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Polypeptide drug for treatment of alzheimer's disease

A technology of a drug and a composition, applied in the field of polypeptide drugs for the treatment of Alzheimer's disease, can solve the problems of large side effects, unsafe, increased incidence of breast cancer, etc., and achieve the effect of prolonging the survival period and widening clinical application value.

Pending Publication Date: 2019-06-21
横琴欣健生物科技研究院有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But these medicines have many deficiencies: (1) there is no ideal drug AD first-line treatment medicine for the treatment or reversal of the course of disease at present, such as acetylcholinease (AChE) inhibitors, which can only alleviate the cognitive impairment of early patients and provide moderate symptoms Improvement effect, unable to prevent the progression of the disease
(2) Some drugs have serious side effects
For example, the use of estrogen replacement therapy can reduce the risk of AD in postmenopausal women and improve the cognitive function of AD patients. However, estrogen can promote feminization and can only be used in postmenopausal women. It also increases breast cancer, uterine The incidence of endometrial cancer, ovarian cancer and other diseases
(3) Imported drugs are expensive
However, after testing, it was found to be unsafe and had great side effects

Method used

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  • Polypeptide drug for treatment of alzheimer's disease
  • Polypeptide drug for treatment of alzheimer's disease
  • Polypeptide drug for treatment of alzheimer's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1: Polypeptide Synthesis by Solid Phase Polypeptide Synthesis

[0050] Solid-phase synthesis, resin selection and activation treatment were purchased from Jill Biochemical (Shanghai) Co., Ltd.; take 1.5g of dichloro resin, add it to the reaction column soaked in DCM, soak in DCM 15ml for 30min to fully expand the resin to activate Stand-by; Weigh Fmoc-Cys(Acm).OH 0.31g to dissolve in DCM, then add 0.5ml DIEA to mix and add to the reaction vessel, blow N2 to react for 2hr, filter the reaction solution and add MeOH 5ml to seal the reaction for 1hr, then use DCM Wash with isopropanol and DMF 3 times; remove the amino protecting group, add about 15ml of 20% piperidine in DMF solution for 5 minutes, filter, then add 15ml and react for 20 minutes, wash the resin twice with isopropanol, and wash the resin 3 times with DMF; For the formation of peptide bonds, weigh 0.55g Fmoc-Trp(600)-OH, dissolve 0.35g TBTU in DMF, mix with 0.6ml HoBt (2mol / L) 0.2ml DIEA and add to the...

Embodiment 2

[0051] Example 2: Polypeptide Synthesis by Solid-Phase Polypeptide Synthesis

[0052] The peptide synthesizer adopts the American AB1431A model, and the peptide solid-phase synthesis, resin selection and activation treatment are purchased from Jill Biochemical (Shanghai) Co., Ltd. The N-terminal is acetylated, and the C-terminal is aminated. MBHA resin is used. Note that DIPF (deprotection reagent) cannot be added to the reaction kettle before using DCM. The reaction should not exceed 85°C. After the synthesis reaction, cut, precipitate with glacial ether, put in the refrigerator for 2 hours, and collect by centrifugation.

[0053] Peptide synthesis is actually a process of repeated addition of amino acids, generally from the carboxy-terminus (C-terminus) to the amino-terminus (N-terminus). In the past, peptide synthesis was carried out in solution. Now solid-phase synthesis has become a common method for synthesizing peptides and proteins. Many aspects of it cannot be achiev...

Embodiment 3

[0061] Example 3: Using Gene Recombination to Express Synthetic Polypeptides

[0062] Use genetic engineering technology to use probiotics and yeast to secrete and produce the polypeptide drug of the present invention, and use methods such as yogurt, solid drinks, beer, etc. to use probiotics and yeast to grow and reproduce in the intestinal tract to continuously secrete and produce various diseases. Preventive and therapeutic Peptide drugs. Apply genetic engineering technology to construct probiotics and yeast polypeptide drug and vaccine vectors, and clone antigen genes and cytokine genes to probiotics and yeast plasmids. After the transformation of probiotics and yeast, the peptide drug products containing the expression of the target gene are screened out and used as seed peptide drugs for cryopreservation, and the seed peptide drugs are scaled up for cultivation.

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Abstract

The invention discloses a polypeptide drug for the treatment of alzheimer's disease and belongs to the technical field of protein engineering. The polypeptide drug is selected from an optional one ofthe following amino acid sequences described in SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6 AND SEQ ID. 7. By the arrangement, the survival of mice with the alzheimer's disease can be prolonged, and the polypeptide drug serving as the candidate drug for the treatment of the alzheimer's disease has broad clinical application value.

Description

technical field [0001] The invention relates to the technical field of protein engineering, in particular to a polypeptide drug for treating senile dementia. Background technique [0002] Alzheimer's disease or senile Alzheimer's disease (Alzheimer's disease, AD) is a common disease of the elderly worldwide, accounting for the fourth cause of human death. It was discovered by Bavarian neuropathologist Alzheimer in 1907. It was first discovered and named after it. AD is a diffuse central neurodegenerative disease characterized by progressive cognitive impairment, mental decline, and personality changes, with brain amyloid Aβ1-42 deposition, neurofibrillary tangles, neuronal loss, and slow inflammation Sexual pathological features. The etiology and pathogenesis of AD are still not very clear, but clinically it can be manifested as progressive memory impairment, cognitive dysfunction and behavioral changes. In particular, AD lacks objective and effective indicators before de...

Claims

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Application Information

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IPC IPC(8): C07K7/06C07K14/00A61K38/08A61K38/16A61P25/28
Inventor 叶学敏罗祖樑叶学维周嘉刘兰英
Owner 横琴欣健生物科技研究院有限公司
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