U.S. patent application number 10/594918 was filed with the patent office on 2007-09-06 for method for treating surface of material, surface-treated material, medical material, and medical instrument.
Invention is credited to Yoshinori Abe, Tatsuyuki Nakatani, Keishi Okamoto, Kohei Shiraishi, Kazuo Sugiyama.
Application Number | 20070207321 10/594918 |
Document ID | / |
Family ID | 35124965 |
Filed Date | 2007-09-06 |
United States Patent
Application |
20070207321 |
Kind Code |
A1 |
Abe; Yoshinori ; et
al. |
September 6, 2007 |
Method For Treating Surface Of Material, Surface-Treated Material,
Medical Material, And Medical Instrument
Abstract
A diamond-like carbon film (DLC film) is formed on the surface
of a base material made of an inorganic material, such as ceramics,
or the like, or an organic material, such as resin, or the like.
The surface of the resultant DLC film is treated with plasma, or
the like, so as to be activated. Various monomers having
biocompatibility, etc., are graft-polymerized to the activated
surface of the DLC film, whereby a polymer layer is formed from the
monomers grafted to the surface of the DLC film. Thus, the base
material coated with the DLC film modified with a polymer which
does not readily separate can be realized.
Inventors: |
Abe; Yoshinori; (Hiroshima,
JP) ; Nakatani; Tatsuyuki; (Hiroshima, JP) ;
Okamoto; Keishi; (Hiroshima, JP) ; Shiraishi;
Kohei; (Hiroshima, JP) ; Sugiyama; Kazuo;
(Hiroshima, JP) |
Correspondence
Address: |
BIRCH STEWART KOLASCH & BIRCH
PO BOX 747
FALLS CHURCH
VA
22040-0747
US
|
Family ID: |
35124965 |
Appl. No.: |
10/594918 |
Filed: |
March 25, 2005 |
PCT Filed: |
March 25, 2005 |
PCT NO: |
PCT/JP05/05534 |
371 Date: |
September 29, 2006 |
Current U.S.
Class: |
428/413 ;
427/2.24; 427/249.7; 427/535; 428/411.1; 428/421; 428/446 |
Current CPC
Class: |
A61L 31/084 20130101;
C01B 32/28 20170801; Y10T 428/31504 20150401; Y10T 428/31511
20150401; C23C 16/26 20130101; A61L 27/303 20130101; A61L 29/103
20130101; Y10T 428/3154 20150401; C23C 16/56 20130101; A61F
2310/0058 20130101 |
Class at
Publication: |
428/413 ;
427/249.7; 427/535; 427/002.24; 428/411.1; 428/421; 428/446 |
International
Class: |
B32B 27/38 20060101
B32B027/38; C23C 16/00 20060101 C23C016/00 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 30, 2004 |
JP |
2004-100186 |
Claims
1. A material, comprising: a diamond-like carbon film formed on a
surface of a base material; and a polymer grafted to a surface of
the diamond-like carbon film.
2. A medical material comprising a biocompatible component
chemically bonded to a surface of a diamond-like carbon film formed
on a surface of a base material.
3. The medical material of claim 2, wherein the biocompatible
component is a polymer introduced by graft polymerization to the
surface of the diamond-like carbon film.
4. The medical material of claim 3, wherein the biocompatible
component is a polymer formed by grafting vinylmonomers which
contain fluorine to the surface of the diamond-like carbon
film.
5. The medical material of claim 3, wherein the biocompatible
component is a molecule containing silicon, the molecule being
grafted to the surface of the diamond-like carbon film.
6. The medical material of claim 2, wherein the biocompatible
component is bonded by a covalent bond to the surface of the
diamond-like carbon film.
7. The medical material of claim 2, wherein the biocompatible
component is bonded by an ionic bond to the surface of the
diamond-like carbon film.
8. The medical material of claim 2, wherein the biocompatible
component contains at least one functional group selected from a
group consisting of an ethylene oxide group, a hydroxy group, a
phosphate group, an amino group, an amido group, a
phosphorylcholine group, a sulfone group, and a carboxyl group.
9. The medical material of claim 2, wherein an intermediate layer
is provided between the base material and the diamond-like carbon
film to improve adhesion between the base material and the
diamond-like carbon film.
10. The medical material of claim 9, wherein the intermediate layer
is an amorphous film containing silicon and carbon as primary
constituents.
11. A medical material, comprising a hydrophilic functional group
introduced to a surface of a diamond-like carbon film formed on a
surface of a base material.
12. The medical material of claim 2, wherein the base material is a
metal material, ceramic material, or macromolecular material, or a
complex thereof.
13. A medical instrument formed by using the medical material of
claim 2.
14. The medical instrument of claim 13, wherein the medical
instrument is a medical instrument which is to be embedded in a
living body.
15. The medical instrument of claim 14, wherein the medical
instrument is a catheter, guide wire, stent, artificial
cardiovalvular membrane, or artificial joint.
16. A material surface treating method, comprising: a diamond-like
carbon film formation step of forming a diamond-like carbon film on
a surface of a base material; an activation step of generating on a
surface of the diamond-like carbon film a reactive region which
serves as a polymerization starting point; and a polymerization
step of polymerizing monomers using the polymerization starting
point to graft the monomers to the surface of the diamond-like
carbon film.
17. The method of claim 16 further comprising, before the
diamond-like carbon film formation step, an intermediate layer
formation step of forming on the surface of the base material an
intermediate layer for improving adhesion between the base material
and the diamond-like carbon film.
