阅读说明：本技术 医疗器械 (Medical instrument ) 是由 加藤智博 中村正孝 于 2018-04-19 设计创作，主要内容包括：公开了具有不易随着干燥而硬化、不易刺激与人体接触的部位的有机硅水凝胶的医疗器械。医疗器械具有满足以下条件的有机硅水凝胶。(1)含水时的含水率在10质量％以上且70质量％以下的范围内,(2)干燥时的硅原子在总质量中所占的含有率在8质量％以上且30质量％以下的范围内,(3)干燥时的拉伸弹性模量在0.1MPa以上且3.5MPa以下的范围内。(Disclosed is a medical device having a silicone hydrogel which is less likely to harden with drying and less likely to irritate a site which comes into contact with the human body. The medical device has a silicone hydrogel satisfying the following conditions. (1) A water content of 10 to 70 mass% when water is contained, (2) a content of silicon atoms in the total mass of the composition is 8 to 30 mass% when dried, and (3) a tensile elastic modulus of 0.1 to 3.5MPa when dried.)

1. A medical device having a silicone hydrogel satisfying the following conditions:

(1) a water content in the water-containing range of 10 to 70 mass%;

(2) a content ratio of silicon atoms in the total mass during drying is in a range of 8 to 30 mass%;

(3) the tensile modulus of elasticity at the time of drying is in the range of 0.1MPa or more and 3.5MPa or less.

2. The medical device according to claim 1, wherein the tensile elastic modulus is in a range of 0.1MPa or more and 1.5MPa or less.

3. The medical device according to claim 1 or 2, which has a silicone hydrogel having a dry modulus of elasticity ratio of 0.1 or more and 10 or less represented by the following formula 1,

(formula 1) dry elastic modulus ratio (tensile elastic modulus at dry time/tensile elastic modulus at water content).

4. The medical device according to any one of claims 1 to 3, wherein the silicone hydrogel has a zero-stress time when hydrated of 0.1 seconds or more and 2 seconds or less,

wherein, the zero stress time is a time when a load cell having a maximum load of 2kg is used for measuring the tensile stress, while continuously obtaining measurement values at intervals of 20 milliseconds, the operation of pulling a test piece having a width of 5mm and a thickness in the range of 0.05mm to 0.2mm at a speed of 100 mm/min to a distance of 10mm between the supporting points from a state where the test piece is held at a distance of 5mm between the supporting points and then returning to a distance of 5mm between the supporting points at the same speed was repeated 3 times, the zero stress time is a length of time from a time point when the stress is zero in the process of recovering from the 2 nd time to the time point when the distance between the fulcrums is 5mm to a time point when the stress is no longer zero after the 3 rd stretching is started, and the zero stress is a state in which the measured value is in a range of-0.05 gf to 0.05 gf.

5. The medical device according to any one of claims 1 to 4, wherein the silicone hydrogel has a tensile elongation at break in water in a range of 200% or more and 1000% or less.

6. The medical device according to any one of claims 1 to 5, wherein the silicone hydrogel has a tensile elastic modulus in water in a range of 0.1MPa or more and 1.5MPa or less.

7. The medical device of any one of claims 1 to 6, wherein the silicone hydrogel comprises repeating units (A) from monomers of formula (I),

[ chemical formula 1]

In the general formula (I), R^aRepresents hydrogen or methyl, R^bRepresents a hydrogen atom, a sulfonic acid group, a phosphoric acid group, or an organic group having 1 to 15 carbon atoms, and n represents an integer in the range of 1 to 40.

8. The medical device according to claim 7, wherein the repeating unit (A) derived from the monomer represented by the general formula (I) is contained in a range of 5% by mass or more and 50% by mass or less with respect to the total mass of the silicone hydrogel at the time of drying.

9. The medical device according to any one of claims 1 to 8, wherein the silicone hydrogel comprises a repeating unit (B) derived from a monofunctional linear silicone monomer.

10. The medical device according to claim 9, wherein the repeating unit (B) derived from the monofunctional linear silicone monomer is contained in a range of 20 mass% or more and 70 mass% or less with respect to the total mass of the silicone hydrogel at the time of drying.

11. The medical device of any one of claims 1 to 10, wherein the silicone hydrogel comprises repeating units (C) from a monomer comprising an amide structure.

12. The medical device according to claim 11, wherein the repeating unit (C) derived from the amide structure-containing monomer is contained in a range of 5% by mass or more and 50% by mass or less with respect to the total mass of the silicone hydrogel at the time of drying.

13. The medical device according to claim 11 or 12, wherein at least either of the repeating unit (a) derived from the monomer represented by the general formula (I) and the repeating unit (C) derived from the monomer having an amide structure has a glass transition temperature of 20 ℃ or lower when formed into a homopolymer.

14. The medical device according to any one of claims 1 to 13, which is any one of the group consisting of an ophthalmic lens, an endoscope, a catheter, an infusion tube, a gas delivery tube, a stent, a sheath, a cuff, a tube fitting, an access port, a drainage bag, a blood circuit, a wound dressing, and various drug carriers.

15. The medical device of any one of claims 1-14, which is a contact lens.

16. The medical device according to any one of claims 1 to 15, wherein the silicone hydrogel is a polymer comprising a repeating unit (A) derived from a monomer represented by general formula (I), a repeating unit (B) derived from a monomer represented by general formula (a), and a repeating unit (C) derived from a monomer represented by general formula (II-1) or general formula (II-2),

[ chemical formula 2]

In the general formula (I), R^aRepresents hydrogen or methyl, R^bRepresents a hydrogen atom, a sulfonic acid group, a phosphoric acid group, or an organic group having 1 to 15 carbon atoms, n represents an integer in the range of 1 to 40,

[ chemical formula 3]

In the general formula (a), R¹Represents a hydrogen atom or a methyl group, R²Represents a C1-20 2-valent organic group, R³～R⁶Each independently represents an optionally substituted alkyl group having 1 to 20 carbon atoms or an optionally substituted aryl group having 6 to 20 carbon atoms, R⁷Represents an optionally substituted alkyl group having 1 to 20 carbon atoms or an optionally substituted alkyl groupA substituted aryl group having 6 to 20 carbon atoms, k represents an integer of 1 to 200,

[ chemical formula 4]

[ chemical formula 5]

In the general formula (II-1) and the general formula (II-2), R⁸And R¹¹Each independently represents a hydrogen atom or a methyl group, R⁹And R¹⁰And R¹²And R¹³Represents a hydrogen atom or an alkyl group having 1 to 20 carbon atoms which may be branched or linear or may contain a cyclic structure and which may be substituted, R¹²And R¹³The rings may be formed with each other via a bond.

17. The medical device according to claim 16, wherein the repeating unit (a) is contained in a range of 5% by mass or more and 50% by mass or less with respect to the total mass of the silicone hydrogel at the time of drying, the repeating unit (B) is contained in a range of 20% by mass or more and 70% by mass or less with respect to the total mass of the silicone hydrogel at the time of drying, and the repeating unit (C) is contained in a range of 5% by mass or more and 50% by mass or less with respect to the total mass of the silicone hydrogel at the time of drying, wherein the total of the repeating units (a), (B), and (C) is not more than 100% by mass with respect to the total mass of the silicone hydrogel at the time of drying.

18. The medical device according to claim 17, wherein the total of the repeating units (a), (B) and (C) exceeds 50 mass% with respect to the total mass of the silicone hydrogel when dried.

Technical Field

The present invention relates to a medical device, and particularly to a medical device using a silicone hydrogel.

Background

Medical devices that come into direct contact with a part of the human body are well known and require soft raw materials that pose a low risk of injury to the human body. Particularly, a hydrogen-containing material having excellent flexibility such as hydrogel is suitable for a medical device which is in contact with a wet site such as mucosa. Examples of the medical device include an ophthalmic lens, an endoscope, and a catheter. In all of the medical devices that come into contact with a wet site such as a mucous membrane, for example, in the case of an ophthalmic lens, a soft contact lens is exemplified as another embodiment.

As a raw material for soft contact lenses, silicone hydrogels are known. The silicone hydrogel is obtained by combining at least 1 silicone component and at least 1 hydrophilic component.

For example, patent documents 1 to 8 disclose methods for producing silicone hydrogels that can be used in ophthalmic lenses.

On the other hand, most users of contact lenses experience discomfort associated with the feeling of dryness when wearing the lenses. The discomfort may impair eye health, and may also cause symptoms such as dry eye when deteriorated. Therefore, it is desired to develop a contact lens material which is less likely to impair eye health, in which discomfort associated with dry feeling is suppressed.

In addition, it is important that the contact lens which does not impair eye health has sufficient surface water wettability and oxygen permeability and has a surface to which dirt derived from living organisms such as proteins and lipids is not easily attached, and a raw material satisfying these properties in a well-balanced manner is required.

Disclosure of Invention

Problems to be solved by the invention

In medical devices that come into contact with a part of the human body, it is important to suppress the hardening associated with drying, and in general, hydrogel materials are often hardened and weakened as they dry. In addition, medical devices that come into contact with the eyeball, skin, and the like, particularly with a movable part of the human body, for a long time have a problem that flexibility is impaired over time and cannot withstand long-term use.

