JP2011500939A - ヒドロキシアパタイト標的化多腕ポリマーならびに、このポリマーから作られるコンジュゲート - Google Patents
ヒドロキシアパタイト標的化多腕ポリマーならびに、このポリマーから作られるコンジュゲート Download PDFInfo
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- JP2011500939A JP2011500939A JP2010531043A JP2010531043A JP2011500939A JP 2011500939 A JP2011500939 A JP 2011500939A JP 2010531043 A JP2010531043 A JP 2010531043A JP 2010531043 A JP2010531043 A JP 2010531043A JP 2011500939 A JP2011500939 A JP 2011500939A
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- hydroxyapatite
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- FCFNRCROJUBPLU-DNDCDFAISA-N valinomycin Chemical compound CC(C)[C@@H]1NC(=O)[C@H](C)OC(=O)[C@@H](C(C)C)NC(=O)[C@@H](C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC(=O)[C@@H](C(C)C)NC(=O)[C@@H](C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC(=O)[C@@H](C(C)C)NC(=O)[C@@H](C(C)C)OC1=O FCFNRCROJUBPLU-DNDCDFAISA-N 0.000 description 1
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Abstract
Description
本出願は、米国特許法第119条(e)に基づいて、2007年10月23日に出願された米国仮特許出願第60/982,012号(その開示内容を本明細書に援用する)の優先権の利益を主張するものである。
式中、
Aは、−(X3)d−(L3)e−(X4)f−POLY2−Z2または−(X3)d−(L3)e−(X4)f−Z2であり、
POLY1およびPOLY2は各々、同一であっても異なっていてもよく、水溶性の非ペプチドポリマーであり、
X1、X2、X3、X4は各々、同一であっても異なっていてもよく、スペーサ部分であり、
L1、L2、L3は各々、同一であっても異なっていてもよく、結合であり、
Z1は各々、同一であっても異なっていてもよく、Z2またはヒドロキシアパタイト標的化部分あるいは、2から約10のヒドロキシアパタイト標的化部分を含み、任意に少なくとも1つの水溶性非ペプチドポリマーも含む多腕構造であり、ただし、bが0である場合、少なくとも1つのZ1が1本以上のポリマー腕を含む多腕構造を有するという条件で、なおかつ、少なくとも1つのZ1がヒドロキシアパタイト標的化部分であるという条件であり、
Z2は、スペーサを介してPOLY2と結合していてもよい官能基であり、
a、b、c、d、e、fは各々、同一であっても異なっていてもよく、0または1のいずれかであり、
Rは、結合に利用できるp+1部位を少なくとも含む分子から誘導されるモノマー性またはオリゴマー性多腕コア分子であり、
pは、2〜32の範囲の整数である。
Z−(X1)a−L1−(X2)b−[POLY1−(X3)c−L2−(X4)d]m−POLY2−(X5)e−Y
を有する、ヘテロ二官能性かつ実質的に線状のヒドロキシアパタイト標的化ポリマーを提供するものであり、
式中、
POLY1およびPOLY2は各々、同一であっても異なっていてもよく、水溶性の非ペプチドポリマーであり、
