JP2007510800A - カルボン酸官能化重合体の調製方法 - Google Patents
カルボン酸官能化重合体の調製方法 Download PDFInfo
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- JP2007510800A JP2007510800A JP2006539659A JP2006539659A JP2007510800A JP 2007510800 A JP2007510800 A JP 2007510800A JP 2006539659 A JP2006539659 A JP 2006539659A JP 2006539659 A JP2006539659 A JP 2006539659A JP 2007510800 A JP2007510800 A JP 2007510800A
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Abstract
Description
1つの態様においては、該発明は、カルボキシル基で官能化された水溶性非ペプチド重合体を調製するための方法において、
(i)エステル試薬R(C=O)OR’(なお式中、R’は第三級基であり、Rは官能基Xを含む)を、水溶性非ペプチド重合体POLY−Y(なお式中、YはXと反応して共有結合を形成する官能基である)と反応させて、該重合体の第三級エステルを形成させる段階;及び
(i)重合体の第三級エステルを水溶液中でアルカリ金属水酸化物といった強塩基を用いて処理し、該重合体のカルボキシラートを形成させる段階を含んで成る方法を提供する。該方法はさらに、(iii)重合体のカルボキシラートを水溶液中で無機酸を用いて処理し、該カルボキシラートをカルボン酸に転換させ、かくしてカルボン酸官能化重合体を形成させる段階を含み得る。該カルボン酸官能化重合体を次に、適切な溶剤、好ましくは塩素化溶媒を用いて水溶液から抽出することができる。
という構造を有している。構造(I)中、Xは離脱基であり;かつR1及びR2の各々は、水素、アルキル、シクロアルキル、アルコキシ、アリール、アラルキル及びヘテロ環の中から独立して選択される。好ましくは、(CR1R2)基は、同一の炭素原子に付着された2つのヘテロ原子を含まない。例えば、同じ炭素原子上のR1及びR2は好ましくは両方共アルコキシではない。R3〜R5の各々は、低級アルキル、アリール、アラルキル及びシクロアルキルの中から独立して選択され、ここで、R3〜R5の任意のものと連結させて1つの環又はアダマンチルといった環系を形成させることができる。水素を除くR1〜R5のいずかを、低級アルキル、低級アルコキシ、C3−C6シクロアルキル、ハロ、シアノ、オキソ(ケト)、ニトロ及びフェニルの中から選択されている基で置換させることができる。変数nは1〜約24、好ましくは1〜6、より好ましくは1〜4、そして最も好ましくは1又は2である。1つの実施形態において、nは1である。
i)第三級エステル試薬R(C=O)OR’(なお式中、R’は第三級アルキル基であり、Rは官能基Xを含む)を、重合体PEG−Y(なお式中、YはXと反応して共有結合を形成する官能基である)と反応させて、PEG第三級エステルを形成させる段階;及び
ii)PEG第三級エステルを水溶液中で、アルカリ金属水酸化物といった強塩基を用いて処理し、PEGカルボキシラートを形成させる段階を含んで成る方法を提供する。該方法はさらに、iii)PEGカルボキシラートを水溶液中で無機酸を用いて処理し、該カルボキシラートをカルボン酸に転換し、かくしてPEGカルボン酸を形成させる段階を含んで成る。該方法の好ましい実施形態は、上述のものに対応する。該方法はさらに、該PEG−カルボン酸を活性化されたエステルといった活性化されたカルボン酸誘導体に転換する段階、及びカルボン酸誘導体を生物活性分子上の官能基と反応させることによって、該分子に対して該重合体を抱合させる段階をさらに含んで成る。
本発明を記述しかつ請求する上で、下記の専門用語は、以下で記述する定義に従って用いられることになる。
A.概要
本発明は、1つの態様において、カルボキシラート塩又はカルボン酸といったカルボキシル基で官能化された水溶性非ペプチド重合体の調製方法を提供する。該方法には、第三級エステル試薬R(C=O)OR’(なお式中、上述のとおりR’は第3級基であり、Rは官能基Xを含む)を水溶性非ペプチド重合体POLY−Y(なお式中、YはXと反応して共有結合を形成する官能基である)と反応させて、POLY−R−(C=O)OR’として表わすことのできる該重合体の第三級エステルを形成させる段階が関与している。POLYとRの間の連結の性質は、官能基Y及びXによって左右される。
好ましいエステル試薬(I)においては、R1及びR2の各々は、H、低級アルキル、シクロアルキル、アルコキシ、アリール、アラルキル及びヘテロ環の中から独立して選択されており;各々上述の定義通りR3〜R5の各々は、低級アルキル、アリール、アラルキルの中から独立して選択されている。好ましくは、(CR1R2)n基は、同じく炭素原子に付着された2つのヘテロ原子を内含せず、例えば同じ炭素原子上のR1及びR2は好ましくは両方共がアルコキシではない。水素を除くR1〜R5のいずれかは、上述の通り不干渉性置換体で置換され得る。
上述のスキームIの例の最上列で示されている該プロセスの第1段階については、成分は好ましくはt−ブタモール、ベンゼン、トルエン、キシレン、テトラヒドロフラン(THF)、ジメチルホルムアミド(DMF)、ジメチルスルホキシド(DMSO)などといったような適切な有機溶媒中に溶解させられる。
