JP6763935B2 - Manufacturing method of natural polymer nanofibers - Google Patents
Manufacturing method of natural polymer nanofibers Download PDFInfo
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- 229920005615 natural polymer Polymers 0.000 title claims description 75
- 239000002121 nanofiber Substances 0.000 title claims description 48
- 238000004519 manufacturing process Methods 0.000 title claims description 13
- 239000001506 calcium phosphate Substances 0.000 claims description 23
- 102000004190 Enzymes Human genes 0.000 claims description 20
- 108090000790 Enzymes Proteins 0.000 claims description 20
- 235000019739 Dicalciumphosphate Nutrition 0.000 claims description 13
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 claims description 13
- 229910000390 dicalcium phosphate Inorganic materials 0.000 claims description 13
- 229940038472 dicalcium phosphate Drugs 0.000 claims description 13
- 239000002861 polymer material Substances 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 12
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 11
- 108010010803 Gelatin Proteins 0.000 claims description 10
- 229920000159 gelatin Polymers 0.000 claims description 10
- 239000008273 gelatin Substances 0.000 claims description 10
- 235000019322 gelatine Nutrition 0.000 claims description 10
- 235000011852 gelatine desserts Nutrition 0.000 claims description 10
- 238000009987 spinning Methods 0.000 claims description 10
- 229940078499 tricalcium phosphate Drugs 0.000 claims description 10
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 10
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 10
- 239000000463 material Substances 0.000 claims description 9
- 102000030523 Catechol oxidase Human genes 0.000 claims description 8
- 108010031396 Catechol oxidase Proteins 0.000 claims description 8
- 102000004316 Oxidoreductases Human genes 0.000 claims description 8
- 108090000854 Oxidoreductases Proteins 0.000 claims description 8
- GBNXLQPMFAUCOI-UHFFFAOYSA-H tetracalcium;oxygen(2-);diphosphate Chemical compound [O-2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GBNXLQPMFAUCOI-UHFFFAOYSA-H 0.000 claims description 8
- 230000005684 electric field Effects 0.000 claims description 7
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 6
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [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
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 5
- 229920001661 Chitosan Polymers 0.000 claims description 5
- 102000008186 Collagen Human genes 0.000 claims description 5
- 108010035532 Collagen Proteins 0.000 claims description 5
- 229920000615 alginic acid Polymers 0.000 claims description 5
- 235000010443 alginic acid Nutrition 0.000 claims description 5
- 229920001436 collagen Polymers 0.000 claims description 5
- 238000004132 cross linking Methods 0.000 claims description 5
- 229920002674 hyaluronan Polymers 0.000 claims description 5
- 229960003160 hyaluronic acid Drugs 0.000 claims description 5
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 4
- 108010029541 Laccase Proteins 0.000 claims description 4
- 102000003992 Peroxidases Human genes 0.000 claims description 4
- 108010003894 Protein-Lysine 6-Oxidase Proteins 0.000 claims description 4
- 102000004669 Protein-Lysine 6-Oxidase Human genes 0.000 claims description 4
- 229940072056 alginate Drugs 0.000 claims description 4
- 108010010779 glutamine-pyruvate aminotransferase Proteins 0.000 claims description 4
- 230000005484 gravity Effects 0.000 claims description 4
- 108040007629 peroxidase activity proteins Proteins 0.000 claims description 4
- 102000035195 Peptidases Human genes 0.000 claims description 3
- 108091005804 Peptidases Proteins 0.000 claims description 3
- -1 Soltase Proteins 0.000 claims description 3
- 108060008724 Tyrosinase Proteins 0.000 claims description 3
- 102000003425 Tyrosinase Human genes 0.000 claims description 3
- 159000000007 calcium salts Chemical class 0.000 claims description 3
- 159000000003 magnesium salts Chemical class 0.000 claims description 3
- 235000019833 protease Nutrition 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- 229910002651 NO3 Inorganic materials 0.000 claims 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 1
- 239000000243 solution Substances 0.000 description 28
- 238000000034 method Methods 0.000 description 11
- 239000003431 cross linking reagent Substances 0.000 description 7
- 229920000642 polymer Polymers 0.000 description 6
