US20060089304A1 - Treatment of psoriasis through down-regulation of the EGF-receptor with topically-applied EGF - Google Patents

Treatment of psoriasis through down-regulation of the EGF-receptor with topically-applied EGF Download PDF

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Publication number
US20060089304A1
US20060089304A1 US11/242,348 US24234805A US2006089304A1 US 20060089304 A1 US20060089304 A1 US 20060089304A1 US 24234805 A US24234805 A US 24234805A US 2006089304 A1 US2006089304 A1 US 2006089304A1
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US
United States
Prior art keywords
egf
receptor
psoriasis
regulation
topically
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US11/242,348
Inventor
Rudi Neirinckx
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to US11/242,348 priority Critical patent/US20060089304A1/en
Publication of US20060089304A1 publication Critical patent/US20060089304A1/en
Priority to US11/464,401 priority patent/US20070087965A1/en
Priority to US12/488,036 priority patent/US20100160222A1/en
Abandoned legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1808—Epidermal growth factor [EGF] urogastrone

Definitions

  • Psoriasis is a chronic skin disorder that affects approximately 4.0 million people in the US., and annual treatment costs in the USA alone are estimated at over $1.5 billion. There are no currently available drugs for this disease that offer satisfactory efficacy and safety. Psoriatic lesions are caused by the hyperproliferation of keratinocytes, but it has been demonstrated that EGF-R signalling is required for the growth of keratinocytes.
  • the upper epidermal layer in psoriatic tissue contains levels of EGF receptors (EGFR) more similar to the levels found in the mitotically-active basal cell layer of skin.
  • EGFR EGF receptors
  • r-EGF is located primarily in the germinative layer, which contains r-EGF levels 4 times higher than those found in the more-diferentiated cells of the upper epidermal layers.
  • the upper epidermal layers shows r-EGF levels 2 ⁇ higher than in normal tissue, while the germanitive layer has normal levels.

Abstract

From unrelated but similar fields it is deduced that certain forms of psoriasis can be effectively treated through topical application of EGF-containing formulations. This patent application summarizes the theoretical basis for this finding and requests protection for the idea, while clinical evaluation is in preparation.

Description

    INTRODUCTION
  • Psoriasis is a chronic skin disorder that affects approximately 4.0 million people in the US., and annual treatment costs in the USA alone are estimated at over $1.5 billion. There are no currently available drugs for this disease that offer satisfactory efficacy and safety. Psoriatic lesions are caused by the hyperproliferation of keratinocytes, but it has been demonstrated that EGF-R signalling is required for the growth of keratinocytes.
  • It has been demonstrated that the upper epidermal layer in psoriatic tissue contains levels of EGF receptors (EGFR) more similar to the levels found in the mitotically-active basal cell layer of skin. In normal epidermis r-EGF is located primarily in the germinative layer, which contains r-EGF levels 4 times higher than those found in the more-diferentiated cells of the upper epidermal layers. In psoriatic lesions the upper epidermal layers shows r-EGF levels 2× higher than in normal tissue, while the germanitive layer has normal levels. (L. A. Nanney et al; J. Invest. Dermat. Vol 85, p 260-265).
  • There is only a poor correlation between the levels of r-EGF and the level of cellular proliferation. An example of cells with elevated metabolism but low mitotic activity is the case of the sweat duct epithelium. Similarly, the high level of r-EGF indicates elevated metabolism rather than lack of differentiation in psoriatic lesions.
    • PROPOSAL
  • As the main difference in r-EGF distribution in normal and psoriatic tissue is the abnormal retention of the receptor beyond the first 2-3 cell rows in the stratum basilis in psoriatic tissue, we propose to reduce these concentrations through a down regulation of the receptor using higher than normal levels of EGF at the level of the receptor.
  • This is similar to the down regulation of FSH and LH excretion through the saturation of pituitary GnRH receptors in response to a constant level of GnRH.

