合わせる場合は、（ａ）成分の総量 ０．０１〜０．５０ｍｇに対し、（ｃ）成分の総量は０．０１〜２５０ｍｇであり、好ましくは０．０１〜１８０ｍｇである。
本発明における（ｃ）成分の１製剤単位あたりの濃度は、通常、０．００１５Ｗ／Ｗ％〜９０Ｗ／Ｗ％であり、好ましくは、０．０５Ｗ／Ｗ％〜９０Ｗ／Ｗ％である。（ｃ）成分を２種以上組み合わせる場合は、その総量の含有量である。
Examples of the antihistamine used in the present invention (hereinafter sometimes referred to as the component (c)) include meclizine, chlorpheniramine, diphenhydramine, diphenylpyraline, dimenhydrinate, phenetazine, promethazine, diphenidol, pheniramine, diphenylpyraline, Or those salts are mentioned, You may contain 2 or more types of those antihistamines. Preferably, meclizine and a salt thereof, diphenhydramine and a salt thereof, and chlorpheniramine and a salt thereof are mentioned, among which, specifically, meclizine hydrochloride, dl-chlorpheniramine maleate, chlorpheniramine d-maleate Particularly preferred are pheniramine maleate, diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, diphenhydramine fumarate, diphenylpyrazine hydrochloride, phenetazine tannate, diphenylpyraline teocrate, promethazine hydrochloride, promethazine methylene disalicylate, dimenhydrinate, and the like. In addition, (a) component: Meclizine hydrochloride is particularly preferable from the viewpoint of the bitterness alleviating effect of scopolamines.
(C) component in this invention: Content of an antihistamine is 1 weight part-500 weight part with respect to 1 weight part of scopolamines, Preferably, it is 10 weight part-350 weight part.
When combining two or more types of component (a) or component (c), the total amount of component (c) is 1 to 500 parts by weight, preferably 10 parts per 1 part by weight of the total amount of component (a). Parts by weight to 350 parts by weight.
Content of (c) component in this invention is 0.01-250 mg with respect to (a) component: scopolamine 0.01-0.50 mg, Preferably it is 0.01-180 mg.
When combining two or more types of component (a) or component (c), the total amount of component (c) is 0.01 to 250 mg with respect to the total amount of component (a) 0.01 to 0.50 mg, preferably 0.01 to 180 mg.
In the present invention, the concentration of component (c) per preparation unit is usually 0.0015 W / W% to 90 W / W%, preferably 0.05 W / W% to 90 W / W%. (C) When combining 2 or more types of component, it is content of the total amount.
本発明は更に別の薬効成分を含んでいてもよい。このような成分の種類は特に制限されず、例えば、スコポラミン以外の副交感神経遮断薬、鎮痙薬、鎮吐薬、鎮静薬、強心利尿薬などが例示できる。本発明において好適な成分としては、例えば、次のような成分が挙げられる。これらを２種以上含んでいてもよい。
スコポラミン以外の副交感神経遮断薬：例えば、塩酸オキシフェンサイクリミン、塩酸ジサイクロミン、塩酸メチキセン、臭化メチルアトロピン、臭化メチルアニソトロピン、臭化メチル−１−ヒヨスチアミン、臭化メチルベナクチジウム、ベラドンナエキス、ヨウ化イソプロパミド、ヨウ化ジフェニルピペリジノメチルジオキソラン、ロートエキスなど。
鎮痙薬：例えば、塩酸パパリンなど。
鎮吐薬：例えば、アミノ安息香酸エチル、シュウ酸セリウム、ピペリジルアセチルアミノ安息香エチルなど。
鎮静薬：例えば、アリルイソプロピルアセチル尿素、ブロムワレリル尿素など
強心利尿薬：例えば、カフェイン、クエン酸カフェイン、無水カフェイン、アミノフィリン、ジプロフィリン、テオフィリンなど。
これらの薬効成分で苦味が更に強くなった場合でも、本発明によりその苦味を緩和され得る。
The present invention may further contain other medicinal ingredients. The kind of such components is not particularly limited, and examples thereof include parasympatholytic agents other than scopolamine, antispasmodics, antiemetics, sedatives, and cardiotonic diuretics. Examples of suitable components in the present invention include the following components. Two or more of these may be included.
