U.S. patent application number 09/429562 was filed with the patent office on 2001-12-13 for therapeutic/cosmetic compositions comprising cgrp antagonists for treating sensitive human skin.
Invention is credited to BRETON, LIONEL, DE LACHARRIERE, OLIVIER.
Application Number | 20010051157 09/429562 |
Document ID | / |
Family ID | 26231712 |
Filed Date | 2001-12-13 |
United States Patent
Application |
20010051157 |
Kind Code |
A1 |
BRETON, LIONEL ; et
al. |
December 13, 2001 |
THERAPEUTIC/COSMETIC COMPOSITIONS COMPRISING CGRP ANTAGONISTS FOR
TREATING SENSITIVE HUMAN SKIN
Abstract
Topically applicable pharmaceutical/dermatological/cosmetic
compositions well suited for the therapeutic treatment or care of
sensitive human skin, hair, mucous membranes, nails and/or the
scalp, in particular for reducing or avoiding the skin-irritant
side effects of a variety of bioactive agents, for example the
.alpha.-hydroxy acids, comprise a therapeutically/cosmetically
effective amount of at least one calcitonin gene related peptide
("CGRP") antagonist, e.g., CGRP 8-37 or an anti-CGRP antibody.
Inventors: |
BRETON, LIONEL; (VERSAILLES,
FR) ; DE LACHARRIERE, OLIVIER; (PARIS, FR) |
Correspondence
Address: |
BURNS DOANE SWECKER & MATHIS L L P
POST OFFICE BOX 1404
ALEXANDRIA
VA
22313-1404
US
|
Family ID: |
26231712 |
Appl. No.: |
09/429562 |
Filed: |
October 28, 1999 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09429562 |
Oct 28, 1999 |
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08592529 |
Jan 26, 1996 |
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6019967 |
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Current U.S.
Class: |
424/133.1 ;
424/130.1; 424/158.1; 424/809; 514/12.2; 514/18.6; 514/20.7;
514/21.3; 530/300; 530/387.1 |
Current CPC
Class: |
A61Q 19/004 20130101;
A61K 8/64 20130101; A61K 31/167 20130101; A61Q 19/00 20130101; A61Q
19/08 20130101; C07K 16/26 20130101; A61K 38/225 20130101; A61K
2800/70 20130101; A61K 2800/75 20130101; A61Q 1/14 20130101; A61Q
5/006 20130101; A61Q 17/00 20130101; A61Q 19/005 20130101 |
Class at
Publication: |
424/133.1 ;
424/158.1; 424/130.1; 424/809; 514/2; 530/387.1; 530/300 |
International
Class: |
A01N 037/18; A61K
038/00; A61K 039/395; A61K 039/40; A61K 039/42; C07K 002/00; C07K
004/00; C07K 005/00; C07K 007/00; C07K 014/00; C07K 016/00; C07K
017/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 26, 1995 |
FR |
95-00900 |
Claims
What is claimed is:
1. A topically applicable therapeutic/cosmetic composition adopted
for the therapeutic treatment or care of sensitive human skin,
hair, mucous membranes, nails and/or the scalp, comprising an
effective therapeutically/cosmetically effective amount of at least
one CGRP antagonist and a therapeutically/cosmetically acceptable
vehicle, diluent or carrier therefor.
2. The therapeutic/cosmetic composition as defined by claim 1, said
at least one CGRP antagonist comprising CGRP 8-37 or an anti-CGRP
antibody.
3. The therapeutic/cosmetic composition as defined by claim 1, said
at least one CGRP antagonist comprising from 0.000001% to 10% by
weight thereof.
4. The therapeutic/cosmetic composition as defined by claim 3, said
at least one CGRP antagonist comprising from 0.0001% to 50% by
weight thereof.
5. The therapeutic/cosmetic composition as defined by claim 1,
comprising a solution, emulsion, milk, lotion, microemulsion, gel,
serum, cream, mousse, soap, shampoo, aerosol, dispersion,
microcapsules, or microparticles.
