WO2016133189A1

WO2016133189A1 - Composition for forming biocompatible coating film

Info

Publication number: WO2016133189A1
Application number: PCT/JP2016/054799
Authority: WO
Inventors: 高広岸岡; 横山　義之
Original assignee: 日産化学工業株式会社; 富山県
Priority date: 2015-02-20
Filing date: 2016-02-19
Publication date: 2016-08-25
Also published as: JPWO2016133189A1; JP6706728B2; TW201630997A

Abstract

The present invention provides a composition for forming a biocompatible coating film on a substrate (e.g., resinous substrate). The present invention relates to a composition for forming biocompatible coating films which comprises (A) an organic polymer and (D) a C_2-5 methoxy alcohol as a solvent. The organic polymer (A) preferably includes a structural unit having, in a side chain, at least one organic group selected from among a hydroxy group, a hydroxymethyl group, and C_1-5 alkoxymethyl groups.

Description

Biocompatible coating film forming composition

The present invention relates to a composition for forming a biocompatible coating film.

In recent years, coating materials having biocompatibility that are harmless to biological substances (cells and proteins) have attracted attention. Examples of the use include a coating material for forming a coating film having an ability to suppress adhesion of biological substances, a coating material used for a cell culture substrate that improves cell culture efficiency, and the like.

Patent Document 1 describes a method for producing a plate for cell culture, which includes using a photosensitive resin composition containing an alcohol-based organic solvent (S).

JP 2014-23508 A

It has already been found by the present applicant that biocompatible fibers and the like can be produced using a composition containing a specific polymer compound capable of forming a crosslinked structure using an acid as a catalyst (international patent). Application PCT / JP2014 / 0777716).

As a material (base material) to which the above composition is applied, synthetic resins (plastics) are mainly used from the viewpoint of its use and handling. The solvent that can dissolve the polymer compound is limited.

An object of the present invention is to provide a coating film forming composition or the like that can form a biocompatible coating film without eroding the substrate.

That is, the present invention is as follows.

[1] A biocompatible coating film-forming composition comprising (A) an organic polymer and (D) methoxy alcohol having 2 to 5 carbon atoms as a solvent.
[2] The composition according to [1], wherein (D) the methoxy alcohol having 2 to 5 carbon atoms is 2-methoxyethanol.
[3] The organic polymer (A) wherein the organic polymer comprises a structural unit having at least one organic group selected from a hydroxy group, a hydroxymethyl group and an alkoxymethyl group having 1 to 5 carbon atoms in the side chain. The composition according to [1] or [2].
[4] The organic polymer (A) is
(A1) General formula (1):

[Where,
R ¹ represents a hydrogen atom or a methyl group,
Q ¹ represents an ester bond or an amide bond,
R ² is an alkyl group having 1 to 10 carbon atoms or 6 to 10 carbon atoms in which at least one hydrogen atom is substituted with a hydroxy group, a hydroxymethyl group or an alkoxymethyl group having 1 to 5 carbon atoms. An aromatic hydrocarbon group is shown. ]
The composition according to any one of [1] to [3], comprising an organic polymer comprising a structural unit represented by:
[5] The (A1) organic polymer is
General formula (2):

[Where,
R ³ represents a hydrogen atom or a methyl group,
R ⁴ and R ⁵ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may be substituted with a hydroxy group or a carboxy group. ]
The composition according to [4], further comprising a structural unit represented by:
[6] The composition according to any one of [1] to [5], further comprising (B) a photoacid generator.
[7] A substrate having on its surface a coating film formed of the composition according to any one of [1] to [6].
[8] The base material according to [7], wherein the base material includes polystyrene.
[9] A method for producing a substrate having a coating film on the surface, comprising a step of forming a coating film on the surface of the substrate using the composition according to any one of [1] to [6].
[10] The production method according to [9], wherein the substrate contains polystyrene.
[11] A substrate having on the surface a pattern formed using the composition according to [6].
[12] A pattern including a step of forming a coating film on the surface of the substrate using the composition according to [6], a step of irradiating the coating film with light, and a step of developing the coating film after exposure A manufacturing method of a substrate with a mark.
[13] A pattern including a step of forming a coating film on the surface of the substrate using the composition according to [6], a step of irradiating the coating film with light, and a step of developing the coating film after exposure Forming method.

When the composition for forming a biocompatible coating film of the present invention (hereinafter, also simply referred to as “the composition of the present invention”) is used, the biocompatible coating is performed without eroding the substrate (particularly, the resin substrate). A film can be formed.
Moreover, when the composition of this invention contains a photo-acid generator, it can form the coating film which has photosensitivity. In this case, a biocompatible coating film pattern can be formed by photolithography. Moreover, the said base material with a pattern can be manufactured.
Moreover, the composition of this invention can form the coating film which has temperature responsiveness, for example, when the temperature responsive organic polymer containing the structural unit represented by following General formula (2) is used. In this case, a specific patterned substrate having temperature responsiveness can be manufactured and provided.