該発明の方法を用いて、カルボキシ官能化重合体が、高純度で、標準的には少なくとも約95重量%、好ましくは少なくとも約96重量%、97重量%又は98重量%、より好ましくは少なくとも約99重量%そして最も好ましくは少なくとも約99.5重量%の純度で生成される。選択された実施形態においては、重合体生成物は、所望のカルボキシル官能化重合体を少なくとも約99.6重量%、99.7重量%、99.8重量%又は99.9重量%含有する。従って、本書に開示されている合成方法の生成物は、出発重合体(例えばmPEG−OH、PEGジオール、又は多官能PEGポリオール)又はその他の重合体不純物を5重量%未満、好ましくは4重量%、3重量%又は2重量%未満、より好ましくは1重量%未満、そして最も好ましくは0.5重量%未満しか含有しない。選択された実施形態では、生成物は0.4重量%、0.3重量%、0.2重量%又は0.1重量%の重合体出発材料(例えばmPEG−OH)又はその他の重合体不純物しか含まない。
本発明では、さまざまな非ペプチド水溶性重合体のいずれのものでも使用することができる。重合体は、非毒性で生体適合性を有するべきであり、このことは、有害性なく生きた組織又は生体と共存する能力を有するということを意味している。適切な重合体の例としては、その全体が本書に参考として内含されている米国特許第5,629,384号に記述されているようなポリ(アルキレングリコール)、エチレングリコールとプロピレングリコールの共重合体、ポリ(オレフィンアルコール)、ポリ(ビニルピロリドン)、ポリ(ヒドロキシアルキルメタクリルアミド)、ポリ(ヒドロキシアルキルメタクリラート)、ポリ(サッカリド)、ポリ(α−ヒドロキシ酢酸)、ポリ(アクリル酸)、ポリ(ビニルアルコール)、ポリホスファゼン、ポリオキサゾリン、ポリ(N−アクリロイルモルホリン)及びその共重合体、ターポリマー及びその混合物が含まれるが、これらに制限されるわけではない。
A.概要
望まれる場合、該発明の方法により調製されたカルボン酸官能化重合体は、当該技術分野において既知の方法を用いさらに修飾を受けてカルボン酸の有用な反応性誘導体を形成することができる。このような誘導体の調製は、例えばTFAといった残留試薬及び/又は残留出発材料などを含有する先行技術の生成物に比べて、該発明のカルボン酸感応化重合体の純度が高いことによって容易になっている。これは、かかる汚染物質の存在及び量が非常に可変的でありかくして該生成物の再現が不可能となることから、特に薬学的生成物にとって有意な利点である。
という構造をもつPEG重合体である。部分Zは好ましくはハロ、アミノ、置換アミノ、−NCO、−NCS、N3、−CN及び−OR’から成る群から選択され、ここでR’はN−スクシンイミジル、ニトロフェニル、ベンゾトリアゾリル、イミダゾリル、N−スルホスクシンイミジル、N−フタルイミジル、N−グルタルイミジル、N−テトラヒドロフタルイミジル、N−ノルボルネン−2,3−ジカルボキシイミジル及びヒドロキシ−7−アザベンゾトリアゾリルから選択される。
かかる重合体抱合体は、生物活性剤に対する活性化PEGといったような活性化された重合体の共有結合による付着のための既知の技術を用いて形成可能である。例えば、ポリ(エチレングリコール):化学及び生物学的応用」、J, M. Harris及びS. Zalipsky, 編、American Chemical Society, Washington, DC (1997)又は「生物抱合体技術」、 G. T. Hermanson, Academic Press (1996)を参照のこと。一般に、抱合反応は、標準的に、室温又は室温に近い温度でリン酸又は酢酸緩衝液といったような緩衝液の中で実施されるが、条件は、実施中の特定の反応によって左右されることになる。標準的には、余剰の重合体試薬が活性作用物質と組合わされる。しかしながら一部のケースでは、重合体試薬上及び活性作用物質上に化学量論的量の反応基を有することが好ましい。
該発明の方法により形成された重合体に対するカップリングにおいて使用するための生物活性作用物質は、以下のもののうちの任意の単数又は複数のものであり得る。適切な作用物質は、例えば睡眠薬及び鎮静剤、精神賦活剤、精神安定剤、呼吸器薬、抗けいれん剤、筋弛緩剤、抗パーキンソン病薬(ドーパミン拮抗薬)、鎮痛剤、抗炎症剤、抗不安薬(不安緩解剤)、食欲抑制剤、片頭痛薬、筋肉収縮剤、抗感染薬(抗生物質、抗ウイルス薬、抗真菌剤、ワクチン)抗関節炎薬、抗マラリア薬、制吐薬、抗てんかん薬、気管支拡張薬、サイトカイン、成長因子、抗ガン剤、抗血栓剤、降圧剤、心臓脈管薬、不整脈治療剤、酸化防止剤、抗ぜん息薬、避妊薬を含むホルモン剤、交換神経刺激薬、利尿薬、脂質調節剤、抗アシドロゲン剤、駆虫薬、抗凝固剤、新生物薬、抗新生物薬、血糖降下薬、栄養剤及びサプリメント、成長サプリメント、抗腸炎剤、ワクチン、抗体、診断薬及び造影剤の中から選択可能である。
本発明は同様に、薬学賦形剤と組合わせた形で本書に提供されているような抱合体を含む薬学調製物をも内含している。賦形剤の例としては、制限的な意味なく、炭水化物、抗菌剤、酸化防止剤、界面活性剤、緩衝液及びそれらの組合せが含まれる。
トルエン(600ml)中のmPEG−30,000(50g、0.00167モル)(NOF Corporation)の溶液を、300mlのトルエンを蒸留することによって共沸乾燥させた。t−ブタノール(70ml)、カリウムtert−ブトキシド(95%、1.75g、0.0148モル、8.9倍余剰)及びtert−ブチルブロモアセタート(3.3g、0.0169モル、10.1倍余剰)を添加し、混合物をアルゴン雰囲気下で45℃で一晩攪拌した。溶媒を減圧下で蒸留させ、残渣を蒸留水(1000ml)中で溶解させた。
NMR(d6−DMSO):3.24ppm(s、−OCH3)、3.51ppm(s、PEG主鎖)、4.01ppm(s、−CH2−COO−)。
