COMPOSITION, CONTACT LENS COATING AGENT, METHOD FOR PRODUCING CONTACT LENS, AND CONTACT LENS

Abstract

The present invention relates to: a composition; a contact lens coating agent; a method of producing a contact lens; and a contact lens. The composition contains: a polymer which includes a repeating unit (A) having an HLB value of 14 or higher and a repeating unit (B) having an HLB value of 1 to less than 14; and a cationic group-containing bactericidal compound.

Claims

1. A composition comprising: a polymer which comprises a repeating unit (A) having an HLB value of 14 or higher and a repeating unit (B) having an HLB value of 1 to less than 14; and a cationic group-containing bactericidal compound.

2. The composition according to claim 1, wherein the polymer is soluble in water.

3. The composition according to claim 1, wherein the repeating unit (A) comprises a structural unit represented by Formula (1): ##STR00010## wherein, R.sup.1 represents a hydrogen atom or a methyl group; R.sup.2 represents O, *-(CO)O, *-(CO)NR.sup.4, or *-NR.sup.4(CO) where R.sup.4 represents a hydrogen atom or an organic group having 1 to 10 carbon atoms, and * represents a position at which the group is bound to the carbon atom bound with R.sup.1 in the Formula (1); and R.sup.3 represents an organic group having 1 to 100 carbon atoms, with a proviso that, when R.sup.2 is *-(CO)NR.sup.4 or *-NR.sup.4(CO), R.sup.3 and R.sup.4 may be bound together to form a ring.

4. The composition according to claim 1, wherein the repeating unit (B) comprises a structural unit represented by Formula (2) or (3): ##STR00011## wherein, R.sup.5 represents a hydrogen atom or a methyl group; R.sup.6 represents O, *-(CO)O, *-(CO)NR.sup.8 or *-NR.sup.8(CO) where R.sup.8 represents a hydrogen atom or an organic group having 1 to 10 carbon atoms, and * represents a position at which the group is bound to the carbon atom bound with R.sup.5 in the Formula (2); and R.sup.7 represents an organic group having 3 to 100 carbon atoms, with a proviso that, when R.sup.6 is *-(CO)NR.sup.8 or *-NR.sup.8(CO), R.sup.7 and R.sup.8 may be bound together to form a ring; or ##STR00012## wherein, R.sup.9 represents a hydrogen atom or a methyl group; R.sup.10 represents O, *-(CO)O, *-(CO)NR.sup.17, *-NR.sup.17(CO) where R.sup.17 represents a hydrogen atom or an organic group having 1 to 10 carbon atoms, and * represents a position at which the group is bound to the carbon atom bound with R.sup.9 in the Formula (3), or a phenylene group; R.sup.11 represents a divalent organic group having 1 to 10 carbon atoms; R.sup.12 and R.sup.13 each independently represent an organic group having 1 to 10 carbon atoms; R.sup.14, R.sup.15 and R.sup.16 each independently represent OSi(R.sup.18).sub.3 where each R.sup.18 independently represents a hydrogen atom or an organic group having 1 to 8 carbon atoms, or an organic group having 1 to 10 carbon atoms; and n represents 0 to 200 as an average value.

