JP6081480B2 - 頑強な徐放性製剤 - Google Patents
頑強な徐放性製剤 Download PDFInfo
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- JP6081480B2 JP6081480B2 JP2014545179A JP2014545179A JP6081480B2 JP 6081480 B2 JP6081480 B2 JP 6081480B2 JP 2014545179 A JP2014545179 A JP 2014545179A JP 2014545179 A JP2014545179 A JP 2014545179A JP 6081480 B2 JP6081480 B2 JP 6081480B2
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
Description
a.少なくとも1つのジアシルグリセロール及び/又は少なくとも1つのトコフェロール、と、
b.リン脂質を含む少なくとも1つのリン脂質成分であって、そのリン脂質が、
i.50%を超えるホスファチジルエタノールアミンを含む極性頭部基と、
ii.それぞれ独立して16個〜20個の炭素原子を有する2つのアシル鎖で、少なくとも1つのアシル鎖が炭素鎖内に少なくとも1つの不飽和を有し、2つの炭素鎖に4つ以下の不飽和があるアシル鎖と、
を有するリン脂質成分と、
c.少なくとも1つの生体適合性酸素含有低粘性有機物と
の低粘性非液晶性混合物を含む予備製剤を提供し、
任意で、少なくとも1つの生物活性物質が前記低粘性混合物に溶解又は分散されており、
前記予備製剤は、水性流体との接触時に、少なくとも1つの非ラメラ(例えば、非ラメラ液晶)相構造を形成するか又は形成できる。
d.成分a)+b)+c)+d)の総量に対して、少なくとも1つの極性溶媒を20重量%以下含み、好ましくは、前記極性溶媒の誘電率は、25℃で測定して少なくとも28、更に好ましくは、25℃で測定して少なくとも30である。
a.少なくとも1つのジアシルグリセロール及び/又は少なくとも1つのトコフェロールと、
b.リン脂質を含む少なくとも1つのリン脂質成分であって、そのリン脂質が、
i.50%を超えるホスファチジルエタノールアミンを含む極性頭部基と、
ii.それぞれ独立して16個〜20個の炭素原子を有する2つのアシル鎖で、少なくとも1つのアシル鎖が炭素鎖内に少なくとも1つの不飽和を有し、2つの炭素鎖に4つ以下の不飽和があるアシル鎖と、
を有するリン脂質成分と、
c.少なくとも1つの生体適合性酸素含有低粘性有機溶媒と、
の非液晶性低粘性混合物を含む予備製剤を投与することを含み、
少なくとも1つの生物活性物質が前記低粘性混合物に溶解又は分散しており、これによって、投与後、in vivoにおいて水性流体と接触時に、少なくとも1つの非ラメラ液晶相構造を形成する。
a.少なくとも1つのジアシルグリセロール及び/又は少なくとも1つのトコフェロールと、
b.リン脂質を含む少なくとも1つのリン脂質成分であって、そのリン脂質が、
i.50%を超えるホスファチジルエタノールアミンを含む極性頭部基と、
ii.それぞれ独立して16個〜20個の炭素原子を有する2つのアシル鎖で、少なくとも1つのアシル鎖が炭素鎖内に少なくとも1つの不飽和を有し、2つの炭素鎖に4つ以下の不飽和があるアシル鎖と、
を有するリン脂質成分と、
c.少なくとも1つの生体適合性酸素含有低粘性有機溶媒と、
の非液晶低粘性混合物と、
任意で、この低粘性混合物に溶解又は分散している少なくとも1つの生物活性物質と、
を含む予備製剤を、in vivoにおいて水性流体に暴露させることを含む。
a.少なくとも1つのジアシルグリセロール及び/又は少なくとも1つのトコフェロールと
b.リン脂質を含む少なくとも1つのリン脂質成分であり、そのリン脂質が、
i.50%を超えるホスファチジルエタノールアミンを含む極性頭部基と、
ii.それぞれ独立して16個〜20個の炭素原子を有する2つのアシル鎖で、少なくとも1つのアシル鎖が炭素鎖内に少なくとも1つの不飽和を有し、2つの炭素鎖に4つ以下の不飽和があるアシル鎖と、
を有するリン脂質成分と、
c.少なくとも1つの生体適合性酸素含有低粘性有機溶媒と
の非液晶低粘性混合物を形成させることと、
この低粘性混合物を形成する前に、低粘性混合物又は成分a、b又はcの少なくとも1つに少なくとも1つの生物活性物質を溶解又は分散させることを含む。
a.少なくとも1つのジアシルグリセロール及び/又は少なくとも1つのトコフェロールと、
b.リン脂質を含む少なくとも1つのリン脂質成分であって、そのリン脂質が、
i.50%を超えるホスファチジルエタノールアミンを含む極性頭部基と、
ii.それぞれ独立して16個〜20個の炭素原子を有する2つのアシル鎖で、少なくとも1つのアシル鎖が炭素鎖内に少なくとも1つの不飽和を有し、2つの炭素鎖に4つ以下の不飽和があるアシル鎖と、
を有するリン脂質成分と、
c.少なくとも1つの生体適合性酸素含有低粘性有機溶媒と、
の非液晶低粘性混合物の使用を更に提供し、
少なくとも1つの生物活性物質の持続投与に使用するための予備製剤の製造において、前記活性物質が低粘性混合物に溶解又は分散され、前記予備製剤が、水性流体との接触時に、少なくとも1つの非ラメラ液晶相構造を形成できる。
a.少なくとも1つのジアシルグリセロール及び/又は少なくとも1つのトコフェロールと、
b.リン脂質を含む少なくとも1つのリン脂質成分であって、そのリン脂質が、
i.50%を超えるホスファチジルエタノールアミンを含む極性頭部基と、
ii.それぞれ独立して16個〜20個の炭素原子を有する2つのアシル鎖で、少なくとも1つのアシル鎖が炭素鎖内に少なくとも1つの不飽和を有し、2つの炭素鎖に4つ以下の不飽和があるアシル鎖と、
を有するリン脂質成分と、
c.少なくとも1つの生体適合性酸素含有低粘性有機溶媒と、
の低粘性混合物を含む予備製剤を少なくとも1回分計量された用量分、あらかじめ充填した使い捨て投与デバイスを提供し、
