JP5435659B2 - トリプタンの経口腔粘膜投与用製剤形態 - Google Patents
トリプタンの経口腔粘膜投与用製剤形態 Download PDFInfo
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- JP5435659B2 JP5435659B2 JP2010544764A JP2010544764A JP5435659B2 JP 5435659 B2 JP5435659 B2 JP 5435659B2 JP 2010544764 A JP2010544764 A JP 2010544764A JP 2010544764 A JP2010544764 A JP 2010544764A JP 5435659 B2 JP5435659 B2 JP 5435659B2
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- Prior art keywords
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- active ingredient
- sumatriptan
- base
- triptan
- Prior art date
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- ZISSAWUMDACLOM-UHFFFAOYSA-N triptane Chemical compound CC(C)C(C)(C)C ZISSAWUMDACLOM-UHFFFAOYSA-N 0.000 title claims abstract description 59
- 239000000203 mixture Substances 0.000 title claims abstract description 46
- 238000009472 formulation Methods 0.000 title claims abstract description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 89
- 239000004480 active ingredient Substances 0.000 claims abstract description 63
- 238000004090 dissolution Methods 0.000 claims abstract description 15
- 150000003839 salts Chemical group 0.000 claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 210000004400 mucous membrane Anatomy 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims description 62
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical group CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 claims description 57
- 229960003708 sumatriptan Drugs 0.000 claims description 37
- KQKPFRSPSRPDEB-XERRXZQWSA-N 1-[3-[2-[bis(trideuteriomethyl)amino]ethyl]-1h-indol-5-yl]-n-methylmethanesulfonamide Chemical compound C1=C(CS(=O)(=O)NC)C=C2C(CCN(C([2H])([2H])[2H])C([2H])([2H])[2H])=CNC2=C1 KQKPFRSPSRPDEB-XERRXZQWSA-N 0.000 claims description 30
- 229960000658 sumatriptan succinate Drugs 0.000 claims description 29
- 238000003756 stirring Methods 0.000 claims description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- 239000008213 purified water Substances 0.000 claims description 22
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 210000000214 mouth Anatomy 0.000 claims description 11
- 206010019233 Headaches Diseases 0.000 claims description 10
- 231100000869 headache Toxicity 0.000 claims description 9
- 239000002552 dosage form Substances 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 4
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- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000001488 sodium phosphate Substances 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
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- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 2
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- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 2
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- 239000011976 maleic acid Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 2
- 235000011008 sodium phosphates Nutrition 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims 1
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- 208000019695 Migraine disease Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
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- 239000012298 atmosphere Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- PORMUFZNYQJOEI-UHFFFAOYSA-N sumatriptan succinate Chemical compound OC(=O)CCC(O)=O.CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 PORMUFZNYQJOEI-UHFFFAOYSA-N 0.000 description 2
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- 229960001360 zolmitriptan Drugs 0.000 description 2
