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Treating Auto-Immune and Auto-Inflammatory Diseases

a technology for auto-immune and auto-inflammatory diseases, applied in the direction of pharmaceutical delivery mechanism, powder delivery, medical preparations, etc., can solve the problems of reduced t cell responsiveness to gcs, high risk of developing very serious side effects, and complex contextual dependence of gc signaling mechanism, so as to restore corticosteroid sensitivity and enhance glucocorticoid sensitivity

Pending Publication Date: 2021-11-25
SHENZHEN EVERGREEN THERAPEUTICS CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides methods for restoring corticosteroid sensitivity or reversing glucocorticoid insensitivity, which can be used to treat a range of conditions where steroids are used but become ineffective or intolerant. The invention involves administering a pharmaceutical composition containing a steroid hormone to a patient suffering from glucocorticoid insensitivity-related conditions. The invention also includes formulations, methods, and kits for administering 17-OHPC or a combination of 17-OHPC and other medicines to treat these conditions. The technical effects of the invention include restoring corticosteroid sensitivity, reversing glucocorticoid insensitivity, and reducing cytokine IL-17 levels to treat auto-immune and auto-inflammatory diseases.

Problems solved by technology

GC signaling mechanisms have “remarkable complexity and contextual dependence” where the mechanism of action of glucocorticoid insensitivity varies amongst different cell types and contexts.
Regardless of whether the resistance arises from a congenital disorder or not, the high doses of GC required for less responsive patients means a high risk of developing very serious side effects.
Studies revealed that “GC-insensitive asthma results from high level expression of IL-2 and IL-4 which leads to reduced [GR] binding affinity and decreased T cell responsiveness to GCs”.
The resultant hypercontractility leads to airway narrowing.
Chronic lung allograft dysfunction, in particular, obliterative bronchiolitis (OB), is the primary limiting factor of successful lung transplantation.
Additionally, II17a− / − mice are defective in their ability to appropriately respond, and are highly susceptible, to systemic infection by C. albicans.
An unfortunate consequence of IL-17 deregulation may result in an overexpression of cytokines and chemokines leading to an excessive pro-inflammatory response and chronic inflammation.
Unfortunately, p38 MAPK inhibitors such as SB203580, BIRB796, SD282, VX745, SCI0469, SD0006, and SB681323 have been reported to target other non-p38 kinases and proteins which may illicit side effects such as liver toxicity.

Method used

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  • Treating Auto-Immune and Auto-Inflammatory Diseases
  • Treating Auto-Immune and Auto-Inflammatory Diseases
  • Treating Auto-Immune and Auto-Inflammatory Diseases

Examples

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Embodiment Construction

lass="d_n">[0069]According to various embodiments, a method of treatment using a pharmaceutical formulation comprising 17-OHPC has shown to be effective in two specific mechanisms: lowering IL-17 levels and inhibiting p38 MAPK activity. Both actions have a therapeutic effect in treating IL-17 and p38 MAPK mediated glucocorticoid resistance. Such a result is surprising given that previous studies using P4 had contrary results.

[0070]P4 and 17-OHPC are both classified as progestogen hormones. P4 is a naturally occurring progestogen endogenous to living organisms and may be considered as the chemical equivalent of a genus. P4 is synthesized within the ovaries, testes, placenta, and adrenal gland. Whereas 17-OHPC is a progestin (a synthetic progestogen) derived from 17α-hydroxyprogesterone (17-OHP) and caproic acid.

[0071]Structurally, progesterone (molecular weight (MW) of 314.46 g / mol and a melting point of 129.5° C.) and 17-OHPC (MW 428.6 g / mol and a melting point of 119° C.) and proge...

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Abstract

The present invention relates to the formulations, methods and kits for reducing cytokine interleukin-17 (IL-17 or IL-17A) levels in both broncheoalveolar lavage fluid (BALF) and blood / serum and / or for the inhibition of p38 mitogen activating protein kinase (MAPK) activity involving the use of 17α-hydroxyprogesterone caproate (17-OHPC) or derivatives thereof. The formulation may be in the form of an inhalant containing effective amounts of 17-OHPC, and the formulation may be used in a method to treat IL-17 cytokine and / or p38 MAPK mediated auto-immune and auto-inflammatory diseases. Such diseases may include glucocorticoid (GC) insensitive related diseases or conditions. In alternate embodiment, the formulation may include the combined use of budesonide (BUD) with 17-OPHC.

Description

RELATED U.S. APPLICATION DATA[0001]This Continuation-In-Part application claims the benefit of the U.S. patent application Ser. No. 13 / 174,939 filed on Jul. 1, 2011. The U.S. patent application Ser. No. 13 / 174,939 is a Continuation-In-Part of application Ser. No. 13 / 021,950, filed on Feb. 7, 2011, and claims the benefit of PCT International Patent Application No. PCT / US11 / 23917, filed Feb. 7, 2011, and U.S. Provisional Patent Application No. 61 / 302,325, filed on Feb. 8, 2010. The entire disclosures of which are incorporated herein by reference. This continuation-in-part application also claims the benefit of U.S. Provisional Patent Application 62 / 195,649 filed on Jul. 22, 2015. The disclosure of all applications are incorporated by reference in their entirety herein this reference.FIELD OF THE INVENTION[0002]The present invention relates to the formulations, methods and kits for reducing cytokine interleukin-17 (IL-17 or IL-17A) levels in both broncheoalveolar lavage fluid (BALF) an...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/573A61K31/58A61K9/00A61K31/57A61K31/56
CPCA61K31/573A61K31/58A61K31/56A61K31/57A61K9/0078A61K9/0075
Inventor DU, TAO TOMLEE, CHANG
Owner SHENZHEN EVERGREEN THERAPEUTICS CO LTD
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