JP5887893B2 - 内服液剤 - Google Patents
内服液剤 Download PDFInfo
- Publication number
- JP5887893B2 JP5887893B2 JP2011264412A JP2011264412A JP5887893B2 JP 5887893 B2 JP5887893 B2 JP 5887893B2 JP 2011264412 A JP2011264412 A JP 2011264412A JP 2011264412 A JP2011264412 A JP 2011264412A JP 5887893 B2 JP5887893 B2 JP 5887893B2
- Authority
- JP
- Japan
- Prior art keywords
- triptan
- acid
- internal
- rizatriptan
- tryptophan
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
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- 229940100688 oral solution Drugs 0.000 title description 9
- ZISSAWUMDACLOM-UHFFFAOYSA-N triptane Chemical compound CC(C)C(C)(C)C ZISSAWUMDACLOM-UHFFFAOYSA-N 0.000 claims description 64
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 45
- 239000007788 liquid Substances 0.000 claims description 20
- 229960000425 rizatriptan Drugs 0.000 claims description 17
- TXHZXHICDBAVJW-UHFFFAOYSA-N rizatriptan Chemical compound C=1[C]2C(CCN(C)C)=CN=C2C=CC=1CN1C=NC=N1 TXHZXHICDBAVJW-UHFFFAOYSA-N 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 16
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 claims description 16
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 15
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 15
- 235000015165 citric acid Nutrition 0.000 claims description 15
- 235000002639 sodium chloride Nutrition 0.000 claims description 14
- 229960003708 sumatriptan Drugs 0.000 claims description 14
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 12
- 229960001360 zolmitriptan Drugs 0.000 claims description 12
- UTAZCRNOSWWEFR-ZDUSSCGKSA-N zolmitriptan Chemical compound C=1[C]2C(CCN(C)C)=CN=C2C=CC=1C[C@H]1COC(=O)N1 UTAZCRNOSWWEFR-ZDUSSCGKSA-N 0.000 claims description 12
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 10
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 10
- 239000001630 malic acid Substances 0.000 claims description 10
- 235000011090 malic acid Nutrition 0.000 claims description 10
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 9
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 9
- 239000011975 tartaric acid Substances 0.000 claims description 9
- 235000002906 tartaric acid Nutrition 0.000 claims description 9
- 239000004310 lactic acid Substances 0.000 claims description 6
- 235000014655 lactic acid Nutrition 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 229960002472 eletriptan Drugs 0.000 claims description 5
- OTLDLQZJRFYOJR-LJQANCHMSA-N eletriptan Chemical compound CN1CCC[C@@H]1CC1=CN=C2[C]1C=C(CCS(=O)(=O)C=1C=CC=CC=1)C=C2 OTLDLQZJRFYOJR-LJQANCHMSA-N 0.000 claims description 5
- 229960005254 naratriptan Drugs 0.000 claims description 5
- UNHGSHHVDNGCFN-UHFFFAOYSA-N naratriptan Chemical compound C=12[CH]C(CCS(=O)(=O)NC)=CC=C2N=CC=1C1CCN(C)CC1 UNHGSHHVDNGCFN-UHFFFAOYSA-N 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 4
- 239000000243 solution Substances 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 9
- 208000019695 Migraine disease Diseases 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 8
- 206010027599 migraine Diseases 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- -1 dimethylaminoethyl Chemical group 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- JPRXYLQNJJVCMZ-UHFFFAOYSA-N Rizatriptan benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1.C1=C2C(CC[NH+](C)C)=CNC2=CC=C1CN1C=NC=N1 JPRXYLQNJJVCMZ-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000012676 herbal extract Substances 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229940100656 nasal solution Drugs 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 229960004789 rizatriptan benzoate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
