JP2013139469A - 二環式化合物を含む医薬組成物およびその二環式化合物の安定化方法 - Google Patents
二環式化合物を含む医薬組成物およびその二環式化合物の安定化方法 Download PDFInfo
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- JP2013139469A JP2013139469A JP2013053902A JP2013053902A JP2013139469A JP 2013139469 A JP2013139469 A JP 2013139469A JP 2013053902 A JP2013053902 A JP 2013053902A JP 2013053902 A JP2013053902 A JP 2013053902A JP 2013139469 A JP2013139469 A JP 2013139469A
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- hydroxy
- halogen
- soft gelatin
- gelatin capsule
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- SZNYYWIUQFZLLT-UHFFFAOYSA-N 2-methyl-1-(2-methylpropoxy)propane Chemical compound CC(C)COCC(C)C SZNYYWIUQFZLLT-UHFFFAOYSA-N 0.000 description 2
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- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 2
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- 235000021360 Myristic acid Nutrition 0.000 description 2
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 2
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- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 2
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Landscapes
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Abstract
Description
に代表される二環式化合物が、便秘の治療または予防に有用であること、その二環式化合物をグリセリドと混合することで二環式化合物の安定性が向上することを明らかにしている(国際公開第2001/027099号パンフレット(米国特許第6583174号明細書)および国際公開第2002/020007号パンフレット(米国特許第6414016および6610732号明細書)を参照。これらの参考文献の内容は参照により本明細書に含まれる)。
Aは、−CH2OH、−COCH2OH、−COOHまたはそれらの官能性誘導体であり;
X1およびX2は、水素、低級アルキルまたはハロゲンであり;
V1およびV2は、炭素または酸素であり;
W1およびW2は、
Zは、炭素、酸素、硫黄または窒素であり;
R1は、非置換またはハロゲン、低級アルキル、ヒドロキシ、オキソ、アリールまたは複素環基で置換された、二価の飽和または不飽和の低〜中級の脂肪族炭化水素残基であり;
R2は、非置換またはハロゲン、オキソ、ヒドロキシ、低級アルキル、低級アルコキシ、低級アルカノイルオキシ、低級シクロアルキル、低級シクロアルキルオキシ、アリール、アリールオキシ、複素環基または複素環−オキシ基で置換された、飽和または不飽和、低〜中級脂肪族炭化水素残基;低級シクロアルキル基;低級シクロアルキルオキシ基;アリール基、アリールオキシ基、複素環基または複素環−オキシ基であり;
R3は、水素、低級アルキル、低級シクロアルキル、アリールまたは複素環基である]。
ゼラチンおよび可塑剤としてポリオールを含有する軟ゼラチンカプセル殻、ならびに
その殻に封入された、一般式(I)の二環式化合物および医薬上許容し得る媒体を含有する混合物。
その二環式化合物を医薬上許容し得る媒体に分散または混合させて液体混合物とすること、および、その液体混合物を、ゼラチンおよび可塑剤としてポリオールを含有する殻を有する軟ゼラチンカプセル内に組み込むこと。
「ハロゲン」の語は、フッ素、塩素、臭素およびヨウ素を包含する。特に好ましくはフッ素である。
「低級」の語は、特にことわりのない限り炭素原子数1〜6を有する基を包含するものである。
「低級アルコキシ」の語は、低級アルキルが上述と同意義である低級アルキル−O−を意味する。
「ヒドロキシ(低級)アルキル」の語は、少なくとも1つのヒドロキシ基で置換された上記のような低級アルキルを意味し、例えばヒドロキシメチル、1−ヒドロキシエチル、2−ヒドロキシエチルおよび1−メチル−1−ヒドロキシエチルである。
「低級シクロアルキル」の語は、炭素原子3個以上を含む上記のような低級アルキル基が閉環して生ずる基であり、例えばシクロプロピル、シクロブチル、シクロペンチル、シクロヘキシルを含む。
「低級シクロアルキルオキシ」の語は、低級シクロアルキルが上述と同意語である低級シクロアルキル−O−を意味する。
「アリールオキシ」の語は、式ArO−(ここで、Arは上記のようなアリール基)で示される基を意味する。
Aの「官能性誘導体」の語は、塩(好ましくは、医薬上許容し得る塩)、エーテル、エステルおよびアミド類を含む。
好ましいX1およびX2の組み合わせは、少なくとも一方がハロゲンであり、より好ましくは両方がハロゲンであり、特に好ましくはフッ素である。
好ましいW1は、=O、またはR4およびR5の一方が水素、他方がヒドロキシであるものである。
好ましいW2は、R4およびR5の両方が水素であるものである。
好ましいZは酸素である。
好ましいR1は非置換の二価の飽和または不飽和、低〜中級脂肪族炭化水素残基である。特に好ましくは1〜10の炭素原子、より好ましくは2〜8の炭素原子を含有する。
