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Peptide factor

a technology of peptides and peptides, applied in the field of peptide factors, can solve problems such as serious side effects of steroids, and achieve the effect of increasing the half life of oxidised thymosin 4

Inactive Publication Date: 2006-10-12
STEVENSON ROBERT DUNCAN +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006] The neutrophil migration stimulating activity of steroid induced factors suggests that dispersive locomotion tends to prevent cells collecting at a focus and this may be important in terminating inflammatory responses.
[0077] The choice of suitable oils or fats for the formulation is based on achieving the desired cosmetic properties, since the solubility of the active compound in most oils likely to be used in pharmaceutical emulsion formulations is very low. Thus the cream should preferably be a non-greasy, non-staining and washable product with suitable consistency to avoid leakage from tubes or other containers. Straight or branched chain, mono- or dibasic alkyl esters such as di-isoadipate, isocetyl stearate, propylene glycol diester of coconut fatty acids, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl palmitate or a blend of branched chain esters known as Crodamol CAP may be used, the last three being preferred esters. These may be used alone or in combination depending on the properties required. Alternatively, high melting point lipids such as white soft paraffin and / or liquid paraffin or other mineral oils can be used.

Problems solved by technology

However, steroids have serious side effects and are therefore only used in cases where non-steroidal anti-inflammatory drugs are not effective.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Preparation of Steroid Treated Monocyte Supernatant (STMS) and Partially Purified STMS Peptide Factor

[0103] Steroid treated monocyte supernatant (STMS) was obtained by the culture of human monocytes which had been plated out in Hams F-10 medium at a concentration of 5×107 cells per ml in the presence of heat-inactivated 10% foetal calf serum (FCS) for 60 mins, rinsed with Phosphate buffered saline (PBS) and then cultured in the absence of FCS for 24 hours in the presence of 10−6M dexamethasone.

STMS Peptide Factor Preparation

[0104] STMS was obtained essentially as described by Chettibi et al. by the culture of human monocytes in Hams F-10 medium with 10% foetal calf serum (FCS) at a concentration of approximately 5×107 cells per ml for 60 minutes, rinsed with PBS, and then cultured without FCS for 24 hours in the presence of 10−6M dexamethasone. Parallel cultures in which dexamethasone was omitted were used to prepare control monocyte supernatant (CMS). Purification of STMS pepti...

example 2

Biological Studies of STMS Peptide Factor

[0108] The biological interest in STMS Peptide Factor lies in its potential role as a mediator of some or all of the anti-inflammatory effects of glucocorticoids. Many preliminary observations using the supernatant as opposed to the peptide factor seemed to support this role, but others, such as the phenomenon of dispersive locomotion, were not obvious anti-inflammatory responses. However, lowered adhesiveness, which appears to be one of the underlying causes of dispersive locomotion, has clear anti-inflammatory implications.

Characteristics of Neutrophil Locomotion

[0109] Agonists were used at concentrations which caused similar, sub-maximal stimulation of basal motility. Previous studies of crude and partially purified STMS peptide factor showed that it stimulated neutrophils to undergo highly dispersive locomotion in a uniform concentration gradient. This was in marked contrast to responses to other agents and in particular to fMLP where...

example 3

Detailed Biological Studies of STMS and Peptide Factor

[0120] Neutrophil Adhesion to Bovine Aorta Endothelial Cells

[0121] The previous data showing that STMS diminished neutrophil adhesion to protein-coated glass [Chettibi et al., 1993] was extended using the more physiological substrate of bovine aorta endothelial cells (FIG. 2).

[0122] Chemotaxis

[0123] Preliminary observations of neutrophil chemotaxis using the modified Boyden chamber revealed a striking contract between the response to STMS and fMLP. Neutrophils showed massive invasion of the filter when fMLP was present in the lower chamber, but gave no such response to STMS. However when the filters were examined by the leading front method it became clear that a few STMS-treated cells were able to invade successfully, in keeping with the predictions for persistent locomotion. These observations suggested that a more suitable analysis would be to measure total invasion, or to determine the number of cells present midway betwe...

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Abstract

The present invention relates to use of oxidised thymosin β4 in therapy, more particularly in the treatment of diseases or conditions associated with an inflammatory response or septic shock. The present invention also provides pharmaceutical formulations comprising oxidised thymosin β4 together with a suitable excipient.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of copending application Ser. No. 10 / 339,271, filed on Jan. 9, 2003, which is a continuation of U.S. patent application Ser. No. 09 / 647,117, now U.S. Pat. No. 6,602,519, filed on Jan. 23, 2001, which claims priority under 37 U.S.C. §371 from PCT Application No. PCT / GB99 / 00833, filed in English on Mar. 29, 1999, which claims the benefit of Great Britain Application Serial No. 9806632.7 filed on Mar. 28, 1998, and also claims the benefit of Great Britain Application Serial No. 0008903.7 filed on Apr. 12, 2000, the disclosures of which are incorporated by reference herein in their entireties.TECHNICAL FIELD [0002] The present invention relates to a peptide factor isolated from steroid-treated monocytes. More particularly the invention relates to a peptide factor which can be used to replace steroid therapy. DISCLOSURE OF THE INVENTION [0003] Steroids are effectively used for anti-inflammatory diseases, su...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/17A61K38/22A61P29/00A61P31/00C07K14/575C12N15/67C12N15/79
CPCC07K14/57581A61K38/00C12N15/79C12N15/67A61P1/00A61P11/00A61P17/00A61P19/02A61P19/04A61P29/00A61P31/00A61P37/06A61P43/00A61P7/00A61P9/14Y02A50/30A61K38/22
Inventor STEVENSON, ROBERT DUNCANLAWRENCE, ANTHONY JOHNYOUNG, JOHNPAPPIN, DARRYL JOHN CECIL
Owner STEVENSON ROBERT DUNCAN
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