JP2006502147A - 心血管薬剤または腎臓薬剤を含む口腔内用極性および非極性スプレーまたはカプセル - Google Patents
心血管薬剤または腎臓薬剤を含む口腔内用極性および非極性スプレーまたはカプセル Download PDFInfo
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- JP2006502147A JP2006502147A JP2004531569A JP2004531569A JP2006502147A JP 2006502147 A JP2006502147 A JP 2006502147A JP 2004531569 A JP2004531569 A JP 2004531569A JP 2004531569 A JP2004531569 A JP 2004531569A JP 2006502147 A JP2006502147 A JP 2006502147A
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Abstract
Description
本願は、1997年10月1日提出のPCT/US97/17899号(その開示全体が本明細書中で参考として援用される)の米国の国内段階指定の一部継続出願である、2000年3月29日提出の出願番号09/537,118号の一部継続出願である。
一定の生物学的に活性な化合物は、胃または小腸などの他の投与経路よりも、口腔粘膜からより良好に吸収されることが知られている。しかし、これらの後者の経路によるこのような投与に適切な処方物自体に問題がある。例えば、生物学的に活性な化合物は、組成物の他の成分(プロペラント、溶媒など)と適合しなければならない。多数のこのような処方物が提案されている。例えば、Dvorsky et al.に付与された米国特許第4,689,233号は、ポリエーテルアルコール混合物に溶解した抗冠状動脈血栓症薬(anti−coronary drug)であるニフェジピンの投与のためのゼラチン軟カプセル剤を記載している。Jones et al.に付与された米国特許第4,755,389号は、ニフェジピンを含むゼラチンチュアブル硬カプセル剤を記載している。薬物の溶液または分散液を含むチュアブルゼラチンカプセルは、Borkan et alに付与された米国特許第4,935,243号に記載されている。Aouda et alに付与された米国特許第4,919,919号およびKlokkers−Bethkeに付与された米国特許第5,370,862号は、ニトログリセリン、エタノール、および他の成分を含む口腔粘膜投与のためのニトログリセリンスプレーを記載している。経口投与されたポンプスプレーは、Cholchaにより米国特許第5,186,925号に記載されている。炭化水素プロペラントおよび粘膜表面投与のための薬物を含むエアゾール組成物は、Suに付与された英国特許第2,082,457号、Silson et alに付与された米国特許第3,155,574号、Wang et alに付与された米国特許第5,011,678号、Parnellに付与された米国特許第5,128,132号に記載されている。これらの文献は投与された膜よりもむしろ吸入による溶液の生物学的利用能を考察していることに留意すべきである。
口腔粘膜を介して迅速に吸収され、それにより迅速に効果が得られる生物学的に活性な化合物が得られる極性または非極性溶媒を使用した口腔内エアゾールスプレーまたはチュアブル(bite)ゼラチン軟カプセル剤を開発した。
本発明の好ましい活性化合物は、イオン化された塩形態またはその薬学的に許容可能な塩の遊離体である(エアゾールまたはポンプスプレー組成物の場合、これらはスプレー溶媒に溶解する)。これらの化合物は有用な濃度で本発明の非極性溶媒に溶解するか、有用な濃度でペーストに調製することができる。口腔粘膜を介した化合物の吸収が増大するので、これらの濃度は、これらの化合物の標準的な投薬量よりも少量であり得る。本発明のこの態様は、特に、初期通過効果が高い場合(40〜99.99%)に重要である。