As an example of the above-described problems, there is a feeling of discomfort due to a dry feeling of a contact lens. One of the causes of the dry feeling and the uncomfortable feeling of the contact lens is eyeball irritation caused by hardening of a lens material which gradually dries. In general, hydrophilic monomers used for forming a silicone hydrogel often have polar groups and many interactions, and thus polymer chains tend to aggregate with dehydration of the gel and to be easily hardened. When the hardening is caused by drying, a part in contact with a human body is stimulated, and in some cases, adverse effects such as damage to a contact part such as a mucous membrane may be caused.

Patent document 1 describes a method for producing a hard contact lens using a branched silicone monomer, but the following problems are present in the raw material having such a composition: the water-repellent fabric has a hard and hardly water-permeable property, and thus is poor in wearing comfort, and has a surface with strong hydrophobicity, so that adsorption of molecules derived from a living body is likely to occur on the surface.

Patent documents 2 to 5 describe a method for producing a contact lens using a silicone hydrogel, but the method requires the preparation of a silicone macromer having a urethane bond, which is industrially disadvantageous. Further, since a branched silicone monomer is used, shape recovery is poor, and for example, when a hydrophilic monomer such as N-vinylpyrrolidone is contained in a large amount, the hydrophilic monomer has a high tensile elastic modulus even in a hydrous state, and may harden with drying to irritate the eyeball.

Patent documents 6 and 7 describe a method for producing a contact lens using a silicone hydrogel, but since a hydrophilic polymer such as polyvinylpyrrolidone is contained as an internal wetting agent, cloudiness is likely to occur, and it is difficult to obtain a balance in composition. In addition, the resin composition has a high tensile elastic modulus even in a hydrated state, and may harden with drying to irritate the eyeball.

Patent document 8 describes a method of obtaining a silicone hydrogel having uniform mechanical properties by unifying polymerizable functional groups of monomers used for copolymerization, but the method uses a branched silicone monomer, and therefore, the silicone hydrogel has poor shape recovery properties, and also has excellent transparency because of large interaction between functional groups, but on the other hand, the silicone hydrogel has a low water content, has a high tensile elastic modulus even in a water-containing state, and may be hardened and irritated by drying.

In general, when the water content is reduced, hardening associated with drying is easily suppressed, but when the water content is reduced, the water wettability is reduced, that is, biocompatibility is impaired, which is not preferable. On the other hand, when the water content is high, the oxygen permeability is impaired although the water wettability is excellent, which is not preferable. In addition, in order to obtain a balance between oxygen permeability and water content, compatibility between the silicone monomer and the hydrophilic monomer is important, but when the interaction between the monomers is used to obtain compatibility, transparency and shape recovery properties may be reduced, and adjustment may be difficult in some cases. It is sometimes difficult to obtain a raw material that satisfies these desired physical properties in a well-balanced manner.

From the above, it is significant to develop a material which is a silicone hydrogel having an appropriate tensile elastic modulus in a hydrated state and excellent in transparency and shape-recovering properties, is less likely to harden with drying, and is less likely to irritate the eyeball.

Further, it is preferable that the material which does not easily irritate the eyeball is a material which has excellent oxygen permeability and is less likely to cause adhesion of molecules derived from living organisms such as proteins and lipids, since eye health is not impaired. Further, it is industrially advantageous, and more preferable, if the above-mentioned raw material can be obtained without producing a special and complicated macromer or the like.

The above-described material is suitable not only for ophthalmic lenses but also for various medical devices represented by endoscopes, catheters, infusion tubes, gas delivery tubes, stents, sheaths, cuffs, tube connectors, access ports, drainage bags, blood circuits, wound dressings, and various drug carriers.

Accordingly, an object of the present invention is to provide a medical device having a silicone hydrogel which is less likely to harden with drying and less likely to irritate a portion which comes into contact with a human body.

Means for solving the problems

The inventors of the present application have made intensive studies to achieve the above object and found that a medical device containing a silicone hydrogel having the following composition is useful.

[1] A medical device having a silicone hydrogel satisfying the following conditions:

(1) a water content in the water-containing range of 10 to 70 mass%;

(2) a content ratio of silicon atoms in the total mass during drying is in a range of 8 to 30 mass%;

(3) the tensile modulus of elasticity at the time of drying is in the range of 0.1MPa or more and 3.5MPa or less.

[2] The medical device according to [1], wherein the tensile elastic modulus is in a range of 0.1MPa or more and 1.5MPa or less.

[3] The medical device according to [1] or [2], which comprises a silicone hydrogel having a dry modulus of elasticity ratio of 1 or more and 10 or less represented by the following formula 1.

(formula 1) Dry modulus of elasticity ratio (tensile modulus of elasticity in dry/tensile modulus of elasticity in Water-containing State)

[4] The medical device according to any one of [1] to [3], wherein the silicone hydrogel has a zero-stress time of 0.1 to 2 seconds in a hydrated state,

wherein, the zero stress time is a time when a load cell having a maximum load of 2kg is used for measuring the tensile stress, while continuously obtaining measurement values at intervals of 20 milliseconds, the operation of pulling a test piece having a width of 5mm and a thickness in the range of 0.05mm to 0.2mm at a speed of 100 mm/min to a distance of 10mm between the supporting points from a state where the test piece is held at a distance of 5mm between the supporting points and then returning to a distance of 5mm between the supporting points at the same speed was repeated 3 times, the zero stress time is a length of time from a time point when the stress is zero in the process of recovering from the 2 nd time to the time point when the distance between the fulcrums is 5mm to a time point when the stress is no longer zero after the 3 rd stretching is started, and the zero stress is a state in which the measured value is in a range of-0.05 gf to 0.05 gf.

[5] The medical device according to any one of [1] to [4], wherein the silicone hydrogel has a tensile elongation at break in water in the range of 200% to 1000%.

[6] The medical device according to any one of [1] to [5], wherein the silicone hydrogel has a tensile elastic modulus in water of 0.1MPa or more and 1.5MPa or less.

[7] The medical device according to any one of [1] to [6], wherein the silicone hydrogel comprises a repeating unit (A) derived from a monomer represented by the general formula (I),

[ chemical formula 1]

In the general formula (I), R^aRepresents hydrogen or methyl, R^bRepresents a hydrogen atom, a sulfonic acid group, a phosphoric acid group, or an organic group having 1 to 15 carbon atoms, and n represents an integer in the range of 1 to 40.

[8] The medical device according to [7], wherein the repeating unit (A) derived from the monomer represented by the general formula (I) is contained in a range of 5% by mass or more and 50% by mass or less with respect to the total mass of the silicone hydrogel at the time of drying.

[9] The medical device according to any one of [1] to [8], wherein the silicone hydrogel contains a repeating unit (B) derived from a monofunctional linear silicone monomer.

[10] The medical device according to item [9], wherein the repeating unit (B) derived from the monofunctional linear silicone monomer is contained in a range of 20 to 70 mass% based on the total mass of the silicone hydrogel at the time of drying.

[11] The medical device according to any one of [1] to [10], wherein the silicone hydrogel contains a repeating unit (C) derived from a monomer having an amide structure.

[12] The medical device according to [11], wherein the repeating unit (C) derived from the amide structure-containing monomer is contained in a range of 5% by mass or more and 50% by mass or less with respect to the total mass of the silicone hydrogel at the time of drying.

[13] The medical device according to [11] or [12], wherein at least one of the repeating unit (A) derived from the monomer represented by the general formula (I) and the repeating unit (C) derived from the monomer having an amide structure has a glass transition temperature of 20 ℃ or lower when formed into a homopolymer.

[14] The medical device according to any one of [1] to [13], which is any one of the group consisting of an ophthalmic lens, an endoscope, a catheter, an infusion tube, a gas delivery tube, a stent, a sheath, a cuff, a tube joint, an access port, a drainage bag, a blood circuit, a wound dressing, and various drug carriers.

[15] The medical device according to any one of [1] to [14], which is a contact lens.

[16] The medical device according to any one of [1] to [15], wherein the silicone hydrogel is a polymer comprising a repeating unit (A) derived from a monomer represented by general formula (I), a repeating unit (B) derived from a monomer represented by general formula (a), and a repeating unit (C) derived from a monomer represented by general formula (II-1) or general formula (II-2).

[ chemical formula 2]

In the general formula (I), R^aRepresents hydrogen or methyl, R^bRepresents a hydrogen atom, a sulfonic acid group, a phosphoric acid group, or an organic group having 1 to 15 carbon atoms, n represents an integer in the range of 1 to 40,

[ chemical formula 3]

In the general formula (a), R¹Represents a hydrogen atom or a methyl group, R²Represents a C1-20 2-valent organic group, R³～R⁶Each independently represents an optionally substituted alkyl group having 1 to 20 carbon atoms or an optionally substituted aryl group having 6 to 20 carbon atoms, R⁷Represents an alkyl group having 1 to 20 carbon atoms or an aryl group having 6 to 20 carbon atoms, k represents an integer of 1 to 200 which may have a distribution,

[ chemical formula 4]

[ chemical formula 5]

In the general formula (II-1) and the general formula (II-2), R⁸And R¹¹Each independently represents a hydrogen atom or a methyl group, R⁹And R¹⁰And R¹²And R¹³Represents a hydrogen atom or an alkyl group having 1 to 20 carbon atoms which may be branched or linear or may contain a cyclic structure and which may be substituted, R¹²And R¹³The rings may be formed with each other via a bond.