Parasympatholytic agents other than scopolamine: for example, oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, methylatropine bromide, methyl anisotropin bromide, methyl-1-hyostiamine bromide, methylbenactidium bromide, belladonna Extracts, isopropamide iodide, diphenylpiperidinomethyldioxolane iodide, funnel extract, etc.
Antispasmodic: for example, paparin hydrochloride.
Antiemetics: for example, ethyl aminobenzoate, cerium oxalate, piperidylacetylaminoethyl ethylbenzoate and the like.
Sedatives: for example, allyl isopropyl acetylurea, bromvalerylurea, etc. Cardiac diuretics: for example, caffeine, caffeine citrate, anhydrous caffeine, aminophylline, diprofylline, theophylline and the like.
Even when the bitterness becomes stronger with these medicinal ingredients, the bitterness can be mitigated by the present invention.
本発明においては、甘味成分や清涼化成分を含有して、その苦味を更に緩和してもよい。甘味成分や清涼化成分としては、例えば、糖、糖アルコール、ハッカ油、ハッカ水、ｄｌ−メントール、ｌ−メントールなどが挙げられ、それらを２種以上含んでいてもよい。 In the present invention, a sweetening component and a refreshing component may be contained to further alleviate the bitterness. Examples of the sweetening component and the refreshing component include sugar, sugar alcohol, mint oil, mint water, dl-menthol, and l-menthol, and may contain two or more thereof.
本発明の医薬組成物は、固形製剤であることが好ましい。固形製剤としては、散剤、粉末剤、細粒剤、顆粒剤、ドライシロップ、丸剤、トローチ剤、錠剤［素錠、糖衣錠、口腔内速崩壊錠、チュアブル錠、発泡錠、トローチ剤、フィルムコーティング錠等を含む］、カプセル剤などが挙げられ、好ましくは顆粒剤および錠剤である。錠剤としては、口腔内崩壊錠、特にチュアブル錠が好ましい。
また、本発明の医薬組成物は、更に常法によりコーティング等を施してもよい。
The pharmaceutical composition of the present invention is preferably a solid preparation. Solid preparations include powders, powders, fine granules, granules, dry syrups, pills, lozenges, tablets [plain tablets, sugar-coated tablets, intraoral quick disintegrating tablets, chewable tablets, effervescent tablets, lozenges, film-coated tablets Etc.], capsules and the like, and granules and tablets are preferable. As the tablet, an orally disintegrating tablet, particularly a chewable tablet is preferable.
In addition, the pharmaceutical composition of the present invention may be further coated by a conventional method.
本発明の医薬組成物は、前記以外の他の製剤成分として、医薬部外品や医薬品又は食品などに使用される慣用の成分、例えば、崩壊剤、賦形剤、結合剤、滑沢剤、抗酸化剤、コーティング剤、着色剤、矯味剤、可塑剤、甘味剤、香料、溶剤、ｐＨ調整剤、懸濁化剤、消泡剤、粘稠剤、溶解補助剤、持続化剤、安定（化）剤、キレート剤、還元剤、流動化剤、光沢化剤、界面活性剤、可溶（化）剤、等を含有してもよい。
以下に任意に配合できる慣用成分を具体的に例示するが、本発明に用いられる成分はこれらに限定されるものではない。
The pharmaceutical composition of the present invention is a conventional ingredient used for quasi-drugs, pharmaceuticals, foods, etc., as other pharmaceutical ingredients other than those described above, such as disintegrants, excipients, binders, lubricants, Antioxidants, coating agents, coloring agents, flavoring agents, plasticizers, sweeteners, fragrances, solvents, pH adjusters, suspending agents, antifoaming agents, thickening agents, solubilizing agents, sustaining agents, stabilizing ( ) Agent, chelating agent, reducing agent, fluidizing agent, brightener, surfactant, solubilizing agent, etc.
Specific examples of conventional components that can be arbitrarily blended are shown below, but the components used in the present invention are not limited thereto.
