JP6461001B2 - Polymer, method for producing the same, and adhesive composition - Google Patents
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- 229920000642 polymer Polymers 0.000 title claims description 58
- 239000000853 adhesive Substances 0.000 title claims description 22
- 230000001070 adhesive effect Effects 0.000 title claims description 22
- 238000004519 manufacturing process Methods 0.000 title claims description 17
- 239000000203 mixture Substances 0.000 title claims description 14
- DZAUWHJDUNRCTF-UHFFFAOYSA-N 3-(3,4-dihydroxyphenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=C(O)C(O)=C1 DZAUWHJDUNRCTF-UHFFFAOYSA-N 0.000 claims description 24
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 24
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 21
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 19
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 10
- 229910052586 apatite Inorganic materials 0.000 claims description 9
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 claims description 9
- QVWAEZJXDYOKEH-UHFFFAOYSA-N 3-(3-hydroxyphenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC(O)=C1 QVWAEZJXDYOKEH-UHFFFAOYSA-N 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 6
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 6
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical group [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 6
- 229960004441 tyrosine Drugs 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 229960004502 levodopa Drugs 0.000 description 12
- MHUWZNTUIIFHAS-CLFAGFIQSA-N dioleoyl phosphatidic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC MHUWZNTUIIFHAS-CLFAGFIQSA-N 0.000 description 11
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 10
- 238000010586 diagram Methods 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000007334 copolymerization reaction Methods 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 239000000178 monomer Substances 0.000 description 8
- 239000002994 raw material Substances 0.000 description 8
- 238000012916 structural analysis Methods 0.000 description 8
- 238000004566 IR spectroscopy Methods 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- 210000000988 bone and bone Anatomy 0.000 description 5
- 229920001577 copolymer Polymers 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 4
- 239000012943 hotmelt Substances 0.000 description 4
- 229960003767 alanine Drugs 0.000 description 3
- 238000012662 bulk polymerization Methods 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- -1 3,4-dihydroxyphenyl Chemical group 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- 239000005639 Lauric acid Substances 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 description 1
- BYRVXROVZBYNOZ-UHFFFAOYSA-N 2-(3-hydroxyphenyl)propionic acid Chemical compound OC(=O)C(C)C1=CC=CC(O)=C1 BYRVXROVZBYNOZ-UHFFFAOYSA-N 0.000 description 1
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 229910014497 Ca10(PO4)6(OH)2 Inorganic materials 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- 206010010149 Complicated fracture Diseases 0.000 description 1
- 229920001651 Cyanoacrylate Polymers 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- MWCLLHOVUTZFKS-UHFFFAOYSA-N Methyl cyanoacrylate Chemical compound COC(=O)C(=C)C#N MWCLLHOVUTZFKS-UHFFFAOYSA-N 0.000 description 1
- 241000237536 Mytilus edulis Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 238000012648 alternating copolymerization Methods 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000021028 berry Nutrition 0.000 description 1
- 229920000704 biodegradable plastic Polymers 0.000 description 1
- 238000012661 block copolymerization Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- 239000002803 fossil fuel Substances 0.000 description 1
- 238000010528 free radical solution polymerization reaction Methods 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 235000020638 mussel Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
- C09J167/00—Adhesives based on polyesters obtained by reactions forming a carboxylic ester link in the main chain; Adhesives based on derivatives of such polymers
- C09J167/04—Polyesters derived from hydroxycarboxylic acids, e.g. lactones
-
- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/68—Polyesters containing atoms other than carbon, hydrogen and oxygen
- C08G63/685—Polyesters containing atoms other than carbon, hydrogen and oxygen containing nitrogen
- C08G63/6852—Polyesters containing atoms other than carbon, hydrogen and oxygen containing nitrogen derived from hydroxy carboxylic acids
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Surgery (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Adhesives Or Adhesive Processes (AREA)
- Polyesters Or Polycarbonates (AREA)
- Polyamides (AREA)
Description
本発明は、ポリマーおよびその製造方法ならびに接着組成物に関する。 The present invention relates to a polymer, a method for producing the same, and an adhesive composition.
