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Application of type II collagen allosteric peptide for treating rheumatoid arthritis with nasal mucosa medicine administration

A technology of allosteric peptide and nasal mucosa, which is applied in the application field of type II collagen allosteric peptide nasal mucosa administration in the treatment of rheumatoid arthritis, and can solve problems such as unacceptable, abnormal liver function, and difficult disease

Inactive Publication Date: 2008-08-20
PEOPLES HOSPITAL PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, in the treatment of rheumatoid arthritis, these drugs do not act on the initial stage of the disease, and it is difficult to control the disease in a targeted manner, resulting in continuous progression of systemic and joint diseases, and eventually disability
Moreover, due to the extensive immunosuppressive effects of these drugs, there are many adverse reactions such as bone marrow suppression and abnormal liver function, many patients cannot accept these drugs.

Method used

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  • Application of type II collagen allosteric peptide for treating rheumatoid arthritis with nasal mucosa medicine administration
  • Application of type II collagen allosteric peptide for treating rheumatoid arthritis with nasal mucosa medicine administration
  • Application of type II collagen allosteric peptide for treating rheumatoid arthritis with nasal mucosa medicine administration

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1: Design and synthesis of polypeptide

[0024] The aforementioned research work (4-7) It has been proved that amino acids 267-270 in the CII polypeptide mainly bind to T cell receptors and activate T cells. In the experiment of the present invention, the CII263-272 prototype peptide and the CII allosteric peptide in which alanine was used to replace the corresponding amino acid were firstly synthesized by solid-phase method (Table 2). In order to improve the absorption rate, utilization and enhance the curative effect of the polypeptide, the amino terminal of each peptide is connected with the myristic acid gene during the synthesis, so as to facilitate the transport of the polypeptide into the cell. The decapeptides used in this study all contain more than 4 hydrophilic residues, such as lysine (K) and glutamic acid (E), which are easy to dissolve and absorb. These peptides do not contain easily degradable methionine (M), tryptophan (W), or easily deamina...

Embodiment 2

[0029] Example 2: The inhibitory effect of nasal mucosal administration of CII allosteric peptide of the present invention on experimental arthritis

[0030] In the immune response leading to arthritis, antigen-presenting cells induce the activation of T cells through antigens, and promote the proliferation of T cells, causing increased levels of CII antibodies and cytokines (such as IFN-γ) in animals, which in turn leads to rheumatoid arthritis. The characteristic pathological changes of inflammation. Therefore, the inhibitory effect of non-T cell-binding peptides on arthritis can be understood by detecting the levels of cytokines in experimental animals. At the same time, the pathological section can also make a comprehensive judgment on the efficacy of the drug from the perspective of histology.

[0031]In the animal experiment scheme of the present invention, collagen-induced arthritis (CIA) in Lewis rats was induced with bovine CII, and then the arthritic rats were treat...

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Abstract

The invention provides a nasal mucosa administration approach using II type collagen altered peptide to cure rheumatoid arthritis, the II type collagen altered peptide nasal mucosa administration specific can inhibit abnormal immune reaction of the rheumatoid arthritis, and control the development of the disease radically aiming at the original tache of disease incidence.

Description

technical field [0001] The invention relates to the application of nasal mucosal administration of type II collagen allosteric peptide to treat rheumatoid arthritis. 1. Background technology [0002] Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic aggressive joint disease. The prevalence rate in China is 0.34%, there are nearly 5 million patients in the whole country, and the disability rate is as high as 93%. The pathogenesis of the disease is a process of "stimulating a chain immune reaction" driven by antigens. Immune injury mediated by infectious agents and autoimmune responses is the basis for the pathogenesis and evolution of rheumatoid arthritis. Antigen polypeptides are expressed by antigen-presenting cells in the body and activate T lymphocytes, resulting in the release of cytokines, increased production of inflammatory media such as immunoglobulins, chemokines and free radicals, and then cause vasculitis, synovial hyperplasia, ...

Claims

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Application Information

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IPC IPC(8): A61K38/16A61P19/02A61P29/02
Inventor 栗占国
Owner PEOPLES HOSPITAL PEKING UNIV
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