WO2003053327A2

WO2003053327A2 - Compositions containing a retinoid and malt extract

Info

Publication number: WO2003053327A2
Application number: PCT/EP2002/014871
Authority: WO
Inventors: Thierry Oddos; Patricia Manissier; Magali Jousselin
Original assignee: Johnson & Johnson Consumer France S.A.S.
Priority date: 2001-12-20
Filing date: 2002-12-19
Publication date: 2003-07-03
Also published as: WO2003053327A3; EP1458346A2; AU2002361241A8; AU2002361241A1

Abstract

The present invention relates to compositions comprising a retinoid and a malt extract for improving the appearance of the skin and to combat the effects of aging of the skin.

Description

Compositions Containing a Retinoid and Malt Extract

Brief description of the invention

The present invention relates to compositions comprising a retinoid and malt extract for improving the appearance of the skin and to combat the effects of skin aging.

Background of the Invention

The skin is composed of three layers: the epidermis, including the outer layer and the stratum comeum, the dermis and, deeper down, the hypodermis. Exchanges exist between these different dermal and epidermal layers, which are intended to ensure cell renewal, cohesion and moisturization of the outer layers.

It is known that skin aging is a physiological phenomenon that follows a period of growth. In particular it is characterized by thinning of the skin and a loss of its elasticity, leading to the appearance of deep or fine wrinkles or both; other phenomena that are observed are surface drying and disorderly pigmentation. All these effects of the skin aging process reflect changes in the three dermal layers.

The dermis results from the biosynthetic activity of fibroblasts, which develop the constituents of the extracellular matrix. The latter contains four families of structural molecules: collagens, elastin, structural glycoproteins and proteoglycans.

Collagen is the most important structural protein of the dermis since it represents 70 % of its dry weight. Different, genetically distinct types of collagen exist. Among the major collagens, type I collagen is present in connective tissues and represents all of the collagen in bone and dentine. Type HI collagen is complexed with type I collagen in most connective tissues, but is not found in bone or tendons. Many active agents have been proposed to prevent or delay the effects of skin aging. It has been shown that retinoids, and in particular retinol, have a favorable effect on the appearance of the skin and are useful in combating the effects of skin aging.

Another part of the skin that plays a role in the skin aging process, including photoaging, is the so-called 'dermal epidermal junction' (DEJ). The function of this part of the skin is to "stick" together the dermis and the epidermis.

Several macromolecules compose the DEJ such as collagen IN and Nil, heparan sulfate and laminins. These molecules are synthesized in the two adjacent tissue layers. The function of laminines was initially described to lie in the attachment of the keratinocytes from the epidermis basal layer to the DEJ. It further became clear that laminins play an important role in skin structuralization as genetic disorders related to laminins cause the skin to become fragile and induce the appearance of diseases like epidermis bullosa. Moreover, during skin restructuralization (healing or skin equivalent building) the addition of laminins improves and accelerates the formation of the dermal epidermal junction.

During the aging process a progressive degradation of the DEJ is observed because of structural changes in it, in particular it becomes thinner and more flat. The DEJ loses its original structure and thereby its funtionality.

Since laminins play an important role in the structuralization of the DEJ, the stimulation of laminin production and release seems a promising route to improve the DEJ structure and the concomitant overall apperance of the skin. Agents that stimulate laminin production and release would therefore be attractive in the treatment of the effects of skin aging, hi particular retinoic acid has been described to be capable of enhancing laminin expression in cultured skin fibroblasts.

It is an object of this invention to provide compositions that have a favorable effect on the appearance of the skin and to provide compositions that act on the effects of skin aging. This object is attained by the compositions of the present invention which in particular act on the production of laminins and therefore have a positive effect on the formation and the constitution of the DEJ.

Summary of the invention

The present invention is directed to a composition comprising at least one retinoid, or a topically acceptable salt thereof and at least one malt extract.

A preferred retinoid is retinol.

A preferred malt extract is aqueous.

A particularly preferred malt extract is the product named 'Basaline™' , available from the company Coletica.

The invention further is concerned with a topical formulation comprising a composition as defined herein and further ingredients. The topical formulation can be for dermatological use but in particular is for cosmetic use.

In another aspect the invention provides the use of a composition as defined herein for manufacturing a topical or more specifically a cosmetic formulation. The topical or cosmetic formulations in particular are useful for combating or treating the effects of skin aging.

In a further aspect the invention provides the use, and in particular the cosmetic use, of a composition as defined herein, or of a topical formulation as defined herein, for combating or treating the effects associated with the aging of skin.