- 239000000835 fiber Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 235000013305 food Nutrition 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 3
- 229940045110 chitosan Drugs 0.000 description 3
- 229960005188 collagen Drugs 0.000 description 3
- 238000010041 electrostatic spinning Methods 0.000 description 3
- 229940014259 gelatin Drugs 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 150000002823 nitrates Chemical class 0.000 description 3
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 3
- 102000004882 Lipase Human genes 0.000 description 2
- 108090001060 Lipase Proteins 0.000 description 2
- 239000004367 Lipase Substances 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 235000019421 lipase Nutrition 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F1/00—General methods for the manufacture of artificial filaments or the like
- D01F1/02—Addition of substances to the spinning solution or to the melt
- D01F1/10—Other agents for modifying properties
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F4/00—Monocomponent artificial filaments or the like of proteins; Manufacture thereof
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F9/00—Artificial filaments or the like of other substances; Manufacture thereof; Apparatus specially adapted for the manufacture of carbon filaments
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F9/00—Artificial filaments or the like of other substances; Manufacture thereof; Apparatus specially adapted for the manufacture of carbon filaments
- D01F9/04—Artificial filaments or the like of other substances; Manufacture thereof; Apparatus specially adapted for the manufacture of carbon filaments of alginates
Landscapes
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Textile Engineering (AREA)
- Manufacturing & Machinery (AREA)
- Artificial Filaments (AREA)
- Chemical Or Physical Treatment Of Fibers (AREA)
Description
本発明は、ナノ繊維の製造方法に関し、特に、天然高分子ナノ繊維材料の製造方法に関する。
The present invention relates to a manufacturing method of Nano繊Wei, more particularly to a method of manufacturing a natural polymer nanofiber materials.
ナノ繊維は、ナノサイズの繊維であり、その繊維の細さの範囲が約数十〜数百ナノの間であり、製造方法の違いに応じてサイズを調整することができる。ナノ繊維は、高い表面積を有し、製造されるメッシュは、低い孔径分布及び高い間隙率を有し、医療方面の応用用途においても徐々に成長している。現在の常用のナノ繊維は、静電紡糸技術により製造される。 The nanofiber is a nano-sized fiber, and the fineness range of the fiber is between about several tens to several hundreds nano, and the size can be adjusted according to the difference in the manufacturing method. The nanofibers have a high surface area, and the produced mesh has a low pore size distribution and a high porosity, and is gradually growing even in medical applications. Today's commonly used nanofibers are manufactured by electrostatic spinning technology.
静電紡糸技術は、高圧静電を利用し、重合体溶液をミクロン又はナノオーダー繊維に製造する方法である。従来の静電紡糸技術が使用する材料は、何れも人工高分子及び有機溶剤で配置される。近年より、天然高分子に対する変性、静電防止装置の改善によって、天然高分子を基材とし、同時に特殊な構造を有するナノ繊維材料を製造しているが、上記天然高分子ナノ繊維は、依然として天然高分子に対して化学変性を行って目的を達成し、これは、天然高分子、例えば、たんぱく質等に対してその構造特性の変化を引き起こし、工業、医療、食品、従来の加工等の用途に大幅な制限を受け、特に、食品及び医療産業においては、有機溶剤、変性変質の高分子又はたんぱく質が、何れも用いることができず、従って、有機溶剤の使用又は物理化学的変性を必要とせず、且つナノ防止に用いることができる天然高分子ナノ繊維としての発展が必要となっている。 Electrostatic spinning technology is a method of producing a polymer solution into micron or nano-order fibers using high-voltage static electricity. The materials used in conventional electrostatic spinning techniques are all arranged with artificial polymers and organic solvents. In recent years, by modifying natural polymers and improving antistatic devices, nanofiber materials using natural polymers as a base material and having a special structure have been manufactured, but the above-mentioned natural polymer nanofibers are still available. Achieved the purpose by chemically denaturing natural polymers, which causes changes in the structural properties of natural polymers, such as proteins, and is used in industrial, medical, food, conventional processing, etc. In particular, in the food and medical industry, no organic solvent, denaturing macromolecules or proteins can be used, thus requiring the use of organic solvents or physicochemical modification. However, it is necessary to develop it as a natural polymer nanofiber that can be used for nano-prevention.
上記問題を解決する為、本発明が提供する天然高分子ナノ繊維は、天然高分子溶液により適用フィールド制御紡糸プロセスで製造され、該天然高分子溶液は、天然高分子材料、無機塩類、酵素を含む。
In order to solve the above problems, the natural polymer nanofibers provided by the present invention are produced by an applied field-controlled spinning process using a natural polymer solution, and the natural polymer solution contains natural polymer materials, inorganic salts and enzymes . Including.
