U.S. patent application number 11/476527 was filed with the patent office on 2007-01-04 for stable organic peroxide compositions.
Invention is credited to Joseph R. Faryniarz, Jose E. Ramirez.
Application Number | 20070001145 11/476527 |
Document ID | / |
Family ID | 37604990 |
Filed Date | 2007-01-04 |
United States Patent
Application |
20070001145 |
Kind Code |
A1 |
Faryniarz; Joseph R. ; et
al. |
January 4, 2007 |
Stable organic peroxide compositions
Abstract
Organic peroxide compositions are stabilized against
decomposition by the use of antioxidants, resulting in increased
shelf life of products made using the compositions.
Inventors: |
Faryniarz; Joseph R.;
(Middlebury, CT) ; Ramirez; Jose E.; (Trumbull,
CT) |
Correspondence
Address: |
CARTER, DELUCA, FARRELL & SCHMIDT, LLP
445 BROAD HOLLOW ROAD
SUITE 225
MELVILLE
NY
11747
US
|
Family ID: |
37604990 |
Appl. No.: |
11/476527 |
Filed: |
June 28, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60695223 |
Jun 29, 2005 |
|
|
|
Current U.S.
Class: |
252/186.42 |
Current CPC
Class: |
A61K 9/0014 20130101;
C11D 3/2058 20130101; A61K 8/38 20130101; C11D 3/3945 20130101;
Y10S 514/937 20130101; A61K 8/4973 20130101; A61K 8/33 20130101;
C11D 3/0084 20130101; A61K 8/678 20130101; A61K 47/10 20130101;
A61K 45/06 20130101; Y10S 514/938 20130101; C11D 3/2093 20130101;
A61K 2800/522 20130101; A61K 8/676 20130101; C11D 3/2034 20130101;
A61K 47/22 20130101; A61Q 19/00 20130101; A61K 31/327 20130101;
C11D 3/382 20130101; C11D 3/2068 20130101; C11D 3/3947 20130101;
A61K 8/347 20130101; Y10S 514/846 20130101; Y10S 514/859
20130101 |
Class at
Publication: |
252/186.42 |
International
Class: |
C11D 3/39 20060101
C11D003/39 |
Claims
1. A composition comprising a stable mixture of organic peroxide
and antioxidant, wherein the weight ratio of organic peroxide to
antioxidant is about 2.5:1 to about 10:1.
2. The composition as in claim 1 comprising a solvent in which the
organic peroxide is soluble.
3. The composition as in claim 1, wherein the organic peroxide is
liquid in which antioxidant is soluble.
4. The composition as in claim 1, wherein the organic peroxide is a
solid in which antioxidant can be dispersed.
5. The composition as in claim 1 wherein the organic peroxide is
benzoyl peroxide.
6. The composition as in claim 1 wherein the antioxidant is
selected from the group consisting of butylated hydroxyl toluene
(BHT), butylated hydroxyanisole (BHA), vitamin E acetate, ascorbyl
palmitate, tetrahydrocurcuminoids, t-butyl hydroquinone, meta and
para cresols, phenolics, and combinations thereof.
7. The composition according to claim 1 further comprising an
aqueous phase.
8. The composition according to claim 7 wherein the aqueous phase
further comprises at least one component selected from the group
consisting of surfactant, humectant, suspending agent, buffer
system, and combinations thereof.
9. The composition of claim 1 wherein the ratio of organic peroxide
to antioxidant is about 10:1 by weight of the composition.
10. The composition of claim 1 wherein the ratio of organic
peroxide to antioxidant is about 2.5:1 by weight of the
composition.
11. The composition of claim 1 wherein the composition is a
solution comprising less than 2% antioxidant, and no more than
about 10% organic peroxide.
12. The composition of claim 1 wherein the composition is a
solution comprising about 5% to about 10% antioxidant, and no more
than about 20% organic peroxide.
13. The composition of claim 1 wherein the composition is a
solution comprising a ratio of organic peroxide to antioxidant in
an amount of about 10:1 by weight of the composition.
14. The composition of claim 1 wherein the composition is a
solution comprising a ratio of organic peroxide to antioxidant in
an amount of about 2.5:1 by weight of the composition.
