U.S. patent application number 09/942565 was filed with the patent office on 2002-02-14 for retinyl carbonate derivatives, preparation process and uses.
This patent application is currently assigned to L'Oreal. Invention is credited to Dalko, Maria, Rubinstenn, Gilles, Tuloup, Remy.
Application Number | 20020019547 09/942565 |
Document ID | / |
Family ID | 9546210 |
Filed Date | 2002-02-14 |
United States Patent
Application |
20020019547 |
Kind Code |
A1 |
Tuloup, Remy ; et
al. |
February 14, 2002 |
Retinyl carbonate derivatives, preparation process and uses
Abstract
The present invention relates to novel retinol derivatives
having the formula (I): 1 and to processes for preparing them. The
invention also relates to the use of these compounds in or for the
preparation of compositions intended for treating conditions of the
skin or scalp, for example in preventing or combating acne and/or
chronological or actinic ageing of the skin.
Inventors: |
Tuloup, Remy; (Paris,
FR) ; Dalko, Maria; (Gif S/yvette, FR) ;
Rubinstenn, Gilles; (Paris, FR) |
Correspondence
Address: |
OBLON SPIVAK MCCLELLAND MAIER & NEUSTADT PC
FOURTH FLOOR
1755 JEFFERSON DAVIS HIGHWAY
ARLINGTON
VA
22202
US
|
Assignee: |
L'Oreal
Paris
FR
|
Family ID: |
9546210 |
Appl. No.: |
09/942565 |
Filed: |
August 31, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
09942565 |
Aug 31, 2001 |
|
|
|
09580833 |
May 30, 2000 |
|
|
|
Current U.S.
Class: |
552/500 |
Current CPC
Class: |
C07C 2601/16 20170501;
A61P 17/14 20180101; A61Q 19/08 20130101; A61Q 7/00 20130101; A61Q
19/00 20130101; A61P 17/16 20180101; A61P 17/10 20180101; C07J 9/00
20130101; C07C 403/12 20130101; A61K 8/671 20130101; C07J 1/0011
20130101; A61P 17/12 20180101; A61P 17/08 20180101; C07J 71/0005
20130101; A61Q 5/00 20130101; C07J 1/00 20130101; A61Q 5/008
20130101 |
Class at
Publication: |
552/500 ;
514/169 |
International
Class: |
C07J 053/00; A61K
031/56 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 1, 1999 |
FR |
99 06872 |
Claims
1. A retinol derivative of formula (I): 7wherein R is selected from
the group consisting of: (a) a linear, cyclic or branched,
saturated or unsaturated C.sub.1-C.sub.18 hydrocarbon-based
radical, which is unsubstituted or substituted with one or more
groups --OH, --OR', --NHCOR, --SH, --SR', --COOH, --CONHR',
--COOR', --CN or --CF.sub.3, in which R' is a C.sub.1-C.sub.4 alkyl
radical; with a halogen atom; or with: (i) one or more saturated or
unsaturated, substituted or unsubstituted C.sub.3-C.sub.7 aliphatic
rings, or (ii) one or more substituted or unsubstituted aromatic
rings, or (iii) one or more saturated or unsaturated, substituted
or unsubstituted C.sub.3-C.sub.7 heterocycles, or (iv) one or more
amino acid or peptide residues, (b) a radical of
cyclopentanephenanthrene structure, which is at least partially
hydrogenated and/or substituted, (c) an aryl radical optionally
substituted with one or more groups --OH, --NH.sub.2, --SH, --COOH,
--CONHR', --NHCOR, --COOR', --OR', --SR', --CN or --CF.sub.3, in
which R' is a C.sub.1-C.sub.4 alkyl; with a halogen atom; or with:
(i) one or more saturated or unsaturated, substituted or
unsubstituted C.sub.3-C.sub.7 aliphatic rings, or (ii) one or more
substituted or unsubstituted aromatic rings, or (iii) one or more
saturated or unsaturated, substituted or unsubstituted
C.sub.3-C.sub.7 heterocycles, wherein substituted chroman groups
are excluded; (d) a group derived from ceramide, sphingosine or
sphinganine; (e) an amino acid or peptide residue bearing a free
hydroxyl group; and (f) a carbohydrate residue.