X1、X2、X3、X4、X5は各々、同一であっても異なっていてもよく、スペーサ部分であり、
L1は、結合であり、
L2は各々、カルバメートおよびアミドからなる群から選択される加水分解的または酵素的に切断可能な結合であり、
Zは、ヒドロキシアパタイト標的化部分であり、
Yは官能基であり、
a、b、c、d、eは各々、同一であっても異なっていてもよく、0または1のいずれかであり、
mは、1〜10の範囲の整数である。
I.定義
本発明について説明および権利請求するにあたって、後述する定義に基づいて以下の専門用語を使用する。
II.ヒドロキシアパタイト標的化ポリマーと、このポリマーから作られるコンジュゲート
一態様では、本発明は、複数のヒドロキシアパタイト標的化部分が存在することを特徴とする、ポリマー試薬、当該ポリマー試薬を用いて作られる生物学的活性剤を含むコンジュゲートを提供するものである。単一のポリマー構造に複数のヒドロキシアパタイト標的化部分を用いることで、骨表面に対するポリマーの結合を強めることができ、これによって骨部位でポリマー構造に結合した薬剤分子の滞留時間を潜在的に長くできよう。
Aは、−(X3)d−(L3)e−(X4)f−POLY2−Z2または−(X3)d−(L3)e−(X4)f−Z2であり、
POLY1およびPOLY2は各々、同一であっても異なっていてもよく、水溶性の非ペプチドポリマーであり、
X1、X2、X3、X4は各々、同一であっても異なっていてもよく、スペーサ部分であり、
L1、L2、L3は各々、同一であっても異なっていてもよく、結合であり、
Z1は各々、同一であっても異なっていてもよく、Z2またはヒドロキシアパタイト標的化部分あるいは、2から約10のヒドロキシアパタイト標的化部分を含み、任意に少なくとも1つの水溶性非ペプチドポリマーも含む多腕構造であり、ただし、bが0である場合、少なくとも1つのZ1が1本以上のポリマー腕を含む多腕構造を有するという条件で、なおかつ少なくとも1つのZ1がヒドロキシアパタイト標的化部分であるという条件であり、
Z2は、スペーサを介してPOLY2に結合していてもよい官能基(イオン化可能な官能基など)であり、
a、b、c、d、e、fは各々、同一であっても異なっていてもよく、0または1のいずれかであり、
Rは、結合に利用できるp+1部位を少なくとも含む分子から誘導されるモノマー性またはオリゴマー性多腕コア分子であり、
pは、2〜32の範囲の整数である。
Z−(X1)a−L1−(X2)b−[POLY1−(X3)c−L2−(X4)d]m−POLY2−(X5)e−Y
を有する、ヘテロ二官能性で実質的に線状のヒドロキシアパタイト標的化ポリマーを提供するものであり、
式中:
POLY1およびPOLY2は各々、同一であっても異なっていてもよく、水溶性の非ペプチドポリマーであり、
X1、X2、X3、X4、X5は各々、同一であっても異なっていてもよく、スペーサ部分であり、
L1は、結合であり、
L2は各々、カルバメートおよびアミドからなる群から選択される加水分解的または酵素的に切断可能な結合であり、
Zは、ヒドロキシアパタイト標的化部分であり、
Yは官能基であり、
a、b、c、d、eは各々、同一であっても異なっていてもよく、0または1のいずれかであり、
mは、1〜10の範囲の整数である。
実験
以上、具体的な特定の好ましい実施形態をあげて本発明について説明してきたが、上記の説明ならびに以下の実施例は、例示を意図したものであり、本発明の範囲を限定されるものではない旨は理解できよう。本発明の範囲に包含される他の態様、利点および修正は、本発明の属する分野の当業者であれば自明であろう。たとえば、特定の用途において、すべての結合が分解可能ではなく安定した上記の式のいずれかのポリマー試薬を用いると望ましい場合もある。
I.PEG(5,000Da)−α−ヒドロキシ−ω−ブタン酸、メチルエステル
PEG(5,000)−α−ヒドロキシ−ω−ブタン酸(70g、0.0140モル)(Nektar Therapeutics)を無水メタノール(400ml)に入れた溶液に、濃硫酸(8.0ml)を加えた後、混合物を室温で3時間攪拌した。NaHCO3(8%水溶液)を加えて混合物のpHを7.0に調整した。メタノールを減圧下で留去し、CH2Cl2(2×350ml)で生成物を抽出した。抽出物を乾燥させ(MgSO4)、溶媒を減圧下で留去した。収量60g。
