U.S. patent application number 11/913884 was filed with the patent office on 2009-12-17 for gel useful for the delivery of cosmetic active ingredients.
This patent application is currently assigned to SIGMA-TAU INDUSTRIE FARMACEUTICHE RIUNITE SpA. Invention is credited to Antonio Longo, Paola Risi, Mose Santaniello.
Application Number | 20090312421 11/913884 |
Document ID | / |
Family ID | 39083240 |
Filed Date | 2009-12-17 |
United States Patent
Application |
20090312421 |
Kind Code |
A1 |
Longo; Antonio ; et
al. |
December 17, 2009 |
GEL USEFUL FOR THE DELIVERY OF COSMETIC ACTIVE INGREDIENTS
Abstract
It is described a gel, for cosmetic use, composed of a mixture
of a polymer which forms a gel, a surfactant, and propionyl
L-carnitine glycinate hydrochloride, useful for treating
disturbances of the skin such as cellulite and wrinkles.
Inventors: |
Longo; Antonio; (Rome,
IT) ; Santaniello; Mose; (Nettuno, IT) ; Risi;
Paola; (Sermoneta, IT) |
Correspondence
Address: |
LUCAS & MERCANTI, LLP
475 PARK AVENUE SOUTH, 15TH FLOOR
NEW YORK
NY
10016
US
|
Assignee: |
SIGMA-TAU INDUSTRIE FARMACEUTICHE
RIUNITE SpA
Pomezia
IT
|
Family ID: |
39083240 |
Appl. No.: |
11/913884 |
Filed: |
May 11, 2007 |
PCT Filed: |
May 11, 2007 |
PCT NO: |
PCT/EP07/54574 |
371 Date: |
April 10, 2008 |
Current U.S.
Class: |
514/561 |
Current CPC
Class: |
A61Q 19/02 20130101;
A61K 8/8147 20130101; A61K 8/042 20130101; A61Q 17/04 20130101;
A61Q 19/08 20130101; A61Q 19/06 20130101; A61K 8/44 20130101 |
Class at
Publication: |
514/561 |
International
Class: |
A61K 31/197 20060101
A61K031/197 |
Claims
1. A solid powder which comprises: a) a carboxy vinyl polymer which
forms a gel; b) a surfactant; and c) at least one active ingredient
selected from the group comprising: agents supporting the
microcirculation; agents for the activation of the lipolysis;
anti-inflammatory compounds; skin whitening compounds; antioxidants
and anti-wrinkling compounds; agents which improve skin penetration
and efficacy of common anticellulite agents; essential fatty acids
(EFAs); sunscreens; or salts of L-carnitine or an alkanoyl
L-carnitine with amino acids having formula (I): ##STR00003## in
which: R is hydrogen or a straight or branched-chain alkanoyl group
having 2-5 carbon atoms selected from the group consisting of
acetyl, propionyl, butyryl, valeryl and isovaleryl; and Y is the
anion of an amino acid occurring in proteins selected from the
group consisting of: leucine, isoleucine, vahine, cysteine,
arginine, glutamic acid, glutamine, asparagine, glycine, alanine,
threonine, serine, proline, hystidine, methionine, phenylalanine
and tryptophane; the anion Y.sup.- can optionally be salified at
the amino group.
2. A gel which comprises: a) a carboxy vinyl polymer; b) a
surfactant; and c) at least one active ingredient selected from the
group comprising: agents supporting the microcirculation; agents
for the activation of the lipolysis; anti-inflammatory compounds;
skin whitening compounds; antioxidants and anti-wrinkling
compounds; agents which improve skin penetration and efficacy of
common anticellulite agents; essential fatty acids
(EFAs);--sunscreens; or salts of an alkanoyl L-carnitine with amino
acids having formula (I): ##STR00004## in which: R is hydrogen or a
straight or branched-chain alkanoyl group having 2-5 carbon atoms
selected from the group consisting of acetyl, propionyl, butyryl,
valeryl and isovaleryl; and Y is the anion of an amino acid
occurring in proteins selected from the group consisting of:
leucine, isoleucine, vahine, cysteine, arginine, glutamic acid,
glutamine, asparagine, glycine, alanine, threonine, serine,
proline, hystidine, methionine, phenylalanine and tryptophane; the
anion Y.sup.- can optionally be salified at the amino group.
3. The solid powder of claim 1 or the gel of claim 2, in which the
carboxy vinyl polymer is Carbopol.
4. The solid powder of claim 1 or the gel of claim 2, in which the
surfactant is selected from the group consisting of sodium dodecyl
sulfate; an amino acid based cationic surfactant and an amino acid
based nonionic surfactant.
5. The solid powder of claim 1, in which the active ingredient is a
compound not stable in water or in solution.
6. The solid powder of claim 1 or the gel of claim 2, in which the
agents supporting the microcirculation is selected from the group
consisting of extracts of Gingko biloba, ruscus, melilot, red vine
and viburnum.
