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Tumor necrosis factor (TNF)-alpha polypeptide inhibitor and application thereof

A technology of tumor necrosis factor and polypeptide inhibitors, applied in the direction of peptides, anti-inflammatory agents, peptide/protein components, etc., to achieve the effect of preventing or treating rheumatoid arthritis

Inactive Publication Date: 2013-09-11
SUZHOU PULUODA BIOLOGICAL SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

2. Steroid hormones. Hormones are very good analgesic and anti-inflammatory drugs, but long-term use alone cannot improve the condition, but bring many side effects. Steroids can be used as a transitional second-line slow-acting drug before it takes effect, but the dosage should be limited. small, not too long
Because these drugs are monoclonal antibodies, there are disadvantages such as large molecular weight and antigenic reaction, which greatly limit their clinical use.

Method used

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  • Tumor necrosis factor (TNF)-alpha polypeptide inhibitor and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Chemical Synthesis of Peptides

[0019] The peptides were synthesized using Fmoc chemistry. The synthesis reaction proceeds from the C-terminus to the N-terminus. There are free amino groups on the Rink medium (available from Advanced ChemTech), and Ser, His, Tyr, Thr and Asp are connected sequentially. During each ligation step, the amino acid residues are activated, and the activation mixture contains 4 times as many HBTU, HOBt, DIEA and Fmoc-amino acids as there are free amino groups on the medium. After each amino acid linking reaction, a mixture of pyridine / acetic acid / N-methylimidazole (4:1:0.5) was used to block unlinked free amino groups for 10 min. After each amino acid ligation reaction and before the next amino acid is ligated, the Fmoc-group on the medium must be removed, and the Fmoc-group is removed using dimethylformamide containing 20% ​​piperidine, which takes 15 minutes. Finally, after all amino acid residues are linked sequentially, the peptide is c...

Embodiment 2

[0022] Immunoprotective effect of tumor necrosis factor-α polypeptide inhibitor 3 in collagen-induced mouse arthritis animal model

[0023] To construct an animal model of collagen-induced arthritis in mice, and to study the therapeutic effect of tumor necrosis factor-α polypeptide inhibitor 3 on collagen-induced arthritis (CIA) in mice. Mice were used as experimental animals, 90 SPF grade DBA / 1 mice (provided by Sino-British SIPPR Lab. Animal Ltd, animal production license number: SCXK (Shanghai )2008-0016), male, 7-8 weeks old, body weight 18-22 g, were randomly divided into 6 groups, namely normal control group, model control group, peptide inhibitor 3 low, middle and high dosage groups (0.4, 0.8 , 1.6 mg / kg) and positive drug control group (methotrexate 2 mg / kg). In addition to the normal group, the mouse CIA model was established in each experimental group on day 0 by dissolving chicken cartilage type II collagen (cII) with 0.1 mol / l acetic acid into a 4 mg / ml solution a...

Embodiment 3

[0028] Protective effect of tumor necrosis factor-α polypeptide inhibitor 3 on the immune protection of adjuvanted rat arthritis animal model in vivo

[0029]To construct an adjuvant rat arthritis animal model to study the therapeutic effect of tumor necrosis factor-α polypeptide inhibitor 3 on adjuvant arthritis (AA) rats. Rats were used as experimental animals, 90 SPF grade SD rats (provided by Sino-British SIPPR Lab. Animal Ltd, animal production license number: SCXK (Shanghai) 2008 -0016), male, weighing 140 g-160 g, were randomly divided into 6 groups, which were normal control group, model control group, and tumor necrosis factor-α polypeptide inhibitor 3 low, middle and high dosage groups (0.2, 0.4, 0.8 mg / kg) and positive drug control group (methotrexate 1 mg / kg). In addition to the normal group, on the 0th day, each experimental group established a rat AA model by injecting complete Freund's adjuvant containing inactivated Mycobacterium tuberculosis (H37RA, 10 mg / ml)...

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Abstract

The invention provides a tumor necrosis factor (TNF)-alpha polypeptide inhibitor and application thereof and relates to the field of drugs and in particular relates to a polypeptide which has the function of inhibiting TNF-alpha and can prevent and treat rheumatoid arthritis (RA). The sequence of the polypeptide is Asp-Thr-Tyr-His-Ser and is a brand new sequence. The inhibitor has the beneficial effects that the inhibitor can be used for treating RA and has potential new drug development value.

Description

Technical field: [0001] The invention relates to the field of medicine, in particular to a tumor necrosis factor-alpha polypeptide inhibitor for preventing and treating or preventing rheumatoid arthritis. Background technique: [0002] Rheumatoid arthritis (RA) is the most common clinical inflammatory joint disease and one of the main disabling factors. It is about 0.5%-1.0% in the world, and the incidence of RA is about 0.4% in my country. RA can occur at any age, and the incidence rate increases with age. The high-incidence age of women is 45-55 years old, and gender is closely related to the incidence of RA, with a male-to-female ratio of about 1:3. RA is a chronic systemic inflammatory disease of unknown etiology, with chronic, symmetrical, polysynovial arthritis and extra-articular lesions as the main clinical manifestations, and belongs to autoimmune inflammatory disease. Patients often have hand or wrist pain and swelling (especially the swelling on the back of t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06A61K38/08A61P19/02A61P29/00
Inventor 罗瑞雪
Owner SUZHOU PULUODA BIOLOGICAL SCI & TECH
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