崩壊剤：デンプン類（トウモロコシデンプン、バレイショデンプン、ヒドロキシプロピルスターチ、カルボキシメチルスターチナトリウム、部分アルファー化デンプンなど）、セルロース類（カルボキシメチルセルロースカルシウム、結晶セルロース、ヒドロキシプロピルセルロース、低置換度ヒドロキシプロピルセルロース、カルメロース、カルメロースカルシウム、クロスカルメロースナトリウムなど）、形質無水ケイ酸など。本発明には好ましくはトウモロコシデンプン、ヒドロキシプロピルセルロース、結晶セルロース、軽質無水ケイ酸などが用いられる。 Disintegrators: starches (corn starch, potato starch, hydroxypropyl starch, sodium carboxymethyl starch, partially pregelatinized starch, etc.), celluloses (carboxymethylcellulose calcium, crystalline cellulose, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, carmellose) , Carmellose calcium, croscarmellose sodium, etc.) and plasma silicic acid. In the present invention, corn starch, hydroxypropyl cellulose, crystalline cellulose, light anhydrous silicic acid and the like are preferably used.
賦形剤：ブドウ糖、白糖、乳糖、果糖などの糖類、結晶セルロース、カルメロースナトリウム、リン酸水素カルシウム、コムギデンプン、コメデンプン、トウモロコシデンプン、バレイショデンプン、デキストリン、β−シクロデキストリン、軽質無水ケイ酸、酸化チタン、メタケイ酸アルミン酸マグネシウム、タルク、カオリンなど。 Excipients: Sugars such as glucose, sucrose, lactose, fructose, crystalline cellulose, carmellose sodium, calcium hydrogen phosphate, wheat starch, rice starch, corn starch, potato starch, dextrin, β-cyclodextrin, light anhydrous silicic acid , Titanium oxide, magnesium aluminate metasilicate, talc, kaolin, etc.
結合剤：セルロース誘導体（メチルセルロース、エチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロースなど）、ポリビニルピロリドン、ポリビニルアルコール、アクリル酸系高分子、ゼラチン、アラビアゴム、プルラン、アルファー化デンプン、カンテン、トラガント、アルギン酸ナトリウム、アルギン酸プロピレングリコールエステルなど。 Binder: Cellulose derivatives (methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, etc.), polyvinylpyrrolidone, polyvinyl alcohol, acrylic polymer, gelatin, gum arabic, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, Alginic acid propylene glycol ester and the like.
滑沢剤：ステアリン酸、ステアリン酸マグネシウム、ステアリン酸カルシウム、ステアリン酸ポリオキシル、セタノール、タルク、硬化油、ショ糖脂肪酸エステル、ジメチルポリシロキサン、ミツロウ、サラシミツロウなど。
抗酸化剤：ジブチルヒドロキシトルエン（ＢＨＴ）、没食子酸プロピル、ブチルヒドロキシアニソール（ＢＨＡ）、トコフェロール、クエン酸など。
Lubricant: stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax, beeswax, etc.
Antioxidants: Dibutylhydroxytoluene (BHT), propyl gallate, butylhydroxyanisole (BHA), tocopherol, citric acid and the like.
コーティング剤：ヒドロキシプロピルメチルセルロース、ヒドロキシプロピルセルロース、メチルセルロース、エチルセルロース、ヒドロキシプロピルメチルセルロースフタレート、ヒドロキシプロピルメチルセルロースアセテートサクシネート、カルボキシメチルエチルセルロース、酢酸フタル酸セルロース、ポリビニルアセタールジエチルアミノアセテート、アミノアルキルメタアクリレートコポリマー、ヒドロキシプロピルメチルセルロースアセテートサクシネート、メタアクリル酸コポリマー、ポリビニルアセタートジエチルアミノアセテート、セラックなど。 Coating agent: Hydroxypropyl methylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, cellulose acetate phthalate, polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer, hydroxypropylmethylcellulose Acetate succinate, methacrylic acid copolymer, polyvinyl acetate diethylaminoacetate, shellac, etc.
