JP6844017B2 - Antithrombotic or antibacterial polymer compounds, methods of producing them, and medical substances containing them - Google Patents
Antithrombotic or antibacterial polymer compounds, methods of producing them, and medical substances containing them Download PDFInfo
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- JP6844017B2 JP6844017B2 JP2019545265A JP2019545265A JP6844017B2 JP 6844017 B2 JP6844017 B2 JP 6844017B2 JP 2019545265 A JP2019545265 A JP 2019545265A JP 2019545265 A JP2019545265 A JP 2019545265A JP 6844017 B2 JP6844017 B2 JP 6844017B2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
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- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
- A61L29/085—Macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G75/00—Macromolecular compounds obtained by reactions forming a linkage containing sulfur with or without nitrogen, oxygen, or carbon in the main chain of the macromolecule
- C08G75/02—Polythioethers
- C08G75/06—Polythioethers from cyclic thioethers
- C08G75/08—Polythioethers from cyclic thioethers from thiiranes
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L2203/00—Applications
- C08L2203/02—Applications for biomedical use
Description
本発明は、抗血栓性または抗菌性の高分子化合物、それを製造する方法、及びそれを含む医療用物質に関するのである。 The present invention relates to an antithrombotic or antibacterial polymer compound, a method for producing the same, and a medical substance containing the same.
既存の血液と接触する心血関係を含んだ多様な分野の医療機器の場合、感染と血栓形成を抑制するために、抗菌性と抗血栓性とを有する物質をコーティングする技術が開発されてきたが、表面コーティングの安全性低下、コーティング工程の難しさ、体内毒性などの問題点が提起され、依然として解決できていない状況である。従って、抗血栓性と共に抗菌性を有し、汎用性が高い高分子化合物、及びそれを利用した化学添加用組成物の開発必要性が非常に高い状況である。 In the case of medical devices in various fields including cardiovascular relationships that come into contact with existing blood, techniques for coating substances with antibacterial and antithrombotic properties have been developed in order to suppress infection and thrombus formation. , The safety of the surface coating is lowered, the difficulty of the coating process, and the toxicity of the body have been raised, and the situation has not been solved yet. Therefore, there is a great need to develop a highly versatile polymer compound having antithrombotic and antibacterial properties, and a composition for chemical addition using the polymer compound.
一般的に、タンパク質吸着現象は、血液と接触する医療用素材の表面で自発的に発生する。その結果として、血液内細胞、及びさまざまな多様な成分は、すでにタンパク質に吸着された医療用素材表面に遅く分散されて付着する。タンパク質吸着は、医療用素材の機能を落とすだけではなく、血栓形成や炎症のような副作用を起こす。また、タンパク質吸着は、患者の健康状態を確認するために挿入された医療器具センサの敏感度を落とし、診断効率を落としたりする。従って、研究開発の観点において、体内に挿入される血液接触型医療機器の場合、一次的な現象であるタンパク質吸着を抑制する戦略が非常に効果的であると言える。 In general, the protein adsorption phenomenon occurs spontaneously on the surface of medical materials that come into contact with blood. As a result, cells in the blood and various diverse components are slowly dispersed and attached to the surface of the medical material already adsorbed on the protein. Protein adsorption not only impairs the function of medical materials, but also causes side effects such as thrombus formation and inflammation. In addition, protein adsorption reduces the sensitivity of the medical device sensor inserted to confirm the patient's health condition, and reduces the diagnostic efficiency. Therefore, from the viewpoint of research and development, in the case of a blood contact type medical device inserted into the body, it can be said that a strategy of suppressing protein adsorption, which is a primary phenomenon, is very effective.
両性イオン性高分子（zwitterionic polymers）は、高分子鎖に沿って均一に分布された陰イオン基と陽イオン基の同等数を有する高分子と定義することができる。そのような相反する電荷を帯びる作用基（zwitter（独語））の組み合わせは、高分子を超親水性でしたりする反面、同時に全体的に、中性電荷を維持するようにする。イオン基を含む高分子は、高分子の最も重要な種類のうち一つである。そのような高分子は、タンパク質や核酸のような自然に発生する生体高分子から、合成増粘剤やせっけんに至るまで多様である。イオン性高分子（ionic polymers）は、高分子電解質（polyelectrolytes）と両性イオン性高分子とに分類される。該イオン性高分子は、陰イオン性または陽イオン性の作用基を含む高分子である一方、該両性イオン性高分子は、陽イオン性と陰イオン性との作用基をいずれも含む高分子である。該両性イオン性高分子は、イオン交換、植樹の微量金属キレート化（chelation）、下水処理、土壌管理、製紙強化、色素残留、シャンプー及びヘアコンディショナーのフォーミュレーションのような広範囲な応用分野を有する。該両性イオン性高分子は、単量体のペンダント側鎖（pendant side chain）に電荷が位置したり、ポリエステル（polyesters）、ポリホスファゼン（polyphosphazenes）及びポリホスホベタイン（polyphosphobetaine）のような場合は、電荷が高分子主鎖に位置したりもする。工学的側面において、該両性イオン性高分子は、非特異的タンパク質吸着を防止し、細菌や、動物・ヒトの細胞付着を最小化させるために広く利用されているポリエチレングリコール（ＰＥＧ）の代替材として考慮されている。しかし、ＰＥＧ高分子の場合は、本質的に、同じ反復単位を有している一方、該両性イオン性高分子は、特定単量体化学構造により、高分子の広範囲な構造変化が可能である。
金属の抗菌活性と係わり、かなり前から多様であって幅広い研究が行われてきた。銀（Ａｇ）、水銀（Ｈｇ）及びテルル（Ｔｅ）のような特定金属は、ほとんどの細菌に極端な毒性を有し、極めて低い濃度でも抗菌効果を有すると知られている。そのような金属の細菌及び酵母に対する内在的毒性のために、特定金属は、古代時代から、抗菌剤として活用されてきた。今日、金属表面、コーティング、キレート化合物及びナノ材料のような抗菌性金属化合物が、産業、農業及びヘルスケアのような広範囲な分野で活用されている。そのような発展は、特定金属が、抗菌剤耐性バイオフィルム（biofilm）の破壊や、他の抗菌剤との抗菌活性シナジー効果、選択的代謝作用の抑制、及び多薬物耐性バクテリア死滅のような革新的な発見を介して行われた。しかし、該特定金属は、体内に挿入または移植される医療機器に適用する場合、細胞及び組織への毒性を、ナノ物質の場合は、全身毒性という問題を引き起こしてしまうことも事実である。また、素材に含有された金属の場合、迅速に流出されたり消耗されたりし、その効果が満足すべきものではない場合が多い。従って、金属の体内挿入医療用素材への適用のためには、長期間維持されながら、体内安全性を有することができる技術と素材との開発が切実に要求されている。
Zwitterionic polymers can be defined as polymers having the same number of anionic and cationic groups uniformly distributed along the polymer chain. The combination of such contradictory charged acting groups (zwitter (German)) makes the macromolecule superhydrophilic, while at the same time maintaining a neutral charge overall. Macromolecules containing ionic groups are one of the most important types of macromolecules. Such macromolecules range from naturally occurring biopolymers such as proteins and nucleic acids to synthetic thickeners and soaps. Ionic polymers are classified into polyelectrolytes and zwitterionic polymers. The ionic polymer is a polymer containing anionic or cationic acting groups, while the amphoteric ionic polymer is a polymer containing both cationic and anionic acting groups. Is. The zwitterionic polymer has a wide range of applications such as ion exchange, trace metal chelation of tree planting, sewage treatment, soil management, papermaking fortification, pigment residue, shampoo and hair conditioner formulation. .. The amphoteric ionic polymer has a charge located on the pendant side chain of the monomer, or in the case of polyesters, polyphosphazenes and polyphosphobetaine. The charge may be located in the polymer main chain. In terms of engineering, the zwitterionic polymer is a widely used alternative to polyethylene glycol (PEG) to prevent nonspecific protein adsorption and minimize bacterial, animal and human cell adhesion. Is considered as. However, while PEG polymers have essentially the same repeating units, the zwitterionic polymers are capable of a wide range of structural changes due to the specific monomeric chemical structure. ..
Involved in the antibacterial activity of metals, diverse and extensive research has been conducted for quite some time. Specific metals such as silver (Ag), mercury (Hg) and tellurium (Te) are known to be extremely toxic to most bacteria and have antibacterial effects even at extremely low concentrations. Due to the intrinsic toxicity of such metals to bacteria and yeast, certain metals have been utilized as antibacterial agents since ancient times. Today, antibacterial metal compounds such as metal surfaces, coatings, chelating compounds and nanomaterials are utilized in a wide range of fields such as industry, agriculture and healthcare. Such developments include innovations such as the destruction of antimicrobial-resistant biofilms by certain metals, the synergistic effect of antibacterial activity with other antibacterial agents, the suppression of selective metabolic effects, and the killing of multidrug-resistant bacteria. It was done through a typical discovery. However, it is also a fact that the specific metal causes a problem of toxicity to cells and tissues when applied to a medical device inserted or transplanted into the body, and systemic toxicity in the case of a nano substance. Further, in the case of the metal contained in the material, the metal is rapidly discharged or consumed, and the effect is often not satisfactory. Therefore, in order to apply metals to medical materials inserted into the body, there is an urgent need to develop technologies and materials that can maintain internal safety while being maintained for a long period of time.
本発明が解決しようとする課題は、抗血栓性または抗菌性を有する高分子化合物を提供することである。 An object to be solved by the present invention is to provide a polymer compound having antithrombotic or antibacterial properties.
