U.S. patent application number 09/367033 was filed with the patent office on 2003-03-27 for compositions comprising a combination of a free sphingoid base and a ceramide and uses thereof.
Invention is credited to LAMBERS, JOHANNES WILHELMUS J.
Application Number | 20030059447 09/367033 |
Document ID | / |
Family ID | 8229019 |
Filed Date | 2003-03-27 |
United States Patent
Application |
20030059447 |
Kind Code |
A1 |
LAMBERS, JOHANNES WILHELMUS
J |
March 27, 2003 |
COMPOSITIONS COMPRISING A COMBINATION OF A FREE SPHINGOID BASE AND
A CERAMIDE AND USES THEREOF
Abstract
The present invention discloses a composition for topical use
comprising a free sphingoid base and a ceramide. The compositions
of the invention are suitable for application to skin conditions
associated with an impaired barrier function, in particular to skin
conditions further associated with a deranged regulation of cell
growth and differentiation, an inflammatory condition and/or an
infectious state
Inventors: |
LAMBERS, JOHANNES WILHELMUS J;
(ALTENA, NL) |
Correspondence
Address: |
WILLIAM F. LAWERENCE, ESQ.
Frommer, Lawrence & Haug - Attorney at Law
745 Fifth Ave
New York
NY
10151
US
|
Family ID: |
8229019 |
Appl. No.: |
09/367033 |
Filed: |
September 13, 1999 |
PCT Filed: |
December 7, 1998 |
PCT NO: |
PCT/EP98/08121 |
Current U.S.
Class: |
424/401 ;
514/42 |
Current CPC
Class: |
A61Q 17/00 20130101;
A61Q 19/00 20130101; A61P 17/00 20180101; A61K 8/68 20130101; A61Q
19/007 20130101; A61K 8/41 20130101 |
Class at
Publication: |
424/401 ;
514/42 |
International
Class: |
A61K 007/00; A61K
031/7008 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 5, 1997 |
EP |
203824.4 |
Claims
1. A composition for topical use comprising a combination of a free
sphingoid base and a ceramide, said free sphingoid base having a
general structure according to Formula 1: 3wherein: A is
CH.sub.2--CH.sub.2, CH.dbd.CH or C(H)OH--CH.sub.2, and R is a
straight chain or branched alkyl group having 10 to 22 carbon atoms
which may optionally contain one or more double bonds and/or may
optionally be substituted with one or more hydroxyl groups,
preferably is a straight chain alkyl group having 12 to 18 carbon
atoms, more preferably is a straight chain alkyl group having 13
carbon atoms, and said ceramide having a general structure
according to Formula 2: 4wherein: A and R are defined as above, and
R' is a straight chain or branched alkyl group having 13 to 55
carbon atoms, preferably 15 to 50 carbon atoms, more preferably 17
to 44 carbon atoms; the alkyl chain may optionally be interrupted
by an oxygen atom or by an internal ester group; may optionally
contain one or more double bonds; and may optionally be substituted
with one or more hydroxyl groups.
2. The composition of claim 1, wherein the free sphingoid base is
selected from the group of sphingosine, sphinganine and
phytosphingosine.
3. The composition of claim 1 or 2, wherein the ceramide is a
ceramide which corresponds in stereochemical configuration to a
ceramide isolatable from mammalian skin.
4. The composition of any one of the claims 1-3, wherein the
ceramide is a mixture of two or more different ceramides.
5. The composition of any one of the claims 1-4, wherein the
composition further comprises one or more additional skin lipid
compounds.
6. The composition of any one of the claims 1-5, wherein a ceramide
is present in addition to or instead of the ceramide according to
Formula 2 which is selected from the group of glycoceramides and
short chain ceramides.
7. The composition of claim 1 which is a dermatological
composition.
8. The composition of claim 1 which is a cosmetic composition.
9. Use of the composition of claim 1 for the manufacture of a
topical composition for the treatment of a skin condition
associated with an impaired barrier function.
