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Therapeutic application of heparin-iron complex on chronic inflammatory anemia

A chronic inflammation and compound technology, applied in the field of medicine and biology, to achieve the effect of shortening bleeding time, prolonging bleeding time and reducing anticoagulant activity

Active Publication Date: 2020-10-02
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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  • Therapeutic application of heparin-iron complex on chronic inflammatory anemia
  • Therapeutic application of heparin-iron complex on chronic inflammatory anemia
  • Therapeutic application of heparin-iron complex on chronic inflammatory anemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] The mensuration of embodiment 1 heparin and heparin iron particle size

[0040] The experiment was set up with heparin group and heparin-iron complex group. Weigh an appropriate amount of heparin and dissolve to obtain a heparin solution.

[0041] Preparation of heparin-iron nanocomposites: Slowly add NaOH solution to FeCl 3 In solution, according to the molar ratio of Fe 3+ :OH - = After 1:2 mixing, adjust the pH to about 2.8 to form ferrous ions [Fe(OH) 2 ] + solution. According to the number of uronic acids in the heparin disaccharide structure, the number of sulfate groups and carboxylate groups contained in the heparin disaccharide structure, and [Fe(OH) 2 ] + Ion binding, 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, ultrasonic conditions Slowly add the ferrous ion solution into the heparin solution, and conti...

Embodiment 2

[0043] Example 2 Investigation of Heparin Iron Complex Targeted Inhibition of Hepcidin in Anti-inflammatory Anemia

[0044] 1. Effect of heparin-iron complex on hepcidin level in plasma of inflammatory anemia model mice

[0045] Establishment of inflammatory anemia mouse model, intervention and blood sample collection: SPF grade BALB / c mice, 6-8 weeks old, weighing 20-25g, were fed adaptively for 1 week, at an ambient temperature of 25-28°C, free to eat and drink, and drink water. They were randomly divided into 4 groups by digital method, namely, the normal control group, the model group, the heparin group, and the heparin-iron nanocomposite group. The model of inflammatory anemia was established by injecting 0.1mL / 20g of turpentine oil into the fat pad of both shoulder blades of mice; the heparin group was injected with 6mg / kg of heparin through the tail vein every day, and the heparin-iron nanocomposite group was injected with 6mg / kg of turpentine through the tail vein ever...

Embodiment 3

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

[0054] The experiment was divided into three groups: normal group, heparin group and heparin-iron nanocomposite group. The mouse tail cutting method was used for the experiment. After 20 minutes of administration, the mouse was placed in a fixer, the tail was vertical, and the mouse vein was punctured, causing the mouse's vein to bleed. The timing started from the blood overflowing by itself, every 30s The blood was aspirated with filter paper until the blood naturally stopped flowing out, and the bleeding time of mice in each group was recorded.

[0055] Experimental results such as Figure 5 shown. The results showed that, compared with the normal group, heparin prolongs the coagulation time very significantly (P0.05). This shows that the heparin-iron complex developed by the present invention can effectively eliminate the anticoagulant activity of heparin, and will be safer when used in ...

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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 technical field of medicine and biology, and in particular relates to the therapeutic application of a heparin-iron complex to chronic inflammatory anemia, in particular to the therapeutic application of low anticoagulant targeting hepcidin. 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 mainly for chronic diseases. If it is effective, anemia can be relieved automatically. The existing anti-anemia drugs are not effective for ACD. [0003] ACD was once known as "sideroblastic anemia with reticuloendothelial hemosiderosis", but with the deepening of research, it was renamed "anemia of chronic disease". The pathogenesis of ACD is still not very clear, and there are thr...

Claims

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Application Information

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Patent Type & Authority Patents(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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