JP2016518485A - 再生医学用及び組織工学用生分解性ネットワークポリマー - Google Patents
再生医学用及び組織工学用生分解性ネットワークポリマー Download PDFInfo
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- JP2016518485A JP2016518485A JP2016506730A JP2016506730A JP2016518485A JP 2016518485 A JP2016518485 A JP 2016518485A JP 2016506730 A JP2016506730 A JP 2016506730A JP 2016506730 A JP2016506730 A JP 2016506730A JP 2016518485 A JP2016518485 A JP 2016518485A
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Abstract
Description
A(BX)n (I)
(式中、
Aは、n価のコアであり、
Bは、ポリエーテルセグメントであり、
Xは、ヒドロキシ官能基であり、かつ、
nは、(BX)基の数を示しており、かつ、少なくとも3である。)
の構造を有する。
R(Y)m (II)
(式中、
Rは、ヒドロカルビル基であり、
mは、Y基の数を示しており、かつ、少なくとも2である。)
の構造を有していてもよい。
Rは、ヒドロカルビル基であり、かつ、
の構造を有していてもよい。
HO−(CH2CH2O)p−H HO−(CH2CH(CH3)O)q−H
A(BX)n (I)
(式中、
Aはn価のコアであり、
Bはポリエーテルセグメントであり、
Xはヒドロキシ官能基であり、かつ
nは(BX)基の数を示しており、かつ、少なくとも3である)の構造を有してもよい。
R(Y)m (II)
(式中、
Rは、ヒドロカルビル基であり、
mは、Y基の数を示し、かつ、少なくとも2である)の構造を有する。
%ESR=((Ws−Wd)/Wd)×100% (1)
に従って算出される平衡膨潤率(%ESR)として測定されてもよく、式中、Ws及びWdはそれぞれ、ネットワークポリマーの膨潤重量及び乾燥重量を指す。
<材料>
Claims (56)
- 多官能性ポリエーテルモノマーと多官能性架橋モノマーとを含むモノマー組成物を重合させることによって製造される、エステル結合を介して架橋されている生分解性ポリエーテルネットワークポリマーであって、前記ポリエーテルモノマーと前記架橋モノマーの一方が、ヒドロキシ官能基を含み、かつ、前記ポリエーテルモノマーと前記架橋モノマーの他方が、前記ヒドロキシ官能基と反応してエステル結合を形成することが可能な相補的な官能基を含み、かつ、前記ポリエーテルモノマー及び前記架橋モノマーより選ばれる少なくとも1つが分岐している、生分解性ポリエーテルネットワークポリマー。
- 前記相補的な官能基が、カルボン酸、カルボン酸エステル、カルボン酸無水物及びカルボン酸ハロゲン化物からなる群より選ばれる、請求項1記載の生分解性ポリエーテルネットワークポリマー。
- 前記相補的な官能基がカルボン酸ハロゲン化物である、請求項1又は請求項2記載の生分解性ポリエーテルネットワークポリマー。
- 前記ポリエーテルモノマーが複数個のヒドロキシ官能基を含む、請求項1〜3のいずれか1項に記載の生分解性ポリエーテルネットワークポリマー。
- 前記ポリエーテルモノマーが分岐している、請求項1〜4のいずれか1項に記載の生分解性ポリエーテルネットワークポリマー。
- 前記ポリエーテルモノマーが、以下の式(I):
A(BX)n (I)
(式中、
Aは、n価のコアであり、
Bは、ポリエーテルセグメントであり、
Xは、ヒドロキシ官能基であり、かつ、
nは、(BX)基の数を示しており、かつ、少なくとも3である。)
の構造を有する、請求項5記載の生分解性ポリエーテルネットワークポリマー。 - 前記ポリエーテルモノマーが、C2〜C3ジオールから誘導されたポリエーテルセグメントを含む、請求項1〜6のいずれか1項に記載の生分解性ポリエーテルネットワークポリマー。