5. The composition according to claim 1, wherein the repeating unit (A) comprises at least one structural unit selected from the group consisting of a repeating unit (A1) represented by Formula (A1), a repeating unit (A2) represented by Formula (A2), a repeating unit (A3) represented by Formula (A3), a repeating unit (A4) represented by Formula (A4), a repeating unit (A5) represented by Formula (A5), and a repeating unit (A6) represented by Formula (A6): ##STR00013## wherein, R.sup.a represents a hydrogen atom or a methyl group; R.sup.b represents O, *-(CO)O, *-(CO)NR.sup.e, or *-NR.sup.e(CO) where R.sup.e represents a hydrogen atom or an organic group having 1 to 10 carbon atoms, and * represents a position at which the group is bound to the carbon atom bound with R.sup.a in the Formula (A1); and R.sup.e represents a polyoxyalkylene group; and R.sup.d represents a hydrogen atom or an alkyl group having 1 to 15 carbon atoms, with a proviso that a total number of carbon atoms of R.sup.e and R.sup.d is 100 or less; ##STR00014## wherein, R.sup.19 represents a hydrogen atom or a methyl group; R.sup.20 represents an alkylene group having 2 to 4 carbon atoms; R.sup.21 represents an alkylene group having 1 to 10 carbon atoms; R.sup.22, R.sup.23 and R.sup.24 each independently represent a hydrogen atom or a hydrocarbon group having 1 to 8 carbon atoms; and q represents 1 to 10 as an average value; ##STR00015## wherein, Y represents (CO)O, (OSO)O.sup., O(OSO)O.sup., (SO)O.sup., O(SO)O.sup., OP(O)(OR.sup.30)O.sup., OP(O)(R.sup.30)O.sup., P(O)(OR.sup.30)O.sup., or P(O)(R.sup.30)O.sup. where R.sup.30 represents an alkyl group having 1 to 3 carbon atoms; R.sup.25 represents a hydrogen atom or a methyl group; R.sup.26 represents a divalent organic group having 1 to 10 carbon atoms; R.sup.27 and R.sup.28 each independently represent a hydrocarbon group having 1 to 10 carbon atoms; and R.sup.29 represents a divalent organic group having 1 to 10 carbon atoms; ##STR00016## wherein, R.sup.31 represents a hydrogen atom or a methyl group; R.sup.32 and R.sup.33 each independently represent a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or a hydroxyalkyl group having 1 to 6 carbon atoms; ##STR00017## wherein, R.sup.34 represents a hydrogen atom or a methyl group; and R.sup.35 and R.sup.36 each independently represent an alkylene group having 1 to 3 carbon atoms; and ##STR00018## wherein, R.sup.37 represents a hydrogen atom or a methyl group; and R.sup.38 represents an alkylene group having 1 to 5 carbon atoms.

6. The composition according to claim 1, comprising the polymer in an amount of from 0.001 to 10% by mass.

7. The composition according to claim 1, which is an ophthalmic composition, a cleaning composition, a cosmetic composition, a medical composition, or a quasi drug composition.

8. The composition according to claim 1, which is a contact lens cleaning solution, a contact lens solution, a contact lens fitting liquid, an eye wash, or an eye drop.

9. A contact lens coating agent, comprising a polymer which comprises a repeating unit (A) having an HLB value of 14 or higher and a repeating unit (B) having an HLB value of 1 to less than 14.

10. A method of producing a contact lens, comprising coating a contact lens coating agent according to claim 9, on at least a part of a surface of a contact lens.

11. A contact lens comprising, on at least a part of a surface thereof, a contact lens coating agent according to claim 9.

12. A silicone hydrogel contact lens comprising, on at least a part of a surface thereof, a contact lens coating agent according to claim 9.

Description

EXAMPLES

[0125] The present invention will now be described in detail by way of examples thereof; however, the present invention is not restricted to the following examples.

<Measurement of Molecular Weight>

[0126] The weight-average molecular weight (Mw) and the number-average molecular weight (Mn) were measured by gel permeation chromatography (GPC) based on a polystyrene standard, using a TSKgel -M column manufactured by Tosoh Corporation under the following analysis conditions: flow rate=0.5 mL/min, elution solvent=NMP solvent (H.sub.3PO.sub.4: 0.016 M, LiBr: 0.030 M), and column temperature=40 C. Further, from the thus measured Mw and Mn, the molecular weight distribution (Mw/Mn) was calculated.

<NMR Spectrum>

[0127] The .sup.1H-NMR spectrum was measured by Model AVANCE 500 (500 MHz) manufactured by Bruker Corp. using d.sub.6-DMSO as a solvent and DSS-d6 manufactured by Wako Pure Chemical Industries, Ltd. as an internal standard substance.

<Measurement of HLB>

[0128] The HLB values of the repeating units (A) and (B) contained in the polymers obtained below were calculated from the ratio of the organic factor and the inorganic factor as described above (Oda method), and the HLB values of the polymers obtained below were determined from the introduction ratios and the structures of the respective repeating units that were derived from .sup.1H-NMR spectrum measured in the same manner as described above.

<Materials Used>

[0129] The materials used for the synthesis of the polymers described below were as follows.