シアノアクリレート系の瞬間接着剤やエポキシ系接着剤等が一般的な接着剤として広く知られている。
これらの接着剤は主に化石燃料由来の原料から合成されたものであり、資源の枯渇が近年の課題となっている。このため、自然界に豊富なバイオマスを利用したポリマー組成物の検討が進められている。
Cyanoacrylate-based instant adhesives and epoxy-based adhesives are widely known as general adhesives.
These adhesives are synthesized mainly from fossil fuel-derived raw materials, and resource depletion has become a problem in recent years. For this reason, a polymer composition using biomass abundant in nature has been studied.
本発明者らも、生分解性、高耐熱性および高接着性を併せもつバイオプラスチック接着剤の検討を種々進めている。
この中で、ヒドロカフェ酸またはその誘導体を構成するモノマーとエステル結合可能なカルボキシル基および水酸基を有するモノマーを、エステル化触媒下で無溶媒エステル交換反応して得られる共重合体は、ホットメルトタイプで使用するときの接着強度が、ガラス・炭素・鉄を用いたずり剥離試験において、工業用最強の接着剤と言われるエポキシ樹脂を凌駕する値を示すものである（特許文献１参照）。
The present inventors are also advancing various studies on bioplastic adhesives having both biodegradability, high heat resistance and high adhesiveness.
Among these, a copolymer obtained by subjecting a monomer constituting hydrocaffeic acid or a derivative thereof to a ester having a carboxyl group and a hydroxyl group capable of ester linkage in a solvent-free transesterification reaction under an esterification catalyst is a hot melt type. In the shear peeling test using glass, carbon, and iron, the adhesive strength when used in the above shows a value that surpasses the epoxy resin that is said to be the strongest industrial adhesive (see Patent Document 1).
ところで、生体の骨の接合について、通常の骨折の場合ギブスで固定し、また複雑な骨折の場合は一度金属類で固定し、治癒後にそれらを取り除く手術が施されている。
アパタイト（人工骨）と骨の接合に有効な接着剤は無く、ポリメタクリル酸メチル等の樹脂を重合させて接着する方法が主に用いられている（非特許文献１参照）。但し、この場合、約８０℃の反応熱を伴うため、周辺の細胞が壊死するおそれがある。
By the way, with regard to the joining of bones in a living body, in the case of a normal fracture, it is fixed with a cast, and in the case of a complicated fracture, it is fixed once with a metal, and an operation for removing them after healing is performed.
There is no adhesive effective for joining apatite (artificial bone) and bone, and a method of polymerizing and bonding a resin such as polymethyl methacrylate is mainly used (see Non-Patent Document 1). However, in this case, the reaction heat of about 80 ° C. accompanies, so that the surrounding cells may be necrotized.
解決しようとする問題点は、骨接合に用いられる従来の接着剤の生体適合性が十分でない点である。 The problem to be solved is that the biocompatibility of conventional adhesives used for osteosynthesis is not sufficient.
本発明に係るポリマーは、３−（３−ヒドロキシフェニル）プロピオン酸および３，４−ジヒドロキシヒドロ桂皮酸のうちからから選ばれるいずれか１つまたは双方と、３，４−ジヒドロキシフェニルアラニンおよび４−ヒドロキフェニルアラニンのうちから選ばれるいずれか１つまたは双方をエステル共重合化してなる。 Polymer according to the present invention, one or with both one selected from among 3- (3-hydroxyphenyl) propionic acid and 3,4-dihydroxy hydrocinnamic acid, 3,4-dihydroxyphenylalanine and 4- hydroxy One or both selected from phenylalanine are ester-copolymerized.
また、本発明に係るポリマーの製造方法は、上記のポリマーの製造方法であって、無水酢酸およびアパタイトを触媒としてエステル共重合化することを特徴とする。 The method for producing a polymer according to the present invention is a method for producing the polymer described above, and is characterized by performing ester copolymerization using acetic anhydride and apatite as a catalyst.
また、本発明に係るポリマーの製造方法は、好ましくは、前記アパタイトがヒドロキシアパタイトであることを特徴とする。 The polymer production method according to the present invention is preferably characterized in that the apatite is hydroxyapatite.
