TWI343818B - - Google Patents
Download PDFInfo
- Publication number
- TWI343818B TWI343818B TW092132009A TW92132009A TWI343818B TW I343818 B TWI343818 B TW I343818B TW 092132009 A TW092132009 A TW 092132009A TW 92132009 A TW92132009 A TW 92132009A TW I343818 B TWI343818 B TW I343818B
- Authority
- TW
- Taiwan
- Prior art keywords
- stomach
- pharmaceutical composition
- powder
- sucralfate
- weight
- Prior art date
Links
- 239000003814 drug Substances 0.000 claims description 39
- 229940079593 drug Drugs 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 239000000843 powder Substances 0.000 claims description 20
- 238000004519 manufacturing process Methods 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 238000007908 dry granulation Methods 0.000 claims description 11
- 210000002784 stomach Anatomy 0.000 claims description 11
- 235000019640 taste Nutrition 0.000 claims description 11
- 229960004291 sucralfate Drugs 0.000 claims description 8
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 claims description 8
- 244000223760 Cinnamomum zeylanicum Species 0.000 claims description 6
- 235000016639 Syzygium aromaticum Nutrition 0.000 claims description 6
- 235000017803 cinnamon Nutrition 0.000 claims description 6
- 235000003392 Curcuma domestica Nutrition 0.000 claims description 5
- 244000273928 Zingiber officinale Species 0.000 claims description 5
- 235000006886 Zingiber officinale Nutrition 0.000 claims description 5
- 235000003373 curcuma longa Nutrition 0.000 claims description 5
- 239000000284 extract Substances 0.000 claims description 5
- 235000008397 ginger Nutrition 0.000 claims description 5
- 230000000873 masking effect Effects 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 235000013976 turmeric Nutrition 0.000 claims description 5
- 241000675108 Citrus tangerina Species 0.000 claims description 4
- 244000163122 Curcuma domestica Species 0.000 claims description 4
- 230000035807 sensation Effects 0.000 claims description 4
- 235000019615 sensations Nutrition 0.000 claims description 4
- 235000007129 Cuminum cyminum Nutrition 0.000 claims description 3
- 244000304337 Cuminum cyminum Species 0.000 claims description 3
- 244000223014 Syzygium aromaticum Species 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 239000004576 sand Substances 0.000 claims description 3
- 238000013329 compounding Methods 0.000 claims description 2
- 235000008216 herbs Nutrition 0.000 claims 2
- 235000002020 sage Nutrition 0.000 claims 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 239000013589 supplement Substances 0.000 claims 1
- 238000000034 method Methods 0.000 description 23
- 230000000694 effects Effects 0.000 description 18
- 239000004480 active ingredient Substances 0.000 description 16
- 238000005469 granulation Methods 0.000 description 15
- 230000003179 granulation Effects 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 239000004615 ingredient Substances 0.000 description 13
- 239000000654 additive Substances 0.000 description 11
- 239000008187 granular material Substances 0.000 description 11
- -1 ascorbate calcium salt Chemical class 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 235000003599 food sweetener Nutrition 0.000 description 9
- 239000003765 sweetening agent Substances 0.000 description 9
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000011230 binding agent Substances 0.000 description 8
- 210000000214 mouth Anatomy 0.000 description 8
- 230000000996 additive effect Effects 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 238000001694 spray drying Methods 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 6
- 235000019658 bitter taste Nutrition 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 5
- 210000002249 digestive system Anatomy 0.000 description 5
- 238000001125 extrusion Methods 0.000 description 5
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 239000004083 gastrointestinal agent Substances 0.000 description 5
