JP5527921B2 - 苦味を隠蔽した経口固形組成物 - Google Patents
苦味を隠蔽した経口固形組成物 Download PDFInfo
- Publication number
- JP5527921B2 JP5527921B2 JP2006345147A JP2006345147A JP5527921B2 JP 5527921 B2 JP5527921 B2 JP 5527921B2 JP 2006345147 A JP2006345147 A JP 2006345147A JP 2006345147 A JP2006345147 A JP 2006345147A JP 5527921 B2 JP5527921 B2 JP 5527921B2
- Authority
- JP
- Japan
- Prior art keywords
- hydrophilic polymer
- manufactured
- drug
- mass
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 235000019658 bitter taste Nutrition 0.000 title claims description 44
- 239000008247 solid mixture Substances 0.000 title description 15
- 239000003814 drug Substances 0.000 claims description 61
- 229920001477 hydrophilic polymer Polymers 0.000 claims description 56
- 229940079593 drug Drugs 0.000 claims description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 40
- 239000008187 granular material Substances 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 28
- 238000001035 drying Methods 0.000 claims description 27
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 25
- 239000002245 particle Substances 0.000 claims description 19
- 230000001747 exhibiting effect Effects 0.000 claims description 15
- -1 hydroxypropoxy groups Chemical group 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 8
- 238000009472 formulation Methods 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 4
- 239000004503 fine granule Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 description 25
- 238000000034 method Methods 0.000 description 19
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 18
- 229910052782 aluminium Inorganic materials 0.000 description 18
- 230000000052 comparative effect Effects 0.000 description 12
- 239000011248 coating agent Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000008213 purified water Substances 0.000 description 9
- 235000010724 Wisteria floribunda Nutrition 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 238000005469 granulation Methods 0.000 description 8
- 230000003179 granulation Effects 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical group 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 7
- 238000000576 coating method Methods 0.000 description 7
- 239000000796 flavoring agent Substances 0.000 description 7
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 6
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 6
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 6
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- 235000003599 food sweetener Nutrition 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 5
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 5
- 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 5
- 229950008138 carmellose Drugs 0.000 description 5
- 239000003086 colorant Substances 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical group CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 5
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 229960001948 caffeine Drugs 0.000 description 4
- 238000001125 extrusion Methods 0.000 description 4
- 239000003205 fragrance Substances 0.000 description 4
- 235000016709 nutrition Nutrition 0.000 description 4
- 230000035764 nutrition Effects 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 235000019640 taste Nutrition 0.000 description 4
- YQSHYGCCYVPRDI-UHFFFAOYSA-N (4-propan-2-ylphenyl)methanamine Chemical compound CC(C)C1=CC=C(CN)C=C1 YQSHYGCCYVPRDI-UHFFFAOYSA-N 0.000 description 3
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- 229940035676 analgesics Drugs 0.000 description 3
- 239000000730 antalgic agent Substances 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 235000000639 cyanocobalamin Nutrition 0.000 description 3
- 239000011666 cyanocobalamin Substances 0.000 description 3
