U.S. patent application number 09/841078 was filed with the patent office on 2001-09-20 for cosmetic, pharmaceutical or dermatological composition comprising a histamine antagonist, an interleukin-1 antagonist and/or a tnf-alpha antagonist.
Invention is credited to Breton, Lionel, Cohen, Catherine, Lacharriere, Olivier De.
Application Number | 20010022978 09/841078 |
Document ID | / |
Family ID | 9470353 |
Filed Date | 2001-09-20 |
United States Patent
Application |
20010022978 |
Kind Code |
A1 |
Lacharriere, Olivier De ; et
al. |
September 20, 2001 |
Cosmetic, pharmaceutical or dermatological composition comprising a
histamine antagonist, an interleukin-1 antagonist and/or a
TNF-alpha antagonist
Abstract
The invention relates to the use of a histamine antagonist, an
interleukin-1 antagonist and/or a TNF-alpha antagonist in a
cosmetic, pharmaceutical or dermatological composition for treating
sensitive skins. It relates especially to the use of a histamine
antagonist, an interleukin-1 antagonist and/or a TNF-alpha
antagonist for preventing and/or combating skin irritations and/or
sores and/or erythema and/or dysaesthesic sensations and/or
sensations of inflammation and/or pruritus and/or prickling and/or
tingling and/or discomfort and/or tightness of the skin and/or
mucosae. It also relates to a composition containing a histamine
antagonist, an interleukin-1 antagonist and/or a TNF-alpha
antagonist which limits or eliminates the irritant side-effects of
certain products, and in particular of certain cosmetic,
dermatological or pharmaceutical active agents.
Inventors: |
Lacharriere, Olivier De;
(Paris, FR) ; Breton, Lionel; (Versailles, FR)
; Cohen, Catherine; (Paris, FR) |
Correspondence
Address: |
Norman H. Stepno
BURNS, DOANE, SWECKER & MATHIS, L.L.P.
P.O. Box 1404
Alexandria
VA
22313-1404
US
|
Family ID: |
9470353 |
Appl. No.: |
09/841078 |
Filed: |
April 25, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09841078 |
Apr 25, 2001 |
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09391394 |
Sep 8, 1999 |
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09391394 |
Sep 8, 1999 |
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08879889 |
Jun 20, 1997 |
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5993833 |
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08879889 |
Jun 20, 1997 |
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08580291 |
Dec 28, 1995 |
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5658581 |
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Current U.S.
Class: |
424/613 ;
514/167; 514/256; 514/557; 514/680; 514/725 |
Current CPC
Class: |
Y10S 514/937 20130101;
A61K 31/00 20130101; A61K 31/4545 20130101; A61K 31/522 20130101;
A61K 2800/70 20130101; A61Q 19/004 20130101; Y10S 514/859 20130101;
Y10S 514/944 20130101; A61K 31/41 20130101; A61Q 19/00 20130101;
A61Q 11/00 20130101; A61Q 19/08 20130101; A61K 31/4402 20130101;
A61Q 5/006 20130101; A61K 8/49 20130101; A61Q 5/02 20130101; A61K
31/44 20130101; Y10S 514/84 20130101; A61K 31/55 20130101; A61Q
1/14 20130101; A61K 31/4439 20130101; A61P 43/00 20180101; A61K
31/635 20130101; A61K 45/06 20130101; A61K 8/4926 20130101; A61K
8/494 20130101; A61K 2800/75 20130101; A61Q 19/005 20130101; Y10S
514/844 20130101; A61P 17/00 20180101; A61K 31/7135 20130101; A61K
8/671 20130101; A61K 8/58 20130101; A61K 31/495 20130101 |
Class at
Publication: |
424/613 ;
514/167; 514/256; 514/557; 514/680; 514/725 |
International
Class: |
A61K 033/40; A61K
031/59; A61K 031/505; A61K 031/19; A61K 031/07 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 28, 1994 |
FR |
94-15796 |
Claims
What we claim is:
1. A composition suitable for pharmaceutical, cosmetic or
dermatological usage, said composition comprising at least one
agent which produces an irritant side-effect, at least one compound
selected from the group consisting of interleukin-1 antagonists,
TNF-alpha antagonists and combinations thereof, in an amount
effective to antagonize said irritant side-effect, and a
cosmetically, dermatologically or pharmaceutically acceptable
medium therefor.
2. The composition of claim 1, wherein the agent which produces an
irritant side-effect is selected from the group consisting of
alpha-hydroxy acids, beta-hydroxy acids, alpha-keto acids,
beta-keto acids, retinoids, anthralins, anthranoids, peroxides,
minoxidil, lithium salts, antimetabolites, vitamin D,
depigmentation agents, solvents, perfumes, preservatives,
surfactants and alcoholic solutions.
3. The composition of claim 1, further comprising at least one
histamine antagonist.
4. The composition of claim 3, wherein the histamine antagonist is
a heterocycle or a nitrogen compound having at least one benzene
ring.
5. The composition of claim 1, wherein the amount of the compound
ranges from about 0.000001 to 5% by weight relative to the total
weight of the composition.
6. The composition of claim 1, wherein the amount of the compound
ranges from about 0.0001 to 0.1% by weight relative to the total
weight of the composition.
7. The composition of claim 1, wherein the cosmetically,
pharmaceutically, or dermatologically acceptable medium comprises
an aqueous, oil or aqueous alcoholic solution, a water-in-oil
emulsion, an oil-in-water emulsion, a microemulsion, an aqueous
gel, an anhydrous gel, a serum, or a dispersion of vesicles,
microcapsules or microparticles.
8. The composition of claim 1, further comprising at least one
active agent selected from the group consisting of anti-bacterial,
antiparasitic, antifungal, anti-inflammatory, antipruriginous,
anesthetic, antiviral, keratolytic, free-radical scavenging,
antiseborrheic, antidandruff and anti-acne agents and/or agents
which modulate the differentiation and/or the proliferation and/or
the pigmentation of skin.
9. The composition of claim 8, wherein the active agent is selected
from the group consisting of lidocaine hydrochloride, antiparasitic
agents and non-steroidal anti-inflammatory agents.
10. A composition suitable for pharmaceutical, cosmetic or
dermatological usage, said composition comprising at least one
agent which produces an irritant side-effect, at least one compound
selected from the group consisting of interleukin-1 antagonists,
TNF-alpha antagonists and combinations thereof, in an amount
effective to antagonize said irritant side-effect, and a
cosmetically, dermatologically or pharmaceutically acceptable
medium therefor, said compound being capable of inhibiting the
IL-1-induced adhesion of macrophages to endothelial cells,
inhibiting the IL-1-induced release of superoxide anions from
neutrophils, inhibiting the TNF-alpha-induced adhesion of
macrophages to endothelial cells, inhibiting the TNF-alpha-induced
release of superoxide anions from neutrophils, inhibiting the
mitogenic activity of TNF-alpha by dermal fiproblasts, or
inhibiting the release of interleukin-1 or TNF-alpha by phorbol
ester induced differentiated monocytes.
11. The composition of claim 10, wherein the agent which produces
an irritant side-effect is selected from the group consisting of
alpha-hydroxy acids, beta-hydroxy acids, alpha-keto acids,
beta-keto acids, retinoids, anthralins, anthranoids, peroxides,
minoxidil, lithium salts, antimetabolites, vitamin D,
depigmentation agents, solvents, perfumes, preservatives,
surfactants and alcoholic solutions.
12. The composition of claim 10, further comprising at least one
histamine antagonist, said histamine antagonist being capable of
inhibiting the contraction of smooth muscles induced by the
administration of histamine or inhibiting the release of histamine
by stimulated mast cells.
13. The composition of claim 12, wherein the histamine antagonist
is a heterocycle or a nitrogen compound having at least one benzene
ring.
14. The composition of claim 10, wherein the amount of the compound
ranges from about 0.000001 to 5% by weight relative to the total
weight of the composition.
15. The composition of claim 10, wherein the amount of the compound
ranges from about 0.0001 to 0.1% by weight relative to the total
weight of the composition.
16. The composition of claim 10, wherein the cosmetically,
pharmaceutically, or dermatologically acceptable medium comprises
an aqueous, oil or aqueous alcoholic solution, a water-in-oil
emulsion, an oil-in-water emulsion, a microemulsion, an aqueous
gel, an anhydrous gel, a serum, or a dispersion of vesicles,
microcapsules or microparticles.
17. The composition of claim 10, further comprising at least one
active agent selected from the group consisting of anti-bacterial,
antiparasitic, antifungal, anti-inflammatory, antipruriginous,
anesthetic, antiviral, keratolytic, free-radical scavenging,
antiseborrheic, antidandruff and anti-acne agents and/or agents
which modulate the differentiation and/or the proliferation and/or
the pigmentation of skin.
18. The composition of claim 17, wherein the active agent is
selected from the group consisting of lidocaine hydrochloride,
antiparasitic agents and non-steroidal anti-inflammatory agents.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of copending U.S.
application Ser. No. 09/391,394, filed Sep. 8, 1999, now allowed,
incorporated by reference herein in its entirety and relied upon,
which is a continuation of application Ser. No. 08/879,889, filed
Jun. 20, 1997, now U.S. Pat. No. 5,993,833, which is a divisional
of application Ser. No. 08/580,291, filed Dec. 28, 1995, now U.S.
Pat. No. 5,658,581.
[0002] The present invention relates to the use of a histamine
antagonist, an interleukin-1 antagonist and/or a TNF-alpha
antagonist in a cosmetic, pharmaceutical or dermatological
composition for topical application, intended, in particular, for
the treatment of sensitive skins, as well as to a composition
containing a histamine antagonist, an interleukin-1 antagonist
and/or a TNF-alpha antagonist for the purpose of decreasing or even
abolishing the irritant effects of certain products, and in
particular of certain active agents used in the cosmetics,
pharmaceutical or dermatological field.
[0003] It is known that some skins are more sensitive than others.
The symptoms of sensitive skin were hitherto poorly characterized
and the problem of these skins was, as a result, poorly defined;
nobody understood precisely the process involved in
sensitivity--non-allergic cutaneous hyperreactivity--of the skin.
Some workers believed that a sensitive skin was a skin which
reacted to cosmetic products, others that such a skin was one which
reacted to several external factors, not necessarily associated
with cosmetic products.
