U.S. patent application number 15/154242 was filed with the patent office on 2017-01-12 for use of veronia extract.
The applicant listed for this patent is BAYER CONSUMER CARE AG. Invention is credited to Alain LOISEAU, Virginie PETIT, Caroline SEGOND, Eric THERON.
Application Number | 20170007654 15/154242 |
Document ID | / |
Family ID | 39864406 |
Filed Date | 2017-01-12 |
United States Patent
Application |
20170007654 |
Kind Code |
A1 |
SEGOND; Caroline ; et
al. |
January 12, 2017 |
USE OF VERONIA EXTRACT
Abstract
The present invention relates to the use of an extract of a
Vernonia plant from Madagascar in cosmetics, pharmaceuticals and
food supplements for improving the skin status, more specifically
by strengthening the dermal-epidermal junction and/or by activating
fibroblasts synthesis of dermis and extracellular matrix
compounds.
Inventors: |
SEGOND; Caroline;
(Labastide-Monrejeau, FR) ; LOISEAU; Alain;
(Bouillon, FR) ; PETIT; Virginie; (Pau, FR)
; THERON; Eric; (Montardon, FR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
BAYER CONSUMER CARE AG |
Basel |
|
CH |
|
|
Family ID: |
39864406 |
Appl. No.: |
15/154242 |
Filed: |
May 13, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12589026 |
Oct 16, 2009 |
9339521 |
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15154242 |
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PCT/EP2008/002689 |
Apr 4, 2008 |
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12589026 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61Q 19/00 20130101;
A61K 2236/333 20130101; A61K 36/28 20130101; A61K 8/9789 20170801;
A61P 43/00 20180101; A61Q 19/08 20130101; A61P 17/00 20180101; A61P
17/18 20180101; A61P 17/16 20180101 |
International
Class: |
A61K 36/28 20060101
A61K036/28; A61K 8/97 20060101 A61K008/97 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 17, 2007 |
EP |
07290472.5 |
Claims
1. A composition for treating a skin disorder comprising an extract
of Vernonia appendiculata leaves in an amount from about 0.01% to
about 5% by weight of the total formulation, and at least one
cosmetically or pharmaceutically acceptable carrier.
2. The composition of claim 1, wherein said extract of Vernonia
appendiculata leaves is obtained by extraction of raw Vernonia
appendiculata leaves with a polar solvent.
3. The composition of claim 1, wherein the polar solvent is alcohol
or a mixture of water and alcohol.
3. The composition of claim 1, wherein said extract comprises at
least 5% by weight of chlorogenic and isochlorogenic acids by
weight of the total extract.
4. A composition of claim 1, wherein the composition produces an
anti-aging effect on skin, the anti-aging effect selected from the
group consisting of densifying said skin, firming said skin,
strengthening the dermal-epidermal junction in said skin, improving
the radiance of said skin; improving restructuring of said skin;
preserving a functional interface between the epidermis and dermis
of said skin; and improving the humidity content of said skin.
Description
[0001] The present invention relates to the use of an extract of a
Vernonia plant from Madagascar in cosmetics, pharmaceuticals and
food supplements for improving the skin status, more specifically
by strengthening the dermal-epidermal junction and/or by activating
fibroblasts synthesis of dermis and extracellular matrix
compounds.
[0002] The Vernoniaceae belongs to the Asteraceae (or Compositae)
family which is the most important family of the angiosperms as it
contains 1600 genus and 22800 species. The genus Vernonia,
dedicated to W. Vernon, contains 500 to 1000 species widespread in
America, Africa and South-East Asia.
[0003] Vernonia appendiculata can be collected in Madagascar where
it is named Ambiaty. This plant is a shrub reaching up to 4 m and
is green most of the year but it can become feathery during the dry
season. The leaves are alternate with pinnate veins and are grouped
at the branch extremity: limb is dentate, hairy, and green on top
and white underneath. Blooming gives abundant violet or white
flowers and is in September and October. Fruits are akenes with
double pappus. In Madagascar, this plant can be found in sunny and
dry areas, along rivers and around villages of the High plateaus
region (800-1500 m high, topical climate). Ambiaty is traditionally
used for e.g. wound healing, antipyretic (malaria), stomach ache,
and new leaves can also be cooked as food.
[0004] Vernonia species are also used for obesity and weight loss
(WO 01/15716) and a natriuretic peptide from Vernonia cinerea is
claimed to have slimming property (WO 01/54659). Vernonia cinerea
is used for its anti-oxidant property owing to its superoxide
dismutase-like and free radicals scavenging activities (EP 1 352
640). Vernonia anthelmintica is claimed in oral use for vitiligo
treatment with the activation of tyrosinase and the melanin
synthesis acceleration (CN1089861, CN1141183). EP 1 854 452
describes extracts of Vernonia sublutea for anti-inflammatory use
in the dermal and cosmetic field. WO 2007/113851 describes
compositions containing active ingredients of Vernonia species for
treating hair disorders. WO 01/15716 describes a mixture of
extracts of plant comprising Vernonia, Cissus and Brillantasia for
controlling weight gain and obesity.
[0005] Chlorogenic acid (3-Caffeoylquinic acid) and isochlorogenic
acid (3,5-dicaffeoylquinic acid) are dihydroxycinnamic compounds
which are phenolic compounds.
Chlorogenic Acid:
##STR00001##
[0006] Isochlorogenic Acid:
##STR00002##
[0007] SUMMARY OF THE INVENTION
[0008] The present invention relates to the use of an extract of a
Vernonia plant from Madagascar for improving the skin status, more
specifically by strengthening the dermal-epidermal junction and/or
by activating fibroblasts synthesis of dermis and extracellular
matrix compounds.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 shows a comparison of two biopsies showing GAGs
staining at day 6 of an ex vivo study. One sample has been treated
with a Vernonia appendiculata extract and the other sample is an
untreated control.
[0010] FIG. 2 shows a comparison of two biopsies showing
cytokeratine 14 immuno marking at day 10 of an ex vivo study. One
sample has been treated with a Vernonia appendiculata extract and
the other sample is an untreated control.
[0011] FIG. 3 shows a comparison of two biopsies showing laminin V
immunomarking at day 10 of an ex vivo study. One sample has been
treated with a Vernonia appendiculata extract ant the other sample
is an untreated control.
DETAILED DESCRIPTION OF THE INVENTION
[0012] The dermal-epidermal junction (DEJ) consists of 2 layers
(Laminae lucida and densa) and multiple connections: this original
organization leads to the typical DEJ functions.
[0013] DEJ is first a support for the epidermis: basal
keratinocytes are linked to the Lamina lucida (upper DEJ part)
thanks to their hemidesmosomes and the Cytokeratin 14 protein
anchoring the keratinocytes actin cytoskeleton in the Lamina lucida
layer.
[0014] DEJ also structures skin as the Collagen IV high content of
the Lamina densa participates to the mechanical resistance with the
typical rete ridge pattern increasing the exchanges surface between
epidermis and dermis.
[0015] DEJ participates to skin communication, for example with the
solute supply and filtration in the Lamina reticularia (which is
also called reticular dermis and is in fact the upper part of the
papillar dermis and is characterized by high cells and vessels
contents).
[0016] DEJ is essential for skin cohesion between epidermis and
dermis, notably with the Laminin V glycoprotein (cohesion filament
distributed throughout L. lucida and L. densa) or with the Collagen
VII (curved fibrils inserting into the L. densa and extending
through the papillar dermis).
[0017] Extracts of the present invention can be used for
improvement of the status of the skin e.g. by strengthening the
dermal-epidermal junction and/or by activating fibroblasts
synthesis of dermis and extracellular matrix compounds. That can be
achieved e.g. by activation of laminin V synthesis, activation of
collagen IV synthesis, activation of cytokeratin 14 synthesis or
activation of glucosaminoglycans synthesis. Therefore compounds,
mixtures, and extracts of the present invention can also be used
for skin anti-aging, densifying and firming of the skin, skin
radiance, improvement of the dermal-epidermis junction cohesion,
improvement of the skin structuring, a preserved functional
interface between epidermis and dermis (communication, nutrition .
. . ), the circulation of vital elements, the skin humidity
content, the fibroblasts mobility and/or the fibres distribution in
the dermis network.
