WO2015093589A1

WO2015093589A1 - Fibers, composition for producing fibers, and biomaterial containing fibers

Info

Publication number: WO2015093589A1
Application number: PCT/JP2014/083658
Authority: WO
Inventors: 高広岸岡; 真紀子梅嵜; 彩子大谷
Original assignee: 日産化学工業株式会社
Priority date: 2013-12-20
Filing date: 2014-12-19
Publication date: 2015-06-25
Also published as: EP3085817A4; US20160305044A1; TW201529620A; JPWO2015093589A1; SG11201605038QA; CN105829590A; EP3085817A1; JP6701733B2

Abstract

　The purpose of the present invention is to provide: fibers having superior safety, that can be produced easily, and are resistant to organic solvents; a raw material composition for producing said fibers; and a biomaterial containing said fibers.　The fibers are produced by spinning a composition containing, (A) a condensation product obtained by condensing one or more of the compounds represented by general formula (1), and (B) an acid compound. (Each symbol in the formula is as defined in the description.)

Description

Fiber, composition for producing the fiber, and biocompatible material containing the fiber

The present invention relates to a composition for producing a fiber containing a condensation product obtained by condensing a specific triazine compound and an acid compound, a fiber produced by spinning the composition, and a biocompatible material containing the fiber. .

In recent years, ultrafine fibers with a diameter of nanometer order to micrometer order have attracted attention, and are used in various fields such as batteries / information, environment / energy, medical treatment (eg, biocompatible materials) / welfare. It is expected that.

As materials for forming the ultrafine fibers, various materials such as organic polymers such as nylon, inorganic substances such as TiO ₂ and SiO ₂ , and polymers derived from living organisms such as cellulose and collagen have been studied.

Melt blowing, composite melt spinning, electrospinning, etc. are known as technologies for spinning ultrafine fibers with nanometer order to micrometer order diameters. Is also attracting attention as a method for making fibers. For example, in addition to the aforementioned bio-derived polymers such as cellulose and collagen, many medical polymers such as polylactic acid and water-soluble polymers such as polyvinyl alcohol have been studied (Patent Documents 1 to 7, Non-patent Documents). Reference 1).

On the other hand, biocompatible materials such as cell culture scaffolds have recently been evaded from the use of biological materials (especially bovine gelatin) due to safety issues. , Synthetic polymers, etc.).

In addition, biocompatible materials such as cell culture scaffold materials use an organic solvent such as ethanol as a sterilization treatment. Therefore, when applying the above ultrafine fibers to biocompatible materials, resistance to organic solvents is also necessary. In the above patent document and non-patent document, as a means for improving the durability of the fiber, a method of cross-linking polymers with a cross-linking agent, etc. is used. In some cases, complicated processing such as hydrogen chloride gas processing is required (for example, Patent Documents 3 and 7 and Non-Patent Document 1). Therefore, there is a demand for a method capable of producing a fiber having resistance to organic solvents only by simple treatment (for example, only heat treatment, preferably only low-temperature and short-time heat treatment).

US Patent Application Publication No. 2002/0192468 Chinese Patent Application No. 101718044 JP 2013-49927 A Special table 2008-514341 International Publication No. 2007/102606 Japanese Unexamined Patent Publication No. 2009-100 US Patent Application Publication No. 2011/0275154 JP 2012-67432 A

An object of the present invention is to provide a fiber that is excellent in safety, can be easily manufactured, and has resistance to organic solvents, a raw material composition for manufacturing the fiber (a composition for manufacturing a fiber), and a biocompatible material including the fiber Is to provide.

As a result of intensive studies by the present inventors, a fiber produced by spinning a composition containing a condensation product obtained by condensing a specific triazine compound and an acid compound has sufficient organic solvent resistance, and Has been found to be useful as a biocompatible material because it has excellent biocompatibility and, as a specific example, a function as a cell culture scaffold, has led to the completion of the present invention.
Further, the present inventors have found that the fiber of the present invention expresses better organic solvent resistance and the production efficiency is improved by performing heat treatment.

That is, the present invention is as follows.

[1] (A) produced by spinning a condensation product obtained by condensing one or more compounds represented by formula (1), and (B) an acid compound. Fiber.

[Where,
R ¹ represents an amino group optionally substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or a carbon atom. Represents an aryl group of formulas 6 to 14;
R ² , R ³ , R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6. ]
[2] The fiber according to [1], wherein the composition further contains (C) a solvent.
[3] R ¹ is an amino group, a vinyl group, a propenyl group, a butenyl group, a phenyl group or a naphthyl group which may be substituted with a methoxymethyl group, an ethoxymethyl group, a propoxymethyl group, a butoxymethyl group or a hydroxymethyl group. Chosen from the group,
R ² , R ³ , R ⁴ and R ⁵ are the same or different and are a hydrogen atom, a hydroxymethyl group, a methoxymethyl group, an ethoxymethyl group, a propoxymethyl group, a butoxymethyl group, a vinyl group, a propenyl group, or a butenyl group. The fiber according to [1] or [2], selected from methyl group, ethyl group, propyl group and butyl group.
[4] (A) The condensation product is represented by the general formula (1A):

[Where,
R ^1A represents an amino group which may be substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group;
R ² , R ³ , R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6. And / or general formula (1B):

[Where,
R ^1B represents an aryl group having 6 to 14 carbon atoms;
R ² , R ³ , R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6. ] The fiber as described in [1] or [2] which is a condensation product obtained by condensing the compound represented by this.
[5] The fiber according to any one of [1] to [4], wherein the condensation product (A) has a weight average molecular weight of 1,000 to 1,000,000.
[6] The fiber according to any one of [1] to [5], wherein the spinning is electrospinning.
[7] The fiber according to any one of [1] to [6], which is a nanofiber and / or a microfiber.
[8] A composition for fiber production containing (A) a condensation product obtained by condensing one or more compounds represented by formula (1), and (B) an acid compound.