- 229940127227 gastrointestinal drug Drugs 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 229940041616 menthol Drugs 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 108010011485 Aspartame Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000000605 aspartame Substances 0.000 description 4
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 4
- 235000010357 aspartame Nutrition 0.000 description 4
- 229960003438 aspartame Drugs 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 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 description 3
- 244000061408 Eugenia caryophyllata Species 0.000 description 3
- 235000004204 Foeniculum vulgare Nutrition 0.000 description 3
- 240000006927 Foeniculum vulgare Species 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 3
- 229940024545 aluminum hydroxide Drugs 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 235000009508 confectionery Nutrition 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 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 description 3
- 238000009775 high-speed stirring Methods 0.000 description 3
- 229960001545 hydrotalcite Drugs 0.000 description 3
- 229910001701 hydrotalcite Inorganic materials 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 3
- 239000001095 magnesium carbonate Substances 0.000 description 3
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 3
- 238000010008 shearing Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000005550 wet granulation Methods 0.000 description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000132012 Atractylodes Species 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 235000008496 Drimys aromatica Nutrition 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 240000002262 Litsea cubeba Species 0.000 description 2
- 235000012854 Litsea cubeba Nutrition 0.000 description 2
- 206010036790 Productive cough Diseases 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 244000269722 Thea sinensis Species 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 150000004645 aluminates Chemical class 0.000 description 2
- 229940069428 antacid Drugs 0.000 description 2
- 239000003159 antacid agent Substances 0.000 description 2
- 229940072107 ascorbate Drugs 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 235000019606 astringent taste Nutrition 0.000 description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
- 238000000748 compression moulding Methods 0.000 description 2
- 239000007799 cork Substances 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 229960001259 diclofenac Drugs 0.000 description 2
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- RRAFCDWBNXTKKO-UHFFFAOYSA-N eugenol Chemical compound COC1=CC(CC=C)=CC=C1O RRAFCDWBNXTKKO-UHFFFAOYSA-N 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 235000019204 saccharin Nutrition 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- 229940081974 saccharin Drugs 0.000 description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 208000024794 sputum Diseases 0.000 description 2
- 210000003802 sputum Anatomy 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- 239000001096 (4-ethenyl-1-azabicyclo[2.2.2]octan-7-yl)-(6-methoxyquinolin-4-yl)methanol hydrochloride Substances 0.000 description 1
- AKYHKWQPZHDOBW-UHFFFAOYSA-N (5-ethenyl-1-azabicyclo[2.2.2]octan-7-yl)-(6-methoxyquinolin-4-yl)methanol Chemical compound OS(O)(=O)=O.C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 AKYHKWQPZHDOBW-UHFFFAOYSA-N 0.000 description 1
- DJAHKBBSJCDSOZ-AJLBTXRUSA-N (5z,9e,13e)-6,10,14,18-tetramethylnonadeca-5,9,13,17-tetraen-2-one;(5e,9e,13e)-6,10,14,18-tetramethylnonadeca-5,9,13,17-tetraen-2-one Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C/CCC(C)=O.CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CCC(C)=O DJAHKBBSJCDSOZ-AJLBTXRUSA-N 0.000 description 1
- CEWQXYIHVSLPDV-WLHGVMLRSA-N (e)-but-2-enedioic acid;pyrrolidine Chemical compound C1CCNC1.OC(=O)\C=C\C(O)=O CEWQXYIHVSLPDV-WLHGVMLRSA-N 0.000 description 1