6. The therapeutic/cosmetic composition as defined by claim 1,
comprising at least one antibacterial agent, antiparasitic agent,
antifungal agent, anti-inflammatory agent, anti-pruriginous agent,
anaesthetic, antiviral agent, keratolytic agent, anti-free-radical
agent, antiseborrhoeic agent, anti-dandruff agent, antiacne agent,
and/or agent that modifies the differentiation and/or proliferation
and/or pigmentation of human skin.
7. The therapeutic/cosmetic composition as defined by claim 6,
comprising lidocaine hydrochloride, an antiparasitic agent or a
nonsteroidal anti-inflammatory.
8. The therapeutic/cosmetic composition as defined by claim 1,
further comprising at least one normally skin-irritating bioactive
agent.
9. The therapeutic/cosmetic composition as defined by claim 8, said
at least one normally skin-irritating bioactive agent comprising a
fragrance, a surfactant, a preservative, a sunscreen, an organic
solvent, or an alcohol.
10. The therapeutic/cosmetic composition as defined by claim 8,
said at least one normally skin-irritating bioactive agent
comprising an .alpha.-hydroxy acid, a .beta.-hydroxy acid, an
.alpha.-keto acid, a .beta.-keto acid, a retinoid, an anthralin, an
anthranoid, a peroxide, minoxidil, a lithium salt, an
antimetabolite, vitamin D or derivative thereof, a hair dye or
colorant, an alcoholic perfume, an antiperspirant, a depilatory, a
permanent-waving active agent, a depigmenting active agent, or an
anti-lice active agent.
11. The therapeutic/cosmetic composition as defined by claim 10,
said at least one normally skin-irritating bioactive agent
comprising an .alpha.-hydroxy acid.
12. A regime for therapeutically preventing and/or combating skin
irritations and/or dartres and/or erythema and/or dysaesthetic
sensations and/or sensations of inflammation and/or pruritis of
human skin, hair, scalp, nails and/or the mucous membranes,
comprising topically applying thereto, for such period of time as
is required to elicit the desired biological response, a
therapeutically/cosmetically effective amount of at least one CGRP
antagonist.
13. A regime for therapeutically preventing and/or combating skin
irritations and/or dartres and/or erythema and/or dysaesthetic
sensations and/or sensations of inflammation and/or pruritis of
human skin, hair, scalp, nails and/or the mucous membranes,
comprising topically applying thereto, for such period of time as
is required to elicit the desired biological response, a
therapeutically/cosmetically effective amount of the
therapeutic/cosmetic composition as defined by claim 1.
14. A regime for therapeutically preventing and/or combating skin
irritations and/or dartres and/or erythema and/or dysaesthetic
sensations and/or sensations of inflammation and/or pruritis of
human skin, hair, scalp, nails and/or the mucous membranes,
comprising topically applying thereto, for such period of time as
is required to elicit the desired biological response, a
therapeutically/cosmetically effective amount of the
therapeutic/cosmetic composition as defined by claim 8.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Technical Field of the Invention
[0002] The present invention relates to the formulation of an
antagonist of CGRP (peptide derived from the calcitonin gene:
Calcitonin Gene Related Peptide, or "CGRP") into topically
applicable cosmetic/pharmaceutical/dermatological compositions, for
the treatment of sensitive skin-types, as well as to cosmetic
compositions containing a CGRP antagonist for reducing or
eliminating the irritant effects elicited by certain active agents,
and especially by certain bioactive agents conventionally employed
in the cosmetics, pharmaceutical or dermatological field.
[0003] 2. Description of the Prior Art
[0004] It is known to this art that certain skin-types are more
sensitive than others. The symptoms of sensitive skin-types were
heretofore poorly characterized and the problem of these skin-types
was, as a result, poorly defined; the exact mechanism involved in
the sensitivity--nonallergic cutaneous hyperreactivity--of the
skin, was unknown. In certain quarters it was believed that a
sensitive skin was a skin which reacted to cosmetic products, while
others believed that it concerned a skin which reacted to a variety
of external factors, not necessarily associated with cosmetic
products.