2 is a graph showing the results of a sensitivity test of the composition for forming a coating film obtained in Example 1. The vertical axis represents the film thickness (nm) of the coating film, and the horizontal axis represents the exposure dose (mJ / cm ² ). 3 is a graph showing the results of a patterning test of the coating film forming composition obtained in Example 1. FIG. The vertical axis shows the thickness (nm) of the part with the pattern (coating film) and the part without the pattern (nm), and the horizontal axis shows the width (μm) of the part with the pattern (coating film) and the part without the pattern.

<Composition for forming coating film>
The biocompatible coating film-forming composition of the present invention is mainly characterized in that it contains (A) an organic polymer and (D) methoxy alcohol having 2 to 5 carbon atoms as a solvent.

(Component A)
(A) The organic polymer is not particularly limited as long as it can be used in the composition for forming a coating film, but is preferably at least one selected from a hydroxy group, a hydroxymethyl group, and an alkoxymethyl group having 1 to 5 carbon atoms. It is an organic polymer containing a structural unit having a seed organic group in the side chain. Examples of the (A) organic polymer include vinyl polymer polymer reacted with olefin, polyamide, polyester, polycarbonate, polyurethane, (meth) acryl polymer polymerized (meth) acrylate compound, and the like. Not limited. These (A) organic polymers are preferably those obtained by radical polymerization, but those obtained by polycondensation or polyaddition reaction can also be used. Among these, a vinyl polymer polymer reacted with an olefin or a (meth) acryl polymer polymerized with a (meth) acrylate compound is particularly desirable.
In the present invention, the (meth) acrylate compound refers to both an acrylate compound and a methacrylate compound. For example, (meth) acrylic acid refers to acrylic acid and methacrylic acid.

Here, the “alkoxymethyl group having 1 to 5 carbon atoms” may be either linear or branched, and specific examples thereof include methoxymethyl group, ethoxymethyl group, n-propoxymethyl group, Propoxymethyl group, n-butoxymethyl group, isobutoxymethyl group, sec-butoxymethyl group, tert-butoxymethyl group, n-pentoxymethyl group, isopentoxymethyl group, neopentoxymethyl group, tert-pentoxy Examples thereof include a methyl group, 1-ethylpropoxymethyl group, 2-methylbutoxymethyl group and the like. The number of carbon atoms of the alkoxymethyl group is preferably 1 to 4, more preferably 1 to 3.

(Component A1)
(A) The organic polymer is preferably represented by the general formula (1):

[Where,
R ¹ represents a hydrogen atom or a methyl group,
Q ¹ represents an ester bond or an amide bond,
R ² is an alkyl group having 1 to 10 carbon atoms or 6 to 10 carbon atoms in which at least one hydrogen atom is substituted with a hydroxy group, a hydroxymethyl group or an alkoxymethyl group having 1 to 5 carbon atoms. An aromatic hydrocarbon group is shown. ]
The organic polymer containing the structural unit represented by (Hereinafter, it is also only called "component A1."). More preferably, the (A) organic polymer is component A1.

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

R ¹ represents a hydrogen atom or a methyl group.

Q ¹ represents an ester bond or an amide bond.

R ² is an alkyl group having 1 to 10 carbon atoms or 6 to 10 carbon atoms in which at least one hydrogen atom is substituted with a hydroxy group, a hydroxymethyl group or an alkoxymethyl group having 1 to 5 carbon atoms. An aromatic hydrocarbon group is shown.
The “alkoxymethyl group having 1 to 5 carbon atoms” may be linear or branched, and specific examples thereof are the same as those described above, and suitable carbon atoms are the same as described above. It is.
The “alkyl group having 1 to 10 carbon atoms” may be linear or branched, and specific examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, Isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, tert-pentyl group, 1-ethylpropyl group, n-hexyl group, isohexyl group, 1,1-dimethylbutyl group 2,2-dimethylbutyl group, 3,3-dimethylbutyl group, 2-ethylbutyl group, hexyl group, pentyl group, octyl group, nonyl group, decyl group and the like. The number of carbon atoms of the alkyl group is preferably 1-6, more preferably 1-4.
Examples of the aromatic hydrocarbon group having 6 to 10 carbon atoms in R ² include a phenyl group, a 1-naphthyl group, and a 2-naphthyl group.
R ² is formed using the composition of the present invention when the composition of the present invention contains a photoacid generator (B) described later and imparts photosensitivity to a coating film formed using the photo acid generator. Preferably, at least one hydrogen atom is a hydroxy group, a hydroxymethyl group, or a carbon atom from the viewpoint of allowing (B) a photoacid generator as a catalyst to act as a reactive crosslinking reaction site after exposure of the applied coating film. An alkyl group having 1 to 10 (more preferably 1 to 6, particularly preferably 1 to 4) carbon atoms substituted by an alkoxymethyl group having 1 to 5 carbon atoms (more preferably a hydroxy group), or at least one A phenyl group in which a hydrogen atom is substituted with a hydroxy group, a hydroxymethyl group or an alkoxymethyl group having 1 to 5 carbon atoms (more preferably a hydroxy group).