- NNKXWRRDHYTHFP-HZQSTTLBSA-N (r)-[(2s,4s,5r)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol;hydron;dichloride Chemical compound Cl.Cl.C([C@H]([C@H](C1)C=C)C2)CN1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 NNKXWRRDHYTHFP-HZQSTTLBSA-N 0.000 description 1
- AFDAUYYWZNNSFV-UHFFFAOYSA-N 1-(5-bromo-2-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC(Br)=CC=C1[N+]([O-])=O AFDAUYYWZNNSFV-UHFFFAOYSA-N 0.000 description 1
- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 description 1
- KGYXYKHTHJPEBX-UHFFFAOYSA-N 5-ethoxy-3-ethoxycarbonyl-3-hydroxy-5-oxopentanoic acid Chemical compound CCOC(=O)CC(O)(CC(O)=O)C(=O)OCC KGYXYKHTHJPEBX-UHFFFAOYSA-N 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241001061264 Astragalus Species 0.000 description 1
- CQONVBIGUJWUFE-UHFFFAOYSA-N Butoctamide hydrogen succinate Chemical compound CCCCC(CC)CNC(=O)CC(C)OC(=O)CCC(O)=O CQONVBIGUJWUFE-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- NPBVQXIMTZKSBA-UHFFFAOYSA-N Chavibetol Natural products COC1=CC=C(CC=C)C=C1O NPBVQXIMTZKSBA-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- ZNIFSRGNXRYGHF-UHFFFAOYSA-N Clonidine hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1NC1=NCCN1 ZNIFSRGNXRYGHF-UHFFFAOYSA-N 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 244000247747 Coptis groenlandica Species 0.000 description 1
- 235000002991 Coptis groenlandica Nutrition 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000218176 Corydalis Species 0.000 description 1
- 244000008991 Curcuma longa Species 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- BALXUFOVQVENIU-GNAZCLTHSA-N Ephedrine hydrochloride Chemical compound Cl.CN[C@@H](C)[C@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-GNAZCLTHSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- 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 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- 239000005770 Eugenol Substances 0.000 description 1
- 239000001576 FEMA 2977 Substances 0.000 description 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 1
- 244000303040 Glycyrrhiza glabra Species 0.000 description 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 102000003710 Histamine H2 Receptors Human genes 0.000 description 1
- 108090000050 Histamine H2 Receptors Proteins 0.000 description 1
- 235000008694 Humulus lupulus Nutrition 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000005569 Iron sulphate Substances 0.000 description 1
- 235000013421 Kaempferia galanga Nutrition 0.000 description 1
- 244000062241 Kaempferia galanga Species 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 241000237502 Ostreidae Species 0.000 description 1
- 240000004371 Panax ginseng Species 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- HLCFGWHYROZGBI-JJKGCWMISA-M Potassium gluconate Chemical compound [K+].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O HLCFGWHYROZGBI-JJKGCWMISA-M 0.000 description 1
- UVMRYBDEERADNV-UHFFFAOYSA-N Pseudoeugenol Natural products COC1=CC(C(C)=C)=CC=C1O UVMRYBDEERADNV-UHFFFAOYSA-N 0.000 description 1
- 235000009694 Quassia amara Nutrition 0.000 description 1
- SMTZFNFIKUPEJC-UHFFFAOYSA-N Roxane Chemical compound CC(=O)OCC(=O)NCCCOC1=CC=CC(CN2CCCCC2)=C1 SMTZFNFIKUPEJC-UHFFFAOYSA-N 0.000 description 1
- 240000004780 Simarouba amara Species 0.000 description 1
- 235000011984 Simarouba amara Nutrition 0.000 description 1
- 235000009689 Simarouba glauca Nutrition 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 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 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- HJLSLZFTEKNLFI-UHFFFAOYSA-N Tinidazole Chemical compound CCS(=O)(=O)CCN1C(C)=NC=C1[N+]([O-])=O HJLSLZFTEKNLFI-UHFFFAOYSA-N 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- FSRLGULMGJGKGI-BTJKTKAUSA-N Trimebutine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=CC=1C(CC)(N(C)C)COC(=O)C1=CC(OC)=C(OC)C(OC)=C1 FSRLGULMGJGKGI-BTJKTKAUSA-N 0.000 description 1