任意により、少なくとも1つの生物活性物質が前記低粘性混合物に溶解又は分散しており、前記予備製剤は、水性流体との接触時に、少なくとも1つの非ラメラ液晶相構造を形成するか又は形成できる。
a.少なくとも1つのジアシルグリセロール及び/又は少なくとも1つのトコフェロールと、
b.リン脂質を含む少なくとも1つのリン脂質成分であって、そのリン脂質が、
i.50%を超えるホスファチジルエタノールアミンを含む極性頭部基と、
ii.それぞれ独立して16個〜20個の炭素原子を有する2つのアシル鎖で、少なくとも1つのアシル鎖が炭素鎖内に少なくとも1つの不飽和を有し、2つの炭素鎖に4つ以下の不飽和があるアシル鎖と、
を有するリン脂質成分と、
c.少なくとも1つの生体適合性酸素含有低粘性有機溶媒と、
の低粘性混合物を含む製剤を計量された用量含み、
任意により、少なくとも1つの生物活性物質が低粘性混合物に溶解又は分散しており、前記予備製剤は、水性流体との接触時に、少なくとも1つの非ラメラ液晶相構造を形成するか又は形成できる。
本明細書中で示されるような成分「a」は、極性「頭部」基及び非極性「尾部」基を含む中性脂質成分である。一般に、脂質の頭部及び尾部は、エステル部分によって結合されるが、この結合は、エーテル、アミド、炭素‐炭素結合、又は他の結合によるものでもよい。具体的には、本発明の予備製剤において、成分aはジアシルグリセロールであり、2つの非極性「尾部」基を有する。
本発明の成分「b」は、
i.50%を超えるホスファチジルエタノールアミンを含む極性頭部基と、
ii.それぞれ独立して16個〜20個の炭素原子を有する2つのアシル鎖で、少なくとも1つのアシル鎖が炭素鎖内に少なくとも1つの不飽和を有し、2つの炭素鎖に4つ以下の不飽和があるアシル鎖と、
を有するリン脂質を含む少なくとも1つのリン脂質成分である。
i.90%を超えるホスファチジルコリンを含む極性頭部基と、
ii.それぞれ独立して16個〜20個の炭素原子を有する2つのアシル鎖で、少なくとも1つのアシル鎖が炭素鎖内に少なくとも1つの不飽和を有し、2つの炭素鎖において、不飽和が4つ以下であるアシル鎖と、
を有する少なくとも1つのリン脂質を更に含む。
本発明の予備製剤の成分「c」は、酸素含有有機溶媒である。予備製剤は投与後に(例えば、in vivoで)デポ組成物を生成するので、水性流体に接触する場合に、この溶媒が対象にとって耐えられるものであり、水性流体と混合でき、且つ/又は予備製剤から水性流体中に拡散若しくは溶出することが望ましい。したがって、少なくとも中程度の水溶性を有する溶媒が好ましい。
これまでに、脂質放出制御組成物は、実質的に水を含まずに調合すべきであるとが示唆されているが、高粘性液晶相への転換を避けるために、わずかな及び注意して制御された量の極性溶媒(水など)は、かなりの利点をもたらし得ることが今では示されている。特に、こうした極性溶媒(好ましくは水を含む)を含有することによって、活性物質の初期放出の制御を更に改善でき、いくつかのペプチド活性物質を更に高度に安定して添加でき、更に高速なデポ形成を提供し、且つ/又は注入時の不快感を更に低減することができる。これらの因子のいずれか1つにより、治療薬の送達、患者の健康及び/又は患者のコンプライアンスの関係に大きな改善をもたらし得る。
本発明の予備製剤は、好ましくは、1つ又は複数の生物活性物質(本明細書において「活性物質」と同等に記述される)を含む。活性物質は、所望の生物学的又は生理学的効果を有する任意の化合物(例えば、ペプチド、タンパク質、薬物、抗原、栄養素、化粧品、芳香剤、香味料、診断薬、薬剤、ビタミン、又は食物剤(dietary agent)など)であってよく、機能的レベルでのin vivo濃度(局所組成物のための局所濃度を含む)を与えるのに十分なレベルで調製される。いくかの状況においては、成分a、b及び/又はcのうちの1つ又は複数が活性物質であってもよいが、活性物質はこれらの成分の1つでないことが好ましい。最も好ましい活性物質は、薬物、ワクチン、及び診断剤などの薬剤である。
インターフェロン、GnRHアゴニスト(ブセレリン、デスロレリン、ゴセレリン、リュープロレリン/ロイプロリド、ナファレリン及びトリプトレリン)、GnRHアンタゴニスト(例えば、セトロレリクス、ガニレリクス、アバレリクス、デガレリクス)、グルカゴン様ペプチド‐1(GLP‐1)及びこれらの類似体(例えば、GLP‐1(7‐37)、GLP‐1(7‐36)アミド、リラグルチド、エキセナチド、及びリキシセナチド(AVE0010))、グルカゴン様ペプチド2アゴニスト(GLP‐2)及びこれらの類似体(例えば、GLP‐2及びエルシグルチド(Elsiglutide)(ZP1846))、DPPIV阻害剤、ソマトスタチンSST‐14及びSST‐28並びにソマトスタチン受容体(SSTR)アゴニスト(例えば、オクトレオチド、ランレオチド、バプレオチド、パシレオチド
a.25〜55重量%の少なくとも1つのジアシルグリセロール及び/又は少なくとも1つのトコフェロールと
b.25〜55重量%の、リン脂質を含む少なくとも1つのリン脂質成分であって、そのリン脂質が、
i.50%を超えるホスファチジルエタノールアミンを含む極性頭部基と、
ii.それぞれ独立して16個〜20個の炭素原子を有する2つのアシル鎖で、少なくとも1つのアシル鎖が炭素鎖内に少なくとも1つの不飽和を有し、2つの炭素鎖に4つ以下の不飽和があるアシル鎖と、
を有するリン脂質成分と、
c.5〜25重量%の少なくとも1つの生体適合性酸素含有低粘性有機溶媒と
の低粘性非液晶性混合物を含む予備製剤であって、
少なくとも1つのソマトスタチン受容体アゴニストを含む少なくとも1つのペプチド活性物質0.1〜10重量%がその低粘性混合物に溶解又は分散しており、
その予備製剤が、水性流体との接触時に、少なくとも1つの非ラメラ液晶相構造を形成するか又は形成できる予備製剤。
