John J Voorhees

US Patent:

6365630, Apr 2, 2002

Filed:

Jul 13, 2000

Appl. No.:

09/615218

Inventors:

Gary J. Fisher - Ann Arbor MI
John J. Voorhees - Ann Arbor MI
Sewon Kang - Ann Arbor MI

Assignee:

Regents of the University of Michigan

International Classification:

A61K 3120

US Classification:

514559, 424 59, 514725

Abstract:

Compositions and methods are provided for ameliorating various effects of UVA and UVB radiation from the sun. The compositions including an ingredient that prevents photoaging from MED and subMED radiation, such as a retinoid, certain other compounds (such as N-acetylcysteine, 2-furildioxime, and vitamin C) and optionally other MMP inhibitors such as tetracyclines and/or compounds that inhibit the P-450-mediated metabolism of retinoids such as ketoconazole and other azole compounds. In the method, the composition is applied prior to exposure to the sun; depending upon the ingredients used in the composition, application should be from 7 to 48 hours prior to exposure. Compounds that prevent erythema (skin reddening, sunburn) do not necessarily protect against UV-mediated elevation of MMP levels and activity, and similarly compounds that prevent UV-mediated elevation of MMP levels and activity are not necessarily effective against UV-induced erythema.

US Patent:

6630516, Oct 7, 2003

Filed:

Feb 24, 1998

Appl. No.:

09/028435

Inventors:

James Varani - Ann Arbor MI
Gary J. Fisher - Ann Arbor MI
John J. Voorhees - Ann Arbor MI
Sewon Kang - Ann Arbor MI

Assignee:

The Regents of the University of Michigan - Ann Arbor MI

International Classification:

A61K 3107

US Classification:

514725, 514167, 514576, 514629, 424 59, 424 60

Abstract:

The deleterious effects of the passage of time on human skin (i. e. , chronological aging of human skin) can be prevented and treated with the topical application of a retinoid, preferably retinol. We have found that some of the same pathways (namely the stress-activated pathways, SAPs) activated in photoaging of human skin (i. e. , sun-induced premature skin aging) are similarly elevated in the skin of elderly people. We have also found that other pathways (namely the mitogen-activated ERK pathway) is depressed in the same skin. Treatment of chronologically-aged skin with a non-retinoid MMP inhibitor and optionally a retinoid both inhibits degradation of dermal collagen and promotes procollagen synthesis. Biopsied sections from skin of elderly (80+ years old) show that a single treatment can increase epidermal thickness, improve the dermal collagen density, and promote the formation of rete pegs and dermal papillae (see FIG. ), and can decrease the amount of c-Jun and increase the amounts of Types I and III procollagen (see FIG. ).

US Patent:

6638543, Oct 28, 2003

Filed:

Feb 27, 2002

Appl. No.:

10/085978

Inventors:

Sewon Kang - Ann Arbor MI
Gary J. Fisher - Ypsilanti MI
John J. Voorhees - Ann Arbor MI

Assignee:

Regents of the University of Michigan - Ann Arbor MI

International Classification:

A61K 3578

US Classification:

424757, 424 59, 424401, 514859

Abstract:

Many human conditions, often skin conditions, are treated topically or orally with a retinoid such as retinoic acid or acetretin, which treatment often has the side effect of dry, irritated, and/or peeling skin. The use of soaps, detergents, chemical irritants, and such can also cause these same side effects. These side effects can be reduced or eliminated by the topical administration of an inhibitor, especially a natural inhibitor, of the epidermal growth factor receptor (EGFR), administered concomitantly with the retinoid, separately from the retinoid (such as on an as needed basis), or both. Administration of the two together is facilitated by a composition suitable for topical application and comprising both the retinoid and a natural EGFR inhibitor. Preferred natural inhibitors are genistein and other isoflavones extracted from natural occurring substances, or simple derivatives of such substances.

US Patent:

6683069, Jan 27, 2004

Filed:

Apr 2, 1999

Appl. No.:

09/285860

Inventors:

Gary J. Fisher - Ann Arbor MI
John J. Voorhees - Ann Arbor MI

Assignee:

Regents of the University of Michigan - Ann Arbor MI

International Classification:

A61K 3107

US Classification:

514167, 514456, 514576, 514629, 514725, 424 59, 424 60, 424400, 424401

Abstract:

Exposure of human skin to ultraviolet (UV) radiation from the sun not only induces the production of enzymes (matrix metalloproteinases) that degrade collagen, but also inhibits the synthesis of new collagen by inhibiting the synthesis of procollagen. This UV-induced inhibition of the synthesis of collagen can be prevented by the topical application of a retinoid or c-JUN inhibitor to the skin prior to its exposure to UV radiation.