[0004] Some tests have been tried in an effort to pinpoint
sensitive skins, for example tests involving lactic acid and DMSO,
which are known to be irritant substances: see, for example, the
paper by K. Lammintausta et al., Dermatoses, 1988, 36, pages 45-49;
and the paper by T. Agner and J. Serup, Clinical and Experimental
Dermatology, 1989, 14, pages 214-217. However, these tests did not
enable sensitive skins to be characterized completely.
[0005] Moreover, sensitive skins were likened to allergic
skins.
[0006] Since the characteristics of sensitive skins were poorly
understood, it was very difficult to treat them hitherto, and they
were treated indirectly, for example by limiting the use of
products having an irritant character, such as surfactants,
preservatives or perfumes as well as certain active agents, in
cosmetic or dermatological compositions.
[0007] The Applicants have carried out numerous clinical tests and
have been able to determine the symptoms associated with sensitive
skins. These symptoms are, in particular, subjective signs which
are essentially dysaesthesic sensations. Dysaesthesic sensations
are understood to mean more or less painful sensations experienced
in an area of the skin, such as prickling, tingling, itching or
pruritus, burning, inflammation, discomfort, tightness, and the
like.
[0008] The Applicants were able to show, in addition, that a
sensitive skin was not an allergic skin. In effect, an allergic
skin is a skin which reacts to an external agent, an allergen,
which triggers an allergic reaction. This is an immunological
process which takes place only when an allergen is present and
which affects only sensitized subjects. The essential
characteristic of sensitive skin is, according to the Applicants,
on the contrary, a mechanism of response to external factors, which
can affect any individual, even if individuals with so-called
sensitive skin react to them more quickly than do others. This
mechanism is not immunological.
[0009] The Applicants have now found that sensitive skins could be
divided into two major clinical forms, irritable skins and
intolerant skins.
[0010] An irritable skin is a skin which reacts by pruritus, that
is to say by itching or by prickling, to different factors such as
the environment, emotions, foods, windy conditions, rubbing,
shaving soap, surfactants, hard water with a high chalk
concentration, temperature changes or wool. In general, these signs
are associated with a dry skin with or without sores, or with a
skin which displays erythema.
[0011] An intolerant skin is a skin which reacts by sensations of
inflammation or of tightness, by pruritus, that is to say by
itching or prickling, by tingling and/or red blotches, to different
factors such as the environment, emotions and foods. In general,
these signs are associated with erythema and with a skin with or
without sores.
[0012] "Sensitive" scalps have a more unequivocal symptomatology:
the sensations of pruritus and/or of prickling and/or of
inflammation are essentially triggered by local factors such as
rubbing, soap, surfactants, hard water with a high chalk
concentration, shampoos or lotions. These sensations are also
sometimes triggered by factors such as the environment, emotions
and/or foods. Erythema and hyperseborrhoea of the scalp as well as
a dandruff state are frequently associated with the above
signs.
[0013] Moreover, in some anatomical regions, such as the major
folds (inguinal, genital, axillary, popliteal, anal and
inframammary regions, bend of the elbow) and the feet, sensitive
skin manifests itself in pruriginous sensations and/or dysaesthesic
sensations (inflammation, prickling) associated especially with
sweating, with rubbing, with wool, with surfactants, with hard
water with a high chalk concentration and/or with temperature
changes.
[0014] To determine whether a skin is sensitive or otherwise, the
Applicants have also developed a test. In effect, after performing
a large number of tests with the object of defining a sensitive
skin, Applicants found, surprisingly, that there was a link between
persons having sensitive skin and those who reacted to a topical
application of capsaicin.
[0015] The capsaicin test consists in applying 0.05 ml of a cream
containing 0.075% of capsaicin to approximately 4 cm.sup.2 of skin,
and noting the appearance of subjective signs caused by this
application, such as prickling, burning and itching. In subjects
having sensitive skins, these signs appear between 3 and 20 minutes
after the application, and are followed by the appearance of an
erythema which begins at the periphery of the area of
application.
[0016] Hitherto, capsaicin was used as a medicinal product,
especially for treating the pains of shingles. Capsaicin causes a
release of neuropeptides, and especially of tachykinins which
originate from nerve endings of the epidermis and the dermis. The
Applicants found that the physiopathological mechanism common to
all the states of sensitive skins was associated with a great
capacity to release tachykinins and more especially substance P in
the skin. It is known, in addition, that substance P released by
epidermal sensory endings induces a cascade of biochemical events
in which the first steps affect the mast cells. The binding of
substance P to mast cell receptors induces a release of numerous
pro-inflammatory mediators, among them histamine, serotonin,
interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8)
and tumor necrosis factor alpha (TNF-alpha).
[0017] Moreover, the Applicants found that sensitive skins as are
defined above are, in addition, characterized by high levels of
interleukin-1 and/or of histamine in the superficial layers of the
epidermis. These levels rise proportionately as the state of
reactivity of the skin increases.
[0018] The Applicants have now discovered that the essential
characteristics of sensitive skins (irritation reactions and
cutaneous intolerance reactions) are associated with the release of
substance P and consequently with the release of histamine, of
interleukin-1 and particularly of TNF-alpha, and that interleukin-1
antagonists and/or TNF-alpha antagonists and/or histamine
antagonists may be used in the preventive and/or curative treatment
of sensitive skins.