18. The method of claim 17 wherein, in the intermediate layer
formation step, the intermediate layer is formed of an amorphous
film containing silicon and carbon as primary constituents.
19. The method of claim 16, wherein the activation step is the step
of generating a free radical as the polymerization starting
point.
20. The method of claim 16, wherein the activation step is a plasma
irradiation step of irradiating the surface of the diamond-like
carbon film with plasma.
21. The method of claim 20, wherein the plasma irradiation step
uses, as the plasma, argon, xenon, neon, helium, krypton, nitrogen,
oxygen, ammonium, hydrogen, or water vapor.
22. The method of claim 16, wherein: the base material is a base
material for a medical material; and the polymer is a biocompatible
component.
23. A material surface treating method, comprising: a diamond-like
carbon film formation step of forming a diamond-like carbon film on
a surface of a base material; a plasma irradiation step of
irradiating a surface of the diamond-like carbon film with plasma
to generate a reactive region on the surface of the diamond-like
carbon film; and a surface modification step of a reaction of the
reactive region and a molecule containing oxygen to introduce a
hydroxy group to the surface of the diamond-like carbon film.
Description
TECHNICAL FIELD
[0001] The present invention relates to a method for treating the
surface of a material with a diamond-like carbon film formed
thereon, a surface-treated material, a medical material having
excellent biocompatibility, and a medical instrument.
BACKGROUND ART
[0002] The diamond-like carbon film (DLC film) has a hard, fine and
inert surface. Therefore, when formed on the surface of a material,
for example, an inorganic material, such as a metal, ceramic, etc.,
or an organic material, such as a resin, etc., the DLC film can
give the surface of the material certain characteristics, such as
abrasion resistance, corrosion resistance, surface smoothness,
etc.
[0003] For example, it has been known that coating the surface of a
mold or tool with a DLC film improves the durability and
releasability. Further, the coating creates a very smooth and inert
surface and therefore has been a promising surface treatment for
materials of medical instruments which should not cause
interactions with biosubstances (see, for example, Patent Document
1 and Non-Patent Document 1).
[0004] Meanwhile, modifying the surface of a material with various
substances to achieve high functionality on the material surface
has been studied. With this, for example, development of
nanodevices for molecular recognition on a semiconductor surface
modified with functionality components, development of
antithrombotic medical materials where the surface of the materials
is modified with an antithrombotic material.
[0005] Various studies have been conducted especially on the means
for providing biocompatibility, such as antithrombogenicity, etc.,
to the surface of a medical material. For example, it has been
known that a hydrogel layer similar to the surface of a biomembrane
can be formed on the surface of a medical material by modifying the
surface of the medical material with a polymer containing as one
component an artificial material having a chemical structure
similar to the components of the biomembrane, such as
2-methacryloyl-oxyethyl phosphorylcholine (MPC),
o-methacryloyl-L-Serine (SerMA), or the like, whereby excellent
biocompatibility can be given to the surface of the medical
material.
[0006] The surface of the material which is to be modified by such
a functionality component is preferably refractory and inert. When
the material surface has high reactivity, there is a possibility
that an interaction between the material surface and a
functionality molecule as a modifier denatures and deactivates the
modifier functionality component. Further, certain environments
degrade the material itself. Therefore, a material coated with a
very smooth, inert DLC film is expected to exhibit excellent
quality as a material which is to be modified with a functionality
component, etc.
[0007] [Patent Document 1] Japanese Laid-Open Patent Publication
No. 10-248923
[0008] [Non-Patent Document 1] Haruo Ito et al., "Biomaterial",
1985, Vol. 3, pp. 45-53
DISCLOSURE OF INVENTION
Problems to be Solved by the Invention
[0009] However, the DLC film is smooth and inert and is therefore
difficult to modify with a functionality component, such as a
biocompatible material, or the like. Since the surface is very
inert, it is almost impossible to cause a chemical reaction between
the surface and a functionality component for generating a covalent
bond therebetween. The very smooth surface is almost incapable of
physical adsorption. Even if a functionality component is
temporarily adsorbed by the surface, the component immediately
separates from the surface.
[0010] The present invention provides a solution to the
above-described problem. An objective of the present invention is
to realize a material where a base material is coated with a DLC
film stably modified for a long term with a functionality
component, typically a biocompatible material, and a medical
material having persistent, excellent biocompatibility.
Means for Solving the Problems
[0011] To achieve the above objective, according to the present
invention, the base material is coated with a diamond-like carbon
film (DLC film) to which a functionality component, typically a
biocompatible material, is grafted.
[0012] Specifically, a material of the present invention includes:
a diamond-like carbon film formed on a surface of a base material;
and a polymer grafted to a surface of the diamond-like carbon film.
Since the material of the present invention includes the polymer
grafted to the surface of the DLC film, the polymer does not
separate from the DLC film. Therefore, it is possible to modify the
surface of the base material with the polymer stably for a long
term.
[0013] The first medical material of the present invention includes
a biocompatible component chemically bonded to a surface of a
diamond-like carbon film formed on a surface of a base
material.
[0014] According to the first medical material, the biocompatible
component is bonded to the surface of the DLC film formed on the
surface of the base material. Therefore, excellent biocompatibility
can be given to the surface of the DLC film. The biocompatible
component is chemically bonded to the surface of the DLC film and
does not readily separate from the surface of the DLC film. Since
the DLC film is capable of a hard, dense coating over the surface
of various base materials, the DLC film itself does not separate,
so that deterioration of the base material itself can be
suppressed. As a result, it is possible to realize a medical
material which exhibits stable biocompatibility for a long term
such that the biocompatible component does not separate.