- 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 description 2
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- WKEMJKQOLOHJLZ-UHFFFAOYSA-N Almogran Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CS(=O)(=O)N1CCCC1 WKEMJKQOLOHJLZ-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241001631457 Cannula Species 0.000 description 1
- 206010021518 Impaired gastric emptying Diseases 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
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- 206010030113 Oedema Diseases 0.000 description 1
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- 229960002133 almotriptan Drugs 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
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- 229960002472 eletriptan Drugs 0.000 description 1
- 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 description 1
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- 239000004615 ingredient Substances 0.000 description 1
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- 210000003097 mucus Anatomy 0.000 description 1
- 229960005254 naratriptan Drugs 0.000 description 1
- 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 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 229940100656 nasal solution Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
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- 229940076279 serotonin Drugs 0.000 description 1
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Classifications
-
- 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
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- 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
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Organic Chemistry (AREA)
- Pain & Pain Management (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
‐塩基及び塩の形態の前記有効成分、及び、
‐少なくとも15度のアルコール含有量を示す含水アルコール溶液、
を含み、前記有効成分が含水アルコール溶液中に安定した、完全な溶解状態で存在する極めて特効のある製剤形態を提案することによって、上記の問題を解決しようとするものである。
‐塩基及び塩の形態の前記有効成分、及び、
‐少なくとも15度のアルコール含有量を示す含水アルコール溶液、
を含み、前記有効成分が含水アルコール溶液中に安定した、完全な溶解状態で存在し、それによって、口腔及び/または中咽頭の粘膜を通して該有効成分を迅速に吸収することができる処方を目的とする。
‐親油性分子で、低分子量のトリプタン族の有効成分の溶媒の役割を果たし、
‐溶解し、従って、親油性膜の位置で分子状態であるこの有効成分の経粘膜通過を活性化し、
‐アルコール度は、浸透作用によって、及び、局所的微小循環流量を増大させる反射微小血管拡張を引き起こして、粘膜吸収速度を倍に増大させ、及び、
‐それ自体の安定化剤であり、それによって、従来の添加剤の使用が避けられる。
‐塩基の形態のトリプタン族の少なくとも一つの有効成分をアルコール中に導入し、
‐前記有効成分が完全に溶解するまで調製物を攪拌し、
‐調製物に精製水、次に、塩の形態の該有効成分を添加し、
‐完全に溶解するまで調製物を攪拌し、
‐所望の容積にするために必要ならば水を添加する、
段階を備える。
‐塩基の形態のトリプタン族の少なくとも一つの有効成分、好ましくは、スマトリプタン塩基を攪拌しながらアルコール中に導入し、
‐完全に溶解するまで、好ましくは、10〜60分間、調製物を攪拌し、
‐調製物に精製水、次に、塩の形態の該有効成分、好ましくは、コハク酸スマトリプタンを添加し、
‐完全に溶解するまで、好ましくは、10〜60分間、調製物を攪拌し、
‐所望の容積にするために必要ならば水を添加し、
‐pH補正剤を添加して、4.0〜9.0、好ましくは、4.0〜8.0の範囲の生理学的に両立するpHにし、
‐調製物を濾過し、
‐得られた溶液を、容量が5mlより小さい、適した容器、好ましくは、茶色のガラスまたは不透明なポリマー製の容量2mlの小瓶に配分し、安定性を確実なものにする
段階を備える。
−スマトリプタン 6.0mg
下記の形態で導入
スマトリプタン塩基 1.20mg
コハク酸スマトリプタン 6.72mg
−エチルアルコール95%V:V: 0.3ml
−精製水 qsp0.75ml
−スマトリプタン 4.0mg
下記の形態で導入
スマトリプタン塩基 0.8mg
コハク酸スマトリプタン 4.48mg
−エチルアルコール95%V:V: 0.3ml
−精製水 qsp0.75ml
−スマトリプタン 2.0mg
下記の形態で導入
スマトリプタン塩基 0.4mg
コハク酸スマトリプタン 2.24mg
−エチルアルコール95%V:V: 0.3ml
−精製水 qsp0.75ml
−スマトリプタン 1.0mg
下記の形態で導入
スマトリプタン塩基 0.20mg
コハク酸スマトリプタン 1.12mg
−エチルアルコール95%V:V: 0.3ml
−精製水 qsp0.75ml
−スマトリプタン 1.0mg
下記の形態で導入
スマトリプタン塩基 0.20mg
コハク酸スマトリプタン 1.12mg
−エチルアルコール95%V:V: 0.3ml
−精製水 qsp0.75ml
−水酸化ナトリウム qsp pH7.5
−スマトリプタン 0.75mg
下記の形態で導入
スマトリプタン塩基 0.15mg
コハク酸スマトリプタン 0.84mg
−エチルアルコール95%V:V: 0.3ml
−精製水 qsp0.75ml
−スマトリプタン 0.50mg
下記の形態で導入
スマトリプタン塩基 0.10mg
コハク酸スマトリプタン 0.56mg
−エチルアルコール95%V:V: 0.3ml
−精製水 qsp0.75ml
−スマトリプタン 0.25mg
下記の形態で導入
スマトリプタン塩基 0.05mg
コハク酸スマトリプタン 0.28mg
−エチルアルコール95%V:V: 0.4ml
−精製水 qsp0.75ml
−スマトリプタン 2.00mg
下記の形態で導入
スマトリプタン塩基 1.6mg