2. The retinol derivative according to claim 1, wherein R
represents a radical selected from the group consisting of steryl
and oxysteryl radicals; a sapogenin residue; and a
dehydro-epi-androsterone residue.
3. The retinol derivative according to claim 1, wherein R
represents a cholesteryl radical.
4. The retinol derivative according to claim 1, wherein R
represents a retinyl radical.
5. A process for preparing the retinol derivative according to
claim 1, comprising reacting a chloroformate with retinol.
6. The process according to claim 5, wherein said reacting is
carried out in an anhydrous medium and under an inert
atmosphere.
7. A process for preparing the retinol derivative according to
claim 1, comprising reacting two equivalents of retinol with one
equivalent of carbonyldiimidazole.
8. The process according to claim 7, wherein said reacting is
carried out in an anhydrous medium and under an inert
atmosphere.
9. A composition, comprising: the retinol derivative according to
claim 1; and a physiologically acceptable medium.
10. The composition according to claim 9, further comprising at
least one active agent selected from the group consisting of
depigmenting agents, emollients, moisturizers, anti-seborrhoeic
agents, anti-acne agents, agents for promoting regrowth of the
hair, keratolytic and/or desquamating agents, anti-irritant agents
or calmants and mixtures thereof.
11. A method of combating or treating at least one condition
selected from the group consisting of acne, chronological aging of
the skin, actinic ageing of the skin, greasy appearance of the
hair, hair loss, and combinations thereof, comprising applying to
the skin or scalp the retinol derivative according to claim 1.
12. A method of combating or treating at least one condition
selected from the group consisting of acne, chronological aging of
the skin, actinic ageing of the skin, greasy appearance of the
hair, hair loss, and combinations thereof, comprising applying to
the skin or scalp the composition according to claim 9.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to novel retinyl carbonate
derivatives. The invention also relates to the use of these
compounds in or for the preparation of compositions intended in
particular for preventing or combating acne and/or chronological or
actinic ageing of the skin.
[0003] 2. Discussion of the Background
[0004] Retinoid-based cosmetic and/or dermatological compositions
have undergone considerable development in recent years. The reason
for this is that it has been found that certain compounds of the
retinoid family, derived from retinoic acid, are advantageous in
skin care, in particular in the treatment of acne and for limiting,
or even eliminating altogether, the effects of ageing on the skin
such as wrinkles, a weathered appearance, yellowing, loss of
elasticity, a ruddy complexion and dryness of the skin, as well as
the appearance of blemishes.
[0005] These signs of ageing are all the more accentuated when the
skin is frequently exposed to sunlight or is particularly sensitive
to exposure to UV radiation. Thus, the effects of intrinsic ageing
of the skin (age-related) and of light-induced ageing (due to
exposure to sunlight) can be cumulative. The manifestations of
ageing usually appear at an advanced age; however, their prevention
should be undertaken from the start of adult life by suitable care
treatments.
[0006] Treatment of the skin with compounds of the retinoid family
forms part of these preventive or curative care treatments for the
signs of ageing.
[0007] Among the compounds of the retinoid family, retinol, also
known as vitamin A, is most particularly advantageous. The reason
for this is that retinol is a natural endogenous constituent of the
human body. It is also well tolerated when applied to the skin up
to levels that are considerably higher than those for retinoic
acid.
[0008] However, when it is introduced into a cosmetic composition
intended for topical application, retinol degrades rapidly under
the effects of light, oxygen, metal ions, oxidizing agents, water
or, in particular, under the effect of elevated temperature. There
is thus a need for compounds with retinoid-type activity which are
more stable than retinol.
[0009] WO 95/16659 discloses conjugate compounds obtained from the
reaction of retinoids with organic acids or derivatives of these
acids. The retinoid, which may be retinol, retinal, retinoic acid
or dehydroretinol, is conjugated to the acid derivative, which may
be an aldehyde, a ketone, an alcohol, an ester, etc. via an ester,
reverse ester, amide or ether bond. Among the very great number of
compounds corresponding to this definition, only the ether obtained
by reaction of retinol with the hydroxyl function of glycolic acid
is described. In particular, no mention is made of retinyl
carbonate derivatives.
