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Medicament using rare earth transferring complex compound as vector

A technology of transferrin and complexes, which is applied in the direction of transferrin, drug combinations, animal/human proteins, etc., can solve the problems of increasing the cost of drug transport systems, achieve high drug transport efficiency, reduce costs, and make simple preparations Effect

Inactive Publication Date: 2007-08-15
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Current solutions include: the use of oligomeric transferrin and the application of various transferrin receptor (TfR) monoclonal antibodies (such as OX26) or their Fab fragments, which greatly increases the cost of drug delivery systems, the latter and Subject to the various limitations of the monoclonal antibody itself

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Preparation of doxorubicin-rare earth transferrin complex targeted anticancer drug

[0064] Doxorubicin is currently a common antibiotic anticancer drug. In order to improve its targeting type, it can be prepared into a doxorubicin-rare earth transferrin complex drug, and the method is briefly described as follows:

[0065] Preparation of rare earth transferrin: Dissolve transferrin Tf (product of Sigma Inc) (2-20mg / ml) in acetic acid buffer solution (0.1M, pH=5.5) containing EDTA (1-10mM) and Vc (10-50mM) ) at 4°C overnight. Then the reaction solution was passed through a Sephadex G-25 gel column (preliminarily equilibrated with 0.1M Tris-HCl buffer solution, pH=7.4) to collect protein components to obtain apo-transferrin Apo-Tf. Add 1:2-5 rare earth trivalent ions (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Sc, Y to the above-mentioned Apo-Tf solution ), react at room temperature for 0.5-1 hour, and then pass through a SephadexG-25 gel column to collec...

Embodiment 2

[0071] Rare earth transferrin modified nano-realgar drug

[0072] Arsenic compounds can effectively treat leukemia, and nano-realgar is a substitute for As 2 o 3 promising alternative medicines. However, the absorption of realgar is not good, and the targeting ability in the blood is poor. Rare-earth transferrin can be modified to increase its absorption capacity and targeting, the method is briefly described as follows:

[0073] Rare earth transferrin was prepared by the aforementioned method.

[0074] Rare earth transferrin was dissolved in PBS (0.1mol / L, pH6.3) at a concentration of 2mg / mL. Add S-acetylmercaptosuccinaldehyde at a molar ratio of 1:5. React at room temperature for 1 hour. Then add 0.05 mol / L hydroxylamine, react at 30° C. for 30 minutes (deacetylation) to obtain thiol-activated rare earth transferrin. Diluted to 0.5mg / ml for use.

[0075] Add realgar powder into a ball mill at a ratio of 1 g of realgar: 100 ml of water, and grind at a speed of 500 r / m...

Embodiment 3

[0079] Rare earth transferrin modified albumin nanospheres loaded with cisplatin

[0080] Cisplatin is one of the main anticancer drugs at present. Cisplatin is highly toxic and cannot be used orally. Rare earth transferrin can be used as a carrier to increase its targeting type and improve oral utilization, and the use of nano-microsphere encapsulation can improve its controlled release efficiency. The method is briefly described as follows:

[0081] Low-ratio biotinylated rare-earth transferrin was prepared by the aforementioned method. Dilute to 0.5mg / ml solution.

[0082] Human serum albumin (200g / L) was added to biotin succinic acid imide activated ester BNHS (20mg / ml, DMSO solution) at a molar ratio of 1:2, and reacted at room temperature for 1 hour to obtain biotinylated human serum albumin.

[0083] Prepare cisplatin-loaded albumin nano-microspheres by emulsification polycondensation method [Zhang Ming et al., Acta Pharmaceutica Sinica, 1994, 29: 380], briefly desc...

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Abstract

This invention relates to a medicine with rare earth transferring complex compound as medicine carrier. The invention provides a medicine comprising effective composition and carrier, wherein carrier is rare earth transferring complex compound. The medicine with rare earth transferring complex compound as carrier can be used as anticancer drug with orient transportation, for oral administration, and absorbent through lung permeation.

Description

technical field [0001] The invention relates to a drug using a rare earth transferrin complex as a drug carrier. Background technique [0002] As a large number of new therapeutic drugs, especially biochemical drugs, are widely used to treat various diseases, many shortcomings of existing drug delivery systems are becoming more and more obvious: low diffusion rate across biological barriers (such as intestinal epithelial cells and blood-brain barrier), Low stability in biological fluids, low affinity for specific pathological sites, non-specific toxicity, and other negative effects caused by high doses, etc. One strategy to solve the above problems is to establish a transport system based on the mechanism of receptor-mediated endocytosis [0003] The transferrin / transferrin receptor drug delivery pathway has shown great potential in the delivery of anticancer drugs, proteins and therapeutic genes to primary malignant tumor cells. The drug delivery system based on transferr...

Claims

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Application Information

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IPC IPC(8): A61K47/42A61K47/48A61P35/00A61P11/00A61P25/00C07K14/79A61K47/64
Inventor 白柯杨晓达袁兰夏青
Owner PEKING UNIV
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