JP7419263B2 - 医薬製剤 - Google Patents
医薬製剤 Download PDFInfo
- Publication number
- JP7419263B2 JP7419263B2 JP2020565473A JP2020565473A JP7419263B2 JP 7419263 B2 JP7419263 B2 JP 7419263B2 JP 2020565473 A JP2020565473 A JP 2020565473A JP 2020565473 A JP2020565473 A JP 2020565473A JP 7419263 B2 JP7419263 B2 JP 7419263B2
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- JP
- Japan
- Prior art keywords
- film
- weight
- alginate
- adrenaline
- acid
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title description 8
- 239000000203 mixture Substances 0.000 claims description 232
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical group CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 claims description 230
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 196
- 235000010443 alginic acid Nutrition 0.000 claims description 147
- 229920000615 alginic acid Polymers 0.000 claims description 147
- 229940072056 alginate Drugs 0.000 claims description 107
- 235000010323 ascorbic acid Nutrition 0.000 claims description 98
- 229960005070 ascorbic acid Drugs 0.000 claims description 98
- 239000011668 ascorbic acid Substances 0.000 claims description 98
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 84
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 claims description 74
- 229960005139 epinephrine Drugs 0.000 claims description 71
- 229930182837 (R)-adrenaline Natural products 0.000 claims description 70
- 239000003963 antioxidant agent Substances 0.000 claims description 69
- 235000006708 antioxidants Nutrition 0.000 claims description 69
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 68
- 239000000243 solution Substances 0.000 claims description 60
- -1 cation alginate Chemical class 0.000 claims description 59
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 56
- 150000003839 salts Chemical class 0.000 claims description 54
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- 125000002091 cationic group Chemical group 0.000 claims description 42
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims description 42
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 40
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 33
- 206010002198 Anaphylactic reaction Diseases 0.000 claims description 31
- 208000003455 anaphylaxis Diseases 0.000 claims description 30
- 238000002156 mixing Methods 0.000 claims description 30
- 230000036783 anaphylactic response Effects 0.000 claims description 29
- 230000015572 biosynthetic process Effects 0.000 claims description 27
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 26
- 229940001584 sodium metabisulfite Drugs 0.000 claims description 26
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
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- 210000000214 mouth Anatomy 0.000 claims description 24
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- 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 claims description 20
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- 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 13
- 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 claims description 12
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 12
- 229910052782 aluminium Inorganic materials 0.000 claims description 10
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 10
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- 239000002585 base Substances 0.000 claims description 9
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- 235000010413 sodium alginate Nutrition 0.000 claims description 8
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- 229940095064 tartrate Drugs 0.000 claims description 8
- 239000011260 aqueous acid Substances 0.000 claims description 7
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical group CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 6
- 235000015165 citric acid Nutrition 0.000 claims description 6
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- 230000007480 spreading Effects 0.000 claims description 6
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- 239000004322 Butylated hydroxytoluene Substances 0.000 claims description 5
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 5
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 5
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- AEMOLEFTQBMNLQ-AZLKCVHYSA-N (2r,3s,4s,5s,6r)-3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound O[C@@H]1O[C@@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-AZLKCVHYSA-N 0.000 claims description 4
- AEMOLEFTQBMNLQ-SYJWYVCOSA-N (2s,3s,4s,5s,6r)-3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound O[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-SYJWYVCOSA-N 0.000 claims description 4
- 229960004106 citric acid Drugs 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims 1
- 239000000728 ammonium alginate Substances 0.000 claims 1
- 235000010407 ammonium alginate Nutrition 0.000 claims 1
- KPGABFJTMYCRHJ-YZOKENDUSA-N ammonium alginate Chemical compound [NH4+].[NH4+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O KPGABFJTMYCRHJ-YZOKENDUSA-N 0.000 claims 1
