JP2005508901A - 活性成分を徐放する剤形 - Google Patents
活性成分を徐放する剤形 Download PDFInfo
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- JP2005508901A JP2005508901A JP2003526383A JP2003526383A JP2005508901A JP 2005508901 A JP2005508901 A JP 2005508901A JP 2003526383 A JP2003526383 A JP 2003526383A JP 2003526383 A JP2003526383 A JP 2003526383A JP 2005508901 A JP2005508901 A JP 2005508901A
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- pharmaceutical dosage
- phenylbutyrate
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Classifications
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Abstract
Description
本発明の根底にある問題は、種々の病気を軽減、及び治癒における4−フェニル酪酸塩の使用に関する欠点の存在を克服することである。この物質及びその有益な治癒能力が長い間知られていたので、生産が技術的に容易で、かつ、安価であり、そして通常の量より少ない経口の1日1回若しくは2回の服用によってその治療的効果を発揮する、固形の経口投与可能な医薬剤形を開発することに関して偏見があったに違いない。
本発明は、活性成分を徐放し、かつ、患者への1日1回又は2回の経口投与によって上記患者の様々な病気を軽減及び治癒させるのに好適である、治療として有効量の4−フェニル酪酸塩を含む医薬の単位剤形に関する。
医薬の単位剤形は、特に錠剤、及びカプセル、例えば硬カプセルに導入された散剤である。
活性成分の徐放は、約6〜12、又は24時間までの期間中の活性成分の放出速度と特に理解されている。
重量及び他の尺度において本明細書中に使用されるとき、用語「約」は、+/−5〜10%の可能性のある逸脱を示すであろう。
− 約250mgのフェニル酪酸ナトリウム、
− 約146mgの、100又は4000cpsのヒドロキシプロピルメチルセルロース 2208 USP XXII型、
− 約261mgのラクトース、
− 約30〜60mg、特に31.25mgの微細結晶性セルロース(Avicel(登録商標) PH102、Select chemie、又はCellactose(登録商標)、Meggle)、
− 約10mgの硬化植物油、又は例えばタルカム(talcum)、
− 約1.5mgのステアリン酸マグネシウム、そして
− 場合により、約1mgの高分散二酸化ケイ素、
を含む。
好ましい医薬剤形は、250mgの4−フェニル酪酸ナトリウムを含み、具体的には実施例1に記載の錠剤である。
さらなる態様において、本発明は、剤形が従来法で製造されることを特徴とする前述の記載による医薬剤形の製造方法にも関する。
必要ならば、錠剤コアの成分は、所望の粒径に砕かれ、同時に又は特定の順番で互いに均一に混ぜられ、そして場合により、水で湿らせることによって粒化されて、粒状塊を分散させ、そして乾かされる。混合物を粒状にする場合、増量剤、流量剤、及び滑沢剤は、粒状化の後に顆粒に加えられることができる。コア成分の混合物は、約50〜100N、好ましくは90Nの硬度がある錠剤を形成するために圧縮されるか、又はそれ自体が硬カプセルに導入される。
以下の実施例は、本発明を説明するが、本発明を制限するものではない。
Triple Crown America,Inc.,製の、6,000.0gの4−フェニル酪酸ナトリウムと、6,280.0gのラクトース一水和物(lactosum monohydricum)、3,500.0 gのMethocel K100 M Premium(Prochem)、及び750.0gのAvicel PH 102(Select Chemie)の混合物を、4,000.0gの精製水(逆浸透によって浄化された水)を用いて湿らせ、冷気中で18時間乾燥させる。混合物を、ふるいIV mmに強制的に通し、そして40℃の大気中で10時間、再度乾燥させる。240.0gのタルクと30.0gのステアリン酸マグネシウムの混合物を、20分間混合し、この混合物を、約6.8mmの厚さ、及び90Newtonの硬度をもつ、各々0.70gの錠剤に圧縮する。収量:24,000個の錠剤コア。
以下の記載は、患者から得られた治療及び試験の結果の記載である。