[0010] Moreover, the publications from Svishchuk et al.,
"Preparation of .alpha.-tocopherol (Vitamin E) Ethers", Farm. Zh.,
29(6), 36-8 (1974) and from Protopova et al., "Insecticidal Action
of 6-hydroxychroman derivatives", Fiziol. Akt. Veshchestva, 7,
142-4 (1975) describe, respectively, a tocopheryl retinyl carbonate
and an analogous compound in which the side chain of the tocopheryl
radical is slightly modified. However, these compounds are not
intended for cosmetic use.
SUMMARY OF THE INVENTION
[0011] Accordingly, it has now been found that the above-described
problems associated with conventional compounds have been solved by
the present invention, the first embodiment of which provides a
retinol derivative corresponding to formula (I): 2
[0012] in which R is selected from the group including:
[0013] (a) a linear, cyclic or branched, saturated or unsaturated
C.sub.1-C.sub.18 hydrocarbon-based radical, which is unsubstituted
or substituted with one or more groups --OH, --OR', --NHCOR, --SH,
--SR', --COOH, --CONHR', --COOR', --CN or --CF.sub.3, in which R'
is a C.sub.1-C.sub.4 alkyl radical; with a halogen atom; or
with:
[0014] (i) one or more saturated or unsaturated, substituted or
unsubstituted C.sub.3-C.sub.7 aliphatic rings, or
[0015] (ii) one or more substituted or unsubstituted aromatic
rings, or
[0016] (iii) one or more saturated or unsaturated, substituted or
unsubstituted C.sub.3-C.sub.7 heterocycles, or
[0017] (iv) one or more amino acid or peptide residues;
[0018] (b) a radical of cyclopentanephenanthrene structure, which
is at least partially hydrogenated and/or substituted,
[0019] (c) an aryl radical optionally substituted with one or more
groups --OH, --NH.sub.2, --SH, --COOH, --CONHR', --NHCOR, --COOR',
--OR', --SR', --CN or --CF.sub.3, in which R' is a C.sub.1-C.sub.4
alkyl; with a halogen atom; or with:
[0020] (i) one or more saturated or unsaturated, substituted or
unsubstituted C.sub.3-C.sub.7 aliphatic rings, or
[0021] (ii) one or more substituted or unsubstituted aromatic
rings, or
[0022] (iii) one or more saturated or unsaturated, substituted or
unsubstituted C.sub.3-C.sub.7 heterocycles,
[0023] wherein substituted chroman groups are excluded;
[0024] (d) a group derived from ceramide, sphingosine or
sphinganine;
[0025] (e) an amino acid or peptide residue bearing a free hydroxyl
group; and
[0026] (f) a carbohydrate residue.
[0027] Another embodiment of the invention provides a composition,
which includes:
[0028] the retinol derivative described above; and
[0029] a physiologically acceptable medium.
[0030] Another embodiment of the invention provides a process for
preparing the retinol derivative described above, including
reacting a chloroformate with retinol.
[0031] Another embodiment of the invention provides a process for
preparing the retinol derivative described above, including
reacting two equivalents of retinol with one equivalent of
carbonyldiimidazole.
[0032] Another embodiment of the invention provides a method of
using the composition described above for the cosmetic treatment of
the skin.
[0033] Another embodiment of the invention provides a method of
using the composition described above for the cosmetic treatment of
the scalp.
[0034] Another embodiment of the invention provides a method of
using retinol derivative described above to prepare a composition
intended for the cosmetic treatment of the skin.
[0035] Another embodiment of the invention provides a method of
using the retinol derivative described above to prepare a
composition intended to combat at least one condition selected from
the group including acne, chronological aging of the skin, actinic
ageing of the skin, and combinations thereof.
[0036] Another embodiment of the invention provides a method of
using the retinol derivative described above to prepare a
composition intended to combat at least one condition selected from
the group including the greasy appearance of the hair and hair
loss.
[0037] Another embodiment of the invention provides a method of
combating or treating at least one condition selected from the
group including acne, chronological aging of the skin, actinic
ageing of the skin, greasy appearance of the hair, hair loss, and
combinations thereof, that includes applying to the skin or scalp
the retinol derivative described above.
[0038] Another embodiment of the invention provides a method of
combating or treating at least one condition selected from the
group including acne, chronological aging of the skin, actinic
ageing of the skin, greasy appearance of the hair, hair loss, and
combinations thereof, that includes applying to the skin or scalp
the composition described above.
