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Use of ferritin to treat iron deficiency disorders

A ferritin and barrier technology, applied in the field of treating patients with iron deficiency disorders, can solve the problem that the concentration of lactoferrin cannot be detected, etc.

Inactive Publication Date: 2011-05-18
CHYNA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Lactoferrin has been proposed to also transport iron into the brain (Ji B. et al. Life Sci. 78:851-855, 2005), but concentrations of lactoferrin in serum are barely detectable and the protein is usually present in cells (neutrophils) and therefore unlikely to play a role in transporting iron to the brain and other organs

Method used

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  • Use of ferritin to treat iron deficiency disorders
  • Use of ferritin to treat iron deficiency disorders
  • Use of ferritin to treat iron deficiency disorders

Examples

Experimental program
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Effect test

Embodiment 1

[0063] Preparation of ferritin

[0064] All experiments in this example used recombinant human H-ferritin or horse spleen ferritin. Recombinant human H-ferritin was prepared by transforming chemically competent Br21 cells with His-tagged recombinant human H-ferritin plasmid. After cell growth, the protein was purified to a final concentration of 2.8 mg / ml using a nickel protein filter column. Horse spleen ferritin was obtained commercially (Sigma) and was selected because it contained an approximate 90:10 ratio of L, H-ferritin subunits.

[0065] Cell culture and preparation of endothelial cell monolayers

[0066] We used bovine retinal cells (BRECs) as an in vitro model of the blood-brain barrier (BBB) ​​to test the hypothesis that ferritin could be transported across the endothelial cell layer and to begin to propose a mechanism for ferritin transport across the BBB. This well-studied model has been shown to possess all the necessary properties and properties of the blood...

Embodiment 2

[0100] introduction

[0101]We developed new dietary approaches to alleviate iron deficiency. This approach is based on our findings in vivo, including the H-ferritin receptor, in the brain, and on the fact that H-ferritin is the preferred means of iron uptake into all organs except the liver relative to L-rich ferritin confirmed. Others have shown that H-ferritin is abundant in breast milk, suggesting that the protein is a mechanism for delivering iron between mother and infant. This latter statement is potentially true for all mammals, not just humans. In addition, the gene sequence and protein structure of H-ferritin are highly conserved in the animal kingdom. Therefore, the use of H-ferritin as an iron delivery protein should not be limited to humans.

[0102] We have devised a method using yeast to deliver H-ferritin as a dietary supplement. To initiate this approach, initial studies transformed yeast to express the human H-ferritin gene, which can be translated into...

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Abstract

H-ferritin receptors on endothelial cells In rat brain rat brain microvasculature are a means for transporting iron across the blood brain barper. A method for treating an iron deficiency disorder in the brain of a patient comprises administepng to a patient in need an H- ferritin-iron complex. A method for using H-ferritin as a targeting moiety comprises attaching H-ferritin to a liposome targeted to the brain or cells within the brain. A method for treating an iron overload disorder in a patient comprises administering to a patient a multi subunit ferritin complex at less than 100% iron binding capacity.

Description

[0001] Continuing Application Information [0002] This application claims the benefit of U.S. Provisional Patent Application No. 60 / 886,972, filed January 29, 2007, and U.S. Provisional Patent Application No. 60 / 984,007, filed October 31, 2007, each of which is hereby incorporated in its entirety This article is incorporated by reference. Background of the invention [0003] Ferritin, the major intracellular iron storage protein in prokaryotes and eukaryotes, is a large multi-subunit complex (almost 480 kDa) comprising 24 polypeptide subunits. This iron storage complex is present in high concentrations in serum and can contain up to 4,500 iron ions (Fe 3+ ). In mammals, there are two distinct subunit species, heavy (H) with a molecular weight of approximately 21 kDa and light (L) with a molecular weight of 19 kDa, which share approximately 54% sequence identity. The H and L subunits exhibit distinct functions: the L subunit increases the stability of the iron core, while ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01N25/00A61K38/40
CPCA61K47/483A61K33/26A61K38/1709A61K45/06A61K47/644A61P1/00A61P13/12A61P15/00A61P25/00A61P25/02A61P25/16A61P25/20A61P25/24A61P25/28A61P3/00A61P35/00A61P7/00A61P7/02A61P7/06A61P3/10A61K2300/00
Inventor J·R·康纳R·L·凯尔
Owner CHYNA
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