- YSIITVVESCNIPR-UHFFFAOYSA-N Troxipide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NC2CNCCC2)=C1 YSIITVVESCNIPR-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 108010059993 Vancomycin Proteins 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- OOIOHEBTXPTBBE-UHFFFAOYSA-N [Na].[Fe] Chemical compound [Na].[Fe] OOIOHEBTXPTBBE-UHFFFAOYSA-N 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 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 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229940024223 alseroxylon Drugs 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 1
- RJZNFXWQRHAVBP-UHFFFAOYSA-I aluminum;magnesium;pentahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Al+3] RJZNFXWQRHAVBP-UHFFFAOYSA-I 0.000 description 1
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229960004543 anhydrous citric acid Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003793 antidiarrheal agent Substances 0.000 description 1
- 229940125714 antidiarrheal agent Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000003904 antiprotozoal agent Substances 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 235000006533 astragalus Nutrition 0.000 description 1
- 229960000796 barbital sodium Drugs 0.000 description 1
- FTOAOBMCPZCFFF-UHFFFAOYSA-N barbitone sodium Natural products CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 1
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 description 1
- 229940093265 berberine Drugs 0.000 description 1
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 208000024330 bloating Diseases 0.000 description 1
- 229950006519 butoctamide Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000000496 cardiotonic agent Substances 0.000 description 1
- 229960005361 cefaclor Drugs 0.000 description 1
- QYIYFLOTGYLRGG-GPCCPHFNSA-N cefaclor Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 QYIYFLOTGYLRGG-GPCCPHFNSA-N 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229910000420 cerium oxide Inorganic materials 0.000 description 1
- 239000010227 chenpi Substances 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 229960002626 clarithromycin Drugs 0.000 description 1
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
- 229960002925 clonidine hydrochloride Drugs 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229940124568 digestive agent Drugs 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 1
- OGAKLTJNUQRZJU-UHFFFAOYSA-N diphenidol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)CCCN1CCCCC1 OGAKLTJNUQRZJU-UHFFFAOYSA-N 0.000 description 1
- 229960003520 diphenidol Drugs 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229960002534 ephedrine hydrochloride Drugs 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229960002217 eugenol Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229940125697 hormonal agent Drugs 0.000 description 1
- POUMFISTNHIPTI-BOMBIWCESA-N hydron;(2s,4r)-n-[(1r,2r)-2-hydroxy-1-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide;chloride Chemical compound Cl.CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 POUMFISTNHIPTI-BOMBIWCESA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- CFUQBFQTFMOZBK-QUCCMNQESA-N ibazocine Chemical compound C12=CC(O)=CC=C2C[C@H]2N(CC=C(C)C)CC[C@]1(C)C2(C)C CFUQBFQTFMOZBK-QUCCMNQESA-N 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000000077 insect repellent Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 229960001595 lincomycin hydrochloride Drugs 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229960004329 metformin hydrochloride Drugs 0.000 description 1
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin hydrochloride Natural products CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229940051020 methylephedrine hydrochloride Drugs 0.000 description 1
- 229960004503 metoclopramide Drugs 0.000 description 1