ペプチドホルモンを含む生物学的に活性なペプチド
A.シクロスポリンの口腔用スプレー
量 好適な量 最も好適な量
シクロスポリン 5‐50 10‐35 15‐25
水 5‐20 7.5‐50 9.5‐12
エタノール 5‐60 7.5‐50 10‐20
ポリエチレングリコール 20‐60 30‐45 35‐40
嬌味嬌臭薬 0.1‐5 1‐4 2‐3
量 好適な量 最も好適な量
シクロスポリン 1‐50 3‐40 5‐30
ミグリオール 20 25 30‐40
ポリオキシエチル化したヒマシ油 20 25 30‐40
ブタン 25‐80 30‐70 33‐50
嬌味嬌臭薬 0.1‐5 1‐4 2‐3
量 好適な量 最も好適な量
シクロスポリン 1‐35 5‐25 10‐20
オリーブ油 25‐60 35‐55 30‐45
ポリオキシエチル化した
オレイン酸グリセリド 25‐60 35‐55 30‐45
嬌味嬌臭薬 0.1‐5 1‐4 2‐3
量 好適な量 最も好適な量
シクロスポリン 5−50 10−35 15−25
ポリエチレングリコール 20−60 30−45 35−40
グリセリン 5−30 7.5−25 10−20
プロピレングリコール 5−30 7.5−25 10−20
嬌味嬌臭薬 0.1−10 1−8 3−6
量 好適な量 最も好適な量
セルモレリン(酢酸塩として) 0.01−5 0.1−3 0.2−1.0
マンニトール 1−25 5−20 10−15
第一リン酸ナトリウム 0.1−5 1−31 0.5−2.5
第二リン酸ナトリウム水 0.01−5 0.05−3 0.1−0.5
エタノール 5−30 7.5−25 9.5−15
ポリエチレングリコール 20−60 30−45 35−40
プロピレングリコール 5−25 10−20 12−17
嬌味嬌臭薬 0.1−5 1−4 2−3
量 好適な量 最も好適な量
酢酸オクトレオチド 0.001−0.5 0.005−0.250 0.01−0.10
酢酸 1−10 2−8 4−6
酢酸ナトリウム 1−10 2−8 4−6
塩化ナトリウム 3−30 0.5−25 15−20
嬌味嬌臭薬 0.1−5 0.5−4 2−3
エタノール 5−30 7.5−20 9.5−15
水 15−95 35−90 65−85
嬌味嬌臭薬 0.1−5 1−4 2−3
量 好適な量 最も好適な量
サケ−カルシトニン 0.001−5 0.005−2 0.01−1.5
エタノール 2−15 3−10 7−9.5
水 30−95 50−90 60−80
ポリエチレングリコール 2−15 3−10 7−9.5
塩化ナトリウム 2.5−20 5−15 10−12.5
嬌味嬌臭薬 0.1−5 1−4 2−3
量 好適な量 最も好適な量
インスリン 20−60 4−55 5−50
グリセリン 0.1−10 0.25−5 0.1−1.5
第二リン酸ナトリウム 1−15 2.5−10 4−8
m−クレゾール 1−25 5−25 7.5−12.5
酸化亜鉛 0.01−0.25 0.05−0.15 0.075−0.10
m−クレゾ−ル 0.1−1 0.2−0.8 0.4−0.6
フェノール 微量 微量 微量
エタノール 5−20 7.5−15 9−12
水 30−90 40−80 50−75
プロピレングリコール 5−20 7.5−15 9−12
嬌味嬌臭薬 0.1−5 0.5−3 0.75−2
HClまたはNaOHでpHを7.0−7.8に調製する
中枢神経系(CNS)活性アミンおよびそれらの塩: 三環系アミンを含むがそれに限定されるものではない、GABA類縁体、チアジド、フェノチアジン誘導体、セロトニンアンタゴニストおよびセロトニン再取り込み阻害剤
量 好適な量 最も好適な量
コハク酸スマトリプタン 0.5−30 1−20 10−15
エタノール 5−60 7.5−50 10−20
プロピレングリコール 5−30 7.5−20 10−15
ポリエチレングリコール 0−60 30−45 35−40
水 5−30 7.5−20 10−15