II.PEG(5,000Da)−α−サクシニミジルカーボネート−ω−ブタン酸、メチルエステル
PEG(5,000Da)−α−ヒドロキシ−ω−ブタン酸、メチルエステル(60g、0.0120モル)をアセトニトリル(300ml)に入れた溶液に、ピリジン(1.60ml)とジサクシニミジルカーボネート(3.92g)を加え、反応混合物をアルゴン雰囲気下で室温にて一晩攪拌した。次に、混合物を濾過し、溶媒を完全に蒸発させた。粗生成物を塩化メチレンに溶解し、イソプロピルアルコールで沈殿させた。湿生成物を減圧下で乾燥させた。収量57g。
III.PEG(5,000Da)−α−AHPDP−ω−ブタン酸
PEG(5,000Da)−α−サクシニミジルカーボネート−ω−ブタン酸、メチルエステル(40g、0.0080モル)をアセトニトリル(400ml)に入れた溶液に、3−アミノ−1−ヒドロキシプロパン−1,1−ジホスホン酸、ジテトラブチルアンモニウム塩(AHPDP−2Bu4N)(6.2g)とトリエチルアミン(2.4ml)を加え、反応混合物をアルゴン雰囲気で室温にて一晩攪拌した。次に、溶媒を完全に蒸発させた。粗生成物をDI水(400ml)に溶解し、1Mの水酸化ナトリウムを用いて溶液のpHを12.0に調整した。1Mの水酸化ナトリウムを定期的に加えてpHを12に維持したまま、この溶液を2時間攪拌した後、Amberlite IR 120(プラス)カラム(200ml)で濾過した。濾液から、減圧下で水を留去した。湿生成物を塩化メチレン(600ml)に溶解した後、溶媒を留去した。最後に、生成物を減圧下で乾燥させた。収量35g。
IV.PEG(5,000)−α−AHPDP−ω−ブタン酸、N−ヒドロキシスクシンイミドエステル
PEG(5,000Da)−α−AHPDP−ω−ブタン酸(30g、0.0060当量)を無水塩化メチレン(300ml)に入れた溶液に、N−ヒドロキシスクシンイミド(0.83g、0.0072モル)を加えた後、1,3−ジシクロヘキシルカルボジイミド(1.0M塩化メチレン溶液、7.2ml、0.0072モル)を加えた。反応混合物をアルゴン雰囲気で室温にて一晩攪拌した。次に、混合物を濾過し、溶媒を完全に蒸発させた。粗生成物を塩化メチレンに溶解し、イソプロピルアルコールで沈殿させた。最後に、生成物を減圧下で乾燥させた。収量27g。
V.PEG(5,000)−α−AHPDP−ω−ブチルアルデヒドジエチルアセタール
PEG(5,000Da)−α−AHPDP−ω−ブタン酸、N−ヒドロキシスクシンイミドエステル(25g、0.0050当量)を無水塩化メチレン(250ml)に入れた溶液に、テトラ(エチレングリコール)−α−アミノ−ω−ブチルアルデヒド、ジエチルアセタール(Nektar Therapeutics;2.0g、0.0059モル)を加えた後、トリエチルアミン(1.70ml)を加えた。反応混合物をアルゴン雰囲気で室温にて一晩攪拌した。次に、混合物を濾過し、溶媒を完全に蒸発させた。粗生成物を塩化メチレンに溶解し、イソプロピルアルコールで沈殿させた。最後に、生成物を減圧下で乾燥させた。収量22g。
VI.PEG(5,000)−α−AHPDP−ω−ブチルアルデヒド
PEG(5,000)−α−AHPDP−ω−ブチルアルデヒドジエチルアセタール(20g)を水300mlに溶解し、希リン酸を用いて溶液のpHを2.5に調整した。この溶液を室温にて3時間攪拌した。次に、0.5Mの水酸化ナトリウムを用いて溶液のpHを7に調整した。生成物を塩化メチレンで抽出し、ジエチルエーテルで沈殿させた。最後に、生成物を減圧下で乾燥させた。収量17.5g。
実施例2
I.グリセロールベースの前駆体分子の調製
化合物2(15.0g)をアセトニトリル(150ml)と蒸留水(35ml)との混合物に溶解した。次に、H3PO4の10%溶液を加えて、pHを4.5に調整した。この混合物をpH=4.5で1時間攪拌した。NaCl(2g)を加え、pHを7.5に調整した。生成物をCH2Cl2(600および150ml)で抽出した。
