METHOD FOR MANUFACTURING MEDICAL DEVICE

Abstract

An objective of the present invention is to provide a method for easily manufacturing a hydrophilized medical device of superior durability. In order to achieve the abovementioned objective, a method for manufacturing a medical device according to the present invention comprises a step for heating an aqueous package fluid, wherein, in the heating step, the aqueous package fluid contains one or more types of hydrophilic polymer, heating is performed with a substrate of the medical device at least partially is contact with the aqueous package fluid, and the following conditions (a) through (c) are all met. (a) The hydrophilic polymer is a (meth)acrylamide (co)polymer comprising two substituents comprising two or more carbon atoms on a nitrogen atom. (b) The mass % concentration of the hydrophilic polymer in the aqueous package fluid is in a range of 0.0001-30 mass %. (c) The pH of the aqueous package fluid after the heating step is in a range of 6.1-8.0.

Claims

1. A method for manufacturing a medical device, the method comprising a step of heating an aqueous packaging solution, wherein the heating step is performed in a state in which the aqueous packaging solution contains at least one type of hydrophilic polymer, and a substrate of the medical device is at least partially in contact with the aqueous packaging solution, and the method satisfies all of requirements (a) to (c) shown below: (a) the hydrophilic polymer is a (co)polymer of a (meth)acrylamide having two substituents each having 2 or more carbon atoms on a nitrogen atom; (b) the aqueous packaging solution has a mass % concentration of the hydrophilic polymer in a range of 0.0001 to 30 mass %; and (c) the aqueous packaging solution has a pH in a range of 6.1 to 8.0 after the heating step.

2. The method according to claim 1, wherein the hydrophilic polymer is a copolymer of the (meth)acrylamide having two substituents each having 2 or more carbon atoms on a nitrogen atom with (meth)acrylic acid.

3. The method according to claim 2, wherein the copolymer of the (meth)acrylamide having two substituents each having 2 or more carbon atoms on a nitrogen atom with (meth)acrylic acid has a copolymerization ratio of [mass of a (meth)acrylic acid monomer]/[mass of a (meth)acrylamide monomer having two substituents each having 2 or more carbon atoms on a nitrogen atom]=1/99 to 99/1.

4. The method according to claim 1, wherein the heating is performed by autoclave sterilization.

5. The method according to claim 1, wherein the substrate contains at least one type of material selected from the group consisting of a hydrogel, a silicone hydrogel, a low water content soft material, and a low water content hard material.

6. The method according to claim 5, wherein the hydrogel is selected from the group consisting of tefilcon, tetrafilcon, helfilcon, mafilcon, polymacon, hioxifilcon, alfafilcon, omafilcon, nelfilcon, nesofilcon, hilafilcon, acofilcon, deltafilcon, etafilcon, focofilcon, ocufilcon, phemfilcon, methafilcon, and vilfilcon.

7. The method according to claim 5, wherein the silicone hydrogel is selected from the group consisting of lotrafilcon, galyfilcon, narafilcon, senofilcon, comfilcon, enfilcon, balafilcon, efrofilcon, fanfilcon, somofilcon, samfilcon, olifilcon, asmofilcon, formofilcon, stenfilcon, abafilcon, mangofilcon, riofilcon, sifilcon, larafilcon, and delefilcon.

8. The method according to claim 5, wherein the low water content soft material is a material containing a silicon atom.

9. The method according to claim 5, wherein the low water content hard material is a material containing a silicon atom.

10. The method according to claim 5, wherein the low water content hard material is polymethyl methacrylate.

11. The method according to claim 5, wherein the low water content hard material is a material selected from the group consisting of neofocon, pasifocon, telefocon, silafocon, paflufocon, petrafocon, and fluorofocon.

12. The method according to claim 1, wherein the medical device is an ophthalmic lens, a skin covering material, a wound covering material, a skin protective material, a drug carrier for skin, an infusion tube, a gas transport tube, a drainage tube, a blood circuit, a covering tube, a catheter, a stent, a sheath biosensor chip, a heart-lung machine, or an endoscope covering material.

13. The method according to claim 12, wherein the ophthalmic lens is a contact lens.

Description

EXAMPLES

[0127] Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited to these examples. First, analysis methods and evaluation methods will be described.

[0128] <Water Wettability (Liquid Film Retention Time)>

[0129] To eliminate the influence of the hydrophilic polymer contained in the aqueous packaging solution and not adsorbed to the medical device, the medical device was left to stand at room temperature for 1 hour or more in 3 mL of a phosphate buffer solution in a glass vial. For the evaluation of only the commercially available contact lenses described in the comparative examples, to eliminate the influence of the hydrophilic polymer contained in the packaging solution and not adsorbed to the lens, the lens was left to stand at room temperature for 1 hour or more in 3 mL of a phosphate buffer solution in a glass vial.

[0130] The medical device was pulled up from the phosphate buffer solution in which the medical device had been immersed and left to stand, and was retained in the air. The time during which the liquid film on the surface was retained was visually observed, and the average of N=3 was judged according to the following criteria.

A: The liquid film on the surface is retained for 20 seconds or more.
B: The liquid film on the surface is broken within 15 seconds or more and less than 20 seconds.
C: The liquid film on the surface is broken within 10 seconds or more and less than 15 seconds.
D: The liquid film on the surface is broken within 1 second or more and less than 10 seconds.
E: The liquid film on the surface is instantaneously broken (within less than 1 second).

[0131] <Water Wettability 2 Hours after Scrubbing and Washing (Liquid Film Retention Time)>

[0132] To eliminate the influence of the hydrophilic polymer contained in the aqueous packaging solution and not adsorbed to the medical device, the medical device was left to stand at room temperature for 1 hour in 3 mL of a phosphate buffer solution in a glass vial. For the evaluation of only the commercially available contact lenses described in the comparative examples, to eliminate the influence of the hydrophilic polymer contained in the packaging solution and not adsorbed to the lens, the lens was left to stand at room temperature for 1 hour in 3 mL of a phosphate buffer solution in a glass vial.

