JP3598418B2 - Polymer gel having nucleobase introduced into side chain and method for producing the same - Google Patents

Description

【０００５】
しかし、この高分子構造体は水素結合性ドナ−とアクセプタ−のそれぞれの役割を有する２種類の高分子鎖間の交互作用を利用するもので、低温度では水素結合性高分子間コンプレックス形成による脱水和と、ある特定温度以上でのそのコンプレックス解離と共にみられるそれぞれの高分子鎖の水和という、高分子間コンプレックスの示す水和−脱水和挙動を利用したものである。
【０００６】
ところで、本発明者はこの２種類の高分子間のコンプレックスによる低温収縮、高温膨潤の挙動の代わるものとして、１種類の高分子鎖からなる高分子ゲルの収縮、膨潤の特性について種々検討した。しかして、従来より１種類の高分子鎖により水和−脱水和挙動にもとづく温度依存性を有する化合物としてポリ（Ｎ−イソプロピルアクリルアミド）が知られている。この化合物は低温で水和して膨潤性が大きくなり、約３２℃付近で急激に脱水和をして膨潤性が小さくなるのである。しかし、薬剤送達システムに利用できる化合物としては、むしろ高温度で水和して膨潤性が大きくなり、薬を放出を生じ、低温度では脱水和して膨潤性が小さく薬の放出を停止するものが好ましい。
【０００７】
【発明が解決しようとする課題】
そこで、本発明者は１種類の高分子鎖だけで低温側で脱水和、高温側で水和する特性を有する高分子について種々検討した結果、本発明を完成したもので本発明は１種類の高分子ゲルで収縮、膨潤の特性を示し、高温側で水和膨潤し、低温度側で脱水素を生する新規な高分子を提供することを目的とする。
【０００８】
【課題を解決するための手段】
本願発明の要旨は、一般式（１）で表わされる側鎖に核酸塩基を導入したポリマ−ゲルである。
【０００９】
【化４】

【００１０】
また、このポリマ−ゲルはアクリロオキシメチルウラシルとアクリル酸とを溶媒中で、ラジカル開始剤と架橋剤としてＮ，Ｎ−メチレンビスアクリルアミドとの存在下反応させることによって得られる。このポリマ−ゲルは水中もしくは生理条件に近い緩衝溶液中において低温で脱水和を行い、４０℃付近（緩衝溶液中で約５０℃）を境にして高温で水和する性質を有する。
【００１１】
このポリマ−ゲルの原料であるアクリロオキシメチルウラシルは公知の方法、例えばＢｒａｈｍｅ方法等によって得られる（Ｊ．Ｐｏｌｙｍｅｒ Ｓｃｉ．，Ｐｏｌｙｍ．Ｃｈｅｍ．Ｅｄ．２２巻８１３頁（１９８４）参照）。得られたアクリロオキシメチルウラシル（ＡＵモノマ−という）を、アクリル酸とを溶媒中で、ラジカル開始剤と架橋剤との存在下反応させるが、この際使用しうる溶媒としてはジメチルスルホキシド（ＤＭＳＯ）、ジメチルホルムアミド（ＤＭＦ）等であり、またラジカル開始剤としては、アゾビスイソブチロニトリル（ＡＩＢＮ）、架橋剤としてはＮ，Ｎ−メチレンビスアクリルアミド等を挙げることができる。
【００１２】
【実施例】
次に実施例として具体的に本発明の高分子ゲルの製造方法を示すが、本発明はこの実施例に限定されるものではない。
実施例１
（ｉ）アクリルウラシル（ＡＵ）モノマ−の合成
アクリル酸（６．１ｍｌ，０．０９ｍｏｌ）の１０ｍｌ水溶液をＫＯＨ（５ｇ０．０９ｍｏｌ）の２０ｍｌ水溶液により中和した。ｐＨ試験紙により中和を確認した溶液に１００ｍｌのベンゼンを加え、この混合液をＤｅａｎ−Ｓｔａｒｋａｐｐａｒａｔｕｓを使用し、一晩還流させて出てきた３１ｍｌの水を除去した。ろ過によりフラスコ中のアクリル酸カリウムを分離し、始めに１００ｍｌのアセトン、次いで５０ｍｌのエ−テルで洗い乾燥した。
得られたアクリル酸カリウム（１．１ｇ、０．０１ｍｏｌ）を１８−クラウン−６−エ−テル（２．６４ｍｏｌ，０．０１ｍｏｌ）と６−クロロメチルウラシル（１．１ｇ，０．０１ｍｏｌ）のＤＭＦ溶液３０ｍｌに加えた。反応混合物を１００℃、１８時間還流し、溶媒のＤＭＦを減圧留去し油状物質を得た。これに２５ｍｌの水を加え２時間放置し、分離した固体を濾過したのち、エタノ−ルで洗浄し乾燥した。この反応式を次に示す。
【００１３】
【化５】