Claims (6)

1-10. (canceled)
11. A topical formulation comprising epidermal growth factor (EGF) and a dermatologically acceptable excipient or carrier.
12. The formulation of claim 11, wherein said EGF is in an amount to down regulate the EGF receptor.
13. The formulation of claim 11, wherein said EGF is present at 0.01 to 50 μg/g.
14. The formulation of claim 13, wherein said EGF is present at 0.5-20 μg/g.
15. The formulation of claim 11, further comprising an anti-inflammatory.
US11/242,348 2000-06-02 2005-10-03 Treatment of psoriasis through down-regulation of the EGF-receptor with topically-applied EGF Abandoned US20060089304A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US11/242,348 US20060089304A1 (en) 2000-06-02 2005-10-03 Treatment of psoriasis through down-regulation of the EGF-receptor with topically-applied EGF
US11/464,401 US20070087965A1 (en) 2005-10-03 2006-08-14 Treatment of psoriasis through down-regulation of the egf-receptor with topically applied egf
US12/488,036 US20100160222A1 (en) 2000-06-02 2009-06-19 Treatment of Psoriasis through Down-Regulation of the EGF-Receptor with Topically Applied EGF

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/584,978 US7015199B1 (en) 2000-06-02 2000-06-02 Treatment of psoriasis through down-regulation of the EGF-receptor with topically-applied EGF
US11/242,348 US20060089304A1 (en) 2000-06-02 2005-10-03 Treatment of psoriasis through down-regulation of the EGF-receptor with topically-applied EGF

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US09/584,978 Division US7015199B1 (en) 2000-06-02 2000-06-02 Treatment of psoriasis through down-regulation of the EGF-receptor with topically-applied EGF

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/464,401 Continuation US20070087965A1 (en) 2000-06-02 2006-08-14 Treatment of psoriasis through down-regulation of the egf-receptor with topically applied egf

Publications (1)

Publication Number Publication Date
US20060089304A1 true US20060089304A1 (en) 2006-04-27

Family

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Family Applications (2)

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US09/584,978 Expired - Fee Related US7015199B1 (en) 2000-06-02 2000-06-02 Treatment of psoriasis through down-regulation of the EGF-receptor with topically-applied EGF
US11/242,348 Abandoned US20060089304A1 (en) 2000-06-02 2005-10-03 Treatment of psoriasis through down-regulation of the EGF-receptor with topically-applied EGF

Family Applications Before (1)

Application Number Title Priority Date Filing Date
US09/584,978 Expired - Fee Related US7015199B1 (en) 2000-06-02 2000-06-02 Treatment of psoriasis through down-regulation of the EGF-receptor with topically-applied EGF

Country Status (1)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080269339A1 (en) * 2007-04-26 2008-10-30 Thomas Robert Sutter Combined use of egf pathway inhibitors and differentiation promoting compounds

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080090769A1 (en) * 2000-06-02 2008-04-17 Neirinckx Rudi D Treatment of psoriasis through down-regulation of the egf-receptor with topically applied egf
US20070087965A1 (en) * 2005-10-03 2007-04-19 Neirinckx Rudi D Treatment of psoriasis through down-regulation of the egf-receptor with topically applied egf

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6337320B1 (en) * 1996-10-11 2002-01-08 Thione International, Inc. Reparatives for ultraviolet radiation skin damage

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0339905A3 (en) * 1988-04-25 1991-05-08 Ethicon, Inc. Wound healing compositions containing growth factors and retinoids
US5130298A (en) * 1989-05-16 1992-07-14 Ethicon, Inc. Stabilized compositions containing epidermal growth factor
US5070188A (en) * 1989-07-24 1991-12-03 Ethicon, Inc. Acylated epidermal growth factor

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6337320B1 (en) * 1996-10-11 2002-01-08 Thione International, Inc. Reparatives for ultraviolet radiation skin damage

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080269339A1 (en) * 2007-04-26 2008-10-30 Thomas Robert Sutter Combined use of egf pathway inhibitors and differentiation promoting compounds

Also Published As

Publication number Publication date
US7015199B1 (en) 2006-03-21

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