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Application of erythropoietin source peptide to preparation of medicament for treating autoimmune disease of nervous system

An erythropoietin and autoimmune technology, applied in the field of biomedicine, can solve the problems of blood pressure restricting the use of erythropoietin, and achieve the effects of recovery of exercise ability, improvement of limb reflex ability, and excellent effect

Active Publication Date: 2011-10-05
ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, large doses and multiple injections of erythropoietin will produce a series of unavoidable potential risk events, including erythropoiesis and blood viscosity caused by increased hematocrit, thrombosis caused by platelet activation, and possible blood pressure increase. Many side effects such as high blood pressure, tumor growth promotion, and induction of anti-erythropoietin antibody production limit the use of erythropoietin in many cases

Method used

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  • Application of erythropoietin source peptide to preparation of medicament for treating autoimmune disease of nervous system
  • Application of erythropoietin source peptide to preparation of medicament for treating autoimmune disease of nervous system
  • Application of erythropoietin source peptide to preparation of medicament for treating autoimmune disease of nervous system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1: Preparation of Erythropoietin-derived Peptides

[0030] The amino acid sequence of the erythropoietin-derived peptide is as follows: Gln Glu Gln Leu Glu Arg Ala Leu Asn Ser Ser (this segment of polypeptide is derived from the 58th (glutamine) and 62nd (glutamic acid) of erythropoietin in turn. ), 65th (glutamine), 69th (leucine), 72nd (glutamic acid), 76th (arginine), 79th (alanine), 80th (leucine), 83rd (asparagine), 84th (serine), 85th (serine);

[0031]Erythropoietin-derived peptides were synthesized on an ARI 431A solid-phase peptide synthesizer (PE Company, USA). Methods The standard fluorenylmethoxycarbonyl (Fmoc) protocol was used, and arginine was coupled twice. Initially select 0.125mmol p-hydroxymethylphenoxymethyl polystyrene resin (HMP resin), extend the peptide chain from the carboxyl terminal to the amino terminal one by one according to the polypeptide sequence, the amount of each amino acid is 0.5mmol, and the mole of the resin The ratio is...

Embodiment 2

[0033] Example 2 Preparation of Erythropoietin-derived Peptide Liposomes

[0034] Erythropoietin-derived peptide liposomes were prepared by reverse evaporation method. Dissolve lecithin and cholesterol in diethyl ether at a mass ratio of 1:1, distill off the organic solvent therein under reduced pressure, and form a uniform W / O emulsion in an ultrasonic water bath for 5 minutes, then add an appropriate amount such as SEQ ID NO: The erythropoietin-derived peptide shown in 1 was repeatedly frozen and thawed in a 42° water bath and dry ice, and passed through a film extruder with a pore size of 100 nm several times. Utilize that the volume of the erythropoietin-derived peptide shown in SEQ ID NO: 1 increases after binding to the liposome, and the erythropoietin-derived peptide that is not bound to the liposome is separated with an agarose gel CL-4B column. The mass ratio of lecithin, cholesterol and small molecule polypeptide in the liposome is 50:50:1. Then the morphological s...

Embodiment 3

[0035] Example 3 Application of Erythropoietin-derived Peptide and Liposome in Autoimmune Peripheral Neuritis

[0036] 1. Animals:

[0037] Lewis rats, male, 8-10 weeks old, weighing 200-220 grams, were purchased from the Experimental Animal Center of Third Military Medical University, and were normally kept in a clean animal room.

[0038] 2. Drugs:

[0039] The treatment group of erythropoietin-derived peptide liposomes: intraperitoneal injection of erythropoietin-derived peptide liposomes for the treatment of nervous system autoimmune diseases at 20 nmol / kg body weight, a total of 6 animals;

[0040] Erythropoietin-derived peptide treatment group: intraperitoneal injection of 20 nmol / kg body weight of erythropoietin-derived peptide shown in SEQ ID NO: 1 for the treatment of nervous system autoimmune diseases, a total of 6 animals;

[0041] PBS group: intraperitoneal injection of the same volume of PBS as the treatment group, a total of 6 rats.

[0042] 3. Test method:

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Abstract

The invention relates to the field of biological medicines, in particular to application of an erythropoietin source peptide to the preparation of a medicament for treating an autoimmune disease of a nervous system. When the erythropoietin source peptide and an erythropoietin source peptide liposome are used for treating the autoimmune disease of the nervous system, the autoimmune diseases athletic ability of the nervous system of a rat is recovered, the limb reflecting capability is remarkably improved, and the activating quantity of macrophages and the expression quantity of inflammatory factors are remarkably suppressed; more importantly, the function of the erythropoietin source peptide liposome is better than that of the erythropoietin source peptide, and the administration frequencyis reduced remarkably; and when the erythropoietin source peptide and the erythropoietin source peptide liposome are used, the hematopoietic function is not induced.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of erythropoietin-derived peptides in the preparation and treatment of nervous system autoimmune diseases. Background technique [0002] Nervous system autoimmune diseases include peripheral and central nervous system autoimmune diseases, among which acute peripheral nerve autoimmune diseases are clinically called Guillain-Barré syndrome, and its internationally recognized and commonly used animal model is experimental autoimmune neurological inflammation (EAN). The central autoimmune disease is clinically called multiple sclerosis syndrome, and its commonly used animal model is EAE. [0003] Guillain-Barre syndrome (Guillain-Barre'Syndrome, GBS), also known as acute inflammatory demyelinating polyneuropathy (AIDP), is an autoimmune demyelinating disease of the peripheral nervous system. One of the common diseases that harm people's health. The disease usually has an...

Claims

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Application Information

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IPC IPC(8): A61K38/18A61P25/02A61P29/00A61P37/02
Inventor 张志仁罗邦伟吴玉章
Owner ARMY MEDICAL UNIV
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