【００１４】
（ｉｉ）ポリアクリルウラシル（ＰＡＵ）の合成
上記の方法によって得られたＡＵモノマ−（１．３４ｇ、０．００６８ｍｏｌ）のＤＭＦ溶液を窒素置換し、開始剤としてα，α’−アゾビスイソブチロニトリル（ＡＩＢＮ）を用いて６０℃、４８時間重合させた。溶媒のＤＭＦを減圧留去し、得られた油分を最小量のＤＭＳＯ（５ｍｌ）で溶解し、アセトンに流し込んで再沈を行った。沈澱した固体をろ過により集め、アセトンから同じように２回再沈させ、最後に９５％エタノ−ルで再沈させ乾燥した。この反応式を次に示す。
【００１５】
【化６】

【００１６】
得られたＰＡＵポリマ−水溶液溶液を作成し、その透過率（Ｔｒａｎｓｍｉｔｔａｎｃｅ％）の測定した。即ち、得られたＰＡＵを超純水とリン酸緩衝水溶液（Ｐｈｏｓｐｈａｔｅ Ｂｕｆｆｅｒ Ｓａｌｉｎｅ，ＰＢＳ（ｐＨ７．４））にそれぞれ溶解させ、１．０ｗｔ％のポリマ−水溶液を調整した。紫外−可視分光光度計に恒温セルを取付け、所定温度でのそれぞれの水溶液の５００ｎｍにおける透過率（Ｔ％）を測定し、この透過率の温度依存性について調べた。その結果を図１に示した。
ＰＡＵポリマ−水溶液は精製水中では４５℃を境にして低温白濁／高温溶解を示した。また、リン酸緩衝溶液では５０℃を境にして低温白濁／高温溶解を示した。これは低温においてはＰＡＵが高分子コンプレックスを形成して不溶化して白濁し、透過率が０％を示したのに対し、高温ではこの高分子コンプレックスが解離して溶解するため透過率が高い値を示すものと考えられる。
温度変化にともない、高分子水溶液の透過率がある温度を境にして急激に変化したことはＰＡＵの分子内における高分子効果による高分子コンプレックスの形成／解離に基づくものと考えられる。この際の分子内相互作用として水素結合、疎水性相互作用、ファンデルワ−ルス力などが考えられる。
【００１７】
（ｉｉｉ）共重合体ポリマ−ゲルの生成
サンプル瓶にアクリルアミド（ＡＡｍ）、アクリル酸（ＡＡｃ）、ジメチルアクリルアミド（ＤＭＡＡｍ）、２，２−アゾビス（２−アミノジプロパン）二塩酸塩（Ｖ−５０）、及びＮ，Ｎ−メチレンビスアクリルアミド（ＭＢＡＡｍ）を表１に示した割合で各試薬を仕込んでＰＵＡｃ，ＰＵＡｃ−１０，ＰＵＡｍを得た。
【００１８】
【表１】

【００１９】
これらの各試薬を脱気した５ｍｌのＤＭＳＯに溶解して共重合体ポリマ−ゲルを調製した。このモノマ−溶液を、厚さ０．５ｍｍのテフロンスペ−サ−を挟みマイラ−シ−トを添付した２枚のガラス板の間に流し込み、６０℃で２４時間反応させた。ポリ（アクリロイルオキシメシルウラシル・アクリル酸）共重合体（ＰＵＡｃ）の場合の反応式を次に示す。
【００２０】
【化７】

