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Chitosan nanoparticle for improving absorption of orally delivered insulin by colon and preparation method of chitosan nanoparticle

A technology of chitosan nanoparticles and insulin, which is applied in the directions of non-active ingredients medical preparations, medical preparations containing active ingredients, pharmaceutical formulas, etc. The degree of utilization needs to be improved to achieve the effect of protective activity, good physical and chemical stability, and increased interaction

Active Publication Date: 2015-11-18
江西省药物研究所
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Literature (JournalofAppliedPolymerScience, 1997,63(1):125-132.InternationalJournalofPharmaceutics, 2002,249(1-2):139-147) reported that chitosan nanoparticles wrapped with insulin were prepared by ion cross-linking. The prepared nanoparticles are unstable in the gastric acid environment and cannot protect the substances they encapsulate
The literature (Journal of Shenyang Pharmaceutical University, 2006,23(2):65-69) reported that hydroxypropyl methylcellulose phthalate (HP55) was used to prepare chitosan nanoparticles loaded with Ins by ion cross-linking. enteric-coated capsules to improve the oral colonic absorption of insulin, but the oral bioavailability of insulin needs to be improved

Method used

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  • Chitosan nanoparticle for improving absorption of orally delivered insulin by colon and preparation method of chitosan nanoparticle
  • Chitosan nanoparticle for improving absorption of orally delivered insulin by colon and preparation method of chitosan nanoparticle
  • Chitosan nanoparticle for improving absorption of orally delivered insulin by colon and preparation method of chitosan nanoparticle

Examples

Experimental program
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Effect test

Embodiment 1

[0076] Weigh 8 mg of chitosan powder with a molecular weight of 100,000 Daltons and a degree of deacetylation of 95%, dissolve it in 4 ml of 0.2% acetic acid solution, adjust the pH value to 5.5 with 1 mol / L sodium hydroxide solution, and call it Solution A. Weigh 2 mg of Tat (amino acid sequence GRKKRRQRRRP), dissolve it in solution A and call it solution B, and stir solution B on a magnetic stirrer at room temperature. Weigh 4.2 mg of insulin, dissolve it in 2 mL of 0.1 mol / L hydrochloric acid solution, adjust the pH value to 8.0 with 1 mol / L sodium hydroxide solution, and call it solution C. Solution C was slowly added to solution B under stirring at room temperature, and stirring was continued for 1 hour to form solution D. Weigh 2.3 mg of sodium tripolyphosphate and dissolve it in 2 mL of distilled water and call it solution E. Slowly add solution E to solution D while stirring at room temperature, and continue stirring for 0.5 hours to form nanoparticle suspension F. W...

Embodiment 2

[0078]Weigh 8 mg of chitosan powder with a molecular weight of 50,000 Daltons and a degree of deacetylation of 85%, dissolve it in 4 ml of 0.2% acetic acid solution, adjust the pH value to 6.0 with 1 mol / L sodium hydroxide solution, and call it Solution A. Weigh 2.3 mg of Tat (amino acid sequence GRKKRRQRRRP), dissolve it in solution A and call it solution B, and stir solution B on a magnetic stirrer at room temperature. Weigh 4 mg of insulin, dissolve it in 2 mL of 0.1 mol / L hydrochloric acid solution, adjust the pH value to 8.0 with 1 mol / L sodium hydroxide solution, and call it solution C. Solution C was slowly added to solution B under stirring at room temperature, and stirring was continued for 1 hour to form solution D. Weigh 2 mg of sodium tripolyphosphate and dissolve it in 2 mL of distilled water and call it solution E. Slowly add solution E to solution D while stirring at room temperature, and continue stirring for 0.5 hours to form nanoparticle suspension F. Weigh...

Embodiment 3

[0080] Weigh 8 mg of chitosan powder with a molecular weight of 100,000 Daltons and a degree of deacetylation of 85%, dissolve it in 4 ml of 0.2% acetic acid solution, adjust the pH value to 5.5 with 1 mol / L sodium hydroxide solution, and call it Solution A. Weigh 2 mg of Tat (amino acid sequence GRKKRRQRRRP), dissolve it in solution A and call it solution B, and stir solution B on a magnetic stirrer at room temperature. Weigh 4 mg of insulin, dissolve it in 2 mL of 0.1 mol / L hydrochloric acid solution, adjust the pH value to 8.0 with 1 mol / L sodium hydroxide solution, and call it solution C. Solution C was slowly added to solution B under stirring at room temperature, and stirring was continued for 1 hour to form solution D. Weigh 2.3 mg of sodium tripolyphosphate and dissolve it in 2 mL of distilled water and call it solution E. Slowly add solution E to solution D while stirring at room temperature, and continue stirring for 0.5 hours to form nanoparticle suspension F. Wei...

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Abstract

The invention relates to an enteric material coated chitosan nanoparticle which covers insulin and cell-penetrating peptide Tat and a preparation method of the chitosan nanoparticle. The chitosan nanoparticle is prepared from an enteric material, namely Eudragit S100, insulin, cell-penetrating peptide and chitosan. With the oral administration of the prepared enteric coated insulin chitosan nanoparticle, the amount of loaded contents released from the chitosan nanoparticle in the stomach and the upper part of the small intestine can be greatly reduced due to the protective effect of the enteric material, namely Eudragit S100. As the chitosan nanoparticle arrives at the lower end of the digestive tract, the enteric coating material on the surface of the chitosan nanoparticle begins to dissolve and the chitosan nanoparticle becomes exposed with the increase of pH value; the chitosan nanoparticle is damaged under a weakly alkaline condition, so that the cell-penetrating peptide and the insulin therein are released. The cell-penetrating peptide is capable of prompting the absorption of colonic epithelial cells to the insulin so as to improve the bioavailability of the insulin through oral administration.

Description

technical field [0001] The invention relates to nanometer particles that can be used in the technical field of biomedicine and a preparation method thereof, in particular to a chitosan nanoparticle that improves oral colonic absorption of insulin and a preparation method thereof. Background technique [0002] Insulin is widely used clinically to treat type Ⅰ diabetes, and its main mode of administration is subcutaneous injection. Diabetic patients need to inject insulin (Ins) multiple times a day in order to control their blood sugar levels, which brings great pain to the patient's body and mind and many inconveniences in daily life. The oral drug delivery system is considered to be the most compliant, natural and safest drug delivery method for patients, but the oral bioavailability of insulin is very low and basically has no pharmacological effect. The main reasons are: first, insulin is easily degraded and inactivated by acid and enzymes in the digestive tract; second, i...

Claims

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Application Information

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IPC IPC(8): A61K38/28A61K47/38A61K9/51A61K47/32A61P5/48A61K38/08
Inventor 钟海军陈双喜罗荣余华邓泽元
Owner 江西省药物研究所
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