前述のように、本発明の予備製剤は、適用される本発明の方法により、治療対象の状態及び使用する生物活性物質に適切な経路を用いて投与されてもよい。本明細書で使用するとき、用語「腸管外」は、すべての「非経口」経路というより、「皮膚を介して」という確立された意味を示す。このため、腸管外投与は、主に、注射、注入、及び類似の技術(無針注入など)による投与を示す。このため、用語「非腸管外」は、皮膚を介する以外の適用経路を網羅する。このため、腸管外デポは、腸管外投与(皮下又は筋肉内投与など、注入可能である投与)によって形成されるものとし、非腸管外(例えば、経口、局所)デポ組成物は、皮膚、粘膜及び/若しくは爪の表面、眼、鼻、口腔若しくは内部表面、又は鼻腔、直腸腔、膣又は口腔前庭などの腔、歯周ポケット、又は自然の若しくはインプラントした構造を取り出した後若しくはインプラント(例えば、関節、ステント、美容インプラント、歯、歯充填材、又は他のインプラント)を挿入する前に形成される腔に投与することによって形成され得る。
本発明の予備製剤により、水性流体に曝露時、特にin vivoにおいて及び体表面との接触時に、非ラメラ液晶デポ製剤が提供される。好ましい実施形態において、本発明の液晶相はin situにおいて形成される。
本発明の予備製剤では、当該技術分野において既知の液体デポ製剤と比べて、頑強性が改善されている。これは、侵食/断片化及び機械的/分解頑強性に関して、改善された性能によって示される。
a.ロイプロリド、
b.オクトレオチド、
c.GLP‐1、
d.ブプレノルフィン、
e.フェンタニル、
f.パシレオチド、
g.ゴセレリン
[図1]0.1重量%タウロコール酸ナトリウム(NaTC)で培養した所定の脂質組成物(重量%)を有するゲルの600nmで計測した水相の見掛け吸光度(濁度)を示す図である。ゲルは、適度に振盪(150rpm)しながら、37℃で6時間培養した。組成物の詳細については表1も参照のこと。
[図2]生理食塩水中において、図に示すとおり、25℃、37℃、及び42℃で、DOPE/GDOの重量比が75/25〜35/65の間で完全水和させたDOPE/GDO混合物のX線回折図形を示す図である。相対的回折ピーク位置から、GDO含有量が増加すると、液晶相構造が、逆六方相から逆ミセル立体相(空間群Fd3m)に変化することがわかる図である。
[図3]生理食塩水中で、25℃、37℃、及び42℃で完全に水和させたDOPE/GDO(重量比で60/40)とDOPE/TOC(重量比で60/40)の混合物のX線回折図形を示す図である。相対的回析ピーク位置から、調査対象の温度範囲内で、同じ逆ミセル性立方相(Fd3m)液晶構造がわかる。
[図4]25℃、37℃及び42℃で完全に水和させた(生理食塩水中(0.9%NaClw/v)DOPE/GDO(重量比で50/50)の、オクトレオチドを含む混合物のX線回折図形を示す図である。図には、それぞれの脂質製剤内のオクトレオチド濃度が示されている。相対的な回折ピークの位置から、調査対象のオクトレオチド濃度及び温度範囲内での同じ逆ミセル立方(Fd3m)液晶構造がわかる。
[図5]本発明の3つの製剤をラットに皮下投与後のブプレノルフィンのin vivo薬物動態プロファイルを示す図である。エラーバーは標準偏差を示す(n=6)。実施例12に製剤組成が示されている。
[図6]ラットに皮下投与後のロイプロリド(LEU)のin vivo薬物動態プロファイルを示す図である。エラーバーは標準偏差を示す(n=8)。実施例13に製剤組成が示されている。
[図7]ラットに皮下投与後のオクトレオチド(OCT)のin vivo薬物動態プロファイルを示す図である。エラーバーは標準偏差を示す(n=6)。実施例14に製剤組成が示されている。
[図8]ラット皮下投与後のオクトレオチド(OCT)のin vivo薬物動態プロファイルを示す図である。エラーバーは標準偏差を示す(n=6)。実施例15に製剤組成が示されている。
[図9]ラット皮下投与後のオクトレオチド(OCT)のin vivo薬物動態プロファイルを示す図である。エラーバーは標準偏差を示す(n=6)。実施例16に製剤組成が示されている。
[図10]DOPE/GDOとSPC/GDOとの混合物によって水溶液(PBS、pH7.4)中で形成される液晶ゲルの機械的頑強性の比較を示す図である。以下のリン脂質/GDO重量比を調査し、比較した。
70:30(a)、65:35(b)、60:40(c)、55:45(d)及び50:50(e)。
材料
大豆ホスファチジルコリン(SPC)‐ドイツ、Lipoid製のLipoid S100
ジオレオイルフォスファチジルエタノールアミン(DOPE)−ドイツ、Lipoid製のLipoid PE18:1/18:1
グリセロールジオレエート(GDO)−デンマーク、Danisco製のRylo DG19 Pharma
α−トコフェロール(TOC)‐スイス、DSM製
エタノール(EtOH)、99.5%Ph.Eur.‐スウェーデン、Solveco製
タウロコール酸ナトリウム(NaTC)‐スウェーデン、Sigma‐Aldrich製
ブプレノルフィン塩基(BUP)‐ベルギー、Jansen製
酢酸ロイプロリド(LEU)‐米国、PolyPeptide Labs製
オクトレオチド塩酸塩(OCT)‐米国、PolyPeptide Labs製
パシレオチド(SOM230)パモエート塩‐スイス、Novartis Pharma製
エキセナチド(EXT)‐スイス、Bachem製
ゴセレリン酢酸塩(GOS)‐米国、PolyPeptide Labs製
プロピレングリコール(PG)‐ドイツ、Dow製
注射用水(WFI)‐ドイツ、B.Braun製
表1に従って、それぞれの脂質及び溶媒成分を3mL(2R)バイアル中において秤量することによって、リン脂質とジアシルグリセロールとの液体予備製剤(2g)を調製し、その後、40℃で均質の液体溶液が得られるまでローラー混合を行った(<20時間)。室温まで冷却後、すべての製剤が、低粘性で均質の液体であることが観察された。
表1の全液体予備製剤に対してゲル化試験を行った。使い捨ての1mLのルアーロック型注射器及び23G針を用いて、各製剤0.20gを6mL(6R)注射用ガラスバイアル内の5mLのPBS(pH7.4)に注入した。すべての製剤は、23G針を使用して簡単に注入した。その結果得られたゲルを1時間後室温で目視検査し、バイアルを軽く振盪させることによって崩壊されることのない粘着ゲルを形成することが明らかになった。