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 229950005216 napadisilate Drugs 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- SGXXNSQHWDMGGP-IZZDOVSWSA-N nizatidine Chemical compound [O-][N+](=O)\C=C(/NC)NCCSCC1=CSC(CN(C)C)=N1 SGXXNSQHWDMGGP-IZZDOVSWSA-N 0.000 description 1
- 229960004872 nizatidine Drugs 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- BMMGVYCKOGBVEV-UHFFFAOYSA-N oxo(oxoceriooxy)cerium Chemical compound [Ce]=O.O=[Ce]=O BMMGVYCKOGBVEV-UHFFFAOYSA-N 0.000 description 1
- 235000020636 oyster Nutrition 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229960005065 paromomycin sulfate Drugs 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- SUWYPNNPLSRNPS-UNTSEYQFSA-N plaunotol Chemical compound CC(C)=CCC\C(C)=C\CC\C(CO)=C\CC\C(C)=C\CO SUWYPNNPLSRNPS-UNTSEYQFSA-N 0.000 description 1
- 229950009291 plaunotol Drugs 0.000 description 1
- SUWYPNNPLSRNPS-UHFFFAOYSA-N plaunotol Natural products CC(C)=CCCC(C)=CCCC(CO)=CCCC(C)=CCO SUWYPNNPLSRNPS-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- UZXRQGSKGNYWCP-UHFFFAOYSA-M potassium 4-hydroxy-3-methoxybenzenesulfonate hydrate Chemical compound O.[K+].COc1cc(ccc1O)S([O-])(=O)=O UZXRQGSKGNYWCP-UHFFFAOYSA-M 0.000 description 1
- 239000004224 potassium gluconate Substances 0.000 description 1
- 229960003189 potassium gluconate Drugs 0.000 description 1
- 235000013926 potassium gluconate Nutrition 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 239000001120 potassium sulphate Substances 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940088417 precipitated calcium carbonate Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229960003857 proglumide Drugs 0.000 description 1
- 229960002189 propyphenazone Drugs 0.000 description 1
- PXWLVJLKJGVOKE-UHFFFAOYSA-N propyphenazone Chemical compound O=C1C(C(C)C)=C(C)N(C)N1C1=CC=CC=C1 PXWLVJLKJGVOKE-UHFFFAOYSA-N 0.000 description 1
- 229960001811 quinine hydrochloride Drugs 0.000 description 1
- 229960003110 quinine sulfate Drugs 0.000 description 1
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
- 229960000620 ranitidine Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229960003320 roxatidine Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 229960001407 sodium bicarbonate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- RGHFKWPGWBFQLN-UHFFFAOYSA-M sodium;5,5-diethylpyrimidin-3-ide-2,4,6-trione Chemical compound [Na+].CCC1(CC)C([O-])=NC(=O)NC1=O RGHFKWPGWBFQLN-UHFFFAOYSA-M 0.000 description 1
- GFWRVVCDTLRWPK-KPKJPENVSA-N sofalcone Chemical compound C1=CC(OCC=C(C)C)=CC=C1\C=C\C(=O)C1=CC=C(OCC=C(C)C)C=C1OCC(O)=O GFWRVVCDTLRWPK-KPKJPENVSA-N 0.000 description 1
- 229950004782 sofalcone Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 210000004233 talus Anatomy 0.000 description 1
- 229950006156 teprenone Drugs 0.000 description 1
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 229960005053 tinidazole Drugs 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 229960005345 trimebutine Drugs 0.000 description 1
- 229960001341 troxipide Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/61—Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Engineering & Computer Science (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
1343818 (1) 玖、發明說明 【發明所屬之技術領域】 本發明係有關服用時口腔內產生苦味 '酸味、收斂味 等不快感之藥效成份進行製劑化時,可有效抑制該不快感 之醫藥組成物及製造方法。本發明更有關該產生苦味等不 快感之藥效成份的掩飾方法’及做爲有效抑制該不快感之 生藥掩飾劑之使用者。 【先前技術】 做爲醫藥品使用之生理活性成份中,口服時於口腔內 多半產生苦味、酸味 '收斂味 '等不快感成份者。爲抑制 或緩和此種服用時之不快感,被嘗試進行各種方法。 先行,爲減輕抗壞血酸鈣鹽之苦味,而配合阿斯巴甜、 水溶性糖類(還原麥芽糖)及必要時之游離生理活性成份 ’進行壓縮成型製劑化之發明被提出。於公報中,被揭示長 時間抑制抗壞血酸鈣鹽之苦味的壓縮成型製劑,其製造方法 ’及其掩飾方法。又,此公報所記載之發明中,亦以抑制阿 斯巴甜之特異不快味者爲目的者(如:專利文獻1 )。 惟’此公報所載之發明中,其添加物之還原麥芽糖用量 大'錠劑大型化造成吞服困難,製造之裝置大型化,特殊化 等問題產生。又,此發明係有關壓縮成型製劑之內容,劑形 受限於滴劑、糖果等嗜好食品、錠劑、含錠、舌下錠等口腔 用錠劑、而無法期待散劑、顆粒劑類等劑形效果。 又’被揭示含有具苦味之生理活性成份金屬鹽與阿斯巴 -4 - (2) (2)1343818 甜、還原麥芽糖水溶性糖類之成型性製劑(如:專利文獻2) 惟,相同於前述之壓縮成型製劑,其添加物之還原麥芽 糖等水溶性糖類用量大、錠劑大型化 '不易服用、製造裝置 大型化、特殊化等問題產生。且,無法期待散劑、顆粒劑等 劑形之效果。 又,揭示於具不快味成份與矯味劑相互混合物中加入剪 切力取得粉粒體,或於此粉粒體添加蠟成份,更使加入剪切 力之粉粒體進行造粒後,不快味被掩飾之造粒組成物。做爲 矯味劑者如:糖類、合成甜味料、胺基酸、酸味劑等例。此 公報所載發明係以提供抑制口中不快感,具良好矯味持續性 效果之造粒組成物爲目的者。又,以提供廉價設備、簡單之 製造方法爲目的者(如:專利文獻3) « 惟,此造粒組成物之製造方法雖由簡單步驟所構成者, 爲取得被掩飾之造粒組成物卻非進行剪切處理不可者。