着色剤：食用赤色２号、食用赤色３号、食用赤色１０２号、食用黄色４号、食用黄色５号、食用青色１号、食用黄色４号金属レーキ、銅クロロフィンナトリウム、リボフラビン、ウコン抽出液、カロチン液など。
矯味剤：アスパルテーム、アスコルビン酸、ステビア、メントール、カンゾウ粗エキス、単シロップなど。
Colorant: Food Red No. 2, Food Red No. 3, Food Red No. 102, Food Yellow No. 4, Food Yellow No. 5, Food Blue No. 1, Food Yellow No. 4, Metal Lake, Copper Chlorofin Sodium, Riboflavin, Turmeric Extract Carotene solution.
Flavoring agents: aspartame, ascorbic acid, stevia, menthol, licorice crude extract, simple syrup, etc.
可塑剤：クエン酸トリエチル、ポリエチレングリコール、トリアセチン、セタノールなど。
甘味剤：ショ糖、アスパルテームなどの天然又は合成甘味剤。
香料：カンフル、ボルネオール、シンナムアルデヒドなど。
Plasticizer: Triethyl citrate, polyethylene glycol, triacetin, cetanol and the like.
Sweetener: Natural or synthetic sweeteners such as sucrose and aspartame.
Fragrance: camphor, borneol, cinnamaldehyde, etc.
溶剤：水、エタノール、イソプロパノール、ラウリルアルコール、セタノール、ステアリルアルコール、オレイルアルコール、ラノリンアルコール、ベヘニルアルコール、２−ヘキシルデカノール、イソステアリルアルコール、２−オクチルドデカノールなど。 Solvent: water, ethanol, isopropanol, lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, lanolin alcohol, behenyl alcohol, 2-hexyl decanol, isostearyl alcohol, 2-octyldodecanol and the like.
ｐＨ調整剤：クエン酸、リンゴ酸、リン酸水素ナトリウム、リン酸二カリウムなど。
懸濁化剤：カオリン、カルメロースナトリウム、キサンタンガム、メチルセルロース、トラガントなど。
消泡剤：ジメチルポリシロキサン、シリコン消泡剤など。
粘稠剤：キサンタンガム、トラガント、メチルセルロース、デキストリンなど。
溶解補助剤：エタノール、ショ糖脂肪酸エステル、マクロゴールなど。
pH adjuster: citric acid, malic acid, sodium hydrogen phosphate, dipotassium phosphate, etc.
Suspending agents: kaolin, carmellose sodium, xanthan gum, methylcellulose, tragacanth, etc.
Antifoaming agent: dimethylpolysiloxane, silicon antifoaming agent, etc.
Thickener: xanthan gum, tragacanth, methylcellulose, dextrin, etc.
Solubilizer: ethanol, sucrose fatty acid ester, macrogol, etc.
上述のような慣用成分の配合割合は、医薬組成物の剤形や大きさ、用途などによって適宜選択でき、例えば、固形製剤の場合、製剤全体に対して０．００１〜９７重量％、好ましくは０．０１〜９０重量％などであり得る。 The blending ratio of the conventional ingredients as described above can be appropriately selected depending on the dosage form, size, use and the like of the pharmaceutical composition. For example, in the case of a solid preparation, 0.001 to 97% by weight, preferably It may be from 0.01 to 90% by weight.
本発明の医薬組成物は、その薬効成分であるスコポラミン類の有する薬効に基づく薬剤として用いられ、例えば、乗り物酔いによるめまい、吐き気、頭痛の予防及び緩和等に用いられ得る。
本発明の医薬組成物は、通常の医薬組成物と同様の方法で投与することができる。
本発明の医薬組成物の投与量は、その形態、投与方法、投与目的及び当該組成物の投与対象者の年齢、体重、症状によって適宜設定される。また、本発明の医薬組成物の経口投与は、所望の投与量範囲内において、１日あたり単回で、又は数回に分けて行ってもよく、食前、食間、食後、又は食事と同時に投与されてもよい。なお、本明細書中の用語「投与」は、「服用」を包含することを意図して用いられる。なお、本明細書中の用語は「経口投与」、「内服」と互換的に用いられ得る。
The pharmaceutical composition of the present invention is used as a drug based on the medicinal properties of scopolamines, which are its medicinal properties, and can be used, for example, for prevention and alleviation of dizziness due to motion sickness, nausea and headache.