嬌味嬌臭薬 0.1−5 1−4 2−3
量 好適な量 最も好適な量
コハク酸スマトリプタン 0.01−5 0.05−3.5 0.075−1.75
ポリエチレングリコール 25−70 30−60 35−50
グリセリン 25−70 30−60 35−50
嬌味嬌臭薬 0.1−10 1−8 3−6
量 好適な量 最も好適な量
クロザピン 0.5−30 1−20 10−15
エタノール 5−60 7.5−50 10−20
プロピレングリコール 5−30 7.5−20 10−15
ポリエチレングリコール 0−60 30−45 35−40
水 5−30 7.5−20 10−15
嬌味嬌臭薬 0.1−5 1−4 2−3
量 好適な量 最も好適な量
クロザピン 0.5−30 1−20 10−15
ミグリオール 20−85 25−70 30−40
ブタノール 5−80 30−75 60−70
嬌味嬌臭薬 0.1−5 1−4 2−3
量 好適な量 最も好適な量
クロザピン 0.5−30 1−20 10−15
ミグリオール 70−99.5 80−99 85−90
嬌味嬌臭薬 0.1−5 1−4 2−3
量 好適な量 最も好適な量
シクロペンザプリン(塩基) 0.5−30 1−20 10−15
ミグリオール 20−85 25−70 30−40
イソブタン 15−80 30−75 60−70
嬌味嬌臭薬 0.1−5 1−4 2−3
量 好適な量 最も好適な量
塩酸デキシフェンフルラミン 5−30 7.5−20 10−15
エタノール 5−60 7.5−50 10−20
プロピレングリコール 5−30 7.5−20 10−15
ポリエチレングリコール 0−60 30−45 35−40
水 5−30 7.5−20 10−15
嬌味嬌臭薬 0.1−5 1−4 2−3
スルフォニル尿素
A.グリブリドの口腔用スプレー
量 好適な量 最も好適な量
グリブリド 0.25−25 0.5−20 0.75−15
エタノール 5−60 7.5−50 10−20
プロピレングリコール 5−30 7.5−20 10−15
ポリエチレングリコール 0−60 30−45 35−40
水 2.5−30 5−20 6−15
嬌味嬌臭薬 0.1−5 1−4 2−3
量 好適な量 最も好適な量
グリブリド 0.01−10 0.025−7.5 0.1−4
オリーブ油 30−60 35−55 30−50
ポリオキシエチレン化したオレイン酸
グリセリド 30−60 35−55 30−50
嬌味嬌臭薬 0.1−5 1−4 2−3
抗真菌性および抗ウイルス性の抗生物質
A.ジドブジン(かつてはアジドチミジン(AZT)(レトロビル)と呼ばれていた)の非極性口腔用スプレー
量 好適な量 最も好適な量
ジドブジン 10−50 15−40 25−35
ダイズ油 20−85 25−70 30−40
ブタン 15−80 30−75 60−70
嬌味嬌臭薬 0.1−5 1−4 2−3
量 好適な量 最も好適な量
エリスロマイシン 25−65 30−50 35−45
ポリオキシエチレングリコール 5−70 30−60 45−55
グリセリン 5−20 7.5−15 10−12.5
嬌味嬌臭薬 1−10 2−8 3−6
量 好適な量 最も好適な量
塩酸シプロフロキサシン 25−65 35−55 40−50
グリセリン 5−20 7.5−15 10−12.5
ポリエチレングリコール 120−75 30−65 40−60
嬌味嬌臭薬 1−10 2−8 3−6
量 好適な量 最も好適な量
ジドブジン 10−50 15−40 25−35
水 30−80 40−75 45−70
エタノール 5−20 7.5−15 9.5−12.5
ポリエチレングリコール 5−20 7.5−15 9.5−12.5
嬌味嬌臭薬 0.1−5 1−4 2−3
抗嘔吐薬
A.塩酸オンダンセトロンの口腔用スプレー
量 好適な量 最も好適な量
塩酸オンダンセトロン 1−25 2−20 2.5−15
クエン酸一水和物 1−10 2−8 2.5−5
クエン酸ナトリウム二水和物 0.5−5 1−4 1.25−2.5