Or, alternatively, the invention concerns a method, and in particular a cosmetic method, of combating or treating the effects of skin aging, which method or cosmetic method comprises applying to the affected skin area an amount of a composition or a topical formulation as defined herein, said amount being effective to treat said effects of skin aging.

Still another aspect of this invention comprises a cosmetic method for the improvement of the external appearance of an individual, said method comprising applying a composition or a topical composition as defined herein to affected skin areas.

Detailed Description of the Invention

The retinoid used in the compositions according to the invention is selected from retinoic acid or tretinoin, retinaldehydes, retinol, their salts, their esters and the stereoisomers thereof. Examples are retinyl palmitate, retinyl acetate, and stereoisomers such as all transretinoic acid, 9-cis retinoic acid, and 13-cis-retinoic acid. In addition, the terms "retinol" and "retinoic acid" should be understood to also include the hydrogenated and non-hydrogenated isomers such as β-cis-retinol, didehydroretinol, β-cis-retinoic acid, β-trans-retinoic acid and didehydroretinoic acid.

Typical salts are alkali metal, ammonium and alkylammonium salts. Sodium, potassium, triethanolammonium and ammonium salts are particularly preferred. As used herein alkylammonium refers to primary, secondary, tertiary and, which is preferred, quaternary alkylammonium, wherein alkyl: in particular is Cι-C ₀alkyl. C_\- C₃₀alkyl refers to hydrocarbon radicals having from 1 to 30 carbon atoms that are preferably saturated. Said Cι-C₃₀alkyl maybe optionally substituted, for example with hydroxy, except that when Cι-C₃₀alkyl is substituted it is other than Ci-alkyl.

The compositions may also contain combinations of one or more of the above mentioned retinoids.

Compositions which are particularly suitable for carrying out the invention contain a combination of retinol and malt extract. Retinoids are known products which can be prepared according to methods known in the art.

The malt extract for use in the compositions of the present invention is prepared according to methods known in the art. The malt extract may be aqueous, with various concentrations of dry material; or it may be in dry form. The malt extract in particular is aqueous and may further contain components selected from preservatives, in particular preservatives commonly used in cosmetic formulations, suitable solvents such as mono- and/or polyols, e.g. glycols, glycerin and the like, and other components.

A preferred malt extract is aqueous and contains from about 1 to about 5 % of dry- material, more preferably from about 2 to about 3 % of dry material.

A particularly preferred malt extract is the product called 'Basaline™' which is commercially available from the company Coletica (Lyon, France). This malt extract is aqueous and contains from about 2 to about 3% of dry material.

In the compositions of the present invention the w/w ratio of the retinoid to the malt extract may vary but in particular is in the range of about 1 : 200 to 2 : 1 , preferably from about 1 : 100 to about 1 : 1, or from about 1 : 100 to 1 : 10; more preferably from about 1 : 50 to about 1 : 3, still more preferably from about 1 : 10 to about 1 : 5. Of particular interest is a ratio which is about 1 : 4. The ratios in this paragraph are based on retinoid in pure form and on malt extract having the preferred concentration of 2 to 3 %. In case the retinoid is used in admixture with other components, or as salt or in solution, the ratio evidently needs to be recalculated correspondingly. Similarly, if malt extract is used in concentrations different from 2 or 3%, or in dry form, the ratios also need recalculation. For example if dry malt extract is used, the amount of malt extract in the above mentioned ranges needs to be divided by a number between 50 and 33.3 (100/3).

The compositions of the invention are prepared by mixing the retinoid and the malt extract, optionally in the presence of a suitable solvent. If desired, other components may be added. Alternatively, the retinoid and the malt extract may be mixed with the other components and the thus prepared mixtures may be combined to the desired composition.

The compositions may also take the form of concentrates which subsequently are transformed into the desired composition by addition of solvent and/or other components.

This invention further relates to topical formulations containing a composition as defined herein. Topical compositions comprise as well dermatological formulations (or topical pharmaceutical formulations), and cosmetical formulations. Said topical formulations may further contain other ingredients or additives suited for external topical administration, in particular dermatologically or cosmetically acceptable ingredients or additives, including other active ingredients. Examples of further ingredients or additives are surfactants, emulsifiers, consistency factors, conditioners, emollients, skin caring ingredients, moisturizers, thickeners, lubricants, fillers, binding agents, anti-oxidants, preservatives, active ingredients, in particular dermatologically active ingredients dyes, fragrances and the like. Active ingredients as mentioned herein comprise, for example, anti-inflammatories, anti-bacterials, anti-fungals and the like agents. Of particular interest are any active ingredients suited for topical applications.

