WO1991000726A1

WO1991000726A1 - USE OF AMPc OR ITS DERIVATIVES FOR THE PREPARATION OF COSMETIC OR PHARMACEUTICAL COMPOSITIONS

Info

Publication number: WO1991000726A1
Application number: PCT/FR1990/000525
Authority: WO
Inventors: Patrice Andre; Gérard Redziniak; Pierre Perrier
Original assignee: Parfums Christian Dior
Priority date: 1989-07-13
Filing date: 1990-07-12
Publication date: 1991-01-24
Also published as: FR2649610A1; FR2649610B1

Abstract

A cosmetic or pharmaceutical composition, particularly for local dermatological use. This composition contains adenosine-3',5'-cyclic monophosphate (AMPc) or one of its derivatives. The AMPc or one of its derivatives can be incorporated in part in hydrated lipidic lamellar phases or in liposome vesicules. According to the invention, the composition has an anti-inflammatory, anti-allergic, anti-seborrhoea, anti-cellulite and skin-and-hair pigmenting activity.

Description

Use of cAMP or its derivatives for the

preparation of cosmetic compositions or

pharmaceutical.

The present invention relates to the use of cAMP or its derivatives for the preparation of cosmetic or pharmaceutical and in particular dermatological composition, with anti-seborrheic, sebo-regulatory, anti-allergic, anti-cellulite, anti-inflammatory and pigmenting activity. of skin and hair, for topical use.

The invention also covers cosmetics or pharmacological and in particular dermatological comoositions containing cAMP or its liposome derivatives, for topical use.

Despite its very important role in biology, cAMP is little used because it has two major drawbacks.

On the one hand, the activity of cAMP is. reduced by phosphodiesterases present in living organisms and which destroy it by enzymatic hydrolysis. To overcome this drawback, it has been proposed to add phosphodiesterase inhibitors such as xanthic bases, such as theophylline or caffeine.

On the other hand, cAMP only penetrates the cells very weakly, which also limits its activity.

However, the solutions which have been proposed so far, to overcome the difficulties of using cAMP have proved to be insufficient, which explains the very low use of cAMP, and the systematic use either of derivatives of this compound, either to complementary agents such as phospnodiesterase inhibitors. For example, document FR-A-2077725 describes cosmetic compositions intended for the physiological maintenance of human skin and its appendices using cAMP or its derivatives. Likewise, document EP-A-0260697 describes the use of cAMP or of its derivatives in a composition for the prevention of gray oneux or for the recoloration of gray hair. By elsewhere, document FR-A-2390159 describes liposomes incorporating various active principles, in particular a drug, a protein, an enzyme, a hormone, a vitamin or a marker (page 4, lines 5 to 8). In the Front document. Matrix Biol. , volume 6, pages 193-205 of Karger, in Basel, 1978, Cehovic describes the inhibitory activity of cAMP on inflammatory reactions of the skin in animals, alone or in combination with theophylline as a phosphodiesterase inhibitor.

The document EP-A-195496 also describes the use of xanthines, as phosphodiesterase inhibitors for the treatment of hyperproliferative skin diseases (Rev., page 5, line 7).

It will thus be observed that the state of the prior art, in particular resulting from Cehovic, proposes the use of cAMP and especially of its derivatives, alone or combined with phosphodiesterase inhibitors such as xanthines in the preparation of cosmetic compositions. Thus, no document describes liposomes containing cAMP for topical use.

The object of the present invention is to solve the technical problem consisting in the supply of new cosmetic or pharmaceutical compositions, in particular dermatological for topical use, having good anti-seborrheic activity or sebo-regulating activity, without notable side effects.

The present invention thus aims to solve the technical problem consisting in the supply of new cosmetic or pharmaceutical compositions, in particular dermatological compositions for topical use based on cAMP with potentiated activity.

The authors of the present invention have carried out extensive research and brought to light, quite unexpectedly, a new interesting activity of cAMP, which consists of an anti-seborrheic activity or a sebo-regulatory activity, or even an activity pigmenting of the water and the hair, whether the cAMP is used in the free state or encapsulated, at least in part, in liposome-type vesicles.