7. The solid powder of claim 1 or the gel of claim 2, in which the
agents for the activation of the lipolysis is selected from the
group consisting of extracts of Ground ivy, root of Angelica,
Paulinia; M and xanthic bases such as caffeine, theobromine and
theophylline.
8. The solid powder of claim 1 or the gel of claim 2, in which the
anti-inflammatory compounds is selected from the group consisting
of rosmarinic acid, glycyrrizinate derivatives, alpha bisabolol,
azulene and derivatives thereof, asiaticoside, sericoside,
ruscogenin, escin, escolin, quercetin, rutin, betulinic acid and
derivatives thereof, catechin and derivatives thereof.
9. The solid powder of claim 1 or the gel of claim 2, in which the
skin whitening compounds is selected from the group consisting of
ferulic acid, hydroquinone, arbutine, and kojic acid.
10. The solid powder of claim 1 or the gel of claim 2, In which the
antioxidants and anti-wrinkling compounds is selected from the
group consisting of retinol and derivatives thereof, tocopherol and
derivatives thereof, salicylates and their derivatives thereof.
11. The solid powder of claim 1 or the gel of claim 2, in which the
agents which improve skin penetration and efficacy of common
anticellulite agents is selected from the group consisting of a
monocarboxylic acids comprising lactic acid, glycolic acid,
mandelic acid and mixtures thereof.
12. The solid powder of claim 1 or the gel of claim 2, in which the
essential fatty acids (EFAs) is selected from the group consisting
of linoleic acid, gamma-linolenic acid, homo-gamma-linolenic acid,
columbinic acid, eicosa-(n-6,9,13)-trienoic acid, arachidonic acid,
timnodonic acid, hexaenoic acid and mixtures thereof.
13. The solid powder of claim 1 or the gel of claim 2, in which the
sunscreens, is selected from the group consisting of PABA and
derivatives thereof, cinnamate and benzophenone derivatives such as
octyl methoxy-cinnamate and 2-hydroxy-4-methoxy-benzophenone.
14. The solid powder of claim 1 or the gel of claim 2, in which
L-carnitine or the alkanoyl L-carnitine with amino acids having
formula (I) is selected from the group consisting of acetyl
L-carnitine L-isoleucinate hydrochloride, propionyl L-carnitine
L-leucinate hydrochloride, L-carnitine L-valinate phosphate, acetyl
L-carnitine L-cysteinate hydrochloride, acetyl L-carnitine
L-arginate dihydrochloride, acetyl L-carnitine L-glutamninate
hydrochloride, acetyl L-carnitine L-asparaginate hydrochloride,
acetyl L-carnitine glycinate hydrochloride, acetyl L-carnitine
L-alaninate hydrochloride, acetyl L-carnitine L-threoninate
hydrochloride, acetyl L-carnitine L-serinate hydrochloride,
propionyl L-carnitine L-prolinate hydrochloride, L-carnitine
L-hystidinate hydrochloride, L-carnitine L-methionate
hydrochloride, propionyl L-carnitine L-phenylalaninate
hydrochloride, and acetyl L-carnitine L-typtophanate hydrochloride
or propionyl L-carnitine glycinate hydrochloride.
15. The solid powder of claim 1 or the gel of claim 2, in which the
active ingredient is propionyl L-carnitine glycinate
hydrochloride.
16. Method of preparation of the powder of claim 1, which comprises
the following steps: a) preparation of the gel dissolving in water,
or in a solution, the gelling agent, the surfactant and one or more
active ingredients for cosmetic use, maintaining the pH from 4.0 to
6.0; b) the gel so obtained is divided in single doses and put into
vials; c) to obtain a powder the vials of step b) are lyophilized;
alternatively the gel of point a) is directly subjected to
Spray-drying procedure and the powder so obtained is put, in a
suitable amount, into vials.
17. The method of claim 16, in which the pH is controlled using an
inorganic or organic acid or base.
18. The method of claim 17, in which the base is selected from the
group comprising: sodium hydroxide, potassium hydroxide, or a basic
amino acid selected from lysine, arginine, histidine, or
ornithine.
19. Cosmetic composition, comprising the powder or the gel of
claims 1 or 2, and optionally one or more cosmetically acceptable
excipient and/or diluent.
20. Cosmetic composition comprising as active ingredient propionyl
L-carnitine glycinate hydrochloride, and optionally at least a
further active ingredient, and/or cosmetically acceptable
excipient, and/or diluent.
21. Cosmetic composition of claim 20, in which the excipient and/or
diluent is selected from the group consisting of thickener agents;
preservatives; silicone polymers; emollients; water; colouring
agents; opacifiers; and perfumes.
22. Cosmetic composition of claim 20, in which the further active
ingredient is selected from the group consisting of agents
supporting the microcirculation; agents for the activation of the
lipolysis; anti-inflammatory compounds; skin whitening compounds;
antioxidants and anti-wrinkling compounds; agents which improve
skin penetration and efficacy of common anticellulite agents;
essential fatty acids (EFAs); and sunscreens.