また、本発明に係る接着組成物は、上記のポリマーを含有する。 The adhesive composition according to the present invention contains the above polymer.
本発明に係るポリマーは、３−（３−ヒドロキシフェニル）プロピオン酸および３，４−ジヒドロキシヒドロ桂皮酸のうちからから選ばれるいずれか１つまたは双方と、３，４−ジヒドロキシフェニルアラニンおよび４−ヒドロキフェニルアラニンのうちから選ばれるいずれか１つまたは双方をエステル共重合化したものであるので、高い接着力を有するとともに、アルコール溶解性、特に、エタノール溶解性を有する。
また、本発明に係るポリマーの製造方法は、無水酢酸およびアパタイトを触媒としてエステル共重合化するので、製造工程が簡易である。
また、本発明に係る接着組成物は、上記のポリマーを含有するため、接着剤として生体に用いるときに、生体適合性に優れる。
Polymer according to the present invention, one or with both one selected from among 3- (3-hydroxyphenyl) propionic acid and 3,4-dihydroxy hydrocinnamic acid, 3,4-dihydroxyphenylalanine and 4- hydroxy Since one or both selected from phenylalanine is ester-copolymerized, it has high adhesive strength and alcohol solubility, particularly ethanol solubility.
In addition, since the polymer production method according to the present invention is ester copolymerized using acetic anhydride and apatite as a catalyst, the production process is simple.
Moreover, since the adhesive composition according to the present invention contains the above-described polymer, it is excellent in biocompatibility when used as an adhesive in a living body.
本発明の実施の形態（以下、本実施の形態例という。）について、以下に説明する。 An embodiment of the present invention (hereinafter referred to as this embodiment) will be described below.
本実施の形態例に係るポリマーは、３−（３−ヒドロキシフェニル）プロピオン酸および３，４−ジヒドロキシヒドロ桂皮酸のうちからから選ばれるいずれか１つまたは双方と、３，４−ジヒドロキシフェニルアラニンおよび４−ヒドロキフェニルアラニンのうちから選ばれるいずれか１つまたは双方をエステル共重合化してなる。 Polymer according to the embodiment of the present embodiment, one or with both one selected from among 3- (3-hydroxyphenyl) propionic acid and 3,4-dihydroxy hydrocinnamic acid, 3,4-dihydroxyphenylalanine and Any one or both selected from 4-hydroxyphenylalanine is ester-copolymerized.
共重合は、交互共重合、ランダム共重合、ブロック共重合およびグラフト共重合のうちのいずれであってもよい。
例えば、Poly(DOPA-co-3HPPA)と略称することができるポリマーは、３，４−ジヒドロキシフェニルアラニン（3,4-Dihydroxyphenyl alanine：略称DOPA）と３−（３−ヒドロキシフェニル）プロピオン酸（3-(3-Hydroxyphenyl)propionic acid：略称３ＨＰＰＡ）の共重合体である。ＤＯＰＡは、ムール貝などに含まれる接着性アミノ酸であり、抽出可能である。本実施の形態例において、原料モノマーとしてのＤＯＰＡは市販試薬として入手することができる。３ＨＰＰＡはベリー類に豊富に含まれ、抽出可能である。本実施の形態例において、原料モノマーとしての３ＨＰＰＡは市販試薬として入手することができる。
The copolymerization may be any of alternating copolymerization, random copolymerization, block copolymerization, and graft copolymerization.
For example, polymers that can be abbreviated as Poly (DOPA-co-3HPPA) are 3,4-dihydroxyphenyl alanine (abbreviation DOPA) and 3- (3-hydroxyphenyl) propionic acid (3- It is a copolymer of (3-Hydroxyphenyl) propionic acid (abbreviation 3HPPA). DOPA is an adhesive amino acid contained in mussels and can be extracted. In this embodiment, DOPA as a raw material monomer can be obtained as a commercially available reagent. 3HPPA is abundant in berries and can be extracted. In this embodiment, 3HPPA as a raw material monomer can be obtained as a commercially available reagent.
また、例えば、Poly(DHHCA-co-Tyrosine)と略称することができるポリマーは、３，４−ジヒドロキシヒドロ桂皮酸（3,4-Dihydroxyhydrocinnamic acid：略称ＤＨＨＣＡ）とタイロジン（Tyrosine：4-Hydroxyphenil alanine チロシンともいう）の共重合体である。ＤＨＨＣＡは、シナモンから抽出可能である。本実施の形態例において、原料モノマーとしてのＤＨＨＣＡは市販試薬として入手することができる。タイロジンは、じゃがいもから抽出可能である。本実施の形態例において、原料モノマーとしてのタイロジンは市販試薬として入手することができる。 Further, for example, Poly polymers which can be abbreviated (DHHCA-co-Tyrosine) and is 3,4-dihydroxy hydrocinnamic acid (3,4-Dihydroxyhydrocinnamic acid: abbreviation DHHCA) and Tairojin (Tyrosine: 4-Hydroxyphenil alanine tyrosine (Also referred to as a copolymer). DHHCA can be extracted from cinnamon. In this embodiment, DHHCA as a raw material monomer can be obtained as a commercially available reagent. Tyrosin can be extracted from potatoes. In this embodiment, tyrosin as a raw material monomer can be obtained as a commercially available reagent.
また、例えば、Poly(DHHCA-co-DOPA)と略称することができるポリマーは、ＤＨＨＣＡとDOPAの共重合体である。また、例えば、Poly(３HPPA-co- Tyrosine)と略称することができるポリマーは、３ＨＰＰＡとＴｙｒｏｓｉｎｅの共重合体である。 Further, for example, a polymer that can be abbreviated as Poly (DHHCA-co-DOPA) is a copolymer of DHHCA and DOPA. For example, a polymer that can be abbreviated as Poly (3HPPA-co-Tyrosine) is a copolymer of 3HPPA and Tyrosine.
本実施の形態例に係るポリマーは、いずれも、ＤＯＰＡまたはＴｙｒｏｓｉｎｅのアミノ基の存在により、アルコール可溶性が付与される。 In any of the polymers according to the present embodiment, alcohol solubility is imparted by the presence of the amino group of DOPA or Tyrosine.
また、本実施の形態例に係るポリマーに長鎖アルキル基を導入したポリマーは、芳香族の剛直な主鎖を有するため、ポリマー構造の隙間に水分子が入りやすい。また、ポリマーの隙間を疎水性のアルキル基で埋めることにより、耐水性言い換えれば分解性を制御することができ、ポリマーは毒性の低いオリゴマーやモノマーに分解される。
長鎖アルキル基原料としては、デカン酸、ラウリル酸、ステアリン酸等の長鎖カルボン酸を好適に用いることができる。
本実施の形態例に係るポリマーに長鎖アルキル基を導入したポリマーの反応スキームの一例を図１に示す。
In addition, since a polymer in which a long-chain alkyl group is introduced into the polymer according to this embodiment has an aromatic rigid main chain, water molecules are likely to enter the gaps in the polymer structure. Further, by filling the gaps between the polymers with hydrophobic alkyl groups, the water resistance, in other words, the decomposability can be controlled, and the polymer is decomposed into oligomers and monomers having low toxicity.
As the long-chain alkyl group raw material, a long-chain carboxylic acid such as decanoic acid, lauric acid or stearic acid can be suitably used.
An example of a reaction scheme of a polymer in which a long-chain alkyl group is introduced into the polymer according to this embodiment is shown in FIG.
本実施の形態例に係るポリマーは、いずれも、接着組成物として好適に用いることができる。特に、これらのポリマーは、アルコール可溶性、特にエタノール可溶性を有するため、エタノールに溶解して、例えば骨を接合するときの接着剤として用いると、常温で取り扱うことができるため、生体へ損傷を与えるおそれが少なく、生体適合性（生体親和性といってもよい。）に優れる。 Any of the polymers according to this embodiment can be suitably used as an adhesive composition. In particular, since these polymers are alcohol-soluble, especially ethanol-soluble, they can be handled at room temperature when dissolved in ethanol and used as an adhesive when, for example, bones are joined. There are few, and it is excellent in biocompatibility (it may be called biocompatibility).