ｌは１０〜５０、ｍは９０〜５０、ｎは１〜１０を表わす。
【００２１】
反応終了後、ＤＭＳＯおよび未反応物を取り除くため、精製水に浸した。その後含水状態のゲルを直径１．３ｍｍディスク状に打ち抜いて、５０℃で２４時間、減圧下５０℃で２４時間乾燥した。
得られたポリ（アクリロイルオキシメシルウラシル・アクリル酸）共重合体（ＰＵＡｃ）のゲルについて膨潤度及び外部変化に伴う膨潤度変化を測定した。このＰＵＡｃのｌは２４．８、ｍは７４．１、ｎは１．１であった。
なお、他の場合、即ちＰＵＡｃ−１０，ＰＵＡｍの場合についても同様にして得られる。
ａ．膨潤度測定
このゲルの乾燥重量（Ｗｐ）を測定し、これを精製水およびリン酸緩衝溶液（ｐＨ７．４）で満たしたサンプル瓶にいれ、１０℃から６０℃における平衡状態の含水量（Ｗｓ）を測定した。このＷｓはゲルを水中から取り出し、余分な水分を薬包紙で取り除いてから測定した。
ｂ．外部変化に伴う膨潤度変化測定
ゲルを精製水の入ったサンプル瓶にいれ低温で１時間３０分、高温で３０分で昇温降温を繰り返し所定の時間でサンプリングした。ゲルの膨潤度の温度変化に対するゲルの質量を測定することにより求めた。水溶液でのＰＵＡｃの平衡膨潤度の温度依存性を図２に、またリン酸緩衝溶液中での平衡膨潤度の温度依存性を図３に示した。
【００２２】
これらの結果よりＰＵＡｃのゲルについて精製水中及びリン酸緩衝溶液中において低温収縮／高温膨潤挙動の温度依存性が見られた。これは低温においてはウラシル−ウラシル間コンプレックスが形成して脱水和することで収縮し、高温ではこのコンプレックスが解離して水和することで膨潤するものと考えられる。また、リン酸緩衝溶液中の膨潤度が精製水中の膨潤度よりもかなり高い値を示したが、リン酸緩衝溶液中においてアクリル酸のＣＯＯＨがプロトン解離し、そのイオン反発のため高膨潤度を示したと考えられる。
【００２３】
次にポリ（アクリロイルオキシメシルウラシル・アクリルアミド）共重合体（ＰＵＡｍ）のゲルについて膨潤度及び外部変化に伴う膨潤度変化を測定した。この結果を図４に示した。この場合も精製水中及びリン酸緩衝溶液中において低温収縮／高温膨潤挙動の温度依存性が見られたが、ＰＵＡｍの場合に比してＰＵＡｍは低い膨潤度を示した。これはＰＵＡｃがアクリル酸のプロトン解離によるイオン反抜のため膨潤してしまうのに対しアクリルアミドはリン酸緩衝溶液（ｐＨ７．４）中に於いてもプロトン解離をしないため膨潤度が抑えられたものと考える。
【００２４】
次にこれら共重合体ポリマ−ゲルの３５℃と４０℃との範囲で外部温度を変化させた場合のＰＵＡｃとＰＵＡｃ−１０のゲルにおける精製水中での膨潤度変化を測定した。その結果を図５及び図６に示した。低温及び高温の繰り返しを３回及び４回行っても一定範囲内で可逆的な膨潤度変化を示した。この膨潤度変化は平衡膨潤度同様、低温においてはウラシル間コンプレックスが形成し、脱水和することで収縮し、高温ではこのコンプレックスが解離して水和することによって膨潤し畳めと考えられる。また、架橋濃度が１ｍｏｌ％の時（ＰＵＡｃ）に比べ１０ｍｏｌ％（ＰＵＡｃ−１０）の膨潤度はかなり低い値を示し、架橋濃度を挙げても可逆性の良い膨潤度を得ることが出来た。
【００２５】
【発明の効果】
以上述べたように、ウラシル基を導入した高分子ゲルは、１種類の高分子鎖で低温収縮・高温膨潤の挙動を示し、更に、ＡＡｍとの共重合で得られたＰＵＡｍゲルはリン酸緩衝溶液中においても同様な挙動を示した。また、温度変化に伴うゲルの膨潤度変化の可逆性が認められ、温度応答性の高分子ゲルとしての可能性が期待された。
【図面の簡単な説明】
【図１】ＰＡＵを溶解した水及びリン酸緩衝溶液の透過率の温度依存性
【図２】水溶液中でのＰＵＡｃゲルの平衡膨潤度の温度依存性
【図３】リン酸緩衝溶液中でのＰＵＡｃゲルの平衡膨潤度の温度依存性
【図４】水及びリン酸緩衝溶液中でのＰＵＡｍゲルの平衡膨潤度の温度依存性
【図５】３５〜４０℃間の温度変化にともなうＰＵＡｃゲルの生成水中での膨潤度変化
【図６】３５〜４０℃間の温度変化にともなうＰＵＡｃ−１０ゲルの生成水中での膨潤度変化[0001]
[Industrial applications]
The present invention relates to a novel polymer gel exhibiting a low-temperature shrinkage / high-temperature swelling behavior in response to temperature and a method for producing the same, and more particularly, to a drug delivery system that delivers a drug by a change in temperature. New polymer gels that can be made.
[0002]
[Prior art]
Pharmaceuticals capable of retaining an effective concentration of the drug in the blood for a long period of time, or pharmaceuticals capable of allowing the drug to act where needed, are new drug delivery systems. Attention and research has been done. The use of an alkyl-substituted amide gel was considered as a drug used in a system that releases a drug in response to temperature in this drug delivery system. It has been reported that polyacrylamide gels partially hydrolyze with alkali, which shows a gel phase inversion phenomenon in water-acetone system, and that alkyl-substituted amides show extremely large swelling changes in water with changes in temperature. It was considered to adapt to use. However, the alkyl-substituted amide gel has a disadvantage of low mechanical strength.
[0003]
Therefore, the present inventors have proposed a polymer having an inter-venate network structure (IPN) in order to improve the above-mentioned drawbacks. The IPN refers to a polymer composed of two polymers in which a crosslinked polymer is physically entangled with an alternating wet network structure, not by a covalent bond, but is a tertiary compound of the following general formula A as the two polymer compounds. We have proposed an alternating wet network polymer structure of a base copolymer and a three-dimensional copolymer of the general formula B (see, for example, JP-A-3-79608).
