U.S. patent application number 13/227838 was filed with the patent office on 2011-12-29 for stabilized ascorbic acid solutions; method of use thereof; process for their obtention; and compositions comprising the same.
Invention is credited to Anthony COSTA, Ghislain VIVIER.
Application Number | 20110319486 13/227838 |
Document ID | / |
Family ID | 22867624 |
Filed Date | 2011-12-29 |
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United States Patent
Application |
20110319486 |
Kind Code |
A1 |
VIVIER; Ghislain ; et
al. |
December 29, 2011 |
STABILIZED ASCORBIC ACID SOLUTIONS; METHOD OF USE THEREOF; PROCESS
FOR THEIR OBTENTION; AND COMPOSITIONS COMPRISING THE SAME
Abstract
This invention relates to improved solutions comprising ascorbic
acid (vitamin C). These solutions may comprise as much as 15%
ascorbic acid; they are stable for at least two years, without no
significant development of yellowish coloration and no substantial
(not more than 10%) degradation of the vitamin. The process
involves sequential additions of ascorbic acid and ethoxydiglycol
to a first solution of vitamin in water, which are followed by
addition of propylene glycol. The stirring speed that occurs during
the additions favors a process of micronization. Mild heating is
used to achieve ascorbic acid concentrations equivalent to about 6%
in 10% water or higher.
Inventors: |
VIVIER; Ghislain;
(St-Lazare, CA) ; COSTA; Anthony; (Vimont,
CA) |
Family ID: |
22867624 |
Appl. No.: |
13/227838 |
Filed: |
September 8, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12019991 |
Jan 25, 2008 |
8053469 |
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13227838 |
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10363929 |
Mar 7, 2003 |
7342045 |
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12019991 |
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PCT/CA01/01270 |
Sep 10, 2001 |
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10363929 |
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60231068 |
Sep 8, 2000 |
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Current U.S.
Class: |
514/474 |
Current CPC
Class: |
A61K 8/345 20130101;
A61K 2800/52 20130101; A61P 17/10 20180101; A61P 35/00 20180101;
A61K 8/34 20130101; A61P 17/18 20180101; A61K 36/752 20130101; A61Q
19/08 20130101; A61K 31/375 20130101; A61P 17/06 20180101; A61Q
19/00 20130101; A61Q 17/04 20130101; A61P 39/06 20180101; A61P
17/16 20180101; A61K 2300/00 20130101; A61P 37/08 20180101; A61P
17/00 20180101; A61P 17/04 20180101; A61K 36/752 20130101; A61K
8/676 20130101 |
Class at
Publication: |
514/474 |
International
Class: |
A61K 31/375 20060101
A61K031/375; A61P 39/06 20060101 A61P039/06; A61P 17/00 20060101
A61P017/00 |
Claims
1. A process for obtaining a stabilized ascorbic acid of a desired
concentration of 15% (w/w) or less in solution, which comprises a)
dissolving a first amount of ascorbic acid in water, thereby
obtaining a first solution; b) adding a first amount of glycol to
said first solution, under a stirring speed sufficient to micronize
same, ascorbic acid and water, thereby obtaining a second solution;
c) adding a second amount of ascorbic acid to said second solution
under a stirring speed sufficient to micronize same, thereby
obtaining a third solution; d) adding a second amount of glycol to
said third solution under high stirring speed sufficient to
micronize same, thereby obtaining a fourth solution; and e) adding
another glycol, which results into the obtention of a solution of
ascorbic acid having the desired concentration.
2. The process of claim 1, which further comprises a step f) of
adding an anti-oxidant to the solution of step e).
3. The process of claim 2, which further comprises after step f),
adding a fragrance material to the solution.
4. The process of claim 1, which further comprises the step of
adding a third amount of ascorbic acid between steps d) and e).
5. The process of claim 2, which further comprises the step of
adding a third amount of ascorbic acid between steps d) and e) and,
when the desired concentration of ascorbic acid is more than 6%
(w/w), further comprises a step of adding a fourth amount of
ascorbic acid after step f), followed by a step of heating at a
temperature of about 37 to 42.degree. C. until a clear solution is
obtained, followed by a step of cooling down.
6. The process of claim 5, wherein said temperature is about
40.degree. C.
7. The process of claim 6, which comprises adding a fragrance
material after the cooling down.
8. The process of claim 5, which further comprises after step f)
adding a fragrance material to the solution.
9. The process of claim 8, which further comprises adding at least
one topically suitable carrier or compound after the cooling
step.
10. The process of claim 9, wherein the at least one topically
suitable carrier or compound comprises a topically suitable carrier
or compound selected from the group consisting of tocopherol,
tocopheryl acetate, retinol, retinyl palmitate, hydroquinone,
proanthocyanidins, butylated hydroxytoluene, butylated
hydroxyanisole, astaxanthin, alpha lipoic acid, tocotrienols,
coenzyme Q10, .alpha.-hydroxy acid, kojic acid, kinetin, wine
extract, vitamin K, ascorbyl palmitate, magnesium ascorbyl
phosphate, sodium ascorbyl phosphate, a sun blocking agent and any
combination thereof.
