JP2017218681A - Nanofiber and method for producing the same - Google Patents
Nanofiber and method for producing the same Download PDFInfo
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- 239000002121 nanofiber Substances 0.000 title claims abstract description 68
- 238000004519 manufacturing process Methods 0.000 title claims description 14
- 229920000903 polyhydroxyalkanoate Polymers 0.000 claims abstract description 50
- 239000005014 poly(hydroxyalkanoate) Substances 0.000 claims abstract description 48
- 239000004372 Polyvinyl alcohol Substances 0.000 claims abstract description 41
- 229920002451 polyvinyl alcohol Polymers 0.000 claims abstract description 41
- 239000000835 fiber Substances 0.000 claims abstract description 33
- 239000000203 mixture Substances 0.000 claims abstract description 30
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- 238000001523 electrospinning Methods 0.000 claims description 20
- AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical compound FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 8
- 229920001020 poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) Polymers 0.000 claims description 4
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- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HPMGFDVTYHWBAG-UHFFFAOYSA-N 3-hydroxyhexanoic acid Chemical compound CCCC(O)CC(O)=O HPMGFDVTYHWBAG-UHFFFAOYSA-N 0.000 description 1
- SJZRECIVHVDYJC-UHFFFAOYSA-M 4-hydroxybutyrate Chemical compound OCCCC([O-])=O SJZRECIVHVDYJC-UHFFFAOYSA-M 0.000 description 1
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- SHBUUTHKGIVMJT-UHFFFAOYSA-N Hydroxystearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OO SHBUUTHKGIVMJT-UHFFFAOYSA-N 0.000 description 1
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- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
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Abstract
Description
本発明は、生分解性材料を利用したナノ繊維及びその製造方法に関する。 The present invention relates to a nanofiber using a biodegradable material and a method for producing the nanofiber.
近年、プラスチック廃棄物が、生態系への影響、燃焼時の有害ガス発生、大量の燃焼熱量による地球温暖化等、地球環境に大きな負荷を与える原因になっていることが懸念されており、これを解決できるプラスチックとして、生分解性プラスチックの開発が盛んになっている。 In recent years, plastic waste has been a cause of concern for the impact on the ecosystem, generation of harmful gases during combustion, global warming due to large amounts of combustion heat, etc. Development of biodegradable plastics has become active as a plastic that can solve this problem.
なかでも、植物由来の生分解性プラスチックは、これを燃焼させた際に出る二酸化炭素がもともと空気中にあったもので、大気中の二酸化炭素は増加しないとされている。このことをカーボンニュートラルと称し、二酸化炭素の削減目標値を課したパリ協定の下、重要視され、植物由来の生分解性プラスチックの積極的な使用が望まれている。 In particular, plant-derived biodegradable plastics are the ones that originally had carbon dioxide in the air when they were burned, and it is said that carbon dioxide in the atmosphere does not increase. This is called carbon neutral, and it is regarded as important under the Paris Agreement that imposes a target for reducing carbon dioxide, and active use of plant-derived biodegradable plastics is desired.
最近、生分解性およびカーボンニュートラルの観点から、植物由来の生分解性プラスチックとして脂肪族ポリエステル系樹脂が注目されている。なかでも、ポリヒドロキシアルカノエート（以下、ＰＨＡと略する場合がある）、このうち特に、ポリ（３−ヒドロキシブチレート）単独重合体、ポリ（３−ヒドロキシブチレート−コ−３−ヒドロキシバリレート）共重合体、ポリ（３−ヒドロキシブチレート−コ−３−ヒドロキシヘキサノエート）共重合体（以下、ＰＨＢＨと称する場合がある）、ポリ（３−ヒドロキシブチレート−コ−４−ヒドロキシブチレート）共重合体、ポリ乳酸等が注目されている。 Recently, aliphatic polyester resins have attracted attention as plant-derived biodegradable plastics from the viewpoint of biodegradability and carbon neutrality. Among them, polyhydroxyalkanoate (hereinafter sometimes abbreviated as PHA), among them, poly (3-hydroxybutyrate) homopolymer, poly (3-hydroxybutyrate-co-3-hydroxyvalerate) ) Copolymer, poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) copolymer (hereinafter sometimes referred to as PHBH), poly (3-hydroxybutyrate-co-4-hydroxybutyrate) (Rate) copolymers, polylactic acid and the like are attracting attention.
このＰＨＡのうちポリ−３−ヒドロキシアルカン酸などをナノ繊維にする検討が進められているが、そのような生分解性のナノ繊維として、一般的なナノ繊維と比較して市場の要求を満たすような機械的物性を有するものは得られていなかった。また、ＰＨＡの中でも、ＰＨＢＨは結晶化が遅いため、通常の溶融紡糸法による繊維化が難しいことに加えて、作製したナノ繊維の形状にばらつきがあり、均一なナノ繊維を得ることができないという問題があった。 Although studies are being made to use poly-3-hydroxyalkanoic acid as a nanofiber in this PHA, as such a biodegradable nanofiber, it meets the market demand compared to a general nanofiber. Those having such mechanical properties were not obtained. In addition, among PHAs, PHBH is slow to crystallize, so that it is difficult to fiberize by a normal melt spinning method, and in addition, there are variations in the shape of the produced nanofibers, and uniform nanofibers cannot be obtained. There was a problem.
そこで、溶融紡糸法ではなく、電界紡糸法（エレクトロスピニング法）を用いた繊維化が検討されている。電界紡糸法によると、ＰＨＢＨなどの結晶化が遅い材料であっても紡糸が可能となるためである。非特許文献１及び２では、各種ＰＨＡを用いて電界紡糸法により繊維マットを作製する方法が開示されている。さらに、作製した繊維マットが生体適合性及び生体吸収性を有する足場として医療材料用途に利用できる可能性が開示されている。 Therefore, fiber formation using an electrospinning method (electrospinning method) instead of a melt spinning method is being studied. This is because according to the electrospinning method, spinning is possible even with a material that is slow to crystallize, such as PHBH. Non-Patent Documents 1 and 2 disclose a method for producing a fiber mat by electrospinning using various PHA. Furthermore, the possibility that the produced fiber mat can be used for medical materials as a scaffold having biocompatibility and bioabsorbability is disclosed.
ＰＨＡは疎水性を示し、親水性に乏しいポリマーであることから、ＰＨＡを材料としたナノ繊維を医療材料に応用するにあたっては細胞接着性を如何に制御するかが課題であった。 Since PHA exhibits hydrophobicity and is a poorly hydrophilic polymer, it has been a problem how to control cell adhesion when applying nanofibers made of PHA to medical materials.
本発明は上記現状に鑑み、ポリヒドロキシアルカノエートを原料としながら、親水性と疎水性が制御され、均一性の高い繊維形状を有するナノ繊維を提供することを目的とする。 In view of the above situation, an object of the present invention is to provide a nanofiber having a highly uniform fiber shape with hydrophilicity and hydrophobicity controlled while using polyhydroxyalkanoate as a raw material.
本発明者らは、かかる問題を解決すべく鋭意検討を行い、ポリヒドロキシアルカノエート共重合体に親水性材料としてポリビニルアルコールを混合して電界紡糸法によりナノ繊維を形成することで、ナノ繊維の親水性と疎水性を制御するとともに、均一性の高い繊維形状を有するナノ繊維が得られることを見出し、本発明に至った。 すなわち本発明は、ポリヒドロキシアルカノエート共重合体とポリビニルアルコールの混合物から形成されたナノ繊維に関する。 The present inventors have intensively studied to solve such problems, and by mixing polyvinyl alcohol as a hydrophilic material with a polyhydroxyalkanoate copolymer to form nanofibers by electrospinning, The inventors have found that nanofibers having a highly uniform fiber shape can be obtained while controlling hydrophilicity and hydrophobicity, and the present invention has been achieved. That is, the present invention relates to a nanofiber formed from a mixture of a polyhydroxyalkanoate copolymer and polyvinyl alcohol.
好ましくは、ポリヒドロキシアルカノエート共重合体がポリ（３−ヒドロキシブチレート−コ−３−ヒドロキシヘキサノエート）である。 Preferably, the polyhydroxyalkanoate copolymer is poly (3-hydroxybutyrate-co-3-hydroxyhexanoate).
好ましくは、ポリヒドロキシアルカノエート共重合体とポリビニルアルコールの質量基準の割合が、９５：５〜５：９５である。 Preferably, the ratio by mass of the polyhydroxyalkanoate copolymer and polyvinyl alcohol is 95: 5 to 5:95.
好ましくは、ナノ繊維の繊維径が１００ｎｍ以上１，０００ｎｍ未満である。 Preferably, the fiber diameter of the nanofiber is 100 nm or more and less than 1,000 nm.
また本発明は、ナノ繊維からなるシートを複数枚積層してなる、繊維積層構造体に関する。 The present invention also relates to a fiber laminate structure formed by laminating a plurality of sheets made of nanofibers.
さらに本発明は、前記ナノ繊維を製造する方法であって、ポリヒドロキシアルカノエート共重合体とポリビニルアルコールとの混合物を含む溶液を電界紡糸する工程を含む製造方法に関する。 The present invention further relates to a method for producing the nanofiber, the method comprising electrospinning a solution containing a mixture of a polyhydroxyalkanoate copolymer and polyvinyl alcohol.
好ましくは、前記溶液を構成する溶媒が、フルオロアルコールと水の混合液である。 Preferably, the solvent constituting the solution is a mixed liquid of fluoroalcohol and water.
好ましくは、フルオロアルコールと水の混合液全体に対する水の含量が、５０質量％以下である。 Preferably, the content of water with respect to the entire mixture of fluoroalcohol and water is 50% by mass or less.
本発明によれば、ポリヒドロキシアルカノエートを原料としながら、親水性と疎水性が制御され、均一性の高い繊維形状を有するナノ繊維を提供することができる。 According to the present invention, it is possible to provide a nanofiber having a highly uniform fiber shape with hydrophilicity and hydrophobicity controlled while using polyhydroxyalkanoate as a raw material.
以下に本発明を詳細に説明する。 The present invention is described in detail below.
本発明は、ポリヒドロキシアルカノエート共重合体とポリビニルアルコールの混合物から形成されたナノ繊維に関する。本発明では、疎水性のポリヒドロキシアルカノエート共重合体と、親水性のポリビニルアルコールを組み合わせて使用することで、親水性と疎水性が制御されたナノ繊維を提供することができる。 The present invention relates to nanofibers formed from a mixture of a polyhydroxyalkanoate copolymer and polyvinyl alcohol. In the present invention, by using a combination of a hydrophobic polyhydroxyalkanoate copolymer and hydrophilic polyvinyl alcohol, nanofibers with controlled hydrophilicity and hydrophobicity can be provided.
［ポリヒドロキシアルカノエート共重合体］
本発明で用いるポリヒドロキシアルカノエート共重合体（以下、ＰＨＡ共重合体と略する場合がある）は、一般式（１）：［−ＣＨＲ−ＣＨ２−ＣＯ−Ｏ−］（式中、ＲはＣｎＨ２ｎ＋１で表されるアルキル基で、ｎは１以上１５以下の整数である。）で示される繰り返し単位を２種類以上含む脂肪族ポリエステル共重合体である。共重合の形式としては特に限定されず、ランダム共重合、交互共重合、ブロック共重合、グラフト共重合等であってよいが、入手が容易であるためランダム共重合が好ましい。ＰＨＡ共重合体は、ポリ（３−ヒドロキシブチレート）単独重合体と比較して、融点が低く、延性及び柔軟性が高いという利点がある。
[Polyhydroxyalkanoate copolymer]
The polyhydroxyalkanoate copolymer used in the present invention (hereinafter sometimes abbreviated as PHA copolymer) has the general formula (1): [—CHR—CH 2 —CO—O—] (wherein R Is an alkyl group represented by C n H 2n + 1 , and n is an integer of 1 to 15, and an aliphatic polyester copolymer containing two or more types of repeating units. The type of copolymerization is not particularly limited and may be random copolymerization, alternating copolymerization, block copolymerization, graft copolymerization, or the like, but random copolymerization is preferred because it is easily available. The PHA copolymer has the advantages of a low melting point, high ductility and flexibility as compared with a poly (3-hydroxybutyrate) homopolymer.