−CH2−CH2−CH2−CH2−CH2−CH2−、
−CH2−CH=CH−CH2−CH2−CH2−、
−CH2−CH2−CH2−CH2−CH=CH−、
−CH2−C≡C−CH2−CH2−CH2−、
−CH2−CH2−CH2−CH2−CH(CH3)−CH2−、
−CH2−CH2−CH2−CH2−O−CH2−、
−CH2−CH=CH−CH2−O−CH2−、
−CH2−C≡C−CH2−O−CH2−、
−CH2−CH2−CH2−CH2−CH2−CH2−CH2−、
−CH2−CH=CH−CH2−CH2−CH2−CH2−、
−CH2−CH2−CH2−CH2−CH2−CH=CH−、
−CH2−C≡C−CH2−CH2−CH2−CH2−、
−CH2−CH2−CH2−CH2−CH2−CH(CH3)−CH2−、
−CH2−CH2−CH2−CH2−CH2−CH2−CH2−CH2−、
−CH2−CH=CH−CH2−CH2−CH2−CH2−CH2−、
−CH2−CH2−CH2−CH2−CH2−CH2−CH=CH−、
−CH2−C≡C−CH2−CH2−CH2−CH2−CH2−、
−CH2−CH2−CH2−CH2−CH2−CH2−CH(CH3)−CH2−、
など。
好ましいR3は水素である。
化合物1:
HPLC分析条件:
カラム:内径約5mm、長さ約25cmのステンレス管に5μmのHPLC用オクタデシルシリル化シリカゲルを充てん
移動相:HPLC用アセトニトリル:HPLC用メタノール:酢酸アンモニウム(0.05mol/L)混液
温度:35℃
検出器:分光蛍光検出器
Claims (8)
- 一般式(I)の二環式化合物の軟ゼラチンカプセル製剤であって、ゼラチンおよび可塑剤としてグリセリン、プロピレングリコール、およびポリエチレングリコールから選ばれるポリオールを含有する軟ゼラチンカプセル殻、ならびに該殻に封入された該二環式化合物および医薬上許容し得る媒体を含有する混合物を含む、軟ゼラチンカプセル製剤:
Aは、−CH2OH、−COCH2OH、−COOHまたはそれらの官能性誘導体であり;
X1およびX2は、水素、低級アルキルまたはハロゲンであり;
V1およびV2は、炭素または酸素であり;
W1およびW2は、
Zは、炭素、酸素、硫黄または窒素であり;
R1は、非置換またはハロゲン、低級アルキル、ヒドロキシ、オキソ、アリールまたは複素環基で置換された、二価の飽和または不飽和の低〜中級の脂肪族炭化水素残基であり;
R2は、非置換またはハロゲン、オキソ、ヒドロキシ、低級アルキル、低級アルコキシ、低級アルカノイルオキシ、低級シクロアルキル、低級シクロアルキルオキシ、アリール、アリールオキシ、複素環基または複素環−オキシ基で置換された、飽和または不飽和、低〜中級脂肪族炭化水素残基;低級シクロアルキル基;低級シクロアルキルオキシ基;アリール基、アリールオキシ基、複素環基または複素環−オキシ基であり;
R3は、水素、低級アルキル、低級シクロアルキル、アリールまたは複素環基である]。 - Aが−COOHまたはその官能性誘導体であり;
X1およびX2がハロゲンであり;
W1が、=O、またはR4およびR5の一方が水素、他方がヒドロキシであるものであり;
W2が、R4およびR5の両方が水素であるものであり;
Zが酸素であり;
R1が非置換の二価の飽和または不飽和、低〜中級脂肪族炭化水素残基であり;
R2が非置換の飽和または不飽和、低〜中級脂肪族炭化水素残基であり;
R3が水素である、請求項1記載の軟ゼラチンカプセル製剤。 - 医薬上許容し得る媒体が、脂肪酸エステルまたはポリオールである、請求項1記載の軟ゼラチンカプセル製剤。
- 脂肪酸エステルがグリセリドである、請求項3記載の軟ゼラチンカプセル製剤。
- グリセリドが中鎖脂肪酸グリセリドである、請求項4記載の軟ゼラチンカプセル製剤。
- 医薬上許容し得る媒体が、グリセリンおよびポリエチレングリコールから選ばれるポリオールまたはプロピレングリコールおよび炭素数1〜6の一価のアルコールから選ばれるアルコールと脂肪酸のエステルである脂肪酸エステルである、請求項1記載の軟ゼラチンカプセル製剤。
- 可塑剤がグリセリンである、請求項1記載の軟ゼラチンカプセル製剤。
- 一般式(I)の二環式化合物を安定化する方法であって、該二環式化合物を、医薬上許容し得る媒体に分散または混合させて液体混合物とし、該液体混合物を、ゼラチンおよび可塑剤としてグリセリン、プロピレングリコール、およびポリエチレングリコールから選ばれるポリオールを含有する殻を有する軟ゼラチンカプセル内に組み込むことを含む方法:
Aは、−CH2OH、−COCH2OH、−COOHまたはそれらの官能性誘導体であり;
X1およびX2は、水素、低級アルキルまたはハロゲンであり;
V1およびV2は、炭素または酸素であり;
W1およびW2は、
Zは、炭素、酸素、硫黄または窒素であり;
R1は、非置換またはハロゲン、低級アルキル、ヒドロキシ、オキソ、アリールまたは複素環基で置換された、二価の飽和または不飽和の低〜中級の脂肪族炭化水素残基であり;
R2は、非置換またはハロゲン、オキソ、ヒドロキシ、低級アルキル、低級アルコキシ、低級アルカノイルオキシ、低級シクロアルキル、低級シクロアルキルオキシ、アリール、アリールオキシ、複素環基または複素環−オキシ基で置換された、飽和または不飽和、低〜中級脂肪族炭化水素残基;低級シクロアルキル基;低級シクロアルキルオキシ基;アリール基、アリールオキシ基、複素環基または複素環−オキシ基であり;
R3は、水素、低級アルキル、低級シクロアルキル、アリールまたは複素環基である]。
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WO2014159679A1 (en) | 2013-03-12 | 2014-10-02 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Methods for using lubiprostone to absorb fluid from the subretinal space |
CN108619107A (zh) * | 2018-05-28 | 2018-10-09 | 青海制药厂有限公司 | 一种含鲁比前列酮的软胶囊及其制备方法 |
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