JP2005047932A - 浸透増強および刺激減少システム - Google Patents
浸透増強および刺激減少システム Download PDFInfo
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- JP2005047932A JP2005047932A JP2004313201A JP2004313201A JP2005047932A JP 2005047932 A JP2005047932 A JP 2005047932A JP 2004313201 A JP2004313201 A JP 2004313201A JP 2004313201 A JP2004313201 A JP 2004313201A JP 2005047932 A JP2005047932 A JP 2005047932A
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Abstract
【解決手段】 本発明は、浸透性増強システムは経皮および局所の薬物送達を増加させる一方で皮膚刺激性を減少させ、これによって受容できない有害皮膚反応を引き起こすことなく高レベルの薬物送達の達成を可能とする。
【選択図】 なし
Description
本発明は、経皮および局所的な薬物送達の技術に関する。特に本発明は、経皮的または局所的に適用される薬物の浸透性の増強、ならびに経皮的および局所的に適用される薬物送達にしばしば伴う皮膚刺激性の減少に関する。
過去10年間の間に、全身性薬物送達のための皮膚経路の可能性が確立された。経皮的な治療系として、スコポラミン、トリニトログリセリン、クロニジン、フェンタニル、ニコチンおよびエストラジオールを含有するものが挙げられる。しかしながら、皮膚または粘膜に適用される薬物のひとつの欠点は、それらがしばしば刺激を引き起こすことである。さらに、局所、経皮および経粘膜処方ならびに送達デバイスに必要な多数の成分(例えば、溶解剤、懸濁剤、分散剤、保存剤、動物性および植物性脂肪、オイルまたはワックス、安定化剤、増粘剤、またはゲル化剤、緩衝剤、接着剤ならびに特に浸透性増強剤)が、単独でまたは組み合わせて刺激性である。しかしながら浸透性増強剤がない場合に、治療的に有効な濃度で皮膚または粘膜に浸透し得る薬剤は少ない。典型的には、浸透性を増強する化合物を使用して薬物の浸透性を増加させるプロセスまたはデバイスがこの問題を解決する。これらの中には、化学的エンハンサー、イオン泳動、超音波伝達(sonophoresis)および種々の送達デバイスが含まれる。
本発明の組成物は、局所または経皮適用のための多くの型の製品に利用し得る浸透性増強システム(PES)に関し、これには溶液、クリーム、ローション、軟膏、ゲル、エアロゾルおよびパッチデバイスが含まれるが、これらに限らない。特定の局面では、本発明は浸透性増強特性を有する局所適用のための組成物に関し、この組成物は、活性な薬剤;およびオレイン酸を含む浸透性増強システム;C1〜C4アルコール;およびグリコールを含有する。必要に応じて、この組成物はさらにゲル化剤を含有する。好ましい実施態様では、このゲル化剤はポリアクリル酸であるCARBOPOL(登録商標)である。特定の実施態様では、好ましい活性成分はテストステロンまたはテストステロン誘導体である。
特定の局面では、本発明は経皮および局所の薬物送達に関する。特に、この様式の薬物送達を使用した局所適用の薬物の浸透性の増強は、典型的には皮膚刺激性の増加を伴う。そのようなひとつの局面では、本発明は浸透性増強特性を有する局所適用のための組成物に関し、この組成物は:a)活性な薬剤;b)以下を含む浸透性増強システム:(i)膜流動化剤;(ii)C1〜C4アルコール;および(iii)グリコールを含有する。特定の実施態様では、この組成物はさらに、(iv)ゲル化剤を含有する。本発明のこの浸透性増強システムは経皮および局所の薬物送達を増加させる一方で皮膚刺激性を減少させ、これによって受容できない有害皮膚反応を引き起こすことなく高レベルの薬物送達の達成を可能とする。
次の実施例は、膜流動化剤としてオレイン酸を使用する処方物とオレイルアルコールを使用する処方物との間の比較を示す。
T テストステロン
PG プロピレングリコール
ET エチルアルコール
IPA イソプロピルアルコール
KH クルーセル(Klucel) HF(ヒドロキシプロピルセルロース:ゲル化剤)
O Acd オレイン酸
O Alc オレイルアルコール
Cl カルボポール(Carbopol)1342
TEA トリエタノールアミン
SD 標準偏差
次の実施例は、本発明のゲル生成物の好ましい組成を示す。
成分 範囲
エタノール 0.1〜50%
プロピレングリコール 0.1〜50%
イソプロピルアルコール 0.1〜50%
オレイン酸 0.1〜50%
ゲル化剤 0.01〜50%
追加の刺激減少剤 0.1〜50%
防腐剤 0(処方物が自己保存的であり得る)〜0.1%
薬物 0%〜飽和
次の実施例は、本発明の軟膏生成物の好ましい組成を示す。
成分 範囲
プロピレングリコール 0.1〜50%
ブチレングリコール 0.1〜50%
ミリスチン酸イソプロピル 0.1〜50%
オレイン酸 0.1〜50%
ミグリオール 0.1〜50%
ワセリン 0.1〜80%
ポラワックス 0.1〜20%
ゲル化剤 0.01〜50%
追加の刺激減少剤 0.1〜50%
防腐剤 0(処方物が自己保存的であり得る)〜0.1%
薬物 0%〜飽和
次の実施例は、本発明のエマルジョン生成物の好ましい組成を示す。
成分 範囲
脱イオン水 10〜50%
プロピレングリコール 0.1〜50%
ブチレングリコール 0.1〜50%
ミリスチン酸イソプロピル 0.1〜30%
オレイン酸 0.1〜20%
セチルアルコール 0.1〜5%
ミグリオール 0.1〜30%
ワセリン 0.1〜80%
ゲル化剤 0.1〜30%
ポラワックス 0.1〜10%
追加の刺激減少剤 0.1〜50%
防腐剤 0(処方物が自己保存的であり得る)〜0.1%