本発明で使用するＰＨＡ共重合体としては特に限定されないが、例えば、ＰＨＢＨ〔ポリ（３−ヒドロキシブチレート−コ−３−ヒドロキシヘキサノエート）、ポリ（３−ヒドロキシ酪酸−ｃｏ−３−ヒドロキシヘキサン酸）〕、ＰＨＢＶ〔ポリ（３−ヒドロキシブチレート−コ−３−ヒドロキシバレレート）、ポリ（３−ヒドロキシ酪酸−ｃｏ−３−ヒドロキシ吉草酸）〕、Ｐ３ＨＢ４ＨＢ〔ポリ（３−ヒドロキシブチレート−コ−４−ヒドロキシブチレート）、ポリ（３−ヒドロキシ酪酸−ｃｏ−４−ヒドロキシ酪酸）〕、ポリ（３−ヒドロキシ酪酸−ｃｏ−３-ヒドロキシ吉草酸−ｃｏ−３-ヒドロキシヘキサン酸）、ポリ（３−ヒドロキシブチレート−コ−３−ヒドロキシオクタノエート）、ポリ（３−ヒドロキシブチレート−コ−３−ヒドロキシオクタデカノエート）等が挙げられる。これらのなかでも、工業的に生産が容易であるものとして、ＰＨＢＨ、ＰＨＢＶ、Ｐ３ＨＢ４ＨＢが挙げられる。これらの共重合体のなかでも、ＰＨＢＨが特に好ましい。ＰＨＢＨは、加熱加工時に適用可能な加工温度の幅が広いため、ナノ繊維からなるシートを二次加工する時の加工性が良好となり、また、結晶性が低いため、生分解性が高くてＰＶＡと均一に混ざりやすいという利点があるためである。 The PHA copolymer used in the present invention is not particularly limited, and examples thereof include PHBH [poly (3-hydroxybutyrate-co-3-hydroxyhexanoate), poly (3-hydroxybutyrate-co-3-hydroxy]. Hexanoic acid)], PHBV [poly (3-hydroxybutyrate-co-3-hydroxyvalerate), poly (3-hydroxybutyric acid-co-3-hydroxyvaleric acid)], P3HB4HB [poly (3-hydroxybutyrate) -Co-4-hydroxybutyrate), poly (3-hydroxybutyric acid-co-4-hydroxybutyric acid)], poly (3-hydroxybutyric acid-co-3-hydroxyvaleric acid-co-3-hydroxyhexanoic acid), Poly (3-hydroxybutyrate-co-3-hydroxyoctanoate), poly (3-hydroxybutyrate-co-3) Hydroxy octadecanoate), and the like. Among these, PHBH, PHBV, and P3HB4HB are listed as those that are industrially easy to produce. Of these copolymers, PHBH is particularly preferable. PHBH has a wide range of processing temperatures that can be applied during heat processing, so that the processability when secondary-processing a nanofiber sheet is good, and the crystallinity is low, so it is highly biodegradable and PVA. This is because it has the advantage of being easily mixed uniformly.
ＰＨＡ共重合体、特にＰＨＢＨにおける繰り返し単位の平均組成比は、得られるナノ繊維の柔軟性と強度のバランスの観点から、３−ヒドロキシブチレート繰り返し単位の組成比が８０モル％〜９９モル％であることが好ましく、８５モル％〜９７モル％であることがより好ましい。３−ヒドロキシブチレート繰り返し単位の組成比が８０モル％未満であると剛性が不足する傾向があり、９９モル％より多いと柔軟性が不足する傾向がある。 The average composition ratio of the repeating units in the PHA copolymer, particularly PHBH is such that the composition ratio of the 3-hydroxybutyrate repeating units is from 80 mol% to 99 mol% from the viewpoint of the balance between flexibility and strength of the obtained nanofibers. It is preferable that it is 85 mol% to 97 mol%. If the composition ratio of the 3-hydroxybutyrate repeating unit is less than 80 mol%, the rigidity tends to be insufficient, and if it exceeds 99 mol%, the flexibility tends to be insufficient.
本発明において、ＰＨＡ共重合体は単独で使用してもよいし、少なくとも２種以上を混合して使用してもよい。例えば、３−ヒドロキシブチレート繰り返し単位の組成比が異なる２種以上のＰＨＡ共重合体を混合して使用することができる。 本発明で用いられるＰＨＡ共重合体の分子量は、目的とする用途で実質的に十分な物性を示すものであれば特に制限されない。分子量が低いと得られるナノ繊維の強度が低下する場合がある。逆に高いと繊維化が困難になる場合がある。それらを勘案して本発明に使用するＰＨＡ共重合体の重量平均分子量の範囲は、５０，０００〜３，０００，０００が好ましく、１００，０００〜１，５００，０００がより好ましい。なお、ここでの重量平均分子量は、クロロホルム溶離液を用いたゲルパーミエーションクロマトグラフィー（ＧＰＣ）を用い、ポリスチレン換算分子量分布より測定されたものをいう。当該ＧＰＣにおけるカラムとしては、前記分子量を測定するのに適切なカラムを使用すればよい。 In the present invention, the PHA copolymer may be used alone or in combination of at least two kinds. For example, two or more PHA copolymers having different composition ratios of 3-hydroxybutyrate repeating units can be mixed and used. The molecular weight of the PHA copolymer used in the present invention is not particularly limited as long as it exhibits substantially sufficient physical properties for the intended application. If the molecular weight is low, the strength of the resulting nanofiber may be reduced. Conversely, if it is high, fiberization may be difficult. In consideration of these, the range of the weight average molecular weight of the PHA copolymer used in the present invention is preferably 50,000 to 3,000,000, more preferably 100,000 to 1,500,000. In addition, the weight average molecular weight here means what was measured from the polystyrene conversion molecular weight distribution using the gel permeation chromatography (GPC) which used chloroform eluent. As a column in the GPC, a column suitable for measuring the molecular weight may be used.
ＰＨＡ共重合体は微生物から産生されるものが好ましく、ＰＨＡ共重合体を生産する微生物としては、ＰＨＡ類生産能を有する微生物であれば特に限定されない。例えば、ヒドロキシブチレートとその他のヒドロキシアルカノエートとの共重合体生産菌としては、ＰＨＢＶおよびＰＨＢＨ生産菌であるアエロモナス・キヤビエ（Ａｅｒｏｍｏｎａｓ ｃａｖｉａｅ）、Ｐ３ＨＢ４ＨＢ生産菌であるアルカリゲネス・ユートロファス（Ａｌｃａｌｉｇｅｎｅｓ ｅｕｔｒｏｐｈｕｓ）などが知られている。特に、ＰＨＢＨに関し、ＰＨＢＨの生産性を上げるために、ＰＨＡ合成酵素群の遺伝子を導入したアルカリゲネス・ユートロファス ＡＣ３２株（Ａｌｃａｌｉｇｅｎｅｓ ｅｕｔｒｏｐｈｕｓ ＡＣ３２，ＦＥＲＭ ＢＰ−６０３８）（Ｔ．Ｆｕｋｕｉ，Ｙ．Ｄｏｉ，Ｊ．Ｂａｔｅｒｉｏｌ．，１７９，ｐ４８２１−４８３０（１９９７））などがより好ましい。上記以外にも、生産したいＰＨＡ共重合体に合わせて、各種ＰＨＡ合成関連遺伝子を導入した遺伝子組み替え微生物を用いることができる。 The PHA copolymer is preferably produced from a microorganism, and the microorganism producing the PHA copolymer is not particularly limited as long as it is a microorganism capable of producing PHAs. For example, the copolymer-producing bacteria of hydroxybutyrate and other hydroxyalkanoates include PHBV and PHBH-producing bacteria such as Aeromonas cavaeae and P3HB4HB-producing bacteria such as Alcaligenes eutrophus. Are known. In particular, with respect to PHBH, in order to increase the productivity of PHBH, Alkaligenes eutrophus AC32 strain (Alcaligenes eutrophus AC32, FERM BP-6038) into which genes of the PHA synthase group have been introduced (T. Fukui, Y. Doi, J. Bateriol). , 179, p4821-4830 (1997)). In addition to the above, genetically modified microorganisms into which various PHA synthesis-related genes have been introduced can be used according to the PHA copolymer to be produced.
