JP5013867B2 - 副作用が低減されたトラネキサム酸製剤 - Google Patents
副作用が低減されたトラネキサム酸製剤 Download PDFInfo
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- JP5013867B2 JP5013867B2 JP2006521917A JP2006521917A JP5013867B2 JP 5013867 B2 JP5013867 B2 JP 5013867B2 JP 2006521917 A JP2006521917 A JP 2006521917A JP 2006521917 A JP2006521917 A JP 2006521917A JP 5013867 B2 JP5013867 B2 JP 5013867B2
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- Prior art keywords
- tranexamic acid
- release
- delayed
- acid
- use according
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- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
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- A61K9/2004—Excipients; Inactive ingredients
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Description
経口トラネキサム酸治療を受けている患者、例えば月経過多(重い月経出血)の治療を受けている女性の望ましくない胃腸の副作用を最小化又は除去するトラネキサム酸製剤が開示されている。1つの実施形態は持続放出製剤であり、制御放出製剤とも呼ばれるが、該製剤は、剤形からのトラネキサム酸の放出が持続され又は制御された方式で起こるように作製され、トラネキサム酸のボーラスが胃中に投与されて胃内容物に溶解利用されることを防止する。別の実施形態は、遅延放出製剤である。遅延放出剤形は、胃中における該薬物の溶解を最小化し又は抑制するように作製される。トラネキサム酸の放出は、剤形が胃を出て小腸に到達するまで遅延される。持続放出剤形及び遅延放出剤形は両方とも改変放出剤形と呼ばれる。この改変放出剤形は、胃内容物中で溶解するトラネキサム酸の濃度を低減する。この低減したトラネキサム酸濃度の有益な効果は、胃内容物中のトラネキサム酸量を低下させ、その結果、トラネキサム酸療法に伴う胃の副作用を減らすことである。胃の副作用の低減は、治療に対する患者のコンプライアンスの改善をもたらすが、これは患者が前記の有害な副作用を避けるために、意図的に服用しないといったことがなくなるからである。医師もまた、患者の不満が減るため、患者に対してトラネキサム酸治療を開始し、持続することができるであろう。
(1)トラネキサム酸と、胃腸管において製剤からのトラネキサム酸の放出を改変する少なくとも1種の剤とを含む製薬上許容可能で経口摂取可能な固体製剤を含む組成物。
(2)前記剤が、胃及び腸において前記組成物からのトラネキサム酸放出の速度を遅らせる、(1)に記載の組成物。
(3)前記剤が、胃においてトラネキサム酸放出を実質的に妨げる、(1)に記載の組成物。
(4)前記剤が、pH<5.5においてトラネキサム酸放出を実質的に妨げる、(1)に記載の組成物
(5)前記剤が、少なくとも1種のワックス、ポリマー、又は時間放出性マトリクスを含む、(1)に記載の組成物。
(6)トラネキサム酸の量が、約375mgから約1gの間の範囲内である、(1)に記載の組成物。
(7)製薬上許容可能な改変放出性経口摂取製剤中にトラネキサム酸を含む組成物。
(8)遅延放出錠剤中の(7)に記載の組成物。
(9)持続放出錠剤中の(7)に記載の組成物。
(10)前記製剤が、錠剤、カプセル、顆粒、粉末、ペレット、糖衣錠、トローチ、ノンパレイユ、サシェ及び丸薬の少なくとも1種から選択される、(7)に記載の組成物。
(11)トラネキサム酸を含む組成物であって、前記組成物からのトラネキサム酸の持続放出を提供するのに十分な量の剤を少なくとも1種有する経口摂取可能な製薬上許容可能な固体製剤中にトラネキサム酸を含む、前記組成物。