[0005] Certain tests have been conducted in attempting to define
sensitive skin-types, for example tests using lactic acid and DMSO
which are known to be irritant substances: see, for example, the
article by K. Lammintausta et al, Dermatoses, 36, pages 45-49
(1988); and the article by T. Agner and J. Serup, Clinical and
Experimental Dermatolooy, 14, pages 214-217 (1989). However, these
tests did not make it possible to characterize sensitive
skin-types.
[0006] Moreover, sensitive skin-types were likened to allergic
skin-types.
[0007] Taking account of the ignorance of the characteristics of
sensitive skin-types, it was hitherto very difficult to treat them
and they were treated indirectly, for example by limiting, in the
cosmetic compositions, active species eliciting an irritant effect,
such as surfactants, preservatives or perfumes, as well as certain
otherwise bioactive agents.
[0008] The assignee hereof has now conducted many clinical tests
and has been able to determine the symptoms associated with
sensitive skin-types. These symptoms are, in particular, subjective
signs, which are essentially dysaesthesic sensations. By the term
"dysaesthesic sensations" are intended more or less painful
sensations experienced in an area of the skin, such as stinging,
tingling, itching or pruritus, burning, inflammation, discomfort,
pulling, etc.
[0009] The assignee hereof has also been able to demonstrate that a
sensitive skin-type is not an allergic skin-type. Indeed, an
allergic skin-type is a skin-type 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 individuals. To the
contrary, the essential characteristic of sensitive skin, according
to the assignee hereof, is a mechanism of response to external
factors, which may be the case for any individual, even if the
individuals said to have sensitive skin react faster thereto than
the other individuals. This is a nonspecific mechanism and not an
immunological one.
[0010] It has now been determined that sensitive skin-types can be
divided into two major clinical forms; irritable and/or reactive
skin-types and intolerant skin-types.
[0011] An irritable and/or reactive skin-type is a skin-type which
reacts by a pruritus, i.e., by itching, or by stinging, to various
factors such as the environment, emotions, foods, the wind,
rubbing, shaving, soap, surfactants, hard water having a high
calcium concentration, temperature variations or wool. In general,
these signs are associated with a dry skin with or without dartres,
or with a skin which displays an erythema.
[0012] An intolerant skin-type is a skin-type which reacts, by
sensations of inflammation, pulling, tingling and/or redness, to
various factors such as the environment, emotions and foods. In
general, these signs are associated with a hyperseborrhoeic or
acneic skin-type with or without dartres, and with an erythema.
[0013] "Sensitive" scalps have a more unequivocal clinical
semeiology: the sensations of pruritus and/or of stinging and/or of
inflammation are essentially triggered by local factors such as
rubbing, soap, surfactants, hard water with a high calcium
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 and the
presence of dandruff are often associated with the above signs.
[0014] Moreover, in certain anatomical regions such as the major
folds (groin, genital, axillary, popliteal, anal and submammary
regions, and in the crook of the elbow) and the feet, sensitive
skin is reflected in pruriginous sensations and/or dysaesthesic
sensations (inflammation, stinging) associated in particular with
sweat, rubbing, wool, surfactants, hard water with a high calcium
concentration and/or temperature variations.
[0015] The assignee hereof has also now developed a test in order
to determine whether or not a skin-type is sensitive. Indeed, after
having carried out a multitude of tests for the purpose of defining
sensitive skin, it has now surprisingly been found that there is a
nexus between individuals with sensitive skin and those who react
to a topical application of capsaicin.
[0016] The capsaicin test entails applying, to about 4 cm.sup.2 of
skin, 0.05 ml of a cream containing 0.075% of capsaicin and in
noting the appearance of subjective signs induced by this
application, such as stinging, burning and itching. In individuals
having sensitive skin, these signs appear between 3 and 20 minutes
after application and are succeeded by the appearance of an
erythema which begins at the edge of the zone of application.