[17] The medical device according to [16], wherein the repeating unit (A) is contained in a range of 5 to 50 mass% based on the total mass of the silicone hydrogel at the time of drying, the repeating unit (B) is contained in a range of 20 to 70 mass% based on the total mass of the silicone hydrogel at the time of drying, and the repeating unit (C) is contained in a range of 5 to 50 mass% based on the total mass of the silicone hydrogel at the time of drying, wherein the total of the repeating units (A), (B), and (C) is not more than 100 mass% based on the total mass of the silicone hydrogel at the time of drying.

[18] The medical device according to [17], wherein the total of the repeating units (A), (B) and (C) is more than 50% by mass based on the total mass of the silicone hydrogel at the time of drying.

ADVANTAGEOUS EFFECTS OF INVENTION

According to the present invention, a medical device having a silicone hydrogel which is less likely to harden with drying and less likely to irritate a human body, particularly a wet part such as a mucous membrane, can be obtained.

Detailed Description

In the present invention, the term "water-containing" means a state in which the silicone hydrogel is immersed in a boric acid buffer solution at room temperature (25 ℃) for 24 hours or more. The measurement of the physical property values with water was carried out by taking out the test piece from the boric acid buffer, wiping off the boric acid buffer on the surface with a clean cloth within 10 seconds at room temperature of 20 ℃ and humidity of 50%, and then carrying out the measurement at room temperature of 20 ℃ and humidity of 50% within 1 minute.

In the present invention, the term "drying" means a state in which the silicone hydrogel in a hydrated state is dried in a vacuum dryer at 40 ℃ for 16 hours or more. The measurement of the physical property values in the dry state was carried out under the conditions of room temperature 20 ℃ and humidity 50% within 5 minutes after the test piece was taken out from the drying apparatus.

In the present invention, the water content is a value calculated by measuring the mass of the silicone hydrogel when it is hydrated (W1) and when it is dried (W2) and using the following equation.

Water content (%) - (W1-W2)/W1X 100

The silicone hydrogel used in the present invention has a water content in the range of 10 mass% or more and 70 mass% or less when hydrated. When the water content is 10% by mass or more, the possibility of deterioration of biocompatibility is small, and when the water content is 20% by mass or more, adsorption of proteins and lipids is less likely to occur, and in the case of a contact lens, adhesion to the cornea is less likely to occur, and therefore, the possibility of adverse effects on eye health is small. On the other hand, if the water content is 70 mass% or less, the possibility of deterioration of oxygen permeability is small, and if it is 50 mass% or less, the shape change accompanying drying is small, and therefore the possibility of irritation to a part of a human body such as an eyeball is small. The lower limit is preferably 10% by mass, more preferably 20% by mass, still more preferably 25% by mass, and still more preferably 30% by mass. The upper limit is preferably 70% by mass, more preferably 60% by mass, still more preferably 50% by mass, and yet more preferably 45% by mass. The upper and lower limits may be arbitrarily combined.

In the present invention, the content of silicon atoms in the total mass of the silicone hydrogel during drying is a value calculated by the following formula.

The content (%) of silicon atoms in the total mass of the silicone hydrogel during drying ∑ Si { (Si ∑ Si [)_m×C_m}×100

Here, Si_mIs the mass ratio of silicon atoms to the molecular weight of the silicone monomer used in the formation of the silicone hydrogel. C_mDenotes the dry mass of the silicone monomer relative to the silicone hydrogelMass ratio of the amounts. When a plurality of organosilicon monomers are present, Si is determined for each component_mIs multiplied by C_mAnd the sum thereof is determined. In the present specification, the content ratio of silicon atoms in the total mass of the silicone hydrogel during drying may be referred to as the silicon atom content ratio during drying.

As an example, a silicone hydrogel which will contain 3- [ tris (trimethylsiloxy) silyl group will be described]25% by mass of propyl methacrylate (abbreviated as TRIS), 24% by mass of 3- (trimethoxysilyl) propyl methacrylate (abbreviated as TMSM), 49% by mass of N, N-dimethylacrylamide and 2% by mass of ethylene glycol dimethacrylate. For TRIS, since it has 4 silicon atoms at a molecular weight of 422.82, Si can be calculated when the mass of the silicon atoms is 28.09(g/mol)_m，TRIS28.09 × 4/422.82 ≈ 0.266. For TMSM, it has 1 silicon atom at molecular weight 248.35, and thus can be calculated as Si_m，_TMSM28.09 × 1/248.35 ≈ 0.113. Therefore, the silicon atom content (%) of the silicone hydrogel can be calculated as (0.266 × 0.25+0.113 × 0.24) × 100 ═ 9.842.

The content of silicon atoms in the total mass of the silicone hydrogel at the time of drying can be measured by ICP emission spectrometry. Specifically, the measurement was performed according to the following procedure. A sample was washed with reverse osmosis water to remove salts and dirt, and the dried sample (4 to 5mg) was put into a platinum crucible, added with sulfuric acid, and heated and ashed with a hot plate and a burner. And (3) melting the ashes by using sodium carbonate, adding water, heating and dissolving, adding nitric acid, and performing constant volume by using water. The amount of Si element in this solution was measured by ICP emission spectrometry to determine the content in the sample.

The content of silicon atoms in the total mass of the silicone hydrogel used in the present invention during drying is in the range of 8 mass% to 30 mass%. When the content is 8% by mass or more, the possibility that oxygen permeability cannot be sufficiently obtained is reduced, and when the content is 30% by mass or less, the hydrophobicity is too high, the water wettability is reduced, the possibility that biocompatibility is deteriorated is small, and the possibility that tensile elastic modulus is increased and hardening is small. The lower limit is preferably 8% by mass, more preferably 10% by mass, still more preferably 12% by mass, and still more preferably 15% by mass. The upper limit value is preferably 30% by mass, more preferably 28% by mass, still more preferably 25% by mass, and still more preferably 22% by mass. The upper and lower limits may be arbitrarily combined.

The silicone hydrogel used in the present invention preferably has a particle size of 30X 10 from the viewpoint of being less harmful to eye health^-11(cm²Second) mLO₂/(mL. hPa) or more, preferably has an oxygen transmission coefficient of 40X 10^-11(cm²Second) mLO₂An oxygen permeability coefficient of 50X 10 is more preferable^-11(cm²Second) mLO₂/(. mL. hPa) or more. Further preferably 70X 10^-11(cm²Second) mLO₂An oxygen permeability coefficient of not less than/(mL. hPa), more preferably 90X 10^-11(cm²Second) mLO₂/(. mL. hPa) or more. The silicone hydrogel having such oxygen permeability does not inhibit gas exchange with the skin or the like, and therefore can be suitably used as a medical device such as a wound dressing. The upper limit of the oxygen permeability coefficient is not particularly limited, and the upper limit is actually 200X 10^-11(cm²Second) mLO₂about/("mL. hPa), the upper limit value of more practical use is 150X 10^-11(cm²Second) mLO₂And/(. mL. hPa).

The oxygen permeability coefficient of the silicone hydrogel used in the present invention is a value measured by an electrode-method membrane oxygen permeability measuring instrument.

In the present invention, the term "water wettability" refers to the length of time that a surface liquid film is held. The silicone hydrogel used in the present invention is important to have excellent surface water wettability from the viewpoint of biocompatibility, and preferably has a long liquid film retention time on the surface of the silicone hydrogel. Here, the liquid film holding time is a time during which, when the silicone hydrogel immersed in the boric acid buffer solution is lifted from the liquid and held in the air so that the surface (diameter direction in the case of an ophthalmic lens) is vertical, the liquid film on the surface of the silicone hydrogel is held without interruption. The liquid film holding time is preferably 10 seconds or more, more preferably 15 seconds or more, further preferably 20 seconds or more, further more preferably 30 seconds or more. Here, the diameter refers to the diameter of a circle formed by the edge of the ophthalmic lens. The liquid film holding time was measured using a sample in a wet state with a boric acid buffer, that is, in a state containing water. The upper limit of the liquid film holding time is not particularly limited, and the upper limit is actually about 100 seconds.

The silicone hydrogel used in the present invention is preferably 6mm or more and 25mm or less in diameter from the viewpoint of being suitably used for an ophthalmic lens, and particularly, when used as a soft contact lens, is more preferably a spherical cap shape having a diameter of 10mm or more and 17mm or less, and further preferably a spherical cap shape having a diameter of 13mm or more and 15mm or less. The lower limit value is preferably 6mm, more preferably 10mm, and still more preferably 13 mm. The upper limit value is preferably 25mm, more preferably 17mm, and still more preferably 15 mm. The upper and lower limits may be arbitrarily combined.

The silicone hydrogel used in the present invention has a tensile modulus of elasticity in drying of 0.1MPa or more and 3.5MPa or less. When the tensile elastic modulus during drying is 0.1MPa or more, sufficient followability is easily obtained, and when the tensile elastic modulus is 3.5MPa or less, the spherical cap shape is easily maintained, and when the tensile elastic modulus is 3.1 MPa or less, a part of a human body such as an eyeball is stimulated with drying, and thus the wearing feeling is deteriorated and the possibility of damage is low. The lower limit is preferably 0.35MPa, more preferably 0.4MPa, still more preferably 0.55MPa, still more preferably 0.7MPa, and yet more preferably 0.8 MPa. The upper limit is preferably 3.5MPa, more preferably 2.8MPa, still more preferably 2.4MPa, still more preferably 2MPa, still more preferably 1.7MPa, and still more preferably 1.5 MPa. The upper and lower limits may be arbitrarily combined.

