A copolymer-based sugar-sensitive microneedle patch containing 3-acrylamidophenylboronic acid

An acrylamide-based phenylboronic acid and acrylamide-based technology, which is applied in the field of copolymer-based sugar-sensitive microneedle patches, can solve the problems of insulin's weak hypoglycemic ability, insulin inactivation, and inhibition, and achieve good biocompatibility and good biocompatibility. Mechanical properties, mild effect of load process

Active Publication Date: 2022-01-04
ZHEJIANG UNIV
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  • Application Information

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Problems solved by technology

Chen et al[1] introduced silk fibroin into the precursor solution formulation of phenylboronic acid derivative copolymer-based microneedle patches to improve the mechanical strength of the microneedles. It is greatly suppressed, and it is difficult to meet the actual demand for lowering blood sugar
Yu et al[2] introduced N-vinylpyrrolidone into the precursor solution formulation of phenylboronic acid derivative copolymer-based microneedle patch, and the sugar-sensitive microneedle patch obtained had excellent strength, but insulin inactivation occurred during the preparation process. problem, resulting in less blood sugar-lowering insulin released from the microneedles
Chen Xiang et al. reported a phenylboronic acid hydrogel-based microneedle patch in patent CN109675185A. The microneedle patch exhibited glucose-responsive swelling behavior and drug release behavior at 23°C, but it did not exhibit glucose-responsive swelling behavior and drug release behavior at a human body temperature of 37°C. Does not have the above properties; according to the corresponding document Preparation of phenylboronic acid-based hydrogelmicroneedle patches for glucose-dependent insulin delivery (Figure 5(a)), at 37°C, low sugar (glucose concentration 1g / L) and high sugar (glucose concentration 1g / L) and high sugar ( There is almost no difference in the insulin release curve under the condition of glucose concentration 4g / L), that is, there is no glucose-responsive drug release behavior[3]

Method used

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  • A copolymer-based sugar-sensitive microneedle patch containing 3-acrylamidophenylboronic acid
  • A copolymer-based sugar-sensitive microneedle patch containing 3-acrylamidophenylboronic acid
  • A copolymer-based sugar-sensitive microneedle patch containing 3-acrylamidophenylboronic acid

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Experimental program
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Embodiment 1

[0045] 57.0mg of 3-acrylamidophenylboronic acid, 70.8mg of N-acrylamidoglucose, 272.5mg of N-isopropylacrylamide, 4.5mg of N,N'-methylenebisacrylamide, 2-hydroxy-4' -(2-Hydroxyethoxy)-2-methylpropiophenone 6.9 mg and dimethyl sulfoxide 300 mg were mixed and dissolved to obtain a precursor solution, then added to the microneedle female mold, and centrifuged at 4000 rpm for 60 min. The precursor solution located in the negative mold of the microneedle was initiated by ultraviolet light for radical polymerization, the ultraviolet light wavelength was 365nm, the power was 100W, and the time was 90min. The obtained copolymer-based sugar-sensitive microneedle patch containing 3-acrylamidophenylboronic acid was washed with deionized water, and then soaked in an aqueous insulin solution with a mass fraction of 0.2% for loading. After the loading is completed, the copolymer-based sugar-sensitive microneedle patch containing 3-acrylamidophenylboronic acid is dried to a constant weight t...

Embodiment 2

[0051] 172.1mg of 3-acrylamidophenylboronic acid, 210.0mg of N-acrylamidoglucose, 500.0mg of N-isopropylacrylamide, 14.1mg of N,N'-methylenebisacrylamide, 2-hydroxy-4' -(2-Hydroxyethoxy)-2-methylpropiophenone 20.2mg and dimethyl sulfoxide 1320mg were mixed and dissolved to obtain a precursor solution, then added to the microneedle female mold, and placed in a negative pressure environment with a pressure of 0.01MPa 1h. The precursor solution located in the negative mold of the microneedle was initiated by ultraviolet light for free radical polymerization, the ultraviolet light wavelength was 350nm, the power was 75W, and the time was 120min. The obtained copolymer-based sugar-sensitive microneedle patch containing 3-acrylamidophenylboronic acid was washed with deionized water, and then soaked in an aqueous insulin solution with a mass fraction of 0.2% for loading. After the loading is completed, the copolymer-based sugar-sensitive microneedle patch containing 3-acrylamidophen...

Embodiment 3

[0053] 171.0mg of 3-acrylamidophenylboronic acid, 205.7mg of N-acrylamidoglucose, 400.4mg of N-isopropylacrylamide, 15.0mg of N,N'-methylenebisacrylamide, 2-hydroxy-4' -(2-Hydroxyethoxy)-2-methylpropiophenone 19.7 mg and dimethyl sulfoxide 1350 mg were mixed and dissolved to obtain a precursor solution, then added to the microneedle female mold, and centrifuged at 4000 rpm for 60 min. The precursor solution located in the negative mold of the microneedle was initiated by ultraviolet light for radical polymerization, the ultraviolet light wavelength was 365nm, the power was 100W, and the time was 90min. The obtained copolymer-based sugar-sensitive microneedle patch containing 3-acrylamidophenylboronic acid was washed with deionized water, and then soaked in an aqueous solution of metformin hydrochloride with a mass fraction of 1% for loading. After the loading is completed, the copolymer-based sugar-sensitive microneedle patch containing 3-acrylamidophenylboronic acid is dried ...

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Abstract

The invention discloses a copolymer-based sugar-sensitive microneedle patch containing 3-acrylamidophenylboronic acid. The microneedle patch is composed of a microneedle body and a substrate, the microneedle body and the substrate are 3-acrylamidophenylboronic acid, N-acrylamide-glucose, N-isopropylacrylamide and N,N'-substrate Copolymer of methylbisacrylamide, microneedle body and substrate can load drugs. The preparation method of the invention is simple; at a human body temperature of 37°C, it has suitable mechanical properties, can effectively pierce the skin, and can regulate the release rate and release dose of the drug according to the difference in glucose concentration.

Description

technical field [0001] The invention belongs to the technical field of polymer materials, and in particular relates to a copolymer-based sugar-sensitive microneedle patch containing 3-acrylamidophenylboronic acid. Background technique [0002] Diabetes mellitus is a chronic disease caused by the lack or impairment of insulin secretion function. It is mainly characterized by high blood sugar. In severe cases, it can further induce damage to the functions of the heart, nerves, eyes, and kidneys. According to statistics from the International Diabetes Federation, in 2017, the number of people with diabetes worldwide reached 425 million. With the aggravation of the disease, diabetic patients gradually increase their dependence on antidiabetic drugs, especially exogenous insulin. At present, insulin injection is a common method for diabetic patients to supplement exogenous insulin. However, the pain of injection is obvious, and frequent injections impose a heavy burden on patie...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/00A61K38/28A61K47/32A61M37/00A61P3/10C08F220/54C08F220/58C08F230/06C08F222/38
CPCA61K9/0021A61K38/28A61K47/32A61P3/10A61M37/0015C08F220/54A61M2037/0053C08F220/58C08F230/065C08F222/385
Inventor 俞豪杰沈迪王立
Owner ZHEJIANG UNIV
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