CA1273580A - Pharmaceutical composition containing as active ingredient at least one dihydroxi-1,8 phenyl-10 anthrone-9 anthranol-9 mono-, di- or tri-ester - Google Patents

Abstract

The invention relates to new pharmaceutical compositions containing in a pharmaceutically acceptable excipient, at least one of the mono, di and tri-esters of 1,8-dihydroxy-phenyl-10 anthrone-9 or anthranol-9 corresponding to the general formula (I) : <IMG> (I) in which p is 0 or 1, (a) when p = 0, t = 1 and R2 represents a hydrogen atom or -COR3, (b) when p = 1, t = 0 and R1 and R2 independently of one another represent a hydrogen atom or -COR3, R3 representing an alkyl radical, linear or branched having from 1 to 17 carbon atoms, a cycloalkyl radical, or a phenyl radical optionally substituted by lower alkyl, lower alkoxy, halogen atom, nitro function, -CF3 radical or hydroxyl function, and mixtures of said esters. These compositions are useful as anti-proliferative agents, especially in the treatment of psoriasis and warts, or as anti-inflammatory agents in the treatment of rheumatism, dermatosis and eczema or as anti-acne agents.

Description

1 ~ 73 ~ 8 ~

The subject of the present invention is new pharmaceutical compositions containing as a principle active, in a pharmaceutically acceptable excipient, minus one of the mono, di and tri-esters of dihydroxy-1,8 phenyl-10 anthrone-9 or anthranol-9.
In human or veterinary therapy, these positions find particular application in as anti-proliferative agents, especially in the treatment of psoriasis and warts, or as anti-inflammatory drugs in the treatment of rheumatism, dermatitis and eczema or as anti-acne agents.
These compositions are also useful as products anti-dandruff, anti-seborrheic and against falling hair.
The compositions according to the invention containing active ingredient, mono, di and tri-esters of dihydroxy-1,8 phenyl-10 anthrone-9 or anthranol-9, present additionally compared to dihydroxy-1,8 phenyl-10 anthrone the advantage of being more stable and when used by route topically, to less stain the skin and clothing in particular in basic washing.
The subject of the invention is very particularly, new pharmaceutical compositions containing, as active ingredient, at least one of mono, di and tri-esters dihydroxy-1,8 phenyl-10 anthrone-9 or anthranol-9 / can be represented by the general formula (I):

[~
(He) t C611s ~ Z7358 ~
- the -in which:
p is 0 or 1 (a) when p = 0, t = l and R2 represents an atom of hydrogen or -COR3, (b) when p = l, t = 0 and Rl and R2 independently represent one atom hydrogen or -COR3, R3 representing an alkyl radical, linear or branched, having from 1 to 17 carbon atoms, a radical cycloalkyl, or an optionally substituted phenyl radical killed by lower alkyl, lower alkoxy, a halogen atom, a nitro function, a -CF3 radical or by a hydroxyl function, andmixtures of said esters, in a pharmaceutical excipient only acceptable.
By alkyl radical, linear or branched, having 1 to 17 carbon atoms we can hear a methyl radical, ethyl, propyl, isopropyl, /

3L273 ~ BI ~

butyl, isobutyl, tertlobutyl, pentyl, isopentyl, heptyle, nonyl, undecyle, pentadécyle et heptadécyle.
By cycloalkyl radlcal can be understood a radlcal having from 3 to 6 carbon atoms, preferably the cyclopentyl or cyclohexyl radical.
~ when the phenyl radical is substituted by an alkyl radical inflereur, the latter is preferably a radlcal ~ ethyl, ethyl or tertiobutyl.
When the phenyl radlcal is substituted by an alkoxy radlcal inferler, this is preferably the methoxy or ethoxy radlcal.
IC When the phenyl radical is substituted by a halogen atom, this the latter is preferably a chlorine or fluorine atom.
According to a preferred form of réallsatlon of lnventlon, co ~ posed of formula (I) are di-esters or tri-esters represented by the following formulas:

c6l ~ 5 C6H5 (LI ~ ~ III) Among the esters of formula ~ I) it is possible in particular cite the following:
- 10-phenyltracetoxy-1,8,9 anthracene, - 10-phenyltrlpropionyloxy-1,8,9 anthracene, - phenyl-10 tributyryloxy-1,8,9 anthracene, - 10-phenyl trilsobutyryloxy-1,8,9 anthracene, - 1,8-diisobutyryloxyphenyl-10 anthrone-9, - 10-phenyl tricyclohexylcarbonyloxy-1,8,9 anthracene, - 1,8-dlpivaloyloxy phenyl-10 anthrone-9 - phenyl-10 tribenzoyloxy-1,8,9 anthracene, - 10-phenyl tricyclopentylcarbonyloxy-1,8,9 anthracene, - 10-phenyl trloctanoyloxy-1,8,9 anthracèr.e, - 10-phenyl trlundecanoyloxy-1,8,9 anthracene, - 10-phenyl trloctadecanoyloxy-1,8,9 anthracene, - 10-phenyl tritolylcarbonyloxy-1,8,9 anthracene, - phenyl-10 trl (p-methoxybenzoyloxy) -1,8,9 anthracene, - phenyl-10 trl ~ m- ~ trifluoromethyl) benzoyloxy ~ -1,8,9 anthrscene, ~ L27358 ~

Esters of 1,8-dihydroxy phenyl-10 anthrone-9 or anthranol-9 above defined can be obtained by reacting, on 1,8-dihydroxy phenyl-10 anthrone-9, an activated form of acid such as an acid anhydride, (R3CO) 2O, or an acid chloride, R3COCl, in the presence of a base and preferably an aromatic amine such as pyridine, optionally in an aromatic solvent medium such than in toluene and at a temperature between 20 and 130 C.
The formation of mono, di or tri-esters is a function molar proportions of acid anhydride or chloride of acid reacted and reaction time.
For the preparation of mono and di-esters we use preferably 1.5 to 2.5 equivalents of acid chloride or of acid anhydride and the reaction is followed by chromatography phie on thin layer in order to stop it either at the mono- stage either at the di-ester stage.
For the preparation of triesters we use a large excess of acid chloride or acid anhydride and in order to complete the reaction, the temperature is preferably rence increased to 80-110 C.
When using a particular acid chloride largely congested such as for example pivaloyl chloride, it is particularly easy to access the di-esters even in presence of excess without significant training aunt of the corresponding tri-ester.
Insofar as an acid chloride is used easily removable either by evaporation or by washing in basic medium, it is desirable to carry out the reaction using acid chloride as both a solvent and as a reagent and add 4 to 8 equivalents of pyridine.
In this case, we then operate at a temperature taken between 20 and 60 C and the reaction is particularly fast.

~ 73 ~ i8 ~
~ - 4 -After 12 end of the reaction, when this cl is carried out in a solvent, poured into the medium water reaction and various washes are carried out especially using a sodium bicarbonate solution.
The organi ~ ue phase is then dried over magnesium sulfate then filtered. The product can be purified either by recris-tallization, either by chromatography on silica gel preferably using toluene or a toluene / mixture ethyl acetate as eluent.
In human or veterinary therapy, compositions according to the invention are anti-proliferative agents particularly in the treatment of psoriasis and warts and useful as anti-inflammatory agents in particular in the treatment of rheumatism, dermatosis and eczema, as well as in the treatment of acne, dandruff, seborrhea and hair loss.
The pharmaceutical compositions can be prepared for example by adding an ester of formula (I), at a concentration between 0.01 and 5%, in various inert non-toxic, solid or liquid supports, generally Lely used in compositions for therapeutic use.
The pharmaceutical compositions can be administered enterally, parenterally or topically.
For enteral administration, the compositions are in the form of tablets, powders, granules, capsules, pills, syrups, suspensions or solutions.
The dosage is of course a function of the route administration and the activity sought.
The pharmaceutical compositions may contain additionally inert additives. Tablets or granules may contain, for example, binders, fillers, carriers or thinners.
Liquid compositions can be presented 1 ~ 3 ~ i ~ 30 - 4a -for example in the form of a miscible sterile solution at the water. In addition to the active compound, the capsules can contain a filler or thickener. The essays oral pharmaceuticals may also contain flavor enhancers and substances usually used as preservatives, stabilizers, antioxidants, regulators and emulsifiers. We can also add salts and buffers.
The supports and diluents as listed below above may consist of organic substances or mineral, for example with gelatin, lactose, starch, magnesium stear ~ e, talc, gum arabic, vegetable and mineral oils, fillers, thickeners, colorants, humectants or polyalkylene glycols.

