Protein adsorption inhibitors

Abstract

To provide a protein adsorption inhibitor that can suppress the adsorption of proteins to surfaces such as immunoreaction vessels and measuring instruments to a high degree, while also reducing variability between measurements. [Solution] Formula (1): Z-{O-[(PO) a (EO) b ]-(AO) c -H]} x A protein adsorption inhibitor comprising an alkylene oxide derivative represented by (the definition of the symbols in the formula is as described in the specification), wherein the cloud point of a 1% by mass aqueous solution of the alkylene oxide derivative is 0°C or higher and 30°C or lower.

Description

Technical Field

[0001] The present invention relates to a protein adsorption inhibitor.

Background Art

[0002] In the fields of clinical examinations and diagnostic agents used for early detection of diseases, measurement methods utilizing immune reactions are widely used, and improving sensitivity has become a major issue. One of the factors affecting the detection sensitivity when measuring using an immune reaction is the adsorption of the antibody or antigen to be measured, or these labeled substances used for measurement, onto the surfaces of immune reaction containers, measuring instruments, etc. Further, when using substances in which multiple types of biomolecules coexist, such as serum, plasma, cell extracts, urine, etc. as samples, proteins, etc. in the coexisting substances adsorb onto the surfaces of immune reaction containers, measuring instruments, etc., which may result in a decrease in measurement sensitivity.

[0003] In order to prevent a decrease in measurement sensitivity, as shown in Non-Patent Document 1, a method is generally used in which a solution obtained by dissolving a protein derived from a living organism such as bovine serum albumin (BSA), casein, gelatin, etc., which does not participate in the immune reaction, in a buffer solution is used to treat the surfaces of immune reaction containers, measuring instruments, etc., thereby suppressing the adsorption of proteins involved in the immune reaction.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Non-Patent Documents

[0005]

Non-Patent Document 1

[0006] However, the adsorption inhibitory effect of the conventional adsorption inhibitors mentioned above is insufficient, especially in measurements requiring high sensitivity. Furthermore, when using the bio-derived adsorption inhibitors mentioned above, there is a problem in that there is a large variability between measurements, making it difficult to obtain accurate measurement results with a small number of samples.

[0007] As adsorption inhibitors, Patent Document 1 proposes acrylamide derivatives, Patent Document 2 proposes specific polyethylene glycol monomethacrylate polymers, and Patent Document 3 proposes polypropylene glycol, etc. However, these adsorption inhibitors were still insufficient in suppressing variability between measurements.

[0008] The problem that this invention aims to solve is to provide a protein adsorption inhibitor that can suppress the adsorption of proteins such as antibodies and enzymes onto surfaces such as immunoreaction vessels and measuring instruments to a high degree, and reduce variability between measurements. [Means for solving the problem]

[0009] As a result of diligent research by the inventors, we have found that alkylene oxide derivatives having a specific cloud point and a specific structure can solve the above problems, and have completed the present invention. Based on this finding, the present invention is as follows.

[0010] [1] Equation (1): Z-{O-[(PO) a (EO) b ]-(AO) c -H]} x ... (1) (In the formula, x represents a number between 1 and 4, Z represents a residue having a structure obtained by removing hydroxyl groups from a compound with 1 to 20 carbon atoms that has x hydroxyl groups. PO indicates an oxypropylene group. EO indicates an oxyethylene group. AO represents an oxyalkylene group having 3 or 4 carbon atoms. a, b, and c represent the number of oxypropylene groups, oxyethylene groups, and oxyalkylene groups, respectively, with 1 ≤ a ≤ 50, 1 ≤ b ≤ 50, 0 ≤ c ≤ 50, 10 ≤ (a + b + c) ≤ 150, and 0.05 ≤ b / (a + c) ≤ 0.5, and [(PO) a (EO) b ] represents a polyoxyalkylene group in which a PO group and b EO groups are bonded randomly and / or in a block-like manner. It includes alkylene oxide derivatives represented by and The cloud point of a 1% by mass aqueous solution of the alkylene oxide derivative is between 0°C and 30°C. Protein adsorption inhibitor. [Effects of the Invention]