水 1−90 5−85 10−75
エタノール 5−30 7.5−20 9.5−15
プロピレングリコール 5−30 7.5−20 9.5−15
ポリチレングリコール 5−30 7.5−20 9.5−15
嬌味嬌臭薬 1−10 3−8 5−7.5
量 好適な量 最も好適な量
ジメンヒドリナート 0.5−30 2−25 3−15
グリセリン 5−20 7.5−15 10−12.5
ポリチレングリコール 45−95 50−90 55−85
嬌味嬌臭薬 1−10 2−8 3−6
量 好適な量 最も好適な量
ジメンヒドリナート 3−50 4−40 5−35
水 5−90 10−80 15−75
エタノール 1−80 3−50 5−10
ポリエチレングリコール 1−80 3−50 5−15
ソルビトール 0.1−5 0.2−40 0.4−1.0
アスパルテーム 0.01−0.5 0.02−0.4 0.04−0.1
嬌味嬌臭薬 0.1−5 1−4 2−3
ヒスタミンH−2受容体アンタゴニスト
A.塩酸シメチジンのチュアブルカプセル
量 好適な量 最も好適な量
塩酸シメチジン 10−60 15−55 25−50
グリセリン 5−20 7.5−15 10−12.5
ポリチレングリコール 20−90 25−85 30−75
嬌味嬌臭薬 1−10 2−8 3−6
量 好適な量 最も好適な量
ファモチジン 1−35 5−30 7−20
水 2.5−25 3−20 5−10
L−アスパラギン酸 0.1−20 1−15 5−10
ポリチレングリコール 20−97 30−95 50−85
嬌味嬌臭薬 0.1−10 1−7.5 2−5
量 好適な量 最も好適な量
ファモチジン 1−35 5−30 7−20
ダイズ油 10−50 15−40 15−20
ブタン 5−80 30−75 45−70
ポリオキシエチル化した
オレイン酸グリセリド 10−50 15−40 15−20
嬌味嬌臭薬 0.1−5 1−4 2−3
バルビツール酸
A.フェニトインナトリウムの口腔用スプレー
量 好適な量 最も好適な量
フェニトインナトリウム 10−60 15−55 20−40
水 2.5−25 3−20 5−10
エタノール 5−30 7.5−20 9.5−15
プロピレングリコール 5−30 7.5−20 9.5−15
ポリエチレングリコール 5−30 7.5−20 9.5−15
嬌味嬌臭薬 1−10 3−8 5−7.5
量 好適な量 最も好適な量
フェニトイン 5−45 10−40 15−35
ミグリオール 10−50 15−40 15−20
ブタン 15−80 30−75 60−70
ポリオキシエチル化した
オレイン酸グリセリド 10−50 15−40 15−20
嬌味嬌臭薬 0.1−10 1−8 5−7.5
プロスタグランジン
カルボプロストスロメタミンの口腔用スプレー
量 好適な量 最も好適な量
カルボプロストスロメタミン 0.05−5 0.1−3 0.25−2.5
水 50−95 60−80 65−75
エタノール 5−20 7.5−15 9.5−12.5
ポリエチレングリコール 5−20 7.5−15 9.5−12.5
塩化ナトリウム 1−20 3−15 4−8
嬌味嬌臭薬 0.1−5 1−4 2−3
pHは水酸化ナトリウム及び/又は塩酸で調整された
量 好適な量 最も好適な量
カルボプロスト 0.05−5 0.1−3 0.25−2.5
ミグリオール 25−50 30−45 35−40
ブタン 5−60 10−50 20−35
ポリオキシエチル化した
オレイン酸グリセリド 25−50 30−45 35−40
嬌味嬌臭薬 0.1−10 1−8 5−7.5
栄養補助食品
A.チュアブルカプセルとしてのカルニチン(含有物はペースト)
量 好適な量 最も好適な量
フマル酸カルニチン 6−80 30−70 45−65
ダイズ油 7.5−50 10−40 12.5−35
ダイズレシチン 0.001−1.0 0.005−0.5 0.01−0.1
ダイズ油脂 7.5−50 10−40 12.5−35
嬌味嬌臭薬 1−10 2−8 3−6
量 好適な量 最も好適な量