23-30. (canceled)
31. Kit comprising the powder of claim 1, and separately, in the
same or in a different container, water or a liquid solution.
32. Kit comprising the powder of claim 1, in which the active
ingredient is propionyl L-carnitine glycinate hydrochloride, and
separately, in the same or in a different container, water or a
liquid solution.
33. A method of preventing or treating disturbances of the skin,
comprising topically administering an effective amount of the
cosmetic composition of claim 20 to an area of the skin requiring
such treatment.
Description
[0001] The present invention relates to a cosmetic composition,
topically administrable, in the form of a solid powder, which
comprises a mixture of: a polymer which forms a gel; a surfactant
and one or more active ingredients useful for treating disturbances
of the skin, in which said powder once is reconstituted with a
suitable amount of water, or a liquid solution, provides a gel
useful for preventing or treating said disturbances of the
skin.
[0002] The present invention further relates to a cosmetic use of a
salt of L-carnitine or an alkanoyl L-carnitine with amino acids
having formula (I):
##STR00001##
[0003] in which:
[0004] R is hydrogen or a straight or branched-chain alkanoyl group
having 2-5 carbon atoms selected from the group consisting of
acetyl, propionyl, butyryl, valeryl and isovaleryl;
[0005] Y is the anion of an amino acid occurring in proteins
selected from the group consisting of: leucine, isoleucine, valine,
cysteine, arginine, glutamic acid, glutamine, asparagine, glycine,
alamine, threonine, serine, proline, hystidine, methionine,
phenylalanine and tryptophane;
[0006] the anion Y can optionally be salified at the amino group,
preferably with a hydrohalogen acid such as hydrochloric acid or
phosphoric acid;
[0007] The salts of L-carnitine or an alkanoyl L-carnitine with
amino acids of formula (I) are useful agents for preparing a
cosmetic composition topically administrable for supporting the
fibrous matrix layer of tissue beneath the skin; for preventing
subdermal tissue from entering or protruding into to the dermis;
for treating patients having cellulite, or for the purpose of
causing the contraction of laxed or wrinkled tissues below the
surface of the epidermis.
FIELD OF THE INVENTION
[0008] The distribution of adipose tissue throughout the body is
not uniform. In certain portions of the body it is present in great
abundance such as in the subcutaneous tissue. A distinction must be
made between fat and adipose tissue; the latter being a distinct
tissue, the former an oily substance. Adipose tissue consists of
small vesicles referred to hereinafter as "fat cells" lodged within
the matrix of areolar connective tissue. Fat cells vary greatly in
size; having an approximate diameter of about 0.05 mm. They are
formed of a delicate protoplasmic membrane filled with the oily
substance which is liquid during life but solidifies after death.
These fat cells are contained in discrete clusters in the areolae
of fine connective tissue.
[0009] Areolar tissue is a form of connective tissue wherein the
investing connective tissue matrix is separated into areolae or
spaces which open into one another and are easily permeated by
fluids. Areolar tissue binds different parts of the body together.
The elasticity of areolar tissue and the permeability of its
areolae allows the various parts of the body to move relative to
one another. Most particularly, areolar connective tissue is found
beneath the skin in a continuous layer all over the body,
connecting the skin (dermis) to subjacent tissues. In many parts
the areolae are occupied by fat cells; the matrix and fat cells
constituting adipose tissue which is referred to alternatively
herein as "depot fat".
[0010] Cellulite is typically characterized by dermal deterioration
due to a breakdown in blood vessel integrity and a loss of
capillary networks in the dermal and subdermal levels of the skin.
The vascular deterioration tends to decrease the dermal metabolism.
This decreased metabolism hinders protein synthesis and repair
processes, which results in dermal thinning. The condition is
further characterized by fat cells becoming engorged with lipids,
swelling, and clumping together, as well as excess fluid retention
in the dermal and subdermal regions of the skin. Thus, individuals
afflicted with cellulite tend to have a thicker subcutaneous fatty
layer of skin. In the advanced stages of cellulite, reticular
protein deposits called septa begin to form around the fatty
deposits in the skin and occlude the fat cells. As the condition
further progresses, hard nodules of fat cells and clumps of fat
surrounded by septa form in the dermal region. This leads to the
surface of the skin displaying considerable heterogeneity and being
characterized as having a "cottage cheese" appearance. This
appearance is most pronounced in overweight individuals.
Individuals with cellulite also tend to have a thinner epidermis
and dermis in the affected region, decreased firmness of the skin,
and decreased rate of cell renewal.
[0011] There is no quick fix solution for cellulite reduction, and
the obvious and most inexpensive way to treat cellulite is to watch
what we eat and drink, and burn those calories by exercising on a
regular basis.