長期型デポ製剤及び/又は経口製剤のでは、重大な性質は、内因性界面活性剤及び/又は脂質分解酵素による浸食/断片化に対するゲルの頑強性に関する。In vitroにおいて頑強性を調べる方法は、脂質ゲルを界面活性剤が豊富な水性環境にさらし、その後、界面活性剤で浸食された脂質フラグメントから得られた水相の増大した濁度(又は見掛け吸光度)を測定することである。このような脂質フラグメントでは、光散乱により、溶液の濁度が大幅に増大する。胆汁酸塩は、生物学的関連性及び内因性の性質をもたらす、製剤の分解度を調べるための選択肢である界面活性剤として使用されることが多い。したがって、表1に示されている製剤によってPBS中に形成されたゲル(0.20g)をPBS中の0.1重量%タウロコール酸ナトリウム(NaTC)溶液5mLに入れた。その結果得られた試料は、その後37℃で回転速度を150rpmとして保持されたインキュベーターに移した。6時間後、試料をインキュベーターから取り出し、2回上下を逆さにし、吸光度測定のために、各水性溶液を使い捨てセミマイクロの1.5mLキュベットに移した。(見掛け)吸光度又は濁度は、PerkinElmerのLambda 40紫外可視分光計を用いて計測し、空気は、バックグラウンド補正のためのみに使用した。頑強性調査の結果は図1に示されている。
表1の製剤#1〜10(実施例1)0.475gに、25mgブプレノルフィン塩基(BUP)を添加し、総量で5wt%BUPとし、その結果得られた試料(2R注射用ガラスバイアル中)を40℃で約20時間、ローラーミキサーに入れた。室温まで冷却後、すべての製剤が、低粘性で均質且つ透明な液体であることが観察された。
表1(実施例1)の製剤#5、0.485gに、15mg酢酸ロイプロリド(LEU)を添加し、総量で3重量%LEUとし、その結果得られる試料(2R注射用ガラスバイアル中)を室温で約48時間、ローラーミキサーに入れた。
リン脂質とジアシルグリセロールの液体予備製剤(1g)を、実施例1に記載されているとおり調製した。混和後、すべての製剤が、室温において低粘性で均質の液体であることが観察された。これらの製剤の組成は、表2に示す。
リン脂質とトコフェロール(TOC)との液体予備製剤(2g)を、表3に従って、3mL(2R)バイアルで、それぞれの脂質及び溶媒成分を秤量することによって調製し、その後、40℃で、均質の液体溶液が得られるまでローラー混合を行った(<20時間)。室温まで冷却後、すべての製剤が、低粘性で均質の液体であることが観察された。
必要な量の各脂質成分を3mL(2R)バイアル内で秤量することによって、DOPEとGDOとの液体予備製剤(2g)を調製し、その後、総濃度が10〜15重量%となるまでEtOHを添加した。異なる試料での脂質の重量比は、DOPE:GDO=75:25〜35:65の範囲であった。均質な脂質溶液が得られるまで、試料を40℃でローラー混合した(<20時間)。室温まで冷却後、すべての製剤が、低粘性で均質の液体であることが観察された。その後、使い捨ての1mLのルアーロック型注射器及び23G針を使用して、各製剤(0.5g)を6mL(6R)注入ガラスバイアル内の5mLの生理食塩水(0.9%w/vNaCl)に注入した。いずれの製剤も針サイズ23Gを使用して、簡単に注入した。その結果得られたゲルは、小角X線散乱(SAXS)測定前に、室内周囲温度で10日間、ローラーミキサー上で平衡化させた。
必要な量の各脂質成分を3mL(2R)バイアル内で秤量することによって、DOPE/GDOとDOPE/TOCとの液体予備製剤(2g)を調製し、その後、総濃度が10重量%となるまでEtOHを添加した。異なる試料での脂質の重量比は、DOPE:GDO対DOPE:TOC=60:40であった。均質な液体溶液が得られるまで、試料を40℃でローラー混合した(<20時間)。室温まで冷却後、製剤が、低粘性で均質の液体であることが観察された。その後、使い捨ての1mLのルアーロック型注射器及び23G針を使用して、各製剤(0.5g)を6mL(6R)注入ガラスバイアル内の5mLの生理食塩水(0.9%w/vNaCl)に注入した。製剤は、針サイズ23Gを使用して、簡単に注入した。その結果得られたゲルは、小角X線散乱(SAXS)測定前に、室内周囲温度で10日間、ローラーミキサー上で平衡化させた。
必要な量の各脂質成分を10mL(10R)バイアル内で秤量することによって、DOPEとGDOとを含む液体予備製剤(5g)を調製し、その後、EtOHを添加した。均質な液体溶液が得られるまで、試料を40℃でローラー混合した(<20時間)。室温まで冷却後、オクトレオチド塩酸塩(OCT)を、それぞれ、濃度30mg及び45mgOCT遊離塩基/mLで製剤に添加し、その後、製剤が低粘性の均質液体になるのが見られるまで磁気攪拌する。その後、使い捨ての1mLのルアーロック型注射器及び23G針を使用して、各製剤(0.5g)を6mL(6R)注入ガラスバイアル内の5mLの生理食塩水(0.9%w/vNaCl)に注入した。製剤は、針サイズ23Gを使用して、簡単に注入した。その結果得られたゲルは、小角X線散乱(SAXS)測定前に、室内周囲温度で10日間、ローラーミキサー上で平衡化させた。OCTを含む予備製剤の最終組成物を表4に示す。
必要な量の各脂質成分を2mL(2R)バイアル内で秤量することによって、DOPEとGDOとを含む液体予備製剤(2g)を調製し、その後、必要な量のEtOH及びPGを添加した。均質液体溶液が見られるまで、試料を40℃でローラー混合した(<20時間)。室温まで冷却後、パシレオチドパモエート(又はSOM230)を製剤に添加して、最終濃度を約30mg/mLパシレオチド(遊離塩基として換算)とした。試料の最終組成は、表5に示す。
必要な量の各組成物を10mL(10R)バイアル内で秤量することによって、BUP、DOPE、及びGDOを含む液体予備製剤(6g)を調製し、その後、EtOHを添加した。均質な液体溶液が得られるまで、試料を40℃でローラー混合した(約6時間)。その後、0.2ミクロンの滅菌PVDF膜フィルター(Millipore製)を用いて、2.5bar窒素圧で各製剤を滅菌ろ過した。製剤組成物は、表6に示す。