- 229960002104 cyanocobalamin Drugs 0.000 description 3
- 229960003782 dextromethorphan hydrobromide Drugs 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 229960000310 isoleucine Drugs 0.000 description 3
- 229960003136 leucine Drugs 0.000 description 3
- 229960002983 loperamide hydrochloride Drugs 0.000 description 3
- PGYPOBZJRVSMDS-UHFFFAOYSA-N loperamide hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 PGYPOBZJRVSMDS-UHFFFAOYSA-N 0.000 description 3
- 229960005489 paracetamol Drugs 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000002831 pharmacologic agent Substances 0.000 description 3
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 3
- 239000002151 riboflavin Substances 0.000 description 3
- 235000019192 riboflavin Nutrition 0.000 description 3
- 229960002477 riboflavin Drugs 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 229960000278 theophylline Drugs 0.000 description 3
- 229960004295 valine Drugs 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 108010011485 Aspartame Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 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 2
- 241000207199 Citrus Species 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- 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 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- 240000007049 Juglans regia Species 0.000 description 2
- 235000009496 Juglans regia Nutrition 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 2
- 229930064664 L-arginine Natural products 0.000 description 2
- 235000014852 L-arginine Nutrition 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 229930182844 L-isoleucine Natural products 0.000 description 2
- 239000004395 L-leucine Substances 0.000 description 2
- 235000019454 L-leucine Nutrition 0.000 description 2
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 description 2
- 102000016943 Muramidase Human genes 0.000 description 2
- 108010014251 Muramidase Proteins 0.000 description 2
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000954 anitussive effect Effects 0.000 description 2
- 230000001754 anti-pyretic effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000002221 antipyretic Substances 0.000 description 2
- 229940124584 antitussives Drugs 0.000 description 2
- KSUUMAWCGDNLFK-UHFFFAOYSA-N apronal Chemical compound C=CCC(C(C)C)C(=O)NC(N)=O KSUUMAWCGDNLFK-UHFFFAOYSA-N 0.000 description 2
- 229960004459 apronal Drugs 0.000 description 2
- 239000000605 aspartame Substances 0.000 description 2
- 235000010357 aspartame Nutrition 0.000 description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 2
- 229960003438 aspartame Drugs 0.000 description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 2
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 2
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 2
- 235000020971 citrus fruits Nutrition 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229960001681 croscarmellose sodium Drugs 0.000 description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
- 229960001193 diclofenac sodium Drugs 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 2
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- SBNKFTQSBPKMBZ-UHFFFAOYSA-N ethenzamide Chemical compound CCOC1=CC=CC=C1C(N)=O SBNKFTQSBPKMBZ-UHFFFAOYSA-N 0.000 description 2
- 239000003172 expectorant agent Substances 0.000 description 2
- 230000003419 expectorant effect Effects 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 239000001848 glycyrrhiza glabra l. root extract powder Substances 0.000 description 2
- 239000012676 herbal extract Substances 0.000 description 2
