PH sensitive/membrane adhesive bifunctional insulin-loaded mixed micelle nanoparticle and preparation method thereof

A technology for mixing micelles and insulin, applied in the field of insulin mixed micelle nanoparticles and their preparation, pH sensitive/membrane adhesive bifunctional insulin-loaded mixed micelle nanoparticles and their preparation fields, which can solve the problem that the absorption efficiency is less than 1 % and other problems to achieve the effect of promoting drug absorption, good stability and dispersion, and prolonging residence time

Inactive Publication Date: 2019-12-03
XIANGTAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Reported absorption efficiency of less than 1%

Method used

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  • PH sensitive/membrane adhesive bifunctional insulin-loaded mixed micelle nanoparticle and preparation method thereof
  • PH sensitive/membrane adhesive bifunctional insulin-loaded mixed micelle nanoparticle and preparation method thereof
  • PH sensitive/membrane adhesive bifunctional insulin-loaded mixed micelle nanoparticle and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] pH-sensitive / membrane-adhesive bifunctional insulin-loaded mixed micelle nanoparticles, prepared by the following method:

[0032] (1) The polymer P(MMA 30 -co-MAA 35 )-b-PPEGMA 10 (average molecular weight 9179) and polymer P (MMA 30 -co-MAA 35 )-b-PAEMA 40 (Average molecular weight = 11529) each 25mg (i.e. 1:1 mass ratio), dissolved in 20ml of organic solvent N,N-dimethylformamide according to the mass ratio of 0.025:1, mixed and stirred at 25°C for 12h to form a polymer mixed solution, the critical micelle concentration as figure 1 , it can be seen that it can form stable micellar nanoparticles at low concentrations, which ensures the stability of drug-loaded micellar nanoparticles;

[0033] Dissolve 10mg of insulin in 10ml of medicinal hydrochloric acid solution with a concentration of 0.001mol / L and stir at 25°C for 30min at a mass ratio of 0.001:1 to make an insulin acid solution;

[0034] Add the insulin acid solution dropwise to the polymer mixed solution...

Embodiment 2

[0060] pH-sensitive / membrane-adhesive bifunctional insulin-loaded mixed micelle nanoparticles, prepared by the following method:

[0061] (1) The polymer P(MMA 30 -co-MAA 35 )-b-PPEGMA 10 (average molecular weight 9179) and polymer P (MMA 30 -co-MAA 35 )-b-PAEMA 40 (Average molecular weight = 11529) 50mg in total (mass ratio 7:3), dissolved in 20ml of organic solvent N,N-dimethylformamide according to the mass ratio of 0.025:1, mixed and stirred at 25°C for 12h to form a polymer mixture solution;

[0062] Dissolve 10mg of insulin in 10ml of medicinal hydrochloric acid solution with a concentration of 0.001mol / L and stir at 25°C for 30min at a mass ratio of 0.001:1 to make an insulin acid solution;

[0063] Add the insulin acid solution dropwise to the polymer mixed solution, so that the mass ratio of the polymer to insulin is 10:1, and continue stirring and mixing for 30 minutes after the dropwise addition to obtain a mixed solution;

[0064] (2) Transfer the mixed solu...

Embodiment 3

[0068] pH-sensitive / membrane-adhesive bifunctional insulin-loaded mixed micelle nanoparticles, prepared by the following method:

[0069] (1) The polymer P(MMA 30 -co-MAA 35 )-b-PPEGMA 10 (average molecular weight 9179) and polymer P (MMA 30 -co-MAA 35 )-b-PAEMA 40 (Average molecular weight = 11529) 50mg in total (mass ratio 3:7), dissolved in 20ml of organic solvent N,N-dimethylformamide according to the mass ratio of 0.025:1, mixed and stirred at 25°C for 12h to form a polymer mixture solution;

[0070] Dissolve 10mg of insulin in 10ml of medicinal hydrochloric acid solution with a concentration of 0.001mol / L and stir at 25°C for 30min at a mass ratio of 0.001:1 to make an insulin acid solution;

[0071] Add the insulin acid solution dropwise to the polymer mixed solution, so that the mass ratio of the polymer to insulin is 10:1, and continue stirring and mixing for 30 minutes after the dropwise addition to obtain a mixed solution;

[0072] (2) Transfer the mixed solu...

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Abstract

The invention discloses a preparation method of a pH sensitive / membrane adhesive bifunctional insulin-loaded mixed micelle nanoparticle. The preparation method comprises the following steps: dissolving a polymer poly(methyl methacrylate-co-methacrylic acid)-b-polymethyl methacrylate monomethoxypolyethylene glycol ester P(MMA-co-MAA)-b-PPEGMA and a polymer poly(methyl methacrylate-co-methacrylic acid)-b-polyaminoethyl methacrylate P(MMA-co-MAA)-b-PAEAMA into a polymer solution in an organic solvent, dissolving insulin in an acid solution with a pH value of 2-3, after fully dissolving, mixing the insulin solution and the polymer solution evenly, and then transferring the mixed solution into a dialysis bag, dialyzing the mixed solution in an environment of pH = 5 to 5.5 to form a polymer drug-loaded micelle, removing the organic solvent, and freeze-drying the polymer drug-loaded micelle to obtain the insulin-loaded mixed micelle nanoparticles with obvious pH sensitivity and excellent membrane adhesion.

Description

technical field [0001] The invention relates to an insulin mixed micelle nanoparticle and a preparation method thereof, in particular to a pH-sensitive / membrane-adhesive bifunctional insulin-loaded mixed micelle nanoparticle and a preparation method thereof, belonging to the technical field of medical materials. Background technique [0002] As quality of life improves and dietary sugar intake increases, the risk of developing diabetes increases, and the World Organization predicts that diabetes will become the seventh leading cause of death by 2030. [0003] Insulin is an essential drug for the treatment of type 1 diabetes and an adjuvant drug for type 2 diabetes. Insulin is currently mainly administered by injection, but injection will bring severe pain to the patient, and also cause subcutaneous fat atrophy, hypoglycemia and other adverse reactions. The normal dynamics of endogenous insulin secretion may not be replicated, which may reduce the efficiency of glycemic cont...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/32A61K47/34A61K38/28A61P3/10
CPCA61K9/5138A61K9/5153A61K38/28A61P3/10
Inventor 吴志民陆腾飞段鳗珍刘跃进熊迪李蓉
Owner XIANGTAN UNIV
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