11. The process of claim 9, wherein the at least one topically
suitable carrier or compound comprises tocopherol.
12. The process of claim 9, wherein the at least one topically
suitable carrier or compound comprises hydroquinone.
13. A solution comprising a stabilized ascorbic acid of a
concentration of 15% (w/w) or less prepared by a process which
comprises: a) dissolving a first amount of ascorbic acid in water,
thereby obtaining a first solution; b) adding a first amount of
glycol to said first solution under a stirring speed sufficient to
micronize the glycol, ascorbic acid and water, thereby obtaining a
second solution; c) adding a second amount of ascorbic acid to said
second solution under a stirring speed sufficient to micronize
same, thereby obtaining a third solution; d) adding a second amount
of glycol to said third solution under a stirring speed sufficient
to micronize same, thereby obtaining a fourth solution; and e)
adding another glycol, which results into the obtention of a
solution of ascorbic acid having the desired concentration.
14. The solution of claim 13, the process further comprising a step
f) of adding an anti-oxidant to the solution of step e).
15. The solution of claim 13, the process further comprising the
step of adding a third amount of ascorbic acid between steps d) and
e).
16. The solution of claim 14, which further comprises adding a
fragrance material to the solution obtained after step f).
17. The solution of claim 14, the process further comprising the
step of adding a third amount of ascorbic acid between steps d) and
e) and which, when the desired concentration of ascorbic acid is
more than 6% (w/w), further comprises a step of adding a fourth
amount of ascorbic acid after step f), followed by a step of
heating at a temperature of about 37 to 42.degree. C. until a clear
solution is obtained, followed by a step of cooling down.
18. The solution of claim 17, wherein said temperature is about
40.degree. C.
19. The solution of claim 18, which comprises adding a fragrance
material after the cooling down.
20. The solution of claim 18, which further comprises adding a
fragrance material to the solution.
21. The solution of claim 20, which further comprises adding at
least one topically suitable carrier or compound after the cooling
step.
22. The solution of claim 21, wherein the at least one topically
suitable carrier or compound comprises a topically suitable carrier
or compound selected from the group consisting of tocopherol,
tocopheryl acetate, retinol, retinyl palmitate, hydroquinone,
proanthocyanidins, butylated hydroxytoluene, butylated
hydroxyanisole, astaxanthin, alpha lipoic acid, tocotrienols,
coenzyme Q10, .alpha.-hydroxy acid, kojic acid, kinetin, wine
extract, vitamin K, ascorbyl palmitate, magnesium ascorbyl
phosphate, sodium ascorbyl phosphate, a sun blocking agent and any
combination thereof.
23. The solution of claim 21, wherein the at least one topically
suitable carrier or compound comprises tocopherol.
24. The solution of claim 21, wherein the at least one topically
suitable carrier or compound comprises hydroquinone.
25. A topical composition comprising the solution of claim 13, and
further comprising at least one topically suitable carrier or
compound.
26. The topical composition of claim 25, wherein the at least one
topically suitable carrier or compound comprises a topically
suitable carrier or compound selected from the group consisting of
tocopherol, tocopheryl acetate, retinol, retinyl palmitate,
hydroquinone, proanthocyanidins, butylated hydroxytoluene,
butylated hydroxyanisole, astaxanthin, alpha lipoic acid,
tocotrienols, coenzyme Q10, .alpha.-hydroxy acid, kojic acid,
kinetin, wine extract, vitamin K, ascorbyl palmitate, magnesium
ascorbyl phosphate, sodium ascorbyl phosphate, a sun blocking agent
and any combination thereof.
27. The topical composition of claim 26, wherein the at least one
topically suitable carrier or compound comprises tocopherol.
28. The topical composition of claim 26, wherein the at least one
topically suitable carrier or compound comprises hydroquinone.
29. A method for preventing or treating a disease or disorder
involving or caused by reactive oxygen species, which comprises the
step of topically administering a suitable amount of the solution
of claim 13.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a Continuation Application of U.S.
patent application Ser. No. 12/019,991 now pending, which is a
Continuation Application of U.S. patent application Ser. No.
10/363,929 now U.S. Pat. No. 7,342,045 issued on Mar. 11, 2008
which is a Continuation-in-Part Application of PCT application no.
PCT/CA01/01270 filed on Sep. 10, 2001 and published in English
under PCT Article 21(2), which itself claims benefit of U.S.
provisional application No. 60/231,068, filed on Sep. 8, 2000. All
documents above are incorporated herein in their entirety by
reference.
FIELD OF THE INVENTION
[0002] The present invention relates to stabilized ascorbic acid
solutions; method of use thereof; and compositions comprising the
same. This invention further relates to processes for the obtention
of such stabilized ascorbic acid solutions and compositions.
