WO1997046221A1

WO1997046221A1 - Cosmetic method for treating and preventing the signs of skin ageing

Info

Publication number: WO1997046221A1
Application number: PCT/IB1997/000642
Authority: WO
Inventors: Dominique Castelli; Gerd Ries
Original assignee: Roc
Priority date: 1996-06-07
Filing date: 1997-06-05
Publication date: 1997-12-11
Also published as: EP0845979A1; HUP9802916A3; HUP9802916A2; FR2749511B1; CZ31798A3; CA2228750A1; EA199800194A1; AU2786197A; JPH11510824A; CN1198092A; FR2749511A1; BR9702284A; KR19990036233A; PL324929A1

Abstract

The invention relates to a cosmetic method for treating and preventing the signs of skin ageing and in particular wrinkles, characterized in that: a) a composition containing at least one retinoid at a sub-irritant dose which is effective for combating skin ageing, in a support which is suitable for topical administration, is applied to the skin once a day; b) a composition containing a higher dose of at least one retinoid, in a cosmetologically acceptable support which is suitable for topical administration, is applied about 10 to 16 hours after the composition mentioned in a). The invention also relates to a combination product containing such compositions.

Description

COSMETIC METHOD FOR TREATING AND PREVENTING THE SIGNS OF SKIN AGEING The present invention relates to the treatment of the skin using compositions containing retmoids, in order to combat skin ageing and the formation of wrinkles More particularly, the invention relates to a method for the cosmetic treatment of the skin, m particular the face, the neck or the hands, with retinoid compositions, which is less irritant than the known methods and allows the individual to use higher and more effective doses during the treatment, and at an earlier stage than previously

It is known m the prior art that compounds of the retinoid type are useful for treating skin ageing and may be used very effectively for combating wrinkles, irregular hyperpigmentation and lentigos, as well as skin roughness and other skin anomalies For example, in patents US-4 , 603 , 146, 4,887,805 and 4,888,342, Kligman describes the use of retmoids to reduce and prevent the damage caused to the skm by light radia¬ tion. However, it has also been established that the use of retmoids is extremely irritant to the skin during the first weeks of application This may lead users to stop the programme of treatment with retmoids during this initial period of use, particularly in cosmetology, where the consumer is less disposed to accepting this type of inconvenience.

Several methods and formulations have been proposed to reduce this irritation induced by retmoids. For example, patent US-5,401,517 suggests using a lower dose of retmoids for several days and then increasing the dose of retmoids in the composition on the following days, when the sk has become accustomed to the compounds. However, this method has drawbacks since it requires a change in the application regime to use a different formulation containing a higher dose of retinoid. This places the onus on the user to remember to change product and to buy an additional product before the first one has been used up.

In contrast, according to the present inven¬ tion, compositions containing low doses of retmoids are used during the day but allow the individual to apply formulations containing a higher, more effective dose in the evening before going to bed. All of each tube of product will be used during the treatment, thus avoiding any loss of product and excessive costs.

In addition, the application procedure will remain similar from the initial day of the treatment, which will thereby encourage the individual to acquire suitable habits and to maintain these habits from the first day of use. The individual applies high doses of retinoids from the start of the treatment and thus obtains the benefits of high doses immediately.

Consequently, one of the subjects of the inven¬ tion is to provide a method for treating the skin by applying an effective amount of retinoid onto the skin during the day, in order to combat the ageing process.

Another of the subjects of the invention is to provide a method for treating the skin with retinoids and for attenuating the irritation produced by retinoids.

Another of the subjects of the invention is to provide a method for treating the skin which allows a high dose of retinoids to be applied from the first day of use . Another subject of the invention is to provide a method for treating the skin which allows the individual to use the retinoid-based product on a daily basis from the start of the treatment.

Consequently, the invention relates to a method for treating the skin according to the following procedure : a) application of a composition containing a weak dose of retinoids, comprising a compound of retinoid type which is effective for combating skin ageing, at a sub-irritant dose, once a day; and b) application of a composition containing a higher dose of retinoids approximately 10 to 16 hours, advantageously 12 hours, after the first dose.

In addition, a composition formulated specifi- cally for a part of the face, for example the eyes, may be applied once or twice a day at a low, sub-irritant dose.

The formulations serving as vehicle for each of the applications of the product in the method according to the invention may be identical or may be different, depending upon the particular requirements of the regime and of the user. For example, a base or a lighter formulation may be used during the day whilst a richer emulsion of firmer consistency may be used at night for greater skin comfort while the individual is resting.

The aim pursued in developing the invention is to allow the individual using retinoid-based compositions to become more tolerant to retinoids more quickly. Often, individuals react by developing red¬ ness, itchiness, stinging, a burning sensation and desquamation when retinoids are applied. However, by using retinoids in an application procedure according to the present invention, the individuals may tolerate the application of retinoids at an effective dose more quickly then if an amount which produces the irritation had to be applied immediately on a daily basis.

In order to understand the present invention, the term "retinoids" should be understood to include retinoic acid or tretinoin, retinol, retinaldehydes and salts and esters thereof. Typical salts are alkali metal, ammonium and C₂-C₃₀ ammonium salts. The sodium, potassium, triethanolammonium and ammonium salts are particularly preferred. Combinations of all the above compounds may be present in the compositions. In addi¬ tion, the terms "retinol" and "retinoic acid" should be understood to include hydrogenated and non-hydrogenated isomers such as 9-cis-retinol, didehydroretinol, 13-cis- retinoic acid, 13-trans-retinoic acid and didehydro- retinoic acid. Other retinoids which are effective in treating skin ageing, wrinkles and other anomalies are present in US patents Nos. 4,603,146, 4,887,805 and 4,888,342, the contents of which are incorporated herein by way of reference . They may be present in the compositions used according to the invention at concen¬ trations from about 0.0001 % to about 5 %. Preferably, they will be present in amounts of between 0.0001 % and about 0.3 %. Even more preferably, they must be present in amounts of between about 0.01 % and about 0.075 %. Even more preferably, they are present in amounts of between about 0.015 % and about 0.04 %.

The concentrations will be determined by those skilled in the art according to the nature of the retinoids specifically present in the composition. They will also be adapted as a function of the excipients and of the ability of the formulation to release active retinoid molecules which can be used by the skin. A large variety of pharmaceutically and/or cosmetologically acceptable supports may be used for the present invention. The amounts of vehicles may be from about 1 to 99.9 % and preferably from about 80 to 98 %, advantageously between about 95 and about 99.950 % of the composition by weight.

The compositions used in the products according to the invention as vehicles or bases may be in the form of emulsions, such as oil-in-water or water-in-oil emulsions. They may also be in the form of liposomal emulsions or any other emulsion known to those skilled in the art, which are physically and chemically stable. For example, the compositions which may be used in the method according to the invention comprise water-in-oil emulsions as described in EP 91 9137059 which is incorporated herein by way of reference. Oil-in-water formulations which may be used in the method according to the invention are presented in WO/US 95/11750 which is incorporated herein by way of reference . Liposomal compositions wnich may be used as vehicles for the retinoid compositions in the method according to the invention are described in WO/US 96/04557 which is incorporated herein by way of reference.

The compositions may also be formulated in gel or lotion form with cosmetologically acceptable excipients known to those skilled in the art.

Other agents which are active on the skin may also be included in the compositions according to the invention. These ingredients may include, in parti- cular, sunscreens and screening agents, tanning agents, antiacne agents, in particular salicylic acid, antiinflammatories (in particular panthenol, Gingko biloba, glycyrrhetinic acid, etc.) , depigmenting agents, hydrating agents, plant extracts and other anti-wrinkle agents.

Among the screening agents which may be used, mention may be made of titanium dioxide, zinc oxide and talc; the sunscreens comprise, in particular, 4-aminobenzoic acid and derivatives thereof, dibenzoyl- methane, camphor derivatives, homosalate, oxybenzone, cinnamic esters, 3-imidazol-4-ylacrylic acid and benz- imidazole derivatives such as 2-phenylbenzimidazole- 5-sulphonic acid and its sodium and TEA salts.

