JP5913105B2 - 両親媒性酸分子による塩基性活性成分の協同輸送 - Google Patents
両親媒性酸分子による塩基性活性成分の協同輸送 Download PDFInfo
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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
- A61K9/0012—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
- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
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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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- 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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- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/541—Organic ions forming an ion pair complex with the pharmacologically or therapeutically active agent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/08—Antibacterial agents for leprosy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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Description
本発明は、塩基性活性成分と酸性界面活性剤との、その活性成分の保護、可溶化、および輸送のための、分子間カタニオニック会合体(intermolecular catanionic association)に関する。
活性成分の有害な効果を低減する目的でその安定性を改善することは、今日でも依然として非常に重要な課題である。一般的に、この安定化は、活性成分の保存時に、保存剤および抗酸化剤を用いることにより、ならびに活性成分の投与時に、前記活性成分を安定化し、場合により免疫系による分解から保護し、その作用部位へ向けての輸送を行う担体を用いることにより、これらの両面から行なわれる。
−角質層脂質の抽出
−脂質二重層構造の破壊
−結合水の置換
−角質層の剥離
−角層の破壊
−Sは、単糖または多糖の炭水化物断片を表し、
−Rは、水素原子、一もしくは二つ以上のフッ素原子で置換されていてよく、特にペルフルオロ化(perfluorinated)されていてよいC1‐C20、有利にはC1‐C10である飽和もしくは不飽和の直鎖状、分岐鎖状、環状、または芳香族炭化水素鎖を表し、
−Xは、好ましくは直鎖状である、C4‐C10アルキル、アルケニル、またはアルキニル鎖を表し、
−Y−は、カルボキシレート(−CO2 −)、サルフェート(−O−SO3 −)、スルホネート(−SO3 −)、ホスフェート(−O−P(O)(ORa)O−)、ホスホネート(−O−P(O)RbO−)、またはホスフィネート(−P(O)RbO−)基を表し、
ここで、Raは、C1‐C6アルキル基を表し、Rbは、水素原子またはC1‐C6アルキル基を表し、ならびに、
−Gは、少なくとも一つの一級、二級、もしくは三級アミン、またはグアニジン(−NH−C(=NH)−NH2)官能基を含む活性成分を表し、特に、抗ヒスタミン剤、抗うつ剤、降圧剤(hypotensors)、神経伝達剤、アンフェタミン、麻酔剤、抗片頭痛剤、強心剤、ニコチン受容体アゴニスト、ビタミンまたはプロビタミン、および抗悪性腫瘍剤を含む群より選択される)。
−上記に記載されたものと同義である式(II)の両親媒性輸送体と、上記に記載されたものと同義である活性成分Gとを混合する工程、ならびに、
−このようにして得られた両親媒性輸送体と活性成分との分子間会合複合体を、反応媒体から分離する工程。
・サンプルの製剤
研究に用いたヒドロゲルは、Lac6Pの小胞体水溶液(8×10−4M、活性成分2重量%)、またはやはり2重量%のプロメタジン塩酸塩水溶液を、同一体積にて2重量%のNatrosol(商標)水性ゲルに添加することによって作製する。従って、1重量%Natrosol(商標)および1重量%活性成分の製剤が得られる。
−配合A:1%Natrosol(商標)ヒドロゲル中1%プロメタジンの製剤、および
−配合B:1%Natrosol(商標)ヒドロゲル中1%会合体Lac6Pの製剤
種々の配合の皮膚透過を、1cm2のダイナミックフロー型フランツ拡散セル(dynamic-flow Franz diffusion cells)で評価した。この研究は、ブタの耳部皮膚に対して、ex vivoにて、限定された用量を用いて24時間にわたって行った。
−t0:94%H2O 0.1%HCOOH/6%アセトニトリル勾配
−t0から15分:50%H2O 0.1%HCOOH/50%アセトニトリル勾配
−15〜16分:40%H2O 0.1%HCOOH/60%アセトニトリル勾配
皮膚投与が想定される場合、活性成分の光安定性は重要な基準である。実際、表皮内に感光性物質(プロメタジンまたはメキタジンなど)が存在し、それが太陽光への曝露と組み合わさると、活性の喪失および皮膚の光毒性を招く場合がある。
− プロメタジン塩酸塩溶液は、24時間の曝露後、ピンク色となり、数日後には青‐青紫色に変わる。そして、自然光下にて約2週間の後、不溶性化合物が現れる。
−Lac6Pの小胞体溶液は、およそ1週間の曝露後、ピンク色となり、その後青‐青紫色に変わる。約20日後、対応する塩酸塩の場合と同様に、水相の不溶性生成物の出現も観察される。
−メキタジン塩酸塩溶液は、10日間の曝露後、ピンク色となり、その後はそれ以上変化しない。
−Lac6Mのミセル溶液は、数ヶ月の間、無色透明のままである。
Claims (6)
- 下記から選択される、両親媒性輸送体と活性成分との分子間会合複合体:
- 薬物として用いるための、請求項1に記載の両親媒性輸送体と活性成分との分子間会合複合体。