[0011] By bringing an aqueous solution of the protein adsorption inhibitor of the present invention, which contains a specific alkylene oxide derivative, into contact with the surface of a reaction vessel or the like at a temperature above its cloud point, and then removing it, the adsorption of proteins such as antibodies and enzymes to the surface can be suppressed to a high degree. Furthermore, by using the above aqueous solution, the variability between measurements can be reduced, and accurate measurement results can be obtained with a smaller number of samples. [Modes for carrying out the invention]

[0012] The protein adsorption inhibitor of the present invention is of formula (1): Z-{O-[(PO) a / (EO) b -(AO) c -H]} x ··· (1) It contains an alkylene oxide derivative represented by (hereinafter, may be abbreviated as "derivative (1)") in this specification.

[0013] In this specification, the "protein adsorption inhibitor" means an agent used for treating the surface before the protein and the surface come into contact in order to suppress the adsorption of the protein on the surface of a reaction vessel or the like. The treatment of the surface can be carried out, for example, by contacting an aqueous solution of the protein adsorption inhibitor of the present invention containing derivative (1) with the surface at a temperature above its cloud point and then removing the aqueous solution.

[0014] In this specification, "alkylene oxide" means a cyclic ether compound having a structure in which two carbon atoms are bonded by an oxygen atom. Examples of alkylene oxide include ethylene oxide, propylene oxide, butylene oxide, tetrahydrofuran (tetramethylene oxide), and the like.

[0015] The protein adsorption inhibitor of the present invention preferably consists of derivative (1). Only one kind of derivative (1) may be used, or two or more kinds may be used in combination. Also, within a range not inhibiting the effects of the present invention, derivative (1) and other components may be used in combination.

[0016] In formula (1), x represents a number of 1 or more and 4 or less. From the viewpoint of the protein adsorption inhibitory effect, x is preferably 1 or more and 3 or less more preferably 1 or 2, and still more preferably 1.

[0017] In formula (1), Z represents a residue having a structure obtained by removing hydroxyl groups from a compound having 1 to 20 carbon atoms and x hydroxyl groups. From the viewpoint of suppressing protein adsorption and reducing variability between measurements, the number of carbon atoms in Z is preferably 3 to 18, more preferably 5 to 18, and even more preferably 12 to 18.

[0018] Examples of compounds with one hydroxyl group and 1 to 20 carbon atoms include methanol, ethanol, propanol, butanol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, isodecyl alcohol, and isostearyl alcohol. Examples of compounds with two hydroxyl groups and 1 to 20 carbon atoms include ethylene glycol, propylene glycol, and hexylene glycol. Examples of compounds with three hydroxyl groups and 1 to 20 carbon atoms include glycerin and trimethylolpropane. Examples of compounds with four hydroxyl groups and 1 to 20 carbon atoms include erythritol, pentaerythritol, sorbitan, diglycerin, and alkyl glycosides.

[0019] Z is preferably a residue having a structure obtained by removing a hydroxyl group from cetyl alcohol, stearyl alcohol, propylene glycol, glycerin, or pentaerythritol, from the viewpoint of suppressing protein adsorption and suppressing variability between measurements, and more preferably a residue having a structure obtained by removing a hydroxyl group from cetyl alcohol or stearyl alcohol.

[0020] In formula (1), PO represents an oxypropylene group, EO represents an oxyethylene group, and AO represents an oxyalkylene group having 3 or 4 carbon atoms. O-[(PO) in equation (1) a (EO) b ] is the O at the left end of the above formula, and [(PO) a (EO) b This indicates that a propylene group or ethylene group is bonded to it. If c is 0, (AO) c It does not exist, and in equation (1) [(PO) a (EO) b ]-(AO) c -H is the H at the right end of the above formula, and [(PO) a (EO) b This indicates that the oxy group in the compound is bonded to the compound. If c is not 0, then [(PO) in equation (1) a (EO) b ]-(AO) c is [(PO) a (EO) b ] the oxy group and (AO) c This indicates that the alkylene group inside is bonded, and in formula (1) (AO) c -H is the H at the right end of the above formula, and (AO) c This indicates that it is bonded to the oxy group inside.

[0021] Examples of AO include oxypropylene group, oxy-1-ethylethylene group, and oxytetramethylene group. Among these, oxypropylene group and oxy-1-ethylethylene group are preferred, and oxypropylene group is more preferred. When c is 2 or more, AO may be only one type or two or more types. When AO is two or more types, (AO) c This represents a polyoxyalkylene group in which c AOs are bonded randomly and / or in a block-like manner. AO is preferably at least one selected from the group consisting of oxypropylene groups and oxy-1-ethylethylene groups, and more preferably an oxypropylene group.

[0022] In equation (1), a, b, and c represent the numbers of PO, EO, and AO, respectively. a to c may all be average values ​​and therefore may be decimals.

[0023] a is between 1 and 50 (1 ≤ a ≤ 50), preferably between 5 and 45 (5 ≤ a ≤ 45), more preferably between 10 and 40 (10 ≤ a ≤ 40), and even more preferably between 20 and 40 (20 ≤ a ≤ 40). If a is 0, the protein adsorption inhibitory effect may decrease or the variability between measurements may increase, and if a is too large, the water solubility of derivative (1) may decrease.

[0024] b is between 1 and 50 (1 ≤ b ≤ 50), preferably between 1 and 20 (1 ≤ b ≤ 20), more preferably between 2 and 10 (2 ≤ b ≤ 10), and even more preferably between 3 and 5 (3 ≤ b ≤ 5). If b is 0, the water solubility of derivative (1) is low, and if b is too large, the variability between measurements may increase.

[0025] c is between 0 and 50 (0 ≤ c ≤ 50), preferably between 0 and 20 (0 ≤ c ≤ 20), more preferably between 0 and 10 (0 ≤ c ≤ 10), and even more preferably 0 (c = 0). If c is too large, the protein adsorption inhibitory effect may decrease.

[0026] (a+b+c) is 10 or greater (10≦(a+b+c)), preferably 15 or greater (15≦(a+b+c)), and more preferably 20 or greater (20≦(a+b+c)). If (a+b+c) is less than 10, the protein adsorption inhibitory effect may decrease. Also, (a+b+c) is 150 or less ((a+b+c)≦150), preferably 100 or less ((a+b+c)≦100), and more preferably 50 or less ((a+b+c)≦50). If (a+b+c) exceeds 150, the protein adsorption inhibitory effect may decrease.

[0027] b / (a+c) is between 0.05 and 0.5 (0.05 ≤ b / (a+c) ≤ 0.5), preferably between 0.1 and 0.4 (0.1 ≤ b / (a+c) ≤ 0.4), and more preferably between 0.1 and 0.2 (0.1 ≤ b / (a+c) ≤ 0.2). If b / (a+c) is less than 0.05, the protein adsorption inhibitory effect may decrease, and if it exceeds 0.5, the variability between measurements may increase.

[0028] x(a+b+c), which represents the total number of oxyalkylene groups in one molecule of derivative (1), is preferably 10 to 200 (10≦x(a+b+c)≦200), more preferably 20 to 100 (20≦x(a+b+c)≦100), and even more preferably 25 to 45 (25≦x(a+b+c)≦45), from the viewpoint of suppressing protein adsorption and suppressing variability between measurements.

[0029] In formula (1), [(PO) a (EO) b ] represents a polyoxyalkylene group in which a PO and b EO are bonded randomly and / or in a block-like manner.