10. Use according to claim 9, wherein said skin condition is
further associated with a condition selected from the group
consisting of a deranged regulation of cell growth and
differentiation, an imflammatory condition or an infectious
state.
11. A method for the treatment of a skin condition associated with
an impaired barrier function comprising the topical application of
a composition according to claim 1.
12. The method of claim 11, wherein said skin condition is further
associated with a condition selected from the group consisting of a
deranged regulation of cell growth and differentiation, an
imflammatory condition or an infectious state.
13. The method of claim 12 which is a non-therapeutical method.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to the field of topical use of
compositions comprising a selected combination of
sphingolipids.
BACKGROUND OF THE INVENTION
[0002] The human skin forms a structural and adapted barrier to the
environment. It further plays an important physiological role since
it provides not only protection and thermoregulation, but also has
a metabolic and sensorial function and storage capacity.
[0003] It has been shown that the lipid composition of the
epidermal cells within the skin changes considerably when the cells
migrate to the outer surface and differentiate. The cells in the
basal layer contain a complex lipid composition, with phospholipids
as the major constituent. In the granular layer the phospholipid
content is diminished while the amount of cerebrosides
(glycosylceramides), ceramides, cholesterol and cholesterol
sulphate is increased as result of de novo synthesis and storage
into the so-called lamellar bodies. In the outermost lipid layer of
the epidermis, called the stratum corneum (horny layer) the
phospholipids and cerebrosides have vanished completely. The most
abundant lipids in this layer are ceramides, which mainly have been
formed by enzymatic deglycosylation of cerebrosides.
[0004] The barrier function of the skin mainly is provided by the
stratum corneum. The stratum corneum consists of corneocytes
embedded in an extracellular matrix of multiple bilayers of lipids.
The intercellular lipid phase of the stratum corneum has roughly
the following composition: 40% ceramides, 25% cholesterol, 10%
cholesteryl sulphate and 25% free fatty acids. As long as the
"bricks and mortar" construction of the stratum corneum is not
affected, the skin is provided with both a perfect protective layer
and a filter-active permeability layer.
[0005] Several categories of skin conditions or disorders are known
which are characterized by an impaired lipid barrier function,
further accompanied by characteristics like a deranged regulation
of cell growth and differentiation (e.g. hyperproliferation and/or
decreased differentiation of keratinocytes, decreased desquamation
of corneocytes), an imflammatory response and/or an infectious
state. In these skin conditions, the skin generally displays a
rough, red, dry, chapped and/or swollen character. Typical examples
of such disorders are xerosis, acne vulgaris, psoriasis, atopic
dermatitis, contact dermatitis, UV-induced erythema, and the
like.
[0006] Satisfactory treatment methods for these disorders presently
are not available. Emollient creams and lotions may relieve part of
the symptoms, but often only temporarily. Conventional
antiimflammatory creams, of which corticosteroid creams form the
main part, are more effective for the treatment of certain
disorders but continued use may reduce the effectiveness of the
treatment and/or may give side reactions. In addition, conventional
antiinflammatory as well as antimicrobial creams typically are not
adapted to restore an impaired barrier function.
[0007] Ceramides are generally applied in cosmetics because of
their moisture-retaining properties (see for instance Japanese
patent application J61-260008).
[0008] In International patent application WO94/00127 it has been
described that formulations containing specific lipid mixtures
should be applied for an optimal treatment of skin disorders
associated with a disrupted epidermal barrier. Said lipid mixtures
comprise lipids selected from the three major classes of
naturally-occurring epidermal lipids, i.e. the classes of
ceramides, cholesterol and free fatty acids. However, in order to
be optimally effective for skin conditions associated with
inflammatory or infectious phenomena, these formulations have to be
applied together with conventionally used therapeutic agents.
[0009] Surprisingly, it is shown by the present invention that
topical compositions comprising a combination of a free sphingoid
base and a ceramide have a beneficial effect when applied on skin
conditions associated with an impaired barrier function, and
especially when applied on skin conditions further associated with
a deranged regulation of cell growth and differentiation,
inflammatory and/or infectious phenomena.
DESCRIPTION OF THE INVENTION
[0010] The present invention discloses compositions suitable for
topical use comprising a combination of a free sphingoid base and a
ceramide. The topical compositions of the invention can be cosmetic
as well as dermatologic compositions.
[0011] It is shown by the present invention that topical
compositions comprising a combination of a free sphingoid base and
a ceramide have a positive and beneficial effect on skin conditions
associated with an impaired lipid barrier function. The synergistic
effects of the combination of a free sphingoid base and a ceramide
become even more apparent when the compositions according to the
invention are used for the treatment of skin conditions wherein an
impaired lipid barrier function further is associated with a
deranged regulation of cell growth and differentiation, an
imflammatory condition and/or an infectious state. Said deranged
regulation of cell growth and differentiation is characterized by
conditions like hyperproliferation of keratinocytes, decreased
differentiation of keratinocytes and/or decreased desquamation of
corneocytes.
[0012] The present invention shows that the presence of a free
sphingoid base especially improves the efficacy of the composition
of the invention with regard to its antiinflammatory and/or its
antimicrobial activity. It is shown that this efficacy improvement
is due to, in particular, an antimicrobial and antiinflammatory
activity of the free sphingoid base.
[0013] The free sphingoid base present in the composition according
to the invention has a general structure according to Formula 1:
1
[0014] wherein:
[0015] A is CH.sub.2--CH.sub.2, CH.dbd.CH or C(H)OH--CH.sub.2,
and
[0016] R is a straight chain or branched alkyl group having 10 to
22 carbon atoms which may optionally contain one or more double
bonds and/or may optionally be substituted with one or more
hydroxyl groups, preferably is a straight chain alkyl group having
12 to 18 carbon atoms, more preferably is a straight chain alkyl
group having 13 carbon atoms.
[0017] The ceramide present in the composition according to the
invention has a general structure according to Formula 2: 2
[0018] wherein:
[0019] A and R are defined as above, and
[0020] R' is a straight chain or branched alkyl group having 13 to
55 carbon atoms, preferably 15 to 50 carbon atoms, more preferably
17 to 44 carbon atoms; the alkyl chain may optionally be
interrupted by an oxygen atom or by an internal ester group; may
optionally contain one or more double bonds; and may optionally be
substituted with one or more hydroxyl groups.
[0021] The free sphingoid base which is present in the composition
of the invention preferably is a sphingosine, a sphinganine or a
phytosphingosine. More preferably, the free sphingoid base is a
phytosphingosine obtainable by deacetylation of
tetraacetylphytosphingosi- ne obtainable by fermentation of the
yeast Pichia ciferri.
[0022] The ceramide which is present in the composition of the
invention can be extracted from a natural source, for instance a
mammalian source, or can be obtained via synthetic means. An
example of a suitable chemical synthesis method is the acylation of
a free sphingoid base with a suitable fatty acid, for instance via
the acylation method as disclosed in international patent
application WO93/20038.
[0023] In a preferred embodiment of the invention, the ceramide
present in the composition of the invention is a ceramide which
corresponds in stereochemical configuration to a ceramide
isolatable from mammalian skin. Ceramides as isolated from
mammalian skin typically can be subdivided in six heterogeneous
classes of compounds, ceramide 1, 2, 3, 4, 5, 6I and 6II. In
general, these ceramides consist of a free sphingoid base in amide
linkage with a nonhydroxy or an .alpha.-hydroxy fatty acid, or an
.omega.-hydroxy fatty acid esterified with an additional fatty
acid. A ceramide which corresponds in stereochemical configuration
to a mammalian skin ceramide may for instance be obtained by
acylation of Pichia ciferri-derived phytosphingosine. Examples of
such ceramides are the ceramides disclosed in international patent
applications WO93/20038, WO95/11881, WO95/25716 and WO96/10557.
[0024] Within the context of the present invention, an individual
ceramide as well as a mixture of two or more different ceramides
can be applied in a topical composition.
[0025] In that regard, said mixture of two or more different
ceramides may include various ceramide combinations, the choice of
a specific combination depending among others on the desired
application.
[0026] A combination of two or more representatives of each
ceramide class may for instance be applied, since said combination
may lead to an increased ceramide solubility in the composition
according to the invention. Individual ceramides may tend to
crystallize and consequently become inert and unfunctional.
[0027] A further option is a combination of, on the one hand, a
sphinganine- and/or sphingosine-containing ceramide and, on the
other hand, a phytosphingosine-containing ceramide (e.g. ceramide 1
and/or 2 and/or 4/5 with ceramide 3 and/or Ceramide 6). Such a
combination consists of two types of ceramides having a head group
which differs in hydrophilicity and this may increase barrier
enhancing properties of the same.
[0028] For the same reason, a combination is feasible of a ceramide
containing an .alpha.-hydroxy fatty acid with a ceramide containing
a non-hydroxylated fatty acid (e.g. ceramide 1 and/or ceramide 2
and/or ceramide 3 with ceramide 4/5 and/or ceramide 6).
[0029] Further feasible is a combination of a ceramide containing a
medium chain fatty acyl group of 16 to 22 carbon atoms with a
ceramide containing a long chain fatty acyl groups of 22 to 32
carbon atoms, since such a combination naturally occurs in the
stratum corneum and may also be important for a stronger barrier
structure (Bouwstra et al. (1996), J. Lipid Res. 37, 999-1011).
[0030] The composition of the invention optionally may comprise one
or more additional skin lipid compounds, such as cholesterol,
cholesterol esters like cholesteryl sulphate, free fatty acids like
palmitic, stearic, behenic, oleic and/or linoleic acid and/or other
sphingolipids like glycoceramides. The composition of the invention
may further comprise ceramide compounds having a short-chain acyl
group, said short chain acyl group optionally being
.alpha.-hydroxylated (so-called short-chain ceramides).
[0031] With respect to glycoceramides, two groups of these
compounds are typically distinguished, i.e. cerebrosides and
gangliosides. A cerebroside is understood to be a glycoceramide
wherein a monosaccharide, mostly glucose or galactose, is attached
to the oxygen of the --CH.sub.2OH group of the ceramide according
to Formula 2. In gangliosides oligosaccharides, frequently
including sialic acid, are attached to the same.
[0032] With respect to short-chain ceramides, a short chain acyl
group is meant to comprise acyl groups having 2 to 14 carbon atoms.
A preferred ceramide with a short-chain acyl group is
acetylphytosphingosine. Examples of ceramides having a short-chain
.alpha.-hydroxyacyl group are disclosed in international patent
application WO95/29151.
[0033] In one embodiment of the invention, a composition comprising
a free sphingoid base and a ceramide may contain as the sole type
of ceramide compound a glycoceramide or a short-chain ceramide. In
another embodiment, the ceramide compound in the composition of the
invention may be a mixture of a glycoceramide and a short-chain
ceramide.
[0034] Next to the free sphingoid base and the ceramide, other
active ingredients may be present in the composition according to
the invention. For instance, the combination of a free sphingoid
base and a ceramide may advantageously be applied in combination
with a conventional antiinflammatory and/or antimicrobial agent,
where said conventional antiinflammatory and/or antimicrobial agent
may be applied in substantially lower concentrations than typically
used, because of the activity of the free sphingoid base.
[0035] An example of a conventionally used antiinflammatory agent
is a corticosteroid.
[0036] Other active ingredients which may advantageously be applied
in the compositions according to the invention, in combination with
a free sphingoid base and a ceramide, are agents which have an
effect on skin appearance.
[0037] For instance, yeast .beta.-glucan may be applied in the
composition according to the invention to reduce UV-induced
erythema. Skin-peeling agents, like .alpha.-hydroxyacids, urea,
salicylic acid or proteases, may be applied in the composition
according to the invention to improve desquamation and/or decrease
roughness of the skin. Retinoids may be applied in the composition
according to the invention to stimulate the mitotic and metabolic
activity of epidermal cells. Vitamin C and/or E may be applied in
the composition of the invention for their antioxidant activity on
skin components, which favours their application as, for instance,
antiageing agents.
[0038] The free sphingoid base as well as the ceramide may be
present in the composition according to the invention in a
concentration of 0.001 to 10%, preferably in a concentration of
0.005 to 5%, more preferably in a concentration of 0.01-2%, most
preferably in a concentration of 0.02-1.0%.
[0039] The ratio of free sphingoid base to ceramide in the
composition according to the invention may lie within a range of 1
to 10 to 10 to 1. Preferably, said ratio may vary from about 1 to 5
to about 5 to 1. More preferably, said ratio may vary from about 1
to 5 to about 1 to 1.
[0040] Next to the active ingredients, the topical preparations of
the invention further include the usual components.
[0041] The composition comprises a vehicle to enable the active
ingredients to be conveyed to the skin.
[0042] The vehicle enables proper application on skin and/or hair,
to provide both a dermatological as well as a cosmetic treatment.
The composition may comprise a solid, semi-solid or liquid
cosmetically and/or physiologically acceptable vehicle. The nature
of the vehicle will depend upon the method chosen for topical
administration of the composition. Vehicles other than water can
include liquid or solid emollients, solvents, humectants,
thickeners, powders, surfactants, which are also sometimes
designated as emulsifiers, solubilizers, propellants and other
active ingredients.
[0043] Emollients can be classified under such general chemical
categories as (fatty acid) esters, fatty acids, (fatty) alcohols,
polyols, (natural) waxes, natural oils, silicone oils, both
volatile and non-volatile and hydrocarbons such as mineral oil,
petroleum jelly, vaseline, squalens and (iso)paraffin.
[0044] Surfactants including emulsifiers may be cationic, nonionic,
anionic or amphoteric in nature. A single type of surfactant and/or
combinations of surfactants may be employed.
[0045] Illustrative for nonionic surfactants are alkoxylated
compounds based upon fatty alcohols, fatty acids and sorbitan.
[0046] Anionic-type surfactants may include fatty acid soaps,
lauryl sulphate salts, lauryl ether sulphate salts, alkyl benzene
sulphonates, alkyl acid phosphates.
[0047] Amphoteric surfactants include materials as dialkylamine
oxide and various types of betaines, such as cocoamido propyl
betaine.
[0048] Cationic surfactants comprise quaternary ammonium compounds
(Quats) such as cetyl trimethyl ammonium chloride or bromide.
[0049] A special class of surfactants are silicone surfactants,
which are high molecular weight polymers of dimethyl polysiloxane
with polyoxyethylene and/or polyoxypropylene side chains having a
molecular weight of 10,000 to 50,000 D.
[0050] In general, surfactants used for the preparation of
emulsions include emulsifiers comprising compounds having a HLB
(hydrophilic/lipophilic balance) value which is in the lower as
well as in the higher ranges, i.e. compounds which are able to form
a water-in-oil as well as compounds which are able to form an
oil-in-water emulsion, respectively. Typically, if a water-in-oil
emulsion is required, the HLB value of the emulsifier or mixture of
emulsifiers varies between about 1 and 7. For an oil-in-water
emulsion, said HLB value is higher than about 7.
[0051] Specific emulsifiers comprise emulsifiers which are able to
form a lamellar phase (liquid crystalline or gel phase). Lamellar
phases are formed at the oil-water interphase of an oil-in-water
emulsion and directly incorporate the free sphingoid base and the
ceramide. Examples of such specific emulsifiers are:
[0052] 1. Fatty acids+neutralized fatty acids:
[0053] e.g. stearic acid, isostearic acid, etc.
[0054] 2. Glyceryl mono-fatty acid ester+neutralized fatty
acids:
[0055] glyceryl stearate SE, glyceryl oleate SE
[0056] 3. Glyceryl mono-fatty acid ester+ethoxylated fatty
alcohols/esters:
[0057] glyceryl stearate+Ceteareth-20+various
[0058] glyceryl stearate+PEG-20 glyceryl stearate
[0059] 4. High-ethoxylated fatty alcohols+low-ethoxylated fatty
alcohols (+polar emollients):
[0060] Steareth-2+Steareth-21 (+PPG-15 stearyl ether/fatty
alcohol)
[0061] Ceteareth-6+Ceteareth-25
[0062] Cetearyl Alcohol+Ceteareth-20
[0063] 5. Various polyglyceryl esters+combinations:
[0064] polyglyceryl-3-methyl glucose distearate.
[0065] polyglyceryl-10 pentastearate+behenyl alcohol+sodium
stearoyl lactylate
[0066] polyglyceryl-2 isostearate (or resp. di/tri/tetra
isostearate)
[0067] polyglyceryl-3 diisostearate
[0068] 6. Various other sugar-esters:
[0069] Cetearylglucoside+Cetearyl alcohol
[0070] methyl glucose sesquistearate+PEG-20 methyl glucose
sesquistearate
[0071] Sorbitan stearate+sucrose cocoate
[0072] Sorbitan stearate+polysorbate 60
[0073] sucrose esters
(laurate/palmitate/stearate/oleate/isostearate)
[0074] 7. Lecithins and other Phospholipids:
[0075] lecithin
[0076] Propellants include propane, butane, isobutane, dimethyl
ether, chlorofluoroalkanes, carbon dioxide, nitrous oxide.
[0077] Solvents include ethyl alcohol, methylene chloride,
isopropanol, ethyl ethers such as ethoxyethanol and butoxyethanol,
acetone, tetrahydrofuran, dimethyl formamide, DMSO, propylene
glycol, butylene glycol.
[0078] Humectants include proteins and protein hydrolysates, amino
acids, sorbitol, glycerin, sorbitol, glycols preferably PEG
200-4000 and other polyols.
[0079] Thickeners include cross linked polyacrylates, silicone gums
and polysaccharide gums such as xanthan, carrageenan, gelatin,
pection and locust beans gum, hyaluronic acid and carboxylic
group-containing polymers
[0080] Powders include chalk, talc, starch, kaolin, clays,
silicates, carboxyvinyl polymers.
[0081] Other active ingredients include:
[0082] anti-oxidants like butyl hydroxy toluene, ascorbic acid and
salts, EDTA, hydroquinone, tocopherols, gallates;
[0083] preservatives like para-hydroxy benzoate esters, sorbic
acid, EDTA, quaterniums, benzoic acid, imidazolidinyl urea,
(benzyl)alcohol;
[0084] enzyme regulators like vitamins and other co-factors;
[0085] penetration enhancers like mono- or di-esters of C2 to C10
alcohols and C8 to C18 fatty acids, propanols, urea, sugar esters,
POE esters or ethers of fatty acids and/or alcohols, butan-1,4
diol, tetrahydrofuran, salicylate salts, pyrrolidones,
N-alkyl-aza-cycloheptanones, oleic acid, linoleic acid;
[0086] sunscreens, blocking UV light, like PABA's, cinnamate and
salicylate derivatives;
[0087] other actives like coloring agents or perfumes.
[0088] The combination of the said components can account for 5 to
99% of the composition.
[0089] The positive and beneficial effects of the compositions
according to the invention on affected skin areas are various and
are summarized as follows: a reduction of redness, dryness,
roughness and/or scaling of the skin, a reduction of pruritis, a
reduction of skin lesions, an improvement in healing of small
wounds, a decrease of inflammatory symptoms in affected areas, a
decrease of an infectious state of the skin in affected areas.
[0090] Examples of skin conditions which benefit from topical
application of a composition according to the invention are
psoriasis, atopic dermatitis, irritant and allergic contact
dermatitis, seborrheic and sebostatic dermatitis, photodermatitis
(UV-induced erythema), acne, ichthyosis, xerosis, aged skin. The
skin infections which benefit from topical application of the
compositions of the invention include bacterial, fungal, yeast and
viral infections. For example dandruff, impetigo, Pityriasis
vesicolor, Tinea corporis, Rosacea, Herpes, venereal diseases.
[0091] For specific skin conditions, i.e. wounds, burns, scalds, a
combination of a free sphingoid base and a cerebroside is
preferred, since cerebrosides (contrary to ceramides) tend to
stimulate the proliferation of keratinocytes.
[0092] On the other hand, for skin diseases where, next to an
impaired barrier function and skin infections, hyperproliferation,
reduced differentation and reduced desquamation are general
symptoms, the inclusion of ceramides with a short-chain acyl group
may be advantageous. These short-chain ceramides will have the
additional effect that they are cell-permeable and known to reduce
proliferation, increase differentiation and increase
desquamation.
[0093] The present invention is exemplified by several formulations
and by an efficacy study using test persons with different skin
disorders. Furthermore, the antiimflammatory activity of a free
sphingoid base is demonstrated.
EXAMPLE 1
Formulations Comprising Phytosphingosine and Several Ceramides
[0094] Below, several examples of suitable formulations according
to the invention are given.
[0095] The ceramides and the free sphingoid base used in these
formulations are the following:
[0096] Ceramide III: N-stearoyl-phytosphingosine
[0097] Ceramide IIIB: N-oleoyl-phytosphingosine
[0098] Ceramide VI: N-alpha-hydroxystearoyl-phytosphingosine
[0099] Phytosphingosine: 2-amino-octadecane-1,3,4-triol
[0100] Phytoceramide I:
N-stearoyloxyheptacosanoyl-phytosphingosine
1 Waterless Barrier Cream I comprising Ceramide III, Ceramide VI
and Phytosphingosine INCI-name Trade name Percentage (% w/w)
Hydrogenated lecithin 4.0 Glycerin 48.0 Butylene glycol 18.0 Jojoba
oil 5.0 Propylene glycol Miglyol 840 (Huls) 10.0
dicaprylate/dicaprate Isocetyl alcohol Eutanol G16 (Henkel) 3.0
Tocopheryl acetate 5.0 Dimethicone copolyol 5.0 eicosonate Ceramide
3 Ceramide III 0.5 (Cosmoferm) Ceramide IIIB 0.5 (Cosmoferm)
Ceramide 6 Ceramide VI 0.5 (Cosmoferm) Phytosphingosine
Phytosphingosine 0.5 (Cosmoferm) Waterless Barrier Creams II and
III comprising Ceramide III, Ceramide VI and Phytosphingosine, and
additionally cholesterol and stearic acid INCI-name Trade name
Percentage (% w/w) Hydrogenated Lecithin Amisol 905 (Lucas 4.0 4.0
Meyer) Glycerin 30.0 24.0 Butylene glycol 20.0 20.0 Glycero
phospholipids Biophilic S (Lucas 1.5 1.5 Meyer) Jojoba oil 5.0 5.0
Paraffin 10.0 10.0 Propylene glycol Myritol PC (Henkel) 10.0 10.0
dicaprylate/ dicaprate Isocetyl alcohol Eutanol G16 (Henkel) 8.0
8.0 Hydrogenated Cremeol HF52 (Aarhus) 5.0 5.0 vegetable oil
Tocopheryl acetate BASF 5.0 5.0 Ceramide 3 Ceramide III 0.25 1.25
(Cosmoferm) Ceramide IIIB 0.25 1.25 (Cosmoferm) Ceramide 6 Ceramide
VI 0.25 1.25 (Cosmoferm) Phytosphingosine Phytosphingosine 0.25
1.25 (Cosmoferm) Cholesterol 0.25 1.25 Stearic acid Unichema 0.25
1.25 Amisol 905 40% Hydrogenated lecithin, 30% Glycerin, 30%
Butylene glycol. Percentages have been corrected for glycerin and
butylene glycol in the INCI-formulation Barrier Cream IV comprising
Phytoceramide I, Ceramide III and IIIB, Ceramide VI,
Phytosphingosine and Acetyl-phytosphingosine INCI-name Trade name
Percentage (% w/w) Lecithin (and) C12-16 Biophilic S 2.0 alcohols
(and) palmitic (Lucas Meyers) acid Polyglyceryl-3 Methyl- Tego Care
450 2.0 glucose Distearate (Goldschmidt) Cetearyl alcohol Lanette O
1.0 (Henkel) Propylene glycol Myritol PC 10.0 dicaprylate/dicaprate
(Henkel) Isocetyl alcohol Eutanol G16 10.0 (Henkel) Rice Bran oil
5.0 Tocopheryl acetate BASF 2.0 Ceramide 3 Ceramide III 0.5
(Cosmoferm Ceramide IIIB 0.5 (Cosmoferm) Ceramide 6 Ceramide VI 0.5
(Cosmoferm) Phytosphingosine Phytosphingosine 0.5 (Cosmoferm)
Ceramide 1 Phytoceramide 1 0.1 (Cosmoferm) Acetyl-Phytosphingosine
C2-Ceramide 0.1 (Cosmoferm) Stearic acid 0.5 Cholesterol 0.5
Butylene glycol 6.0 Mixed parabens in Phenonip 0.6 Phenoxyethanol
Water 64.4 Liposomal formulation comprising Ceramide III, Ceramide
IIIB, Ceramide VI and phytosphingosine, and additionally
cholesterol and linoleic acid INCI-name Trade name Percentage (%
w/w) Sodium lauroyl lactylate 9.0 Tocopherol acetate 0.01 Carbomer
0.3 Ceramide 3 Ceramide III 0.2 (Cosmoferm Ceramide IIIB 0.2
(Cosmoferm) Ceramide 6 Ceramide VI 0.1 (Cosmoferm) Phytosphingosine
Phytosphingosine 0.5 (Cosmoferm) Linoleic acid 0.25 Cholesterol
0.25 Water 89.2
EXAMPLE 2
Efficacy Evaluation of Barrier Cream I
[0101] To test the efficacy of a composition comprising a free
sphingoid base and a ceramide, barrier cream I was applied daily by
several test persons suffering from various skin disorders. The
results are indicated in Table 1. It is clear that the use of a
barrier cream according to the invention results in a significant
improvement of the affected skin areas.
2TABLE 1 Person Condition Application Effect 1 Psoriatic 8 weeks
Strong improvement; lesions on right 1* per day lesions have
practically leg disappeared; small wounds appear to heal faster 2
Dry xerotic 3 weeks Clear improvement; skin is skin, in 1* per day
less scaly and red particular on cheeks 3 Ichtyosis over 8 weeks
Improvement is visible; no whole body 1* per day, itching feeling
like with only on the urea cream face 4 Atopic skin 4 weeks
Improvement; comparable to 1* per day corticosteroid cream 5
Psoriatic 4 weeks Improvement; lesions lesions on the 1* per day
return upon withdrawal elbow
EXAMPLE 3
Effect of the Free Sphingoid Base Phytosphingosine on the Secretion
of Cytokines as a Marker for Antiinflammatory Activity
[0102] Principle:
[0103] The effect of phytosphingosine was assessed ex vivo on
excised human skin explants.
[0104] The explant was exposed to UV-B rays as a physical,
proinflammatory stress.
[0105] The antiinflammatory effect of phytosphingosine was
evaluated by measurement of the amount of the cytokine IL-1.alpha.
secreted in the incubation medium of the skin explants.
[0106] Protocol:
[0107] Preparation of the human skin explants obtained after
plastic surgery using standard techniques.
[0108] Application of the test product: resp. 0% (Placebo), 0.2 and
0.5% phytosphingosine (PS) in Propylene glycol:Ethanol (60:40).
Dexamethasone (1 .mu.M) was used as the reference product.
[0109] The products were applied before and after irradiation
(.about.2 mg/cm.sup.2)
[0110] IL-1.alpha. secretion was measured in the incubation medium
of the skin explants, using a standard ELISA technique.
[0111] Each experimental condition was performed in triplicate.
[0112] Results:
3 Before After UV-B UV-B Dexamethasone Placebo 0.2% PS 0.5% PS 48
205 116* 165 82* 92* *Significant effect p < 0.05 -Results are
expressed in pg per ml IL-1.alpha..
* * * * *