- 前記ポリエーテルセグメントの各々が、約100〜約10,000Da、約150〜約5000Da、及び、約200〜約1000Daの範囲内の分子量を有する、請求項7記載の生分解性ポリエーテルネットワークポリマー。
- 前記ポリエーテルモノマーが、グリセロールエトキシレート及びペンタエリスリトールエトキシレートからなる群より選ばれる、請求項1〜8のいずれか1項に記載の生分解性ポリエーテルネットワークポリマー。
- 前記架橋モノマーが、カルボン酸ハロゲン化物の官能基を少なくとも2つ含む、請求項1〜9のいずれか1項に記載の生分解性ポリエーテルネットワークポリマー。
- 前記架橋モノマーが、以下の式(II):
R(Y)m (II)
(式中、
Rは、ヒドロカルビル基であり、
Yは、相補的な官能基であって、カルボン酸、カルボン酸エステル、カルボン酸無水物及びカルボン酸ハロゲン化物からなる群より選ばれる相補的な官能基であり、かつ、
mは、Y基の数を示しており、かつ、少なくとも2である。)
の構造を有する、請求項1〜10のいずれか1項に記載の生分解性ポリエーテルネットワークポリマー。 - 式(II)の前記架橋モノマーが、以下の式(IIa)又は式(IIb):
Rは、ヒドロカルビル基であり、かつ、
Yは、相補的な官能基であって、カルボン酸、カルボン酸エステル、カルボン酸無水物及びカルボン酸ハロゲン化物からなる群より選ばれる相補的な官能基である。)
の構造を有する、請求項11記載の生分解性ポリエーテルネットワークポリマー。 - Rが2〜12個の炭素原子を含む、請求項11又は請求項12記載の生分解性ポリエーテルネットワークポリマー。
- Yがカルボン酸ハロゲン化物の官能基である、請求項11〜13のいずれか1項に記載の生分解性ポリエーテルネットワークポリマー。
- 前記カルボン酸ハロゲン化物の官能基が、塩化物及び臭化物からなる群より選ばれるハロゲン化物の部位を含む、請求項14記載の生分解性ポリエーテルネットワークポリマー。
- 前記架橋モノマーが、塩化スクシニル、塩化アジポイル、塩化セバコイル、塩化グルタロイル、塩化ピメロイル、塩化スベロイル、及び塩化トリメソイル、好ましくは、塩化スクシニル及び塩化セバコイルからなる群より選ばれる、請求項1〜15のいずれか1項に記載の生分解性ポリエーテルネットワークポリマー。
- 前記モノマー組成物中における前記ポリエーテルモノマーの前記架橋モノマーに対するモル比が、およそ5:1〜1:5、好ましくはおよそ3:1〜1:3の範囲内にあり、そして最も好ましくはおよそ1:2である、請求項1〜16のいずれか1項に記載の生分解性ポリエーテルネットワークポリマー。
- 前記モノマー組成物がさらに機械特性改質剤を含む、請求項1〜17のいずれか1項に記載の生分解性ポリエーテルネットワークポリマー。
- 前記モノマー組成物が、前記機械特性改質剤を最大で20%(w/w)、好ましくは最大で15%(w/w)、より好ましくは最大で10%(w/w)含む、請求項18記載の生分解性ポリエーテルネットワークポリマー。
- 前記機械特性改質剤が、疎水性高分子又は疎水性オリゴマーである、請求項18又は請求項19記載の生分解性ポリエーテルネットワークポリマー。
- 前記疎水性高分子が、ポリエステルポリオールである、請求項20記載の生分解性ポリエーテルネットワークポリマー。
- 前記疎水性高分子が、ジヒドロキシポリ(カプロラクトン)である、請求項21記載の生分解性ポリエーテルネットワークポリマー。
- 多孔性であり、平均細孔直径が約1nm〜約3mmの範囲内にある、請求項1〜22のいずれか1項に記載の生分解性ポリエーテルネットワークポリマー。
- 請求項1〜22のいずれか1項に記載の生分解性ポリエーテルネットワークポリマーを含む、インビトロ細胞培養基材。
- フィルム形状をなしている、請求項24記載の細胞培養基材。
- 請求項1〜22のいずれか1項に記載の生分解性ポリエーテルネットワークポリマーを含む、基材。
- 請求項1〜22のいずれか1項に記載の生分解性ポリエーテルネットワークポリマーを含む、足場材。
- 請求項1〜22のいずれか1項に記載の生分解性ポリエーテルネットワークポリマーを含む、ナノ多孔性フィルム。