[0017] Hitherto, capsaicin was used as a medicinal active agent, in
particular for treating zona pains. Capsaicin induces a release of
neuropeptides from sensitive nerve fibers, and in particular of
CGRP which originates from epidermal and dermal nerve endings. It
has been observed that the physiopathological pattern common to the
conditions of sensitive skin-types was associated with a marked
ability to release neuropeptides, and more particularly CGRP, into
the skin. The dysaesthesic manifestations which are induced by
their release are referred to as "neurogenic."
[0018] CGRP is a polypeptide chemical species produced and released
by a nerve ending. CGRP is involved, in particular, in respiratory
and inflammatory diseases, in allergic diseases and in certain
dermatological diseases such as eczema or prurigo.
SUMMARY OF THE INVENTION
[0019] It has now been determined that one of the essential
characteristics of sensitive skin-types is associated with the
release of CGRP and, thus, that the use of CGRP antagonists could
permit a preventive and/or curative effect to be obtained for
sensitive skin-types induced by an exogeneous factor, said factor
being able to modify biophysical and biochemical skin parameters.
Furthermore, one of particularities of sensitive skin is to answer
to external irritation signals more quickly and easily than normal
skins. In addition, each irritation of a sensitive skin begins by
subjective signs (stinging, burning, etc.).
[0020] To treat sensitive skin-types, the CGRP antagonists are
hereby employed. Indeed, it has now surprisingly been observed that
the incorporation of a CGRP antagonist into a cosmetic,
pharmaceutical or dermatological composition avoids the irritation
of and/or dysaesthesic sensations in and/or pruritus of the skin
and/or of the mucous membranes and/or erythema.
[0021] Briefly, the present invention features the formulation of
at least one CGRP antagonist into compositions comprising a
cosmetically, pharmaceutically or dermatologically acceptable
medium, for treating sensitive skin-types, and for correcting
neurogenic indications.
[0022] The present invention also features the use of at least one
CGRP antagonist for preventing and/or combating skin irritations
and/or dartres and/or erythema and/or inflammation sensations
and/or dysaesthesia and/or pruritus of the skin and/or the mucous
membranes.
DETAILED DESCRIPTION OF BEST MODE AND SPECIFIC/PREFERRED
EMBODIMENTS OF THE INVENTION
[0023] More particularly according to the present invention, by a
"cosmetically, pharmaceutically or dermatologically acceptable
medium" is intended a medium which is compatible with the skin, the
scalp, the nails and the mucous membranes. The composition
containing the CGRP antagonist may be topically applied to the
face, the neck, the hair and the nails, or any other area of body
skin such as the major folds (axillary and submammary regions, the
crook of the elbow, and the like).
[0024] By "CGRP antagonist" is intended any molecule, whether
organic or inorganic, which is capable of effecting an inhibition
of the receptor binding of the CGRP or of effecting an inhibition
of the synthesis and/or release of CGRP by sensitive nerve
fibers.
[0025] In order for a chemical species to be recognized as a CGRP
antagonist, it must comply in particular with the following
characteristic: have a pharmacological antagonist activity towards
CGRP, i.e., induce a coherent pharmacological response, in
particular, in one of the following tests:
[0026] (a) the antagonist species must reduce the vasodilation
induced by capsaicin, and/or
[0027] (b) the antagonist species must induce an inhibition of the
release of CGRP by sensitive nerve fibers, and/or
[0028] (c) the antagonist species must induce an inhibition of the
contraction of the smooth muscle of the deferent canal induced by
CGRP.
[0029] In addition, the antagonist must have an affinity for the
CGRP receptors.
[0030] Hitherto, a correlation had not been established between
CGRP and sensitive skin. The clinical signs of sensitive skin are
essentially subjective: stinging, tingling, pruritus, pulling,
inflammation and erythema. These signs are due to nonspecific
external factors. The symptoms appear to be essentially localized
on the face, the neck and the scalp, but may also appear on the
entire body.
[0031] CGRP 8-37, an anti-CGRP antibody, is suitable for use
according to this invention, for example, as a CGRP antagonist.
[0032] In the compositions according to the invention, the CGRP
antagonist is preferably employed in an amount ranging from
0.000001% to 10% by weight relative to the total weight of the
composition, and in particular in an amount ranging from 0.0001% to
5% by weight relative to the total weight of the composition.