必要な量の各脂質成分を15mL(15R)バイアル内で秤量することによって、リン脂質とGDOとを含む液体予備製剤を調製し、その後、EtOHを添加した。均質な液体溶液が得られるまで、試料を40℃でローラー混合した。必要な量のWFIを含む0.1mgEDTA/mLに必要な量のLEUを溶解した。その後、各脂質/EtOH溶液を、LEU/WFI溶液に添加した。その結果得られた製剤は最終的に周囲室温でローラー混合し、2.5bar窒素圧下で、0.2ミクロンの滅菌PVDF膜フィルター(Millipore製)を用いて、滅菌ろ過した。合計バッチサイズは7gであり、最終製剤組成は表7に示す。
必要な量の各脂質成分を15mL(15R)バイアル内で秤量することによって、DOPE/GDO及びSPC/GDOを含む液体予備製剤を調製し、その後、EtOHを添加した。均質な液体溶液が得られるまで、試料を40℃でローラー混合した。必要な量のオクトレオチド塩酸塩を10mL(10R)ガラスバイアル内に秤量して、その後、各脂質/EtOH溶液を添加した。均質な液体溶液が得られるまで、その結果得られた製剤を周囲室温でローラー混合した。その後、0.2ミクロンの滅菌PVDF膜フィルター(Millipore製)を用いて、2.5bar窒素圧で、各製剤を滅菌ろ過した。バッチサイズは7gであり、最終製剤組成物は表8に示す。
実施例14に記載されているように、リン脂質、GDO、共溶媒、及びオクトレオチド含有液体予備製剤(5g)を調製した。最終製剤組成は、表9に提示する。
実施例14に記載されているように、リン脂質、GDO、共溶媒、及びオクトレオチド含有液体予備製剤(5g)を調製した。最終製剤組成物は、表10に提示する。
必要な量の各脂質成分を2mL(2R)バイアル内で秤量することによって、DOPEとGDOを含む液体予備製剤(2g)を調製し、続いて、必要な量のEtOH及びPGを添加する。均質な液体溶液が得られるまで、試料を40℃でローラー混合する。室温に冷却後、エキセナチド(EXT)及びリラグルチド(LIR)をそれぞれ製剤に添加し、最終濃度を約10mg GLP−1受容体アゴニスト/mLとする。試料の最終組成は、表11に示す。
必要な量の各脂質成分を3mL(2R)バイアル内で秤量することによって、DOPE/GDO及びSPC/GDO混合物の液体予備製剤(1g)を調製し、その後、総濃度が10重量%となるまでEtOHを添加した。異なる試料での脂質の重量比は、DOPE:GDO=70:30〜50:50及びSPC:GDO=70:30〜50:50の範囲であった。均質な液体溶液が得られるまで、試料を40℃でローラー混合した(<20時間)。室温まで冷却後、製剤が、低粘性で均質の液体であることが観察された。その後、使い捨ての1mLのルアーロック型注射器及び23G針を使用して、各製剤(0.5g)を10mL(10R)注入ガラスバイアル内の5mLのリン酸緩衝食塩水(pH7.4)に注入した。製剤は、針サイズ23Gを使用して、簡単に注入した。その結果得られたゲルは、頑強性測定前の20日間、37℃、150rpmにて機械的混合テーブル上で平衡化させた。
Claims (40)
- a.少なくとも1つのジアシルグリセロール及び/又は少なくとも1つのトコフェロールと、
b.リン脂質を含む少なくとも1つのリン脂質成分であって、前記リン脂質が、
i.50%を超えるホスファチジルエタノールアミンを含む極性頭部基と、
ii.それぞれ独立して16個〜20個の炭素原子を有する2つのアシル鎖で、少なくとも1つのアシル鎖が炭素鎖内に少なくとも1つの不飽和を有し、2つの炭素鎖に4つ以下の不飽和があるアシル鎖と、
を有し、
前記リン脂質成分b)がPEを50%超含むリン脂質成分と、
c.少なくとも1つの生体適合性酸素含有低粘性有機溶媒と、
の低粘性非液晶性混合物を含む予備製剤であって、
a)対b)の重量比が80:20〜20:80であり、
前記予備製剤の粘度が、20℃で1〜1000mPasの範囲であり、
前記予備製剤が、水性流体との接触時に、少なくとも1つの非ラメラ液晶相構造を形成するか又は形成できる予備製剤。 - 前記少なくとも1つの生物活性物質が、前記低粘性混合物中に溶解又は分散している、請求項1に記載の予備製剤。
- 前記液晶相構造が、逆六方相構造若しくは逆立方相構造、又はこれらの混合物である、請求項1または2に記載の予備製剤。
- 前記液晶相構造が、H2、I2、又はこれらの混合物から選択される、請求項3に記載の前製剤。
- 成分a)が、実質的に不飽和C18基からなる非極性尾部基を含む、少なくとも1つのジアシルグリセロールである、請求項1〜4のいずれか一項に記載の予備製剤。
- 成分a)が実質的に少なくとも1つのトコフェロールからなる、請求項1〜4のいずれ
か一項に記載の予備製剤。 - 成分a)が実質的にGDOとトコフェロールとの混合物からなる、請求項1〜4のいずれか一項に記載の予備製剤。
- 成分b)が、ホスファチジルエタノールアミン、又はホスファチジルエタノールアミンとホスファチジルコリン、ホスファチジルイノシトール、及びスフィンゴミエリンから選択される少なくとも1つ、好ましくは、SPC及び/又はDOPCなどのホスファチジルコリンとの混合物から選択される、請求項1〜7のいずれか一項に記載の予備製剤。
- 前記リン脂質成分b)が、PEを少なくとも75%、例えばPEを少なくとも80%又はPEを少なくとも90%含み、最も好ましくは実質的に100%PEを含む、請求項1〜8のいずれか一項に記載の予備製剤。
- 前記リン脂質成分b)が、実質的に100%ホスファチジルエタノールアミンからなる極性頭部基を有するリン脂質を含む、請求項1〜9のいずれか一項に記載の予備製剤。
- 前記リン脂質成分b)が更に、
i.少なくとも90%のホスファチジルコリンを含む極性頭部基と、
ii.それぞれ独立して16個から20個の炭素原子を有する2つのアシル鎖で、少なくとも1つのアシル鎖が炭素鎖内に少なくとも1つの不飽和を有し、2つの炭素鎖に4つ以下の不飽和があるアシル鎖と、
