JP2008512434A - ベータ擬似剤の異性体及び抗コリン作用剤を含む医薬組成物 - Google Patents
ベータ擬似剤の異性体及び抗コリン作用剤を含む医薬組成物 Download PDFInfo
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- JP2008512434A JP2008512434A JP2007530766A JP2007530766A JP2008512434A JP 2008512434 A JP2008512434 A JP 2008512434A JP 2007530766 A JP2007530766 A JP 2007530766A JP 2007530766 A JP2007530766 A JP 2007530766A JP 2008512434 A JP2008512434 A JP 2008512434A
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Landscapes
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- Engineering & Computer Science (AREA)
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Abstract
【解決手段】 吸入に適した剤形の医薬組成物は、ベータ擬似剤の治療効果の低い異性体を実質的に含んでいない前記擬似剤の治療上有効な異性体、又はその塩、溶媒和物、エステル、誘導体若しくは多形体と、場合によって抗コリン作用剤又はその塩、溶媒和物、エステル、誘導体、異性体若しくは多形体とを含む。好ましい組成物は、R−サルブタモール硫酸塩及び臭化イプラトロピウムを含む。本発明の組成物の製造方法をも提供する。
【選択図】 なし
Description
米国特許第2002189610号は、イプラトリウムと一緒にベータ擬似剤を含む医薬製剤であって、ベータ擬似剤が、吸入に適した緩衝溶液中におけるホルモテロール又はサルメテロール、或いはそれらからのそれらの塩である医薬製剤を特許請求している。
Suzhou Junning New Drug Dev CT(中国)による特許出願CN第1413976号は、レボサルブタモールの合成を記述し、またCIPLA Limitedへの米国特許出願第2004054215号は、アルブテロールの光学的に純粋なR−異性体を得る方法を開示している。
サルメテロールのR及びS異性体が知られている。欧州特許出願EP第0422889号及び米国特許第5919827号は、共にサルメテロールのR−異性体に関しており、R−異性体が特に有利な作用プロフィルを有することを示唆している。より詳細には、米国特許第5919827号は、とりわけ喘息の治療向けにR−異性体を使用することにより、安全且つ有効な治療が提供される一方、ベータ擬似剤に通常付随している望ましくない副作用が低減されることを示唆している。
米国特許出願第20040136918号は、キシナホ酸R−サルメテロール及びプロピオン酸フルチカゾンの組合せを、喘息、慢性閉塞性肺障害、及び気道障害を治療するための定量エーロゾル吸入物として特許請求している。
ベータ擬似剤の治療上有効な異性体又はその塩、溶媒和物、エステル、多形体、若しくは誘導体を用いることによって、効力のある、且つ選択的な治療活性の利点をもたらす製剤を提供することが、本発明の1つの目的である。
本発明の他の目的は、喘息、慢性閉塞性肺障害(COPD)、及び気管支収縮の原因となる障害などの呼吸障害の治療向けの医薬組成物を提供することである。
本発明の医薬組成物の調製方法を提供することが、本発明のさらに他の目的である。
本発明による医薬組成物の調製方法をも提供している。
新規な医薬組成物であって、喘息、COPDなどの呼吸の及び関連障害、並びに気管支収縮の原因となるこのような他の障害を治療するための医薬組成物をも提供している。
レボサルブタモールを希釈剤、結合剤、崩壊剤、流動促進剤、滑剤とブレンドし、得られた混合物を圧縮することができる。
本発明による液体製剤は、3.0〜5.0の範囲にあるpHを有するのが好ましい。
この製造方法は、指定量の精製水中に保存剤、金属イオン封鎖剤、及び緩衝剤を溶解し、続いて本医薬を添加するステップを含む。これに続いて上記溶液に他の成分を添加する。pHをチェックし、最後に体積を調整する。
本発明によるレボサルブタモールは、30mcg〜8mgの用量で投与することができる。
