WO2017026044A1

WO2017026044A1 - Glucose detector and method for detecting glucose

Info

Publication number: WO2017026044A1
Application number: PCT/JP2015/072700
Authority: WO
Inventors: 桂史塚本; モウアッドラムラニ
Original assignee: 株式会社メニコン
Priority date: 2015-08-10
Filing date: 2015-08-10
Publication date: 2017-02-16
Also published as: JP6194127B2; JPWO2017026044A1

Abstract

This glucose detector contains a polymer that is configured at least of a hydrophilic monomer, a hydrophobic monomer and a boronic acid-containing monomer. The turbidity of the polymer is changed by the action of a boronic acid group of the boronic acid-containing monomer and glucose, and glucose is detected on the basis of the turbidity change. A method for detecting glucose according to the present invention uses this glucose detector and detects glucose on the basis of turbidity change of the polymer caused by the action of a boronic acid group of the boronic acid-containing monomer and glucose.

Description

Glucose detector and glucose detection method

The present invention relates to a glucose detector and a glucose detection method.

Conventionally, as a glucose detector, for example, a sensor for detecting a cis-type diol-containing specimen, which has a holographic element containing a boronic acid group and changes optical properties by reacting with glucose is proposed. (For example, refer to Patent Document 1). As a glucose detector, a contact lens having a holographic element containing a boronic acid group and reacting with glucose to change optical characteristics has been proposed (for example, see Patent Document 2). In this glucose detector, an optical change is detected as a change in peak wavelength using a visible light source.

JP 2006-519979 A JP 2007-506999 A

However, in the above-described detectors of

Patent Documents

1 and 2, a component of a polymer used as a medium of a holographic element containing a boronic acid group has not been sufficiently studied, and the action of a boronic acid group and glucose is It cannot be fully utilized for the change in physical properties of the polymer. Moreover, in the detection body of the

patent documents

1 and 2 mentioned above, it was necessary to form the special polymer structure which expresses a hologram after superposition | polymerization of the said polymer. In addition, for example, when this polymer is used for a contact lens, sterilization may be performed. However, the polymer structure may be modified by such external factors, and its function is fully expressed. There was a risk of not being able to.

The present invention has been made in view of such problems, and a glucose detector and a glucose detection method capable of detecting glucose by effectively utilizing the action of a boronic acid group and glucose by changing the physical properties of the polymer. The main purpose is to provide

As a result of diligent research to achieve the above-described object, the present inventors have used a polymer composed of a hydrophilic monomer, a hydrophobic monomer, and a boronic acid-containing monomer, and the action of a boronic acid group and glucose. By combining the hydrophilic and hydrophobic balance of the whole polymer, it was found that glucose can be detected by effectively utilizing the action of boronic acid groups and glucose by changing the physical properties of the polymer, and the present invention has been completed.

That is, the glucose detector of the present invention is
It includes a polymer composed of at least a hydrophilic monomer, a hydrophobic monomer, and a boronic acid-containing monomer represented by the chemical formula (1), and the turbidity of the polymer changes depending on the amount of glucose present. .

The glucose detection method of the present invention includes
Using the glucose detector comprising a polymer composed of at least a hydrophilic monomer, a hydrophobic monomer, and a boronic acid-containing monomer represented by the chemical formula (1), the turbidity of which varies depending on the amount of glucose present. Glucose is detected based on the change in turbidity.

The glucose detector and glucose detection method of the present invention can detect glucose by effectively utilizing the action of boronic acid groups and glucose by changing physical properties of the polymer. The reason why such an effect is obtained is estimated as follows, for example. FIG. 1 is a scheme showing an example of an equilibrium relationship between a phenylboronic acid group and glucose. Regarding the binding and dissociation of the boronic acid group and glucose, there is the equilibrium relationship of FIG. 1, and the boron atom of the boronic acid group is most likely to bind to glucose when taking a tetrahedral structure (FIG. 1 (2)). (See Non-Patent Document 1: Tetrahedron 2002, 58, 5291-5300, for example). In the present invention, for example, by combining a hydrophilic monomer, a hydrophobic monomer, and a boronic acid-containing monomer represented by the chemical formula (1) into a polymer, the hydrophilic monomer and the hydrophobic monomer in the polymer chain are combined. It is presumed that the side chain affects the boron atom of the boronic acid group and can be stabilized with a tetrahedral structure. Furthermore, by adjusting the hydrophilic-hydrophobic balance appropriately so that the hydrophilic-hydrophobic change of the polymer chain accompanying the binding and dissociation of boronic acid group and glucose affects the hydrophilic-hydrophobic property of the whole polymer, It is presumed that the detection sensitivity of the action of acid groups and glucose can be further increased. In addition, since the glucose detector of the present invention does not require special processing (formation of a hologram or the like) after polymer preparation, it can be prepared more easily, leading to efficiency during mass production.