[0133] Then, the lens was sandwiched between the thumb and the forefinger, and scrubbed and washed 50 times. The lens was then returned to the phosphate buffer solution in which the lens had been immersed and left to stand, and left to stand for 2 hours.

[0134] The medical device was pulled up from the phosphate buffer solution in which the medical device had been immersed and left to stand, and was retained in the air. The time during which the liquid film on the surface was retained was visually observed, and the average of N=3 was judged according to the following criteria.

A: The liquid film on the surface is retained for 20 seconds or more.
B: The liquid film on the surface is broken within 15 seconds or more and less than 20 seconds.
C: The liquid film on the surface is broken within 10 seconds or more and less than 15 seconds.
D: The liquid film on the surface is broken within 1 second or more and less than 10 seconds.
E: The liquid film on the surface is instantaneously broken (within less than 1 second).

[0135] <Water Content of Substrate and Medical Device>

[0136] The substrate was immersed in a phosphate buffer solution and left to stand at room temperature for 24 hours or more. The substrate was pulled up from the phosphate buffer solution, the surface moisture was wiped off with a wiping cloth (“Kimwipe (registered trademark)” manufactured by NIPPON PAPER CRECIA CO., LTD.), and then the mass (Ww) of the substrate was measured. Then, the substrate was dried at 40° C. for 2 hours with a vacuum dryer, and then the mass (Wd) was measured. From these masses, the water content of the substrate was calculated by the following formula (1). When the obtained value was less than 1%, it was judged as not more than the measurement limit, and was described as “less than 1%”. The average of N=3 was taken as the water content. The water content was similarly calculated for the substrate after sterilization, that is, the medical device.

Water content (%) of substrate=100×(Ww−Wd)/Ww   Formula (1)

[0137] <Amount of Change of Water Content of Substrate Before and After Sterilization>

[0138] From the measurement results of the water content of the substrate and the medical device, the amount of change of the water content was calculated by the following formula (2).

Amount of change (percentage point) of water content of substrate before and after sterilization=water content (mass %) of medical device−water content (mass %) of substrate   Formula (2)

[0139] <Friction Coefficient>

[0140] Under the following conditions, the friction coefficient of the surface of the medical device in a state of being wetted with a phosphate buffer solution was measured at N=5, and the average was taken as the friction coefficient.

Apparatus: Friction tester KES-SE (manufactured by KATO TECH CO., LTD.)

Friction SENS: H

[0141] Measurement SPEED: 2×1 mm/sec
Friction load: 44 g

[0142] <Lipid Adhesion Amount>

[0143] Into a 20 cc screw tube, 0.03 g of methyl palmitate, 10 g of pure water, and one contact lens-shaped sample were put. The screw tube was shaken at 37° C. and 165 rpm for 3 hours. After shaking, the sample in the screw tube was scrubbed and washed with tap water at 40° C. and a household liquid detergent (“Mama Lemon (registered trademark)” manufactured by Lion Corporation). The washed sample was placed in a screw tube containing a phosphate buffer solution, and stored in a refrigerator at 4° C. for 1 hour. Then, the sample was visually observed, and if there was a cloudy portion, it was determined that methyl palmitate adhered to the sample. The area of the portion to which methyl palmitate adhered with respect to the entire surface of the sample was observed.

[0144] <Tensile Elastic Modulus>

[0145] A test piece having a width (smallest portion) of 5 mm and a length of 14 mm was cutout from each of contact lens-shaped and sheet-shaped substrates using a prescribed blanking die. The test piece was subjected to a tensile test using TENSILON model RTG-1210 manufactured by A & D Company, Limited. The tensile speed was 100 mm/min, and the distance between grips (initial) was 5 mm. Measurements were made on both the substrate before sterilization and the medical device after sterilization. The measurement was performed at N=8, and the average of the values of N=6 excluding the maximum value and the minimum value was taken as the tensile elastic modulus.

[0146] <Tensile Elastic Modulus Change Rate of Substrate Before and After Sterilization>

[0147] From the measurement results of the tensile elastic modulus of the substrate and the medical device, the tensile elastic modulus change rate was calculated by the following formula (3). The average of N=6 was taken as the tensile elastic modulus change rate before and after sterilization.

Tensile elastic modulus change rate (%) of substrate before and after sterilization=(tensile elastic modulus of medical device after sterilization−tensile elastic modulus of substrate before sterilization)/tensile elastic modulus of substrate before sterilization×100  Formula (3)

[0148] <Size>

[0149] For the contact lens-shaped and sheet-shaped substrates (N=3), the diameters were measured, and the average was taken as the size. The size was similarly measured for the substrate after sterilization, that is, the medical device.

[0150] <Size Change Rate Before and After Sterilization>

[0151] From the measurement results of the size of the substrate and the medical device, the size change rate was calculated by the following formula (4). The average of N=3 was taken as the size change rate before and after sterilization.

Size change rate (%) before and after sterilization=(size of device after sterilization−size of substrate before sterilization)/size of substrate before sterilization×100   Formula (4)

[0152] <Measurement of Molecular Weight>

[0153] The molecular weight of the hydrophilic polymer was measured under the following conditions.