アニオン交換クロマトグラフィ分析:mPEG(30,000)−カルボン酸100%。この分析は、エーテル沈殿した生成物中には基本的に出発材料又はその他の重合体不純物が全く存在しないことを示した。
トルエン(600ml)中にPEG−10,000(35.25g、0.00705当量)(NOF Corporation)(両端がヒドロキシで終端)を溶解させ、トルエンを蒸発することにより共沸乾燥させた。残渣を無水トルエン(500ml)中に溶解させた。tert−ブタノール(40ml)、カリウムtert−ブトキシド(4g、0.0356モル、5.1倍余剰)及び無水トルエン(40ml)を組合わせ、上述の反応混合物に添加しその後約3.5時間攪拌した。t−ブチルブロモアセタート(7ml、0.0474モル、6.7倍余剰)を添加し、混合物をアルゴン雰囲気下で40℃で一晩攪拌した。溶媒を減圧下で蒸留し、残渣を蒸留水(1000ml)中で溶解させた。
NMR(d6−DMSO):3.51ppm(s、PEG主鎖)、4.01ppm(s、−CH2−COO−)。
アニオン交換クロマトグラフィ分析:PEG(10,000)−2カルボン酸100%。
アセトニトリルを蒸留することによりアセトニトリル(800ml)中のPEG−5,000(35g、0.01400当量)(NOF Corporation)の溶液を共沸乾燥させ、残渣を無水トルエン(300ml)中に再溶解させた。t−ブタノール(50ml)、カリウムtert−ブトキシド(4.7g、0.0419モル、2.99倍余剰)及び無水トルエン(50ml)を組合せ、上述の反応混合物に添加し、その後約3.5時間攪拌した。t−ブチルブロモアセタート(7.2ml、0.0488モル、3.48倍余剰)を添加し、混合物をアルゴン雰囲気下で室温で20時間攪拌した。溶媒を減圧下で蒸留させ、残渣を蒸留水(1000ml)中で溶解させた。
NMR(d6−DMSO):3.51ppm(s、PEGI主鎖)、4.01ppm(s、−CH2−COO−)アニオン交換クロマトグラフィ分析:PEG(5,000)−2カルボン酸100%。
トルエン(2300ml)中の多腕PEG(4−腕)、分子量10kDa(Nektar, アリゾナ州ハンツビル)(160g、0.064当量)の溶液を減圧下で80℃で1000mlのトルエンを蒸留することによって共沸乾燥させた。もう1つの容器の中で、tert−ブタノール(17.3ml)及びカリウムtert−ブトキシド(7.18g、0.148モル、2.00倍余剰)を混合し、その後以上からの乾燥済みトルエン溶液に添加した。結果として得た溶液を45℃で約3.5時間攪拌した。t−ブチルブロモアセタート(20.8ml、0.141モル、2.20倍余剰)を添加し、混合物をアルゴン雰囲気下で45℃で12時間攪拌した。溶媒を減圧下で蒸発させ、残渣を蒸留水(1.600ml)中で溶解させた。
NMR(d6−DMSO):3.51ppm(s、PEGI主鎖)、4.01ppm(s、−CH2−COO−)、置換100%。
Claims (60)
- カルボキシル基で官能化された水溶性非ペプチド重合体を調製するための方法において、
i) エステル試薬R(C=O)OR’(なお式中、R’は第三級基であり、Rは官能基Xを含む)を、水溶性非ペプチド重合体POLY−Y(なお式中、YはXと反応して共有結合を形成する官能基である)と反応させて、該重合体の第三級エステルを形成させる段階;及び
ii) 重合体の第三級エステルを水溶液中で強塩基を用いて処理し、該重合体のカルボン酸塩を形成させる段階、
を含んで成る方法。 - iii) 重合体のカルボン酸塩を水溶液中で無機酸を用いて処理し、該カルボン酸塩をカルボン酸に転換し、かくしてカルボン酸官能化重合体を形成させる段階、をさらに含んで成る請求項1に記載の方法。
- Xが離脱基でありかつYがヒドロキシル基である、請求項1又は2に記載の方法。
- 前記強塩基がアルカリ金属水酸化物である、請求項1又は2に記載の方法。
- 前記強塩基を用いた処理段階が、約11〜13の反応pHを生成するのに有効である、請求項1又は2に記載の方法。
- 前記無機酸が、水溶液中で非求核性アニオンを生成する酸である、請求項2に記載の方法。
- 前記酸が、硫酸、硝酸、リン酸及び塩酸から成る群から選択されている、請求項6に記載の方法。
- 前記第三級エステル試薬が、
− Xが離脱基であり;
− R1及びR2の各々が、水素、アルキル、シクロアルキル、アルコキシ、アリール、アラルキル及びヘテロ環の中から独立して選択されており;
− R3〜R5の各々が、低級アルキル、アリール、アラルキル及びシクロアルキルの中から独立して選択されており(なお、任意のR3〜R5を連結させて1つの環又は環系を形成させることができる);
− 水素を除く任意のR1〜R5を、低級アルキル、低級アルコキシ、C3−C6シクロアルキル、ハロ、シアノ、オキソ(ケト)、ニトロ及びフェニルの中から選択された基で置換させることができ;かつ
− nは1〜約24である、
請求項1に記載の方法。 - 前記nが1〜6である請求項8に記載の方法。
- 前記nが1又は2である請求項9に記載の方法。
- 前記R1及びR2の各々が独立して水素又は未置換低級アルキルであり、かつR3〜R5の各々が独立して未置換低級アルキル又はフェニルである、請求項8〜10のいずれかに記載の方法。
- 前記R1及びR2の各々が独立して水素又はメチルであり、かつR3〜R5の各々が独立してメチル、エチル又はフェニルである、請求項8〜10のいずれかに記載の方法。
- 前記R1及びR2の各々がHでありかつnが1である、請求項12に記載の方法。
- 前記第三級エステル試薬がt−ブチルハロ酢酸である、請求項13に記載の方法。