A scheme showing an example of an equilibrium relationship between phenylboronic acid and glucose.

The glucose detector of the present invention comprises a polymer composed of at least (A) a hydrophilic monomer, (B) a hydrophobic monomer, and (C) a boronic acid-containing monomer represented by chemical formula (1). In the present application, the hydrophilic monomer means a monomer having an octanol / water-partition coefficient (LogPow value) of 1.0 or less, and the hydrophobic monomer means an octanol / water-partition coefficient (LogPow value) of 1.0. We will refer to the larger monomer.

The hydrophilic monomer is a monomer having a LogPow value of 1.0 or less, but the LogPow value is preferably −1.0 or more, more preferably −0.8 or more. Further, the LogPow value of the hydrophilic monomer is preferably 0.8 or less, and more preferably 0.6 or less. The hydrophilic monomer has, for example, one or more of nitrogen-containing groups (for example, amino groups) and hydroxy groups as hydrophilic groups, and one or more of acryloyl group, methacryloyl group, vinyl group and the like as bonding groups. It may be included. Examples of the hydrophilic monomer include acrylamide (AA), 2-hydroxyethyl acrylate (HEA), 2-hydroxyethyl methacrylate, N, N′-dimethylacrylamide (DMAA), N-vinyl-2-pyrrolidone, 1- 1 or more selected from methyl-3-methylene-2-pyrrolidinone and the like. Of these, AA, HEA, DMAA and the like are preferable.

The hydrophobic monomer is a monomer having a LogPow value exceeding 1.0, but the LogPow value is preferably 1.1 or more, and more preferably 1.2 or more. Further, the LogPow value of the hydrophobic monomer is preferably 5.0 or less, and more preferably 3.0 or less. The hydrophobic monomer may have, for example, one or more of hydrophobic alkyl group, alkylene group, phenyl group, and the like, and one or more of acryloyl group, methacryloyl group, vinyl group, and the like as a bonding group. Good. Examples of the hydrophobic monomer include one or more selected from ethyl acrylate (EA), N-phenylacrylamide (NPA), and the like.

Examples of the boronic acid-containing monomer include those represented by chemical formula (1). Moreover, as a boronic acid containing monomer, it is good also as a monomer of Chemical formula (2), for example. Alternatively, examples of the boronic acid-containing monomer include Z-acrylamide phenylboronic acid (Z-APB: where Z is 2 to 4) represented by chemical formula (3).

The content Mi of the hydrophilic monomer is preferably in the range of 30 (mol%) to 80 (mol%), for example. The content Mo of the hydrophobic monomer is preferably in the range of, for example, 10 (mol%) to 60 (mol%). For example, the content Mb of the boronic acid-containing monomer is preferably in the range of 4 (mol%) to 30 (mol%). In addition, each content rate shall say the content rate with respect to the total amount (mol) of a hydrophilic monomer, a hydrophobic monomer, and a boronic acid containing monomer. The molar ratio Mi / Mb, which is the content Mi (mol%) of the hydrophilic monomer with respect to the content Mb (mol%) of the boronic acid-containing monomer, is preferably 1 or more, and is preferably 3.2 or more. Is more preferable. Further, the molar ratio Mi / Mb is preferably 10 or less, and more preferably 7.6 or less. When the molar ratio Mi / Mb is in the range of 1 to 10, the change in turbidity with respect to the amount of glucose present is clear and preferable. The molar ratio Mo / Mb, which is the content Mo (mol%) of the hydrophobic monomer with respect to the content Mb (mol%) of the boronic acid-containing monomer, is preferably 1 or more, and is 1.5 or more. Is more preferable. Further, the molar ratio Mo / Mb is preferably 15 or less, and more preferably 11.4 or less. When the molar ratio Mo / Mb is in the range of 1 to 15, the change in turbidity with respect to the amount of glucose present is clear and preferable.