15. The composition of claim 1 further comprising a thickener.
16. A method of increasing the stability of organic peroxide
comprising combining an antioxidant with an organic peroxide to
provide a stable peroxide composition having a weight ratio of
organic peroxide to antioxidant at about 2.5:1 to about 10:1.
17. The method as in claim 16 wherein the composition containing
organic peroxide is a solution of the organic peroxide in a
solvent.
18. The method as in claim 16 wherein the organic peroxide is
benzoyl peroxide.
19. The method as in claim 18 further comprising the step of
formulating a product suitable for topical application to the skin
containing the stable peroxide composition.
20. A method comprising combining an antioxidant with benzoyl
peroxide and at least one solvent to provide a stable peroxide
solution wherein the weight ratio of benzoyl peroxide to
antioxidant is about 2.5:1 to about 10:1; and formulating a product
suitable for topical application to the skin containing the stable
peroxide solution.
21. The method of claim 20 further comprising adding an aqueous
phase to the benzoyl peroxide solution to form an emulsion.
22. The method of claim 21 wherein the aqueous phase comprises at
least one component selected from the group consisting of
surfactant, humectant, suspending agent, buffer system, and
combinations thereof.
23. The method of claim 22 wherein the humectant is glycerin.
24. A method of treating acne comprising applying a product
prepared in accordance with the method of claim 20 to the skin of a
subject afflicted with acne.
25. Use of antioxidant in the manufacture of an organic peroxide
medicament for treatment of a skin condition.
26. The use in accordance with claim 25 wherein the organic
peroxide is benzoyl peroxide.
27. The use in accordance with claim 25 wherein the skin condition
is acne Vulgaris.
28. The use in accordance with claim 25 wherein the use is
characterized as cosmetic.
Description
RELATED APPLICATION
[0001] This application claims priority benefit of U.S. Provisional
Application No. 60/695,223 filed Jun. 29, 2005, herein incorporated
by reference in its entirety.
BACKGROUND
[0002] 1. Technical Field
[0003] This disclosure relates to the preparation of compositions
containing stable organic peroxide in solution. The compositions
are useful for topical application to human skin and/or allow
stable organic peroxides to be utilized in new product forms.
Products (e.g., industrial, pharmaceutical or consumer based
products) formulated using these compositions exhibit extended
shelf life. Such compositions also have unique processing
capabilities.
[0004] 2. Background of Related Art
[0005] Organic peroxides are used in many products. For example,
benzoyl peroxide is used in pharmaceutical and consumer products as
an active ingredient for therapeutic treatments. Organic peroxides
are unstable. This instability is a desired trait when these
materials are used for free radical initiation. When organic
peroxides are used for purposes other than free radical initiation,
however, it is desirable to have the material be as stable as
possible. Instability is problematic and leads to short shelf
lives, required expiration dating, higher product costs, special
storage considerations, product returns as well as reduced efficacy
due to loss of active.
[0006] Accordingly, what are needed are compositions of organic
peroxides with improved stability for use in products where
increased shelf life would be an advantage.
SUMMARY
[0007] Organic peroxide compositions including one or more
antioxidants are described herein. These compositions exhibit
excellent stability. Such compositions can be formulated into
products with increased shelf life. The excellent stability also
leads to product forms that were previously not obtainable, such
as, for example, solutions of benzoyl peroxide (a material which is
inherently unstable when stored at elevated temperatures). The
present compositions may further include a solvent constituent in
which the organic peroxide is soluble. Moreover, the compositions
have been found to be useful in forming organic peroxide containing
emulsions.
[0008] In embodiments, suitable stable corrective compositions in
accordance with the present disclosure provide a solvent vehicle
formulation for the treatment of acne in which the major active
ingredient is benzoyl peroxide. The benzoyl peroxide is provided in
clear product forms such as serums, toners, pump or aerosol sprays,
clear gels, sticks, creams, lotions and mousses. The clear product
forms can be incorporated into other pharmaceutical or cosmetic
product forms such as emulsions.
[0009] In some embodiments, compositions include a stable mixture
of organic peroxide and antioxidant. The weight ratio of organic
peroxide to antioxidant may be about 2.5:1 to about 10:1. The
composition may include a solvent in which the organic peroxide is
soluble. Furthermore, the organic peroxide, such as benzoyl
peroxide, may be a liquid in which antioxidant is soluble. In other
embodiments, the organic peroxide may be a solid in which
antioxidant can be dispersed.
