Insulin oral nano-preparation and preparation method thereof

A nano-formulation, insulin technology, applied in the field of medicine, can solve the problems of insulin inability to absorb and low bioavailability

Inactive Publication Date: 2017-11-21
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, after oral administration, insulin is degraded by enzymes in the digestive tract, and insulin cannot be absorbed by the body through the intestinal mucosa and epit

Method used

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  • Insulin oral nano-preparation and preparation method thereof
  • Insulin oral nano-preparation and preparation method thereof
  • Insulin oral nano-preparation and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] The preparation of embodiment 1. quaternized chitosan (HTCC)

[0015] Dissolve 2g chitosan (molecular weight 5-50kDa, deacetylation degree 85-95%) in 100mL aqueous solution containing 1% (v) acetic acid, add 50mL isopropanol and heat the solution to 60°C, dropwise After adding a certain volume of glycidyltrimethylammonium chloride, the solution was heated to 80° C. and stirred for 24 hours to carry out quaternization reaction. Precipitate the reaction product with acetone, then dissolve the precipitate in deionized water, repeat three times; then dissolve the precipitate in deionized water and dialyze against deionized water, and finally freeze-dry the solution to obtain a purified quaternized shell polysaccharides. with AgNO 3 Standard solution measures the chloride ion concentration in the quaternized chitosan solution, thereby calculates the degree of quaternization of chitosan, see table 1, the result shows under the situation of fixing chitosan charging amount, a...

Embodiment 2

[0019] Embodiment 2. Preparation of quaternized chitosan (HTCC-CA) modified by cholic acid

[0020] 0.5 g of quaternized chitosan with different degrees of quaternization was dissolved in 100 mL of deionized water. Dissolve 0.1-0.5g cholic acid (CA) in 50mL of anhydrous methanol, add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) to the cholic acid methanol solution ( EDC) and N-hydroxysuccinimide (NHS), wherein cholic acid: EDC: NHS = 1: 1.5: 1.5 (molar ratio), after stirring at room temperature for 30 minutes, the methanol solution was slowly added dropwise to the quaternized shell The polysaccharide aqueous solution was stirred at 37° C. for 24 hours to react. The reaction product is firstly dialyzed against a weak base solution, then dialyzed against deionized water, and the dialyzed solution is freeze-dried to obtain purified cholic acid-modified quaternized chitosan. pass 1 H nuclear magnetic resonance spectrum calculates the degree of modification of ch...

Embodiment 3

[0026] Embodiment 3. Preparation of Insulin (INS) / HTCC-CA Nanoparticles - Blending Method

[0027] Dissolve insulin in 0.01mol / L HCl solution, adjust the pH of the solution to 7.4 to prepare 0.1-5.0 mg / mL insulin solution A. Cholic acid-modified quaternized chitosan (HTCC-CA) was dissolved in deionized water, and the pH of the solution was adjusted to 7.4 to prepare 0.1-20 mg / mL HTCC-CA solution B. A certain volume of insulin solution A was slowly added dropwise into a certain volume of HTCC-CA solution B and stirred to obtain INS / HTCC-CA nanoparticles 1 . The particle size of the nanoparticles was determined by light scattering (hydration diameter D h ) and ζ-potential. The unembedded free insulin in the solution was separated by ultrafiltration, the concentration of free insulin in the ultrafiltrate was measured by BCA kit, and the embedding efficiency of insulin was calculated by the following formula:

[0028] Embedding efficiency (%)=((total insulin mass-free insulin m...

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Abstract

The invention belongs to the technical field of medicines, and particularly relates to an insulin oral nano-preparation and a preparation method thereof. The insulin oral nano-preparation is an insulin loaded nano-particle solution prepared by taking cholic acid modified quaternized chitosan and hydroxypropyl methylcellulose phthalate as an insulin composite carrier. A quaternary amine group and a cholic acid group are irregularly connected to chitosan to obtain the cholic acid modified quaternized chitosan, the cholic acid modified quaternized chitosan and insulin interact in an electrostatic and hydrophobic manner to form nano-particles, and the nano-particles can deliver the insulin to the liver to play a role by a bile acid liver and intestine circulation channel in ilea and the liver through intestinal wall cells; and the hydroxypropyl methylcellulose phthalate is added in the nano-particles, the nano-particles can be protected from dissociating in the stomach, therefore, the insulin is protected from being degraded in the digestive tract, the staying time of the nano-particles in a small intestine part is prolonged, and then the nano-particles can be assisted to pass through an intestinal mucosa and the intestinal wall cells.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to an oral insulin nano-preparation and a preparation method thereof. Background technique [0002] Diabetes is a metabolic disease characterized by high blood sugar. At present, subcutaneous injection of insulin is the most effective way to control blood sugar for diabetics [China Practical Medicine, 2009, 4(29): 220-222]. After subcutaneous administration of insulin, insulin is easily absorbed by subcutaneous peripheral tissues [Diabetes Technology & Therapeutics.2004, 6(4): 510-517] and it is easy to cause hyperinsulinemia [China New Drug Journal, 2011, 20(21): 2095 ~2099]. Insulin is administered orally, and insulin can be absorbed from the intestine and enter the hepatic portal vein system, and then reach the liver through blood circulation [Chinese Journal of New Drugs, 2015, 24(22): 2560-2571]. Oral administration is close to the insulin secretion pattern unde...

Claims

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Application Information

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IPC IPC(8): A61K38/28A61K9/08A61K47/36A61K47/38A61P3/10
CPCA61K38/28A61K9/0053A61K9/08A61K47/36A61K47/38
Inventor 姚萍张喆
Owner FUDAN UNIV
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