好適実施形態において、前記高分子材料は、これに制限するものではないが、ゼラチン(gelatin)、コラーゲン(collagen)、ヒアルロン酸(hyaluronic acid)、アルギン酸塩(alginate)、キトサン(chitosan)からなる群から選択される。 In a preferred embodiment, the polymer material is, but is not limited to, a group consisting of gelatin, collagen, hyaluronic acid, alginate, chitosan. Is selected from.
好適実施形態において、前記無機塩は、これに制限するものではないが、ヒドロキシアパタイト(hydroxyapatite，Hap)、リン酸三カルシウム(tricalcium phosphate，TCP)、リン酸二カルシウム(dicalcium phosphate，DCP)、リン酸二カルシウム二水和物(dicalcium phosphate dehydrate，DCPD)、リン酸四カルシウム(tetracalcium phosphate，TTCP)、炭酸塩、硝酸塩、硫酸塩、カルシウム、カリウム、ナトリウム、マグネシウムからなる群から選択される。 In a preferred embodiment, the inorganic salt is, but is not limited to, hydroxyapatite (Hap), tricalcium phosphate (TCP), dicalcium phosphate (DCP), phosphorus. It is selected from the group consisting of dicalcium phosphate dehydrate (DCPD), tetracalcium phosphate (TTCP), carbonates, nitrates, sulfates, calcium, potassium, sodium and magnesium.
好適実施形態において、前記酵素は、これに制限するものではないが、グルタミントランスアミナーゼ、リパーゼ(Lipase)、ペプチダーゼ（Peptidases）、ソルターゼ(Sortase)、オキシドレダクターゼ（Oxidoreductases）、チロシナーゼ(Tyrosinase)、ポリフェノールオキシターゼ(Polyphenoloxidase，PPO)、ラッカーゼ(laccase)、ペルオキシダーゼ(peroxidase)、リシルオキシダーゼ(Lysyl oxidase)、およびアミンオキシダーゼ(amine oxidases)である。 In a preferred embodiment, the enzyme is, but is not limited to, glutamine transaminase, Lipase, Peptidases, Soltase, Oxidoreductases, Tyrosinase, polyphenol oxidase ( Polyphenol oxidase (PPO), laccase (laccase), peroxidase (peroxidase), lysyl oxidase (Lysyl oxidase), and amine oxidase (amine oxidases).
好適実施形態において、前記適用フィールドは、これに制限するものではないが、電界、磁界又は重力である。 In a preferred embodiment, the applicable field is, but is not limited to, an electric field, a magnetic field or gravity.
好適実施形態において、前記ナノ繊維の平均繊度は、１０ｎｍ〜９００ｎｍである。 In a preferred embodiment, the average fineness of the nanofibers is 10 nm to 900 nm.
好適実施形態において、前記天然高分子溶液の前記天然高分子材料は、０．０１％（Ｗ／Ｖ）〜１００％（「Ｗ／Ｖ」：重量体積％）である。
In a preferred embodiment, the natural polymer material of the natural polymer solution is 0.01% (W / V) to 100% (“W / V”: weight by volume%) .
好適実施形態において、前記天然高分子溶液の無機塩類は、０．０１％（Ｗ／Ｖ）〜１００％（Ｗ／Ｖ）である。
In a preferred embodiment, the inorganic salts of the natural polymer solution are 0.01% (W / V) to 100% (W / V).
本発明は、また一方で、（ａ）天然高分子溶液を提供し、該天然高分子溶液は、天然高分子材料、無機塩類、酵素を含み、（ｂ）天然高分子溶液に適用フィールド紡糸プロセスを行い、天然高分子ナノ繊維を得ることを含む天然高分子ナノ繊維の製造方法を提供する。
The present invention also on the other hand, (a) providing a natural polymer solution, the natural polymer solution, applied natural polymer materials, inorganic salt acids, include enzyme, in (b) natural polymer solution performs field spinning process, to provide a method of manufacturing a natural polymer nanofibers include obtaining natural polymer nanofibers.
好適実施形態において、前記方法中の天然高分子材料は、ゼラチン(gelatin)、コラーゲン(collagen)、ヒアルロン酸(hyaluronic acid)、アルギン酸塩(alginate)、キトサン(chitosan)からなる群から選択される。 In a preferred embodiment, the natural polymeric material in the method is selected from the group consisting of gelatin, collagen, hyaluronic acid, alginate, chitosan.
