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Chitosan lipoprotein nasal delivery nanocomposite as well as preparation method and application thereof

A nanocomposite, nasal administration technology, applied in the directions of nanomedicine, drug combination, drug delivery, etc., can solve problems such as burden, and achieve the effect of favorable absorption, no nasal mucosal toxicity, and efficient brain targeting.

Active Publication Date: 2021-07-16
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this type of nanocomposite involves the catabolism of chitosan after entering the brain, which brings unnecessary burden to the body

Method used

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  • Chitosan lipoprotein nasal delivery nanocomposite as well as preparation method and application thereof
  • Chitosan lipoprotein nasal delivery nanocomposite as well as preparation method and application thereof
  • Chitosan lipoprotein nasal delivery nanocomposite as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Weigh 0.5g chitosan (molecular weight is 150KDa, deacetylation degree is 98%) and dissolve in 60mL 0.5% acetic acid solution. In addition, 4-carboxyphenylboronic acid (PBA) and 206.6 mg N-hydroxysuccinimide (NHS) of 0.45 times the molar amount of chitosan units were weighed and dissolved in 30 mL methanol, and stirred at room temperature for 30 min. Weigh 342.57 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC·HCl) into the PBA / NHS mixture, stir to dissolve evenly. Then the PBA / NHS / EDC·HCl mixed solution was added to the acetic acid solution of chitosan (the volume ratio of methanol and water in the reaction system was 1:2), stirred at room temperature for 24h, and the reaction solution was transferred to a molecular weight cut-off of 14 ×10 3 In a dialysis bag, dialyze in deionized water for 72 hours, changing the water every 4 hours. The dialyzed sample was freeze-dried to obtain light yellow powder chitosan-phenylboronic acid grafted polymer. Disperse the ...

Embodiment 2

[0046] With reference to the processing condition of embodiment 1, chitosan (molecular weight is 150KDa, degree of deacetylation is 98%) is adjusted to chitosan (molecular weight is 150KDa, degree of deacetylation is 60%), makes chitosan-phenylboronic acid For the grafted polymer, the grafting rate is 9% obtained by calculating the area of ​​the nuclear magnetic resonance peak.

Embodiment 3

[0048] Referring to the process conditions of Example 1, chitosan (molecular weight is 150KDa, degree of deacetylation is 98%) is adjusted to chitosan (molecular weight is 150KDa, degree of deacetylation is 80%), and chitosan-phenylboronic acid is obtained For the grafted polymer, the grafting rate is 12% obtained by calculating the area of ​​the nuclear magnetic resonance peak.

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Abstract

The invention belongs to the field of pharmaceutical preparations, and discloses a chitosan lipoprotein nasal delivery nanocomposite. The chitosan lipoprotein nasal delivery nanocomposite comprises lipoprotein nanoparticles and chitosan or / and chitosan derivatives with a nasal mucosa absorption promoting effect. The invention also discloses a preparation method of the chitosan lipoprotein nasal delivery nanocomposite. The preparation method comprises the following steps of self-assembling the chitosan or / and the chitosan derivative and the lipoprotein nanoparticles into a nasal preparation with good membrane permeability through dynamic acting force. The chitosan lipoprotein nasal delivery nanocomposite is mild in preparation condition, simple in process and easy for industrial production. The system is safe and non-toxic, the biodegradability is good, the nasal mucosa absorption of lipoprotein drugs can be improved, and the efficient brain targeting property is ensured. The dosage form is administrated in a nasal dripping mode, a spraying mode and the like, operation is easy, patients taking medicine for a long time can take the medicine conveniently, and good clinical application prospects are achieved in the aspect of treatment of central nervous system diseases.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a chitosan lipoprotein nasal administration nanocomposite and a preparation method and application thereof. Background technique [0002] In recent years, the research and development of diseases of the central nervous system (CNS) such as Alzheimer's disease, Parkinson's disease, stroke, and glioma are very rapid. However, due to the existence of the blood-brain barrier (BBB), a natural physiological barrier of brain tissue, more than 98% of the drugs with central therapeutic activity lose their curative effect because they cannot cross the BBB. Although peptides and small protein molecules can reach the brain across the BBB through systemic administration, a series of adverse reactions are caused by high therapeutic doses. Although the drug can be delivered directly to the brain by direct injection into the ventricle or brain parenchyma, this invasive del...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K9/19A61K47/61A61K45/00A61P25/16A61P25/28A61P35/00B82Y5/00B82Y30/00B82Y40/00
CPCA61K9/0043A61K9/5169A61K9/19A61K45/00A61K47/61B82Y5/00B82Y30/00B82Y40/00A61P25/28A61P25/16A61P35/00
Inventor 周建平丁杨张华清于淼金熠
Owner CHINA PHARM UNIV
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