# US 2014/0193529 A1 · Modulation of Thymosin Beta-4 in Skin

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- Number: US 2014/0193529 A1
- Document ID: US20140193529A1
- Status: Published application
- Kind: A1
- Application number: 13/735,659
- Filed: 2013-01-07
- Published: 2014-07-10
- Earliest claimed: 2013-01-07
- Assignees: Avon Products, Inc.
- Applicants: Avon Products, Inc.
- Inventors: Ying Cheng; Qian Zheng; Russell J. Wyborski
- Web page: https://patentgrep.com/patent/US20140193529A1

## CPC

- A61K 31/451: having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
- A61K 8/365: Hydroxycarboxylic acids; Ketocarboxylic acids
- A61K 8/671: {Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal}
- A61K 8/9789: Magnoliopsida [dicotyledons]
- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61K 31/4155: non condensed and containing further heterocyclic rings
- A61K 31/438: The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
- A61K 36/185: Magnoliopsida (dicotyledons)
- A61K 36/21: Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
- A61K 36/36: Caryophyllaceae (Pink family), e.g. babysbreath or soapwort
- A61K 36/74: Rubiaceae (Madder family)
- A61K 36/81: Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
- A61Q 19/005: {Preparations for sensitive skin}
- G01N 2500/10: involving cells
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Methods for preventing, ameliorating, or reducing dermatological signs of inflammation are provided which employ active agents, other than a retinoid, that stimulate thymosin beta-4 expression in the skin and inhibit production of pro-inflammatory chemokines and/or cytokines. Also provided are methods for screening for substances which stimulate thymosin beta-4 expression levels and the methods of using active agents identified by the screening protocol in the treatment of skin.

## Claims

### Claim 1

A method for inhibiting the inflammatory response of human skin comprising topically applying to an area of the skin in need thereof an effective amount of an active agent, other than a retinoid, that stimulates human thymosin beta-4 expression and inhibits inflammatory response, for a time sufficient to inhibit the inflammatory response of said human skin.

### Claim 2 (depends on 1)

The method according to claim 1, wherein said inhibition of inflammatory response of said human skin is selected from the group consisting of:
(a) improvement in skin texture and/or promotion of retexturization;
(b) improvement in skin barrier repair and/or function;
(c) improvement in appearance of skin contours;
(d) restoration of skin luster and/or brightness;
(e) improvement of skin appearance decreased by aging and/or menopause;
(f) increase in skin elasticity and/or resiliency;
(g) reduction of pigment spots and/or mottled skin;
(h) decrease, prevention and/or elimination of skin inflammation;
(i) treatment, reduction and/or prevention of eczema and other forms of atopic dermatitis;
(j) treatment, reduction and/or prevention of contact dermatitis;
(k) treatment, reduction and/or prevention of dermatitis herpetiformis;
(l) treatment, reduction and/or prevention of generalized exfoliative dermatitis; and/or
(m) treatment, reduction and/or prevention of seborrheic dermatitis.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the ability of said active agent to stimulate thymosin beta-4 expression has been determined by an assay which measures expression levels of thymosin beta-4 in a cell that has been contacted with said active agent.

### Claim 4 (depends on 3)

The method of claim 3, wherein the ability of said active agent to inhibit skin inflammation has been determined by an assay which measures expression levels of pro-inflammatory chemokines and/or cytokines in a cell that has been contacted with said active agent and subsequently challenged with TNF-alpha or another inflammation stimulant.

### Claim 5 (depends on 3)

The method according to claim 3, wherein said assay measures the expression level of the human gene TMSB4X encoding thymosin beta-4.

### Claim 6 (depends on 5)

The method according to claim 5, wherein said expression level is determined by measuring the expression level of a corresponding mRNA.

### Claim 7 (depends on 3)

The method according to claim 3, wherein said cell is a dermal fibroblast or an epidermal keratinocyte.

### Claim 8

A method for identifying at least one active agent useful for inhibiting the inflammation response of skin comprising assaying at least one candidate substance for ability to stimulate thymosin beta-4 expression in at least one of a dermal fibroblast or a epidermal keratinocyte by incubating human dermal fibroblasts or human epidermal keratinocytes with said candidate substance and subsequently measuring the levels of mRNA encoding thymosin beta-4.

### Claim 9 (depends on 8)

The method of claim 8, wherein the human dermal fibroblasts incubated with TB-4 are subsequently challenged with TNF-alpha or another pro-inflammation stimulant and then measured as to levels of mRNA encoding inflammatory chemokines and/or cytokines.

### Claim 10 (depends on 1)

The method according to claim 1, wherein said active agent is applied to said skin at least once daily for a period of at least four weeks.

### Claim 11

A cosmetic composition for improving the aesthetic appearance of human skin comprising a cosmetically acceptable vehicle, and an effective amount of an active agent, other than a retinoid, that inhibits skin inflammation and upregulates thymosin beta-4, wherein said effective amount of active agent comprises from about 0.00001% to about 90% by weight of the total composition.

### Claim 12 (depends on 11)

The cosmetic composition according to claim 11, wherein said active agent is a botanical extract from a plant selected from the group consisting of Maesa japonica, Celosia argentea, Berchemia lineata, Ixora chinesis, Physalis minima, and combinations thereof.

### Claim 13 (depends on 11)

The cosmetic composition according claim 11, wherein said effective amount of active agent is between about 0.01% to about 10% by weight of the total composition.

### Claim 14 (depends on 11)

The cosmetic composition according to claim 11, wherein said botanical extract is selected from the group consisting of Maesa japonica, Celosia argentea, Berchemia lineata, Ixora chinesis, Physalis minima, and combinations thereof.

### Claim 15 (depends on 11)

The composition according to claim 11, wherein said active agent is selected from the group consisting of:
and combinations thereof.

### Claim 16 (depends on 15)

The composition according to claim 15 wherein said agent is: