JP4398124B2 - Balloon catheter that can control the release of pharmacologically active substances by temperature - Google Patents
Balloon catheter that can control the release of pharmacologically active substances by temperature Download PDFInfo
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Description
【0001】
【発明の属する技術分野】
本発明は、血管、胆管や尿管などの管腔系器官の治療法に用いるバルーンカテーテルに関係する。さらに詳しくは、カテーテルの先端部位近くに位置するバルーンに薬理活性物質を担持させ、これを管腔系器官の疾患部位に誘導し、疾患部に特異的に薬理活性物質を投与することを可能にするバルーンカテーテルに関する。
【0002】
【従来の技術】
従来からバルーンカテーテルを用いて薬理活性物質を疾患部位に投与する種々の試みが行われてきた。例えば、バルーン上に形成されたハイドロゲル層に薬理活性物質を含浸させ、これを疾患部位に持って行き、疾患部位に薬理活性物質を特異的に投与する試みも行われた。しかし、通常疾患部位へバルーンを誘導するのに数分、場合によっては数十分も要することも多く、この時間の間にバルーン上の薬理活性物質は流れさってしまい、有効な局所投与が行えなかった。また、微細孔を有するバルーンを用いて、疾患部位で薬理活性物質溶液を噴射することが行われたが、用いた薬理活性物質で疾患部位に注入されるのは極めて僅かでであり、投与した薬理活性物質の大部分は例えば血流にのって全身に運ばれ、その副作用が問題になっていた。以上が、疾患部に効率的に薬理活性物質を投与できるバルーンカテーテルの開発が望まれるゆえんである。
【0003】
【発明が解決しようとする課題】
バルーンカテーテルのバルーン部位を疾患部位に誘導する数十分の間は、バルーンは薬理活性物質を保持し、疾患部位でバルーンを膨らませたときにバルーンは疾患部位に押しつけられるとともに、保持していた薬理活性物質を放出し、疾患部位に効率よく薬理活性物質が投与できるバルーンカテーテルを開発する。
【0004】
【課題を解決するための手段】
本発明者は、鋭意研究を重ねてきた結果、バルーンに、相転移して膨潤する相転移温度が人体の体温以下、例えば36℃以下で且つ薬理活性物質を含有しているハイドロゲル層を有するバルーンカテーテル、特にバルーンに薬理活性物質を含むイソプロピルアクリルアミドを主成分とする共重合体のハイドロゲル層を有するバルーンカテーテルを試作し、このカテーテルが上記の目的を達成し得ることを見いだし本発明に到達した。薬理活性物質は、化学合成された薬剤、動植物等から抽出された天然薬剤、タンパク及び遺伝子を含む。
【0005】
本発明のバルーンカテーテルの好適例は、温度の変化で物質透過性が劇的に変化するイソプロピルアクリルアミドを主成分とする共重合体のハイドロゲル層を表面に有するバルーン(A)と、カテーテルの手元から体温以下の造影剤又は冷水の如き液体を注入することでバルーンの温度を低下させることが可能な内腔を有するカテーテル(B)とからなる。
【0006】
【発明の実施の形態】
まず、(A)について説明する。本発明において、バルーン表面にハイドロゲル層を形成させるのに用いるイソプロピルアクリルアミドを主成分とする共重合体は、イソプロピルアクリルアミド、反応性の残基である2−メタクリロイルオキシエチルイソシアネートまたはそのイソシアネート基をメチルエチルケトオキシムでブロックした化合物を第2の成分として、物質透過性が劇的に変化する転移温度の設定を行うための第3の成分とをラジカル共重合することで合成される。
【0007】
該共重合体中には第2の反応性成分が少量でも含まれていることがバルーン上でハイドロゲル層の形成に必要である。含まれていないと、バルーンと共重合体との接着不良、また、ハイドロゲルが形成されない。
【0008】
該共重合体の分子量は5,000から1,000,000、共重合体中のイソプロピルアクリルアミド残基のモル分率は10%から99.999%であり、望ましくは90%から99.9%、第2の成分である反応性の残基のモル分率は0.001%から20%であり、望ましくは0.1%から10%、転移温度の調整に用いる第3の成分モル分率は1%から49.999%であり、望ましくは1%から20%である。
【0009】
該共重合体中には転移温度の調整に用いる第3の成分を組み込むが、転移温度を低く設定したい場合はメチルメタクリレート、ブチルメタクリレートやブチルアクリレート等の疎水性モノマーを用い、転移温度を高く設定したい場合はアクリルアミド等の親水性モノマーを用いる。
【0010】
該共重合体は、ラジカル重合によって容易に得られるが、2−メタクリロイルオキシエチルイソシアネートを第2の成分として用いる場合には、イソシアネートが容易に水や水蒸気により容易に加水分解されるため、用いる溶媒は十分に脱水しておく必要がある。
【0011】
次に、カテーテル(B)について説明する。各社から市販されているバルーンカテーテルはバルーンを広げるための内腔を有する。この内腔に液体を注入することでバルーン温度を低下させることも可能である。効率よくバルーン部の温度を低下させるには、温度の低い液体を持続的に注入・排出する必要がある。このため、バルーンに通じる2つの内腔を有するバルーンカテーテルが望ましい。カテーテルまたバルーンの素材としては、ポリウレタン、ナイロン、ポリエステル等現行のバルーンカテーテルの作製に用いられている素材は総て用いることが可能であり、特に限定しない。
【0012】
バルーン表面に形成させるイソプロピルアクリルアミドを主成分とする共重合体層の厚さは、乾燥状態で0.1μmから100μm、好ましくは1μmから50μmである。共重合体層の厚さがこの範囲であると、薬理活性物質を担持でき、また、温度を変えることでハイドゲルにすることができ薬理活性物質を素早く放出できる。また、この厚さであればバルーンの広げやすさ等の操作性に影響を与えることない。
【0013】
バルーン上へのイソプロピルアクリルアミドを主成分とする共重合体のコーティング方法には、特に制限はなく、例えば、(1)共重合体の溶液にバルーンを浸漬した後加熱乾燥する方法、(2)共重合体の溶液を刷毛でバルーンに塗った後加熱乾燥する方法、(3)共重合体の溶液をスプレーでバルーン上に噴霧した後加熱乾燥する方法、これらの方法で、共重合体層とバルーンとの強固な接着が得られない場合、バルーン表面の加水分解を行うことやシランカップリング剤処理することで、イソシアネートと反応する水酸基やアミノ基等の表面密度を高くするなどの処理を行う。更に、分子鎖中に光反応性基、エポキシ基、イソシアネート基及び酸無水物基の少なくとも1個を有し、イソプロピルアクリルアミド又はイソプロピルアクリルアミドを主成分とする共重合体との相溶性が良好な反応性高分子をハイドロゲル層に溶解させることもできる。
【0014】
バルーン上の共重合体層への薬理活性物質の担持方法は、(1)患者の治療に用いる直前に、バルーン部分を4℃の薬理活性物質溶液に30分程度漬けることで、共重合体層へ薬理活性物質を含浸させ、37℃あるいは60℃の温水に漬けて薬理活性物質を担持させる方法、(2)工場でバルーン部分を4℃の薬理活性物質溶液に30分程度漬けることで、共重合体層へ薬理活性物質を含浸させ、37℃あるいは60℃の温水に漬けて薬理活性物質を担持させて、さらに乾燥させた後出荷する方法、(3)薬理活性物質がイソシアネート基と反応しない場合は、共重合体の水溶液に薬理活性物質を混ぜ、バルーンに上記の方法でこの溶液をコーティングする。
【0015】
実施例1
イソプロピルアクリルアミド(NIPAM)とKarenzMOI−BM(登録商標)(昭和電工)(MOIBM)との98.4:1.6の共重合体ポリ(NIPAM−co−MOIBM)をラジカル重合にて作製した。2.5×2.5cmのガラス基板上の金薄膜上に11−メルカプト−1−ウンデカノールの自己組織化膜を形成させる。この表面に2.0w/v%のポリ(NIPAM−co−MOIBM)のアセトン溶液を300μl滴下し、さらに150℃で90分加熱することでポリNIPAMの架橋薄膜を形成させた。このポリNIPAMの架橋薄膜の乾燥状態での厚さは2μmであった。
【0016】
ポリNIPAMの架橋薄膜担持ガラスプレートを4℃の蛍光物質であるカルセインの180μg/ml水溶液に浸漬し、ポリNIPAMハイドロゲル層にカルセイン(分子量622.5)を含浸させた。その後この表面を60℃のイオン交換水で洗浄することで、表面に付着しているカルセインを取り除き、リリース実験に用いた。先ず、カルセイン担持ガラスプレートを37℃の100mlのイオン交換水に漬け、37℃の温水で温めた状態で、30分と60分後にイオン交換水中のカルセイン濃度を測定する。次ぎに、4℃の氷水で冷やした状態で、5分毎にイオン交換水中のカルセイン濃度を測定する。それぞれのカルセイン濃度からポリNIPAM層からのカルセインリリース速度を算出した。その結果を図1に示した。37℃の水中では7ng/cm2・minであったが、4℃の水中では160ng/cm2・minへと上昇した。すなわち、4℃の水中では37℃の水中の23倍もリリース速度が上昇した。
【0017】
実施例2
NIPAM と2−メタクリロイルエチルイソシアネート(KarenzMOI)(昭和電工)(MOIBM)との98.1:1.9の共重合体ポリ(NIPAM−co−MOI)をラジカル重合にて作製した。このときKarenzMOI中のイソシアネートの加水分解が起こらないように、重合時に用いる溶媒は十分脱水し、さらに加熱を必要としないレドックス系の開始剤(過酸化ベンゾイル−ジメチルアニリン)を用いた。
【0018】
2.5×2.5cmの厚さ200μmのナイロン膜を1規定の水酸化ナトリウム水溶液に室温で3時間浸漬して、膜表面の加水分解を行った。この表面に2.5w/v%のポリ(NIPAM−co−MOI)のアセトン溶液を300μl滴下し、風乾した。これを10回繰り返した後、50℃で5時間加熱することでポリNIPAMの架橋薄膜を形成させた。このポリNIPAMの架橋薄膜の乾燥状態での厚さは25μmであった。
【0019】
ポリNIPAMの架橋薄膜担持ナイロン膜を4℃の蛍光物質であるカルセインの180μg/ml水溶液に浸漬し、ポリNIPAMハイドロゲル層にカルセイン(分子量622.5)を含浸させた。その後この表面を60℃のイオン交換水で洗浄することで、表面に付着しているカルセインを取り除き、リリース実験に用いた。先ず、カルセイン担持ナイロン膜を37℃の100mlのイオン交換水に漬け、37℃の温水で温めた状態で、30分と60分後にイオン交換水中のカルセイン濃度を測定する。次ぎに、4℃の氷水で冷やした状態で、5分毎にイオン交換水中のカルセイン濃度を測定する。それぞれのカルセイン濃度よりポリNIPAM層からのカルセインリリース速度を算出した。37℃の水中では5ng/cm2・minであったが、4℃の水中では150ng/cm2・minへと上昇した。すなわち、4℃の水中では37℃の水中の30倍もリリース速度が上昇した。
【0020】
実施例3
実施例2で作製したポリ(NIPAM−co−MOI)を用いた。川澄化学工業株式会社から商品名「エンデバー」として販売されているバルーンカテーテルのバルーン部分に1%トリレンジイソシアネートのメチルエチルケトン溶液を刷毛塗りした後、室温で軽く乾燥させる。この表面に3.0w/v%のポリ(NIPAM−co−MOI)のジオキサン溶液を刷毛塗りした後、さらに50℃で5時間加熱することでバルーン上にポリNIPAMの架橋薄膜を形成させた。このポリNIPAMの架橋薄膜の乾燥状態での厚さは約30μmであった。
【0021】
ポリNIPAMの架橋薄膜担持バルーン部分を4℃の蛍光物質であるカルセインの180μg/ml水溶液に浸漬し、ポリNIPAMハイドロゲル層にカルセイン(分子量622.5)を含浸させた。その後この表面を60℃のイオン交換水で洗浄することで、表面に付着しているカルセインを取り除き、リリース実験に用いた。先ず、カルセイン担持バルーン部分を37℃の100mlのイオン交換水に漬け、37℃の温水で温めた状態で、30分と60分後にイオン交換水中のカルセイン濃度を測定する。次ぎ、4℃の氷水で冷やした状態で、5分毎にイオン交換水中のカルセイン濃度を測定する。それぞれのカルセイン濃度からポリNIPAM層からのカルセインリリース速度を算出した。37℃の水中では8ng/cm2・minであったが、4℃の水中では200ng/cm2・minへと上昇した。すなわち、4℃の水中では37℃の水中の約25倍もリリース速度が上昇した。
【0022】
実施例4
エタノール100ml及び水25mlにイソプロピルアクリルアミド7gと分子鎖中にベンゾフェノン基を有するポリビニルピロリドン共重合体0.6g及び光反応性スルフォン酸ナトリウム0.18gとを溶解してコーティング溶液を調整した。このコーティング溶液をPTCAバルーンカテーテルのバルーン部に塗布、一晩室温で乾燥した後、バルーン部260nmの紫外線を5mWa/cm2照射してコーティング層を固定化した。実施例3と同じ方法でカルセインリリース速度を測定したところ、4℃の水中では37℃の約16倍のリリース速度を示した。
【0023】
【発明の効果】
本発明のバルーンカテーテルによれば、バルーンカテーテルのバルーン部位を疾患部位に誘導する数十分の間は、バルーンは薬理活性物質を保持し、疾患部位でバルーンを膨らませたときにバルーンは疾患部位に押しつけられるとともに、保持していた薬理活性物質を放出し、疾患部位に効率よく薬理活性物質が投与できる。
【図面の簡単な説明】
【図1】実施例1におけるカルセインリリース速度を示す線図。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a balloon catheter used for the treatment of luminal organs such as blood vessels, bile ducts and ureters. More specifically, a pharmacologically active substance is supported on a balloon located near the distal end of the catheter, and this is guided to a diseased part of a luminal organ so that the pharmacologically active substance can be administered specifically to the diseased part. The present invention relates to a balloon catheter.
[0002]
[Prior art]
Conventionally, various attempts have been made to administer a pharmacologically active substance to a diseased site using a balloon catheter. For example, an attempt has been made to impregnate a hydrogel layer formed on a balloon with a pharmacologically active substance, take it to a diseased site, and specifically administer the pharmacologically active substance to the diseased site. However, it usually takes several minutes, sometimes tens of minutes, to guide the balloon to the diseased site, and the pharmacologically active substance on the balloon flows during this time, so that effective local administration is possible. There wasn't. In addition, a pharmacologically active substance solution was sprayed at the diseased site using a balloon having micropores, but very little was injected into the diseased site with the pharmacologically active substance used. Most of the pharmacologically active substances are transported to the whole body, for example, in the bloodstream, and their side effects have been a problem. The above is the reason why development of a balloon catheter that can efficiently administer a pharmacologically active substance to a diseased part is desired.
[0003]
[Problems to be solved by the invention]
The balloon retains the pharmacologically active substance for several tens of minutes when the balloon part of the balloon catheter is guided to the diseased part, and when the balloon is inflated at the diseased part, the balloon is pressed against the diseased part and the retained pharmacology. Develop balloon catheters that release active substances and can efficiently administer pharmacologically active substances to diseased sites.
[0004]
[Means for Solving the Problems]
As a result of intensive research, the present inventor has a hydrogel layer containing a pharmacologically active substance, which has a phase transition temperature that is swollen by phase transition and is below the body temperature of the human body, for example, 36 ° C. or less. A balloon catheter, in particular, a balloon catheter having a hydrogel layer of a copolymer mainly composed of isopropylacrylamide containing a pharmacologically active substance in the balloon was prototyped, and it was found that this catheter could achieve the above-mentioned purpose, and the present invention was achieved. did. Pharmacologically active substances include chemically synthesized drugs, natural drugs extracted from animals and plants, proteins and genes.
