JPH0428705A - Hydrogel for medical use - Google Patents
Hydrogel for medical useInfo
- Publication number
- JPH0428705A JPH0428705A JP2131241A JP13124190A JPH0428705A JP H0428705 A JPH0428705 A JP H0428705A JP 2131241 A JP2131241 A JP 2131241A JP 13124190 A JP13124190 A JP 13124190A JP H0428705 A JPH0428705 A JP H0428705A
- Authority
- JP
- Japan
- Prior art keywords
- group
- alkyl group
- carbon atoms
- tables
- coor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000017 hydrogel Substances 0.000 title claims abstract description 19
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 19
- 239000000178 monomer Substances 0.000 claims abstract description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
- 238000007334 copolymerization reaction Methods 0.000 claims abstract description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 4
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 4
- 238000010894 electron beam technology Methods 0.000 claims 1
- 125000004185 ester group Chemical group 0.000 claims 1
- 230000005251 gamma ray Effects 0.000 claims 1
- GCRIIVPDNWHODP-UHFFFAOYSA-N 2-(2-oxopyrrolidin-1-yl)ethyl prop-2-enoate Chemical compound C=CC(=O)OCCN1CCCC1=O GCRIIVPDNWHODP-UHFFFAOYSA-N 0.000 abstract description 2
- 239000000499 gel Substances 0.000 abstract description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 229920001577 copolymer Polymers 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- -1 Poly(N-vinylpyrrolidone) Polymers 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 229920001519 homopolymer Polymers 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 210000000695 crystalline len Anatomy 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 150000002148 esters Chemical group 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- VAMFXQBUQXONLZ-UHFFFAOYSA-N n-alpha-eicosene Natural products CCCCCCCCCCCCCCCCCCC=C VAMFXQBUQXONLZ-UHFFFAOYSA-N 0.000 description 2
- 229920005604 random copolymer Polymers 0.000 description 2
- 229940106006 1-eicosene Drugs 0.000 description 1
- FIKTURVKRGQNQD-UHFFFAOYSA-N 1-eicosene Natural products CCCCCCCCCCCCCCCCCC=CC(O)=O FIKTURVKRGQNQD-UHFFFAOYSA-N 0.000 description 1
- XMNIXWIUMCBBBL-UHFFFAOYSA-N 2-(2-phenylpropan-2-ylperoxy)propan-2-ylbenzene Chemical compound C=1C=CC=CC=1C(C)(C)OOC(C)(C)C1=CC=CC=C1 XMNIXWIUMCBBBL-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- YIVJZNGAASQVEM-UHFFFAOYSA-N Lauroyl peroxide Chemical compound CCCCCCCCCCCC(=O)OOC(=O)CCCCCCCCCCC YIVJZNGAASQVEM-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 239000003082 abrasive agent Substances 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000002473 artificial blood Substances 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 210000004195 gingiva Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 229940088644 n,n-dimethylacrylamide Drugs 0.000 description 1
- YLGYACDQVQQZSW-UHFFFAOYSA-N n,n-dimethylprop-2-enamide Chemical compound CN(C)C(=O)C=C YLGYACDQVQQZSW-UHFFFAOYSA-N 0.000 description 1
- WDFKEEALECCKTJ-UHFFFAOYSA-N n-propylprop-2-enamide Chemical compound CCCNC(=O)C=C WDFKEEALECCKTJ-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000003505 polymerization initiator Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- BWJUFXUULUEGMA-UHFFFAOYSA-N propan-2-yl propan-2-yloxycarbonyloxy carbonate Chemical compound CC(C)OC(=O)OOC(=O)OC(C)C BWJUFXUULUEGMA-UHFFFAOYSA-N 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000007870 radical polymerization initiator Substances 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Materials For Medical Uses (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、生体適合性に優れた医療用ヒドロゲルに関す
るものである。詳しく述へると、熱応答ゲル、コンタク
トレンズ、人工水晶体、人工血管、人工皮膚、抗血栓性
材料、医療用基材の表面親水化なとに用いることができ
る生体適合性に優れた医療用ヒドロゲルに関するもので
ある。DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a medical hydrogel with excellent biocompatibility. In detail, it is a medical product with excellent biocompatibility that can be used for heat-responsive gels, contact lenses, artificial crystalline lenses, artificial blood vessels, artificial skin, antithrombotic materials, and surface hydrophilization of medical base materials. It concerns hydrogels.
