U.S. patent application number 10/464553 was filed with the patent office on 2004-03-04 for composition containing oxidation-sensitive hydrophilic active principle and maleic anhydride copolymer, and use thereof.
This patent application is currently assigned to L'OREAL, Paris, France. Invention is credited to Biatry, Bruno.
Application Number | 20040042990 10/464553 |
Document ID | / |
Family ID | 29717063 |
Filed Date | 2004-03-04 |
United States Patent
Application |
20040042990 |
Kind Code |
A1 |
Biatry, Bruno |
March 4, 2004 |
Composition containing oxidation-sensitive hydrophilic active
principle and maleic anhydride copolymer, and use thereof
Abstract
The invention relates to the use of a composition, especially
for preventing and/or treating cutaneous signs of intrinsic ageing,
the composition containing at least one oxidation-sensitive
hydrophilic active principle selected from the group consisting of
ascorbic acid and its compounds and at least one maleic anhydride
copolymer.
Inventors: |
Biatry, Bruno; (Vincennes,
FR) |
Correspondence
Address: |
OBLON, SPIVAK, MCCLELLAND, MAIER & NEUSTADT, P.C.
1940 DUKE STREET
ALEXANDRIA
VA
22314
US
|
Assignee: |
L'OREAL, Paris, France
|
Family ID: |
29717063 |
Appl. No.: |
10/464553 |
Filed: |
June 19, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60394255 |
Jul 9, 2002 |
|
|
|
Current U.S.
Class: |
424/70.11 ;
424/70.15; 514/474 |
Current CPC
Class: |
A61Q 17/00 20130101;
A61P 39/06 20180101; A61P 43/00 20180101; A61K 8/4973 20130101;
A61P 17/16 20180101; A61P 17/00 20180101; A61K 8/8182 20130101;
A61Q 17/04 20130101; A61K 8/11 20130101; A61Q 19/08 20130101; A61K
2800/522 20130101; A61Q 5/08 20130101; A61Q 19/007 20130101; A61K
2800/412 20130101; A61Q 19/00 20130101; A61K 8/347 20130101; A61K
8/676 20130101; A61Q 19/02 20130101; A61K 8/8164 20130101; A61K
2800/52 20130101 |
Class at
Publication: |
424/070.11 ;
514/474; 424/070.15 |
International
Class: |
A61K 007/06; A61K
007/11 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 20, 2002 |
FR |
0207638 |
Claims
1. A method for preventing and/or treating cutaneous signs of
intrinsic ageing, comprising applying to skin a composition
comprising at least one oxidation-sensitive hydrophilic active
principle selected from the group consisting of ascorbic acid and
its compounds and at least one maleic anhydride copolymer
comprising one or more maleic anhydride comonomer units and one or
more comonomer units selected from the group consisting of vinyl
acetate, vinyl alcohol, vinylpyrrolidone, olefins comprising from 2
to 20 carbon atoms, and styrene, in a physiologically acceptable
medium comprising an aqueous phase.
2. The method according to claim 1, wherein said method is a method
of treating cutaneous signs of intrinsic ageing comprising applying
said composition to skin in need thereof.
3. The method according to claim 1, wherein said method is a method
of preventing cutaneous signs of intrinsic ageing comprising
applying said composition to skin in need thereof.
4. The method according to claim 1, wherein the hydrophilic active
principle is selected from the group consisting of
5,6-di-O-dimethylsilylascorbate, the dl-.alpha.-tocopheryl
dl-ascorbyl phosphate potassium salt of ascorbic acid, magnesium
ascorbyl phosphate, sodium ascorbyl phosphate and ascorbyl
glucoside.
5. The method according to claim 1, wherein the oxidation-sensitive
hydrophilic active principle is ascorbic acid.
6. The method according to claim 1, wherein the maleic anhydride
units of the copolymer are in the hydrolysed form and in the form
of alkaline salts.
7. The method according to claim 1, wherein the oxidation-sensitive
active principle and the copolymer are both in the aqueous
phase.
8. The method according to claim 1, wherein the copolymer has a
molar fraction of maleic anhydride units of between 0.1 and 1.
9. The method according to claim 8, wherein the copolymer has a
molar fraction of maleic anhydride units of between 0.4 and
0.9.
10. The method according to claim 1, wherein the copolymer is a
copolymer of styrene and of maleic anhydride in a 50/50 ratio.
11. The method according to claim 1, wherein the copolymer is a
copolymer of styrene and of maleic anhydride in a 50/50 ratio in
the form of an ammonium or sodium salt.
12. The method according to claim 1, wherein the molar ratio of the
maleic anhydride unit equivalent to the oxidation-sensitive
hydrophilic active principle varies between 0.005 and 10.
13. The method according to claim 1, wherein the molar ratio of the
maleic anhydride unit equivalent to the oxidation-sensitive
hydrophilic active principle varies between 0.01 and 1.
14. The method according to claim 1, wherein the copolymer is
present at a concentration of between 0.1 and 40% by weight of the
aqueous phase.
15. The method according to claim 1, wherein the copolymer is
present at a concentration of between 0.1 and 10% by weight of the
aqueous phase.
16. The method according to claim 1, wherein the composition
further comprises at least one non-ascorboc acid active principle
which stimulates dermal macromolecules or which prevents their
decomposition and/or an agent which stimulates the proliferation of
fibroblasts or keratinocytes and/or the differentiation of
keratinocytes.
17. A method for preventing and/or treating cutaneous signs of
intrinsic ageing, comprising applying to skin or mucous membranes a
composition comprising at least one oxidation-sensitive hydrophilic
active principle selected from the group consisting of ascorbic
acid and its compounds and at least one maleic anhydride copolymer
comprising one or more maleic anhydride comonomer units and one or
more comonomer units selected from the group consisting of vinyl
acetate, vinyl alcohol, vinylpyrrolidone, olefins comprising from 2
to 20 carbon atoms, and styrene, in a physiologically acceptable
medium comprising an aqueous phase.
