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Sap and peptidomimetic compositions for reducing symptoms of inflammation

A composition and inflammation technology, applied in the direction of drug combination, peptide, specific peptide, etc., can solve side effects, gastric ulcer and other problems

Pending Publication Date: 2021-01-01
ARCH BIOSURGERY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, both groups of drugs can show serious side effects, ranging from full-blown Cushing's syndrome if taking steroids to stomach ulcers if taking NSAIDs

Method used

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  • Sap and peptidomimetic compositions for reducing symptoms of inflammation
  • Sap and peptidomimetic compositions for reducing symptoms of inflammation
  • Sap and peptidomimetic compositions for reducing symptoms of inflammation

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0275] Example 1: SAP reduces the effect of immune cells

[0276] The anti-inflammatory effects of SAP were examined using an in vitro assay to assess cytokine release by human THP-1 cells in the presence of SAP. Measurements of THP-1 cell activation in response to antigen were assessed by cytokine release.

[0277] Measuring the effect of SAP on control (resting) T cells

[0278] The medium containing human THP-1 cells (containing 1 × 10 6 1 ml culture medium of cells) were exposed to the self-assembling peptide RADARADARADARADA ("RADA-16"; SEQ ID NO: 1) at a concentration of 1 μg / well, 10 μg / well or 100 μg / well.

[0279] Human THP-1 cells in the absence of RADA-16 were used as a control to assess baseline levels of cytokine production in "quiescent" inactive THP-1 cells.

[0280] To assess cytokine release upon activation of THP-1 cells, lipopolysaccharide (LPS) from Salmonella typhimurium (Cat. No. L-7261; Sigma-Aldrich, St.Louis, MO) ,MO)) was added to THP-1 cells at a...

example 2

[0293] Example 2: SAP exhibits anti-inflammatory effects in the liver

[0294] method

[0295] The anti-inflammatory effects of EARA-16 (SEQ ID NO: 89) and RADA-16 (SEQ ID NO: 1 ) SAP were examined using a liver injury model. Inflammation levels were determined by immunohistochemical ED-1 reactivity (ED-1 as a marker of macrophage activation).

[0296] Pigs or adult Sprague-Dawley rats are anesthetized and their intraperitoneal cavity opened under aseptic conditions. For each animal, the liver was exposed and then subjected to 8mm (pig) or 4mm (rat) punch biopsy.

[0297] The puncture site was then cauterized or treated with acid (for pH control), saline, or a solution of RADA-16 (SEQ ID NO: 1 ) or EARA-16 (SEQ ID NO: 89). Animals were kept alive for up to 14 days. Animals were then sacrificed and their livers harvested and sectioned. ED-1 antibody was used to determine the level of inflammation and macrophage activation in the liver by immunohistochemistry (IHC).

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example 3

[0302] Example 3: SAP exhibits anti-inflammatory effects in an acute kidney injury model

[0303] method

[0304] EARA-16 (SEQ ID NO:89) and RADA-kidney specific peptide conjugate (Ac-(RADA) 3 CVSVPQAL-CONH 2 ; SEQ ID NO:413; known as the anti-inflammatory effect of KS). Specifically, the effects of EARA-16 and KS on burn-induced inflammation were examined using an acute kidney injury model. Inflammation levels were determined by immunohistochemical ED-1 reactivity (ED-1 as a marker of macrophage activation).

[0305] Adult Sprague-Dawley rats were anesthetized and their intraperitoneal cavity opened under aseptic conditions. For each animal, the kidney was exposed and then subjected to stab wound injury.

[0306] Then, cauterization is performed at the site of injury to stop bleeding. After cauterization, the lesion site was left untreated, and the animal was closed, or the site was treated with a 3% EARA-16 (SEQ ID NO:89) solution or a 1% KS (SEQ ID NO:413) solution....

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Abstract

Self-assembling peptides or self-assembling peptidomimetics ("SAP") can treat inflammation or inflammatory diseases, or reduce one or more symptoms of diseases and disorders associated with undesirable inflammation. Topical and injectable compositions of SAP for local administration to a site of inflammation for reduction or prevention of symptoms of inflammatory diseases and disorders are described. The compositions include one or more SAP in an amount and concentration effective to reduce or prevent one or more symptoms of undesirable inflammation. The SAP can assemble prior to or after thecomposition is administered. The SAP form a structure within or at the surface of the body that prevents and / or reduces symptoms associated with inflammation and other dysregulated immune processes. The peptides can assemble upon contact with bodily fluids (e.g., synovial fluid), or can be contacted with ionic solutions to initiate assembly.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of and priority to U.S.S.N. 62 / 647,082, filed March 23, 2018, which is hereby incorporated by reference in its entirety. [0003] References to Sequence Listings [0004] A sequence listing created on March 19, 2019 and 109,949 bytes in size and filed on March 25, 2019 as a text file named "CNS_110_ST25.txt" passed under 37 C.F.R. §1.52(e)(5) References are hereby incorporated. technical field [0005] The present invention is in the field of therapeutic agents, in particular compositions of SAP that control (eg, reduce or prevent) inflammation and undesired signs or symptoms of inflammatory diseases and disorders. Background technique [0006] In many diseases, suppression of deleterious symptoms of inflammation caused by injury, disease and surgery may be of high clinical importance. Inflammation is the body's physiological response to harmful stimuli, such as pathogens, dama...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/08A61K38/16A61K38/03A61K38/07A61K38/10A61P29/00A61P11/06A61P25/00A61P1/00A61P37/08A61P7/08A61P19/02A61P19/08A61P31/12A61P31/04
CPCA61K38/03A61K38/07A61K38/08A61K38/10A61K38/16C07K14/001A61P11/06A61K9/1658A61K9/0014A61P29/00C07K2/00A61K38/00C07K7/06C07K7/08A61K9/0019A61P19/02
Inventor T·W·诺奇R·埃利斯-比恩克
Owner ARCH BIOSURGERY