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Brain targeted medicine lipidosome preparation as well as preparation method and application thereof

A pharmaceutical preparation and brain-targeting technology, which is applied in liposome delivery, drug combination, pharmaceutical formulation, etc., can solve the problems of not being able to penetrate the blood-brain barrier and not having brain-targeting properties, and achieve low toxicity and good stability , the effect of promoting intake

Inactive Publication Date: 2014-10-01
谢英 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Aiming at defects such as lack of brain targeting and inability to penetrate the blood-brain barrier in the existing liposome preparations, the inventor first discovered through diligent research that a non-biologically active, non-immunogenic arginine-rich The short peptides of acid residues are used as targeting molecules, and the anti-brain cancer drug liposomes with a certain enhancement effect are prepared by the film hydration method and the three-bottle method, which are easy for industrial production, and solve the problem that the existing liposome preparations do not have brain targets. Tropism, technical issues of not being able to penetrate the blood-brain barrier

Method used

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  • Brain targeted medicine lipidosome preparation as well as preparation method and application thereof
  • Brain targeted medicine lipidosome preparation as well as preparation method and application thereof
  • Brain targeted medicine lipidosome preparation as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1 2

[0037] Preparation of Preliminary Example 1 Distearoylphosphatidylethanolamine-Polyethylene Glycol-P167 / P168 Complex

[0038] Weigh an appropriate amount of P167 peptide into an eggplant-shaped bottle, dissolve it with anhydrous DMF, and add triethylamine equivalent to 2.5-3 times the molar amount of the P167 / P168 peptide to adjust the pH of the solution to 7.4. Add an appropriate amount of DSPE-PEG-NHS (DSPE-PEG-NHS:P167 peptide=1.2:1, molar ratio) and react on a magnetic stirrer at room temperature for 2 days in the dark. The reaction mixture was dialyzed in 500 mL of distilled water in a dialysis bag with a molecular weight cut-off of 3500 Da for 3 days, and the dialyzed fluid was changed every 12 hours to remove incompletely reacted reactants, triethylamine and DMF. The liquid in the dialysis bag was freeze-dried at -40°C and 0.22 mbar for 24 hours to obtain a white solid powder.

experiment example 1

[0039] Experimental example 1 P167 modified Adriamycin liposome preparation process

[0040] 1. Determination of the binding mode of P167 peptide and liposome

[0041] In order to quantitatively detect the P167 peptide modification density and optimize the preparation process of P167 peptide modified liposomes with high binding rate, the P167A peptide (RRRRRRRRRK(β-Ala-FITC)-amide) with similar sequence to P167 peptide (GGRRRRRRR) was used instead. The P167A peptide introduces lysine residues on the basis of the P167 peptide, and FITC is labeled on one amino site of the lysine residues, while the other amino group can react with the activation group of PEGylated phospholipids to generate a guiding compound . In this way, the quantitative detection of the modified ligand on the liposome can be realized, which provides a research means for further investigation of the preparation process of the P167 peptide modified liposome.

[0042] Targeted compound method is a widely used ...

experiment example 2

[0059] Optimization of P167 modified density in experimental example 2 preparation

[0060] 1. The relationship between P167 peptide modification density and liposome properties

[0061] (1) Experimental method:

[0062] Adjust the dosage of P167 in the prescription in the preparation process of Example 1, and the modification densities of the P167 peptides were 0%, 1%, 2%, 4%, and 8%, respectively. Prepare doxorubicin liposome preparations without density modification by P167. The encapsulation efficiency ee% of DOX-P167-SSL preparation was determined by dextran G50 column separation method (Jiang J, Yang SJ, Wang JC, et al. Sequential treatment of drug-resistant tumors with RGD-modified liposomes containing siRNA or doxombicin[ J]. Eur J Pharm Biopharm, 2010; 76: 170-178.). The particle size of DOX-P167-SSL preparation was measured by laser light scattering instrument.

[0063] DPH is used as a fluorescent probe, the degree of fluorescence polarization p is measured by a ...

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Abstract

The invention discloses a brain targeted medicine lipidosome preparation as well as a preparation method and an application thereof. The brain targeted medicine lipidosome which has an enhancement effect is prepared by taking oligopeptide with arginine residues as a target molecule and by using a thin film hydration method and a three-bottle method, and the technical problems that a conventional lipidosome preparation cannot penetrate through blood brain barrier and has no brain targeting are solved. The galenic pharmacy observation shows that the encapsulation efficiency and the particle size of the brain targeted medicine lipidosome preparation disclosed by the invention meet the medicine requirements, and compared with ordinary lipidosome, the brain targeted medicine lipidosome disclosed by the invention is good in acid sensitivity and good in stability in serum, and has in-vitro cell medicine effect and in-vivo mouse glioma medicine effect which are higher than those of long circulation Doxorubicin lipidosome.

Description

technical field [0001] The invention relates to a liposome preparation, in particular to a brain-targeted anti-tumor drug liposome preparation and a preparation method thereof, and belongs to the field of brain-targeted drug liposome preparations. Background technique [0002] Anthracyclines or anthracycline antibiotics are a class of chemotherapy drugs derived from Streptomyces peucetius var.caesius. They are capable of treating more types of cancer than any other type of chemotherapy drug, and chemotherapy using them is one of the most effective anticancer therapies currently available; cancers that can be used include leukemia, lymphoma, breast cancer, uterine cancer, ovarian cancer cancer and lung cancer etc. Commonly used anthracyclines include doxorubicin, daunorubicin, and epirubicin. The main side effect of this class of drugs is cardiotoxicity, which greatly limits their further use. [0003] As a new type of drug carrier, liposome can enrich antineoplastic drugs...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/42A61K9/127A61K9/19A61K31/704A61P35/00
Inventor 谢英陈建华
Owner 谢英
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