この患者は、1995年4月24日に36μg/lの前立腺特異抗原(PSA)によって、及び前立腺の腺癌を示す陽性の前立腺生検によって前立腺の癌を認めた。陽性の骨のスキャンが、腰及び胸椎、並びに肋骨及び骨盤による複数の骨転移が明らかにした。進行性の骨の痛みのために、彼は1996年2月に両方の睾丸摘出術を受けた。主に彼の背骨の痛みに再び苦しむ1998年11月まで、彼は、苦痛から解放された。そして彼を、実施例1による250mgのフェニル酪酸ナトリウムの遅延型錠剤を用いて1日2回、経口的に治療した。4週間後、彼は苦痛から解放された。彼は、前立腺癌の他の徴候なしに2001年6月までこの投薬を継続した。PSA及びアルカリホスファターゼは、常に正常な範囲内にあった。この治療に起因する副作用は観察されなかった。
この患者は、1997年3月に転移性の破壊(metastatic distruction)によって引き起こされた第8胸椎の病的骨折によって認められた。わずかに肥大した前立腺の複数の生検は、両方の腺癌に関して陽性であった。骨スキャンは、肋骨及び脊椎骨における複数の取り込みを示した。1997年4月10日に、彼は両方の睾丸切除術を受けた。1997年5月から2000年9月まで、彼は、250mgの4−フェニル酪酸ナトリウムの、実施例1による遅延型錠剤によって、1日2回経口的に治療した。2001年8月の最後の制御は、症状を示さなかった。骨スキャンは、病理的な取り込みを示さなかった。4−フェニル酪酸は、副作用なしに十分な耐用性を示した。
1997年10月に、高いPSA(17.5μg/l)によって前立腺の生検は、前立腺癌を示した。彼は、LH−RHアゴニスト(Decapeptyl、遅延型、月1回)によって治療された。1998年中に、彼のアルカリホスファターゼは、132から167U/lまで上がり始めた(正常値<110U/l)。1998年11月に始まって、彼は、実施例1の遅延型錠剤により250mgの4−フェニル酪酸ナトリウムで1日2回、経口的に治療された。1999年12月14日に、彼のPSAは、検出不可能なレベルまで減少し、そして彼のアルカリホスファターゼは、114U/lまで徐々に減少した。彼は骨の痛みを訴えることは決してなかった。うっ血性心不全による心臓発作のために、彼は2000年4月24日に亡くなった。フェニル酪酸は、副作用なしに十分な耐用性を示した。
Claims (9)
- 治療として有効量の4−フェニル酪酸塩を含み、当該活性成分を徐放し、かつ、患者への1日1回又2回の経口投与によって当該患者の様々な病気を軽減又は治癒させるために好適である単位医薬剤形。
- 前記4−フェニル酪酸塩が4−フェニル酪酸ナトリウムであることを特徴とする、請求項1に記載の医薬剤形。
- 前記徐放が、20,000〜120,000の分子量を有するヒドロキシプロピルメチルセルロースによって達成されることを特徴とする、請求項1に記載の医薬剤形。
- 活性成分として250mgの4−フェニル酪酸ナトリウムを含むことを特徴とする、請求項1に記載の医薬剤形。
- 調製されたコアが約0.7gの重さとなるように、以下の:
− 約250mgのフェニル酪酸ナトリウム、
− 約146mgの、100又は4000cpsのヒドロキシプロピルメチルセルロース2208 USP XXII型、
− 約261mgのラクトース、
− 約30〜60mg、特に31.25mgの微細結晶性セルロース(Avicel(登録商標)PH102、Select chemie又はCellactose(登録商標)、Meggle)、
− 約10mgの硬化植物油、又は例えばタルカム、
− 約1.5mgのステアリン酸マグネシウム、及び
− 場合により、約1mgの高分散二酸化ケイ素、
を含むことを特徴とする、請求項1に記載の医薬剤形。 - 24,000個のコアが、約7,850gのイソプロピルアルコール、約3,360gのEudragit(登録商標)L 12.5、約66gのフタル酸ジブチル、約18.0gのMiglyol(登録商標)812、及び56gのポリエチレングリコールPEG400から製造されたフィルムコーティングを与えられることを特徴とする、請求項1に記載の医薬剤形。
- 前記剤形が従来法によって調製されることを特徴とする、請求項1に記載の医薬剤形の製造方法。
- 良性前立腺肥大症、癌、白血病、嚢胞性線維症、AIDS、腎不全及び肝不全、サラセミア、並びに尿素サイクル障害の治療ための、請求項1に記載の医薬剤形の使用であって、治療上有効な投与量の上記医薬剤形の1日2回の患者への経口投与を含む上記使用。
- 癌の治療のための、請求項1に記載の医薬剤形の使用であって、治療上有効な投与量の上記医薬剤形の1日2回の患者への経口投与を含む上記使用。
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JP2019509345A (ja) * | 2016-03-15 | 2019-04-04 | エイサー セラピューティクス インコーポレーテッド | フェニル酪酸ナトリウムを含む口当たりの良い組成物及びその使用 |
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-
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- 2001-09-10 EP EP01810865A patent/EP1291015A1/en not_active Withdrawn
-
2002
- 2002-09-04 DE DE60235178T patent/DE60235178D1/de not_active Expired - Lifetime
- 2002-09-04 CA CA2459165A patent/CA2459165C/en not_active Expired - Fee Related
- 2002-09-04 AU AU2002322964A patent/AU2002322964B2/en not_active Ceased
- 2002-09-04 CN CNB028176308A patent/CN100508965C/zh not_active Expired - Fee Related
- 2002-09-04 PT PT02754105T patent/PT1427396E/pt unknown
- 2002-09-04 ES ES02754105T patent/ES2339536T3/es not_active Expired - Lifetime
- 2002-09-04 WO PCT/CH2002/000486 patent/WO2003022253A1/en active Search and Examination
- 2002-09-04 JP JP2003526383A patent/JP2005508901A/ja active Pending
- 2002-09-04 US US10/488,276 patent/US7611729B2/en not_active Expired - Fee Related
- 2002-09-04 EP EP02754105A patent/EP1427396B1/en not_active Expired - Lifetime
- 2002-09-04 AT AT02754105T patent/ATE455539T1/de active
- 2002-09-04 DK DK02754105.1T patent/DK1427396T3/da active
-
2005
- 2005-06-01 HK HK05104615.2A patent/HK1071847A1/xx not_active IP Right Cessation
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009528301A (ja) * | 2006-02-28 | 2009-08-06 | ハッチソン メディファーマ エンタープライズ リミテッド | アンドログラフィス抽出物製剤 |
JP2019509345A (ja) * | 2016-03-15 | 2019-04-04 | エイサー セラピューティクス インコーポレーテッド | フェニル酪酸ナトリウムを含む口当たりの良い組成物及びその使用 |
US11433041B2 (en) | 2016-03-15 | 2022-09-06 | Acer Therapeutics Inc. | Palatable compositions including sodium phenylbutyrate and uses thereof |
JP7136763B2 (ja) | 2016-03-15 | 2022-09-13 | エイサー セラピューティクス インコーポレーテッド | フェニル酪酸ナトリウムを含む口当たりの良い組成物及びその使用 |
Also Published As
Publication number | Publication date |
---|---|
EP1427396A1 (en) | 2004-06-16 |
HK1071847A1 (en) | 2005-08-05 |
PT1427396E (pt) | 2010-04-14 |
CN1553799A (zh) | 2004-12-08 |
EP1291015A1 (en) | 2003-03-12 |
US7611729B2 (en) | 2009-11-03 |
DK1427396T3 (da) | 2010-05-25 |
ES2339536T3 (es) | 2010-05-21 |
ATE455539T1 (de) | 2010-02-15 |
EP1427396B1 (en) | 2010-01-20 |
CN100508965C (zh) | 2009-07-08 |
WO2003022253A1 (en) | 2003-03-20 |
CA2459165A1 (en) | 2003-03-20 |
US20040180962A1 (en) | 2004-09-16 |
CA2459165C (en) | 2011-07-19 |
DE60235178D1 (de) | 2010-03-11 |
AU2002322964B2 (en) | 2008-10-16 |
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