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Application of heparin iron compound in treatment of chronic inflammatory anemia

A technology of chronic inflammation and complex, applied in the field of medicine and biology, to achieve the effect of increasing the level of hemoglobin, reducing the content of hepcidin and shortening the bleeding time

Active Publication Date: 2018-06-22
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Studies by Maura Poli and others found that heparin has good anti-hepcidin activity, and regulates the content of hepcidin in the body through the BMPs or IL-6 pathway (Maura Poli et al, Heparin: a potent inhibitor of hepcidin expression in vitro and in vivo, BLOOD, VOLUME 117, NUMBER 3), which provides a way for the treatment of chronic inflammatory anemia; however, due to the side effects such as hemorrhage, thrombocytopenia, and bleeding complications caused by the anticoagulant activity of heparin, it is limited to small Dosage or short-term use

Method used

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  • Application of heparin iron compound in treatment of chronic inflammatory anemia
  • Application of heparin iron compound in treatment of chronic inflammatory anemia
  • Application of heparin iron compound in treatment of chronic inflammatory anemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1 Determination of heparin and heparin iron particle size

[0040] The experiment set up heparin group and heparin iron complex group for experiment. Weigh an appropriate amount of heparin and dissolve the heparin solution.

[0041] Preparation of heparin iron nanocomposite: slowly add NaOH solution to FeCl 3 In solution, according to the molar ratio of Fe 3+ :OH - =1:2 After mixing, adjust the pH to about 2.8 to form ferrous ion [Fe(OH) 2 ] + Solution. According to the number of uronic acids in the heparin disaccharide structure, the number of sulfuric acid groups and carboxylate groups in the heparin disaccharide structure, and [Fe(OH) 2 ] + Ion combination, prepared into heparin: [Fe(OH) 2 ] + =1:1, 1:2, 1:3, 1:4 complex solutions, respectively called heparin iron complex 1, heparin iron complex 2, heparin iron complex 3, heparin iron complex 4, ultrasound conditions Next, slowly add the ferrous ion solution to the heparin solution, and continue ultrasonication f...

Embodiment 2

[0043] Example 2 Investigation of heparin iron complex targeted inhibition of hepcidin to play an anti-inflammatory anemia effect

[0044] 1. The effect of heparin iron complex on the level of hepcidin in the plasma of inflammatory anemia model mice

[0045] Establishment, intervention and blood sample collection of inflammatory anemia mouse model: SPF BALB / c mice, 6-8 weeks, weight 20-25g, adaptive feeding for 1 week, environmental temperature 25-28℃, free eating and drinking. Randomly divided into 4 groups by digital method, namely normal control group, model group, heparin medication group, heparin iron nanocomposite medication group. The scapular fat of mice was injected into the pad with 0.1mL / 20g of turpentine to establish an inflammatory anemia model; the heparin group was injected with 6mg / kg of heparin daily in the tail vein, and the heparin-iron nanocomposite group was injected with 6mg / kg of heparin daily in the tail vein. Heparin iron. After the administration, 8 mice...

Embodiment 3

[0053] Example 3 Investigation of anticoagulant effect of heparin iron complex

[0054] The experiment was divided into three groups: normal group, heparin group and heparin iron nanocomposite group. The experiment was carried out using the mouse tail-cutting method. After the administration for 20 minutes, the mouse was placed in a fixation device, the tail was vertical, and the vein of the mouse was pierced, causing the mouse to bleed. The timing starts when the blood overflows by itself, every 30s The blood was sucked with filter paper until the blood stopped flowing out naturally, and the bleeding time of each group of mice was recorded.

[0055] The experimental results are as Figure 5 Shown. The results showed that, compared with the normal group, heparin prolonged the clotting time significantly (P 0.05). This indicates that the heparin iron complex developed by the present invention can effectively eliminate the anticoagulant activity of heparin, and will be safer when u...

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Abstract

The invention discloses application of a heparin iron compound in treatment of chronic inflammatory anemia. The heparin iron nano-compound is proved to have effects of obviously reducing hepcidin content, increasing hemoglobin level in an inflammatory anemia model, significantly lowering the transcription of the hepcidin in HepG2 cells at a lower concentration, and reducing the anticoagulant activity of the hepcidin. The heparin iron nano-compound is prepared and is safely applied to the treatment of the inflammatory anemia taking the hepcidin as a target, and the bleeding risk is avoided.

Description

Technical field [0001] The invention belongs to the field of medical biotechnology, and specifically relates to the therapeutic application of a heparin iron complex to chronic inflammatory anemia, in particular to the application of low anticoagulation therapy with hepcidin as a target. Background technique [0002] The incidence of anemia of chronic disease (ACD) is very high, second only to iron deficiency anemia. ACD is more common in patients with chronic diseases, such as rheumatic diseases, tumors, chronic infections and other chronic diseases. In the treatment of ACD, it is usually carried out mainly for chronic diseases. If effective, the anemia can be relieved automatically. The existing anti-anemia drugs are not effective for ACD. [0003] ACD was once called "Sideroblastic anemia with hemosiderinosis of the reticuloendothelial system". With the continuous deepening of research, it was changed to "Anemia of chronic disease". The pathogenesis of ACD is not very clear. T...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/26A61K9/14A61P7/06A61P29/00A61K31/727
CPCA61K9/14A61K31/727A61K33/26A61K2300/00
Inventor 崔慧斐王晓雪
Owner SHANDONG UNIV
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