[0004]
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[0005]
However, this polymer structure utilizes the interaction between two types of polymer chains having respective roles of a hydrogen-bonding donor and an acceptor. It utilizes the hydration-dehydration behavior of an interpolymer complex, namely, dehydration and hydration of each polymer chain observed along with its complex dissociation at a certain temperature or higher.
[0006]
By the way, the present inventor has studied various shrinkage and swelling characteristics of a polymer gel composed of one kind of polymer chain as an alternative to the behavior of low-temperature shrinkage and high-temperature swelling due to a complex between these two kinds of polymers. Thus, poly (N-isopropylacrylamide) has been conventionally known as a compound having a temperature dependency based on hydration-dehydration behavior by one kind of polymer chain. This compound hydrates at low temperature to increase its swelling property, and rapidly dehydrates at about 32 ° C. to decrease its swelling property. However, compounds that can be used in drug delivery systems, rather, hydrate at high temperatures to increase swelling and release the drug, and at low temperatures to dehydrate and reduce swelling to stop drug release. Is preferred.
[0007]
[Problems to be solved by the invention]
Thus, the present inventor has conducted various studies on polymers having the property of dehydration at a low temperature side and hydration at a high temperature side using only one type of polymer chain, and as a result, the present invention has been completed. It is an object of the present invention to provide a novel polymer which exhibits properties of contraction and swelling in a polymer gel, hydrates and swells at a high temperature side, and generates dehydrogenation at a low temperature side.
[0008]
[Means for Solving the Problems]
The gist of the present invention is a polymer gel having a nucleobase introduced into a side chain represented by the general formula (1).
[0009]
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[0010]
This polymer gel can be obtained by reacting acryloxymethyluracil and acrylic acid in a solvent in the presence of a radical initiator and N, N-methylenebisacrylamide as a crosslinking agent. This polymer gel has the property of dehydrating at low temperature in water or a buffer solution close to physiological conditions, and hydrating at a high temperature around 40 ° C. (about 50 ° C. in a buffer solution).
[0011]
The polymer - raw der Luer methacrylonitrile oxymethyl uracil gel is obtained by known methods, for example Brahme methods such as (. J.Polymer Sci, Polym.Chem.Ed.22 Vol 813 pp (1984)). The obtained acryloxymethyluracil (referred to as AU monomer) is reacted with acrylic acid in a solvent in the presence of a radical initiator and a crosslinking agent. In this case, dimethyl sulfoxide (DMSO ), Dimethylformamide (DMF) and the like, and azobisisobutyronitrile (AIBN) as a radical initiator and N, N-methylenebisacrylamide as a crosslinking agent.
[0012]
【Example】
Next, a method for producing the polymer gel of the present invention is specifically described as an example, but the present invention is not limited to this example.
Example 1