因此 ,重覆進行該剪切處理而增加步驟數,造成製造成本提高之 問題點。更且,具不快感成份外包蠟成份之形態,因此,投 服後,不易由造粒物溶出有效成份之問題點產生。 如上述,先行技術中1係共通主藥成份之外的添加劑用 量大,主要使用甘味劑抑制不快味者》做爲甜味劑者如:阿 斯巴甜、糖精、還原麥芽糖等例。惟,出現胃部不快感症狀 者服用量多 '甜味強之製劑則不適用。又,如糖尿病之受限 糖份攝取者,實質上有投藥之困難點。 [專利文獻1 ] (3) (3)1343818 專利第31 1 0299號公報(第1〜4欄) [專利文獻2] 特開2000- 1 03 74 6號公報(第I〜3欄) [專利文獻1 ] 特開2 000-] 9] 5 ] 7號公報(第1〜3欄) 如前述,先行技術文獻所揭示之發明中,由於多量添 加主藥成份以外之添加劑使用之,因此,做成錠劑之製劑 化時,出現錠劑大型化、不易服用之問題點。又,主要使 用甜味劑抑制有效成份之不快味,做爲甜味劑例者如:阿 斯巴甜、糖精、還原麥芽糖等。惟,出現胃部不快感症狀 者其服用量大之甜味強製劑爲不適者。又,糖尿病之受限 糖份攝取者實質上亦有投藥困難之問題。 因此,被期待開發一種降低甜味料等添加劑之使用量 ,可抑制服用感不佳成份之味道的醫藥組成物,及其製造 方法。且,被期待其製造方法由簡單步驟所構成,同時, 減少步驟數、降低成本之製造方法者。 【發明內容】 本發明者爲解決上述課題,進行精密硏討後結果發現 ,將服用時產生不快感之生理活性成份配合健胃生藥後, 服用該組成物時,該不快感被緩和之,進而完成本發明。 健胃生藥成份維持原本之健胃效果,同時,對於生理活性 成份具矯味劑作用,因此,先行被做爲矯味劑使用,成功 的減少甜味料等添加物之使用量。而,本發明醫藥組成物 -6 - 1343818
之製造時發現’非使用常例之濕式造粒法,而適用乾式造 粒法者。亦即,藉由乾式造粒法所製造之本發明醫藥組成 物中,意外發現,相較於簡單之混合物,其所配合生藥之 矯味效果大增,進而提昇醫藥組成物之服用感。 使用消化系統出現副作用之藥物,或,服用時口中產 生不快感之生理活性成份,藉由本發明醫藥組成物後,可 減少或消失該副作用,且,可掩飾不快味者。 又,健胃生藥以外之胃腸藥成份者,配合於服用時口 中產生不快感之生理活性成份與健胃生藥後,可掩飾不快 味道。更可取得胃腸藥與健胃生藥分別藥效之相乘效果。 【實施方式】 [發明實施之形態] 本發明係可使服用時產生不快感之生理活性成份進行製 劑化時,被廣泛利用之。做爲此等成份者如:下記例者。於 製劑化時,亦可配合下記成份之I或2以上者。更可組合此等 與其他藥效成份後進行製劑化者。 (1 )胃腸藥成份中服用感不良之成份例 1)做爲消化性潰瘍治療劑者如以下成份例者。 硫糖鋁、乙醯谷醯胺鋁、合次香叶、硫苯醯胺、胃長寧 、丙谷胺、Sofalcone、teprenone ' clebopride malate、 troxipide plaunotol '組織胺H2 受容體指抗劑(Ranitidine 、西米替丁 ' Famolidine、Nizatidine' Roxatidine)、質子 (5) (5)1343818 泵.抑制系 (Omeprazo丨e )。 2) 做爲消化系統用劑者 甲氧氯普胺 (m e t 〇 c 1 〇 p r a in i d e ) 、 a c ] a t ο π i u in napadisilate '馬來酸曲美布汀等。 3) 做爲制酸劑者 乾燥氫氧化鋁凝膠、矽酸鋁酸鎂、矽酸鎂、合成矽酸鋁 、合成水滑石 '氧化鎂、氫氧化鋁鎂、氫氧化鋁•碳酸氫鈉 共沈生成物、氫氧化鋁、碳酸鎂混合乾燥凝膠、氫氧化鋁* 碳酸鎂共沈生成物、氫氧化鎂、碳酸氫鈉、碳酸鎂、沈降碳 酸鈣、矽酸鋁酸鎂、無水磷酸氫鈣、磷酸氫鈣等。 (2)消化系統出現副作用之生理活性物質於服用時口中產 生不快感之成份例 】)催眠鎭靜劑: 巴比妥 '漠化鈉、butoctamide semisuccinate 、 zepiclone 等 ° 2)解熱鎭痛劑: 捕熱息痛' 捕濕痛、阿斯匹林、止痛靈、異丙基安替比 林、雙氯芬酸、布袼芬、凱托洛芬、消炎痛、鹽酸替諾立定 等。 (6) 1343818 3) 鎭咳去痰劑: 磷酸二氫可待因 '溴化氫右甲啡烷、檸檬酸咳得平、依 普拉酮 '鹽酸氯呱拉斯丁'鹽酸諾司卡品、愈創木酚磺酸鉀 、鹽酸麻黃鹼、d丨-鹽酸甲基麻黃鹼等。 4) 抗組織胺劑: 馬來酸氯苯那敏、鹽酸苯海拉明、延胡索酸吡咯醇胺等 5) 強心劑: 胺茶驗、喘定、毛地黃毒素。 6) 鎭暈劑: 茶苯.海明、鹽酸地芬尼多、d]-鹽酸喘息定等。 7) 糖尿病用劑: 鹽酸二甲雙胍、鹽酸丁雙胍等。 8)降壓劑: 鹽酸托战卩秦、蘿芙驗(Alseroxylon)、硫酸胍乙D定、 鹽酸可樂定等。 9)無機質製劑: 葡糖酸鉀 '氯.化鉀、硫酸鐵' 芴胺酸、檸檬酸第一鐵鈉 -9 - (7) (7)1343818 ΑΆ- 寺 1 〇)激素劑: 地塞米松、yS -美松等。 1】)抗生素: 西法安生、頭孢克羅、紅黴素、Clarithromycin 、貴 田霉毒、米地霉素' 四環素、鹽酸羥四環素、氯霉素、鹽酸 林可霉素、一硫酸卡那霉素、硫酸巴龍霉素、鹽醆萬古霉素 等。 ]2)驅蟲劑、抗原蟲劑: 檸檬酸二乙基胍、涕必靈、鹽酸奎寧、硫酸奎寧、替硝 唑等。 針對上記生理活性成份’所謂服用時產生不快感係指有 苦味、澀味、辣喉味、收斂味、鐵味、粉感、沙沙的感覺等 謂之。 又’做爲該消化系統之副作用者如:食慾不振' 胃部不 舒服、胃痛、腹脹、便秘 '噁心、嘔吐感、腹瀉、等症狀顯 示者。 做爲本發明醫藥組成物所使用之健胃生藥者如:下記生 藥群。其生藥末可組合1或2以上選自下記所示生藥群者。 生藥群:桂皮、丁香、生薑、小茴香、歐龍胆、姜黃' 山椒、陳皮、高良姜、黃柏、延胡索、黃連、當藥、啤酒花 -10 - (8) (8)1343818 '勺藥、縮砂 '甘箪、黃芩 '若木、蒼朮 '人穸、吳茱萸, 選自此等生藥群之有效組合如下。投服量爲本發明適當範圍 者。又,本發明醫藥組成物所使用生藥組合未受限於此。 投與量 桂皮 5 0〜3 3 3 m g 丁香 I 0 〜5 0 m g 生薑 1 0 〜]0 0 m g 小茴香 ]0 〜1 0 0 m g 歐龍胆 1 0 〜5 0 m g 姜黃 1 0 〜I 0 0 m g 山椒 2 〜3 0 m g 適於本發明醫藥組成物之其他生藥類與投用量如下。 針對此等組合亦可配合取代上記成份者,或加入上記成份者 均可。 投與量 陳皮 ]0 〜]0 0 m g 1¾良姜 1 0 〜1 0 0 m g 黃柏 1 0 〜5 0 m g 延胡索 】0〜1 5 0 m g 黃連 1 0 〜5 0 m g 當藥 】0〜5 0 m g 啤酒花 ]0 〜1 0 0 m g -11 - (9) (9)1343818 勺藥 1 0 〜1 0 0 m g 縮砂 1 0 〜1 5 0 m g 甘草 1 0 〜I 5 0 】n g 黃芩 1 0 〜5 0 ni g 苦木 1 0 〜5 0 m g 蒼朮 1 0 〜5 0 m g 人參 10 〜]5 0 m g 吳茱萸 1 0 〜I 0 0 m g 做爲本發明醫藥組成物所使用之健胃生藥劑形者以粉 末或乾燥萃取物者宜。更以粉末爲較佳者。生藥粉末之粒徑 以5 00 以下者宜,更佳者爲300 μηΐ以下,最佳者爲15〇 μπί以下。生藥粉末之配合量當]重量份服用感不良成份時 爲0.2重量份〜2重量份者宜,更佳者爲〇.2〜1.0重量份。 該生藥進行粉碎時,可利用常用之方法,如:滾筒式、 流體式、撞擊式等粉碎方式。另外,亦可以液體氮涑結生藥 後,再進行凍結粉碎者。 本發明醫藥組成物中可進行如下之製劑化者。 以V型混合機等進行混合1或2以上服用時產生不快感之 生理活性成份與健胃生藥,以及必要時之其他生理活性成份 ’添加劑等後,將此,以滾筒混合器等進行壓縮成型後,製 造碎片,更將此利用滾筒顆粒器、振動網篩等進行整粒。 上記之混合’除使用V型混合器以外,亦可使用W型混 合器、齊射集裝混合器、高速攪拌造粒器、萬能攪拌混合器 -12- (10) (10)1343818 等。 進行濕式造粒時’可使用轉動造粒機、攪拌造粒器、流 動層造粒痛、噴霧造粒器、離心轉動造粒器、轉動流動造粒 器等濕式造粒器。另外’進行乾式造粒法時,可使用以粉粒 狀之結合劑使用之密壓造粒器等乾式造粒器等者。無論任何 方式進行造粒均不會損及掩飾不快味之效果,惟,乾式造粒 法由於未含加熱步驟,而殘留生藥風味,更可取得更具良好 服用感之醫藥組成物者。乾式造粒法係指以具高壓之滾輥 、密壓粉體後’進行成型’更將此進行整粒後取得造粒物之 方法者。 做爲該濕式造粒法者係使用攪拌造粒機,流相層造粒機 等’於粉體中添加水等之溶媒'溶解結合劑之溶液後,進行 造粒者。又,亦可使用將粉體於水等溶媒中進行溶解或分散 ’此經噴霧乾燥後進行造粒之噴霧乾燥造粒法者。此等製法 中爲乾燥造粒品而於製品進行長時間之加熱。藉由此加熱, 將降低本發明之生藥矯味作用,因此,以此等製造方法進行 製造時,以此等方法進行生藥以外成份之造粒後,以非加熱 條件下混合生藥者較具效果。 只要未進行加熱之製造方法下所製成之粉體,即使將此 進行壓縮成型(打錠)亦無妨。錠劑之形態可爲單層錠' 或雙層、三層均可。 本發明醫藥組成物亦可爲不快味生理活性成份與生藥 粉末相互做成水分散液製劑之劑形者。 本發明醫藥組成物除含有不快服用感之成份及生藥之 -13- (11) 1343818 外’亦可含有其他之生理活性物質。如:胃腸藥亦可配合制 酸劑、消化劑、整腸劑、黏膜修復劑、止瀉劑者。 進行製劑化時,更可配合慣用之添加物。該添加物種類 與量並未特別限定,一般添加量多,因此,一次投服量不宜 過多爲其重點者。又,多量使用糖類後,務必注意製劑不宜 太甜。做爲添加劑者可使用如下者。