[0019] Histamine, interleukin-1 and/or TNF-alpha "antagonists" are
understood to mean all substances capable of inhibiting the release
and/or synthesis and/or receptor binding of histamine, of
interleukin-1 and/or of TNF-alpha, respectively. The antagonists
inhibiting the receptor binding of histamine are agents specific
for the type 1 histamine (H.sub.1) receptor.
[0020] In addition, the Applicants found that the addition of
interleukin-1 antagonists and/or of TNF-alpha antagonists to
cosmetic, pharmaceutical or dermatological compositions for topical
application containing irritant products (alpha-hydroxy acids,
retinoids, benzoyl peroxide, etc.) also enabled the irritation
reactions usually caused by these products to be decreased or even
eliminated. These irritation reactions manifest themselves within
moments following application, in dysaesthesic sensations
(inflammation, burning, itching or pruritus sensations, prickling
sensations, tightness, etc.), and/or in red blotches, and/or in
edema. These irritation states may also manifest themselves some
time after application, in the persistence, appearance or
reappearance of the above-mentioned dysaesthesic sensations and/or
in red blotches and/or scales; these skin irritation states may
assume the appearance of plaques of cutaneous xerosis and/or
sores.
[0021] Moreover, histamine release induced by neurogenic
inflammation causes a vasodilatation which manifests itself in
erythema, edema and pruritus. Thus, the addition of histamine
antagonists specific for the H.sub.1 receptors to irritant
cosmetic, pharmaceutical or dermatological compositions also
enables the irritation reactions usually caused by these products
to be decreased or even eliminated.
[0022] To treat sensitive skins, the Applicants hence envisaged the
use of histamine antagonists, interleukin-1 antagonists and/or
TNF-alpha antagonists. Applicants found, in effect, surprisingly,
that the incorporation of histamine antagonists, interleukin-1
antagonists and/or TNF-alpha antagonists in a cosmetic,
pharmaceutical or dermatological composition enables the irritation
and/or dysaesthesic sensations and/or pruritus of the skin and/or
mucosae to be avoided.
[0023] Hence the subject of the present invention is the use of at
least one compound chosen from interleukin-1 antagonists, TNF-alpha
antagonists and combinations thereof, in a composition containing a
cosmetically, pharmaceutically or dermatologically acceptable
medium, for treating sensitive skins.
[0024] The subject of the present invention is also the use in a
topical composition of at least one compound chosen from
interleukin-1 antagonists, TNF-alpha antagonists and combinations
thereof, for preventing and/or combating skin irritations and/or
sores and/or erythema and/or sensations of inflammation and/or of
dysaesthesia and/or pruritus and/or prickling and/or tingling
and/or discomfort and/or tightness of the skin and/or mucosae.
[0025] According to the invention, the topical composition may
contain, in addition, a constituent chosen from histamine
antagonists and combinations thereof.
[0026] The subject of the present invention is also the use in a
topical composition of at least one constituent chosen from
histamine antagonists and combinations thereof, for preventing
and/or combating skin irritations and/or sores and/or sensations of
inflammation and/or of dysaesthesia and/or prickling and/or
tingling and/or discomfort and/or tightness of the skin and/or
mucosae.
[0027] A cosmetically, dermatologically or pharmaceutically
acceptable medium is a medium which is compatible with the skin,
scalp, nails and mucosae. The composition containing a histamine
antagonist and/or an interleukin-1 antagonist and/or a TNF-alpha
antagonist may hence be applied to the face, neck, hair and nails,
or any other area of the skin of the body such as the major folds
(axillary or inframammary regions, bend of the elbow and the
like).
[0028] For a substance to be recognized as a histamine,
interleukin-1 (IL-1) or TNF-alpha receptor antagonist, it must
satisfy, in particular, the following characteristic:
[0029] have a histamine, IL-1 or TNF-alpha receptor antagonist
pharmacological activity, that is to say, induce a coherent
pharmacological response in at least one of the following
tests:
[0030] for histamine receptor antagonists: an inhibition of the
contraction of smooth muscles induced by the administration of
histamine;
[0031] for IL-1 receptor antagonists: inhibition of the
IL-i-induced adhesion of macrophages to endothelial cells, or
inhibition of the IL-1-induced release of superoxide anions from
neutrophils;
[0032] for TNF-alpha receptor antagonists: inhibition of the
TNF-alpha-induced adhesion of macrophages to endothelial cells, or
inhibition of the TNF-alpha-induced release of superoxide anions
from neutrophils or inhibition of the mitogenic activity of
TNF-alpha with respect to the fibroblasts of the dermis.
[0033] The histamine, interleukin-1 (IL-1) or TNF-alpha antagonist
may, in addition, have a selective affinity for the specific
receptors for these compounds: H.sub.1, IL-1 and TNF-alpha.
[0034] For a substance to be recognized as an antagonist of the
release and/or synthesis of histamine, of interleukin-1 or of
TNF-alpha, it must satisfy, in particular, the following
characteristic:
[0035] inhibition of histamine release by mast cells stimulated
with the compound 48/80 or stimulated with a calcium ionophore (A23
187)
[0036] inhibition of the release of interleukin-1 or of TNF-alpha
by monocytes (U937 cells) differentiated with a phorbol ester
(PMA).