好適実施形態において、前記方法中の無機塩は、ヒドロキシアパタイト(hydroxyapatite，Hap)、リン酸三カルシウム(tricalcium phosphate，TCP)、リン酸二カルシウム(dicalcium phosphate，DCP)、リン酸二カルシウム二水和物(dicalcium phosphate dehydrate，DCPD)、リン酸四カルシウム(tetracalcium phosphate，TTCP)、炭酸塩、硝酸塩、硫酸塩、カルシウム塩、カリウム塩、ナトリウム塩、マグネシウム塩からなる群から選択される。
In a preferred embodiment, the inorganic salts in the method are hydroxyapatite (Hap), tricalcium phosphate (TCP), dicalcium phosphate (DCP), dicalcium phosphate dihydration. It is selected from the group consisting of dicalcium phosphate dehydrate (DCPD), tetracalcium phosphate (TTCP), carbonates, nitrates, sulfates, calcium salts , potassium salts , sodium salts , and magnesium salts .
好適実施形態において、前記方法中の酵素は、グルタミントランスアミナーゼである。 In a preferred embodiment, the enzyme in the method is glutamine transaminase.
好適実施形態において、前記方法中の適用フィールドは、電界、磁界又は重力である。 In a preferred embodiment, the field of application in the method is an electric field, a magnetic field or gravity.
好適実施形態において、前記方法は、更に、（ｃ）該天然高分子ナノ繊維を酵素に接触させて外部架橋を行うことを含む。 In a preferred embodiment, the method further comprises (c) contacting the natural polymeric nanofibers with an enzyme for external cross-linking.
本発明は、また一方で、バイオメディカル材料とする天然高分子ナノ繊維の用途を提供する。 The present invention, on the other hand, provides applications for natural polymeric nanofibers as biomedical materials.
本発明は、先行技術に比較し、天然高分子材料の物理化学性質を変化させず、有機溶剤を使用せず、均一な繊維繊度及び形態を有するナノ繊維を形成することができる。人工高分子及び有機溶剤を使用しないことによって、安全性が大幅に向上され、且つ応用が広がり、特に食品及びバイオメディカル産業に安全に応用することができる。 Compared with the prior art, the present invention can form nanofibers having uniform fiber fineness and morphology without changing the physicochemical properties of natural polymer materials and without using organic solvents. By not using artificial polymers and organic solvents, the safety is greatly improved and the application is widened, and it can be safely applied especially to the food and biomedical industries.
別途定義がない限り、本文中の全ての技術及び科学用語は、当業者が理解する含意のとおりである。本願で使用する以下の用語は、以下の意味を有する。 Unless otherwise defined, all technical and scientific terms in the text are as implied by those skilled in the art. The following terms used in this application have the following meanings.
前後の文において、別途指定していない限りは、要素の数量は、単数の場合及び複数の場合を含むものとする。 Unless otherwise specified in the preceding and following sentences, the quantity of elements shall include the case of singular and the case of plural.
また、本文に記載の「及び／又は」は、２つの特定特徴又は組成物の１つ又は全部を表現することに用いられる。従って、「Ａ及び／又はＢ」は、「Ａ及びＢ」、「Ａ又はＢ」、「Ａ（単独）」、「Ｂ（単独）」の意味を表す。同様に、「Ａ、Ｂ及び／又はＣ」は、Ａ、Ｂ及びＣ；Ａ、Ｂ又はＣ；Ａ又はＣ；Ａ又はＢ；Ｂ又はＣ；Ａ及びＣ；Ａ及びＢ；Ｂ及びＣ；（単独）Ａ；（単独）Ｂ；（単独）Ｃを含む。 In addition, "and / or" described in the text is used to express one or all of two specific features or compositions. Therefore, "A and / or B" represents the meaning of "A and B", "A or B", "A (single)", and "B (single)". Similarly, "A, B and / or C" refers to A, B and C; A, B or C; A or C; A or B; B or C; A and C; A and B; B and C; Includes (single) A; (single) B; (single) C.
本発明の天然高分子ナノ繊維は、天然高分子溶液が適用フィールド制御紡糸プロセスにより得られ、該天然高分子溶液は、天然高分子材料、無機塩類、酵素を含む。
The natural polymer nanofibers of the present invention are obtained by a field-controlled spinning process to which a natural polymer solution is applied, the natural polymer solution containing natural polymer materials, inorganic salts and enzymes .