[0010] These and other aspects of this disclosure will be evident
upon reference to the following detailed description.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0011] Compositions in accordance with this disclosure include at
least one antioxidant in combination with one or more organic
peroxides. The antioxidant may be any of the type materials that
are soluble in the solvent carrier for the desired organic
peroxide, and/or soluble or dispersible in the organic peroxide
itself. Suitable non-limiting examples of antioxidants for oil
soluble systems include, but are not limited to, butylated hydroxyl
toluene (BHT), butylated hydroxyanisole (BHA), vitamin E acetate,
ascorbyl palmitate, tetrahydrocurcuminoids, t-butyl hydroquinone,
meta and para cresols, phenolics and the like, and combinations of
these antioxidants. It should, of course, be understood that
combinations of antioxidants can be used in making the present
compositions and/or formulations. The amount of antioxidant
employed in the composition will depend on a number of factors
including, but not limited to the nature of the organic peroxide,
the concentration of the organic peroxide, the nature of any
solvents present and the nature of the ultimate product to be
formulated using the composition. Typically however, the
antioxidant is present in an amount of about 0.1 to 30 percent by
weight of the total composition. In particularly useful
embodiments, the antioxidant is present in an amount of about 1.0
percent to 10 percent by weight of the total composition.
[0012] Organic peroxides have long been used in industry to
initiate free radical polymerization of unsaturated monomers. The
free radical that is formed from the decomposition of the peroxide
attaches itself to an unsaturated carbon of the monomer with its
electron rich double bond. The free electron then causes an
electron shift to the carbon adjacent to where the double bond
existed. This unpaired electron forms an unstable free radical and
requires another electron to be paired with it. The new free
radical will now seek out another double bonded carbon to which it
can attach. This process repeats itself until the monomer is
depleted or the polymer chain encounters a species of molecule that
stabilizes the free radicals.
[0013] Organic peroxide refers generally to any organic molecule
containing the peroxide functional group ROOR'. Suitable
non-limiting examples of organic peroxides for use in accordance
with the present disclosure include any in the following classes:
diacyl, dialkyl, hydroperoxides, ketone peroxides, peroxyesters,
peroxyketals, peroxydicarbonates, and combinations thereof.
Additional non-limiting examples of organic peroxides include
acetone peroxide, benzoyl peroxide, cumene hydroperoxide, methyl
ethyl ketone peroxide, pinane peroxide, diethyl ether peroxide. In
embodiments, the organic peroxide is benzoyl peroxide. The amount
of organic peroxide employed in the composition will depend on a
number of factors including, but not limited to the nature of the
organic peroxide, the concentration of the organic peroxide, the
nature of any solvents present and the nature of the ultimate
product to be formulated using the composition. Typically however,
the organic peroxide will be present in an amount of about 1 to 70
percent by weight of the total composition. In particularly useful
embodiments, the organic peroxide will be present in an amount of
about 2 to 35 percent by weight of the total composition.
[0014] In embodiments, compositions in accordance with the present
disclosure include benzoyl peroxide with one or more antioxidants.
Benzoyl peroxide is normally commercially available as either pure
(98% active) crystals or in a wet crystalline state containing 70
to 80% active benzoyl peroxide in 20-30% water. Such benzoyl
peroxide products are commercially available from The Norac Company
Inc., Azusa, Calif. under the BENOX.RTM. tradenames or from Elf
Atochem North America, Inc., Philadelphia, Pa. under the
LUCIDOL.RTM. tradenames. Any of these or other forms of benzoyl
peroxide can be mixed with the disclosed solvents to form
compositions in accordance with this disclosure.
[0015] The amount of benzoyl peroxide mixed with the antioxidant
will vary depending on a number of factors, including, for example,
the activity of benzoyl peroxide, the ultimate form of the product
and the particular disclosed solvent employed. Generally, the
benzoyl peroxide will be present in an amount of about 1 to about
70 weight percent of the benzoyl peroxide/antioxidant mixture. In
embodiments, the benzoyl peroxide is present in an amount of about
2 to about 35 weight percent of total composition. In embodiments,
the benzoyl peroxide is present in an amount of about 2 to about 15
weight percent of the total composition.