Apparatus: Prominence GPC system manufactured by Shimadzu Corporation

Pump: LC-20AD

Autosampler: SIL-20AHT

[0154] Column oven: CTO-20A

Detector: RID-10A

[0155] Column: GMPWXL (7.8 mm (internal diameter)×30 cm, particle size: 13 μm) manufactured by Tosoh Corporation
Solvent: water/methanol=1/1 (0.1 N lithium nitrate added)
Flow rate: 0.5 mL/min
Measurement time: 30 minutes
Sample concentration: 0.1 to 0.3 mass %
Sample injection volume: 100 μL
Standard sample: a polyethylene oxide standard sample (0.1 kD to 1258 kD) manufactured by Agilent

[0156] <pH Measurement Method>

[0157] The pH of a solution was measured using a pH meter Eutech pH 2700 (manufactured by Eutech Instruments). In the tables, the pH before sterilization of the aqueous packaging solution containing a hydrophilic polymer was measured after all the hydrophilic polymers were added to the solution described in each of the examples and comparative examples, and the solution was stirred at room temperature (20 to 23° C.) for 30 minutes using a rotor so as to be uniform. In the tables, the “pH after sterilization” was determined by performing the sterilization treatment once, cooling the solution to room temperature (20 to 23° C.), and measuring the pH immediately after that.

[0158] <Determination of Separation of Hydrophilic Polymer Layer>

[0159] Whether or not the hydrophilic polymer layer was separated was determined by observing a cross section of the medical device using a transmission electron microscope.

Apparatus: transmission electron microscope
Condition: acceleration voltage of 100 kV
Sample preparation: A sample was prepared by ultrathin sectioning using RuO.sub.4 staining. When it is difficult to distinguish between the substrate and the hydrophilic polymer layer, OsO.sub.4 staining may be additionally performed. In the examples, when the substrate was a silicone hydrogel-based substrate or a silicone-based substrate, RuO.sub.4 staining was performed.

[0160] An ultramicrotome was used to produce the ultrathin section.

[0161] <Elemental Composition Analysis of Hydrophilic Polymer Layer>

[0162] Elemental composition analysis of the hydrophilic polymer layer was performed according to scanning transmission electron microscopy and electron energy loss spectroscopy by analyzing a cross section of a medical device frozen in a water-containing state using a cryotransfer holder.

Apparatus: field emission electron microscope
Acceleration voltage: 200 kV
Measurement temperature: about −100° C.
Electron energy loss spectroscopy: GATAN GIF Tridiem
Image capturing: Digital Micrograph
Sample preparation: A sample was prepared by ultrathin sectioning using RuO.sub.4 staining. When it is difficult to distinguish between the substrate and a coat layer, OsO.sub.4 staining may be additionally performed. In the examples, when the substrate was a silicone hydrogel-based substrate or a silicone-based substrate, RuO.sub.4 staining was performed.

[0163] An ultramicrotome was used to produce the ultrathin section.

[0164] <Film Thickness of Hydrophilic Polymer Layer>

[0165] A cross section of the medical device in a dry state was observed using a transmission electron microscope. Measurement was performed under the conditions described in <Determination of separation of hydrophilic polymer layer>. The film thickness was measured at one point per visual field in three different points, and the average of the film thicknesses at the total of three points was described.

Production Example 1

[0166] First, 28 parts by mass of polydimethylsiloxane having methacryloyl groups at both ends and represented by a formula (M1) (FM-7726, JNC CORPORATION, Mw: 30,000), 7 parts by mass of a silicone monomer represented by a formula (M2) (FM-0721, JNC Corporation, Mw: 5,000), 57.9 parts by mass of trifluoroethyl acrylate (“Viscoat (registered trademark)” 3F, OSAKA ORGANIC CHEMICAL INDUSTRY LTD.), 7 parts by mass of 2-ethylhexyl acrylate (Tokyo Chemical Industry Co., Ltd.), and 0.1 parts by mass of dimethylaminoethyl acrylate (Kohjin Co., Ltd.) were prepared. Then, 5,000 ppm of a photoinitiator “Irgacure (registered trademark)” 819 (NAGASE & CO., LTD.), 5,000 ppm of an ultraviolet absorber (RUVA-93, Otsuka Chemical Co., Ltd.), and 100 ppm of a colorant (RB246, Arran chemical) with respect to the total mass of the above-mentioned monomers were prepared, and 10 parts by mass of t-amyl alcohol with respect to 100 parts by mass in total of the above-mentioned monomers were further prepared, and all the components were mixed and stirred. The stirred mixture was filtered through a membrane filter (pore size: 0.45 μm) to remove insoluble matters, thereby obtaining a monomer mixture.

[0167] The monomer mixture was injected into a contact lens mold made of a transparent resin (material on the base curve side: polypropylene, material on the front curve side: polypropylene), and polymerized by light irradiation (wavelength: 405 nm (±5 nm), illuminance: 0 to 0.7 mW/cm.sup.2, 30 minutes) to produce a molded article containing a silicon atom-containing low water content soft material.

[0168] After the polymerization, the resulting molded article, together with the mold including the front curve mold and the base curve mold released from each other, was immersed in a 100 mass % aqueous solution of isopropyl alcohol at 60° C. for 1.5 hours to peel off the contact lens-shaped molded article from the mold. The obtained molded article was immersed in a large excess amount of a 100 mass % aqueous solution of isopropyl alcohol kept at 60° C. for 2 hours to extract impurities such as residual monomers. Then, the molded article was dried at room temperature (23° C.) for 12 hours.

##STR00001##

[0169] <Phosphate Buffer Solution>

[0170] The phosphate buffer solution used in the processes of the following examples and comparative examples and the above-mentioned measurements has the following composition. In the following composition, EDTA2Na represents disodium dihydrogen ethylenediaminetetraacetate.