Description
REFERENCE TO PRIOR APPLICATIONS
[0001] This application claims priority to U.S. Provisional
application No. 60/394,255, filed Jul. 9, 2002, and to French
patent application 0207638, filed Jun. 20, 2002, both of which are
incorporated herein by reference.
SUMMARY OF THE INVENTION
[0002] The present invention relates to the use, preferably the
cosmetic and/or dermatological use, of a composition comprising at
least one oxidation-sensitive hydrophilic active principle and at
least one maleic anhydride copolymer in a physiologically
acceptable medium comprising an aqueous phase. Preferably the use
is for preventing and/or treating cutaneous signs of intrinsic
ageing. The compositions described also make up a part of the
invention.
DISCUSSION OF THE BACKGROUND
[0003] It is known to introduce, into cosmetic compositions,
various active principles intended to contribute specific
treatments to the skin and/or hair. However, some of these active
principles exhibit the disadvantage of being unstable in an aqueous
medium and of easily decomposing on contact with water, in
particular because of oxidation phenomena. They thus rapidly lose
their activity over time and this instability conflicts with the
desired effectiveness.
[0004] Attempts have thus been made for a long time to formulate
ascorbic acid or vitamin C because of its numerous beneficial
properties. In particular, ascorbic acid stimulates the synthesis
of the connective tissue and in particular of collagen, strengthens
the defences of the cutaneous tissue against external attacks, such
as ultraviolet radiation and pollution, compensates for vitamin E
deficiency of the skin, depigments the skin and has a role in
combating free radicals. These last two properties make it an
excellent candidate as cosmetic or dermatological active principle
for combating ageing of the skin or for preventing ageing of the
skin. Unfortunately, because of its chemical structure (of
.alpha.-ketolactone), ascorbic acid is highly sensitive to certain
environmental parameters and in particular to oxidation phenomena.
There thus ensues rapid decomposition of formulated ascorbic acid
in the presence of these parameters and in particular in the
presence of oxygen, light or metal ions, as a function of the
temperature or under certain pH conditions (Pharm. Acta. Helv.,
1969, 44, 611-667; STP Pharma, 1985, 4, 281-286).
[0005] Several solutions have thus been envisaged in the prior art
for reducing and/or slowing down the decomposition of ascorbic
acid.
[0006] Provision has thus been made to use ascorbic acid in the
form of a compound thereof (sometimes referred to as a derivative
or chemical derivative thereof) (magnesium ascorbyl phosphate or
esters of fatty acids and ascorbic acid), but the bioavailability
of these compounds is very low (J. Am. Acad. Dermatol., 1996, 34,
29-33).
[0007] The instability of ascorbic acid with respect to oxygen can
be improved by using specific packagings, such as twin compartments
under an inert atmosphere, as disclosed in Patent U.S. Pat. No.
5,935,584, or alternatively by the use of two-phase emulsions, one
phase of which is composed of a dry powder comprising ascorbic acid
and the second phase of which is a liquid phase. The mixing of the
two phases has to be carried out at the time of use (WO 98/43598).
These solutions have disadvantages with regard to the cost and the
complexity of the manufacturing operations and significant
restrictions with regard to use.
[0008] Another solution provided in the prior art consists in using
a high concentration of glycols or polyols in order to reduce the
solubility of oxygen in the formulation, thus protecting the
ascorbic acid (WO 96/24325, EP 0 755 674, U.S. Pat. No. 5,981,578).
The polyols can optionally be incorporated in liposomes, as
disclosed in Patent U.S. Pat. No. 6,020,367. However, these
solutions exhibit the disadvantage of resulting in sticky
formulations, the cosmetic quality of which is difficult to
improve. Furthermore, the presence of a high concentration of these
compounds can lead to phenomena of irritation.
[0009] Ascorbic acid can also be formulated in anhydrous media,
such as silicones (U.S. Pat. No. 6,194,452), which are capable of
creating an anhydrous barrier around ascorbic acid. A major
disadvantage of such solutions results from the lack of freshness
on application.
DEETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0010] The need thus remains for a composition employable in
particular in the cosmetics field, in which a hydrophilic active
principle which is unstable in an oxidizing medium is stabilized,
which is comfortable on application, which does not lead to any
skin irritation after application and which is compatible with the
constraints of an industrial implementation of its manufacturing
process.
[0011] The effect of ascorbic acid on the biosynthesis of collagen,
a protein macromolecule predominantly present in the dermis, has
been known for several years (Arch. Biochem. Biophys., 152, 1972,
p. 318-328). It acts at two levels. First of all, as cofactor of
hydroxylases, enzymes involved in the hydroxylation of proline and
of lysine, ascorbic acid promotes this essential stage in the
assembling of procollagen molecules (Biochemistry, 78(5), 1981, p.
2279-2282; The Yale Journal of Biology and Medecine, 58, 1985, p.
553-559). Furthermore, it stimulates the biosynthesis of collagen
by increasing the amount of mRNA coding for procollagens of type I
and III (The Journal of Investive Dermatology, 90(4), 1988, p.
420-424).
[0012] Magnesium ascorbyl phosphate also stimulates the synthesis
of collagen (Skin Pharmacol., 6, 1993, p. 65-71).
[0013] At the same time as these properties, the ascorbic acid used
to treat cutaneous fibroblasts has made it possible to demonstrate
an increase in proteoglycans (Journal of Biochemical Engineering,
1991, 113).
[0014] More recently, the Applicant Company has shown that
magnesium ascorbyl phosphate, added to a medium for the culturing
of reconstructed skin, led to a significant increase in the number
of fibroblasts in the lattice, in combination with significant
stimulation of the synthesis of proteins of the extracellular
matrix (FR-02/01510). This was observed in particular at the
dermoepidermal junction, where stimulation of the synthesis of the
major components, which are collagens IV and VII, and laminin, is
measured. This phenomenon has the consequence of reinforcing the
relief of this junction, promoting exchanges between dermis and
epidermis, and the cohesion of these two tissues, and thus makes it
possible to combat the harmful effects of ageing on these
factors.
