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Use of steroid compounds for inflammatory and autoimmune disorders

A technology for autoimmune diseases and compounds, applied in the field of application of steroids in inflammatory and autoimmune diseases, can solve problems such as limiting clinical application

Inactive Publication Date: 2012-10-03
BIONATURE E A LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, steroids from natural sources are metabolized into estrogen, androgen or progesterone in the human body, producing systemic and important hormone-like side effects, including the formation of hormone-dependent tumors Front.Neuroendocrinol.21, 1 (2000) (Neuroendocrinol. Preface to Endocrinology. 21. (2000)), thus limiting their clinical application

Method used

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  • Use of steroid compounds for inflammatory and autoimmune disorders
  • Use of steroid compounds for inflammatory and autoimmune disorders
  • Use of steroid compounds for inflammatory and autoimmune disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0131] Synthetic Spirosteroid Inhibits T Cell Response Activity in Vitro

[0132] Lymph node (LN) cells were cultured from DO11.10T cell receptor transgenic (DO11.10TCR Tg) mice that were not exposed to antigen (which responded to OVA peptide 323-329), in DHEA or the spiro compound BNN-50, BNN- 93 and BNN-124 or control RPMI were stimulated with OVA. Treatment with DHEA and spiro-analogues resulted in a significant reduction in the proliferation of T cells responding to the antigen ( figure 1 ).

[0133] In order to determine whether DHEA and its analogs are effective on CD4 + T cells exert their immunosuppressive effect directly, and pure T cells were cultured from unexposureed DO11.10 T cell receptor transgenic (DO11.10TCR Tg) mice with mitomycin C-treated splenocytes and OVA peptide 323-329. CD4 + T cells. Furthermore, treatment with DHEA and spiro compounds resulted in a marked reduction in the secretion and proliferation of interleukin-2 and gamma-interferon (Fig. 2)...

Embodiment 2

[0136] Ability of synthetic steroids to protect against MOG peptide-induced experimental autoimmune encephalomyelitis (EAE).

[0137] To evaluate the immunosuppressive effects of DHEA and spiro compounds in vitro, a study was conducted to determine whether DHEA and its spiro analogs could protect against experimental autoimmune encephalomyelitis (EAE). EAE is an autoimmune state of the central nervous system (CNS), caused by infiltration of the central nervous system by destroyed autoreactive T lymphocytes and subsequent demyelination and axonal and neuronal degeneration.

[0138] Acute EAE was induced in C57BL / 6 mice by immunizing mice with pathogenic sphingomyelin oligodendrocyte glycoprotein (MOG) peptide (amino acids 35-55). From the day of EAE induction until the mice were euthanized on day 26, BNN-93, BNN-124, BNN-50 or DHEA (2 mg / mouse) or PBS (control) were administered intraperitoneally every day ( Figure 5 ). Routine care of mice was blinded to clinical signs (par...

Embodiment 3

[0146] Activity of synthetic steroids in suppressing TH-2 immune responses and preventing allergic airway inflammation.

[0147] Using an established mouse model of allergic asthma, the in vivo effects of DHEA and spiro compounds were investigated during TH-2-mediated immune responses and subsequent disease development. BALB / c mice were sensitized by intraperitoneal administration of 0.01 mg chicken ovalbumin (OVA) in 0.2 ml alum on days 0 and 12, and exposed to aerosolized OVA on days 18-20 (5 %20min). On days 0, 1, 2, 12, 13, 14, 18, 19 and 20., mice were given 2 mg / mouse of DHEA or spiro compound (BNN-93 or BNN-124 or BNN-50) or PBS.

[0148] In bronchoalveolar lavage (BAL) of mice treated with DHEA or spiro compounds, the numbers of eosinophils and lymphomonocytes were significantly reduced compared with PBS-treated mice ( Figure 14a ). Leukocyte infiltration in the lungs of mice treated with DHEA and spiro compounds was also significantly reduced ( Figure 14b ). Fu...

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Abstract

This invention pertains to the use of steroid compounds including spirosteroid analogues in treating, preventing or ameliorating the symptoms of inflammatory conditions. The steroid compounds are useful for treating a range of inflammatory conditions, including, but not limited to asthma, lung inflammation, retinal inflammatory conditions, autoimmune diseases such as rheumatoid arthritis, diabetes type I, systemic lupus erythematosus, ulcerative colitis and inflammatory bowel diseases and myopathies, as well as multiple sclerosis. The active compounds are represented by Formula (I): wherein R1, R2, R3, R4, R5, R6, R7, A, B, X, Y and Z are defined in the description of the invention.

Description

technical field [0001] The present invention relates to the application of steroid compounds, including spirosteroid analogues, in the treatment, prevention or improvement of symptoms of inflammatory conditions, such as asthma. The mechanism of action of the immune system suggests that steroids can be used in the treatment of a range of inflammatory conditions, including but not limited to asthma, lung inflammation, retinal inflammatory conditions, autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus, inflammatory bowel disease and myopathy. Background technique [0002] Inflammation is an adaptive response triggered by a variety of noxious stimuli and states. Inflammation triggers the recruitment of granulocytes and plasma proteins to infected tissue sites. It underlies many diseases related to the human immune system. The spectrum of inflammatory conditions continues to expand to include conventional diseases that were no...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/56A61K31/575A61P11/06A61P17/06A61P21/04A61P43/00
CPCA61K31/56A61K31/575A61P1/00A61P1/04A61P1/16A61P11/00A61P11/06A61P17/00A61P17/06A61P19/02A61P21/04A61P27/02A61P29/00A61P37/00A61P37/02A61P37/06A61P43/00A61P5/14A61P7/06A61P3/10A61K2121/00
Inventor V·帕诺特萨科波乌罗M·安吉拉科波乌罗T·卡罗盖洛波乌罗A·加拉瓦尼斯L·拉泽瑞第斯C·尼奥菲托
Owner BIONATURE E A LTD
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