（従来の技術）
従来、医療用ヒドロゲルに用いられる材料としては、セ
ルロース、コラ−ケン、セラチン、ポリビニルアルコー
ルおよびアクリル系の祠料では、ポリ−２−ヒドロキシ
エチル（メタ）アクリレ−１・で代表されるヒドロキシ
アルキル（メタ）アクリレート系共重体、Ｎ−イソプロ
ピル（メタ）アクリルアミド、Ｎ−ｎ−プロピルアクリ
ルアミド、Ｎ、Ｎ−ジメチルアクリルアミド等のアクリ
ルアミド系重合体か知られている（特開昭５８−１７４
、．４０８す、特開昭５８−１７９，２５６舅、特開平
１−１２９，００８可等）。しかしながら、これらは生
体適合性か未だ不充分である。(Prior art) Conventionally, materials used for medical hydrogels include cellulose, Kolaken, Seratin, polyvinyl alcohol, and acrylic abrasive materials such as poly-2-hydroxyethyl (meth)acrylate-1. Acrylamide polymers such as hydroxyalkyl (meth)acrylate copolymers, N-isopropyl (meth)acrylamide, N-n-propylacrylamide, N,N-dimethylacrylamide, etc. 174
,． 408, JP-A-58-179,256, JP-A-1-129,008, etc.). However, their biocompatibility is still insufficient.
−／１７、ピロリドン環をｈするポリマーとしてはポリ
（Ｎ−ビニルピロリドン）およびこれとの共重合体や
ブレンド体（特開昭５１−５５，３５１号等）か知られ
ているが、Ｎ−ビニルピロリドン単量体の共重合性や生
体適合性が不充分で、ｌシ足できるヒドロケルは得られ
ていない。-/17, Poly(N-vinylpyrrolidone) and copolymers and blends thereof (JP-A No. 51-55,351, etc.) are known as polymers with a pyrrolidone ring. The copolymerizability and biocompatibility of the vinylpyrrolidone monomer are insufficient, and a sufficient hydrokel has not been obtained.
本発明で用いたＮ−２−メタクリロイルオキシエチル−
２−ピロリドン系重合体としては、ンリコーンとの共重
合体（ＷＯ８２１０３３９７）、１．３−ブタジェンと
のＪＩ−Ｉ′１１′合体（西独特許公開第２，０４８，
３１２弓）、１−エイコセンとの共重合体（英国特許第
１．１０１．１６３す）等が知られている。しかしなか
ら、これらの共重合体についても未たｌ工足すべき生体
適合性は得られていない。N-2-methacryloyloxyethyl used in the present invention
Examples of 2-pyrrolidone-based polymers include a copolymer with licone (WO82103397), a JI-I'11' polymer with 1,3-butadiene (West German Patent Publication No. 2,048,
312), a copolymer with 1-eicosene (British Patent No. 1.101.163), etc. are known. However, these copolymers have not yet achieved biocompatibility that should be improved.
（発明か解決しようとする課題）
したかって、本発明の目的は、生体適合性に優れた医療
用ヒドロゲルを提供することにある。(Problems to be Solved by the Invention) Therefore, an object of the present invention is to provide a medical hydrogel with excellent biocompatibility.
（３題を解決するための手段）
これらの諸口的は、Ｎ−２−メタクリロイルオキシエチ
ル−２−ピロリドンおよび／またはＮ−アクリロイルオ
キシエチル−２−ピロリドンを物理手段および／または
金属をＳ白°しないＧ機単量体との共重合により水不可
／８溶化した医療用ヒドロケルにより達成される。(Means for Solving the 3 Problems) These various methods include N-2-methacryloyloxyethyl-2-pyrrolidone and/or N-acryloyloxyethyl-2-pyrrolidone by physical means and/or metal by S white. This is achieved by a medical hydrokel that is made water-impossible/8-solubilized by copolymerization with a G monomer that does not contain water.