[0015] By enhancing the overall content of collagen, the
proliferative capability and the synthetic activity of fibroblasts
and the amount of procollagen I and III, but also by reinforcing
the cohesion and the effectiveness of the dermoepidermal junction,
ascorbic acid and its compounds are therefore particularly useful
in preventing and/or treating cutaneous signs of intrinsic
ageing.
[0016] One object of the present invention is to provide a
composition comprising an oxidation-sensitive active principle
selected from the group consisting of ascorbic acid and its
compounds, which exhibits good cosmetic properties, both with
regard to touch and with regard to tolerance, the preservation of
which over time does not require specific precautions, and which
retains the activity of the active principle in the prevention
and/or the treatment of cutaneous signs of intrinsic ageing.
[0017] The inventor has discovered, fortuitously, that the use of
maleic anhydride copolymers in compositions in which the aqueous
phase includes an oxidation-sensitive active principle, such as
ascorbic acid, makes it possible to achieve the abovementioned
aim.
[0018] To the knowledge of the inventor, such polymers comprising
maleic anhydride units have never been used in combination with
hydrophilic active principles sensitive to decomposition by
oxidation for the purpose of improving their stability. This is
true in particular in the case of ascorbic acid.
[0019] A subject-matter of the present invention is therefore the
cosmetic and/or dermatological use of a composition for preventing
and/or treating cutaneous signs of intrinsic ageing, the
composition comprising at least one oxidation-sensitive hydrophilic
active principle selected from the group consisting of ascorbic
acid and its compounds and at least one maleic anhydride copolymer
in a physiologically acceptable medium comprising an aqueous phase.
The copolymer is present in an amount sufficient to stabilize the
oxidation-sensitive hydrophilic active principle. Preferably, the
oxidation-sensitive active principle and the copolymer are both in
the aqueous phase.
[0020] Another subject-matter of the present invention is the use
of a combination composed of at least one oxidation-sensitive
hydrophilic active principle selected from the group consisting of
ascorbic acid and its compounds and of at least one maleic
anhydride copolymer in a cosmetic composition comprising an aqueous
phase as agent for preventing and/or treating cutaneous signs of
intrinsic ageing.
[0021] Another aspect of the invention relates to the use of at
least one oxidation-sensitive hydrophilic active principle selected
from the group consisting of ascorbic acid and its compounds and of
at least one maleic anhydride copolymer in the preparation of a
dermatological composition comprising an aqueous phase intended for
preventing and/or treating cutaneous signs of intrinsic ageing.
[0022] According to the invention, the term "hydrophilic active
principle" is understood to mean a compound having a solubility in
water of at least 0.25% at ambient temperature (25.degree. C.).
[0023] According to the invention, the term "oxidation-sensitive
hydrophilic active principle" is understood to mean any active
principle of natural or synthetic origin capable of undergoing
decomposition by an oxidation mechanism. This oxidation phenomenon
can have several causes, in particular the presence of oxygen, of
light or of metal ions, a high temperature or certain pH
conditions.
[0024] Mention may be made, among ascorbic acid compounds, by way
of example and without implied limitation, of: the salts or esters,
in particular the 5,6-di-O-dimethylsilylascorbate (sold by Exsymol
under the reference PRO-AA), the potassium salt of
dl-.alpha.-tocopheryl dl-ascorbyl phosphate (sold by Senju
Pharmaceutical under the reference SEPIVITAL EPC), magnesium
ascorbyl phosphate, sodium ascorbyl phosphate (sold by Roche under
the reference Stay-C 50) and ascorbyl glucoside (sold by
Hayashibara).
[0025] In a particularly advantageous aspect, the
oxidation-sensitive hydrophilic active principle is ascorbic
acid.
[0026] According to the invention, the term "maleic anhydride
copolymer" is understood to mean any polymer obtained by
copolymerization of one or more maleic anhydride comonomers and of
one or more comonomers selected from the group consisting of vinyl
acetate, vinyl alcohol, vinylpyrrolidone, olefins comprising from 2
to 20 carbon atoms, such as octadecene, ethylene, isobutylene,
diisobutylene or isooctylene, and styrene, the maleic anhydride
comonomers optionally being partially or completely hydrolysed. Use
will preferably be made of hydrophilic polymers, that is to say
polymers having a solubility in water of greater than or equal to 2
g/l.
[0027] Copolymers which are more particularly suitable for the
implementation of the invention are copolymers obtained by
copolymerization of one or more maleic anhydride units and in which
the maleic anhydride units are in the hydrolysed form and
preferably in the form of alkaline salts, for example in the form
of ammonium, sodium, potassium or lithium salts.
[0028] In an advantageous aspect of the invention, the copolymer
has a molar fraction of maleic anhydride units of between 0.1 and
1, more preferably between 0.4 and 0.9.
[0029] According to an advantageous aspect of the invention, the
molar ratio of the maleic anhydride unit equivalent to the
oxidation-sensitive hydrophilic active principle varies between
0.005 and 10 and preferably between 0.01 and 1.
[0030] The weight-average molar mass (molecular weight) of the
maleic anhydride copolymers will advantageously be between 1 000
and 500 000 and preferably between 1 000 and 50 000.
[0031] Use will preferably be made of a copolymer of styrene and of
maleic anhydride in a 50/50 ratio.
[0032] Use may be made, for example, of the styrene/maleic
anhydride (50/50) copolymer in the form of a 30% ammonium salt in
water sold under the reference SMA1000H.RTM. by Atofina or the
styrene/maleic anhydride (50/50) copolymer in the form of a 40%
sodium salt in water sold under the reference SMA1000HNa.RTM. by
Atofina.
[0033] The copolymer is present in the composition according to the
invention in an amount sufficient to produce the desired effect,
that is to say in an amount sufficient to stabilize the
oxidation-sensitive hydrophilic active principle. Preferably, the
copolymer is present at a concentration of between 0.1 and 40% by
weight with respect to the total weight of the aqueous phase and
more particularly at a concentration of between 0.1 and 10% by
weight with respect to the total weight of the aqueous phase.
[0034] The compositions used according to the invention are
intended for topical application to the skin and/or its superficial
body growths and therefore comprise a physiologically acceptable
medium, that is to say a medium compatible with cutaneous tissues,
such as the skin, scalp, eyelashes, eyebrows, hair, nails and
mucous membranes. This physiologically acceptable medium may more
particularly be composed of water and optionally of a
physiologically acceptable organic solvent chosen, for example,
from lower alcohols comprising from 1 to 8 carbon atoms and in
particular from 1 to 6 carbon atoms, such as ethanol, isopropanol,
propanol or butanol; polyethylene glycols having from 6 to 80
ethylene oxide units; or polyols, such as propylene glycol,
isoprene glycol, butylene glycol, glycerol or sorbitol.
[0035] When the physiologically acceptable medium is an aqueous
medium, it generally has a pH which is compatible with the skin,
preferably ranging from 3 to 9 and better still from 3.5 to
7.5.
[0036] The compositions according to the invention can be provided
in any pharmaceutical dosage form used conventionally for topical
application and in particular in the form of aqueous or
aqueous/alcoholic solutions, of oil-in-water (O/W) or water-in-oil
(W/O) or multiple (triple: W/O/W or O/W/O) emulsions, of aqueous
gels or of dispersions of a fatty phase in an aqueous phase using
spherules, it being possible for these spherules to be polymeric
nanoparticles, such as nanospheres and nanocapsules, or lipid
vesicles of ionic and/or nonionic type (liposomes, niosomes or
oleosomes). These compositions are prepared according to the usual
methods.
[0037] In addition, the compositions used according to the
invention can be more or less fluid and can have the appearance of
a white or coloured cream, of an ointment, of a milk, of a lotion,
of a serum, of a paste or of a foam. They can optionally be applied
to the skin in the form of an aerosol. They can also be provided in
a solid form, for example in the form of a stick.
[0038] When the composition used according to the invention
comprises an oily phase, the latter preferably comprises at least
one oil. It can additionally comprise other fatty substances.
[0039] Mention may be made, as oils which can be used in the
composition of the invention, of, for example:
[0040] hydrocarbonaceous oils of animal origin, such as
perhydrosqualene;
[0041] hydrocarbonaceous oils of vegetable origin, such as liquid
triglycerides of fatty acids comprising from 4 to 10 carbon atoms,
such as triglycerides of heptanoic acid or octanoic acid, or
alternatively, for example, sunflower, maize, soybean, gourd, grape
seed, sesame, hazelnut, apricot, macadamia, arara, castor or
avocado oils, triglycerides of caprylic/capric acids, such as those
sold by Starineries Dubois or those sold under the names Miglyol
810, 812 and 818 by Dynamit Nobel, jojoba oil, or karite butter
oil;
[0042] synthetic esters and ethers, in particular of fatty acids,
such as the oils of formulae R.sup.1COOR.sup.2 and R.sup.1OR.sup.2
in which R.sup.1 represents the residue of a fatty acid comprising
from 8 to 29 carbon atoms and R.sup.2 represents a branched or
unbranched hydrocarbonaceous chain comprising from 3 to 30 carbon
atoms, such as, for example, purcellin oil, isononyl isononanoate,
isopropyl myristate, 2-ethylhexyl palmitate, 2-octyldodecyl
stearate, 2-octyldodecyl erucate or isostearyl isostearate;
hydroxylated esters, such as isostearyl lactate, octyl
hydroxystearate, octyldodecyl hydroxystearate, diisostearyl malate,
triisocetyl citrate or heptanoates, octanoates or decanoates of
fatty alcohols; polyol esters, such as propylene glycol
dioctanoate, neopentyl glycol diheptanoate and diethylene glycol
diisononanoate; and pentaerythritol esters, such as pentaerythrityl
tetraisostearate;
[0043] linear or branched hydrocarbons of mineral or synthetic
origin, such as volatile or nonvolatile liquid paraffins and their
compounds, liquid petrolatum, polydecenes or hydrogenated
polyisobutene, such as parleam oil;
[0044] fatty alcohols having from 8 to 26 carbon atoms, such as
cetyl alcohol, stearyl alcohol and their mixture (cetearyl
alcohol), octyldodecanol, 2-butyloctanol, 2-hexyldecanol,
2-undecylpentadecanol, oleyl alcohol or linoleyl alcohol;
[0045] partially hydrocarbon-comprising and/or silicone-comprising
fluorinated oils, such as those disclosed in the document
JP-A-2-295912;
[0046] silicone oils, such as volatile or nonvolatile
polymethylsiloxanes (PDMS) comprising a linear or cyclic silicone
chain which are liquid or pasty at ambient temperature, in
particular cyclopolydimethylsiloxanes (cyclomethicones), such as
cyclohexasiloxane; polydimethylsiloxanes comprising pendent alkyl,
alkoxy or phenyl groups or alkyl, alkoxy or phenyl groups at the
end of the silicone chain, which groups have from 2 to 24 carbon
atoms; or phenylated silicones, such as phenyl trimethicones,
phenyl dimethicones, phenyltrimethylsiloxydiphenylsiloxane- s,
diphenyl dimethicones, diphenylmethyldiphenyltrisiloxanes,
(2-phenylethyl)trimethylsiloxysilicates and
polymethylphenylsiloxanes;
[0047] their mixtures.
[0048] The term "hydrocarbonaceous oil" is understood to mean, in
the list of the oils mentioned above, any oil predominantly
comprising carbon and hydrogen atoms and optionally ester, ether,
fluorinated, carboxylic acid and/or alcohol groups.