[0005]
A suitable example of the balloon catheter of the present invention includes a balloon (A) having a hydrogel layer of a copolymer based on isopropylacrylamide whose surface changes dramatically with changes in temperature, and a hand of the catheter. And a catheter (B) having a lumen capable of lowering the temperature of the balloon by injecting a liquid such as a contrast medium or cold water below body temperature.
[0006]
DETAILED DESCRIPTION OF THE INVENTION
First, (A) will be described. In the present invention, a copolymer mainly composed of isopropylacrylamide used for forming a hydrogel layer on the balloon surface is isopropylacrylamide, 2-methacryloyloxyethyl isocyanate which is a reactive residue, or its isocyanate group is methylethylketo. It is synthesized by radical copolymerizing a compound blocked with oxime as a second component and a third component for setting a transition temperature at which the substance permeability changes dramatically.
[0007]
It is necessary for formation of the hydrogel layer on the balloon that the copolymer contains the second reactive component even in a small amount. If it is not included, poor adhesion between the balloon and the copolymer, and no hydrogel is formed.
[0008]
The molecular weight of the copolymer is 5,000 to 1,000,000, and the molar fraction of isopropylacrylamide residues in the copolymer is 10% to 99.999%, preferably 90% to 99.9%. The molar fraction of the reactive residue as the second component is 0.001% to 20%, preferably 0.1% to 10%, the third component molar fraction used for adjusting the transition temperature. Is from 1% to 49.999%, preferably from 1% to 20%.
[0009]
A third component used for adjusting the transition temperature is incorporated into the copolymer, but when the transition temperature is to be set low, a hydrophobic monomer such as methyl methacrylate, butyl methacrylate or butyl acrylate is used, and the transition temperature is set high. If you want to do this, use a hydrophilic monomer such as acrylamide.
[0010]
The copolymer can be easily obtained by radical polymerization. However, when 2-methacryloyloxyethyl isocyanate is used as the second component, the isocyanate is easily hydrolyzed by water or water vapor, so that the solvent to be used is used. Need to be fully dehydrated.
[0011]
Next, the catheter (B) will be described. Commercially available balloon catheters have a lumen for expanding the balloon. It is also possible to lower the balloon temperature by injecting liquid into this lumen. In order to efficiently lower the temperature of the balloon part, it is necessary to continuously inject and discharge a liquid having a low temperature. For this reason, a balloon catheter having two lumens leading to the balloon is desirable. As materials for catheters and balloons, all materials currently used for producing balloon catheters such as polyurethane, nylon, and polyester can be used and are not particularly limited.
[0012]
The thickness of the copolymer layer mainly composed of isopropylacrylamide formed on the balloon surface is 0.1 μm to 100 μm, preferably 1 μm to 50 μm in a dry state. When the thickness of the copolymer layer is within this range, the pharmacologically active substance can be supported, and a hydride gel can be formed by changing the temperature, so that the pharmacologically active substance can be quickly released. In addition, this thickness does not affect operability such as ease of balloon expansion.
[0013]
There are no particular restrictions on the method of coating the copolymer containing isopropylacrylamide as a main component on the balloon. For example, (1) a method in which the balloon is immersed in a solution of the copolymer and then heated and dried; A method in which a polymer solution is applied to a balloon with a brush and then heat-dried. (3) A method in which a copolymer solution is sprayed on a balloon and then heat-dried. In the case where strong adhesion to the surface cannot be obtained, the balloon surface is hydrolyzed or treated with a silane coupling agent to increase the surface density of hydroxyl groups and amino groups that react with isocyanate. Furthermore, it has at least one photoreactive group, epoxy group, isocyanate group and acid anhydride group in the molecular chain, and has a good compatibility with isopropylacrylamide or a copolymer based on isopropylacrylamide. The functional polymer can be dissolved in the hydrogel layer.
[0014]
The method for supporting the pharmacologically active substance on the copolymer layer on the balloon is as follows: (1) Immediately before use for treatment of a patient, the balloon part is immersed in a pharmacologically active substance solution at 4 ° C. for about 30 minutes. A method of impregnating a pharmacologically active substance in water and immersing it in warm water at 37 ° C. or 60 ° C. to carry the pharmacologically active substance; (2) immersing the balloon part in a pharmacologically active substance solution at 4 ° C. for about 30 minutes at the factory; A method in which a pharmacologically active substance is impregnated into a polymer layer, immersed in warm water at 37 ° C. or 60 ° C. to carry the pharmacologically active substance, and dried before shipping; (3) the pharmacologically active substance does not react with an isocyanate group In this case, a pharmacologically active substance is mixed in an aqueous solution of the copolymer, and this solution is coated on a balloon by the above-described method.
[0015]
Example 1
A 98.4: 1.6 copolymer poly (NIPAM-co-MOIBM) of isopropylacrylamide (NIPAM) and KarenzMOI-BM (registered trademark) (Showa Denko) (MOIBM) was prepared by radical polymerization. A self-assembled film of 11-mercapto-1-undecanol is formed on a gold thin film on a 2.5 × 2.5 cm glass substrate. 300 μl of a 2.0 w / v% poly (NIPAM-co-MOIBM) acetone solution was dropped on this surface, and further heated at 150 ° C. for 90 minutes to form a crosslinked polyNIPAM thin film. The thickness of this crosslinked polyNIPAM thin film in a dry state was 2 μm.
[0016]
A polyNIPAM crosslinked thin film-supported glass plate was immersed in a 180 μg / ml aqueous solution of calcein, which is a fluorescent material at 4 ° C., and the polyNIPAM hydrogel layer was impregnated with calcein (molecular weight 622.5). Thereafter, this surface was washed with ion exchange water at 60 ° C. to remove calcein adhering to the surface, and used for a release experiment. First, a calcein-carrying glass plate is immersed in 100 ml of ion exchange water at 37 ° C., and the calcein concentration in the ion exchange water is measured after 30 minutes and 60 minutes in a state where the glass plate is warmed with warm water at 37 ° C. Next, the calcein concentration in ion-exchanged water is measured every 5 minutes in a state cooled with ice water at 4 ° C. The calcein release rate from the poly NIPAM layer was calculated from each calcein concentration. The results are shown in FIG. It was 7 ng / cm 2 · min in water at 37 ° C., but increased to 160 ng / cm 2 · min in water at 4 ° C. That is, in 4 ° C water, the release speed increased 23 times compared to 37 ° C water.
[0017]
Example 2
A 98.1: 1.9 copolymer poly (NIPAM-co-MOI) of NIPAM and 2-methacryloylethylisocyanate (KarenzMOI) (Showa Denko) (MOIBM) was prepared by radical polymerization. At this time, in order to prevent hydrolysis of isocyanate in KarenzMOI, the solvent used in the polymerization was sufficiently dehydrated, and a redox initiator (benzoyl peroxide-dimethylaniline) that does not require heating was used.
[0018]
A 2.5 × 2.5
[0019]
A nylon film carrying a crosslinked thin film of polyNIPAM was immersed in a 180 μg / ml aqueous solution of calcein, which is a fluorescent substance at 4 ° C., and the polyNIPAM hydrogel layer was impregnated with calcein (molecular weight 622.5). Thereafter, this surface was washed with ion exchange water at 60 ° C. to remove calcein adhering to the surface, and used for a release experiment. First, the calcein-carrying nylon membrane is immersed in 100 ml of ion exchange water at 37 ° C., and the calcein concentration in the ion exchange water is measured after 30 minutes and 60 minutes in a state heated with 37 ° C. warm water. Next, the calcein concentration in the ion-exchanged water is measured every 5 minutes while being cooled with ice water at 4 ° C. The calcein release rate from the polyNIPAM layer was calculated from each calcein concentration. Although it was 5 ng / cm 2 · min in water at 37 ° C., it increased to 150 ng / cm 2 · min in water at 4 ° C. That is, in 4 ° C water, the release speed increased 30 times as much as that in 37 ° C water.
[0020]
Example 3
The poly (NIPAM-co-MOI) produced in Example 2 was used. After applying a 1% tolylene diisocyanate methylethylketone solution to the balloon portion of a balloon catheter sold by Kawasumi Chemical Co., Ltd. under the trade name “Endeavor”, it is lightly dried at room temperature. A 3.0 w / v% poly (NIPAM-co-MOI) dioxane solution was brushed on the surface, and further heated at 50 ° C. for 5 hours to form a crosslinked polyNIPAM thin film on the balloon. The thickness of this crosslinked polyNIPAM thin film in a dry state was about 30 μm.
[0021]
The polyNIPAM crosslinked thin film-supported balloon portion was immersed in a 180 μg / ml aqueous solution of calcein, which is a fluorescent substance at 4 ° C., and the polyNIPAM hydrogel layer was impregnated with calcein (molecular weight 622.5). Thereafter, this surface was washed with ion exchange water at 60 ° C. to remove calcein adhering to the surface, and used for a release experiment. First, the calcein-carrying balloon portion is dipped in 100 ml of ion exchange water at 37 ° C., and the calcein concentration in the ion exchange water is measured after 30 minutes and 60 minutes in a state heated with 37 ° C. warm water. Next, the calcein concentration in the ion-exchanged water is measured every 5 minutes while being cooled with ice water at 4 ° C. The calcein release rate from the poly NIPAM layer was calculated from each calcein concentration. Although it was 8 ng / cm 2 · min in water at 37 ° C., it increased to 200 ng / cm 2 · min in water at 4 ° C. That is, the release speed increased by about 25 times in water at 4 ° C compared to water at 37 ° C.
[0022]
Example 4
A coating solution was prepared by dissolving 7 g of isopropylacrylamide, 0.6 g of polyvinylpyrrolidone copolymer having a benzophenone group in the molecular chain and 0.18 g of photoreactive sodium sulfonate in 100 ml of ethanol and 25 ml of water. This coating solution was applied to the balloon portion of a PTCA balloon catheter, dried overnight at room temperature, and then irradiated with 5 mWa / cm 2 of 260 nm ultraviolet rays to immobilize the coating layer. When calcein release rate was measured by the same method as in Example 3, the release rate was about 16 times that of 37 ° C. in 4 ° C. water.
[0023]
【The invention's effect】
According to the balloon catheter of the present invention, the balloon retains the pharmacologically active substance for several tens of minutes to guide the balloon site of the balloon catheter to the diseased site, and when the balloon is inflated at the diseased site, the balloon becomes the diseased site. While being pressed, the held pharmacologically active substance is released, and the pharmacologically active substance can be efficiently administered to the disease site.
[Brief description of the drawings]
1 is a diagram showing calcein release speed in Example 1. FIG.
Claims (10)
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US20070155907A1 (en) * | 2005-12-30 | 2007-07-05 | Zhao Jonathon Z | Biologically active block copolymers |
JP2007229249A (en) * | 2006-03-01 | 2007-09-13 | Olympus Corp | Method of supplying cell sheet |
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GB8519071D0 (en) * | 1984-12-18 | 1985-09-04 | Tahan M | Hydrogel-forming polymers |
JPH0274264A (en) * | 1988-09-12 | 1990-03-14 | Olympus Optical Co Ltd | Drug gradual release device |
JP3319004B2 (en) * | 1993-02-03 | 2002-08-26 | 東レ株式会社 | Method of forming positive polyimide pattern |
JPH06293632A (en) * | 1993-04-07 | 1994-10-21 | Nippon Kayaku Co Ltd | Temperature response type medicinal composition |
JPH0724056A (en) * | 1993-07-06 | 1995-01-27 | Olympus Optical Co Ltd | Device for halting equipment in organism |
JP3631777B2 (en) * | 1994-06-03 | 2005-03-23 | テルモ株式会社 | Drug administration catheter |
JP3599784B2 (en) * | 1994-07-18 | 2004-12-08 | テルモ株式会社 | Medical device with lubricious surface when wet |
JPH0898893A (en) * | 1994-09-29 | 1996-04-16 | Terumo Corp | Medicine dosing catheter |
JP3248425B2 (en) * | 1996-04-24 | 2002-01-21 | 凸版印刷株式会社 | Surface-reinforced decorative paper and its manufacturing method |
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