また、本実施の形態例に係るポリマーに長鎖アルキル基を導入したポリマーは、いずれも、接着組成物として好適に用いることができる。これらのポリマーは、例えば骨を接合するときの接着剤として用いると、生体内で長期間分解されないことが期待できる。 In addition, any polymer in which a long-chain alkyl group is introduced into the polymer according to this embodiment can be suitably used as an adhesive composition. These polymers can be expected not to be decomposed in vivo for a long period of time, for example, when used as an adhesive when joining bones.
以上説明した本実施の形態例に係るポリマーを好適に得ることができる本実施の形態例に係るポリマーの製造方法について、以下に説明する。 A method for producing a polymer according to this embodiment, in which the polymer according to this embodiment described above can be suitably obtained, will be described below.
本実施の形態例に係るポリマーの製造方法は、上記のポリマーの製造方法であって、３−（３−ヒドロキシフェニル）プロピオン酸および３，４−ジヒドロキシヒドロ桂皮酸のうちからから選ばれるいずれか１つまたは双方と、３，４−ジヒドロキシフェニルアラニンおよび４−ヒドロキフェニルアラニンうちから選ばれるいずれか１つまたは双方を、無水酢酸およびアパタイトを触媒としてエステル共重合化する。 Method for producing a polymer according to the embodiment of the present embodiment is a manufacturing method of the polymer, 3- (3-hydroxyphenyl) any one selected from among the propionic acid and 3,4-dihydroxy hydrocinnamic acid One or both and one or both selected from 3,4-dihydroxyphenylalanine and 4-hydroxyphenylalanine are ester copolymerized using acetic anhydride and apatite as a catalyst.
共重合方法は、任意の方法を採用することができるが、塊状重合法または溶液重合法が好ましく、このうち塊状重合法がより好ましい。
例えば、塊状重合法の場合、原料モノマーを必要に応じてアセチル化した後、エステル化反応する。
反応温度は、好ましくは１００〜３００℃、より好ましくは１５０〜２００℃である。反応時間は、好ましくは３〜３０時間、より好ましくは１２〜２４時間である。
３−（３−ヒドロキシフェニル）プロピオン酸と３，４−ジヒドロキシフェニルアラニンを共重合化する反応スキームの例を図２に、および３，４−ジヒドロキシヒドロ桂皮酸と４−ヒドロキフェニルアラニンを共重合化する反応スキームの例を図３に、それぞれ例示する。
Although any method can be adopted as the copolymerization method, a bulk polymerization method or a solution polymerization method is preferable, and among these, the bulk polymerization method is more preferable.
For example, in the case of a bulk polymerization method, the raw material monomer is acetylated as necessary and then esterified.
The reaction temperature is preferably 100 to 300 ° C, more preferably 150 to 200 ° C. The reaction time is preferably 3 to 30 hours, more preferably 12 to 24 hours.
Examples of reaction schemes for copolymerizing the 3- (3-hydroxyphenyl) propionic acid with 3,4-
ＤＯＰＡおよびＴｙｒｏｓｉｎｅのうちから選ばれるいずれか１つまたは双方と３ＨＰＰＡおよびＤＨＨＣＡののうちから選ばれるいずれか１つまたは双方の配合比率は、質量比で、好ましくは、ＤＯＰＡおよびＴｙｒｏｓｉｎｅのうちから選ばれるいずれか１つまたは双方：３ＨＰＰＡおよびＤＨＨＣＡののうちから選ばれるいずれか１つまたは双方＝１０：９０〜９０：１０である。
エステル化触媒として用いる無水酢酸およびアパタイトの量は、原料モノマーの総量１００質量部に対して、好ましくは０．０１〜１０質量部、より好ましくは０．１〜１質量部である。アパタイトとしてヒドロキシアパタイト（Ca10(PO4)6(OH)2）を用いることは、好適な実施態様である。
The blending ratio of either one or both selected from DOPA and Tyrosine and one or both selected from 3HPPA and DHCCA is a mass ratio, preferably selected from DOPA and Tyrosine. Any one or both: Any one or both selected from 3HPPA and DHCCA = 10: 90 to 90:10.
The amount of acetic anhydride and apatite used as the esterification catalyst is preferably 0.01 to 10 parts by mass, more preferably 0.1 to 1 part by mass with respect to 100 parts by mass of the total amount of raw material monomers. The use of hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ) as the apatite is a preferred embodiment.
本実施の形態例に係るポリマーの製造方法は、ポリマーをワンポイント・ツーステップのシンプルな方法で得ることができる。 In the polymer manufacturing method according to this embodiment, the polymer can be obtained by a simple one-point-to-step method.
以下、本発明の実施例について説明する。本発明はこの実施例に限定されるものではない。 Examples of the present invention will be described below. The present invention is not limited to this embodiment.
＜ポリマーの製造＞
（実施例１）
Poly(DOPA-co-3HPPA)の製造
３，（３、４−ジヒドロキシフェニル）―L―アラニン（DOPA）（東京化成工業株式会社製、商品コード：YBO８E）３．６ｇと３−（３−ヒドロキシフェニル）プロピオン酸（AK Scientific社製、商品コード：MFCD00002598）１３．３ｇの混合物に無水酢酸１０ｇおよびヒドロキシアパタイト（純正化学株式会社製、商品コード：59272-1606）０．２ｇを加え、常圧、１５０℃の温度で２時間加熱し、３，（３、４−ジヒドロキシフェニル―L―アラニン（DOPA）およびL-Tyrosineをアセチル化した。ついで、５００Pa以下の真空引き条件下で１８０℃の温度で２０時間さらに加熱し、エステル共重合化した。
（実施例２）
Poly(DHHCA-co-Tyrosine)の製造
３，４−ジヒドロキシヒドロ桂皮酸（Sigma-Aldrich社製、商品コード：102601）３．６ｇとL-Tyrosine（Wako社製、商品コード：WEG2496）１３．３ｇの混合物に無水酢酸１０ｇおよびヒドロキシアパタイト（純正化学株式会社製、商品コード：59272-1606）０．２ｇを加え、常圧、１５０℃の温度で２時間加熱し、３，４−ジヒドロキシヒドロ桂皮酸およびL-Tyrosineをアセチル化した。ついで、５００Pa以下の真空引き条件下で１８０℃の温度で２０時間さらに加熱し、エステル共重合化した。
（実施例３）
Poly(DOPA-co-Tyrosine)の製造
３，（３、４−ジヒドロキシフェニル）―L―アラニン（DOPA）（東京化成工業株式会社製、商品コード：MFCD00002598）３．６ｇとL-Tyrosine（Wako社製、商品コード：WEG2496）１３．３ｇの混合物に無水酢酸１０ｇおよびヒドロキシアパタイト（純正化学株式会社製、商品コード：59272-1606）０．２ｇを加え、常圧、１５０℃の温度で２時間加熱し、３，（３、４−ジヒドロキシフェニル―L―アラニン（DOPA）およびL-Tyrosineをアセチル化した。ついで、５００Pa以下の真空引き条件下で１８０℃の温度で２０時間さらに加熱し、エステル共重合化した。
<Manufacture of polymer>
Example 1
Manufacture of Poly (DOPA-co-3HPPA) 3.6 g of 3, (3,4-dihydroxyphenyl) -L-alanine (DOPA) (manufactured by Tokyo Chemical Industry Co., Ltd., product code: YBO8E) and 3- (3-hydroxy To a mixture of 13.3 g of phenyl) propionic acid (manufactured by AK Scientific, product code: MFCD00002598) was added 10 g of acetic anhydride and 0.2 g of hydroxyapatite (product code: 59272-1606), and normal pressure. Heating was performed at a temperature of 150 ° C. for 2 hours to acetylate 3, (3,4-dihydroxyphenyl-L-alanine (DOPA) and L-Tyrosine, and then at a temperature of 180 ° C. under a vacuum of 500 Pa or less. The mixture was further heated for 20 hours for ester copolymerization.