- 前記重合体が、ポリ(アルキレングリコール)、ポリ(オレフィンアルコール)、ポリ(ビニルピロリドン)、ポリ(ヒドロキシアルキルメタクリルアミド)、ポリ(ヒドロキシアルキルメタクリラート)、ポリ(サッカリド)、ポリ(α−ヒドロキシ酢酸)、ポリ(アクリル酸)、ポリ(ビニルアルコール)、ポリホスファゼン、ポリオキサゾリン、ポリ(N−アクリロイルモルホリン)、及びそれらの共重合体又は三元重合体から成る群から選択される、請求項1又は2に記載の方法。
- 前記重合体が、ポリ(エチレングリコール)である、請求項15に記載の方法。
- 前記ポリ(エチレングリコール)が線状であって、一方の末端において前記官能基Yで、かつ他方の末端においてもう1つの官能基Y’又はキャッピング基で終端している、請求項16に記載の方法。
- 前記カルボン酸を活性化されたカルボン酸誘導体に転換させる段階をさらに含んで成る、請求項2に記載の方法。
- 前記誘導体が活性化されたエステルである、請求項18に記載の方法。
- 前記カルボン酸誘導体を生物活性分子上の官能基と反応させることによって、前記分子と前記重合体を抱合させる段階をさらに含んで成る、請求項18に記載の方法。
- 前記カルボン酸誘導体が活性化されたエステルであり、前記分子上の官能基が求核基である、請求項20に記載の方法。
- 前記求核基がアミノ基、ヒドロキシル基又はチオールである、請求項21に記載の方法。
- カルボキシル基で官能化されたポリ(エチレングリコール)(PEG)を調製するための方法において、
i) 第三級エステル試薬R(C=O)OR’(なお式中、R’は第三級アルキル基であり、Rは官能基Xを含む)を、重合体PEG−Y(なお式中、YはXと反応して共有結合を形成する官能基である)と反応させて、PEG第三級エステルを形成させる段階;及び
ii) PEG第三級エステルを水溶液中で強塩基を用いて処理し、PEGカルボン酸塩を形成させる段階、
を含んで成る方法。 - iii) PEGカルボン酸塩を水溶液中で無機酸を用いて処理し、該カルボン酸塩をカルボン酸に転換させ、かくしてPEGカルボン酸を形成させる段階、をさらに含んで成る請求項23又は24に記載の方法。
- 前記Xが離脱基でありかつYがヒドロキシル基である、請求項23又は24に記載の方法。
- 前記強塩基がアルカリ金属水酸化物である、請求項23に記載の方法。
- 前記酸が、硫酸、硝酸、リン酸及び塩酸から成る群から選択されている、請求項24に記載の方法。
- 前記第三級エステル試薬が、
− Xが離脱基であり;
− R1及びR2の各々が、水素、アルキル、シクロアルキル、アルコキシ、アリール、アラルキル及びヘテロ環の中から独立して選択されており;
− R3〜R5の各々が、低級アルキル、アリール、アラルキル及びシクロアルキルの中から独立して選択されており(なお、任意のR3〜R5を連結させて1つの環又は環系を形成させることができる);
− 水素を除く任意のR1〜R5を、低級アルキル、低級アルコキシ、C3−C6シクロアルキル、ハロ、シアノ、オキソ(ケト)、ニトロ及びフェニルの中から選択されている基で置換させることができ;かつ
− nは1〜約24である、
請求項23に記載の方法。 - 前記nが1〜6である請求項28に記載の方法。
- 前記nが1又は2である請求項29に記載の方法。
- 前記R1及びR2の各々が独立して水素又は未置換低級アルキルであり、かつR3〜R5の各々が独立して未置換低級アルキル又はフェニルである、請求項28〜30のいずれかに記載の方法。
- 前記R1及びR2の各々がHでありかつnが1である、請求項28〜30のいずれかに記載の方法。
- 前記第三級エステル試薬がt−ブチルハロ酢酸である、請求項32に記載の方法。
- 前記ポリ(エチレングリコール)が線状であって、一方の末端において前記官能基Yで、かつ他方の末端においてもう1つの官能基Y’又はキャッピング基で終端している、請求項23,24又は33のいずれかに記載の方法。
- 前記PEGが、約100〜約100,000Daの分子量を有している、請求項23,24又は33に記載の方法。
- 前記PEGが、約300〜約60,000Daの分子量を有している、請求項35に記載の方法。
- 前記PEGカルボン酸を活性化されたカルボン酸誘導体に転換させる段階をさらに含んで成る、請求項24に記載の方法。
- 前記誘導体が活性化されたエステルである、請求項37に記載の方法。
- 前記カルボン酸誘導体を生物活性分子上の官能基と反応させることによって、前記分子と前記PEGを抱合させる段階をさらに含んで成る、請求項37に記載の方法。
- 前記生成物が5重量%未満の前記POLY−Y重合体を含有し、残りは、基本的に前記カルボン酸官能化重合体で構成されている、請求項2に記載の方法によって作られたカルボン酸官能化重合体を含んで成る、単離された重合体生成物。
- 2重量%未満の前記POLY−Y重合体を含んで成る、請求項40に記載の重合体生成物。
- 0.5重量%未満の前記POLY−Y重合体を含んで成る請求項40に記載の重合体生成物。
- 低分子量有機酸を実質的に全く含有していない、請求項40〜42のいずれかに記載の重合体生成物。
- 単量体有機カルボン酸を実質的に全く含有していない、請求項40〜42のいずれかに記載の重合体生成物。
- トリフルオロ酢酸を実質的に全く含有していない、請求項40〜42のいずれかに記載の重合体生成物。
- 前記カルボン酸官能化重合体がPEGカルボン酸である、請求項40に記載の重合体生成物。
- 前記カルボン酸官能化重合体がmPEG−CH2−COOHであり、かつ前記重合体生成物が5重量%未満のmPEG−OHを含有する、請求項46に記載の重合体生成物。
- 2重量%未満のmPEG−OHを含んで成る、請求項47に記載の重合体生成物。
- 0.5重量%未満のmPEG−OHを含んで成る、請求項48に記載の重合体生成物。