- 238000007865 diluting Methods 0.000 claims 1
- 235000010408 potassium alginate Nutrition 0.000 claims 1
- 239000000737 potassium alginate Substances 0.000 claims 1
- MZYRDLHIWXQJCQ-YZOKENDUSA-L potassium alginate Chemical compound [K+].[K+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O MZYRDLHIWXQJCQ-YZOKENDUSA-L 0.000 claims 1
- 238000007789 sealing Methods 0.000 claims 1
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- 239000001257 hydrogen Substances 0.000 description 28
- 229910052739 hydrogen Inorganic materials 0.000 description 28
- 239000000126 substance Substances 0.000 description 26
- 230000000694 effects Effects 0.000 description 23
- 239000003795 chemical substances by application Substances 0.000 description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 19
- 239000003381 stabilizer Substances 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000003961 penetration enhancing agent Substances 0.000 description 18
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- 229910019142 PO4 Inorganic materials 0.000 description 14
- 239000002535 acidifier Substances 0.000 description 14
- 125000000217 alkyl group Chemical group 0.000 description 14
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- KSCKTBJJRVPGKM-UHFFFAOYSA-N octan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-] KSCKTBJJRVPGKM-UHFFFAOYSA-N 0.000 description 1
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- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
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- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
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- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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Landscapes
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- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| SE544672C2 (en) | 2020-05-07 | 2022-10-11 | Liw Innovation Ab | New compositions for oral or nasal use |
| US12414916B2 (en) | 2021-06-10 | 2025-09-16 | Belhaven BioPharma Inc. | Dry powder formulations of epinephrine and associated methods |
| EP4302750A1 (en) * | 2022-07-07 | 2024-01-10 | LTS Lohmann Therapie-Systeme AG | Oral thin films comprising adrenaline |
| EP4302751A1 (en) * | 2022-07-07 | 2024-01-10 | LTS Lohmann Therapie-Systeme AG | Oral thin films with low water activity |
| CN115950999B (zh) * | 2022-12-21 | 2024-08-30 | 武汉嘉诺康医药技术有限公司 | 一种同时检测重酒石酸去甲肾上腺素中api游离碱与配对有机酸的hplc检测方法 |
| US20260108686A1 (en) | 2024-10-21 | 2026-04-23 | Belhaven BioPharma Inc. | Compositions, devices, and methods for intranasal delivery of dry powder epinephrine |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009521433A (ja) | 2005-12-23 | 2009-06-04 | ステンバーグ，カージェル | 低粘度アルギン酸塩含有水溶性薄膜 |
| JP2016513736A (ja) | 2013-03-15 | 2016-05-16 | モノソル アールエックス リミテッド ライアビリティ カンパニー | 舌下及び頬用フィルム組成物 |
| JP2016521759A (ja) | 2013-06-17 | 2016-07-25 | リグスホスピタルＲｉｇｓｈｏｓｐｉｔａｌｅｔ | アドレナリンおよびクエン酸を含む注射用医薬組成物 |
| WO2017135195A1 (ja) | 2016-02-03 | 2017-08-10 | 社会医療法人蘇西厚生会 まつなみリサーチパーク | アレルギー症状の予防又は治療剤 |
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| GB933462A (en) * | 1958-12-17 | 1963-08-08 | Simone Marie Antoinette Radouc | Improvements in or relating to the treatment of meat |
| US5288498A (en) | 1985-05-01 | 1994-02-22 | University Of Utah Research Foundation | Compositions of oral nondissolvable matrixes for transmucosal administration of medicaments |
| US5288497A (en) | 1985-05-01 | 1994-02-22 | The University Of Utah | Compositions of oral dissolvable medicaments |
| US5785989A (en) | 1985-05-01 | 1998-07-28 | University Utah Research Foundation | Compositions and methods of manufacturing of oral dissolvable medicaments |
| WO1998001134A1 (en) | 1996-07-10 | 1998-01-15 | Novartis Consumer Health S.A. | Oral pharmaceutical combinations of antihistaminic compounds and terpenoids |
| AU3444297A (en) | 1996-07-12 | 1998-02-09 | Novartis Consumer Health S.A. | Oral pharmaceutical combinations of nsaids with terpenoids |
| US6596298B2 (en) | 1998-09-25 | 2003-07-22 | Warner-Lambert Company | Fast dissolving orally comsumable films |
| KR100452972B1 (ko) | 2000-05-16 | 2004-10-14 | 주식회사 삼양사 | 경피투여용 하이드로젤 조성물 |
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| US20250099374A1 (en) | 2025-03-27 |
| KR20210031857A (ko) | 2021-03-23 |
| IL278927B2 (en) | 2025-01-01 |
| MX2020012336A (es) | 2021-01-29 |
| JP2024050598A (ja) | 2024-04-10 |
| MA52704A (fr) | 2021-03-31 |
| DK3796896T3 (da) | 2026-03-30 |
| AU2019274772B2 (en) | 2024-11-21 |
| CN112236133A (zh) | 2021-01-15 |
| GB201808462D0 (en) | 2018-07-11 |
| IL278927B1 (en) | 2024-09-01 |
| FI3796896T3 (fi) | 2026-03-26 |
| JP2021526519A (ja) | 2021-10-07 |
| CN112236133B (zh) | 2025-02-25 |
| AU2019274772A1 (en) | 2020-11-19 |
| EP3796896A1 (en) | 2021-03-31 |
| US20210369601A1 (en) | 2021-12-02 |
| IL278927A (en) | 2021-01-31 |
| WO2019224323A1 (en) | 2019-11-28 |
| CA3098112A1 (en) | 2019-11-28 |
| EP3796896B1 (en) | 2025-12-31 |
| BR112020023741A2 (pt) | 2021-02-09 |
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