In the structural unit represented by the general formula (1), R ¹ is a hydrogen atom or a methyl group, Q ¹ is an ester bond, and R ² is substituted with at least one hydrogen atom by a hydroxy group. The alkyl group is preferably an alkyl group having 1 to 10 carbon atoms (more preferably 1 to 6, particularly preferably 1 to 4).

The structural unit represented by the general formula (1) is preferably a structural unit represented by the general formula (1A).

[Wherein R ⁶ has the same meaning as R ¹ above, and R ⁷ has the same meaning as R ² above. ]

Component A1 may contain one type of structural unit represented by general formula (1), or may contain two or more types.

Component A1 may contain structural units other than the structural unit represented by general formula (1) as long as the object of the present invention is not impaired, and is represented by general formula (1) for all structural units of component A1. The content of the structural unit is preferably 5 mol% or more, more preferably 15 mol% or more, from the viewpoint of efficiently performing the crosslinking reaction.

Component A1 is further represented by general formula (2):

[Where,
R ³ represents a hydrogen atom or a methyl group,
R ⁴ and R ⁵ may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may be substituted with a hydroxy group or a carboxy group. ]
It is desirable to contain the structural unit represented by these.

Component A1 may contain one type of structural unit represented by general formula (2), or may contain two or more types.

The “alkyl group having 1 to 4 carbon atoms” in R ⁴ and R ⁵ in the general formula (2) may be linear or branched, and specific examples thereof include a methyl group, an ethyl group, n -Propyl group, isopropyl group, n-butyl group and isobutyl group can be mentioned.
In the present invention, “may be substituted with a hydroxy group or a carboxy group” means that part or all of the hydrogen atoms contained in the above “alkyl group having 1 to 4 carbon atoms” are substituted with a hydroxy group or a carboxy group. Indicates that it may be.
In the structural unit represented by the general formula (2), R ³ is more preferably a hydrogen atom or a methyl group, and both R ⁴ and R ⁵ are more preferably a methyl group.

The weight average molecular weight of component A1 is preferably in the range of 1,000 to 1,000,000, more preferably in the range of 5,000 to 500,000, particularly from the viewpoint of forming an appropriate coating film thickness. The range is preferably 10,000 to 200,000. In the present invention, “weight average molecular weight” means a molecular weight in terms of polystyrene measured by gel permeation chromatography (GPC).

Component A1 may be used alone or in combination of two or more.

Component A1 can be produced by a method known per se or a method analogous thereto. For example, a monomer corresponding to each structural unit (a monomer corresponding to the structural unit represented by the general formula (1), a structural unit other than the structural unit represented by the general formula (1) (preferably the general formula The monomer corresponding to the structural unit represented by (2)) in a suitable solvent (eg, propylene glycol monoethyl ether, etc.) and a suitable polymerization initiator (eg, 2,2′-azobis). Although it can manufacture by superposing | polymerizing using isobutyronitrile etc.), it is not limited to this. Moreover, you may use a commercial item.

Examples of the monomer corresponding to the structural unit represented by the general formula (1) include 2-hydroxyethyl (meth) acrylate (for example, a compound having CAS number: 868-77-9), 2-hydroxypropyl ( (Meth) acrylate (for example, a compound having CAS number: 923-26-2), 4-hydroxybutyl (meth) acrylate (for example, a compound having CAS number: 2478-10-6), N-hydroxymethyl (meth) acrylamide ( For example, a compound having CAS number: 923-02-4), N- (2-hydroxyethyl) (meth) acrylamide (for example, a compound having CAS number: 5238-56-2), N- (2-hydroxypropyl) ( (Meth) acrylamide (for example, a compound having CAS number: 26099-09-2), p-hydroxy (meth) actyl Examples include ruanilide (for example, a compound having CAS number: 19243-95-9), N-methoxymethyl (meth) acrylamide, N-butoxymethyl (meth) acrylamide, and the like. 2-hydroxyethyl (meth) acrylate, 2-hydroxy Propyl (meth) acrylate, N-methoxymethyl (meth) acrylamide or N-butoxymethyl (meth) acrylamide is preferred, and 2-hydroxyethyl (meth) acrylate is most preferred.

