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 PDFInfo
- 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
- Authority
- 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
Links
- 102000001301 EGF receptor Human genes 0.000 title claims description 4
- 108060006698 EGF receptor Proteins 0.000 title claims description 4
- 201000004681 Psoriasis Diseases 0.000 title abstract description 3
- 230000003828 downregulation Effects 0.000 title description 3
- 238000009472 formulation Methods 0.000 claims abstract 5
- 239000000203 mixture Substances 0.000 claims abstract 5
- 102000009024 Epidermal Growth Factor Human genes 0.000 claims description 4
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims 4
- 101800003838 Epidermal growth factor Proteins 0.000 claims 3
- 229940116977 epidermal growth factor Drugs 0.000 claims 3
- 230000003110 anti-inflammatory effect Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000012049 topical pharmaceutical composition Substances 0.000 claims 1
- 238000011156 evaluation Methods 0.000 abstract 1
- 230000000699 topical effect Effects 0.000 abstract 1
- 230000001185 psoriatic effect Effects 0.000 description 6
- 210000002615 epidermis Anatomy 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- NMJREATYWWNIKX-UHFFFAOYSA-N GnRH Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CC(C)C)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 NMJREATYWWNIKX-UHFFFAOYSA-N 0.000 description 1
- 102000008238 LHRH Receptors Human genes 0.000 description 1
- 108010021290 LHRH Receptors Proteins 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 210000000270 basal cell Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
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.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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
- 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.
- 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.
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
ID=36045516
Family Applications (2)
| 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 |
| 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)
| Country | Link |
|---|---|
| US (2) | US7015199B1 (en) |
Cited By (1)
| 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)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
Citations (1)
| 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)
| 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 |
-
2000
- 2000-06-02 US US09/584,978 patent/US7015199B1/en not_active Expired - Fee Related
-
2005
- 2005-10-03 US US11/242,348 patent/US20060089304A1/en not_active Abandoned
Patent Citations (1)
| 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)
| 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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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |