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Application of S-(carboxymethyl)-L-cysteine to preparation of medicines for preventing and treating respiratory system diseases

A respiratory system disease, cysteine ​​technology, applied in the field of medicine, can solve the problem that the influence of NF-κB signaling pathway has not been seen, etc.

Inactive Publication Date: 2016-02-10
GUANGZHOU BAIYUNSHAN PHARMA HLDG CO LTD BAIYUNSHAN PHARMA GENERAL FACTORY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But no effect on NF-κB signaling pathway

Method used

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  • Application of S-(carboxymethyl)-L-cysteine to preparation of medicines for preventing and treating respiratory system diseases
  • Application of S-(carboxymethyl)-L-cysteine to preparation of medicines for preventing and treating respiratory system diseases
  • Application of S-(carboxymethyl)-L-cysteine to preparation of medicines for preventing and treating respiratory system diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 CMC inhibits the expression of NF-κB and the release of IL-6 and IL-8

[0030] 1 Experimental method

[0031] 1.1 Western blot and ELISA method

[0032] A549 cells were cultured in RPMI-1640 containing 10% fetal bovine serum at 37°C and 5% CO 2 cultured in an incubator. Cells in the logarithmic growth phase were taken, and after trypsinization, the cell concentration was adjusted to 1×10 with RPMI-1640 6 cells / mL, inoculated in 6-well culture plate, after 12 hours of attachment, starved overnight, divided into H according to different treatments 2 o 2 Group (or TNF-α, CSE group), CMC group and its salt (add CMC or its salt, pre-incubation for 24h), control group added equal volume of PBS. The culture supernatant was taken, and the contents of IL-6 and IL-8 were determined by ELISA. At the same time, cells were collected, BCA protein quantification kit was used to measure protein concentration, 25 μg protein was quantitatively loaded, run on SDS polya...

Embodiment 2

[0042] Example 2 Inhibitory effect of CMC on the expression of NF-κB and the release of IL-6 and IL-8 in mice with acute lung injury

[0043] 1 Experimental method

[0044] Sixty male C57BL / 6 mice were randomly divided into 4 groups, namely normal group, model group, CMC group and ammonium salt group, with 15 mice in each group. The normal group and the model group were fed with 0.5% sodium carboxymethylcellulose, and the other groups were given corresponding drugs (suspension or dissolution of sodium carboxymethylcellulose). Continuous administration for 15 days.

[0045] 24 hours after the last administration, the mice in the normal group were intraperitoneally injected with the same amount of normal saline, and the other mice were injected with lipopolysaccharide (10 mg / kg body weight). Six hours after the above treatment, the mice were killed, and bronchoalveolar lavage fluid (BALF ), to determine the content of IL-6 and IL-8; after the lungs were taken to prepare ti...

Embodiment 3

[0048] Example 3 Inhibitory effect of CMC on expression of NF-κB and release of IL-6 and IL-8 in mice with bronchial asthma

[0049] 1 Experimental method

[0050] Sixty male BALB / c mice were randomly divided into 4 groups, namely normal group, model group, CMC group and ammonium salt group, with 15 mice in each group. The mice in the latter three groups were intraperitoneally injected with a mixed solution of 2% OVA and aluminum hydroxide (dissolved in 0.2mL PBS) on days 0, 7, and 14; Nebulization challenge, 1 time / day, 7 days in total. The normal group was sensitized and challenged with an equal amount of normal saline. From the 21st day, each group was intragastrically administered half an hour before the nebulization challenge (the normal group and the model group were administered with the same amount of normal saline). Within 24 hours of the last challenge, the mice were sacrificed, and the bronchoalveolar lavage fluid (BALF) was collected to determine the content...

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Abstract

The invention relates to novel application of medicines, in particular to application of S-(carboxymethyl)-L-cysteine and pharmaceutically acceptable salts thereof to preparation of medicines for preventing and treating respiratory system diseases caused by NF-kappa B signal pathway activation. The application has the advantages that the S-(carboxymethyl)-L-cysteine and the pharmaceutically acceptable salts thereof can remarkably inhibit not only NF-kappa B signal pathway activation and release of inflammatory factors interleukin-6 and interleukin-8 due to H2O2, TNF (rumor necrosis factor)-alpha and cigarette smoke extract but also acute lung injury, release of the interleukin-6 and the interleukin-8 in bronchial asthma mice bronchoalveolar lavage fluid and expression of NF-kappa B in lung tissues remarkably, thereby being applied to prevention and treatment of NF-kappa B-mediated respiratory system diseases such as bronchial asthma, acute lung injury and acute respiratory distress syndrome.

Description

technical field [0001] The invention relates to the field of medicine, in particular, the invention relates to a new medicine application of S-(carboxymethyl)-L-cysteine ​​and a pharmaceutically acceptable salt thereof. Background technique [0002] NF-κB is a nuclear protein factor that can specifically bind to the sequence of the immunoglobulin light chain gene enhancer κB, which was first detected by Sen et al. in 1986 from the nuclear extract of B lymphocytes, and can promote the expression of light chain genes , play a transcriptional and regulatory role (SenR, BaltimoreD.Inducibilityofkappaimmunoglobulinenhancer-bindingproteinNf-kappaBbyaposttranslationalmechanism. Cell .1986;47(6):921-8.). As a multifunctional nuclear transcription factor, NF-κB is a dimeric complex composed of two members of the Rel protein family, P65 and P50, and mainly exists in the form of P65 subunit in lung tissue. In the resting state, NF-κB binds with the inhibitor IκB and exists in the cyt...

Claims

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Application Information

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IPC IPC(8): A61K31/198A61P11/06A61P11/00
Inventor 朱少璇陈矛钟南山郑劲平王玮
Owner GUANGZHOU BAIYUNSHAN PHARMA HLDG CO LTD BAIYUNSHAN PHARMA GENERAL FACTORY
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