(Example 2)
Poly (DHHCA-co-Tyrosine) of manufacturing 3,4-dihydroxy hydrocinnamic acid (Sigma-Aldrich Co., product code: 102601) 3.6g and L-Tyrosine (Wako Co., Product Code: WEG2496) 13.3g mixture of acetic anhydride 10g and hydroxyapatite (Junsei chemical Co., Ltd., product code: 59272-1606) of 0.2g was added, normal pressure, heated for 2 hours at a temperature of 0.99 ° C., 3,4-dihydroxy-hydrocinnamic acid And L-Tyrosine was acetylated. Subsequently, the mixture was further heated at a temperature of 180 ° C. for 20 hours under a vacuuming condition of 500 Pa or less to carry out ester copolymerization.
(Example 3)
Manufacture of Poly (DOPA-co-Tyrosine) 3.6 g of 3, (3,4-dihydroxyphenyl) -L-alanine (DOPA) (manufactured by Tokyo Chemical Industry Co., Ltd., product code: MFCD00002598) and L-Tyrosine (Wako) (Product code: WEG2496) Add 1 g of acetic anhydride and 0.2 g of hydroxyapatite (product code: 59272-1606) to 13.3 g of mixture and heat at normal pressure and 150 ° C for 2 hours Then, 3, (3,4-dihydroxyphenyl-L-alanine (DOPA) and L-Tyrosine were acetylated. Then, the mixture was further heated at a temperature of 180 ° C. for 20 hours under a vacuuming condition of 500 Pa or less. Polymerized.
（実施例４）
アルキル基導入例
実施例１で製造した各ポリマー１ｇに対して、界面活性剤であるラウリル酸（純正化学株式会社製、商品コード：81071-9001）を０．０５ｇ加え、５００Pa以下の真空引き条件下で１８０℃で５時間加熱し、エステル共重合化した。
(Example 4)
Example of introduction of alkyl group 0.05 g of lauric acid (product code: 81071-9001) as a surfactant is added to 1 g of each polymer produced in Example 1, and vacuuming conditions of 500 Pa or less Under heating at 180 ° C. for 5 hours, ester copolymerization was carried out.
＜ポリマーの構造解析＞
実施例１、２で製造したポリマーについて赤外分光法で構造解析した結果を、実施例１のポリマーについて図４〜図６に、実施例２のポリマーについて図７〜図９に、それぞれ示す。
<Structural analysis of polymer>
The results of structural analysis of the polymers produced in Examples 1 and 2 by infrared spectroscopy are shown in FIGS. 4 to 6 for the polymer of Example 1, and FIGS. 7 to 9 for the polymer of Example 2, respectively.
＜ポリマーの接着性能評価＞
実施例１のポリマーについて、ガラスーガラスをホットメルトで接着した結果を図１０に示す。また、実施例１のポリマー１ｇをエタノール５ｇに溶解したものでガラスーガラスを接着した結果を図１１に示す。図１０、１１中、横軸のＤｉｓｐｌａｃｅｍｅｎｔは接着部位の変位長さを示す。
接着強度は、ホットメルトの場合で接着強度は１０〜１５ＭＰａの範囲であり、エタノール溶解の場合で１〜１０ＭＰａの範囲である。
<Polymer adhesion performance evaluation>
About the polymer of Example 1, the result of having adhered glass-glass with the hot melt is shown in FIG. Further, FIG. 11 shows the result of bonding glass-glass by dissolving 1 g of the polymer of Example 1 in 5 g of ethanol. 10 and 11, Displacement on the horizontal axis indicates the displacement length of the adhesion site.
The adhesive strength is in the range of 10-15 MPa in the case of hot melt, and in the range of 1-10 MPa in the case of ethanol dissolution.
＜ポリマーの耐水性能評価＞
実施例４のポリマーについて、時間経過による分解率の変化を調べた結果を図１２に示す。比較として実施例１のポリマーの結果を併せて示す。実施例４のポリマーは実施例１のポリマーに比べて分解による減少率が大幅に抑制されていることが分かる。
<Evaluation of water resistance of polymer>
FIG. 12 shows the results of examining the change in the decomposition rate over time for the polymer of Example 4. For comparison, the results of the polymer of Example 1 are also shown. It can be seen that the decrease rate due to decomposition of the polymer of Example 4 is significantly suppressed as compared with the polymer of Example 1.
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