Furthermore, in the context of this research, it has or has also been highlighted a potentiating effect unexpected cAMP activity, when it is incorporated in hydrated lipidic lamellar phases or in liposome-type vesicles, in particular in the case of anti-inflammatory or anti-allergic activity, or concerning a pigmenting activity for skin and hair, or even an anti-cellulite activity.

These improvements in activity are remarkable on the cAMP itself, so that it is not necessary to use derivatives, contrary to what was previously recommended, since only the derivatives were more active than CAMP.

Thus, according to a first aspect, the present invention relates to the use of adenosine-3 ', 5'-cyclic-monoonosphate (cAMP) or one of its derivatives, for the preparation of a cosmetic or pharmaceutical composition, and in particular dermatologic for topical use, with anti-secorrheic or sebo-regulatory activity, or with anti-inflammatory or anti-allergic activity, with pigmenting activity, or with anti-cellulite activity.

According to a particular embodiment, cAMP, or one of its derivatives, such as its salts or its acylated derivatives, in particular its mono- or di-butyryy derivatives, its salts with basic compounds. mineral or organic, is incorporated. at least in part, in hydrated lipid lamellar onases in these liposome-type vesicles.

According to a second aspect, the present invention also provides a cosmetic or pharmaceutical, and in particular dermatological, composition for topical use, with activity regulating sebaceous secretions, called sebo-regulatory activity, or anti-seoorrneic activity, characterized in that it contains adenosme-3 ', 5'-cycliaue-monophosphate (cAMP), or any of its derivatives. CAMP can be in the free state or incorporated, at least in part, into hydrated lipid lamellar pnases or into liposome-type vesicles.

The present invention also provides, according to a third aspect, a cosmetic or pharmaceutical composition, and in particular a dermatological composition. topical, containing adenosine-3'-5'-cyclic-monophosphate, or cAMP, or one of its derivatives, characterized in that cAMP or one of its derivatives, such as its salts or its acylated derivatives, in particular its mono- or di-butyryl derivatives, its salts with basic, mineral or organic compounds, is incorporated at least in part in hydrated lipidic lamellar phases or in vesicles of liposome type.

Various particular embodiments, of any of the previous three aspects of the invention, are now described.

According to a particular embodiment, the cosmetic or dermatological composition for the aforementioned topical use, is a topical cosmetic or dermatological composition with regulating activity of sebaceous secretions (said: secoregulatory activity).

According to another particular embodiment of the invention, the topical cosmetic or dermatological composition is a topical cosmetic or dermatological composition with anti-allergic activity.

According to another particular embodiment of the invention, the above-mentioned cosmetic or dermatological composition is a cosmetic or dermatological composition with anti-inflammatory activity.

According to another particular embodiment of the invention, the above-mentioned cosmetic or dermatological composition is a cosmetic or dermatological composition with anti-cellulite activity.

According to another particular embodiment of the invention, the above-mentioned cosmetic or dermatological composition is a cosmetic or dermatological composition with pigmenting activity of the skin and hair.

According to a particular embodiment of the invention, the above-mentioned cosmetic or dermatological composition is characterized in that it also comprises a phosphodiesterase inhibitor. in particular a flavonoid or a xanthine, in particular caffeine, theophylline, aminophylline or a plant extract containing xantnines such as plant extracts, in particular cola, catechins, etc. The phosphodiesterase inhibitor can be placed in the hydrophilic phase or in the hydrophobic phase of the hydrated lipic lamellar phases or of the liposomes depending on its affinity. In particular, the ethylene diamine derivative of theophylline or aminophylline allows dissolution in the hydrophilic phase of theophylline. In general, the phosphodiesterase inhibitor will be used in an amount equal to or greater than the amount of corresponding cAMP.

According to another particular characteristic of the compositions according to the invention, they are characterized in that they also comprise another complementary active principle.

This combination with other active substances is particularly advantageous, either to obtain potentiation or to eliminate an undesirable side effect of the substance, such as an irritant effect.

In particular, it is advantageous to include in the compositions according to the invention vitamin A acid.

The incorporation of cAMP or one of its derivatives into the hydrated lipioic lamellar phases or into the liposomes can be carried out according to known preparation techniques, described for example in document FR-A-2521565. possibly in combination with document FR-A-2534587.

In these compositions according to the invention. the orooortion in peaks of cAMP or one of its derivatives, compared to the total ooics that the composition can vary within a wide range of values. The preferred proportions are these proportions of between 0.001% and 5% by weight, preferably between 0.01 and 5% by weight, relative to the total weight of the cosmetic or dermatological composition.

CAMP or its derivatives are incorporated in the aqueous phase or in the iipid phase of hydrated lioïnique lamellar pnases or liposome-type vesicles, depending on their more or less nyαrconile or liopphile nature. For example, the soαium salt ce cAMP can be used for its incorporation into the aqueous phase.

In the present specification and the claims, the The term "lipids" in the expression "lamellar lipid phases" covers all substances comprising a so-called fatty carbon chain, generally comprising more than five carbon atoms, this substance usually being called "lipid".

According to the invention, amphiphilic lipids are used as lipid to form either the lipid lamellar phases or the aforementioned liposome, that is to say made up of molecules having a hydrophilic group either ionic or nonionic and a lipophilic group, these amphiphilic lipids being capable of forming liciαic lamellar phases in the presence of an aqueous phase.

In particular, among these lipids, there may be mentioned: oncspholipids, phosonpaminplipids, glycclipids, polyoxyethylenated fatty alcohols, esters of pplvols optionally oolyoxyethylenated. Such substances consist, for example, of egg or soy phospholipids, a phosonatiαyicnoline, a phosphatidylserine, a sphyngomyelin, a cereorpside or an oxyethylenated polyglycerol etereate.

These lioid-hydrated lamellar phases or liposomes can be prepared as follows:

Step 1-A An aminiphilic lioid (s) such as, for example, these soybeans, hydrogenated or not.

It is also possible to dissolve a hydroonooe suostance such as a sterol such as cholesterol or! -Sosterosterol, a lipid carrying electrical charges (diketylpnosohate) and advantageously an antioxidant such as §-tocopherol or BHT.

Step 1-B In the organic solution prepared according to step 1-A, add the curing case of cAMP or the cAMP derivative which it is desired to incorporate into the lipid phase, if the latter has a lipophilic character. .

The quantity expressed in moles of hydrophopic substances in the organic solution of steps 1-A or 1-B should generally not be greater than the amount of ampnipnilic lipids, and preferably it should not be greater than 0.5 times this amount.

2nd step

Separately, an aqueous solution is prepared containing a cAMP salt or a hydrophilic cAMP derivative, by dissolving these products in water or preferably in a suitable aqueous solution such as a buffer solution of the PBS phosphate buffer type.

Step 3-A

The mixture obtained at the end of stage 1-A or of stage 1-B mentioned above is introduced into a rotary flask, and evaporated by heating in a water bath, optionally under reduced pressure.

After evaporation with organic solvent, the lipid film deposited on the walls is taken up with stirring with water or with a suitable aqueous solution such as a buffer solution of the PBS phosphate buffer type, if the mixture obtained is used. step 1-B.

On the other hand, the lipid film is taken up by the aqueous solution obtained at the end of step 2, if the mixture obtained in step 1-A has been used directly.

Preferably, the quantity of water or aqueous solution is at least equal, by weight, to 8 times the quantity of lipids contained in this balloon.

A suspension of liposomes is thus obtained, which can then be nomogenized by an appropriate means, such as for example ultrasound.