The tensile modulus during drying can be measured using a tensile tester such as Tensilon within 5 minutes after being taken out from a dryer under conditions of room temperature 20 ℃ and humidity 50% in a dried state.

The silicone hydrogel used in the present invention is preferably excellent in shape-recovery properties. The shape-recovering property in the present invention means a time required for the silicone hydrogel to recover to its original shape after a certain deformation is imparted thereto. The faster the recovery to the original shape, the better the shape-recovering property, and the slower the recovery to the original shape, the lower the shape-recovering property. In the case of a raw material having poor shape recovery properties, particularly when used as a soft contact lens, there are cases where: the shape recovery of the lens deformed by friction with the eyelid during blinking causes a delay, resulting in deterioration of wearing comfort. The shape recovery properties of the present invention can be evaluated by measuring the zero stress time of the silicone hydrogel when it is hydrated.

The term "zero stress time when water is contained" as used herein means that a load cell having a maximum load of 2kg is used for measuring tensile stress, repeating 3 times while continuously obtaining measurement values at intervals of 20 milliseconds, an operation of pulling a test piece of a silicone hydrogel when water is contained having a width of 5mm and a thickness in a range of 0.05mm to 0.2mm at a speed of 100 mm/min until the distance between the supporting points is 10mm from a state (state A) in which the test piece is held at a distance between the supporting points of 5mm, and then returning to the distance between the supporting points of 5mm at the same speed, the zero stress time is a length of time from a time point when the stress is zero in the process of recovering from the 2 nd time to the time point when the distance between the fulcrums is 5mm to a time point when the stress is no longer zero after the 3 rd stretching is started, and the zero stress is a state in which the measured value is in a range of-0.05 gf to 0.05 gf. In state a, the test piece is held so that the test piece is not relaxed as much as possible and the stress becomes zero.

The zero stress time of the silicone hydrogel used in the present invention when it is hydrated is preferably in the range of 0.1 seconds or more and 2 seconds or less. When the zero stress time is 0.1 seconds or more, the flexibility is not deteriorated, and when the zero stress time is 2 seconds or less, the shape-recovering property is not deteriorated, and particularly in the case of a contact lens, the zero stress time does not cause a feeling of discomfort at the time of wearing. The lower limit value is preferably 0.1 second, more preferably 0.2 second, further preferably 0.5 second, and further more preferably 0.7 second. The upper limit value is preferably 2 seconds, more preferably 1.8 seconds, further preferably 1.6 seconds, further more preferably 1.5 seconds, and further particularly preferably 1.0 second. The upper and lower limits may be arbitrarily combined.

The zero stress time when hydrated is obtained by: after the test piece was taken out from the boric acid buffer solution, the boric acid buffer solution on the surface was gently wiped off with a clean cloth at room temperature of 20 ℃ and humidity of 50% within 10 seconds, and then the test piece was set on a mechanical property tester such as a rheometer (product name, SUN SCIENTIFIC co., LTD.) at room temperature of 20 ℃ and humidity of 50% within 1 minute to measure.

The silicone hydrogels used in the present invention are more suitable for use in ophthalmic lenses among medical devices. In this case, the thickness of the spherical crown-shaped central portion of the silicone hydrogel used in the present invention is preferably 0.02mm or more and 1mm or less, and particularly when used as a soft contact lens, the spherical crown shape is more preferably 0.05mm or more and 0.5mm or less, and still more preferably 0.06mm or more and 0.2mm or less in diameter. The lower limit is preferably 0.04mm, more preferably 0.05mm, and still more preferably 0.07 mm. The upper limit value is preferably 0.2mm, more preferably 0.18mm, and still more preferably 0.15 mm. The upper and lower limits may be arbitrarily combined.

The silicone hydrogels used in the present invention are preferably non-tearable when hydrated. The material which is not easily torn is excellent in handling properties during scrubbing and removal, and is therefore important for applications such as soft contact lenses. The tearability in the presence of water can be evaluated by measuring the tensile elongation at break in the presence of water.

The silicone hydrogel used in the present invention preferably has a tensile elongation at break in the presence of water in the range of 200% to 1000%. When the tensile elongation at break in water is 200% or more, flexibility is preferable because it does not cause a feeling of discomfort when worn and handling property when scrubbed or removed is excellent. On the other hand, it is preferable that the tensile elongation at break in the presence of water is 1000% or less because the shape recovery is excellent. The lower limit value is preferably 200%, more preferably 220%, still more preferably 230%, still more preferably 250%. The upper limit is preferably 1000%, more preferably 800%, still more preferably 600%, and still more preferably 500%. The upper and lower limits may be arbitrarily combined.

The silicone hydrogel used in the present invention preferably has flexibility that does not irritate the eyeball while worn. The flexibility can be evaluated by measuring the tensile modulus of elasticity in water.

The silicone hydrogel used in the present invention preferably has a tensile modulus of elasticity in water of 0.1MPa or more and 1.5MPa or less. When the tensile elastic modulus in water is o.1mpa or more, the spherical cap shape of the contact lens can be maintained, and when it is 1.5MPa or less, the possibility of deterioration of wearing feeling due to irritation of the eyeball from the time of wearing is reduced. The lower limit is preferably 0.1MPa or more, more preferably 0.25MPa, still more preferably 0.35MPa, yet more preferably 0.4MPa, and particularly preferably 0.48 MPa. The upper limit is preferably 1.5MPa, more preferably 1.4MPa, still more preferably 1.2MPa, and still more preferably 1 MPa. The upper and lower limits may be arbitrarily combined.

The tensile elongation at break in water and the tensile elastic modulus in water can be measured by taking out a test piece from a boric acid buffer, wiping off the boric acid buffer on the surface with a clean cloth at room temperature of 20 ℃ and humidity of 50% within 10 seconds, and then measuring the tensile elongation at break in water and the tensile elastic modulus in water using a tensile tester such as Tensilon at room temperature of 20 ℃ and humidity of 50% within 1 minute.

The silicone hydrogel used in the present invention preferably has a small change in tensile elastic modulus due to hardening with drying. That is, the tensile elastic modulus in the water-containing state is preferably within the above-described preferred range and the change in tensile elastic modulus before and after drying is small. From the viewpoint of having flexibility that is less likely to damage the human body, the dry elastic modulus ratio represented by the following formula 1 is preferably 0.1 or more and 10 or less.

(formula 1) Dry modulus of elasticity ratio (tensile modulus of elasticity in dry/tensile modulus of elasticity in Water-containing State)

The lower limit value is preferably 0.1, more preferably 0.5, still more preferably 1, still more preferably 1.2, and particularly preferably 1.5. The upper limit is preferably 10, more preferably 7, still more preferably 5, still more preferably 3, and particularly preferably 2.5. The upper and lower limits may be arbitrarily combined.

The term (methyl) as used in the present specification denotes optional methyl substitution. Thus, for example, the term "(meth) acrylate" refers to both methacrylate and acrylate. The same applies to the terms "(meth) acrylamide", "(meth) acryloyl group", and the like.

The term "meth (acrylate)" used in the present specification means (meth) acrylate.

The term "monomer" used in the present specification means a compound having 1 or more radical polymerizable functional groups.

The term "monomer composition" as used herein refers to a mixture of a radically polymerizable monomer, a polymerization initiator, a solvent, and the like before polymerization.

The term "repeating unit" used in the present specification means a unit derived from a repeating structure of a monomer structure.

Here, the "repeating unit derived from a monomer" in the present invention will be explained. In the present invention, the "repeating unit derived from a monomer" refers to a structural unit in a polymer corresponding to the structure of a radically polymerizable functional group generated by a polymerization reaction when the radically polymerizable monomer is polymerized. That is, the "repeating unit derived from a monomer" means a structural unit represented by the following formula (v) which is generated by a radical polymerizable functional group being changed by a polymerization reaction when a radical polymerizable monomer represented by the following formula (x) is polymerized.

[ chemical formula 6]

In the above formulae (x) and (y), R^w、R^x、R^y、R^zEach independently may be a group of a monomer having radical polymerizability, which is represented by the formula (x).

The silicone hydrogel used in the present invention preferably contains repeating units (a) derived from a monomer represented by the general formula (I).

[ chemical formula 7]

In the general formula (I), R^aRepresents a hydrogen atom or a methyl group, R^bRepresents 1 selected from the group consisting of a hydrogen atom, a sulfonic acid group, a phosphoric acid group, and an organic group having 1 to 15 carbon atoms. n represents an integer in the range of 1 to 40.

The silicone hydrogel used in the present invention may contain a substance having a distribution within the aforementioned range of n with respect to the repeating unit (a) derived from the monomer represented by the general formula (I).

