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Folate-modified medicine-carrying hydroxylapatite and preparation method thereof

A technology of drug-loaded hydroxyapatite and hydroxyapatite, which can be used in pharmaceutical formulations, medical preparations without active ingredients, and medical preparations containing active ingredients, etc., can solve problems such as normal tissue damage and damage, and achieve High load capacity, reduced leakage rate, good chemical stability and biocompatibility

Inactive Publication Date: 2017-01-25
DALIAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although inorganic drug carriers such as silicon dioxide and ferric oxide have high drug loading capacity, good chemical stability and biocompatibility, if they accumulate excessively in the body, they will cause damage to normal tissues. Accumulated silica is particularly damaging to the lungs and liver

Method used

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  • Folate-modified medicine-carrying hydroxylapatite and preparation method thereof
  • Folate-modified medicine-carrying hydroxylapatite and preparation method thereof
  • Folate-modified medicine-carrying hydroxylapatite and preparation method thereof

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preparation example Construction

[0021] The present invention aims to provide a preparation method of folic acid-modified drug-loaded hydroxyapatite (FA@D@HAP), and a product prepared by the method. The preparation method includes: first preparing drug-loaded hydroxyapatite (D@HAP), and using a silane coupling agent or an amino polymer to carry out surface amination treatment, and using folic acid to aminate the surface The step of modifying the drug-loaded hydroxyapatite.

[0022] Unless otherwise specified, the symbols FA used in this manual represent folic acid, D represents the drug contained, DOX represents doxorubicin, HAP represents hydroxyapatite, D@HAP represents drug-loaded hydroxyapatite, FA@ D@HAP stands for folate-modified drug-loaded hydroxyapatite.

[0023] In the specific embodiment, in the method, drug-loaded hydroxyapatite is prepared by gas-liquid precipitation hydrothermal method: water-soluble calcium salt, phosphate and drug are prepared by reacting in an ethanol-water system at 100-120...

Embodiment 1

[0040] Example 1. Preparation of FA@DOX@HAP

[0041] 1.1 Synthesis of drug-loaded hydroxyapatite (DOX@HAP)

[0042] Adopt gas-liquid precipitation hydrothermal method to combine, weigh 30mg doxorubicin hydrochloride, 1.490g Ca(NO 3 ) 2 4H 2 O and 0.495g of (NH 4 ) 2 HPO 4 respectively dissolved in 2mL of ultrapure water, 30mL of absolute ethanol and 2mL of ultrapure water, and Ca(NO 3 ) 2 4H 2 The pH of the ethanol solution of O was adjusted to about 10.5. In this alkaline environment, slowly add the aqueous solution of doxorubicin hydrochloride dropwise while stirring, and after stabilizing for 10 minutes, continue to add dropwise (NH 4 ) 2 HPO 4 Aqueous solution, after the dropwise addition, continue to stir for 1 hour, then pour the turbid solution into the reaction kettle, conduct a hydrothermal reaction at 120°C for 24 hours, then centrifuge at a high speed, wash the product with ultrapure water and absolute ethanol several times, vacuum it at 60°C Dry for 12 ...

Embodiment 2

[0047] Example 2. Test of basic properties of drug-loaded hydroxyapatite modified by folic acid

[0048] 2.1 Size and morphology of folic acid-modified drug-loaded hydroxyapatite

[0049] The morphology and size of the folic acid-modified drug-loaded hydroxyapatite obtained in Example 1 is determined by observation with a transmission electron microscope, and the test results are shown in figure 1 . It can be clearly seen from the transmission electron microscope pictures that the FA@DOX@HAP nanoparticles synthesized by co-precipitation and hydrothermal combination are rod-shaped, with an average length of 50-100nm and an average diameter of 5-20nm, and are not easy to aggregate. Good dispersion.

[0050] 2.2 Advanced Fourier Transform Infrared Spectroscopy

[0051] Take 1-2mg folic acid-modified drug-loaded hydroxyapatite sample, mix it with dry potassium bromide powder (A.R. grade) in an agate mortar and grind it into a fine powder, put it into a mold, and compress it in...

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Abstract

The invention discloses a folate-modified medicine-carrying hydroxylapatite and a preparation method thereof. The method comprises the following steps: firstly preparing medicine-carrying hydroxylapatite, performing surface amination treatment on the medicine-carrying hydroxylapatite by use of a silane coupling agent or an amino polymer, and modifying the surface-aminated medicine-carrying hydroxylapatite by use of folic acid. The folate-modified medicine-carrying hydroxylapatite, which is prepared by the method, is capable of sensitively recognizing and combining folate receptors highly expressed in most of tumors; the folate-modified medicine-carrying hydroxylapatite penetrates through cytomembranes in an endocytosis manner, so that slow targeted release of anti-cancer medicines can be realized. Not only can the coating rate of anti-cancer medicines be improved, but also the leakage rate of nano carriers in the anti-cancer medicines during a blood circulation process can be effectively reduced, further the release efficiency and local concentration of the anti-cancer medicines are improved, the dosage, toxic and side effects and the like of the anti-cancer medicines are reduced, and the folate-modified medicine-carrying hydroxylapatite has great research value and application prospects in the field of cancer treatment.

Description

technical field [0001] The invention relates to the field of biological nanomaterials, in particular to a folic acid molecule-targeted and acid-sensitive responsive hydroxyapatite nano drug compound, a preparation method and application thereof. Background technique [0002] Cancer is one of the most important diseases that endanger the health of all human beings. At present, there are more than 10 million new cancer patients in the world every year, and more than 6 million deaths. The seriousness of the harm and the difficulty of treatment have attracted great attention from the public, government and scientific circles in many countries. The development of means that can treat such diseases more effectively is of great significance to the promotion of human health. [0003] Anticancer drugs Chemotherapy is the most important cancer treatment after surgery. At present, most small molecule anticancer drugs are poor in water solubility, and surfactants are usually used to e...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/22A61K47/04A61K31/704A61P35/00
CPCA61K47/22A61K31/704A61K47/02
Inventor 樊江莉王素真康垚杜健军彭孝军
Owner DALIAN UNIV OF TECH
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