本発明はまた、有機単量体か一般式■
ＣＨ２＝ＣＲＩ
（Ｉ）
［ただし、Ｒ１は水素またはメチル基、Ｘはまたはハロ
ケン） 、−ＣＮ、−Ｃρまたは−Ｃ００Ｒ４（Ｒ４は
炭素数か１〜１６のアルキル基またはアルキル基の水素
が二重結合を含釘するエスチル残基で置換されたもの、
フェニル基またはフェニレン基である］て表わされる医
療用ヒドロゲルである。本発明はさらに、一般式■
［ただし、式中Ｒ１およびＲ２は水素またはメチアルキ
ル基またはハロゲン）または−ＣＯＯＲ４（Ｒ４は炭素
数が１〜１６のアルキル基、フェニル基またはフェニレ
ン基）であり、かつ２／８くｍ ／ ｎ ＜ ７ ／
３であるコで表わされる医療用ヒドロゲルである１本発
明はまた、一般式■［ただし、式中、Ｒ１およびＲ２は
水素またはメのアルキル基またはハロゲン）または−Ｃ
ＯＯＲ４（Ｒ４は炭素数か１〜１６のアルキル基、フェ
ニル基またはフェニレン基）であり、かつｍ／ｎ≦２／
８である）］で表わされる共重合体または単独重合体を
γ線照射、電子線照射等の物的手段、多官能の架橋性単
量体との共重合、プラズマ法等による表面グラフト反応
のいずれか一つの方法により耐水性を付与した医療用ヒ
ドロゲルである。The present invention also provides organic monomers having the general formula (1) CH2=CRI (I) [wherein R1 is hydrogen or methyl group, ~16 alkyl groups or those in which the hydrogen of the alkyl group is replaced with an ester residue containing a double bond,
It is a medical hydrogel represented by a phenyl group or a phenylene group. The present invention further provides a general formula (1) in which R1 and R2 are hydrogen, methylalkyl group, or halogen) or -COOR4 (R4 is an alkyl group having 1 to 16 carbon atoms, a phenyl group, or a phenylene group), and 2/8 km / n < 7 /
1, which is a medical hydrogel represented by
OOR4 (R4 is an alkyl group having 1 to 16 carbon atoms, a phenyl group, or a phenylene group), and m/n≦2/
The copolymer or homopolymer represented by This is a medical hydrogel that has been made water resistant by any one of these methods.
本発明はさらに、一般式ＩＩにおけるＸが−ＣＯＯＲ４
（ただし、式中、Ｒ４は炭素数か１〜１６のアルキル基
、フェニル基またはフェニレン基である）である医療用
ヒドロゲルである。本発明はまた一般式ＩＩＩにおける
Ｘが−ＣＯＯＲ４（ただし、式中、Ｒ４は炭素数が１〜
１６のアルキル基、フェニル基またはフェニレン基であ
る）である医療用トビロゲルである。The present invention further provides that X in general formula II is -COOR4
(In the formula, R4 is an alkyl group having 1 to 16 carbon atoms, a phenyl group, or a phenylene group.) The present invention also provides that X in the general formula III is -COOR4 (wherein R4 has 1 to 1 carbon atoms)
16 alkyl group, phenyl group or phenylene group).
（作用）
生体適合性に優れた医療用ヒドロケルは、前記のごとく
、Ｎ−２−（メタ）アクリロイルオキシエチル−２−ピ
ロリドンを物理的手段および／または金属をａｉｌ′１
−シない有機単量体との３Ｆ：重合により水不溶化した
ものである。特に、前記一般式■または■で表わされる
ランダム共重合体または単独重合体を架橋不溶化あるい
はグラフト反応させてなるものである。(Function) As mentioned above, medical hydrokels with excellent biocompatibility are produced by preparing N-2-(meth)acryloyloxyethyl-2-pyrrolidone by physical means and/or by ail'1 metal.
- 3F with a free organic monomer: It is made insoluble in water by polymerization. In particular, it is made by subjecting a random copolymer or homopolymer represented by the general formula (1) or (2) above to crosslinking and insolubilization or grafting reaction.