- 5 - ~ 73 ~ BO

When the pharmaceutical compositions are intended for topical applicatlon, these are in the form of an ointment, a ointment, gel, telnture, cream, solutlon, lotlon, an mlcronized powder, a spray, a suspension, a shampoo or soaked pads.
Ointments or ointments are preferred and are prepared in mixing an ester, according to the invention ~ with non-toxic inert supports suitable for topical traling.
We will now give by way of illustration and without any limiting character several examples of preparation of esters used as well as several examples of compositions for therapeutic use.

Preparation of dihydro ~ y-1,8 phenyl-10 anthrone-9 a) Preparation of phenyl-10 trihydroxy-1,8,10 anthrone-9 In a 2 liter reactor fitted with mechanical agitation, a arrival of argon, a refrigerant and an introduction bulb, we place 30g of dihydrcxy-1,8 anthraquinone and 2 liters of anhydrous tetrahydrofuran.
The solution obtained is then cooled to -70C.
At this temperature, the anthraqulnone is crystallized. We have ~ all then with stirring, in 30 minutes, a solution which contains 4 equivalents of phenyllithium.
The temperature is maintained throughout the addition between -60C and -70C. At the end of the addition, a sample is checked taken that all 1,8-dihydroxy anthraquinone is transformed. At this temperature, the reaction medium is acidified by adding 400 cm3 of acid acetyl> then the mixture is allowed to return to room temperature.
solvent is evaporated to dryness under reduced pressure. The product obtained, in the form an oily mass, crystallized by stirring in water.
The crystals obtained are drained, washed with dichloromethane and then dried. This gives 32g of yellow crystals which are recrystallized from the methanol. The product has a melting point of 216C.
Ana'yse C20H14O4 Calculated: C: 75.46 H: 4.43 0: 20.10 Found: 75.48 4.35 19.95 b) Preparation of 1,8-dihydroxy-phenyl-10 anthrone-9 In a 2-liter reactor fitted with mechanical agitation and a arrival of argon, 50 g of phenyl-10 trlhydroxy-1,8,10 anthrone-9 are introduced, puls 200g of ground stannous chloride and 2 liters of acetic acid.
To this mixture, stirred at room temperature, then added drop by drop, in 30 minutes, 200cm3 of concentrated hydrochloric acid La - 6 ~ l 2 7 3 ~ 8 ~