Examples of the monomer corresponding to the structural unit represented by the general formula (2) include N-isopropyl (meth) acrylamide, N- (1-methylpropyl) (meth) acrylamide, and N- (1-ethylpropyl). ) (Meth) acrylamide, N- (1-propylbutyl) (meth) acrylamide, N- (1-butylpentyl) (meth) acrylamide, 2-carboxyisopropyl (meth) acrylamide, 2-hydroxyisopropyl (meth) acrylamide, etc. N-isopropyl (meth) acrylamide, 2-carboxyisopropyl (meth) acrylamide or 2-hydroxyisopropyl (meth) acrylamide is most preferable.
When component A1 has a structural unit represented by general formula (2), the coating film formed using the composition of the present invention has temperature responsiveness. In this case, the content ratio of the structural unit represented by the general formula (2) with respect to all the structural units of the component A1 is preferably 60 to 95 mol%. Note that the coating film formed using the composition of the present invention has temperature responsiveness, so that, for example, a coating film pattern whose size changes with temperature can be formed. For example, (i) a drug delivery system (DDS) that allows water or a drug to stay in or release from the coating film or application to a drug sheet, and (ii) control the hydrophobicity / hydrophilicity of the surface. This is advantageous in that application to devices that can control the adhesion of substances is expected.

Component A1 may further contain an arbitrary structural unit in addition to the structural unit represented by the general formula (1) and the structural unit represented by the general formula (2). Such an arbitrary structural unit does not impair the performance of the coating film formed using the composition of the present invention, and the monomer corresponding to the structural unit represented by the general formula (1) and the general formula (2) If it is a structural unit derived from the monomer which can superpose | polymerize with the monomer corresponding to the structural unit represented, there will be no restriction | limiting in particular. Examples of such monomers include (meth) acrylic acid esters having 1 to 10 carbon atoms in the alkyl group, benzyl (meth) acrylate, acrylamides (eg, acrylamide, N-alkylacrylamide, N- Arylacrylamide, N, N-dialkylacrylamide, N, N-diarylacrylamide, N-methyl-N-phenylacrylamide, N-2-acetamidoethyl-N-acetylacrylamide, etc.), methacrylamides (eg, methacrylamide, N -Alkyl methacrylamide, N-aryl methacrylamide, N, N-dialkyl methacrylamide, N, N-diaryl methacrylamide, N-methyl-N-phenyl methacrylamide, N-ethyl-N-phenyl methacrylamide, etc.) It is done. These may be used alone or in combination of two or more.
For example, when a (meth) acrylic acid ester having 1 to 10 carbon atoms in the alkyl group having a hydrophobic side chain or benzyl (meth) acrylate is used, the hydrophilicity / hydrophobicity balance of component A1 can be adjusted. it can.

The content of component A in the coating film forming composition of the present invention is suitable for forming a coating film with an appropriate thickness and for coating film formation excluding the solvent from the viewpoint of storage stability of the coating film forming composition of the present invention. The amount is preferably 60 to 95% by weight, more preferably 70 to 90% by weight, based on the solid content of the composition.

(Component B)
The coating film forming composition of the present invention may contain (B) a photoacid generator (hereinafter also simply referred to as “component B”). Component B is not particularly limited as long as it is a compound that generates an acid directly or indirectly upon exposure. For example, a diazomethane compound, an onium salt compound, a sulfonimide compound, a nitrobenzyl compound, an iron arene complex, a benzoin tosylate compound, Examples include halogen-containing triazine compounds, cyano group-containing oxime sulfonate compounds, and naphthalimide compounds.

Examples of the diazomethane compound include bis (p-toluenesulfonyl) diazomethane, bis (1,1-dimethylethylsulfonyl) diazomethane, bis (cyclohexylsulfonyl) diazomethane, and bis (2,4-dimethylphenylsulfonyl) diazomethane. .

Examples of the onium salt compound include bis (4-tert-butylphenyl) iodonium trifluoromethanesulfonate, triphenylsulfonium trifluoromethanesulfonate, and the like.

Examples of the sulfonimide compound include N- (trifluoromethanesulfonyloxy) succinimide, N- (nonafluoro-normalbutanesulfonyloxy) succinimide, N- (camphorsulfonyloxy) succinimide, N- (trifluoromethanesulfonyloxy) naphthalimide, and the like. Is mentioned.

Examples of the nitrobenzyl compound include 2-nitrobenzyl p-toluenesulfonate, 2,6-dinitrobenzyl p-toluenesulfonate, 2,4-dinitrobenzyl p-toluenesulfonate, and the like.

Examples of the iron arene complex include biscyclopentadienyl- (η6-isopropylbenzene) -iron (II) hexafluorophosphate.

Examples of the benzoin tosylate compound include benzoin tosylate and α-methylbenzoin tosylate.

Examples of the halogen-containing triazine compound include 2- (4-methoxyphenyl) -4,6-bis (trichloromethyl) -1,3,5-triazine, 2- (4-methoxynaphthyl) -4,6-bis. (Trichloromethyl) -1,3,5-triazine, 2- [2- (2-furyl) ethenyl] -4,6-bis (trichloromethyl) -1,3,5-triazine, 2- [2- ( 5-methyl-2-furyl) ethenyl] -4,6-bis (trichloromethyl) -1,3,5-triazine and the like.