[0015] In the first medical material, the biocompatible component
is preferably a polymer introduced by graft polymerization to the
surface of the diamond-like carbon film.
[0016] With such a structure, it is possible to introduce a variety
of freely designed molecules to the surface of the DLC film.
[0017] In the first medical material, the biocompatible component
may be a polymer formed from vinylmonomers which contain fluorine
and are grafted to the surface of the diamond-like carbon film, or
may be a molecule containing silicon. The biocompatible component
may be bonded by a covalent bond to the surface of the diamond-like
carbon film or may be bonded by an ionic bond to the surface of the
diamond-like carbon film. With such structures, it is possible to
surely obtain a medical material in which separation of the
biocompatible component from the DLC film does not occur.
[0018] In the first medical material, the biocompatible component
preferably contains at least one functional group selected from a
group consisting of an ethylene oxide group, a hydroxy group, a
phosphate group, an amino group, an amido group, a
phosphorylcholine group, a sulfone group, and a carboxyl group.
With such functional groups contained, the biocompatibility can be
surely given to the surface of the medical material.
[0019] In the first medical material, an intermediate layer may be
provided between the base material and the diamond-like carbon film
to improve adhesion between the base material and the diamond-like
carbon film. With such a structure, the surface of the base
material can be more firmly coated with the DLC film. The
intermediate layer is preferably an amorphous film containing
silicon and carbon as primary constituents.
[0020] The second medical material of the present invention
includes a hydrophilic functional group introduced to a surface of
a diamond-like carbon film formed on a surface of a base material.
According to the second medical material, the hydrophilic
functional group is introduced to the surface of the DLC film, so
that the DLC film itself exhibits hydrophilicity. Therefore, it is
possible to achieve a medical material which exhibits stable
biocompatibility for a long term.
[0021] In the medical material of the present invention, the base
material is preferably a metal material, ceramic material, or
macromolecular material, or a complex thereof.
[0022] A medical instrument of the present invention is formed by
using the medical material of the present invention. With such a
structure, a medical instrument having excellent biocompatibility
can be obtained.
[0023] The medical instrument of the present invention is
preferably a medical instrument which is to be embedded in a living
body. The medical instrument may be a catheter, guide wire, stent,
artificial cardiovalvular membrane, or artificial joint.
[0024] The first material surface treating method of the present
invention, includes: a diamond-like carbon film formation step of
forming a diamond-like carbon film on a surface of a base material;
an activation step of generating on a surface of the diamond-like
carbon film a reactive region which serves as a polymerization
starting point; and a polymerization step of polymerizing monomers
using the polymerization starting point to graft the monomers to
the surface of the diamond-like carbon film.
[0025] The first material surface treating method of the present
invention includes the activation step of generating on a surface
of the diamond-like carbon film a reactive region which serves as a
polymerization starting point and the step of polymerizing monomers
using the polymerization starting point. Therefore, it is possible
to graft the polymer to the surface of the inert diamond-like
carbon film. It is possible to modify the surface of the DLC film
with the polymer stably for a long term. It is possible to give
both the characteristics of the DLC film, such as durability, etc.,
and the characteristics of the polymer.
[0026] The first material surface treating method preferably
includes, before the diamond-like carbon film formation step, an
intermediate layer formation step of forming on the surface of the
base material an intermediate layer for improving adhesion between
the base material and the diamond-like carbon film. With this, it
is possible to surely coat the surface of the base material with
the DLC film. In the intermediate layer formation step, the
intermediate layer is preferably formed of an amorphous film
containing silicon and carbon as primary constituents.
[0027] In the first material surface treating method, the
activation step is preferably the step of generating a free radical
as the polymerization starting point. The activation step is
preferably a plasma irradiation step of irradiating the surface of
the diamond-like carbon film with plasma. With these features, the
polymerization starting point can be surely generated on the
surface of the DLC film. The plasma irradiation step preferably
uses, as the plasma, argon, xenon, neon, helium, krypton, nitrogen,
oxygen, ammonium, hydrogen, or water vapor.
[0028] In the first material surface treating method, the base
material is preferably a base material for a medical material. The
polymer is preferably a biocompatible component. With such
features, a base material which exhibits stable biocompatibility
for a long term can be obtained, and a medical material with
excellent biocompatibility can be realized.
[0029] The second material surface treating method of the present
invention includes: a diamond-like carbon film formation step of
forming a diamond-like carbon film on a surface of a base material;
a plasma irradiation step of irradiating a surface of the
diamond-like carbon film with plasma to generate a reactive region
on the surface of the diamond-like carbon film; and a surface
modification step of causing a reaction of the reactive region and
a molecule containing oxygen to introduce a hydroxy group to the
surface of the diamond-like carbon film.
[0030] The second material surface treating method includes the
plasma irradiation step of irradiating a surface of the
diamond-like carbon film with plasma to generate a reactive region
on the surface of the diamond-like carbon film, and the surface
modification step of causing a reaction of the reactive region and
a molecule containing oxygen to introduce a hydroxy group to the
surface of the diamond-like carbon film. Therefore, it is possible
to change the surface of the DLC film to be hydrophilic. It is
possible to realize a material with excellent biocompatibility.