[0018] Furthermore the extracts of the present invention can be
used for treating RDEB (recessive dystrophic epidermolysis
bullosa), sub-epidermic dermatosis bullosa, pemphigoides (bullosa,
etc), erythemateous lupus as well as wound healing, ECM renewal,
fibrolysis treatment and treatment of the fibrous reticulation
(glycation, etc.)
[0019] The use of Vernonia extract is an appropriate and safe
method for the treatment of the skin.
[0020] Vernonia extracts according to the invention are extracts of
plants of the Vernonia family from Madagascar which include but are
not limited to Vernonia appendiculata, Vernonia chapelieri,
Vernonia diversifolia, Vernonia sublutea, Vernonia trinervis,
Vernonia trichoderma, Vernonia pectoralis, Vernonia moquinoides and
Vernonia eryophylla. Preference is given to Vernonia
appendiculata.
[0021] The extraction can be performed on all parts of the
plant(s). Preferably the leaves of Vernonia appendiculata are
extracted.
[0022] The extraction can be done by standard extraction methods.
Preferably the extraction is carried out with a polar solvent
applicable for extraction. Leaves are first extracted with a polar
solvent optionally by several times. The obtained solution is then
mixed and extracted with a non polar solvent e.g. heptan to remove
the waxes, essential oils, pigments and most of the non polar
molecules. After phase separation, glycerin is added to the aqueous
solution in order to adjust the vegetal extract content at a
minimum of 10% by weight of the dried extract in a glycerin-water
blend 1:1.
[0023] An extract according to the invention is normally an extract
in solution. Nevertheless the extract can also be used as a dried
extract (e.g. after freeze-drying) or be further used in
encapsulation process.
[0024] The polar solvent used for extraction is preferably alcohol
or a mixture of water and alcohol wherein the alcohol is preferably
ethanol. The ratio of the volume between water and alcohol can be
from 50:50 up to 90:10, preferably 70:30.
[0025] The dry plant extract can contain chlorogenic and/or
isochlorogenic acids in a total amount of more than 5% by weight of
the total extract, or a solution thereof. Most preferably the plant
extract is an extract of Vernonia appendiculata.
[0026] Extracts of the present invention can be administered in any
form by any effective route, including, e.g., oral, parenteral,
enteral, intravenous, intraperitoneal, topical, transdermal (e.g.,
using any standard patch), ophthalmic, nasally, local, non-oral,
such as aerosal, inhalation, subcutaneous, intramuscular, buccal,
sublingual, rectal, vaginal, intra-arterial, and intrathecal, etc.
They can be administered alone, or in combination with any
ingredient(s), active or inactive. Preference is given to a topical
administration.
[0027] Extracts of the present invention can be converted in a
known manner into the usual formulations such as cosmetic or
pharmaceutical compositions or compositions used as food
supplement. These may be liquid or solid formulations e.g. without
limitation normal and enteric coated tablets, capsules, pills,
powders, granules, elixirs, tinctures, solution, suspensions,
suppositories, syrups, solid and liquid aerosols, emulsions,
pastes, creams, ointments, milks, gels, salves, serums, foams,
shampoos, sticks or lotions.
[0028] Preference is given to a cosmetic composition in a form of
an aqueous solution, a white or colored cream, ointment, milk, gel,
salve, serum, foam, shampoo, stick, cream, paste, or lotion.
[0029] Extracts of the present invention can be further combined
with any other suitable additive or pharmaceutically acceptable
carrier. Such additives include any of the substances already
mentioned, as well as any of those used conventionally, such as
those described in Remington: The Science and Practice of Pharmacy
(Gennaro and Gennaro, eds, 20th edition, Lippincott Williams &
Wilkins, 2000); Theory and Practice of Industrial Pharmacy (Lachman
et al., eds., 3rd edition, Lippincott Williams & Wilkins,
1986); Encyclopedia of Pharmaceutical Technology (Swarbrick and
Boylan, eds., 2nd edition, Marcel Dekker, 2002). These can be
referred to herein as "pharmaceutically or cosmetically acceptable
carriers" to indicate they are combined with the active drug and
can be administered safely to a subject for therapeutic
purposes.