disappearance of phenyl-10 trihydroxy -], 8,10 anthrone-9 is evolved by thin-layer chromotography. After about two hours, the reaction of reduction is finished. Dihydroxy-1,8 phenyl-10 anthrone-9 precipitated in the medium is drained, washed with water and dried. This gives 42g of light yellow crystals. The filtrate is poured onto a mixture of 1 liter of water and kg of crushed ice. The rest of the product precipitates, it is wrung, washed at water and dried. This isolates an additional 4g of the product.
expected.
The 1,8-dihydroxy-phenyl-10 anthrone-9 thus obtained is pure.
It has a melting point of 193-194C.
Analysis C20H1403 Calculated: C: 79.45 H: 4.66 0: 15.87 Found: 79.25 4.71 16.00 The structure of 1,8-dihydroxy-phenyl-10 anthrone-9 is confirmed by mass spectrography where we observe on the spectrum the parent peak at m / e: 302 by direct ionization and at m / e: 303 by chemical ionization at isobutane corresponding to M + H. These results are in agreement with the mass 30Zg molar of the product.
The NMR spectrum also confirms this structure. We observe in particular a singlet at 5.30 p.pm whose integration corresponds to a proton. It is this which is linked to carbon in position 10 of the anthrone nucleus.
The signal of the eleven aromatic protons is a multiplet whose is from 6.60 to 7.50 p.pm (11).
Finally, the spectrum shows another singlet at 12.40 ppm, which disappears by exchange with heavy water ec whose integration corresponds well to two protons of the hydroxyl groups in positions 1 and 8.
EXAMPLE I
Preparation of 10-phenyl-triacetoxy-1,8,9 anthracene.
A mixture of 40g of 1,8-dihydroxy-phenyl-10 anthrone and 0.5cm3 of pyrldine in 400 cc of acetic anhydride is stirred under an inert atmosphere and gradually brought to a temperature between 60 and 70C. The deposition product is quantitatively transformed into the corresponding triacetate after three hours. After cooling with an ice bath, the product crystallizes. It is drained, washed with dried pulsed ethyl ether. We thus obtains 45g of solid of color ~ greenish alder which is dissolved in a mixture of 200 cm 3 of acetic acid and 200 cm 3 of 1,2-dichloroethane brought to a temperature of around 80C. The solution is then filtered, at this temperature and by cooling the filtrate, the product crystallizes. It is wrung, washed with ethyl ether and dried.
35 g of phenyl-10 triacetoxy-1,8,9 anthracene are obtained, in the form of crystals ~ a clear melting point: 279C.

