Temperature-resistant sugar-responsive gel

A sugar-responsive, gel-based technology, applied in the field of temperature-resistant glucose-responsive gels and drug delivery devices using the gel to respond to blood sugar concentration, and insulin drug delivery devices, can solve problems such as damage and prevent over-delivery Effect

Pending Publication Date: 2021-01-15
NAT UNIV CORP TOKAI NAT HIGHER EDUCATION & RES SYST +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But taking too much insulin can cause brain damage

Method used

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  • Temperature-resistant sugar-responsive gel
  • Temperature-resistant sugar-responsive gel
  • Temperature-resistant sugar-responsive gel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0102] Embodiment 1: the preparation of gel

[0103] N-isopropyl methacrylate (NIPMAAm) was used as the gelling agent (main chain), and 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AmECFPBA) was used as the N-hydroxyethylacrylamide (HEAAm) as a hydroxyl-based monomer, N,N'-methylenebisacrylamide (MBAAm) as a crosslinker, 2,2'-azobisisobutyronitrile as a polymer Initiator, by blending at a molar ratio of 62 / 27 / 11 / 5 / 0.1 and performing radical polymerization, a gel with a columnar shape (diameter of 1 mm in dimethyl sulfoxide (DMSO) as a reaction solvent) was prepared. Colloidal gel. Next, a phosphate-buffered aqueous solution (155 mM NaCl) at pH 7.4 containing FITC (fluorescein isothiocyanate)-modified (bovine-derived) insulin (hereinafter abbreviated as FITC-modified insulin) at a concentration of 0.5 mg / 1 mL. Immerse in the gel and keep at 4°C for 24 hours to diffuse the FITC-modified insulin into the gel.

[0104] Then the gel was removed from the phosphate b...

Embodiment 2

[0107] Example 2: Temperature Sensitivity Analysis of Gels. By the same method as in Example 1, with N-isopropylmethacrylamide (NIPMAAm), 4-(2-acrylamido-ethylcarbamoyl)-3-fluorophenylboronic acid (AmECFPBA) and N -Hydroxyethylacrylamide (HEAAm) Fifteen samples a to o with different mixing ratios (mol%) were prepared. Here, by mixing N-isopropyl methacrylate (NIPMAAm) and 4-(2-acrylamidoethylcarbamoyl)-3-fluorobenzene at a mixing ratio of 90:10 (mol%) Boronic acid (AmECFPBA) was used to prepare gel sample a. To this composition, N-hydroxyethylacrylamide (HEAAm) was added in a volume ratio of 90:10 to the mixture (final molar ratio: 81 / 9 / 10). Similarly, gel sample b was obtained by mixing N-isopropyl methacrylate (NIPMAAm) and 4-(2-acrylamidoethylcarbamoyl)-3- A mixture prepared from fluorophenylboronic acid (AmECFPBA). N-hydroxyethylacrylamide (HEAAm) was added to the composition so that the volume ratio was 80:20 (final molar ratio: 85 / 10 / 5). Other gel samples also conta...

Embodiment 4

[0109] Example 4: Release behavior of heat-resistant gels. A hollow fiber used in a polysulfone dialyzer (APS-15SA4537693003682) of Asahi Medeikaru Corp. was used as a device (inner diameter 185 μm, thickness 45 μm). In this example, a commercially available silicon force tester for rental (4Fr: inner diameter of about 600 μm, Prime Tech Co., Ltd.) was connected to the device to serve as a reservoir for supplying insulin.

[0110] In the insulin release experiments, two pumps and a refractive index (RI), high performance liquid chromatography (HPLC) system (JASCO, Japan) with internal detectors for UV and fluorescence intensity were performed.

[0111] FITC-labeled insulin was incorporated in the gel by soaking the gel prepared in the same manner as in Example 1 in PBS containing 130 mg / L FITC-labeled bovine insulin (WAKO, Japan) at 4°C for 24 hours. The gel was then filled into the device of the present invention, and the device was quickly placed in 0.01 M HCl aqueous solut...

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Abstract

The present invention provides a sugar-responsive gel that is highly resistant to temperature changes, and a sugar-responsive drug delivery device including such a gel. The sugar-responsive gel, whichcomprises a gel composition including a monomer having a hydroxyl group in addition to a phenylboronic-acid-based monomer, can exhibit suitable temperature resistance. A sugar-responsive drug delivery device including such a sugar-responsive gel is less susceptible to the effects of temperature changes, and therefore can prevent undesirable excessive delivery of a drug (such as insulin) even if the body temperature of a patient wearing the device has dropped for any reason.

Description

technical field [0001] This application claims priority and benefit from Japanese Patent Application No. 2018-105788 filed June 1, 2018, the disclosure of which is incorporated herein by reference in its entirety. [0002] The present invention relates to a sugar-responsive gel and a drug delivery device using the gel. More specifically, the present invention relates to a temperature-resistant glucose-responsive gel and a drug delivery device, particularly an insulin delivery device (artificial pancreas device), using the gel to respond to blood glucose concentration. Background technique [0003] The glucose concentration (blood sugar level) in the blood is regulated to a certain range by the action of various hormones such as insulin, but when this regulation function is destroyed, the sugar content in the blood will increase abnormally, leading to diabetes. Treatment for diabetes usually involves measuring blood sugar levels and injecting insulin. However, taking too mu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/32A61K9/00A61K38/28A61K47/18A61K47/24A61P3/10
CPCA61P3/10A61K47/32A61K47/24A61K38/28A61K47/18A61K9/0024C08F220/54C08F230/065C08F220/58C08F222/385A61K9/06A61M37/0015A61M2037/0023
Inventor 菅波孝祥田中都松元亮松本裕子诸冈由桂宫原裕二
Owner NAT UNIV CORP TOKAI NAT HIGHER EDUCATION & RES SYST
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