POLYMER BLEND FOR CONTROLLING BLOOD GLUCOSE INFLUX, AND CONTINUOUS GLUCOSE MONITORING BIOSENSOR COMPRISING SAME

Abstract

The present disclosure relates to a continuous glucose monitoring biosensor, and more specifically, to: a biosensor which controls the flow of blood glucose flowing into a body during implantation, thereby enabling continuous detection and quantification of the blood glucose with high sensitivity; and a continuous glucose monitoring device and method using same. When a polymer blend composition including a hydrophilic polymer and a hydrophobic polymer according to the present disclosure, a diffusion control membrane formed therefrom and a continuous glucose monitoring biosensor including the same are used, they have the advantage capable of controlling an excessive influx of blood glucose due to an increase in the rate of diffusion in the sensor, thus enabling manufacture of a sensor having excellent accuracy and durability.

Claims

1. A polymer blend composition for a diffusion control membrane of a continuous blood glucose monitoring sensor comprising a hydrophilic polymer having a water uptake rate of 10 to 200% and a hydrophobic polymer having a water uptake rate of 0 to 10%.

2. The polymer blend composition for a diffusion control membrane of a continuous blood glucose monitoring sensor according to claim 1, wherein the hydrophilic polymer contains 26 to 70% by weight based on the total weight of the polymer blend composition.

3. The polymer blend composition for a diffusion control membrane of a continuous blood glucose monitoring sensor according to claim 1, wherein the hydrophobic polymer contains 30 to 74% by weight based on the total weight of the polymer blend composition.

4. The polymer blend composition for a diffusion control membrane of a continuous blood glucose monitoring sensor according to claim 1, wherein the hydrophilic polymer is polyvinylpyrrolidone (PVP), an aliphatic polyether-based thermoplastic polyurethane, or a combination thereof.

5. The polymer blend composition for a diffusion control membrane of a continuous blood glucose monitoring sensor according to claim 1, wherein when immersed in 20 mL of PBS buffer, the amount of water uptake after 3 hours is 15 to 90%.

6. A diffusion control membrane of a continuous blood glucose monitoring sensor comprising the polymer blend composition for a diffusion control film of the continuous blood glucose monitoring sensor of claim 1.

7. A continuous blood glucose monitoring sensor comprising the diffusion control membrane of the continuous blood glucose monitoring sensor according to claim 6.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0039] FIG. 1 is a result of confirming the intensity of current over time of a biosensor for continuous blood glucose measurement including a diffusion control membrane produced using the polymer blend composition (SP-80A-150+SG93A) according to the present disclosure, each prepared in various ratios of hydrophilic and hydrophobic polymers.

[0040] FIG. 2 is a result of confirming the intensity of current over time of a biosensor for continuous blood glucose measurement including a diffusion control membrane produced using the polymer blend composition (PVP+SG93A) according to the present disclosure, each prepared in various ratios of hydrophilic and hydrophobic polymers.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0041] Hereinafter, the present disclosure will be described with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present disclosure is not limited thereto.

EXAMPLE

Example 1

Production of a Diffusion Control Membrane Consisting of a Polymer Blend Composition Containing Hydrophilic and Hydrophobic Polymers, and Confirmation of Electrochemical Signal 1

[0042] A diffusion control membrane made of a polymer blend composition containing hydrophilic and hydrophobic polymers according to the present disclosure was produced as follows.

[0043] For the thermoplastic polyurethane, SP-80A-150 (Lubrizol), a solution grade, medical grade aliphatic, polyether-based polymer, which is also known under the trade name of Tecophilic™, and exhibits a water uptake rate of 150% of dry weight, was used as the hydrophilic polymer, and SG93A (Lubrizol), a solution grade, medical grade aliphatic, polyether-based hydrophobic polymer, which is also known under the trade name Tecoflex™, was used as the hydrophobic polymer. 50 mg of each of the hydrophilic and hydrophobic polymers was weighed and dissolved in 1 mL of tetrahydrofuran (THF). These were mixed in a volume ratio of SP-80A-150:SG93A of (i) 100:0, (ii) 85:15, (iii) 75:25, (iv) 25:75, respectively, to prepare a polymer blend.