<Hydrophilic Monomers>

[0130] ACMO: acryloyl morpholine (manufactured by KJ Chemicals Corporation)

[0131] DMAA: N,N-dimethylacrylamide (manufactured by KJ Chemicals Corporation)

[0132] HEAA: N-(2-hydroxyethyl)acrylamide (manufactured by KJ Chemicals Corporation)

[0133] GLBT: N-methacryloyloxyethyl-N,N-dimethylammonium--N-methylcarboxy betaine (manufactured by Osaka Organic Chemical Industry Ltd.)

[0134] NVP: N-vinyl-2-pyrrolidone (manufactured by Wako Pure Chemical Industries, Ltd.)

[0135] MPC: 2-methacryloyloxyethyl-2-(trimethylammonio)ethyl phosphate (manufactured by NOF Corporation)

<Hydrophobic Monomers>

[0136] DDAA: dodecylacrylamide (manufactured by Tokyo Chemical Industry Co., Ltd.)

[0137] NBMA: N-butoxymethylacrylamide (manufactured by MRC Unitec Co., Ltd.)

[0138] TRIS: 3-[tris(trimethylsiloxy)silyl]propyl methacrylate (manufactured by JNC Corporation)

[0139] EHA: 2-ethylhexyl acrylate (manufactured by Wako Pure Chemical Industries, Ltd.)

<Polymerization Initiators>

[0140] AIBN: 2,2-azobis(isobutyronitrile) (manufactured by Wako Pure Chemical Industries, Ltd.)

[0141] VA-044: 2,2-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride (manufactured by Wako Pure Chemical Industries, Ltd.)

<Molecular Weight Modifier>

[0142] TG: 1-thioglycerol (manufactured by Asahi Kagaku Kogyo Co., Ltd.)

<Solvents>

[0143] ACN: acetonitrile (manufactured by Wako Pure Chemical Industries, Ltd.)

[0144] EtOH: ethanol (manufactured by Wako Pure Chemical Industries, Ltd.)

[0145] water

Synthesis Example 1

Synthesis of Copolymer (N-1)

[0146] In a flask, 14.25 g of DMAA, 0.75 g of DDAA, 0.3 g of AIBN as a polymerization initiator, and 61.2 g of ACN were added and mixed together. Then, nitrogen was blown into this flask, and the resulting mixture was heated to 70 C. and allowed to polymerize at this temperature for 8 hours, after which the resultant was cooled to room temperature. The thus obtained solution was dialyzed with pure water, whereby a copolymer (N-1) was obtained. In the thus obtained copolymer (N-1), the DMAA content was 95% by mass, and the DDAA content was 5% by mass. It is noted here that these content values were measured by .sup.1H-NMR. The thus obtained copolymer (N-1) had a weight-average molecular weight of 156,000, a number-average molecular weight of 37,000, and a molecular weight distribution of 4.22.

[0147] Further, using the thus obtained copolymer (N-1), a 0.5%-by-mass aqueous solution of the copolymer (N-1) was obtained. This aqueous solution was visually observed, and the copolymer (N-1) was evaluated to be soluble in water when the aqueous solution was transparent.

Synthesis Examples 2 to 6 and 8 to 11

Synthesis of Copolymers (N-2 to N-6 and N-8 to N-11)

[0148] Copolymers (N-2 to N-6 and N-8 to N-11) were obtained in the same manner as in Synthesis Example 1, except that the respective monomer species shown in Table 1 were used in such amounts that yielded amounts (% by mass) of the repeating units (A) and (B) in each copolymer as shown in Table 1; the respective polymerization initiator shown in Table 1 was used in the amount shown in Table 1; and the respective solvent shown in Table 1 was used. Further, using the thus obtained copolymers, 0.5%-by-mass aqueous solutions of the copolymer (N-2) to (N-6) and (N-8) to (N-10) were each obtained. It is noted here that, when the copolymer (N-11) was used, an aqueous solution could not be prepared due to cloudiness.

Synthesis Example 7

Synthesis of Copolymer (N-7)

[0149] A block copolymer (N-7) was synthesized by a widely used RAFT polymerization method using DTMPA (2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid, manufactured by Sigma-Aldrich) as a RAFT (Reversible Addition-Fragmentation Chain Transfer) agent, and DOX (1,4-dioxane, manufactured by Wako Pure Chemical Industries, Ltd.) as a solvent.