Examples of the cyano group-containing oxime sulfonate compound include α- (methylsulfonyloxyimino) -4-methoxybenzyl cyanide, α- (trifluoromethylsulfonyloxyimino) -4-methoxybenzyl cyanide, α- (ethyl And sulfonyloxyimino) -4-methoxybenzyl cyanide, α- (propylsulfonyloxyimino) -4-methylbenzyl cyanide, and the like.

Examples of naphthalimide compounds include 6- (n-butylthio) -2- (perfluorobutylsulfonyloxy) -2-aza-2H-phenalene-1,3-dione, 6- (n-butylthio) -2 -(Trifluoromethylsulfonyloxy) -2-aza-2H-phenalene-1,3-dione and 6- (isopropylthio) -2- (trifluoromethylsulfonyloxy) -2-aza-2H-phenalene-1, 3-dione and the like can be mentioned.

(B) The photoacid generator is preferably a naphthalimide compound, more preferably 6- (n-butylthio) -2- (perfluorobutylsulfonyloxy) -2-aza-2H-phenalene-1,3. -Dione, 6- (n-butylthio) -2- (trifluoromethylsulfonyloxy) -2-aza-2H-phenalene-1,3-dione and 6- (isopropylthio) -2- (trifluoromethylsulfonyloxy) ) -2-aza-2H-phenalene-1,3-dione.

When the composition of the present invention contains (B) a photoacid generator, the content of (B) the photoacid generator is such that the coating film forming composition of the present invention obtains good patterning performance by exposure. Based on the solid content of the composition for forming a coating film excluding the solvent, it is preferably 0.1 to 20% by weight, more preferably 0.5 to 15% by weight, and still more preferably 1 to 13% by weight.

When the composition for forming a coating film of the present invention contains (B) a photoacid generator, only one type of (B) photoacid generator may be used, or two or more types may be used in combination.

(Component C)
The composition for forming a coating film of the present invention preferably contains (C) a cross-linking agent (hereinafter also simply referred to as “component C”) that reacts with a reactive group in the presence of an acid. (C) A crosslinking agent may use only 1 type and may use 2 or more types together. When (A) two or more types of reactive groups that react with each other are present in the organic polymer, (A) the organic polymer can be crosslinked without a crosslinking agent (self-crosslinking). In such a case, the composition for forming a coating film of the present invention may not contain (C) a crosslinking agent.

Component C is not particularly limited as long as it reacts with the reactive group in the presence of an acid, and those usually used in the field of photosensitive compositions can be used in the present invention.

Examples of component C include glycoluril compounds and melamine compounds.

Examples of the glycoluril compound include 1,3,4,6-tetrakis (methoxymethyl) glycoluril, 1,3,4,6-tetrakis (ethoxymethyl) glycoluril, 1,3,4,6-tetrakis ( And propoxymethyl) glycoluril and 1,3,4,6-tetrakis (butoxymethyl) glycoluril.

Examples of the melamine compound include hexamethoxymethyl melamine, hexaethoxymethyl melamine, hexapropoxymethyl melamine, hexabutoxymethyl melamine and the like.

Component C is preferably a glycoluril compound, more preferably 1,3,4,6-tetrakis (methoxymethyl) glycoluril, 1,3,4,6-tetrakis (ethoxymethyl) glycoluril, It is at least one selected from the group consisting of 3,4,6-tetrakis (propoxymethyl) glycoluril and 1,3,4,6-tetrakis (butoxymethyl) glycoluril, more preferably 1,3,4 , 6-tetrakis (methoxymethyl) glycoluril.

When component C is used, its content is preferably 0.1 to 40, based on the solid content of the coating film forming composition excluding the solvent, in order to obtain good patterning characteristics and sufficient temperature responsiveness. % By weight, more preferably 0.5 to 30% by weight, still more preferably 1 to 20% by weight.

(Component D)
The composition for forming a coating film of the present invention contains (D) a methoxy alcohol having 2 to 5 carbon atoms (hereinafter also simply referred to as “component D”) as a solvent. By using the component D as a solvent, the composition of the present invention can form a biocompatible coating film without particularly eroding the resin substrate.

Specific examples of the methoxy alcohol having 2 to 5 carbon atoms include methoxymethanol (CAS number; 4461-52-3), 2-methoxyethanol (CAS number; 109-86-4), 2-methoxy-1-propanol. (CAS number; 1589-47-5), 3-methoxy-1-propanol (CAS number; 1589-49-7), 2-methoxy-1-butanol (CAS number; 15467-25-1), 3-methoxy -1-butanol (CAS number; 2517-43-3) and the like. The number of carbon atoms of the methoxy alcohol is preferably 2-4, more preferably 3-4.