BACKGROUND OF THE INVENTION
[0003] Skin appearance and elasticity has always been a cosmetic
concern for almost everybody. Skin protection against actinic
radiations has become a great health concern over the past ten to
twenty years. UV exposure results in the formation of noxious
reactive oxygen species (ROS). Skin damages cannot only be life
threatening, but they contribute for premature skin ageing. The
most popular way by which UV damages are prevented is to block
their penetration through the skin using sunscreen formulations.
The notion that antioxidants may also be used to improve the
therapeutic or cosmetic performance of dermatological formulations
is more recent. Antioxidants would in that case have a role in
neutralizing ROS or preventing their formation into the skin.
Antioxidants include compounds such as ascorbic acid and complexes,
tocopherol, tocopheryl acetate, retinol, retinyl palmitate,
hydroquinone, proanthocyaniadins, butylated hydroxytoluene,
butylated hydroxyanisole, astaxanthin, alpha lipoic acid,
tocotrienols, certain proteins and coenzyme Qio. Each antioxidant
may be used alone or in combination with each another as active
ingredients or as stabilizing and preservation agents to protect
other active ingredients against oxidative damages. Antioxidants
may also be used alone or in combination with reducing agents such
as L-cysteine or glutathione.
[0004] Antioxidants need to remain in their unoxidized form in
order to be efficacious against ROS. Maintenance of antioxidants
stability in solutions has been a challenge over the past
years.
[0005] Ascorbic acid, also known as vitamin C, is certainly one of
the most popular antioxidants. This vitamin is known for its
general essential role in maintaining health. In dermatology,
vitamin C is known for its implication in collagen synthesis as
well as for its antioxidant function, which ultimately helps reduce
the expression of skin ageing, translated into the appearance of
fine lines or wrinkles in the skin. Vitamin C also has an
anti-tyrosinase effect on the skin for skin whitening effect.
[0006] Vitamin C is a moderately strong reducing agent, which makes
it unstable in aqueous solutions, especially at high pHs. It is
particularly subject to oxidative degradation.
[0007] Water is one of the best solvents to dissolve ascorbic acid.
Its limit of solubility appears to be about 330 mg/ml in water.
Ascorbic acid is therefore relatively soluble in water. It is much
less soluble in glycols such as propylene glycol (50 mg/ml) and in
alcohols such as ethanol (10 mg/ml in absolute ethanol).
[0008] Although water is the best solvent to provide an ascorbic
acid solution, it is paradoxically one of the worst to protect
ascorbic acid against oxidative damages. A proportion of water
needs to be replaced with another solvent that provides more
stability.
[0009] The problem to be solved with ascorbic acid formulations has
always been to find a compromise between solubilization and
stability.
[0010] U.S. Pat. No. 5,140,043 discloses an ascorbic acid
formulation that has a pH below 3.5, preferably below 2.5. A low pH
insures that a high proportion of ascorbic acid remains in the
protonated, uncharged form. The protonated form is more stable and
more easily permeant through skin and mucosae membranes than the
non-protonated counterpart. Metals also negatively influence the
preponderance of the protonated form of ascorbic acid in a
solution. A chelator may therefore be added in ascorbic acid
solutions to stabilize the vitamin. The carrier in which the
ascorbic acid is dissolved comprises an alkylene glycol, namely
propylene glycol. The carrier further comprises
hydroxyalkylcellulose, the polyhydroxyl function of which
apparently participates in the typical reactions of alcohols. The
proportion of water remains very high (more than 50% by weight),
which may lead to a relatively rapid degradation at room
temperature.
[0011] U.S. Pat. No. 4,983,382 discloses the use of polyhydric
liquids to solubilize and stabilize ascorbic acid. A mixture of
ethanol 55-65% and propylene glycol 20-25% is especially preferred
for its excellent cosmetic properties. Water may be present in
concentrations up to 12% without adversely affecting the stability
of ascorbic acid solubilized in a mixture of alcohol and propylene
glycol. The organic solvents, all combined, represent up to 90% by
weight of a composition. The low water contents recommended does
not appear to permit solubilization of more than 10% of ascorbic
acid.
[0012] U.S. Pat. No. 6,124,348 proposes to combine ascorbic acid, a
volatile organic solvent such as isodecane and a gelling base. The
solvent does not react with or solubilize the vitamin. Such a
suspension is applied to the skin. The skin moisture penetrates the
suspension and solubilizes the ascorbic acid which then can
permeate the skin layer. The solubility of ascorbic acid in the
formulation is not dealt with in this patent.
[0013] Another type of dispersion of ascorbic acid is disclosed in
U.S. Pat. No. 6,103,267. Again, this patent does not describe a
solution of ascorbic acid.
[0014] Another approach to stabilize ascorbic acid solution has
been to decrease water activity in the same. U.S. Pat. No.
5,736,567 discloses compositions wherein water activity is
decreased below 0.85. The lowest water activity achieved with the
descriptive examples has been 0.63. At this value, the water
content is 21%, the ascorbic acid concentration is 3%, the
polypropylene glycol content is 39.4% and polyethylene glycol
content is 13% (all percentages given by weight of formulation).
