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Micromolecule polypeptide and micromolecule polypeptide liposome as well as applications thereof

A technology of small molecule peptides and liposomes, applied in the field of biomedicine, can solve problems such as blood pressure limiting the use of erythropoietin

Active Publication Date: 2011-10-12
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 promoting tumor growth and inducing anti-erythropoietin antibody production limit the use of erythropoietin in many cases

Method used

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  • Micromolecule polypeptide and micromolecule polypeptide liposome as well as applications thereof
  • Micromolecule polypeptide and micromolecule polypeptide liposome as well as applications thereof
  • Micromolecule polypeptide and micromolecule polypeptide liposome as well as applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1: Preparation of Small Molecular Peptides

[0037] The amino acid sequence of the small molecule polypeptide is as follows: Gln Glu Gln Leu Glu Arg Ala Leu Asn Ser Ser (, this section of polypeptide is derived from the 58th (glutamine), 62nd (glutamic acid), and erythropoietin successively. 65th (glutamine), 69th (leucine), 72nd (glutamic acid), 76th (arginine), 79th (alanine), 80th (leucine) amino acid), 83rd (asparagine), 84th (serine), 85th (serine).

[0038] Small molecule peptide synthesis was performed on an ABI 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 i...

Embodiment 2

[0040] The preparation of embodiment 2 small molecule polypeptide liposomes

[0041] Small molecule polypeptide liposomes were prepared by reverse evaporation method. Dissolve an appropriate amount of lecithin and cholesterol (mass ratio 1:1) in ether, distill off the organic solvent therein under reduced pressure, and use an ultrasonic water bath for 5 minutes to form a uniform W / O emulsion, then add an appropriate amount such as SEQ ID The small molecule polypeptide shown in NO: 1 (peptide: lecithin: cholesterol mass ratio is 1:50:50), was repeatedly frozen and thawed in a 42° water bath and dry ice, and passed through a film extruder with a pore size of 100nm several times in a row . Utilizing that the volume of the small molecule polypeptide shown in SEQ ID NO: 1 becomes larger after being combined with the liposome, the small molecule polypeptide not combined with the liposome is separated with an agarose gel CL-4B column. Then observe the morphological structure of the...

Embodiment 3

[0042] Example 3 Application of Small Molecular Polypeptides and Small Branch Polypeptide Liposomes in the Treatment of Traumatic Brain Injury in Rats

[0043] 1. Animals:

[0044] Male SD rats, weighing 250-300 grams, were purchased from the Animal Laboratory of the Third Military Medical University, and were normally kept in a clean animal room.

[0045] 2. Drugs:

[0046] Small molecule polypeptide liposome treatment group: intraperitoneal injection of polypeptide small molecule polypeptide liposome 20nmol / kg body weight, a total of 6;

[0047] Small molecule polypeptide treatment group: 20nmol / kg body weight of the small molecule polypeptide shown in SEQ ID NO: 1 was given for intraperitoneal injection, a total of 6 mice;

[0048] Blank group: intraperitoneal injection of the same volume of PBS as the treatment group, a total of 6 rats.

[0049] 3. Experimental method:

[0050] The free-fall striking method is a common animal modeling method for traumatic brain injury....

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Abstract

The invention relates to the field of biomedicine and in particular relates to micromolecule polypeptide liposome with an amino acid sequence shown in SEQ IDNO:1. The motor function and sense function of a traumatic cerebral injury rat are obviously improved by the micromolecule polypeptide liposome, the number of apoptotic nerve cells in brain tissues is obviously decreased, the number of survival nerve cells in the brain tissues is obviously increased, and the mRNA (messenger ribonucleic acid) levels of brain tissue inflammation factor tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) are obviously lowered; and compared with the hemopoietin, the micromolecule polypeptide liposome has the advantage that the hematopoietic function of the rat can not be induced when the micromolecule polypeptide liposome is injected continuously.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to small molecule polypeptides and small molecule polypeptide liposomes and their application. Background technique [0002] Traumatic brain injury (Traumatic brain injury, TBI) refers to various reasons that cause the brain to be subjected to blunt, sharp or acceleration / deceleration force, resulting in impaired brain function, which is an important cause of human life-threatening. and globally is the leading cause of death in people under 40 years of age. The annual incidence of TBI is about 200 / 100,000 population in developed countries, and about 56 / 100,000 population in my country in the 1980s. Its annual incidence rate is also increasing, and it is currently believed that the annual incidence rate of TBI in my country exceeds 100 / 100,000 population. TBI in my country has a mortality rate of about 10.8%, a vegetative state of about 2.6%, a severe disability rate of about 2.2%, and a ...

Claims

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Application Information

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IPC IPC(8): C07K7/06A61K9/127A61K47/24A61K47/28A61P25/00
Inventor 张志仁罗邦伟吴玉章
Owner ARMY MEDICAL UNIV
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