CN114617971A - Application of magnetic drug-loaded microspheres and related product - Google Patents

Application of magnetic drug-loaded microspheres and related product Download PDF

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Publication number
CN114617971A
CN114617971A CN202011458023.9A CN202011458023A CN114617971A CN 114617971 A CN114617971 A CN 114617971A CN 202011458023 A CN202011458023 A CN 202011458023A CN 114617971 A CN114617971 A CN 114617971A
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Prior art keywords
magnetic
drug
product
microspheres
endothelial cell
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CN202011458023.9A
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Inventor
林晓曦
马刚
应涵汝
岑卿卿
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Ninth Peoples Hospital Shanghai Jiaotong University School of Medicine
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Ninth Peoples Hospital Shanghai Jiaotong University School of Medicine
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Priority to CN202011458023.9A priority Critical patent/CN114617971A/en
Publication of CN114617971A publication Critical patent/CN114617971A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1611Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/14Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Vascular Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses application of magnetic drug-loaded microspheres in preparation of a product for treating vascular malformation. The invention develops the application field of the magnetic drug-carrying microspheres, the product obtains better target tissue selectivity and stability, the release of the drug in the transportation process is reduced by carrying the endothelial cell damage drug by the magnetic mesoporous ferroferric oxide, the targeted aggregation of the drug is realized by using the magnet, and the endothelial cell damage drug delivery system based on the magnetic microspheres is constructed, the operation is simple and convenient, and the cost is low.

