JP7263359B2 - トリプタン化合物のイオントフォレーシス経皮送達のための寒冷安定性組成物 - Google Patents
トリプタン化合物のイオントフォレーシス経皮送達のための寒冷安定性組成物 Download PDFInfo
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- JP7263359B2 JP7263359B2 JP2020533752A JP2020533752A JP7263359B2 JP 7263359 B2 JP7263359 B2 JP 7263359B2 JP 2020533752 A JP2020533752 A JP 2020533752A JP 2020533752 A JP2020533752 A JP 2020533752A JP 7263359 B2 JP7263359 B2 JP 7263359B2
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- 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
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
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- 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
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- 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
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- 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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/20—Applying electric currents by contact electrodes continuous direct currents
- A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Description
概ね3.0%から約5.0%のスマトリプタンコハク酸塩;
概ね84%から約88%の水;
概ね4.0%から約7.0%のアルキル化メタクリレートコポリマー;
概ね1.0%から約6.0%の脂肪酸(例えば、約1.0%から約5.0%のラウリン酸および概ね約0.05%から約0.75%のアジピン酸);ならびに
概ね0.05%から約0.75%のパラ-ヒドロキシ安息香酸メチル
を含む。
- トリプタン化合物の塩、好ましくはコハク酸塩
- ポリアミン
- ジカルボン酸
- モノカルボン酸
- 水または水性溶媒混合物;および
- 場合により、1種またはそれ以上の添加剤
を含む前記組成物に関する。
(アジピン酸およびコハク酸の価数は2であり、ただし、スマトリプタンに結合している対応する量のコハク酸については価数が1であることを除く;ラウリン酸の価数は1である)。
ポリアミンの量[グラム]×0.18(=製造業者の仕様書による、Eudragitのアルカリ数)=KOH(塩基に相当)のグラム数。
「塩基のモル数」対「酸のモル数」の比が、塩基/酸比である。
導電率測定は、VWR EC 300導電率計によって実施した。
組成物は、標準的な実験器具(撹拌機、水浴、ガラス器具)を用いて製造した。組成物は、以下のように製造した:
1.反応容器に水を充填した
2.パラ-ヒドロキシ安息香酸メチル(ニパギン)を連続撹拌下で添加した
3.Eudragit E100、ラウリン酸およびアジピン酸のプレミックスを容器中に添加した
4.溶液を連続撹拌しながら80℃に2時間加熱した
5.溶液を25℃まで冷却した。
寒冷安定性組成物は、アジピン酸およびEudragit E 100の量を増加させることによって得た。得られた製剤およびその主要なパラメーターを表2に示す。
製剤ごとに3匹の雌のゲッチンゲンSPFミニブタにおいて、US-A8,366,600の段落[0063]の比較例による組成物(表1参照)および本発明の実施例4による組成物(表2参照)の使用によって、前臨床研究を実施した。同じ製剤を含有する2つのイオントフォレーシス経皮パッチ(活性化されたものおよび不活性化されたもの)を、各動物の皮膚に4時間の期間配置した。パッチ中の全ての薬物パッドは、スマトリプタンコハク酸塩104mgを含有していた。曝露期間は、4時間であった。採血を以下の時点:処置前、ならびに処置後15分、30分、60分、90分、2、3、4、4.5、5、6、8、10、12および16時間で実施した。サンプル調製のための固相抽出に続いて、LC-MS/MSを使用して、血漿サンプル中のスマトリプタンの濃度を決定した。研究の結果を図3に示す。
Claims (9)
- トリプタン化合物の塩のイオントフォレーシス経皮送達のための組成物であって、
- トリプタン化合物の塩、
- (該組成物の総重量を基準として)15.0から25.0重量%のポリアミンであって、約2:1:1の比の3種の異なるメタクリレートモノマー:ジメチルアミノエチルメタクリレート、メタクリル酸ブチルおよびメタクリル酸メチルから作られる前記ポリアミン、
- (該組成物の総重量を基準として)1.0から5.0重量%の1種またはそれ以上のジカルボン酸、
- (該組成物の総重量を基準として)2.0から4.0重量%の1種またはそれ以上の、カプリン酸、ラウリン酸、ミリスチン酸、パルミチン酸、ステアリン酸、アラキジン酸、ミリストレイン酸、パルミトレイン酸、オレイン酸、およびリノール酸から選択されるモノカルボン酸、および
- 水または水性溶媒混合物
を含む前記組成物。 - トリプタン化合物は、2-(1H-インドール-3-イル)-N,N-ジメチルエタンアミン部分を含有する化合物である、請求項1に記載の組成物。
- トリプタン化合物は、アルモトリプタン、フロバトリプタン、エレトリプタン、ゾルミトリプタン、リザトリプタン、スマトリプタンまたはナラトリプタン、好ましくはスマトリプタンである、請求項2に記載の組成物。
- 塩は、コハク酸塩である、請求項1~3のいずれか1項に記載の組成物。
- 1種またはそれ以上のジカルボン酸は、C4~C10ジカルボン酸から選択される、請求項1~4のいずれか1項に記載の組成物。
- 1種またはそれ以上のジカルボン酸は、コハク酸、グルタル酸、アジピン酸およびピメリン酸からなる群から、好ましくはコハク酸およびアジピン酸から選択される、請求項5に記載の組成物。
- 1種またはそれ以上の添加剤をさらに含む、請求項1~6のいずれか1項に記載の組成物。
- イオントフォレーシスパッチの一体構成要素としての、好ましくはパッチのアノードリザーバーとしての、請求項1に記載の組成物の使用。
- トリプタン化合物の経皮投与のためのイオントフォレーシス方法に使用するための請求項1に記載の組成物であって、請求項1に記載の組成物を対象の皮膚に適用して、組成物中に含有されるトリプタン化合物が、組成物から放出され、皮膚を透過し、前記対象の血液循環に入ることを可能にする工程を含み、このプロセスが、イオントフォレーシスによって増強される、前記方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP17208956.7 | 2017-12-20 | ||
EP17208956 | 2017-12-20 | ||
PCT/EP2018/084703 WO2019121297A1 (en) | 2017-12-20 | 2018-12-13 | Frigostable composition for iontophoretic transdermal delivery of a triptan compound |
Publications (2)
Publication Number | Publication Date |
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JP2021506865A JP2021506865A (ja) | 2021-02-22 |
JP7263359B2 true JP7263359B2 (ja) | 2023-04-24 |
