Insulin-loaded sugar-sensitive phenylboronic acid-based epsilon-polylysine particle and preparation method thereof

The technology of polylysine and phenylboronic acid is applied in the directions of non-active ingredients medical preparations, active ingredients-containing medical preparations, pharmaceutical formulas, etc., and can solve the problems of high scale production cost, complex synthesis process and the like, Achieve the effects of low production cost, simple synthesis process and simple preparation method

Inactive Publication Date: 2021-08-06
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the problems of phenylboronic acid-based polymer particles are complex synthesis process and high cost of large-scale production

Method used

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  • Insulin-loaded sugar-sensitive phenylboronic acid-based epsilon-polylysine particle and preparation method thereof
  • Insulin-loaded sugar-sensitive phenylboronic acid-based epsilon-polylysine particle and preparation method thereof
  • Insulin-loaded sugar-sensitive phenylboronic acid-based epsilon-polylysine particle and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044]Put 1.0780g of 4-carboxy-3-fluorophenylboronic acid, 1.1245g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.6739g of N-hydroxysuccinimide into Stir in 100 mL of dimethyl sulfoxide to obtain mixture A, the stirring rate is 400 rpm, the stirring time is 90 min, and the stirring temperature is normal temperature. Put 1.0001g of ε-polylysine into 10mL of water and stir at a stirring rate of 400rpm for 10min at room temperature to obtain a mixture B. The mixture A and the mixture B were mixed and stirred, the stirring rate was 500 rpm, the stirring time was 2000 min, and the stirring temperature was 30° C. to obtain the mixture C. Put the mixture C into a dialysis bag, the dialysis bag has a molecular weight cut-off of 1000Da, place the dialysis bag containing the mixture C in water for dialysis, and replace the dialysis water with fresh water every once in a while, and the time interval for each water change is 6h. The number of times is 9 times. Afte...

Embodiment 2

[0047] 1.3345g of 2-carboxyphenylboronic acid and 1.5087g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were dropped into 50mL of water and 150mL of N,N-dimethylformamide, To obtain mixture A, the stirring rate was 0 rpm, the stirring time was 0 min, and the stirring temperature was normal temperature. Put 1.2010g of ε-polylysine into 10mL of water and 2mL of N,N-dimethylformamide and stir at a stirring rate of 400rpm for 5min at room temperature to obtain a mixture B. The mixture A and the mixture B were mixed and stirred, the stirring rate was 300 rpm, the stirring time was 300 min, and the stirring temperature was normal temperature to obtain the mixture C. Put the mixture C into a dialysis bag, the molecular weight cut-off of the dialysis bag is 3500Da, place the dialysis bag containing the mixture C in water for dialysis, and replace the dialysis water with fresh water every once in a while, and the time interval for each water change is 8h. The number o...

Embodiment 3

[0049] Put 1.0001g of 4-carboxy-3-chlorophenylboronic acid, 0.9122g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.7397g of N-hydroxysuccinimide into In 50 mL of water and 150 mL of N,N-dimethylacetamide, a mixture A was obtained, the stirring rate was 200 rpm, the stirring time was 60 min, and the stirring temperature was normal temperature. Put 1.0212g ε-polylysine into 15mL water and 1mL N,N-dimethylacetamide and stir at a stirring rate of 200rpm for 15min at room temperature to obtain a mixture B. The mixture A and the mixture B were mixed and stirred, the stirring rate was 200 rpm, the stirring time was 1200 min, and the stirring temperature was normal temperature, and the mixture C was obtained. Put the mixture C into a dialysis bag, the molecular weight cut-off of the dialysis bag is 500Da, place the dialysis bag containing the mixture C in water for dialysis, and replace the dialysis water with fresh water every once in a while, and the time inter...

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Abstract

The invention discloses an insulin-loaded sugar-sensitive phenylboronic acid-based epsilon-polylysine particle and a preparation method thereof. The phenylboronic acid-based epsilon-polylysine is obtained by grafting carboxyl modified phenylboronic acid on epsilon-polylysine through a grafting reaction, wherein the mass part ratio of the carboxyl modified phenylboronic acid to the epsilon-polylysine is 1: (0.1-10), and then soaking phenylboronic acid-based epsilon-polylysine particles in an insulin solution to prepare the insulin-loaded phenylboronic acid-based epsilon-polylysine particle. The preparation method is simple; the insulin-loaded phenylboronic acid-based epsilon-polylysine particles have glucose response performance, and can automatically adjust the release rate and release dose of insulin; and the insulin-loaded phenylboronic acid-based epsilon-polylysine particles can be used for delivering insulin in a subcutaneous injection manner.

Description

technical field [0001] The invention belongs to the technical field of polymer materials, and in particular relates to insulin-loaded sugar-sensitive phenylboronic acid-based ε-polylysine particles and a preparation method thereof. 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, the number of people with diabetes in the world reached 463 million in 2019. With the aggravation of the disease, diabetic patients gradually increase their dependence on antidiabetic drugs, especially exogenous insulin. At present, subcutaneous insulin injection is a common method for diabetic patients to supplement exogenous insulin. However, patients need to adopt the strategy of injecting insuli...

Claims

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Application Information

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IPC IPC(8): A61K9/19A61K38/28A61K47/34A61K47/54A61P3/10C08G69/48
CPCA61K38/28A61K9/19A61K47/34A61K47/542A61P3/10C08G69/48
Inventor 俞豪杰沈迪王立
Owner ZHEJIANG UNIV
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