The repeating unit (a) is hydrophilic but does not have a functional group capable of forming a hydrogen bond with each other, and therefore, the repeating unit (a) is preferably used because the interaction between the functional groups by the hydrogen bond is small and the repeating unit (a) has a property of being hard to harden when dried. In particular, the structure having a (poly) ethylene glycol chain is useful because it has a high effect of lowering the elastic modulus during drying. Since the glass transition temperature of the repeating unit (a) when it forms a homopolymer is not higher than room temperature, the tensile modulus of elasticity during drying can be suppressed to be low.

For R in the formula (I)^aFrom the viewpoint of excellent polymerizability and easy availability, a hydrogen atom or a methyl group is preferable, and from the viewpoint of a tendency to impart a low tensile elastic modulus, a hydrogen atom is more preferable.

N in the general formula (I) is preferably an integer in the range of 1 to 40. When n is 40 or less, the following is less likely to occur: cloudiness occurs due to poor compatibility with other monomers, and the silicone hydrogel is liable to tear due to a decrease in the crosslinking density of the entire silicone hydrogel. The upper limit value of n is preferably 40, more preferably 25, still more preferably 12, and still more preferably 10.

n may have a distribution. In the present invention, the term "having a distribution" means that the number of repetitions of a certain structural unit (n in this case) is not limited to 1 value, but is a state in which a plurality of values of substances are mixed. When n has a distribution, n is determined based on the number average molecular weight of the monomer represented by the general formula (I).

R in the general formula (I)^bAny of hydrogen atoms, sulfonic acid groups, phosphoric acid groups, and organic groups having 1 to 15 carbon atoms can be used. R is not likely to cause interaction such as hydrogen bonding and pi-pi stacking, and is not likely to increase the tensile elastic modulus during drying^bThe alkyl group has preferably 1 to 15 carbon atoms, more preferably any one structure of ethylhexyl, butyl, propyl, ethyl and methyl, even more preferably any one structure of propyl, ethyl and methyl, and even more preferably ethyl or methyl.

R^bThe structure of (b) may have a cyclic structure such as a furfuryl group or a crown ether group.

R^aIn the case of a hydrogen atom, R^bThe structure of (2) may have 1 aromatic ring, and for example, a group derived from 2-phenoxyethyl acrylate, 2- (2-phenoxyethoxy) ethyl acrylate, or the like can be used. Here, the "group derived from … …" refers to a group corresponding to the structure of a radical polymerizable functional group generated by a polymerization reaction when the radical polymerizable monomer is bonded, similarly to the "repeating unit derived from … …" described above.

R^bThe structure of (2) may have a fluorine-substituted alkyl group, and for example, a group derived from 2- (2, 2, 2-trifluoroethoxy) ethyl acrylate, 2- (2, 2, 3, 3, 4, 4, -heptafluorobutoxy) ethyl acrylate, or the like can be used.

To improve the water wettability of the silicone hydrogels, R^bA structure having a sulfonic acid group or a phosphoric acid group can be used. Further, an organic acid structure such as a carboxyl group may be contained.

The monomers represented by the general formula (I) may be used alone or in combination of two or more.

The silicone hydrogel used in the present invention preferably contains the repeating unit (a) in a range of 5 mass% to 50 mass% with respect to the total mass of the silicone hydrogel at the time of drying. When the content of the repeating unit (A) is 5% by mass or more, the elastic modulus does not become too high during drying, and when the content is 50% by mass or less, the oxygen permeability is not insufficient. The lower limit is preferably 5% by mass, more preferably 7% by mass, still more preferably 10% by mass, and still more preferably 12% by mass. The upper limit is preferably 50% by mass, more preferably 45% by mass, still more preferably 40% by mass, and still more preferably 35% by mass. The upper and lower limits may be arbitrarily combined.

In the present invention, the silicone monomer means a monomer containing a polymerizable group and a siloxane group. Siloxane groups refer to groups having at least 1 Si-O-Si bond. For the silicone hydrogel used in the present invention, silicone (meth) acrylate or silicone (meth) acrylamide may be preferably used as the silicone monomer. From the viewpoint of relatively easy availability, silicone (meth) acrylates are preferably used.

In the present invention, the silicone (meth) acrylate refers to a monomer containing a (meth) acryloyloxy group and a siloxane group. Silicone (meth) acrylamide refers to a monomer that contains a (meth) acrylamide group and a siloxane group.

In the present invention, monofunctional means having only 1 radical polymerizable functional group [ e.g., (meth) acryloyloxy ] in the molecule.

The linear silicone in the monofunctional linear silicone monomer of the present invention means a structure in which when a line is drawn along a siloxane bond (a bond formed by repeating a group of — Si — O-) of the silicone, the line forms 1 linear without branching, with a silicon atom bonded to an organic group having a (meth) acryloyloxy group or a (meth) acrylamide group as a starting point. In other words, the monofunctional linear silicone monomer means a structure represented by the following general formula (p).

[ chemical formula 8]

In the formula (p), R^pRepresents an alkyl group having a (meth) acryloyloxy group or a (meth) acrylamide group. R^c～RⁱRepresents a group containing no silicon atom, and j represents an integer of 1 or more.

In the present invention, the branched silicone monomer refers to a structure in which, when a line is drawn along a siloxane bond with a silicon atom bonded to an organic group having a (meth) acryloyloxy group or a (meth) acrylamide group as a starting point, the line extends in two or more directions, and/or a structure in which the line has at least one branch and cannot be represented by 1 line. As a typical example of the branched silicone monomer, 3- [ TRIS (trimethylsiloxy) silyl ] propyl methacrylate (abbreviated as TRIS) is known. The branched silicone monomer may have poor shape recovery properties, may provide a higher elastic modulus than the linear silicone monomer, and may cause cloudiness due to compatibility problems.

The silicone hydrogel used in the present invention preferably contains a repeating unit (B) derived from a monofunctional linear silicone monomer.

The inclusion of the repeating unit (B) is preferable for imparting excellent oxygen permeability. In addition, it is important to impart excellent flexibility and mechanical properties that are not easily torn and flexible.

The silicone hydrogel used in the present invention preferably contains the repeating unit (B) derived from the monofunctional linear silicone monomer in a range of 20 to 70 mass% based on the total mass of the silicone hydrogel at the time of drying. When the repeating unit (B) is 20 mass% or more, sufficient oxygen permeability can be obtained, and when it is 70 mass% or less, water wettability is lowered and hydrophobicity is enhanced, so that it is possible to suppress the adhesion of protein and lipid from easily occurring. The lower limit is preferably 20% by mass, more preferably 25% by mass, still more preferably 30% by mass, and still more preferably 35% by mass. The upper limit is preferably 70% by mass, more preferably 65% by mass, still more preferably 60% by mass, and still more preferably 55% by mass. The upper and lower limits may be arbitrarily combined.

For the monofunctional linear silicone monomer used in the silicone hydrogel used in the present invention, silicone (meth) acrylate is preferably used. Examples thereof include monomers represented by the following general formula (a).

[ chemical formula 9]

In the general formula (a), R¹Represents a hydrogen atom or a methyl group. R²Represents a C1-20 2-valent organic group. R³～R⁶Each independently represents an alkyl group having 1 to 20 carbon atoms or an aryl group having 6 to 20 carbon atoms. R⁷Represents an optionally substituted alkyl group having 1 to 20 carbon atoms or an optionally substituted aryl group having 6 to 20 carbon atoms. k represents an integer of 1 to 200 which may have a distribution.

In the general formula (a), R¹Represents a hydrogen atom or a methyl group. Among these, methyl is more preferable from the viewpoint of easy availability.

In the general formula (a), R²Represents a C1-20 2-valent organic group. Examples thereof include alkylene groups such as methylene, ethylene, propylene, butylene, pentylene, octylene, decylene, dodecylene, and octadecylene, and arylene groups such as phenylene and naphthylene. These alkylene groups and arylene groups may be linear or branched. When the number of carbon atoms of the 2-valent organic group is 20 or less, it is possible to suppress the difficulty in obtaining compatibility with the hydrophilic monomer, and when it is 1 or more, the elongation of the obtained silicone hydrogel decreases and the possibility of easy breakage decreases, so the number of carbon atoms is more preferably 1 to 12, and the number of carbon atoms is most preferably 2 to 8. The alkylene unit of the aforementioned 2-valent organic group may be substituted with an oxygen atom or a sulfur atom, and a hydrogen atom adjacent to a carbon may be substituted with a hydroxyl group, an amino group, or a halogen atom. Examples of suitable substituents when the 2-valent organic group is substituted include a hydroxyl group, a carboxyl group, a sulfonic acid group, a phosphoric acid group, an ester, an ether, an amide, and a combination thereof. Among these, hydroxyl groups, esters, ethers, and amides are preferable from the viewpoint of hardly causing decomposition of the silicone site, and hydroxyl groups and ethers are more preferable from the viewpoint of improving the transparency of the obtained silicone hydrogel.

As R²More preferable examples of (3) include ethylene, propylene, butylene, and 2-valent organic groups represented by the following formulae (a1) to (a4)。

-CH₂CH(OH)CH₂- (a1)

-CH₂CH(OH)CH₂OCH₂CH₂CH₂- (a2)

-CH₂CH₂OCH₂CH₂CH₂- (a3)

-CH₂CH₂OCH₂CH₂OCH₂CH₂CH₂- (a4)

Among them, propylene and the 2-valent organic groups represented by the formulae (a1) to (a4) are preferable, and propylene or the 2-valent organic group represented by the formula (a2) is particularly preferable.