(I) Synthesis of acrylic uracil (AU) monomer A 10 ml aqueous solution of acrylic acid (6.1 ml, 0.09 mol) was neutralized with a 20 ml aqueous solution of KOH (5 g 0.09 mol). 100 ml of benzene was added to the solution whose neutralization was confirmed by pH test paper, and this mixture was refluxed overnight using Dean-Starkapparatus to remove 31 ml of water that came out. The potassium acrylate in the flask was separated by filtration, washed first with 100 ml of acetone and then with 50 ml of ether and dried.
The obtained potassium acrylate (1.1 g, 0.01 mol) was mixed with 18-crown-6-ether (2.64 mol, 0.01 mol) and 6-chloromethyluracil (1.1 g, 0.01 mol). Added to 30 ml of DMF solution. The reaction mixture was refluxed at 100 ° C. for 18 hours, and the solvent DMF was distilled off under reduced pressure to obtain an oily substance. 25 ml of water was added thereto, and the mixture was allowed to stand for 2 hours. The separated solid was filtered, washed with ethanol and dried. The reaction formula is shown below.
[0013]
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[0014]
(Ii) Synthesis of polyacryluracil (PAU) The DMF solution of AU monomer (1.34 g, 0.0068 mol) obtained by the above method was replaced with nitrogen, and α, α′-azobisisobuty was used as an initiator. Polymerization was performed at 60 ° C. for 48 hours using lonitrile (AIBN). The solvent DMF was distilled off under reduced pressure, and the obtained oil was dissolved in a minimum amount of DMSO (5 ml) and poured into acetone for reprecipitation. The precipitated solid was collected by filtration, reprecipitated twice from acetone and finally reprecipitated with 95% ethanol and dried. The reaction formula is shown below.
[0015]
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[0016]
The resulting aqueous solution of the PAU polymer was prepared, and its transmittance (Transmittance%) was measured. That is, the obtained PAU was dissolved in ultrapure water and a phosphate buffer aqueous solution (Phosphate Buffer Saline, PBS (pH 7.4)) to prepare a 1.0 wt% aqueous polymer solution. A constant temperature cell was attached to the ultraviolet-visible spectrophotometer, and the transmittance (T%) at 500 nm of each aqueous solution at a predetermined temperature was measured, and the temperature dependence of the transmittance was examined. The result is shown in FIG.
The PAU polymer aqueous solution showed low-temperature opacity / high-temperature dissolution in purified water at around 45 ° C. Further, the phosphate buffer solution showed low-temperature opacity / high-temperature dissolution at 50 ° C. as a boundary. This is because, at low temperatures, PAU forms a polymer complex, insolubilizes it and becomes cloudy, and has a transmittance of 0%, whereas at high temperatures this polymer complex dissociates and dissolves, resulting in a high transmittance. It is considered to indicate.
It is considered that the rapid change of the transmittance of the aqueous polymer solution at a certain temperature with the temperature change is based on the formation / dissociation of the polymer complex due to the polymer effect in the PAU molecule. Hydrogen bonding, hydrophobic interaction, van der Waals force, etc. can be considered as the intramolecular interaction at this time.
[0017]
(Iii) Formation of copolymer polymer gel In a sample bottle, acrylamide (AAm), acrylic acid (AAc), dimethylacrylamide (DMAAm), 2,2-azobis (2-aminodipropane) dihydrochloride (V-50) ) And N, N-methylenebisacrylamide (MBAAm) at the ratios shown in Table 1 to prepare PUAc, PUAc-10, and PUAm.
[0018]
[Table 1]