これらの微生物を適切な条件で培養して菌体内にＰＨＡ共重合体を蓄積させた後、菌体を破砕してＰＨＡ共重合体を分離することができる。 After culturing these microorganisms under appropriate conditions to accumulate the PHA copolymer in the microbial cells, the microbial cells can be crushed to separate the PHA copolymers.
［ポリビニルアルコール］
本発明で使用するポリビニルアルコール（以下、ＰＶＡと略する場合がある）としては市販のＰＶＡを使用することができ、特に限定されない。使用できるＰＶＡのケン化度は例えば８８〜１００％、好ましくは８８〜９９．８％の範囲にあってよい。また、重合度としては８００〜８０００の範囲にあってよい。ＰＶＡの立体規則性としても特に限定されず、アタクチック、アイソタクチック、シンジオタクチックといずれの構造を持つＰＶＡも使用することができる。また、エチレン−ビニルアルコール共重合体等のＰＶＡ共重合体や、ＰＶＡに置換基を導入した変性ＰＶＡも、本発明のＰＶＡとして使用することが可能である。ＰＶＡは親水性が高く、生体適合性に優れているため、これを重合体成分の１つとして含むナノ繊維は医療材料用途に適することになる。
[Polyvinyl alcohol]
Commercially available PVA can be used as the polyvinyl alcohol (hereinafter sometimes abbreviated as PVA) used in the present invention, and is not particularly limited. The saponification degree of the PVA that can be used may be, for example, in the range of 88 to 100%, preferably 88 to 99.8%. Moreover, as a polymerization degree, you may exist in the range of 800-8000. The stereoregularity of PVA is not particularly limited, and PVA having any structure of atactic, isotactic, and syndiotactic can be used. Moreover, PVA copolymers, such as an ethylene-vinyl alcohol copolymer, and the modified PVA which introduce | transduced the substituent into PVA can also be used as PVA of this invention. Since PVA has high hydrophilicity and excellent biocompatibility, nanofibers containing this as one of the polymer components are suitable for medical material applications.
本発明のナノ繊維において、ＰＨＡ共重合体とＰＶＡの割合は特に限定されないが、親水性と疎水性制御のため、質量基準で９５：５〜５：９５が好ましく、９０：１０〜１０：９０がより好ましい。両重合体の割合を調節することでナノ繊維の親水性と疎水性を制御することができ、用途に適した親水性と疎水性をナノ繊維に付与することができる。また、後述する特定の混合溶媒を用いた製造方法によると、ＰＨＡ共重合体とＰＶＡの合計に対するＰＶＡの割合が５０質量％を超え親水性が比較的高いナノ繊維を製造することができる。この場合、ＰＨＡ共重合体とＰＶＡの割合は質量基準で４０：６０〜５：９５が好ましく、３０：７０〜１０：９０がより好ましい。 In the nanofiber of the present invention, the ratio of the PHA copolymer and PVA is not particularly limited, but is preferably 95: 5 to 5:95 on a mass basis for controlling hydrophilicity and hydrophobicity, and 90:10 to 10:90. Is more preferable. By adjusting the ratio of both polymers, the hydrophilicity and hydrophobicity of the nanofiber can be controlled, and hydrophilicity and hydrophobicity suitable for the application can be imparted to the nanofiber. Moreover, according to the manufacturing method using the specific mixed solvent mentioned later, the ratio of PVA with respect to the sum total of a PHA copolymer and PVA exceeds 50 mass%, and a nanofiber with comparatively high hydrophilic property can be manufactured. In this case, the ratio of the PHA copolymer and PVA is preferably 40:60 to 5:95, more preferably 30:70 to 10:90 on a mass basis.
本発明のナノ繊維は、ＰＨＡ共重合体とＰＶＡ以外の成分を、本発明の効果を奏する範囲において含有していてもよい。そのような成分としては、他のポリマー成分；酸化防止剤、紫外線吸収剤、染料や顔料などの着色剤、可塑剤、滑剤、無機充填剤、帯電防止剤などの添加剤成分；結晶化速度を調整するための核剤等が挙げられる。これら他の成分の含有量としては、本発明の効果を損なわない限り特に制限されるものではない。 The nanofiber of the present invention may contain components other than the PHA copolymer and PVA within the range where the effects of the present invention are exhibited. Such components include other polymer components; antioxidants, UV absorbers, colorants such as dyes and pigments, plasticizers, lubricants, inorganic fillers, antistatic agents and other additive components; crystallization speed Examples include a nucleating agent for adjustment. The content of these other components is not particularly limited as long as the effects of the present invention are not impaired.
［ナノ繊維］
本発明のナノ繊維とは、好ましくは繊維径が１，０００ｎｍ未満であるナノサイズの繊維をいう。ナノサイズの繊維は、空隙率が小さい、比表面積が大きいなどの形態に起因して、ろ過性能、払拭性能、液保持性能などに優れることが知られているが、これらの効果を発現するには繊維径は１０００ｎｍ未満が好ましく、より好ましくは８００ｎｍ未満であり、さらに好ましくは７００ｎｍ未満である。さらに、本発明によると、繊維径が２００ｎｍ以下という極めて細いナノ繊維を製造することができる。繊維径の下限値は特に限定されないが、１００ｎｍ以上が好ましい。
[Nanofiber]
The nanofiber of the present invention preferably refers to a nanosized fiber having a fiber diameter of less than 1,000 nm. Nano-sized fibers are known to have excellent filtration performance, wiping performance, liquid retention performance, etc. due to their low porosity and large specific surface area. The fiber diameter is preferably less than 1000 nm, more preferably less than 800 nm, and even more preferably less than 700 nm. Furthermore, according to the present invention, extremely fine nanofibers having a fiber diameter of 200 nm or less can be produced. Although the lower limit of a fiber diameter is not specifically limited, 100 nm or more is preferable.
