Growth factor mediated cosmeceuticals and use thereof to enhance skin quality

a growth factor and cosmeceutical technology, applied in the direction of viruses/bacteriophages, drug compositions, peptide/protein ingredients, etc., can solve the problems of harmful combination, achieve the effect of increasing collagen deposition, promoting the migration of activated cells, and increasing the migration of keratinocytes

Inactive Publication Date: 2008-09-25
NEW YORK UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0013]It has been discovered that vascular endothelial growth factor (“VEGF”) promotes migration of activated (but not differentiating) keratinocytes to skin. This growth factor specifically increases migration of keratinocytes of the “wounded skin” phenotype but does not have significant effects upon differentiated keratinocytes. It also increases collagen deposition and reduces wrinkles, enhances skin quality, and increases skin thickness to normal levels in individuals where skin has thinned due to age or disorder such as diabetes. It is particularly well suited for use as cosmeceuticals when applied in purified form and in known amounts. The data presented in the examples demonstrate efficacy and specificity of VEGF in enhancing migration of normal human keratinocytes as well as formation of new granulation tissue including collagen formation. VEGF induces keratinocyte and fibroblast migration, formation of new tissue, and not only induces deposition of collagen but improves alignment of the collagen fibers. Accordingly, this growth factor is highly suitable for use as a cosmeceutical, especially for skin resurfacing and reduction in wrinkles.
[0014]Formulations and methods of use thereof are described. A preferred formulation is a sustained release formulation, most preferably in an easy to administer topical formulation which enhances prolonged delivery and uptake of the growth factor to the skin, or a gene therapy vector. In a preferred embodiment, the carrier includes a pH buffering or neutralizing agent. The formulations may be applied topically to the skin, or adjacent to the site where increased keratinocyte and collagen deposition is desired, or injected or implanted within a sponge or other materials for use as a bulking agent which forms tissue in place of the implant. The formulation provides an effective amount of the growth factor over the necessary time to improve the skin quality, form new tissue, or enhance healing. It has been discovered that there is no additional beneficial effect with using a mixture of growth factors and such a combination may be detrimental. The effects of VEGF are not dependent on angiogenesis.

Problems solved by technology

It has been discovered that there is no additional beneficial effect with using a mixture of growth factors and such a combination may be detrimental.

Method used

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  • Growth factor mediated cosmeceuticals and use thereof to enhance skin quality

Examples

Experimental program
Comparison scheme
Effect test

example 1

Non-Angiogenic Mechanism of VEGF Stimulation of Keratinocyte and Fibroblast Migration

[0116]Human Recombinant VEGF Stimulates Only the Epidermal Cells (Keratinocytes) That Have Regenerative Potential

[0117]To test the effects of VEGF on epithelialization, which is very important in cosmetology especially for laser resurfacing, recombinant VEGF was tested using an in vitro scratch model to measure keratinocyte migration. When normal human keratinocytes grown in a tissue culture dish are “wounded” by a scratch, they migrate over the scratch to close the gap. This approach was used to test how VEGF effects keratinocyte migration and proliferation.

[0118]Materials and Methods

[0119]Primary human keratinocytes were incubated in the presence and absence of recombinant VEGF. Keratinocyte migration was observed during a 48 hr period. Epidermal Growth Factor (EGF) was used as a positive control because it is a well established stimulant of both keratinocyte migration and proliferation. Cells wer...

example 2

VEGF Enhances Skin Healing in Experimental Models as Measured by Tensile Properties of the Skin and Increased Epithelialization

[0130]Materials and Methods

[0131]Using methods and materials as described above with respect to VEGF local sustained release of VEGF using adenoviral vector mediated gene transfer reversed the reduced angiogenic response observed in diabetic wounds and accelerated wound healing. This was tested by determining the specific effects of VEGF165 application on all components of the wound healing process: epithelialization, skin biomechanical properties, histology, and time to 100% wound closure. To determine the effects of VEGF on wound healing in vivo, ADV / VEGF165 and controls (vehicle and saline) were injected into excisional and incisional wounds created on dorsum of BKS.Cg-m+ / +Leprdb and NOD mice and mechanical properties and histological evaluations were performed 10, 14 or 21 days post injury.

[0132]Linear incisional wounds were created on the dorsum of 57 f...

example 7

VEGF Induces Collagen Formation with Alignment of Fibers

[0150]One of the contributing factors to wrinkle formation is loss of alignment in collagen fibers. To test if the VEGF-mediated collagen deposition is properly aligned, Sirius red staining with polarized light microscopy was employed on the three treatment groups of Example 6.

[0151]Saline treated control wounds showed modest birefringence intensity from organized collagen fibers. These collagen fibers were short, thin and arranged in a random pattern. The greenish-yellow birefringence of these collagen fibers was typical of young immature granulation tissue. The red birefringence on the surface of the granulation tissue was from the keratin laid-down by keratinocytes within the epidermal cell layer. There was little collagen deposited in these saline treated mice and that newly deposited collagen was poorly organized. Empty viral particles treated wounds show an increase in the greenish-yellow birefringence intensity, where co...

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Abstract

It has been discovered that vascular endothelial growth factor (“VEGF”) promotes migration of activated (but not differentiating) keratinocytes to skin. This growth factor specifically increases migration of keratinocytes of the “wounded skin” phenotype but does not have significant effects upon differentiated keratinocytes. It also increases collagen deposition and reduces wrinkles, enhances skin quality, and increases skin thickness to normal levels in individuals where skin has thinned due to age or disorder such as diabetes. It is particularly well suited for use as cosmeceuticals when applied in purified form and in known amounts. The data presented in the examples demonstrate efficacy and specificity of VEGF in enhancing migration of normal human keratinocytes as well as formation of new granulation tissue including collagen formation. VEGF induces keratinocyte and fibroblast migration, formation of new tissue, and not only induces deposition of collagen but improves alignment of the collagen fibers. Accordingly, this growth factor is highly suitable for use as a cosmeceutical, especially for skin resurfacing and reduction in wrinkles.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application claims priority to U.S. Provisional Application No. 60 / 895,942, filed Mar. 20, 2007.FIELD OF THE INVENTION[0002]The present invention is a cosmeceutical formulation containing VEGF, and methods of use thereof to improve skin quality, for example skin quality decreased by diabetes or aging.BACKGROUND OF THE INVENTION[0003]Current popular methods to treat facial signs of aging are many and very limited. The popular BOTOX® Cosmetic-with 3.3 million people receiving treatment last year-works by using a low dose of a potent toxin to temporarily paralyze the muscles surrounding the wrinkles, thus smoothing their appearance. However it is limited. Popular ingredients such as alpha-hydroxy acids and retinols can cause the skin to dry and tighten, which could worsen the appearance of wrinkles. Collagen injections can trigger allergic reactions or yield uneven results.[0004]Vascular endothelial growth factor (VEGF), is known...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/18A61P17/02
CPCA61K8/64A61Q19/08A61K38/1866C12N2799/04C12N2799/022A61P17/02
Inventor BREM, HAROLDTOMIC, MARJANA
Owner NEW YORK UNIV
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