DETAILED DESCRIPTION OF THE INVENTION
[0039] Various other objects, features and attendant advantages of
the present invention will be more fully appreciated as the same
becomes better understood from the following detailed description
of the preferred embodiments of the invention.
[0040] Preferably, the derivatives of formula (I) can be defined as
the products of condensation of retinol with other compounds
bearing an alcohol function, via a carbonate bond.
[0041] Preferable linear hydrocarbon-based radicals containing from
1 to 18 carbon atoms include methyl, ethyl, propyl, butyl, hexyl,
octyl, decyl, dodecyl, hexadecyl and octadecyl radicals.
[0042] Preferable branched hydrocarbon-based radicals containing
from 1 to 18 carbon atoms include 2-ethylhexyl, 2-butyloctyl and
2-hexyldecyl radicals.
[0043] The unsaturated hydrocarbon-based radicals are preferably
radicals containing one or more ethylenic unsaturations, such as
2-nonyl-2-butenyl, geranyl, 2,4-cyclohexadienyl and allyl
radicals.
[0044] Preferable cyclic hydrocarbon-based radicals containing from
1 to 18 carbon atoms and C.sub.3-C.sub.7 aliphatic rings include
cyclobutyl, cyclohexyl and tert-butylcyclohexyl radicals.
[0045] The linear, branched or cyclic C.sub.1-C.sub.18
hydrocarbon-based radicals substituted with hydroxyl groups
preferably include polyol residues, such as 2,3-dihydroxypropyl,
2,3,4-trihydroxybutyl, 2,3,4,5-tetrahydroxypentyl and
2,3,4,5,6-penta-hydroxyhexyl radicals or a pentaerythritol residue,
and more preferably sugar residues derived, for example, from
glucose, galactose or mannose, or alternatively from glucuronic
acid.
[0046] The linear, branched or cyclic C.sub.1-C.sub.18
hydrocarbon-based radicals substituted with --COOH groups
preferably include a-hydroxy acid residues, optionally in
lactonized form, or .beta.-hydroxy acid residues, such as a malic
acid, tartaric acid, glycolic acid, lactic acid, ascorbic acid or
salicylic acid residue or derivatives thereof.
[0047] The radicals of cyclopentanephenanthrene structure which are
at least partially hydrogenated and/or substituted preferably
include steryl and oxysteryl radicals, and in particular the
cholesteryl radical; sapogenin residues, and in particular
diosgenin, hecogenin and smilagenin residues; and a
dehydro-epi-androsterone residue.
[0048] The term "C.sub.3-C.sub.7 heterocycle" preferably means
pyridine, furan, thiophene and pyrrole.
[0049] The terms "aryl radical" and "aromatic ring" preferably mean
a phenyl radical optionally substituted with at least one halogen
atom, one hydroxyl or one nitro function.
[0050] The term "amino acid residue" preferably means a residue
derived from lysine, glycine, aspartic acid or cysteine, and the
term "peptide residue" more preferably means a dipeptide or
tripeptide residue resulting from the combination of amino acids.
Preferable amino acid residues bearing a free hydroxyl group
include serine and tyrosine.
[0051] The term "carbohydrate residue" preferably means a residue
derived from glucose, galactose, mannose, lactose, melibiose or
sorbitol, or alternatively from glucuronic acid.
[0052] Preferably, the retinol derivative according to the
invention is a retinyl cholesteryl carbonate, which corresponds to
the general formula (I) above in which R is a cholesteryl
radical.
[0053] According to another preferred embodiment of the invention,
the retinol derivative of formula (I) is retinyl carbonate, i.e. R
represents a retinyl radical.
[0054] The invention also extends its scope to a process for
preparing the abovementioned retinyl carbonate derivatives.
[0055] According to a first synthetic route, which makes it
possible to prepare the set of compounds of formula (I), the
process according to the invention preferably includes the step of
reacting a chloroformate with retinol. The reaction is preferably
carried out in anhydrous medium and under inert atmosphere, so as
to protect the retinol against the oxidation which it has a
tendency to undergo in aqueous medium and/or on contact with
atmospheric oxygen.