本文中に記載の「天然高分子材料」とは、自然界に存在し、人工合成の高分子ではなく、例えば、ゼラチン、コラーゲン、ヒアルロン酸、アルギン酸、キトサン及び前記天然高分子の誘導体を指すが、これに制限するものではない。好適実施例において、該天然高分子材料の重量平均分子量は、１万〜２０万の間であり、好ましくは、１．５万〜１５万の間であり、更に好ましくは、２万〜１０万の間である。 The "natural polymer material" described in the text refers to, for example, gelatin, collagen, hyaluronic acid, alginic acid, chitosan, and derivatives of the natural polymer, which exist in nature and are not artificially synthesized polymers. It is not limited to this. In a preferred embodiment, the weight average molecular weight of the natural polymeric material is between 10,000 and 200,000, preferably between 15,000 and 150,000, more preferably between 20,000 and 100,000. Between.
本文中に記載の天然高分子溶液は、上記の天然高分子溶液を溶剤に溶かしたものであり、該溶剤は、如何なる極性溶剤であってもよく、好適実施例において、該極性溶剤は、水である。該天然高分子溶液の該天然高分子材料は、０．１％（Ｗ／Ｖ）〜５０％（Ｗ／Ｖ）であり、好ましくは、０．５％（Ｗ／Ｖ）〜４０％（Ｗ／Ｖ）であり、更に好ましくは、１％（Ｗ／Ｖ）〜３０％（Ｗ／Ｖ）であり、例えば、１０％（Ｗ／Ｖ）、１５％（Ｗ／Ｖ）、２０％（Ｗ／Ｖ）である。 The natural polymer solution described in the text is a solution of the above-mentioned natural polymer solution in a solvent, and the solvent may be any polar solvent. In a preferred embodiment, the polar solvent is water. Is. The natural polymer material of the natural polymer solution is 0.1% (W / V) to 50% (W / V), preferably 0.5% (W / V) to 40% (W). / V), more preferably 1% (W / V) to 30% (W / V), for example, 10% (W / V), 15% (W / V), 20% (W). / V).
本文中に記載の天然高分子溶液は、更に、無機塩類を含む。本文に記載の無機塩類は、天然高分子材料の受電性を変化できる無機塩類であり、これに制限するものではないが、例えば、ヒドロキシアパタイト(hydroxyapatite，Hap)、リン酸三カルシウム(tricalcium phosphate，TCP)、リン酸二カルシウム(dicalcium phosphate，DCP)、リン酸二カルシウム二水和物(dicalcium phosphate dehydrate，DCPD)、リン酸四カルシウム(tetracalcium phosphate，TTCP)、炭酸塩、硝酸塩、硫酸塩、カルシウム塩、カリウム塩、ナトリウム塩、マグネシウム塩である。該天然高分子溶液の該無機塩類は、０．１％（Ｗ／Ｖ）〜５０％（Ｗ／Ｖ）であり、好ましくは、０．５％（Ｗ／Ｖ）〜４０％（Ｗ／Ｖ）であり、更に、好ましくは、１％（Ｗ／Ｖ）〜３０％（Ｗ／Ｖ）であり、例えば、１０％（Ｗ／Ｖ）、１５％（Ｗ／Ｖ）、２０％（Ｗ／Ｖ）である。
The natural polymer solutions described in the text further contain inorganic salts. The inorganic salts described in the text are inorganic salts that can change the power receiving property of natural polymer materials and are not limited to these, but for example, hydroxyapatite (Hap), tricalcium phosphate, TCP), dicalcium phosphate (DCP), dicalcium phosphate dehydrate (DCPD), tetracalcium phosphate (TTCP), carbonates, nitrates, sulfates, calcium Salts , potassium salts , sodium salts , magnesium salts . The inorganic salts of the natural polymer solution are 0.1% (W / V) to 50% (W / V), preferably 0.5% (W / V) to 40% (W / V). ), More preferably 1% (W / V) to 30% (W / V), for example, 10% (W / V), 15% (W / V), 20% (W / V). V).