[0150] Specifically, 0.4 g of EHA, 0.0326 g of DTMPA, 0.0007 g of AIBN, and 10 mL of DOX were added to a flask and, after subjecting the resulting solution to nitrogen bubbling, the solution was stirred at 70 C. for 13 hours. Then, 7.60 g of DMAA and 10 mL of DOX were added thereto, and the resultant was further stirred at 70 C. for 24 hours. After the completion of the reaction, the reaction solution was added to diethyl ether and further washed with diethyl ether three times, after which the resultant was vacuum-dried, whereby an A-B type block copolymer (N-7) was synthesized.

[0151] Thereafter, the thus obtained copolymer was dissolved in water to obtain a 0.5%-by-mass aqueous solution.

Reference Examples 1 and 2

Synthesis of (Co)polymers (N-12 and N-13)

[0152] (Co)polymers (N-12 and N-13) were obtained in the same manner as in Synthesis Example 1, except that the respective monomer species shown in Table 1 were used in such amounts that yielded amounts (% by mass) of the repeating units (A) and (B) in each (co)polymer as shown in Table 1; the respective polymerization initiator and molecular weight modifier shown in Table 1 were used in the amounts shown in Table 1; and the respective solvent shown in Table 1 was used.

[0153] Thereafter, the thus obtained (co)polymers were each dissolved in water at a concentration of 0.5% by mass to obtain aqueous solutions.

[0154] It is noted here that the amounts (parts) of the polymerization initiators and molecular weight modifiers shown in Table 1 mean parts by mass of the respective polymerization initiators and molecular weight modifiers with respect to a total of 100 parts by mass of the monomers.

TABLE-US-00001 TABLE 1 Synthesis Examples and Reference Examples Synthesis Synthesis Synthesis Synthesis Synthesis Synthesis Synthesis Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Polymer Repeating unit (A-1)-forming DMAA HEAA DMAA HEAA NVP MPC DMAA synthesis monomer species materials Repeating unit (A-2)-forming monomer species Repeating unit (B)-forming DDAA DDAA NBMA TRIS TRIS TRIS EHA monomer species Polymerization initiator AIBN AIBN AIBN AIBN AIBN AIBN AIBN 2 parts 2 parts 2 parts 2 parts 2 parts 2 parts 0.009 parts Solvent ACN EtOH ACN EtOH ACN EtOH DOX Molecular weight modifier DTMPA 0.42 parts Polymer Temperature [ C.] 70 70 70 70 70 70 70 synthesis Time [hr] 8 8 8 8 8 8 24 conditions Polymer name N-1 N-2 N-3 N-4 N-5 N-6 N-7 Polymer Amount of repeating unit 95.0 95.0 85.0 95.0 98.0 95.0 95.0 formulation (A-1) [% by mass] HLB of repeating unit (A-1) 22.2 30.0 22.2 30.0 17.6 33.3 22.2 Amount of repeating unit (A-2) [% by mass] HLB of repeating unit (A-2) Amount of repeating unit 5.0 5.0 15.0 5.0 2.0 5.0 5.0 (B) [% by mass] HLB of repeating unit (B) 6.7 6.7 13.8 3.6 3.6 3.6 2.9 Polymer Polymer HLB 21.2 28.4 20.8 28.8 17.3 32.8 21.0 properties Weight-average molecular 15.6 4.5 14.8 4.3 8.5 2.5 8.0 weight (10,000) Number-average molecular 3.7 1.8 3.6 1.9 1.9 1.2 6.5 weight (10,000) Molecular weight distribution 4.22 2.50 4.10 2.26 4.47 2.08 1.23 Solubility in water transparent transparent transparent transparent transparent transparent transparent (0.5% by weight) Synthesis Examples and Reference Examples Synthesis Synthesis Synthesis Synthesis Reference Example 8 Example 9 Example 10 Example 11 Example 1 Reference Example 2 Polymer Repeating unit (A-1)-forming GLBT ACMO DMAA DMAA DMAA HEAA synthesis monomer species materials Repeating unit (A-2)-forming GLBT monomer species Repeating unit (B)-forming DDAA DDAA DDAA DDAA monomer species Polymerization initiator AIBN AIBN AIBN AIBN VA-044 VA-044 2 parts 2 parts 2 parts 2 parts 4 parts 4 parts Solvent EtOH ACN EtOH EtOH water water Molecular weight modifier TG TG 0.1 parts 0.2 parts Polymer Temperature [ C.] 70 70 70 70 60 80 synthesis Time [hr] 8 8 8 8 8 8 conditions Polymer name N-8 N-9 N-10 N-11 N-12 N-13 Polymer Amount of repeating unit 95.0 95.0 90.0 60.0 100.0 100.0 formulation (A-1) [% by mass] HLB of repeating unit (A-1) 41.8 17.7 22.2 22.2 22.2 30.0 Amount of repeating unit 5.0 (A-2) [% by mass] HLB of repeating unit (A-2) 41.8 Amount of repeating unit 5.0 5.0 5.0 40.0 (B) [% by mass] HLB of repeating unit (B) 6.7 6.7 6.7 6.7 Polymer Polymer HLB 40.3 17.6 22.8 14.8 22.2 30.0 properties Weight-average molecular 3.6 13.9 4.4 16.4 18.3 17.3 weight (10,000) Number-average molecular 1.5 4.5 1.7 4.5 5.5 5.9 weight (10,000) Molecular weight distribution 2.40 3.09 2.59 3.64 3.33 2.93 Solubility in water transparent transparent transparent cloudy transparent transparent (0.5% by weight)