[0037] Hitherto, histamine antagonists were used to treat allergic
disorders systemically. Interleukin-1 antagonists are currently
being tested in certain chronic inflammatory disorders such as
rheumatic disorders, septic shock, asthma, psoriasis and ocular
allergies. TNF-alpha antagonists are currently being tested for
treating fever, septic shock and cachexia.
[0038] The antagonists of the invention are, in particular,
compounds comprising at least one heterocycle and nitrogen
compounds comprising at least one benzene ring.
[0039] The histamine H.sub.1 receptor antagonists which can be used
in the invention are those traditionally used in the treatment of
allergic and anaphylactic states, as well as those for combating
travel sickness. These compounds can be, for example,
diethylenediamine derivatives such as cinnarizine, cyclizine;
aminopropane derivatives such as dexchlorpheniramine, triprolidine;
phenothiazine derivatives such as promethazine, alimemazine; and
also the compounds mentioned on pages 116 to 118 of the book by
Joseph R. Prous, The Year's Drug News, Therapeutic Targets, 1994
edition, Prous Science Publishers, such as cetirizine HCl,
ebastine, loratadine, setastine HCl.
[0040] The histamine release inhibitors are, in particular, oxygen-
or sulfur-containing heterocyclic compounds such as furan
derivatives, benzofuran derivatives, thiophene derivatives and
benzothiophene derivatives, optionally containing nitrogenous
substituents, such as those described in the documents U.S. Pat.
No. 4,931,459, U.S. Pat. No. 4,910,317 and EP-A-299,457, and more
especially alkoxy- and/or aryloxytetrazolylbenzofurancarboxamides
or alkoxy- and/or aryloxytetrazolylbenzothiophenecarboxamides. By
way of example,
5-methoxy-3-phenoxy-N-(1H-tetrazol-5-yl)benzothiophene-2-carboxamide,
5-methoxy-3-(1-methylethoxy)-N-(1H-tetrazol-5-yl)benzothiophene-2-carboxa-
mide,
6-methoxy-3-(1-methylethoxy)-N-(1H-tetrazol-5-yl)benzothiophene-2-ca-
rboxamide,
5-methoxy-3-(1-methylethyl)-N-(1H-tetrazol-5-yl)benzothiophene--
2-carboxamide,
3-benzyloxy-5-methoxy-N-(1H-tetrazol-5-yl)benzothiophene-2--
carboxamide and
5-methoxy-3-phenoxy-N-(1H-tetrazol-5-yl)benzothiophene-2-c-
arboxamide may be mentioned.
[0041] An interleukin-1 release antagonist which can be used in the
invention can be auranofin or SKF-105809. SKF-105809 is
6,7-dihydro-2-[4-(methylsulfinyl)phenyl]-3-(4-pyridinyl)-5H-pyrrolo[1,2-a-
]imidazole. An interleukin-1 synthesis antagonist can be
lactoferin.
[0042] The TNF-alpha receptor antagonists and the inhibitors of
TNF-alpha release and/or synthesis which can be used in the
invention are, in particular, lisophyline, A802715 and
sulphasalazine. A802715 is a xanthine derivative available from
Hoechst which inhibits both TNF release and TN4 action having the
following structure: 1
[0043] The histamine antagonists, interleukin-1 antagonists and
TNF-alpha antagonists may be synthesized or extracted from natural
products (plant or animal).
[0044] In the compositions according to the invention, the
histamine antagonists, interleukin-1 antagonists and/or TNF-alpha
antagonists are preferably used in an amount ranging from 0.000001
to 5% by weight relative to the total weight of the composition,
and especially in an amount ranging from 0.0001 to 0.1% by weight
relative to the total weight of the composition.
[0045] The compositions according to the invention may be presented
in all pharmaceutical dosage forms normally used for topical
application, in particular in the form of aqueous,
aqueous-alcoholic or oily solutions, of dispersions of the lotion
or serum type, of anhydrous or lipophilic gels, of emulsions of
liquid or semi-solid consistency of the milk type, obtained by
dispersing a fatty phase in an aqueous phase (O/W) or vice versa
(W/O), or of suspensions or emulsions of soft, semi-solid or solid
consistency of the cream or gel type, or alternatively of
microemulsions, of microcapsules, of microparticles or of vesicular
dispersions of the ionic and/or nonionic type. These compositions
are prepared according to standard methods.
[0046] They may also be used for the scalp in the form of aqueous,
alcoholic or aqueous-alcoholic solutions, or in the form of creams,
gels, emulsions or foams or alternatively in the form of aerosol
compositions also containing a propellent agent under pressure.
[0047] The amounts of the different constituents of the
compositions according to the invention are those traditionally
used in the fields in question.
[0048] These compositions constitute, in particular, cleansing,
protective, treatment or skin care creams for the face, hands,
feet, major anatomical folds of the body (for example day creams,
night creams, make-up removal creams, foundation creams,
sun-protection creams), fluid foundations, make-up removal milks,
protective or skin care body milks, sun-protection or, better
still, after-sun milks, skin care lotions, gels or foams, such as
cleansing or disinfecting lotions, sun-protection lotions,
artificial tanning lotions, bath compositions, deodorant
compositions containing a bactericidal agent, aftershave gels or
lotions, depilatory creams, compositions for treating insect bites,
pain relief compositions or compositions for treating certain skin
disorders such as those mentioned above.