薬物 0%〜飽和
この実施例は、成分およびそれぞれの成分の重量%について処方物を示す。
コンピューターモデルを使用して、この実施例は、(1)テストステロン濃度および(2)pHを調節することによって‘601処方物を最適化する。
結果は約5〜約6のpHを有する処方物が最適の処方物を与えたことを示した。
1.0%または2.0%テストステロン局所的ゲルの典型的なバッチの調製手順:
1)95%の純水(USP)を適切な容器にチャージし、カルボマー(USP)を混合しながら加える。カルボマーが完全に分散し水和されるまで20℃〜30℃でスラリーを混合する。
6)バルクのゲルを容器/ビンに満たす。
Claims (11)
- 局所適用のための0.5%〜2.0%テストステロン組成物であって、浸透増強特性を有し、オレイン酸、C1〜C4アルコールおよびグリコールを含み、また、約5から約6に調整されたpH値を有する組成物。
- さらにゲル化剤を含む、請求項1に記載の組成物。
- C1〜C4アルコールが、エタノール、プロパノール、イソプロパノール、またはそれらの混合物である、請求項1または2に記載の組成物。
- グリコールが、エチレングリコール、プレピレングリコール、ブチレングリコール、またはそれらの混合物である、請求項1から3いずれか一項に記載の組成物。
- テストステロンが、テストステロン、プロピオン酸テストステロン、またはそれらの混合物の形で提供される、請求項1から4いずれか一項に記載の組成物。
- ゲル化剤がポリアクリル酸ゲル化剤である、請求項2に記載の組成物。
- 約5から約6に調整されたpH値を有する0.5%〜2.0%テストステロン組成物における増強された経皮輸送性によってテストステロン欠乏症を治療するための薬剤を製造するための、該組成物の使用であって、該組成物が、さらにオレイン酸、C1〜C4アルコールおよびグリコールを含むものである使用。
- 組成物が、さらにポリアクリル酸ゲル化剤を含む、請求項7に記載の使用。
- C1〜C4アルコールが、エタノール、プロパノール、イソプロパノール、またはそれらの混合物である、請求項7または8に記載の使用。
- グリコールが、エチレングリコール、プレピレングリコール、ブチレングリコール、またはそれらの混合物である、請求項7から9いずれか一項に記載の使用。
- テストステロンが、テストステロン、プロピオン酸テストステロン、またはそれらの混合物の形で提供される、請求項7から10いずれか一項に記載の使用。
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CN102327253A (zh) * | 2000-04-26 | 2012-01-25 | 沃特森药物公司 | 最小化与奥昔布宁疗法有关的副作用 |
US7029694B2 (en) * | 2000-04-26 | 2006-04-18 | Watson Laboratories, Inc. | Compositions and methods for transdermal oxybutynin therapy |
US7897559B2 (en) * | 2000-06-29 | 2011-03-01 | Parks L Dean | Dermatological composition and kit containing avermectin compound for treating dermatological conditions |
US8512718B2 (en) | 2000-07-03 | 2013-08-20 | Foamix Ltd. | Pharmaceutical composition for topical application |
US7198801B2 (en) | 2000-08-03 | 2007-04-03 | Antares Pharma Ipl Ag | Formulations for transdermal or transmucosal application |
US20040198706A1 (en) * | 2003-03-11 | 2004-10-07 | Carrara Dario Norberto R. | Methods and formulations for transdermal or transmucosal application of active agents |
US8980290B2 (en) | 2000-08-03 | 2015-03-17 | Antares Pharma Ipl Ag | Transdermal compositions for anticholinergic agents |
ATE485837T1 (de) | 2000-08-03 | 2010-11-15 | Antares Pharma Ipl Ag | Zusammensetzung zur transdermalen und/oder transmukosalen verabreichung von wirkstoffen, die ausreichende therapeutische spiegel garantiert |
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-
1998
- 1998-11-09 DE DE69840426T patent/DE69840426D1/de not_active Expired - Lifetime
- 1998-11-09 CN CNB988130491A patent/CN1172674C/zh not_active Expired - Fee Related
- 1998-11-09 DK DK04028426T patent/DK1510213T3/da active
- 1998-11-09 KR KR1020007005094A patent/KR100648536B1/ko active IP Right Grant