Preferably, the first application of the day should be made in the morning, after cleansing the skin, on waking up. The first application should contain a sub-irritant dose of retinoids, for example from about 0.0001 % to about 0.04 % and preferably less than 0.04 %, advantageously from 0.01 % to 0.02 %. A particularly suitable concentration is 0.015 % by weight. The first application may preferably be made in an oil-in-water emulsion which is relatively light and easy to apply and to wear.

The second application should preferably be made in the evening, just before going to bed and approximately 10 to 16 hours after the first applica¬ tion. The second application should contain a relatively large amount of retinoids, which will allow the administration of a larger amount of retinoids onto the skin. This higher-concentration formulation will be more effective as a remedy for skin anomalies, since it contains a higher dose of active principles. This second application may be made in an oil-in-water emulsion. However, it may also be placed in a water-in- oil emulsion. Water-in-oil emulsions have a tendency to be slightly more nourishing and "greasy" than oil-in- water compositions. However, such formulations may be well tolerated at night and provide the skin with complementary moisturization. The retinoid content in the second application should preferably be from about 0.04 % to 0.3 %, although it may be higher if the patient is capable of tolerating this dosage.

In addition, compositions specially formulated for particular areas of the upper part of the body, such as the neck and around the eyes or the mouth, may be used in lower retinoid doses along with other formulations in order to provide additional assistance to these areas without causing any further irritation. The examples which follow are intended to illustrate the present invention without limiting its scope in any way.

EXAMPLE 1 A composition containing retinol, having the formulation A and containing 0.015 % by weight of retinol, is applied daily to the face and the neck in the morning after cleansing the appropriate areas. In the evening, the neck and the face are again cleansed and a retinol formulation, having the composition B and containing 0.075 % by weight of retinol, is applied to the same area. The irritation symptoms are expected to be less than if a formulation containing about 0.04 % retinol was applied twice a day. The compositions corresponding to formulae A,

B, C and D respectively are prepared.

Formulation A: %

- Water 70.085 - Octyl methoxycinnamate 6.000

- Glyceryl stearate and PEG 100 stearate 5.000

- Glycerol 5.000

- C12-15 alkyl benzoate 4.000

- Denatured alcohol 2.780 - Petrolatum 1 , .500

- Cetyl palmitate 1. .000

- Cetyl alcohol 1. .000

- Stearyl alcohol 0, .500 - Lauroyllysine 0 .500

- Retinol solution

(10 % in a suitable solvent! 0, .150

- Panthenol 0 .500

- Allantoin 0 .150 - Carbomer 0. .300

- Tocopheryl acetate 0. .100

- Phenoxyethanol 0, .730

- Methylparaben 0, .200

- Propylparaben 0. .070 - Sodium hydroxide 0. .135

- Disodium EDTA 0 .200

- BHT 0 .100

100 .000

Formulation B: %

- Water 49.952

- Squalane 15.000

- Glycerol 10.000

- Macadamia nut oil 7.000 - Pentaerythrityl tetraoctanoate 5.000

- Butylene glycol 4.000

- Petrolatum 3.000

- Quaternium-18 hectorite 2.200

- Polyglyceryl-2 diisostearate 2.000 - PEG-150 1.000

- Retinol solution

(45 % in a suitable solvent) 0.198

- Tocopheryl acetate 0.100

- Ascorbic acid 0.100 - Sodium citrate 0.100

- Disodium EDTA 0.100

- Ethylparaben 0.100

- Butylparaben 0.100

- BHT 0.050 100.000

Formulation C: o, o

- Water 69.775

- Octyl methoxycinnamate 6.000

- Glyceryl stearate and PEG 100 stearate 5.000

- Glycerol 5.000

- C12-15 alkyl benzoate 4.000

- Denatured alcohol 2.780

- Petrolatum 1.500

- Cetyl palmitate 1.000

- Cetyl alcohol 1.000

- Stearyl alcohol 0.500

- Lauroyllysine 0.500

- Retinol solution

(10 % in a suitable solvent) 0.460

- Panthenol 0.500

- Allantoin 0.150

- Carbomer 0.300

- Tocopheryl acetate 0.100

- Phenoxyethanol 0.730

- Methylparaben 0.200

Propylparaben 0.070

- Sodium hydroxide 0.135

- Disodium EDTA 0.200

- BHT 0.100

100.000

Formulation D:

- Water 83. 908 - C12-15 alkyl benzoate 4. ,000

- Glycerol 3. .000

- Cetyl alcohol 2. .500

- Cetearyl alcohol and cetearyl glucoside 1. .400

- Extract of Japanese green tea 1. .000 - Octyl hydroxystearate 1 .000

- Dimethicone 1 .000

- Retinol solution

(45 % in a suitable solvent) 0 .102

- Panthenol 0 .500 Tocopherol 0 .. 050

Carbomer 0 . . 350

Chlorhexidine digluconate 0 , . 03 0

Methylparaben 0 . . 3 00

Propylparaben 0 . . 050

Sodium hydroxide 0 . . 110

Disodium EDTA 0 . . 100

BHT 0 . 100

100 . 000

The tolerance results are compared after treat¬ ment for 15 days and 1 month in 2 groups of users, according to two different administration procedures.

The 1st group applies formulation A in the morning and formulation B in the evening as indicated above. A second group applies formulation C in the morning and formulation D in the evening under the same conditions.

Possible local reactions, which may be a slight heating sensation, stinging or transient or longer- lasting redness, are noted.

The results are reported in the following tables :

TOLERANCE RESULTS AT 15 DAYS

15 DAYS

Number of Reactions Stopping because results of skin reactions

n =

Formulation A 104 22 21.1 4 3.84

+ Formulation B TOLERANCE RESULTS AT 1 MONTH

1 MONTH

Number of Further Stopping because results individuals with of skin reactions skin reactions

n = n =

Formulation A 98 3.1 + Formulation B

TOLERANCE RESULTS AT 15 DAYS

15 DAYS

Number of Reactions Stopping because results of skin reactions

Formulation C 99 26 26 + Formulation D

TOLERANCE RESULTS AT 1 MONTH

l MONTH

Formulation C 84 8.3 + Formulation D

It is observed that in the second group, 26 % of the individuals complain of a skin intolerance after treatment for 15 days, leading 9 % of them to abandon the treatment .

The tolerance is better in the 1st group, where less than 4 % of the individuals stop the application after 15 days.

These results are confirmed after treatment for 1 month, where only a further 3 individuals (3.1 %) experience intolerance reactions in the group applying formulations A and B: on the other hand, in 8 % of the individuals of the second group, the appearance of skin reactions which had not been observed at 15 days is noted and a further 5 % stop applying the products during the treatment . It is thus observed that in the group applying formulations A and B according to the invention, the tolerance is significantly better, enabling the treat¬ ment to be complied with and an effective daily dose of retinol to be administered regularly. Although this dose is slightly lower in the group applying formulations C and D, the occurrence of intolerance reactions is higher and leads to stoppage of the treatment in more than twice as many cases.

EXAMPLE 2

In order to evaluate the effect of applying formulation A in the morning, a control group is treated with formulation B alone, once a day, prefer¬ ably in the evening after the face and neck have been carefully cleansed. The tolerance results at 15 days and 1 month are reported below: TOLERANCE RESULTS AT 15 DAYS

15 DAYS

Number of Reactions Stopping because results of skin reactions

n =

Formulation B 100 15 15

TOLERANCE RESULTS AT I MONTH

1 MONTH

n =

Formulation B 95 4.21 2.1

It is seen that the occurrence of irritation reactions is lower but similar to that observed when formulations A and B are applied.

The application of formulation A in the morning thus entails virtually no additional irritation but allows the skin to be prepared to receive the dose present in formulation B and to adjust the total daily dose administered.

EXAMPLE 3

It is desired to evaluate the acceptability of a treatment including the application of a composition formulated for the specific area around the eyes.