「HO−PEG2(20K)−ブタン酸、N−ヒドロキシスクシンイミドエステル」
前駆体分子でのヒドロキシル基の活性化
化合物1(2.0g、0.0208当量)を無水アセトニトリル(50ml)に溶解し、無水ピリジン(2.2ml、0.272モル)とN,N−ジサクシニミジルカーボネート(5.86g、0.0229モル、DSC)とを加えた。この溶液をアルゴン雰囲気で室温にて一晩攪拌した。次に、混合物を濾過し、溶媒を留去した。粗生成物をCH2Cl2(50ml)に溶解し、5%H3PO4溶液で洗浄した。次に、この溶液を乾燥させ(MgSO4)、溶媒を留去した。得られる生成物(化合物5)の収量は2.8gであった。
ベンジルオキシ−PEG(5K)−アミン(BzO−PEG(5K)−アミン)(20g、0.0040モル)(Nektar Therapeutics、Huntsville、AL)と、塩化メチレン(200ml)と、トリエチルアミン(1.4ml)との混合物に、化合物5(0.901g、0.0038当量)を加えた。この混合物をアルゴン雰囲気で室温にて一晩攪拌した。次に、溶媒を減圧下で留去した。
得られた化合物6(本明細書ではBzO−PEG2(20K)−ブタン酸、メチルエステルと呼ぶ)を蒸留水400mlに溶解し、0.5MのNaOH溶液で溶液のpHを12.2に調整した。この溶液をpH範囲12.0〜12.2で3時間攪拌した。次に、NaCl(20g)を加え、5%H3PO4溶液でpHを3.0に調整した。生成物をCH2Cl2で抽出(150ml×2)した。抽出物を乾燥させ(MgSO4)、溶媒を減圧下で留去して固体生成物19gを得た。この生成物を、米国特許第5,932,462号明細書に記載されているようにしてイオン交換クロマトグラフィで精製し、100%純粋な生成物14.5gを得た。
HO−PEG2(10K)−ブタン酸、N−ヒドロキシスクシンイミドエステルの調製
HO−PEG2(20K)−ブチルアルデヒド、ジエチルアセタールの調製
HO−(CH2CH2O)4CH2(CH2)2−CH(OCH2CH2)2
テトラ(エチレングリコール)(97.1g、0.500モル)とトルエン(200ml)との混合物を、減圧下にてトルエンを留去(ロータリーエバポレータ)して共沸乾燥させた。乾燥後のテトラ(エチレングリコール)を無水トルエン(180ml)に溶解し、カリウムtert−ブトキシドをtert−ブタノール(120.0ml、0.120モル)に入れた1.0M溶液と4−クロロブチルアルデヒドジエチルアセタール(18.1g、0.100モル)(Alfa Aesar、Ward Hill、MA)とを加えた。この混合物をアルゴン雰囲気にて95〜100℃で一晩攪拌した。室温まで冷ました後、混合物を濾過し、溶媒を減圧下で留去した。粗生成物を1000mlの脱イオン水に溶解し、得られる溶液を活性炭で濾過した。塩化ナトリウム(100g)を加え、生成物をジクロロメタンで抽出(250、200、150ml)した。抽出物を乾燥させ(MgSO4上)、溶媒を減圧下で留去した(回転蒸発)。
テトラ(エチレングリコール)−α−メシレート−ω−ブチルアルデヒド、ジエチルアセタールの調製
CH3−S(O)2−O−(CH2CH2O)4CH2(CH2)2−CH(OCH2CH2)2
テトラ(エチレングリコール)モノブチルアルデヒド、ジエチルアセタール(12.5g、0.037モル)とトルエン(120ml)との混合物を、減圧下にてトルエンを留去(ロータリーエバポレータ)して共沸乾燥させた。乾燥後のテトラ(エチレングリコール)モノブチルアルデヒド、ジエチルアセタールを無水トルエン(100ml)に溶解した。この溶液に、20mlの無水ジクロロメタンと5.7mlのトリエチルアミン(0.041モル)とを加えた。続いて4.5gのメタンスルホニルクロリド(0.039モル)を滴下して加えた。この溶液を窒素雰囲気にて室温で一晩攪拌した。次に、炭酸ナトリウム(5g)を加え、混合物を1時間攪拌した。続いて溶液を濾過し、溶媒を減圧下で留去した(ロータリーエバポレータ)。
テトラ(エチレングリコール)−α−アミノ−ω−ブチルアルデヒド、ジエチルアセタール
H2N−(CH2CH2O)4CH2(CH2)2−CH(OCH2CH2)2
テトラ(エチレングリコール)−α−メシレート−ω−ブチルアルデヒド、ジエチルアセタール(14.0g)と、濃水酸化アンモニウム(650ml)と、エチルアルコール(60ml)との混合物を、室温にて42時間攪拌した。次に、揮発性物質をすべて減圧下で留去した。粗生成物を150mlの脱イオン水に溶解し、溶液のpHを1.0MのNaOHで12に調整した。生成物をジクロロメタンで抽出(3×100ml)した。抽出物を乾燥させ(MgSO4)、溶媒を減圧下で留去した(ロータリーエバポレータ)。収量10.6g。
AHPDP−PEG2(10KDa)−ブチルアルデヒド
実施例3
1.トリリシンベースのBzO−PEG4(20K)−酸の調製
2.トリリシンベースのHO−PEG4(20K)−酸
3.トリリシンベースのHO−PEG4(20K)−ブチルアルデヒド、ジエチルアセタール
4.トリリシンベースのBTC−PEG4(20K)−ブチルアルデヒド、ジエチルアセタールの調製
5.トリリシンベースのAHPDP−PEG2(20K)−ブチルアルデヒドの調製
Claims (28)
- 以下の構造を有するポリマーであって、
Aは、−(X3)d−(L3)e−(X4)f−POLY2−Z2または−(X3)d−(L3)e−(X4)f−Z2であり、
POLY1およびPOLY2は各々、同一であっても異なっていてもよく、水溶性の非ペプチドポリマーであり、
X1、X2、X3、X4は各々、同一であっても異なっていてもよく、スペーサ部分であり、
L1、L2、L3は各々、同一であっても異なっていてもよく、結合であり、
Z1は各々、同一であっても異なっていてもよく、Z2と、ヒドロキシアパタイト標的化部分と、2から約10のヒドロキシアパタイト標的化部分を含み、任意に少なくとも1つの水溶性非ペプチドポリマーも含む多腕構造と、からなる群から選択され、ただし、bが0である場合、少なくとも1つのZ1が1本以上のポリマー腕を含む多腕構造を有するという条件で、なおかつ少なくとも1つのZ1がヒドロキシアパタイト標的化部分であるという条件であり、
Z2は、スペーサ部分を介してPOLY2と結合していてもよい官能基であり、
a、b、c、d、e、fは各々、同一であっても異なっていてもよく、0または1のいずれかであり、
Rは、結合に利用できるp+1部位を少なくとも含む分子から誘導されるモノマー性またはオリゴマー性多腕コア分子であり、
pは、2〜32の範囲の整数である、ポリマー。 - POLY1およびPOLY2が各々、存在する場合、約22,000Da未満の数平均分子量を有する、請求項1に記載のポリマー。
- POLY1およびPOLY2が各々、存在する場合、約15,000Da未満の数平均分子量を有する、請求項2に記載のポリマー。
- POLY1およびPOLY2が各々、存在する場合、約8,000Da未満の数平均分子量を有する、請求項3に記載のポリマー。
- Z1が各々、テトラサイクリン、カルセイン、ビスホスホネート、ポリアスパラギン酸、ポリグルタミン酸、およびアミノホスホ糖からなる群から独立して選択される、請求項1に記載のポリマー。
- L1、L2、L3のうちの少なくとも1つが、加水分解的に切断可能または酵素的に切断可能である、請求項1に記載のポリマー。
- POLY1とPOLY2のうちの一方または両方が、存在する場合、結合によって結合された2から約5個の水溶性の非ペプチドポリマーセグメントを含むセグメント化構造を有する、請求項1に記載のポリマー。
- POLY1とPOLY2のうちの一方または両方が、存在する場合、式−POLY−L−POLY−で表される構造を有し、式中、各POLYは水溶性の非ペプチドポリマーであり、Lは結合である、請求項7に記載のポリマー。
- POLY1およびPOLY2が各々、存在する場合、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レート)、ポリ(サッカライド)、ポリ(α−ヒドロキシ酸)、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)ならびに、これらのコポリマー、ターポリマーまたは混合物からなる群から独立して選択されるポリマーである、請求項1に記載のポリマー。