[0030] In equation (1), Z-{O and [(PO) a (EO) b There is no particular restriction on the order of combination with ], (i)Z-{O and [(PO) a (EO) b ] may be joined with the PO block in the middle, (ii) Z-{O and [(PO) a (EO) b ] may be joined with the EO block in the middle, (iii) Z-{O and [(PO) a (EO) b ] may be bonded to a portion in which PO and EO are randomly bonded. Preferably Z-{O and [(PO) a (EO) b ] is bonded with the PO block in, or Z-{O and [(PO) a (EO) b] contains a region where PO and EO are randomly bonded, and more preferably Z-{O and [(PO) a (EO) b The PO block within is connected to it.

[0031] In equation (1) [(PO) a (EO) b ] and (AO) c -There is no particular restriction on the order of bonding with H, (i)[(PO) a (EO) b ] EO block and (AO) c -H may be bonded, (ii)[(PO) a (EO) b ] PO block and (AO) c -H may be bonded, (iii)[(PO) a (EO) b ] The part in which PO and EO are randomly joined, and (AO) c -H may be bonded to it. Preferably [(PO) a (EO) b ] EO block and (AO) c -H is bonded to it, or [(PO) a (EO) b ] The part in which PO and EO are randomly joined, and (AO) c -H is bonded, more preferably [(PO) a (EO) b ] EO block and (AO) c -H is bonded to it.

[0032] [(PO) a (EO) b ] is preferably a polyoxyalkylene group in which a PO and b EO are bonded randomly or in a block-like manner, and more preferably a polyoxyalkylene group in which a PO and b EO are bonded in a block-like manner. Even more preferably [(PO) a (EO) b] is a polyoxyalkylene group formed by the block-like bonding of a PO and b EO, and Z-{O and [(PO) a (EO) b (PO) a The block and are joined, and [(PO) a (EO) b (EO) b Block and (AO) c -H is bonded to it.

[0033] The cloud point of a 1% by mass aqueous solution of derivative (1) is 0°C to 30°C, from the viewpoint of suppressing protein adsorption and reducing variability between measurements. The cloud point is preferably 0°C to 20°C, and more preferably 0°C to 10°C. Regarding the cloud point, JIS K 3211:1990 "Terminology for Surfactants" states, "The temperature at which an aqueous solution of a nonionic surfactant begins to become cloudy when its temperature is increased. Usually, cloudiness occurs and phase separation takes place."

[0034] The cloud point of a 1% by mass aqueous solution of derivative (1) is measured by the following method: After pouring a 1% by mass aqueous solution of derivative (1) into a test tube to a height of approximately 40 mm, place a thermometer inside and heat while stirring well with the thermometer to a temperature approximately 2-3°C higher than the temperature at which clouding occurs. Then, while stirring well again, allow to air cool until the solution becomes clear, and this temperature is defined as the cloud point. Alternatively, if the aqueous solution is cloudy at room temperature, cool while stirring well until the solution becomes clear, then gradually heat while stirring well again to the temperature at which turbidity occurs, and then gradually cool while stirring until the solution becomes clear, and this temperature is defined as the cloud point.

[0035] Derivative (1) can be produced by known methods. [(PO) a (EO) bWhen [(PO) is a polyoxyalkylene group in which a PO and b EO are bonded in a block-like manner, for example, under an alkaline catalyst, either propylene oxide or ethylene oxide is added to the alcohol corresponding to Z at a temperature of 50°C to 160°C and a pressure of 0.5 MPa (gauge pressure) or less, then the other is added, and then, if necessary, an alkylene oxide having 3 or 4 carbon atoms is added. After that, the reaction mixture is neutralized with an acid such as hydrochloric acid, phosphoric acid, or acetic acid, and the water and neutralized salt are removed to obtain derivative (1). a (EO) b If ] is a polyoxyalkylene group in which a PO and b EO are randomly bonded, then derivative (1) can be obtained by the same method as described above, except that a mixture of propylene oxide and ethylene oxide is added to the alcohol corresponding to Z.