本発明のナノ繊維は、後述する電界紡糸法により製造することができ、これによってナノ繊維からなるシート（不織布）を形成することができる。電界紡糸法により製造されたナノ繊維は多孔質のものであるため、生体適合性及び生体吸収性を有する足場として好適である。 The nanofibers of the present invention can be produced by an electrospinning method described later, whereby a sheet (nonwoven fabric) made of nanofibers can be formed. Since nanofibers produced by electrospinning are porous, they are suitable as a scaffold having biocompatibility and bioabsorbability.
また、このようなシートを複数枚積層することで、厚みのある繊維積層構造体を製造することができる。このような繊維積層構造体は、積層枚数によって、その厚みを容易に調節することが可能であり、生分解性を有する医療用材料として好適に使用することができる。 Moreover, a thick fiber laminated structure can be manufactured by laminating a plurality of such sheets. Such a fiber laminate structure can be easily adjusted in thickness depending on the number of laminated layers, and can be suitably used as a biodegradable medical material.
［製造方法］
本発明のナノ繊維は、ＰＨＡ共重合体とＰＶＡの混合物を含む溶液を電界紡糸することにより製造できる。電界紡糸を行うには、市販の電界紡糸装置を使用することができる。電界紡糸の条件は特に限定されず、所望のナノ繊維が得られるように適宜選択すればよい。
[Production method]
The nanofiber of the present invention can be produced by electrospinning a solution containing a mixture of a PHA copolymer and PVA. In order to perform electrospinning, a commercially available electrospinning apparatus can be used. The conditions for electrospinning are not particularly limited, and may be appropriately selected so that desired nanofibers can be obtained.
上記溶液を構成するための溶媒としては、ＰＨＡ共重合体とＰＶＡを溶解できる溶媒を選択する。そのような溶媒としては、例えば、ＨＦＩＰ（正式名：１，１，１，３，３，３−ヘキサフルオロ−２−プロパノール）、ＴＦＥ（ＣＦ３ＣＨ２ＯＨ）、ＴＦＰ（ＨＣＦ２ＣＦ２ＣＨ２ＯＨ）、Ｃ６Ｆ１３Ｃ２Ｈ４ＯＨ等のフルオロアルコール；ジオキサン；ジメチルスルホキシド；水等が挙げられる。このうち、フルオロアルコールが好ましく、特にＨＦＩＰが好ましい。これらは１種類以上を使用してもよいし、ＰＨＡ共重合体とＰＶＡ双方の溶解性を考慮して２種類以上を混合して使用してもよい。また、ＰＨＡ共重合体とＰＶＡの合計に対するＰＶＡの割合が５０質量％を超えて重合体成分の親水性が高くなると、フルオロアルコールに対する溶解度が低下するため、上記溶媒として、フルオロアルコールと水の混合液を使用することが好ましく、ＨＦＩＰと水の混合液を使用することがより好ましい。このような混合液を電界紡糸の際の溶媒として使用することで、ＰＶＡの割合が５０質量％を超えて親水性が高いナノ繊維を製造することが可能となる。 As a solvent for constituting the solution, a solvent capable of dissolving the PHA copolymer and PVA is selected. As such a solvent, for example, HFIP (official name: 1,1,1,3,3,3-hexafluoro-2-propanol), TFE (CF 3 CH 2 OH), TFP (HCF 2 CF 2 CH) 2 OH), fluoro alcohols such as C 6 F 13 C 2 H 4 OH; dioxane; dimethyl sulfoxide; water and the like. Of these, fluoroalcohol is preferable, and HFIP is particularly preferable. One or more of these may be used, or two or more may be mixed and used in consideration of the solubility of both the PHA copolymer and PVA. Moreover, since the solubility with respect to fluoroalcohol falls when the ratio of PVA with respect to the sum total of a PHA copolymer and PVA exceeds 50 mass% and the hydrophilicity of a polymer component becomes high, mixing of fluoroalcohol and water as said solvent is carried out. It is preferable to use a liquid, and it is more preferable to use a mixed liquid of HFIP and water. By using such a mixed solution as a solvent for electrospinning, it becomes possible to produce nanofibers having a high hydrophilicity with a PVA ratio exceeding 50 mass%.
フルオロアルコールと水の混合液において、フルオロアルコールと水の割合は特に限定されず、ＰＨＡ共重合体とＰＶＡとの混合物が溶解する程度に応じて適宜決定すればよい。しかし、ナノ繊維の製造が容易であることから、フルオロアルコールと水の混合液全体に対する水の含量が５０質量％以下であることが好ましい。さらには、フルオロアルコールと水の質量基準の割合が９５：５〜５０：５０の範囲にあることがより好ましく、９５：５〜６０：４０の範囲にあることがさらに好ましく、９０：１０〜７０：３０の範囲にあることが特に好ましい。また、フルオロアルコールと水の割合を調節して水の割合を比較的大きくすることで、繊維径が２００ｎｍ以下という極めて細いナノ繊維を製造することが可能となる。この場合のフルオロアルコールと水の質量基準の割合は、ＰＨＡ共重合体とＰＶＡの割合にも依存するので一概には規定できないが、例えば、８０：２０〜５０：５０が好ましく、８０：２０〜６０：４０がより好ましく、８０：２０〜７０：３０がさらに好ましい。 In the mixed liquid of fluoroalcohol and water, the ratio of fluoroalcohol and water is not particularly limited, and may be appropriately determined according to the degree to which the mixture of the PHA copolymer and PVA is dissolved. However, since it is easy to produce nanofibers, it is preferable that the content of water is 50% by mass or less based on the entire mixture of fluoroalcohol and water. Furthermore, the ratio by mass of fluoroalcohol and water is more preferably in the range of 95: 5 to 50:50, further preferably in the range of 95: 5 to 60:40, and 90:10 to 70. Is particularly preferably in the range of 30. In addition, by adjusting the ratio of the fluoroalcohol and water to relatively increase the ratio of water, it is possible to produce extremely thin nanofibers having a fiber diameter of 200 nm or less. In this case, the mass-based ratio of fluoroalcohol and water depends on the ratio of the PHA copolymer and PVA and cannot be defined unconditionally. For example, 80:20 to 50:50 is preferable, and 80:20 to 60:40 is more preferable, and 80:20 to 70:30 is more preferable.