カノコソウ抽出物 0.1−10 0.2−7 0.25−5
水 50−95 60−80 65−75
エタノール 5−20 7.5−15 9.5−12.5
ポリエチレングリコール 5−20 7.5−15 9.5−12.5
嬌味嬌臭薬 1−10 2−8 3−6
量 好適な量 最も好適な量
エキナシア抽出物 30−85 40−75 45−55
ダイズ油 7.5−50 10−40 12.5−35
ダイズレシチン 0.001−1.0 0.005−0.5 0.01−0.1
ダイズ油脂 7.5−50 10−40 12.5−35
嬌味嬌臭薬 1−10 2−8 3−6
量 好適な量 最も好適な量
酸化マグネシウム 15−40 20−35 25−30
ピコリン酸クロム 0.01−1.0 0.02−0.5 0.025−0.75
葉酸 0.025−3.0 0.05−2.0 0.25−0.5
ビタミンB−12 0.01−1.0 0.02−0.5 0.025−0.75
ビタミンE 15−40 20−35 25−30
ダイズ油 10−40 12.5−35 15−20
ダイズレシチン 0.1−5 0.2−4 0.5−1.5
ダイズ油脂 10−40 15−35 17.5−20
催眠剤(中枢神経系活性アミンも)
A.塩酸ジフェンヒドラミンの口腔用スプレー
量 好適な量 最も好適な量
ジフェンヒドラミン 3−50 4−40 5−35
HCl(塩酸)水 5−90 10−80 50−75
エタノール 1−80 3−50 5−10
ポリエチレングリコール 1−80 3−50 5−15
ソルビトール 0.1−5 0.2−4 0.4−1.0
アスパルテーム 0.01−0.5 0.02−0.4 0.04−01
嬌味嬌臭薬 0.1−5 1−4 2−3
抗喘息気管支拡張薬
A.極性口腔用スプレーとしての塩酸イソプロテレノール
量 好適な量 最も好適な量
塩酸イソプロテレノール 0.1−10 0.2−7.5 0.5−6
水 5−90 10−80 50−75
エタノール 1−80 3−50 5−10
ポリエチレングリコール 1−80 3−50 5−15
ソルビトール 0.1−5 0.2−4 0.4−1.0
アスパルテーム 0.01−0.5 0.02−0.4 0.04−0.1
嬌味嬌臭薬 0.1−5 1−4 2−3
量 好適な量 最も好適な量
硫酸テルブタリン 0.1−10 0.2−7.5 0.5−6
水 5−90 10−80 50−75
エタノール 1−10 2−8 2.5−5
ソルビトール 0.1−5 0.2−4 0.4−1.0
アスパルテーム 0.01−0.5 0.02−0.4 0.04−0.1
嬌味嬌臭薬 0.1−5 1−4 2−3
量 好適な量 最も好適な量
テルブタリン 0.1−10 0.2−7.5 0.5−6
ミグリオール 25−50 30−45 35−40
イソブタン 5−60 10−50 20−35
ポリオキシエチル化した
オレイン酸グリセリド 25−50 30−45 35−40
嬌味嬌臭薬 0.1−10 1−8 5−7.5
量 好適な量 最も好適な量
テオフィリン 5−50 10−40 15−30
ポリエチレングリコール 20−60 25−50 30−10
グリセリン 25−50 35−45 30−40
プロピレングリコール 25−50 35−45 30−40
嬌味嬌臭薬 0.1−5 1−4 2−3
量 好適な量 最も好適な量
硫酸アルブテロール 0.1−10 0.2−7.5 0.5−6
水 5−90 10−80 50−75
エタノール 1−10 2−8 2.5−5
ソルビトール 0.1−5 0.2−4 0.4−1.0
アスパルテーム 0.01−0.5 0.02−0.4 0.04−0.1
嬌味嬌臭薬 0.1−5 1−4 2−3
プロペラントを使用した極性溶媒の処方:
A.スルフォニル尿素
量 好適な量 最も好適な量
グリブリド 0.1−25% 0.5−15% 0.6−10%
エタノール 40−99% 60−67% 70−97%
水 0.01−5% 0.1−4% 0.2−2%
嬌味嬌臭薬 0.05−10% 0.1−5% 0.1−2.5%