The pharmaceutical composition of the present invention can be administered in the same manner as a normal pharmaceutical composition.
The dosage of the pharmaceutical composition of the present invention is appropriately determined depending on the form, administration method, administration purpose, and age, weight, and symptoms of the subject of administration of the composition. In addition, the oral administration of the pharmaceutical composition of the present invention may be performed once per day or divided into several times within a desired dose range, and administered before meals, between meals, after meals, or simultaneously with meals. May be. In addition, the term “administration” in the present specification is intended to include “taking”. The terms in this specification may be used interchangeably with “oral administration” and “internal use”.
以下に、実施例に基づいて本発明を説明するが、本発明はこれらの実施例によって制限されるものではない。 Hereinafter, the present invention will be described based on examples, but the present invention is not limited to these examples.
試験１
炭酸マグネシウムによるスコポラミンの苦味の緩和効果を確認するために、下記の表１に従い、各成分を秤量し、常法に従い混合したものを、試料として調製した。なお、各成分の効果を確認する際に調製した個々の成分を除いた混合試料では、除いた成分の代わりに乳糖またはバレイショデンプンを用いた。
Test 1
In order to confirm the effect of mitigating the bitter taste of scopolamine by magnesium carbonate, each component was weighed according to Table 1 below and mixed according to a conventional method to prepare a sample. In the mixed sample excluding the individual components prepared when confirming the effect of each component, lactose or potato starch was used in place of the excluded component.
（官能試験）
ビジュアルアナログスケール（ＶＡＳ）法を用いて、各試料の苦味の強さを評価した。具体的には、調査シートに１０ｃｍの直線を引き、この直線の左端（０ｃｍ）を０点（全く苦味がない）、右端（１０ｃｍ）を１０点（非常に強い苦味）とし、上記試料（混合粉）を１回あたり０．４ｇ服用した時に感じられる「苦味」について、パネラーが感じた程度を調査シートに記載した。なおパネラーは、比較例１Ａを服用するとき、苦味の強さ（スコア値）４．０点以上の苦味を感ずるものとした。また、苦味の評価は、４人のパネラーのスコア平均値及び苦味抑制率を算出することにより行った。苦味抑制率は、下記の式１により算出した。
式１：苦味抑制率（％）＝
[１−(実施例の苦味の強さ：スコア値平均)／(比較例の苦味の強さ：スコア値平均)]
×100
結果を表１に示し、各試料の苦味の強さをグラフにまとめた（図１および図２）。
(Sensory test)
The bitterness intensity of each sample was evaluated using a visual analog scale (VAS) method. Specifically, a 10 cm straight line is drawn on the survey sheet, the left end (0 cm) of this line is 0 point (no bitterness at all), the right end (10 cm) is 10 points (very strong bitterness), and the sample (mixed) About the “bitterness” felt when taking 0.4 g of (powder) at a time, the degree to which the panel felt was described in the survey sheet. In addition, when taking the comparative example 1A, a panelist shall feel the bitterness of the bitterness intensity (score value) 4.0 points or more. Moreover, bitterness evaluation was performed by calculating the average score value and bitterness suppression rate of four panelists. The bitterness suppression rate was calculated by the following formula 1.
Formula 1: Bitterness suppression rate (%) =
[1- (Intensity of bitterness in Examples: average score value) / (Intensity of bitterness in Comparative Examples: average score value)]
× 100
The results are shown in Table 1, and the bitterness intensity of each sample is summarized in a graph (FIGS. 1 and 2).
（結果）
臭化水素酸スコポラミン（比較例１Ａ）では、いずれのパネラーも強い苦味を感じた。この苦味は、炭酸マグネシウムが加わることにより軽減した（実施例1Ａ）。さらにメクリジン塩酸塩が加わることにより、さらに苦味は軽減され（実施例１Ｂ）、臭化水素酸スコポラミに炭酸マグネシウム及びメクリジン塩酸塩が加わることにより、より高い苦味緩和作用を得ることが出来た。
なお、乳糖に代えてバレイショデンプンで倍散とした場合も、臭化水素酸スコポラミン苦味は軽減されず（比較例１Ａと比較例２との比較）、乳糖、バレイショデンプン共に苦味の緩和作用がないことを確認した。
With scopolamine hydrobromide (Comparative Example 1A), all panelists felt a strong bitter taste. This bitterness was reduced by adding magnesium carbonate (Example 1A). Furthermore, bitterness was further reduced by adding meclizine hydrochloride (Example 1B), and by adding magnesium carbonate and meclizine hydrochloride to scopolami hydrobromide, a higher bitterness mitigating action could be obtained.
In addition, even when triturating with potato starch instead of lactose, the scopolamine hydrobromide bitterness is not reduced (comparison between Comparative Example 1A and Comparative Example 2), and neither lactose nor potato starch has an alleviating action on bitterness. It was confirmed.
試験２
各種制酸剤によるスコポラミンの苦味の緩和効果を確認するために、下記の表２−１及び表２−２に従い、各成分を秤量し、常法に従い混合したものを、試料として調製した。
Test 2
In order to confirm the effect of alleviating the bitter taste of scopolamine by various antacids, each component was weighed according to the following Table 2-1 and Table 2-2 and mixed according to a conventional method to prepare a sample.
（官能試験）
試験１と同様の方法で行った。結果を表２−１及び表２−２に示し、各試料の苦味の強さをグラフにまとめた（図２〜図５）。なお、実施例２と比較例２の結果は、試験１の結果を用いた。
(Sensory test)
The same method as in Test 1 was performed. The results are shown in Table 2-1 and Table 2-2, and the bitterness intensity of each sample is summarized in a graph (FIGS. 2 to 5). The results of Test 1 were used as the results of Example 2 and Comparative Example 2.
（結果）
炭酸マグネシウムに代えて、種々の制酸剤を臭化水素酸スコポラミン及びメクリジン塩酸塩に配合し、苦味を評価した。いずれの制酸剤の場合にも、臭化水素酸スコポラミンの苦味が低減した。炭酸マグネシウムの場合に、最も顕著な苦味緩和作用がみられた。
Instead of magnesium carbonate, various antacids were blended with scopolamine hydrobromide and meclizine hydrochloride to evaluate the bitterness. In any of the antacids, the bitter taste of scopolamine hydrobromide was reduced. In the case of magnesium carbonate, the most remarkable bitterness mitigating action was observed.
なお、抗ヒスタミン剤を含まない場合の、種々の制酸剤によるスコポラミン類の苦味緩和効果を確認するために、上記表２及び表４の結果から抗ヒスタミン剤を含まない臭化水素酸スコポラミンと各制酸剤との組み合わせの結果を下記の表３にまとめた。各種制酸剤の中で、抗ヒスタミン剤を含まない場合にも、炭酸マグネシウムが最も顕著なスコポラミン類の苦味緩和作用を示した。
下記の表４に従い、各成分を秤量し、常法でチュアブル錠を調製した。調製した各チュアブル錠をヒトに水なしで服用させたが、いずれの場合にも、結果として苦味をほとんど感じることなく、支障なく服用することができた。
また、同処方で、常法で顆粒剤を調製した。顆粒剤の場合も同様に、ヒトに水なしで服用させたが、いずれの場合にも、結果として苦味をほとんど感じることなく、支障なく服用することができた。
以上のように、本発明の表４の製剤においては、水なしで服用するのに支障がない程、苦味は緩和されることが確認された。
Moreover, the granule was prepared by the conventional method with the same formulation. Similarly, in the case of granules, humans were allowed to take without water, but in any case, they were able to be taken without any difficulty with almost no bitterness.
As described above, it was confirmed that the bitterness was alleviated in the preparations of Table 4 of the present invention so that there was no hindrance to taking without water.
Claims (9)
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| CN105326803A (en) * | 2015-12-05 | 2016-02-17 | 翔宇药业股份有限公司 | Difenidol hydrochloride tablets for treating motion sickness and preparation method thereof |
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