[Where,
R ¹ represents an amino group optionally substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or a carbon atom. Represents an aryl group of formulas 6 to 14;
R ² , R ³ , R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6. ]
[9] The composition according to [8], further comprising (C) a solvent.
[10] The condensation product (A) is represented by the general formula (1A):

[Where,
R ^1B represents an aryl group having 6 to 14 carbon atoms;
R ² , R ³ , R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6. ] The composition of [8] or [9] which is a condensation product obtained by condensing the compound represented by this.
[11] The composition according to any one of [8] to [10], wherein the condensation product (A) has a weight average molecular weight of 1,000 to 1,000,000.
[12] The composition according to any one of [8] to [11], wherein the content of the solid content of the (A) condensation product is 1 to 90% by weight.
[13] (First step) (A) A step of obtaining a condensation product solution by condensing a monomer composition containing one or more compounds represented by general formula (1),
(Second step) (A) A step of adding an acid compound and (C) solvent to the condensation product solution to obtain a composition for fiber production, and (Third step) a composition for fiber production. A method for producing a fiber, comprising a step of spinning.

[Where,
R ¹ represents an amino group optionally substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or a carbon atom. Represents an aryl group of formulas 6 to 14;
R ² , R ³ , R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6. ]
[14] The method according to [13], further comprising a step of heating the spun fiber in the range of 50 to 300 ° C.
[15] The method according to [13] or [14], wherein the spinning is electrospinning.
[16] A biocompatible material comprising the fiber according to any one of [1] to [7].

According to the present invention, it is possible to provide a fiber that is excellent in safety, can be easily produced, and has resistance to organic solvents, a raw material composition for producing the fiber, and a biocompatible material containing the fiber.

It is a SEM photograph before the heating of the fiber obtained from the composition for fiber manufacture of Example 1 by the electrospinning method. It is a SEM photograph (enlarged view) before heating of the fiber obtained by the electrospinning method from the composition for producing fibers of Example 1. It is a SEM photograph after heat-processing the fiber obtained by the electrospinning method from the composition for fiber manufacture of Example 1 for 10 minutes at 80 degreeC. It is a SEM photograph (enlarged view) after heat-processing the fiber obtained by the electrospinning method from the composition for fiber manufacture of Example 1 at 80 degreeC for 10 minutes. It is a SEM photograph after heat-processing the fiber obtained by the electrospinning method from the composition for fiber manufacture of Example 1 at 80 degreeC for 10 minutes, and being immersed in acetone. It is a SEM photograph (enlarged view) after heat-processing the fiber obtained by the electrospinning method from the composition for fiber manufacture of Example 1 at 80 degreeC for 10 minutes, and being immersed in acetone. It is a SEM photograph after heat-processing the fiber obtained by the electrospinning method from the composition for fiber manufacture of Example 1 at 205 degreeC for 10 minutes. It is a SEM photograph (enlarged view) after heat-processing the fiber obtained by the electrospinning method from the composition for fiber manufacture of Example 1 at 205 degreeC for 10 minutes. It is a SEM photograph after heat-treating the fiber obtained by the electrospinning method from the composition for fiber manufacture of Example 1 at 205 degreeC for 10 minutes, and being immersed in acetone. It is a SEM photograph (enlarged view) after heat-treating the fiber obtained by the electrospinning method from the composition for fiber manufacture of Example 1 at 205 degreeC for 10 minutes, and immersing in acetone. 2 is a SEM photograph before heating of a fiber obtained from the composition for producing a fiber of Comparative Example 1 by an electrospinning method. It is a SEM photograph (enlarged view) before heating the fiber obtained by the electrospinning method from the composition for fiber manufacture of Comparative Example 1. It is a SEM photograph after heat-processing the fiber obtained by the electrospinning method from the composition for fiber manufacture of the comparative example 1 at 80 degreeC for 10 minutes. It is a SEM photograph (enlarged view) after heat-processing the fiber obtained by the electrospinning method from the composition for fiber manufacture of the comparative example 1 at 80 degreeC for 10 minutes.

The fiber of the present invention comprises (A) a condensation product obtained by condensing one or more compounds represented by the general formula (1) (hereinafter referred to as “condensation product of component A” or simply “component”). A "), and (B) an acid compound (hereinafter also referred to as" component B acid compound "or simply" component B "). Is the main feature.

The diameter of the fiber of the present invention can be appropriately adjusted according to the use of the fiber and the like, and is not particularly limited. However, from the viewpoint of application to a substrate serving as a cell scaffold, medical material, cosmetic material, etc. The fibers of the invention are preferably fibers (nanofibers) having a diameter on the order of nanometers (eg, 1 to 1000 nm) and / or fibers (microfibers) on the order of micrometers (eg, 1 to 1000 μm). In the present invention, the diameter of the fiber is measured with a scanning electron microscope (SEM).