[0049] The compositions according to the invention may also consist
of solid preparations constituting cleansing bars or soaps.
[0050] The compositions may also be packaged in the form of an
aerosol composition also containing a propellent agent under
pressure.
[0051] The histamine antagonists, interleukin-1 antagonists and/or
TNF-alpha antagonists may also be incorporated in various hair care
or treatment compositions, and in particular shampoos, where
appropriate antiparasitic, setting lotions, treatment lotions,
styling creams or gels, dyeing (normally oxidation dyeing)
compositions, where appropriate in the form of coloring shampoos,
hair restructuring lotions, permanent-waving compositions (in
particular compositions for the first stage of permanent waving),
lotions or gels for combating hair loss, and the like.
[0052] The compositions of the invention may also be for
dentibuccal use, for example a toothpaste or a mouthwash. In this
case, the compositions can contain standard adjuvants and additives
for compositions for buccal use, and in particular surfactants,
thickening agents, humectant agents, polishing agents such as
silica, various active ingredients such as fluorides, especially
sodium fluoride, and, where appropriate, sweetening agents such as
saccharin sodium.
[0053] When the composition of 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 oils, emulsifiers and coemulsifiers
used in the composition in emulsion form are chosen from those
traditionally used in the cosmetics, pharmaceutical or
dermatological fields. The emulsifier and the coemulsifier are
present in the composition in a proportion ranging from 0.3% to 30%
by weight, and preferably from 0.5 to 30% or, better still, from
0.5 to 20%, by weight relative to the total weight of the
composition. The emulsion can, in addition, contain lipid
vesicles.
[0054] When the composition of the invention is an oily gel or
solution, the fatty phase can represent more than 90% of the total
weight of the composition.
[0055] In a known manner, the composition of the invention may also
contain adjuvants which are customary in the cosmetics,
pharmaceutical or dermatological field, such as hydrophilic or
lipophilic gelling agents, hydrophilic or lipophilic active agents,
preservatives, antioxidants, solvents, perfumes, fillers, screening
agents, bactericides, odor absorbers and coloring matter. The
amounts of these different adjuvants are those traditionally used
in the cosmetic, pharmaceutical or dermatological field, and are,
for example, from 0.01% to 10% of the total weight of the
composition. These adjuvants, depending on their nature, may be
introduced into the fatty phase, into the aqueous phase and/or into
lipid spherules.
[0056] As oils which can be used in the invention, mineral oils
(liquid paraffin), vegetable oils (liquid fraction of shea butter,
sunflower oil), animal oils (perhydrosqualene), synthetic oils
(Purcellin oil), silicone oils (cyclomethicone) and fluorinated
oils (perfluoro polyethers) may be mentioned. Fatty alcohols, fatty
acids (stearic acid) and waxes (paraffin, carnauba, beeswax) may
also be used as fatty substances.
[0057] As emulsifiers which can be used in the invention, glyceryl
stearate, polysorbate 60 and the PEG-6/PEG-32/glycol stearate
mixture sold under the name Tefose.RTM. 63 by the company
Gattefosse may be mentioned as examples.
[0058] As solvents which can be used in the invention, lower
alcohols, in particular ethanol and isopropanol, and propylene
glycol may be mentioned.
[0059] As hydrophilic gelling agents, carboxyvinyl polymers
(carbomer), acrylic copolymers such as acrylate/alkylacrylate
copolymers, polyacrylamides, polysaccharides such as
hydroxypropylcellulose, clays and natural gums may be mentioned,
and as lipophilic gelling agents, modified clays such as bentones,
metal salts of fatty acids such as aluminum stearates and
hydrophobic silica, or alternatively ethylcellulose and
polyethylene may be mentioned.
[0060] As hydrophilic active agents, proteins or protein
hydrolysates, amino acids, polyols, urea, allantoin, sugars and
sugar derivatives, water-soluble vitamins, starch and plant
extracts, in particular those of Aloe vera may be used.
[0061] As lipophilic active agents, retinol (vitamin A) and its
derivatives, tocopherol (vitamin E) and its derivatives, essential
fatty acids, ceramides and essential oils may be used.
