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Preparation and application of glucose-sensitive insulin dosing system

A glucose-sensitive, drug delivery system technology, applied in the field of preparation of a new glucose-sensitive insulin drug delivery system, can solve problems restricting clinical applications, etc.

Active Publication Date: 2021-01-12
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the accuracy of administration of glucose-sensitive drug controlled release system still restricts the clinical application of the drug delivery system. It is still a big problem to control the drug carrier to release the drug on demand. Insulin, so as to control the blood sugar concentration at a normal level; and does not release drugs at normal human blood sugar concentration to keep the blood sugar level stable and not too low

Method used

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  • Preparation and application of glucose-sensitive insulin dosing system
  • Preparation and application of glucose-sensitive insulin dosing system
  • Preparation and application of glucose-sensitive insulin dosing system

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0060] The preparation of example 1 mesoporous silica

[0061] sample 1

[0062] Weigh 0.5g CTAB and dissolve it in 500mL double-distilled water, stir it at 600rpm for 0.5h in a water bath at 80°C to make it fully dissolved, add 150mL n-octane dropwise to the above clear solution, connect the condensing reflux device , and continued to stir for 2h to obtain a uniform emulsion. Slowly add 26 mL of styrene monomer dropwise into the emulsion. Under nitrogen protection, 0.075g of lysine, 5.0mL of tetraethyl orthosilicate, and 0.125g of azobisisobutylamidine hydrochloride were sequentially added to the reaction solution. After reacting for 2 hours, the suspension was cooled naturally, left to stand for about 10 hours, an equal volume of absolute ethanol was added, centrifuged at 10000 rpm for 8 minutes, and the precipitate was washed 3 times with absolute ethanol. After the precipitate was dried at 60°C for 12h, it was calcined at 550°C for 6h to remove the pore-enlarging agent ...

example 2

[0067] Example 2 Preparation of 4-formylphenylboronic acid grafted chitosan glucose sensitive material

[0068] sample 1

[0069] Weigh 5 mg of 4-formylphenylboronic acid and dissolve it in 0.5 mL of methanol, weigh 10 mg of chitosan CTS (10kD) and dissolve it in 7 mL of 1% acetic acid solution, mix the two solutions, react for 2 hours, and weigh sodium borohydride 7.2mg was added to the above mixed solution, the reaction was stirred at 25°C for 24 hours, centrifuged at 10000rpm for 5min and washed with methanol, ethanol and water, and the polymer of the obtained 4-formylphenylboronic acid grafted chitosan was freeze-dried, and Store at 2-8°C until use (FPBA-CTS).

[0070] sample 2

[0071] Weigh 2.5mg of 4-formylphenylboronic acid and dissolve it in 0.5mL of methanol, weigh 10mg of chitosan (50kD) and dissolve it in 7mL of 1% acetic acid solution, mix the two solutions, react for 2 hours, and weigh sodium borohydride 7.2mg was added to the above mixed solution, the reactio...

example 3

[0072] Example 3 Preparation of 4-carboxy-3-fluorophenylboronic acid grafted chitosan glucose-sensitive material

[0073] sample 1

[0074] Weigh 9.6mg EDC and 17.3mg NHS in the dark, fully dissolve in 1.5mL distilled water, add 2mg of 4-carboxy-3-fluorophenylboronic acid after 0.5h, add 8mg chitosan after fully dissolved, and wash with 0.01M hydrochloric acid Adjust the pH value to 4.7, stir and react at 4°C for 72 hours, concentrate with ultrafiltration centrifuge tube 5000rpm for 5min, freeze-dry the polymer of the gained 4-carboxy-3-fluorophenylboronic acid grafted chitosan, and in Store at 2-8°C until use (FCPBA-CTS).

[0075] sample 2

[0076] Weigh 9.6mg of EDC and 17.3mg of NHS in the dark, fully dissolve in 1.5mL of distilled water, add 4mg of 4-carboxy-3-fluorophenylboronic acid after 0.5h, add 8mg of chitosan after fully dissolved, and wash with 0.01M hydrochloric acid Adjust the pH value to 6, stir and react at 8°C for 24 hours, concentrate with ultrafiltration ...

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Abstract

The invention belongs to the field of biomedicines and relates to a preparation method for a glucose-sensitive insulin dosing system and application of the glucose-sensitive insulin dosing system. Theglucose-sensitive insulin dosing system is composed of an inner core and an outer layer, wherein insulin and mesoporous silicon dioxide serve as the inner core, and a glucose-sensitive material capable of responding to different blood glucose concentrations and an anionic polymer for promoting mucus-layer-cross absorption of the system serve as the outer layer. The glucose-sensitive material is selected from 4-formyl phenylboronic acid grafted chitosan or 4-carboxyl-3-fluoro phenylboronic acid grafted chitosan; and a mass ratio of the mesoporous silicon dioxide to the insulin to the 4-formylphenylboronic acid grafted chitosan or 4-carboxyl-3-fluoro phenylboronic acid grafted chitosan is (1-2): (0.5-2): (0.5-2). The anionic polymer for promoting the mucus-layer-cross absorption of the system is selected from phosphoserine. The glucose-sensitive insulin oral-dosing system prepared by the preparation method has a particle size of 90nm to 900nm, and the drug load rate can reach 25% or more and is higher than that of an ordinary organic nano-particle dosing system. The system has an obvious blood glucose reducing effect.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to a preparation method and application of a novel glucose-sensitive insulin delivery system. Background technique [0002] Diabetes has become an important disease that endangers human health. At present, the most effective treatment method is still subcutaneous injection of insulin. However, this treatment method often has symptoms such as pain, infection, repeated induration of the injection site, and inflammation. Long-term injection of insulin to control blood sugar , the patient's tolerance and compliance weakened. Compared with the injection route of administration, the oral route of administration is more convenient and has higher patient compliance. However, due to the presence of a large number of proteolytic enzymes in the gastrointestinal tract during oral administration, insulin will be hydrolyzed into small molecular polypeptides or amino acids and lost. Active, unable to exer...

Claims

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Application Information

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IPC IPC(8): A61K9/50A61K9/52A61K38/28A61K45/00A61K47/36A61K47/32A61K47/24A61K47/69A61P3/10C01B33/18C08B37/08
CPCA61K9/5026A61K9/5015A61K47/6949A61K47/36A61K38/28A61K45/00A61P3/10C01B33/18C08B37/003C01P2004/62
Inventor 高亦鲲王思玲高天斌
Owner SHENYANG PHARMA UNIVERSITY
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