The topical formulations according to the invention can further include one or more of a variety of optional ingredients, such as coloring agents, opacifying agents and the like.

The retinoid and more specifically the retinol should be used in the formulations for topical application at concentrations from 0,001% to 0.5%, preferably from 0.01% to 0.2%), more preferably from 0.03%. to 0.15%, most preferably between 0.05% and 0.15%). The malt extract should be used in the formulations for topical application at a concentration between 0.01% to 5% and preferably from 0.1 to 3%, most preferably between 0.2%> and 1%>. As used in this paragraph, retinol refers to pure retinol, and malt extract refers to extract containing 2-3 %> of solid material. In case the retinoid is used in admixture with other components, or as salt or in solution, or if malt extract is used in concentrations different from 2 or 3%, or in dry form, the above percentages need to be recalculated accordingly.

Unless indicated otherwise, all percentages in the preceding and following paragraphs are w/w percentages.

The formulations according to the present invention can be prepared by adding the appropriate ingredients to a composition of the invention, or vice versa by adding the composition to an appropriate cosmetic or dermatological formulation base. It is also possible to mix all the ingredients individually, i.e. without making a separate composition as defined herein.

The topical formulations according to the invention may be in various forms, e.g. in the form of a solution, a hydrophilic lotion, an ointment, a cream, a gel, an emulsion, in liposome form or formulated as a foaming product. Emulsions can be, for example, in the form of oil-in- water, water-in-oil or multiple emulsions.

Preferred formulations are gel and cream based formulations. Of particular interest are formulations based on oil-in-water emulsions.

h the latter instance an oily phase, containing the oil-soluble components, is made separately which is added to any of the aqueous phases containing suitable emulsifiers.

Preferably the first aqueous phase is made containing one or more suitable emulsifiers.

The oily phase is made and added to the first phase while building an emulsion. Subsequently the second aqueous phase is added. In the instance where the first or oily phase contains solid or semi-solid components, it is recommendable to heat the phase or phases and to conduct the emulsifying process at elevated temperature.

The topical formulations according to the invention can further include one or more of a variety of additional ingredients commonly found in skin care compositions, such as for example, emollients, skin conditioning agents, emulsifying agents, humectants, preservatives, antioxidants, active ingredients, perfumes, chelating agents, dyes, opacifying agents, etc., provided that they are physically and chemically compatible with the other components of the composition.

Examples of active agents which maybe incorporated comprise anti-microbials, e.g. anti-bacterials and antifungals, anti-inflammatory agents, anti-irritating compounds, anti-itching agents, moisturising agents, skin caring ingredients, plant extracts, vitamins, and the like. Also included are sunscreen actives which may be inorganic or organic in nature.

Examples of suitable preservatives for use in the compositions or formulations of the invention include the Cι-C₄ alkyl parabens and phenoxyethanol. Generally, the preservative is present in an amount ranging from about 0.5 to about 2.0, preferably about 1.0 to about 1.5, weight percent based on the total composition. In a preferred embodiment, the preservative is mixture of from about 0.2 to about 0.5 weight percent methylparaben, from about 0.2 to about 5.0 weight percent propylparaben and from about 0.05 to about 0.10 weight percent butylparaben. A particularly preferred commercially available preservative that may be used in the skin care composition according to this invention is Phenonip™ which is a practically colorless, viscous, liquid mixture of phenoxyethanol, methylparaben, ethylparaben, propylparaben, and butylparaben available from Nipa Laboratories, Inc.

Preferably, antioxidants should be present in the compositions or formulations according to the invention. Suitable antioxidants include butylated hydroxy toluene (BHT), ascorbyl palmitate, butylated hydroanisole (BHA), phenyl-α-naphthylamine, hydroquinone, propyl gallate, nordihydroquiaretic acid, vitamin E or derivatives of vitamin E, vitamin C and derivatives thereof, calcium pantothenic, green tea extracts and mixed polyphenosls, and mixtures thereof of the above. When utilized the antioxidant can be present in an amount ranging from about 0.02 to about 0.5%> by weight, more preferably from about 0.002 to about 0.1 %> by weight of the total composition.