[0056] The reaction carried out is illustrated in FIG. (II): 3
[0057] According to a second synthetic route, which can be used
when the retinyl carbonate derivative is retinyl carbonate, the
process according to the invention preferably includes the step of
reacting two equivalents of retinol with one equivalent of
carbonyldiimidazole. As previously, the reaction is preferably
carried out in anhydrous medium and under an inert atmosphere.
[0058] The reaction scheme is illustrated in FIG. (III): 4
[0059] The invention also preferably relates to a composition
including, in a physiologically acceptable medium, at least one
retinyl carbonate derivative as defined above. The expression
"physiologically acceptable" preferably means a medium which is
compatible with the skin and its superficial body growths (nails,
hairs) and/or with head hair.
[0060] The physiologically acceptable medium in which the compounds
according to the invention may be used, as well as its
constituents, their amount, the pharmaceutical form of the
composition and the method for preparing it, can be chosen by a
person skilled in the art on the basis of his or her general
knowledge as a function of the type of composition desired.
[0061] The composition according to the invention can be in any
pharmaceutical form normally used for topical application to the
skin, in particular in the form of an aqueous, aqueous-alcoholic or
oily solution, an oil-in-water or water-in-oil or multiple
emulsion, a silicone emulsion, a microemulsion or nanoemulsion, an
aqueous or oily gel, a liquid, pasty or solid anhydrous product, a
dispersion of oil in an aqueous phase in the presence of spherules,
these spherules possibly being polymer nanoparticles such as
nanospheres and nanocapsules or, better still, lipid vesicles of
ionic and/or nonionic type.
[0062] This composition can be more or less fluid and can have the
appearance of a white or coloured cream, an ointment, a milk, a
lotion, a serum, a paste, a mousse or a gel. It can optionally be
applied to the skin in the form of an aerosol. It can also be in
solid form, and for example in the form of a stick. It can be used
as a care product and/or as a make-up product for the skin, or as a
hair product, for example as a shampoo or conditioner.
[0063] In a known manner, the composition of the invention can also
contain adjuvants that are common in cosmetics and dermatology,
such as hydrophilic or lipophilic gelling agents, hydrophilic or
lipophilic active agents, preserving agents, antioxidants,
solvents, fragrances, fillers, screening agents, pigments, odour
absorbers and dyestuffs. The amounts of these various adjuvants are
those conventionally used in the fields under consideration, and
for example from 0.01 to 20% relative to the total weight of the
composition. Depending on their nature, these adjuvants can be
introduced into the fatty phase, into the aqueous phase, into the
lipid vesicles and/or into the nanoparticles. These adjuvants and
their concentrations should be such that they do not harm the
advantageous properties of the retinol derivative or retinyl
carbonate derivative according to the invention.
[0064] When the composition according to the invention is an
emulsion, the proportion of the fatty phase can range from 5 to 80%
by weight, and preferably from 5 to 50% by weight, relative to the
total weight of the composition. The fatty substances, the
emulsifiers and the co-emulsifiers used in the composition in
emulsion form are chosen from those conventionally used in the
field under consideration. The emulsifier and the co-emulsifier are
preferably present in the composition in a proportion ranging from
0.3 to 30% by weight, and preferably from 0.5 to 20% by weight,
relative to the total weight of the composition.
[0065] As fatty substances which can be used in the invention, oils
and in particular mineral oils (liquid petroleum jelly), oils of
plant origin (avocado oil, soybean oil), oils of animal origin
(lanolin), synthetic oils (perhydrosqualene), silicone oils
(cyclomethicone) and fluoro oils (perfluoropolyethers) can be used.
Fatty alcohols such as cetyl alcohol, fatty acids, waxes and gums
and in particular silicone gums, can also be used as fatty
substances.
[0066] As emulsifiers and co-emulsifiers which can be used in the
invention, mention may be made for example of fatty acid esters of
polyethylene glycol, such as PEG-100 stearate; fatty acid esters of
glycerol, such as glyceryl stearate; fatty acid esters of sorbitan,
which are optionally oxyalkylenated; and mixtures thereof.
[0067] Hydrophilic gelling agents which may be mentioned in
particular are carboxyvinyl polymers (carbomer), acrylic copolymers
such as acrylate/alkylacrylate copolymers, polyacrylamides,
polysaccharides,-natural gums and clays, and lipophilic gelling
agents which may be mentioned are modified clays such as bentones,
metal salts of fatty acids and hydrophobic silica.