~ 273 ~ 80 E1 ~ mental analysis: C2hH20O6 Calculated: C: 72.88 H: 4.70 0: 22.40 Found: 72.87 4.73 22.15 EXE ~ PLE II
Preparation of phenyl-10 tripropionyloxy-1,8,9 anthracene.
To a stirred mixture under an argon atmosphere of 2.5 g of dihydroxy-1,8 phenyl ~ 10 anthrone in 25cm3 of propionic anhydride, O, 100cm3 of anhydrous pyridine. The reaction mixture is then brought for one hour to 70C, time after which all the starting material is transformed. Excess of reagent is then removed by evaporation under vacuum. The solid obtained is solubilized in the minimum amount of toluene, deposited on a column of sillce gel then eluted with toluene. After evaporation of the eluent, 1.3 g of a solid which is recrystallized from a toluene / hexane mixture.
1.1 g of white crystals with a melting point of 216C are thus isolated.
Elemental analysis: C29H26O6 Calculated: C: 74.02 H: 5.56 0: 20.40 Found: 74.14 5.59 20.19 XAMPLE III
Preparation of 10-phenyl-triisobutyryloxy-1,8,9 anthracene.
A mixture, stirred under a light atmosphere, of 3 g of dihydroxy-1,8 phenyl-10 anthrone, 3.16 cm3 of pyridine (4 equivalents) and 4.26 cm3 of isobutyryl chloride (4 equivalents) in 100cm3 of anhydrous toluene is brought to reflux of the solvent for 10 hours. The reaction medium is then washed several times with water. The organic phase is then decanted, dried over magnesium sulfate and concentrated. The product obtained in the form of a viscous liquid is dissolved in the minimum amount of toluene and deposited on a silica gel column. The expected tri-ester is eluted with the mixture toluene-methylene chloride (3/1). After concentration of the eluent, 2.3 g of solid are obtained which are recrystallized from toluene. We isolate 1.4g 30 of phenyl-10 triisobutyryloxy-1,8,9 anthracene in the form of crystals ~ aunes melting point: 224C.
Ana] elementary vse: C32H3206 Calculated: C: 74.98 H: 6.29 0: 18.72 Found: 74.78 6.2718.57 EXAMPLE IV
Preparation of phenyl-10 tri (cyclohexylcarbonyloxy? -1,8,9 anthracene.
To a mixture of 3g of dihydroxy-1,8 phenyl-10 anthrone in 15cm3 of cyclohexane carboxylic acid chloride, was slowly stirred 3.2 cm 3 of pyridine. The reaction medium is then brought to 100C for 3 hours. he is then diluted to the normal temperature, by adding 200 cc of 3L27. ~; 8 ~
methy1 chloride ~ ne, ~ uis washed with blcarbonated water and then with water. The organic phase is dried over sodlum sulfate. After evaporation of the methylene chloride, 4.2 g of yellow solid are obtained which is recrystallized in a toluene / ethyl ether mixture. After filtration and drying we obtains 3.75 g of phenyl-10 tri- (cyclohexylcarbonyloxy) -1,8,9 anthracene under form of yellow color crystals with melting point: 235CC, Elementary analysis: C41H4406 Calculated: C: 77.82 H: 7.00 0: 15.17 Found: 77.97 7.00 15.01 lo EXAMPLE V
Preparation of dipivaloyloxy-1,8 phenyl-10 anthrone.
A mixture of 3 g of dihydroxy-1,8 phenyl-10 anthrone, of 3.16 cm3 pyridine, 4.8 cm3 of pivaloyl chloride in 100 cm3 of anhydrous toluene is stirred under an argon atmosphere for 10 hours at temperature solvent boiling. After cooling to the room temperature, the reaction medium is washed several times with water. The organic phase is decanted, dried over magnesium sulfate and concentrated. The residue deposited on a column of silica gel is then eluted using toluene. After concentration of the elution phases, 2.38 g of a solid are obtained which is recrystallized from a toluene / hexane mixture.
1.4 g of dipivaloyloxy-1,8 phenyl-10 anthrone are thus isolated under shape of white crystals of fuslon point: 160C.
Elementary analysis: C30H3005 Calculated: C: 76.57 H: 6.42 0: 16.99 Found: 76.40 6.40 16.92 EXE ~ iPLE VI
Preparation of phenyl-10 tribenzoyloxy-1,8,9 anthracene To a mixture stirred at room temperature and under atmosphere inert of lg of 1,8-dihydroxy-phenyl-10 anthrone-9 in 15cm3 of chloride Benzoyl 1.2 cm3 of pyridine are added dropwise.
After one hour of agitation the whole of the starting anthron is transformed er. matching triester. The reaction medium is concentrated under reduced pressure, dissolved in 100cm3 of methylene chloride, washed several times with water and then dried over sodium sulfate.
The organic phase is then deposited on a column of gel of silica and eluted with toluene / methylene chloride, gradually enriched in methylene chloride.
After concentrating the elution phases, 1.55 g of expected triester which is recrystallized from toluene. The crystals are ~ 9 - ~ 273 ~ 80 wrung and dried. We thus sole Ig of phenyl-10 tribenzoyloxy-1,8,9 anthracene in the form of crystals ~ aunes of melting point: 255C.
Elemental analysis: C41H2606 Calculated: C: 80.12 H: 4.26 0: 15.62 Found: 80.08 4.32 15.79 EXE ~ PLE VII
Preparation of diisobutyryloxy-1,8 phenyl-10 anthrone.
A mixture, stirred away from light and under an inert atmosphere, 18 g of 1,8-dihydroxy-10-phenyl anthrone, 19 cm3 of pyridine and 25 cm3 of isobutyryl chloride in 500 cm3 of anhydrous toluene is brought to reflux solvent for five hours.
After cooling, the reaction mixture is washed three times with water and dry over magnesium sulfate.
The residue obtained after evaporation under reduced pressure is then deposited on a column of silica gel. The column is eluted with toluene then with toluene - methylene chloride mixture, the latter being gradually enriched with methylene chloride.
At the top of the chromatography, after isolation of the solvent, 5 g of phenyl-10 triisobutyryloxy-1,8,9 anthracene described in Example III.
The following diester-rich fractions are concentrated and the product obtained is recrystallized from a toluene - pentane mixture.
1.5 g of diisobutyryloxy-1,8 phenyl-10 anthrone are obtained under form of beige crystals with melting point 136 C.
Elementary analysis: C28H2605 Calculates: C: 76.00 H: 5.92 0: 18.08 Found: 75.75 5.99 18.36.
EXAMPLE ~ III
Preparation of 10-phenyl-tributryryloxy-1,8,9 anthracene.
.
A suspension stirred away from light and under atmosphere inert of 18 g of dihydroxy-1,8 phenyl-10 anthrone in 5CO cm of toluene anhydrous, 19 cm3 of pyridine and 24.5 cm3 of butyryl chloride are added.
The mixture is then brought to toluene reflux for three hours, time to finish.
from which the starting material is completely transformed.
After cooling, the mixture is washed three times with water and the toluene phase is dried over sodium sulfate. After concentration1 on residue is deposited on a column of silica gel. The expected product is eluted with hexane - toluene mixture.