Component D is preferably 2-methoxyethanol (CAS number; 109-86-4, alternatively named ethylene glycol monomethyl ether, methyl cellosolve, methyl glycol).

In order to control the film thickness of the coating film and to obtain good patterning characteristics when the coating film forming composition of the present invention has photosensitivity, the content of component D is Preferably, it is 50 to 99.5% by weight, more preferably 70 to 99.5% by weight, and still more preferably 85 to 99% by weight.

The content ratio of component A in the coating film forming composition of the present invention (that is, the content of component A based on the composition for forming a coating film) is suitable for the production of a coating film having an appropriate thickness or the coating film of the present invention. From the viewpoint of storage stability of the forming composition, 0.1 to 90% by weight is preferable, and 0.5 to 70% by weight is more preferable.
When the composition for forming a coating film of the present invention contains component B, the content ratio of component B in the composition for forming a coating film (that is, the content of component B based on the composition for forming a coating film) is: From the viewpoint of maintaining the characteristics of the temperature-responsive resin, it is preferably 0.01 to 50% by weight, more preferably 0.05 to 40% by weight, and particularly preferably 0.1 to 20% by weight.
When the composition for forming a coating film of the present invention contains component B, the weight ratio of component A and component B (weight of component A / weight of component B) contained in the composition for forming a coating film of the present invention is: From the viewpoint of reaction efficiency between component A and component B, 0.01 to 50 is preferable, and 0.1 to 40 is more preferable.
When the composition for forming a coating film of the present invention contains component C, the content ratio of component C in the composition for forming a coating film of the present invention (that is, the content of component C based on the composition for forming a coating film) Is preferably from 0.01 to 15% by weight, more preferably from 0.03 to 10% by weight, particularly preferably from 0.05 to 5% by weight, from the viewpoint of reaction efficiency with Component A.

The coating film-forming composition of the present invention may contain additives as necessary in addition to the components A to D as long as the object of the present invention is not significantly impaired. Examples of the additive include a surfactant, a rheology modifier, a drug, and fine particles.

The composition for forming a coating film of the present invention is prepared by mixing component A and component D, and optionally mixing component B and / or 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.

(Substrate having a coating film, substrate with pattern, method for producing the substrate, and pattern forming method)
The substrate having a coating film formed using the coating film forming composition of the present invention on at least a part of the surface is obtained by applying the coating film forming composition of the present invention by a method such as spin coating or slit coating. It can manufacture by forming a coating film in at least one part of the surface of a base material by apply | coating to at least one part of the surface of a base material, and removing a solvent. The present invention also provides a substrate having such a coating film.

The patterned substrate of the present invention is a step of forming a coating film on at least a part of the surface of the substrate using the coating film forming composition of the present invention containing at least Component A, Component B and Component D, It can be manufactured by a manufacturing method including a patterning step by photolithography (specifically, a step of irradiating the coating film with light and a step of developing the coating film after exposure). The present invention also provides such a patterned substrate. The substrate with a pattern of the present invention may be a substrate having one type of pattern produced using only one type of composition for forming a coating film of the present invention. The base material which has 2 or more types of patterns manufactured using 2 or more types may be sufficient.

The shape of the pattern is not particularly limited, and when observed from the upper side of the substrate, for example, a square shape, a round shape, a linear shape, a line and space, and the like can be mentioned. When two or more patterns having different response temperatures exist, they may be formed adjacent to each other or may be formed apart from each other. There is no particular limitation on the size of the pattern observed from above and the height observed from the pattern cross section. The size of the pattern (that is, the width of one side of the square, the diameter of the circle, the width of the line, the line and space line width and space width, etc.) is, for example, 0.1 to 1000 μm, and the height of the pattern is, for example, 5 nm to 1000 μm. The shape of these patterns can be controlled by using a plurality of masks having different shapes of transmitted light during the exposure process.

The patterned substrate of the present invention can be produced by a method known per se, for example, the method described below. First, the composition for forming a coating film of the present invention containing at least Component A, Component B, and Component D is applied to a substrate by a method such as spin coating or slit coating, and the solvent is removed to remove the surface of the substrate. A coating film is formed on at least a part. For example, g-line (wavelength 436 nm), h-line (wavelength 405 nm), i-line (wavelength 365 nm), ultraviolet light, deep ultraviolet light, electron beam, various lasers (eg, KrF excimer laser (wavelength 248 nm), ArF excimer) When light such as laser (wavelength 193 nm), excimer laser such as F2 excimer laser (wavelength 157 nm), mercury lamp light, LED light, etc. is irradiated through a mask in order to obtain a desired pattern, the acid is exposed only at the exposed portion. Is generated, thereby causing cross-linking (curing). Among these, g-line (wavelength 436 nm), h-line (wavelength 405 nm), i-line (wavelength 365 nm), ultraviolet rays, deep ultraviolet rays, and electron beams are preferably used for the coating film of the present invention. Thereafter, it is desirable to perform post-exposure baking (PEB). The coated film after exposure is developed with a developer or the like, and an unexposed portion (uncured portion of the coating film) is removed to produce a substrate with a pattern.
The base material which has 2 or more types of patterns can be manufactured by repeating the said operation for every composition for coating film formation from which a composition differs.

Examples of the base material used for the base material having a coating film and the base material with a pattern include metals, metalloids, metal-containing compounds, metalloid-containing compounds, and resins. When the composition of the present invention is used, a biocompatible coating film can be formed without eroding the resin substrate, and therefore the present invention is particularly useful when a resin substrate is used.

Examples of the metal or semimetal include aluminum, nickel titanium, stainless steel (SUS304, SUS316, SUS316L, etc.), silicon, and the like.

Examples of the metal-containing compound or metalloid-containing compound include ceramics, metal oxide or metalloid oxide (glass, silicon oxide, alumina, etc.), metal carbide or metalloid carbide, metal nitride or metalloid nitride (nitriding). Silicon, etc.), metal borides, metalloid borides and the like.

The resin may be a natural resin, a modified natural resin, or a synthetic resin. Examples of natural resins include cellulose. Examples of the modified natural resin include cellulose triacetate (CTA), cellulose on which dextran sulfate is immobilized, and the like. Examples of the synthetic resin include polyacrylonitrile (PAN), polyester polymer alloy (PEPA), polystyrene (PS), polysulfone (PSF), polyethylene terephthalate (PET), polymethyl methacrylate (PMMA), polyvinyl alcohol (PVA), Examples include polyurethane (PU), ethylene vinyl alcohol (EVAL), polyethylene (PE), polyester (PE), polypropylene (PP), polyvinylidene fluoride (PVDF), polyethersulfone (PES), and poly-N-isopropylacrylamide. Among these, polystyrene (PS), which is generally used as a cell culture substrate that requires biocompatibility, for example, is particularly desirable.

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited by the following examples, and appropriate modifications are made within a range that can meet the above and the following purposes. Of course, it is possible to implement them, and they are all included in the technical scope of the present invention.

[Measurement of weight average molecular weight]
In this example, the weight average molecular weight of the organic polymer 1 was measured by gel permeation chromatography (GPC). Equipment used for measurement and measurement conditions 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

<Production Example 1: Synthesis of organic polymer 1>
20.0 g (0.177 mol) of N-isopropylacrylamide, 5.13 g (0.044 mol) of 2-hydroxyethyl acrylate, and 0.25 g of 2,2′-azobisisobutyronitrile (manufactured by Wako Pure Chemical Industries, Ltd.) Was dissolved in 25.1 g of propylene glycol monomethyl ether and reacted at 80 ° C. for 24 hours in a nitrogen atmosphere to obtain a solution containing the organic polymer 1. Thereafter, reprecipitation was performed with hexane, and the resulting precipitate was dried at 40 ° C. in a vacuum oven. Assuming that the reaction proceeds as prepared, the content of the structural unit derived from N-isopropylacrylamide with respect to all the structural units of the organic polymer 1 is 80 mol%, and the structure derived from 2-hydroxyethyl acrylate. The content ratio of the unit is 20 mol%. The weight average molecular weight of the organic polymer 1 was 19,000 in terms of polystyrene.

(Preparation of coating film forming composition)
<Example 1>
Organic polymer 1: 0.5 g, crosslinking agent (1,3,4,6-tetrakis (methoxymethyl) glycoluril) 0.035 g, photoacid generator (6- (n-butylthio) -2- (tri Fluoromethylsulfonyloxy) -2-aza-2H-phenalene-1,3-dione) (0.075 g) and 2-methoxyethanol (50.2 g) were added to obtain a coating film forming composition 1.

<Comparative Examples 1 to 17>
Coating film-forming compositions 2 to 18 were obtained in the same manner as in Example 1 except that 2-methoxyethanol in Example 1 was changed to the solvents shown in Table 1.

[Plastic solvent resistance]
1 mL of the solvent described in Table 1 was added to polystyrene aznole petri dish (φ (Phi) 40 × 15) (manufactured by Azwan Co., Ltd.) and left at room temperature for 24 hours. Then, after recovering the solvent in the plastic dish, the solvent resistance of the plastic dish was confirmed by observing the properties of the plastic dish. Evaluation of the properties after the solvent test on the plastic dish was made with no change (white turbidity, dissolution and cracking were not confirmed), and one with at least one of white turbidity, dissolution and cracking was confirmed. X ". The results are shown in Table 1.

[Solubility of coating film forming composition in various solvents]
The dissolved state of the solid content contained in the coating film forming compositions of Example 1 and Comparative Examples 1 to 17 was visually observed. The solubility of each coating film forming composition was evaluated according to the following criteria.
○: Precipitation or the like does not occur, and a transparent liquid state
X: The solid content in the composition was not completely dissolved and precipitated.
The results are shown in Table 1.