[0062] The histamine antagonists, interleukin-1 antagonists and/or
TNF-alpha antagonists may, inter alia, be combined with active
agents intended, in particular, for preventing and/or treating skin
complaints. Among these active agents, there may be mentioned, by
way of example:
[0063] agents which modulate differentiation and/or proliferation
and/or skin pigmentation, such as retinoic acid and its isomers,
retinol and its esters, vitamin D and its derivatives, estrogens
such as estradiol, kojic acid or hydroquinone;
[0064] antibacterials such as clindamycin phosphate, erythromycin
or antibiotics of the tetracycline class;
[0065] antiparasitics, especially metronidazole, crotamiton or
pyrethrinoids;
[0066] antifungals, especially compounds belonging to the imidazole
class such as econazole, ketoconazole or miconazole or their salts,
polyene compounds such as amphotericin B, compounds of the
allylamine family such as terbinafine, or alternatively
octopirox;
[0067] steroidal anti-inflammatory agents such as hydrocortisone,
betamethasone valerate or clobetasol propionate, or non-steroidal
anti-inflammatory agents such as ibuprofen and its salts,
diclofenac and its salts, acetylsalicylic acid, acetaminophen or
glycyrrhetinic acid;
[0068] anesthetic agents such as lidocaine hydrochloride and its
derivatives;
[0069] antipruriginous agents such as thenalidine, trimeprazine or
cyproheptadine;
[0070] antiviral agents such as acyclovir;
[0071] keratolytic agents such as alpha- and beta-hydroxycarboxylic
or beta-ketocarboxylic acids, their salts, amides or esters, and
more especially alpha-hydroxy acids such as glycolic acid, lactic
acid, tartaric acid, citric acid and, generally speaking, the fruit
acids, and beta-hydroxy acids such as salicylic acid and its
derivatives, in particular its alkylated derivatives such as
5-n-octanoylsalicylic acid;
[0072] free-radical scavenging agents such as alpha-tocopherol or
its esters, superoxide dismutases, some metal chelators or ascorbic
acid and its esters;
[0073] antiseborrheic agents such as progesterone;
[0074] antidandruff agents such as octopirox or pyrithione
zinc;
[0075] anti-acne agents such as retinoic acid or benzoyl
peroxide.
[0076] Advantageously, the histamine antagonists, interleukin-1
antagonists and/or TNF-alpha antagonists are combined with products
having an irritant side-effect, and in particular active agents
commonly used in the cosmetics, pharmaceutical or dermatological
field. The presence of a histamine antagonist, an interleukin-1
antagonist and/or a TNF-alpha antagonist in a cosmetic,
pharmaceutical or dermatological composition containing a product
or even an active agent having an irritant effect enables this
irritant effect to be greatly attenuated or even eliminated.
[0077] In particular, the histamine antagonist, interleukin-1
antagonist and/or TNF-alpha antagonist make it possible, in
particular, to increase the amount of cosmetic, pharmaceutical or
dermatological active agent relative to the amount normally used,
with a view to improved efficacy.
[0078] Thus, the subject of the invention is also a composition
containing, in a cosmetically, pharmaceutically or dermatologically
acceptable medium, at least one product having an irritant
side-effect, characterized in that it contains at least one agent
antagonistic to this effect, chosen from interleukin-1 antagonists,
TNF-alpha antagonists and combinations thereof.
[0079] The subject of the invention is also the use, in a topical
composition containing a cosmetically, pharmaceutically or
dermatologically acceptable medium and at least one product having
an irritant side-effect, of at least one compound chosen from
histamine antagonists, interleukin-1 antagonists, TNF-alpha
antagonists and combinations thereof, for eliminating this irritant
effect.
[0080] The irritant products to which the invention applies are, in
particular, perfumes, surfactants (ionic or nonionic),
preservatives, some sunscreen agents, organic solvents, alcoholic
solutions and some cosmetic, pharmaceutical or dermatological
active agents.
[0081] In particular, the active agents having an irritant
side-effect are chosen from .alpha.-hydroxy acids (glycolic,
lactic, malic, citric, tartaric, mandelic), .beta.-hydroxy acids
(salicylic acid and its derivatives), .alpha.-keto acids,
.beta.-keto acids, retinoids (retinol and its esters, retinal,
retinoic acid and its derivatives, retinoids, in particular those
described in the documents FR-A-2,570,377, EP-A-199,636,
EP-A-325,540, EP-A-402,072), anthralins (dioxyanthranol),
anthranoids, peroxides (in particular benzoyl peroxide), minoxidil,
lithium salts, antinetabolites, vitamin D and its derivatives, hair
dyes or colorants (para-phenylenediamine and its derivatives,
aminophenols), alcoholic perfuming solutions (perfumes, toilet
water, aftershave, deodorants), antiperspirant agents (some
aluminum salts), depilatory or permanent-waving active agents
(thiols), depigmenting agents (hydroquinone) and delousing active
agents (pyrethrin).
[0082] The use of a histamine antagonist, interleukin-1 antagonist
and/or TNF-alpha antagonist makes it possible, in particular, to
multiply from 2- to 10-fold the amount of product, and more
especially of active agent, having an irritant side-effect,
relative to the prior state of the art, without all the unpleasant
sensations mentioned above being experienced. Thus, it is possible
to use hydroxy acids up to 50% of the weight of the composition or
retinoids up to 5%, without any discomfort.
[0083] In particular, the composition contains one or more
histamine antagonists, one or more interleukin-1 antagonists and/or
one or more TNF-alpha antagonists chosen from alkoxy- and/or
aryloxytetrazolylbenzofu- rancarboxamides or an alkoxy- and/or
aryloxytetrazolylbenzothiophenecarbox- amides and one or more
active agents having an irritant side-effect, chosen from
alpha-hydroxy acids and beta-hydroxy acids.
[0084] The subject of the present invention is, in addition, a
cosmetic treatment process, characterized in that a composition as
described above, containing at least one TNF-alpha antagonist in a
cosmetically acceptable medium is applied to the skin, to the scalp
and/or to the mucosae.