- トリフルオロ酢酸を実質的に全く含有していない、請求項47〜49のいずれかに記載の重合体生成物。
- 前記カルボン酸官能化重合体がHOOC−CH2−PEG−CH2−COOHであり、かつ前記生成物が5重量%未満のHO−PEG−OHを含有する、請求項46に記載の重合体生成物。
- 0.5重量%未満のOH−PEG−OHを含んで成る、請求項51に記載の重合体生成物。
- トリフルオロ酢酸を実質的に全く含有していない、請求項51又は52に記載の重合体生成物。
- 前記カルボン酸官能化重合体が、xを3〜8として、PEG−(CH2−COOH)xで表わされる多官能性有枝又は多腕カルボン酸官能化PEGであり、かつ前記生成物が5重量%未満のPEG−(OH)xを含有する、請求項46に記載の重合体生成物。
- トリフルオロ酢酸を実質的に含有していない、請求項54に記載の重合体生成物。
- PEG第三級エステルを形成させるべく、第三級エステル試薬R(C=O)OR’(なお式中、R’は第三級アルキル基であり、Rは官能基Xを含む)を重合体PEG−Y(なお式中、YはXと反応して共有結合を形成する官能基である)と反応させて、カルボキシル基で官能化されたポリ(エチレングリコール)(PEG)重合体を調製する方法において、水溶液中で強塩基を用いてPEG第三級エステルを処理して、PEGカルボン酸塩を形成させる段階を含んで成ることを特徴とする方法。
- 前記方法が、水溶液中で無機酸を用いてPEGカルボン酸塩を処理し、該カルボン酸をカルボン酸に転換し、かくしてPEGカルボン酸を形成させる段階をさらに含んで成ることを特徴とする、請求項56に記載の方法。
- 前記強塩基がアルカリ金属水酸化物であることを特徴とする、請求項56に記載の方法。
- 強塩基を用いた前記処理段階が約11〜13の反応pHを生成するのに有効であることを特徴とする、請求項56に記載の方法。
- 前記酸が、硫酸、硝酸、リン酸及び塩酸から成る群から選択されていることを特徴とする、請求項57に記載の方法。
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007538111A (ja) * | 2004-01-21 | 2007-12-27 | ネクター セラピューティクス アラバマ,コーポレイション | プロピオン酸末端ポリマーの調製方法 |
JP2008308690A (ja) * | 2007-06-13 | 2008-12-25 | Bio-Cancer Treatment Internatl Ltd | ポリ(エチレングリコール)機能性誘導体およびその製造方法 |
JP2017081885A (ja) * | 2015-10-30 | 2017-05-18 | 株式会社日本触媒 | 生体適合性医療用材料 |
JP2018172645A (ja) * | 2017-03-30 | 2018-11-08 | 日油株式会社 | カルボキシル基を一つ有するポリエチレングリコールの精製方法 |
JP2018178072A (ja) * | 2017-04-13 | 2018-11-15 | 株式会社日本触媒 | 生体適合性医療用材料 |
Families Citing this family (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050214250A1 (en) * | 2003-11-06 | 2005-09-29 | Harris J M | Method of preparing carboxylic acid functionalized polymers |
US7612153B2 (en) * | 2004-10-25 | 2009-11-03 | Intezyne Technologies, Inc. | Heterobifunctional poly(ethylene glycol) and uses thereof |
US7989554B2 (en) * | 2006-01-10 | 2011-08-02 | Enzon Pharmaceuticals, Inc. | Reacting polyalkylene oxide with base, tertiary alkyl haloacetate, then acid to prepare polyalkylene oxide carboxylic acid |
US8133707B2 (en) | 2006-01-17 | 2012-03-13 | Enzon Pharmaceuticals, Inc. | Methods of preparing activated polymers having alpha nitrogen groups |
US7671067B2 (en) * | 2006-02-09 | 2010-03-02 | Enzon Pharmaceuticals, Inc. | Treatment of non-hodgkin's lymphomas with multi-arm polymeric conjugates of 7-ethyl-10-hydroxycamtothecin |
US7462627B2 (en) * | 2006-02-09 | 2008-12-09 | Enzon Pharmaceuticals, Inc. | Multi-arm polymeric conjugates of 7-ethyl-10-hydroxycamptothecin for treatment of breast, colorectal, pancreatic, ovarian and lung cancers |