(1)トリプタン又はその薬理上許容される塩と、クエン酸、リンゴ酸、酒石酸、乳酸及びこれらの塩からなる群から選ばれる一種以上の酸味料、さらにトリプトファンを配合したことを特徴とする内服液剤、
(2)トリプタンがリザトリプタン、ゾルミトリプタン、スマトリプタン、エレトリプタン、ナラトリプタンから選択される(1)に記載の内服液剤、
(3)クエン酸、リンゴ酸、酒石酸、乳酸及びこれらの塩からなる群から選ばれる一種以上の酸味料を、トリプタン又はその薬理上許容される塩を含有する内服液剤に配合した際に生じる、トリプタンの安定性の低下を、トリプトファンを配合することにより抑制する方法、
である。
(1)各内服液剤の調製
表1〜3に記載の処方の各成分を秤量して、精製水に溶解させ、pHを2.5、4.0及び5.0になるよう、かつ、内服液剤の全量が10mLとなるよう調整した。その後にガラス瓶に充填し、キャップを施して本発明の実施例1〜9及び比較例1〜12の内服液剤を得た。
表1〜2に記載の実施例1〜9及び比較例1〜10で示す組成のリザトリプタン含有内服液剤を65℃の恒温槽中で14日間保存し、内服液剤中のリザトリプタン含有量をHPLCで測定した。安息香酸リザトリプタンを溶解させた直後の内服液剤中のリザトリプタン含有量に対して、65℃、14日間保存後の内服液剤中のリザトリプタン含有量(残存率)を計算した。また、表3の実施例10〜11及び比較例11〜12で示す組成のスマトリプタン及びゾルミトリプタン含有内服液剤を65℃の恒温槽中で14日間保存し、内服液剤中のスマトリプタン及びゾルミトリプタン含有量をHPLCで測定した。コハク酸スマトリプタン及びゾルミトリプタンを溶解させた直後の内服液剤中のスマトリプタン及びゾルミトリプタン含有量に対して、65℃、14日間保存後の内服液剤中のスマトリプタン及びゾルミトリプタン含有量(残存率)を計算した。結果を表1〜3に示す。
表1〜2に示す実験結果より、クエン酸を配合した比較例1では、65℃、14日間保存後の内服液剤中のリザトリプタンの残存率が低くなることが分かった。しかし、トリプトファンを配合した実施例1〜5では、クエン酸を配合した際に生じる内服液剤中のリザトリプタンの安定性の低下を抑制できていることが分かった。
Claims (2)
- リザトリプタン、ゾルミトリプタン、スマトリプタン、エレトリプタン、ナラトリプタンから選択されるトリプタン又はその薬理上許容される塩と、クエン酸、リンゴ酸、酒石酸、乳酸及びこれらの塩からなる群から選ばれる一種以上の酸味料、さらにトリプトファンを配合したことを特徴とする内服液剤。
- クエン酸、リンゴ酸、酒石酸、乳酸及びこれらの塩からなる群から選ばれる一種以上の酸味料を、リザトリプタン、ゾルミトリプタン、スマトリプタン、エレトリプタン、ナラトリプタンから選択されるトリプタン又はその薬理上許容される塩を含有する内服液剤に配合した際に生じる、前記トリプタンの安定性の低下を、トリプトファンを配合することにより抑制する方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2011264412A JP5887893B2 (ja) | 2010-12-10 | 2011-12-02 | 内服液剤 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010275317 | 2010-12-10 | ||
JP2010275317 | 2010-12-10 | ||
JP2011264412A JP5887893B2 (ja) | 2010-12-10 | 2011-12-02 | 内服液剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2012136512A JP2012136512A (ja) | 2012-07-19 |
JP5887893B2 true JP5887893B2 (ja) | 2016-03-16 |
Family
ID=46674241
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011264412A Active JP5887893B2 (ja) | 2010-12-10 | 2011-12-02 | 内服液剤 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP5887893B2 (ja) |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0341033A (ja) * | 1989-07-07 | 1991-02-21 | Kyowa Hakko Kogyo Co Ltd | 安定なモチリン類含有製剤 |
JP3021312B2 (ja) * | 1994-03-15 | 2000-03-15 | 千寿製薬株式会社 | プラノプロフェンの安定化方法および安定なプラノプロフェン水性液剤 |
TW518219B (en) * | 1996-04-26 | 2003-01-21 | Chugai Pharmaceutical Co Ltd | Erythropoietin solution preparation |
ID24528A (id) * | 1997-07-03 | 2000-07-20 | Pfizer | Komposisi-komposisi obat farmasi yang mengandung eletriptan hemisulfat dan kafein |
EP2170063A1 (en) * | 2007-07-23 | 2010-04-07 | Teikoku Pharma USA, Inc. | Organoleptically acceptable indole serotonin receptor agonist oral dosage formulations and methods of using the same |
EP2198889A1 (en) * | 2008-12-22 | 2010-06-23 | Almirall, S.A. | Liquid pharmaceutical compositions comprising a triptan compound and Xylitol |
-
2011
- 2011-12-02 JP JP2011264412A patent/JP5887893B2/ja active Active
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Publication number | Publication date |
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JP2012136512A (ja) | 2012-07-19 |
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