上記天然高分子溶液中の天然高分子材料及び無機塩類は、１〜９６時間、好ましくは、１２〜４８時間、更に好ましくは２４〜３６時間、例えば、２４時間、２８時間、３０時間、３２時間、３４時間、３６時間、混合する。 The natural polymer material and the inorganic salts in the natural polymer solution last for 1 to 96 hours, preferably 12 to 48 hours, more preferably 24 to 36 hours, for example, 24 hours, 28 hours, 30 hours, 32 hours. , 34 hours, 36 hours, mix.
本文中に記載の天然高分子溶液は酵素を含む。好適実施例において、該天然高分子溶液は、酵素を含み、該酵素は、該天然高分子に内部架橋を行わせることができ、天然高分子ナノ繊維の強度を増加させる。使用可能な酵素は、これに制限するものではないが、好ましくは、グルタミントランスアミナーゼ、リパーゼ(Lipase)、ペプチダーゼ（Peptidases）、ソルターゼ(Sortase)、オキシドレダクターゼ（Oxidoreductases）、チロシナーゼ(Tyrosinase)、ポリフェノールオキシターゼ(Polyphenoloxidase，PPO)、ラッカーゼ(laccase)、ペルオキシダーゼ(peroxidase)、リシルオキシダーゼ(Lysyl oxidase)、およびアミンオキシダーゼ(amine oxidases)であり、使用可能な濃度は、１％〜１００％である。 The natural polymer solutions described in the text contain enzymes . In a preferred embodiment, the natural polymer solution comprises an enzyme , which can cause the natural polymer to undergo internal cross-linking, increasing the strength of the natural polymer nanofibers. The enzymes that can be used are not limited to this, but preferably glutamine transaminase, lipase, peptidases, sortase, oxidoreductases, tyrosinase, polyphenol oxidase ( Polyphenol oxidase, PPO, laccase, peroxidase, Lysyl oxidase, and amine oxidases, with usable concentrations ranging from 1% to 100%.
本発明の天然高分子ナノ繊維の製造方法は、（ａ）天然高分子溶液を提供し、該天然高分子溶液は、天然高分子材料、無機塩類、酵素を含み、（ｂ）該天然高分子溶液に適用フィールド紡糸プロセスを行い、該天然高分子ナノ繊維を得ることを含む。
The method for producing a natural polymer nanofiber of the present invention provides (a) a natural polymer solution, and the natural polymer solution contains a natural polymer material, inorganic salts , and enzymes, and (b) the natural polymer. The solution involves performing an applied field spinning process to obtain the natural polymeric nanofibers.
本発明の製造方法が称する「適用フィールド制御紡糸プロセス」とは、該天然高分子溶液が防止装置に取り込まれ、防止プロセスを行い、プロセスにおいて、これに制限するものではないが、電界、磁場、重力を含む適用フィールドを施し、天然高分子溶液の陰陽イオンを連動し、伴って、高分子材料を連動し、ナノ繊維を形成する。本発明の好適実施例に基づき、該適用フィールド紡糸プロセスは、放電紡糸プロセスであり、引火電圧を有し、該印加電圧の範囲は、１μボルト〜１００００００ボルトであり、好ましくは、１０００ボルト〜７００００ボルトであり、更に好ましくは、３００００ボルト〜５００００ボルトである。また、該放電紡糸プロセスの紡糸口から収集領域までの距離は、１〜３０ｃｍの間であり、且つ該放電紡糸プロセスの液排出速度は、１０μｌ／ｍｉｎ以上であることができる。 The "applicable field control spinning process" referred to by the manufacturing method of the present invention means that the natural polymer solution is taken into a prevention device, a prevention process is performed, and the process is not limited to the electric field, the magnetic field, and the like. An application field that includes gravity is applied, and the anions and cations of the natural polymer solution are linked, and the polymer material is linked to form nanofibers. Based on preferred embodiments of the present invention, the applied field spinning process is a discharge spinning process, has a flammable voltage, and the applied voltage range is 1 μV to 1000000 V, preferably 1000 V to 70000. It is a volt, more preferably 30,000 to 50,000 volt. The distance from the spinneret of the discharge spinning process to the collection region can be between 1 and 30 cm, and the liquid discharge rate of the discharge spinning process can be 10 μl / min or more.