プロペラント 2−10% 3−5% 3−4%
量 好適な量 最も好適な量
プロスタグランジンE1 0.01−10% 0.1−5% 0.2−3%
エタノール 10−90% 20−75% 25−50%
プロピレングリコール 1−90% 5−80% 10−75%
水 0.01−5% 0.1−4% 0.2−2%
嬌味嬌臭薬 0.05−10% 0.1−5% 0.1−2.5%
プロペラント 2−10% 3−5% 3−4%
量 好適な量 最も好適な量
プロメタジン 1−25% 3−15% 5−12%
エタノール 10−90% 20−75% 25−50%
プロピレングリコール 1−90% 5−80% 10−75%
水 0.01−5% 0.1−4% 0.2−2%
嬌味嬌臭薬 0.05−10% 0.1−5% 0.1−2.5%
プロペラント 2−10% 3−5% 3−4%
量 好適な量 最も好適な量
メクリジン 1−25% 3−15% 5−12%
エタノール 1−15% 2−10% 3−6%
プロピレングリコール 20−98% 5−90% 10−85%
水 0.01−5% 0.1−4% 0.2−2%
嬌味嬌臭薬 0.05−10% 0.1−5% 0.1−2.5%
プロペラント 2−10% 3−5% 3−4%
Claims (20)
- 抗不整脈薬、降圧剤、心臓調整剤(heart regulator)、心血管作動薬、プラーク安定剤、血管拡張薬、抗狭心症薬、抗凝血薬、抗低血圧薬、抗血栓薬、鬱血性心不全の治療薬、p−FOX(脂肪酸酸化)インヒビター、およびその混合物からなる群から選択される総組成物の0.001重量%と60重量%との間の量の活性化合物ならびに総組成物の30重量%と99重量%との間の量の極性溶媒を含む薬理学的に活性な化合物の経粘膜投与のためのプロペラントを含まない口腔内用スプレー組成物。
- 抗不整脈薬、降圧剤、心臓調整剤、心血管作動薬、プラーク安定剤、血管拡張薬、抗狭心症薬、抗凝血薬、抗低血圧薬、抗血栓薬、鬱血性心不全の治療薬、p−FOX(脂肪酸酸化)インヒビター、およびその混合物からなる群から選択される総組成物の0.1重量%と25重量%との間の量の活性化合物、総組成物の10重量%と97重量%との間の量の極性溶媒、ならびに総組成物の2重量%と10重量%との間の量のプロペラントを含み、前記プロペラントが直鎖または分岐配置のC3〜C8炭化水素である、薬理学的に活性な化合物の経粘膜投与のための口腔内用スプレー組成物。
- 抗不整脈薬、降圧剤、心臓調整剤、心血管作動薬、プラーク安定剤、血管拡張薬、抗狭心症薬、抗凝血薬、抗低血圧薬、抗血栓薬、鬱血性心不全の治療薬、p−FOX(脂肪酸酸化)インヒビター、およびその混合物からなる群から選択される総組成物の0.005重量%と55重量%との間の量の活性化合物ならびに総組成物の30重量%と99重量%との間の量の非極性溶媒を含む薬理学的に活性な化合物の経粘膜投与のためのプロペラントを含まない口腔内用スプレー組成物。
- 抗不整脈薬、降圧剤、心臓調整剤、心血管作動薬、プラーク安定剤、血管拡張薬、抗狭心症薬、抗凝血薬、抗低血圧薬、抗血栓薬、鬱血性心不全の治療薬、p−FOX(脂肪酸酸化)インヒビター、およびその混合物からなる群から選択される総組成物の0.05重量%と50重量%との間の量の活性化合物、総組成物の19重量%と85重量%との間の量の非極性溶媒、ならびに総組成物の5重量%と80重量%との間の量のプロペラントを含み、前記プロペラントが直鎖または分岐配置のC3〜C8炭化水素である、薬理学的に活性な化合物の経粘膜投与のための口腔内用スプレー組成物。
- 抗不整脈薬、降圧剤、心臓調整剤、心血管作動薬、プラーク安定剤、血管拡張薬、抗狭心症薬、抗凝血薬、抗低血圧薬、抗血栓薬、鬱血性心不全の治療薬、p−FOX(脂肪酸酸化)インヒビター、およびその混合物からなる群から選択される総組成物の0.01重量%と40重量%との間の量の活性化合物、総組成物の25重量%と89重量%との間の量の非極性溶媒、ならびに総組成物の10重量%と70重量%との間の量のプロペラントを含み、前記プロペラントが直鎖または分岐配置のC3〜C8炭化水素であり、嬌味嬌臭薬が総組成物の1重量%と8重量%との間の量で存在する、薬理学的に活性な化合物の経粘膜投与のための口腔内用スプレー組成物。