Step 3-B

According to an alternative embodiment to the process for preparing the compositions according to the invention containing this cAMP in hyαratated lipid lamellar pnases or iippsomes. using the method described in document EP-E1-G087993, comprising atomization with the mixture obtained at the end of step 1-A or from step 1-B. followed by the dispersion of the loric oouαre thus obtained in a predetermined quantity of water or an aqueous solution of substances to be encapsulated, in particular that obtained in step 2. This gives hydrated lipidic lamellar phases or a suspension of liposomes, depending on whether it has been chosen to disperse the lipid powder in little or a lot of aqueous medium, as described in the aforementioned European document.

The dispersion of hydrated lipid lamellar phases or of liposomes can then be homogenized, for example according to the method described in document EP-B1-0107559.

Step 4 (if applicable)

Optionally, the dispersion of the hydrated lipid lamellar phases or the liposome suspensions obtained in step 3-A. or 3-B above, can be gelled, for example by mixing with a gel prepared separately, such as a vinyl polymer gel.

Other objects, characteristics and advantages of the invention will appear more clearly on reading the explanatory description which follows, made with reference to several examples of the invention given solely by way of illustration and which therefore cannot no way to limit its scope. In these examples, the percentages are given in noids, unless otherwise indicated.

EXAMPLE 1

Step A: Preparation of an aqueous solution containing cAMP.

85 g of distilled water are brought to pH 11.6 by addition of molar sodium hydroxide. Then dissolved in 1 g of cAMP, then it returns to pH = 7 by adding molar hydrochloric acid, and distilled water is added qs 96 g.

Step B: Preparation of a Liposomal Composition According to the Invention, Containing cAMP.

A composition is prepared in liposomal form having a cAMP content of 1%, as follows:

to the aqueous solution containing the cAMP prepared in step A, add 4 g of lipid oouαre obtained by the atomization process described in the document EP-B1-0087993, (and briefly described in step 3-B above) and which comprises 9 parts by weight of soy phospholipids (Alcolec F 100) for one part by weight of β-sitosterol.

The lipid powder is then dispersed under mechanical stirring in said aqueous solution for example by means of a homogenizer of the type Ultraturrax ^® for 40 min.

This dispersion is then followed by a homogenization carried out either by ultrasonication, for example using a device called LABSONIC 1510 ^® for approximately 10 min at 200 W and at 4ºC, or by passing through a pressurized homogenizer of the MICRO-FLUIDIZER type. (4 passages for a pressure of 45,000 kPa and a temperature of 4ºC), in order to maintain these liposomes whose size is between 100 and 150 nm.

A liposomal composition containing 1% of cAMP is thus obtained, which can be used as it is, to constitute cosmetic or pharmaceutical compositions, or in combination with other active agents and / or excipients, as will be exemplified below. . EXAMPLE 2

In accordance with the procedure described in Example 1, a lioosomal composition is prepared containing 0.4% by weight of cAMP.

EXAMPLE 3

Preparation of a gelled Liposomal suspension containing 0.25% of cAMP

25 α lioosomale of 1% suspension of cAMP prepared in Example 1 is mixed 75 g of a gel Caroopol 940 ^® prepared as indicated below.

The composition of the gel is as follows:

Nipagine M ^® : 0.15 g

Caroopol 940 ^® : 0.80 g

Germall II ^® : 0.20 g

NaOH tablets: 0.35 g

distilled water gsp 100 g. The gel preparation consists of first mixing Nipagine M ^® with 90 g of water at 80 ° C, then we add Carbopol 940 ^® at 70 ° C, then Germall II ^® at 30 ° C, then soda at 25ºC (up to pH = 7) and make up to 100% with water.

EXAMPLE 4

Preparation of a gelled Liposoma Le suspension containing cAMP and aminophylline

The composition of this suspension is as follows:

soy phospholipids 0.9 g

β-sitosterol 0.1 g

CAMP 0.1 g aminophylline 0.4 g

Carbopol 940 ® 0.6 g

0.22625 g soda

Nipagine M ^® 0.1125 g

Germall II ^® 0.15 g

distilled water qs 100 g

Separately prepared: an aqueous solution of cAMP according to step A of Example 1, and an aqueous solution of aminophylline by dissolving this product in water at pH 7.

These two solutions are then combined, then the lipid powder composed of lec ith ine and β-sitosterol is dispersed therein and the procedure is carried out as in step B of Example 1.

The homogenized liposomal suspension obtained is then gelled as in Example 3.

A gelled liposomal composition is thus obtained containing 0.1% of cAMP and 0.4% of aminophylline.

EXAMPLE 5

Preparation of a gelled liposomal suspension containing cAMP and caffeine

We proceed as in Example 4 except that we use 0.4 g of cAMP instead of 0.1 g, and 0.4 g of caffeine instead of aminophylline.

If necessary, to dissolve the caffeine in water, it may be necessary to heat it to around 80 or 90 ° C.

EXAMPLE 6

Preparation of a gelled Liposomal suspension containing cAMP and acidic vitamin A

8 g of soy phospholipids and 0.1 g of acidic vitamin A are dissolved in 60 ml of dichloromethane in the presence of a lipophilic antioxidant, for example 0.006 g of α-tocopherol.

The solution obtained is atomized at 65ºC, as indicated in step 3-B of the general process described above.

The fine powder obtained is dispersed in 89.9 g of an aqueous solution containing 2 g of cAMP, prepared according to step A of Example 1. This dispersion is then homogenized as indicated in step B of the example 1.

Preferably, the homogenized suspension of liposomes obtained was gelled by adding equal amounts of a salt Caroopol 940 ^® 0.8% prepared as described in Example 3.

A gelled liposomal composition containing 1% cAMP and 0.05% acid vitamin A is obtained.

This composition can be used as a tail in dermatology, for example to treat acne, or it can enter into the composition of a cosmetic formula as indicated below.

EXAMPLE 7

Preparation of a gelled composition according to the invention containing cAMP

To 25 g of aqueous solution containing cAMP as du'obtenu to Exemole 1 étaoe A, gold, 75 g of a gel Carboput 940 ^® as Dréoaré exemcie to 3, in obtaining a composition ainoi gel containing 1% by weight of cAMP in the free state. EXAMPLE 8

Evaluation of the antiallergic activity of the compositions according to the invention

The action of a gelled composition according to the invention is studied on an erythema caused by injection of histamine.

Guinea pigs are used which are standard animals recognized for studies of this nature. These guinea pigs are of Hartley strain supplied by Charles River Laboratories, Inc. Wilmington, Massachussets, USA of male and female sex, weighing at the beginning between 300 and 600 g which are subjected to an acclimatization period of at least 4 days, arranged in numbered cages indicating sex and dose level.

The animals are fed ad libitum with the same food, the food and the water being checked to not contain any contaminating agent. The histamine used in the dichlorhyorate form is supplied by Sigma Milwaukee, Wisconsin under the reference 15F-0169.

Before carrying out the test, the back of each animal is shorn. The remaining hair is removed using a commercial depilatory device. After careful cleaning of the depilated parts, the αorsal area of each animal is divided into 6 test sites and marked using a black laora marker. After at least two hours, a subcutaneous injection is carried out at each of the 6 sites as follows:

Sites 1 to 5 receive an injection of histamine at a dose of 100 ug / 0.05 ml. Site No. 6, the control site, receives an injection of 0.05 ml of normal saline.

Immediately after the injection, each site is treated with a product, except sites 1 and 6 which are not treated.

Sites 2 to 5 are treated respectively by products A to D:

product A: gelled liposomal suspension according to the invention containing 0.25% of cAMP (exemole 3). product B: gelled liposomal suspension prepared according to Example 3 and of the same composition, except that it does not contain cAMP.

product C: gelled solution of cAMP prepared from 25 g of an aqueous splution of 1% cAMP according to step A of example 1, mixed with 75 g of gel identical to that prepared in example 3 (example 7).

product D: whose composition differs from that of product C only by the absence of cAMP.

In order to minimize the variations from site to site, as regards the reactivity of the skin, the administration of the various products was carried out by alternating the test sites. Immediately after administration of the histamine, the proαuits were applied topically (0.1 ml / site) and massaged with a finger.