- YOZNUFWCRFCGIH-BYFNXCQMSA-L hydroxocobalamin Chemical compound O[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O YOZNUFWCRFCGIH-BYFNXCQMSA-L 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 229960001680 ibuprofen Drugs 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000004325 lysozyme Substances 0.000 description 2
- 229960000274 lysozyme Drugs 0.000 description 2
- 235000010335 lysozyme Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000000873 masking effect Effects 0.000 description 2
- 235000005152 nicotinamide Nutrition 0.000 description 2
- 239000011570 nicotinamide Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- NHZMQXZHNVQTQA-UHFFFAOYSA-N pyridoxamine Chemical compound CC1=NC=C(CO)C(CN)=C1O NHZMQXZHNVQTQA-UHFFFAOYSA-N 0.000 description 2
- 235000008160 pyridoxine Nutrition 0.000 description 2
- 239000011677 pyridoxine Substances 0.000 description 2
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 2
- 229960004172 pyridoxine hydrochloride Drugs 0.000 description 2
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 2
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 2
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 235000019157 thiamine Nutrition 0.000 description 2
- 229960003495 thiamine Drugs 0.000 description 2
- 239000011721 thiamine Substances 0.000 description 2
- 235000020234 walnut Nutrition 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- DKSZLDSPXIWGFO-BLOJGBSASA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.OP(O)(O)=O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC DKSZLDSPXIWGFO-BLOJGBSASA-N 0.000 description 1
- RBCOYOYDYNXAFA-UHFFFAOYSA-L (5-hydroxy-4,6-dimethylpyridin-3-yl)methyl phosphate Chemical group CC1=NC=C(COP([O-])([O-])=O)C(C)=C1O RBCOYOYDYNXAFA-UHFFFAOYSA-L 0.000 description 1
- YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
- LLQHSBBZNDXTIV-UHFFFAOYSA-N 6-[5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-4,5-dihydro-1,2-oxazol-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC1CC(=NO1)C1=CC2=C(NC(O2)=O)C=C1 LLQHSBBZNDXTIV-UHFFFAOYSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-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
- 108010076119 Caseins Proteins 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 244000163122 Curcuma domestica Species 0.000 description 1
- 235000003392 Curcuma domestica Nutrition 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- IELOKBJPULMYRW-NJQVLOCASA-N D-alpha-Tocopheryl Acid Succinate Chemical compound OC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C IELOKBJPULMYRW-NJQVLOCASA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- AZJUFRDUYTYIHV-NKFKGCMQSA-N Dibenzoyl Thiamine Chemical compound C=1C=CC=CC=1C(=O)OCC\C(SC(=O)C=1C=CC=CC=1)=C(/C)N(C=O)CC1=CN=C(C)N=C1N AZJUFRDUYTYIHV-NKFKGCMQSA-N 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 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
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- XLRHXNIVIZZOON-WFUPGROFSA-L Flavin adenine dinucleotide disodium Chemical compound [Na+].[Na+].C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1COP([O-])(=O)OP([O-])(=O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C2=NC(=O)NC(=O)C2=NC2=C1C=C(C)C(C)=C2 XLRHXNIVIZZOON-WFUPGROFSA-L 0.000 description 1
- 240000006927 Foeniculum vulgare Species 0.000 description 1
- 235000004204 Foeniculum vulgare Nutrition 0.000 description 1
- 235000011201 Ginkgo Nutrition 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- 235000008100 Ginkgo biloba Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 240000004670 Glycyrrhiza echinata Species 0.000 description 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 description 1
- 235000008694 Humulus lupulus Nutrition 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 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
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-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