TABLE-US-00001 KCl  0.2 g/L KH.sub.2PO.sub.4  0.2 g/L NaCl  8.0 g/L Na.sub.2HPO.sub.4 1.19 g/L EDTA2Na  0.5 g/L

Example 1

[0171] As a substrate, a commercially available silicone hydrogel lens “MyDay (registered trademark)” (manufactured by CooperVision Japan, Inc., stenfilcon A) containing silicone as a main component was used. The substrate was immersed in a solution obtained by adding 0.05 mass % of an acrylic acid/N,N-diethylacrylamide copolymer (molar ratio of copolymerization: 1/9, Mw: 280,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 2

[0172] As a substrate, a commercially available silicone hydrogel lens “MyDay (registered trademark)” (manufactured by CooperVision Japan, Inc., stenfilcon A) containing silicone as a main component was used. The substrate was immersed in a solution obtained by adding 0.05 mass % of poly(N,N-diethylacrylamide) (Mw: 290,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 3

[0173] As a substrate, a commercially available silicone hydrogel lens “MyDay (registered trademark)” (manufactured by CooperVision Japan, Inc., stenfilcon A) containing silicone as a main component was used. The substrate was immersed in a solution obtained by adding 0.04 mass % of an acrylic acid/N,N-diethylacrylamide copolymer (molar ratio of copolymerization: 1/9, Mw: 280,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 4

[0174] As a substrate, a commercially available silicone hydrogel lens “MyDay (registered trademark)” (manufactured by CooperVision Japan, Inc., stenfilcon A) containing silicone as a main component was used. The substrate was immersed in a solution obtained by adding 0.04 mass % of poly(N,N-diethylacrylamide) (Mw: 290,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 5

[0175] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.05 mass % of an acrylic acid/N,N-diethylacrylamide copolymer (molar ratio of copolymerization: 1/9, Mw: 280,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 6

[0176] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.05 mass % of poly(N,N-diethylacrylamide) (Mw: 290,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 7

[0177] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.04 mass % of poly(N,N-diethylacrylamide) (Mw: 290,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 8

[0178] As a substrate, the molded article obtained in Production Example 1 was used. The substrate was immersed in a solution obtained by adding 0.04 mass % of an acrylic acid/N,N-diethylacrylamide copolymer (molar ratio of copolymerization: 1/9, Mw: 280,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 9

[0179] As a substrate, the molded article obtained in Production Example 1 was used. The substrate was immersed in a solution obtained by adding 0.04 mass % of poly(N,N-diethylacrylamide) (Mw: 290,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 10

[0180] As a substrate, a commercially available PF catheter tube (manufactured and sold by Toray Industries, Inc.) containing polyurethane as a main component was used. The substrate was immersed in a solution obtained by adding 0.04 mass % of an acrylic acid/N,N-dimethylacrylamide copolymer (molar ratio of copolymerization: 1/9, Mw: 800,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and heated in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 11

[0181] As a substrate, a commercially available PF catheter tube (manufactured and sold by Toray Industries, Inc.) containing polyurethane as a main component was used. The substrate was immersed in a solution obtained by adding 0.04 mass % of poly(N,N-diethylacrylamide) (Mw: 290,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and heated in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 12

[0182] As a substrate, a commercially available film “MICTRON (registered trademark)” (manufactured by Toray Industries, Inc.) containing a para-type aromatic polyamide (aramid) as a main component was used. The substrate was immersed in a solution obtained by adding 0.04 mass % of an acrylic acid/N,N-dimethylacrylamide copolymer (molar ratio of copolymerization: 1/9, Mw: 800,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and heated in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 13

[0183] As a substrate, a commercially available film “MICTRON (registered trademark)” (manufactured by Toray Industries, Inc.) containing a para-type aromatic polyamide (aramid) as a main component was used. The substrate was immersed in a solution obtained by adding 0.04 mass % of poly(N,N-diethylacrylamide) (Mw: 290,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and heated in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 14

[0184] As a substrate, a commercially available hydrogel lens “1-DAY ACUVUE (registered trademark)” (manufactured by Johnson & Johnson K.K., etafilcon A) containing 2-hydroxyethyl methacrylate as a main component was used. The substrate was immersed in a solution obtained by adding 0.04 mass % of an acrylic acid/N,N-diethylacrylamide copolymer (molar ratio of copolymerization: 1/9, Mw: 280,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 15

[0185] As a substrate, a commercially available hydrogel lens “1-DAY ACUVUE (registered trademark)” (manufactured by Johnson & Johnson K.K., etafilcon A) containing 2-hydroxyethyl methacrylate as a main component was used. The substrate was immersed in a solution obtained by adding 0.04 mass % of poly(N,N-diethylacrylamide) (Mw: 290,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 16

[0186] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.05 mass % of an N,N-dimethylacrylamide/N,N-diethylacrylamide copolymer (molar ratio of copolymerization: 1/9, Mw: 280,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 17

[0187] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.05 mass % of an acrylic acid/N,N-dimethylaminopropyl acrylamide methyl chloride quaternary salt/N,N-diethylacrylamide copolymer (molar ratio of copolymerization: 1/1/8, Mw: 280,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 18

[0188] As a substrate, the molded article obtained in Production Example 1 was used. The substrate was immersed in a solution obtained by adding 0.05 mass % of an acrylic acid/N,N-diethylacrylamide copolymer (molar ratio of copolymerization: 1/9, Mw: 280,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

Example 19

[0189] As a substrate, the molded article obtained in Production Example 1 was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of an acrylic acid/N,N-diethylacrylamide copolymer (molar ratio of copolymerization: 1/9, Mw: 280,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device by the above-mentioned methods are shown in Tables 1 to 3.

TABLE-US-00002 TABLE 1 Water content of Hydrophilic sub- polymer and pH pH strate concentration of Before After (mass hydrophilic polymer sterili- sterili- Substrate %) solution zation zation Exam- “MyDay 54.0 0.05 mass % 7.0 7.1 ple 1 (registered acrylic acid/ trademark)” N,N-diethylacrylamide copolymer Exam- “MyDay 54.0 0.05 mass % 7.1 7.2 ple 2 (registered poly(N,N- trademark)” diethylacrylamide) Exam- “MyDay 54.0 0.04 mass % 7.0 7.1 ple 3 (registered acrylic acid/ trademark)” N,N-diethylacrylamide copolymer Exam- “MyDay 54.0 0.04 mass % 7.1 7.2 ple 4 (registered poly(N,N- trademark)” diethylacrylamide) Exam- “ACUVUE 38.0 0.05 mass % 7.0 7.1 ple 5 OASYS acrylic acid/ (registered N,N-diethylacrylamide trademark)” copolymer Exam- “ACUVUE 38.0 0.05 mass % 7.1 7.2 ple 6 OASYS poly(N,N- (registered diethylacrylamide) trademark)” Exam- “ACUVUE 38.0 0.04 mass % 7.1 7.2 ple 7 OASYS poly(N,N- (registered diethylacrylamide) trademark)” Exam- Production <1 0.04 mass % 7.0 7.1 ple 8 Example 1 acrylic acid/ N,N-diethylacrylamide copolymer Exam- Production <1 0.04 mass % 7.1 7.2 ple 9 Example 1 poly(N,N- diethylacrylamide) Exam- PF catheter <1 0.04 mass % 7.0 7.1 ple 10 tube acrylic acid/ N,N-diethylacrylamide copolymer Exam- PF catheter <1 0.04 mass % 7.1 7.2 ple 11 tube poly(N,N- diethylacrylamide) Exam- “MICTRON <1 0.04 mass % 7.0 7.2 ple 12 (registered acrylic acid/ trademark)” N,N-diethylacrylamide copolymer Exam- “MICTRON <1 0.04 mass % 7.1 7.3 ple 13 (registered poly(N,N- trademark)” diethylacrylamide) Exam- “1-DAY 58.0 0.04 mass % 7.0 7.1 ple 14 ACUVUE acrylic acid/ (registered N,N-diethylacrylamide trademark)” copolymer Exam- “1-DAY 58.0 0.04 mass % 7.1 7.2 ple 15 ACUVUE poly(N,N- (registered diethylacrylamide) trademark)” Exam- “ACUVUE 38.0 0.05 mass % 7.0 7.1 ple 16 OASYS N,N-dimethylacryl- (registered amide/ trademark)” N,N-diethylacrylamide copolymer Exam- “ACUVUE 38.0 0.05 mass % 7.0 7.1 ple 17 OASYS acrylic acid/ (registered N,N-dimethylamino- trademark)” propyl acrylamide methyl chloride quaternary salt/ N,N-diethylacrylamide copolymer Exam- Production <1 0.05 mass % 7.0 7.1 ple 18 Example 1 acrylic acid/ N,N-diethylacrylamide copolymer Exam- Production <1 0.03 mass % 7.0 7.0 ple 19 Example 1 acrylic acid/ N,N-diethylacrylamide copolymer

TABLE-US-00003 TABLE 2 Liquid film retention Film Amount of time 2 Water thickness change of Liquid film hours after content of Results of elemental of water retention scrubbing medical composition analysis of hydrophilic content time and washing device hydrophilic polymer (percentage Friction (sec) (sec) (mass %) polymer layer layer (nm) point) coefficient Example A (120 sec) A (120 sec) 54.5 Coating polymer was 15 0.5 0.205 1 separated into two layers (one of layers is mixed with substrate) Example A (120 sec) A (120 sec) 54.3 Coating polymer was 16 0.3 0.249 2 separated into two layers (one of layers is mixed with substrate) Example A (120 sec) A (120 sec) 54.2 Coating polymer was 13 0.2 0.224 3 separated into two layers (one of layers is mixed with substrate) Example A (120 sec) A (120 sec) 54.2 Coating polymer was 10 0.2 0.289 4 separated into two layers (one of layers is mixed with substrate) Example A (120 sec) A (120 sec) 38.2 Coating polymer was 12 0.2 0.150 5 separated into two layers (one of layers is mixed with substrate) Example A (120 sec) A (120 sec) 38.5 Coating polymer was 10 0.5 0.179 6 separated into two layers (one of layers is mixed with substrate) Example A (120 sec) A (120 sec) 38.3 Coating polymer mixed 9 0.3 0.250 7 with substrate, and coating polymer alone Example A (60 sec)  A (60 sec)  1.9 Coating polymer mixed 10 1.9 0.245 8 with substrate, and coating polymer alone Example A (60 sec)  A (60 sec)  1.5 Coating polymer mixed 11 1.5 0.179 9 with substrate, and coating polymer alone Example A (120 sec) A (120 sec) 0.9 Coating polymer mixed 9 0.9 Not measurable 10 with substrate, and because medical coating polymer alone device had tubular shape Example A (120 sec) A (120 sec) 0.9 Coating polymer mixed 8 0.9 Not measurable 11 with substrate, and because medical coating polymer alone device had tubular shape Example B (15 sec)  B (15 sec)  0.3 Coating polymer mixed 5 0.3 Not measurable 12 with substrate, and because medical coating polymer alone device had sheet shape Example B (15 sec)  B (15 sec)  0.4 Coating polymer mixed 4 0.4 Not measurable 13 with substrate, and because medical coating polymer alone device had sheet shape Example A (120 sec) A (120 sec) 58.3 Coating polymer mixed 10 0.3 0.290 14 with substrate, and coating polymer alone Example A (120 sec) A (120 sec) 58.4 Coating polymer mixed 10 0.4 0.283 15 with substrate, and coating polymer alone Example A (120 sec) A (120 sec) 38.6 Coating polymer mixed 15 0.6 0.149 16 with substrate, and coating polymer alone Example A (120 sec) A (120 sec) 38.5 Coating polymer mixed 12 0.5 0.138 17 with substrate, and coating polymer alone Example A (120 sec) A (120 sec) 1.8 Coating polymer mixed 15 1.8 0.175 18 with substrate, and coating polymer alone Example A (60 sec)  A (60 sec)  1.5 Coating polymer mixed 12 1.5 0.170 19 with substrate, and coating polymer alone

TABLE-US-00004 TABLE 3 Tensile Tensile elastic Tensile elastic modulus of elastic Size of Lipid modulus of medical modulus Size of medical Size change adhesion substrate device change rate substrate device rate amount (MPa) (MPa) (%) (mm) (mm) (%) Example No 0.61 0.61 0.2 14.20 14.21 0.07 1 adhesion Example No 0.61 0.60 −0.9 14.20 14.22 0.14 2 adhesion Example No 0.61 0.61 0.7 14.20 14.16 −0.28 3 adhesion Example No 0.61 0.62 1.4 14.20 14.15 −0.35 4 adhesion Example No 0.70 0.72 2.9 14.20 14.21 0.07 5 adhesion Example No 0.70 0.73 4.3 14.20 14.31 0.77 6 adhesion Example No 0.70 0.72 2.9 14.20 14.22 0.14 7 adhesion Example No 0.53 0.55 3.7 14.20 14.15 −0.35 8 adhesion Example No 0.53 0.56 5.6 14.20 14.18 −0.14 9 adhesion Example No Not measurable Not measurable Not measurable Not measurable Not measurable Not measurable 10 adhesion because medical because medical because medical because medical because medical because medical device had device had device had device had device had device had tubular shape tubular shape tubular shape tubular shape tubular shape tubular shape Example No Not measurable Not measurable Not measurable Not measurable Not measurable Not measurable 11 adhesion because medical because medical because medical because medical because medical because medical device had device had device had device had device had device had tubular shape tubular shape tubular shape tubular shape tubular shape tubular shape Example No 1.10 1.15 4.5 15.00 15.10 0.66 12 adhesion Example No 1.10 1.15 4.5 15.00 15.10 0.66 13 adhesion Example No 0.3 0.31 3.3 14.20 14.22 0.14 14 adhesion Example No 0.3 0.31 3.3 14.20 14.28 0.56 15 adhesion Example No 0.70 0.72 2.9 14.20 14.32 0.84 16 adhesion Example No 0.70 0.72 2.9 14.20 14.29 0.63 17 adhesion Example No 0.53 0.55 3.7 14.20 14.19 −0.07 18 adhesion Example No 0.53 0.55 3.7 14.20 14.21 0.07 19 adhesion

Comparative Example 1

[0190] A commercially available silicone hydrogel lens “MyDay (registered trademark)” (manufactured by CooperVision Japan, Inc., stenfilcon A) containing silicone as a main component was immersed in a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 2

[0191] As a substrate, a commercially available silicone hydrogel lens “MyDay (registered trademark)” (manufactured by CooperVision Japan, Inc., stenfilcon A) containing silicone as a main component was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of an acrylic acid/acrylamide copolymer (molar ratio of copolymerization: 1/9, Mw: 250,000, internally manufactured) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 3

[0192] As a substrate, a commercially available silicone hydrogel lens “MyDay (registered trademark)” (manufactured by CooperVision Japan, Inc., stenfilcon A) containing silicone as a main component was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of an acrylic acid/N,N-dimethylacrylamide copolymer (molar ratio of copolymerization: 1/9, Mw: 200,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 4

[0193] As a substrate, a commercially available silicone hydrogel lens “MyDay (registered trademark)” (manufactured by CooperVision Japan, Inc., stenfilcon A) containing silicone as a main component was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of an acrylic acid/N,N-dimethylacrylamide copolymer (molar ratio of copolymerization: 1/9, Mw: 800,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 5

[0194] As a substrate, a commercially available silicone hydrogel lens “MyDay (registered trademark)” (manufactured by CooperVision Japan, Inc., stenfilcon A) containing silicone as a main component was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of an acrylic acid/acryloylmorpholine copolymer (molar ratio of copolymerization: 1/9, Mw: 500,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 6

[0195] As a substrate, a commercially available silicone hydrogel lens “MyDay (registered trademark)” (manufactured by CooperVision Japan, Inc., stenfilcon A) containing silicone as a main component was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of an acrylic acid/acryloylmorpholine copolymer (molar ratio of copolymerization: 1/9, Mw: 320,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 7

[0196] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of an acrylic acid/vinylpyrrolidone/N,N-dimethylacrylamide copolymer (molar ratio of copolymerization: 1/1/2, Mw: 550,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 8

[0197] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of an acrylic acid/vinylpyrrolidone/N,N-dimethylacrylamide copolymer (molar ratio of copolymerization: 1/1/2, Mw: 330,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 9

[0198] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of an acrylic acid/vinylpyrrolidone/N,N-dimethylacrylamide copolymer (molar ratio of copolymerization: 1/1/8, Mw: 500,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 10

[0199] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of an acrylic acid/vinylpyrrolidone/N,N-dimethylacrylamide copolymer (molar ratio of copolymerization: 1/1/8, Mw: 370,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 11

[0200] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of an acrylic acid/vinylpyrrolidone copolymer (molar ratio of copolymerization: 1/4, Mw: 590,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 12

[0201] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of an acrylic acid/vinylpyrrolidone copolymer (molar ratio of copolymerization: 1/9, Mw: 390,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 13

[0202] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of an acrylic acid/2-hydroxyethyl methacrylate/N,N-dimethylacrylamide copolymer (molar ratio of copolymerization: 1/1/2, Mw: 430,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 14