コハク酸スマトリプタン 0.56mg
−エチルアルコール95%V:V: 0.4ml
−精製水 qsp0.75ml
−重炭酸ナトリウム qs pH7.5
Claims (13)
- トリプタン族の少なくとも一つの有効成分の経口腔粘膜投与用の製剤形態であって、少なくとも、
‐塩基及び塩の形態の前記有効成分、及び、
‐唯一の溶媒として、溶媒中の組成が体積比で、15%乃至70%を占める水と85%乃至30%を占めるエタノールからなる含水アルコール溶液
を含み、前記有効成分が前記含水アルコール溶液中に安定した、完全な溶解状態で存在し、それによって、口腔の粘膜を通して該有効成分を迅速に吸収することができる製剤形態。 - 前記有効成分は、塩基の形態で5〜95%、及び、塩の形態で5〜95%の範囲で存在することを特徴とする請求項1に記載の製剤形態。
- 前記有効成分は、塩基の形態で5〜40%、及び、塩の形態で60〜95%の範囲で存在することを特徴とする請求項1または2に記載の製剤形態。
- 前記の少なくとも一つの有効成分は、塩基の形態及び該有効成分のコハク酸塩、塩酸塩または硫酸塩の形態であることを特徴とする請求項1〜3のいずれか一つに記載の製剤形態。
- 前記の少なくとも一つの有効成分は、スマトリプタンであることを特徴とする請求項1〜4のいずれか一つに記載の製剤形態。
- 前記含水アルコール溶液は、pH補正剤を含むことを特徴とする請求項1〜5のいずれか一つに記載の製剤形態。
- 前記pH補正剤は、好ましくは、炭酸ナトリウム、重炭酸ナトリウム、リン酸ナトリウム、リン酸二ナトリウム、トリエタノールアミン、ソーダ、カリウム、及び/または、塩酸剤、硫酸剤、コハク酸剤、酪酸剤、リン酸剤、クエン酸剤、マレイン酸剤及び/または乳酸剤の中から選択されることを特徴とする請求項6に記載の製剤形態。
- pHは、4.0〜9.0の範囲であることを特徴とする請求項1〜7のいずれか一つに記載の製剤形態。
- 前記含水アルコール溶液の容積は、5mlであることを特徴とする請求項1〜8のいずれか一つに記載の製剤形態。
- 前記粘膜が歯肉及び/または頬粘膜である、請求項1〜9のいずれか一つに記載の製剤形態。
- 下記の;
‐塩基の形態のトリプタン族の少なくとも一つの有効成分をエタノール中に導入し、
‐前記有効成分が完全に溶解するまで調製物を攪拌し、
‐調製物に精製水、次に、塩の形態の該有効成分を添加し、
‐完全に溶解するまで調製物を攪拌し、
‐所望の容積にするために必要ならば水を添加する、
段階を備えることを特徴とする請求項1〜10のいずれか一つに記載の製剤形態の調製方法。 - 下記の;
‐スマトリプタン塩基を攪拌しながらアルコール中に導入し、
‐完全に溶解するまで、好ましくは、10〜60分間、調製物を攪拌し、
‐調製物に精製水、次に、コハク酸スマトリプタンを添加し、
‐完全に溶解するまで、好ましくは、10〜60分間、調製物を攪拌し、
‐所望の容積にするために必要ならば水を添加し、
‐pH補正剤を添加して、4.0〜9.0の範囲の生理学的に両立するpHにし、
‐調製物を濾過し、
‐得られた溶液を、容量が5mlより小さい、適した容器に配分する、
段階を備えることを特徴とする請求項11に記載の調製方法。 - 頭痛の発作の治療及び救急治療用の薬品製造への請求項1〜10に記載の製剤形態への使用。
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FR0850571 | 2008-01-30 | ||
FR0850571A FR2926721B1 (fr) | 2008-01-30 | 2008-01-30 | Forme galenique pour l'adminsitration par voie trans-muqueuse de triptans |
PCT/FR2009/050134 WO2009095621A1 (fr) | 2008-01-30 | 2009-01-29 | Forme galenique pour l'administration de triptans par voie trans-muqueuse buccale |
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DK (1) | DK2252263T3 (ja) |
ES (1) | ES2369747T3 (ja) |
FR (1) | FR2926721B1 (ja) |
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FR3031668A1 (fr) | 2015-01-20 | 2016-07-22 | Philippe Perovitch | Dispositif d'administration d'un principe actif par voie per-muqueuse buccale. |
FR3053244A1 (fr) | 2016-07-01 | 2018-01-05 | Philippe Perovitch | Dispositif d'administration d'au moins un principe actif par voie per-muqueuse buccale. |
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US4888354A (en) * | 1987-12-21 | 1989-12-19 | Theratech, Inc. | Skin penetration enhancement using free base and acid addition salt combinations of active agents |
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US6166025A (en) * | 1997-07-03 | 2000-12-26 | Pfizer Inc. | Pharmaceutical compositions containing eletriptran hemisulphate and caffeine |
US20040136913A1 (en) * | 1997-10-01 | 2004-07-15 | Dugger Harry A. | Buccal, polar and non-polar spray containing sumatriptan |
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EP2252263B1 (fr) | 2011-07-13 |
FR2926721B1 (fr) | 2011-07-22 |
EP2252263A1 (fr) | 2010-11-24 |
BRPI0907203A2 (pt) | 2015-07-14 |
US9801815B2 (en) | 2017-10-31 |
CN101983052A (zh) | 2011-03-02 |
US20100298401A1 (en) | 2010-11-25 |
ES2369747T3 (es) | 2011-12-05 |
PT2252263E (pt) | 2011-10-19 |
PL2252263T3 (pl) | 2011-12-30 |
JP2011510962A (ja) | 2011-04-07 |
WO2009095621A1 (fr) | 2009-08-06 |
RU2492852C2 (ru) | 2013-09-20 |
MX2010008285A (es) | 2010-10-04 |
CA2713163C (fr) | 2016-11-08 |
CA2713163A1 (fr) | 2009-08-06 |
DK2252263T3 (da) | 2011-10-31 |
FR2926721A1 (fr) | 2009-07-31 |
ATE516015T1 (de) | 2011-07-15 |
CN101983052B (zh) | 2013-03-20 |
RU2010136277A (ru) | 2012-03-10 |
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