Example 1

[0155] A liquid agent was obtained by mixing 0.5 parts by mass of the copolymer (N-1) obtained in Synthesis Example 1, 0.0001 parts by mass of polyhexamethylene biguanide (hereinafter, also referred to as PHMB), and 99.5 parts by mass of physiological saline.

Examples 2 to 10

[0156] Liquid agents were each obtained in the same manner as in Example 1 by mixing 0.5 parts by mass of the respective copolymers (N-2) to (N-10) obtained in Synthesis Examples 2 to 10, 0.0001 parts by mass of PHMB, and 99.5 parts by mass of physiological saline.

Example 11

[0157] A liquid agent was obtained by mixing 0.5 parts by mass of the copolymer (N-1) obtained in Synthesis Example 1, 0.003 parts by mass of benzalkonium chloride, and 99.5 parts by mass of physiological saline.

Example 12

[0158] A liquid agent was obtained in the same manner as in Example 11 by mixing 0.5 parts by mass of the copolymer (N-4) obtained in Synthesis Example 4, 0.003 parts by mass of benzalkonium chloride, and 99.5 parts by mass of physiological saline.

Comparative Examples 1 and 2

[0159] Liquid agents were each obtained in the same manner as in Example 1 by mixing 0.5 parts by mass of the respective copolymers (N-12) and (N-13) obtained in Reference Examples 1 and 2, 0.0001 parts by mass of PHMB, and 99.5 parts by mass of physiological saline.

Comparative Example 3

[0160] A liquid agent was obtained in the same manner as in Example 11 by mixing 0.5 parts by mass of the copolymer (N-12) obtained in Reference Example 1, 0.003 parts by mass of benzalkonium chloride, and 99.5 parts by mass of physiological saline.

[0161] In the following tests, the below-described Controls 1 and 2 were used as controls.

[0162] As Control 1, a liquid agent obtained by mixing 0.0001 parts by mass of PHMB and 100.0 parts by mass of physiological saline was used. Further, as Control 2, a liquid agent obtained by mixing 0.003 parts by mass of benzalkonium chloride and 100.0 parts by mass of physiological saline was used.

Test Example 1

Lipid Cleaning Test

[0163] First, prior to the test, a lipid solution was prepared by heat-dissolving 1% by mass of Sudan Black B (dye) in 99% by mass of lipid triglyceride, and 200 L of this lipid solution was added dropwise to a screw cap bottle such that a smooth solution surface was obtained, after which the solution was cooled at room temperature, whereby a screw cap bottle containing colored pseudo-eye discharge pellets was prepared.

[0164] Subsequently, 1 mL of each of the liquid agents of Examples 1 to 12, Comparative Examples 1 to 3 and Controls 1 and 2 was added to this pellet-containing screw cap bottle, and the bottle was shaken at room temperature for 14 hours to dissolve the colored pseudo-eye discharge pellets. Then, after the completion of the shaking, the resulting solution was taken out of the screw cap bottle, and the absorbance at a wavelength of 570 nm was measured using Model 680 Microplate Reader (manufactured by Bio-Rad Laboratories, Inc.). The results thereof are shown in Table 2.

[0165] It is noted here that a higher absorbance shows a greater colored pseudo-eye discharge pellet-dissolving power, that is, superior lipid-cleaning effect.

[0166] In Table 2, the numerical values of Examples 1 to 10 and Comparative Examples 1 and 2 each indicate the absorbance, taking the absorbance of Control 1 as 0.000. Further, in Table 2, the numerical values of Examples 11 and 12 and Comparative Example 3 each indicate the absorbance, taking the absorbance of Control 2 as 0.000. As shown in Table 2, those liquid agents containing the present polymer (Examples 1 to 12) exhibited a lipid-cleaning power.

[0167] On the other hand, those liquid agents containing a polymer consisting of only the repeating unit (A) (Comparative Examples 1 to 3) exhibited substantially no lipid-cleaning power.

Test Example 2

Disinfecting Effect Test

[0168] Trophozoites of pre-cultured Acanthamoeba (Acanthamoeba castellanii ATCC50370) were collected from a flask, and a suspension thereof having a concentration of 510.sup.5 cells/mL was prepared using a Ringer's solution. Subsequently, 5 mL of each of the liquid agents of Examples 1 to 12, Comparative Examples 1 to 3 and Controls 1 and 2 was placed in a test tube, and 50 L of the thus obtained Acanthamoeba suspension was added to each test tube, followed by stirring, whereby diluted suspensions containing 510.sup.3 cells/mL of the amoeba were prepared.

[0169] Then, after leaving the diluted suspensions for 4 hours at 22 C., 20 L of each suspension was collected, and 10-fold serial dilutions thereof were performed by a method of mixing the suspension with 180 L of a neutralizing solution ( Ringer's solution to which lecithin polysorbate was added). To each diluted suspension of the serial dilution steps, 50 L of Escherichia coli suspension adjusted to 110.sup.8 cfu was added, and the amoeba were cultured in wells for 14 days. After the culturing, the number of remaining amoebae was measured in the wells. From this measured value, the number of remaining amoebae per 1 mL of the diluted suspension after the treatment at 22 C. for 4 hours was calculated. Thereafter, the log reduction value was calculated using the following equation (), and the bactericidal action was evaluated based on the following evaluation criteria. The results thereof are shown in Table 2.

Log reduction=log(Number of amoebae per 1 mL of diluted suspension immediately after preparation)log(Number of remaining amoebae per 1 mL of diluted suspension after treatment at 22 C. for 4 hours) ()

<Evaluation Criteria>

[0170] : The log reduction was 3 or greater.

[0171] : The log reduction was 1 to less than 3.

[0172] : The log reduction was less than 1.

[0173] As shown in Table 2, those liquid agents containing the present polymer (Examples 1 to 12) exhibited a disinfecting effect (bactericidal action) at an equivalent level as the liquid agents containing no polymer (Controls 1 and 2).

Test Example 3

Cytotoxicity Test

[0174] As a commercially available silicone hydrogel contact lens, ACUVUE OASYS (manufactured by Johnson & Johnson K.K.) belonging to the Group II of FDA classification (non-ionic, low water content) was taken out of the wrapping package and allowed to swell in physiological saline maintained at 25 C. Subsequently, the lens was removed from physiological saline and left to stand for about 4 hours in 4 mL of each of the liquid agents of Examples 1 to 12, Comparative Examples 1 to 3 and Controls 1 and 2. Then, the lens was removed from each liquid agent, and immersed again and left to stand for about 4 hours in 4 mL of each of fresh liquid agents of Examples 1 to 12, Comparative Examples 1 to 3 and Controls 1 and 2 that were separately prepared from the liquid agents used above. This operation of immersing the lens in each liquid agent was repeated for a total of 30 times to prepare a treated lens.

[0175] About 100 V79 cells (Chinese hamster lung-derived fibroblasts) were inoculated into a cell culture medium (5%-by-volume fetal bovine serum-added MEM medium) accommodated in wells and left to stand for 4 hours, after which the above-prepared treated lens was placed in each well. Then, the cells were cultured for one week in this state, and the number of colonies was counted. Further, also for control wells in which treated lens was not placed, one-week culturing was performed in the same manner, and the number of colonies was counted. The above-described operations were performed for 4 wells each. Thereafter, the colony formation rate was calculated using the following equation (3) and evaluated based on the following evaluation criteria. The results thereof are shown in Table 2.

