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Use of low-dose erythropoietin for stimulating endothelial precursor cells, regenerating organs, and slowing down progression of end organ damages

A technology of erythropoietin and endothelial progenitor cells, which can be used in medical preparations containing active ingredients, anti-inflammatory agents, skin diseases, etc. The effect of increasing, increasing the number

Inactive Publication Date: 2009-12-16
埃博普鲁斯股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] However, the mechanism of EPC migration and differentiation has not been fully elucidated

Method used

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  • Use of low-dose erythropoietin for stimulating endothelial precursor cells, regenerating organs, and slowing down progression of end organ damages
  • Use of low-dose erythropoietin for stimulating endothelial precursor cells, regenerating organs, and slowing down progression of end organ damages
  • Use of low-dose erythropoietin for stimulating endothelial precursor cells, regenerating organs, and slowing down progression of end organ damages

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0161] Example 1 The effect of EPO on patients with renal anemia

[0162] The effect of EPO on renal anemia (Hb < 10.5 g / dl) caused by end-stage renal disease (before death from renal failure; creatinine clearance < 35 ml / min) was studied. Eleven patients were treated with an average weekly dose of 5000 IU rhEPO (recombinant human EPO) by intravenous or subcutaneous injection for at least 8 weeks. After EPO treatment, the endothelial progenitor cells in the patient's blood were examined over 20 weeks, and the number of endothelial progenitor cells was measured by flow cytometry and culture test at 0, 2, 4, 6 and 8 weeks after EPO treatment and differentiation status were analyzed.

[0163] Circulating peripheral blood stem cells (CPBSC) represent a small population of cells that express both the CD34 and CD45 antigens. With the aid of flow cytometry, a method for detecting the number of CPBSCs has been developed based on the ISHAGE method (Sutherland et al., J. Hematother....

Embodiment 2

[0170] Example 2 , Promoting wound healing through systemic use of rhEPO

[0171] FVB / N mice were anesthetized with isoflurane by means of inhalational anesthesia. Both hind limbs were depilated with depilatory solution and disinfected with 70% alcohol. Skin wounds were made on the right abdomen of each test rat using a 4 mm disposable sterile biopsy punch. The opposite side was used as an internal control. After the operation, penicillin G (20000 units / kg) was used for one-time antibiotic treatment. The human recombinant EPO analog Aranesp (0.1 μg / kg body weight) was injected subcutaneously once a week throughout the experiment. Treatment began 7 days prior to tissue punch wounding. The result is as Figure 8 shown. The figure shows that the use of EPO can significantly speed up the wound repair process. Figure 19 Shows the effect of EPO on wound repair. The figure shows that a typical skin wound was made on a mouse with a tissue punch, and after 7-8 days of treatm...

Embodiment 3

[0172] Example 3 , slowing the progress of chronic kidney injury by EPO treatment

[0173] Eight-week-old Sprague Dawley rats were anesthetized with ketamine (120 mg / kg) and ropon (10 mg / kg). The right kidney was excised on day 0 and immediately placed in formalin for histological examination. The arteries feeding the upper and lower poles of the left kidney were ligated. In this way, kidney damage occurs in the corresponding kidney area, and only the middle third remains functional. The rats were subcutaneously injected with Aranesp (0.1 μg / kg body weight) once a week, while the control group was injected with NaCl.

[0174] Figure 10 Kaplan-Mayer survival curves for the two experimental groups are shown. Animals treated with Aranesp showed a clear survival advantage compared to animals treated with saline.

[0175] Figures 15-18 It has been shown that the kidney tissue processed by EPO does not show obvious pathological changes, but serious pathological changes can...

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Abstract

The invention relates to the use of low-dose erythropoietin for stimulating physical mobilization, proliferation, and differentiation of endothelial precursor cells, stimulating vasculogenesis, treating diseases that are linked to a dysfunction of endothelial precursor cells, and producing pharmaceutical compositions used for the treatment of such diseases as well as pharmaceutical compositions containing erythropoietin and other appropriate agents for stimulating endothelial precursor cells.

Description

[0001] This application is an invention patent with an application date of January 22, 2005, an application number of 200580009425.8, and an invention titled "Application of low-dose erythropoietin for stimulating endothelial progenitor cells, organ regeneration and slowing down the process of end organ damage" Divisional application of the application. technical field [0002] The present invention relates to the use of erythropoietin (EPO), especially in low doses, alone or in combination with other chemical, thermal, mechanical and biological agents, for inducing the physiological migration, proliferation and differentiation of endothelial progenitor cells, with For the stimulation of angiogenesis, for the treatment of diseases associated with endothelial progenitor cell dysfunction, and for the production of pharmaceutical compositions for the treatment of these diseases, in addition to the production of pharmaceutical compositions containing EPO and other suitable active i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61K45/00A61K8/64A61Q1/00A61Q7/00A61Q17/00A61Q19/00A61Q19/08A61P17/00A61P17/14A61P17/16A61P19/08A61P1/16A61P1/00A61P13/12A61P5/50
CPCA61K38/1816A61Q19/00A61Q1/00A61K8/64A61Q17/00A61Q7/00A61Q19/08A61P1/00A61P1/04A61P1/16A61P1/18A61P13/12A61P15/06A61P17/00A61P17/02A61P17/14A61P17/16A61P19/00A61P19/04A61P19/08A61P25/28A61P29/00A61P3/00A61P3/10A61P3/06A61P41/00A61P43/00A61P5/50A61P9/00A61P9/10A61P9/12A61K2300/00A61K38/18A61K38/17
Inventor 费迪南德·赫尔曼·巴尔曼赫尔曼·哈勒尔
Owner 埃博普鲁斯股份有限公司
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