[Sensitivity test]
The coating film forming composition 1 was applied onto a silicon wafer using a spin coater, and pre-baked on a hot plate at 80 ° C. for 1 minute to form a coating film on the silicon wafer. Next, the coating film was exposed using an i-line aligner PLA-501 (manufactured by Canon Inc.) while changing the exposure amount. It was then post-exposure baked (PEB) in an oven at 80 ° C. for 20 hours. After the exposure, the baked coating film was exposed to isopropyl alcohol for 1 minute, and then rinsed with shaking at 60 ° C. for 3 minutes. Thereafter, the coating film was dried at 60 ° C. for 10 minutes, and the thickness of the coating film in the exposure area was measured. The results are shown in FIG.
In addition, the same result as the above was obtained also when it carried out like the above except having changed the time of post-exposure baking (PEB) from 20 hours to 5 hours.

[Patterning test]
The coating film forming composition 1 was applied onto a Nunc Thermonox cover slip (made of polyester) (Thermo Fisher Scientific, Inc.) using a spin coater, and prebaked on a hot plate at 80 ° C. for 1 minute. A coating film was formed on the wafer. Next, using an i-line aligner PLA-501 (manufactured by Canon Inc., exposure amount: 2000 mJ / cm ² ), a line pattern mask with an interval of 20 μm (that is, a mask with an opening width of 20 μm and a mask width of 20 μm) Exposed through. Then, it was post-exposure baked (PEB) at 80 ° C. for 20 hours in an oven. After the exposure, the baked coating film was exposed to isopropyl alcohol for 1 minute, and then rinsed with shaking at 60 ° C. for 3 minutes. Then, it was made to dry at 60 degreeC for 10 minute (s), and the base material with a pattern was obtained. The surface of the substrate with the pattern is observed using an atomic force microscope (AFM) (“Dimension Icon” manufactured by Bruker AXS Co., Ltd.). The thickness and width of the missing part were measured. The results are shown in FIG.

The base material (base material with a pattern) which has a favorable pattern (a line and space pattern with a line width of 20 μm and a space width of 20 μm) was obtained from the coating film forming composition 1.

The composition for forming a biocompatible coating of the present invention is particularly useful when a biocompatible coating film is formed on a resin substrate.

This application is based on Japanese Patent Application No. 2015-32149 (filing date: February 20, 2015) filed in Japan, the contents of which are incorporated in full herein.

Claims

A biocompatible coating film-forming composition comprising (A) an organic polymer and (D) methoxy alcohol having 2 to 5 carbon atoms as a solvent.
The composition according to claim 1, wherein (D) the methoxy alcohol having 2 to 5 carbon atoms is 2-methoxyethanol.
The (A) organic polymer includes an organic polymer containing a structural unit having at least one organic group selected from a hydroxy group, a hydroxymethyl group and an alkoxymethyl group having 1 to 5 carbon atoms in the side chain. The composition according to claim 1 or 2.
The (A) organic polymer is
(A1) General formula (1):

[Where,
R 1 represents a hydrogen atom or a methyl group,
Q 1 represents an ester bond or an amide bond,
R 2 is an alkyl group having 1 to 10 carbon atoms or 6 to 10 carbon atoms in which at least one hydrogen atom is substituted with a hydroxy group, a hydroxymethyl group or an alkoxymethyl group having 1 to 5 carbon atoms. An aromatic hydrocarbon group is shown. ]
The composition according to any one of claims 1 to 3, comprising an organic polymer comprising a structural unit represented by:
The (A1) organic polymer is
General formula (2):

[Where,
R 3 represents a hydrogen atom or a methyl group,
R 4 and R 5 may be the same or different and each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may be substituted with a hydroxy group or a carboxy group. ]
The composition of Claim 4 which further contains the structural unit represented by these.
The composition according to any one of claims 1 to 5, further comprising (B) a photoacid generator.
A substrate having on its surface a coating film formed from the composition according to any one of claims 1 to 6.
The substrate according to claim 7, wherein the substrate comprises polystyrene.
A method for producing a substrate having a coating film on the surface, comprising a step of forming a coating film on the surface of the substrate using the composition according to any one of claims 1 to 6.
The manufacturing method according to claim 9, wherein the substrate contains polystyrene.
A substrate having on the surface a pattern formed using the composition according to claim 6.
A patterned substrate comprising a step of forming a coating film on the surface of the substrate using the composition according to claim 6, a step of irradiating the coating film with light, and a step of developing the coating film after exposure. Manufacturing method.
A pattern forming method comprising a step of forming a coating film on the surface of a substrate using the composition according to claim 6, a step of irradiating the coating film with light, and a step of developing the coating film after exposure.