を有する少なくとも1つのリン脂質を含む、
請求項1〜10のいずれか一項に記載の予備製剤。 - 前記リン脂質成分b)が、PC(好ましくは、SPC、DOPC、又はこれらの混合物)を少なくとも10%、例えば、PCを少なくとも20%、又はPCを少なくとも30%を含む、請求項1〜11のいずれか一項に記載の予備製剤。
- 成分b)が、PEを50%超及びPCを50%未満、例えば、PEを51%及びPCを49%、好ましくは、PEを約70%及びPCを約30%、更に好ましくは、PEを約80%及びPCを約20%、最も好ましくは、PEを約90%及びPCを約10%含む、請求項1〜12のいずれか一項に記載の予備製剤。
- 前記リン脂質成分b)が、温度範囲36℃から40℃において、過剰な水と接触して六方相を形成する、請求項1〜13のいずれか一項に記載の予備製剤。
- 分子溶液、L2及び/又はL3相構造を有する、請求項1〜14のいずれか一項に記載の予備製剤。
- a)対b)が、重量比で40:60から60:40の間の範囲内である、請求項1〜15のいずれか一項に記載の予備製剤。
- 成分a)+b)+c)の総重量に対して、成分a)が少なくとも15重量%、及び/又は成分b)が少なくとも15重量%である、請求項1〜16のいずれか一項に記載の予備製剤。
- 成分a)+b)+c)の総重量に対して、成分c)が2〜40重量%である、請求項1〜17のいずれか一項に記載の予備製剤。
- 成分c)が、アルコール、ケトン、エステル、エーテル、アミド、スルホキシド、及びこれらの混合物から選択される、請求項1〜18のいずれか一項に記載の予備製剤。
- 成分c)が、エタノール、NMP、又はこれらの混合物を含む、請求項1〜19のいずれか一項に記載の予備製剤。
- 成分a)+b)の総重量に対して、追加的に10%以下の荷電両親媒性物質を含む、請求項1〜20のいずれか一項に記載の予備製剤。
- 成分a)+b)+c)の総重量に対して、0.1〜10重量%の前記活性物質を有する、請求項1〜21のいずれか一項に記載の予備製剤。
- 成分a)+b)+c)+d)の総重量に対して、少なくとも1つの極性溶媒(成分(d))を20重量%以下更に含み、好ましくは、前記極性溶媒の誘電率が、25℃で測定して少なくとも28、更に好ましくは、25℃で測定して少なくとも30である、請求項1〜22のいずれか一項に記載の予備製剤。
- 成分d)が、水若しくはプロピレングリコール、又はこれらの混合物を含むか、あるいは、水若しくはプロピレングリコール、又はこれらの混合物からなる、請求項23に記載の予備製剤。
- 成分d)が少なくとも水を2%含む、請求項23又は請求項24に記載の予備製剤。
- 成分d)が、1.2〜20重量%、好ましくは2〜20重量%、更に好ましくは5〜18重量%、最も好ましくは8〜15重量%の濃度で存在する、請求項23〜25のいずれか一項に記載の予備製剤。
- 成分c)が、少なくとも1つの生体適合性、有機、モノアルコール溶媒、好ましくはエタノール、プロパノール、イソプロパノール、又はこれらの混合物からなる群から選択される少なくとも1つ、より好ましくはエタノールを含む、請求項23〜26のいずれか一項に記載の予備製剤。
- 成分c)が、NMP又はNMPとエタノールとの混合物を含む、請求項23〜27のいずれか一項に記載の予備製剤。
- 成分c)及びd)の組み合わせが、40重量%以下、好ましくは30重量%、より好ましくは25重量%、例えば、15〜20重量%の範囲の総濃度で存在する、請求項23〜28のいずれか一項に記載の予備製剤。
- 前記活性物質が、薬剤、抗原、栄養素、化粧品、芳香剤、香味料、診断薬、ビタミン、補助食品、及びこれらの混合物から選択される、請求項1〜29のいずれか一項に記載の予備製剤。
- 前記薬剤が、親水性小分子薬剤、親油性小分子薬剤、両親媒性小分子薬剤、ペプチド、タンパク質、オリゴヌクレオチド、及びこれらの混合物から選択される、請求項30に記載の予備製剤。
- 前記薬剤が、オピオイドアゴニスト(ブプレノルフィン及びフェンタニル)、GnRHアゴニスト(ブセレリン、デスロレリン、ゴセレリン、リュープロレリン/ロイプロリド、ナファレリン、及びトリプトレリン)、GnRHアンタゴニスト(セトロレリクス、ガニレリクス、アバレリクス、デガレリクス)、ソマトスタチン(SST‐14及びSST‐28)、及びソマトスタチン受容体(SSTR)アゴニスト、例えば、オクトレオチド、ランレオチド、バプレオチド、パシレオチド、グルカゴン様ペプチド1(GLP‐1)受容体アゴニスト(GLP‐1(7〜37)、GLP‐1(7〜36)アミド)、リラグルチド、エキセナチド、及びリキシセナチド(AVE0010))、及びグルカゴン様ペプチド2アゴニスト(例えばZP1846)、並びにこれらの混合物から選択される、請求項31に記載の予備製剤。
- 注射によって投与されうる、請求項1〜32のいずれか一項に記載の予備製剤。
- 噴霧、浸漬、洗浄、パッド又はボールローラーからの塗布、塗布、滴下、エアロゾール噴霧又はポンプ噴霧によって投与される、請求項1〜33のいずれか一項に記載の予備製剤。
- 少なくとも2週間、活性物質の連続放出を提供するデポー製剤を形成し、前記活性物質が、
a.ロイプロリド、
b.オクトレオチド、
c.GLP−1、
d.ブプレノルフィン、
e.フェンタニル、
f.パシレオチド、
g.ゴセレリン、
から選択される少なくとも1つを含む、請求項1〜34のいずれか一項に記載の注入可能な予備製剤。 - 前記活性物質が、アシクロビル、ジクロフェナク、ピロカルピン、レボカバスチン塩酸塩、ケトプロフェンフマル酸、チモロール、ベタキソロール、カルテオロール、レボブノロール、ドルゾラミド、ブリンゾラミド、エピネフリン、ジピベフリン、クロニジン、アプラクロニジン、ブリモニジン、ラタノプロスト(atanoprost)、トラボプロスト、ビマトプロスト、ウノプロストン、ピロカルピン塩酸塩、デキサメタゾン、クロラムフェニコール、ウンデカン酸テストステロン、及びインドメタシンから選択される少なくとも1つを含む、請求項1〜35のいずれか一項に記載の眼内投与に好適な非腸管外製剤。