本発明が解決しようとする課題は、また、前記高分子化合物を含む化学添加用組成物を提供することである。 An object to be solved by the present invention is also to provide a composition for chemical addition containing the above-mentioned polymer compound.
本発明が解決しようとする課題は、また、前記高分子化合物または化学添加用組成物を含む医療用物質を提供することである。 An object to be solved by the present invention is also to provide a medical substance containing the polymer compound or a composition for chemical addition.
本発明が解決しようとする課題は、また、前記高分子化合物を製造する方法を提供するすることである。 An object to be solved by the present invention is also to provide a method for producing the polymer compound.
一様相による高分子化合物、それを含む化学添加用組成物、それを含む医療用物質、及びそれを製造する方法によれば、抗血栓性または抗菌性を有し、汎用性が高い医療用物質を製造するのに利用することができる。 A highly versatile medical substance having antithrombotic or antibacterial properties according to a polymer compound having a uniform phase, a composition for chemical addition containing the compound, a medical substance containing the compound, and a method for producing the compound. Can be used to manufacture.
一様相は、化学式１ないし３からなる群から選択された２以上の反復単位を含む共重合体を含む高分子化合物を提供する： The uniform phase provides a polymeric compound containing a copolymer containing two or more repeating units selected from the group consisting of chemical formulas 1-3:
前記高分子化合物は、例えば、化学式１の反復単位、及び化学式２の反復単位を含む高分子化合物、または化学式１の反復単位、化学式２の反復単位、及び化学式３の反復単位を含む高分子化合物でもある。 The polymer compound is, for example, a polymer compound containing a repeating unit of Chemical Formula 1 and a repeating unit of Chemical Formula 2, or a polymer compound containing a repeating unit of Chemical Formula 1, a repeating unit of Chemical Formula 2, and a repeating unit of Chemical Formula 3. But also.
前記Ｒ１は、置換もしくは非置換のＣ１−Ｃ３０アルキル基、置換もしくは非置換のＣ２−Ｃ３０アルケニル基、置換もしくは非置換のＣ２−Ｃ３０アルキニル基、置換もしくは非置換のＣ６−Ｃ３０アリール基、置換もしくは非置換のＣ６−Ｃ３０ヘテロアリール基、置換もしくは非置換のＣ５−Ｃ２０芳香族環基、置換もしくは非置換のＣ３−Ｃ３０環状基、置換もしくは非置換のＣ３−Ｃ２０ヘテロ環状基、またはそれらの組み合わせでもある。前記Ｒ１は、置換もしくは非置換のＣ１−Ｃ３０，Ｃ１−Ｃ２０，Ｃ１−Ｃ１０またはＣ１−Ｃ５アルキル基（例えば、メチル）、置換もしくは非置換のＣ６−Ｃ３０，Ｃ６−Ｃ２０，Ｃ６−Ｃ１０またはＣ６−Ｃ８アリール基、置換もしくは非置換のＣ３−Ｃ３０，Ｃ３−Ｃ２０，Ｃ３−Ｃ１０またはＣ３−Ｃ６環状基、置換もしくは非置換のＣ３−Ｃ２０，Ｃ３−Ｃ１０またはＣ３−Ｃ６ヘテロ環状基、あるいはそれらの組み合わせでもある。前記Ｒ１は、アルキレンジフェニル基でもある。例えば、Ｒ１は、メチレンジフェニルである。 The R 1 is a substituted or unsubstituted C 1- C 30 alkyl group, a substituted or unsubstituted C 2- C 30 alkenyl group, a substituted or unsubstituted C 2- C 30 alkynyl group, a substituted or unsubstituted C. 6- C 30 aryl group, substituted or unsubstituted C 6- C 30 heteroaryl group, substituted or unsubstituted C 5- C 20 aromatic ring group, substituted or unsubstituted C 3- C 30 cyclic group, substituted Alternatively, it is an unsubstituted C 3- C 20 heterocyclic group, or a combination thereof. The R 1 is a substituted or unsubstituted C 1- C 30 , C 1- C 20 , C 1- C 10 or C 1- C 5 alkyl group (eg, methyl), substituted or unsubstituted C 6- C. 30 , C 6- C 20 , C 6- C 10 or C 6- C 8 aryl groups, substituted or unsubstituted C 3- C 30 , C 3- C 20 , C 3- C 10 or C 3- C 6 It is also a cyclic group, a substituted or unsubstituted C 3- C 20 , C 3- C 10 or C 3- C 6 heterocyclic group, or a combination thereof. The R 1 is also an alkylene diphenyl group. For example, R 1 is methylene diphenyl.
前記化学式１の反復単位は、メチレンジフェニルジイソシアネート（ＭＤＩ：methylene diphenyl diisocyanate）、４，４’−ジイソシアネートジシクロヘキシルメタン（diisocyanato dicyclohexylmethane；hydrogenated methylene diphenyl diisocyanate）、ヘキサメチレンジイソシアネート（ＨＤＩ：hexamethylene diisocyanate）、イソホロンジイソシアネート（ＩＰＤＩ：isophorone diisocyanate）、トルエンジイソシアネート（ＴＤＩ：toluene diisocyanate）及びメチルイソシアネート（ＭＩＣ：methyl isocyanate）からなる群からも選択される。 The repeating unit of the chemical formula 1 is methylene diphenyl diisocyanate (MDI), 4,4'-dicyclohexylmethane (hydrogenated methylene diphenyl diisocyanate), hexamethylene diisocyanate (HDI), isophorone diisocyanate (HDI). It is also selected from the group consisting of IPDI: isophorone diisocyanate), toluene diisocyanate (TDI: toluene diisocyanate) and methyl isocyanate (MIC).
前記ｘは、１ないし１００、１ないし８０、１ないし６０、１ないし４０、１ないし２０、１ないし１０、または１ないし５の整数でもある。 The x is also an integer of 1 to 100, 1 to 80, 1 to 60, 1 to 40, 1 to 20, 1 to 10, or 1 to 5.
前述のＲ２及びＲ３は、互いに独立して、置換もしくは非置換のＣ１−Ｃ３０アルキル基、置換もしくは非置換のＣ２−Ｃ３０アルケニル基、置換もしくは非置換のＣ２−Ｃ３０アルキニル基、置換もしくは非置換のＣ６−Ｃ３０アリール基、置換もしくは非置換のＣ６−Ｃ３０ヘテロアリール基、置換もしくは非置換のＣ５−Ｃ２０芳香族環基、置換もしくは非置換のＣ３−Ｃ３０環状基、置換もしくは非置換のＣ３−Ｃ２０ヘテロ環状基、またはそれらの組み合わせでもある。 The aforementioned R 2 and R 3 are independent of each other, a substituted or unsubstituted C 1- C 30 alkyl group, a substituted or unsubstituted C 2- C 30 alkenyl group, and a substituted or unsubstituted C 2- C 30. Alkinyl group, substituted or unsubstituted C 6- C 30 aryl group, substituted or unsubstituted C 6- C 30 heteroaryl group, substituted or unsubstituted C 5- C 20 aromatic ring group, substituted or unsubstituted It is also a C 3- C 30 cyclic group, a substituted or unsubstituted C 3- C 20 heterocyclic group, or a combination thereof.
前記Ｒ２は、置換もしくは非置換のＣ１−Ｃ３０，Ｃ１−Ｃ２０，Ｃ１−Ｃ１０またはＣ１−Ｃ５アルキル基、置換もしくは非置換のＣ６−Ｃ３０，Ｃ６−Ｃ２０，Ｃ６−Ｃ１０またはＣ６−Ｃ８アリール基、置換もしくは非置換のＣ３−Ｃ３０，Ｃ３−Ｃ２０，Ｃ３−Ｃ１０またはＣ３−Ｃ６環状基、あるいはそれらの組み合わせでもある。例えば、前記Ｒ２は、メチル基である。 The R 2 is a substituted or unsubstituted C 1- C 30 , C 1- C 20 , C 1- C 10 or C 1- C 5 alkyl group, substituted or unsubstituted C 6- C 30 , C 6-. C 20 , C 6- C 10 or C 6- C 8 aryl groups, substituted or unsubstituted C 3- C 30 , C 3- C 20 , C 3- C 10 or C 3- C 6 cyclic groups, or theirs. It is also a combination of. For example, the R 2 is a methyl group.
前記Ｒ３は、置換もしくは非置換のＣ１−Ｃ３０，Ｃ１−Ｃ２０，Ｃ１−Ｃ１０またはＣ１−Ｃ５アルキル基でもある。例えば、前記Ｒ３は、プロピル基である。 The R 3 is also a substituted or unsubstituted C 1- C 30 , C 1- C 20 , C 1- C 10 or C 1- C 5 alkyl group. For example, the R 3 is a propyl group.
前記Ａは、−ＣＯ２、−ＳＯ３、−ＰＯ３、置換もしくは非置換のＣ１−Ｃ３０アルキル基、またはそれらの組み合わせであり、前記アルキル基は、ハロゲン原子でも置換される。 The A is -CO 2 , -SO 3 , -PO 3 , a substituted or unsubstituted C 1- C 30 alkyl group, or a combination thereof, and the alkyl group is also substituted with a halogen atom.
