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Application of polypeptides in preparation of medicament for treating or preventing rheumatoid arthritis

一种类风湿性、关节炎的技术,应用在治疗或预防类风湿性关节炎的多肽领域,能够解决不能改善病情、时间不宜过长、未公开其他疾病治疗效果等问题,达到显著社会价值和市场价值、显著类风湿型关节炎、治疗类风湿型关节炎的效果

Active Publication Date: 2014-11-05
CHINA PHARM UNIV
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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
Although the previous patent ZL200510040378.5 discloses that the sequence has a therapeutic effect on melanoma, it does not disclose the therapeutic effect on other diseases

Method used

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  • Application of polypeptides in preparation of medicament for treating or preventing rheumatoid arthritis
  • Application of polypeptides in preparation of medicament for treating or preventing rheumatoid arthritis
  • Application of polypeptides in preparation of medicament for treating or preventing rheumatoid arthritis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Polypeptide Ⅰ, polypeptide Ⅱ and polypeptide Ⅲ were all synthesized by solid-phase synthesis, purified by high-performance liquid chromatography, and the purity of the polypeptide was determined by RP-HPLC. The synthesis method refers to patents 201110194918.0 and 201110370529.9.

[0049] Results: The purity identification results of the synthesized peptides were analyzed by reverse liquid chromatography as follows: the purity of polypeptide Ⅰ, polypeptide Ⅱ and polypeptide Ⅲ were 96.94%, 99.30%, and 96.34%, respectively, and the purity was greater than 95%, meeting the design requirements.

Embodiment 2

[0051] Immunoprotective Effect of Polypeptide Ⅰ in Collagen-Induced Arthritis Mouse Model

[0052] A collagen-type mouse arthritis animal model was constructed to study the therapeutic effect of peptides on collagen-induced arthritis (CIA) in mice. Mice were used as experimental animals, and 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, with a body weight of 18-22g, were randomly divided into 9 groups, which were normal control group, model control group, 3 low, middle and high dose groups of polypeptide Ⅰ (0.2, 0.4, 0.8mg / kg) and positive drug control group (methotrexate 1mg / kg). Except the normal group, mice CIA models were established in each experimental group on the 0th day by dissolving chicken cartilage type II collagen (cII) with 0.1 mol / l acetic acid into a 4 mg / ml solution and overnight in a refrigerator at 4°C. On the day of the experiment, fully emulsify...

Embodiment 3

[0067] Protective Effect of Polypeptide Ⅰ on In Vivo Immunoprotective Effect of Adjuvanted Rat Arthritis Animal Model

[0068] An animal model of adjuvant arthritis in rats was constructed to study the therapeutic effect of the polypeptide 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, body weight 140g-160g, were randomly divided into 9 groups, namely normal control group, model control group, 3 low, middle and high dose groups of polypeptide Ⅰ (0.1, 0.2, 0.4 mg / kg) and positive drug control group (Methotrexate 1mg / 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, 10mg / ml) in the left rear of the rat. 0.08ml caused rat adjuvant arthritis model. Subcutaneous inje...

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Abstract

The invention discloses application of polypeptides in preparation of medicament for treating or preventing rheumatoid arthritis, belongs to the field of medicament and particularly relates to polypeptides with integrin affinity and binding capacity. The polypeptides comprise a polypeptide I, a polypeptide II and a polypeptide III which can be used for preventing or treating rheumatoid arthritis; the polypeptide I has the following amino acid sequence: Ala-Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys-Gly-Gly-Gly-Gly-Ile-Val-Arg-Arg-Ala-Asp-Arg-Ala-Ala-Val-Pro, wherein the amino acid sequence comprises two pairs of disulfide bonds, and the disulfide bonds have the pairing mode of 1-4 and 2-3; the polypeptide II has the following amino acid sequence: Ile-Val-Arg-Arg-Ala-Asp-Arg-Ala-Ala-Val-Pro-Gly-Gly-Gly-Gly-Arg-Gly-Asp; and the polypeptide III has the following amino acid sequence: mPEG-SC20k-Ile-Val-Arg-Arg-Ala-Asp-Arg-Ala-Ala-Val-Pro-Gly-Gly-Gly-Gly-Arg-Gly-Asp. The polypeptides can be used for treating the rheumatoid arthritis.

Description

[0001] This application is a divisional application with an application date of December 27, 2011, an application number of 201110443067.9, and an invention title of "Application of Polypeptides in the Preparation of Drugs for Treating or Preventing Rheumatoid Arthritis". technical field [0002] The invention relates to the field of medicine, in particular to a polypeptide for treating or preventing rheumatoid arthritis. Background technique [0003] 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 our 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, polysynovia...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/16A61K47/48A61P19/02A61P29/00A61K38/10
CPCA61K38/10A61K38/16A61P19/02A61P29/00A61K47/50C07K7/08C07K14/00
Inventor 徐寒梅浦春艳沈鸿
Owner CHINA PHARM UNIV
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