[0068] Active agents which can be used in particular are
depigmenting agents, emollients, moisturizers, anti-seborrhoeic
agents, anti-acne agents, agents for promoting the regrowth of the
hair, keratolytic and/or desquamating agents, anti-irritant agents
or calmants and mixtures thereof. Advantageously, in the
composition according to the invention, the retinyl carbonate
derivatives defined above will be used in combination with other
compounds of retinoid-type activity, with free-radical scavengers
or with .alpha.-hydroxy or .alpha.-keto acids or derivatives
thereof. The expression "free-radical scavenger" preferably means,
for example, .alpha.-tocopherol, superoxide dismutase, ubiquinol or
certain metal-chelating agents. The expression ".alpha.-hydroxy or
.alpha.-keto acids or derivatives thereof" preferably means, for
example, lactic acid, malic acid, citric acid, glycolic acid,
mandelic acid, tartaric acid or glyceric acid or their salts,
amides or esters.
[0069] In the event of incompatibility, the active agents mentioned
above can be incorporated into spherules, in particular ionic or
nonionic vesicles and/or nanoparticles (nanocapsules and/or
nanospheres), so as to isolate them from each other in the
composition.
[0070] The composition according to the invention is particularly
suitable in the applications of body and hair hygiene and
especially for the care of squamous or acne-prone skin, to combat
the greasy appearance of the skin or the hair, to combat hair loss,
in protecting against the harmful aspects of sunlight or to prevent
and/or combat actinic or chronological ageing.
[0071] A preferred embodiment of the present invention is thus also
the use of the composition mentioned above for the cosmetic
treatment of the skin, in particular against acne and/or
chronological or actinic ageing. The invention also relates to the
use of this composition for the cosmetic treatment of the scalp, in
particular to combat the greasy appearance of the hair and hair
loss.
[0072] A preferred embodiment of the present invention is also the
use of the retinol derivatives defined above to prepare a
composition intended to combat acne and/or chronological or actinic
ageing of the skin. The invention also relates to the use of these
retinol derivatives to prepare a composition intended to combat the
greasy appearance of the hair and hair loss.
[0073] Another preferred embodiment of the invention relates to the
use of the retinol derivatives and compositions containing them for
preventing or combating acne and/or the chronological or actinic
ageing of the skin.
[0074] The composition according to the invention preferably
includes an effective amount of at least one retinol derivative as
defined above, which is sufficient to obtain the desired effect,
and a physiologically acceptable medium. The composition according
to the invention thus preferably includes, for example, from 0.001
to 20% by weight, more preferably from 0.01 to 10% by weight and
most preferably from 0.1 to 5% by weight, of retinol derivative
relative to the total weight of the composition. Most preferably,
the retinol derivative is a retinyl carbonate derivative.
EXAMPLES
[0075] Having generally described this invention, a further
understanding can be obtained by reference to certain specific
examples which are provided herein for purposes of illustration
only and are not intended to be limiting unless otherwise
specified.
Example 1
[0076] retinyl cholesteryl carbonate
[0077] a) Preparation process
[0078] One molar equivalent of retinol and one molar equivalent of
cholesteryl chloroformate are dissolved in anhydrous
dichloromethane, under an inert atmosphere, at room temperature.
Pyridine (3.5 molar equivalents) is added and the reaction medium
is stirred for 20 minutes.
[0079] After dilution with dichloromethane, washing with water,
concentration and co-evaporation of the pyridine with toluene, the
final product of formula (IV) below is recrystallized from acetone.
5
[0080] b) NMR characterization
[0081] C.sup.13NMR (100 MHz in CDCl.sub.3) d (in ppm): 154.82,
139.57, 139.42, 137.83, 137.57, 136.7, 135.72, 129.9, 125.35,
127.06, 126.02, 123.84, 122.89, 77.89, 64.26, 56.72, 56.18, 50.5,
42.34, 39.75, 39.66, 39.54, 38.07, 36.89, 36.56, 36.20, 35.78,
34.26, 33.06, 31.91, 31.87, 28.95 (2 C), 28.21, 28.00, 27.73,
24.28, 23.84, 22.79, 22.54, 21.69, 21.06, 19.27, 19.25, 18.72,
12.78, 12.72, 11.85.