Since the hydroxy group can be further substituted, it is possible
to freely introduce a functional group to the surface of the DLC
film and modify the surface with various compounds.
EFFECTS OF THE INVENTION
[0031] According to the present invention, a material wherein the
surface of a base material is coated with a DLC film, and the DLC
film is modified with a functionality component, typically a
biocompatible material, stably for a long term, and a medical
material and medical instrument with excellent biocompatibility can
be realized.
BRIEF DESCRIPTION OF DRAWINGS
[0032] FIG. 1 is a schematic view of an ionic vapor deposition
apparatus according to an embodiment of the present invention.
[0033] FIG. 2 is a schematic view of a plasma irradiation apparatus
which is used for a medical material production method according to
an embodiment of the present invention.
[0034] FIG. 3(a) and FIG. 3(b) show results of XPS measurement of
the surface of a DLC film formed on a base material of aluminum
based on a medical material production method according to an
embodiment of the present invention. FIG. 3(a) shows the
measurement result obtained before HMPA graft. FIG. 3(b) shows the
measurement result obtained after HMPA graft.
DESCRIPTION OF REFERENCE NUMERALS
[0035] 1 Substrate
[0036] 2 Arc Discharge Plasma Generator
[0037] 11 Base Material
[0038] 21 Chamber
[0039] 22 Vacuum Pump
[0040] 23 Electrode
[0041] 24 Electrode
[0042] 25 High Frequency Power Supply
[0043] 26 Matching Network
BEST MODE FOR CARRYING OUT THE INVENTION
[0044] The present inventors found that irradiating an inert DLC
film, which has no reactivity in nature, with plasma, or the like,
can activate the DLC film, so that monomers can be grafted to the
surface of the DLC film by graft polymerization, or various
functional groups can be introduced to the surface of the DLC
film.
[0045] Thus, for example, after the surface of a DLC film formed on
the surface of a base material, such as a metal, ceramic, resin,
rubber, or the like, is activated, various functionality components
are chemically bonded to the surface of the DLC film by means of
graft polymerization, covalent bond, ionic bond, or the like,
whereby the surface of the material is protected while various
characteristics can be given to the material stably for a long
term.
[0046] The present inventors also found that, when a biocompatible
component is chemically bonded to the surface of the DLC film, a
medical material which exhibits excellent biocompatibility for a
long term can be realized wherein none of separation of the
biocompatible component from the material surface and deterioration
of the material occurs, and completed the present invention.
Hereinafter, a structure of the present invention is described.
[0047] The base material used in the present invention is a metal
material, a semiconductor material, such as silicon, or the like, a
ceramic material, rubber, a polymeric material, such as a resin, or
the like, or a complex thereof. The base material is subjected to
various processes for medical uses, semiconductor uses, or other
uses. For example, in medical uses, the base material of the
present invention is used as a base material of a medical material
used for manufacturing a medical instrument which comes in contact
with a living body or organic component, typically a catheter,
guide wire, stent, artificial cardiovalvular membrane, and
artificial joint. The medical material includes materials used for
medical instruments, such as wires, tubes, plates, etc., one that
obtained by processing any of these materials in the shape of a
medical instrument, and one that is in the midst of the formation
of the medical instrument. As for semiconductor uses, the base
material may be, for example, a semiconductor substrate which is a
constituent of a semiconductor device.
[0048] Although the type of the base material is not limited to
anything particular, a metal, such as iron, nickel, chrome, copper,
titanium, platinum, tungsten, tantalum, or the like, can be used.
Also, alloys of these metals, for example, stainless steel, such as
SUS316L, or the like, a shape memory alloy, such as a Ti--Ni alloy,
a Cu--Al--Mn alloy, or the like, other alloys, such as a Cu--Zn
alloy, a Ni--Al alloy, a titanium alloy, a tantalum alloy, a
platinum alloy, a tungsten alloy, or the like, can be used.
[0049] Alternatively, the base material may be a silicon or gallium
semiconductor material, aluminum, silicon or zirconium oxide,
silicon or zirconium nitride, ceramic or apatite, such as a
carbide, or bioactive ceramic, such as bioglass, or the like. The
base material may be a macromolecular resin, such as polymethyl
methacrylate (PMMA), high density polyethylene, polyacetal, or the
like, a silicon polymer, such as polydimethylsiloxane, or the like,
or a fluoric polymer, such as polytetrafluoroethylene, or the
like.
[0050] The DLC film formed on the surface of the base material is a
film formed of diamond-like carbon (which may contain a very small
amount of any other component as an impurity). This film is very
smooth and inert in nature. However, free radicals or ion species
can be generated by irradiating the surface of the DLC film with
plasma, or the like, and cleaving some of diamond (carbon to
carbon) bonds on the surface. Accordingly, a functionality
component can be grafted by graft polymerization to the surface of
the DLC film, or various functional groups can be introduced to the
surface of the DLC film by means of reactions with various
substances after activation.
[0051] Although the surface of the base material has irregularities
on the order of microscale or nanoscale, formation of a DLC film on
the surface of the base material can achieve a smooth surface. With
the smooth surface, it is possible to uniformly irradiate the
surface of the base material with plasma, so that uniform graft
polymerization can be performed over the surface of the base
material. Since the DLC film is a very dense and hard film, a
foreign component can be prevented from permeating the DLC film and
deteriorating the base material. Therefore, the material of the
present invention can be used for a product used in an environment
in which the acid resistance or alkali resistance is required or a
product used in a living body.
[0052] In the present invention, the DLC film can be formed on the
surface of the base material using a known method, such as
sputtering, DC magnetron sputtering, RF magnetron sputtering,
chemical vapor deposition (CVD), plasma CVD, plasma-based ion
implantation, plasma-based ion implantation with superimposed RF
and high-voltage pulses, ionic plating, arc ionic plating, ion beam
deposition, laser ablation, or the like. The thickness of the DLC
film is not limited to any particular thickness but is preferably
in the range of 0.01 to 3 .mu.m and, more preferably, in the range
of 0.02 to 1 .mu.m.
[0053] Although the DLC film can be directly formed on the surface
of the base material, an intermediate layer may be provided between
the base material and the DLC film for more firmly adhering the
base material and the DLC film. The material of the intermediate
layer can be selected among various materials according to the type
of the base material. Any known material, such as an amorphous film
of silicon (Si) and carbon (C), an amorphous film of titanium (Ti)
and carbon (C), an amorphous film of chromium (Cr) and carbon (C),
or the like, can be used for the intermediate layer. The thickness
of the intermediate layer is not limited to any particular
thickness but is preferably in the range of 0.005 to 0.3 .mu.m and,
more preferably, in the range of 0.01 to 0.1 .mu.m.
[0054] The intermediate layer can be formed using a known method.
For example, sputtering, CVD, plasma CVD, flame spraying, ionic
plating, arc ionic plating, or the like, may be used.
[0055] According to the present invention, the surface of a DLC
film is activated by energy irradiation on the DLC film with
plasma, light, or the like, whereby a radical, ion, or the like,
which serves as a polymerization starting point, can be generated
on the surface of the DLC film. In the case of plasma irradiation,
a gas capable of disconnecting a carbon to carbon bond present on
the surface of the DLC film, such as argon (Ar), neon (Ne), helium
(He), krypton (Kr), xenon (Xe), nitrogen gas (N.sub.2), oxygen gas
(O.sub.2), ammonium gas (NH.sub.4), hydrogen gas (H.sub.2), water
vapor (H.sub.2O), or the like, or a mixture gas thereof can be used
as a plasma gas source. Alternatively, the surface of the DLC film
can be activated by means of irradiation with ultraviolet light or
ultraviolet ozone.
[0056] The activated surface of the DLC film has radicals, or the
like, which serve as polymerization starting points. Therefore,
various organic components can be grafted to the surface of the DLC
film by graft-polymerizing various radical-polymerizable monomers
on the activated surface of the DLC film. Therefore, an
addition-polymerizable monomer, such as a vinylmonomer having the
general formula of Formula 1, a vinylidene monomer having the
general formula of Formula 2, a vinylene monomer having the general
formula of Formula 3, a cyclic vinylene monomer having the general
formula of Formula 4, or the like, can be graft-polymerized at a
polymerization starting point generated on the surface of the DLC
film.
[0057] Since the polymerization starting points can be generated on
only part of the surface of the DLC film subjected to energy
irradiation, a polymer can be introduced by graft polymerization
only at a desired position over the surface of the base material
using an appropriate mask. Further, the density of the polymer on
the surface of the base material can be freely adjusted. For
example, in the case where antithrombogenicity is given to the base
material, the adjustment of the surface density of an
antithrombotic macromolecular material grafted to the surface of
the DLC film is important. According to the present invention, the
surface density is readily adjustable. ##STR1##
[0058] In the monomer structures of Formula 1 to Formula 3,
substituents X and Y are ester or amido, typically --COOR.sub.1,
--CONR.sub.2, or the like. Substituents X and Y in the same
molecule may be identical or may be different. In the monomer
structure of Formula 4, substituent Z is ester or amido which is a
constituent of a cyclic structure and typically is --CO--O--CO--,
--CO--NR.sub.3--CO--, or the like.
[0059] Especially in the case where the material is applied to
medical uses, R1 to R3 are each has a structure containing a highly
biocompatible constituent, for example, a functional group, such as
an ethyleneoxide group, hydroxy group, amino group,
phosphorylcholine group, phosphate group, sulfone group,
nucleobase, or the like, a monosaccharide, or a polysaccharide. It
is preferably a molecule which forms a hydrogel layer at the
interface with water when graft-polymerized.
[0060] Other than hydrophilic monomers, it may be a monomer
containing dimethylsiloxane, fluorine, or the like, which is
unlikely to adsorb protein and exhibits high hydrophobicity and
biocomparibility.
[0061] Specifically, a known polymerizable monomer from which a
biocompatible polymer is obtained when graft polymerized, such as
2-methacryloyl-oxyethyl phosphorylcholine (MPC),
2-acryloyl-oxyethyl phosphorylcholine,
1-methyl-2-methacryloyl-amideethyl phosphorylcholine,
2-glucoxy-oxyethyl methacryl acid, sulfated 2-glucoxy-oxyethyl
methacryl acid, p-N-vinylbenzyl-D-lactone amide,
p-N-vinylbenzyl-D-propione amide, p-N-vinylbenzyl-D-malto-trione
amide, o-methacryloyl-L-serine, o-methacryloyl-L-threonine,
o-methacryloyl-L-tyrosine, o-methacryloyl-L-hydroxyproline,
2-methoxyethyl methacryl amide, 2-methoxyethyl acryl amide,
2-hydroxyethyl acryl acid, N-2-hydroxypropyl methacryl amide,
N-isopropyl acryl amide, N-vinylpyrrolidone, vinylphenol;
N-2-hydroxy acryl amide, acryl amide derivative monomer, methacryl
amide derivative monomer, phospholipid-like vinylmonomer,
mocromonomer of polyethylenoxyde, or the like, can be used.