[0033] The compositions of the invention may be formulated into all
the pharmaceutical forms normally employed for topical application,
in particular in the form of aqueous, aqueous/alcoholic or oily
solutions or dispersions of the lotion or serum type, anhydrous or
lipophilic gels, emulsions of liquid or semi-liquid consistency of
the milk type, obtained by dispersion of a fatty phase in an
aqueous phase (O/W) or conversely (W/O), or suspensions or
emulsions of smooth, semi-solid or solid consistency of the cream
or gel type, or alternatively microemulsions, microcapsules or
microparticles, or vesicle dispersions of ionic and/or nonionic
type. These compositions are formulated according to conventional
techniques.
[0034] They may also be used for the hair in the form of aqueous,
alcoholic or aqueous/alcoholic solutions, or in the form of creams,
gels, emulsions or mousses or alternatively in the form of aerosol
compositions also containing a propellant under pressure.
[0035] The amounts of the various constituents of the compositions
according to the invention are those conventionally used in the
fields under consideration.
[0036] These compositions constitute, in particular, cleansing,
protective, treatment or care creams for the is face, for the
hands, for the feet, for the major anatomical folds or for the body
(for example day creams, night creams, makeup-removing creams,
foundation creams and sun creams), makeup products such as fluid
foundations, makeup-removing milks, body milks for care or
protection, after-sun products in the form of milks, lotions, gels
or mousses for skin care, such as cleansing or disinfecting
lotions, antisun lotions, artificial tanning lotions, compositions
for the bath, deodorizing compositions containing a bactericide,
aftershave products (gels or lotions), hair-removing creams,
compositions to counter insect bites, pain-relief compositions,
compositions for treating acne, hyperseborrhoeic skin or
seborrhoeic dermatitis, and compositions for treating certain skin
diseases such as severe pruritus, rosacea, acne, leg ulcers,
psoriasis, pustules and vibices.
[0037] The compositions according to the invention may also be
formulated as solid preparations constituting cleansing bars or
soaps.
[0038] The CGRP antagonist may also be incorporated into various
haircare or hair treatment compositions, and in particular
shampoos, which may be antiparasitic shampoos, hairsetting lotions,
treating lotions, styling creams or gels, dye compositions (in
particular oxidation dyes) optionally in the form of coloring
shampoos, restructuring lotions for the hair, permanent-wave
compositions (in particular compositions for the first stage of a
permanent-waving operation), lotions or gels for combating hair
loss, and the like.
[0039] The compositions of the invention may also be formulated for
buccodental use, for example as a toothpaste or a mouthwash. In
this event, the subject compositions may contain adjuvants and
additives which are conventional for compositions for buccal use
and, in particular, surfactants, thickeners, wetting agents,
polishing agents such as silica, various active ingredients such as
fluorides, in particular sodium fluoride, and optionally sweeteners
such as sodium saccharinate.
[0040] When the compositions of the invention are formulated as an
emulsion, the proportion of the fatty phase advantageously ranges
from 5% to 80% by weight, and preferably from 5% to 50% by weight,
relative to the total weight of the composition. The oils, the
emulsifiers and the coemulsifiers employed in the compositions in
emulsion form are selected from among those used conventionally in
the cosmetics field. The emulsifier and the coemulsifier are
advantageously present in the compositions at 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. The
emulsion may also contain lipid vesicles.
[0041] When the compositions of the invention comprise an oily
solution or gel, the fatty phase may constitute more than 90% of
the total weight of the composition.
[0042] In known manner, the cosmetic compositions of the invention
may also contain additives and adjuvants which are common in the
cosmetics, pharmaceutical or dermatological field, such as
hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic
active agents, preservatives, antioxidants, solvents, fragrances,
fillers, screening agents, bactericides, odor absorbers and
dyestuffs and colorants. The amounts of these various additives and
adjuvants are those used conventionally in the cosmetics field and
range, for example, from 0.01% to 10% of the total weight of the
composition. Depending on their nature, these adjuvants may be
introduced into the fatty phase, into the aqueous phase and/or into
the lipid spherules.