The aqueous phase is combined with an oil phase to provide a
composition that has a "structure". This particular formulation has
been tested for its stability. After two months at 20.degree. C.,
0.7% of ascorbic acid has degraded which is fairly good compared to
the same solution prepared with 28% water (3.5% degradation) and a
composition also comprising 28% water but without the glycols (6.2%
degradation). The concentration of ascorbic acid that may be
present in these formulations is not higher than 10%.
[0015] U.S. Pat. No. 6,087,393 discloses a composition comprising
ascorbic acid in a mixed glycerol carrier. The glycerol carrier
comprises propylene glycol and butylene glycol, as well as a
stabilizer which may be diethylene glycol monoethylether. The
preferred proportions of propylene glycol, butylene glycol and
diethylene glycol monoethylether are 25-80%, 5-30% and 5-10%,
respectively. Ascorbic acid may be present in concentrations
comprised between 2% and 15%. In these solutions, the major glycol
component is clearly propylene glycol while butylene glycol is
added as a solubilizing aid and diethylene glycol monoethylether is
added in minor proportion as a stabilizer. The stability of these
solutions is not excellent because, at best, the samples admittedly
start to develop a yellowish colour after one month at room
temperature.
[0016] Another approach to formulate and use ascorbic acid in
dermatology has been not to deal with its stability. U.S. Pat. No.
5,935,584 proposes to provide separate compartments that are
extemporaneously mixed together prior to use. One compartment
comprises vitamin C, the other one comprises an aqueous phase. Once
reconstituted by admixing the contents of both compartments,
ascorbic acid is provided in a solution that is more alkaline than
usual solutions of ascorbic acid. The limit of solubility of the
vitamin achieved with such a solution is close to 50%. Further,
once reconstituted, the ascorbic acid formulation comprises about
half-and-half polyethylene glycol and water.
[0017] In view of the foregoing, there is still a need to develop a
solubilized ascorbic acid in suitable concentrations, and which
remains stable for a practical shipping and storage amount of time,
and which keeps a clear substantially non-coloured visual aspect
for the same amount of time.
SUMMARY OF THE INVENTION
[0018] It is a first goal of this invention to provide a solution
of ascorbic acid that is stable at least for about twenty-four
months. The solution may comprise concentrations of ascorbic acid
as high as 5 to 15%.
[0019] The solution comprises a carrier essentially formed of
water, ethoxydiglycol and propylene glycol. Ethoxydiglycol is the
major glycol component. The solution may be used as is or combined
to other carriers to provide a plurality of different topical
formulations or compositions. Sprays, emulsions, droplets, creams,
ointments, milks and lotions are all examples of suitable
compositions. The solutions and compositions may be used to prevent
or treat a disease or disorder caused by ROS, namely consequent to
U.V. or sun exposure. They may further include an anti-oxidant or a
reducing agent and they may also include sunblocking ingredients,
and depigmentation (skin whitening) agents or other cosmetically
valuable compounds. Compositions comprising the present vitamin C
solution and one or more of an .alpha.-hydroxy acid, retinol, kojic
acid, hydroquinone, wine extracts kinetin, vitamin K, ascorbyl
palmitate, and magnesium and sodium ascorbyl phosphate are all
examples of specific cosmetic compositions which are objects of
this invention.
[0020] It is another object of this invention to provide a process
by which such a stable vitamin C solution can be obtained, which
involves sequential additions of vitamin and ethoxydiglycol,
followed by propylene glycol, under high stirring speed. If needed,
a last addition of ascorbic acid and heating steps are performed to
achieve high concentrations of the vitamin. The high stirring speed
provides for micronizaton of the components, which is responsible
for the stability of the solutions.
[0021] As used herein, the terminology "anti-oxidant plant extract"
is meant to refer to plant, seed, herb, spice or fruit extract.
[0022] More particularly, there is provided a process for obtaining
a stabilized ascorbic acid of a desired concentration of 15% (w/w)
or less in solution, which comprises dissolving a first amount of
ascorbic acid in water, thereby obtaining a first solution; adding
a first amount of ethoxydiglycol to said first solution, under high
stirring speed to micronize ethoxydiglycol, ascorbic acid and
water, thereby obtaining a second solution; adding a second amount
of ascorbic acid to said second solution under high stirring speed,
thereby obtaining a third solution; adding a second amount of
ethoxydiglycol to said third solution under high stirring speed,
thereby obtaining a fourth solution; and adding propylene glycol,
which results into the obtention of a solution of ascorbic acid
having substantially the desired concentration.
[0023] In a specific embodiment, there is provided a process of the
present invention, which further comprises a step f) of adding a
anti-oxidant plant extract to the solution of step e).
[0024] In another specific embodiment, there is provided a process
of the present invention, wherein said first and second amounts of
ascorbic acid achieve a concentration of 3% and 2% respectively,
said first and second amounts of ethoxydiglycol are both 27.35%,
propylene glycol and water are added to achieve 29% and 10%,
respectively, and said anti-oxidant plant extract achieves a
concentration of 1%, the percentages being given by weight of the
final solution.