(12)少なくとも1種の剤が、前記組成物からのトラネキサム酸放出の速度を低減する、(11)に記載の組成物。
(13)前記速度が、実質的に均一に低減される、(11)に記載の組成物。
(14)前記剤が、少なくとも1種の、ゲル形成ポリマー、水和ポリマー、水溶性ポリマー又は水膨潤性ポリマーから選択される、(11)に記載の組成物。
(15)前記ポリマーが、少なくとも1種の、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、カルボキシメチルセルロース、ポリビニルアルコール、ポリビニルピロリドン、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、メチルセルロース、酢酸ビニル/クロトン酸共重合 体、メタクリル酸共重合体、無水マレイン酸/メチルビニルエーテル共重合体、それらの誘導体及びそれらの混合物から選択される、(11)に記載の組成物。
(16)前記ポリマーの総濃度が、前記組成物の約5重量%から約50重量%の範囲内である、(11)に記載の組成物。
(17)前記ポリマーの総濃度が、前記組成物の約10重量%から約35重量%の範囲内である、(11)に記載の組成物。
(18)前記ポリマーの総濃度が、前記組成物の約10重量%から約30重量%の範囲内である、(11)に記載の組成物。
(19)前記ポリマーが、Methocel(登録商標)K 100 LVである、(11)に記載の組成物。
(20)トラネキサム酸を含む組成物であって、pH>約5.5に遭遇するまで該組成物からのトラネキサム酸の放出を遅延させるのに十分な剤を少なくとも1種有する経口摂取可能な製薬上許容可能な固体製剤中にトラネキサム酸を含む、前記組成物。
(21)前記剤が、少なくとも1種の、ビニルポリマーのフタル酸誘導体、ビニル共重合体のフタル酸誘導体、ヒドロキシアルキルセルロース、アルキルセルロース、酢酸セルロース、酢酸ヒドロキシアルキルセルロース、セルロースエーテル、酢酸アルキルセルロース、及びそれらの部分エステル、並びに低アルキルアクリル酸 及び低アルキルアクリレートのポリマー及び共重合体、及びそれらの部分エステルである、(20)に記載の組成物。
(22)少なくとも1種の前記剤の総濃度が、前記組成物の約1重量%から約20重量%の範囲内である、(20)に記載の組成物。
(23)少なくとも1種の前記剤の総濃度が、前記組成物の約5重量%から約12重量%の範囲内である、(20)に記載の組成物。
(24)少なくとも1種の前記剤の総濃度が、前記組成物の約10重量%である、(20)に記載の組成物。
(25)治療の間、胃中のトラネキサム酸濃度を低減する方法に使用するためのトラネキサム酸であって、該方法が、治療用量のトラネキサム酸と、胃中でトラネキサム酸の放出を遅らせる少なくとも1種の賦形剤とを含む製薬上許容可能な経口製剤を患者に提供することを含む、前記トラネキサム酸。
(26)胃腸の治療上有害な副作用をさらに低減する、(25)に記載の方法。
(27)吐き気、嘔吐、下痢、便秘、痙攣又は膨満感の少なくとも1つを低減する、(26)に記載の方法。
(28)月経過多の患者に用いる、(25)に記載の方法。
(29)前記製剤が、持続放出又は遅延放出製剤の少なくとも1種である、(25)に記載の方法。
(30)治療中実質的にトラネキサム酸を小腸で放出することによって、胃中のトラネキサム酸濃度を低減させる、(25)に記載の方法。
(31)少なくとも1種の前記賦形剤が、胃中でトラネキサム酸の放出を制御する、(25)に記載の方法。
(32)少なくとも1種の前記賦形剤が、胃中でトラネキサム酸の放出を遅らせる、(25)に記載の方法。
(33)前記治療用量が、約375mgトラネキサム酸/投与から約1gトラネキサム酸/投与の範囲内である、(25)に記載の方法。
(34)前記用量が、3回/日又は4回/日投与される、(25)に記載の方法。
(35)前記用量が、少なくとも2つの固体錠剤、又は顆粒を含む1つのサシェである、(30)に記載の方法。
(36)医薬の製造におけるトラネキサム酸の使用であって、該医薬が、治療用量のトラネキサム酸と、少なくとも1種の、胃中でトラネキサム酸の放出を遅らせて実質 的にトラネキサム酸を小腸で放出する賦形剤とを含み、前記治療における少なくとも1つの胃腸に対する副作用を低減させる、前記使用。