[0043] Exemplary oils which are suitable for the compositions of
the invention include mineral oils (liquid petrolatum), plant oils
(liquid fraction of karite butter, sunflower oil), animal oils
(perhydrosqualene), synthetic oils (Purcellin oil), silicone oils
(cyclomethicone) and fluoro oils (perfluoropolyethers). Fatty
alcohols, fatty acids (stearic acid) and waxes beeswax, carnauba
wax or paraffin wax may also be used as fats.
[0044] Exemplary emulsifiers according to the invention include
glyceryl stearate, polysorbate 60 and the PEG-6/PEG-32/glycol
stearate mixture marketed under the trademark Tefose.RTM. 63 by
Gattefosse.
[0045] Exemplary solvents accorrding to the invention include the
lower alcohols, in particular ethanol and isopropanol, and
propylene glycol.
[0046] Exemplary hydrophilic gelling agents which are suitable
include carboxyvinyl polymers (carbomer), acrylic copolymers such
as acrylate/alkylacrylate copolymers, polyacrylamides,
polysaccharides such as hydroxypropyl cellulose, natural gums and
clays, and, as lipophilic gelling agents, representative thereof
are the modified clays such as bentones, fatty acid metal salts
such as aluminum stearates, and hydrophobic silica, ethyl cellulose
and polyethylene.
[0047] Exemplary hydrophilic active agents which may be
incorporated include 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.
[0048] And exemplary lipophilic active agents include retinol
(vitamin A) and derivatives thereof, tocopherol (vitamin E) and
derivatives thereof, essential fatty acids, ceramides and essential
oils.
[0049] It is also intended, inter alia, to combine the CGRP
antagonists with active agents intended in particular for the
prevention and/or treatment of skin conditions, complaints and
afflictions. Exemplary of these active agents are:
[0050] (1) Agents which modify cutaneous differentiation and/or
proliferation and/or pigmentation such as retinoic acid and isomers
thereof, retinol and esters thereof, vitamin D and derivatives
thereof, estrogens such as estradiol, kojic acid or
hydroquinone;
[0051] (2) Antibacterial agents such as clindamycin phosphate,
erythromycin or antibiotics from the tetracycline family;
[0052] (3) Antiparasitic agents, in particular metronidazole,
crotamiton or pyrethroids;
[0053] (4) Antifungal agents, in particular compounds of the
imidazole family such as econazole, ketoconazole or miconazole or
salts thereof, polyene compounds such as amphotericin B, compounds
of the allylamine family such as terbinafine, or alternatively
octopirox;
[0054] (5) Steroidal anti-inflammatory agents such as
hydrocortisone, betamethasone valerate or clobetasol propionate, or
nonsteroidal anti-inflammatory agents such as ibuprofen and salts
thereof, diclofenac and salts thereof, acetylsalicylic acid,
acetaminophen or glycyrrhetinic acid;
[0055] (6) Anaesthetics such as lidocaine hydrochloride and
derivatives thereof;
[0056] (7) Antipruriginous agents such as thenaldine, trimeprazine
or cyproheptadine;
[0057] (8) Antiviral agents such as acyclovir;
[0058] (9) Keratolytic agents such as alpha- and
beta-hydroxycarboxylic acids or beta-ketocarboxylic acids, the
salts, amides or esters thereof and more particularly hydroxy acids
such as glycolic acid, lactic acid, salicylic acid, citric acid and
fruit acids in general, and 5-n-octanoylsalicylic acid;
[0059] (10) Anti-free-radical agents such as alpha-tocopherol or
esters thereof, superoxide dismutases, certain metal chelating
agents or ascorbic acid and esters thereof;
[0060] (11) Antiseborrhoeic agents such as progesterone;
[0061] (12) Antidandruff agents such as octopirox or zinc
pyrithione;
[0062] (13) Antiacne agents such as retinoic acid or benzoyl
peroxide.