In the general formula (a), R³～R⁶Each independently represents an alkyl group having 1 to 20 carbon atoms which may be substituted, or an aryl group having 6 to 20 carbon atoms which may be substituted. Examples thereof include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, eicosyl, phenyl, naphthyl and the like. These alkyl groups and aryl groups may be linear or branched. In the case of an alkyl group having 1 to 20 carbon atoms which may be substituted or an aryl group having 6 to 20 carbon atoms which may be substituted, since the decrease in the silicone content and the decrease in the oxygen permeability of the obtained silicone hydrogel can be suppressed, the number of carbon atoms is more preferably 1 to 12, still more preferably 1 to 6, and still more preferably 1 to 4. When an alkyl group or an aryl group is substituted, examples of the substituent include an aldehyde group, a carboxyl group, an alcohol group, an alkoxy group, an ether group, a halogen group, an alkylene glycol group, an alkyl sulfide group, an amino group, a nitro group, a cyano group, a sulfuric acid group, and a phosphoric acid group.

In the general formula (a), R⁷Represents an optionally substituted alkyl group having 1 to 20 carbon atoms or an optionally substituted aryl group having 6 to 20 carbon atoms. R⁷When the number of carbon atoms of (b) is 1 or more, the polysiloxane chain can be inhibited from becoming easily hydrolyzed, and when it is 20 or less, the oxygen permeability of the silicone hydrogel can be prevented from being lowered. Therefore, the temperature of the molten metal is controlled,more preferably an alkyl group having 1 to 10 carbon atoms or an aryl group having 6 to 10 carbon atoms, further preferably an alkyl group having 1 to 6 carbon atoms, and further more preferably an alkyl group having 1 to 4 carbon atoms. Suitable examples of the alkyl group having 1 to 20 carbon atoms and the aryl group having 6 to 20 carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, sec-pentyl group, neopentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, dodecyl group, eicosyl group, phenyl group, naphthyl group and the like. These alkyl groups and aryl groups may be linear or branched. When an alkyl group or an aryl group is substituted, examples of the substituent include an aldehyde group, a carboxyl group, an alcohol group, an alkoxy group, an ether group, a halogen group, an alkylene glycol group, an alkyl sulfide group, an amino group, a nitro group, a cyano group, a sulfuric acid group, and a phosphoric acid group.

In the general formula (a), k represents an integer of 1 or more and 200 or less which may have a distribution. When k is 200 or less, it is easy to suppress the decrease in compatibility with the hydrophilic monomer due to the excessive number of hydrophobic silicone sites, and when k is 1 or more, oxygen permeability and shape recovery properties are obtained, so k is more preferably 1 or more and 100 or less, further preferably 2 or more and 50 or less, and particularly preferably 3 or more and 20 or less. The lower limit value is preferably 1, more preferably 2, and still more preferably 3. The upper limit is preferably 200, more preferably 100, still more preferably 50, and still more preferably 20. The aforementioned lower and upper limits may be arbitrarily combined. Where k has a distribution, k is determined based on the number average molecular weight of the monofunctional linear silicone monomer. The monofunctional linear silicone monomer used in the silicone hydrogel used in the present invention may be 1 type, or a plurality of types having different k may be used in combination. The monofunctional linear silicone monomer used in the silicone hydrogel used in the present invention may use a plurality of monofunctional linear silicone monomers different from each other in chemical structure other than k in combination.

The silicone hydrogel used in the present invention preferably contains a repeating unit (C) derived from a monomer containing an amide structure. The repeating unit (C) is used to impart an appropriate water content to the silicone hydrogel. The repeating unit (a) may not contribute much to the water content, and therefore, it is preferable to use the repeating unit (C) as an aid.

In the present invention, the amide structure is represented by the following formula (q). For example, amide compounds, imide compounds, urea compounds, and derivatives thereof have an amide structure.

[ chemical formula 10]

The amide structure is less susceptible to hydrolysis than an ester bond or the like, and can exhibit excellent durability, and for example, it is expected that decomposition, detachment, alteration, or the like of a part of the polymer structure can be suppressed even under a severe environment such as steam sterilization. In addition, it is preferable because it provides a structure excellent in hydrophilicity and slipperiness.

As the repeating unit (C), a repeating unit derived from a monomer represented by the following general formula (II-1) or general formula (II-2) is preferable.

[ chemical formula 11]

In the general formula (II-1) and the general formula (II-2), R⁸And R¹¹Each independently represents a hydrogen atom or a methyl group, R⁹And R¹⁰And R¹²And R¹³Represents a hydrogen atom or an alkyl group having 1 to 20 carbon atoms which may be branched or linear or may contain a cyclic structure and which may be substituted, R¹²And R¹³The rings may be formed with each other via a bond. When the alkyl group is substituted, examples of the substituent include an aldehyde group, a carboxyl group, an alcohol group, an alkoxy group, an ether group, a halogen group, an alkylene glycol group, an alkyl sulfide group, an amino group, a nitro group, a cyano group, a sulfuric acid group, and a phosphoric acid group.

Here, R is added to the water content so that hydrophilicity contributing to the water content is not easily impaired⁹And R¹⁰Each independently preferably represents a hydrogen atom or a branched or linear alkyl group. In the case of an alkyl group, the carbon number of the alkyl group is preferably 1 or more and 6 or less, more preferably 1 or more and 4 or less, and still more preferably 1 or more and 2 or less.

Similarly, R is for the purpose of preventing the hydrophilicity contributing to the water content from being impaired¹²And R¹³Each independently preferably represents a hydrogen atom or a branched or linear alkyl group, R¹²And R¹³More preferably, they form a ring with each other via a bond. In the case of an alkyl group, the carbon number of the alkyl group is preferably 1 or more and 6 or less, more preferably 1 or more and 4 or less, and still more preferably 1 or more and 2 or less. R¹²And R¹³When the two rings form a ring through a bond, R is a group which does not easily impair the stability of the structure¹²And R¹³The sum of carbon numbers of (a) is preferably 3 or more and 6 or less, more preferably 3 or more and 5 or less, and further preferably 3 or more and 4 or less.

The silicone hydrogel used in the present invention preferably contains the repeating unit (C) in a range of 5 mass% to 50 mass% based on the total mass of the silicone hydrogel at the time of drying. When the repeating unit (C) is 5% by mass or more, sufficient water content can be obtained, and the water wettability is not deteriorated, and when it is 50% by mass or less, the following situation can be alleviated: oxygen permeability is lowered, a balance of compatibility is lacking to cause cloudiness, or strength of the gel is deteriorated due to excessive swelling. The lower limit is preferably 5% by mass, more preferably 8% by mass, still more preferably 10% by mass, and still more preferably 12% by mass. The upper limit is preferably 50% by mass, more preferably 45% by mass, still more preferably 40% by mass, and still more preferably 35% by mass. The upper and lower limits may be arbitrarily combined.

Examples of monomers from which the repeating unit (C) is derived include compounds containing at least one of the following: vinyl amides, vinyl imides, vinyl lactams, hydrophilic (meth) acrylates, (meth) acrylamides and derivatives thereof (examples of the derivatives include N, N-dimethylacrylamide, N-diethylacrylamide, N-hydroxyethylacrylamide.), hydrophilic styrenic compounds, vinyl ethers, vinyl carbonates, vinyl carbamates, and vinyl ureas.

More specifically, the above-mentioned suitable monomers include (meth) acrylamides, N-vinylcarboxylic acid amides, cyclic N-vinyllactams, cyclic N-vinylpyridines and N-vinylimidazoles. In particular, (meth) acrylamides are preferable because they are excellent in hydrophilicity.

Suitable examples of the monomer capable of obtaining the repeating unit (C) include acrylamide, N-methylacrylamide, N-ethylacrylamide, N-isopropylacrylamide, N-dimethylacrylamide, N-diethylacrylamide, N-diisopropylacrylamide, acryloylmorpholine, diacetoneacrylamide, N-vinylformamide, N-vinylacetamide, N-vinyl-N-methylacetamide, N-vinylpyrrolidone, N-vinyl-2-piperidone, N-vinyl-2-caprolactam, N-vinyl-3-methyl-2-caprolactam, N-vinyl-4-methyl-2-caprolactam, N-isopropylacrylamide, N-diethylacrylamide, N-diisopropylacrylamide, acryloylmorpholine, N-vinylacrylamide, N-vinylpyrrolidone, N-vinyl-2-piperidone, N-vinyl-2-caprolactam, N-vinyl-3-methyl-2-caprolactam, 2-ethyloxazoline, N- (2-hydroxypropyl) (meth) acrylamide, N- (2-hydroxyethyl) (meth) acrylamide, 3- ((3-acrylamidopropyl) dimethylammonio) propane-1-sulfonate (AMPDAPS), 3- ((3-methacrylamidopropyl) dimethylammonio) propane-1-sulfonate (MAMPDAPS), 3- ((3- (acryloyloxy) propyl) dimethylammonio) propane-1-sulfonate (APDAPS), 3- ((3-methacryloyloxy) propyl) dimethylammonio) propane-1-sulfonate (MAPLDPS), N-vinyl-2-methylpropanamide, N-vinyl-N, N' -dimethylurea, N- (2-hydroxyethyl) (meth) acrylamide, N- (2-hydroxypropyl) propane-1-sulfonate (MAPLDPS), N- (2-hydroxyethyl) (meth) acrylamide, N- (3-acrylamidopropyl) dimethyl (meth) propane, N- (3-acrylamidopropyl, Dimethylaminopropyl (meth) acrylamide, dimethylaminoethyl (meth) acrylamide, dimethylaminopropyl (meth) acrylate, dimethylaminoethyl (meth) acrylate, and the like.