[0062] For example, a hydrogel layer, which has the function of
inhibiting recognition of a foreign substance by a living body
similarly to the surface of a biomembrane, can be formed on the
surface of a DLC film by introducing MPC to the surface of the DLC
film by graft polymerization. Since phospholipid present in blood
is oriented/disposed on the basis of MPC grafted to the surface of
the DLC film as a core, a function similar to that of the
biomembrane can be given to the surface of the DLC film.
[0063] The above-listed monomers may be solely graft-polymerized or
may be graft-polymerized in the form of a multidimensional
copolymer. The graft polymerization may be performed at a single
step or may be repeatedly performed in multi steps.
[0064] Although the optimum molecular weight of a polymer obtained
by the graft polymerization depends on the use of the material, the
type of a monomer to be grafted, etc., the component to be grafted
to the surface is not limited to a macromolecule but may be an
oligomer where the molecular weight of the polymer is 1000 or less.
Especially when the material is applied to a medical use, the
component may be one that the characteristics, such as the surface
wettability of the material, etc., are changeable.
[0065] Although the above-described example uses radical
polymerization, the graft can be achieved with anion polymerization
or cation polymerization instead of radical polymerization by
generating cation species or anion species as polymerization
starting points on the surface of the DLC film. These
polymerization starting points can be generated by means of
low-temperature plasma irradiation, ultraviolet or ultraviolet
ozone irradiation, .gamma.-ray, or the like.
[0066] The method for modifying with a functionality component the
surface of the DLC film which serves as a coating over the surface
of the base material is not limited to the graft polymerization of
monomers. For example, the technique of grafting a molecular chain
may be employed wherein, for example, a functional group, such as
an amino group, a carboxyl group, or the like, is introduced to the
surface of the DLC film, and the functional group introduced to the
surface of the DLC film and a functional group of the molecular
chain are brought into a reaction.
[0067] The surface of the DLC film is activated by, for example, a
plasma treatment so that an active point, such as a radical, or the
like, is generated, and then, the active point is brought into a
reaction with water or oxygen, whereby a hydroxy group can readily
be introduced to the surface of the DLC film.
[0068] The hydroxy group introduced to the surface of the DLC film
can readily be converted into an amino group, a carboxyl group, an
isocyanate group, or a vinyl group by means of a reaction with a
functional alkoxy silane derivative, such as
3-aminopropyltrimethoxysilane, or the like, a functional carboxylic
acid, such as 2-mercaptoacetic acid, or the like, a diisocyanate
derivative, 2-methacryloyl-oxyethyl isocyanate, 2-acryloyl-oxyethyl
isocyanate, N-methacryloyl-succinimide, or N-acryloyl-succinimide.
A functionality component containing in the molecule a functional
group which cause a reaction with the functional group introduced
to the surface of the DLC film, for example, an amino group, a
carboxyl group, an isocyanate group, or a trialkyloxysilane group
such as trimethoxysilane, triethoxysilane, etc., can readily be
covalent-bonded to the surface of the DLC film. Even when the
functionality component does not include a functional group which
causes a direct reaction with the functional group on the surface
of the DLC film, a functional group can be covalent-bonded to the
surface of the DLC film by using a bifunctional reagent.
[0069] Especially when the material is applied to a medical use, a
tissue-derived component having a functional group, such as
peptide, protein, nucleobase, sugar chain, chitin, chitosan, or the
like, or a biocompatible macromolecular chain including a hydroxy
group, a carboxyl group, or amino group introduced by chain
transfer reaction at a terminal may be brought into a coupling
reaction with a functional group introduced to the surface of the
DLC film in advance and fixed by covalent bond. The functionality
component is not limited to a macromolecular chain but may be a low
molecular component, such as an amino acid and a monosaccharide,
and oligomers thereof. The reaction for converting the functional
group is not limited to a single step reaction but may be a
multi-step reaction. For example, the functional group may be
converted in multi steps such that a hydroxy group is converted to
an amino group and then to a vinyl group.
[0070] A biocompatible component may be introduced to the surface
of the DLC film by forming an ionic bond between the surface of the
DLC film and the biocompatible component using an ionic functional
group present in the biocompatible component, such as a carboxyl
group, amino group, phosphate group, or the like. In this case, the
biocompatible component can readily be introduced to the surface of
the DLC film even if it is an inorganic component, such as
hydroxyapatite, or the like.
[0071] Biocompatibility may be given to the DLC film itself by
introducing a functional group to the surface of the DLC film to
alter the surface of the DLC film into a hydrophilic surface
instead of introducing another biocompatible component to the
surface of the DLC film.
EXAMPLE
[0072] Hereinafter, the present invention is described in more
detail along with an example but is not limited to this example in
any respect.
[0073] --Coating with DLC Film--
[0074] Coating of a DLC film over the base material is first
described. In this example, an aluminum alloy (equivalent to
JIS-8021 alloy) having a length of 50 mm, a width of 5 mm, and a
thickness of 55 .mu.m and polyethylene terephthalate (PET) were
used for the base material.