Colony formation rate (%)=(Average number of colonies formed in the culture medium in which the treated lens was immersed)/(Average number of colonies formed in the culture medium in which the treated lens was not immersed)100 ()

<Evaluation Criteria>

[0176] : The colony formation rate was 80% or higher.

[0177] : The colony formation rate was 10% to less than 80%.

[0178] : The colony formation rate was less than 10%.

[0179] The liquid agents of Examples 1 to 12 were found to have a low cytotoxicity.

Test Example 4

Lipid Stain Inhibition Test

[0180] First, a homogenized lipid solution was prepared by heat-stirring 1.20% by mass of oleic acid, 1.20% by mass of linoleic acid, 16.23% by mass of tripalmitin, 4.01% by mass of cetyl alcohol, 1.20% by mass of palmitic acid, 16.23% by mass of cetyl palmitate, 1.60% by mass of cholesterol, 1.60% by mass of cholesterol palmitate and 56.73% by mass of lecithin, and 0.5 parts by mass of this lipid solution and 99.5 parts by mass of water were mixed and emulsified to prepare an artificial lipid solution.

[0181] Next, as contact lenses, commercially available contact lenses composed of silicone hydrogel (ACUVUE OASYS, manufactured by Johnson & Johnson K. K.) were prepared and washed with PBS buffer three times. The thus washed contact lenses were immersed in 1 mL of each of the liquid agents of Examples 1 to 12, Comparative Examples 1 to 3 and Controls 1 and 2 and left to stand at room temperature for 2 hours, after which the lenses were taken out of each liquid agent and washed with PBS buffer three times.

[0182] Subsequently, the thus treated contact lenses were each immersed in 1 mL of the above-described artificial lipid solution and, after shaking for 1 hour, the contact lenses were each taken out, washed with PBS buffer three times and vacuum-dried. Then, the contact lenses were each immersed in 1 mL of an ethanol/diethyl ether (75/25% by volume) solution and left to stand for 30 minutes, whereby lipids adhered to each contact lens were extracted. The resulting extracts were each collected in an amount of 0.5 mL in a test tube, and the solvent was evaporated at 90 C. Thereafter, 0.5 mL of concentrated sulfuric acid was added to each test tube from which the solvent had been evaporated, and the resultant was heated for 30 minutes at 90 C. After cooling the thus obtained solution to room temperature, 2.5 mL of a 0.6%-by-mass aqueous vanillin solution/phosphoric acid (20/80% by volume) solution was added to each test tube, which was then maintained for 15 minutes at 37 C. This solution was cooled to room temperature, and the absorbance at 540 nm was subsequently measured using Model 680 Microplate Reader (manufactured by Bio-Rad Laboratories, Inc.).

[0183] Solutions of known lipid concentrations were measured in advance by the same method as described above to prepare a calibration curve, and the weight of lipids adsorbed to each contact lens was determined from the results of measuring the absorbance.

[0184] The test results (comparisons of the amounts of adsorbed lipids) are shown in Table 2. It is noted here that, for Examples 1 to 10 and Comparative Examples 1 and 2, the numerical values shown in Table 2 indicate the values obtained by subtracting the lipid weight of Control 1 from the lipid weight determined in the respective tests and, for Example 11 and 12 and Comparative Example 3, the numerical values shown in Table 2 indicate the values obtained by subtracting the lipid weight of Control 2 from the lipid weight determined in the respective tests.

[0185] As shown in Table 2, when those liquid agents containing the present polymer were used (Examples 1 to 12), a prominent lipid adhesion-inhibiting effect was attained.

[0186] On the other hand, those liquid agents containing a polymer consisting of only the repeating unit (A) (Comparative Examples 1 to 3) exhibited a low lipid adhesion-inhibiting effect.

Test Example 5

Method of Testing Inhibition of PHMB Adsorption

[0187] A liquid agent obtained by mixing 0.0001 parts by mass of PHMB and 100.0 parts by mass of physiological saline was used as a control.