[0049] The other fatty substances which can be present in the oily
phase are, for example, fatty acids comprising from 8 to 30 carbon
atoms, such as stearic acid, lauric acid, palmitic acid and oleic
acid; waxes, such as lanolin, beeswax, carnauba or candelilla wax,
paraffin or lignite waxes or microcrystalline waxes, ceresin or
ozokerite, or synthetic waxes, such as polyethylene waxes or
Fischer-Tropsch waxes; silicone resins, such as trifluoromethyl
C.sub.1-4 alkyl dimethicone and trifluoropropyl dimethicone; and
silicone elastomers, such as the products sold under the names
"KSG" by Shin-Etsu, under the names "Trefil", "BY29" or "EPSX" by
Dow Corning or under the names "Gransil" by Grant Industries.
[0050] These fatty substances can be chosen in a way varied by a
person skilled in the art in order to prepare a composition having
the desired properties, for example of consistency or of
texture.
[0051] According to a specific embodiment of the invention, the
composition according to the invention is a water-in-oil (W/O) or
oil-in-water (O/W) emulsion. The proportion of the oily phase in
the emulsion can range from 5 to 80% by weight and preferably from
5 to 50% by weight with respect to the total weight of the
composition.
[0052] The emulsions generally comprise at least one emulsifier
selected from the group consisting of amphoteric, anionic, cationic
or nonionic emulsifiers, used alone or as a mixture, and optionally
a coemulsifier. The emulsifiers are appropriately chosen according
to the emulsion to be obtained (W/O or O/W). The emulsifier and the
coemulsifier are generally present in the composition in a
proportion ranging from 0.3 to 30% by weight and preferably from
0.5 to 20% by weight with respect to the total weight of the
composition.
[0053] Mention may be made, for the W/O emulsions, for example, as
emulsifiers, of dimethicone copolyols, such as the mixture of
cyclomethicone and of dimethicone copolyol sold under the name "DC
5225 C" by Dow Corning, and alkyl dimethicone copolyols, such as
the laurylmethicone copolyol sold under the name "Dow Corning 5200
Formulation Aid" by Dow Corning and the cetyl dimethicone copolyol
sold under the name Abil EM 90.sup.R by Goldschmidt. Use may also
be made, as surfactant of W/O emulsions, of a crosslinked solid
organopolysiloxane elastomer comprising at least one oxyalkylenated
group, such as those obtained according to the procedure of
Examples 3, 4 and 8 of the document U.S. Pat. No. 5,412,004 and the
examples of the document U.S. Pat. No. 5,811,487, in particular the
product of Example 3 (synthetic example) of Patent U.S. Pat. No.
5,412,004, and such as that sold under the reference KSG 21 by Shin
Etsu.
[0054] Mention may be made, for the O/W emulsions, for example, as
emulsifiers, of nonionic emulsifiers, such as esters of fatty acids
and of glycerol which are oxyalkylenated (more particularly
polyoxyethylenated); esters of fatty acids and of sorbitan which
are oxyalkylenated; esters of fatty acids which are oxyalkylenated
(oxyethylenated and/or oxypropylenated); ethers of fatty alcohols
which are oxyethylenated (oxyethylenated and/or oxypropylenated);
sugar esters, such as sucrose stearate; and their mixtures, such as
the mixture of glyceryl stearate and of PEG-40 stearate.
[0055] In a known way, the cosmetic or dermatological composition
of the invention can also comprise adjuvants conventional in the
cosmetics or dermatological field, such as hydrophilic or
lipophilic gelling agents, preservatives, solvents, fragrances,
fillers, UV screening agents, bactericides, odour absorbers,
colouring materials, plant extracts or salts. The amounts of these
various adjuvants are those conventionally used in the field under
consideration, for example from 0.01 to 20% of the total weight of
the composition. These adjuvants, depending on their nature, can be
introduced into the fatty phase, into the aqueous phase and/or into
the lipid spherules.
[0056] Mention may be made, as fillers which can be used in the
composition of the invention, for example, of pigments, silica
powder; talc; particles of polyamide and in particular those sold
under the name Orgasol by Atochem; polyethylene powders;
microspheres based on acrylic copolymers, such as those made of
ethylene glycol dimethacrylate/lauryl methacrylate copolymer which
are sold by Dow Corning under the name Polytrap; expanded powders,
such as hollow microspheres and in particular the microspheres sold
under the name Expancel by Kemanord Plast or under the name
Micropearl F 80 ED by Matsumoto; silicone resin microbeads, such as
those sold under the name Tospearl by Toshiba Silicone; and their
mixtures. These fillers can be present in amounts ranging from 0 to
20% by weight and preferably from 1 to 10% by weight with respect
to the total weight of the composition.