[0203] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of an acrylic acid/2-hydroxyethyl methacrylate/N,N-dimethylacrylamide copolymer (molar ratio of copolymerization: 1/1/8, Mw: 480,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 15

[0204] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of polyvinylpyrrolidone (Mw: 360,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 16

[0205] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was used. The substrate was immersed in a solution obtained by adding 0.03 mass % of poly(N,N-dimethylacrylamide) (Mw: 360,000, manufactured by OSAKA ORGANIC CHEMICAL INDUSTRY LTD.) to a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 17

[0206] As a substrate, a commercially available silicone hydrogel lens “ACUVUE OASYS (registered trademark)” (manufactured by Johnson & Johnson K.K., senofilcon A) containing polyvinylpyrrolidone and silicone as main components was immersed in a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 18

[0207] As a substrate, the molded article obtained in Production Example 1 was immersed in a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 19

[0208] As a substrate, a commercially available hydrogel lens “1-DAY ACUVUE (registered trademark)” (manufactured by Johnson & Johnson K.K., etafilcon A) containing 2-hydroxyethyl methacrylate as a main component was immersed in a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

[0209] The substrate of this comparative example had a relatively satisfactory liquid film retention time and had good durability even without the application of the manufacturing method of the present invention. However, in comparison with Examples 14 and 15 in which the manufacturing method of the present invention was applied to the same substrate, it was shown that application of the manufacturing method of the present invention significantly improves the liquid film retention time (20 seconds.fwdarw.120 seconds).

Comparative Example 20

[0210] As a substrate, a commercially available PF catheter tube (manufactured and sold by Toray Industries, Inc.) containing polyurethane as a main component was immersed in a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

Comparative Example 21

[0211] As a substrate, a commercially available film “MICTRON (registered trademark)” (manufactured by Toray Industries, Inc.) containing a para-type aromatic polyamide (aramid) as a main component was immersed in a phosphate buffer solution, and sterilized in an autoclave at 121° C. for 30 minutes. The results of evaluating the obtained medical device (no hydrophilic polymer layer was observed) by the above-mentioned methods are shown in Tables 4 to 6.

TABLE-US-00005 TABLE 4 Water Hydrophilic content polymer and of concentration of pH pH substrate hydrophilic Before After (mass polymer sterili- sterili- Substrate %) solution zation zation Com- “MyDay 54.0 No 7.0 7.2 parative (registered Exam- trademark)” ple 1 Com- “MyDay 54.0 0.03 mass % 7.0 7.2 parative (registered acrylic acid/ Exam- trademark)” acrylamide ple 2 copolymer Com- “MyDay 54.0 0.03 mass % 7.0 7.1 parative (registered acrylic acid/ Exam- trademark)” N,N-dimethyl- ple 3 acrylamide copolymer Com- “MyDay 54.0 0.03 mass % 7.0 7.1 parative (registered acrylic acid/ Exam- trademark)” N,N-dimethyl- ple 4 acrylamide copolymer Com- “MyDay 54.0 0.03 mass % 7.0 7.2 parative (registered acrylic Exam- trademark)” acid/acryloylmor- ple 5 pholine copolymer Com- “MyDay 54.0 0.03 mass % 7.0 7.2 parative (registered acrylic Exam- trademark)” acid/acryloylmor- ple 6 pholine copolymer Com- “ACUVUE 38.0 0.03 mass % 7.0 7.0 parative OASYS acrylic Exam- (registered acid/vinylpyrro- ple 7 trademark)” lidone/ N,N-dimethyl- acrylamide copolymer Com- “ACUVUE 38.0 0.03 mass % 7.0 7.1 parative OASYS acrylic Exam- (registered acid/vinylpyrro- ple 8 trademark)” lidone/ N,N-dimethyl- acrylamide copolymer Com- “ACUVUE 38.0 0.03 mass % 7.0 7.2 parative OASYS acrylic Exam- (registered acid/vinylpyrro- ple 9 trademark)” lidone/ N,N-dimethyl- acrylamide copolymer Com- “ACUVUE 38.0 0.03 mass % 7.0 7.2 parative OASYS acrylic Exam- (registered acid/vinylpyrro- ple 10 trademark)” lidone/ N,N-dimethyl- acrylamide copolymer Com- “ACUVUE 38.0 0.03 mass % 7.0 7.1 parative OASYS acrylic Exam- (registered acid/vinylpyrro- ple 11 trademark)” lidone copolymer Com- “ACUVUE 38.0 0.03 mass % 7.0 7.2 parative OASYS acrylic Exam- (registered acid/vinylpyrro- ple 12 trademark)” lidone copolymer Com- “ACUVUE 38.0 0.03 mass % 7.0 7.1 parative OASYS acrylic acid/ Exam- (registered 2-hydroxyethyl ple 13 trademark)” methacrylate/ N,N-dimethyl- acrylamide copolymer Com- “ACUVUE 38.0 0.03 mass % 7.0 7.1 parative OASYS acrylic acid/ Exam- (registered 2-hydroxyethyl ple 14 trademark)” methacrylate/ N,N-dimethyl- acrylamide copolymer Com- “ACUVUE 38.0 0.03 mass % 7.0 7.2 parative OASYS polyvinylpyrro- Exam- (registered lidone ple 15 trademark)” Com- “ACUVUE 38.0 0.03 mass % 7.1 7.2 parative OASYS poly(N,N- Exam- (registered dimethyl- ple 16 trademark)” acrylamide) Com- “ACUVUE 38.0 No 7.0 7.2 parative OASYS Exam- (registered ple 17 trademark)” Com- Production <1 No 7.0 7.0 parative Example 1 Exam- ple 18 Com- “1-DAY 58.0 No 7.0 7.1 parative ACUVUE Exam- (registered ple 19 trademark)” Com- PF catheter <1 No 7.0 7.1 parative tube Exam- ple 20 Com- “MICTRON <1 No 7.0 7.1 parative (registered Exam- trademark)” ple 21