[Component A]
Component A has the general formula (1):

[Where,
R ¹ represents an amino group optionally substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or a carbon atom. Represents an aryl group of formulas 6 to 14;
R ² , R ³ , R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6. ]
It is a condensation product obtained by condensing 1 type (s) or 2 or more types of the compound represented by these.

The definition of each group in the general formula (1) will be described in detail below.

R ¹ represents an amino group optionally substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or a carbon atom. An aryl group represented by formulas 6 to 14 is shown.

The “alkoxymethyl group having 2 to 6 carbon atoms” in the “amino group optionally substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group” represented by R ¹ is linear or branched Specific examples of the chain may include a methoxymethyl group, an ethoxymethyl group, a propoxymethyl group, an isopropoxymethyl group, a butoxymethyl group, an isobutoxymethyl group, a sec-butoxymethyl group, and a tert-butoxymethyl group. Pentoxymethyl group, isopentoxymethyl group, neopentoxymethyl group, tert-pentoxymethyl group, 1-ethylpropoxymethyl group, 2-methylbutoxymethyl group and the like. The number of carbon atoms of the alkoxymethyl group is preferably 2 to 5, and more preferably 2 to 4.

The “alkyl group having 1 to 6 carbon atoms” represented by R ¹ may be either linear or branched, and specific examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, and a butyl group. , Isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group, tert-pentyl group, 1-ethylpropyl group, hexyl group, isohexyl group, 1,1-dimethylbutyl group, 2, Examples include 2-dimethylbutyl group, 3,3-dimethylbutyl group, 2-ethylbutyl group and the like. The number of carbon atoms of the alkyl group is preferably 1 to 5, more preferably 1 to 4.

The “alkenyl group having 2 to 6 carbon atoms” represented by R ¹ may be linear or branched, and specific examples thereof include a vinyl group, an allyl group, a propenyl group, a butenyl group, and a pentenyl group. Hexenyl group and the like. The number of carbon atoms of the alkenyl group is preferably 2-5, more preferably 2-4.

The “aryl group having 6 to 14 carbon atoms” represented by R ¹ may be monocyclic or condensed polycyclic, and specific examples thereof include phenyl group, naphthyl group, azulenyl group, indenyl group, indanyl. Group, anthryl group, phenanthryl group, acenaphthylenyl group and the like. The number of carbon atoms of the aryl group is preferably 6 to 12, and more preferably 6 to 10.

From the viewpoint of the reactivity of the condensation reaction, R ¹ is preferably an amino group optionally substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group, an alkenyl group having 2 to 6 carbon atoms, or An aryl group having 6 to 14 carbon atoms, more preferably an amino group, a vinyl group, a propenyl group, which may be substituted with a methoxymethyl group, an ethoxymethyl group, a propoxymethyl group, a butoxymethyl group or a hydroxymethyl group, A butenyl group, a phenyl group or a naphthyl group, particularly preferably an amino group or a phenyl group which may be substituted with a methoxymethyl group, an ethoxymethyl group, a butoxymethyl group or a hydroxymethyl group.

R ² , R ³ , R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6.

“Alkoxymethyl group having 2 to 6 carbon atoms”, “alkenyl group having 2 to 6 carbon atoms” and “alkyl group having 1 to 6 carbon atoms” represented by R ² , R ³ , R ⁴ or R ⁵ it is "alkoxymethyl group having 2 to 6 carbon atoms" in the above R ^1, respectively, is synonymous with "alkenyl group having 2 to 6 carbon atoms" and the "alkyl group having 1 to 6 carbon atoms."

R ² , R ³ , R ⁴ and R ⁵ are the same or different from the viewpoint of reactivity with an alkoxymethyl group or a hydroxymethyl group for performing a condensation reaction, preferably a hydrogen atom, a hydroxymethyl group or a methoxymethyl group. , Ethoxymethyl group, propoxymethyl group, butoxymethyl group, vinyl group, propenyl group, butenyl group, methyl group, ethyl group, propyl group or butyl group, more preferably methoxymethyl group, ethoxymethyl group, butoxymethyl group Or it is a hydroxymethyl group.

The compound represented by the general formula (1) is:
R ¹ is an amino group, vinyl group, propenyl group, butenyl group, phenyl group and naphthyl group (more preferably) which may be substituted with a methoxymethyl group, an ethoxymethyl group, a propoxymethyl group, a butoxymethyl group or a hydroxymethyl group. Is an amino group and a phenyl group which may be substituted with a methoxymethyl group, an ethoxymethyl group, a butoxymethyl group or a hydroxymethyl group, particularly preferably a methoxymethyl group, a butoxymethyl group or a hydroxymethyl group. Amino groups and phenyl groups);
R ² , R ³ , R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, a hydroxymethyl group, a methoxymethyl group, an ethoxymethyl group, a propoxymethyl group, a butoxymethyl group, a vinyl group, a propenyl group, a butenyl group, It is selected from a methyl group, an ethyl group, a propyl group and a butyl group (more preferably a methoxymethyl group, an ethoxymethyl group, a butoxymethyl group and a hydroxymethyl group, particularly preferably a methoxymethyl group, a butoxymethyl group and a hydroxymethyl group). Is preferred.

The compound represented by the general formula (1) can be produced by a method known per se or a method analogous thereto. Moreover, you may use a commercial item.