前記Ｍは、金属原子でもある。前記Ｍは、例えば、銀（Ａｇ）、セリウム（Ｃｅ）、亜鉛（Ｚｎ）、銅（Ｃｕ）、水銀（Ｈｇ）、ヒ素（Ａｓ）、アンチモン（Ｓｂ）、スズ（Ｓｎ）、バリウム（Ｂａ）、鉄（Ｆｅ）、チタン（Ｔｉ）、パラジウム（Ｐｄ）、金（Ａｕ）、ガリウム（Ｇａ）、鉛（Ｐｂ）及びビスマス（Ｂｉ）からなる群から選択されたものである。 The M is also a metal atom. The M is, for example, silver (Ag), cerium (Ce), zinc (Zn), copper (Cu), mercury (Hg), arsenic (As), antimony (Sb), tin (Sn), palladium (Ba). , Iron (Fe), Titanium (Ti), Palladium (Pd), Gold (Au), Gallium (Ga), Lead (Pb) and Bismuth (Bi).
前記ｙは、１ないし１００、１ないし８０、１ないし６０、１ないし４０、１ないし２０、１ないし１０、または１ないし５の整数でもある。 The y is also an integer of 1 to 100, 1 to 80, 1 to 60, 1 to 40, 1 to 20, 1 to 10, or 1 to 5.
前記Ｒ４は、置換もしくは非置換のＣ１−Ｃ３０アルキル基、置換もしくは非置換のＣ６−Ｃ３０アリール基、置換もしくは非置換のＣ６−Ｃ３０ヘテロアリール基、置換もしくは非置換のＣ３−Ｃ３０環状基、置換もしくは非置換のＣ３−Ｃ２０ヘテロ環状基、またはそれらの組み合わせでもある。前記ヘテロアリール基またはヘテロ環状基は、Ｎ、Ｏ及びＳからなる群から選択された１以上の異種原子を含む。前記Ｒ４は、置換もしくは非置換のＣ１−Ｃ３０，Ｃ１−Ｃ２０，Ｃ１−Ｃ１０またはＣ１−Ｃ５アルキル基、置換もしくは非置換のＣ２−Ｃ３０，Ｃ２−Ｃ２０，Ｃ２−Ｃ１０またはＣ２−Ｃ６アルケニル基、置換もしくは非置換のＣ２−Ｃ３０，Ｃ２−Ｃ２０，Ｃ２−Ｃ１０またはＣ２−Ｃ６アルキニル基、置換もしくは非置換のＣ６−Ｃ３０，Ｃ６−Ｃ２０，Ｃ６−Ｃ１０またはＣ６−Ｃ８アリール基、置換もしくは非置換のＣ６−Ｃ３０，Ｃ６−Ｃ２０，Ｃ６−Ｃ１０またはＣ６−Ｃ８ヘテロアリール基、置換もしくは非置換のＣ１−Ｃ３０，Ｃ３−Ｃ２０，Ｃ３−Ｃ１０またはＣ３−Ｃ６環状基、置換もしくは非置換のＣ３−Ｃ２０，Ｃ３−Ｃ１０またはＣ３−Ｃ６ヘテロ環状基、あるいはそれらの組み合わせでもある。前記Ｒ４は、置換もしくは非置換のＣ１−Ｃ２０アルキル基、ジメチレンオキシド、トリメチレンオキシド、テトラメチレンオキシド、ブタジエン、イソブチレン、イソソルビド、またはそれらの組み合わせでもある。前記Ｒ４は、ハロゲン原子で置換されたＣ１−Ｃ３０アルキル基でもある。前記Ｒ４は、過フッ化された（perfluorinated）Ｃ１−Ｃ３０アルキル基でもある。例えば、前記Ｒ４は、イソソルビドである。 Wherein R 4 is a substituted or unsubstituted C 1 -C 30 alkyl group, a substituted or unsubstituted C 6 -C 30 aryl group, a substituted or unsubstituted C 6 -C 30 heteroaryl groups, substituted or unsubstituted It is also a C 3- C 30 cyclic group, a substituted or unsubstituted C 3- C 20 heterocyclic group, or a combination thereof. The heteroaryl group or heterocyclic group contains one or more heteroatoms selected from the group consisting of N, O and S. The R 4 is a substituted or unsubstituted C 1- C 30 , C 1- C 20 , C 1- C 10 or C 1- C 5 alkyl group, substituted or unsubstituted C 2- C 30 , C 2- C 20 , C 2- C 10 or C 2- C 6 alkenyl groups, substituted or unsubstituted C 2- C 30 , C 2- C 20 , C 2- C 10 or C 2- C 6 alkynyl groups, substituted or Unsubstituted C 6- C 30 , C 6- C 20 , C 6- C 10 or C 6- C 8 aryl groups, substituted or unsubstituted C 6- C 30 , C 6- C 20 , C 6- C 10 or C 6- C 8 heteroaryl groups, substituted or unsubstituted C 1- C 30 , C 3- C 20 , C 3- C 10 or C 3- C 6 cyclic groups, substituted or unsubstituted C 3- It is also a C 20 , C 3- C 10 or C 3- C 6 heterocyclic group, or a combination thereof. Wherein R 4 is a substituted or unsubstituted C 1 -C 20 alkyl group, dimethylene oxide, trimethylene oxide, tetramethylene oxide, there butadiene, isobutylene, isosorbide or a combination thereof. Wherein R 4 is also a C 1 -C 30 alkyl group substituted with a halogen atom. Wherein R 4 is also a is perfluorinated (perfluorinated) C 1 -C 30 alkyl group. For example, the R 4 is isosorbide.
前記ｚは、１ないし１００、１ないし８０、１ないし６０、１ないし４０、１ないし２０、１ないし１０、または１ないし５の整数でもある。 The z is also an integer of 1 to 100, 1 to 80, 1 to 60, 1 to 40, 1 to 20, 1 to 10, or 1 to 5.
前記高分子化合物は、１以上の末端に、ハロゲン原子で置換されたＣ１−Ｃ３０アルキル基、カルボキシ基、またはそれらの組み合わせを含んでもよい。前記高分子化合物は、１以上の末端に、ハロゲン原子で置換されたＣ１−Ｃ３０，Ｃ１−Ｃ２０，Ｃ１−Ｃ１０またはＣ１−Ｃ５アルキル基、クエン酸、またはそれらの組み合わせを含んでもよい。前記ハロゲン原子で置換されたＣ１−Ｃ３０アルキル基は、過フッ化されたＣ１−Ｃ３０アルキル基でもある。例えば、前記高分子化合物は、ある１末端または両末端に、クエン酸と重合された化合物である。 The polymer compound, the one or more terminal, C 1 -C 30 alkyl group substituted with a halogen atom may include a carboxy group, or a combination thereof. The polymer compound, the one or more terminal, C 1 -C 30 substituted with a halogen atom, C 1 -C 20, C 1 -C 10 or C 1 -C 5 alkyl group, citric acid or their, Combinations may be included. The C 1- C 30 alkyl group substituted with the halogen atom is also a perfluorinated C 1- C 30 alkyl group. For example, the polymer compound is a compound polymerized with citric acid at one end or both ends.
前記高分子化合物は、金属複合体でもある。前記金属複合体は、前記高分子化合物と、前述の金属イオンとの複合体でもある。 The polymer compound is also a metal complex. The metal complex is also a complex of the polymer compound and the above-mentioned metal ion.
前記「置換」は、有機化合物のうち１以上の水素原子を、他の原子団で置換し、誘導体を形成した場合、水素原子の代わりに導入することを言い、「置換基」は、導入された原子団を言う。 The above-mentioned "substitution" means that when one or more hydrogen atoms of an organic compound are substituted with another atomic group to form a derivative, the introduction is carried out in place of the hydrogen atom, and the "substituent group" is introduced. Say the atomic group.
前記化学式１ないし化学式３で使用されるアルキル基、アルケニル基、アルキニル基、アリール基、ヘテロアリール基、芳香族環基、環状基、ヘテロ環状基の「置換」は、ハロゲン原子、ハロゲン原子で置換されたＣ１−Ｃ５アルキル基（例：ＣＣＦ３、ＣＨＣＦ２、ＣＨ２Ｆ、ＣＣｌ３など）、ヒドロキシ基、ニトロ基、シアノ基、アミノ基、アミジノ基、アセトアミノ基、ヒドラジン、ヒドラゾン、カルボン酸基やその塩、スルホン酸基やその塩、リン酸基やその塩、Ｃ１−Ｃ５アルキル基、Ｃ２−Ｃ５アルケニル基、Ｃ２−Ｃ５アルキニル基、Ｃ３−Ｃ１０シクロアルキル基、Ｃ６−Ｃ１０アリール基、Ｃ６−Ｃ１０ヘテロアリール基、Ｃ６−Ｃ２０アリールアルキル基、Ｃ６−Ｃ２０ヘテロアリールアルキル基、またはそれらの組み合わせで置換されたものを意味する。 The "substitution" of the alkyl group, alkenyl group, alkynyl group, aryl group, heteroaryl group, aromatic ring group, cyclic group, or heterocyclic group used in the chemical formulas 1 to 3 is replaced with a halogen atom or a halogen atom. has been C 1 -C 5 alkyl group (eg: CCF 3, CHCF 2, CH 2 F, etc. CCl 3), hydroxy group, a nitro group, a cyano group, an amino group, amidino group, acetamino group, hydrazine, hydrazone, a carboxyl acid group or a salt thereof, a sulfonic acid group or a salt thereof, phosphoric acid group or a salt thereof, C 1 -C 5 alkyl group, C 2 -C 5 alkenyl group, C 2 -C 5 alkynyl group, C 3 -C 10 cycloalkyl Means an alkyl group, a C 6- C 10 aryl group, a C 6- C 10 heteroaryl group, a C 6- C 20 arylalkyl group, a C 6- C 20 heteroarylalkyl group, or a combination thereof. To do.
他の様相は、一様相による高分子化合物を含む化学添加用組成物を提供する。 The other aspect provides a composition for chemical addition comprising a polymeric compound with a uniform phase.
前記化学添加用組成物は、医療用物質の製造段階において添加したり、医療用物質をコーティング、浸漬または塗布したりするための組成物でもある。 The composition for chemical addition is also a composition for adding, dipping or applying the medical substance in the production stage of the medical substance.
前記組成物は、吸着防止（antifouling）、抗血栓、抗菌、またはそれらの組み合わせのためのものでもある。前記組成物は、タンパク質の吸着防止のためのものでもある。前記高分子化合物、またはそれを含む組成物が血液と接触する場合、前記高分子化合物、またはそれを含む組成物に、血液内のタンパク質が付着または吸着されることを阻害し、血栓が形成されることを阻害することができる。前記組成物は、前記高分子化合物、またはそれを含む組成物に、微生物（例えば、細菌）が付着または吸着されることを阻害したり、微生物が死滅したりするようにする。 The composition is also for anti-adsorption (antifouling), antithrombotic, antibacterial, or a combination thereof. The composition is also for preventing protein adsorption. When the polymer compound or a composition containing the same comes into contact with blood, it inhibits the attachment or adsorption of proteins in the blood to the polymer compound or the composition containing the same, and a thrombus is formed. Can be prevented from doing so. The composition inhibits the attachment or adsorption of microorganisms (for example, bacteria) to the polymer compound or a composition containing the same, or causes the microorganisms to die.
他の様相は、一様相による高分子化合物または化学添加用組成物を含む医療用物質でもある。 Other aspects are also medical materials, including macromolecular compounds with uniform phases or compositions for chemical addition.
前記医療用物質は、前記高分子化合物または前記組成物と組み合わされるか、あるいはそれらにコーティングされたものでもある。前記高分子化合物は、例えば、ポリ塩化ビニルとも組み合わされる。 The medical material may also be combined with or coated with the polymeric compound or composition. The polymeric compound is also combined with, for example, polyvinyl chloride.
前記医療用物質は、フィルム、チューブ、シート、ステント、カテーテル、インプラント、縫合糸、ヒドロゲル、またはそれらの組み合わせでもある。 The medical material may also be a film, tube, sheet, stent, catheter, implant, suture, hydrogel, or a combination thereof.
他の様相は、置換もしくは非置換のジエタノールアミンと、プロパンスルトンまたはブタンスルトンのうちいずれか一つを重合、て両性イオン性ジオール（diol）化合物を生成する段階と、
得られた両性イオン性ジオール化合物とジイソシアネート化合物とを重合し、両性イオン性ポリウレタン重合体を生成する段階と、を含む高分子化合物を製造する方法を提供する。
Another aspect is the step of polymerizing either substituted or unsubstituted diethanolamine with either propane sultone or butane sultone to produce a zwitterionic diol compound.
Provided is a method for producing a polymer compound containing a step of polymerizing the obtained zwitterionic diol compound and a diisocyanate compound to produce a zwitterionic polyurethane polymer.
前記方法は、置換もしくは非置換のジエタノールアミンと、プロパンスルトンまたはブタンスルトンのうちいずれか一つとを重合し、両性イオン性ジオール化合物を生成する段階を含む。 The method comprises the step of polymerizing a substituted or unsubstituted diethanolamine with any one of propane sultone or butane sultone to produce an amphoteric ionic diol compound.
前記ジエタノールアミンは、Ｃ１−Ｃ２０，Ｃ１−Ｃ１０またはＣ１−Ｃ５アルキル基で置換されたものでもある。例えば、前記ジエタノールアミンは、メチルジエタノールアミン（ＭＤＥＡ：methyl diethanol amine）である。 The diethanolamine is also one which is substituted by C 1 -C 20, C 1 -C 10 or C 1 -C 5 alkyl group. For example, the diethanolamine is methyl diethanolamine (MDEA).
前記方法は、得られた両性イオン性ジオール化合物とジイソシアネート化合物とを重合し、両性イオン性ポリウレタン重合体を生成する段階を含む。 The method comprises the step of polymerizing the obtained zwitterionic diol compound and the diisocyanate compound to produce a zwitterionic polyurethane polymer.
前記ジイソシアネート化合物は、例えば、メチレンジフェニルジイソシアネート（ＭＤＩ）、４，４’−ジイソシアネートジシクロヘキシルメタン（ＨＭＤＩ）、ヘキサメチレンジイソシアネート（ＨＤＩ）、イソホロンジイソシアネート（ＩＰＤＩ）、トルエンジイソシアネート（ＴＤＩ）及びメチルイソシアネート（ＭＩＣ）である。 The diisocyanate compounds include, for example, methylene diphenyl diisocyanate (MDI), 4,4'-diisocyanate dicyclohexylmethane (HMDI), hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), toluene diisocyanate (TDI) and methyl isocyanate (MIC). Is.
前記方法は、両性イオン性ジオール化合物とジイソシアネート化合物とに可塑剤を加える段階をさらに含んでもよい。前記可塑剤は、置換もしくは非置換のＣ１−Ｃ２０アルキル基、ジメチレンオキシド、トリメチレンオキシド、テトラメチレンオキシド、ブタジエン、イソブチレン、イソソルビド、またはそれらの組み合わせでもある。 The method may further include the step of adding a plasticizer to the zwitterionic diol compound and the diisocyanate compound. The plasticizer is a substituted or unsubstituted C 1 -C 20 alkyl group, dimethylene oxide, trimethylene oxide, tetramethylene oxide, there butadiene, isobutylene, isosorbide or a combination thereof.
前記方法は、得られた両性イオン性ポリウレタン重合体を、ハロゲン原子で置換されたＣ１−Ｃ３０アルキル（過フッ化されたアルキル基含む）、クエン酸、またはそれらの組み合わせでキャッピング（capping）する段階をさらに含んでもよい。前記高分子化合物は、１以上の末端に、ハロゲン原子で置換されたＣ１−Ｃ３０アルキル基、カルボキシ基、またはそれらの組み合わせを含んでもよい。 The method and the resulting zwitterionic polyurethane polymer, C 1 -C 30 alkyl substituted with halogen atom (including perfluorinated alkyl group), citric acid or capping a combination thereof, (capping) It may further include the steps to be performed. The polymer compound, the one or more terminal, C 1 -C 30 alkyl group substituted with a halogen atom may include a carboxy group, or a combination thereof.
前記方法は、得られた両性イオン性ポリウレタン重合体と金属イオンとを混合し、両性イオン性ポリウレタン金属重合体を生成する段階をさらに含んでもよい。 The method may further include the step of mixing the obtained zwitterionic polyurethane polymer with metal ions to produce a zwitterionic polyurethane metal polymer.
以下、実施例を介して、さらに詳細に説明する。しかし、それら実施例は、例示的に説明するためのものであり、本発明の範囲がそれら実施例に限定されるものではない。 Hereinafter, it will be described in more detail with reference to Examples. However, these examples are for illustration purposes only, and the scope of the present invention is not limited to these examples.
［実施例１．抗菌性または抗血栓性の高分子化合物の製造、及び製造された高分子化合物の物理化学的特性分析］
［１．両性イオン性ジオールの合成］
３口（３−neck）丸底フラスコに、３０ｍｌのジメチルホルムアミド無水物（ＤＭＦ：dimethylformamide anhydrous）（Sigma−Aldrich）を加えた。
[Example 1. Production of antibacterial or antithrombotic polymer compounds, and physicochemical property analysis of the produced polymer compounds]
[1. Synthesis of zwitterionic diols]
To a 3-neck round bottom flask, 30 ml of dimethylformamide anhydride (DMF) (Sigma-Aldrich) was added.
該ＤＭＦに、０．０６ｍｏｌ（６．９ｍｌ）のメチルジエタノールアミン（ＭＤＥＡ：methyldiethanolamine）（Sigma−Aldrich）、及び０．０６ｍｏｌ（７．３ｇ）の１，３−プロパンスルトン（propanesultone）（Sigma−Aldrich）を加え、約５０℃の温度で約５時間、窒素ガス存在下で撹拌した。その後、アセトン（Sigma−Aldrich）溶液に反応物を加えて沈澱させた。沈殿物を、約４，０００ｒｐｍの速度で約２分間遠心分離させた後、上澄み液を除去し、沈殿物を得た。そのような過程を３回反復し、反応物を沈澱及び洗浄した。該沈殿物を真空で一日乾燥させ、パウダー状の両性イオン性ジオール（zwitterionic diol）を得た。 In the DMF, 0.06 mol (6.9 ml) of methyldiethanolamine (MDEA: methyldiethanolamine) (Sigma-Aldrich) and 0.06 mol (7.3 g) of 1,3-propanesultone (Sigma-Aldrich) are added. Was added, and the mixture was stirred at a temperature of about 50 ° C. for about 5 hours in the presence of nitrogen gas. Then, the reaction product was added to a solution of acetone (Sigma-Aldrich) and precipitated. The precipitate was centrifuged at a rate of about 4,000 rpm for about 2 minutes, and then the supernatant was removed to obtain a precipitate. Such a process was repeated 3 times to precipitate and wash the reactants. The precipitate was dried in vacuo for one day to give a powdery zwitterionic diol.
該両性イオン性ジオールを合成する化学反応を示す模式図を図２に示した。 A schematic diagram showing a chemical reaction for synthesizing the zwitterionic diol is shown in FIG.