[0012] Thousands of OTC potions, creams and pills to combat
cellulite have flooded the market but the fact remains that
cellulite is still stubborn and refuses to budge easily.
[0013] The appearance of cellulite currently tends to be treated by
administering xanthines, which include caffeine, theophylline, and
aminophylline. Xanthines acts as a diuretic that removes water from
the fat cells and thus reduces the size of the fat cells. The
effect of xanthines, however, is temporary and the fat cells become
rehydrated as soon as the individual replenishes the lost
water.
[0014] A variety of vitamins and minerals have individually been
administered to treat certain skin and other problems that occur
when the patient has a deficiency of that vitamin or mineral.
Vitamin A, for example, assists in the treatment of acne and to
facilitate wound healing; vitamin C (ascorbic acid) assists in the
prevention of skin bruising and wound healing; vitamin E is an
antioxidant; and copper assists in the treatment of elastic tissue
defects. [Neldner, K. H., Amer. Acad. Derm. Annl. Mtg., Wash. D.C.,
Dec. 6, 1993]. Topical use of vitamin C is also believed to ward
off sun damage, reduce breakdown of connective tissues, and
possibly promote collagen synthesis. [Dial, W., Medical World News,
p. 12, March 1991]. Vitamin E is used topically as an
anti-inflammatory agent, for enhancement of skin moisturization,
for UV-ray protection of cells, and for retardation of premature
skin aging.
[0015] It is known that preservatives are added to cosmetics
composition to prevent the growth of microorganisms (eg, bacteria
and fungi), which can spoil the product and possibly harm the user.
It is also known that said preservatives are irritant for the
skin.
[0016] In fact, "U.S. Food and Drug Administration, FDA Consumer,
November 1991; revised May 1995" reports that according to a study
of cosmetic reactions conducted by the North American Contact
Dermatitis Group, preservatives are the second most common cause of
allergic and irritant reactions to cosmetics. FDA also reports that
in 1994 received approximately 200 reports of adverse reactions to
cosmetics; skin-care products and makeup accounted for about 65;
most of the 65 reports were either allergic reactions or skin
irritations.
[0017] In "Nutrition Health Review, Fall, 1990" and in "In Contact
Dermatitis; 1987, July; 17(1):26-34" is reported that a
preservative for cosmetics "Kathon" is a "major cause of cosmetic
allergy.
[0018] In Dermatol. Nurs. 2006; 18(2):130-136, is reported that
formaldehyde-releasing preservatives [the five most commonly used
chemicals in this category are quaternium-15, dimethyl-dimethyl
(DMDM) hydantoin, imidazolidinyl urea, diazolidinyl urea, and
2-bromo-2-nitropropane-1,3-diol (bronopol)], useful for preventing
growth of gram-negative bacteria in cosmetics product cause
localized allergic reactions and eruptions.
[0019] In spite of the large number of products useful for treating
skin disturbances, in cosmetic field it is still a perceived need
to have new vehicles and new active ingredients, useful for
preparing cosmetic compositions for the preventing or treating skin
disturbances, which do not show the drawbacks of the products known
in the art.
DETAILED DESCRIPTION OF THE INVENTION
[0020] It has now been found that a solid powder, which comprises a
mixture of a natural or synthetic polymer which forms a gel, a
surfactant, and one or more active ingredients useful for the
prevention or treatment of disturbances of the skin; once is
reconstituted with a solution provides a gel suitable for cosmetic
use.
[0021] The powder according to the present invention, respect to
the gel or cosmetic compositions present on the market, presents
the following advantages:
[0022] (a) is useful for preparing composition for the delivery of
cosmetic active ingredients which are not stable in solution;
[0023] (b) may not contain irritant preservatives;
[0024] (c) is useful for preparing extemporaneous liquid or semi
liquid composition to be directly applied to the skin [as a
mono-dose or a dose for a day (or more) application].