In addition, when the hydrophilic monomer is acrylamide, it is particularly preferable that the molar ratio Mi / Mb is in the range of 3.2 to 7.6 and the molar ratio Mo / Mb is in the range of 5 to 11.4. In addition, when the hydrophilic monomer is 2-hydroxyethyl acrylate, the molar ratio Mi / Mb is in the range of 5 to 7.5 and the molar ratio Mo / Mb is in the range of 1.5 to 4 in particular. preferable. Further, when the hydrophilic monomer is N, N-dimethylacrylamide, the molar ratio Mi / Mb is in the range of 4.5 to 5, and the molar ratio Mo / Mb is in the range of 4 to 4.5. Particularly preferred.

In the glucose detector of the present invention, the hydrophilic / hydrophobic balance value HHB is preferably 25 or more, and more preferably 33 or more. Further, the hydrophilic / hydrophobic balance value HHB is preferably 75 or less, more preferably 69 or less. When the hydrophilic / hydrophobic balance value HHB is in the range of 25 to 75, the change in turbidity with respect to the amount of glucose is clear and preferable. The hydrophilic / hydrophobic balance value HHB is determined by the distribution coefficient Li and content ratio Mi (mol%) of the hydrophilic monomer, the distribution coefficient Lo and content ratio Mo (mol%) of the hydrophobic monomer, and the distribution coefficient Lb of the boronic acid-containing monomer. And the content Mb (mol%) is a value obtained using the mathematical formula (1). The partition coefficient Li of the hydrophilic monomer is the octanol / water-partition coefficient (LogPow value) of the hydrophilic monomer, and the partition coefficient Lo of the hydrophobic monomer is the octanol / water-partition coefficient (LogPow value) of the hydrophobic monomer. The partition coefficient Lb of the boronic acid-containing monomer is the octanol / water-partition coefficient (LogPow value) of the boronic acid-containing monomer. As the LogPow value, for example, a calculated value using software such as ALGOPS which is online software can be used. Moreover, the experimental value obtained from well-known literature can also be used.

(Equation 1)
Hydrophilic / hydrophobic balance value HHB = Li × Mi + Lo × Mo + Lb × Mb Formula (1)

When this glucose detector contains acrylamide (AA) as a hydrophilic monomer, ethyl acrylate (EA) as a hydrophobic monomer, and Z-phenylacrylamide boronic acid (Z-APB) as a boronic acid-containing monomer, the molar ratio is Mi / Mb is preferably in the range of 3.2 to 7.6, and the molar ratio Mo / Mb is preferably in the range of 5 to 11.4. In this glucose detector, the hydrophilic / hydrophobic balance value HHB is preferably in the range of 41 to 56.

When this glucose detector contains 2-hydroxyethyl acrylate (HEA) as a hydrophilic monomer, ethyl acrylate (EA) as a hydrophobic monomer, and Z-phenylacrylamide boronic acid (Z-APB) as a boronic acid-containing monomer, The molar ratio Mi / Mb is preferably in the range of 5 to 7.5, and the molar ratio Mo / Mb is preferably in the range of 1.5 to 4. In this glucose detector, the hydrophilic / hydrophobic balance value HHB is preferably in the range of 33 to 57.

This glucose detector contains N, N-dimethylacrylamide (DMAA) as a hydrophilic monomer, ethyl acrylate (EA) as a hydrophobic monomer, and Z-phenylacrylamide boronic acid (Z-APB) as a boronic acid-containing monomer. The molar ratio Mi / Mb is preferably in the range of 4.5 to 5, and the molar ratio Mo / Mb is preferably in the range of 4 to 4.5. In this glucose detector, the hydrophilic / hydrophobic balance value HHB is preferably in the range of 63 to 69.

In the glucose detector of the present invention, the turbidity of the polymer changes depending on the amount of glucose due to the action of the boronic acid group of the boronic acid-containing monomer and glucose. The turbidity change of the glucose detector can be visually determined, for example, colorless and transparent, partially turbid, or entirely turbid. Here, the turbidity T is a value obtained by imaging a glucose detector and performing image processing. The turbidity T is obtained as follows. First, the glucose detector after being immersed in a predetermined solution is imaged, and ImageJ which is image processing software in the public domain is used for the captured image, and the gray value G of the captured image is measured. The turbidity T is obtained by Equation (2), where Gs is the gray value of the glucose detector and Gb is the gray value of the background on which the sample is placed. When the turbidity T is 1.0, the glucose detector is colorless and transparent, and the turbidity increases as the value increases.