本発明の製造方法は、更に、外部架橋ステップを含むことができ、即ち、上記獲得した天然高分子繊維は、酵素架橋剤に接触して架橋を行い、天然高分子ナノ繊維の強度を向上させ、分解時間を延長することができ、該架橋時間は、１〜９６時間であり、好ましくは、約２４〜４８時間であり、例えば、２４時間、２６時間、２８時間、３０時間、３２時間、３４時間、３６時間、３８時間、４０時間、４２時間、４４時間、４６時間、４８時間等である。上述の「接触」とは、酵素架橋剤を天然高分子ナノ繊維と作用させることができる任意の方式を指し、例えば、天然高分子ナノ繊維を酵素架橋剤に浸漬するか、酵素架橋剤を天然高分子ナノ繊維にスプレー塗布することであるが、これに制限するものではない。 The production method of the present invention can further include an external cross-linking step, that is, the obtained natural polymer fibers are crosslinked in contact with an enzyme cross-linking agent to improve the strength of the natural polymer nanofibers. The decomposition time can be extended and the cross-linking time is 1-96 hours, preferably about 24-48 hours, eg, 24 hours, 26 hours, 28 hours, 30 hours, 32 hours, 34 hours, 36 hours, 38 hours, 40 hours, 42 hours, 44 hours, 46 hours, 48 hours and the like. The above-mentioned "contact" refers to any method capable of allowing the enzyme cross-linking agent to act with the natural polymer nanofibers, for example, immersing the natural polymer nanofibers in the enzyme cross-linking agent or naturalizing the enzyme cross-linking agent. It is, but is not limited to, spray-applying to polymer nanofibers.
上記方法で製造される天然高分子ナノ材料は、そのうち、該ナノ繊維の平均繊度は、１０ｎｍ〜５００ｎｍであり、好ましくは、１０ｎｍ〜５０ｎｍであり、例えば、１０ｎｍ、２０ｎｍ、３０ｎｍ、４０ｎｍ、５０ｎｍ等である。本発明の天然高分子ナノ繊維は、更に良好な繊度を有し、且つ向上した安全性を有し、従って、人工高分子ポリマーのナノ繊維に比較し、本発明の天然高分子ナノ繊維は、食品、バイオメディカル等の分野に広く用いることができ、例えば、バイオメディカルの３Ｄプリントのナノ繊維材料に用いることができる。 Among the natural polymer nanomaterials produced by the above method, the average fineness of the nanofibers is 10 nm to 500 nm, preferably 10 nm to 50 nm, for example, 10 nm, 20 nm, 30 nm, 40 nm, 50 nm and the like. Is. The natural polymer nanofibers of the present invention have even better fineness and improved safety, and therefore, the natural polymer nanofibers of the present invention are compared to artificial polymer nanofibers. It can be widely used in fields such as food and biomedical, and can be used, for example, as a biomedical 3D printed nanofiber material.
当業者に本発明の内容を理解させて実施させるため、且つ本明細書の開示内容、請求項及び図面に基づき、当業者が本発明の関連目的及び利点を容易に理解できるようにするため、実施例において、本発明の詳細な特徴及び利点を詳細に説明する。以下の実施例は、説明用とするのみであり、本願の請求項の範囲を制限するものではない。 To make a person skilled in the art understand and implement the contents of the present invention, and to enable a person skilled in the art to easily understand the related object and advantage of the present invention based on the disclosure contents, claims and drawings of the present specification. In the examples, detailed features and advantages of the present invention will be described in detail. The following examples are for illustration purposes only and do not limit the scope of the claims of the present application.
[実施例1]
２０％（ｗ／ｖ）のゼラチン（gelatin）水溶液を配置し、該ゼラチン水溶液に２０％（ｗ／ｖ）のハイドロキシアパタイトを添加し、２４時間混合撹拌を持続する。その後、温度を５０℃±５℃に制御し、１０ｍＬ注射器に装填し、糸引き高さ６０ｍｍ、射出速度２ｍＬ／ｈｒ、電界電圧２０ｋＶとする。得られる天然高分子ナノ繊維は、図１に示すとおりである。
[Example 1]
A 20% (w / v) aqueous gelatin solution is placed, 20% (w / v) hydroxyapatite is added to the aqueous gelatin solution, and mixing and stirring are continued for 24 hours. After that, the temperature is controlled to 50 ° C. ± 5 ° C., loaded into a 10 mL syringe, and the stringing height is 60 mm, the injection speed is 2 mL / hr, and the electric field voltage is 20 kV. The obtained natural polymer nanofibers are as shown in FIG.