[0057] According to a preferred embodiment, the compositions in
accordance with the invention can additionally comprise at least
one organic photoprotective agent and/or at least one inorganic
photoprotective agent which is active in the UV-A and/or UV-B
regions (absorbers), which are soluble in water or in fats or else
are insoluble in the cosmetic solvents commonly used, and which are
selected from the group consisting of the following agents, denoted
below under their INCI name:
[0058] p-aminobenzoic acid (PABA) compounds, in particular PABA,
ethyl PABA, ethyl dihydroxypropyl PABA, ethylhexyl dimethyl PABA
(sold in particular under the name "Escalol 507" by ISP), glyceryl
PABA or PEG-25 PABA (sold under the name "Uvinul P25" by BASF),
[0059] salicylic compounds, in particular homosalate (sold under
the name "Eusolex HMS" by Rona/EM Industries), ethylhexyl
salicylate (sold under the name "Neo Heliopan OS" by Haarmann and
Reimer), dipropylene glycol salicylate (sold under the name
"Dipsal" by Scher), or TEA salicylate (sold under the name "Neo
Heliopan TS" by Haarmann and Reimer),
[0060] dibenzoylmethane compounds, in particular butyl
methoxydibenzoylmethane (sold in particular under the trade name
"Parsol 1789" by Hoffmann-LaRoche), or isopropyl
dibenzoylmethane,
[0061] cinnamic compounds, in particular ethylhexyl
methoxycinnamate (sold in particular under the trade name "Parsol
MCX" by Hoffmann-LaRoche), isopropyl methoxycinnamate, isoamyl
methoxycinnamate (sold under the trade name "Neo Heliopan E 1000"
by Haarmann and Reimer), cinoxate, DEA methoxycinnamate,
diisopropyl methyl cinnamate, or glyceryl ethylhexanoate
dimethoxycinnamate,
[0062] .beta.,.beta.-diphenylacrylate compounds, in particular
octocrylene (sold in particular under the trade name "Uvinul N539"
by BASF) or etocrylene (sold in particular under the trade name
"Uvinul N35" by BASF),
[0063] benzophenone, in particular benzophenone-1 (sold under the
trade name "Uvinul 400" by BASF), benzophenone-2 (sold under the
trade name "Uvinul D50" by BASF), benzophenone-3 or oxybenzone
(sold under the trade name "Uvinul M40" by BASF), benzophenone-6
(sold under the trade name "Helisorb 11" by Norquay),
benzophenone-8 (sold under the trade name "Spectra-Sorb UV-24" by
American Cyanamid), benzophenone-12, or n-hexyl
2-(4-diethylamino-2-hydroxybenzoyl)benzoate,
[0064] benzylidene camphor compounds, in particular 3-benzylidene
camphor (manufactured under the name "Mexoryl SD" by Chimex),
4-methylbenzylidene camphor (sold under the name "Eusolex 6300" by
Merck), or polyacrylamidomethyl benzylidene camphor (manufactured
under the name "Mesoryl SW" by Chimex),
[0065] triazine compounds, in particular anisotriazine (sold under
the trade name "Tinosorb S" by Ciba Specialty Chemicals),
ethylhexyl triazone (sold in particular under the trade name
"Uvinul T150" by BASF), diethylhexyl butamido triazone (sold under
the trade name "Uvasorb HEB" by Sigma 3V) or 2,4,6-tris(diisobutyl
4'-amino-benzalmalonate)-s-triazine- ,
[0066] benzotriazole compounds, in particular drometrizole
trisiloxane (sold under the name "Silatrizole" by Rhodia Chimie) or
methylene bis-benzotriazolyl tetramethylbutylphenol (sold in the
solid form under the trade name "Mixxim BB/100" by Fairmount
Chemical or in the micronized form in aqueous dispersion under the
trade name "Tinosorb M" by Ciba Specialty Chemicals),
[0067] anthranilic compounds, in particular menthyl anthranilate
(sold under the trade name "Neo Heliopan MA" by Haarmann and
Reimer),
[0068] imidazoline compounds, in particular ethylhexyl
dimethoxybenzylidene dioxoimidazoline propionate,
[0069] benzalmalonate compounds, in particular polyorganosiloxane
comprising benzalmalonate functional groups (sold under the trade
name "Parsol SLX" by Hoffmann-LaRoche),
[0070] and their mixtures,
[0071] the inorganic photoprotective agents selected from the group
consisting of pigments or alternatively nanopigments (mean size of
the primary particles: generally between 5 nm and 100 nm,
preferably between 10 nm and 50 nm) formed from coated or uncoated
metal oxides, such as, for example, titanium oxide (amorphous or
crystalline in the rutile and/or anatase form), iron oxide, zinc
oxide, zirconium oxide or cerium oxide nanopigments, which are all
UV photoprotective agents well known per se; or conventional
coating agents, such as alumina and/or aluminium stearate; the
nanopigments formed from coated or uncoated metal oxides are
disclosed in particular in Patent Applications EP 518 772 and EP
518 773.
[0072] The organic photoprotective agents which are more
particularly preferred are selected from the group consisting of
ethylhexyl salicylate, ethylhexyl methoxycinnamate, octocrylene,
benzophenone-3, 4-methylbenzylidene camphor, 2,4,6-tris(diisobutyl
4'-aminobenzalmalonate)-s-triazine, anisotriazine, ethylhexyl
triazone, diethylhexyl butamido triazone, methylene
bis-benzotriazolyl tetramethylbutylphenol, drometrizole
trisiloxane, and their mixtures.
[0073] The photoprotective agents are generally present in the
compositions according to the invention in proportions ranging from
0.1 to 20% by weight with respect to the total weight of the
composition and preferably ranging from 0.2 to 15% by weight with
respect to the total weight of the composition.
[0074] In another advantageous aspect of the invention, the
composition used can additionally comprise at least one other
active principle which stimulates dermal macromolecules or which
prevents their decomposition and/or one agent which stimulates the
proliferation of fibroblasts or keratinocytes and/or the
differentiation of keratinocytes.
[0075] Mention may be made, among the active principles which
stimulate dermal macromolecules or which prevent their
decomposition, of those which act:
[0076] either on the synthesis of collagen, such as extracts of
Centella asiatica; asiaticosides and compounds; ascorbic acid or
vitamin C and its compounds, synthetic peptides, such as iamine,
biopeptide CL or the palmitoyloligopeptide sold by Sederma;
peptides extracted from plants, such as the soybean hydrolysate
sold by Coletica under the trade name Phytokine.RTM.; and plant
hormones, such as auxins;
[0077] or on the synthesis of elastin, such as the extract of
Saccharomyces cerevisiae sold by LSN under the trade name
Cytovitin.RTM.; and the extract of the alga Macrocystis pyrifera
sold by Secma under the trade name Kelpadelie.RTM.;
[0078] or on the synthesis of glycosaminoglycans, such as the
product of fermentation of milk by Lactobacillus vulgaris sold by
Brooks under the trade name Biomin yogourth.RTM.; the extract of
the brown alga Padina pavonica sold by Alban Muller under the trade
name HSP3.RTM.; and the extract of Saccharomyces cerevisiae
available in particular from Silab under the trade name
Firmalift.RTM. or from LSN under the trade name Cytovitin.RTM.;
[0079] or on the synthesis of fibronectin, such as the extract of
Salina zooplankton sold by Seporga under the trade name GP4G.RTM.;
the yeast extract available in particular from Alban Muller under
the trade name Drieline.RTM.; and the palmitoyl pentapeptide sold
by Sederma under the trade name Matrixil.RTM.;
[0080] or on the inhibition of metalloproteinases (MMP), such as
more particularly MMP 1, 2, 3 or 9. Mention may be made of:
retinoids and compounds; oligopeptides and lipopeptides, lipoamino
acids; the malt extract sold by Coletica under the trade name
Collalift.RTM.; extracts of blueberry or of rosemary; lycopene; or
isoflavones, their compounds or the plant extracts comprising them,
in particular extracts of soybean (sold, for example, by Ichimaru
Pharcos under the trade name Flavosterone SB.RTM.), of red clover,
of flax, of kakkon or of sage;
[0081] or on the inhibition of serine proteases, such as leukocyte
elastase or cathepsin G. Mention may be made of: the peptide
extract of Leguminosae (Pisum sativum) seeds sold by LSN under the
trade name Parelastyl.RTM.; heparinoids; and pseudodipeptides.