[0019]
Each of these reagents was dissolved in 5 ml of degassed DMSO to prepare a copolymer polymer gel. This monomer solution was poured between two glass plates with a Mylar sheet sandwiched between 0.5 mm thick Teflon spacers, and reacted at 60 ° C. for 24 hours. The reaction formula for a poly (acryloyloxymesyluracil-acrylic acid) copolymer (PUAc) is shown below.
[0020]
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1 represents 10 to 50, m represents 90 to 50, and n represents 1 to 10.
[0021]
After the completion of the reaction, the product was immersed in purified water to remove DMSO and unreacted substances. Thereafter, the hydrous gel was punched out into a disk having a diameter of 1.3 mm and dried at 50 ° C. for 24 hours and at 50 ° C. under reduced pressure for 24 hours.
The gel of the obtained poly (acryloyloxymesyluracil / acrylic acid) copolymer (PUAc) was measured for the degree of swelling and the change in degree of swelling due to external change. 1 of this PUAc was 24.8, m was 74.1, and n was 1.1.
In the other cases, that is, in the case of PUAc-10 and PUAm, the same can be obtained.
a. Swelling degree measurement The dry weight (Wp) of this gel was measured, and this was placed in a sample bottle filled with purified water and a phosphate buffer solution (pH 7.4), and the equilibrium water content (Ws) at 10 ° C. to 60 ° C. ) Was measured. This Ws was measured after removing the gel from the water and removing excess water with a medicine wrapper.
b. The swelling degree change measurement gel accompanying the external change was put into a sample bottle containing purified water, and the temperature was repeatedly raised and lowered at a low temperature for 1 hour and 30 minutes and at a high temperature for 30 minutes, and sampled at a predetermined time. The degree of swelling of the gel was determined by measuring the mass of the gel with respect to the temperature change. FIG. 2 shows the temperature dependence of the degree of equilibrium swelling of PUAc in an aqueous solution, and FIG. 3 shows the temperature dependence of the degree of equilibrium swelling in a phosphate buffer solution.
[0022]
From these results, the temperature dependence of the low-temperature shrinkage / high-temperature swelling behavior of the PUAc gel in purified water and phosphate buffer solution was observed. It is considered that this complex shrinks due to the formation and dehydration of the uracil-uracil complex at low temperatures, and swells due to dissociation and hydration of this complex at high temperatures. In addition, the degree of swelling in the phosphate buffer solution was significantly higher than the degree of swelling in purified water.However, in the phosphate buffer solution, COOH of acrylic acid was dissociated by protons, resulting in a high degree of swelling due to ion repulsion. It is considered to have shown.
[0023]
Next, the degree of swelling of the gel of the poly (acryloyloxymesyluracil / acrylamide) copolymer (PUAm) and the change in the degree of swelling due to external changes were measured. The result is shown in FIG. In this case as well, the temperature dependence of the low-temperature shrinkage / high-temperature swelling behavior was observed in purified water and in a phosphate buffer solution, but PUAm exhibited a lower degree of swelling than PUAm. This is because PUAc swells due to ion repulsion due to the proton dissociation of acrylic acid, whereas acrylamide does not dissociate protons even in a phosphate buffer solution (pH 7.4), so the degree of swelling is suppressed. Think.
[0024]
Next, the change in the degree of swelling of the PUAc and PUAc-10 gels in purified water when the external temperature was changed in the range of 35 ° C. and 40 ° C. was measured for these copolymer gels. The results are shown in FIGS. Even when the low temperature and the high temperature were repeated 3 times and 4 times, reversible swelling degree change was observed within a certain range. Similar to the equilibrium swelling degree, this change in swelling degree is considered to be due to the formation of the complex between uracils at a low temperature, contraction by dehydration, and swelling and folding by dissociation and hydration of the complex at a high temperature. In addition, the swelling degree of 10 mol% (PUAc-10) was much lower than that when the cross-linking concentration was 1 mol% (PUAc), and even if the cross-linking concentration was increased, a good reversible swelling degree could be obtained.
[0025]
【The invention's effect】
As described above, a polymer gel into which a uracil group has been introduced exhibits low-temperature shrinkage and high-temperature swelling behavior with one type of polymer chain, and further, a PUAm gel obtained by copolymerization with AAm has a phosphate buffer. Similar behavior was exhibited in the solution. In addition, the reversibility of the change in the degree of swelling of the gel with the change in temperature was observed, and the possibility of the gel as a temperature-responsive polymer was expected.
[Brief description of the drawings]
FIG. 1: Temperature dependence of the transmittance of water and phosphate buffer solutions in which PAU is dissolved. FIG. 2: Temperature dependence of the equilibrium swelling of PUAc gel in aqueous solution. FIG. Temperature dependence of equilibrium swelling degree of PUAc gel [FIG. 4] Temperature dependence of equilibrium swelling degree of PUAm gel in water and phosphate buffer solution [FIG. 5] PUAc gel with temperature change between 35 and 40 ° C. Swelling degree change in formed water [Fig. 6] Swelling degree change of PUAc-10 gel in formed water with temperature change between 35 and 40 ° C

Claims (2)

A polymer gel having a nucleobase introduced into a side chain represented by the general formula (1) .

1 represents 10 to 50, m represents 90 to 50, and n represents 1 to 10. Acrylooxymethyluracil , acrylic acid and N, N-methylenebisacrylamide as a crosslinking agent are reacted in a solvent in the presence of a radical initiator to form a nucleic acid on the side chain represented by the general formula (1). A method for producing a polymer gel into which a base has been introduced.

1 represents 10 to 50, m represents 90 to 50, and n represents 1 to 10.

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