JP7404239B2 - 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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- JP7404239B2 JP7404239B2 JP2020533842A JP2020533842A JP7404239B2 JP 7404239 B2 JP7404239 B2 JP 7404239B2 JP 2020533842 A JP2020533842 A JP 2020533842A JP 2020533842 A JP2020533842 A JP 2020533842A JP 7404239 B2 JP7404239 B2 JP 7404239B2
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- composition
- polyamine
- methacrylate
- weight
- triptan
- Prior art date
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- 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 22
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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
- A61K9/70—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
- A61K9/0002—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
-
- 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
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
-
- 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
-
- 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
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- 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
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- A—HUMAN NECESSITIES
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- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/0404—Electrodes for external use
- A61N1/0408—Use-related aspects
- A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/0404—Electrodes for external use
- A61N1/0472—Structure-related aspects
- A61N1/0492—Patch electrodes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
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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
- 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
を含み、モノカルボン酸を含まない前記組成物に関する。
m=5~8、好ましくは6または7であり、
n=2~4、好ましくは3または4である)
を有する。
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。Eudragit E 100を含む組成物は、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。
Kollicoat Smartsealでの結果(実施例1および2)に基づいて、Eudragit E 100を含む寒冷安定性組成物(実施例3)は、アジピン酸を使用し、固形分をそれに応じて増加させるように改変した。得られた製剤およびその主要なパラメーターを表3に示す。
製剤ごとに3匹の雌のゲッチンゲンSPFミニブタにおいて前臨床研究を実施した。表4による3種の組成物を前臨床研究において使用した。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4および5に示す。図4は、比較例による組成物および実施例3(希釈物5)による組成物を使用したスマトリプタンの時間依存的血漿濃度を示す。図5は、比較例による組成物および実施例2aによる組成物を使用したスマトリプタンの時間依存的血漿濃度を示す。
図4:比較例および実施例3(希釈物5)の時間依存的血漿濃度
図5:比較例および実施例2aの時間依存的血漿濃度
Claims (8)
- 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、
- 0.5から10重量%のトリプタン化合物の塩であって、塩がコハク酸塩である前記化合物の塩、
- 10から60重量%のポリアミン、
- 0.5から10.0重量%のコハク酸および/または0.5から10.0重量%のアジピン酸、および
- 少なくとも40重量%の水または水性溶媒混合物
を含み、モノカルボン酸を含まず、
ここで、ポリアミンは、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か、または
ポリアミンは、以下の化学構造:
m=5~8であり、
n=2~4である)
を有するか、または
ポリアミンは、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ポリアミンと、以下の化学構造:
m=5~8であり、
n=2~4である)
を有するポリアミンとの組み合わせである、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である、請求項2に記載の組成物。
- ポリアミンは、N,N-ジエチルアミノエチルメタクリレート-メタクリル酸メチルコポリマーである、請求項1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1~4のいずれか1項に記載の組成物。
- 請求項1に記載の組成物を一体構成要素として使用するイオントフォレーシスパッチ。
- 請求項1に記載の組成物をアノードリザーバーとして使用するイオントフォレーシスパッチ。
- 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。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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EP17208940 | 2017-12-20 | ||
EP17208940.1 | 2017-12-20 | ||
PCT/EP2018/084699 WO2019121293A1 (en) | 2017-12-20 | 2018-12-13 | Frigostable composition for iontophoretic transdermal delivery of a triptan compound |
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JP7404239B2 true JP7404239B2 (ja) | 2023-12-25 |
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US (1) | US11744806B2 (ja) |
EP (1) | EP3727330A1 (ja) |
JP (1) | JP7404239B2 (ja) |
CN (1) | CN111491618B (ja) |
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CA3145203A1 (en) * | 2019-06-28 | 2020-12-30 | Passport Technologies, Inc. | Triptan microporation delivery system |
DE102020106115A1 (de) | 2020-03-06 | 2021-09-09 | Lts Lohmann Therapie-Systeme Ag | Iontophoretische Zusammensetzung zur Verabreichung von S-Ketamin |
Citations (5)
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 |
JP2013523660A (ja) | 2010-03-30 | 2013-06-17 | フォスファジェニクス リミティド | 経皮送達パッチ |
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 (7)
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 |
US8155737B2 (en) | 2008-06-19 | 2012-04-10 | Nupathe, Inc. | Pharmacokinetics of iontophoretic sumatriptan administration |
KR101656537B1 (ko) | 2008-06-19 | 2016-09-09 | 에르테에스 로만 테라피-시스테메 아게 | 양이온성 활성제의 경피 전달용 조성물 |
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2018
- 2018-12-13 JP JP2020533842A patent/JP7404239B2/ja active Active
- 2018-12-13 BR BR112020010195-8A patent/BR112020010195A2/pt unknown
- 2018-12-13 US US16/772,775 patent/US11744806B2/en active Active
- 2018-12-13 CA CA3086432A patent/CA3086432A1/en active Pending
- 2018-12-13 EP EP18829265.0A patent/EP3727330A1/en active Pending
- 2018-12-13 WO PCT/EP2018/084699 patent/WO2019121293A1/en unknown
- 2018-12-13 CN CN201880081998.9A patent/CN111491618B/zh active Active
Patent Citations (5)
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 |
JP2013523660A (ja) | 2010-03-30 | 2013-06-17 | フォスファジェニクス リミティド | 経皮送達パッチ |
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BR112020010195A2 (pt) | 2020-11-03 |
US11744806B2 (en) | 2023-09-05 |
WO2019121293A1 (en) | 2019-06-27 |
CA3086432A1 (en) | 2019-06-27 |
EP3727330A1 (en) | 2020-10-28 |
CN111491618B (zh) | 2023-08-22 |
US20200323787A1 (en) | 2020-10-15 |
CN111491618A (zh) | 2020-08-04 |
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