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- VCUFZILGIRCDQQ-KRWDZBQOSA-N N-[[(5S)-2-oxo-3-(2-oxo-3H-1,3-benzoxazol-6-yl)-1,3-oxazolidin-5-yl]methyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C1O[C@H](CN1C1=CC2=C(NC(O2)=O)C=C1)CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F VCUFZILGIRCDQQ-KRWDZBQOSA-N 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 241000237502 Ostreidae Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000006484 Paeonia officinalis Nutrition 0.000 description 1
- 244000170916 Paeonia officinalis Species 0.000 description 1
- 241000218996 Passiflora Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- MJNIWUJSIGSWKK-BBANNHEPSA-N Riboflavin butyrate Chemical compound CCCC(=O)OC[C@@H](OC(=O)CCC)[C@@H](OC(=O)CCC)[C@@H](OC(=O)CCC)CN1C2=CC(C)=C(C)C=C2N=C2C1=NC(=O)NC2=O MJNIWUJSIGSWKK-BBANNHEPSA-N 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000032140 Sleepiness Diseases 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- 229930006000 Sucrose Natural products 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
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 244000126014 Valeriana officinalis Species 0.000 description 1
- 235000013832 Valeriana officinalis Nutrition 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 244000273928 Zingiber officinale Species 0.000 description 1
- 235000006886 Zingiber officinale Nutrition 0.000 description 1
- NTCYWJCEOILKNG-ROLPUNSJSA-N [(1r,2s)-1-hydroxy-1-phenylpropan-2-yl]-dimethylazanium;chloride Chemical compound Cl.CN(C)[C@@H](C)[C@H](O)C1=CC=CC=C1 NTCYWJCEOILKNG-ROLPUNSJSA-N 0.000 description 1
- 235000010358 acesulfame potassium Nutrition 0.000 description 1
- 229960004998 acesulfame potassium Drugs 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000001139 anti-pruritic effect Effects 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 239000002216 antistatic agent Substances 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 230000002763 arrhythmic effect Effects 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- BTNNPSLJPBRMLZ-LGMDPLHJSA-N benfotiamine Chemical compound C=1C=CC=CC=1C(=O)SC(/CCOP(O)(O)=O)=C(/C)N(C=O)CC1=CN=C(C)N=C1N BTNNPSLJPBRMLZ-LGMDPLHJSA-N 0.000 description 1
- 229960002873 benfotiamine Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- PBUBJNYXWIDFMU-UHFFFAOYSA-L calcium;butanedioate Chemical compound [Ca+2].[O-]C(=O)CCC([O-])=O PBUBJNYXWIDFMU-UHFFFAOYSA-L 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 239000000496 cardiotonic agent Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- ASARMUCNOOHMLO-WLORSUFZSA-L cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2s)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@H](C)OP([O-])(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O ASARMUCNOOHMLO-WLORSUFZSA-L 0.000 description 1
- FDJOLVPMNUYSCM-UVKKECPRSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7, Chemical group [Co+3].N#[C-].C1([C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)[N-]\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O FDJOLVPMNUYSCM-UVKKECPRSA-L 0.000 description 1
- 235000006279 cobamamide Nutrition 0.000 description 1
- 239000011789 cobamamide Substances 0.000 description 1
- ZIHHMGTYZOSFRC-UWWAPWIJSA-M cobamamide Chemical compound C1(/[C@](C)(CCC(=O)NC[C@H](C)OP(O)(=O)OC2[C@H]([C@H](O[C@@H]2CO)N2C3=CC(C)=C(C)C=C3N=C2)O)[C@@H](CC(N)=O)[C@]2(N1[Co+]C[C@@H]1[C@H]([C@@H](O)[C@@H](O1)N1C3=NC=NC(N)=C3N=C1)O)[H])=C(C)\C([C@H](C/1(C)C)CCC(N)=O)=N\C\1=C/C([C@H]([C@@]\1(CC(N)=O)C)CCC(N)=O)=N/C/1=C(C)\C1=N[C@]2(C)[C@@](C)(CC(N)=O)[C@@H]1CCC(N)=O ZIHHMGTYZOSFRC-UWWAPWIJSA-M 0.000 description 1
- 229960004415 codeine phosphate Drugs 0.000 description 1