(Equation 2)
Turbidity T = Gs / Gb Equation (2)

The glucose detector can use turbidity change (Turbidity Change Ratio: TCR) due to the amount of glucose as an index. The turbidity change TCR is, for example, when the turbidity at the first concentration of glucose is T (+), and the turbidity at the second concentration lower than the first concentration is T (−). Suppose you want. The turbidity T (+) is a value in a 1M glucose phosphate buffer solution as a first concentration, and the turbidity T (−) is a value in a phosphate buffer solution as a second concentration. The turbidity change TCR may be obtained. The turbidity change TCR is preferably 1.3 or more, more preferably 1.5 or more, and further preferably 2.0 or more. The larger the value of the turbidity change TCR, the clearer the change in turbidity T, which is preferable. The phosphate buffer solution was disodium hydrogen phosphate dodecahydrate 0.6 w / v%, sodium dihydrogen phosphate dihydrate 0.05 w / v%, sodium chloride 0.83 w / v% Consists of

(Equation 3)
Turbidity change TCR = T (−) / T (+) Equation (3)

The polymer contained in the glucose detector may be a hydrogel. The glucose detector may be incorporated in an ophthalmic member, and the ophthalmic member may be a contact lens. For example, it is known that the glucose concentration contained in tear fluid has a correlation with blood glucose level (see Non-Patent Document 2: Current Eye Research, 2006, Vol. 31, No. 11, 895-901). Moreover, it is known that the glucose concentration contained in saliva has a correlation with the blood glucose level (see Non-Patent Document 3: Journal of Biomedicine and Biotecnology, Vol2009, Article ID430426). Therefore, with this glucose detector, it is possible to determine the blood glucose level from, for example, tears or saliva. For this reason, the glucose detection body of this invention can grasp | ascertain the change of a blood glucose level, without requiring blood collection by incorporating in the member for ophthalmology.

Moreover, the glucose detector of the present invention may further contain a cross-linking agent. Examples of the crosslinking agent include compounds having a plurality of polymerization groups among acryloyl group, methacryloyl group, vinyl group and allyl group. The glucose detector of the present invention may further contain a polymerizable dye, may further contain an ultraviolet absorber, may further contain a photopolymerization initiator, and may be photosensitized. An agent may be further included. In addition, the glucose detector may include non-polymerizable additives such as a water-soluble organic solvent, a surfactant, a refreshing agent, and a thickening agent.

The ophthalmic member incorporating the glucose detector is not particularly limited as long as the change in turbidity of the glucose detector can be confirmed, but a contact lens is preferable.

The contact lens incorporating the glucose detector is preferably a conventionally known contact lens such as an oxygen permeable hard contact lens, a hydrogel lens, or a silicone hydrogel lens, and more preferably a hydrogel lens. It is also possible to combine with a contact lens having a colored portion as typified by a fashionable contact lens so that the change in turbidity can be confirmed more effectively.

The oxygen permeable hard contact lens is a non-water-containing contact lens containing at least one or more of fluorine-containing methacrylate compound, silicon-containing methacrylate compound, silicon-containing styrene compound and the like as a main component. The hydrogel lens is a hydrous contact lens containing at least one or more of (meth) acrylate compound, vinyl compound and the like as main components, and more specifically, 2-hydroxyethyl methacrylate, methacrylic acid, A contact lens comprising at least one or more of DMAA, N-vinyl-2-pyrrolidone, ethylene glycol dimethacrylate, glycerol methacrylate and the like as main components. The silicone hydrogel lens is a hydrous contact lens containing at least one or more of silicon-containing (meth) acrylate compounds, silicon-containing macromonomers and the like as main components.