- 抗ヒスタミン剤として用いるための、請求項1に記載の両親媒性輸送体と活性成分との分子間会合複合体。
- 請求項1に記載の両親媒性輸送体と活性成分との分子間会合複合体を少なくとも一つ含む、医薬組成物。
- 局所または経皮投与のために用いられる、請求項4に記載の医薬組成物。
- ヒドロゲルまたはエマルジョンの形態である、請求項5に記載の医薬組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0956893 | 2009-10-02 | ||
FR0956893A FR2950902B1 (fr) | 2009-10-02 | 2009-10-02 | Transport cooperatif de principes actifs basiques par des molecules amphiphiles acides |
PCT/EP2010/064756 WO2011039379A1 (fr) | 2009-10-02 | 2010-10-04 | Transport cooperatif de principes actifs basiques par des molecules amphiphiles acides |
Publications (2)
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JP2013506642A JP2013506642A (ja) | 2013-02-28 |
JP5913105B2 true JP5913105B2 (ja) | 2016-04-27 |
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JP2012531455A Active JP5913105B2 (ja) | 2009-10-02 | 2010-10-04 | 両親媒性酸分子による塩基性活性成分の協同輸送 |
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US (1) | US8895518B2 (ja) |
EP (1) | EP2482853B1 (ja) |
JP (1) | JP5913105B2 (ja) |
BR (1) | BR112012007301B8 (ja) |
CA (1) | CA2776198C (ja) |
FR (1) | FR2950902B1 (ja) |
WO (1) | WO2011039379A1 (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
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FR3019039B1 (fr) | 2014-03-28 | 2017-06-02 | Affichem | Composition cosmetique et/ou dermatologique pour la coloration de la peau |
JP7285040B2 (ja) * | 2018-06-08 | 2023-06-01 | シオノギヘルスケア株式会社 | 光安定性を向上させた固形状組成物 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
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FR2727110B1 (fr) * | 1994-11-17 | 1997-01-17 | Stepan Europe | Composes amphiphiles mixtes |
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- 2009-10-02 FR FR0956893A patent/FR2950902B1/fr not_active Expired - Fee Related
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2010
- 2010-10-04 EP EP10762659.0A patent/EP2482853B1/fr not_active Not-in-force
- 2010-10-04 JP JP2012531455A patent/JP5913105B2/ja active Active
- 2010-10-04 WO PCT/EP2010/064756 patent/WO2011039379A1/fr active Application Filing
- 2010-10-04 BR BR112012007301A patent/BR112012007301B8/pt not_active IP Right Cessation
- 2010-10-04 US US13/499,197 patent/US8895518B2/en not_active Expired - Fee Related
- 2010-10-04 CA CA2776198A patent/CA2776198C/fr not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
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CA2776198C (fr) | 2018-08-28 |
US20120214756A1 (en) | 2012-08-23 |
BR112012007301B1 (pt) | 2021-04-20 |
FR2950902A1 (fr) | 2011-04-08 |
EP2482853A1 (fr) | 2012-08-08 |
US8895518B2 (en) | 2014-11-25 |
WO2011039379A1 (fr) | 2011-04-07 |
JP2013506642A (ja) | 2013-02-28 |
CA2776198A1 (fr) | 2011-04-07 |
EP2482853B1 (fr) | 2018-11-14 |
BR112012007301A2 (pt) | 2016-04-19 |
BR112012007301B8 (pt) | 2021-05-25 |
FR2950902B1 (fr) | 2012-03-30 |
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