The condensation product of component A may be a product obtained by condensing one type of compound represented by the general formula (1), or a product obtained by condensing two or more types of compounds represented by the general formula (1). However, it is preferable to condense 4 or less of the compound represented by the general formula (1), more preferable to condense 3 or less of the compound represented by the general formula (1). What condensed 2 or less types of compounds represented by Formula (1) is especially preferable.

As one aspect of component A, for example, general formula (1A):

[Where,
R ^1A represents an amino group which may be substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group;
R ² , R ³ , R ⁴ and R ⁵ are as defined above. And / or general formula (1B):

[Where,
R ^1B represents an aryl group having 6 to 14 carbon atoms;
R ² , R ³ , R ⁴ and R ⁵ are as defined above. ] The condensation product obtained by condensing the compound represented by this, etc. are mentioned.

“An alkoxymethyl group having 2 to 6 carbon atoms” in the “amino group optionally substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group” represented by R ^1A , and represented by R ^1B The “aryl group having 6 to 14 carbon atoms” has the same meaning as the “alkoxymethyl group having 2 to 6 carbon atoms” and the “aryl group having 6 to 14 carbon atoms” in R ¹ .

The compound represented by the general formula (1A) is
R ^1A is an amino group which may be substituted with a methoxymethyl group, an ethoxymethyl group, a propoxymethyl group, a butoxymethyl group or a hydroxymethyl group (more preferably, a methoxymethyl group, an ethoxymethyl group, a butoxymethyl group or a hydroxymethyl group). An amino group optionally substituted with a group, particularly preferably an amino group optionally substituted with a methoxymethyl group, a butoxymethyl group or a hydroxymethyl group;
R ² , R ³ , R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, a hydroxymethyl group, a methoxymethyl group, an ethoxymethyl group, a propoxymethyl group, a butoxymethyl group, a vinyl group, a propenyl group, a butenyl group, It is selected from a methyl group, an ethyl group, a propyl group and a butyl group (more preferably a methoxymethyl group, an ethoxymethyl group, a butoxymethyl group and a hydroxymethyl group, particularly preferably a methoxymethyl group, a butoxymethyl group and a hydroxymethyl group). Is preferred.

The compound represented by the general formula (1B) is:
R ^1B is selected from a phenyl group and a naphthyl group (more preferably a phenyl group);
R ² , R ³ , R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, a hydroxymethyl group, a methoxymethyl group, an ethoxymethyl group, a propoxymethyl group, a butoxymethyl group, a vinyl group, a propenyl group, a butenyl group, It is selected from a methyl group, an ethyl group, a propyl group and a butyl group (more preferably a methoxymethyl group, an ethoxymethyl group, a butoxymethyl group and a hydroxymethyl group, particularly preferably a methoxymethyl group, a butoxymethyl group and a hydroxymethyl group). Is preferred.

When the compound represented by the general formula (1A) and the compound represented by the general formula (1B) are condensed, the weight ratio (1A: 1B) of each compound used is not particularly limited. 10: 1.

Component A can be produced by a method known per se or a method analogous thereto. For example, one or more of the compounds represented by the general formula (1) are mixed with an appropriate condensation initiator (eg, p-toluenesulfonic acid) in an appropriate solvent (eg, ethyl lactate). Although it can manufacture by superposing | polymerizing using, etc., it is not limited to this. Moreover, you may use a commercial item.

When one or more of the compounds represented by the general formula (1) are polymerized, the compound represented by the general formula (1) and other polymerizable compounds are combined together unless the purpose of the present invention is impaired. May be polymerized. Examples of the other compounds include, but are not limited to, known acrylic compounds and known methacrylic compounds. The other compounds may be used alone or in combination of two or more. The ratio of the compound represented by the general formula (1) to all the compounds to be polymerized is usually 10 mol% or more, preferably 30 mol% or more, particularly preferably 50 mol% or more.

As the known acrylic compound or known methacrylic compound, for example, the following general formula (2):

[Where,
R ⁶ and R ⁷ are the same or different and each represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms. ] The compound represented by this is preferable.
The “alkyl group having 1 to 6 carbon atoms” represented by R ⁶ and R ⁷ has the same meaning as described above.

The weight average molecular weight of component A is preferably in the range of 1,000 to 1,000,000, more preferably in the range of 5,000 to 500,000, and particularly preferably in the range of spinnability. The range is from 000 to 200,000, and most preferably from 10,000 to 100,000. In the present invention, “weight average molecular weight” means a molecular weight in terms of polystyrene measured by gel permeation chromatography (GPC).

Component A may be used alone or in combination of two or more, but is preferably 4 or less, more preferably 3 or less, and particularly preferably 2 or less.

[Component B]
Component B is an acid compound, and the components A are reacted with each other as long as the condensation products of compounds other than the compound represented by the general formula (1) are further condensed unless the object of the present invention is impaired. It acts as a catalyst for Even if the fiber containing the said component B is a case where heat processing is performed, it can maintain a favorable fiber shape, and has the favorable organic solvent tolerance. Component B may be in the form of a salt, that is, the term “acid compound” in the present invention is a concept including a salt.

Examples of the acid compound of component B include organic acid compounds such as sulfonic acid compounds, carboxylic acid compounds, and phosphoric acid compounds; inorganic acid compounds such as hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, and hydrobromic acid.