EP2010477A4 (en) | 2006-04-27 | 2012-05-30 | Intezyne Technologies Inc | POLY (ETHYLENE GLYCOL) CONTAINING CHEMICALLY DISPARATE ENDOGROUP |
PT2054074E (pt) | 2006-08-04 | 2014-11-07 | Prolong Pharmaceuticals Llc | Eritropoietina modificada |
RU2009133793A (ru) * | 2007-02-09 | 2011-03-20 | Энзон Фармасьютикалз, Инк. (Us) | Лечение резистентных или невосприимчивых форм рака конъюгатами 7-этил-10-гидроксикампотецина с множеством ответвлений цепи |
WO2010025337A1 (en) * | 2008-08-29 | 2010-03-04 | Enzon Pharmaceuticals, Inc. | Method of treating ras associated cancer |
US8119742B2 (en) * | 2008-09-28 | 2012-02-21 | Knc Ner Acquisition Sub, Inc. | Multi-armed catechol compound blends |
EP2341774B1 (en) * | 2008-10-21 | 2013-12-04 | Belrose Pharma Inc. | Treatment of neuroblastoma with multi-arm polymeric conjugates of 7-ethyl-10-hydroxycamptothecin |
WO2010091302A1 (en) * | 2009-02-06 | 2010-08-12 | Nerites Corporation | Multi-linked star-shaped polymers and synthetic methods therfor |
US20130123144A1 (en) * | 2010-05-06 | 2013-05-16 | Cornell University | Tunable lcst polymers and methods of preparation |
EP2606884A1 (en) | 2011-12-21 | 2013-06-26 | Ecole Polytechnique Fédérale de Lausanne (EPFL) | Inhibitors of notch signaling pathway and use thereof in treatment of cancers |
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WO2016167759A1 (en) * | 2015-04-15 | 2016-10-20 | Multisorb Technologies, Inc. | Surface modification of a resin |
EP3187254B1 (en) * | 2015-12-30 | 2020-09-02 | Italmatch SC, LLC | Polymeric emulsifier and lubricity additives for aqueous metal removal, forming, rolling or other applications |
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EP4008324A1 (en) | 2020-12-07 | 2022-06-08 | Cellestia Biotech AG | Combinations comprising an inhibitor of an anti-apoptotic protein, such as bcl-2, bcl-xl, bclw or mcl-1, and a notch signaling pathway inhibitor for treating cancer |
TW202313020A (zh) | 2021-06-02 | 2023-04-01 | 瑞士商西萊絲蒂亞生物科技股份有限公司 | 自體免疫及發炎性疾病的治療方法 |
WO2023079132A1 (en) | 2021-11-08 | 2023-05-11 | Cellestia Biotech Ag | Pharmaceutical combinations for treating cancer |
EP4223292A1 (en) | 2022-02-07 | 2023-08-09 | Cellestia Biotech AG | Pharmaceutical combinations for treating cancer |
CN115193363B (zh) * | 2022-09-16 | 2023-02-24 | 世名(苏州)新材料研究院有限公司 | 高酸值低酯值氧化蜡、其制备工艺及由其制得的酯化蜡 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06135889A (ja) * | 1992-10-26 | 1994-05-17 | Tokuyama Soda Co Ltd | 直鎖状脂肪族カルボン酸 |
JPH1087815A (ja) * | 1996-08-22 | 1998-04-07 | Enzon Inc | ポリアルキレンオキシドカルボン酸の改良製造方法 |
