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Uses of modified chitosan, and nanometer complex containing modified chitosan

A nano-composite, chitosan technology, applied in the field of medicine, can solve the problems of difficulty in permeation, the influence of insulin stability, and the improvement of oral absorption of incapable protein polypeptide drugs.

Pending Publication Date: 2017-12-05
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] CN 102614498A discloses an insulin-anionic surfactant nanocomposite to improve the stability of insulin in the gastrointestinal tract and promote the penetration of drugs through biofilms. sexual influence
CN 102120781A discloses a nano-carrier based on chitosan, which improves the water solubility and absorption-promoting effect of chitosan by modifying chitosan with arginine and lysine, but due to the Strong hydrophilicity and large molecular weight, it is extremely difficult for such drugs to passively diffuse through the small intestinal epithelial cell monolayer, and ordinary nanocarriers cannot improve the oral absorption of protein and polypeptide drugs to an ideal level

Method used

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  • Uses of modified chitosan, and nanometer complex containing modified chitosan
  • Uses of modified chitosan, and nanometer complex containing modified chitosan
  • Uses of modified chitosan, and nanometer complex containing modified chitosan

Examples

Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0083] Preparation of Example 1 Modified Chitosan

[0084] Take raw material chitosan (Mw is 100,000, dynamic viscosity is 65mpa s, Zhejiang gold shell, degree of deacetylation is 90%) 3g, add 1% (v / v) acetic acid aqueous solution and stir at room temperature, then add sodium deoxycholate (900mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (528mg), adjust the pH to 5.5 with aqueous sodium hydroxide solution, after 24 hours of reaction, use hydrogen oxidation Adjust the pH to 9.0 with sodium aqueous solution, centrifuge the precipitate, dialyze with a dialysis bag (MWCO 50,000), freeze-dry, and obtain 2.5 g of yellow floc after drying, which is modified chitosan.

[0085] The prepared modified chitosan and the raw material chitosan were dissolved in deuterated acetic acid and then analyzed by proton nuclear magnetic resonance (Varian-MERCURY Plus-300, USA).

[0086] Compared figure 1 The NMR spectra of chitosan (CS) and deoxycholic acid-coupled chitosa...

preparation Embodiment 2

[0091] The preparation of preparation example 2 modified chitosan

[0092] Get raw material chitosan (Mw is 200,000, dynamic viscosity is 140mpa s, Zhejiang gold shell, deacetylation degree is 85%) 3g add 1% (v / v) acetic acid aqueous solution and stir at room temperature, add sodium deoxycholate successively (1800mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (1056mg), adjust the pH to 5.5 with aqueous sodium hydroxide solution, after 24 hours of reaction, use hydrogen oxidation Adjust the pH to 9.0 with sodium aqueous solution, centrifuge the precipitate, dialyze with a dialysis bag (MWCO 100,000), freeze-dry, and obtain 2.5 g of yellow floc after drying, which is modified chitosan.

[0093] The degree of substitution of deoxycholic acid was measured with an elemental analyzer to be about 3.2%.

preparation Embodiment 3

[0094] Preparation of Example 3 Modified Chitosan

[0095] Get raw material chitosan (Mw is 100,000, dynamic viscosity is 65mpa s, Zhejiang gold shell, deacetylation degree is 90%) 3g adds 1% (v / v) acetic acid aqueous solution and stirs at room temperature, adds taurocholic acid successively Sodium (900mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (528mg), adjust the pH to 5.5 with aqueous sodium hydroxide solution, after 24 hours of reaction, use hydrogen Adjust the pH to 9.0 with sodium oxide aqueous solution, centrifuge the precipitate, dialyze with a dialysis bag (MWCO 50,000), freeze-dry, and obtain 2.4 g of yellow floc after drying, which is modified chitosan.

[0096] The degree of substitution of sodium taurocholate was measured by an elemental analyzer to be about 1.5%.

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Abstract

The present invention relates to uses of modified chitosan as a protein polypeptide drug carrier, wherein the modified chitosan has a structural unit represented by the following formula defined in the specification, R in each structure unit can be the same or different, and respectively and independently are hydrogen, acetyl, or the residue obtained after an amidation reaction between a cholic acid-based compound and the amino group in a raw material chitosan, the weight average molecular weight of the raw material chitosan is 1000-1000000, the deacetylation degree is 70-95%, and the substitution degree of the cholic acid-based compound in the modified chitosan is 0.5-20%. The invention further relates to a nanometer complex containing the modified chitosan, a preparation method and uses thereof, wherein the nanometer complex is mainly used for promoting the oral absorption of protein polypeptide drugs, and can well improve the biological treatment effects of protein polypeptide drugs.

Description

technical field [0001] The invention relates to the technical field of medicine, more specifically, relates to the use of a modified chitosan, a nanocomposite comprising the modified chitosan, its preparation method and use. The nanocomposite of the present invention is mainly used to promote the oral absorption of protein polypeptide drugs, and has a better effect of improving the biological efficacy of protein polypeptide drugs. technical background [0002] With the development of biotechnology, protein and peptide drugs with specific pharmacological activities are playing an increasing role in clinical applications. So far, dozens of protein and peptide drugs have been marketed globally. As the most convenient way of administration, the research on the oral administration route of protein and polypeptide drugs has increasingly shown its urgency and urgency. [0003] However, since protein and polypeptide drugs are easily degraded by the acidic environment in the stomach...

Claims

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Application Information

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IPC IPC(8): A61K47/36A61K47/28A61K38/28A61K38/18
Inventor 甘勇范未伟郭仕艳朱春柳夏登宁
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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