Description

Application of magnetic drug-loaded microspheres and related product
Technical Field
The invention relates to the field of medicines, in particular to application of magnetic medicine carrying microspheres and related products.
Background
Vascular malformations are a common vascular disease with difficulties, mainly including venous malformations, arteriovenous malformations, wine stains, lymphatic malformations and the like, about twenty million people are ill in China, the morbidity in newborns is up to 1 percent, and the vascular malformations are listed as one of thirty diseases of modern surgical Problems (Current Problems in Surgery) by the American surgeon society.
Vascular malformations (vasular malformations) are born, do not regress by themselves except for the midline venular malformation, and increase with age. Ultrastructural characterization of vascular malformed endothelial cells is mature vascular endothelial cells, with a normal proliferation cycle. Such vascular lesions have potential teratogenic ability, affect the appearance and normal physiological functions of patients, and occasionally endanger life due to complications such as secondary hemorrhage. At present, the oral and maxillofacial vascular malformations are treated by a plurality of methods, and the drug therapy mainly adopts the injection therapy of a hardening agent for destroying vascular endothelial cells. Can be used as single treatment method, or combined treatment with surgery, laser, etc.
However, for vascular malformations with wide range of pathological changes or high flow rate, the medicine is difficult to inject into the focus, or after the medicine is injected, the medicine is difficult to stay in the tumor cavity, so how to increase the local concentration of the medicine, prolong the action time of the medicine and improve the curative effect needs to find a completely innovative idea to try to overcome the acknowledged problem.
Disclosure of Invention
In view of the above-mentioned drawbacks of the prior art, the present invention aims to provide a use of magnetic drug-loaded microspheres and related products.
In a first aspect of the invention, the invention provides a use of magnetic drug-carrying microspheres for preparing a product for treating vascular malformation, wherein the magnetic drug-carrying microspheres comprise a magnetic microcarrier and an endothelial cell destruction drug, and the endothelial cell destruction drug is loaded on the magnetic microcarrier.
In a second aspect of the present invention, a vascular malformation treatment product is provided, which at least comprises magnetic drug-loaded microspheres, wherein the magnetic drug-loaded microspheres comprise a magnetic microcarrier and an endothelial cell disruption drug, and the endothelial cell disruption drug is loaded on the magnetic microcarrier.
In a third aspect of the present invention, there is provided a method for preparing a product for treating vascular malformation, comprising the steps of: dispersing the magnetic microcarrier in the endothelial cell destruction drug water solution, centrifuging, and taking the precipitate to obtain the product.
The invention has the beneficial effects that: the invention provides application of magnetic drug-loaded microspheres in preparation of vascular malformation treatment products, and develops the application field of the magnetic drug-loaded microspheres, the products obtain better target tissue selectivity and stability, release of drugs in the transportation process is reduced by carrying endothelial cell destruction drugs through magnetic mesoporous ferroferric oxide, targeted aggregation of the drugs is realized by using a magnet, an endothelial cell destruction drug delivery system based on the magnetic microspheres is constructed, and the magnetic drug-loaded microspheres are simple and convenient to operate and low in cost.
Detailed Description
The embodiments of the present invention are described below with reference to specific embodiments, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention.
Before the present embodiments are further described, it is to be understood that the scope of the invention is not limited to the particular embodiments described below; it is also to be understood that the terminology used in the examples is for the purpose of describing particular embodiments, and is not intended to limit the scope of the present invention; in the description and claims of the present application, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise.
When numerical ranges are given in the examples, it is understood that both endpoints of each of the numerical ranges and any value therebetween can be selected unless the invention otherwise indicated. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In addition to the specific methods, devices, and materials used in the examples, any methods, devices, and materials similar or equivalent to those described in the examples may be used in the practice of the invention in addition to the specific methods, devices, and materials used in the examples, in keeping with the knowledge of one skilled in the art and with the description of the invention.
Unless otherwise indicated, the experimental methods, detection methods and preparation methods disclosed in the present invention all employ conventional techniques in the art.
The embodiment of the invention provides application of magnetic drug-loaded microspheres in preparation of vascular malformation treatment products, wherein the magnetic drug-loaded microspheres comprise magnetic microcarriers and endothelial cell destruction drugs, and the endothelial cell destruction drugs are loaded on the magnetic microcarriers.
The endothelial cell-disrupting drug is a drug which can disrupt endothelial cells, and examples thereof include sodium morrhuate, absolute alcohol and pingyangmycin (bleomycin which is commonly used abroad), and sodium tetradecyl sulfate, ethanolamine, prolamin, diatrizoic acid, quinoline, poppy oil, hypertonic glucose, tetracycline or doxycycline, OK-432 (streptolysin), Ethibloc, hampsofil and urea.
Furthermore, the particle size of the magnetic drug-loaded microsphere is 50-100 nm. It is easy to pass through capillary (malformed capillary diameter is 20 μm-200 μm).
Optionally, the vascular malformation treating product is a product for treating one or more of venous malformation, arteriovenous malformation, wine stain or lymphatic malformation.
Preferably, the magnetic microcarrier is ferroferric oxide magnetic microspheres. It is easy to pass through capillary.
Optionally, the ferroferric oxide magnetic microspheres are mesoporous ferroferric oxide magnetic microspheres.
One embodiment of the present invention provides a product for treating vascular malformation, which at least comprises magnetic drug-loaded microspheres, wherein the magnetic drug-loaded microspheres comprise a magnetic microcarrier and an endothelial cell destruction drug, and the endothelial cell destruction drug is loaded on the magnetic microcarrier.
Optionally, the vascular malformation treating product is a product for treating one or more of venous malformation, arteriovenous malformation, wine stain or lymphatic malformation.
The particle size of the magnetic drug-carrying microsphere is 50-100 nm.
Preferably, the magnetic microcarrier is ferroferric oxide magnetic microspheres.
Optionally, the ferroferric oxide magnetic microspheres are mesoporous ferroferric oxide magnetic microspheres.
One embodiment of the present invention provides a method for preparing a product for treating vascular malformation, comprising the steps of: dispersing the magnetic microcarrier in the endothelial cell destruction drug water solution, centrifuging, and taking the precipitate to obtain the product.
The magnetic microcarrier is ferroferric oxide magnetic microspheres.
Optionally, the magnetic microcarrier is prepared by the following method:
(1) dispersing KIT-6 into toluene to obtain a mixture I;
(2) dropwise adding a concentrated ferric nitrate solution into the mixture I, and stirring to volatilize toluene to obtain a mixture II;
(3) and calcining the mixture II in air, and removing KIT-6 to obtain the magnetic microcarrier.
Example 1
The mesoporous magnetic microspheres carrying endothelial cell destruction drugs with a certain dose are injected intravenously, the magnetic field is applied to the focus part to realize the enrichment of magnetic drug-carrying particles at the focus part and avoid the ingestion of a reticuloendothelial system, so that the drug concentration at the target part is obviously improved, the toxic and side effects are reduced, and the drug utilization rate is improved. The magnetic microspheres for transporting endothelial cell destruction drugs can selectively stay in the vascular malformation lesion area, so that the selective vascular destruction of the lesion malformation can be realized, and other surrounding tissues are intact. The ferroferric oxide (Fe3O4) required by the method has small magnetic particle diameter, is easy to pass through malformed vessels (the diameter of the smallest vessel in vascular malformation, namely malformed capillary vessels is 20-200 mu m, and the malformed veins, arteriovenous vessels and lymphatic vessels can reach several centimeters), has low toxicity, simple experimental conditions, simple and convenient operation and low cost.
Example 2
1. Mesoporous ferroferric oxide synthesis
(1) 1g of KIT-6 was weighed out and dispersed in 20ml of toluene and stirred for 5 minutes by a magnetic stirrer. (2) Dropwise adding 0.8mL of concentrated ferric nitrate solution into the mixed solution, fully volatilizing toluene under the vigorous stirring of a magnetic stirrer, (3) calcining the obtained solid in air at 600 ℃, and (4) removing a KIT-6 template by using a sodium hydroxide solution, washing and drying to obtain the mesoporous ferroferric oxide material.
2. Drug loading of mesoporous ferroferric oxide magnetic microspheres
Dispersing 100mg of mesoporous ferroferric oxide magnetic microspheres in 100ml of endothelial cell destruction medicine solution, wherein the concentration of the endothelial cell destruction medicine is 1mg/ml, stirring for 5 hours at room temperature, centrifuging, and taking supernatant for later use. Drying the precipitate at 60 deg.C under vacuum for 10 hr, and storing the lyophilized powder in refrigerator at 2-8 deg.C under sealed condition.
3. Characteristics of drug-loaded mesoporous ferroferric oxide magnetic microspheres
After the mesoporous ferroferric oxide and the magnetic endothelial cell-carried damaged drug microspheres are synthesized under the optimal preparation conditions, the mesoporous ferroferric oxide and the magnetic endothelial cell-carried drug microspheres are subjected to relevant characterization through X-ray powder diffraction (XRD), a Transmission Electron Microscope (TEM), particle size, Zeta potential (DLS) and magnetic property detection (SQUID). Simulating the drug sustained release analysis and stability evaluation of the magnetic endothelial cell-carried destroyed drug microspheres in human body environment.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Those skilled in the art can modify or change the above-described embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which may be made by those skilled in the art without departing from the spirit and scope of the present invention as defined in the appended claims.