JPH10231270A (ja) * | 1997-02-19 | 1998-09-02 | Nof Corp | ポリオキシアルキレンカルボン酸の製造方法 |
JP2003511422A (ja) * | 1999-10-08 | 2003-03-25 | シアウォーター・コーポレイション | ヘテロ二官能性ポリエチレングリコール誘導体およびその調製方法 |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4721579A (en) * | 1980-08-15 | 1988-01-26 | Basf Corporation | Sodium carboxymethyl derivatives of polyoxyalkylene glycols, their production, and use in functional fluids |
DE3032061C1 (de) * | 1980-08-26 | 1982-06-09 | Chem-y, Fabriek van Chemische Produkten B.V., Bodegraven | Verfahren zur Herstellung eines verpumpbaren oberflaechenaktiven Produktes auf Basis von Polyaetheressigsaeuren |
DE3120195C2 (de) * | 1981-05-21 | 1986-09-04 | Degussa Ag, 6000 Frankfurt | Polymere Ammoniumverbindungen mit kieselsäureartigem Grundgerüst, Verfahren zu ihrer Herstellung und Verwendung |
JPH04199152A (ja) * | 1990-11-29 | 1992-07-20 | Toshiba Corp | 感光性組成物 |
US5483008A (en) * | 1992-02-07 | 1996-01-09 | Research Development Corporation Of Japan | Polyether having heterofunctional groups at both ends, process for the preparation thereof and polymerization initiator therefor |
US5278303A (en) * | 1992-06-12 | 1994-01-11 | University Of Toronto Innovations Foundation | Polymer-supported solution synthesis of oligosaccharides |
US5605976A (en) * | 1995-05-15 | 1997-02-25 | Enzon, Inc. | Method of preparing polyalkylene oxide carboxylic acids |
US5919455A (en) * | 1993-10-27 | 1999-07-06 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
US5693609A (en) | 1994-11-17 | 1997-12-02 | Eli Lilly And Company | Acylated insulin analogs |
US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
US5672662A (en) | 1995-07-07 | 1997-09-30 | Shearwater Polymers, Inc. | Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications |
US6448369B1 (en) * | 1997-11-06 | 2002-09-10 | Shearwater Corporation | Heterobifunctional poly(ethylene glycol) derivatives and methods for their preparation |
EP1061954B1 (en) | 1998-03-12 | 2004-06-09 | Nektar Therapeutics Al, Corporation | Poly(ethylene glycol) derivatives with proximal reactive groups |
DE19928128C1 (de) * | 1999-06-19 | 2000-11-30 | Clariant Gmbh | Verfahren zur Herstellung von Ethercarbonsäuren mit niedrigem Restalkohol |
TWI246524B (en) | 2001-01-19 | 2006-01-01 | Shearwater Corp | Multi-arm block copolymers as drug delivery vehicles |
DK1539857T3 (da) * | 2002-07-24 | 2007-03-12 | Hoffmann La Roche | Polyethylenglycol-aldehydderivater |
US20050214250A1 (en) | 2003-11-06 | 2005-09-29 | Harris J M | Method of preparing carboxylic acid functionalized polymers |