[0025] In another specific embodiment, there is provided a process
of the present invention, which further comprises adding a
fragrance material to the solution obtained after step f).
[0026] In another specific embodiment, there is provided a process
of the present invention, which further comprises the steps of
adding a third amount of ascorbic acid between steps d) and e).
[0027] In another specific embodiment, there is provided a process
of the present invention, which, when the desired concentration of
ascorbic acid is more than 6% (w/w), further comprises a step of
adding a fourth amount of ascorbic acid after step f), followed by
a step of heating at a temperature of about 37 to 42.degree. C.
until a clear solution is obtained, followed by a step of cooling
down to room temperature.
[0028] In another specific embodiment, there is provided a process
of the present invention, wherein said temperature is 40.degree.
C.
[0029] In another specific embodiment, there is provided a process
of the present invention, wherein said first, second, third and
fourth amounts of ascorbic acid are 3%, 1.5%, 3.5% and 2%,
respectively.
[0030] In another specific embodiment, there is provided a process
of the present invention, wherein said first and second amounts of
ethoxydiglycol are added to achieve both 25.85%, said propylene
glycol, water and anti-oxidant plant extract are added to achieve
27%, 10%, and 1%, respectively, the percentages being given by
weight of the final solution.
[0031] In another specific embodiment, there is provided a process
of the present invention, wherein said first and second amounts of
ethoxydiglycol are added to achieve both 24.45%, said propylene
glycol, water and anti-oxidant plant extract are added to achieve
26%, 10%, and 1%, respectively, and hydroquinone is added to
achieve 2% after the step of cooling down to room temperature, the
percentages being given by weight of the final solution.
[0032] In another specific embodiment, there is provided a process
of the present invention, wherein said first and second amounts of
ethoxydiglycol are added to achieve 23.45%, said propylene glycol,
water and anti-oxidant plant extract are added to achieve 26%, 10%,
and 1%, respectively, and hydroquinone is added to achieve 4% after
the step of cooling down to room temperature, the percentages being
given by weight of the final solution.
[0033] In another specific embodiment, there is provided a process
of the present invention, wherein said first and second amounts of
ethoxydiglycol are added to achieve both 25.935%, said propylene
glycol, water and anti-oxidant plant extract are added to achieve
27%, 10%, and 1%, respectively, and kinetin is added to achieve
0.03% after the step of cooling down to room temperature, the
percentages being given by weight of the final solution.
[0034] In another specific embodiment, there is provided a process
of the present invention, wherein said first, second, third and
fourth amounts of ascorbic acid are 4.5%, 2.25%, 5.25% and 3%,
respectively, said first and second amounts of ethoxydiglycol are
both 23.4%, propylene glycol and water are added to achieve 22% and
15%, respectively, and said anti-oxidant plant extract achieves a
concentration of 0.9%, the percentages being given by weight of the
final solution.
[0035] In another specific embodiment, there is provided a process
of the present invention, which comprises adding a fragrance
material of 0.3% after the cooling down step.
[0036] In accordance with another aspect of the present invention,
there is provided a solution which comprises more than zero and up
to 15% L-ascorbic acid in a carrier comprising 10 to 15% water,
46.8 to 54.7% ethoxydiglycol, 22 to 29% propylene glycol, all
percentages given by weight of final composition, the balance to
100% comprising a percentage of at least one anti-oxidant
agent.
[0037] In a specific embodiment, there is provided a solution of
the present invention, wherein the at least one anti-oxidant agent
comprises an anti-oxidant plant extract.
[0038] In a specific embodiment, there is provided a solution of
the present invention, wherein the anti-oxidant plant extract is a
grapefruit plant extract.
[0039] In a specific embodiment, there is provided a solution of
the present invention, further comprising an additional
anti-oxidant selected from the group consisting of kinetin and
hydroquinone.
[0040] In a specific embodiment, there is provided a solution of
the present invention, further comprising a fragrance material,
which has the following composition: water 10%; L-ascorbic acid 5%;
ethoxydiglycol 54.7%; propylene glycol 29%; anti-oxidant plant
extract 1%; and fragrance material 0.3%, all percentages given by
weight of final composition.
[0041] In a specific embodiment, there is provided a solution of
the present invention, further comprising a fragrance material,
which has the following composition:
TABLE-US-00001 water 10%; L-ascorbic acid 10%; ethoxydiglycol
51.7%; propylene glycol 27%; anti-oxidant plant extract 1%; and
fragrance material 0.3%,
[0042] all percentages given by weight of final composition.
[0043] In a specific embodiment, there is provided a solution of
the present invention, further comprising a fragrance material,
which has the following composition:
TABLE-US-00002 water 15%; L-ascorbic acid 15%; ethoxydiglycol
46.8%; propylene glycol 22%; anti-oxidant plant extract 0.9%; and
fragrance material 0.3%,
[0044] all percentages given by weight of final composition.