［実施例２］
実施例１と同じ配合を使用し、差異は、１０ｗｔ％の酵素架橋剤を添加することにあり、その他は、何れも同じである。得られる天然高分子ナノ繊維は、図２に示すとおりである。
[Example 2]
The same formulation as in Example 1 is used, the difference being the addition of 10 wt% enzyme cross-linking agent, all the others being the same. The obtained natural polymer nanofibers are as shown in FIG.
［実施例３］
本実施例と実施例１の差異は、２０％（ｗ／ｖ）のハイドロキシアパタイトをリン酸三カルシウム（ＴＣＰ）に換えた点にあり、その他は、何れも同じであり、得られる天然高分子ナノ繊維は、図２に示すとおりである。
[Example 3]
The difference between this example and Example 1 is that 20% (w / v) of hydroxyapatite is replaced with tricalcium phosphate (TCP), and the others are the same, and the obtained natural polymer is obtained. The nanofibers are as shown in FIG.
［実施例４］
本実施例と実施例３の差異は、１０ｗｔ％の酵素架橋剤を添加し、射出速度を１．３Ｌ／ｈｒ、電界電圧１３．５ｋＶに調整した点にあり、その他は何れも同じであり、得られる天然高分子ナノ繊維は、図４に示すとおりである。
[Example 4]
The difference between this example and Example 3 is that 10 wt% of an enzyme cross-linking agent was added to adjust the injection speed to 1.3 L / hr and the electric field voltage to 13.5 kV, and the others are the same. The obtained natural polymer nanofibers are as shown in FIG.
［実施例５］
５％（ｗ／ｖ）のゼラチン（ｇｅｌａｔｉｎ）水溶液を配置し、該ゼラチン水溶液中に５％（ｗ／ｖ）のリン酸三カルシウム塩を添加し、２４時間混合撹拌を持続する。その後、温度を５０℃±５℃に制御し、１０ｍＬ注射器に装填し、糸引き高さ６０ｍｍ、射出速度０．９ｍＬ／ｈｒ、電界電圧７ｋＶとする。得られる天然高分子ナノ繊維は、図５に示すとおりである。
[Example 5]
A 5% (w / v) aqueous gelatin (gelatin) solution is placed, a 5% (w / v) tricalcium phosphate salt is added to the aqueous gelatin solution, and mixing and stirring are continued for 24 hours. After that, the temperature is controlled to 50 ° C. ± 5 ° C., and the mixture is loaded into a 10 mL syringe so that the stringing height is 60 mm, the injection speed is 0.9 mL / hr, and the electric field voltage is 7 kV. The obtained natural polymer nanofibers are as shown in FIG.
［実施例６］
本実施例及び実施例５の差異は、１０ｗｔ％の酵素架橋剤を添加することにあり、その他は、何れも同じであり、得られる天然高分子ナノ繊維は、図６に示すとおりである。
[Example 6]
The difference between this example and Example 5 is that 10 wt% of the enzyme cross-linking agent is added, and the others are the same, and the obtained natural polymer nanofibers are as shown in FIG.
上記各実施例は、本発明の特徴を説明するために用いるものであり、その目的は、当業者に本発明の内容を理解させ、実施できるようにするものであり、本発明の保護範囲を制限するものではなく、その他の本発明が開示する精神を脱することなく完成する均等の修飾又は修正は、依然として下記の保護範囲に含まれるべきである。 Each of the above examples is used to explain the features of the present invention, and an object thereof is to allow a person skilled in the art to understand and carry out the contents of the present invention, and to cover the scope of protection of the present invention. Other equal modifications or modifications that are not limiting and that are completed without breaking the spirit disclosed by the present invention should still be included in the scope of protection below.
Claims (5)
（ｂ）該天然高分子溶液に適用フィールド紡糸プロセスを行い、天然高分子ナノ繊維を得ることを含み、(B) Including applying a field spinning process to the natural polymer solution to obtain natural polymer nanofibers.
更に、（ｃ）前記天然高分子ナノ繊維を酵素に接触させて外部架橋を行うことを含む天然高分子ナノ繊維の製造方法。Further, (c) a method for producing a natural polymer nanofiber, which comprises contacting the natural polymer nanofiber with an enzyme to perform external cross-linking.
The method for producing a natural polymer nanofiber according to any one of claims 1 to 4, wherein the applicable field is an electric field, a magnetic field, or gravity.
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| TW201938857A (en) | 2019-10-01 |
| EP3543381A1 (en) | 2019-09-25 |
| JP2019167664A (en) | 2019-10-03 |
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