Among these, N-methacrylamide, N-dimethylacrylamide, N-vinylpyrrolidone, N-vinylcaprolactam, N-vinylacetamide, and N-vinyl-N-methylacetamide are more preferable from the viewpoint of obtaining a hydrophilic polymer excellent in water wettability and slipperiness. These may be used alone, or 2 or more of them may be used in combination.

The monomers represented by the general formula (II-1) and the general formula (II-2) may be used alone or in combination of two or more.

The silicone hydrogel used in the present invention is preferably a polymer comprising the aforementioned repeating unit (A) derived from the monomer represented by the aforementioned general formula (I), the aforementioned repeating unit (B) derived from the monomer represented by the aforementioned general formula (a), and the repeating unit (C) derived from the monomer represented by the aforementioned general formula (II-1) or general formula (II-2). Here, the symbols in each general formula are as defined above, preferable examples thereof are also as described above, and the respective repeating units may be singly or in combination of plural kinds thereof.

In the polymer including the repeating units (a), (B), and (C), it is preferable that the repeating unit (a) is included in a range of 5% by mass or more and 50% by mass or less with respect to the total mass of the silicone hydrogel at the time of drying, the repeating unit (B) is included in a range of 20% by mass or more and 70% by mass or less with respect to the total mass of the silicone hydrogel at the time of drying, and the repeating unit (C) is included in a range of 5% by mass or more and 50% by mass or less with respect to the total mass of the silicone hydrogel at the time of drying. Of course, the total of the repeating units (a), (B) and (C) is not more than 100% by mass based on the total mass of the silicone hydrogel at the time of drying. In the polymer, the total of the repeating units (a), (B), and (C) is preferably more than 50 mass%, more preferably 70 mass% or more, and still more preferably 85 mass% or more, based on the total mass of the silicone hydrogel at the time of drying.

The silicone hydrogel used in the present invention may also contain a repeating unit derived from a polyfunctional monomer (crosslinking monomer) having 2 or more polymerizable groups. In this case, the silicone hydrogel used in the present invention will have solvent resistance. Preferable examples of the polyfunctional monomer having 2 or more polymerizable groups include polyethylene dimethylsiloxanes having (meth) acryloyloxy groups at both ends, such as ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, tetraethylene glycol di (meth) acrylate, neopentyl glycol di (meth) acrylate, tetraethylene glycol di (meth) acrylate, 1, 3-bis (3- (meth) acryloyloxypropyl) -1, 1, 3, 3-tetramethyl-disiloxane, 1, 3-bis (3- (meth) acryloyloxypropyl) -1, 1, 3, 3-tetrakis (trimethylsiloxy) disiloxane, Silaplane (registered trademark) FM7711 available from shin-Etsu chemical Co., Ltd., "Silaplane" (registered trademark) FM7711, Di-or polyfunctional (meth) acrylates such as glycerol tri (meth) acrylate, pentaerythritol tetra (meth) acrylate and trimethylolpropane tri (meth) acrylate, and bisacrylamides such as N, N ' -methylenebisacrylamide, N ' -ethylenebisacrylamide and N, N ' -propylenebiacrylamide, and the like.

Among these, from the viewpoint of easily obtaining a silicone hydrogel having a low tensile elastic modulus, a bifunctional (meth) acrylate is more preferable, and from the viewpoint of improving the shape-recovering property of the obtained silicone hydrogel, more preferred is an organosilicon di (meth) acrylate such as 1, 3-bis (3- (meth) acryloyloxypropyl) -1, 1, 3, 3-tetramethyldisiloxane, 1, 3-bis (3- (meth) acryloyloxypropyl) -1, 1, 3, 3-tetrakis (trimethylsiloxy) disiloxane, and polydimethylsiloxane having (meth) acryloyloxy groups at both terminals, such as "Silaplane" (registered trademark) FM7711 or FM7721 manufactured by shin-Etsu chemical Co., Ltd.

When the amount of the repeating unit derived from the polyfunctional monomer having 2 or more polymerizable groups is 25% by mass or less, the silicone hydrogel is less likely to be excessively hard, and when it is 0.1% by mass or more, it is possible to prevent the shape of the silicone hydrogel from becoming difficult to maintain, and therefore, it is preferably 0.1 to 25% by mass, more preferably 0.5 to 20% by mass, most preferably 0.8 to 12% by mass of the silicone hydrogel. The lower limit is preferably 0.1% by mass, more preferably 0.5% by mass, still more preferably 1% by mass, and still more preferably 5% by mass. The upper limit is preferably 25% by mass, more preferably 20% by mass, still more preferably 15% by mass, and still more preferably 12% by mass. The lower limit value and the upper limit value may be arbitrarily combined.

The silicone hydrogel used in the present invention preferably has a glass transition temperature of 20 ℃ or lower when a homopolymer is formed from at least either of the repeating unit (a) derived from the monomer represented by the general formula (I) and the repeating unit (C) derived from the amide structure-containing monomer.

When the glass transition temperature in the formation of a homopolymer is room temperature or lower, the tensile elastic modulus in drying can be suppressed to be low, which is preferable. The repeating unit (a) is preferably used because the glass transition temperature in forming a homopolymer is usually room temperature or lower, and the repeating unit (C) is also more preferably room temperature or lower when the glass transition temperature in forming a homopolymer is also preferably room temperature or lower, and at least one of the repeating unit (a) and the repeating unit (C) may have the above-described properties.

The glass transition temperature in the formation of a homopolymer can be measured by synthesizing a homopolymer by an arbitrary method using the target monomer and using a Differential Scanning Calorimeter (DSC).

The silicone hydrogel used in the present invention may be used by itself as a desired shape, or may be mixed with other materials and then molded. Further, the surface of the molded article may be coated.

When the silicone hydrogel used in the present invention is molded and used as an ophthalmic lens, the polymerization method and the molding method thereof may be the following standard methods. Examples are: first, a method of forming a silicone hydrogel into a round bar or a plate shape, and then finishing the formed product into a desired shape by cutting, turning, or the like, a mold polymerization method, a spin casting method, or the like.

For example, a case of producing an ophthalmic lens from the silicone hydrogel used in the present invention by a cast polymerization method will be described below.

The monomer composition was injected into the space between 2 molds having a lens shape. Then, photopolymerization or thermal polymerization is performed to form a lens shape. The mold is made of resin, glass, ceramic, metal, or the like, and in the case of photopolymerization, a material through which a photopolymerization wavelength passes is used, and resin or glass is generally used. In the case of producing a silicone hydrogel, a void was formed by 2 opposing molds, and the monomer composition was injected into the void. Subsequently, the mold having the space filled with the monomer composition is irradiated with active light such as ultraviolet light, visible light, or a combination thereof, or placed in an oven or a liquid bath and heated to polymerize the monomer. The photopolymerization may be followed by heating polymerization or, conversely, may be followed by heating polymerization and then photopolymerization. In the case of photopolymerization, light including light of a high level from a light source such as a mercury lamp or a fluorescent lamp is generally irradiated in a short time (generally 1 hour or less). When the thermal polymerization is carried out, it is preferable to increase the temperature from around room temperature to a high temperature of 60 to 200 ℃ over several hours or several tens of hours in order to maintain the optical uniformity and grade of the polymer and to improve the reproducibility.

As the polymerization solvent, various organic and inorganic solvents can be used. Examples of the solvent include various alcohol solvents such as water, methanol, ethanol, propanol, 2-propanol, butanol, t-amyl alcohol, 3, 7-dimethyl-3-octanol and tetrahydrolinalool, various aromatic hydrocarbon solvents such as benzene, toluene and xylene, various aliphatic hydrocarbon solvents such as hexane, heptane, octane, decane, petroleum ether, kerosene, volatile oil (ligroin) and paraffin, various ketone solvents such as acetone, methyl ethyl ketone and methyl isobutyl ketone, various ester solvents such as ethyl acetate, butyl acetate, methyl benzoate, dioctyl phthalate and ethylene glycol diacetate, various ester solvents such as diethyl ether, tetrahydrofuran, dioxane, ethylene glycol dialkyl ether, diethylene glycol dialkyl ether, triethylene glycol dialkyl ether, tetraethylene glycol dialkyl ether, polyethylene glycol-polypropylene glycol block copolymer, and the like, Various glycol ether solvents such as polyethylene glycol-polypropylene glycol random copolymer can be used alone or in combination. Among these, water, t-butanol, t-amyl alcohol, 3, 7-dimethyl-3-octanol are preferable, and water is most preferable, from the viewpoint of preventing radical polymerization.