［２．ポリウレタン化合物の準備］
［２．１．両性イオン性ポリウレタンの準備］
１．に記載されたように、両性イオン性ジオールを準備した。
[2. Preparation of polyurethane compound]
[2.1. Preparation of zwitterionic polyurethane]
1. 1. Zwitterionic diols were prepared as described in.
３口丸底フラスコに、３０ｍｌのＤＭＦを加え、窒素ガスで充填（purging）し、水分を除去した。充填されたフラスコに、０．０１８ｍｏｌ（４．３６ｇ）の両性イオン性ジオール、及び０．０２７ｍｏｌ（６．８ｇ）のメチレンジフェニルジイソシアネート（ＭＤＩ：methylene diphenyl diisocyanate）（Sigma−Aldrich）を加え、触媒剤として、５８μｌのＴｉｎ（ＩＩ）を加えた。 To a three-necked round-bottom flask, 30 ml of DMF was added and purged with nitrogen gas to remove water. 0.018 mol (4.36 g) of zwitterionic diol and 0.027 mol (6.8 g) of methylene diphenyl diisocyanate (MDI) (Sigma-Aldrich) were added to the filled flask as a catalyst. As a result, 58 μl of Tin (II) was added.
反応物を、約８０℃の温度で約２０分間、窒素ガス存在下で撹拌した。その後、クロロホルム（Sigma−Aldrich）溶液に反応物を加えて沈澱させた。濾紙を利用し、沈澱された反応物を得た。そのような過程を３回反復し、反応物を沈澱及び洗浄した。該沈殿物を真空で一日乾燥させ、パウダー状の両性イオン性ポリウレタン（ＳＰＵ）を得た。 The reaction was stirred at a temperature of about 80 ° C. for about 20 minutes in the presence of nitrogen gas. Then, the reaction product was added to a chloroform (Sigma-Aldrich) solution and precipitated. A precipitated reaction product was obtained using a filter paper. Such a process was repeated 3 times to precipitate and wash the reactants. The precipitate was dried in vacuo for one day to give a powdery zwitterionic polyurethane (SPU).
両性イオン性ポリウレタン（ＳＰＵ）を合成する化学反応を示す模式図を図３Ａに示した。 A schematic diagram showing a chemical reaction for synthesizing an amphoteric ionic polyurethane (SPU) is shown in FIG. 3A.
［２．２．両性イオン性イソソルビドポリウレタンの準備］
１．に記載されたように、両性イオン性ジオールを準備した。
[2.2. Preparation of Zwitterionic Isosorbide Polyurethane]
1. 1. Zwitterionic diols were prepared as described in.
３ 口丸底フラスコに３０ｍｌのＤＭＦを加え、窒素ガスで充填して水分を除去した。充填されたフラスコに、０．００９ｍｏｌ（２．１８ｇ）の両性イオン性ジオール、及び０．００９ｍｏｌ（１．３２ｇ）のイソソルビド（Sigma−Aldrich）を加え、イソソルビドを溶解させた。反応物に０．０２７ｍｏｌ（６．８ｇ）のＭＤＩ（Sigma−Aldrich）を加え、触媒剤として、５８μｌのＴｉｎ（ＩＩ）を加えた。 30 ml of DMF was added to a 3-necked round bottom flask and filled with nitrogen gas to remove water. To the filled flask, 0.009 mol (2.18 g) of zwitterionic diol and 0.009 mol (1.32 g) of isosorbide (Sigma-Aldrich) were added to dissolve the isosorbide. 0.027 mol (6.8 g) of MDI (Sigma-Aldrich) was added to the reaction product, and 58 μl of Tin (II) was added as a catalyst.
該反応物を、約８０℃の温度で約２０分間、窒素ガス存在下で撹拌した。その後、クロロホルム（Sigma−Aldrich）溶液に反応物を加えて沈澱させた。濾紙を利用し、沈澱された反応物を得た。そのような過程を３回反復し、反応物を沈澱及び洗浄した。沈殿物を真空で一日乾燥させ、パウダー状の両性イオン性イソソルビドポリウレタン（ＳＩＰＵ）を得た。 The reaction was stirred at a temperature of about 80 ° C. for about 20 minutes in the presence of nitrogen gas. Then, the reaction product was added to a chloroform (Sigma-Aldrich) solution and precipitated. A precipitated reaction product was obtained using a filter paper. Such a process was repeated 3 times to precipitate and wash the reactants. The precipitate was dried in vacuo for one day to give a powdery zwitterionic isosorbide polyurethane (SIPU).
両性イオン性イソソルビドポリウレタン（ＳＩＰＵ）を合成する化学反応を示す模式図を図３Ｂに示した。 A schematic diagram showing a chemical reaction for synthesizing an amphoteric ionic isosorbide polyurethane (SIPU) is shown in FIG. 3B.
［３．ポリウレタンの末端キャッピング］
［３．１．クエン酸性両性イオン性ポリウレタンの準備］
２．１．に記載されたように、両性イオン性ポリウレタン（ＳＰＵ）を準備した。
[3. Polyurethane end capping]
[3.1. Preparation of citrate-acid zwitterionic polyurethane]
2.1. Zwitterionic polyurethane (SPU) was prepared as described in.
３口丸底フラスコに３０ｍｌのＤＭＦを加え、窒素ガスで充填して水分を除去した。充填されたフラスコに、０．００４５ｍｏｌ（０．７５ｇ）のクエン酸（Sigma−Aldrich）を加え、クエン酸を溶解させた。反応物に０．０１５ｍｏｌ（１．５ｇ）のＳＰＵを加え、該反応物を約９０℃の温度で約１２時間撹拌した。その後、クロロホルム（Sigma−Aldrich）溶液に反応物を加えて沈澱させた。濾紙を利用し、沈澱された反応物を得た。そのような過程を３回反復し、反応物を沈澱及び洗浄した。沈殿物を真空で一日乾燥させ、パウダー状のクエン酸末端両性イオン性ポリウレタン（ＣＳＰＵ：citrate-endcapped zwitterionic polyurethane）を得た。 30 ml of DMF was added to a 3-necked round bottom flask and filled with nitrogen gas to remove water. To the filled flask, 0.0045 mol (0.75 g) of citric acid (Sigma-Aldrich) was added to dissolve the citric acid. 0.015 mol (1.5 g) of SPU was added to the reaction product, and the reaction product was stirred at a temperature of about 90 ° C. for about 12 hours. Then, the reaction product was added to a chloroform (Sigma-Aldrich) solution and precipitated. A precipitated reaction product was obtained using a filter paper. Such a process was repeated 3 times to precipitate and wash the reactants. The precipitate was dried in vacuum for one day to obtain a powdery citric acid-terminated zwitterionic polyurethane (CSPU).
クエン酸末端両性イオン性ポリウレタン（ＣＳＰＵ）を合成する化学反応を示す模式図を図４Ａに示した。 A schematic diagram showing a chemical reaction for synthesizing citrate-terminated zwitterionic polyurethane (CSPU) is shown in FIG. 4A.
［３．２．クエン酸性両性イオン性イソソルビドポリウレタンの準備］
２．２．に記載されたように、両性イオン性イソソルビドポリウレタン（ＳＩＰＵ）を合成した。
[3.2. Preparation of Citrate Zwitterionic Isosorbide Polyurethane]
2.2. Zwitterionic isosorbide polyurethane (SIPU) was synthesized as described in.
３口丸底フラスコに３０ｍｌのＤＭＦを加え、窒素ガスで充填して水分を除去した。充填されたフラスコに、０．００３６ｍｏｌ（０．６ｇ）のクエン酸（Sigma−Aldrich）を加え、クエン酸を溶解させた。反応物に０．００１２ｍｏｌ（１．５ｇ）のＳＩＰＵを加え、反応物を約９０℃の温度で約１２時間撹拌した。その後、クロロホルム（Sigma−Aldrich）溶液に反応物を加えて沈澱させた。濾紙を利用し、沈澱された反応物を得た。そのような過程を３回反復し、反応物を沈澱及び洗浄した。沈殿物を真空で一日乾燥させ、パウダー状のクエン酸末端両性イオン性イソソルビドポリウレタン（ＣＳＩＰ：citrate-endcapped zwitterionic isosorbide polyurethane）を得た。 30 ml of DMF was added to a 3-necked round bottom flask and filled with nitrogen gas to remove water. To the filled flask, 0.0036 mol (0.6 g) of citric acid (Sigma-Aldrich) was added to dissolve the citric acid. 0.0012 mol (1.5 g) of SIPU was added to the reaction, and the reaction was stirred at a temperature of about 90 ° C. for about 12 hours. Then, the reaction product was added to a chloroform (Sigma-Aldrich) solution and precipitated. A precipitated reaction product was obtained using a filter paper. Such a process was repeated 3 times to precipitate and wash the reactants. The precipitate was dried in vacuum for one day to obtain a powdery citrate-endcapped zwitterionic isosorbide polyurethane (CSIP).
クエン酸末端両性イオン性イソソルビドポリウレタン（ＣＳＩＰＵ）を合成する化学反応を示す模式図を図４Ｂに示した。 A schematic diagram showing a chemical reaction for synthesizing citrate-terminated zwitterionic isosorbide polyurethane (CSIPU) is shown in FIG. 4B.