[0016] The use of benzoyl peroxide in pharmaceutical industry is
based on several chemical properties. Benzoyl peroxide is
considered a mild antimicrobial compound that will control P. Acnes
bacteria. Benzoyl peroxide free radicals can attack the cell walls
of the bacteria thus destroying the bacteria. Secondly, the
decomposition of the benzoyl peroxide will result in forming
benzoic acid, benzene, phenyl benzoate and biphenyls, all such
materials can be toxic to cell. Lastly, it has even been proposed
that because anaerobic P. Acnes cannot live in the presence of
oxygen, oxygen available from the benzoyl peroxide may also kill
the bacteria. The exact mechanism for the antimicrobial properties
for benzoyl peroxide is however unknown. What is known is that
chemical reactions take place on an individual molecular level.
Molecules in solution will react much more readily than in solid
crystal form.
[0017] The individual molecules present in a solution will
penetrate the skin much easier than a particulate dispersion.
Secondly the benzoyl peroxide in solution form is much more mobile
and reactive than is the crystalline form. This increased mobility
and reactivity can lead to much more effective products. However
this increased mobility and reactivity has the negative of reduced
chemical stability in the solution.
[0018] Thus, while the use of an antioxidant in accordance with the
present disclosure can be used to improve the stability of organic
peroxides in any type of composition, such as for example,
emulsions or suspensions, in particularly useful embodiments, the
antioxidants are used to stabilize organic peroxides in solutions
of the organic peroxide.
[0019] The decomposition of the organic peroxide (although believed
to be desired in order to achieve effectiveness) must be controlled
in order to allow use of solutions while providing sufficient
storage life. Decomposition of organic peroxides can occur via a
variety of mechanisms, such as the following three mechanisms 1.
The thermolysis decomposition of diacyl peroxide (benzoyl peroxide
is given below): ##STR1## 2. Induced decomposition is represented
by the following equation where a free radical attacks a peroxide
to generate and ester and a different free radical, but no carbon
dioxide. ##STR2## 3. Heterolytic decomposition which can occur when
strong acids or polar solvents are present. ##STR3##
[0020] Organic peroxides will have different stability depending on
a variety of factors including, but not limited to solvent type,
solvent polarity, impurities, peroxide concentration and the
occurrence of radical-induced decomposition. Peroxides decompose in
more polar or polarizable solvents. Solvents such as benzoates have
greater solution stability, which may be attributed to the
delocalized electrons of the benzene ring.
[0021] Without being bound by any particular theory, using reducing
agent antioxidants in solutions with oxidizer organic peroxides can
be used to decrease the effects of thermal decomposition.
Antioxidants are normally used as sacrificial materials that are
more easily oxidized over the material that is to be protected. For
some unknown reason, the quenching of the free radicals formed,
prevents the further decomposition of the organic peroxide. As seen
from the equations for decomposition mechanisms listed above, the
generation of carbon dioxide gas is possible by thermolysis or
heterolytic decomposition. The heterolytic decomposition reaction
does not involve generation of a free radical so it is not evident
that use of an antioxidant will affect this reaction outcome. In
thermolysis, the free radical is a direct consequence of the
peroxide splitting at the oxygen bonds. The antioxidant might
prevent the intermediate free radical from further splitting and
giving off CO.sub.2, but does not give an indication that the
organic peroxide would be kept from splitting in the first
place.
[0022] The reduced decomposition of the organic peroxide provided
by the present compositions improves the shelf life of products
formulated using the compositions, a result which would not
normally be obtained. It has been found that the degree to which
carbon dioxide gas is generated provides direct evidence of the
degree of stability of the organic peroxide. Stability was also
determined experimentally by analytical analysis. Accordingly,
methods are available to compare the stability of a first
composition containing organic peroxide with the stability of a
second composition containing organic peroxide and an antioxidant.
By monitoring the amount of carbon dioxide by the first and second
compositions, one can easily compare stability. The generation of
less carbon dioxide has been found to indicate greater stability of
the organic peroxide composition. In the case where organic
peroxide contains an antioxidant, relatively smaller amounts of
carbon dioxide will be generated indicating that the composition is
stable. In cases where an organic peroxide is combined with a
solvent, and no antioxidant is present, higher volumes of carbon
dioxide will be generated, indicating that the organic peroxide is
unstable. Suitable carbon dioxide tests for comparing stability of
organic peroxides are further described in the examples below.