ＰＨＡ共重合体とＰＶＡの混合物を含む溶液の濃度としては、電界紡糸による繊維化が可能になるように適宜選択すればよい。一般には濃度が高くなればナノ繊維の繊維径が大きくなる傾向があるが、高すぎると繊維にならず、塊状になりやすい。一方、濃度が低すぎても繊維にならず、粒子状になりやすい。これらのことから、前記溶液の濃度としては０．５〜５質量％程度が好ましく、０．５〜３質量％程度がより好ましい。 What is necessary is just to select suitably as the density | concentration of the solution containing the mixture of a PHA copolymer and PVA so that fiberization by electrospinning becomes possible. In general, if the concentration is high, the fiber diameter of the nanofiber tends to increase, but if it is too high, the fiber does not become a fiber and tends to be agglomerated. On the other hand, even if the concentration is too low, it does not become a fiber and tends to be particulate. For these reasons, the concentration of the solution is preferably about 0.5 to 5% by mass, and more preferably about 0.5 to 3% by mass.
以下に実施例を掲げて本発明をさらに詳細に説明するが、本発明はこれら実施例に限定されるものではない。 The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.
＜製造例１＞ＰＨＢＨの製造
培養生産にはＫＮＫ−００５株（米国特許ＵＳ７３８４７６６参照）を用いた。
<Production Example 1> Production of PHBH KNK-005 strain (see US Pat. No. 7,384,766) was used for culture production.
種母培地の組成は１ｗ／ｖ％ Ｍｅａｔ−ｅｘｔｒａｃｔ、１ｗ／ｖ％ Ｂａｃｔｏ−Ｔｒｙｐｔｏｎｅ、０．２ｗ／ｖ％ Ｙｅａｓｔ−ｅｘｔｒａｃｔ、０．９ｗ／ｖ％ Ｎａ2ＨＰＯ4・１２Ｈ2Ｏ、０．１５ｗ／ｖ％ ＫＨ2ＰＯ4、とした（ｐＨ６．８）。 The composition of the seed medium is 1 w / v% Meat-extract, 1 w / v% Bacto-Tryptone, 0.2 w / v% Yeast-extract, 0.9 w / v% Na 2 HPO 4 · 12H 2 O, 0.15 w / V% KH 2 PO 4 (pH 6.8).
前培養培地の組成は１．１ｗ／ｖ％ Ｎａ2ＨＰＯ4・１２Ｈ2Ｏ、０．１９ｗ／ｖ％
ＫＨ2ＰＯ4、１．２９ｗ／ｖ％ （ＮＨ4）2ＳＯ4、０．１ｗ／ｖ％ ＭｇＳＯ4・７Ｈ2Ｏ、０．５ｖ／ｖ％ 微量金属塩溶液（０．１Ｎ塩酸に１．６ｗ／ｖ％ ＦｅＣｌ3・６Ｈ2Ｏ、１ｗ／ｖ％ ＣａＣｌ2・２Ｈ2Ｏ、０．０２ｗ／ｖ％ ＣｏＣｌ2・６Ｈ2Ｏ、０．０１６ｗ／ｖ％ ＣｕＳＯ4・５Ｈ2Ｏ、０．０１２ｗ／ｖ％ ＮｉＣｌ2・６Ｈ2Ｏを溶かしたもの。）、とした。炭素源はパーム油を１０ｇ／Ｌの濃度で一括添加した。
The composition of the preculture medium is 1.1 w / v% Na 2 HPO 4 · 12H 2 O, 0.19 w / v%
KH 2 PO 4 , 1.29 w / v% (NH 4 ) 2 SO 4 , 0.1 w / v% MgSO 4 .7H 2 O, 0.5 v / v% Trace metal salt solution (1. 6 w / v% FeCl 3 .6H 2 O, 1 w / v% CaCl 2 .2H 2 O, 0.02 w / v% CoCl 2 .6H 2 O, 0.016 w / v% CuSO 4 .5H 2 O, 0. 012 w / v% NiCl 2 .6H 2 O dissolved in the mixture. As a carbon source, palm oil was added at a concentration of 10 g / L.
生産培地の組成は０．３８５ｗ／ｖ％ Ｎａ2ＨＰＯ4・１２Ｈ2Ｏ、０．０６７ｗ／ｖ％ ＫＨ2ＰＯ4、０．２９１ｗ／ｖ％ （ＮＨ4）2ＳＯ4、０．１ｗ／ｖ％ ＭｇＳＯ4・７Ｈ2Ｏ、０．５ｖ／ｖ％ 微量金属塩溶液（０．１Ｎ 塩酸に１．６ｗ／ｖ％ ＦｅＣｌ3・６Ｈ2Ｏ、１ｗ／ｖ％ ＣａＣｌ2・２Ｈ2Ｏ、０．０２ｗ／ｖ％ ＣｏＣｌ2・６Ｈ2Ｏ、０．０１６ｗ／ｖ％ ＣｕＳＯ4・５Ｈ2Ｏ、０．０１２ｗ／ｖ％ ＮｉＣｌ2・６Ｈ2Ｏを溶かしたもの。）、０．０５ｗ／ｖ％ ＢＩＯＳＰＵＲＥＸ２００Ｋ（消泡剤：コグニスジャパン社製）とした。 The composition of the production medium is 0.385 w / v% Na 2 HPO 4 · 12H 2 O, 0.067 w / v% KH 2 PO 4 , 0.291 w / v% (NH 4 ) 2 SO 4 , 0.1 w / v % MgSO 4 .7H 2 O, 0.5 v / v% trace metal salt solution (1.6 w / v% FeCl 3 .6H 2 O in 0.1 N hydrochloric acid, 1 w / v% CaCl 2 .2H 2 O, 0. 02 w / v% CoCl 2 .6H 2 O, 0.016 w / v% CuSO 4 .5H 2 O, 0.012 w / v% NiCl 2 .6H 2 O dissolved in a glass.), 0.05 w / v% BIOSPUREX 200K (Antifoamer: manufactured by Cognis Japan).