ランダム共重合体の組成比は、２／８＜ｍ／ｎく７／３
が好ましい。ｍ／ｎ≧７／３でｍが過剰であると、親水
性が減少して生体適合性が低下し、一方、ｍ／ｎ≦２／
８であると、得られる共重合体または単独重合体は水溶
性となるためである。The composition ratio of the random copolymer is 2/8<m/n 7/3
is preferred. When m/n≧7/3 and m is excessive, hydrophilicity decreases and biocompatibility decreases, while m/n≦2/
This is because when it is 8, the obtained copolymer or homopolymer becomes water-soluble.
したがって、ｍ／ｎ≦２／８のときは、物理的手段、多
官能の架橋性単量体との共重合または疎水性単量体をク
ラフト反応させることにより不溶化して用いることが必
須となる。Therefore, when m/n≦2/8, it is essential to use it after making it insolubilized by physical means, copolymerization with a polyfunctional crosslinking monomer, or craft reaction with a hydrophobic monomer. .
本発明により得られる２ ／ ８ ＜ ｍ ／ ｎ ＜
７ ／ ３の非架橋の水不溶性ヒドロゲルは、クロロ
ホルム、ジメチルホルムアミド、アセトン、テトラヒド
ロフラン、ｌ！ＩＩ酸エチル等に可溶であるか、水、ｎ
ヘキサン、エーテル等に不溶である。また、得られたヒ
ドロゲルは、細胞毒性が低いために生体適合性か極めて
良好である。2/8<m/n<obtained by the present invention
The 7/3 non-crosslinked water-insoluble hydrogel contains chloroform, dimethylformamide, acetone, tetrahydrofuran, l! Is soluble in ethyl II acid etc., water, n
Insoluble in hexane, ether, etc. Furthermore, the obtained hydrogel has very good biocompatibility due to its low cytotoxicity.
このようなヒドロケルは、例えは一般式■［ただし、Ｒ
１は水素またはメチル基、Ｘかまたはハロケン） 、−
ＣＮ、ＣＤまたは−Ｃ００Ｒ４（Ｒ４は炭素数か１〜１
６のアルキル基またはアルキル基の水素か二重結合をＳ
白°するエステル残基て置換されたもの、フェニル基ま
たはフェニレン基であり］て表わされる共重合性単量体
、特にＸか−ＣＯＯＲ４（Ｒ４は前記のとおり）である
（メタ）アクリレートとＮ−２−（メタ）アクリロイル
オキシエチル−２−ピロリドンとを２／８を越えかつ７
／３未ｌ工のモル比て共重合させることにより得られる
。反応は、０機溶媒の存在下または不存在下に、ラジカ
ル重合開始剤を用いて２０〜１００℃、好ましくは３０
〜８０℃の温度で１〜２０時間、好ましくは２〜１０時
間行なわれる。通常、１機溶媒中で反応を行なうことが
好ましい。０機溶媒としては、例えば、クロロホルム、
ジメチルホルムアミド、アセトン等かある。Such a hydrokel, for example, has the general formula ■ [where R
1 is hydrogen or methyl group, X or haloken), -
CN, CD or -C00R4 (R4 is the number of carbon atoms or 1 to 1
The alkyl group of 6 or the hydrogen or double bond of the alkyl group is S
A copolymerizable monomer represented by a phenyl group or a phenylene group substituted with a white ester residue, in particular a (meth)acrylate represented by X or -COOR4 (R4 is as above) and N -2-(meth)acryloyloxyethyl-2-pyrrolidone and more than 2/8 and 7
It can be obtained by copolymerizing at a molar ratio of /3%. The reaction is carried out using a radical polymerization initiator in the presence or absence of a solvent at 20 to 100°C, preferably 30°C.
It is carried out at a temperature of ~80°C for 1 to 20 hours, preferably 2 to 10 hours. Usually, it is preferable to carry out the reaction in one solvent. Examples of solvents include chloroform,
Dimethylformamide, acetone, etc.
重合開始剤としては、例えは、アゾビスイソブチロニト
リル、ラウロイルパーオキサイド、ベンゾイルパーオキ
サイド、ジクミルパーオキサイド、ジイソプロピルパー
オキシジカーボネート等がある。Examples of the polymerization initiator include azobisisobutyronitrile, lauroyl peroxide, benzoyl peroxide, dicumyl peroxide, and diisopropyl peroxydicarbonate.
（実施例）
つきに、実施例を上げて本発明をさらに詳細に説明する
。(Example) The present invention will now be described in more detail with reference to Examples.