[0044] 5 uL of the polymer blend was placed on the electrode to which the sensing membrane was fixed, and then dried in an oven for 24 hours to produce a diffusion control membrane. Using electrochemical measuring equipment (CHI1030), the electrode thus produced was immersed in 10 mM PBS, pH 7.4 solution and stabilized, and then the change in the current value due to the change in glucose concentration was measured using i-t measurement method. As for glucose, a signal was measured until the glucose concentration reached 0˜5 mM by using a method of injecting a certain amount of a high-concentration glucose solution into a PBS solution containing an electrode. The results are shown in FIG. 1. As can be seen in FIG. 1, when a volume ratio of hydrophilic polymer: hydrophobic polymer was 100:0, the change in the current value due to the change in glucose concentration was measured to be the largest, and as the proportion of the hydrophilic polymer decreased, the change in the current value decreased. It was found that when the volume ratio of the hydrophilic polymer: hydrophobic polymer was 25:75, the change in the current value due to the change in the glucose concentration was hardly observed.

Example 2

Production of a Diffusion Control Membrane Consisting of a Polymer Blend Composition Containing Hydrophilic and Hydrophobic Polymers, and Confirmation of Electrochemical Signal 2

[0045] A diffusion control membrane made of a polymer blend composition containing hydrophilic and hydrophobic polymers according to the present disclosure was produced as follows. Polyvinylpyrrolidone (PVP, Sigma Aldrich) was used as the hydrophilic polymer, and SG93A (Lubrizol) was used as the hydrophobic polymer. 100 mL of the SG93A was dissolved in 1 mL of tetrahydrofuran (THF), and 200 mg of PVP was dissolved in 1 mL of ethanol to prepare each solution. These solutions were mixed in a volume ratio of SG93A:PVP of (i) 100:0, (ii) 90:10, (iii) 80:20, (iv) 70:30, respectively, to prepare a polymer blend.

[0046] 5 uL of this polymer blend was placed on the electrode to which the sensing membrane was fixed, and then dried in an oven for 24 hours to produce a diffusion control membrane. Using electrochemical measuring equipment (CHI1030), the electrode thus produced was immersed in 10 mM PBS, pH 7.4 solution and stabilized, and then the change in the current value due to the change in glucose concentration was measured using i-t measurement method. As for glucose, a signal was measured until the glucose concentration reached 0˜5 mM by using a method of injecting a certain amount of a high-concentration glucose solution into a PBS solution containing an electrode. The results are shown in FIG. 2. As can be seen in FIG. 2, when a volume ratio of hydrophilic polymer: hydrophobic polymer was 30:70, the change in the current value due to the change in glucose concentration was measured to be the largest, and as the proportion of the hydrophilic polymer increased, the change in the current value decreased.

Example 3

Analysis of Water Uptake Capacity of a Diffusion Control Membrane Made of a Polymer Blend Composition Containing Hydrophilic and Hydrophobic Polymers

[0047] A polymer membrane containing a polymer blend mixed according to the composition of

[0048] Table 1 below was prepared by the following preparation method.

TABLE-US-00001 TABLE 1 Composition ratio (wt %) Stock description SP-80A-150 SG-93A SP-80A-150:SG-93A SP-80A-150 SG-93A (mL) (mL) 100:0  10 wt % 10 wt % 4 0 75:25 in THF in THF 3 1 50:50 2 2 25:75 1 3  0:100 0 4

[0049] First, 1.7 g of each of the hydrophilic polymer and the hydrophobic polymer was dissolved in 1.7 mL THF and stirred while heating the temperature to 40° C. to prepare a stock solution. Respective stock solutions were mixed according to the ratio, and then mixed in a rotator for about half a day. Thereafter, 1.5 mL of the mixed solution was dispensed on a Teflon plate according to the ratio. After dispensing, it was left at room temperature for 30 minutes and dried in an oven at 25° C. overnight when the outer surface dried slightly. In order to prevent the solution from flowing down, it was left at room temperature and then placed in an oven.

[0050] The polymer membrane prepared as described above was immersed in 20 mL of PBS buffer (10 mM PBS pH 7.4 (137 mM NaCl, 3 mM KC1)), and the amount of water uptake was calculated as 0% at 0 hours, and the amount of water uptake after 3 hours and 70 hours was confirmed and shown in Table 2 below.

TABLE-US-00002 TABLE 2 Confirmation of the amount of water uptake of the polymer blend SP-80A-150:SG-93A (wt. %) 100:0 75:25 50:50 25:75 0:100  3 h 112% 83% 50% 16% 0% 70 h 125% 87% 47% 21% 1%

[0051] As can be seen in Table 2, it was confirmed that the water uptake capacity of the hydrophilic polymer progressed in the direction of reaching the limit of the uptake capacity after absorbing a certain ratio. And, when the membrane was prepared by blending the hydrophilic polymer and the hydrophobic polymer, it can be confirmed that as the proportion of hydrophilic polymer decreases, the water uptake capacity decreases proportionally. Through these properties, it could be expected that the degree of diffusion of glucose could be adjusted by adjusting the blend ratio of the hydrophilic polymer and the hydrophobic polymer.