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New use of MAPK inhibitor and its composition thereof

A technology of inhibitors and compositions, applied in drug combinations, medical preparations containing active ingredients, cardiovascular system diseases, etc.

Inactive Publication Date: 2006-03-08
ZENSUN (SHANGHAI) SCI & TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no report on the effect of inhibiting the MAPK signal transduction pathway on the myocardium and heart function

Method used

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  • New use of MAPK inhibitor and its composition thereof
  • New use of MAPK inhibitor and its composition thereof
  • New use of MAPK inhibitor and its composition thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] Example 1. Inhibition of Wortmannin on PI3K signaling in rat left ventricular cells

[0075] Method: Select 90-100g male SD rats, inject 0.4mg / Kg Wortmannin into the tail vein, kill the rats at 15, 30, 60, and 120min after Wortmannin injection, take out the left ventricle of the rat quickly and cut it into pieces, add The lysate (50 mM Tris, pH 7.4, 5 mM EDTA, 150 mM NaCl, 1% TritonX-100, 2 mM sodium orthovanadate, 50 mM NaF, 2 mM phenylmethylsulfonylfluoride, protease inhibitor cocktail [Boeringher, Roche]) was homogenized in an ice bath. After determining the protein concentration, direct electrophoresis, after SDS-PAGE, all proteins were electrotransferred onto PVDF membrane. After blocking with milk or BSA, the PVDF membrane is bound to the antibody and finally developed. Western blot refers to the method of Kodama F, Circ.Res.81:656-663,1997. Anti-Akt, anti-p-Akt antibodies were purchased from CellSignaling Technology.

[0076] result

[0077] Wortmannin can re...

Embodiment 2

[0078] Example 2. Inhibition of U0126 on MAPK signaling in rat left ventricular cells

[0079] method:

[0080]Select 90-100g male SD rats, inject 0.8mg / Kg U0126 into the tail vein, kill the rats at 15, 30, 60, and 120 minutes after U0126 injection, take out the left ventricle of the rat quickly and cut it into pieces, and add the lysate (50 mM Tris, pH 7.4, 5 mM EDTA, 150 mM NaCl, 1% Triton X-100, 2 mM sodium orthovanadate, 50 mM NaF, 2 mM phenylmethylsulfonyl fluoride, protease inhibitor cocktail [Boeringher, Roche]), homogenized in an ice bath. After determining the protein concentration, direct electrophoresis, after SDS-PAGE, all proteins were electrotransferred onto PVDF membrane. After blocking with milk or BSA, the PVDF membrane is bound to the antibody and finally developed. Western blot refers to the method of Kodama F, Circ.Res.81:656-663,1997. Anti-erk1, anti-p-erk antibodies were purchased from Santa Cruz Biotechnology.

[0081] result:

[0082] U0126 can red...

Embodiment 3

[0083] Embodiment 3. U0126, Wortmannin and rhNRG are respectively combined with U0126 and Wortmannin to improve heart function in rats with heart failure

[0084] method:

[0085] Rats were intraperitoneally injected with 100 mg / kg of ketamine. After anesthesia, the rats were fixed on the mouse board in a supine position, and the neck and chest were shaved and then disinfected with bromogeramine. Make a midline incision in the neck, bluntly dissect the anterior neck muscles to find the trachea, use an 18G arteriovenous indwelling needle to penetrate the trachea between the 3rd and 5th tracheal cartilages, withdraw the needle core, and push the plastic sleeve into the trachea 1-2cm, After fixation, a small animal ventilator (tidal volume about 20ml, frequency 80 times / min) was connected. After incision of the left front skin of the chest, the chest muscles were bluntly separated to expose the 4th and 5th ribs, and the chest wall was penetrated from the intercostal space with ...

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Abstract

The present invention finds that PI3-K inhibitor and MAPK inhibitor can obviously improve heart failure cardiac function of mammal, also finds that the combined application of PI3-K inhibitor, MAPK inhibitor and medicine rh NRG for curing heart failure of mammal can obviously improve heart failure cardiac function of mammal, they have synergistic action. Said invention also provides a method for preventing, curing and delaying heart disease of mammal by using PI3-k inhibitor and MAPK inhibitor and it's composite.

Description

Technical field: [0001] The present invention finds that PI3-K inhibitors and MAPK inhibitors can obviously improve cardiac function of mammals with heart failure. The present invention also finds that the combined use of PI3-K inhibitors, MAPK inhibitors and rhNRG, a drug for treating heart failure in mammals, can obviously improve the heart function of heart failure in mammals, and the two have synergistic effect. The present invention provides methods and compositions for preventing, treating or delaying heart disease in mammals, especially humans. Specifically, the present invention provides a PI3K inhibitor and a MAPK inhibitor for preventing, treating or delaying a mammalian heart disease method and composition, the method comprising administering an effective amount of PI3K to a mammal needing or wishing to prevent, treat or delay Inhibitors, MAPK inhibitors or in combination with other mammalian heart disease drugs to prevent, treat or delay the heart disease. Backg...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61P9/00A61P9/04A61P9/10
Inventor 周明东
Owner ZENSUN (SHANGHAI) SCI & TECH CO LTD
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