When the ophthalmic member in which the glucose detector of the present invention is incorporated is used as an ophthalmic lens material, for example, the glucose detector of the present invention can be directly used as a lens shape. In addition, the glucose detector of the present invention prepared in advance can be incorporated at the time of manufacturing the contact lens. Furthermore, the glucose detector of the present invention can be prepared and incorporated on a contact lens prepared in advance. When the polymer of the present invention is molded as it is, the monomer composition can be cured by a mold method. When the monomer composition is polymerized by irradiating with light, the monomer composition containing the photopolymerization initiator is filled in a mold corresponding to the shape of the desired ophthalmic lens material, and then the mold composition is irradiated with light. Polymerization may be performed by irradiation. The material of the mold used for polymerization by light irradiation is not particularly limited as long as it is a material that can transmit light necessary for polymerization and curing, and general-purpose resins such as polypropylene, polystyrene, nylon, and polyester are preferable. It may be. By molding and processing these materials, a mold having a desired shape can be obtained.

The glucose detection method of the present invention includes a polymer that is composed of at least a hydrophilic monomer, a hydrophobic monomer, and a boronic acid-containing monomer represented by the chemical formula (1), and whose turbidity changes depending on the amount of glucose present. A glucose detector is used to detect glucose based on a change in turbidity of the polymer. This turbidity change of the polymer may be caused by the action of the boronic acid group of the boronic acid-containing monomer and glucose. In this glucose detection method, the glucose can be detected by immersing the above-described glucose detector in a solution to be detected and measuring the turbidity T. In addition, turbidity can also be confirmed visually. For example, when the turbidity of the glucose detector increases, it can be seen that the amount of glucose has increased, and when it becomes transparent, it has been found that the amount of glucose has decreased. What is necessary is just to set suitably the magnitude | size of the glucose detection body, and the quantity of the solution to be examined according to the density | concentration etc. Moreover, in this glucose detection method, the glucose concentration and content can be detected in addition to the presence or absence of glucose by the turbidity T or turbidity change TCR described above. Further, for example, not only visual observation of turbidity but also a method of quantifying glucose by polymerizing the polymer of the present invention on an electrode and detecting an electrical signal (conductivity, etc.) can be employed.

In the glucose detector and glucose detection method of the present embodiment described in detail above, the action of the boronic acid group and glucose can be effectively utilized by changing the physical properties of the polymer, and glucose can be detected. The reason why such an effect is obtained is that, for example, by combining a hydrophilic monomer, a hydrophobic monomer, and a boronic acid-containing monomer represented by the chemical formula (1) into a polymer, the hydrophilicity in the polymer chain can be obtained. It is presumed that the side chain of the monomer or hydrophobic monomer affects the boron atom of the boronic acid group and can be stabilized with a tetrahedral structure. Furthermore, by changing the hydrophilic / hydrophobic balance of the polymer chain due to the action of the boronic acid group and glucose appropriately so that the hydrophilic / hydrophobic balance of the polymer as a whole is affected, the boronic acid group It is speculated that the detection sensitivity of the action of glucose and glucose can be further increased. This glucose detector is preferably used for an ophthalmic member, for example, an ophthalmic lens such as a contact lens.

It should be noted that the present invention is not limited to the above-described embodiment, and it goes without saying that the present invention can be implemented in various modes as long as it belongs to the technical scope of the present invention.

Hereinafter, an example in which the polymerizable composition of the present invention was specifically produced will be described as an experimental example. Experimental Examples 20-23, 26-28, 30-32, 34, 37, 39-41 correspond to Examples of the present invention, and Experimental Examples 1-19, 24, 25, 29, 33, 35, 36 38 correspond to the comparative example.

[Use ingredients]
Abbreviations of the compounds used in the experimental examples are shown below.
3APB: 3-acrylamidophenylboronic acid 4APB: 4-acrylamidophenylboronic acid AA: acrylamide HEA: 2-hydroxyethyl acrylate DMAA: N, N-dimethylacrylamide EA: ethyl acrylate NPA: N-phenylacrylamide MBA: N, N ′ -Dimethylene bisacrylamide