- 239000008373 coffee flavor Substances 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000003373 curcuma longa Nutrition 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 229940099418 d- alpha-tocopherol succinate Drugs 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 229940124568 digestive agent Drugs 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 229960000920 dihydrocodeine Drugs 0.000 description 1
- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 229960002534 ephedrine hydrochloride Drugs 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229940066493 expectorants Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- FVTCRASFADXXNN-SCRDCRAPSA-N flavin mononucleotide Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-SCRDCRAPSA-N 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 235000002864 food coloring agent Nutrition 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000004083 gastrointestinal agent Substances 0.000 description 1
- 229940127227 gastrointestinal drug Drugs 0.000 description 1
- 235000008397 ginger Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 235000003969 glutathione Nutrition 0.000 description 1
- 229960002146 guaifenesin Drugs 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 235000014304 histidine Nutrition 0.000 description 1
- 235000004867 hydroxocobalamin Nutrition 0.000 description 1
- 239000011704 hydroxocobalamin Substances 0.000 description 1
- 229960001103 hydroxocobalamin Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 229940069445 licorice extract Drugs 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 239000001683 mentha spicata herb oil Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229930182817 methionine Natural products 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
- 235000007672 methylcobalamin Nutrition 0.000 description 1
- 239000011585 methylcobalamin Substances 0.000 description 1
- JEWJRMKHSMTXPP-BYFNXCQMSA-M methylcobalamin Chemical compound C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O JEWJRMKHSMTXPP-BYFNXCQMSA-M 0.000 description 1
- 229940051020 methylephedrine hydrochloride Drugs 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 235000020636 oyster Nutrition 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229960000293 pirenzepine hydrochloride Drugs 0.000 description 1
- FFNMBRCFFADNAO-UHFFFAOYSA-N pirenzepine hydrochloride Chemical compound [H+].[H+].[Cl-].[Cl-].C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 FFNMBRCFFADNAO-UHFFFAOYSA-N 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 229960002244 promethazine hydrochloride Drugs 0.000 description 1
- XXPDBLUZJRXNNZ-UHFFFAOYSA-N promethazine hydrochloride Chemical compound Cl.C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 XXPDBLUZJRXNNZ-UHFFFAOYSA-N 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- PXWLVJLKJGVOKE-UHFFFAOYSA-N propyphenazone Chemical compound O=C1C(C(C)C)=C(C)N(C)N1C1=CC=CC=C1 PXWLVJLKJGVOKE-UHFFFAOYSA-N 0.000 description 1
- 229960002189 propyphenazone Drugs 0.000 description 1
- 235000008151 pyridoxamine Nutrition 0.000 description 1
- 239000011699 pyridoxamine Substances 0.000 description 1
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229950001574 riboflavin phosphate Drugs 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 230000037321 sleepiness Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000019721 spearmint oil Nutrition 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 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 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- UIERGBJEBXXIGO-UHFFFAOYSA-N thiamine mononitrate Chemical compound [O-][N+]([O-])=O.CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N UIERGBJEBXXIGO-UHFFFAOYSA-N 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 235000015961 tonic Nutrition 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 229960000716 tonics Drugs 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 235000013976 turmeric Nutrition 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 235000016788 valerian Nutrition 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Inorganic Chemistry (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