(37)持続放出、遅延放出及びこれらの組み合わせからなる群から選択される経口製剤中の医薬であり、経口投与の際、実質的にトラネキサム酸が小腸において放出される、(36)に記載の医薬。
上記の及び別の利点は、下記の詳細な説明及び実施例に照らしてみれば明らかであろう。
経口投与のための改変放出トラネキサム酸錠剤が開示されている。前記錠剤は、少なくとも1種の賦形剤(本明細書中において、活性物質、すなわちトラネキサム酸、以外の任意の物質と定義される)を含有し、該賦形剤は、患者の前記胃腸の有害な副作用を最小化し又は除去する。患者は、例えば月経過多の治療のために経口トラネキサム酸を投薬されている女性である。
Claims (13)
- 月経過多の治療用の製薬上許容可能な経口固体遅延放出製剤の製造のための、トラネキサム酸の使用であって、前記製剤が、トラネキサム酸又はその製薬上許容可能な塩を含むコアと、胃において該製剤からのトラネキサム酸の放出を遅らせる、前記コア上にコーティングされる少なくとも1種の遅延放出剤とを含み、前記製剤中のトラネキサム酸の量が375mgから1gの範囲内であり、また、前記遅延放出剤が、1種以上の低級アルキルアクリル酸単位を含むポリマー又は共重合体或いは該ポリマー又は共重合体の部分エステルを含有することを特徴とする使用。
- 前記遅延放出剤が、胃においてトラネキサム酸放出を妨げるものである、請求項1に記載の使用。
- 前記遅延放出剤が、pH<5.5においてトラネキサム酸放出を妨げるものである、請求項1に記載の使用。
- 前記遅延放出剤が、少なくとも1種のワックス、又は時間放出性マトリクスをさらに含む、請求項1に記載の使用。
- 前記遅延放出剤が賦形剤であり、胃中でトラネキサム酸の放出を遅らせる前記賦形剤がトラネキサム酸を小腸で放出させるものであり、それによってトラネキサム酸治療における少なくとも1つの副作用が低減される、請求項1に記載の使用。
- 前記経口固体遅延放出製剤が、持続放出、遅延放出及びこれらの組み合わせからなる群から選択される、及び、経口投与の際、トラネキサム酸が小腸において放出される、請求項1に記載の使用。
- 前記副作用が胃腸に対する作用である、請求項5に記載の使用。
- 前記遅延放出剤が、低級アルキルアクリル酸共重合体を含有する、請求項1〜7のいずれか1項に記載の使用。
- 前記遅延放出剤が、メタクリル酸共重合体を含有する、請求項1〜7のいずれか1項に記載の使用。
- 前記遅延放出剤が、メタクリル酸と、アクリル酸エステル又はメタクリル酸エステルとの共重合体を含有する、請求項1〜7のいずれか1項に記載の使用。
- 前記遅延放出剤が、メタクリル酸とアクリル酸エチルとの共重合体を含有する、請求項1〜7のいずれか1項に記載の使用。
- 前記遅延放出剤が、メタクリル酸とメタクリル酸メチルとの共重合体を含有する、請求項1〜7のいずれか1項に記載の使用。
- 前記遅延放出剤が、メタクリル酸共重合体C型を含有する、請求項1〜7のいずれか1項に記載の使用。
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US10/631,371 US20050025825A1 (en) | 2003-07-31 | 2003-07-31 | Tranexamic acid formulations with reduced adverse effects |
PCT/US2004/023528 WO2005011650A1 (en) | 2003-07-31 | 2004-07-21 | Tranexamic acid formulations with reduced adverse effects |
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US20050025825A1 (en) | 2005-02-03 |
US8968777B2 (en) | 2015-03-03 |
US20090017114A1 (en) | 2009-01-15 |
US20060127476A1 (en) | 2006-06-15 |
JP2011093938A (ja) | 2011-05-12 |
WO2005011650A1 (en) | 2005-02-10 |
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