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Application of erythropoietin microspheres to preparation of drugs for treating motor complications in Parkinson's disease

A technology for erythropoietin and Parkinson's disease, which is applied in the directions of drug combinations, medical preparations containing active ingredients, and pharmaceutical formulations to achieve the effects of alleviating the pain of patients, having no toxic and side effects, and being environmentally friendly.

Inactive Publication Date: 2013-01-16
XIN HUA HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Experimental studies on the protective effect of erythropoietin on PD models and its mechanism have been reported, but the application of microspheres prepared from erythropoietin, polysaccharides, and sustained-release materials to treat and prevent PD motor complications has not yet been reported. see the report

Method used

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  • Application of erythropoietin microspheres to preparation of drugs for treating motor complications in Parkinson's disease
  • Application of erythropoietin microspheres to preparation of drugs for treating motor complications in Parkinson's disease
  • Application of erythropoietin microspheres to preparation of drugs for treating motor complications in Parkinson's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1 Preparation of erythropoietin microspheres

[0028] 1. Preparation of erythropoietin polysaccharide particles

[0029] ①Use ultrapure water to prepare 10% (w / w) polyethylene glycol (PEG) aqueous solution and 10% (w / w) dextran aqueous solution respectively. Accurately weigh 800 mg of naturally extracted erythropoietin and dissolve in 7.2 ml of ultrapure water for use.

[0030] ②Under the condition of 0℃~4℃, mix the above-mentioned dextran aqueous solution, erythropoietin aqueous solution and PEG aqueous solution according to the volume ratio of 1:1:5, 1:1:10, 1:1:20 or 1:1: Mix at a ratio of 1:40, then vortex for 30s to 60s to mix thoroughly.

[0031] ③ The mixed solution of erythropoietin, PEG and dextran was frozen overnight, and then vacuum freeze-dried.

[0032] ④ Wash the sample obtained in step ③ three times with dichloromethane to remove the PEG continuous phase, and obtain erythropoietin-loaded polysaccharide particles.

[0033] The obtained ery...

Embodiment 2

[0042] Example 2 Preclinical test of microspheres prepared from naturally extracted erythropoietin in treating motor complications of PD

[0043] 1. Experimental method

[0044] 1. Preparation of levodopa-induced dyskinesia (LID) model

[0045] After the rats were anesthetized by intraperitoneal injection of 3% pentobarbital, the cranial position was strictly fixed on the rat brain stereotaxic instrument, the skin of the head was disinfected with povidone iodine after shearing, the scalp was incised along the midline, and the periosteum was cauterized with 15% hydrogen peroxide. Expose the sutures of the skull and bregma, determine the coordinates of bregma, and determine the injection site of the right medial forebrain bundle (MFB) according to the "Rat Brain Stereotaxic Atlas" written by Bao Xinmin et al. mm, 1.7mm to the right of the sagittal suture, 8.0mm below the skull, and 2.4mm to the incisor line; ②4.4mm behind the anterior bregma, 1.2mm to the right of the sag...

Embodiment 3

[0079] Example 3 Preclinical test of microspheres prepared by gene recombination expressing erythropoietin in treating motor complications of PD

[0080] See Example 1 for the preparation method of recombinantly expressed erythropoietin microspheres, and the experimental method is the same as that of Example 2. Microspheres are prepared by gene recombinantly expressed EPO instead of naturally extracted EPO, injected subcutaneously or intracranially into LID rats, and then detected Corresponding indicators. Table 2 shows the effect of the microspheres prepared by genetically recombinantly expressing EPO on the number of rotations of the rat model.

[0081] Table 2 The effect of different doses of gene recombinant expression EPO microspheres on the number of rotations of the rat model

[0082]

[0083] It can be seen from the table that the microspheres prepared by gene recombination expressing EPO can reduce the number of involuntary rotations of LID rats, and high-dose E...

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Abstract

The invention discloses application of erythropoietin microspheres to preparation of drugs for treating motor complications in the Parkinson's disease. The erythropoietin microspheres are obtained by means of preparing one of naturally extracted erythropoietin, genetic recombination expression erythropoietin, polyethylene glycol modified erythropoietin, glycosylation modified erythropoietin or human serum fused erythropoietin with polysaccharides into particles, and preparing the particles with sustained-release materials into the microspheres. The application has the advantages that a novel medicinal use of the erythropoietin microspheres is cultivated, a novel application field is developed, treating and preventing the motor complications in the Parkinson's disease by the erythropoietin microspheres have the advantages of long-acting sustained release, no toxic and side effects, fine compliance, patient pain relieving, low cost and the like and are easily accepted by patients, and the erythropoietin microspheres are simple in preparation process and environment-friendly and have excellent application prospects in treating and preventing the motor complications in the Parkinson's disease.

Description

technical field [0001] The invention relates to a new application of erythropoietin microspheres, in particular to the application of erythropoietin microspheres in the preparation of drugs for treating motor complications of Parkinson's disease. Background technique [0002] Parkinson's disease (PD) is a common neurodegenerative disorder in middle-aged and elderly people, which is mainly related to the degeneration and loss of dopaminergic neurons in the substantia nigra compact area and the resulting reduction of dopamine transmitters in the nigrostriatal pathway. After years of clinical practice, it is generally believed that levodopa is still the most effective drug for the treatment of Parkinson's disease. However, after long-term use of levodopa, most patients will experience symptom fluctuations, dyskinesia (1evodopa-induced dyskinesia, LID) and mental symptoms, that is, PD motor complications. Dopa will produce free radicals due to its own oxidation, which can lead ...

Claims

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Application Information

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IPC IPC(8): A61K9/16A61K9/19A61K38/18A61K47/36A61P25/16
Inventor 刘振国袁伟恩张奇昕戚辰
Owner XIN HUA HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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