[0082] .sup.1NMR (400 MHz in CDCl.sub.3) d (in ppm): 6.64 (dd, 11.3
Hz, 15.2 Hz, 1H), 6.26 (d, 15.2 Hz, 1H), 6.18 (d, 16.1 Hz, 1H),
6.10 (d, 16.3 Hz, 1H), 6.09 (d, 11.2 Hz, 1H), 5.40-5.38 (m, 1H),
4.77 (d, 7.25, 2H), 4.51-4.44 (m, 1H), 2.40-0.85 (m, 62H), 09.67
(s, 3H).
Example 2
[0083] retinyl carbonate
[0084] a) Preparation process
[0085] Two equivalents of retinol and one molar equivalent of
carbonyldiimidazole are dissolved in anhydrous tetrahydrofuran,
under an inert atmosphere, at room temperature. The reaction medium
is stirred for two hours, with the tetrahydrofuran maintained at
reflux.
[0086] After concentrating, taking the residue up in ether, washing
the ether phase with water and concentrating, the product of
formula (V) below is obtained in a purity of greater than 90% (only
traces of retinol are detected by .sup.1H NMR). 6
[0087] b) NMR characterization
[0088] C.sup.13 NMR (50 MHz in CDCl.sub.3) d (in ppm): 155.2,
139.9, 137.9, 137.7, 136.9, 135.8, 130.0, 129.5, 127.2, 126.6,
123.8, 64.72, 37.3, 34.3, 33.2, 29.1, 21.9, 19.4, 12.9.
[0089] .sup.1H NMR (200 MHz in CDCl.sub.3) d (in ppm): 6.59 (dd,
11.2 Hz, 15.0 Hz, 2H), 6.20 (d, 15.0 Hz, 2H), 6.10-5.97 (m, 4H),
5.60-5.52 (m, 2H), 4.72 (d, 7.26 Hz, 4H), 1.97-1.36 (m, 32H), 0.95
(s, 12H).
Example 3
[0090] This example illustrates various cosmetic formulations based
on the retinol derivatives according to the invention.
1 Anti-ageing cream in the form of a W/O emulsion Oxyethylenated
polymethylcetyl dimethyl methylsiloxane 1.5% Polyglyceryl
isostearate 0.5% Isohexadecane 12.7% Compound of Example 1 0.2%
Butyl hydroxytoluene 0.1% Mixture of acetylated ethylene glycol
stearate and glyceryl 1% tristearate, sold by the company Guardian
under the name Unitwix Preserving agents 0.4% Apricot kernel oil 5%
Glycerol 5% Magnesium sulphate 0.7% Disodium salt of EDTA 0.1%
Imidazolinylurea 0.3% Water qs 100% Anti-ageing fluid in the form
of an O/W emulsion Mixture of glyceryl monostearate and
poly-ethylene glycol 2.1% stearate (100 EO) Cetyl alcohol 2.6%
Hydrogenated isoparaffin 14.8% Preserving agents 0.4% Compound of
Example 1 0.1% Butyl hydroxytoluene 0.1% Oxyethylenated sorbitan
monostearate (20 EO) 0.9% Glycerol 3% Xanthan gum 0.1% Carbomer
0.4% Imidazolidinylurea 0.3% Triethanolamine 0.3% Water qs 100%
Anti-ageing fluid in the form of an O/W emulsion Sorbitan
tristearate 0.9% Polyethylene glycol stearate (40 EO) 2% Cetyl
alcohol 4% Glyceryl stearate 3% Compound of Example 2 0.4% Butyl
hydroxytoluene 0.1% Hydrogenated isoparaffin 1.8% Preserving agents
0.40% Cyclopentasiloxane 10% Imidazolidinylurea 0.3% Water qs
100%
[0091] Obviously, numerous modifications and variations of the
present invention are possible in light of the above teachings. It
is therefore to be understood that within the scope of the appended
claims, the invention may be practiced otherwise than as
specifically described herein.
[0092] This application is based on French Patent Application FR
9906872, filed Jun. 1, 1999, and incorporated herein by reference
in its entirety.
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