- 総組成物の0.1重量%と10重量%との間の量の嬌味嬌臭薬をさらに含む、請求項1〜請求項4のいずれか1項に記載の組成物。
- 前記極性溶媒が、400と1000との間の分子量のポリエチレングリコール、C2〜C8モノアルコールおよびポリアルコール、ならびにC7〜C18の直鎖または分岐配置のアルコールからなる群から選択される、請求項1または請求項2のいずれか1項に記載の組成物。
- 前記プロペラントが、プロパン、N−ブタン、イソブタン、N−ペンタン、イソペンタン、ネオペンタン、およびその混合物からなる群から選択される、請求項2、請求項4、または請求項5のいずれか1項に記載の組成物。
- 前記溶媒が、(C2〜C24)脂肪酸(C2〜C6)エステル、直鎖または分岐配置のC7〜C18炭化水素、C2〜C6アルカノイルエステル、およびC2〜C6カルボン酸のトリグリセリドからなる群から選択される、請求項3〜請求項5のいずれか1項に記載の組成物。
- 前記活性化合物が、アデノシン、アミオダロン、ベプリジル、ブレチリウム、ジギトキシン、ジゴキシン、ジルチアゼム、ジソピラミド、ドフェチリド、D−ソトロール、フレカイニド、リドカイン、メキシレチン、ミルリノン、フェニトイン、ピルシカイニド、プロカイナミド、プロパフェノン、プロパラノロール、キニジン、トカイニド、ドフェチリド、およびその混合物からなる群から選択される抗不整脈薬である、請求項1〜請求項5のいずれか1項に記載の組成物。
- 前記活性化合物が、アセブトロール、アルフゾシン、アムロジピン、アテノロール、アムロジピン/ベナゼプリル、バルニジピンベンザゼプリル、ベプリジル、ベタキソロール、ビスプロロール、ボセンタン、カンデサルタン、カプトプリル、カリポリド、カルベジロール、セリプロロール、シラザプリル、クロニジン、ジルチアゼム、ドキサゾシン、エナラプリル、エプレレノン、エプロサルタン、エスモロール、フェロジピン、フェノルドパム、フォシノプリル、グアンファシン、イミダプリル、イルベサルタン、イスラジピン、ラベタロール、レルカニジピン、リシノプリル、ロサルタン、マニジピン、メチルドパ、メトプロロール、モキソニジン、ナドロール、ニカルジピン、ニコランダール、ニフェジピン、ニトレンジピン、ノソルジピン、オマパトリラト、ペリンドプリルエルブミン、ピンドロール、プラゾシン、プロプラノロール、キナプリル、ラミプリ、ソタロール、スピラプリル、タムスロシン、テルミサルタン、テトラゾシン、トルセミド、トランドラプリル、バルサルタン、バタニジピン、ミドドリン、およびその混合物からなる群から選択される降圧剤である、請求項1〜請求項5のいずれか1項に記載の組成物。
- 前記活性化合物が、ジゴキシン、ジギトキシン、ドブタミン、およびその混合物からなる群から選択される心臓調整剤である、請求項1〜請求項5のいずれか1項に記載の組成物。
- 前記活性化合物が、エダラボン、イロプロスト、レボシメンダン、モルシドミン、テゾセンタン、チリラザド、YM087、アデノシン、アバシミベ(avasimibe)、フェノフィブレート、およびその混合物からなる群から選択される心血管作動薬である、請求項1〜請求項5のいずれか1項に記載の組成物。
- 前記活性化合物が、ブフロメジル、シロスタゾール、ジピリダモール、ジアゾキシド、ヒドララジン、ミノキシジル、ナフチドロフリル、ニコランジル、ニトロプルシド、アルプロスタジル、アポモルフィン、メシル酸フェントラミン、シルデナフィル、タダラフィル、バルデニフィル(vardenifil)、およびその混合物からなる群から選択される血管拡張薬である、請求項1〜請求項5のいずれか1項に記載の組成物。
- 前記活性化合物が、アミロジピン、亜硝酸アミル、アテノロール、ベプリジル、ジルチアゼム、四硝酸エリスリチル、フェロジピン、二硝酸イソソルビド、イスラジピン、メトプロロール、ナドロール、ニカルジピン、ニフェジピン、ニモジピン、四硝酸ペンタエリスリトール、プロプラノロール、およびその混合物からなる群から選択される抗狭心症薬である、請求項1〜請求項5のいずれか1項に記載の組成物。