実施例１〜９
第１表に示す組成の単量体および０．５モル％濃度のア
ゾビスイソブチロニトリルをクロロホルム１０ｍ１に溶
解させ、窒素置換後、ガラス封管中で６０°の温度で３
〜５時間市合を行なった。開管後、エーテルで再沈澱し
て重合体を取出した。Examples 1 to 9 Monomers having the compositions shown in Table 1 and azobisisobutyronitrile at a concentration of 0.5 mol% were dissolved in 10 ml of chloroform, and after purging with nitrogen, the mixture was heated at a temperature of 60° in a glass sealed tube. 3
The market was held for ~5 hours. After opening the tube, the polymer was recovered by reprecipitation with ether.
共重合体（ヒドロゲル）の組成は、元素分析および赤外
線吸収スペクトルから決定した。その結果を、第１表に
示す。The composition of the copolymer (hydrogel) was determined from elemental analysis and infrared absorption spectrum. The results are shown in Table 1.
上記実施例１〜６のヒドロケルのクロロホルム／８液（
濃度１０重量％）を、組織培養用プラスチツクシート（
和光純薬株式会社製）にコーチインクし、乾燥したシー
トをシャーレに入れ、２０％の仔牛血清をＳむ細胞浮汲
液（ヒト歯肉由来のト皮性の株化細胞Ｃａ、９．２２）
をまいてからシャーレをポリテトラフルオロエチレンチ
ーブてンールし、３７℃の恒温器中で培養した。３０秒
間に０．１秒の割合で細胞を撮影し、ＶＴＲに録画した
。３〜７０間培養したのち、ＶＴＲを再生して細胞の様
子を観察した。その結果は、いずれも生体Ｊ１！！ｉ合
性であることを示した。Hydrokel chloroform/8 solution of Examples 1 to 6 above (
10% by weight) on a tissue culture plastic sheet (
Coat the sheet with coach ink (manufactured by Wako Pure Chemical Industries, Ltd.), place the dried sheet in a petri dish, and add 20% calf serum to make a cell suspension (human gingiva-derived skin cell line Ca, 9.22).
After sowing, the petri dish was filled with polytetrafluoroethylene and cultured in a thermostat at 37°C. Cells were photographed at a rate of 0.1 seconds over 30 seconds and recorded on a VTR. After culturing for 3 to 70 minutes, the state of the cells was observed by playing the VTR. The results were all biological J1! ! It was shown that it was compatible with i.
（発明の効果）
以ｌ一連へたように、本発明は、Ｎ−２−（メタ）アク
リロイルオキシエチル−２−ピロリドンを物理的手段お
よび／または金属を含有しない有機単量体との共重合に
より水不溶化してなる医療用ヒドロゲルであるから、細
胞の付着性か良好でかつ生体適合性が良好で、しかもペ
ンダント基としてのピロリドン環のために、ヨード、フ
ェノール、各種薬剤との相互作用にも優れているので、
医用
材料として極めて白゛用である。(Effects of the Invention) As described above, the present invention provides a method for copolymerizing N-2-(meth)acryloyloxyethyl-2-pyrrolidone by physical means and/or with a metal-free organic monomer. Because it is a medical hydrogel made by water insolubilization, it has good cell adhesion and biocompatibility, and because of the pyrrolidone ring as a pendant group, it is resistant to interactions with iodine, phenol, and various drugs. is also excellent, so
It is extremely useful as a medical material.
Claims (6)
リドンおよび／またはＮ−アクリロイルオキシエチル−
２−ピロリドンを物理手段および／または金属を含有し
ない有機単量体との共重合により水不可溶溶化した医療
用ヒドロゲル。(1) N-2-methacryloyloxyethyl-2-pyrrolidone and/or N-acryloyloxyethyl-
A medical hydrogel in which 2-pyrrolidone is made insoluble in water by physical means and/or copolymerization with a metal-free organic monomer.