この合剤は、適切な製剤を提供するために、医薬として許容し得る賦形剤とさらに組み合わせることができる。この組合せは、例えば噴霧用吸入溶液として、エーロゾル組成物として、吸入用乾燥粉末組成物として製剤できる。
本発明により、レボサルブタモールとイプラトロピウムとを含む乾燥粉末吸入器の製造方法であって、有効成分を場合によって適切な担体と混合するステップと、これらの成分を適切な乾燥粉末吸入器中に供給するステップとを含む方法をも提供している。
カスケード分析により、肺に到達する可能性を有する粒子量の目安を示すFPDの値(微粒子投与率:4.7ミクロン未満粒子)/%FPF(微粒子分率)を求めている。
試験は、カスケードインパクタを使用しUSP(アメリカ薬局方)により行っている。
本発明者らは、レボサルブタモールはラセミ体よりも易流動性であり、またより良好な懸濁及び分散特性を示す利点を有することを見出している。
下記の実施例は、例証のためのものであるが、本発明の範囲を限定するものではない。
CFC吸入器
(b)生成したスラリーを缶内に充填した。
(c)この缶に適切な弁を圧着し、
(d)この弁を通して噴射剤12を装填した。
HFA吸入器
b)アルコール及び界面活性剤を(a)に添加し、超音波処理した。
c)この缶に計量弁を圧着し、また
d)1,1,1,2−テトラフルオロエタン(HFA134a)を装填した。
b)ラクトースを(a)に添加した。
c)缶に計量弁を圧着し、
d)1,1,1,2−テトラフルオロエタン(HFA134a)を装填し、超音波処理した。
錠剤処方
1、及び2の一部を同時にふるいにかけて、プレミックスAを形成した。プレミックスAと一緒に2、3、4、5を製品ボウルに装填した。6、7、8を使用してデンプンゼラチンペーストを形成した。デンプンゼラチンペーストを、製品ボウル内のブレンドに噴霧して、顆粒を形成した。そのようにして得られた顆粒を、9、10、11で滑らかにし、圧縮した。
1、及び2の一部を同時にふるいにかけて、プレミックスAを形成した。プレミックスAと一緒に2、3、4、5を製品ボウルに装填した。6、7、8を使用してデンプンゼラチンペーストを噴霧した。デンプンゼラチンペーストを、製品ボウル内のブレンドに噴霧して、顆粒を形成した。そのようにして得られた顆粒を、9、10、11で滑らかにし、圧縮した。
液体
液体
液体
液体
1.エデト酸二ナトリウム及び塩化ナトリウムを、新たに沸騰させ、冷却した水中に添加し、溶解させる。
2.臭化イプラトロピウム及びレボサルブタモール硫酸塩を、上記溶液中に添加し、溶解させる。
3.必要な場合、硫酸を援用して溶液のpHを調節し、体積を100mlにする。
1.レボサルブタモール硫酸塩及び臭化イプラトロピウムをアルミニウム缶中に計り入れる。
2.レシチンを、十分な量の噴射剤P11中に溶解し、ステップ1のアルミニウム缶に加える。
3.アルミニウム缶を圧着し、密閉する。
4.次いで、アルミニウム缶を通して、噴射剤P12を装填する。
1.レボサルブタモール硫酸塩及び臭化イプラトロピウムをアルミニウム缶中に計り入れる。
2.ラクトースを、ステップ1に加える。
3.次いで、缶を圧着処理し、密閉する。
4.次いで、缶に噴射剤P227を充填する。
Claims (22)
- 吸入に適した剤形の医薬組成物であって、ベータ擬似剤の治療効果の低い異性体を実質的に含んでいない、前記擬似剤の治療上有効な異性体、又はその塩、溶媒和物、エステル、誘導体若しくは多形体と、場合によって抗コリン作用剤又はその塩、溶媒和物、エステル、誘導体、異性体若しくは多形体とを含む、前記医薬組成物。
- 前記治療上有効な異性体が、前記ベータ擬似剤のR−異性体である、請求項1記載の医薬組成物。
- 前記ベータ擬似剤が、R−サルブタモール、R−サルメテロール、又はR,R−ホルモテロール、或いはその塩、溶媒和物、エステル、プロドラッグ、多形体、若しくは誘導体である、請求項1又は2記載の医薬組成物。
- 前記抗コリン作用剤が、臭化イプラトロピウム、チオトロピウム、又はアトロピン、或いはその塩、溶媒和物、エステル、異性体、プロドラッグ、多形体、若しくは誘導体である、請求項1、2又は3記載の医薬組成物。
- 前記ベータ擬似剤が、R−サルブタモール硫酸塩である、請求項1から4のいずれかに記載の医薬組成物。
- 前記抗コリン作用剤が、臭化イプラトロピウムである、請求項1から5のいずれかに記載の医薬組成物。
- 吸入製剤を形成するために、適切な医薬として許容し得る賦形剤を含む、請求項1から6のいずれかに記載の医薬組成物。
- 請求項7記載の医薬組成物を含む、定量吸入器。