[Production of Specimen: Experimental Examples 1 to 18]
Any of hydrophilic monomer acrylamide (AA), 2-hydroxyethyl acrylate (HEA) and N-dimethylacrylamide (DMAA) and boronic acid-containing monomer 3-acrylamidophenylboronic acid (3APB) And was dissolved in dimethyl sulfoxide. Further, N, N′-dimethylenebisacrylamide (MBA) as a crosslinking agent is 1.5 mol% with respect to the total amount of monomers, and 2,2-methoxy-2-aminophenylacetophenone as a polymerization initiator is 2 with respect to the total amount of monomers. 0.0 mol% was added. This compounded solution was poured into a mold and irradiated with ultraviolet light (UV, 365 nm) for 30 minutes at room temperature to be polymerized. After the polymerization, the polymer was taken out from the mold, cut into a circle with a diameter of 6 mm, and then immersed in ethanol to extract unpolymerized monomers and the solvent. Thereafter, the polymer was immersed in a phosphate buffer solution containing 1 M glucose for 12 hours or more, and a photograph of the polymer was taken. Thereafter, each polymer was transferred to a phosphate buffer solution, and a photograph of the polymer was taken again after 3-4 minutes.

[Experimental Examples 19 to 36]
Any one of the hydrophilic monomers AA, HEA, and DMAA, the hydrophobic monomer ethyl acrylate (EA), and the boronic acid-containing monomer 3APB so as to have an arbitrary mixing ratio (see Table 2). Except for the above, the same process as in Experimental Example 1 was performed, and the obtained polymers were referred to as Experimental Examples 19 to 36.

[Experimental Examples 37 and 38]
Any one of the hydrophilic monomers AA, HEA, and DMAA, the hydrophobic monomer N-phenylacrylamide (NPA), and the boronic acid-containing monomer 3APB have an arbitrary mixing ratio (see Table 2). Except for the above, the same steps as in Experimental Example 1 were performed, and the obtained polymers were referred to as Experimental Examples 37 and 38. Note that the LogPow value of each monomer is 0.51 for 3APB, -0.65 for AA, 0.04 for HEA, 0.17 for DMAA, 0.17 for EA, according to the calculated value by the online software ALGOPS2.1. 1.24, NPA is 1.67.

[Experimental Examples 39 to 41]
An experiment except that any one of hydrophilic monomers AA, HEA, and DMAA, a hydrophobic monomer EA, and a boronic acid-containing monomer 4APB were mixed at an arbitrary mixing ratio (see Table 2). The polymer obtained through the same steps as in Example 1 was designated as Experimental Examples 39 to 41. Note that the LogPow value of 4APB is 0.48 according to the value calculated by ALGOPS 2.1 of online software.

(Hydrophilic / Hydrophobic Balance Value)
Hydrophilic / hydrophobic balance value HHB is LogPow value of hydrophilic monomer Li, Hydromonomer content rate Mi (mol%), Hydrophobic monomer LogPow value Lo, Hydrophobic monomer content rate Mo (mol%) The LogPow value of the boronic acid-containing monomer was Lb, and the content of the boronic acid-containing monomer was Mb (mol%), and the above formula (1) was used for calculation. In addition, each content rate is a content rate with respect to the total amount (mol) of a hydrophilic monomer, a hydrophobic monomer, and a boronic acid containing monomer.

(Turbidity)
Turbidity is measured using ImageJ, which is image processing software in the public domain, and the gray value is measured from the photograph to be measured, the gray value of the sample is Gs, and the gray value of the background where the sample is placed is Gb. Calculated according to (2). When the turbidity T is 1.0, the sample is colorless and transparent, and the turbidity increases as the value increases. The change in turbidity (Turbidity Change Ratio: TCR) with or without glucose is defined as T (+) in a phosphate buffer solution containing 1 M glucose, and T (+) in the phosphate buffer solution. (−) And calculated by the above formula (3). Tables 1 and 2 also show the results of visual confirmation of turbidity T (+) and turbidity change TCR. Turbidity T (+) is A (T ≦ 1.2; visually colorless and transparent), B (1.2 <T ≦ 1.5; turbidity that can be visually confirmed), C ( T>1.5; turbidity that can be clearly confirmed visually). In addition, the turbidity change TCR is a turbidity change when immersed in a phosphate buffer solution containing 1 M glucose and then immersed in a phosphate buffer solution not containing glucose. A (TCR ≧ 2.0; change in turbidity that can be clearly confirmed visually), B (1.2 <TCR <2.0; change in turbidity that can be visually confirmed), C (TCR ≦ 1.2; It was evaluated as a change in turbidity that could hardly be confirmed visually.