[0063] Advantageously, the CGRP antagonists are combined with
compounds or species, and in particular active agents normally
eliciting an irritant side effect, and, especially, active agents
used conventionally in the cosmetic, pharmaceutical or
dermatological field. The presence of a CGRP antagonist in a
cosmetic, pharmaceutical or dermatological composition containing
an active agent exhibiting an irritant effect makes it possible to
attenuate this irritant effect greatly, or even to eliminate it
altogether.
[0064] In particular, the CGRP antagonists permit increasing the
amount of cosmetic, pharmaceutical or dermatological active agent
relative to the amount normally employed, for the purpose of
improved efficacy.
[0065] Thus, the present invention also features topically
applicable compositions containing a cosmetically, pharmaceutically
or dermatologically acceptable medium and at least one active agent
exhibiting an irritant side effect, and also comprising at least
one CGRP antagonist.
[0066] The irritants according to the invention include, in
particular, fragrances, surfactants (ionic or nonionic
surfactants), preservatives, certain sunscreens, organic solvents,
alcoholic solutions and certain cosmetic, pharmaceutical or
dermatological active agents.
[0067] In particular, the active agents exhibiting an irritant side
effect are selected from among .alpha.-hydroxy acids (glycolic
acid, lactic acid; malic acid, citric acid, tartaric acid and
mandelic acid), .beta.-hydroxy acids (salicylic acid and
derivatives thereof), .alpha.-keto acids, .beta.-keto acids,
retinoids (retinol and esters thereof, retinal, retinoic acid and
derivatives thereof, and retinoids, in particular those described
in FR-A-2,570,377, EP-A-199,636, EP-A-325,540 and EP-A-402,072),
anthralins (dioxyanthranol), anthranoids, peroxides, minoxidil,
lithium salts, antimetabolites, vitamin D and derivatives thereof,
hair dyes or colorants (para-phenylenediamine and derivatives
thereof, and aminophenols), perfumed alcoholic solutions (perfumes,
eaux de toilette, aftershave and deodorants), antiperspirants
(certain aluminum salts), depilatory or permanent-waving active
agents (thiols), depigmenting agents (hydroquinone) and anti-lice
active agents (pyrethrin).
[0068] The use of a CGRP antagonist makes it possible, in
particular, to amplify the amount of product, and more especially
of active agent exhibiting an irritant side effect, by 2 to 10
times compared with the state of the art, without experiencing the
aforesaid discomforts. Thus, it is possible to formulate the
hydroxy acids at up to 50% of the weight of the composition, or the
retinoids at up to 5%, without any discomfort.
[0069] The present invention also features a cosmetic treatment,
comprising topically applying a composition as described above,
containing at least one CGRP antagonist in a cosmetically
acceptable medium, to the skin, to the scalp and/or to the mucous
membranes.
[0070] The cosmetic treatment of the invention may be carried out,
in particular, by applying the cosmetic or hygiene compositions as
described above, via the usual technique for applying these
compositions. For example: application of creams, gels, sera,
lotions, makeup-removing milks or aftersun compositions to the skin
or to dry hair, application of a hair lotion to wet hair,
application of shampoo, or alternatively application of toothpaste
to the gums.
[0071] In order to further illustrate the present invention and the
advantages thereof, the following specific examples are given, it
being understood that same are intended only as illustrative and in
nowise limitative.
[0072] In said examples to follow, all parts and percentages are
given by weight.