- 前記組成物が、定量吸入器向けの組成物を形成するのに適した医薬として許容し得る賦形剤を含む、請求項8記載の医薬組成物を含む定量吸入器。
- 前記組成物が、R−サルブタモール硫酸塩、臭化イプラトロピウム、1種以上のフッ化炭化水素噴射剤、及び場合によって1種以上の界面活性剤、又は1種以上の共溶媒、並びに/或いは1種以上の酸化防止剤を含む、請求項7記載の医薬組成物、或いは請求項8又は9記載の定量吸入器。
- 請求項7記載の医薬組成物を含む、乾燥粉末吸入器。
- 前記組成物が、乾燥粉末吸入器向けの組成物を形成するのに適した医薬として許容し得る賦形剤を含む、請求項11記載の医薬組成物を含む乾燥粉末吸入器。
- 前記組成物が、R−サルブタモール硫酸塩、臭化イプラトロピウム、及び微粉化した医薬として許容し得る担体を含む、請求項7記載の医薬組成物、或いは請求項11又は12記載の乾燥粉末吸入器。
- 吸入用溶液/懸濁液の形態をとる、請求項7記載の医薬組成物。
- 吸入用溶液又は懸濁液を形成するのに適した医薬として許容し得る賦形剤を含む、請求項14記載の医薬組成物。
- R−サルブタモール硫酸塩、臭化イプラトロピウム、極性溶媒、等張性調節剤、酸、及び場合によってキレート化剤を含む、請求項14又は15記載の医薬組成物。
- 請求項8、9、又は10記載の定量吸入器の作製方法であって、前記有効成分を適切な缶に加えるステップと、前記缶に定量弁を圧着するステップと、前記缶に噴射剤を装填するステップとを含む、前記方法。
- 請求項11、12、又は13に記載の乾燥粉末吸入器の作製方法であって、前記有効成分を場合によって適切な担体と混合するステップと、乾燥粉末吸入器中に前記組成物を供給するステップとを含む、前記方法。
- 請求項14、15、又は16に記載の医薬組成物の作製方法であって、場合によってキレート化剤、等張性調節剤、及び任意の他の適切な賦形剤と一緒に、前記有効成分を液体媒体中に溶解させ、若しくは懸濁させるステップと、pHを調節するステップとを含む、前記方法。
- 喘息、COPD、及び他の障害を含む、気管支収縮の原因となる呼吸障害を治療するための、請求項1から16のいずれか一項記載の医薬組成物。
- 喘息、COPD、及び他の障害を含む、気管支収縮の原因となる呼吸障害を治療するための薬物の製造における、請求項1から16のいずれか一項記載の医薬組成物の使用。
- 錠剤、又は経口液体である、請求項1から6のいずれか一項記載の組成物。
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- 2007-03-08 IL IL181828A patent/IL181828A0/en unknown
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001078738A1 (en) * | 2000-04-18 | 2001-10-25 | Glaxo Group Limited | Medical compositions comprising (r,r)-formoterol and rofleponide |
WO2002069979A2 (en) * | 2001-03-07 | 2002-09-12 | Glaxo Group Limited | Pharmaceutical formulation comprising r-salmeterol and fluticasone propionate |
Also Published As
Publication number | Publication date |
---|---|
EA200700600A1 (ru) | 2008-02-28 |
KR20070102659A (ko) | 2007-10-19 |
AU2005281511B2 (en) | 2011-03-31 |
EP1791534A1 (en) | 2007-06-06 |
IL181828A0 (en) | 2007-07-04 |
AU2005281511A1 (en) | 2006-03-16 |
MX2007002899A (es) | 2007-05-16 |
US20070264202A1 (en) | 2007-11-15 |
WO2006027595A1 (en) | 2006-03-16 |
BRPI0515103A (pt) | 2008-07-08 |
CA2580019A1 (en) | 2006-03-16 |
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