[0023] In certain embodiments of the present compositions, the
ratio of organic peroxide to antioxidant is about 10:1 by weight of
the composition, as well as about 2.5:1 by weight of the
composition. In embodiments, suitable compositions include a stable
mixture of organic peroxide and antioxidant, wherein the weight
ratio of organic peroxide to antioxidant is about 2.5:1 to about
10:1. In other embodiments, the composition is a solution having
less than 2% antioxidant, and no more than about 10% organic
peroxide. However other suitable embodiments such as solutions have
an amount of about 5 to 10% antioxidant, and no more than about 20%
organic peroxide. In other solution embodiments, the compositions
may have a ratio of organic peroxide to antioxidant between about
10:1 by weight of the composition. Still yet, other solution
embodiments have a ratio of organic peroxide to antioxidant between
about 2.5:1 by weight of the composition. In embodiments, suitable
solutions include a stable mixture of organic peroxide and
antioxidant, wherein the weight ratio of organic peroxide to
antioxidant is about 2.5:1 to about 10:1. In a typical preparation
process, the organic peroxide is dissolved into a solvent to the
limits of solubility. The additional ingredients and the
antioxidants can then be added to the composition to formulate the
final desired product.
[0024] Solvents useful for preparing solutions in accordance with
the present disclosure include any solvent capable solubilizing the
organic peroxide. Non-limiting examples of such solvents include
short chain alkyl esters, ethers, aldehydes, ketones or alcohols of
benzoic acid, benzyl alcohol, salicylic acid, phenol or phathalic
acid. As used herein "short chain" refers to a molecule having two
to six carbon atoms (C2-C6). Other suitable solvents include aryl
esters, ethers, aldehydes, ketones and alcohols of benzoic acid,
benzyl alcohol, salicylic acid, phenol and phthalic acid. In
certain embodiments, the compositions in accordance with the
present disclosure include one or more of the following classes of
solvent: alkyl esters of benzoic acid, alkyl esters of benzyl
alcohol, alkyl esters of salicylic acid, alkyl esters of phenol,
alkyl esters of phthalic acid, alkyl ethers of benzyl alcohol,
alkyl esters of phthalic acid, alkyl ethers of benzyl alcohol,
alkyl ethers of phenol. Additional non-limiting examples of
suitable solvents include benzoyl benzoate, benzoyl alcohol,
diethyl phthalate, benzoic acid 2-phenyl ethyl ester, methyl
salicylate, ethyl salicylate, propyl salicylate, butyl salicylate,
ethyl benzoate, methyl benzoate, propyl benzoate, butyl benzoate,
dimethyl phthalate, diethyl phthalate, benzyl ethyl ether, benzyl
methyl ether, phenetole, phenyl acetone, phenyl ethyl alcohol,
phenoxyethanol, phenyl acetaldehyde, ethyl phenyl acetate, phenyl
methyl ketone, phenyl acetate, benzyl acetate, benzyl aceto
acetate, benzyl formate, benzaldehyde, benzyl alcohol, ethyl benzyl
alcohol, salicylaldehyde, benzyl salicylate, phenyl tolyl ketone,
phenyl benzoate, phenyl ether, dibenzyl ether, benzyl benzoate,
benzoic acid and 2-phenyl ethyl ester.
[0025] The amount of solvent mixed with the organic peroxide will
vary depending on a number of factors, including, for example, the
ultimate form of the product and the particular solvent employed.
Generally, the solvent will be present in an amount of about 1 to
about 70 weight percent of the total organic peroxide/solvent
mixture. In embodiments, the solvent will be present in an amount
of about 10 to about 50 weight percent of the total composition. In
embodiments, the solvent will be present in an amount of about 20
to about 40 weight percent of the total composition. In
embodiments, solvent is present in amounts effective for dissolving
organic peroxide.
[0026] In addition to the solvent in which organic peroxide is
soluble, the compositions in accordance with the present disclosure
may contain one or more secondary solvents. Suitable secondary
solvents include, for example, ethanol, acetone, dimethyl
isosorbide, and glycol ethers of C.sub.1 to C.sub.6 alcohols with
no greater than 2 moles of ethylene oxide. Suitable glycol ethers
include glycol ethers of phenol with no greater than 2 moles of
ethylene oxide, glycol ethers of methanol with no greater than 2
moles of ethylene oxide, glycol ethers of ethanol with no greater
than 2 moles of ethylene oxide and glycol ethers of propanol with
no greater than 2 moles of ethylene oxide. Non-limiting examples of
such co-solvents include phenoxy ethanol, ethoxy diglycol and
propylene glycol methyl ether.