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JP2020533752A Active JP7263359B2 (ja) | 2017-12-20 | 2018-12-13 | トリプタン化合物のイオントフォレーシス経皮送達のための寒冷安定性組成物 |
Country Status (7)
Country | Link |
---|---|
US (1) | US11464760B2 (ja) |
EP (1) | EP3727331A1 (ja) |
JP (1) | JP7263359B2 (ja) |
CN (1) | CN111491619A (ja) |
BR (1) | BR112020010146A2 (ja) |
CA (1) | CA3086494A1 (ja) |
WO (1) | WO2019121297A1 (ja) |
Families Citing this family (1)
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---|---|---|---|---|
DE102020106115A1 (de) * | 2020-03-06 | 2021-09-09 | Lts Lohmann Therapie-Systeme Ag | Iontophoretische Zusammensetzung zur Verabreichung von S-Ketamin |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001054674A1 (en) | 2000-01-26 | 2001-08-02 | F.T. Holdings S.A. | Patch for local and transdermal administration of active ingredients containing anionic or electron-attracting groups |
JP2004083523A (ja) | 2002-08-28 | 2004-03-18 | Hisamitsu Pharmaceut Co Inc | 貼付剤 |
WO2011046927A1 (en) | 2009-10-13 | 2011-04-21 | Nupathe,Inc. | Transdermal methods and systems for the delivery of rizatriptan |
JP2014237675A (ja) | 2008-06-19 | 2014-12-18 | ニューパス インコーポレーテッド | トリプタン化合物イオントフォレシス用のポリアミン強化製剤 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US222276A (en) | 1879-12-02 | Improvement in combined galvanic and medicated pad | ||
US486902A (en) | 1892-11-29 | Galvanic body-battery | ||
DE4014913C2 (de) | 1990-05-10 | 1996-05-15 | Lohmann Therapie Syst Lts | Miniaturisiertes transdermales therapeutisches System für die Iontophorese |
US6745071B1 (en) | 2003-02-21 | 2004-06-01 | Birch Point Medical, Inc. | Iontophoretic drug delivery system |
WO2008140453A1 (en) * | 2007-05-14 | 2008-11-20 | Vyteris, Inc. | Iontophoretic devices for drug delivery |
AU2009259601B2 (en) | 2008-06-19 | 2014-09-18 | Lts Lohmann Therapie-Systeme Ag | Composition for transdermal delivery of cationic active agents |
US8155737B2 (en) * | 2008-06-19 | 2012-04-10 | Nupathe, Inc. | Pharmacokinetics of iontophoretic sumatriptan administration |
US20100209484A1 (en) * | 2009-02-13 | 2010-08-19 | Hoo-Kyun Choi | Transdermal Triptan Delivery System |
WO2018006069A1 (en) * | 2016-06-30 | 2018-01-04 | Teva Pharmaceuticals International Gmbh | Improved formulations for transdermal pharmaceutical systems |
-
2018
- 2018-12-13 CN CN201880082074.0A patent/CN111491619A/zh active Pending
- 2018-12-13 BR BR112020010146-0A patent/BR112020010146A2/pt unknown
- 2018-12-13 WO PCT/EP2018/084703 patent/WO2019121297A1/en unknown
- 2018-12-13 JP JP2020533752A patent/JP7263359B2/ja active Active
- 2018-12-13 US US16/772,776 patent/US11464760B2/en active Active
- 2018-12-13 EP EP18829266.8A patent/EP3727331A1/en active Pending
- 2018-12-13 CA CA3086494A patent/CA3086494A1/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001054674A1 (en) | 2000-01-26 | 2001-08-02 | F.T. Holdings S.A. | Patch for local and transdermal administration of active ingredients containing anionic or electron-attracting groups |
JP2004083523A (ja) | 2002-08-28 | 2004-03-18 | Hisamitsu Pharmaceut Co Inc | 貼付剤 |
JP2014237675A (ja) | 2008-06-19 | 2014-12-18 | ニューパス インコーポレーテッド | トリプタン化合物イオントフォレシス用のポリアミン強化製剤 |
WO2011046927A1 (en) | 2009-10-13 | 2011-04-21 | Nupathe,Inc. | Transdermal methods and systems for the delivery of rizatriptan |
Also Published As
Publication number | Publication date |
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US11464760B2 (en) | 2022-10-11 |
CA3086494A1 (en) | 2019-06-27 |
CN111491619A (zh) | 2020-08-04 |
JP2021506865A (ja) | 2021-02-22 |
US20200330434A1 (en) | 2020-10-22 |
BR112020010146A2 (pt) | 2020-10-13 |
WO2019121297A1 (en) | 2019-06-27 |
EP3727331A1 (en) | 2020-10-28 |
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