30 min after application, the remaining test oroαuit is gently removed with a tissue. The test sites are evaluated 30, 60, 120 and 240 min and 24 h following the topical application.

All the test sites are evaluated according to the following method:

Erythema

0 = erythema

1 = The water appears pink

2 = Red, well-defined erythema

3 = Dark red, moderate to severe erythema

4 = Dark red, severe erythema up to a slight formation of open lesions.

The average ratings for each site are listed in Table 1.

We observe in particular, if we calculate the arrhythmic average of the 24-hour ratings, that:

The cAMP liposomes according to the invention (product A) are clearly the best inhibitor of a blood reaction to histamine. The gelled liposomes not containing cAMP (product B), correspond to the same average as that of erythritis. untreated.

- The gelled solution of cAMP (product C) does not inhibit this reaction much more than the excipient itself.

The results are also listed in the form of a curve in FIG. 1 appended for easier visual representation.

In Figure 1, cpurbs have the following meaning

Furthermore, it was observed, during another experiment which is not reported here, that the cAMP liposomes according to the invention also give better results on the inhibition of erythema to histamine than the hydrocort isone, commonly used to counter aliergiquee reactions, which is totally surprising for those skilled in the art.

TABLE I

Anti-allergic test

Evaluation of the erythematous reaction

(according to the rating from 0 to 4)

Duration after application

average product

60 min 120 min 240 min 24 h control 0 0 0 0 0 gelled cAMP liposome 1.8 1 0.2 0 0.75 (product A) gelled liposome

(product B) 2.3 1.6 0.6 0 1.125

CAMP in gel

(product C) 1.9 1.8 0 0 0.925 gel

(product D) 1.9 1.8 0.2 0 0.975 untreated erythema 2.2 1.7 0.4 0.2 1.125 EXAMPLE 9

Evaluation of the sebum-regulating activity of the compositions according to the invention

The regulating activity of sebaceous secretions (seboregulatory activity) of oily skin is measured following the bi-daily application of a product according to the invention for 3 consecutive weeks.

The method of measurement consists of the use of a device, called a sephotometer, which makes it possible to evaluate by spectroDhotometry the amount of sebum taken from the surface of the skin following the application of a frosted film on the forehead for 30 s.

To carry out this study of seo-regulatory activity, the product of Example 3 is used, now 0.25% of cAMP in liposomes gn gel, and a product prepared in a similar manner to Example 7, containing CAMP free in gel but reduced to a content of 0.25%, in comparison with empty lippsomes, that is to say containing no cAMP, in gel.

Each product is tested on 10 people with oily skin, the product being applied twice daily (morning and evening) semi-facial for three consecutive weeks. The treatment is preceded by a week without treatment called the control week.

Measurements are made twice weekly, at intervals, regularly for three consecutive weeks in addition to the control week.

The detail is as follows

D1: measurement before any treatment

D2: measurement before any treatment

D3: 1st measurement of the 1st week of treatment

D4: 2nd measurement of the 1st week of treatment

D5: 3rd measurement of the 2nd week of treatment

D6: 4th measurement of the 2nd week of treatment

D7: 5th measurement of the 3rd week of treatment

d8: 6th measurement of the 3rd week of treatment The measurement is repeated for each time (J1 to J8) 6 times at 6 neighboring locations at the edge (i.e. S1 - S2 - S3 - S4 - S5 - S6).

These results are then averaged to give a unique value of sebaceous secretion for a given time, namely:

The results will be respectively listed in Table II for the product of the invention, this example 3 for the cAMP liposome encaosulator, in Table III, for the product of the invention type example 7, containing gel cAMP gel ; and in Table IV, for the comparative product "empty" liposomes in gel.

It can be seen from these tabs that the use of a product containing cAMP in the lice state, or in liposomes, results in a very marked sebo-regulatory efficacy on oily skin in the direction of a reduction sebaceous secretions, following a continuous application of these products, whereas in the case of the oroduït of comoaraison not containing cAMP, no regulation of the separated secretion is noted, so that this product comparatit be present pat de sebo-regulatory properties.

EXAMPLE 10

Anti-inflammatory test

The anti-inflammatory activity is evaluated by application of a test drug on an erythema induced by ultraviolet rays.

We also use Hartley guinea pigs supplied by Buckberg lab Animais, Tomkins Cove, New York, male and female sexes weighing between 300 and 450 g selected by sex, body weight and apparent good health put in numbered cages indicating sex and dose level.

To carry out the test, the back of each animal is subjected to hair removal using a commercial hair removal device, followed by hair removal with cream which is only left in contact with the skin for a maximum of 30 minutes. Then we carefully clean the skin.

After two hours minimum, the copayas are exposed to an ultra-violet lamp for 4 or 5 min at a distance of 15 cm. The back skin is covered with a semi-cylindrical bakelite screen containing 4 holes 1.5 cm in diameter oriented symmetrically. In order to minimize site-to-site variations in skin reactions, these test products are administered alternately at the test sites.

immediately after this ultra-violet exposure, the test products felt teoically applied (0.1 ml per site) and gently massed on the finger.

Three other aoclications or test product are carried out at 60 mm, 122 min and 180 min after the 1st application. the test sites are evaluated 60, 120, 180 and 242 min and 24 h after the first tropical application. A negative control site (untreated) is included for each animal. Before each reading, care is taken to remove the residual product with a tissue.

All the results are listed in Table IV according to the scale of evaluation that the following erythema:

Erythema

0 = no erythema

1 = the wall appears pink (slightly noticeable) 2 = red, well-defined erythema

3 = dark red, moderate to severe erythema

4 = dark red, severe erythema up to a slight formation of open lesions.

The test products are:

- Product A: composition according to the invention (Example 4) consisting of a gelled liposomal suspension containing 0.1% cAMP and 0.4% aminophylline.

- product B: gelled solution of 0.1% cAMP and aminophylline

0.4%, of the same composition as product A, except that no lipid powder has been dispersed in the aqueous solution.

- product C: gelled splution of 0.4% aminophylline, of the same composition as product B, except that it does not contain cAMP.

The sqnt results listed in Table V below:

TABLE V

Inhibition of erythema induced by ultraviolet ray on guinea pigs

(multiple applications)

Time (min) Product A Product B Product C Untreated after exposure (control)

U.V.

60 1, 8 1, 8 1, 8 2.0 120 0.8 1, 2 1, 6 1, 3 180 0.7 1, 2 1, 6 1, 2 240 1, 0 1, 0 1, 4 1 , 2

24 hours 0.5 1, 2 1, 2 1, 2

These results show a very clear inhibitory effect of erythema induced by UV rays for product A (product according to the invention), whereas the two other products tested show only a weak activity in comparison with the result that untreated site (control site).

These results are also represented in FIG. 2 in the form of curves, for an easier visual representation.

Various examples of formulation of cosmetic or dermatological compositions according to the invention are now given below, by way of nonlimiting illustration.

In Figure 2, the curves have the following meaning:

EXAMPLE 11

Anti sunburn product.

0.4% liposomal solution of cARP ............... 25%

(following example 2)

Carbopol glycerol gel ......................... 70%

Hyaluronic acid ............................... 0.1%

Preservatives ..................................... 0 2%

Perfumes ........................................... 2.1%

Water q.s. p. ....................................... 100%

EXAMPLE 12

Anti-Allerdic product and cream for sensitive skin.

Lioosomal solution titrating 1% cAMP ........... 25%

(following example 1)

Vaseline oil ................................ 10%

Self-mutational basis ........................... 5%

Preservative, perfumes, water qs ................ 100% EXAMPLE 13

Anti-seborrheic foam.

Liposomal solution containing 1% cAMP ......... 25%

(following example 1)

Carbopol gel neutralized with soda ............. 0.4%

Glycol ........................................... 5.0%.

Isobutane / propane propellant ..................... 4.0%

Water, preservative and perfumes q.s.p. .............. 100% EXAMPLE 14

Slimming GeL.