[0025] It is therefore an object of the present invention a solid
powder which comprises:
[0026] a) a natural or synthetic polymers which forms a gel, an
example of said polymer is a carboxy vinyl polymer such as
Carbopol;
[0027] b) a suitable surfactant selected from: sodium dodecyl
sulphate; amino acid based cationic surfactant made from, for
example, L-arginine, DL-pyrrolidone carboxylic acid, coconut fatty
acids; or amino acid-based nonionic surfactants; and
[0028] c) at least one active ingredient useful for the prevention
or treatment of disturbances of the skin selected from: [0029]
agents supporting the microcirculation which include, but are not
limited to, extracts of Gingko biloba, ruscus, melilot, red vine,
viburnum; [0030] agents for the activation of the lipolysis which
include, but are not limited to, extracts of Ground ivy (Glechoma),
root of Angelica, extract of Paulinia, Subdued or of the xanthic
bases such as caffeine, theobromine and theophylline; [0031]
anti-inflammatory compounds which include, but are not limited to,
rosmarinic acid, glycyrrizinate derivatives, alpha bisabolol,
azulene and derivatives thereof, asiaticoside, sericosidc,
ruscogenin, escin, escolin, quercetin, rutin, betulinic acid and
derivatives thereof, catechin and derivatives thereof; [0032] skin
whitening compounds which include, but are not limited to, ferulic
acid, hydroquinotne, arbutine, and kojic acid; [0033] antioxidants
and anti-wrinkling compounds which include, but are not limited to,
retinol and derivatives, tocopberol and derivatives, salicylates
and their derivatives; [0034] agents which improve skin penetration
and efficacy of common anticellulite agents which include, but are
not limited to a monocarboxylic acids comprising lactic acid,
glycolic acid, mandelic acid and mixtures thereof; [0035] essential
fatty acids (EFAs) exerting an important role in skin defence
against oxidative stress, by entering in the lipid biosynthesis of
epidermis and providing lipids for the barrier formation of the
epidermis; preferred essential fatty acids are selected from the
group consisting of linoleic acid, gamma-linolenic acid,
homo-gamma-linolenic acid, columbinic acid,
eicosa-(n-6,9,13)-trienoic acid, arachidonic acid, gamma-linolenic
acid, timnodonic acid, hexaenoic acid and mixtures thereof; [0036]
sunscreens, for example, derivatives of Para Amino Benzoic Acid
(PABA), cinnamate and benzophenone derivatives such as octyl
methoxy-cinnamate and 2-hydroxy-4-methoxy-benzophenone; or [0037]
salts of L-carnitine or an alkanoyl L-carnitine with amino acids
having formula (I):
##STR00002##
[0037] in which: R is hydrogen or a straight or branched-chain
alkanoyl group having 2-5 carbon atoms selected from the group
consisting of acetyl, propionyl, butyryl, valeryl and isovaleryl;
and Y is the anion of an amino acid occurring in proteins selected
from the group consisting of: leucine, isoleucine, vahine,
cysteine, arginine, glutamic acid, glutamine, asparagine, glycine,
alanine, threonine, serine, proline, hystidine, methionine,
phenylalanine and tryptophane; the anion Y.sup.- can optionally be
salified at the amino group, preferably with a hydrohalogen acid
such as hydrochloric acid or phosphoric acid; preferred active
ingredients are those which are not stable in water or in solution;
most preferred is propionyl L-carnitine glycinate hydrochloride.
The powder according to the present invention once reconstituted
with water or a solution, provides a gel suitable for cosmetic use.
It is a further object of the present invention a gel which
comprises:
[0038] a) a natural or synthetic polymers which forms a gel, an
example of said polymer is a carboxy vinyl polymer such as
Carbopol;
[0039] b) a suitable surfactant selected from: sodium dodecyl
sulphate; amino acid based cationic surfactant made from, for
example, L-arginine, DL-pyrrolidone carboxylic acid, coconut fatty
acids; or amino acid-based nonionic surfactants; and
[0040] c) one or more active ingredients useful for the prevention
or treatment of disturbances of the skin mentioned above.
[0041] It is a further object of the present invention a method of
preparation of the powder of the invention which comprises the
following steps:
[0042] a) preparation of the gel dissolving in water, or in a
suitable solution, the gelling agent, the surfactant and one or
more active ingredients mentioned above, maintaining the pH from
4.0 to 6.0; to control the pH suitable inorganic and/or organic
basic compounds can be used; an example of inorganic basic compound
is sodium or potassium hydroxide; an example of organic basic
compounds is a basic aminoacid selected from lysine, arginine,
histidine, or ornithine;
[0043] b) the gel so obtained is divided in single doses and put
into vials;
[0044] c) to obtain a powder the vials of step b) are lyophilized;
alternatively the gel of point a) is directly subjected to
Spray-drying procedure and the powder so obtained is put, in a
suitable amount, into vials.
[0045] The powder so obtained before the use needs to be
reconstituted with a suitable amount of water, or a solution, to
obtain the gel to be applied to the skin.
[0046] It is a further object of the present invention a cosmetic
composition, comprising the powder or the gel mentioned above, and
optionally at least one excipient or diluent selected from: [0047]
thickener agents in any suitable proportion well known to the
skilled in the art; exemplary thickener agent are gums such as
xanthan, carrageenan, gelatin, karaya, pectin and locust beans gum;
said water-based cosmetic composition can be protected; [0048]
preservatives against the growth of microorganisms; suitable
preservatives include alkyl esters of p-hydroxybenzoic acid,
hydantoin derivatives, propionate salts, methyl paraben, propyl
paraben, imidazolidinyl urea, sodium dehydroxyacetate benzyl
alcohol, and a variety of quaternary ammonium compounds.
Preservatives, if any, are added any suitable proportion well known
to the skilled in the art; [0049] silicone polymers in any suitable
proportion well known to the skilled in the art; [0050] emollients
acting both as carrier, to facilitate the dispersion of the active
ingredient and skin softners; emollients may be incorporated in the
cosmetic composition of the invention in any suitable proportion
well known to the skilled in the art; suitable emollients may be
classified under such general chemical categories as esters, fatty
acids and alcohols, polyols and hydrocarbons; an example of fatty
di-esters include: dibutyl adipate, diethyl sebacate, diisopropyl
dimerate, propylene glycol myristyl ether acetate, diisopropyl
adipate, and dioctyl succinate; an example of branched chain fatty
esters include 2-ethyl-hexyl myristate, isopropyl stearate and
isostearyl palmitate; an example of tribasic acid esters include
triisopropyl trilinoleate, trilauryl citrate, tributirrine, and
saturated or unsaturated vegetable oils; an example of straight
chain fatty esters include lauryl palmitate, myristyl lactate,
oleyl eurcate, stearyl oleate coco-caprylate/caprate, and cetyl
octanoate; an example of fatty alcohols and acids are
C.sub.10-C.sub.20 compounds such as cetyl, myristyl, palmitic and
stearyl alcohols and acids; an example of polyols are linear and
branched chain alkyl polyhydroxyl compounds, such as propylene and
butylene glycol, sorbitol glycerin, as well as polymeric polyols
such as polypropylene glycol and polyethylene glycol; an example of
hydrocarbons are linear C.sub.12-C.sub.30 hydrocarbon chains such
as mineral oil, petroleum jelly, squalene and isoparaffins; [0051]
water; [0052] colouring agents, [0053] opacifiers; [0054]
perfumes
[0055] It is a further object of the present invention a cosmetic
composition comprising as active ingredient propionyl L-carnitine
glycinate hydrochloride, and optionally a further active ingredient
and/or excipient mentioned above.
[0056] It is a further object of the present invention the use of
the solid powder or the gel mentioned above, for preparing a
cosmetic composition useful for the prevention or treatment of
disturbances of the skin selected from cellulite and wrinkle.
[0057] It is a further object of the present invention the use of
propionyl L-carnitine glycinate hydrochloride, for preparing a
cosmetic composition useful for the prevention or treatment of
disturbances of the skin selected from cellulite and wrinkle.
[0058] According to another of its aspects the present invention
relates to a kit for the topical administration of propionyl
L-carnitine glycinate hydrochloride, optionally comprising one or
more active ingredients, and/or one or more suitable diluents,
and/or one or more excipients.
[0059] Further object of the present invention is a kit comprising
the powder of the invention in admixture with one or more active
ingredients (useful in the cosmetic field) and, separately, in the
same or in a different container/vial, water or a liquid solution
suitable for obtaining the gel of the invention.
[0060] A further object of the present invention is a kit
comprising the powder of the invention, in which the active
ingredient is propionyl L-carnitine glycinate hydrochloride, and
separately, in the same or in a different container, water or a
liquid solution.
[0061] A further object of the present invention is a kit
comprising:
[0062] a) the powder of the invention (not mixed with a compound
useful for cosmetic use);
[0063] b) one or more active ingredient useful for cosmetic use (in
liquid, solid, cream, gel or powder form); and
[0064] c) water or a liquid solution suitable for obtaining the gel
of the invention; in which the (three) ingredients are into the
same container/vial in separate space, and said (three) components
can be easily mixed together to obtain the gel of the invention
which may be directly topically administered.
[0065] The expert in container for cosmetic use can easily suggest
suitable containers which contains, for example, the gel mixed with
one or more drugs; or a powder and separately (in the same
container) a liquid; or 2 or more different powders and a liquid;
for single or multiple applications. Different containers/vials are
also included in the present invention.
[0066] According to the present invention propionyl L-carnitine
glycinate hydrochloride in the form of cosmetic composition is
administered topically, in the form of cream or lotion, comprising
from 0.5 to 45% by weight, preferably from 5 to 35% by weight, more
preferably from 10 to 25% by weight of active ingredient,
optionally in admixture with suitable customary auxiliary agents.
The preferred dose is 20%.
[0067] According to the present invention propionyl L-carnitine
glycinate hydrochloride, in the form of cosmetic composition, is
administered topically in the form of gel, or powder to be
reconstituted with water or a liquid solution, comprising from 0.5
to 35% by weight, preferably from 5 to 25% by weight, more
preferably from 7.5 to 15% by weight of active ingredient,
optionally in admixture with suitable customary auxiliary
agents.
[0068] The topical skin treatment composition of the invention can
be formulated in all the forms topics used in beauty care: lotion,
fluid cream, cream or gel. The composition can be packaged in a
suitable container according to its viscosity and to the intended
use by the user. For example, a lotion or fluid cream can be
packaged in a bottle, in a roll-ball applicator, in a capsule,
patch, in a propellant-driven aerosol device or a container fitted
with a pump suitable for finger operation.
[0069] When the composition is a cream, it can simply be stored in
a non-deformable bottle or in a squeeze container, such as a tube
or a lidded jar.