［４．両性イオン性ポリウレタンを含むフィルム、及びその表面特性］
［４．１．両性イオン性ポリウレタンを含むフィルムの準備］
添加剤として、２．１、２．２、３．１及び３．２に記載されたように、両性イオン性ポリウレタン化合物を合成した。
[4. Film containing zwitterionic polyurethane and its surface properties]
[4.1. Preparation of film containing zwitterionic polyurethane]
As additives, zwitterionic polyurethane compounds were synthesized as described in 2.1, 2.2, 3.1 and 3.2.
基本高分子成分であるポリ塩化ビニル（ＰＶＣ）と、最終含量０％（ｗ／ｗ）、３％（ｗ／ｗ）または１０％（ｗ／ｗ）の両性イオン性ポリウレタン化合物とを混合した。加熱圧着機を使用し、混合物を約１７０℃の温度で、約１分の維持時間及び約４分の圧着時間、熱を加え、フィルムを製造した。 Polyvinyl chloride (PVC), which is a basic polymer component, and a zwitterionic polyurethane compound having a final content of 0% (w / w), 3% (w / w) or 10% (w / w) were mixed. Using a heat crimping machine, the mixture was heated at a temperature of about 170 ° C. for a maintenance time of about 1 minute and a crimping time of about 4 minutes to produce a film.
フィルム製造用組成物の組成比を下記表１に示した。 The composition ratio of the composition for film production is shown in Table 1 below.
製造されたフィルムのイメージを図５に示した。 An image of the produced film is shown in FIG.
［４．２．フィルムの表面特性］
４．１に記載されたように、両性イオン性ポリウレタンを含むフィルムを製造した。
[4.2. Film surface properties]
As described in 4.1, a film containing an amphoteric ionic polyurethane was produced.
準備されたフィルムの表面の構造的特性を確認するために、フーリエ変換赤外分光法（ＧＴＩＲ：Fourier transform infrared spectroscopy）を利用した。ＦＴ／ＩＲ−４１００（Jasco Analytical Instruments、米国）を使用し、フィルムに赤外線を照射し、波数（wavenumber）に対する透過率（transmittance）のグラフを図６Ａに示した。図６Ａに示されているように、カルボニル基は、波数１，７３０ｃｍ−１でピークとして示され、Ｃ−Ｎ基は、波数１，５２８ｃｍ−１でピークとして示されるので、ポリウレタン化合物において、ウレタン結合があるということを確認した。また、スルホベタイン（sulfobetain）のＳＯ３ −は、波数１，７３０ｃｍ−１でピークとして示され、第四級アミンは、９６０ｃｍ−１でピークとして示される、製造されたフィルムが両性イオン性作用基を含むということを確認した。 Fourier transform infrared spectroscopy (GTIR) was used to confirm the structural properties of the surface of the prepared film. Using FT / IR-4100 (Jasco Analytical Instruments, USA), the film was irradiated with infrared rays, and a graph of transmittance with respect to wave number is shown in FIG. 6A. As shown in FIG. 6A, the carbonyl group is shown as a peak at wavenumber 1,730 cm -1 , and the CN group is shown as a peak at wavenumber 1,528 cm -1 , so urethane in polyurethane compounds. I confirmed that there was a bond. In addition, SO 3 − of sulfobetain is shown as a peak at a wave number of 1,730 cm -1 , and quaternary amine is shown as a peak at 960 cm -1 , and the produced film is a zwitterionic acting group. It was confirmed that it contained.
また、フィルムの水接触角（water contact angle）を測定し、フィルムの親水性を測定した。製造されたフィルムを、乾燥条件、または約１日間水和させた条件で準備した。準備されたフィルムを、水接触角測定器ＯＣＡ４０（Dataphysics、ドイツ）に積載し、フィルム表面に３ｍｌの蒸溜水を落とし、水接触角を測定した。５回反復実験を行い、水接触角の平均値を算出した。試料による算出された水接触角のグラフを図６Ｂに示した。図６Ｂに示されているように、添加剤の含量が増加するほど、水接触角が低減した。従って、添加剤の含量が増加するほど、製造されたフィルムの親水性が上昇するということを確認した。また、乾燥されたフィルムと水和させたフィルムとの水接触角を比較すれば、水和させたフィルムの水接触角がさらに大きく低減した。従って、フィルムを水和させた条件で、添加剤の含量が増加するほど、フィルムの親水性が上昇するということを確認した。それは、機能性を有する両性イオン性作用基が、フィルムの表面に多く存在するということを示す。 In addition, the water contact angle of the film was measured, and the hydrophilicity of the film was measured. The produced film was prepared under dry conditions or under hydrated conditions for about 1 day. The prepared film was loaded on a water contact angle measuring device OCA40 (Dataphysics, Germany), 3 ml of distilled water was dropped on the film surface, and the water contact angle was measured. Repeated experiments were performed 5 times, and the average value of the water contact angles was calculated. The graph of the water contact angle calculated by the sample is shown in FIG. 6B. As shown in FIG. 6B, as the content of the additive increased, the water contact angle decreased. Therefore, it was confirmed that the hydrophilicity of the produced film increases as the content of the additive increases. Further, when the water contact angle between the dried film and the hydrated film was compared, the water contact angle of the hydrated film was further significantly reduced. Therefore, it was confirmed that the hydrophilicity of the film increases as the content of the additive increases under the condition that the film is hydrated. It indicates that there are many functional zwitterionic acting groups on the surface of the film.
併せて、Ｘ線光電子分光法（ＸＰＳ：Ｘ−ray photoelectron spectroscopy）によって製造されたフィルムの表面特性を確認した。ＰＨＩ ５０００ ＶｅｒｓａＰｒｏｂｅ（Physical Electronics、米国）にフィルムを積載し、製造されたフィルムの表面特性、構造分析、及び表面における原子間結合エネルギー（ｅＶ）を測定した。測定された結合エネルギー（ｅＶ）に対するピーク強度（ｃ／ｓ）のグラフを図６Ｃに示した。図６Ｃに示されているように、Ｓ２ｐ（硫黄原子の２ｐオービタル）は、１６６ｅＶのピークを示し、Ｎ１ｓ（窒素原子の１ｓオービタル）は、４０２ｅＶのピークを有するので、機能性を有する両性イオン性作用基が、フィルムの表面に多く存在するということを確認した。また、乾燥されたフィルムと水和されたフィルムとのピーク強度を比較した結果、水和されたフィルムのピーク強度がさらに高かった。従って、両性イオン性作用基が、乾燥フィルムに比べ、水和させたフィルムの表面にさらに多く存在し、両性イオン性作用基が、水和条件において、フィルムの表面を露出され、さらに親水性を帯びるということを確認した。 At the same time, the surface characteristics of the film produced by X-ray photoelectron spectroscopy (XPS) were confirmed. The film was loaded on a PHI 5000 VersaProbe (Physical Electronics, USA) and the surface properties, structural analysis, and interatomic binding energy (eV) of the produced film were measured. A graph of peak intensity (c / s) with respect to the measured binding energy (eV) is shown in FIG. 6C. As shown in FIG. 6C, S 2p (2p orbital of sulfur atom) shows a peak of 166 eV, and N 1s (1 s orbital of nitrogen atom) has a peak of 402 eV, so that it is a functional amphoteric. It was confirmed that many ionic action groups were present on the surface of the film. Moreover, as a result of comparing the peak intensities of the dried film and the hydrated film, the peak intensities of the hydrated film were further higher. Therefore, more zwitterionic agonists are present on the surface of the hydrated film than in the dry film, and the zwitterionic agonists expose the surface of the film under hydration conditions, making them more hydrophilic. I confirmed that it was tinged.
乾燥状態と水和状態とにおいて、フィルムのピーク強度を比較した結果、水和させたフィルムの表面の方が、さらに多くの両性イオン性作用基を表出させた。それは、水和条件において、表面に両性イオン性部分が露出され、さらに多くの親水性を示すということを確認することができる。 As a result of comparing the peak intensities of the films in the dry state and the hydrated state, more zwitterionic active groups were expressed on the surface of the hydrated film. It can be confirmed that under hydration conditions, the zwitterionic moiety is exposed on the surface and exhibits more hydrophilicity.
［５．両性イオン性ポリウレタン／金属複合体の形成］
［５．１．両性イオン性ポリウレタン／金属複合体の形成］
２．１に記載されたように、両性イオン性ポリウレタン（ＳＰＵ）を準備した。
[5. Formation of zwitterionic polyurethane / metal complex]
[5.1. Formation of zwitterionic polyurethane / metal complex]
Zwitterionic polyurethane (SPU) was prepared as described in 2.1.
ホイルで覆い包み、光を遮断した丸フラスコに、５０ｍｌの蒸溜水を加えた。そのフラスコに、０．００７５ｍｏｌのＡｇＮＯ３（Sigma−Aldrich）、０．００７５ｍｏｌのＺｎＳＯ４（Sigma−Aldrich）、０．００７５ｍｏｌのＣｕＳＯ４（Sigma−Aldrich）、及び０．００７５ｍｏｌのＣｅ（ＮＨ４）２（ＮＯ３）６（Sigma−Aldrich）を加えて溶解させた。反応物に、０．００２５ｍｏｌのＳＰＵを加え、室温で約２時間撹拌した。 50 ml of distilled water was added to a round flask covered with foil and shielded from light. In the flask, 0.0075 mol of AgNO 3 (Sigma-Aldrich), 0.0075 mol of ZnSO 4 (Sigma-Aldrich), 0.0075 mol of CuSO 4 (Sigma-Aldrich), and 0.0075 mol of Ce (NH 4 ). 2 (NO 3 ) 6 (Sigma-Aldrich) was added and dissolved. 0.0025 mol of SPU was added to the reaction product, and the mixture was stirred at room temperature for about 2 hours.