[0036] As described above, the surface treatment for suppressing the adsorption of proteins onto the surface of a reaction vessel or the like can be performed by using an aqueous solution of the protein adsorption inhibitor of the present invention containing derivative (1) (hereinafter sometimes abbreviated as "inhibitor aqueous solution"). The concentration of derivative (1) in the inhibitor aqueous solution is preferably 0.05% by mass or more and 10% by mass or less, more preferably 0.1% by mass or more and 5.0% by mass or less, and even more preferably 0.2% by mass or more and 1.0% by mass or less, from the viewpoint of protein adsorption inhibitory effect and suppression of variability between measurements.

[0037] Solvents for preparing aqueous solutions of inhibitors include, for example, water (e.g., pure water, deionized water), physiological saline, and buffers used in immunological assays. Examples of buffers include phosphate buffers (e.g., Dulbecco's phosphate buffer), acetate buffers, carbonate buffers, citrate buffers, Tris buffers, and HEPES buffers.

[0038] The aqueous inhibitor solution may contain other components different from derivative (1), as long as they do not inhibit the effects of the present invention. Examples of other components include salts (e.g., sodium chloride contained in the physiological saline solution) and buffers (e.g., buffers contained in the buffer solution). [Examples]

[0039] The present invention will be specifically described below with reference to synthesis examples and test examples.

[0040] <Synthesis Example 1: Synthesis of Alkylene Oxide Derivative 1> 100 g of stearyl alcohol and 3.2 g of potassium hydroxide as a catalyst were charged into an autoclave. After replacing the air in the autoclave with dry nitrogen, the catalyst was dissolved at 140°C while stirring. Subsequently, 854 g of propylene oxide was added dropwise at 120°C and 0.2-0.5 MPa (gauge pressure) using a dropping device, and the mixture was stirred at 120°C for 3 hours. Next, 85 g of ethylene oxide was added dropwise at 120°C and 0.2-0.5 MPa (gauge pressure) using a dropping device, and the mixture was stirred at 120°C for 2 hours. After that, the reaction mixture was removed from the autoclave, neutralized with hydrochloric acid to adjust the pH to 6-7, and the reaction mixture was treated at -0.095 MPa (gauge pressure) and 100°C for 1 hour to remove water. Furthermore, the mixture was filtered to remove the salts formed after treatment, and alkylene oxide derivative 1 (hereinafter abbreviated as "derivative 1") was obtained. Furthermore, the number-average molecular weights of the polyoxyethylene group and the polyoxypropylene group were calculated from the hydroxyl value obtained by hydroxyl value measurement in accordance with JIS K1557-1, and the values ​​of a and b were calculated from these number-average molecular weights.

[0041] <Synthesis Examples 2-11: Synthesis of Alkylene Oxide Derivatives 2-11> Alkylene oxide derivatives 2 to 11 (hereinafter abbreviated as "derivatives 2 to 11" respectively) were obtained using the same method as in Synthesis Example 1.

[0042] Note that in Synthesis Example 2 (Synthesis of Derivative 2) and Synthesis Example 7 (Synthesis of Derivative 7), [(PO) a (EO)b To form [(PO)], a mixture of propylene oxide and ethylene oxide was added to the starting material corresponding to Z. In addition, in Synthesis Example 5 (Synthesis of Derivative 5) and Synthesis Example 6 (Synthesis of Derivative 6), [(PO) a (EO) b After the formation of ], the alkylene oxide corresponding to AO was added. In synthesis example 8 (synthesis of derivative 8), only propylene oxide was added to the starting material corresponding to Z. In synthesis example 10 (synthesis of derivative 10), only ethylene oxide was added to the starting material corresponding to Z.

[0043] Tables 1 and 2 show the starting materials corresponding to Z, the alkylene oxides relative to AO used in Synthesis Example 5 or 6, AO in Derivative 5 or 6, the values ​​of a, b, and c in formula (1), and the values ​​of (a+b+c), b / (a+c), and x(a+b+c) calculated from the above values. The cloud points of 1% by mass aqueous solutions of alkylene oxide derivatives 1 to 10 are also shown in Tables 1 and 2. Derivatives 1 to 6 are the protein adsorption inhibitors of the Examples, and derivatives 7 to 11 are the protein adsorption inhibitors of the Comparative Examples.