まず、ＫＮＫ−００５株のグリセロールストック（５０μｌ）を種母培地（１０ｍｌ）に接種して２４時間培養し種母培養を行なった。次に種母培養液を１．８Ｌの前培養培地を入れた３Ｌジャーファーメンター（丸菱バイオエンジ製ＭＤＬ−３００型）に１．０ｖ／ｖ％接種した。運転条件は、培養温度３３℃、攪拌速度５００ｒｐｍ、通気量１．８Ｌ／ｍｉｎとし、ｐＨは６．７〜６．８の間でコントロールしながら２８時間培養し、前培養を行なった。ｐＨコントロールには１４％水酸化アンモニウム水溶液を使用した。 First, a glycerol stock (50 μl) of the KNK-005 strain was inoculated into a seed medium (10 ml) and cultured for 24 hours to perform seed culture. Next, the seed culture solution was inoculated at 1.0 v / v% into a 3 L jar fermenter (MDL-300, manufactured by Maruhishi Bioengine) containing 1.8 L of preculture medium. The operating conditions were a culture temperature of 33 ° C., a stirring speed of 500 rpm, an aeration rate of 1.8 L / min, and a culture was performed for 28 hours while controlling the pH between 6.7 and 6.8, followed by preculture. A 14% aqueous ammonium hydroxide solution was used for pH control.
次に、前培養液を６Ｌの生産培地を入れた１０Ｌジャーファーメンター（丸菱バイオエンジ製ＭＤＳ−１０００型）に１．０ｖ／ｖ％接種した。運転条件は、培養温度２８℃、攪拌速度４００ｒｐｍ、通気量６．０Ｌ／ｍｉｎとし、ｐＨは６．７〜６．８の間でコントロールした。ｐＨコントロールには１４％水酸化アンモニウム水溶液を使用した。炭素源としてパーム油を使用した。培養は６４時間行い、培養終了後、遠心分離によって菌体を回収、メタノールで洗浄、凍結乾燥し、乾燥菌体重量を測定した。 Next, 1.0 V / v% of the preculture solution was inoculated into a 10 L jar fermenter (MDS-1000, manufactured by Maruhishi Bio-Engine) containing 6 L of production medium. The operating conditions were a culture temperature of 28 ° C., a stirring speed of 400 rpm, an aeration rate of 6.0 L / min, and a pH controlled between 6.7 and 6.8. A 14% aqueous ammonium hydroxide solution was used for pH control. Palm oil was used as the carbon source. Culturing was performed for 64 hours, and after completion of the cultivation, the cells were collected by centrifugation, washed with methanol, freeze-dried, and the weight of the dried cells was measured.
得られた乾燥菌体１ｇに１００ｍｌのクロロホルムを加え、室温で一昼夜攪拌して、菌体内のＰＨＢＨを抽出した。菌体残渣をろ別後、エバポレーターで総容量が３０ｍｌになるまで濃縮後、９０ｍｌのヘキサンを徐々に加え、ゆっくり攪拌しながら、１時間放置した。析出したＰＨＢＨをろ別後、５０℃で３時間真空乾燥してＰＨＢＨを得た。 To 1 g of the obtained dried cells, 100 ml of chloroform was added and stirred overnight at room temperature to extract PHBH in the cells. The bacterial cell residue was filtered off, concentrated with an evaporator until the total volume reached 30 ml, 90 ml of hexane was gradually added, and the mixture was allowed to stand for 1 hour with slow stirring. The precipitated PHBH was filtered off and then vacuum dried at 50 ° C. for 3 hours to obtain PHBH.
得られたＰＨＢＨの３ＨＨ組成分析は以下のようにガスクロマトグラフィーによって測定した。乾燥ＰＨＢＨ２０ｍｇに２ｍｌの硫酸−メタノール混液（１５：８５）と２ｍｌのクロロホルムを添加して密栓し、１００℃で１４０分間加熱して、ＰＨＢＨ分解物のメチルエステルを得た。冷却後、これに１．５ｇの炭酸水素ナトリウムを少しずつ加えて中和し、炭酸ガスの発生がとまるまで放置した。４ｍｌのジイソプロピルエーテルを添加してよく混合した後、遠心して、上清中のポリエステル分解物のモノマーユニット組成をキャピラリーガスクロマトグラフィーにより分析した。ガスクロマトグラフは島津製作所ＧＣ−１７Ａ、キャピラリーカラムはＧＬサイエンス社製ＮＥＵＴＲＡ ＢＯＮＤ−１（カラム長２５ｍ、カラム内径０．２５ｍｍ、液膜厚０．４μｍ）を用いた。キャリアガスとしてＨｅを用い、カラム入口圧１００ｋＰａとし、サンプルは１μｌを注入した。温度条件は、初発温度１００から２００℃まで８℃／分の速度で昇温、さらに２００から２９０℃まで３０℃／分の速度で昇温した。上記条件にて分析した結果、３−ヒドロキシヘキサノエート（３ＨＨ）のモノマー比率が５．４モル％のＰＨＢＨであった。ＧＰＣで測定した重量平均分子量Ｍｗは３５万であり、融点は１４１℃であった。 The 3HH composition analysis of the obtained PHBH was measured by gas chromatography as follows. To 20 mg of dry PHBH, 2 ml of a sulfuric acid-methanol mixture (15:85) and 2 ml of chloroform were added and sealed, and heated at 100 ° C. for 140 minutes to obtain a methyl ester of a PHBH decomposition product. After cooling, 1.5 g of sodium bicarbonate was added little by little to neutralize it, and the mixture was allowed to stand until the generation of carbon dioxide gas stopped. After adding 4 ml of diisopropyl ether and mixing well, the mixture was centrifuged and the monomer unit composition of the polyester degradation product in the supernatant was analyzed by capillary gas chromatography. The gas chromatograph used was Shimadzu Corporation GC-17A, and the capillary column used was GL Science's NEUTRA BOND-1 (column length 25 m, column inner diameter 0.25 mm, liquid film thickness 0.4 μm). He was used as the carrier gas, the column inlet pressure was set to 100 kPa, and 1 μl of the sample was injected. As temperature conditions, the temperature was raised from an initial temperature of 100 to 200 ° C. at a rate of 8 ° C./min, and further from 200 to 290 ° C. at a rate of 30 ° C./min. As a result of analysis under the above conditions, the monomer ratio of 3-hydroxyhexanoate (3HH) was PHBH of 5.4 mol%. The weight average molecular weight Mw measured by GPC was 350,000, and melting | fusing point was 141 degreeC.
（実施例１〜７及び参考例１〜２）
各実施例及び参考例ではＰＨＢＨとして、製造例１で製造したＰＨＢＨを使用した。
(Examples 1-7 and Reference Examples 1-2)
In each example and reference example, PHBH produced in Production Example 1 was used as PHBH.
ＰＶＡとしては、次のものを使用した。アタクチックポリビニルアルコール、ユニチカ株式会社製、ケン化度９９．５ｍｏｌ％、重合度ＤＰ＝１７３０。 The following were used as PVA. Atactic polyvinyl alcohol, manufactured by Unitika Ltd., saponification degree 99.5 mol%, polymerization degree DP = 1730.
表１に記載の重量比のＰＨＢＨ及び／又はＰＶＡを、溶媒である表１に記載の重量比のＨＦＩＰ（和光純薬社製）及び／又は水に、表１に記載の濃度で溶解して各ポリマー溶液を得た。なお、各ポリマー溶液を調製するにあたっては、各重合体成分を溶媒に投入した後、室温で２４時間撹拌することにより均質な溶液を得た。 The PHBH and / or PVA in the weight ratio shown in Table 1 are dissolved in the solvent in HFIP (manufactured by Wako Pure Chemical Industries, Ltd.) and / or water in the weight ratio shown in Table 1 at the concentrations shown in Table 1. Each polymer solution was obtained. In preparing each polymer solution, each polymer component was put into a solvent and then stirred at room temperature for 24 hours to obtain a homogeneous solution.
各ポリマー溶液を入れたガラス注射器（容量１０ｃｃ、アズワン株式会社）を電界紡糸装置（カトーテック株式会社：Ｎａｎｏｆｉｂｅｒ Ｅｌｅｃｔｒｏｓｐｉｎｎｉｎｇ Ｕｎｉｔ）に取り付けて、ターゲットに巻いたクッキングシート又はアルミ箔の上に電界紡糸を行い、ポリマーの組成が異なる各ナノ繊維からなるシートを得た。注射器には、注射針（０．６ｍｍφ×２６ｍｍ）（皮下針１／２、成田注射針製作所）の先端を両刃スリ込ヤスリで削り平らにしたものを用いた。電界紡糸の条件は、射出角度３０°、ターゲットとの距離１５ｃｍ、押出速度０．３−０．４ｍｍ／ｍｉｎ、印加電圧２０ｋＶ、雰囲気温度２３−２５℃、湿度２０−３０％とした。 A glass syringe containing each polymer solution (capacity: 10 cc, ASONE Co., Ltd.) is attached to an electrospinning device (Kato Tech Co., Ltd .: Nanofibre Electrospinning Unit), and electrospinning is performed on a cooking sheet or aluminum foil wound around a target. A sheet made of nanofibers having different polymer compositions was obtained. As the syringe, a syringe needle (0.6 mmφ × 26 mm) (subcutaneous needle 1/2, Narita Needle Manufacturing Co., Ltd.) whose tip was scraped and flattened with a double-edged file was used. The electrospinning conditions were an injection angle of 30 °, a distance of 15 cm from the target, an extrusion speed of 0.3-0.4 mm / min, an applied voltage of 20 kV, an ambient temperature of 23-25 ° C., and a humidity of 20-30%.
得られた各ナノ繊維を走査型電子顕微鏡（ＪＳＭ−６０１０ＬＡ、日本電子社製）により撮影した。撮影した写真を図１〜９に示す。各写真においてスケールバーとの比較により複数の繊維の繊維径を求め、得られた値から、各実施例及び比較例のナノ繊維における最小繊維径、及び最大繊維径を決定すると共に、平均繊維径、及び標準偏差を算出して、その結果を表１に示した。 Each nanofiber obtained was photographed with a scanning electron microscope (JSM-6010LA, manufactured by JEOL Ltd.). Photographs taken are shown in FIGS. In each photograph, the fiber diameters of a plurality of fibers are obtained by comparison with a scale bar, and from the obtained values, the minimum fiber diameter and the maximum fiber diameter in the nanofibers of each Example and Comparative Example are determined, and the average fiber diameter is determined. And the standard deviation were calculated and the results are shown in Table 1.
実施例１〜７では電界紡糸により、ＰＨＢＨとＰＶＡの混合物から、繊維径が１０００ｎｍ未満のナノ繊維を製造することに成功した。図１〜７より、いずれの実施例のナノ繊維も、繊維の形状及び繊維径が揃っており、均一性が高いことが分かる。ＰＶＡ含量が高い実施例４〜７においては、溶媒としてＨＦＩＰと水の混合溶媒を使用することでナノ繊維が得られた。また、実施例４と実施例５の比較、及び実施例６と実施例７の比較より、ＨＦＩＰと水の混合溶媒において水の混合割合を高めることで、ナノ繊維の繊維径が小さくなることが分かる。結果、実施例５及び実施例７では繊維径が２００ｎｍ以下という極めて細いナノ繊維を得ることに成功した。 In Examples 1 to 7, nanofibers having a fiber diameter of less than 1000 nm were successfully produced from a mixture of PHBH and PVA by electrospinning. 1-7, it turns out that the nanofiber of any Example has the uniform shape and fiber diameter, and its uniformity is high. In Examples 4 to 7 having a high PVA content, nanofibers were obtained by using a mixed solvent of HFIP and water as a solvent. Moreover, from the comparison of Example 4 and Example 5 and the comparison of Example 6 and Example 7, the fiber diameter of nanofibers can be reduced by increasing the mixing ratio of water in the mixed solvent of HFIP and water. I understand. As a result, Example 5 and Example 7 succeeded in obtaining extremely thin nanofibers having a fiber diameter of 200 nm or less.
本発明のナノ繊維は、生体適合性及び生体吸収性を有する足場として医療材料用途に利用することができる。
The nanofiber of the present invention can be used for medical materials as a scaffold having biocompatibility and bioabsorbability.
Claims (8)
ポリヒドロキシアルカノエート共重合体とポリビニルアルコールとの混合物を含む溶液を電界紡糸する工程を含む製造方法。 A method for producing the nanofiber according to any one of claims 1 to 4,
A production method comprising a step of electrospinning a solution containing a mixture of a polyhydroxyalkanoate copolymer and polyvinyl alcohol.
The manufacturing method of Claim 7 whose content of the water with respect to the whole liquid mixture of fluoroalcohol and water is 50 mass% or less.
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| JP2019196550A (en) * | 2018-05-07 | 2019-11-14 | 国立大学法人信州大学 | Nanofiber and method for producing the same |
| CN113906194A (en) * | 2019-06-07 | 2022-01-07 | 国立大学法人秋田大学 | Excavation fluid, excavation method, and excavation fluid additive |
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