Emollients which can be included in the compositions or formulations of the invention function by their ability to remain on the skin surface or in the stratum corneum to act as lubricants, to reduce flaking, and to improve the skin appearance. Typical emollients include fatty esters, fatty alcohols, mineral oil, polyether siloxane copolymers and the like. Examples of suitable emollients include, but are not limited to, polypropylene glycol ("PPG")- 15 stearyl ether, PPG- 10 cetyl ether, steareth-10, oleth-8, PPG-4 lauryl ether, vitamin E acetate, PEG-7 glyceryl cocoate, lanolin, cetyl alcohol, octyl hydroxystearate, dimethicone, and combinations thereof. Cetyl alcohol, octyl hydroxystearate, dimethicone, and combinations thereof are preferred. When utilized, the emollient can be present in an amount from about 0.01 to about 5, preferably from about 1 to about 4 percent by weight based on the total composition.

Polyhydric alcohols can be utilized as humectants in the compositions or formulations of the invention. The humectants aid in increasing the effectiveness of the emollient, reduce scaling, stimulate removal of built-up scale and improve skin feel. Suitable polyhydric alcohols include, but are not limited to, glycerol (also known as glycerin), polyalkylene glycols, alkylene polyols and their derivatives, including butylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol and derivatives thereof, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1,3-dibutylene glycol, 1,2,6,-hexanetriol, ethoxylated glycerol, propoxylated glycerol and mixtures thereof. Glycerin is preferred. When utilized, the humectant is present in an amount from about 0.1 to about 5, preferably from about 1 to about 3 percent by weight, based on the total weight of the composition.

All the topical formulations as described above can be applied on the skin by means of wipes.

The compositions and topical formulations subject of the present invention are useful to combat or to treat the effects of skin aging. The latter comprise effects such as the appearance of fine lines, fine wrinkling, wrinkling, loss of skin firmness, skin tightening and suppleness. The effects of skin aging are due to aging as such, but also to aging of the skin caused by external factors such as exposure to environmental factors such as exposure to sunlight, wind, atmospheric pollutants and the like, or a combination of these factors. Retinoids and in particular retinol are known as agents that are effective in combating the effects of skin aging. Malt extract on the other hand is known to stimulate the synthesis of collagen and other extracellular proteins in in vitro experiments.

It now has been found that malt extract has a positive effect on the properties of retinoids and in particular retinol, retinoids and in particular retinol and malt extract act synergistically. For example these combinations show synergistic effects in their stimulation of the synthesis of laminin form human dermal equivalent at a concentration where no significant effect was detected with retinol or malt extract respectively.

The invention further provides a method for treating the effects of skin aging through the stimulation of laminin synthesis using a composition of the invention, in particular a composition containing a retinoid and malt extract.

The invention additionally relates to the management of the skin aging process through the reinforcement of the dermal epidermal junction and to the management of the appearance of skin.

The compositions and formulations according to the invention have an improved effect on the effects of skin aging, in terms of efficacy and speed of action. These effects comprise a reduction in the number and/or depth of wrinkles and fine wrinkles, firming and tightening of the skin and better moisturization. The compositions and formulations according to the invention provide a more youthful and smooth aspect to the skin and also unify the complexion and or prevent or decrease the appearance of age marks. The compositions according to the invention are particularly suitable for combating wrinkles and slackening of the tissues. They also provide protection of the skin against environmental factors, in particular UN light, and environmental pollutants. They may also be used to prepare the skin to receive other cosmetic and make-up products. The topical formulations of the invention may be applied in the morning and/or evening. They maybe applied on those parts of the body where skin aging is prominent, i.e. on the face, the body or the hands.

The compositions and formulations according to the invention may be appropriate for improving the pigmentation and combating the appearance of age marks on the epidermis of the hands, as well as for increasing the firmness of the tissues in these areas, which have a tendency to become flaccid upon aging.

The compositions and formulations according to the invention are particularly appropriate for treating the areas around the eyes and the lips, which are very fragile and are highly susceptible to the appearance of wrinkles and slackening of the skin. They make it possible to reduce visibly the number of wrinkles and the pockets under the eyes; they firm up the particularly sensitive skin around the eyes and the mouth.

According to another aspect, the invention concerns the use of a combination of at least one retinoid with malt extract for the preparation of a composition designed to improve the elasticity of the skin and/or to combat the changes in the skin that are due to aging.

The invention further provides a method for the cosmetic treatment of photo-ageing and of intrinsic aging of the skin, the mucosae or the exoskeleton, in particular the face and the hands, which consists in applying the compositions or formulations as described herein.