When the silicone hydrogel used in the present invention is obtained by polymerization, a polymerization initiator may be added to promote the polymerization. Suitable initiators include thermal polymerization initiators such as peroxides and azo compounds, photopolymerization initiators (in the case of UV light, visible light or a combination thereof), or mixtures thereof. When thermal polymerization is performed, a thermal polymerization initiator having an optimum decomposition characteristic is selected and used for a desired reaction temperature. In general, it is preferable that the 10-hour half-life temperature is 40 ℃ or more and 120 ℃ or less. Examples of the photopolymerization initiator include carbonyl compounds, peroxides, azo compounds, sulfur compounds, halogen compounds, and metal salts.

More specific examples of the photoinitiator include aromatic α -hydroxyketones, alkoxyoxybenzoins, acetophenones, acylphosphine oxides, bisacylphosphine oxides, and tertiary amine + diketones, and mixtures thereof. As further specific examples of the photoinitiator, 1-hydroxycyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenyl-propan-1-one, bis (2, 6-dimethoxybenzoyl) -2, 4-4-trimethylpentylphosphine oxide (DMBAPO), bis (2, 4, 6-trimethylbenzoyl) -phenylphosphine oxide ("Irgacure" (registered trademark) 819), 2, 4, 6-trimethylbenzyldiphenylphosphine oxide (Japanese: 2, 4, 6- ト リ メ チ ル べ ン ヅ ル ヅ フ ェ ニ ル ホ ス フ イ ン オ キ シ ド) and 2, 4, 6-trimethylbenzoyldiphenylphosphine oxide, benzoin methyl ether, and a combination of camphorquinone and ethyl 4- (N, N-dimethylamino) benzoate.

Examples of commercially available visible light initiator systems include "Irgacure" (registered trademark) 819, "Irgacure" (registered trademark) 1700, "Irgacure" (registered trademark) 1800, "Irgacure" (registered trademark) 1850 (mentioned above, manufactured by BASF), and Lucirin TPO initiator (manufactured by BASF). Examples of commercially available UV photoinitiators include "Darocur" (registered trademark) 1173 and "Darocur" (registered trademark) 2959 (manufactured by BASF). These polymerization initiators may be used alone or in combination, and the amount used is in the range of 0.1 to 1 mass% based on the total mass of all monomer components.

Examples of other components that may be present in the reaction mixture used to form the contact lens of the present invention include dyes, compounds, ultraviolet absorbing compounds, pharmaceutical compounds, nutritional supplement compounds, antimicrobial compounds, copolymerizable and non-polymerizable dyes that include various wavelengths that are exposed to light, release agents, reactive colorants, pigments, combinations thereof, and the like that reversibly change color or reflect light.

The silicone hydrogel used in the present invention can be modified by various methods. Specific modification methods include chemical vapor deposition treatment such as electromagnetic wave (including light) irradiation, plasma irradiation, vapor deposition, sputtering, heating, mold transfer coating, alkali treatment, acid treatment, and treatment with another suitable surface treatment agent, and they may be used in combination.

Examples of the alkali treatment or the acid treatment include a method of contacting a molded article with an alkaline or acidic solution, and a method of contacting a molded article with an alkaline or acidic gas. More specific examples of the method include: a method of immersing the molded article in an alkaline or acidic solution, a method of spraying an alkaline or acidic solution or an alkaline or acidic gas on the molded article, a method of applying an alkaline or acidic solution to the molded article with a spatula, a brush, or the like, a method of spin-coating an alkaline or acidic solution on the molded article, a dip-coating method, or the like. The most convenient method for obtaining a large modification effect is a method of immersing a molded article in an alkaline or acidic solution.

The temperature at which the silicone hydrogel is immersed in the alkaline or acidic solution is not particularly limited, and is usually in the range of-50 ℃ to 300 ℃. In view of handling properties, the temperature range of-10 ℃ to 150 ℃ is more preferable, the range of-5 ℃ to 60 ℃ is more preferable, and the range of 0 ℃ to 40 ℃ is even more preferable.

The optimum time for immersing the silicone hydrogel in an alkaline or acidic solution varies depending on the temperature, and is usually preferably within 100 hours, more preferably within 24 hours, and most preferably within 12 hours, in order to prevent adverse effects such as deterioration of workability and productivity due to a prolonged contact time, reduction of oxygen permeability, and reduction of mechanical properties.

As the base, alkali metal hydroxides, alkaline earth metal hydroxides, various carbonates, various borates, various phosphates, ammonia, various ammonium salts, various amines, and high molecular weight bases such as polyethyleneimine and polyvinylamine can be used. Among these, the alkali metal hydroxide is most preferable from the viewpoint of low cost and high treatment effect.

As the acid, various inorganic acids such as sulfuric acid, phosphoric acid, hydrochloric acid, and nitric acid; various organic acids such as acetic acid, formic acid, benzoic acid, and phenol; and various high molecular weight acids such as polyacrylic acid and polystyrene sulfonic acid. Among these, the high molecular weight acid is most preferable because it has a large treatment effect and has a minimal adverse effect on other physical properties.

The solvent of the basic or acidic solution may be any of inorganic and organic solvents. By way of example, water, methanol, ethanol, propanol, 2-propanol, butanol, ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, polyethylene glycol, glycerol and other alcohols, benzene, toluene, xylene and other aromatic hydrocarbons, hexane, heptane, octane, decane, petroleum ether, kerosene, volatile oils, paraffins and other aliphatic hydrocarbons, acetone, methyl ethyl ketone, methyl isobutyl ketone and other ketones, ethyl acetate, butyl acetate, methyl benzoate, dioctyl phthalate and other esters, diethyl ether, tetrahydrofuran, dioxane, ethylene glycol dialkyl ether, diethylene glycol dialkyl ether, triethylene glycol dialkyl ether, tetraethylene glycol dialkyl ether, polyethylene glycol dialkyl ether and other ethers; dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, dimethylimidazolidinone, hexamethylphosphoric triamide, dimethyl sulfoxide and other aprotic polar solvents, dichloromethane, chloroform, dichloroethane, trichloroethane, trichloroethylene, other halogen solvents, and freon solvents. Among these, water is most preferable from the viewpoints of economy, ease of treatment, and chemical stability. The solvent may be a mixture of 2 or more.

In the present invention, the basic or acidic solution used may contain other components than the basic or acidic substance and the solvent.

The silicone hydrogel may be subjected to alkali treatment or acid treatment followed by washing to remove the basic or acidic substances. The cleaning solvent may be any of inorganic and organic solvents. By way of example, water, methanol, ethanol, propanol, 2-propanol, butanol, ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, polyethylene glycol, glycerol and other alcohols, benzene, toluene, xylene and other aromatic hydrocarbons, hexane, heptane, octane, decane, petroleum ether, kerosene, volatile oils, paraffins and other aliphatic hydrocarbons, acetone, methyl ethyl ketone, methyl isobutyl ketone and other ketones, ethyl acetate, butyl acetate, methyl benzoate, dioctyl phthalate and other esters, diethyl ether, tetrahydrofuran, dioxane, ethylene glycol dialkyl ether, diethylene glycol dialkyl ether, triethylene glycol dialkyl ether, tetraethylene glycol dialkyl ether, polyethylene glycol dialkyl ether and other ethers; dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, dimethylimidazolidinone, hexamethylphosphoric triamide, dimethyl sulfoxide and other aprotic polar solvents, dichloromethane, chloroform, dichloroethane, trichloroethane, trichloroethylene, other halogen solvents, and freon solvents.

The cleaning solvent may be a mixture of 2 or more. The cleaning solvent may contain other components than the solvent, such as inorganic salts, surfactants, and cleaning agents.

The modification treatment described above may be performed on the entire silicone hydrogel, or may be performed only on a part of the silicone hydrogel, for example, on the surface. When only the surface is modified, the wettability of the surface can be improved without greatly changing the physical properties of the entire silicone hydrogel.

In the case of visual observation, the transparency of the silicone hydrogel used in the present invention is preferably 5 or 4, more preferably 5. The determination method is described in the following examples. Since the contact portion of the medical device with the human body is easily visually recognized, the transparent material of the present invention is suitable for use in a wound dressing. In addition, the infusion tube, the gas delivery tube, the stent, the sheath, the cuff, the tube joint, the access port, the drainage bag, the blood circuit, and the like are also preferably transparent from the viewpoint of improving visibility of the flow path. In particular, in the case of an ophthalmic lens, the lens preferably has transparency that does not cause blur in the visual field.

Regarding the slipperiness of the silicone hydrogel used in the present invention, in the case of sensory evaluation by touch, 5 or 4 is preferable, and 5 is more preferable. The determination method is described in the following examples.

When the dynamic contact angle of the silicone hydrogel used in the present invention is used for an ophthalmic lens, the advancing contact angle value is preferably 70 ° or less, more preferably 60 ° or less, and still more preferably 50 ° or less. The lower limit of the advancing contact angle is not particularly limited, and the lower limit is actually about 20 °.

In the present invention, the boric acid buffer is the "salt solution" described in example 1 of Japanese patent application laid-open No. 2004-517163. Specifically, 8.48g of sodium chloride, 9.26g of boric acid, 1.0g of sodium borate (sodium tetraborate decahydrate), and 0.10g of ethylenediaminetetraacetic acid were dissolved in pure water to prepare 1000mL of an aqueous solution.