US Patent:

6919072, Jul 19, 2005

Filed:

Jun 10, 2003

Appl. No.:

10/458355

Inventors:

James Varani - Ann Arbor MI, US
Gary J. Fisher - Ann Arbor MI, US
John J. Voorhees - Ann Arbor MI, US
Sewon Kang - Ann Arbor MI, US

Assignee:

The Regents of the University of Michigan - Ann Arbor MI

International Classification:

A61K007/42
A61K007/00
A61K031/59
A61K031/185
A61K031/16
A61K031/07

US Classification:

424 59, 424 60, 424400, 424401, 514167, 514576, 514629, 514725

Abstract:

Chronological aging of human skin can be delayed with the topical application of an MMP inhibitor, preferably a retinoid (an indirect MMP inhbitor); retinoids also normalize procollagen biosynthesis. Chronological aging, or natural aging, is evidenced in elderly (80+ years old) skin by increased MMP levels and decreased procollagen levels when compared with younger individuals. Prophylactic treatment of not yet chronologically-aged skin with a retinoid both inhibits degradation of dermal collagen and restores procollagen synthesis. Biopsied sections from elderly skin show that a single treatment of chronologically-aged skin with a retinoid can increase epidermal thickness, improve the dermal collagen density, and promote the formation of rete pegs and dermal papillae. Such benefits are helpful in preventing bruising, tearing, and ulceration of elderly skin. Accordingly, prophylactic treatment begun much earlier in life with an MMP inhibitor and/or a retinoid delays the onset of such symptoms.

US Patent:

6942870, Sep 13, 2005

Filed:

Apr 2, 2002

Appl. No.:

10/114651

Inventors:

Gary J. Fisher - Ann Abor MI, US
John J. Voorhees - Ann Arbor MI, US
Sewon Kang - Ann Arbor MI, US

Assignee:

The Regents of the University of Michigan - Ann Arbor MI

International Classification:

A61K007/00
A61K006/00
A61K007/42

US Classification:

424401, 424 59, 514725

Abstract:

Compositions and methods are provided for ameliorating various effects of UVA and UVB radiation from the sun. The compositions include an ingredient that prevents photoaging from MED and subMED radiation, namely a direct acting MMP (matrix metalloproteinase) inhibitor. The compositions can include another, indirect MMP inhibitor, such as a retinoid, certain other compounds (such as N-acetylcysteine, 2-furildioxime, and vitamin C), tetracyclines, and if a retinoid is used then in addition optional compounds that inhibit the CYP-26 (chytochrome P-450) mediated metabolism of retinoids such as ketoconazole and other azole compounds. In the method, the composition is applied prior to exposure to the sun; for direct acting MMP inhibitors, application should be just prior to exposure, and if indirect inhibitors such as retinoids are used in addition, then application of the indirect inhibitor should be at least about seven hours prior to exposure. Compounds that prevent erythema (skin reddening, sunburn) do not necessarily protect against UV-mediated elevation of MMP levels and activity, and similarly compounds that prevent UV-mediated elevation of MMP levels and activity are not necessarily effective against UV-induced erythema.

US Patent:

7078048, Jul 18, 2006

Filed:

May 9, 2002

Appl. No.:

10/142724

Inventors:

Sewon Kang - Ann Arbor MI, US
John J. Voorhees - Ann Arbor MI, US
Gary J. Fisher - Ypsilanti MI, US

Assignee:

The Regents of the University of Michigan - Ann Arbor MI

International Classification:

A61K 6/00
A61K 7/00
A61K 31/44

US Classification:

424401, 514725, 514729, 514356, 514461, 514572

Abstract:

Rosacea is treated with a composition comprising an antimicrobial and at least one of an anti-inflammatory and a non-retinoid inhibitor of at least one of NF-κβ, AP-1, MMPs, adhesion molecules, TLRs, and CD14. The composition may further comprise a retinoid.

US Patent:

7141238, Nov 28, 2006

Filed:

Oct 22, 2003

Appl. No.:

10/691076

Inventors:

Gary J. Fisher - Ann Arbor MI, US
John J. Voorhees - Ann Arbor MI, US

Assignee:

The Regents of the University of Michigan - Ann Arbor MI

International Classification:

A61K 7/42
A61K 7/00
A61K 31/07
A61K 31/35
A61K 31/185

US Classification:

424 59, 424 60, 424400, 424401, 514167, 514456, 514576, 514629, 514725

Abstract:

Exposure of human skin to ultraviolet (UV) radiation from the sun not only induces the production of enzymes (matrix metalloproteinases) that degrade collagen, but also inhibits the synthesis of new collagen by inhibiting the synthesis of procollagen. This UV-induced inhibition of the synthesis of collagen can be prevented by the topical application of a retinoid or c-JUN inhibitor to the skin prior to exposure to UV radiation.