[0030] The dosage of the extracts of the present invention can be
selected with reference to the other and/or the type of disease
and/or the disease status in order to provide the desired
therapeutic activity. These amounts can be determined routinely for
a particular patient, where various parameters are utilized to
select the appropriate dosage (e.g., type of disease, age of
patient, disease status, patient health, weight, etc.), or the
amounts can be relatively standard.
[0031] The amount of the administered extract can vary widely
according to such considerations as the particular compound and
dosage unit employed, the mode and time of administration, the
period of treatment, the age, sex, and general condition of the
patient treated, the nature and extent of the condition treated,
the rate of drug metabolism and excretion, the potential drug
combinations and drug-drug interactions, and the like.
[0032] Preference is given to a composition comprising the dried
extract of the present invention in an amount of from 0.01% to 5%,
preferably 0.1 to 1% by weight of the total composition.
[0033] Preference is also given to a composition containing a
solution, preferably a water-based solution, of the extract
according to the invention in an amount of from 0.1% up to 10%,
preferably 1% up to 7% by weight of the total composition.
[0034] The composition according to the invention is administered
one or more, preferably up to three, more preferably up to two
times per day. Preference is given to a topical administration.
[0035] Nevertheless, it may in some cases be advantageous to
deviate from the amounts specified, depending on body weight,
individual behaviour toward the active ingredient, type of
preparation and time or interval over which the administration is
effected. For instance, less than the aforementioned minimum
amounts may be sufficient in some cases, while the upper limit
specified has to be exceeded in other cases. In the case of
administration of relatively large amounts, it may be advisable to
divide these into several individual doses over the day.
[0036] Extracts of the present invention can also be combined with
at least one further active substance or plant extract e.g.
substances or plant extracts usually employed for dermatological or
cosmetic use.
[0037] Further active substances include but are not limited to
desquamating and/or moisturizing agents, UV filtering or blocking
agents, depigmenting or propigmenting agents, antiglycation agents,
anti-inflammatory agents, anti-microbial agents, agents stimulating
the synthesis of dermal, epidermal, hair or nail macromolecules
and/or preventing the degradation thereof, agents stimulating the
differentiation of keratinocytes, muscle relaxants, antipollution
and/or anti-free radical agents, slimming agents, agents acting on
the microcirculation, agents acting on the energy metabolism of the
cells, tightening agents, agents preventing the loss or stimulating
the growth of hair, agents preventing grey or white hair, or a
mixture thereof. Preferably that combination is contained in a
topically dermatological or cosmetically composition.
EXAMPLES
Example 1
Vernonia appendiculata Extract
[0038] Dried leaves of Vernonia appendiculata are first extracted
with heptan before percolation with ethanol. Fat removal is then
obtained thanks to a liquid-liquid extraction with heptan. After
concentration into the aqueous phase, glycerine is added to adjust
the solution to 10% w/v of vegetal extract in a water-glycerin
blend. The final product is then a liquid form.
[0039] The composition can be tested by HPLC and a typical
composition of the (dried) vegetal extract contains more than 5% of
chlorogenic and isochlorogenic acids by weight of the total
extract.
Example 2
Anti-Aging Cream
TABLE-US-00001 [0040] INCI Name Amount Glyceryl Stearate (and)
PEG-100 Stearate 2.00 Cetearyl alcohol (and) Cetearyl glucoside
3.00 Octyldodecyl Myristate 4.00 Vegetable Squalane 3.00 Dicaprylyl
Ether 3.00 C8/C10 Triglycerides 2.00 Cyclomethicone 3.00
Phenoxyethanol (and) Methylparaben (and) 0.80 Ethylparaben (and)
Propylparaben (and) Isobutylparaben Glycerin 1.50 Ethoxydiglycol
0.75 Water (and) Glycerin (and) Vernonia Appendiculata 1.00 Leaf
Extract (Vernonia extract according to example 1) Water Qs 100%
Example 3
Ex Vivo Evaluation of Glucosaminoglycans, Cytokeratine 14 and
Laminin V Activation
[0041] Biopsies from abdominal plastic surgery are used in this ex
vivo experiment. They are cultured in a specific survival explants
medium: BEM (BIO-EC's Explants Medium).
[0042] 2 mg of a formulation containing 7% of the extract according
to example 1 is applied on the skin stripes at the following times:
Day D0, D1, D2, D4, D6 and D8. The results are compared with the
untreated skin stripes.
[0043] Histological studies are performed at D6 and D10. For
morphological analysis, explants are fixed after dehydration and
paraffin impregnation, with Bouin's solution. They are then cut and
stained by Masson's trichome stain. Specific staining and
immunomarking are performed on frozen cryostat cut tissues.
a--Evaluation of Glucosaminoglycans (GAGs):
[0044] Specific immunostaining of GAGs is performed by Mowry
staining method (Alcian blue stain) and enables to visualize the
GAGs present in the papillar dermis and along the dermal-epidermal
junction (DEJ) due to pink-violet staining.
Observations of the GAGs at D6:
[0045] For all the biopsies, there is no activation of the acid
GAGs present in the papillar dermis. Concerning the untreated skin
stripes, neutral GAGs are present along the DEJ with moderate
staining on an irregular and thin band. For the explants treated
with Vernonia appendiculata extract, neutral GAGs are clearly
marked along the DEJ and form a regular and thin band (FIG. 1).
[0046] The amplified marking indicates that the treatment with
Vernonia appendiculata extract increases the GAGs content in the
dermis.
b--Evaluation of Cytokeratin 14:
[0047] Specific immunomarking of Cytokeratin 14 is performed thanks
to monoclonal antibodies Anti-Keratin 14 (Progen ref RCK107) and
revealed by FITC. Cells nuclei are then stained with propodium
iodide. Keratin 14 can then be observed in the dermal-epidermal
junction area due to fluorescent marking.
Observations of the Cytokeratin 14 at D10:
[0048] Concerning the untreated skin stripes, the marking is clear
and more and less regular on the basal keratinocytes layer. It is
light on the second cells layer. For the explants treated with
Vernonia appendiculata extract, the marking is very clear and
regular on the basal keratinocytes layer and moderate on the second
cells layer (FIG. 2).
[0049] The treatment with Vernonia appendiculata extract helps to
upregulate the Cytokeratin 14 release in the epidermis.
c--Evaluation of Laminin V:
[0050] Specific immunomarking of Laminin V is performed thanks to
monoclonal antibodies Anti-Laminin V (Santa Cruz ref sc 13587) and
revealed by FITC. Cells nuclei are then stained with propodium
iodide. Laminin V can then be observed in the dermal-epidermal
junction area due to fluorescent marking.
Observations of the Laminin V Synthesis:
[0051] Whereas the marking is quite clear and more and less regular
on the cells membrane for the untreated biopsies, it is very clear
and very regular after treatment with Vernonia appendiculata
extract (FIG. 3).
[0052] The treatment with Vernonia appendiculata extract helps to
upregulate the Laminin V content.
Example 4
Ex Vivo Evaluation of Collagen IV Activation
[0053] Biopsies from abdominal plastic surgery are used in this ex
vivo experiment. They are cultured in a specific survival explants
medium: BEM (BIO-EC's Explants Medium).
[0054] 2 mg of a formulation containing 1% of the extract according
to example 1 is applied on the skin punches at the following times:
Day D0, D1, D2, D4, D6 and D8. The results are compared to a
control formulation (excipient without active compounds) and to a
reference formulation (commercial formulation containing
retinol).
[0055] Histological studies are performed at D6 and D10.
[0056] For morphological analysis, explants are fixed after
dehydration and paraffin impregnation, with Bouin's solution. They
are then cut and stained by Masson's trichome.
[0057] Specific immunomarking of Collagen IV is performed on frozen
cryostat cut tissues thanks to monoclonal antibodies Anti-Collagen
IV (SBA) and revealed by FITC. Cells nuclei are then stained with
propodium iodide. Collagen IV can then be observed in the
dermal-epidermal junction area and in the upper papillar dermis due
to fluorescent marking.
Collagen IV Evaluation by Image Analysis
[0058] Image analysis is performed after image digitization and
evaluates the surface occupied by the staining. The percentage of
the surface occupied by collagen IV is greater for the biopsies
treated with Vernonia appendiculata extract than for the untreated
excised skin or those treated with the excipient: +23.4% versus
excipient, +24.8% versus untreated. These values are comparable to
the results obtained with a retinol formulation.
* * * * *