Component B is preferably an organic acid compound, and more preferably a sulfonic acid compound. Examples of the sulfonic acid compound include p-toluenesulfonic acid, pyridinium-p-toluenesulfonate, trifluoromethanesulfonic acid and the like, and p-toluenesulfonic acid or pyridinium-p-toluenesulfonate is preferable.

Component B acid compounds may be used alone or in combination of two or more.

The acid compound of component B can be produced by a method known per se or a method analogous thereto. Moreover, you may use a commercial item.

The fiber of the present invention preferably contains (C) a solvent (hereinafter also referred to as “solvent of component C” or simply “component C”) in addition to the condensation product of component A and the acid compound of component B. A composition (that is, a composition for producing a fiber of the present invention (hereinafter also simply referred to as “the composition of the present invention”)) is prepared, and the composition is spun to produce.

More particularly, the fiber of the present invention comprises:
(First step) (A) A step of obtaining a condensation product solution by condensing a monomer composition containing one or more compounds represented by general formula (1),
(Second step) (A) A step of adding an acid compound and (C) solvent to the condensation product solution to obtain a composition for fiber production, and (Third step) a composition for fiber production. It is preferably produced by a production method including a spinning step.

The solvent of component C is not particularly limited as long as it can uniformly dissolve or disperse component A and component B and does not react with each component, but from the viewpoint of solubility of components A and B, a polar solvent is used. preferable.
Examples of the polar solvent include water, methanol, ethanol, 2-propanol, propylene glycol monomethyl ether, acetone, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, ethyl lactate and the like. From this viewpoint, ethyl lactate is preferable.

Component C may be used alone or in combination of two or more.

The solid content of component A in the composition of the present invention is preferably 1 to 90% by weight, more preferably 1 to 70% by weight from the viewpoint of spinnability. Here, the solid content of component A is measured by using a halogen moisture meter (HR83) manufactured by METTLER TOLEDO Co., Ltd. as shown in the examples described later.

The content of component B in the composition of the present invention is preferably 1 to 10% by weight, more preferably 1 to 5% by weight, from the viewpoint of reaction efficiency during the crosslinking reaction.

The weight ratio of the solid content of component A to component B contained in the composition of the present invention (weight of solid content of component A / weight of component B) is preferably 5 to 40 from the viewpoint of reaction efficiency during the crosslinking reaction. 10 to 30 is more preferable.

The content of component C in the composition of the present invention is preferably 5 to 80% by weight, more preferably 10 to 50% by weight, from the viewpoint of spinnability of the composition for fiber production.

The composition of the present invention may contain, in addition to components A to C, additives conventionally used in the field of fiber production, if necessary, as long as the object of the present invention is not impaired. Examples of the additive include a crosslinking agent, a surfactant, a rheology modifier, a drug, fine particles, a condensation product other than Component A, and the like.

In the above (second step), the composition of the present invention is prepared by mixing Component A with Component B and Component C, or further mixing the above additives. The mixing method is not particularly limited, and may be mixed by a method known per se or a method analogous thereto.

In the above (third step), the method for spinning the composition of the present invention is not particularly limited as long as it can form fibers, and examples thereof include a melt blow method, a composite melt spinning method, an electrospinning method, and the like. From the viewpoint of the ability to form ultrafine fibers (nanofibers and microfibers), the electrospinning method is preferred.

The electrospinning method is a known spinning method and can be performed using a known electrospinning apparatus. Speed (discharge speed) at which the composition of the present invention is discharged from the tip of a nozzle (eg, needle); applied voltage; distance from the tip of the nozzle that discharges the composition of the present invention to the substrate that receives it (discharge distance) ) And the like can be appropriately set according to the diameter of the fiber to be produced. The discharge rate is usually from 0.1 to 100 μl / min, preferably from 0.5 to 50 μl / min, more preferably from 1 to 20 μl / min. The applied voltage is usually 0.5 to 80 kV, preferably 1 to 60 kV, more preferably 3 to 40 kV. The discharge distance is usually 1 to 60 cm, preferably 2 to 40 cm, more preferably 3 to 30 cm.
The electrospinning method may be performed using a drum collector or the like. By using a drum collector or the like, the orientation of the fibers can be controlled. For example, a nonwoven fabric or the like can be obtained when the drum is rotated at a low speed, and an oriented fiber sheet or the like can be obtained when the drum is rotated at a high speed.

The diameter of the fiber of the present invention produced by the electrospinning method can be made smaller than that produced by other conventional spinning methods, and is usually 1 nm to 3 μm, preferably 1 nm to 1 μm.

The fiber manufacturing method of the present invention may further include a step of heating the spun fiber at a specific temperature in addition to the above-described spinning step.

The temperature at which the spun fiber is heated is usually in the range of 50 to 300 ° C., preferably from 80 to 250 ° C., more preferably from 90 to 220 ° C. from the viewpoint of the heat resistance of Component A. When the temperature is less than 50 ° C., the crosslinking reaction between the components A becomes insufficient, and the resistance of the produced fiber to the organic solvent tends to be low. When the temperature exceeds 300 ° C., the component A is decomposed or dissolved by heat. In some cases, fibers cannot be formed.

The method for heating the spun fiber is not particularly limited as long as it can be heated at the above heating temperature, and can be appropriately heated by a method known per se or a method analogous thereto. Specific examples of the heating method include a method using a hot plate or an oven in the atmosphere.

The time for heating the spun fiber can be appropriately set according to the heating temperature and the like, but from the viewpoint of the crosslinking reaction rate and production efficiency, it is preferably 1 minute to 48 hours, more preferably 5 minutes to 36 hours, and more preferably 5 minutes. ˜24 hours is particularly preferred.