[0075] FIG. 1 is a schematic view of an ionic vapor deposition
apparatus used in this example. The ionic vapor deposition
apparatus is a commonly-employed ionic vapor deposition apparatus
wherein benzene (C.sub.6H.sub.6) gas is introduced as a carbon
source into a DC arc discharge plasma generator 2 provided inside a
vacuum chamber to generate plasma, and the generated plasma is
collided with a substrate 1 biased to a negative voltage, which is
a subject of the coating, whereby the plasma is solidified over the
substrate 1 to form a film.
[0076] The base material was set inside the chamber of the ionic
vapor deposition apparatus shown in FIG. 1, and argon gas (Ar) at
the pressure of 10.sup.-3 to 10.sup.-5 Torr was introduced into the
chamber, and then, a bombardment cleaning was carried out for about
30 minutes wherein Ar ions were generated by electric discharge,
and the generated Ar ions were collided with the surface of the
base material.
[0077] Then, tetramethylsilane (Si(CH.sub.3).sub.4) was introduced
into the chamber to form, as an intermediate layer, an amorphous
film having a thickness of 0.02 .mu.m to 0.05 .mu.m containing
silicon (Si) and carbon (C) as primary constituents.
[0078] After the formation of the intermediate layer,
C.sub.6H.sub.6 gas was introduced into the chamber, and the gas
pressure was set to 10.sup.-3 Torr. Electric discharge was
performed while C.sub.6H.sub.6 was continuously introduced at the
rate of 30 ml/min to ionize C.sub.6H.sub.6. Then, ionic vapor
deposition was performed for about 10 minutes to form a DLC film
having a thickness of 0.1 .mu.m over the surface of the base
material.
[0079] The formation of the DLC film was carried out under the
following conditions: Substrate Voltage 1.5 kV, Substrate Current
50 mA, Filament Voltage 14 V, Filament Current 30 A, Anode Voltage
50V, Anode Current 0.6 A, Reflector Voltage 50 V, Reflector Current
6 mA. The temperature of the substrate was about 160.degree. C.
[0080] The intermediate layer was provided for improving the
adherence between the base material and the DLC film but may be
omitted if sufficient adherence can be secured between the base
material and the DLC film.
[0081] In this example, C.sub.6H.sub.6 gas was solely used as the
carbon source, but mixture gas of C.sub.6H.sub.6 and fluorocarbon
gas, such as CF.sub.4, or the like, may be used for forming a DLC
film containing fluorine over the surface of the base material.
[0082] --Activation of DLC Film--
[0083] The DLC film formed over the surface of the base material
was irradiated with plasma to activate the surface, and then a
functionality component was grafted to the surface of the DLC film.
FIG. 2 is a schematic view of a plasma irradiation apparatus used
in this example.
[0084] As shown in FIG. 2, the plasma irradiation apparatus is a
commonly-employed plasma irradiation apparatus wherein a chamber 21
formed by a separable flask, to which a vacuum pump 22 is connected
and with which gas replacement is possible, is provided with
electrodes 23 and 24 at the barrel and bottom, respectively, and a
high frequency wave is applied to the electrodes through a matching
network from a high frequency source 26 to generate plasma inside
the chamber 21.
[0085] Firstly, the base material 11 with the DLC film formed
thereon was set inside the chamber 21 of the plasma irradiation
apparatus, and Ar gas was introduced so that the inner pressure of
the chamber 21 was 1.3 Pa. Then, a high frequency wave of 20 W was
applied to the electrodes 23 and 24 using the high frequency source
26 (JRF-300 manufactured by JEOL Ltd.; Frequency 13.56 MHz) to
generate plasma inside the chamber 21. The DLC film formed on the
base material 11 was irradiated with the plasma for about 2 minutes
to produce radicals on the surface of the DLC film.
[0086] --Graft to DLC Film--
[0087] In this example illustrated herein, hydrophilic
2-hydroxypropyl methacryl amide (HPMA) was grafted to the activated
DLC film.
[0088] After the plasma irradiation, the base material was exposed
to air for about 1 minute and then inserted into a glass
polymerization tube together with 10 ml of ethanol solution of HPMA
(concentration: 0.17 g/ml). The cycle of
freezing--deaeration--nitride replacement in liquid nitrogen was
repeated several times to purge dissolved oxygen from the
polymerization tube. Thereafter, the polymerization tube was sealed
under a reduced pressure, and polymerization was carried out at
80.degree. C. for 24 hours, whereby HPMA was graft-polymerized over
the surface of the DLC film to graft the polymer of HPMA.
[0089] After the polymerization, the base material was immersed
into an abundant amount of ethanol and then washed with an abundant
amount of phosphoric acid buffer solution (pH=7.4) before freeze
drying. As a result, a graft base material with a grafted HPMA
polymer was obtained. It should be noted that, after the plasma
irradiation, the base material is not necessarily exposed to
air.
[0090] We measured the composition of elements present at the
surface of the obtained graft base material using X-ray
photoelectron spectroscopy (XPS) and confirmed introduction of
HPMA. The XPS measurement was carried out using a XPS/ESCA
apparatus, Model 5600 CiMC, manufactured by Perkin Elmer, Inc., and
the X-ray source was a monochromatized Alk.alpha. (1486.5 eV) at
the power of 100 w (14 kV, 7 mA). In the measurement, a neutralizer
was used as a neutralizing electron gun, and the depth of the
measurement was 4 nm.
[0091] FIG. 3 shows the results of XPS measurement of the
distribution of elements present at the surface of a DLC film
formed on a base material of aluminum. FIG. 3(a) shows the result
of a base material surface measurement before a HPMA polymer was
grafted. FIG. 3(b) shows the result of a base material surface
measurement after the HPMA polymer was grafted.