[0082] Mention may in particular be made, among the active
principles which stimulate epidermal macromolecules, such as
filaggrin and keratins, of the extract of lupin sold by Silab under
the trade name Structurine.RTM.; the extract of beech Fagus
sylvatica buds sold by Gattefoss under the trade name
Gatuline.RTM.; and the extract of Salina zooplankton sold by
Seporga under the trade name GP4G.RTM..
[0083] The agents which stimulate the proliferation of fibroblasts
which can be used in the composition according to the invention
can, for example, be selected from the group consisting of plant
proteins or polypeptides, extracts, in particular of soybean (for
example, a soybean extract sold by LSN under the name Eleseryl
SH-VEG 8.RTM. or sold by Silab under the trade name
Raffermine.RTM.); and plant hormones, such as gibberellins and
cytokinins.
[0084] The agents which stimulate the proliferation of
keratinocytes which can be used in the composition according to the
invention comprise in particular retinoids, such as retinol and its
esters, including retinyl palmitate; phloroglucinol; the extracts
of walnut meal sold by Gattefoss; and the extracts of Solanum
tuberosum sold by Sederma.
[0085] The agents which stimulate the differentiation of
keratinocytes comprise for example inorganic materials, such as
calcium; the extract of lupin sold by Silab under the trade name
Photoprventine.RTM.; sodium .beta.-sitosteryl sulphate, sold by
Seporga under the trade name Phytocohsine.RTM.; and the extract of
maize sold by Solabia under the trade name Phytovityl.RTM..
[0086] The composition according to the invention can be applied to
the skin or mucous membranes. It can thus be used in a cosmetic
treatment process for the purpose of preventing and/or treating
cutaneous signs of intrinsic ageing, comprising the application of
the composition according to the invention to the skin or mucous
membranes.
[0087] The examples which follow serve to illustrate the invention
without, however, exhibiting a limiting nature. The compounds are,
depending on the situation, cited according to chemical names or
according to CTFA (International Cosmetic Ingredient Dictionary and
Handbook) names.
EXAMPLES
Example 1
Accelerated Storage Test
[0088] The aim of this test is to study the decomposition of an
oxidation-sensitive hydrophilic active principle after storing for
two months at 45.degree. C. Various solutions were prepared and
their compositions are collated in the following table:
1 TABLE I Compositions Ascorbic (in water) acid Polymer 1 Polymer 2
Solution A 15% -- -- (Control 1) Solution B 15% 1% -- Solution C
15% -- 1% Solution D 5% -- -- (Control 2) Solution E 5% 1% --
Solution F 5% -- 1%
[0089] All the solutions are brought to pH 6 with 8.9 mol/l
KOH.
[0090] The percentages of the polymers are given as active
material.
[0091] Polymer 1: Styrene/maleic anhydride (50/50) copolymer in the
form of a 30% ammonium salt in water, sold under the reference
SMA1000H.RTM. by Atofina.
[0092] Polymer 2: Styrene/maleic anhydride (50/50) copolymer in the
form of a sodium salt, sold under the reference SMA1000HNa.RTM. by
Atofina.
[0093] The degree of decomposition measured is given by the
ratio:
(C.sub.0-C.sub.2 months)/C.sub.0
[0094] with C.sub.0 concentration of ascorbic acid at t=0 and
C.sub.2 months the concentration of ascorbic acid at t=2 months,
under the conditions indicated in the above table.
[0095] The concentration of ascorbic acid is determined by the HPLC
technique (LaChrom Merck system). The analytical conditions are as
follows:
[0096] Column: Lichrosphere100 RP18 (250 mm)
[0097] Eluent: 0.1M phosphate buffer, pH 2.1
[0098] Flow rate: 1 ml/min
[0099] Detection at 257 nm
[0100] Dilution of the sample such that the concentration of
ascorbic acid is between 0.05 and 1 mg/ml.
[0101] The results obtained are collated in the following Table
II:
2 TABLE II Degree of decomposition after 2 months at 45.degree. C.
(in %) under air, amber under nitrogen, glass bottle aluminium
flask Solution A 43 19.4 (Control 1) Solution B 16 13.8 Solution C
17.6 9.7 Solution D 45.4 29.6 (Control 2) Solution E 13.4 4.1
Solution F 9 5.1
[0102] It is found, from Table II, that the stability of ascorbic
acid, at a concentration of 5 or 15%, is improved in the presence
of Polymer 1 and Polymer 2 of the invention, even in the presence
of atmospheric oxygen, in comparison with the control. As the
polymers mentioned are hydrophilic, it will be sufficient to add
them to an aqueous ascorbic acid solution to stabilize the ascorbic
acid.
Example 2
Observation of the Effect of the Addition of a Combinationaccording
to the Invention on the Synthesis of Tenascin and of Collagen
VII:
[0103] The present example describes the effects of the addition of
a combination according to the invention, comprising ascorbic acid
and a copolymer according to the invention, on reconstructed skin
by observation with a microscope of a skin section with
immunohistochimical labelling of the proteins of tenascin and
collagen VII.