TABLE-US-00006 TABLE 5 Liquid film retention Film Amount of time 2 Water thickness change of Liquid film hours after content of of water retention scrubbing medical Results of elemental hydrophilic content time and washing device composition analysis of polymer (percentage Friction (sec) (sec) (mass %) hydrophilic polymer layer layer (nm) point) coefficient Comparative D (1 sec) D (1 sec) 54.0 No layer observed 0 0 0.355 Example 1 Comparative D (1 sec) D (1 sec) 54.0 No layer observed 0 0 0.342 Example 2 Comparative D (1 sec) D (1 sec) 54.1 No layer observed 0 0.1 0.339 Example 3 Comparative D (1 sec) D (1 sec) 54.1 No layer observed 0 0.1 0.349 Example 4 Comparative D (4 sec) D (1 sec) 54.1 No layer observed 0 0.1 0.351 Example 5 Comparative D (4 sec) D (1 sec) 54.0 No layer observed 0 0 0.350 Example 6 Comparative D (1 sec) D (1 sec) 38.0 No layer observed 0 0 0.250 Example 7 Comparative D (1 sec) D (1 sec) 38.0 No layer observed 0 0 0.252 Example 8 Comparative D (1 sec) D (1 sec) 38.0 No layer observed 0 0 0.255 Example 9 Comparative D (1 sec) D (1 sec) 38.0 No layer observed 0 0 0.249 Example 10 Comparative D (1 sec) D (1 sec) 38.0 No layer observed 0 0 0.248 Example 11 Comparative D (1 sec) D (1 sec) 38.0 No layer observed 0 0 0.257 Example 12 Comparative D (1 sec) D (1 sec) 38.0 No layer observed 0 0 0.260 Example 13 Comparative D (1 sec) D (1 sec) 38.0 No layer observed 0 0 0.259 Example 14 Comparative D (1 sec) D (1 sec) 38.0 No layer observed 0 0 0.263 Example 15 Comparative D (1 sec) D (1 sec) 38.0 No layer observed 0 0 0.266 Example 16 Comparative D (1 sec) D (1 sec) 38.0 No layer observed 0 0 0.300 Example 17 Comparative E (less.sup.  E (less.sup.  <1 No layer observed 0 0 0.850 Example 18 than 1 sec) than 1 sec) Comparative  A (20 sec)  A (20 sec) 58.0 No layer observed 0 0 0.460 Example 19 Comparative E (less.sup.  E (less.sup.  <1 No layer observed 0 0 Not measurable Example 20 than 1 sec) than 1 sec) because medical device had tubular shape Comparative E (less.sup.  E (less.sup.  <1 No layer observed 0 0 Not measurable Example 21 than 1 sec) than 1 sec) because medical device had sheet shape

TABLE-US-00007 TABLE 6 Tensile Tensile elastic Tensile elastic modulus of elastic Size of Lipid modulus of medical modulus Size of medical Size change adhesion substrate device change rate substrate device rate amount (MPa) (MPa) (%) (mm) (mm) (%) Comparative Adhered to 0.61 Not Not 14.20 Not Not Example 1 ⅕ of measured measured measured measured total area Comparative Adhered to 0.61 0.60 −1.1 14.20 14.20 0 Example 2 ⅕ of total area Comparative Adhered to 0.61 0.61 0.1 14.20 14.19 −0.07 Example 3 ⅕ of total area Comparative Adhered to 0.61 0.61 0.3 14.20 14.17 −0.20 Example 4 ⅕ of total area Comparative Adhered to 0.61 0.61 0.2 14.20 14.19 −0.07 Example 5 ⅕ of total area Comparative Adhered to 0.61 0.61 0.2 14.20 14.21 0.07 Example 6 ⅕ of total area Comparative Adhered to 0.70 0.73 4.3 14.20 14.21 0.07 Example 7 ⅕ of total area Comparative Adhered to 0.71 0.70 −1.3 14.20 14.20 0 Example 8 ⅕ of total area Comparative Adhered to 0.71 0.70 −1.4 14.20 14.19 −0.07 Example 9 ⅕ of total area Comparative Adhered to 0.71 0.71 0.16 14.20 14.22 0.14 Example 10 ⅕ of total area Comparative Adhered to 0.71 0.71 0.16 14.20 14.21 0.07 Example 11 ⅕ of total area Comparative Adhered to 0.71 0.70 −2.4 14.20 14.20 0.04 Example 12 ⅕ of total area Comparative Adhered to 0.71 0.70 −1.1 14.20 14.20 0.01 Example 13 ⅕ of total area Comparative Adhered to 0.71 0.71 0.8 14.20 14.21 0.07 Example 14 ⅕ of total area Comparative Adhered to 0.71 0.71 0.9 14.20 14.22 0.14 Example 15 ⅕ of total area Comparative Adhered to 0.71 0.71 0.7 14.20 14.23 0.21 Example 16 ⅕ of total area Comparative Adhered to 0.71 0.71 0 14.20 14.20 0 Example 17 ⅕ of total area Comparative Adhered to 0.53 0.53 0 14.20 14.20 0 Example 18 whole surface Comparative No adhesion 0.30 0.30 0 14.20 14.20 0 Example 19 Comparative Adhered to Not measurable Not measurable 0 Not measurable Not measurable Not measurable Example 20 whole because medical because medical because medical because medical because medical surface device had device had device had device had device had tubular shape tubular shape tubular shape tubular shape tubular shape Comparative Adhered to 1.10 1.10 0 15.00 15.00 0 Example 21 whole surface