[0092] Referring to FIG. 3(b), as for the DLC film surface after
the HPMA polymer graft, we found the 1 s peak of nitrogen (N),
which was not seen before the graft (FIG. 3(a)). The constitution
ratio of carbon (C), oxygen (O), and nitrogen (N) obtained from the
peak areas was C: 85.1%, O: 13.93%, N:0.89% before the graft, but
C: 85.1%, O: 13.93%, N: 0.89% after the graft. That is, nitrogen
(N) and oxygen (O) were greatly increased with respect to carbon
(C). This indicates that a HPMA polymer was grafted to the surface
of the DLC film and, as a result, an amido group was introduced to
the surface of the DLC film.
[0093] We also grafted a HPMA polymer to a DLC film formed on a
base material of PET and carried out the above-described
measurement on this sample. We also found the Is peak of nitrogen
after the HPMA polymer graft, which was not seen before the graft,
and confirmed introduction of the HPMA polymer as in the case of
the aluminum base material.
[0094] Then, the wettability of the surface of the obtained graft
base material was measured using a contact angle measurement
apparatus. The measurement of the contact angle was carried out
using a goniometer-based contact angle measurement apparatus G-I
manufactured by ERMA Inc.), wherein a water drop of 15 .mu.l was
placed on the surface of the medical material, and 50 seconds
later, the left contact angle was measured, and 70 seconds later,
the right contact angle was measured. The measurement value was the
average of values at 10 measurement points.
[0095] In the case where a HPMA polymer was grafted to the surface
of the DLC film formed on the aluminum base material, the contact
angle of 67.8.+-.3.50 before the graft of the HPMA polymer was
decreased to 51.8.+-.3.00 after the graft. This indicates that the
HPMA polymer grafted to the surface of the DLC film changed the
surface to be hydrophilic, thereby improving the biocompatibility
of the graft base material.
[0096] In the case of the PET base material, the contact angle of
80.2.+-.2.20 before the graft of the HPMA polymer was decreased to
52.1.+-.2.50 after the graft. This indicates that the surface was
changed to be hydrophilic as was in the case of the aluminum base
material.
[0097] As described above, a polymer of HPMA is grafted to the
surface of a DLC film formed on a medical material so that the
surface of the DLC film becomes hydrophilic, whereby a hydrogel
layer which inhibits foreign substance recognition by a living body
is formed on the surface of the DLC film. Therefore, the
biocompatibility of the medical material is improved. Since the
HPMA polymer is introduced to the surface of the DLC film by graft
polymerization so as not to readily separate, stable
biocompatibility can be maintained for a long term.
[0098] By using the procedure of this example, a hydrophilic
hydroxy group can be introduced to the surface of a DLC film. A DLC
film was treated with plasma according to the procedure of this
example and subjected to an exposure treatment in air for 2
minutes. The resultant sample was subjected to the XPS measurement
and contact angle measurement. In the XPS measurement, we saw a C1s
peak based on C--O bonds near 287 eV, which was not seen in an
untreated DLC film, and confirmed introduction of a hydroxy group.
The contact angle of 79.2.+-.3.00 before the plasma treatment was
decreased to 69.8.+-.3.20 after the plasma treatment, which means
an improvement in the wettability of the surface of the DLC film.
This indicates that exposure of the plasma-treated DLC film to air
caused a reaction of radicals produced at the surface of the DLC
film and oxygen in air, whereby a hydroxy group was introduced to
the surface of the DLC film.
[0099] As described above, according to the present invention, it
is possible to cover the surface of a base material with an inert
DLC film and freely modify the surface of the DLC film with various
molecules. With this, it is possible not only to improve the
durability of the base material but also to give a functionality of
a molecule with which the surface of the DLC film is modified. For
example, if the DLC film is modified with a molecule having the
function of biocompatibility, a medical material which exhibits
high durability and stable biocompatibility for a long term is
obtained. Alternatively, by grafting stimuli-sensitive
biocompatible gel to the surface of a DLC film, it is possible to
achieve a cell culture material which causes less damage when
separated or a highly-active bioreactor material.
[0100] Still alternatively, for example, the surface of a
semiconductor substrate, such as a silicon, or the like, is coated
with a DLC film, and then, a polymer is graft-polymerized to the
DLC film, whereby the polymer is stably introduced to the surface
of the semiconductor substrate. The resultant material can be used
for an organic semiconductor device wherein molecular recognition
is performed at the surface of the substrate. Since it is possible
not only to perform the graft over the entire surface of the DLC
film but also to perform the graft in an arbitrary pattern, the
material can be applied to a microsensor which is used for
measurement of a minute amount of substance, or the like.
INDUSTRIAL APPLICABILITY
[0101] According to a material surface treatment method,
surface-treated material, medical material, and medical instrument
of the present invention, a material with a coating of diamond-like
carbon film can be realized wherein the surface of a base material
is coated with a diamond-like carbon film, and the diamond-like
carbon film is modified with a functionality component, such as a
biocompatible component, or the like, stably for a long term.
Therefore, the present invention is useful not only as a method for
treating the surface of a material with a diamond-like carbon film
formed thereon and a surface-treated material but also as a medical
material with excellent biocompatibility and a medical instrument
formed of the medical material. Further, it is possible to give the
material a functionality other than biocompatibility. The present
invention is also useful as a material for an organic semiconductor
device, or the like.
* * * * *