- 生物活性物質を対象(好ましくは、哺乳類)に投与するのに好適な予備製剤を形成するためのプロセスであり、
a.少なくとも1つのジアシルグリセロール及び/又は少なくとも1つのトコフェロールと、
b.リン脂質を含む少なくとも1つのリン脂質成分であって、前記リン脂質が、
i.50%を超えるホスファチジルエタノールアミンを含む極性頭部基と、
ii.それぞれ独立して16個〜20個の炭素原子を有する2つのアシル鎖で、少なくとも1つのアシル鎖が炭素鎖内に少なくとも1つの不飽和を有し、2つの炭素鎖に4つ以下の不飽和があるアシル鎖と、
を有し、
前記リン脂質成分b)がPEを50%超含むリン脂質成分と、
c.少なくとも1つの生体適合性酸素含有低粘性有機溶媒と、
の混合物で、
a)対b)の重量比が80:20〜20:80である混合物を形成することと、
前記混合物を形成する前に、少なくとも1つの生物活性物質を前記混合物、又は成分a、b又はcの少なくとも1つに溶解又は分散させることを含み、
形成した前記予備製剤が、非液晶性であり、かつ、粘度が、20℃で1〜1000mPasの範囲である、プロセス。 - 前記形成した予備製剤が、請求項1〜37のいずれか一項に記載の予備製剤である、請求項38に記載のプロセス。
- 細菌感染症、真菌感染症、皮膚の痛み、目の疾患、性器の痛み、指及び/又はつま先の爪の感染及び疾患、乗り物酔い、ニコチン中毒などの依存症、歯周炎、結膜炎、緑内障、並びにホルモンの欠乏又は不均衡から選択される状態の治療において使用される薬剤の製造におけるか、または、
手術中の感染、インプラント中の感染、日焼け、火傷、切り傷、又は擦り傷部位での感染、経口感染、生殖器感染、及び感染体への曝露を引き起こす活動による感染から選択される少なくとも1つの状態に対する予防のための薬剤の製造における、請求項1〜37のいずれか一項に記載の予備製剤の使用。
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Publication number | Priority date | Publication date | Assignee | Title |
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EP1768650B1 (en) * | 2004-06-04 | 2008-07-16 | Camurus Ab | Liquid depot formulations |
GB0711656D0 (en) * | 2007-06-15 | 2007-07-25 | Camurus Ab | Formulations |
WO2012160213A1 (en) * | 2011-05-25 | 2012-11-29 | Camurus Ab | Controlled release peptide formulations |
MX350964B (es) * | 2012-05-25 | 2017-09-27 | Camurus Ab | Formulaciones de agonistas del receptor de somatostatina. |
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EP2823808A1 (en) * | 2013-07-09 | 2015-01-14 | Ipsen Pharma S.A.S. | Pharmaceutical composition for a sustained release of lanreotide |
KR20160075665A (ko) | 2013-10-22 | 2016-06-29 | 프로린크스 엘엘시 | 소마토스타틴 및 그 유사체의 컨쥬게이트 |
WO2016092569A1 (en) * | 2014-12-10 | 2016-06-16 | Council Of Scientific & Industrial Research | A discontinuous reverse micellar composition in cubic fd3m phase for sustained release of therapeutic drugs |
JP6822962B2 (ja) * | 2014-12-23 | 2021-01-27 | カムルス エービー | 制御放出製剤 |
GB201516554D0 (en) * | 2015-09-18 | 2015-11-04 | Camurus Ab | Controlled-release formulations |
ITUB20160416A1 (it) * | 2016-01-28 | 2017-07-28 | Italfarmaco Spa | Uso di una formulazione a lento rilascio di octreotide per la prevenzione della formazione di seroma |
WO2017168435A1 (en) * | 2016-03-31 | 2017-10-05 | Sun Pharma Advanced Research Company Limited | Viscoelastic gel of liraglutide adapted for once-weekly or once bi-weekly administration |
DK3512495T3 (da) * | 2016-09-15 | 2022-12-05 | Camurus Ab | Formuleringer af prostacyklinanaloger |
EP3518978A1 (en) * | 2016-09-27 | 2019-08-07 | Camurus AB | Mixtures and formulations comprising an alkyl ammonium edta salt |