結晶纖維素、乳糖、白糖、玉米澱粉、馬鈴薯澱粉、聚 乙二醇、硬脂酸鈣、硬脂酸鎂 '蔗糖脂肪酸酯' 硬脂酸、羧 甲基纖維素、羧甲基纖維素鈣、羧甲基纖維素鈉、羧甲基纖 維素鈉 (croscanmellose sodium)、低取代度羥丙基纖維素 '羧甲基澱粉鈉 '含水二氧化矽、輕質無水矽酸、氧化鈦、 滑石、eudragit 、阿拉伯膠、羧基乙烯聚合物、羥丙基纖 維素、甲基纖維素、乙基纖維素、羥丙基甲基纖維素等。
根據本發明醫藥組成物之製造方法,可以廉價設備簡 便製造之。且,藉由本發明可減低甜味料等添加物之使用量 ’因此’可解除先行技術之錠劑大型化問題。更且,亦可做 成散劑、顆粒劑等劑型。 [實施例] 本發明可藉由以下實施例進行更詳細說明,惟,本發 明未受限於此等實施例者。 [實施例卜9 ] 如表I所示處方’將所定量乾燥粉末狀之各成份置入 -14 - 1343818 (13) [表]] 比較處方(nig) 實施例 (mg) 處方No. ① ② ③ ④ 1 2 3 4 5 6 7 8 9 硫糖鋁 500 500 500 500 500 500 500 500 500 500 500 500 500 . 甘菊環磺酸鈉 2 2 2 2 2 2 2 2 2 2 2 2 2 L-谷胺酸 134 134 134 134 134 134 134 134 134 134 134 134 134 碳酸氫鈉 150 300 150 300 150 150 150 300 150 150 300 300 150 合成水滑石 160 160 160 160 ]60 160 160 160 160 160 ]60 160 160 diasmen SS 20 20 20 20 20 1 脂肪酶A96 20 20 20 20 20 桂皮 120 150 100 60 100 100 100 】00 100 縮砂 80 50 30 丁香 30 10 10 10 10 20 40 生蠆 25 25 20 30 30 30 30 30 40 小茴香 25 50 15 12 20 20 10 20 歐龍胆 12 10 】0 10 10 陳皮 50 30 12 30 30 15 山椒 15 18 10 15 4 i 姜黃 30 20 生藥合計 300 305 220 Π4 180 no 200 200 234 針對硫糖鋁之 生藥重量比 0.6 0.61 0.44 0.35 0.36 0.34 0.4 0.4 0.47 甘露糖醇 50 80 50 50 50 50 50 50 50 % L-薄荷醇 ]〇 5 3 6 2 2 2 2 2 合計 946 1096 986 ]136 1307 ]337 1219 1326 1178 1208 1388 1388 1232 (1次服用量) 3 2.5 2.5 2.5 6.6 6 6.4 6.4 5.2 6.5 7.5 7.3 8 評定點10階段 X _ —— X X 〇 〇 〇 〇 〇 〇 〇 〇 © -16- (14) (14)1343818 由官能試驗結果證明,藉由配合健胃生藥後,可改善 硫糖鋁之服用感。 [試驗例] 利用表2所示處方,將下記各種造粒方法所製造之製劑 投與1 0名專門試驗者,藉由試驗者取得服用感之評定。
-17 - (15) (15)1343818 [表2] 秤量 値[g] \\^製法 處方 單純混合 噴霧乾燥1 噴霧乾燥2 乾式造粒 擠壓 造粒 流動層 造粒 硫糖鋁 96.9 7 5 0 96.9 96.9 合成水滑石 3 1 240 3 1 3 1 碳酸氫鈉 29.1 225 29.1 29.1 桂皮 19.4 1 50 19.4 19.4 丁香 1.9 1 5 1 . 9 1 .9 生薑 5.8 45 5.8 5.8 小茴香 3.9 3 0 3.9 3.9 歐龍胆 1.9 15 1.9 1 .9 L-薄荷醇 0.4 3 0.4 0.4 D -甘露糖醇 9.7 75 9.7 9.7 結合劑 8 2 崩散劑 1 6 計 200 154 8 224 202 (】)擠壓造粒 取3 g部份結合劑,加水做成總量2 5 g後做成黏合液。 除L-薄荷醇秤取上記成份量,置入高速攪拌造粒機ΝΜ Ο-ΐ L (股份 ) 奈良機 械製作 所製) ,進行混合】分鐘。隨後投 -18 - (16) (16)1343818 入該黏合液’以高速攪拌造粒機進行混煉1分鐘。針對此煉 合物,裝置0 0.6mm網篩之擠壓造粒機domeglan DGL-] (DomeCranDGL-I)(不二粉末(股份)製)進行擠壓造粒。 更將造粒物以約30秒之馬默氣門(Marmerizei·) 0-230 (不二 粉末公司Fuji paud a 1 Co.,Ltd製)進行圓形處理。將此於 60 °C、3小時安全烤箱(Safty Oven) SPH-101 (Espec (股份) 製)進行乾燥。依製造物收率,算取薄荷量,進行秤量後 ,將此以乳鉢進行粉碎,加入所製造顆粒中。 (2)流動層造粒 取2g結合劑,於此加水成50g,溶解後將此做成結合液 。更,除薄荷醇評取上記成份量,過篩後,於聚袋中進行混 合。將混合物置入流動層造粒機 New Marmerizer NQ-I25 型(不二粉末(股份)製)內,於top spray使該結合劑 溶液進行流動層造粒(給氣60 °C,品溫35 °C ),更藉由 流動層於60 °C下進行30分鐘之乾燥。以30網篩進行造粒物 之整粒後,30網篩通過品與(1)相同之薄荷醇乳鉢粉碎品 進行混合之。 (3 )噴霧乾燥1 除薄荷醇秤取上記成份量,調整固形份30wt%之水分散 液。針對此分散液利用噴霧乾燥器L-8型(大川原化工機( 股份)製)以入口溫度約]2 〇 °C進行噴霧乾燥。於此造粒 物與(])、(2 )相同進行混合薄荷醇粉碎物。 -19- (17) 1343818 (4 )噴霧乾燥2 除薄荷醇與健胃生藥秤取上記成份量,調整固形份 30wt%之水分散液。針對此水分散液利用噴霧乾燥器L-8 型(大川原化工機公司製)於入口溫度約1 2 0 t下進行噴 霧乾燥。將薄荷粉碎末與生藥粉末與造粒物同時於聚袋進 行混合之。
(5 )乾式造粒 秤取上記成份量,過篩後,置入滾輥混煉器WP90 X 30 (TURBO KOGYO工業(股份)製)進行壓縮,做成碎 片。更將此碎片以滾輥顆粒器GRN-T53S (日本顆粒器 ( 股份)製)與3 0網篩之振動網篩進行整粒。 (6)單純混合 秤取上記成份量,於聚袋內進行混合。
分別將該(1) ~ (6)製法所製造之製劑投與1 0名專門試 驗者,依以下基準進行評定其服用感。 基準:χ不易服用、△梢難服用、〇尙可服用、◎易於 服用。 結果示於表3。 -20- (18) 1343818 [表3] 結果〜 ___ — _^製法 -— 評價 _ 單純混合 〇 噴霧乾燥I Δ 噴霧乾燥2 〇 乾式造粒 ◎ 擠壓造粒 Δ ___流動層造輕____ .. Δ
結果顯示,未長時間加熱生藥之造粒步驟之理想使用 者’特別以乾式造粒法爲最理想之結果。 [發明效果]
服用時產生不快感之生理活性成份配合健胃生藥後’ 健胃生藥成份維持原本健胃效果之同時,對於生理活性成 份可做爲矯味劑之作用’成功減少先行此目的所使用甜味 料等添加物之使用量。更藉由乾式造粒法進行製造後’更 增加做爲矯味劑之效果,提昇服用感。 藉由本發明醫藥組成物可有效降低或消去使用出現消 化系統副作用之藥物、服用時口中出現不快感之生理活性 成份所出現之副作用’且’可有效掩飾不快味道。另外^ 使用健胃生藥以外之胃腸藥 '服用時口中產生不快感之生 -21 - (19) 1343818 理活性成份時’可藉由配合健胃生藥進行掩飾不快味道。 更可期待取得胃腸藥與健胃生藥分別藥效之相乘效果者。 本發明醫藥組成物更適於受限糖尿病糖份攝取者之服 用’因此’治療方法之選擇廣,提昇服藥順從性之極有利 者。 本發明醫藥組成物之製造方法可以廉價設備、簡便之 製造者。且’可解除錠劑大型化之問題,除錠劑之外可以 散劑、顆粒劑等各種劑形供給之。 -22-
Claims (1)
1343818 第092 1 32009號專利申請案中文申請專利範圍修正本 民國 修正 拾、申請專利範圍 | 補充j 1. 一種改善服用感之醫藥組成物,其特徵係含有硫糖 鋁與1種或2種以上選自桂皮、縮砂、丁香、生薑、小茴 香、歐龍、陳皮、山椒及姜黃所成群之健胃生藥,以粉末 或乾燥萃取物的單純混合或由乾燥造粒法所製造,其中該 健胃生藥之配合量針對1重量份之硫糖鋁爲0.2〜2重量 份。 2. 如申請專利範圍第1項之醫藥組成物,其中該健胃 生藥之粉末或乾燥萃取物粒徑爲500 μτη以下者。 3. —種掩飾劑(masking agent),其爲使用於抑制硫 糖鋁之不快感味者,其特徵爲含有1種或2種以上選自桂 皮、縮砂、丁香、生薑、小茴香、歐龍、陳皮、山椒及姜 黃所成群之健胃生藥,使用於藉由單純混合或乾燥造粒而 製造的醫藥製造上,而該健胃生藥爲粉末或乾燥萃取物, 其中該健胃生藥之配合量針對1重量份之硫糖鋁爲〇.2~2 重量份。 4. 如申請專利範圍第3項之掩飾劑,其中該健胃生藥 的粉末或乾燥萃取物之粒徑爲500μπι以下者。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2002346393A JP2004175757A (ja) | 2002-11-28 | 2002-11-28 | 医薬組成物 |