-
2004
- 2004-11-04 US US10/982,303 patent/US20050214250A1/en not_active Abandoned
- 2004-11-05 DK DK04810369.1T patent/DK1692206T3/da active
- 2004-11-05 JP JP2006539659A patent/JP5101884B2/ja active Active
- 2004-11-05 ES ES04810369T patent/ES2342294T3/es active Active
- 2004-11-05 AT AT04810369T patent/ATE465204T1/de active
- 2004-11-05 KR KR1020067008804A patent/KR101157007B1/ko active IP Right Grant
- 2004-11-05 CN CN200480039882A patent/CN100580005C/zh active Active
- 2004-11-05 PL PL04810369T patent/PL1692206T3/pl unknown
- 2004-11-05 CA CA2544697A patent/CA2544697C/en active Active
- 2004-11-05 SI SI200431461T patent/SI1692206T1/sl unknown
- 2004-11-05 EP EP04810369A patent/EP1692206B1/en active Active
- 2004-11-05 PT PT04810369T patent/PT1692206E/pt unknown
- 2004-11-05 WO PCT/US2004/036850 patent/WO2005047366A1/en active Application Filing
- 2004-11-05 DE DE602004026770T patent/DE602004026770D1/de active Active
- 2004-11-05 AU AU2004289992A patent/AU2004289992B2/en active Active
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- 2006-05-04 IL IL175406A patent/IL175406A/en active IP Right Grant
-
2010
- 2010-07-09 CY CY20101100646T patent/CY1110303T1/el unknown
-
2011
- 2011-02-09 US US13/023,960 patent/US8067505B2/en active Active
- 2011-10-21 US US13/279,134 patent/US20120041155A1/en not_active Abandoned
-
2013
- 2013-06-19 US US13/922,020 patent/US10011682B2/en active Active
-
2018
- 2018-06-05 US US16/000,561 patent/US11111335B2/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06135889A (ja) * | 1992-10-26 | 1994-05-17 | Tokuyama Soda Co Ltd | 直鎖状脂肪族カルボン酸 |
JPH1087815A (ja) * | 1996-08-22 | 1998-04-07 | Enzon Inc | ポリアルキレンオキシドカルボン酸の改良製造方法 |
JPH10231270A (ja) * | 1997-02-19 | 1998-09-02 | Nof Corp | ポリオキシアルキレンカルボン酸の製造方法 |
JP2003511422A (ja) * | 1999-10-08 | 2003-03-25 | シアウォーター・コーポレイション | ヘテロ二官能性ポリエチレングリコール誘導体およびその調製方法 |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007538111A (ja) * | 2004-01-21 | 2007-12-27 | ネクター セラピューティクス アラバマ,コーポレイション | プロピオン酸末端ポリマーの調製方法 |
JP2008308690A (ja) * | 2007-06-13 | 2008-12-25 | Bio-Cancer Treatment Internatl Ltd | ポリ(エチレングリコール)機能性誘導体およびその製造方法 |
JP2017081885A (ja) * | 2015-10-30 | 2017-05-18 | 株式会社日本触媒 | 生体適合性医療用材料 |
JP2018172645A (ja) * | 2017-03-30 | 2018-11-08 | 日油株式会社 | カルボキシル基を一つ有するポリエチレングリコールの精製方法 |
JP2018178072A (ja) * | 2017-04-13 | 2018-11-15 | 株式会社日本触媒 | 生体適合性医療用材料 |
JP7158143B2 (ja) | 2017-04-13 | 2022-10-21 | 株式会社日本触媒 | 生体適合性医療用材料 |
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