A group of female users is asked to apply regularly, once a day, a formulation containing 0.01 % retinol, the composition of which is given below. Formulation E:

- Water 83. 910

- C12-15 alkyl benzoate 4. 000 - Glycerol 3. 000

- Cetyl alcohol 2. ,500

- Cetearyl alcohol and cetearyl glucoside 1. ,400

- Extract of Japanese green tea 1. .000

- Octyl hydroxystearate 1. .000 - Dimethicone 1. .000

- Retinol solution

(10 % in a suitable solvent) 0, .100

- Panthenol 0. .500

- Tocopheryl acetate 0. .500 - Tocopherol 0 .050

- Carbomer 0. .350

- Sodium hydroxide 0. .110

- Methylparaben 0 .300

- Propylparaben 0 .050 - Chlorhexidine digluconate 0 .030

- Disodium EDTA 0 .100

- BHT 0 .100

100 .000

The possible irritation reactions are noted after treatment for 15 days and 1 month respectively.

TOLERANCE RESULTS AT 15 DAYS

15 DAYS

Number of Reactions Stopping because results of skin reactions

100 11 11 TOLERANCE RESULTS AT 1 MONTH

1 MONTH

Number of Further individuals with Stopping because results skin reactions of skin reactions

94 3.2

It is observed that the tolerance to this product is good and leads to good compliance with the regime.

The application of formulation E in the morning may thus be combined with that of a stronger-dosed formulation, such as formulation B, in the evening, onto the entire face.

Claims

1. Cosmetic method for treating and preventing the signs of skin ageing and in particular wrinkles, characterized in that : a) a composition containing at least one retinoid at a sub-irritant dose which is effective for combating skin ageing, in a support which is suitable for topical administration, is applied to the skin once a day, b) a composition containing a higher dose of at least one retinoid, in a cosmetologically acceptable support which is suitable for topical administra¬ tion, is applied about 10 to 16 hours after the composition mentioned in a) .

2. Method according to Claim 1, characterized in that the retinoid concentration in the compositions mentioned in a) and in b) respectively is between 0.0001 % and 5 % relative to the total weight of the composition.

3. Method according to either of Claims 1 and 2, characterized in that, in the composition mentioned in a) , the total retinoid concentration is greater than or equal to about 0.0001 % and less than 0.04 % by weight, and in that, in the composition mentioned in b) , the total retinoid concentration is between about 0.04 % and 5 % by weight .

4. Method according to one of Claims 1 to 3, characterized in that, in the composition mentioned in a) , the retinoid concentration is within the range from about 0.01 % to about 0.02 % by weight.

5. Method according to one of Claims 1 to 4, characterized in that, in the composition mentioned in b) , the retinoid concentration is within the range from about 0.04 % to about 0.3 %.

6. Method according to Claim 5, characterized in that, in the composition mentioned in b) , the retinoids are present at a concentration of about 0.075 %.

7. Method according to one of Claims 1 to 6, characterized in that the retinoids are chosen from the group comprising retinoic acid in the form of its various isomers, tretinoin, retinol, retinaldehydes and salts and esters thereof.

8. Method according to Claim 7, characterized in that the retinoid salts are chosen from the group comprising the sodium, potassium, ammonium and C₂-C₃₀ alkanolamine salts.

9. Method according to one of Claims 1 to 8, characterized in that at least one of the compositions mentioned in a) or in b) is in the form of an oil-in- water emulsion.

10. Method according to one of Claims 1 to 9, characterized in that at least one of the compositions mentioned in a) or in b) contains at least one other active principle.

11. Method according to Claim 10, characterized in that the additional active principle is chosen from sunscreens and screening agents, tanning agents, antiacne agents, antiinflammatories, depig enting agents and anti-wrinkle agents other than retinoids.

12. Method according to Claims 1 to 11, charac¬ terized in that it is a method for the cosmetic treat¬ ment of the skin of the face and/or the neck.

13. Method according to Claim 12, characterized in that in step a) , a specific composition is applied around the eyes and/or the mouth, this composition containing retinoids in a lower concentration than that of the composition applied to the rest of the face and/or the neck.

14. Combination products for separate use or for use spread out over time in the treatment of wrinkles and the signs of skin ageing, comprising: a) a composition containing at least one retinoid in a sub-irritant dose which is effective for combating skin ageing, in a support which is suitable for topical administration, b) a composition containing a higher dose of at least one retinoid, in a support which is suitabl- for topical administration.