その後、アセトン（Sigma−Aldrich）溶液が入っているビーカーに反応物を入れて沈澱させた。遠心分離機を使用し、４，０００ｒｐｍ、２分間行った。上澄み液を除去し、沈んだ沈殿物をもって、３回反復して沈澱及び洗浄した。沈殿物を真空状態で一日乾燥させ、最終産物をパウダー状で得た。 Then, the reaction product was placed in a beaker containing an acetone (Sigma-Aldrich) solution and precipitated. Using a centrifuge, the operation was performed at 4,000 rpm for 2 minutes. The supernatant was removed, and the precipitated precipitate was repeatedly precipitated and washed three times. The precipitate was dried in vacuum for one day to give the final product in powder form.
その後、アセトン（Sigma−Aldrich）溶液に反応物を加えて沈澱させた。沈殿物を、約４，０００ｒｐｍの速度で約２分間遠心分離した後、上澄み液を除去し、沈殿物を得た。そのような過程を３回反復し、反応物を沈澱及び洗浄した。沈殿物を真空で一日乾燥させ、パウダー状の両性イオン性ポリウレタン金属複合体を得た。 Then, the reaction product was added to a solution of acetone (Sigma-Aldrich) and precipitated. The precipitate was centrifuged at a speed of about 4,000 rpm for about 2 minutes, and then the supernatant was removed to obtain a precipitate. Such a process was repeated 3 times to precipitate and wash the reactants. The precipitate was dried in vacuo for one day to give a powdery zwitterionic polyurethane metal complex.
［５．２．両性イオン性イソソルビドポリウレタンの金属複合体形成］
２．２に記載されたように、両性イオン性イソソルビドポリウレタン（ＳＩＰＵ）を製造した。
[5.2. Metal complex formation of zwitterionic isosorbide polyurethane]
Zwitterionic isosorbide polyurethane (SIPU) was produced as described in 2.2.
ホイルで覆い包み、光を遮断した丸フラスコに、５０ｍｌの蒸溜水を加えた。そのフラスコに、０．００７５ｍｏｌのＡｇＮＯ３（Sigma−Aldrich）、０．００７５ｍｏｌのＺｎＳＯ４（Sigma−Aldrich）、０．００７５ｍｏｌのＣｕＳＯ４（Sigma−Aldrich）、及び０．００７５ｍｏｌのＣｅ（ＮＨ４）２（ＮＯ３）６（Sigma−Aldrich）を加えて溶解させた。反応物に０．００２５ｍｏｌのＳＩＰＵを加え、室温で約２時間撹拌した。 50 ml of distilled water was added to a round flask covered with foil and shielded from light. In the flask, 0.0075 mol of AgNO 3 (Sigma-Aldrich), 0.0075 mol of ZnSO 4 (Sigma-Aldrich), 0.0075 mol of CuSO 4 (Sigma-Aldrich), and 0.0075 mol of Ce (NH 4 ). 2 (NO 3 ) 6 (Sigma-Aldrich) was added and dissolved. 0.0025 mol of SIPU was added to the reaction product, and the mixture was stirred at room temperature for about 2 hours.
その後、アセトン（Sigma−Aldrich）溶液が入っているビーカーに反応物を入れて沈澱させた。遠心分離機を使用し、４，０００ｒｐｍ、２分間行った。上澄み液を除去し、沈んだ沈殿物をもって３回反復して沈澱及び洗浄した。沈殿物を真空状態で一日乾燥させ、最終産物をパウダー状で得た。 Then, the reaction product was placed in a beaker containing an acetone (Sigma-Aldrich) solution and precipitated. Using a centrifuge, the operation was performed at 4,000 rpm for 2 minutes. The supernatant was removed, and the precipitated precipitate was repeatedly precipitated and washed 3 times. The precipitate was dried in vacuum for one day to give the final product in powder form.
その後、アセトン（Sigma−Aldrich）溶液に反応物を加えて沈澱させた。沈殿物を、約４，０００ｒｐｍの速度で約２分間遠心分離させた後、上澄み液を除去し、沈殿物を得た。そのような過程を３回反復し、反応物を沈澱及び洗浄した。沈殿物を真空で一日乾燥させ、パウダー状の両性イオン性イソソルビドポリウレタン／金属複合体を得た。 Then, the reaction product was added to a solution of acetone (Sigma-Aldrich) and precipitated. The precipitate was centrifuged at a rate of about 4,000 rpm for about 2 minutes, and then the supernatant was removed to obtain a precipitate. Such a process was repeated 3 times to precipitate and wash the reactants. The precipitate was dried in vacuo for one day to give a powdery zwitterionic isosorbide polyurethane / metal composite.
［６．両性イオン性ポリウレタンの特性確認］
［６．１．両性イオン性ポリウレタンフィルムの抗血栓効果］
４．１に記載されたように、フィルムを準備し、準備されたフィルムを１ｃｍｘ１ｃｍの大きさに切り、試料を準備した。
[6. Confirmation of characteristics of zwitterionic polyurethane]
[6.1. Antithrombotic effect of zwitterionic polyurethane film]
As described in 4.1, the film was prepared, the prepared film was cut to a size of 1 cm x 1 cm, and a sample was prepared.
準備されたフィルムを、２４ウェル（well）プレートの各ウェルに加えた。該フィルムをリン酸塩緩衝塩水（ＰＢＳ：phosphate-buffered saline）に浸漬し、約３７℃の温度で約２時間維持した。ＰＢＳを除去し、各ウェルに、１ｍｇ／ｍｌの牛血清アルブミン（ＢＳＡ：bovine serum albumin）（Sigma−Aldrich）、または０．１ｍｇ／ｍｌのフィブリノーゲン（fibrinogen，Sigma−Aldrich）を１ｍｌずつ加えた。プレートを、約３０ｒｐｍの速度で撹拌しながら、約１時間維持した。その後、ＢＳＡまたはフィブリノーゲン溶液を除去し、フィルムを、ＰＢＳで４ないし５回反復して洗浄した。各ウェルに、１ｍｌの２ｗ％ドデシル硫酸ナトリウム（ＳＤＳ）溶液を加え、室温で約３０ｒｐｍの速度で、約１時間撹拌した。その後、マイクロＢＣＡ溶液とＳＤＳ反応物とを１：１比率で混合し、９６ウェルプレートで、約３７℃の温度で約３０ｒｐｍの速度で撹拌しながら、約２時間維持した。ＵＶ検出器を使用し、５６２ｎｍの波長で、反応物の吸光度を測定し、測定された吸光度から、タンパク質を定量した。フィルムに吸着されたタンパク質の量を、図７Ａ及び図７Ｂに示した（図７Ａ：ＢＳＡ、図７Ｂ：フィブリノーゲン）。 The prepared film was added to each well of a 24-well plate. The film was immersed in phosphate-buffered saline (PBS) and maintained at a temperature of about 37 ° C. for about 2 hours. PBS was removed and 1 mg / ml bovine serum albumin (BSA) (Sigma-Aldrich) or 0.1 mg / ml fibrinogen (Sigma-Aldrich) was added to each well. The plate was maintained for about 1 hour with stirring at a rate of about 30 rpm. The BSA or fibrinogen solution was then removed and the film was washed with PBS 4-5 times repeatedly. To each well, 1 ml of 2 w% sodium dodecyl sulfate (SDS) solution was added and stirred at room temperature at a rate of about 30 rpm for about 1 hour. Then, the micro BCA solution and the SDS reaction were mixed at a ratio of 1: 1 and maintained on a 96-well plate at a temperature of about 37 ° C. at a rate of about 30 rpm for about 2 hours. Using a UV detector, the absorbance of the reactants was measured at a wavelength of 562 nm and the protein was quantified from the measured absorbance. The amount of protein adsorbed on the film is shown in FIGS. 7A and 7B (FIG. 7A: BSA, FIG. 7B: fibrinogen).
図７Ａ及び図７Ｂに示されているように、フィルムに吸着されたタンパク質の量は、両性イオン性ポリウレタン含量が少ないフィルムに比べ、両性イオン性ポリウレタンの含量が多いフィルムで減少した。従って、両性イオン性ポリウレタンの含量が多いフィルムは、タンパク質の吸着抑制効果があり、それにより、吸着防止効果だけではなく、抗血栓効果があるということを確認した。 As shown in FIGS. 7A and 7B, the amount of protein adsorbed on the film was reduced in the film with a high content of zwitterionic polyurethane compared to the film with a low content of zwitterionic polyurethane. Therefore, it was confirmed that the film having a high content of zwitterionic polyurethane has an effect of suppressing protein adsorption, and thereby has an antithrombotic effect as well as an effect of preventing adsorption.
［６．２．両性イオン性ポリウレタンの抗菌効果］
５．１及び５．２に記載されたように、両性イオン性ポリウレタン／金属複合体を製造した。
[6.2. Antibacterial effect of zwitterionic polyurethane]
Zwitterionic polyurethane / metal complexes were produced as described in 5.1 and 5.2.
グラム陽性菌である黄色ブドウ球菌（Staphylococcus aureus、ＡＴＣＣ１４４５８）、表皮ブドウ球菌（Staphylococcus epidermidis、ＡＴＣＣ１２２２８）と、グラム陰性菌である大膓菌（Escherichia coli、ＡＴＣＣ１１７７５）、緑膿菌（Pseudomonas aeruginosa、ＡＴＣＣ９０２７）とを準備した。各細菌別に、塩類溶液で菌を作り、寒天固体培地に各細菌を塗抹した。その後、細菌が塗抹された固体培地に、両性イオン性ポリウレタン／金属複合体を薬さじで載せ、約１８時間３７℃で培養した。 Gram-positive Staphylococcus aureus (ATCC14458), Staphylococcus epidermidis (ATCC12228), and Gram-negative Escherichia coli (ATCC11775), Pseudomonas aeruginosa (ATCC9027) And prepared. For each bacterium, a bacterium was prepared with a salt solution, and each bacterium was smeared on an agar solid medium. Then, the zwitterionic polyurethane / metal complex was placed on a solid medium smeared with bacteria with a spatula and cultured at 37 ° C. for about 18 hours.
細菌のゾーン（zone）形成抑制程度を肉眼で観察し、そのイメージを図８に示した。図８に示されているように、クエン酸末端両性イオン性ポリウレタン（ＣＳＰＵ）とクエン酸末端両性イオン性イソソルビドポリウレタン（ＣＳＩＰＵ）とにおいて、細菌のゾーン形成が観察された。従って、ＣＳＰＵ及びＣＳＩＰＵは、微生物の増殖を抑制するか、あるいは殺菌して抗菌効果があると確認された。 The degree of suppression of bacterial zone formation was observed with the naked eye, and the image is shown in FIG. As shown in FIG. 8, bacterial zone formation was observed in the citrate-terminated zwitterionic polyurethane (CSPU) and the citrate-terminated zwitterionic isosorbide polyurethane (CSIPU). Therefore, it was confirmed that CSPU and CSIPU have an antibacterial effect by suppressing the growth of microorganisms or by sterilizing them.
Claims (22)
前記高分子化合物は、１以上の末端に、ハロゲン原子で置換されたＣ１−Ｃ３０アルキル基、カルボキシ基、またはそれらの組み合わせを含むことを特徴とする高分子化合物：
化学式１で、Ｒ１は、置換もしくは非置換のＣ１−Ｃ３０アルキレン基、置換もしくは非置換のＣ２−Ｃ３０アルケニレン基、置換もしくは非置換のＣ２−Ｃ３０アルキニレン基、置換もしくは非置換のＣ６−Ｃ３０アリーレン基、置換もしくは非置換のＣ６−Ｃ３０ヘテロアリーレン基、置換もしくは非置換のＣ５−Ｃ２０芳香族環基、置換もしくは非置換のＣ３−Ｃ３０環状基、置換もしくは非置換のＣ３−Ｃ２０ヘテロ環状基、またはそれらの組み合わせであり、
ｘは、１ないし１００の整数である；
化学式２で、Ｒ２は、置換もしくは非置換のＣ１−Ｃ３０アルキル基、置換もしくは非置換のＣ２−Ｃ３０アルケニル基、置換もしくは非置換のＣ２−Ｃ３０アルキニル基、置換もしくは非置換のＣ６−Ｃ３０アリール基、置換もしくは非置換のＣ６−Ｃ３０ヘテロアリール基、置換もしくは非置換のＣ５−Ｃ２０芳香族環基、置換もしくは非置換のＣ３−Ｃ３０環状基、置換もしくは非置換のＣ３−Ｃ２０ヘテロ環状基、またはそれらの組み合わせであり、
Ｒ３は置換もしくは非置換のＣ１−Ｃ３０アルキレン基、置換もしくは非置換のＣ２−Ｃ３０アルケニレン基、置換もしくは非置換のＣ２−Ｃ３０アルキニレン基、置換もしくは非置換のＣ６−Ｃ３０アリーレン基、置換もしくは非置換のＣ６−Ｃ３０ヘテロアリーレン基、置換もしくは非置換のＣ５−Ｃ２０芳香族環基、置換もしくは非置換のＣ３−Ｃ３０環状基、置換もしくは非置換のＣ３−Ｃ２０ヘテロ環状基、またはそれらの組み合わせであり、
Ａは、−ＣＯ２、−ＳＯ３、−ＰＯ３、置換のＣ１−Ｃ３０アルキル基、またはそれらの組み合わせであり、前記アルキル基は、ハロゲン原子でも置換され、
Ｍは、金属原子であり、
ｙは、１ないし１００の整数である。 A polymer compound containing a copolymer containing the repeating units of Chemical Formula 1 and Chemical Formula 2.
The polymer compound, the one or more terminal, C 1 -C 30 alkyl group substituted with a halogen atom, a carboxy group or a polymer compound characterized in that it comprises a combination thereof:
In Formula 1, R 1 is a substituted or unsubstituted C 1 -C 30 alkylene group, a substituted or unsubstituted C 2 -C 30 alkenylene group, a substituted or unsubstituted C 2 -C 30 alkynylene group, a substituted or unsubstituted Substituted C 6- C 30 arylene group, substituted or unsubstituted C 6- C 30 heteroarylene group, substituted or unsubstituted C 5- C 20 aromatic ring group, substituted or unsubstituted C 3- C 30 cyclic Group, substituted or unsubstituted C 3- C 20 heterocyclic group, or a combination thereof.
x is an integer from 1 to 100;
In Chemical Formula 2, R 2 is a substituted or unsubstituted C 1- C 30 alkyl group, a substituted or unsubstituted C 2- C 30 alkenyl group, a substituted or unsubstituted C 2- C 30 alkynyl group, a substituted or unsubstituted C 2-C 30 alkynyl group. Substituted C 6- C 30 aryl group, substituted or unsubstituted C 6- C 30 heteroaryl group, substituted or unsubstituted C 5- C 20 aromatic ring group, substituted or unsubstituted C 3- C 30 cyclic Group, substituted or unsubstituted C 3- C 20 heterocyclic group, or a combination thereof.
R 3 is a substituted or unsubstituted C 1- C 30 alkylene group, a substituted or unsubstituted C 2- C 30 alkenylene group, a substituted or unsubstituted C 2- C 30 alkynylene group, a substituted or unsubstituted C 6- C 30 arylene group, substituted or unsubstituted C 6- C 30 heteroarylene group, substituted or unsubstituted C 5- C 20 aromatic ring group, substituted or unsubstituted C 3- C 30 cyclic group, substituted or unsubstituted. Substituted C 3- C 20 heterocyclic group, or a combination thereof,
A is, -CO 2, -SO 3, -PO 3, a C 1 -C 30 alkyl group, or a combination thereof, of substitution, the alkyl group may be substituted with a halogen atom,
M is a metal atom
y is an integer from 1 to 100.
化学式３で、Ｒ４は、置換もしくは非置換のＣ１−Ｃ３０アルキレン基、置換もしくは非置換のＣ２−Ｃ３０アルケニレン基、置換もしくは非置換のＣ２−Ｃ３０アルキニレン基、置換もしくは非置換のＣ６−Ｃ３０アリーレン基、置換もしくは非置換のＣ６−Ｃ３０ヘテロアリーレン基、置換もしくは非置換のＣ３−Ｃ３０環状基、置換もしくは非置換のＣ３−Ｃ２０ヘテロ環状基、またはそれらの組み合わせであり、
前記ヘテロアリーレン基またはヘテロ環状基は、Ｎ、Ｏ及びＳからなる群から選択された１以上の異種原子を含むものであり、
ｚは、１ないし１００の整数である。 The polymeric compound of claim 1, further comprising a repeating unit of formula 3.
In Formula 3, R 4 is a substituted or unsubstituted C 1 -C 30 alkylene group, a substituted or unsubstituted C 2 -C 30 alkenylene group, a substituted or unsubstituted C 2 -C 30 alkynylene group, a substituted or unsubstituted Substituted C 6- C 30 arylene group, substituted or unsubstituted C 6- C 30 heteroarylene group, substituted or unsubstituted C 3- C 30 cyclic group, substituted or unsubstituted C 3- C 20 heterocyclic group. , Or a combination of them,
The heteroarylene group or heterocyclic group contains one or more heteroatoms selected from the group consisting of N, O and S.
z is an integer from 1 to 100.
前記ヘテロアリーレン基またはヘテロ環状基は、Ｎ、Ｏ及びＳからなる群から選択された１以上の異種原子を含むことを特徴とする請求項２に記載の高分子化合物。 The R 4 is a substituted or unsubstituted C 1- C 30 alkylene group, a substituted or unsubstituted C 6- C 30 arylene group, a substituted or unsubstituted C 6- C 30 heteroarylene group, a substituted or unsubstituted C 6-C 30 arylene group. A C 3- C 30 cyclic group, a substituted or unsubstituted C 3- C 20 heterocyclic group, or a combination thereof.
The polymer compound according to claim 2, wherein the heteroarylene group or heterocyclic group contains one or more heteroatoms selected from the group consisting of N, O and S.
得られた両性イオン性ジオール化合物とジイソシアネート化合物とを重合し、両性イオン性ポリウレタン重合体を生成する段階と、
得られた両性イオン性ポリウレタン重合体を、ハロゲン原子で置換されたＣ１−Ｃ３０アルキル基、カルボン酸、またはそれらの組み合わせでキャッピングする段階と、を含む高分子化合物を製造する方法。 A step of reacting a substituted or unsubstituted diethanolamine with either propane sultone or butane sultone to produce an amphoteric ionic diol compound.
At the stage of polymerizing the obtained zwitterionic diol compound and diisocyanate compound to produce a zwitterionic polyurethane polymer,
The resulting zwitterionic polyurethane polymer, C 1 -C 30 alkyl group substituted with a halogen atom, a carboxylic acid or a method of producing a polymer comprising the steps, a to cap a combination thereof.
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