[0085] The cosmetic treatment process of the invention may be
carried out, in particular, by applying the hygiene or cosmetic
compositions as are defined above according to the customary
technique for using these compositions. For example: application of
creams, gels, serums, lotions, make-up removal milks or after-sun
compositions to the skin or to dry hair, application of a hair
lotion to wet hair or of shampoos, or alternatively application of
dentifrice to the gums.
[0086] The examples which follow illustrate the invention. In these
examples, the proportions shown are percentages by weight.
EXAMPLE 1
[0087] Make-up removal lotion for the face
1 Loratidine 0.05 Antioxidant 0.05 Isopropanol 40.00 Preservative
0.30 Water qs 100%
EXAMPLE 2
[0088] Make-up removal lotion for the face
2 Cetirizine 0.001 Antioxidant 0.05 Isopropanol 40.00 Preservative
0.30 Water qs 100%
EXAMPLE 3
[0089] Face care gel
3 Auranofin 0.05 Hydroxypropylcellulose (Klucel H 1.00 sold by the
company Hercules) Antioxidant 0.05 Isopropanol 40.00 Preservative
0.30 Water qs 100%
EXAMPLE 4
[0090] Face care gel
4 Lisophyline 0.04 Hydroxypropylcellulose (Klucel H 1.00 sold by
the company Hercules) Antioxidant 0.05 Isopropanol 40.00
Preservative 0.30 Water qs 100%
EXAMPLE 5
[0091] Face care cream (oil-in-water emulsion)
5 Sulphasalazine 0.02 Glyceryl stearate 2.00 Polysorbate 60 (Tween
60 sold by the 1.00 company ICI) Stearic acid 1.40 Triethanolamine
0.70 Carbomer 0.40 Liquid fraction of shea butter 12.00
Perhydrosqualene 12.00 Antioxidant 0.05 Perfume 0.5 Preservative
0.30 Water qs 100%
EXAMPLE 6
[0092] Treatment shampoo
6 Loratadine 0.02 Hydroxypropylcellulose (Klucel H 1.00 sold by the
company Hercules) Perfume 0.50 Preservative 0.30 Water qs 100%
EXAMPLE 7
[0093] Antiwrinkle skin care cream for the face (oil-in-water
emulsion)
7 Cetirizine 0.15 Glyceryl stearate 2.00 Polysorbate 60 (Tween 60
sold by the 1.00 company ICI) Stearic acid 1.40
5-n-Octanoylsalicylic acid 0.50 Triethanolamine 0.70 Carbomer 0.40
Liquid fraction of shea butter 12.00 Perhydrosqualene 12.00
Antioxidant 0.05 Perfume 0.50 Preservative 0.30 Water qs 100%
EXAMPLE 8
[0094] Emulsified gel for treating insect bites (oil-in-water
emulsion)
8 Cyclomethicone 3.00 Purcellin oil (sold by the company 7.00
Dragoco) PEG-6/PEG-32/glycol stearate (Tefose .RTM. 63 from
Gattefosse) 0.30 Setastine 0.02 Preservative 0.30 Perfume 0.40
Carbomer 0.60 Crotamiton 5.00 Glycyrrhetinic acid 2.00 Ethyl
alcohol 5.00 Triethanolamine 0.20 Water qs 100%
EXAMPLE 9
[0095] Pain relief gel
9 Cetirizine 0.03 Hydroxypropylcellulose (Klucel H 1.00 sold by the
company Hercules) Antioxidant 0.05 Lidocaine hydrochloride 2.00
Isopropanol 40.00 Preservative 0.30 Water qs 100%
EXAMPLE 10
[0096] Cream for treating solar erythema (oil-in-water
emulsion)
10 Dexchlorpheniramine 0.25 Glyceryl stearate 2.00 Polysorbate 60
(Tween 60 sold by the 1.00 company ICI) Stearic acid 1.40
Glycyrrhetinic acid 2.00 Triethanolamine 0.70 Carbomer 0.40 Liquid
fraction of shea butter 12.00 Sunflower oil 10.00 Antioxidant 0.05
Perfume 0.5 Preservative 0.30 Water qs 100%
EXAMPLE 11
[0097] Antiwrinkle skin care cream for the face (oil-in-water
emulsion) This example differs from EXAMPLE 7 by the replacement of
cetirizine by
3-benzyloxy-5-methoxy-N-(1H-tetrazol-5-yl)benzothiophene-2-carboxamide,
manufactured according to EXAMPLE 1 of the document EP-A-299,457,
and 5-n-octanoylsalicylic acid by glycolic acid.
EXAMPLE 12
[0098] Antiwrinkie skin care cream for the face (oil-in-water
emulsion) This example differs from EXAMPLE 7 by the replacement of
sulphasalazine by
5-methoxy-3-phenoxy-N-(1H-tetrazol-5-yl)benzothiophene-2-carboxamide,
manufactured according to EXAMPLE 2 of the document EP-A-299,457,
and 5-n-octanoylsalicylic acid by a fruit acid mixture (lactic,
glycolic, tartaric, citric and malic acids).
EXAMPLE 13
[0099] Gel for treating acne
11 all-trans-Retinoic acid 0.05 Loratidine 0.55
Hydroxypropylcellulose (Klucel H 1 sold by the company Hercules)
Antioxidant 0.05 Isopropanol 40 Preservative 0.3 Water qs 100%
* * * * *