Stabilized glycerin water ......................... 60%

Gelling substances ........................... 0.6%

Perfume and solubilizer ........................... 1.2%

Liposomal solution comprising 0.4% cAMP and

0.4% caffeine (according to Example 5) ............ 25%

Ruscus extract ................................ 10%

Aqueous excipient q.s.p. .......................... 100% EXAMPLE 15

Anti-wrinkle light emulsion.

Liposomal solution containing 1% cAMP and

0.05% retinoic acid (according to Example 6) ... 25%

Oil in water emulsified excipient q.s.p. ....... 100%

EXAMPLE 16

Hair toning lotion against gray hair.

Liposomal solution containing 1% cAMP (according to

example 1) ........................................ 25%

Aqueous excipient perfume + preservative ........... 75%

In daily application, preferably in the evening, directly on the hairline, this lotion slows the appearance of gray hair. EXAMPLE 17

GeL tan.

Liposomal solution containing 0.5% cAMP ........ 25%

Stabilized glycerin water .......................... 60%

Carbopol gel at 1% neutralized + a.s.p. 100%

This tanning gel, prepared in the classic way, is applied to the skin exposed to the sun, this promotes skin pigmentation and prolongs the tan.

Claims

1. Use Ge adenosine, 3 ′, 5′-cyclic-monophosphate or cAMP, or one of its derivatives, for the preparation of a cosmetic or pharmaceutical composition, and in particular dermatological, with anti-seborrheic activity or seboregulatory activity, with anti-allergic activity, with anti-cellulite activity, with anti-inflammatory activity or with pigmenting activity of the skin and hair.

2. Use according to claim 1, characterized in that the cAMP or one of its derivatives, is, at least in part, incorporated in the hydrated lioioal lamellar phases or in vesicles of liposome type.

3. Use according to claim lou 2, characterized in that the cAMP derivative is a salt, in particular a salt with a basic, mineral or organic compound, or an acylated derivative, in particular a mono- or di-butyryl derivative.

4. Use according to one of claims 1 to 3, characterized in that it is a cosmetic or pharmaceutical composition, in particular dermatological, with anti-allergic activity.

5. Use according to one of the revenoicaticns 1 to 3, characterized in that it is a cosmetic or onarmaceutioue composition, especially dermatological, with sebo-regulatory activity.

B. Use according to one of claims 1 to 3, characterized in that it is a cosmetic or pnarmaceutical composition, in particular oermatdldgic, has anti-cellulitic activity.

7. Use according to one of claims 1 to 3, characterized in that it is a cosmetic or pnarmaceutioue composition, especially dermatological. with anti-inflammatory activity.

8. Use according to one of claims 1 to 2, characterized in that 'it is a cosmetic cosmetics ccmoositidn eu, especially dermatological, with pigmenting activity skin and hair.

9. Use according to one of claims 1 to 8, characterized in that the total concentration of cAMP in cosmetic or dermatological compositions is between 0.001% and 5% by weight relative to the total weight of the composition.

10. Use according to one of claims 1 to 9, characterized in that it further comprises, a phosphodiesterase inhibiting agent, in particular a flavonoid, a catechin, a xanthine. such as caffeine, theophylline or a plant extract containing such substances, in particular an extract of It.

11. Use according to one of claims 1 to 10, characterized in that it also comprises an additional active principle, in particular acid vitamin A, this preference at a concentration between 0.0001% to 0.1% .

12. Cosmetic or pharmaceutical composition, in particular dermatological composition, with anti-seborrheic or sebo-regulating activity, characterized in that it comprises an effective amount of cAMP having one of its derivatives.

13. Cosmetic or pharmaceutical composition, in particular dermatological, with topical usgae containing aαenosine 2 ', 5'-cyclic-monoohosphate (cAMP) or one of its derivatives characterized in that cAMP or one of its derivatives is. at least in part, incorporated into hydrated libidic lamellar Dnases or into liposome-type vesicles.

14. Composition according to Claim 13, characterized in that it is as defined in any one of the claims

2 to 11.