Description
また、本発明は、(B)親水性高分子に水を加え含水親水性高分子とし、これを(A)苦味を呈する薬物と混合し、造粒し、次いで水分量7.5質量%以下になるまで乾燥することにより得られる経口固形製剤である。
(B)親水性高分子に水を加え含水親水性高分子とし、これを(A)苦味を呈する薬物と混合し、造粒するが、後者の方法が好ましい。
本発明において用いる親水性高分子は、親水基を分子内に含有し、親水性高分子自体と同量以上の質量の水を保持することができ、水を保持した状態で固形または半固形の状態であるが、水には溶解せずに不溶性であり、親水性高分子自体が不快な味を呈しないことが必要である。このような親水性高分子としては、低置換度ヒドロキシプロピルセルロース、結晶セルロース、クロスカルメロースナトリウム、クロスポピドン、カルボキシメチルセルロースカルシウム、カルボキシメチルセルロースナトリウム、カルボキシメチルセルロース等を挙げることができ、これらは1種又は2種以上を混合して用いてもよい。これらの中でも好ましい親水性高分子としては、低置換度ヒドロキシプロピルセルロース、カルボキシメチルセルロースカルシウム、カルボキシメチルセルロースナトリウム、クロスカルメロースナトリウム、結晶セルロースから選ばれる1種又は2種以上を挙げることができる。さらに特に好ましい親水性高分子としては、低置換度ヒドロキシプロピルセルロースを挙げることができ、これを親水性高分子全体の50質量%以上使用することが望ましく、特に65質量%以上使用することが好ましい。
カンゾウエキス末(日本粉末薬品(株)製)100g(原生薬換算700g)、および、含水親水性高分子物質3118g[低置換度ヒドロキシプロピルセルロース((ヒドロキシプロポキシ基10.0〜12.9質量%)LHPC:LH−31:信越化学(株)製)800gと精製水2318g]からなる混合物をバーチカルグラニュレーターVG−10(パウレック(株))で均一に混合後、ツインドームグランTDG−80(不二パウダル(株)製)0.8mmスクリーンで押し出し造粒し、マルメライザー(不二パウダル(株)製)を用いて球形処理を施した。次に、流動層乾燥装置FLO−5A/2(フロイント産業(株)製)にて乾燥し、平均粒径約0.65mmの顆粒剤を製し、四方アルミヒートシールにて一包あたりの質量が300mgになるように分包した。この顆粒剤の乾燥減量は50℃10分で1.2%であった。
カンゾウエキス末(日本粉末薬品(株)製)10g、および、低置換度ヒドロキシプロピルセルロース(LHPC:LH−31:信越化学(株)製)80gを均一に混合し、四方アルミヒートシールにて一包あたりの質量が300mgになるように分包した。
葛根湯乾燥エキス末(日本粉末薬品(株)製)357.1g(原生薬換算3.571kg)、および、含水親水性高分子物質1755g(低置換度ヒドロキシプロピルセルロース(LHPC:LH−31:信越化学(株)製)200g、カルメロースカルシウム(五徳薬品(株)製)300gと精製水1255g)からなる混合物をバーチカルグラニュレーターVG−10(パウレック(株))で均一に混合後、ツインドームグランTDG−80(不二パウダル(株)製)0.6mmスクリーンで押し出し造粒した。次に、流動層乾燥装置FLO−5A/2(フロイント産業(株)製)にて乾燥し、平均粒径約0.5mmの顆粒剤を製し、四方アルミヒートシールにて一包あたりの質量が2gになるように分包した。この顆粒剤の乾燥減量は50℃10分で1.5%であった。
葛根湯乾燥エキス末(日本粉末薬品(株)製)50g、低置換度ヒドロキシプロピルセルロース(LHPC:LH−31:信越化学(株)製)28g、および、カルメロースカルシウム(五徳薬品(株)製)42gを均一に混合し、四方アルミヒートシールにて一包あたりの質量が2gになるように分包した。
ウワウルシ乾燥エキス(松浦薬業(株)製)250g(原生薬換算2kg)、および、含水親水性高分子物質1235g[低置換度ヒドロキシプロピルセルロース LHPC:LH−32、信越化学(株)製(ヒドロキシプロポキシ基7.0〜9.9質量%)280g、カルメロースカルシウム(五徳薬品(株)製)70gと精製水885g]からなる混合物をバーチカルグラニュレーターVG−10(パウレック(株))で均一に混合後、ツインドームグランTDG−80(不二パウダル(株)製)0.6mmスクリーンで押し出し造粒した。次に、流動層乾燥装置FLO−5A/2(フロイント産業(株)製)にて乾燥し、平均粒径約0.5mmの顆粒剤を製し、四方アルミヒートシールにて一包あたりの質量が1gになるように分包した。この顆粒剤の乾燥減量は50℃10分で0.9%であった。
ウワウルシ乾燥エキス(松浦薬業(株)) 50g、低置換度ヒドロキシプロピルセルロース(LHPC:LH−32:信越化学(株)製)56g、および、カルメロースカルシウム(五徳薬品(株))14gを均一に混合し、四方アルミヒートシールにて一包あたりの質量が2gになるように分包した。
ビスベンチアミン(田辺製薬(株)製)100g、塩酸ピリドキシン(第一ファインケミカル(株)製)100g、リボフラビン(三菱ウェルファーマ(株)製)12g、シアノコバラミン(DSMニュートリッション ジャパン(株)製)1.5g、ビタミンEコハク酸エステルカルシウム(エーザイ(株)製)103.58g、ニコチン酸アミド(DSMニュートリッション ジャパン(株)製)60g、および、含水親水性高分子物質2032.92g(低置換度ヒドロキシプロピルセルロース(LHPC:LH−31:信越化学(株)製)522.92gと精製水1510g)からなる混合物をバーチカルグラニュレーターVG−10(パウレック(株))で均一に混合後、ツインドームグランTDG−80(不二パウダル(株)製)0.5mmスクリーンで押し出し造粒した。次に、流動層乾燥装置FLO−5A/2(フロイント産業(株)製)にて乾燥し、平均粒径約0.4mmの顆粒剤を製し、四方アルミヒートシールにて一包あたりの質量が300mgになるように分包した。この顆粒剤の乾燥減量は50℃10分で0.6%であった。
ビスベンチアミン(田辺製薬(株)製)10g、塩酸ピリドキシン(第一ファインケミカル(株)製)10g、リボフラビン(三菱ウェルファーマ(株)製)1.2g、シアノコバラミン(DSMニュートリッション ジャパン(株)製)0.15g、ビタミンEコハク酸エステルカルシウム(エーザイ(株)製)10.358g、ニコチン酸アミド(DSMニュートリッション ジャパン(株)製)6g、および、低置換度ヒドロキシプロピルセルロース(LHPC:LH−31:信越化学(株)製)52.292gを均一に混合し、四方アルミヒートシールにて一包あたりの質量が300mgになるように分包した。
L−バリン(味の素(株)製)60g、L−ロイシン(協和醗酵(株)製)90g、L−イソロイシン(協和醗酵(株)製)60g、L-グルタミン(味の素(株)製)120g、L−アルギニン(味の素(株)製)120g、塩酸L−リジン(協和醗酵(株)製)120gおよび、含水親水性高分子物質1705g(低置換度ヒドロキシプロピルセルロース(LHPC:LH−31:信越化学(株)製)430gと精製水1275g)からなる混合物をバーチカルグラニュレーターVG−10(パウレック(株))で均一に混合後、ツインドームグランTDG−80(不二パウダル(株)製)0.8mmスクリーンで押し出し造粒し、マルメライザー(不二パウダル(株)製)を用いて球形処理を施した。次に、流動層乾燥装置FLO−5A/2(フロイント産業(株)製)にて乾燥し、平均粒径約0.6mmの顆粒剤を製し、四方アルミヒートシールにて一包あたりの質量が1gになるように分包した。この顆粒剤の乾燥減量は50℃10分で0.9%であった。
L−バリン(味の素(株)製)6g、L−ロイシン(協和醗酵(株)製)9g、L−イソロイシン(協和醗酵(株)製)6g、L-グルタミン(味の素(株)製)12g、L−アルギニン(味の素(株)製)12g、塩酸L−リジン(協和醗酵(株)製)12gおよび、低置換度ヒドロキシプロピルセルロース(LHPC:LH−31:信越化学(株)製)43gを均一に混合し、四方アルミヒートシールにて一包あたりの質量が1gになるように分包した。
塩酸ロペラミド(ISFI製)10g、および、含水親水性高分子物質5000g(低置換度ヒドロキシプロピルセルロース(LHPC:LH−32:信越化学(株)製)990gと精製水4010g)からなる混合物をバーチカルグラニュレーターVG−10(パウレック(株))で均一に混合後、ツインドームグランTDG−80(不二パウダル(株)製)0.2mmスクリーンで押し出し造粒した。次に、流動層乾燥装置FLO−5A/2(フロイント産業(株)製)にて乾燥し、平均粒径約0.15mmの細粒剤を製し、四方アルミヒートシールにて一包あたりの質量が500mgになるように分包した。この顆粒剤の乾燥減量は50℃10分で0.5%であった。
塩酸ロペラミド(ISFI製)1g、および、低置換度ヒドロキシプロピルセルロース(LHPC:LH−32:信越化学(株)製)99gを均一に混合し、四方アルミヒートシールにて一包あたりの質量が500mgになるように分包した。
塩酸ジフェンヒドラミン(金剛化学(株)製)50g、および、含水親水性高分子物質3955g(低置換度ヒドロキシプロピルセルロース(LHPC:LH−31:信越化学(株)製)950gと精製水3005g)からなる混合物をバーチカルグラニュレーターVG−10(パウレック(株))で均一に混合後、ツインドームグランTDG−80(不二パウダル(株)製)0.6mmスクリーンで押し出し造粒した。次に、流動層乾燥装置FLO−5A/2(フロイント産業(株)製)にて乾燥し、平均粒径約0.5mmの顆粒剤を製し、四方アルミヒートシールにて一包あたりの質量が1gになるように分包した。この顆粒剤の乾燥減量は50℃10分で0.8%であった。
塩酸ジフェンヒドラミン(金剛化学(株)製)5g、および、低置換度ヒドロキシプロピルセルロース(LHPC:LH−31:信越化学(株)製)95gを均一に混合し、四方アルミヒートシールにて一包あたりの質量が1gになるように分包した。
アセトアミノフェン(山本化学工業(株)製)225g、エテンザミド(静岡カフェイン工業所(株)製)285g、含水親水性高分子物質1470g(低置換度ヒドロキシプロピルセルロース(LHPC:LH−31:信越化学(株)製)390g、精製水864g、日本薬局方エタノール(ワコーケミカル(株)製)216g)からなる混合物をバーチカルグラニュレーターVG−10(パウレック(株))で均一に混合後、ツインドームグランTDG−80(不二パウダル(株)製)0.6mmスクリーンで押し出し造粒した。次に、流動層乾燥装置FLO−5A/2(フロイント産業(株)製)にて乾燥し、平均粒径約0.5mmの顆粒剤を製し、四方アルミヒートシールにて一包あたりの質量が1.2gになるように分包した。この顆粒剤の乾燥減量は50℃10分で0.4%であった。
アセトアミノフェン(山本化学工業(株)製)22.5g、エテンザミド(静岡カフェイン工業所(株)製)28.5g、および、低置換度ヒドロキシプロピルセルロース(LHPC:LH−31:信越化学(株)製)39gを均一に混合し、四方アルミヒートシールにて一包あたりの質量が1.2gになるように分包した。
臭化水素酸デキストロメトルファン(ワタナベケミカル(株)製)40g、テオフィリン(白鳥製薬(株))200g、塩化リゾチーム(エーザイ(株))40g、含水親水性高分子物質2790g(低置換度ヒドロキシプロピルセルロース(LHPC:LH−31:信越化学(株)製)720g、精製水2070g)からなる混合物をバーチカルグラニュレーターVG−10(パウレック(株))で均一に混合後、ツインドームグランTDG−80(不二パウダル(株)製)0.4mmスクリーンで押し出し造粒した。次に、流動層乾燥装置FLO−5A/2(フロイント産業(株)製)にて乾燥し、平均粒径約0.3mmの顆粒剤を製し、四方アルミヒートシールにて一包あたりの質量が500mgになるように分包した。この顆粒剤の乾燥減量は50℃10分で0.9%であった。
臭化水素酸デキストロメトルファン(ワタナベケミカル(株)製)4g、テオフィリン(白鳥製薬(株))20g、塩化リゾチーム(エーザイ(株))4g、および、低置換度ヒドロキシプロピルセルロース(LHPC:LH−31:信越化学(株)製)72gを均一に混合し、四方アルミヒートシールにて一包あたりの質量が500mgになるように分包した。
被験者10名を用い官能試験を行った結果を下記に示す。服用方法は実施例1〜9及び比較例1〜9の製剤それぞれ1包を10秒間口に含んだのち、吐き出し、服用感を比較した。評価は、5段階に分け、苦味(非常に強い苦み:5点、やや強い苦み:4点、苦い:3点、やや苦い:2点、苦くない:1点)について、評価を行った。この結果を表1に示す。
Claims (5)
- (B)親水性高分子としてヒドロキシプロポキシ基が7.0〜13.0質量%である低置換度ヒドロキシプロピルセルロースを用い、該親水性高分子に水を、水:親水性高分子=1〜10:1の範囲で加え含水親水性高分子とし、これを(A)苦味を呈する薬物と混合し、造粒し、次いで水分量7.5質量%以下になるまで乾燥することにより得られる経口固形製剤。
- (A)苦味を呈する薬物1質量部に対し、(B)親水性高分子を0.05質量部以上含有する請求項1記載の経口固形製剤。
- 低置換度ヒドロキシプロピルセルロースの平均粒径が60μm以下である請求項1又は2記載の経口固形製剤。
- 顆粒剤、細粒剤、カプセル剤又は錠剤である請求項1〜3の何れか1項記載の経口固形製剤。
- 乾燥して得られた顆粒の平均粒径が25μm以上である請求項1〜4の何れか1項記載の経口固形製剤。
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2006345147A JP5527921B2 (ja) | 2006-12-22 | 2006-12-22 | 苦味を隠蔽した経口固形組成物 |
TW096139925A TWI426921B (zh) | 2006-12-22 | 2007-10-24 | 遮蔽苦味之經口固形組合物 |
KR1020070113702A KR20080059035A (ko) | 2006-12-22 | 2007-11-08 | 쓴 맛을 은폐한 경구 고형 조성물 |
CNA2007103005026A CN101239042A (zh) | 2006-12-22 | 2007-12-19 | 遮蔽了苦味的口服固体组合物 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2006345147A JP5527921B2 (ja) | 2006-12-22 | 2006-12-22 | 苦味を隠蔽した経口固形組成物 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2008156258A JP2008156258A (ja) | 2008-07-10 |
JP5527921B2 true JP5527921B2 (ja) | 2014-06-25 |
Family
ID=39657597
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006345147A Active JP5527921B2 (ja) | 2006-12-22 | 2006-12-22 | 苦味を隠蔽した経口固形組成物 |
Country Status (4)
Country | Link |
---|---|
JP (1) | JP5527921B2 (ja) |
KR (1) | KR20080059035A (ja) |
CN (1) | CN101239042A (ja) |
TW (1) | TWI426921B (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010241760A (ja) * | 2009-04-09 | 2010-10-28 | Takada Seiyaku Kk | 不快な味の軽減された口腔内速崩壊錠及びその製造方法 |
CN103239412A (zh) * | 2013-05-15 | 2013-08-14 | 北京科源创欣科技有限公司 | 一种含洛哌丁胺或其盐酸盐的药物组合物及其制备方法 |
CN104546736A (zh) * | 2014-12-25 | 2015-04-29 | 北京科源创欣科技有限公司 | 小儿盐酸洛哌丁胺颗粒及其制备工艺 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4837030A (en) * | 1987-10-06 | 1989-06-06 | American Cyanamid Company | Novel controlled release formulations of tetracycline compounds |
JP3317444B2 (ja) * | 1989-07-20 | 2002-08-26 | 大日本製薬株式会社 | 不快な味が遮蔽された速放性製剤 |
JP2841267B2 (ja) * | 1993-12-17 | 1998-12-24 | エスエス製薬株式会社 | イブプロフェン含有粒剤 |
JPH09208458A (ja) * | 1996-02-02 | 1997-08-12 | Ss Pharmaceut Co Ltd | 不快な味がマスキングされた製剤 |
JP4711478B2 (ja) * | 1999-08-13 | 2011-06-29 | 旭化成ケミカルズ株式会社 | 味がマスクされた薬物 |
AU2001267865A1 (en) * | 2000-06-30 | 2002-01-14 | Yamanouchi Pharmaceutical Co..Ltd. | Tablet rapidly disintegrating in mouth and process for producing the same |
EP1701707A2 (en) * | 2003-12-29 | 2006-09-20 | Alza Corporation, Inc. | Drug granule coatings that impart smear resistance during mechanical compression |
PL1750862T3 (pl) * | 2004-06-04 | 2011-06-30 | Teva Pharma | Kompozycja farmaceutyczna zawierająca irbesartan |
EP1789022A2 (en) * | 2004-08-31 | 2007-05-30 | Pfizer Products Incorporated | Controlled release dosage forms combining immediate release and sustained release of low-solubility drug |
GT200600119A (es) * | 2005-03-24 | 2006-10-25 | Composiciones farmaceuticas |
-
2006
- 2006-12-22 JP JP2006345147A patent/JP5527921B2/ja active Active
-
2007
- 2007-10-24 TW TW096139925A patent/TWI426921B/zh active
- 2007-11-08 KR KR1020070113702A patent/KR20080059035A/ko not_active Application Discontinuation
- 2007-12-19 CN CNA2007103005026A patent/CN101239042A/zh active Pending
Also Published As
Publication number | Publication date |
---|---|
TW200826962A (en) | 2008-07-01 |
KR20080059035A (ko) | 2008-06-26 |
JP2008156258A (ja) | 2008-07-10 |
TWI426921B (zh) | 2014-02-21 |
CN101239042A (zh) | 2008-08-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6092936B2 (ja) | 口腔内崩壊錠の製造方法 | |
EP2893940B1 (en) | Granulated material for tablet that rapidly disintegrates in mouth | |
DK1886678T3 (en) | STABLE TABLET CONTAINING DROXIDOPA | |
KR101465803B1 (ko) | 구강내 붕괴 정제 | |
US20120171296A1 (en) | Rapidly disintegrating solid preparation | |
JP5209876B2 (ja) | 速崩壊性錠剤及びその製造方法 | |
JP5490347B2 (ja) | 経口投与用製剤 | |
JP5201819B2 (ja) | 固形組成物 | |
JP2008094837A (ja) | 苦味マスキング | |
JP5527921B2 (ja) | 苦味を隠蔽した経口固形組成物 | |
JP6803250B2 (ja) | エレトリプタン臭化水素酸塩含有口腔内崩壊錠 | |
JP5572321B2 (ja) | 被覆微粒子含有口腔内崩壊錠 | |
JP5201837B2 (ja) | 口腔内速崩壊錠 | |
WO2003053415A1 (en) | Pharmaceutical composition comprising skim milk powder | |
JP5828280B2 (ja) | 錠剤及びその製造方法 | |
JP4716063B2 (ja) | 不快味マスキング粒子及びこれを含有する経口製剤 | |
JP6538321B2 (ja) | 経口組成物 | |
JP7148319B2 (ja) | プラスグレルを含む口腔内崩壊錠 | |
JP3778240B2 (ja) | 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 | |
JP4845087B2 (ja) | 経口投与用製剤 | |
KR20180098282A (ko) | 압축 성형 제제 | |
JP2008280316A (ja) | 経口投与用錠剤 | |
TW201609193A (zh) | 含有碳酸鹽之口腔內崩解錠劑用組成物及口腔內崩解錠劑 | |
KR20140122017A (ko) | 엔테카비르 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 속붕해성 제제 및 이의 제조방법 | |
JP6150564B2 (ja) | 口腔内速崩壊性錠剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090918 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20120614 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120626 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120824 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120829 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120925 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130402 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140107 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140303 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140408 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140415 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5527921 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |