U.S. patent application number 11/802807 was filed with the patent office on 2008-07-24 for pharmaceutical and cosmetic compositions for the protection of the skin from damages induced by sun radiations.
This patent application is currently assigned to INDENA S.P.A.. Invention is credited to Francesco Di Pierro.
Application Number | 20080175802 11/802807 |
Document ID | / |
Family ID | 11447085 |
Filed Date | 2008-07-24 |
United States Patent
Application |
20080175802 |
Kind Code |
A1 |
Di Pierro; Francesco |
July 24, 2008 |
Pharmaceutical and cosmetic compositions for the protection of the
skin from damages induced by sun radiations
Abstract
Pharmaceutical and cosmetic compositions for the protection of
the skin from damages induced by sun radiations, containing
ingredients of vegetable origin, in addition to conventional sun
filters and excipients.
Inventors: |
Di Pierro; Francesco;
(Milano, IT) |
Correspondence
Address: |
YOUNG & THOMPSON
209 Madison Street, Suite 500
ALEXANDRIA
VA
22314
US
|
Assignee: |
INDENA S.P.A.
MILAN
IT
|
Family ID: |
11447085 |
Appl. No.: |
11/802807 |
Filed: |
May 25, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10469300 |
Jan 9, 2004 |
7374748 |
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PCT/EP02/02027 |
Feb 26, 2002 |
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11802807 |
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Current U.S.
Class: |
424/59 |
Current CPC
Class: |
A61K 36/28 20130101;
A61K 8/553 20130101; A61K 2300/00 20130101; A61K 2300/00 20130101;
A61K 2300/00 20130101; A61K 36/48 20130101; A61P 17/00 20180101;
A61K 36/87 20130101; A61K 8/922 20130101; A61K 36/48 20130101; A61K
36/28 20130101; A61Q 17/04 20130101; A61P 17/16 20180101; A61K
36/87 20130101 |
Class at
Publication: |
424/59 |
International
Class: |
A61K 8/97 20060101
A61K008/97; A61Q 17/04 20060101 A61Q017/04 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 2, 2001 |
IT |
MI2001A000429 |
Claims
1. A composition comprising at least two of the following
compositions: TABLE-US-00004 a) phospholipid complexes of
flavanolignanes 0.1-5 extracted from Silybum marianum b)
phospholipid complexes of standardized 0.1-5% extract of Vitis
vinifera, and c) phospholipid complexes of triterpenes 0.1-5%
extracted from Glycyrrhiza glabra
in combination with an agent that filters the sun and filters and
excipients.
2. The composition according to claim 1, wherein the composition is
in the form of a liquid.
3. The composition according to claim 1, wherein the composition is
in a form selected from the group consisting of a gel, lotion,
milk, emulsion, and foam.
4. The composition according to claim 1, wherein the composition is
in the form of a solid or semi-solid.
5. The composition according to claim 1, wherein the composition is
in the form of a solid or semi-solid.
6. A method of treating skin damage induced by sun radiation in a
subject in need thereof comprising administering to said subject an
effective amount of at least two of the following components:
TABLE-US-00005 a) phospholipid complexes of flavanolignanes 0.1-5
extracted from Silybum marianum b) phospholipid complexes of
standardized 0.1-5% extract of Vitis vinifera, and c) phospholipid
complexes of triterpenes 0.1-5% extracted from Glycyrrhiza
glabra
in combination with an agent that filters the sun and filters and
excipients.
7. The composition according to claim 6, wherein the composition is
administered in the form of a liquid.
8. The composition according to claim 6, wherein the composition is
administered in a form selected from the group consisting of a gel,
lotion, milk, emulsion, and foam.
9. The composition according to claim 6, wherein the composition is
administered in the form of a solid or semi-solid.
10. The composition according to claim 6, wherein the composition
is administered in the form of a solid or semi-solid.
Description
[0001] The present invention relates to pharmaceutical and cosmetic
compositions for the protection of the skin from damages induced by
sun radiations, containing ingredients of vegetable origin, in
addition to conventional sun filters and excipients.
[0002] More particularly, the present invention relates to
pharmaceutical and cosmetics compositions for the protection of the
skin from damages induced by sun radiations, containing
phospholipid complexes of flavanolignanes extracted from Silybum
marianum; phospholipid complexes of Vitis vinifera standardized
extract and phospholipid complexes of triterpenes extracted from
Glycyrrhiza glabra, in addition to conventional sun filters and
excipients.
[0003] The formulation of preparations containing high-protection,
specific sun filters has been one of the leading sectors of
dermocosmetic research. This is due to the increasing market demand
on the ground of both an ever increasing awareness of the public of
the harmful effects of sun radiations and to the problem of the
reduction of the ozone levels in the atmosphere.
[0004] Research in this field has allowed the formulation of
diversified preparations, depending on the needs: products for
intense exposure to sunlight (for example at the sea or in the
mountains), for daily use (anti-aging) or for special uses, as is
the case with exposure to UV rays for occupational reasons or in
diseases of the pigmentary system (albinism, vitiligo).
[0005] Furthermore, there has recently been growth in the knowledge
of the molecular mechanisms responsible for the consequences of the
lack of protection from sunlight. This allows the formulation of
preparations, capable of opposing, at any level, the serious
consequences which may be caused by non-protected exposure to
sunlight.
[0006] As it is well known, long exposure to sunlight, as well as
to ultraviolet radiations, may cause dermatological disorders, even
to a serious degree.
[0007] The non-ionizing electromagnetic radiation of the UV
spectrum makes up the sun emission portion which is today
recognized as the main cause of so skin alteration. The UV
radiations which reach the earth's surface are UV-A (320 to 400 nm)
and the UV-B (290 to 320 nm).
[0008] Disorders induced by UV radiations are herein generally
referred to as "photodermatosis".
[0009] Mediated (toxic or allergic reactions to sunlight) and
idiopathic (urticaria solaris, polymorphic dermatitis, actinic
reticuloid) photodermatosis, as well as those liable to be worsened
by sunlight (pellagra, lupus erythematosus, pemphigus
erythematosus, xeroderma pigmentosum, dermatomyositis) may be
considered as somewhat rare consequences of exposure to light.
Conversely, direct photodermatosis is by far more frequent.
[0010] Photodermatosis may appear as erythema/edema vesiculosum
reaction (acute damage), photo-aging and photo-carcinogenesis
(chronic damage).
Erythema
[0011] Erythema is the most frequent skin reaction to UV radiation.
It is dose-dependent and may range from modest, asymptomatic skin
reddening to serious erythema which may be accompanied by pain,
edema and the formation of vesicles. Erythema results from a
peripheral capillary vasodilatation and is the consequence of both
a direct interaction with blood vessels and a photochemical
reaction triggered by sunrays on tissue chromophores (aromatic
amino acids, nitrogenous bases, unsaturated fatty acids, etc.). A
number of mediators are apparently involved in these interactions:
prostaglandins of the E and D series, interleukins and mainly free
radicals. The latter are released as a consequence of the energy
transferred from chromophores to molecular oxygen, and are
responsible for most of the vascular damage caused by exposure to
sunlight.
Photo-Aging
[0012] Skin aging is a complex biological process affecting various
skin layers, including dermis. The aging process of those skin
areas that are exposed to atmospheric agents is due, in addition to
the so-called innate or intrinsic aging, namely the irreversible,
degenerative process connected with aging which affects both the
skin and internal organs, also to the extrinsic or photo-determined
aging, which is mainly linked to ultraviolet exposure.
[0013] According to recent investigations, 80% of total damage in
the areas exposed to atmospheric agents is determined by exposure
to sunlight. From a cosmetic and pharmaceutical point of view,
however, it is clear that action can be taken only against the
second type of aging.
[0014] The above mentioned genesis of oxygen free radicals in turn
promotes oxidative stress which damages such tissutal structures as
endothelial membranes, proteins, nucleic acids and connective
fibers. The consequences are: [0015] excessive microcirculation
permeability, which causes tissue hypoxia and edema; [0016] protein
denaturization, which is particularly dangerous in the case of
structural proteins and enzymes; [0017] lipidic peroxidation, which
leads to cell death; [0018] connective sclerosis.
[0019] A further damage induced by UV radiation is an increase in
the transcription and translation processes of a particular DNA
segment encoding for some metalloproteins exerting an effective
digestive activity on collagen. This occurs at a speed markedly
higher than that of reparative processes that act on the connective
matrices, resulting in skin damage and the appearance of
wrinkles.
Photo-Carcinogenesis
[0020] Epidemiologic and clinical evidence has now demonstrated how
deeply sun radiations, an in particular UV radiation, are involved
in the development of some pre-cancerous conditions (actinic
keratoses) which may evolve into neoplastic lesions, such as basal
cell epithelioma, spinocellular epithelioma and melanoma, which is
the most dangerous.
[0021] So far, three are the mechanisms apparently involved in the
development of neoplasms caused by UV radiation: mutation induced
by the direct interaction with nitrogenous bases, interaction
between free radicals and DNA, and UV-mediated immunosuppression
induced at the skin level on the key cells in the immune response,
namely dendritic cells, which are no longer capable of exerting an
effective immune response that could suppress tumoral lesion.
[0022] In conclusion, it is clear that a tool aimed at providing a
complete protection of the skin against any UV-mediated damage
should be able to filter UV radiation, as well as act against
oxidative stress, digestion of the connective tissue
mucopolysaccharide fibers, mutagenic activity and UV-mediated
immunosuppression. However, the preparations at present marketed do
not meet all of the above cited requirements.
[0023] The present invention meets the above indicated
requirements, providing pharmaceutical and cosmetic, compositions
which, in addition to conventional sun filters and excipients, also
contain at least two of the following ingredients of vegetable
origin:
TABLE-US-00001 a) phospholipid complexes of flavanolignanes 0.1-5%
extracted from Silybum marianum b) phospholipid complexes of
standardized 0.1-5% extract of Vitis vinifera c) phospholipid
complexes of triterpenes 0.1-5% extracted from Glycyrrhiza
glabra
[0024] The pharmaceutical and cosmetic compositions of the present
invention preferably contain at least two of the following
ingredients of vegetable origin in the following percentages:
TABLE-US-00002 a) phospholipid complexes of flavanolignanes 0.5%
extracted from Silybum marianum b) phospholipid complexes of
standardized 1.5% extract of Vitis vinifera c) phospholipid
complexes of triterpenes 1.5% extracted from Glycyrrhiza glabra
in combination with conventional sun filters and excipients.
[0025] The phospholipid complexes of flavanolignanes extracted from
Silybum marianum (also referred to as "components a") are disclosed
in EP 0.209.038.
[0026] They are characterized by excellent antioxidizing and
antiinflammatory properties. In tests using CCl.sub.4 as a
pro-oxidant stimulus and hepatic microsomes as the target, the LC50
(micrograms per ml) of components a) corresponds to 25.0, while
that of vitamin E (as the reference compound) is 30.0. As far as
the antiinflammatory activity is concerned, components a) proved
capable of inhibiting by 75% edema induced in the experimental
animal paw through inoculation of croton oil. In man, components
a), tested in 20 healthy volunteers against placebo, proved capable
of inhibiting by 25% the erythematous reaction produced by skin
exposure to ultraviolet radiation.
[0027] The phospholipid complexes of standardized extract of Vitis
vinifera (also referred to as "components b") are disclosed in EP
0.275.224.
[0028] In-vitro assays demonstrated the extremely powerful
antioxidant activity of components b). In tests using Fe+++/ADP as
a stimulus and liposomial preparations as the target of oxidation,
components b) proved to be 35 times more active than catechin and
50 times more active than vitamin E. It should also be underlined
that these complexes inhibit by 95% lipidic peroxidation induced by
ultraviolet radiation, even at concentrations as low as 10
micromoles.
[0029] Components b) also proved to be able to inhibit, though in a
non-competitive way, any elastase, collagenase and hyaluronidase
present in inflamed tissue: this characteristic is extremely useful
for a product developed to contrast skin photo-aging.
[0030] In recent mutagenesis assays, components b) showed excellent
anti-mutagenic properties. Tests on spontaneous mutation of
Saccharomyces cerevisiae (yeast and eukaryotic cells) demonstrated
that these complexes can reverse mutation of the mitochondrial and
nuclear DNA by 60% and 90%, respectively (0.5 mg/ml).
[0031] The anti-immunosuppressive properties of components b) were
also evaluated. Components b), applied topically on the skin of
nude mice and tested against placebo, inhibit UV-mediated skin
immunosuppression by about 50%. In man, test in 18 healthy
volunteers showed an 30% inhibition of the erythematous reaction
produced by skin exposure to ultraviolet radiation.
[0032] The phospholipid complexes of triterpenes extracted from
Glycyrrhiza glabra (also referred to as "components c") are
disclosed in EP 0.283.713.
[0033] They exert powerful anti-inflammatory action upon topical
administration, inhibiting the conversion of cortisol from its
active to inactive form through inhibition of tissular 11-beta
hydroxysteroidehydrogenese, extending the anti-inflammatory action
of cortisol released following an inflammatory stimulus. Components
c) proved capable of inhibiting by 95% the edema induced in the
experimental animal paw through inoculation of croton oil, showing
greater effectiveness than common non-steroidal anti-inflammatories
(in this case indomethacin).
[0034] Components a), b) and c) were also toxicologically tested.
The results of the acute toxicity tests carried out in the rat are
summarized in the following Table.
TABLE-US-00003 oral LD50 intraperitoneal LD50 Component mg/kg mg/kg
a) >3.000 >2.000 b) >5.000 >2.221 c) >2.000
>4.432
[0035] Furthermore, acute and chronic cutaneous irritation tests in
the eye carried out on the rabbit proved that components a), b) and
c) do not exert irritative action.
[0036] Neither sensitization nor intolerance symptoms were observed
in skin tests on healthy volunteers.
[0037] The compositions of the present invention will be
administered topically, in the form of suitable formulations both
liquid (such as gel, lotions, milks, emulsions, foams and the like)
and solid or semi-solid (such as creams, ointments, lipsticks, and
the like). Said formulations will be prepared according to
conventional methods, such as those described in "Remington's
Pharmaceutical Handbook", Mack Publishing Co, NY, USA, together
with suitable excipients, such as emollients, moisturizers,
thickening agents, emulsifiers, dyes, flavours and the like.
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