WO2018217926A1 (en) | 2017-05-24 | 2018-11-29 | Vmr Products Llc | Flavor disk |
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KR20220012316A (ko) | 2019-05-29 | 2022-02-03 | 캐머러스 에이비 | 지질-제어 방출 조성물 |
EP4103587A1 (en) | 2020-02-14 | 2022-12-21 | Immunor AS | Corona virus vaccine |
US20230372317A1 (en) * | 2020-10-27 | 2023-11-23 | Pts Consulting, Llc | A liquid injectable composition of donepezil |
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Family Cites Families (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE8206744D0 (sv) | 1982-11-26 | 1982-11-26 | Fluidcarbon International Ab | Preparat for kontrollerad avgivning av substanser |
US4938763B1 (en) | 1988-10-03 | 1995-07-04 | Atrix Lab Inc | Biodegradable in-situ forming implants and method of producing the same |
US5538739A (en) | 1989-07-07 | 1996-07-23 | Sandoz Ltd. | Sustained release formulations of water soluble peptides |
MY107937A (en) | 1990-02-13 | 1996-06-29 | Takeda Chemical Industries Ltd | Prolonged release microcapsules. |
DK0752855T3 (da) * | 1994-03-30 | 2000-01-03 | Gs Dev Ab | Anvendelse af fedtsyreestere som bioadhæsive substanser |
SE518578C2 (sv) * | 1994-06-15 | 2002-10-29 | Gs Dev Ab | Lipidbaserad komposition |
DE69730093T2 (de) | 1996-10-31 | 2006-07-20 | Takeda Pharmaceutical Co. Ltd. | Zubereitung mit verzögerter Freisetzung |
BE1011899A6 (fr) * | 1998-04-30 | 2000-02-01 | Ucb Sa | Compositions pharmaceutiques gelifiables utilisables. |
JP3952617B2 (ja) | 1998-12-11 | 2007-08-01 | 株式会社日立製作所 | 内燃機関の排ガス浄化装置,排ガス浄化方法及び排ガス浄化触媒 |
GB0018891D0 (en) | 2000-08-01 | 2000-09-20 | Novartis Ag | Organic compounds |
US20080112915A1 (en) | 2003-10-24 | 2008-05-15 | Marianna Foldvari | Dna Delivery with Gemini Cationic Surfactants |
PL1682091T3 (pl) * | 2003-11-07 | 2017-09-29 | Camurus Ab | Kompozycje lipidów i kationowych peptydów |
GB0401513D0 (en) | 2004-01-23 | 2004-02-25 | Camurus Ab | Compositions |
US8182834B2 (en) | 2004-01-23 | 2012-05-22 | Camurus Ab | Ternary non-lamellar lipid compositions |
EP1768650B1 (en) * | 2004-06-04 | 2008-07-16 | Camurus Ab | Liquid depot formulations |
JP2008502690A (ja) * | 2004-06-15 | 2008-01-31 | アンドリュー シァン チェン, | リン脂質組成物ならびにその調製方法および使用方法 |
EP1843746B1 (en) * | 2005-01-14 | 2011-03-16 | Camurus Ab | Somatostatin analogue formulations |
CA2594718C (en) | 2005-01-14 | 2012-01-24 | Camurus Ab | Gnrh analogue formulations |
JP5127466B2 (ja) | 2005-01-21 | 2013-01-23 | カムルス エービー | 医薬脂質組成物 |
CN101217940B (zh) | 2005-06-06 | 2013-03-27 | 卡穆鲁斯公司 | Glp-1类似物制剂 |
GB0711656D0 (en) | 2007-06-15 | 2007-07-25 | Camurus Ab | Formulations |
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