Although the use of the fiber of the present invention is not particularly limited, as shown in the examples below, the fiber of the present invention has excellent organic solvent resistance and is a non-biological material, Excellent safety and suitable for biocompatible materials. Moreover, since the fiber of the present invention has a sufficient function as a cell culture scaffold, it is also suitable as a cell culture scaffold material.
Accordingly, the present invention also provides a biocompatible material comprising the fiber of the present invention (hereinafter also simply referred to as “the biocompatible material of the present invention”). In the present invention, the “biocompatible material” refers to a material that does not adversely affect a living body and can be used as a medical material, a cosmetic material, or the like.

The type of the biocompatible material of the present invention is not particularly limited, and examples thereof include a cell culture scaffold material, a wound covering material, and a face mask (for cosmetics and hygiene management). Especially, since the fiber of this invention has sufficient function as a cell culture scaffold, it is preferable to be used as a cell culture scaffold material.

The biocompatible material of the present invention can be produced by a method known per se or a method analogous thereto, using the fiber of the present invention as one of the raw materials.

Hereinafter, specific examples according to the present invention will be described, but the present invention is not limited thereto.

<Preparation of condensation product solution>
10.0 g of hexamethoxymethyl melamine compound (trade name “Cymel 303” manufactured by Mitsui Cytec Co., Ltd.) and 10.0 g of tetramethoxymethyl benzoguanamine compound (trade name “Cymel 1123” manufactured by Mitsui Cytec Co., Ltd.) Then, 0.5 g of p-toluenesulfonic acid was added and reacted at 120 ° C. for 24 hours to obtain a condensation product solution 1 containing a condensation product (condensation product 1) of these triazine compounds. .
Thereafter, the solvent was appropriately distilled off from the condensation product solution 1 using a 50 ° C. hot water bath, and the acid and ions in the condensation product solution 1 were removed by ion exchange with a known cationic ion exchange resin. The solid content of the condensation product 1 in the condensation product solution 1 after distilling off the solvent was 79% by weight. Moreover, the weight average molecular weight of the condensation product 1 was 16,000 in terms of polystyrene.
The measurement of the content rate of the solid content of the condensation product 1 in the condensation product solution 1 and the measurement of the weight average molecular weight of the condensation product 1 were performed as follows.

[Measurement of solid content of condensation product 1 in condensation product solution 1]
The solid content of the condensation product 1 in the condensation product solution 1 was measured by the following procedure using a halogen moisture meter (HR83) manufactured by METTLER TOLEDO Co., Ltd. as a measuring device.
(1) A Whatman (registered trademark) glass fiber filter paper (GF / D, diameter 70 mm) is stacked on an aluminum sample pan (HA-D90) manufactured by METTLER TOLEDO Co., Ltd. and placed in the apparatus.
(2) After calibrating the apparatus to zero grams, 1.0 g of the condensation product solution 1 is weighed and heated at 120 ° C.
(3) When all the solvent contained in the condensation product solution 1 is distilled off, the measurement is automatically terminated, and the solid content (unit: wt%) of the condensation product 1 is indicated.

[Measurement of weight average molecular weight of condensation product 1]
The weight average molecular weight of the condensation product 1 was measured by gel permeation chromatography (GPC). The apparatus and measurement conditions used for the measurement are as follows.
Equipment: TOSOH HLC-8320GPC system
Column: Shodex® KF-803L, KF-802 and KF-801
Column temperature: 40 ° C
Eluent: DMF
Flow rate: 0.6 ml / min Detector: RI
Standard sample: Polystyrene

<Preparation of composition for fiber production (solution)>
Example 1
Condensation product solution 1 2.5 g (condensation product 1 solid content: 2.0 g), p-toluenesulfonic acid 0.10 g and ethyl lactate 0.44 g were mixed, and then mixed rotor VMR-5 (As One Corporation) The composition for fiber production of Example 1 was obtained by stirring at 80 rpm until dissolved. The content rate of the solid content of the condensation product 1 in the composition for producing fibers of Example 1 is about 65% by weight.

(Comparative Example 1)
Condensation product solution 1 2.5 g (condensation product 1 solid content: 2.0 g) and ethyl lactate 0.54 g were mixed and then dissolved at 80 rpm until dissolved in Mixrotor VMR-5 (manufactured by ASONE Corporation). Stirring was performed to obtain the fiber manufacturing composition of Comparative Example 1. The content rate of the solid content of the condensation product 1 in the composition for producing fibers of Comparative Example 1 is about 65% by weight.

<Test Example 1: Heat treatment and solvent resistance test>
The fiber production compositions of Example 1 and Comparative Example 1 were each spun onto an aluminum foil by an electrospinning method, and then the resulting fibers were subjected to heat treatment (heating temperatures: 80 ° C., 160 ° C., 205 ° C., Heating time: 10 minutes each), and the fiber shape after the heat treatment was confirmed.
Moreover, after the fiber which heat-processed was immersed in acetone for 10 second, the fiber shape was confirmed again and the diameter of the fiber was measured.
Production of the fiber by electrospinning, confirmation of the fiber shape, and measurement of the fiber diameter were performed as follows.