Examples

Example 1

Ingredients % Weight g

steareth 10 1.4000 700.0 glyceryl distearate 2.8000 1400.0 cholesterol 1.0000 500.0 ceteareth 20 /stearyl alcohol 3.0000 1500.0 ceteareth 20 /cetearyl alcohol 3.0000 1500.0 stearyl alcohol 0.5000 250.0 octyl hydroxystearate 5.8014 2900.7 polysorbate 80 0.7000 350.0

BHT (butylated hydroxy toluene) 0.1000 50.0 tocopheryl acetate 0.1000 50.0

Retinol (40%) polysorbate 20/BHT 0.3130 156.50

aqua 55.6886 27844.3 glycerin 2.5000 1250.0 phenoxyethanol 0.5000 250.0 methyl paraben 0.2500 125.0 propyl paraben 0.1500 75.0 disodium EDTA 0.2000 100.0 butylene glycol 2.0000 1000.0

PEG 8 2.5000 1250.0 lactose 5.0000 2500.0

acrylates /C 10-30 alkyl acrylate 0.1800 90.0 crosspolymer isodecyl neopentanoate 2.5000 1250.0 sodium hydroxyde 0.0970 48.50 aqua 2.5000 1250.0

aluminium starch octenyl succinate 1.5000 750.0 cyclomethicone 3.0000 1500.0

aqua 1.0000 500.0 ascorbic acid 0.0500 25.0

chlorhexidine digluconate (20%) / aqua 0.1500 75.0

(80%)

Basaline ™ 0.5000 250.0

sodium hydroxyde 0.0200 10.0 aqua 1.0000 500.0

Total 100.000 50000.0

The components of a group in the above list (groups being separated by a space in the above list) are mixed together using standard formulation equipment. Subsequently the group mixtures are added to one another and mixed to the end product.

Example 2

Effect of retinol and Basaline ™ (Malt extract) on laminines in production in fibroblasts in dermis equivalent test model.

Dermis equivalent was obtained by seeding fibroblasts in a collagen gel and cultivating it during 3 weeks. Two different sets of dermis equivalent were prepared: one set with fibroblasts from donors aged between 25-35 and an other with fibroblasts from donors aged between 55-65. Dermis was then treated during 48 hours with retinol (2.10^"5 %) and Basaline™ (0.5%>). Culture supemantant was recovered and laminin level released in the culture medium was measured using ELISA methodology.

A statistical significant decrease in the release of laminin was found between dermis equivalent obtained from the 55-65 year old donor group compared to the dermis derived from fibroblasts from the younger donor group. Treatment of the dermis prepared with fibroblast from aged donors with Basaline ™ or retinol alone did stimulate the release of laminin in the medium. On the other hand, treatment of the dermis equivalent with a mixture of retinol and Basaline ™ result in a marked and statistical significant increase in laminin production. (Table 1).

Table 1 : Effect of retinol and Basaline™ on laminin production in dermis equivalent.

Treatment Laminin J2 Significance

% vs expression control vs control

Control 55-60 year old 100.00 -

Retinol 2.10^"4 % 114.90 NS

Basaline™ 0,5 % 105.50 NS

Retinol 2.10^"4 % + Basaline™ 124.10 ρ<0.05

0.5 %

Control 25-35 year old 125.10 p<0.05

Values are expressed as the percentage of laminin expression versus the aged control. Laminin expression was expressed in nmol of laminin / mg of protein.

Claims

Clai s

1. A composition comprising a retinoid, or a topically acceptable salt thereof, and malt extract.

2. A composition according to claim 1 wherein the retinoid is retinol.

3. A composition according to claim 1 wherein the malt extract is aqueous.

4. A composition according to claim 3 wherein the malt extract contains between 2 and 3%> of dry material.

5. A composition according to any of claims 1-4 wherein the w/w ratio of retinoid to malt extract is in the range of 1 :200 to 1 : 1.

6. A composition according to claim 5 wherein the w/w ratio of retinoid to malt extract is in the range of 1 : 10 to 1 :5.

7. A topical or cosmetic formulation comprising a composition as claimed in any of claims 1 - 6 and further ingredients.

8. Use of a composition as claimed in any of claims 1-6 for manufacturing a topical or in particular a cosmetic formulation.

9. Use of a topical formulation as claimed in claim 7, or of a composition as claimed in any of claims 1-6 for combating or treating effects associated with the aging of skin.

10. The use according to claim 9, limited to cosmetic use.