(Results and discussion)
The molar ratio of the monomers of Experimental Examples 1 to 18 and the hydrophilic / hydrophobic balance value HHB, turbidity T (+) in a phosphate buffer solution containing 1 M glucose, turbidity T (−) in a phosphate buffer solution, and The turbidity change TCR is summarized in Table 1. Similarly, the results of Experimental Examples 19 to 38 are summarized in Table 2. As shown in Table 1, in Examples 1 to 18 in which no hydrophobic monomer was used, there was almost no turbidity change TCR, whereas in Examples 19 to 38, a relatively good change in turbidity occurred. I understood it. In particular, the turbidity change was clearly clearly understood when the hydrophilic / hydrophobic balance value HHB was in the range of 25 to 75, more preferably in the range of 33 to 69. In Experimental Examples 19 to 23, 33 to 36, and 39, the molar ratio Mi / Mb is preferably in the range of 3.2 to 7.6, and the molar ratio Mo / Mb is preferably in the range of 5 to 11.4. The hydrophilic / hydrophobic balance value HHB was preferably in the range of 41 to 56. In Experimental Examples 24 to 28, 37, 38, and 40, the molar ratio Mi / Mb is preferably in the range of 5 to 7.5, the molar ratio Mo / Mb is preferably in the range of 1.5 to 4 and hydrophilic. The hydrophobic balance value HHB was preferably in the range of 33 to 57. In Experimental Examples 29 to 32, 41, the molar ratio Mi / Mb is preferably in the range of 4.5 to 5, the molar ratio Mo / Mb is preferably in the range of 4 to 4.5, and the hydrophilic / hydrophobic balance value HHB is 63. A range of 69 or less was preferred.

[Experimental Example 42]
A polymer in which the polymer of the present invention was incorporated in a contact lens was produced, and this was designated as Experimental Example 42. The polymer of Experimental Example 26 soaked in a phosphate buffer solution containing 1 M glucose was placed in the center of the lens mold, and 2 mol containing 2,2-methoxy-2-aminophenylacetophenone and MBA were added from above. -A monomer solution of hydroxyethyl methacrylate (HEMA) was injected. Thereafter, ultraviolet light (UV, 365 nm) was irradiated at room temperature for 30 minutes for polymerization. After the polymerization, the contact lens was removed from the lens mold and immersed in a phosphate buffer solution containing 1M glucose. When the glucose responsiveness of the polymer part of this contact lens was confirmed, T (+) was 1.2 and T (−) was 3.7. The turbidity change TCR was 3.1, and good glucose responsiveness was obtained in a contact lens mainly composed of HEMA.

The glucose detector of the present invention can be used in the field of detecting glucose and can be used for applications such as contact lenses.

Claims

A glucose detection comprising a polymer composed of at least a hydrophilic monomer, a hydrophobic monomer, and a boronic acid-containing monomer represented by the chemical formula (1), wherein the turbidity of the polymer changes depending on the amount of glucose present body.
Partition coefficient Li and content rate Mi (mol%) of the hydrophilic monomer, partition coefficient Lo and content rate Mo (mol%) of the hydrophobic monomer, partition coefficient Lb and content rate Mb (of the boronic acid-containing monomer) 2. The glucose detector according to claim 1, wherein the hydrophilic / hydrophobic balance value HHB determined by the formula (mol%) is in the range of 25 to 75.
The molar ratio Mi / Mb, which is the content ratio Mi (mol%) of the hydrophilic monomer with respect to the content ratio Mb (mol%) of the boronic acid-containing monomer, satisfies the range of 1 to 10, and the content of the boronic acid-containing monomer The glucose detector according to claim 1 or 2, wherein a molar ratio Mo / Mb, which is a content Mo (mol%) of the hydrophobic monomer with respect to a rate Mb (mol%), satisfies a range of 1 or more and 15 or less.
The glucose detector according to any one of claims 1 to 3, wherein the polymer is a hydrogel.
The glucose detector according to any one of claims 1 to 4, which is incorporated in an ophthalmic member.
The glucose detector according to any one of claims 1 to 5, wherein the ophthalmic member is a contact lens.
Using the glucose detector comprising a polymer composed of at least a hydrophilic monomer, a hydrophobic monomer, and a boronic acid-containing monomer represented by the chemical formula (1), the turbidity of which varies depending on the amount of glucose present. Detecting glucose based on turbidity change of
Glucose detection method.