[Production of fibers by electrospinning]
Fabrication of the fiber by the electrospinning method was carried out using Esplayer ES-2000 (manufactured by Fuence, Inc.). The composition for fiber production was poured into a 1 ml lock-type glass syringe (manufactured by As One Co., Ltd.), and a lock-type metal needle 22G (manufactured by Musashi Engineering Co., Ltd.) having a needle length of 13 mm was attached. The distance (discharge distance) from the tip of the needle to the substrate that receives the fibers was 20 cm. The applied voltage was 25 kV, and the ejection speed was 10 μl / min.

[Confirmation of fiber shape]
The fiber shape was confirmed by depositing Pt-Pd on the fiber for 1 minute by ion sputtering (E-1030, manufactured by Hitachi High-Technologies Corporation), and then using a scanning electron microscope (SEM) (S-4800, Hitachi High Corporation). (Manufactured by Technologies) and observed at an enlargement magnification of 10,000 times.

[Measurement of fiber diameter]
The fiber diameter (fiber thickness) was measured using an attached length measuring tool after storing an image with a magnification of 10,000 times using a scanning electron microscope (SEM).

The results are shown in Table 1 (shape after heat treatment), Table 2 (shape after immersion in acetone and fiber diameter) and FIGS. 1 to 14 (SEM photographs before heat treatment, after heat treatment, and after acetone immersion).

The fiber obtained by electrospinning the composition for producing a fiber of Example 1 had a good shape at any heating temperature of 80 ° C. to 205 ° C. The fiber obtained by electrospinning the fiber production composition of Comparative Example 1 barely retained its shape at a heating temperature of 80 ° C. and became a network solidified product, but did not have a shape at 160 ° C. and 205 ° C. It could not be maintained and dissolved to form a film-like membrane (Table 1).
Further, the fiber obtained by electrospinning the fiber production composition of Example 1 maintained good organic solvent (acetone) resistance under any heating temperature conditions, but the fiber production of Comparative Example 1 After the electrospinning, the network solidified product obtained by heat treatment at 80 ° C. was dissolved in acetone and disappeared from the aluminum foil (Table 2).

<Test Example 2: Cell culture evaluation>
After spinning the composition for producing fibers of Example 1 by electrospinning, cell culture evaluation was performed on the obtained fibers. In the following, the concentration (%) of CO ₂ in the CO ₂ incubator is indicated by volume% of CO _{2 in} the atmosphere. PBS means phosphate buffered saline (manufactured by Sigma Aldrich Japan), and FBS means fetal bovine serum (manufactured by Biological Industries).

[Preparation of cells]
As a cell, a human fetal kidney cell line Hek293 (manufactured by DS Pharma Biomedical) was used. The medium used for cell culture was EMEM medium (Wako Pure Chemical Industries, Ltd.) containing 10% (v / v) FBS and 1% (v / v) NEAA (GIBCO). The cells were statically cultured for 2 days or more using a 10 cm diameter petri dish (medium 10 mL) in a state where 5% carbon dioxide concentration was maintained in a 37 ° C. CO ₂ incubator. Subsequently, the cells were washed with 10 mL of PBS, 1 mL of trypsin-EDTA solution (manufactured by Wako Pure Chemical Industries, Ltd.) was added to peel the cells, and the cells were suspended in 10 mL of the above medium. This suspension was centrifuged (Tomy Seiko Co., Ltd., LC-200, 1000 rpm / 3 minutes, room temperature), the supernatant was removed, and the above medium was added to prepare a cell suspension.

[Production of fiber of Example 1]
The fiber manufacturing composition of Example 1 was spun by electrospinning as in Test Example 1, sprayed on a glass substrate for 10 minutes, and then heat-treated at 205 ° C. for 10 minutes. For the glass substrate, TEMPAX Float (registered trademark) (Φ12 mm, thickness 1 mm) was used. The obtained fiber was washed with ethanol and air-dried, and then the fiber shape was confirmed with a scanning electron microscope (SEM). The diameter of the fiber obtained from the fiber manufacturing composition of Example 1 was about 1 μm.
In the following, the glass substrate on which fibers are formed by spinning the composition for fiber production of Example 1 is referred to as “fiber substrate of Example 1” for convenience.

[Cell culture]
An EMEM containing a 1% (v / v) penicillin / streptomycin solution (GIBCO) containing the fiber substrate of Example 1 and an untreated glass substrate as a control on a 24-hole flat bottom microplate (Corning). It was immersed in a medium (Wako Pure Chemical Industries, Ltd.) for 15 minutes. After removing this medium, 1 mL each of a cell suspension of Hek293 (human embryonic kidney cells) prepared to 1.0 × 10 ⁵ cells / well was added. Then, it was allowed to stand in a CO ₂ incubator at 37 ° C. for 24 hours while maintaining a 5% carbon dioxide concentration.

[Cell count using trypan blue]
After 24 hours of cell culture, the fiber substrate of Example 1 where the cell culture was performed and the supernatant of the glass substrate were removed, and the plate was washed with 2 mL of PBS. After removing PBS, 300 μL of trypsin-EDTA solution (manufactured by Wako Pure Chemical Industries, Ltd.) was added. After leaving still in a CO ₂ incubator at 37 ° C. for 5 minutes, 1 mL of EMEM medium containing 10% (v / v) FBS was added, and the cells were detached by pipetting. The peeled cells were transferred to a 1.5 mL micro test tube (Eppendorf), the same amount of trypan blue staining solution (GIBCO) was added to a part of the culture solution, and then a cell counter (Bio-Rad, TC20). The number of viable cells was counted.