[0044] [Table 1]

[0045] [Table 2]

[0046] <Synthesis Example 12: Synthesis of Methoxydiethylene Glycol Monoacrylate Polymer 12> In a four-necked flask, 20 g of methoxydiethylene glycol monoacrylate was added as the monomer, 10 mg of azobisisobutyronitrile was added as a polymerization initiator, and 60 g of dioxane was added. The monomer and polymerization initiator were dissolved in the dioxane. The polymerization reaction was carried out at 70°C for 8 hours. After the reaction was complete, the reaction mixture was diluted and washed with hexane, and the resulting solid was recovered by filtration. The recovered solid was redissolved in 70 mL of tetrahydrofuran, and the resulting solution was again diluted and washed with hexane. The resulting solid was recovered by filtration and dried under reduced pressure to obtain methoxydiethylene glycol monoacrylate polymer 12 (hereinafter abbreviated as "polymer 12"). Analysis by GPC showed that the number-average molecular weight (Mn) of polymer 12 was 18000. The cloud point of a 1% by mass aqueous solution of polymer 12 was 41°C. This polymer 12 is the protein adsorption inhibitor of the comparative example.

[0047] <Test Example 1> <Preparation of aqueous solution of protein adsorption inhibitor> Derivatives 1-11 and polymer 12 obtained in Synthesis Examples 1-12 were each dissolved in Dulbecco's phosphate buffer (Sigma-Aldrich, hereinafter abbreviated as "DPBS") to a concentration of 0.5% by mass to prepare aqueous solutions of protein adsorption inhibitors.

[0048] <Evaluation of protein adsorption inhibitory effect> The protein adsorption inhibitory effect was evaluated using the following method with the aqueous solution of the obtained protein adsorption inhibitor.

[0049] An aqueous solution of a protein adsorption inhibitor was dispensed into a MaxiSoap plate (a polystyrene plate manufactured by Thermofisher Scientific) at a volume of 200 μL / well at room temperature and allowed to stand at 37°C for 1 hour. The solution was then completely removed using an aspirator, and 200 μL / well of DPBS containing 0.05% by mass of Tween20 (hereinafter abbreviated as "DPBS-T") was dispensed. The DPBS-T was then completely removed using an aspirator. This dispensing and removal of DPBS-T was repeated a total of three times.

[0050] Next, 100 μL / well of POD-IgG (peroxidase-labeled immunoglobulin G, Biorad), diluted 5,000-fold with DPBS, was dispensed and allowed to stand at room temperature for 1 hour. Then, 200 μL / well of DPBS-T was dispensed, and the aforementioned solution (a mixture of POD-IgG and DPBS-T diluted 5,000-fold with DPBS) was completely removed using an aspirator. The dispensing and removal of DPBS-T was repeated a total of three times, and the plate surface was washed.

[0051] After washing, a chromogenic solution prepared using TMB Microwell Peroxidase Substrate (KPL) was added at a volume of 100 μL / well, and the enzyme (peroxidase) bound to the protein (immunoglobulin G) adsorbed on the MaxiSoap plate was reacted with TMB (tetramethylbenzidine) in the chromogenic solution at room temperature for 10 minutes.

[0052] The color reaction was stopped by dispensing a 1 mol / L sulfuric acid solution at a volume of 50 μL / well, and the absorbance at 450 nm was measured. A lower absorbance indicates suppressed protein adsorption to the MaxiSoap plate. An Infinite 200 PRO M-Plex (TECAN) was used for absorbance measurement.

[0053] The absorbance at 450 nm was measured in the same manner as described above, except that bovine serum albumin (BSA) was used as the protein adsorption inhibitor. Tables 3 and 4 show the relative values ​​of the absorbance obtained using each protein adsorption inhibitor, normalized to 100 based on the absorbance obtained using BSA. A lower relative value indicates that protein adsorption to the MaxiSoap plate is suppressed. The protein adsorption inhibitory effect was evaluated as ◎ when the relative value was less than 10, ○ when the relative value was less than 100, and × when the relative value was 100 or more. The evaluation results are shown in Tables 3 and 4. Protein adsorption inhibitors that received ◎ or ○ ratings for their protein adsorption inhibitory effect were judged to be acceptable.

[0054] <Evaluation of variability between measurements> To evaluate the variability between measurements, the above <Evaluation of Protein Adsorption Inhibition Effect> was repeated 10 times, and the standard deviation of the absorbance over 10 measurements and the coefficient of variation were calculated by dividing them by the average absorbance over 10 measurements (coefficient of variation = standard deviation of absorbance over 10 measurements / average absorbance over 10 measurements).

[0055] The coefficient of variation of absorbance was calculated in the same manner as above, except that bovine serum albumin (BSA) was used as the protein adsorption inhibitor. For inter-measurement variability, the ratio (%) of the coefficient of variation of absorbance obtained using each protein adsorption inhibitor to the coefficient of variation of absorbance obtained using BSA was calculated (= 100 × coefficient of variation of absorbance obtained using BSA / coefficient of variation of absorbance obtained using each protein adsorption inhibitor). The ratios of the coefficient of variation of absorbance are shown in Tables 3 and 4. A lower ratio indicates that the inter-measurement variability is suppressed. Inter-measurement variability was evaluated as ◎ when the ratio was less than 50%, ○ when the ratio was 50% or more but less than 80%, △ when the ratio was 80% or more but less than 100%, and × when the ratio was 100% or more. The evaluation results are shown in Tables 3 and 4. Protein adsorption inhibitors with an evaluation of ◎ and ○ for inter-measurement variability were judged to be acceptable.

[0056] [Table 3]

[0057] [Table 4]

[0058] The protein adsorption inhibitors (derivatives 1-6) in the examples exhibited excellent protein adsorption inhibitory effects and showed minimal variability between measurements.

[0059] In contrast, the protein adsorption inhibitors in the comparative examples (derivatives 7-11 and polymer 12) were inferior in either or both of the protein adsorption inhibitory effect and the variability between measurements. [Industrial applicability]

[0060] The protein adsorption inhibitor of the present invention can suppress the nonspecific adsorption of proteins such as antibodies and enzymes to surfaces such as immunoreaction vessels and measuring instruments to a high degree, and can also reduce variability between measurements. Therefore, the protein adsorption inhibitor of the present invention is useful for in vitro diagnostics and the like.

Claims

[Claim 1] Formula (1): Z-{O-[(POO) ａ / (EO) ｂ ]-(AO) ｃ -H]} ｘ ・・・ (1) (In the formula, x represents a number between 1 and 4, Z represents a residue having a structure obtained by removing hydroxyl groups from a compound with 1 to 20 carbon atoms that has x hydroxyl groups. PO indicates an oxypropylene group. EO indicates an oxyethylene group. AO represents an oxyalkylene group having 3 or 4 carbon atoms. a, b, and c represent the number of oxypropylene groups, oxyethylene groups, and oxyalkylene groups, respectively, with 1 ≤ a ≤ 50, 1 ≤ b ≤ 50, 0 ≤ c ≤ 50, 10 ≤ (a + b + c) ≤ 150, and 0.05 ≤ b / (a ​​+ c) ≤ 0.5, and [(PO) ａ / (EO) ｂ ] represents a polyoxyalkylene group in which a PO group and b EO groups are bonded randomly and / or in a block-like manner. It includes alkylene oxide derivatives represented by and The cloud point of the 1% by mass aqueous solution of the alkylene oxide derivative is 0°C or higher and 30°C or lower. Protein adsorption inhibitor.

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