Claims (10)

1. The magnetic drug-loaded microspheres comprise magnetic microcarriers and endothelial cell destruction drugs, and the endothelial cell destruction drugs are loaded on the magnetic microcarriers.
2. The use of claim 1, wherein the magnetic drug-loaded microspheres have a particle size of 50-100 nm.
3. The use according to claim 1, wherein the vascular malformation-treating product is a product for treating one or more of venous malformations, arteriovenous malformations, wine stains or lymphatic malformations.
4. The use according to claim 1, wherein the magnetic microcarrier is a ferroferric oxide magnetic microsphere.
5. The product for treating vascular malformation is characterized by at least comprising magnetic drug-loaded microspheres, wherein the magnetic drug-loaded microspheres comprise magnetic microcarriers and endothelial cell destruction drugs, and the endothelial cell destruction drugs are loaded on the magnetic microcarriers.
6. The product for treating vascular malformation of claim 1 wherein the magnetic drug-loaded microspheres have a particle size of 50-100 nm.
7. The product for treating vascular malformation of claim 1, wherein the magnetic microcarriers are ferroferric oxide magnetic microspheres.
8. A preparation method of a product for treating vascular malformation comprises the following steps: dispersing the magnetic microcarrier in the endothelial cell destruction drug water solution, centrifuging, and taking the precipitate to obtain the product.
9. The method for producing a product for treating vascular malformation of claim 8, wherein the magnetic microcarriers are ferroferric oxide magnetic microspheres.
10. The method for producing a product for treating vascular malformation of claim 9, wherein the magnetic microcarrier is produced by:
(1) dispersing KIT-6 into toluene to obtain a mixture I;
(2) dropwise adding a concentrated ferric nitrate solution into the mixture I, and stirring to volatilize toluene to obtain a mixture II;
(3) and calcining the mixture II in air, and removing KIT-6 to obtain the magnetic microcarrier.
CN202011458023.9A 2020-12-11 2020-12-11 Application of magnetic drug-loaded microspheres and related product Pending CN114617971A (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009073193A2 (en) * 2007-12-03 2009-06-11 The Johns Hopkins University Methods of synthesis and use of chemospheres
CN102100928A (en) * 2010-12-27 2011-06-22 微创医疗器械(上海)有限公司 Liquid embolism material composition and preparation method thereof
CN104027808A (en) * 2014-04-03 2014-09-10 广州一代医药科技有限公司 Pharmaceutical composition capable of resisting vascular anomalies and tumors, and application thereof
CN107185054A (en) * 2017-03-30 2017-09-22 向建平 A kind of novel liquid embolic material and preparation method thereof
CN108079366A (en) * 2017-01-24 2018-05-29 珠海神平医疗科技有限公司 A kind of liquid embolic material and preparation method thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009073193A2 (en) * 2007-12-03 2009-06-11 The Johns Hopkins University Methods of synthesis and use of chemospheres
CN102100928A (en) * 2010-12-27 2011-06-22 微创医疗器械(上海)有限公司 Liquid embolism material composition and preparation method thereof
CN104027808A (en) * 2014-04-03 2014-09-10 广州一代医药科技有限公司 Pharmaceutical composition capable of resisting vascular anomalies and tumors, and application thereof
CN108079366A (en) * 2017-01-24 2018-05-29 珠海神平医疗科技有限公司 A kind of liquid embolic material and preparation method thereof
CN107185054A (en) * 2017-03-30 2017-09-22 向建平 A kind of novel liquid embolic material and preparation method thereof

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