EXAMPLE 1
[0073]
1 Makeup-removing lotion for the face: CGRP 8-37 0.50 Antioxidant
0.05 Isopropanol 40.00 Preservative 0.30 Water qs 100%
EXAMPLE 2
[0074]
2 Makeup-removing lotion for the face: CGRP 8-37 0.0001 Antioxidant
0.05 Isopropanol 40.00 Preservative 0.30 Water qs 100%
EXAMPLE 3
[0075]
3 Facial care gel: Anti-CGRP antibody 0.05 Hydroxypropyl cellulose
(Klucel 1.00 H marketed by Hercules) Antioxidant 0.05 Isopropanol
40.00 Preservative 0.30 Water qs 100%
EXAMPLE 4
[0076]
4 Acne treatment gel: Anti-CGRP antibody 0.10 all-trans-Retinoic
acid 0.05 Hydroxypropyl cellulose (Klucel 1.00 H marketed by
Hercules) Antioxidant 0.05 Isopropanol 40.00 Preservative 0.30
Water qs 100%
EXAMPLE 5
[0077]
5 Facial care cream (oil-in-water emulsion): CGRP 8-37 0.02
Glyceryl stearate 2.00 Polysorbate 60 (Tween 60 marketed by ICI)
1.00 Stearic acid 1.40 Triethanolamine 0.70 Carbomer 0.40 Liquid
fraction of karite butter 12.00 Perhydrosqualene 12.00 Antioxidant
0.05 Fragrance 0.5 Preservative 0.30 Water qs 100%
EXAMPLE 6
[0078]
6 Shampoo: Sodium lauryl; ether sulfate (2.2 EO) 12.00 Anti-CGRP
antibody 0.02 Hydroxypropyl cellulose (Klucel H marketed 1.00 by
Hercules) Fragrance 0.50 Preservative 0.30 Water qs 100%
EXAMPLE 7
[0079]
7 Facial anti-wrinkle care cream (oil-in-water emulsion): CGRP 8-37
0.15 Glyceryl stearate 2.00 Polysorbate 60 (Tween 60 marketed by
ICI) 1.00 Stearic acid 1.40 5-n-Octanoylsalicylic acid 0.50
Triethanolamine 0.70 Carbomer 0.40 Liquid fraction of karite butter
12.00 Perhydrosqualene 12.00 Antioxidant 0.05 Fragrance 0.5
Preservative 0.30 Water qs 100%
EXAMPLE 8
[0080]
8 Emulsified care gel for countering insect bites (oil-in water
emulsion): Cyclomethicone 3.00 Purcellin oil (marketed by Dragoco)
7.00 PEG-6/PEG-32/glycol stearate (Tefose .RTM. 63 0.30 marketed by
Gattefosse) Anti-CGRP antibody 0.02 Preservative 0.30 Fragrance
0.40 Carbomer 0.60 Crotamiton 5.00 Glycyrrhetinic acid 2.00 Ethyl
alcohol 5.00 Triethanolamine 0.20 Water qs 100%
EXAMPLE 9
[0081]
9 Pain-relief gel: CGRP 8-37 0.03 Hydroxypropyl cellulose (Klucel H
marketed 1.00 by Hercules) Antioxidant 0.05 Lidocaine hydrochloride
2.00 Isopropanol 40.00 Preservative 0.30 Water qs 100%
EXAMPLE 10
[0082]
10 Care cream for facial rosacea (oil-in-water emulsion): CGRP 8-37
0.25 Glyceryl stearate 2.00 Polysorbate 60 (Tween 60 marketed by
ICI) 1.00 Stearic acid 1.40 Metronidazole 1.00 Triethanolamine 0.70
Carbomer 0.40 Liquid fraction of karite butter 12.00 Liquid
petrolatum 12.00 Antioxidant 0.05 Fragrance 0.50 Preservative 0.30
Water qs 100%
EXAMPLE 11
[0083]
11 Care cream for solar erythema (oil-in-water emulsion): Anti-CGRP
antibody 0.25 Glyceryl stearate 2.00 Polysorbate 60 (Tween 60
marketed by ICI) 1.00 Stearic acid 1.40 Glycyrrhetinic acid 2.00
Triethanolamine 0.70 Carbomer 0.40 Liquid fraction of karite butter
12.00 Sunflower oil 10.00 Antioxidant 0.05 Fragrance 0.50
Preservative 0.30 Water qs 100%
[0084] While the invention has been described in terms of various
preferred embodiments, the skilled artisan will appreciate that
various modifications, substitutions, omissions, and changes may be
made without departing from the spirit thereof. Accordingly, it is
intended that the scope of the present invention be limited solely
by the scope of the following claims, including equivalents
thereof.
* * * * *