[0045] In a specific embodiment, there is provided a solution of
the present invention, further comprising a fragrance material and
hydroquinone, which has the following composition:
TABLE-US-00003 water 12%; L-ascorbic acid 10%; ethoxydiglycol
48.90%; propylene glycol 26%; anti-oxidant plant extract 1%;
fragrance material 0.1%; and hydroquinone 2%,
[0046] all percentages given by weight of final composition.
[0047] In a specific embodiment, there is provided a solution of
the present invention, further comprising a fragrance material and
hydroquinone, which has the following composition:
TABLE-US-00004 water 12%; L-ascorbic acid 10%; ethoxydiglycol
46.90%; propylene glycol 26%; anti-oxidant plant extract 1%;
fragrance material 0.1%; and hydroquinone 4%,
[0048] all percentages given by weight of final composition.
[0049] In another specific embodiment, there is provided a solution
of the present invention, further comprising a fragrance material
and kinetin, which has the following composition:
TABLE-US-00005 water 10%; L-ascorbic acid 10%; ethoxydiglycol
51.87%; propylene glycol 27%; anti-oxidant plant extract 1%;
fragrance material 0.1%; and kinetin 0.03%,
[0050] all percentages given by weight of final composition.
[0051] In another specific embodiment, there is provided the
solution of the present invention, further comprising a topically
suitable carrier or compound.
[0052] In accordance with another aspect of the present invention,
there is provided a topical composition comprising the solution of
the present invention, and a topically suitable carrier or
compound.
[0053] In another specific embodiment of the solution of the
present invention, said topically suitable carrier or compound is
selected from the group consisting of tocopherol, tocopheryl
acetate, retinol, retinyl palmitate, hydroquinone,
proanthocyanidins, butylated hydroxytoluene, butylated
hydroxyanisole, astaxanthin, alpha lipoic acid, tocotrienols,
coenzyme Q10, .alpha.-hydroxy acid, kojic acid, kinetin, wine
extract, vitamin K, ascorbyl palmitate, magnesium ascorbyl
phosphate, sodium ascorbyl phosphate, a sun blocking agent and any
combination thereof.
[0054] In accordance with another aspect of the present invention,
there is provided a method for preventing or treating a disease or
disorder involving or caused by reactive oxygen species, which
comprises the step of topically administering a suitable amount of
the solution of the present invention.
[0055] In another specific embodiment of the method of the present
invention, said reactive oxygen species are caused by U.V or sun
exposure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0056] This invention will be described hereinbelow by reference to
the following preferred embodiments and appended figures which
purpose is to illustrate rather than to limit its scope.
[0057] In the appended drawings:
[0058] FIG. 1 represents superimposed chromatograms of the present
solution (5% ascorbic acid) and of the two glycols composing the
carrier.
[0059] FIG. 2 represents comparative chromatograms of the solution
of the present invention and a solution of vitamin C submitted to a
controlled degradation.
DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION
[0060] This process comprises the step of dissolving a first
quantity of ascorbic acid in 10% water, which is followed by
addition of a first quantity of ethoxydiglycol, under high stirring
speed. The step of adding ascorbic acid and ethoxydiglycol can be
repeated numerous times (at least one other time), depending on the
concentration of ascorbic acid that is sought. After sequential
additions of second or third quantities of ascorbic acid and
ethoxygylcol, propylene glycol is added to contribute, with water,
in the solubilization of ascorbic acid. The rapid agitation and the
presence of ethoxydiglycol after each sequential addition of
ascorbic acid provide for a micronized and stabilized solution.
[0061] When concentrations of ascorbic acid higher than about 6%
are needed, a mild heating step (at least about 37-42.degree. C.,
preferably 40.degree. C.) is required to solubilize the last added
quantities of vitamin, in the presence of propylene glycol. For
formulating the highest vitamin C concentration of 15%, the
concentration of water is increased from 10% to 15%. In such a
case, sequential additions of ascorbic acid and ethoxydiglycol may
achieve a concentration such that a higher concentration is
achieved (12% again in the presence of propylene glycol) prior to
heating. A last addition of vitamin can be made, followed by a last
heating step. Upon cooling at room temperature, the solution
remains stable.
[0062] The selection of the right solvents which involves
particularly a high concentration of ethoxydiglycol, and of the
right sequential additions of ascorbic acid, ethoxydiglycol and
propylene glycol, combined to a high speed that allows
micronization of ascorbic acid into such a solution, all contribute
to obtaining a stable solution of ascorbic acid. Heat contributes
to increasing the amount of solubilized ascorbic acid.
[0063] A micronization process appears to result in a product
wherein the contact of oxygen with the vitamin, is sharply reduced
once the latter is in solution. This reduces the oxidative damages
to the precious vitamin. The process provides for a solution that
has a shelf life of at least about two years, without any
substantial development of yellowish colour, which is without any
precedent (Data not shown).
[0064] Formulations for the Vitamin-C 5%, -10% and 15% according to
specific embodiments are as follows:
TABLE-US-00006 5% 10% 15% 10% 10% 10% Item Ingredient % w/w % w/w %
w/w % w/w % w/w % w/w 1. Demineralized water 10.0 10.0 15.0 12.0
12.0 10.0 grade USP 2. L-Ascorbic Acid grade 5.0 10.0 15.0 10.0
10.0 10.0 USP 3. Ethoxydiglycol grade 54.7 51.7 46.8 48.90 46.90
51.88 USP 4. Anti-oxidant agent 1.0 1.0 0.9 1.0 1.0 1.0 5.
Propylene Glycol grade 29.0 27.0 22.0 26 26.0 27.0 SUP 6. Fragrance
material 0.30 0.30 0.30 0.10 0.10 0.10 grade MFR 7. Hydroquinone
grade 2.0 4.0 USP 8. Kinetin grade MFR 0.03
[0065] Item 6 appears optional, since it is a fragrance that is
added to confer more attractive properties to the solution for the
consumer. In specific embodiments presented in the examples below,
Apple Crunch.TM. was used as fragrance material because of its
availability on the market. Other fragrance may be used such as
Apple Fresh.TM.. Item 4 is used as an anti-oxidant. Items 7 and 8
are further anti-oxidants used in specific embodiments.
General Manufacturing Procedure
[0066] The following sequence has been adopted to prepare a
vitamin-C 5% to 15% formulations or compositions. The solution is
mixed until clear after every addition. All percentages are given
by weight of final composition. All steps, except the heating step,
if required, are performed at room temperature (18-25.degree.
C.).
Example 1
Ascorbic Acid 5% (w/w)
[0067] Begin with 10.0% Demineralized water,
[0068] add 3.00% L-Ascorbic Acid (Hoffman Laroche) and begin mixing
at a medium to high speed (Lightning Mixer or Agitator) add 27.35%
Ethoxydiglycol Trivalin SF.TM.,
[0069] add 2.00% Vitamin-C (Hoffman Laroche),
[0070] add 27.35% Ethoxydiglycol Trivalin SF.TM.,
[0071] add 29.00% Propylene Glycol,
[0072] add 1.00% Greentech.TM. Grapefruit Extract, and
[0073] add 0.3% Apple Crunch.TM. Fragrance,
[0074] Note: no heating is required.
Example 2
Ascorbic Acid 10% (w/w)
[0075] Begin with 10.0% Demineralized water,
[0076] add 3.00% L-Ascorbic Acid (Hoffman Laroche) and begin mixing
at a medium to high speed,
[0077] add 25.85% Ethoxydiglycol Trivalin SF.TM.,
[0078] add 1.50% Vitamin-C (Hoffman Laroche),
[0079] add 25.85% Ethoxydiglycol Trivalin SF.TM.,
[0080] add 3.50% Vitamin-C (Hoffman Laroche),
[0081] add 27.00% Propylene Glycol, and
[0082] add 1.00% Greentech.TM. Grapefruit Extract.
[0083] Heat is then applied in the formulation process. This is an
important step in order to formulate a concentration of vitamin-C
higher than 6% in the solution comprising 10% water. Interestingly
enough, the vitamin-C does not support heat well as the latter
tends to oxidize the former. However, the medium in which ascorbic
acid is during heating provides protection against oxidative
damage.
[0084] Therefore, a last addition of 2% Vitamin-C is performed,
followed by heating to 40 degrees Celsius until the solution
becomes all clear and until all vitamin-C has been dissolved.
[0085] While stirring continues, the solution is allowed to cool
down at ambient temperature and then, once cooled, 0.3% Apple
Crunch.TM. Fragrance is added.
Example 3
Ascorbic Acid 15% (w/w)
[0086] Begin with 15.0% Demineralized water,
[0087] add 4.5% Vitamin-C (Hoffman Laroche) and being mixing at a
medium to high speed,
[0088] add 23.4% Ethoxydiglycol,
[0089] add 2.25% Vitamin-C (Hoffman Laroche),
[0090] add 23.4% Ethoxydiglycol Trivalin SF.TM.,
[0091] add 5.25% Vitamin-C (Hoffman Laroche),
[0092] add 22.0% Propylene Glycol,
[0093] add 0.09% Greentech.TM. Grapefruit Extract,
[0094] and 3.0% Vitamin-C (Hoffman Laroche) and heat solution to 40
degrees Celsius until solution becomes all clear and when all
vitamin-C has been dissolved
[0095] While stirring continues, the solution is cooled down and
once cooled, 0.3% Apple Crunch.TM. Fragrance is added.
Example 4
Ascorbic Acid 10% (w/w) and Hydroquinone 2% (w/w)
[0096] Begin with 12.0% Demineralized water,
[0097] add 3% Vitamin-C (Hoffman Laroche) and being mixing at a
medium to high speed,
[0098] add 24.45% Ethoxydiglycol,
[0099] add 1.5% Vitamin-C (Hoffman Laroche),
[0100] add 24.45% Ethoxydiglycol Trivalin SF.TM.,
[0101] add 3.5% Vitamin-C (Hoffman Laroche),
[0102] add 26.0% Propylene Glycol,
[0103] add 1% Greentech.TM. Grapefruit Extract,
[0104] and 2.0% Vitamin-C (Hoffman Laroche) and heat solution to 40
degrees Celsius until solution becomes all clear and when all
vitamin-C has been dissolved.