- lo- ~ Z73 ~ 80 After concentration of the eluting solvent, 23 g of product which is recrystallized from a toluene - pentane mixture, which leads to 16 g of phenyl-10 tributyryloxy-1,8,9 anthracene in the form of light yellow crystals with melting point: 150 C ~
Elementary analysis: C32H32O6.
Calculated: C: 74.98 H: 6.29 0: 18.72 Found: 75.00 6.47 18.57 EXAMPLES OF PHARMACEUTICAL COMPOSITIONS ~ TICKS

Example 1 - 0.5 g insoluble tablet - Phenyl-10 triacetoxy-1,8,9 anthracene ........... 0.100g - Lactose ......................................... 0,082g - Stearic acid ................................. 0.003g - Purified talc ........ ~ ............ ..... ~. ~ ...... 0.015g - Sweetener ....................... ............... qs - Colorant ......................... ............ qs - QSP rice starch ................ ............... 0.500g This tablet is prepared by direct dry compression of the mixture of different constituents.
Example 2 - 0.8 g insoluble tablet - Phenyl-10 triisobutyryloxy-1,8,9 anthracene .. 0,200g - Lactose .......................... ............... 0.2008 - Gum arabic at 20 ~ in water ................. 0.080g - Liquid paraffin ............................... 0.004g - Purified talc .................................... 0,0L6g - Amiton QSP ...................................... 0.800g This tablet is obtained by wet granulating the mixture 10-phenyl trlisobutyryloxy-1,8,9 anthracene, starch, lactose and arablque gum at 20 ~ in water.
The granules are then dried and then sieved. These The latter are then mixed with the parafflne and the talc.
Example 3 - Cranules in 3g sachets - Phcnyl-10 trlpropionyloxy-1,8,9 anthracene ...................................... 0.150g - Sucrose ...................................... 21220g - Methylcellulose ...., ............................ 0.030g - Purlfied water ....... ~ .. O ......................... 01600g The dough obtained by mixing the four constituents is granulated by flies wet puls dried.