Publications (2)
Publication Number | Publication Date |
---|---|
TW200507876A TW200507876A (en) | 2005-03-01 |
TWI343818B true TWI343818B (zh) | 2011-06-21 |
Family
ID=32707312
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW092132009A TW200507876A (en) | 2002-11-28 | 2003-11-14 | Medicine composition |
Country Status (5)
Country | Link |
---|---|
JP (1) | JP2004175757A (zh) |
KR (1) | KR20040047588A (zh) |
CN (1) | CN1330378C (zh) |
HK (1) | HK1065477A1 (zh) |
TW (1) | TW200507876A (zh) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4950551B2 (ja) * | 2006-04-25 | 2012-06-13 | 興和株式会社 | 消化管粘膜保護剤 |
CN101507770B (zh) * | 2008-07-18 | 2011-01-05 | 天津生机集团股份有限公司 | 治疗马痉挛疝的中药组合物 |
JP6317190B2 (ja) * | 2014-06-17 | 2018-04-25 | エスエス製薬株式会社 | 胃腸薬 |
CN105944104B (zh) * | 2016-06-17 | 2018-12-14 | 上海凯宝药业股份有限公司 | 一种治疗消化道溃疡的药物组合物 |
KR102428859B1 (ko) * | 2020-05-29 | 2022-08-04 | 동성제약주식회사 | 안전성이 확보된 소화기계 질환 예방 또는 치료를 위한 경구투여용 약학 조성물 |
CN115177593B (zh) * | 2022-08-08 | 2023-08-25 | 锦州奥鸿药业有限责任公司 | 一种谷氨酰胺颗粒剂及其制备方法 |
CN117298086B (zh) * | 2023-11-29 | 2024-03-08 | 中国中医科学院中药研究所 | 索法酮在制备预防和/或治疗nlrp3炎性小体介导的疾病的药物中的应用 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1114885A (zh) * | 1994-05-17 | 1996-01-17 | 内蒙古自治区高等院校科技开发集团赤峰公司 | 健身、补肾清脑外用药粉剂 |
JP2000103746A (ja) * | 1994-10-27 | 2000-04-11 | Takeda Chem Ind Ltd | 成形物およびその製造方法 |
KR20010033001A (ko) * | 1998-04-01 | 2001-04-25 | 나가야마 오사무 | 알콜성 위염 예방제 |
JP2000191517A (ja) * | 1998-12-24 | 2000-07-11 | Lion Corp | 不快な味がマスキングされた造粒組成物及びその製造方法 |
CN1086928C (zh) * | 1999-11-01 | 2002-07-03 | 济南联合大学 | 复合油树脂调味品 |
-
2002
- 2002-11-28 JP JP2002346393A patent/JP2004175757A/ja active Pending
-
2003
- 2003-11-14 TW TW092132009A patent/TW200507876A/zh not_active IP Right Cessation
- 2003-11-14 KR KR1020030080560A patent/KR20040047588A/ko not_active Application Discontinuation
- 2003-11-28 CN CNB2003101186813A patent/CN1330378C/zh not_active Expired - Lifetime
-
2004
- 2004-10-21 HK HK04108298A patent/HK1065477A1/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
CN1330378C (zh) | 2007-08-08 |
KR20040047588A (ko) | 2004-06-05 |
JP2004175757A (ja) | 2004-06-24 |
TW200507876A (en) | 2005-03-01 |
HK1065477A1 (en) | 2005-02-25 |
CN1504185A (zh) | 2004-06-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2189227C2 (ru) | Быстро распадающиеся прессованные в формах материалы и способ их получения | |
TW589177B (en) | Having improved antitussive effect drug preparations | |
JP5074190B2 (ja) | 口腔内速崩壊性錠剤 | |
RU2583935C2 (ru) | Фармацевтическая композиция для перорального введения с маскированным вкусом и способ ее получения | |
NO316662B1 (no) | Intrabukkalt opploselig, presstopt produkter og fremgangsmate for fremstilling dette | |
EP2050448A1 (en) | Oral disintegrating tablet having masked bitter taste and method for production thereof | |
UA73727C2 (uk) | Спосіб приготування кальцієвої композиції для перорального введення у формі таблеток | |
CN101299996A (zh) | 含有唾液诱生剂的口服组合物 | |
KR101203186B1 (ko) | 약물의 맛이 차폐된 경구용 약학 조성물 및 그 제조 방법 | |
KR101400064B1 (ko) | 건식 직타 속붕괴성 정제 | |
JPH1133084A (ja) | 口腔内溶解型錠剤およびその製造方法 | |
CN104968335A (zh) | 具有改善的溶解度的新型快速溶解颗粒制剂 | |
RU2317087C2 (ru) | Улучшенные композиции и улучшения, связанные с композициями | |
WO2006085497A1 (ja) | 口腔内崩壊錠 | |
JP5552400B2 (ja) | 生薬類の苦味・不快味をマスキングした顆粒剤、及び口腔内速崩壊錠 | |
CN102327244B (zh) | 一种盐酸氨溴索口腔崩解片及其制备方法 | |
JPH1135451A (ja) | 口腔内溶解型錠剤およびその製造方法 | |
TWI343818B (zh) | ||
WO2005084703A1 (ja) | 徐放性の口腔用組成物 | |
WO2007018057A1 (ja) | 口腔内速崩壊錠およびその製造法 | |
KR20070049962A (ko) | 경구 고형 제제 및 그의 제조 방법 | |
JP2002255796A (ja) | 口腔内速崩壊型錠剤及びその製造方法 | |
KR101175120B1 (ko) | 나테글리니드 함유 제제 | |
JPH0426618A (ja) | トローチ剤 | |
JPH1135486A (ja) | 薬用固形製剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM4A | Annulment or lapse of patent due to non-payment of fees |