- POLY1およびPOLY2が各々、存在する場合、ポリ(エチレングリコール)である、請求項1に記載のポリマー。
- POLY1およびPOLY2が各々、存在する場合、構造−CH2CH2O(CH2CH2O)n−CH2CH2−を有し、nは1〜350である、請求項1に記載のポリマー。
- pが3から約10である、請求項1に記載のポリマー。
- Rが構造R1(OH)pのポリオールから誘導され、式中、Rは、任意に1つ以上のエーテル結合を含む分岐炭化水素であり、pは、少なくとも3である、請求項1に記載のポリマー。
- ポリオールが、グリセロール、ペンタエリスリトール、および糖から誘導されるアルコールならびに、これらの各々のオリゴマーまたはポリマーからなる群から選択される、請求項14に記載のポリマー。
- pが2から約10であり、Rが、ポリオール、ジスルフィド、ペプチドならびに、これらの各々のオリゴマーまたはポリマー、さらにはこれらの組み合わせからなる群から選択される分子から誘導される、請求項1に記載のポリマー。
- Rが、少なくとも1つのリシン残基を含むジペプチドまたはトリペプチドから誘導される、請求項1に記載のポリマー。
- 請求項1に記載のポリマーと生物学的活性剤との反応生成物を含み、以下の構造
式中、
Bは、−(X3)d−(L3)e−(X4)f−POLY2−L4−Drugまたは−(X3)d−(L3)e−(X4)f−L4−Drugであり、
Drugは、生物学的に活性な部分の残基であり、
L4は、Z2と生物学的に活性な部分の官能基との反応によって得られる結合であり、
Z3は、L5−Drugまたはヒドロキシアパタイト標的化部分であり、式中、L5は、官能基であるZ1と、生物学的に活性な部分の官能基との反応によって得られる結合であり、ただし、少なくとも1つのZ3がヒドロキシアパタイト標的化部分であり、
他の変数はいずれも請求項1に記載したように定義される、ポリマーコンジュゲート。 - Drugが、成長因子、抗生物質、化学療法剤、および鎮痛剤からなる群から選択される、請求項20に記載のポリマーコンジュゲート。
- Drugが、線維芽細胞成長因子、血小板由来成長因子、骨形態形成タンパク質、骨形成タンパク質、トランスフォーミング増殖因子、LIM無機化タンパク質、類骨誘導因子、アンジオゲニン、エンドセリン;増殖分化因子、ADMP−1、エンドセリン、肝細胞増殖因子およびケラチノサイト増殖因子、ヘパリン結合増殖因子、ヘッジホッグタンパク質、インターロイキン、コロニー刺激因子、上皮増殖因子、インスリン様増殖因子、サイトカイン、オステオポンチン、およびオステオネクチンからなる群から選択される成長因子である、請求項21に記載のポリマーコンジュゲート。
- 構造
Z−(X1)a−L1−(X2)b−[POLY1−(X3)c−L2−(X4)d]m−POLY2−(X5)e−Y
を有するヘテロ二官能性かつ実質的に線状のヒドロキシアパタイト標的化ポリマーであって、
式中、
POLY1およびPOLY2は各々、同一であっても異なっていてもよく、水溶性の非ペプチドポリマーであり、
X1、X2、X3、X4、X5は各々、同一であっても異なっていてもよく、スペーサ部分であり、
L1は、結合であり、
L2は各々、カルバメートおよびアミドからなる群から選択される加水分解的または酵素的に切断可能な結合であり、
Zは、ヒドロキシアパタイト標的化部分であり、
Yは官能基であり、
a、b、c、d、eは各々、同一であっても異なっていてもよく、0または1のいずれかであり、
mは、1〜10の範囲の整数である、ヒドロキシアパタイト標的化ポリマー。 - POLY1およびPOLY2が各々、存在する場合、約22,000Da未満の数平均分子量を有する、請求項23に記載のポリマー。
- POLY1およびPOLY2が各々、存在する場合、約15,000Da未満の数平均分子量を有する、請求項24に記載のポリマー。