[0070] For each particular form, one has recourse to suitable
excipients.
[0071] These excipients must have all usually required qualities.
As examples, one can quote: the propylene glycol, the glycerin,
cetyl alcohol, the polyols, the phospholipids put in liposomes or
not, oils vegetated, animal, mineral, preservatives, the dampeners,
the thickeners, stabilizing and emulsifying usually used.
[0072] The expression "cosmetically acceptable ingredients"
according to the present invention are products which are suitable
for their use in cosmetic treatments, for example those included in
the INCI list drawn by the European Cosmetic Toiletry and Perfumery
Association (COLIPA) and issued in 96/335/EC "Annex to Commission
Decision of 8 May 1996".
DISCUSSION OF THE DRAWINGS
[0073] FIG. 1 describes the behaviour of the gel of example 1 which
is obtained adding 17.5 mL of water to 3 gr of the solid of example
1. In this figure it is shown that the viscosity decreases
increasing the deformation velocity .gamma. (shear rates) typical
non-Newtonian flow behaviour.
[0074] FIG. 2 describes the behaviour of the gel of example 2 which
is obtained adding 10 mL of water to 1.7 gr of the solid of example
2. Also in this case the viscosity decreases increasing the
deformation velocity .gamma. (shear rates) typical non-Newtonian
flow behaviour.
[0075] The following not limiting examples further illustrate the
present invention.
Materials
[0076] Carbopol 974P NF (Noveon) and all other chemicals were
purchased from Sigma and were used as received.
Preparation of the "Gel Base"
[0077] 7.5 g of Carbopol 974P (Noveon) were slowly added to 500 mL
of water. The mixture so obtained was kept under stirring at room
temperature for 18 h.
[0078] A gel was obtained.
Example 1
[0079] 400 mg of sodium dodecyl sulfate (SDS) were added to 42.4 gr
of gel base; the mixture so obtained was kept under stirring till
complete solubilization of SDS. 5.03 gr of propionyl L-carnitine
glycinate hydrocloride (PLCGH) were slowly added and the gel
mixture was kept under stirring (about 30 min) till complete
solubilization. 2.25 gr of L-lysine were added and the gel was kept
under stirring for about 2 hours (pH 4-6, preferred 4.5-5). The gel
was diluted with 100 ml of water, kept under stirring for about 10
minutes, and lyophilized for 18 hours.
[0080] A white solid was obtained.
[0081] Adding 5 mL of water to 1 gr of the white solid, a gel
containing 10% of propionyl L-carnitine hydrochloride was readily
obtained.
Example 2
[0082] 1.6 gr of SDS were added to 169.5 gr of the gel base; the
gel mixture so obtained was kept under stirring till complete
solubilization.
[0083] 20 gr of propionyl L-carnitine glycinate hydrocloride were
slowly added to the gel and the mixture was kept under stirring
till complete solubilization.
[0084] 9 gr of L-lysine were added, the gel mixture so obtained (pH
4.5-5) was kept under stirring for about 2 hours.
[0085] The gel was diluted with 300 ml of water, and the viscous
solution, constantly kept under stirring was concentrated through a
Spray-drying (Buchi B-191) under the following conditions: Inlet
70.degree. C., ASP=85%, Pump=0.03.
[0086] A white solid was obtained.
[0087] Adding 5 mL of water to 1 gr of the white solid, a gel
containing 10% of propionyl L-carnitine hydrochloride was readily
obtained.
Reological Studies
[0088] The reological studies were carried out with a rotational
viscometer of the concentric cylinder type (Viscometer TV-10 Toky
Sangyo equipped with a small sample adapter and rotor type M3). The
viscosity of the samples were measured at various rates at
25.degree. C. The temperature was maintained within +/-0.1.degree.
C. by a recirculating bath connected to the viscometer. The samples
were equilibrated for five minutes to reach the running temperature
prior to each measurement.
[0089] The results obtained, using the gel of the Examples 1 and 2,
are reported in FIGS. 1 and 2 respectively.
Example 3
[0090] Topical Anticellulite Activity of Propionyl L-Carnitine
Glycinate Hydrochloride
[0091] The effectiveness of a topically administered product
according to the invention was tested for its ability to reduce the
appearance of cellulite in the thigh area. A total of twenty-two
(22) female subjects ranging in age from 28 to 60 years of age were
selected to evaluate the composition of the invention.
[0092] The subjects were selected based on their cellulite
intensity in the thigh area having a bi-lateral symmetry. Subjects
with grades 1 and 2 cellulite were chosen, as a 5-point grading
scale was used to rate the cellulite severity of each subject. The
scale ranged from 0 to 4, being 0=No cellulite; 1=Small bumps or
depressions; 2=Striations and bumps; 3=Pronounced lumpiness of the
skin and striations; 4=All of the above plus hard sub-surface
nodules.
[0093] All subjects had the absence of any visible skin disease(s)
which might be confused with a skin reaction from the test material
were in general good health with no known allergies, especially to
cosmetic or toiletry products; had no evidence of acute or chronic
disease; were not pregnant or lactating; were not on any diet or
weight reduction program; and were not on any regular exercise
program (immediately prior to or during the course of the
study).
[0094] At baseline each subject received a visual examination
conducted by a qualified technician.
[0095] Subjects were treated on the right thigh and the left thigh
was considered as a "control".
[0096] The test sites were carefully demarcated to ensure
subsequent evaluations were made on the same test areas.
[0097] The test sites were examined by a trained observers and
scored for the degree of cellulite at each clinic visit according
to the following scale: 0=No visible cellulite; 1=Very little
visible cellulite, no dimpling; 2=Visible cellulite, evidence of
shallow dimpling; 3=Easily visible cellulite, moderate to
pronounced dimpling; 4=Extremely visible cellulite, heavy and deep
dimpling.
[0098] The subject were taught to carried out the application using
the gel of Example 1, two times a day at morning and at night, for
6 weeks.
[0099] Subjects were provided with a three (3) week supply of the
test product for use at home and were instructed to discontinue the
use of their normal anti-cellulite products, to avoid introducing
any new products for treating cellulite during the study, and to
not be on any diet or weight reduction program or on any regular
exercise program immediately prior to or during the course of the
study. Each subject was also instructed to keep a diary to document
compliance. After three weeks of product usage, the subjects
returned to the laboratory for a visual evaluation of the test
sites.
[0100] Another three (3) week supply of the test product and a new
diary was then dispensed to each subject. After the second three
(3) weeks of product usage (week 6) the subjects returned to the
laboratory for a final visual evaluation.
[0101] The cellulite evaluation was made according the method
described in Cosmetics &, Toiletries, 61-70, June 1995, by
comparison of the right thigh versus left thigh.
[0102] During the treatment period none of the subject reported
adverse events such as itching and/or redness.
[0103] Results obtained are reported in Table 1.
TABLE-US-00001 TABLE 1 Change of the cellulite condition after 6
weeks application Condition Gel of Example 1 Thigh diameter -10%
Fatty layer thickness -26% Skin firmness +18% Skin hydration +26%
Surface smoothness +40% Subjective improvement +55% Clinical
grading +33% Irritation reactions 0
[0104] The results above show that the composition containing
propionyl L-carnitine glycinate hydrochloride effectively
ameliorate the cellulite condition.
[0105] The use of the gel base containing the same amount of
L-lysine and glycine present in the gel obtained using the powder
of example 1, in which the pH was adjusted to 4.5-5 (without
propionyl L-carnitine glycinate hydrochloride) did not show any
improvement of the cellulite condition (data not shown).
Example 4
Topical Application of Propionyl L-Carnitine Glycinate
Hydrochloride for Reducing Appearance of Wrinkles
[0106] Twelve people participated as subjects in a test of the gel.
Each subject was told it was to be used on the wrinkles around
his/her eves and that the protocol was to be a one-part
application. A technician was assigned the task of measuring the
wrinkles on the faces of the subjects before and after application
of the gel of the invention. This technician drew two ovals on a
piece of paper. A quick representative drawing was made of the
subject's wrinkles and fine lines.
[0107] The gel of Example 1 was then applied to the right eye area,
two times a day, at morning and at night, during 7 days treatment.
At the end of a week treatment, five minutes after the last
application of the gel, a second drawing of the skin's appearance
was made.
[0108] The gel produced a noticeable change in the skin's
appearance.
[0109] The use of the gel base containing the same amount of
L-lysine and glycine present in the gel obtained using the powder
of example 1, in which the pH was adjusted to 4.5-5 (without
propionyl L-carnitine glycinate hydrochloride) did not show any
improvement of the skin's appearance.
[0110] No adverse effect were reported by the subjects treated.
[0111] The results reported in Examples 3 and 4 indicate that use
of compound of the invention is useful for the prevention treatment
of cellulite and wrinkle, the observed degree of improvement is a
function of the length of treatment as indicated above. This
strongly suggests the treatment has imparted an improved skin
infrastructure by beneficially affecting the dermis of the
skin.
[0112] Noveon, Inc. introduced Carbopol.RTM. polymer to the
cosmetic industry in the middle 1950's.
[0113] The salts of L-carnitine or an alkanoyl L-carnitine with
amino acids having formula (I) are known compounds and their
reparation process is described in U.S. Pat. No. 6,703,042.
[0114] The topical use of the salts of L-carnitine or an alkanoyl
L-carnitine with amino acids having formula (I) for preventing or
treating cellulite was never disclosed before.
[0115] The cosmetic compositions according to the present invention
are composed of active ingredients which are familiar to operators
in the cosmetic field, already in use and their toxicological
profiles already known.
[0116] Their procurement therefore is very easy, inasmuch as these
are products which have been on the market now for a long time and
are of a grade suitable for human administration.
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