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Lf-HA-DOX macromolecule prodrug compound, constructing method thereof and application of Lf-HA-DOX macromolecule prodrug compound to treating glioma

A technology of macromolecules and complexes, applied in medical preparations with non-active ingredients, medical preparations containing active ingredients, drug delivery, etc., can solve problems such as limited and poorly targeted side effects, and increase enrichment concentration , Reduce non-specific expression, easy to operate

Active Publication Date: 2016-06-15
SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, its use in intracranial tumors is limited due to poor targeting and severe side effects, especially cardiotoxicity

Method used

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  • Lf-HA-DOX macromolecule prodrug compound, constructing method thereof and application of Lf-HA-DOX macromolecule prodrug compound to treating glioma
  • Lf-HA-DOX macromolecule prodrug compound, constructing method thereof and application of Lf-HA-DOX macromolecule prodrug compound to treating glioma
  • Lf-HA-DOX macromolecule prodrug compound, constructing method thereof and application of Lf-HA-DOX macromolecule prodrug compound to treating glioma

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Experimental program
Comparison scheme
Effect test

Embodiment L

[0031] The structure of embodiment Lf-HA-DOX macromolecular prodrug complex

[0032](1) The preparation method of hyaluronic acid-doxorubicin macromolecular prodrug (HA-DOX) has been published by the applicant in Chinese patent (CN104689338A), and the brief description is as follows: Weigh 0.5g HA and dissolve it in 50mL deionized water , add excess adipic acid dihydrazide ADH6.5325g, stir to dissolve it, and adjust the pH of the solution to 6.8. EDC and HOBt were weighed, dissolved in a mixed solution of DMSO and water (1:1, v / v, 10 mL), dropped into the above reaction solution, and reacted at room temperature for 24 h. Hydrazine hyaluronic acid (HA-ADH) was obtained by dialysis and lyophilization. Weigh 0.50g HA-ADH and add 10mL deionized water, stir it under nitrogen atmosphere to dissolve it, add glacial acetic acid to adjust the pH to 5, weigh a certain amount of doxorubicin hydrochloride and add it, after it dissolves, continue to pass nitrogen gas for 30min , sealed, ...

experiment example L

[0036] Evaluation of the therapeutic effect of Lf-HA-DOX on orthotopic glioma nude mice

[0037] Establishment of orthotopic glioma model: Balb / c nude mice were anesthetized by intraperitoneal injection of 4% chloral hydrate (10ml / kg), and their heads were fixed on a brain stereotaxic apparatus. Determine the right caudate nucleus as the target according to the stereotaxic anatomy map of the mouse head, 1 mm in front of the bregma, and 3 mm to the right of the midline, drill a small hole with a dental drill, and then under the guidance of a stereotaxic instrument, inject a 25 μl microinjector Take out 5 μl of C6 cell suspension (5*105 cells), slowly insert the needle vertically along the bone hole to 4 mm under the dura mater, and then retract it by 1 mm. Slowly inject for 5 minutes, retain the needle for 3 minutes after the injection, slowly pull out the needle, and then seal the bone hole with bone wax, and suture the incision with No. 4 suture.

[0038] On the 10th day aft...

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Abstract

The invention discloses an Lf-HA-DOX macromolecule prodrug compound, a constructing method thereof and an application of the Lf-HA-DOX macromolecule prodrug compound to treating glioma. According to the Lf-HA-DOX macromolecule prodrug compound, lactoferrin (Lf) serves as ligand for targeting modification, Doxorubicin (DOX) serves as a therapeutic drug, hyaluronic acid (HA) serves as a carrier skeleton, tumor targeting of the HA is used, and the double-targeting macromolecule prodrug compound is obtained. The Lf-HA-DOX macromolecule prodrug compound can penetrate through blood brain barriers, and further has quite good glioma targeting; meanwhile, the effect of slowly releasing the drug can be achieved, and the Lf-HA-DOX macromolecule prodrug compound has the quite good application prospects in treatment of glioma.

Description

technical field [0001] The invention relates to the field of drug carriers, in particular to a carrier Lf-HA-DOX macromolecular prodrug complex capable of passing through the blood-brain barrier and double-targeting on glioma, as well as its construction method and application. Background technique [0002] Glioma is the most common and most malignant primary intracranial tumor. However, due to its diffuse invasive growth and resistance to radiotherapy and chemotherapy, glioma is difficult to be completely cured by traditional treatment methods. Therefore, the clinical treatment of glioma is still a difficult problem that needs to be studied and explored. [0003] An important reason for the failure of traditional chemotherapy is that the existence of the blood-brain barrier makes it difficult for anti-tumor drugs to reach the brain parenchyma. However, traditional carriers, including nanocarriers, do not have the ability to penetrate the blood-brain barrier, which severel...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K31/704A61K9/00A61P35/00
CPCA61K9/0019A61K31/704
Inventor 彭英訚亚涛傅超萍张黎明
Owner SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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