化学式、表等があります▼（Ｒ＾３は炭素数が１〜４の
アルキル基、またはハロゲン）、−ＣＮ、−Ｃｌまたは
−ＣＯＯＲ＾４（Ｒ＾４は炭素数が１〜１６のアルキル
基またはアルキル基の水素が二重結合を含有するエステ
ル残基で置換されたもの、フェニル基またはフェニレン
基である］で表わされる請求項１に記載の医療用ヒドロ
ゲル。(2) The organic monomer has the general formula I ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [However, R^1 is hydrogen or methyl group, X is ▲mathematical formula,
There are chemical formulas, tables, etc. ▼ (R^3 is an alkyl group with 1 to 4 carbon atoms, or halogen), -CN, -Cl, or -COOR^4 (R^4 is an alkyl group with 1 to 16 carbon atoms) The medical hydrogel according to claim 1, wherein hydrogen of an alkyl group is substituted with an ester residue containing a double bond, a phenyl group, or a phenylene group.
基、Ｘは▲数式、化学式、表等があります▼（Ｒ＾３は
炭素数が１〜４のアルキル基またはハロゲン）または−
ＣＯＯＲ＾４（Ｒ＾４は炭素数が１〜１６のアルキル基
、フェニル基またはフェニレン基）であり、かつ２／８
＜ｍ／ｎ＜７／３である］で表わされる請求項１または
２に記載の医療用ヒドロゲル。(3) General formula II ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (II) [However, in the formula, R^1 and R^2 are hydrogen or methyl groups, and X is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ( R^3 is an alkyl group having 1 to 4 carbon atoms or halogen) or -
COOR^4 (R^4 is an alkyl group having 1 to 16 carbon atoms, a phenyl group, or a phenylene group), and 2/8
<m/n<7/3] The medical hydrogel according to claim 1 or 2.
ル基、Ｘは▲数式、化学式、表等があります▼（Ｒ＾３
は炭素数が１〜４のアルキル基またはハロゲン）または
−ＣＯＯＲ＾４（Ｒ＾４は炭素数が１〜１６のアルキル
基、フェニル基またはフェニレン基であり、かつｍ／ｎ
≦２／８である）］で表わされる共重合体または単独重
合体をγ線照射、電子線照射等の物的手段、多官能の架
橋性単量体との共重合、プラズマ法等による表面グラフ
ト反応のいずれか一つの方法により耐水性を付与した請
求項１または２に記載の医療用ヒドロゲル。(4) General formula III ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (III) [However, in the formula, R^1 and R^2 are hydrogen or methyl groups, and X is ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (R^3
is an alkyl group having 1 to 4 carbon atoms or halogen) or -COOR^4 (R^4 is an alkyl group having 1 to 16 carbon atoms, a phenyl group, or a phenylene group, and m/n
≦2/8)] by physical means such as γ-ray irradiation, electron beam irradiation, copolymerization with a polyfunctional crosslinkable monomer, plasma method, etc. The medical hydrogel according to claim 1 or 2, which has been imparted with water resistance by any one of graft reactions.
式中、Ｒ＾４は炭素数が１〜１６のアルキル基、フェニ
ル基またはフェニレン基である）である請求項３に記載
の医療用ヒドロゲル。(5) X in general formula II is -COOR^4 (however,
4. The medical hydrogel according to claim 3, wherein R^4 is an alkyl group having 1 to 16 carbon atoms, a phenyl group, or a phenylene group.