- 1998-11-09 IL IL13604298A patent/IL136042A/xx not_active IP Right Cessation
- 1998-11-09 WO PCT/US1998/023750 patent/WO1999024041A1/en active IP Right Grant
- 1998-11-09 PT PT04028426T patent/PT1510213E/pt unknown
- 1998-11-09 EP EP98956663A patent/EP1030668A4/en not_active Withdrawn
- 1998-11-09 US US09/189,090 patent/US6319913B1/en not_active Expired - Lifetime
- 1998-11-09 CA CA002309688A patent/CA2309688C/en not_active Expired - Fee Related
- 1998-11-09 AU AU13132/99A patent/AU747041B2/en not_active Ceased
- 1998-11-09 EP EP04028426A patent/EP1510213B1/en not_active Revoked
- 1998-11-09 ES ES04028426T patent/ES2318233T3/es not_active Expired - Lifetime
- 1998-11-09 NZ NZ504423A patent/NZ504423A/xx not_active IP Right Cessation
- 1998-11-09 AT AT04028426T patent/ATE418988T1/de active
- 1998-11-09 BR BRPI9814014-0A patent/BR9814014B1/pt not_active IP Right Cessation
- 1998-11-09 JP JP2000520133A patent/JP4139860B2/ja not_active Expired - Fee Related
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2000
- 2000-05-10 NO NO20002422A patent/NO20002422L/no not_active Application Discontinuation
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2001
- 2001-09-24 US US09/963,287 patent/US6579865B2/en not_active Expired - Lifetime
-
2003
- 2003-03-12 US US10/389,715 patent/US7157097B2/en not_active Expired - Lifetime
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2004
- 2004-10-28 JP JP2004313201A patent/JP2005047932A/ja not_active Withdrawn
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CA2309688C (en) | 2007-04-24 |
IL136042A (en) | 2005-12-18 |
EP1510213A3 (en) | 2005-03-23 |
CN1172674C (zh) | 2004-10-27 |
AU1313299A (en) | 1999-05-31 |
ES2318233T3 (es) | 2009-05-01 |
ATE418988T1 (de) | 2009-01-15 |
DK1510213T3 (da) | 2009-03-23 |
KR100648536B1 (ko) | 2006-11-24 |
US20020058650A1 (en) | 2002-05-16 |
EP1510213A2 (en) | 2005-03-02 |
EP1030668A1 (en) | 2000-08-30 |
NZ504423A (en) | 2003-04-29 |
JP2001522804A (ja) | 2001-11-20 |
WO1999024041A1 (en) | 1999-05-20 |
DE69840426D1 (de) | 2009-02-12 |
US6319913B1 (en) | 2001-11-20 |
PT1510213E (pt) | 2009-02-12 |
AU747041C (en) | 1999-05-31 |
US7157097B2 (en) | 2007-01-02 |
IL136042A0 (en) | 2001-05-20 |
KR20010031984A (ko) | 2001-04-16 |
EP1030668A4 (en) | 2002-09-25 |
AU747041B2 (en) | 2002-05-09 |
CA2309688A1 (en) | 1999-05-20 |
NO20002422D0 (no) | 2000-05-10 |
NO20002422L (no) | 2000-06-21 |
CN1285749A (zh) | 2001-02-28 |
US20030166625A1 (en) | 2003-09-04 |
US6579865B2 (en) | 2003-06-17 |
BR9814014A (pt) | 2000-09-26 |
EP1510213B1 (en) | 2008-12-31 |
BR9814014B1 (pt) | 2014-10-07 |
JP4139860B2 (ja) | 2008-08-27 |
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