[0104] 1. Preparation of the Reconstructed Skin
[0105] The reconstructed skin used is prepared according to the
protocol described in Asselineau et al. (Models in Dermato.
Published by Loire and Maibach, 1987, Vol III, 1-7). The
modifications to this protocol are:
[0106] the use of normal adult human dermal fibroblasts in a
proportion of 10.sup.6 cells per equivalent dermis;
[0107] the inoculation of the keratinocytes is carried out in a
proportion of 50 000 cells per ring with a diameter of 1.5 cm. The
keratinocytes used originate from the same donor and are at passage
1 during the inoculation of the dermal equivalents;
[0108] the duration of the immersion phase is 7 days;
[0109] the duration of the emergence phase is 7 days.
[0110] 2. Addition of the Combination According to the
Invention:
[0111] The final change in medium of the immersion phase is carried
out in the presence of the combination of ascorbic acid and of the
styrene/maleic anhydride copolymer in the form of a 40% sodium salt
in water. The culture is subsequently mounted on a grid for the
emergence phase (7 days) and, during this phase, all changes in
medium (every 2 days) are carried out in the presence of the above
combination.
[0112] 3.a. Analysis of Collagen VII
[0113] The reconstructed skins are analysed at the end of the
emergence phase. A control sample is systematically prepared and
analysed in parallel.
[0114] The samples are taken and frozen in liquid nitrogen. The
blocks are produced from Tissue Teck. Collagen of type VII is
detected by immunohisto-chemistry on frozen sections with a
thickness of 5 .mu.m. The conventional indirect immunofluorescence
technique is carried out with an anticollagen VII monoclonal
antibody (LH7.2, Chemicon International Inc., USA) and a
fluorescein-coupled conjugate (FITC-conjugated Rabbit anti mouse
immunoglobulins, DAKO, Denmark).
[0115] 3.b. Analysis of Tenascin
[0116] The protocol used is that described in point 3.a. above,
except that, in this case, the tenascin is detected with an
antitenascin monoclonal antibody (TN2, Chemicon) and a
fluorescein-coupled conjugate (FITC-conjugated Rabbit anti mouse
immunoglobulins, DAKO, Denmark).
[0117] 4. Observations:
[0118] On observing with a microscope, it is found that the
intensity and the thickness of the fluorescence region
corresponding to the dermoepidermal junction is much greater in the
sample to which the combination of ascorbic acid and styrene/maleic
anhydride copolymer in the form of a 40% sodium salt in water has
been added. This was observed both for the analysis of collagen VII
and for the analysis of tenascin.
[0119] An increase in the fibroblasts in the lattice with a more
perpendicular arrangement of the basal keratinocytes at the
dermoepidermal junction is also noticed.
Example 3
O/W Anti-ageing Cream
[0120] The following composition is prepared in a way conventional
to a person skilled in the art.
3 Phase A Water 18.33 g Glycerol 3 g Phase B Sorbitan tristearate
0.68 g PEG-40 stearate 1.5 g Cetyl alcohol 3 g Glyceryl stearate
2.25 g Myristyl myristate 1.5 g Ethylhexyl palmitate 1.5 g
Hydrogenated polyisobutene 2.5 g Shorea robusta seed butter 1.5 g
Butyrospermum parkii (shea butter) fruit 0.5 g Cyclopentasiloxane
7.5 g Phenoxyethanol 1 g Phase C Water 43.94 g Ascorbic acid 5 g
Potassium hydroxide (50% solution) 3 g Styrene/maleic anhydride
copolymer, 30% ammonium salt 3.3 g in water (SMA1000H .RTM.,
Atofina)
[0121] A rich and soft cream is obtained which makes it possible to
combat signs of ageing and in which ascorbic acid has good
stability over time.
Example 4
O/W Anti-ageing Cream
[0122] The following composition is prepared in a way conventional
to a person skilled in the art.
4 Phase A Pentaerythrityl tetraethylhexanoate 6 g Ammonium
polyacryloyldimethyl taurate 0.6 g Water 14.95 g Methylparaben 0.2
g Glycerol 3 g Phenoxyethanol 0.5 g Phase B PTFE 4 g Cetearyl
alcohol (and) ceteareth-30 1.5 g Octocrylene 7 g Butyl
methoxydibenzoylmethane 2 g Ethylhexyl salicylate 5 g Glycolipids
0.5 g Propylparaben 0.1 g Petrolatum 1 g Polysorbate 60 1 g Cetyl
alcohol 0.5 g Phase C Caprylyl glycol 0.15 g Glyceryl starch 2 g
Phase D Water 41 g Ascorbic acid 5 g Potassium hydroxide (50%
solution) 3 g Styrene maleic anhydride copolymer, 40% 2.5 g sodium
salt in water (SMA1000HNa .RTM., Atofina)
[0123] A cream is obtained which is soft and fresh on application,
which cream makes it possible to combat wrinkles and fine lines and
in which the ascorbic acid has good stability.
[0124] All documents, tests, patents, applications, references,
articles, publications, etc. mentioned above are incorporated
herein by reference. Where a range or limit is expressed all values
and subranges therewithin are expressly included as if written
out.
[0125] A preferred stabilizing amount of copolymer is any amount
that reduces the amount of decomposition of the active principle
after storage at 45C. for 2 months (e.g., 0.5, 1, 2, 3%, etc.
reduction in decomposition). Preferably the amount of the reduction
in decomposition is 5% or greater (e.g., 10, 15, 20, 25, 30, 35,
40, 45, 50, 55, 60, 65, 70, etc. %). The reduction in decomposition
is calculated as [(% decomposition without copolymer-%
decomposition with copolymer)/% decomposition without
copolymer].times.100%.
[0126] The above description sets forth the manner and process of
making and using the present invention and enables any person
skilled in the art to which it pertains to make and use the same,
such enablement being provided in addition for the embodiments of
the invention included within the claims recited below.
* * * * *