~ 27 ~ 30 - l 1 -Example 4 Capsules Containing 0.05g of Actlf Compound - Phenyl-10 tri (cyclohexylcarbonyloxy) -1,8,9 anthracene ..................................... 0, O50g - QSP cod liver hulle ...................... 0,500g The capsule shell is made by molding and then drying an appropriate mixture of gelatin, glycerin, water and preservative. Ia suspension containing the active compound is introduced into the capsule which is ensulte sealed.
EXAMPLE 5 Capsule Containing 0.3g of Powder powder composition:
- Dlpivaloyloxy-l, ~ phenyl-10 anthrone ............ 0.080g - Corn starch .................................. 0.060g - Lactose QSP ..................................... 0.300g The powder is packaged in a capsule made of gelatin, ~ 5 titanium dioxide and a preservative.
Example 6 - Anti-hair loss and anti-dandruff hair composition - Dipivaloyloxy 1,8 phenyl-10 anthrone ............. 0.50g - Stannous chloride ............................... 0.30g - ~ isopropyl yristate QSP .................... lOO, OOg

Claims (7)

The embodiments of the invention, concerning the-which an exclusive property right or privilege is claimed, are defined as follows: 1. Pharmaceutical compositions, characterized in that they contain, as active ingredient, minus one of the mono, di and tri-esters of dihydroxy-1,8 phenyl-10 anthrone-9 or, anthranol-9 corresponding to the formula general (I):

(I) in which:
p is 0 or 1 (a) when p = 0, t = 1 and R2 represents an atom hydrogen or -COR3, (b) when p = 1, t = 0 and R1 and R2 represent independently of one another a hydrogen atom or -COR3, R3 representing an alkyl radical, linear or branched, having from 1 to 17 carbon atoms, a cyclo radical alkyl, or a phenyl radical unsubstituted or substituted by lower alkyl, lower alkoxy, halogen atom, a nitro function, a -CF3 radical or a function hydroxyl, and mixtures of said esters; in association with a pharmaceutically acceptable excipient. 2. Compositions according to claim 1, character-laughed at by the fact that at least one of the symbols R3 represents a methyl, ethyl, propyl, isopropyl, butyl radical, isobutyle, tertiobutyle, penyle, isopentyle, heptyle, nonyle, undecyle, pentadécyle ou heptadécyle. 3. Compositions according to claim 1, character-laughed at by the fact that at least one of the symbols R3 represents the cyclopentyl or cyclohexyl radical. 4. Compositions according to claim 1, character-laughed at by the fact that at least one of the symbols R3 represents a phenyl radical substituted by at least one methyl radical, ethyl, tert-butyl, methoxy, ethoxy, a fluorine atom or of chlorine, a nitro function, the radical -CF3 or a function hydroxyl. 5. Compositions according to claim 1, character-laughed at by the fact that they contain, as a principle active, at least one of the di-esters of formula:

in which R3 has the same meanings as those given to claim 1. 6. Compositions according to claim 1, character-laughed at by the fact that they contain, as a principle active, at least one of the tri-esters of formula:

in which R3 has the same meanings as those given to claim 1. 7. Compositions according to claim 1, character-laughed at by the fact that they contain, as a principle active, at least one of the compounds chosen from the group consisting killed by:
- 10-phenyl-triacetoxy-1,8,9 anthracene, - 10-phenyl-tripropionyloxy-1,8,9 anthracene, - 10-phenyl-tributyryloxy-1,8,9 anthracene, - 18 phenyl-10 triisobutyryloxy-1,8,9 anthracene, - 1,8-diisobutyryloxy phenyl-10 anthrone-9, - 10-phenyl tricyclohexylcarbonyloxy-1,8,9 anthracene, - 1,8-dipivaloyloxy-phenyl-10 anthrone-9 - phenyl-10 tribenzoyloxy-1,8,9 anthracene, - 10-phenyl tricyclopentylcarbonyloxy-1,8,9 anthracene, - 10-phenyl-trioctanoyloxy-1,8,9 anthracene, - 10-phenyl-triundecanoyloxy-1,8,9 anthracene, - 10-phenyl trioctadecanoyloxy-1,8,9 anthracene, - 10-phenyl tritolylcarbonyloxy-1,8,9 anthracene, - 10-phenyl tri (p-methoxybenzoyloxy) -1,8,9 anthracene, and - 10-phenyl tri [m- (trifluoromethyl) benzoyloxy] -1,8,9 anthracene.