、式中、Ｒ＾４は炭素数が１〜１６のアルキル基、フェ
ニル基またはフェニレン基である）である請求項４に記
載の医療用ヒドロゲル。(6) The medical treatment according to claim 4, wherein X in general formula III is -COOR^4 (wherein R^4 is an alkyl group having 1 to 16 carbon atoms, a phenyl group, or a phenylene group) Hydrogel for use.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2131241A JPH0428705A (en) | 1990-05-23 | 1990-05-23 | Hydrogel for medical use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2131241A JPH0428705A (en) | 1990-05-23 | 1990-05-23 | Hydrogel for medical use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0428705A true JPH0428705A (en) | 1992-01-31 |
Family
ID=15053306
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2131241A Pending JPH0428705A (en) | 1990-05-23 | 1990-05-23 | Hydrogel for medical use |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0428705A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6132462A (en) * | 1995-12-22 | 2000-10-17 | Santen Pharmaceutical Co., Ltd. | Copolymers formed from three components and intraocular lenses made thereof |
| US6268511B1 (en) | 1997-06-05 | 2001-07-31 | Santen Pharmaceutical Co., Ltd. | Itaconate derivatives used for a component of a polymer |
| US6465588B1 (en) | 1997-10-07 | 2002-10-15 | Santen Pharmaceutical Co., Ltd. | Four component copolymers and the ocular lens made thereof |
| WO2003006568A1 (en) * | 2001-07-09 | 2003-01-23 | 3M Innovative Properties Company | Pyrrolidonoethyl (meth)acrylate containing pressure sensitive adhesive compositions |
| GB2410029A (en) * | 2003-12-19 | 2005-07-20 | Michel Guillon | Multi-focal contact lens |
| WO2023013410A1 (en) * | 2021-08-04 | 2023-02-09 | 国立大学法人九州大学 | Polymer composition |
-
1990
- 1990-05-23 JP JP2131241A patent/JPH0428705A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6132462A (en) * | 1995-12-22 | 2000-10-17 | Santen Pharmaceutical Co., Ltd. | Copolymers formed from three components and intraocular lenses made thereof |
| US6268511B1 (en) | 1997-06-05 | 2001-07-31 | Santen Pharmaceutical Co., Ltd. | Itaconate derivatives used for a component of a polymer |
| US6465588B1 (en) | 1997-10-07 | 2002-10-15 | Santen Pharmaceutical Co., Ltd. | Four component copolymers and the ocular lens made thereof |
| WO2003006568A1 (en) * | 2001-07-09 | 2003-01-23 | 3M Innovative Properties Company | Pyrrolidonoethyl (meth)acrylate containing pressure sensitive adhesive compositions |
| US6902740B2 (en) | 2001-07-09 | 2005-06-07 | 3M Innovative Properties Company | Pyrrolidonoethyl (meth)acrylate containing pressure sensitive adhesive compositions |
| GB2410029A (en) * | 2003-12-19 | 2005-07-20 | Michel Guillon | Multi-focal contact lens |
| GB2410029B (en) * | 2003-12-19 | 2008-01-16 | Michel Guillon | Lenses |
| WO2023013410A1 (en) * | 2021-08-04 | 2023-02-09 | 国立大学法人九州大学 | Polymer composition |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4279795A (en) | Hydrophilic-hydrophobic graft copolymers for self-reinforcing hydrogels | |
| US11459415B2 (en) | Method of using hydrophilized bactericidal polymers | |
| US5401508A (en) | Hydrogel compositions and structures made from same | |
| Brøndsted et al. | Hydrogels for site-specific oral drug delivery: synthesis and characterization | |
| US4074039A (en) | Hydrophilic N,N-diethyl acrylamide copolymers | |
| KR101214393B1 (en) | Redox polymers for use in electrochemical-based sensors | |
| US4871785A (en) | Clouding-resistant contact lens compositions | |
| US20130011385A1 (en) | Transparent bacterial cellulose nanocomposite hydrogels | |
| US20020128346A1 (en) | Hydrogels | |
| Refojo et al. | Poly (methyl acrylate‐co‐hydroxyethyl acrylate) hydrogel implant material of strength and softness | |
| JPH09504561A (en) | Polymer surface coating material | |
| WO1991016932A1 (en) | Antithrombogenic polymers | |
| JP2017101162A (en) | Monomer composition for polymer for medical supply, and polymer for medical supply | |
| JPH0428705A (en) | Hydrogel for medical use | |
| JP2004161954A (en) | Blood-compatible polymer, and tool for medical care using the same | |
| US4622367A (en) | X-ray contrast spherical hydrogel particles based on polymer and copolymers of acrylates and methacrylates and the method for preparation thereof | |
| KR19990077661A (en) | Ocular lens material and process for producing the same | |
| JPH0311787B2 (en) | ||
| JPH10139832A (en) | Copolymer and glucose sensor | |
| JPH07184990A (en) | Medical polymer materials and medical materials | |
| JPH115817A (en) | Polymerizable polymer and its polymer | |
| JP3808968B2 (en) | Method for producing blood compatible porous membrane | |
| JPS6294819A (en) | Contact lens | |
| KR100431245B1 (en) | A nonthrombogenic Terpolymer | |
| US6979465B1 (en) | Biocompatible polymer systems carrying triflusal or HTB |