[0188] To a 50-mL centrifuge tube, 2 mL of each of the liquid agents of Examples 1 to 10, Comparative Examples 1 and 2 and Control 1 was added, and a single silicone hydrogel contact lens (ACUVUE OASYS, manufactured by Johnson & Johnson K.K.) was immersed in this liquid agent, after which the centrifuge tube was left to stand in a 35 C. incubator for 24 hours. Then, the contact lens was taken out. To 1 mL of each liquid agent from which the contact lens had been taken out, 0.2 ml of a 0.003-w/v % acetone solution of fluorescamine was added and, after mixing the resulting mixture for 30 seconds, the fluorescence was measured using a spectrofluorometer FP-6200 manufactured by JASCO Corporation (excitation wavelength: 390 nm, wavelength range: 220 to 730 nm, measurement mode: emission). Further, the fluorescence of each liquid agent was also measured in the same manner, except that no contact lens was immersed therein. Using the same liquid agent, the absorbance was measured for a case where the contact lens was immersed and a case where no contact lens was immersed, and the amount of PHMB adsorbed to the contact lens with the use of each liquid agent was determined from the fluorescence intensity at a wavelength showing the maximum fluorescence intensity. The results thereof are shown in Table 2. It is noted here that the adsorption rates shown in Table 2 were calculated using the following equation.

Adsorption rate (%)=B/A100

[0189] A: Amount of adsorbed PHMB when the liquid agent of Control 1 was used.

[0190] B: Amount of adsorbed PHMB when a liquid agent of each test was used.

[0191] As shown in Table 2, when those liquid agents containing the present polymer were used (Examples 1 to 10), a clear PHMB adsorption-inhibiting effect was attained.

[0192] On the other hand, when those liquid agents containing a polymer consisting of only the repeating unit (A) were used (Comparative Examples 1 and 2), no PHMB adsorption-inhibiting effect was observed.

TABLE-US-00002 TABLE 2 Examples and Comparative Examples Example Example Example Example Example Example Example Example Example Example 1 2 3 4 5 6 7 8 9 10 Polymer name N-1 N-2 N-3 N-4 N-5 N-6 N-7 N-8 N-9 N-10 Liquid agent composition ratio (%) Polymer 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 PHMB 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 Benzalkonium 0 0 0 0 0 0 0 0 0 0 chloride Physiological 99.5 99.5 99.5 99.5 99.5 99.5 99.5 99.5 99.5 99.5 saline Test Example 1: 0.040 0.032 0.033 0.033 0.033 0.033 0.033 0.035 0.030 0.039 Lipid cleaning test Test Example 2: Disinfecting effect test Test Example 3: Cytotoxlcity test Test Example 4: 9 11 7 10 15 11 8 7 11 13 Lipid stain Inhibition test Comparison of amounts of adsorbed lipids (g) PHMB 42 38 45 50 48 35 30 56 34 48 adsorption rate (%) Examples and Comparative Examples Example Example Comparative Comparative Comparative 11 12 Example 1 Example 2 Example 3 Control 1 Control 2 Polymer name N-1 N-4 N-12 N-13 N-12 none none Liquid agent composition ratio (%) Polymer 0.5 0.5 0.5 0.5 0.5 0 0 PHMB 0 0 0.0001 0.0001 0 0.0001 0 Benzalkonium 0.003 0.003 0 0 0.003 0 0.003 chloride Physiological 99.5 99.5 99.5 99.5 99.5 100.0 100.0 saline Test Example 1: 0.038 0.033 0.001 0.000 0.001 0.000 0.000 Lipid cleaning test Test Example 2: Disinfecting effect test Test Example 3: Cytotoxlcity test Test Example 4: 10 9 0 0 1 0 0 Lipid stain Inhibition test Comparison of amounts of adsorbed lipids (g) PHMB 97 92 100 adsorption rate (%)

[0193] With regard to the above-described embodiments, the following additional notes are further disclosed.

[Additional Notes]

[0194] A bactericidal composition comprising:

[0195] a polymer which comprises a repeating unit (A) having an HLB value of 14 or higher and a repeating unit (B) having an HLB value of 1 to less than 14; and

[0196] a cationic group-containing bactericidal compound.

[0197] A method of producing a composition comprising a polymer and a bactericidal compound, the method comprising the step of:

[0198] mixing a polymer, which comprises a repeating unit (A) having an HLB value of 14 or higher and a repeating unit (B) having an HLB value of 1 to less than 14, with a cationic group-containing bactericidal compound.