[0105] While stirring continues, the solution is cooled down and
once cooled, 0.1% Apple Crunch.TM. Fragrance and 2.0% hydroquinone
are added.
Example 5
Ascorbic Acid 10% (w/w) and Hydroquinone 4% (w/w)
[0106] Begin with 12.0% Demineralized water,
[0107] add 3% Vitamin-C (Hoffman Laroche) and being mixing at a
medium to high speed,
[0108] add 23.45% Ethoxydiglycol,
[0109] add 1.5% Vitamin-C (Hoffman Laroche),
[0110] add 23.45% Ethoxydiglycol Trivalin SF.TM.,
[0111] add 3.5% Vitamin-C (Hoffman Laroche),
[0112] add 26.0% Propylene Glycol,
[0113] add 1% Greentech.TM. Grapefruit Extract,
[0114] and 2.0% Vitamin-C (Hoffman Laroche) and heat solution to 40
degrees Celsius until solution becomes all clear and when all
vitamin-C has been dissolved.
[0115] While stirring continues, the solution is cooled down and
once cooled, 0.1% Apple Crunch.TM. Fragrance and 4.0% hydroquinone
are added.
Example 6
Ascorbic Acid 10% (w/w) and Kinetin
[0116] Begin with 10.0% Demineralized water,
[0117] add 3% Vitamin-C (Hoffman Laroche) and being mixing at a
medium to high speed,
[0118] add 25.935% Ethoxydiglycol,
[0119] add 1.5% Vitamin-C (Hoffman Laroche),
[0120] add 25.935% Ethoxydiglycol Trivalin SF.TM.,
[0121] add 3.5% Vitamin-C (Hoffman Laroche),
[0122] add 27.0% Propylene Glycol,
[0123] add 1% Greentech.TM. Grapefruit Extract,
[0124] and 2.0% Vitamin-C (Hoffman Laroche) and heat solution to 40
degrees Celsius until solution becomes all clear and when all
vitamin-C has been dissolved.
[0125] While stirring continues, the solution is cooled down and
once cooled, 0.1% Apple Crunch.TM. Fragrance and 0.03% kinetin are
added.
[0126] These solutions remain stable (+/-10% degradation) for
approximately 24 months, which is unheard of.
[0127] FIG. 1 shows the location of the peaks of pure vitamin C.
FIG. 2 shows that the maintenance of the peaks confirm that no
significant degradation has occurred during the first 24 months of
storage. A peak that would appear consequently to degradation is
not observed in the chromatogram of the present solution.
[0128] The pH (dilution of 100 mL in water) for all 3 solutions
ranges between 2.8 and 3.1.
[0129] The medium to high stirring of each ingredient added may be
responsible to help form tiny water and vitamin-C spheres by
"micronization" in the ethoxydiglycol/propylene glycol (both
glycols) solution and because of the micronization occurring, it
helps to reduce access of air which would inevitably oxidize the
vitamin in the solution. It is also possible that a complex be
formed between ascorbic acid and ethoxydiglycol.
Example 7
Uses and Compositions
[0130] Therefore, the above solutions comprising a vitamin C that
keeps all its integrity are intended to be used as is or through
the making of a composition or a medication, to prevent or to treat
any disease or disorder that involves or is caused by ROS or
involving collagen synthesis. The disease or disorder includes but
is not limited to skin cancer (melanoma), skin irritation or
inflammation, dermatitis, skin allergy, psoriasis, acne, eczema,
rosacea, radiations exposure including U.V. or sun exposure,
depigmentation (skin whitening) and skin ageing (reduction of
wrinkles inter alia). Compositions may comprise any suitable
carrier which may include structuring agents (oils, fatty acids,
surfactants, etc.) and a reducing agent or an anti-oxidant which
would increase the stability of the ascorbic acid or which would
complement its anti-oxidant properties. Further, compositions
comprising any active ingredient which would benefit or not from
the protective effect provided by vitamin C against oxidation are
within the scope of the invention.
[0131] In adjunction with the present vitamin C, hydroquinone and
kinetin have been used in examples provided herein to produce
stabilized vitamin C compositions. The following currently used
cosmetic or dermatologic products can all also be formulated in
"combined" compositions: .alpha.-hydroxy acid, retinol, kojic acid,
vitamin K, ascorbyl palmitate, magnesium ascorbyl phosphate and
sodium ascorbyl phosphate. The combinations may include more than
one of these products. The combination should remain at an acidic
pH (below 7.0), and ideally below the pKa of ascorbic acid, when
this pH (4.17) is compatible with the stability of the other
products.
[0132] Although the present invention has been described
hereinabove by way of preferred embodiments thereof, it can be
modified, without departing from the spirit and nature of the
subject invention as defined in the appended claims.
* * * * *