- エステル結合を介して架橋されている生分解性ポリエーテルネットワークポリマーを製造するための方法であって、当該方法は、多官能性ポリエーテルモノマーと多官能性架橋モノマーとを含むモノマー組成物を、当該ポリエーテルモノマーと当該架橋モノマーとの間でのエステル結合の形成を可能にする条件下で反応させる工程を含み、ここで、前記ポリエーテルモノマーと前記架橋モノマーの一方が、ヒドロキシ官能基を含み、かつ、前記ポリエーテルモノマーと前記架橋モノマーの他方が、前記ヒドロキシ官能基と反応してエステル結合を形成することが可能な相補的な官能基を含み、かつ、前記ポリエーテルモノマー及び前記架橋モノマーより選ばれる少なくとも1つが分岐している、方法。
- 前記相補的な官能基が、カルボン酸、カルボン酸エステル、カルボン酸無水物及びカルボン酸ハロゲン化物からなる群より選ばれる、請求項29記載の方法。
- 前記相補的な官能基がカルボン酸ハロゲン化物である、請求項29又は請求項30記載の方法。
- 前記ポリエーテルモノマーが複数個のヒドロキシ官能基を含む、請求項29〜31のいずれか1項に記載の方法。
- 前記ポリエーテルモノマーが分岐している、請求項29〜32のいずれか1項に記載の方法。
- 前記ポリエーテルモノマーが、以下の式(I):
A(BX)n (I)
(式中、
Aは、n価のコアであり、
Bは、ポリエーテルセグメントであり、
Xは、ヒドロキシ官能基であり、かつ、
nは、(BX)基の数を示しており、かつ、少なくとも3である。)
の構造を有する、請求項33記載の方法。 - 前記ポリエーテルモノマーが、C2〜C3ジオールから誘導されたポリエーテルセグメントを含む、請求項29〜34のいずれか1項に記載の方法。
- 前記ポリエーテルセグメントの各々が、約100〜約10,000Da、約150〜約5000Da、及び、約200〜約1000Daの範囲内の分子量を有する、請求項34又は請求項35記載の方法。
- 前記ポリエーテルモノマーが、グリセロールエトキシレート及びペンタエリスリトールエトキシレートからなる群より選ばれる、請求項29〜36のいずれか1項に記載の方法。
- 前記架橋モノマーが、カルボン酸ハロゲン化物の官能基を少なくとも2つ含む、請求項29〜37のいずれか1項に記載の方法。
- 前記架橋モノマーが、以下の式(II):
R(Y)m (II)
(式中、
Rは、直鎖状、分岐状、又は環状の炭化水素であり、
Yは、相補的な官能基であって、カルボン酸、カルボン酸エステル、カルボン酸無水物及びカルボン酸ハロゲン化物からなる群より選ばれる相補的な官能基であり、かつ、
mは、Y基の数を示しており、かつ、少なくとも2である。)
の構造を有する、請求項29〜38のいずれか1項に記載の方法。 - 式(II)の前記架橋モノマーが、以下の式(IIa)又は式(IIb):
Rは、直鎖状、分岐状、又は環状の炭化水素であり、かつ、
Yは、相補的な官能基であって、カルボン酸、カルボン酸エステル、カルボン酸無水物及びカルボン酸ハロゲン化物からなる群より選ばれる相補的な官能基である。)
の構造を有する、請求項39記載の方法。 - Rが2〜12個の炭素原子を含む、請求項39又は請求項40記載の方法。
- Yがカルボン酸ハロゲン化物の官能基である、請求項39〜41のいずれか1項に記載の方法。
- 前記カルボン酸ハロゲン化物の官能基が、塩化物及び臭化物からなる群より選ばれるハロゲン化物の部位を含む、請求項42記載の方法。
- 前記架橋モノマーが、塩化スクシニル、塩化アジポイル、塩化セバコイル、塩化グルタロイル、塩化ピメロイル、塩化スベロイル、及び塩化トリメソイル、好ましくは、塩化スクシニル及び塩化セバコイルからなる群より選ばれる、請求項29〜43のいずれか1項に記載の方法。
- 前記モノマー組成物中における前記ポリエーテルモノマーの前記架橋モノマーに対するモル比が、およそ5:1〜1:5、好ましくはおよそ3:1〜1:3の範囲内にあり、そして最も好ましくはおよそ1:2である、請求項29〜44のいずれか1項に記載の方法。
- 前記モノマー組成物がさらに機械特性改質剤を含む、請求項29〜45のいずれか1項に記載の方法。