- 前記活性化合物が、アブキシマブ、アルデパリン(ardeparin)、アルガトロバン、ビバリルジン、クロピドグレル、ダルテパリン、ダナパロイド、デシルジン、ジピリダモール、エノキサパリン、エプチフィバチド、フォンダパリヌクス、H376/95、レピルジン、メラガトラン(melagatran)、ナドロパリン、メシル酸ナファモスタット、ペントサン、ペントキシフィリン、レビパリン、サルポグレラート、SNAC/SNAD−ヘパリン、チクロピジン、チンザパリン、チロフィバン、ワルファリン、およびその混合物からなる群から選択される抗凝血薬である、請求項1〜請求項5のいずれか1項に記載の組成物。
- 前記活性化合物が、ミドドリン、ドブタミン、フルドロコルチゾン、およびその混合物からなる群から選択される抗低血圧薬である、請求項1〜請求項5のいずれか1項に記載の組成物。
- 前記活性化合物が、アスピリン、アブキシマブ、エノキサパリン、インテグレリン(integrelin)、チクロピジン、およびその混合物からなる群から選択される抗血栓薬である、請求項1〜請求項5のいずれか1項に記載の組成物。
- 前記活性化合物が、アムリノン、ベナゼプリル、ブメタニド、カプトプリル、ジギトキシン、ジゴキシン、ドブタミン、ドーパミン、エナラプリル、エタクリン酸、フォシノプリル、フロセミド、ヒドララジン、リシノプリル、ミルリノン、ミノキシジル、モエキシプリル、キナプリル、ラミプリル、トルセミド、およびその混合物からなる群から選択される、請求項1〜請求項5のいずれか1項に記載の組成物。
- 薬理学的に活性な化合物を哺乳動物の口腔粘膜に噴霧する工程を含む、前記請求項のいずれか1項に記載の組成物の使用。
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US10/230,075 US20030077229A1 (en) | 1997-10-01 | 2002-08-29 | Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs |
PCT/US2003/026853 WO2004019909A2 (en) | 2002-08-29 | 2003-08-27 | Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs |
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JP2010173864A Pending JP2010241843A (ja) | 2002-08-29 | 2010-08-02 | 心血管薬剤または腎臓薬剤を含む口腔内用極性および非極性スプレーまたはカプセル |
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JP2010241843A (ja) | 2010-10-28 |
US20030077229A1 (en) | 2003-04-24 |
CA2496769A1 (en) | 2004-03-11 |
US20050025713A1 (en) | 2005-02-03 |
US20080170995A1 (en) | 2008-07-17 |
EP2452675A1 (en) | 2012-05-16 |
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AU2003270014A1 (en) | 2004-03-19 |
WO2004019909A2 (en) | 2004-03-11 |
EP1536769A2 (en) | 2005-06-08 |
US20090123387A1 (en) | 2009-05-14 |
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