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Use of interleukin-1receptor antagonist (IL-1Ra), and pharmaceutical compositions of IL-1Ra

A composition and drug technology, applied in the field of biomedicine, can solve the problem of no species specificity in biological effects, and achieve the effect of reducing cardiotoxicity

Inactive Publication Date: 2011-11-16
SHANGHAI JIAO TONG UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Human and mouse IL-1Ra have 77% homology, and the biological role of IL-1Ra has no species specificity

Method used

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  • Use of interleukin-1receptor antagonist (IL-1Ra), and pharmaceutical compositions of IL-1Ra
  • Use of interleukin-1receptor antagonist (IL-1Ra), and pharmaceutical compositions of IL-1Ra
  • Use of interleukin-1receptor antagonist (IL-1Ra), and pharmaceutical compositions of IL-1Ra

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] After doxorubicin injection, the death of the mice in the two groups was closely observed, and the body weight of the mice was weighed every day. Myocardial tissue samples were collected at fixed points, and the heart weight was weighed at the same time to calculate the cardiac index (heart weight / body weight).

[0070] The experimental results showed that the toxic damage of doxorubicin was obvious. Some of the mice died after doxorubicin injection, and the body weight, heart index and other indicators decreased significantly. After subcutaneous injection of rhIL-1Ra, the above indicators were improved to varying degrees. As shown in Table 1, 8 days after doxorubicin injection, the mortality rate of mice in the DOX+normal saline group was 53.3% (16 / 30), while that in the DOX+rhIL-1Ra group was 36.7% (11 / 30). Can significantly increase the survival of mice after DOX action. The surviving mice all showed different degrees of weight loss, and rhIL-1Ra could significant...

Embodiment 2

[0075] Fourteen days after doxorubicin injection, the mice were sacrificed, and the hearts were taken out, and paraffin sections and H&E staining were performed according to conventional methods, and normal mouse hearts were used as normal controls. The pathological scoring standard is as follows: take 9 high-power fields of view (×400) for pathological scoring: (1) no lesion, 0 points; (2) cardiomyocyte degeneration: less than or equal to 3, 0.5 points, more than 3 and less than or equal to 6 1.0 points, more than 6 points, 1.5 points; (3) cardiomyocyte necrosis: less than or equal to 3 points, 2.0 points, more than 3, less than or equal to 6 points, 2.5 points, more than 7 points, 3.0 points, the final average score. The higher the pathological score, the more severe the myocardial lesion [ Bertinchant JP , Polge A , Juan JM , et al. Clinica Chimica Acta. 2003, 329(1-2): 39-51.].

[0076] The result is as figure 1 Shown, (A) normal group; (B) DOX+normal saline group; ...

Embodiment 3

[0078] Configuration of Tris buffer: pH7.4, 0.01mol / L Tris-HCL, 0.0001mol / L EDTA-2Na, 0.01mol / L sucrose, 0.8% NaCl, configured into 1000ml solution;

[0079] Homogenization of myocardial tissue: mix myocardial tissue with Tris buffer at a weight-to-volume ratio of 10%, fully mix with a homogenizer, let stand for 30 minutes, centrifuge at 2000rmp / min, and absorb the supernatant;

[0080] operation table

[0081]

[0082] Mix well (shake the test tube rack a few times)

[0083]

[0084] Vortex mixer to mix evenly, tie the mouth of the test tube tightly with plastic wrap, prick a small hole with a needle, bathe in water at 95 degrees Celsius for 40 minutes, take it out and cool it in running water, adjust to zero with distilled water at 532 nm, 1 cm optical path, and measure the absorbance value of each tube.

[0085] a* indicates the sample volume, standard product volume, absolute ethanol volume, and reagent 1 volume taken, all of which are equal. For example, if the sa...

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Abstract

The invention belongs to the technical field of biomedicine, specifically relates to a use of an interleukin-1receptor antagonist (IL-1Ra), and pharmaceutical compositions of the IL-1Ra. The invention discloses a use of protein selected from the following (a) or (b) in preparing drugs for treating or preventing a cardiac toxic reaction due to chemotherapeutics: (a) amino acid sequence of the protein is represented by SEQ ID NO.1; (b) the protein shares 70% amino acid sequence identity with the protein provided by the (a), and has activities for treating or preventing the cardiac toxic reaction due to the chemotherapeutics. According to the protein provided by the present invention, the cardiac toxic reaction due to the chemotherapeutics can be effectively removed or reduced, and a new selectivity may be provided for the future clinical treatment of tumor.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the use of IL-1Ra and its pharmaceutical composition. Background technique [0002] In recent years, tumor treatment has developed by leaps and bounds. Some new drugs for the treatment of tumors emerge in an endless stream, and the prognosis of cancer patients has also been significantly improved. But at the same time, various side effects brought by chemotherapy drugs are also the main factors affecting the progress of chemotherapy. While anti-tumor drugs kill tumor cells, they can also cause damage to normal tissues and organs of the human body, especially the toxic reaction to the heart, which often leads to death of cancer patients not from tumors but from cardiac complications [Yeh ET, Tong AT, Lenihan DJ, et al. Circulation. 2004, 109(25): 3122-3131]. Anthracycline anticancer antibiotics are the first to be used for cardiotoxicity of chemotherapy drugs [Fe...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61K45/00A61K9/00A61K9/14A61P9/00A61P39/02A61P35/00A61K31/704A61K31/136
Inventor 韩伟朱劲舟
Owner SHANGHAI JIAO TONG UNIV
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