- 前記モノマー組成物が、前記機械特性改質剤を最大で20%(w/w)、好ましくは最大で15%(w/w)、より好ましくは最大で10%(w/w)含む、請求項46記載の方法。
- 前記機械特性改質剤が、疎水性高分子又は疎水性オリゴマーである、請求項46又は請求項47記載の方法。
- 前記疎水性高分子が、ポリエステルポリオールである、請求項48記載の方法。
- 前記疎水性高分子が、ジヒドロキシポリ(カプロラクトン)である、請求項49記載の方法。
- 前記ポリエーテルモノマーと前記架橋モノマーとの反応を室温で行う、請求項29〜50のいずれか1項に記載の方法。
- 前記ポリエーテルモノマーと前記架橋モノマーとの反応によって、前記ポリエーテルネットワークポリマー内に細孔を生じるガス状形態縮合生成物が生成される、請求項29〜51のいずれか1項に記載の方法。
- 前記モノマー組成物がさらに固形ポロゲンを含む、請求項29〜52のいずれか1項に記載の方法。
- 前記モノマー組成物がポロゲン粒子を含む、請求項53記載の方法。
- 前記ポロゲン粒子が塩粒子である、請求項54記載の方法。
- エステル結合を介して架橋されている多孔性の生分解性ポリエーテルネットワークポリマーを製造するための方法であって、当該方法は、多官能性ポリエーテルモノマーと多官能性架橋モノマーとを含むモノマー組成物を、エステル結合を介して架橋しているポリエーテルネットワークポリマーの形成を可能にし、かつ、前記ネットワークポリマー内部に複数の細孔を生じさせるガス状縮合生成物のインサイチュでの生成を可能にする条件下で反応させる工程を含み、ここで、前記ポリエーテルモノマーと前記架橋モノマーの一方が、ヒドロキシ官能基を含み、かつ、前記ポリエーテルモノマーと前記架橋モノマーの他方が、前記ヒドロキシ官能基と反応してエステル結合を形成することが可能な相補的な官能基を含み、かつ、前記ポリエーテルモノマー及び前記架橋モノマーより選ばれる少なくとも1つが分岐している、方法。
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GB9700508D0 (en) | 1997-01-11 | 1997-02-26 | Smith & Nephew | Hydrogels |
EP1305056B1 (en) | 2000-08-04 | 2005-12-21 | Orthogem Limited | Porous synthetic bone graft and method of manufacture thereof |
JP2003274800A (ja) * | 2002-03-22 | 2003-09-30 | Daisee Kogyo Kk | 疑似餌用生分解性素材 |
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2014
- 2014-04-10 US US14/783,838 patent/US10179834B2/en active Active
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US20160060392A1 (en) | 2016-03-03 |
CN105358185A (zh) | 2016-02-24 |
WO2014165917A1 (en) | 2014-10-16 |
AU2014252769A1 (en) | 2015-11-26 |
CN105358185B (zh) | 2019-08-06 |
US10179834B2 (en) | 2019-01-15 |
BR112015025904A2 (pt) | 2017-07-25 |
US20190194389A1 (en) | 2019-06-27 |
EP2983726A1 (en) | 2016-02-17 |
EP2983726A4 (en) | 2016-12-14 |
AU2014252769B2 (en) | 2017-11-30 |
JP6403754B2 (ja) | 2018-10-10 |
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