[Counting the number of cells using WST-8]
After 24 hours of cell culture, the fiber substrate of Example 1 where the cell culture was performed and the supernatant of the glass substrate were removed, and the plate was washed with 2 mL of PBS. After removing PBS, 1 mL of EMEM medium containing 10% (v / v) FBS and 1% (v / v) NEAA (GIBCO) was added, and 100 μL of WST-8 reagent (Kishida Chemical) was added. Was added. After standing at 37 ° C. for 100 minutes in a CO ₂ incubator, 100 μL of the reaction solution was transferred to a 96-well flat bottom microplate, and the absorbance at 450 nm was measured with an absorptiometer (SpectraMax, manufactured by Molecular Devices).

Table 3 shows the results of each cell count measurement (average value of n = 2).

From the results in Table 3, it was found that cells proliferated on the fiber substrate of Example 1, and it was shown that the fiber formed from the composition for producing fiber of Example 1 was harmless to the living body. Furthermore, when it culture | cultivated on the fiber substrate of Example 1, the increase in the number of cells was shown compared with the glass substrate. In particular, in the cell count measurement using WST-8, a 30% increase in cell count was observed. In the cell count measurement using trypan blue, not all cells were recovered and the cell count could be measured, but an increase of about 20% was observed.

This application is based on Japanese Patent Application No. 2013-264435 filed in Japan (filing date: December 20, 2013), the contents of which are incorporated in full herein.

Claims

(A) A condensation product obtained by condensing one or more compounds represented by general formula (1), and (B) a fiber produced by spinning a composition containing an acid compound.

[Where,
R 1 represents an amino group optionally substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or a carbon atom. Represents an aryl group of formulas 6 to 14;
R 2 , R 3 , R 4 and R 5 are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6. ]
The fiber according to claim 1, wherein the composition further comprises (C) a solvent.
R 1 is selected from an amino group, a vinyl group, a propenyl group, a butenyl group, a phenyl group, and a naphthyl group, which may be substituted with a methoxymethyl group, an ethoxymethyl group, a propoxymethyl group, a butoxymethyl group, or a hydroxymethyl group. And
R 2 , R 3 , R 4 and R 5 are the same or different and are a hydrogen atom, a hydroxymethyl group, a methoxymethyl group, an ethoxymethyl group, a propoxymethyl group, a butoxymethyl group, a vinyl group, a propenyl group, or a butenyl group. The fiber according to claim 1, wherein the fiber is selected from methyl group, ethyl group, propyl group, and butyl group.
(A) The condensation product is represented by the general formula (1A):

[Where,
R 1A represents an amino group which may be substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group;
R 2 , R 3 , R 4 and R 5 are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6. And / or general formula (1B):

[Where,
R 1B represents an aryl group having 6 to 14 carbon atoms;
R 2 , R 3 , R 4 and R 5 are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6. The fiber of Claim 1 or 2 which is a condensation product obtained by condensing the compound represented by this.
(A) The fiber according to any one of claims 1 to 4, wherein the condensation product has a weight average molecular weight of 1,000 to 1,000,000.
The fiber according to any one of claims 1 to 5, wherein the spinning is electrospinning.
The fiber according to any one of claims 1 to 6, which is a nanofiber and / or a microfiber.
(A) A condensation product obtained by condensing one or more of the compounds represented by the general formula (1), and (B) a composition for fiber production containing an acid compound.

[Where,
R 1 represents an amino group optionally substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or a carbon atom. Represents an aryl group of formulas 6 to 14;
R 2 , R 3 , R 4 and R 5 are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6. ]
The composition according to claim 8, further comprising (C) a solvent.
(A) The condensation product is represented by the general formula (1A):

[Where,
R 1A represents an amino group which may be substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group;
R 2 , R 3 , R 4 and R 5 are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6. And / or general formula (1B):

[Where,
R 1B represents an aryl group having 6 to 14 carbon atoms;
R 2 , R 3 , R 4 and R 5 are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6. The composition of Claim 8 or 9 which is a condensation product obtained by condensing the compound represented by this.
The composition according to any one of claims 8 to 10, wherein (A) the condensation product has a weight average molecular weight of 1,000 to 1,000,000.
The composition according to any one of claims 8 to 11, wherein the content ratio of the solid content of the (A) condensation product is 1 to 90% by weight.
(First step) (A) A step of obtaining a condensation product solution by condensing a monomer composition containing one or more compounds represented by general formula (1),
(Second step) (A) A step of adding an acid compound and (C) solvent to the condensation product solution to obtain a composition for fiber production, and (Third step) a composition for fiber production. A method for producing a fiber, comprising a step of spinning.

[Where,
R 1 represents an amino group optionally substituted with an alkoxymethyl group having 2 to 6 carbon atoms or a hydroxymethyl group, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or a carbon atom. Represents an aryl group of formulas 6 to 14;
R 2 , R 3 , R 4 and R 5 are the same or different and each represents a hydrogen atom, a hydroxymethyl group, an alkoxymethyl group having 2 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or 1 carbon atom. Represents an alkyl group of ˜6. ]
The method according to claim 13, further comprising a step of heating the spun fiber in the range of 50 to 300 ° C.
The method according to claim 13 or 14, wherein the spinning is electrospinning.
A biocompatible material comprising the fiber according to any one of claims 1 to 7.