- POLY1およびPOLY2が各々、存在する場合、約8,000Da未満の数平均分子量を有する、請求項25に記載のポリマー。
- Zが、テトラサイクリン、カルセイン、ビスホスホネート、ポリアスパラギン酸、ポリグルタミン酸、およびアミノホスホ糖からなる群から選択される、請求項23に記載のポリマー。
- X1、X2、X3、X4、X5が各々、存在する場合、−C(O)O−、−OC(O)−、−CH2−C(O)O−、−CH2−OC(O)−、−C(O)O−CH2−、−OC(O)−CH2−、−C(O)−、−C(O)−NH−、−NH−C(O)−NH−、−O−C(O)−NH−、−C(S)−、−CH2−、−CH2−CH2−、−CH2−CH2−CH2−、−CH2−CH2−CH2−CH2−、−O−CH2−、−CH2−O−、−O−CH2−CH2−、−CH2−O−CH2−、−CH2−CH2−O−、−O−CH2−CH2−CH2−、−CH2−O−CH2−CH2−、−CH2−CH2−O−CH2−、−CH2−CH2−CH2−O−、−O−CH2−CH2−CH2−CH2−、−CH2−O−CH2−CH2−CH2−、−CH2−CH2−O−CH2−CH2−、−CH2−CH2−CH2−O−CH2−、−CH2−CH2−CH2−CH2−O−、−C(O)−NH−CH2−、−C(O)−NH−CH2−CH2−、−CH2−C(O)−NH−CH2−、−CH2−CH2−C(O)−NH−、−C(O)−NH−CH2−CH2−CH2−、−CH2−C(O)−NH−CH2−CH2−、−CH2−CH2−C(O)−NH−CH2−、−CH2−CH2−CH2−C(O)−NH−、−C(O)−NH−CH2−CH2−CH2−CH2−、−CH2−C(O)−NH−CH2−CH2−CH2−、−CH2−CH2−C(O)−NH−CH2−CH2−、−CH2−CH2−CH2−C(O)−NH−CH2−、−CH2−CH2−CH2−C(O)−NH−CH2−CH2−、−CH2−CH2−CH2−CH2−C(O)−NH−、−C(O)−O−CH2−、−CH2−C(O)−O−CH2−、−CH2−CH2−C(O)−O−CH2−、−C(O)−O−CH2−CH2−、−NH−C(O)−CH2−、−CH2−NH−C(O)−CH2−、−CH2−CH2−NH−C(O)−CH2−、−NH−C(O)−CH2−CH2−、−CH2−NH−C(O)−CH2−CH2−、−CH2−CH2−NH−C(O)−CH2−CH2−、−C(O)−NH−CH2−、−C(O)−NH−CH2−CH2−、−O−C(O)−NH−CH2−、−O−C(O)−NH−CH2−CH2−、−NH−CH2−、−NH−CH2−CH2−、−CH2−NH−CH2−、−CH2−CH2−NH−CH2−、−C(O)−CH2−、−C(O)−CH2−CH2−、−CH2−C(O)−CH2−、−CH2−CH2−C(O)−CH2−、−CH2−CH2−C(O)−CH2−CH2−、−CH2−CH2−C(O)−、−CH2−CH2−CH2−C(O)−NH−CH2−CH2−NH−、−CH2−CH2−CH2−C(O)−NH−CH2−CH2−NH−C(O)−、−CH2−CH2−CH2−C(O)−NH−CH2−CH2−NH−C(O)−CH2−、−CH2−CH2−CH2−C(O)−NH−CH2−CH2−NH−C(O)−CH2−CH2−、−C(O)−NH−(CH2)1−6−NH−C(O)−、−NH−C(O)−NH−(CH2)1−6−NH−C(O)−、および−O−C(O)−NH−(CH2)1−6−NH−C(O)−、−O−C(O)−NH−[CH2]h−(OCH2CH2)j−、−NH−C(O)−O−[CH2]h−(OCH2CH2)j−、二価シクロアルキル基、−O−、−S−、−N(R6)−、これらの組み合わせからなる群から選択され、式中、R6は、Hであるか、またはアルキル、置換アルキル、アルケニル、置換アルケニル、アルキニル、置換アルキニル、アリール、および置換アリールからなる群から選択される有機ラジカルであり、(h)は0から6であり、(j)は0から20である、請求項1または23に記載のポリマー。
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