[0027] The amount of secondary solvent mixed with the organic
peroxide/solvent mixture will vary depending on a number of
factors, including, for example, the ultimate form of the product
and the particular solvent and/or secondary solvent employed.
Generally, the secondary solvent will be present in an amount of
about 1 to about 40 weight percent of the total composition. In
embodiments, the secondary solvent will be present in an amount of
about 5 to about 30 weight percent of the total composition. In
embodiments, the secondary solvent will be present in an amount of
about 10 to about 20 weight percent of the total composition.
[0028] In embodiments, thickeners and/or rheology modifiers such as
fumed silica may be added to the organic peroxide solutions of the
present disclosure to increase the viscosity of the compositions
and/or gel the compositions. In embodiments, the thickener and/or
rheology modifiers may be present in an amount of about 0.1 to
about 10 weight percent of the total composition. Any thickener or
rheology modifier can be used so long as it does not react with the
organic peroxides.
[0029] The organic peroxide corrective compositions and/or stable
mixtures of organic peroxide and antioxidant in accordance with the
present disclosure can be added to product forms. In embodiments,
products containing organic peroxide compositions in accordance
with the present disclosure can be in the form of solutions,
emulsions (including microemulsions), suspensions, creams, fluid
cream, oils, lotions, gels, powders, sticks, or other typical solid
or liquid compositions used for treatment of undesirable skin
conditions. Such compositions may contain, in addition to the
organic peroxide and/or organic peroxide compositions in accordance
with this disclosure, other ingredients typically used in such
products, such as other active cosmetic substances such as retinol,
retinol derivatives, allantoin, tocopherol, tocopherol derivatives,
niacinamide, phytosterols, isoflavones, panthenol, panthenol
derivatives, bisabolol, farnesol, and combinations thereof, other
active drug substances such as corticosteroid, metronidazole,
sulfacetamide, sulfur, and combinations thereof, antioxidants,
antimicrobials, coloring agents, detergents, dyestuffs,
emulsifiers, emulsifying wax, emollients, fillers, fragrances,
gelling agents, hydration agents, moisturizers, odor absorbers,
natural or synthetic oils, penetration agents, powders,
preservatives, solvents, surfactants, thickeners,
viscosity-controlling agents, water, distilled water, waxes, and
optionally including anesthetics, anti-itch actives, botanical
extracts, conditioning agents, darkening or lightening agents,
glitter, humectant, mica, minerals, polyphenols, phytomedicinals,
silicones or derivatives thereof, skin protectants, sunblocks,
vitamins, and mixtures or combinations thereof. Such compositions
may also contain, in addition to the organic peroxide and/or
organic peroxide compositions in accordance with this disclosure,
one or more: fatty alcohols, fatty acids, organic bases, inorganic
bases, wax esters, steroid alcohols, triglyceride esters,
phospholipids, polyhydric alcohol esters, fatty alcohol ethers,
hydrophilic lanolin derivatives, hydrophilic beeswax derivatives,
cocoa butter waxes, silicon oils, pH balancers, cellulose
derivatives, hydrocarbon oils, or mixtures and combinations
thereof.
[0030] In embodiments, product forms can be formulated to contain
humectant in amounts from about 1% to about 15% by weight of the
total composition. For example glycerine can be added to the
composition in amounts from about 1% to about 15% by weight of the
total composition. In particular embodiments, glycerine can be
added to the composition in amounts from about 1% to about 5% by
weight of the total composition.
[0031] In embodiments, product forms can be formulated to contain
solvent in an amount of about 1% to about 45% by weight of the
total composition. For example petroleum derivatives such as
propylene glycol can be added to the composition in an amount of
about 1% to about 45% by weight of the total composition. In
particular embodiments, propylene glycol, polyethylene glycol,
ethoxy diglycol can be added to the composition in an amount of
about 15% to about 30% by weight of the total composition.
[0032] In embodiments, product forms can be formulated to contain
water in an amount of about 40% to about 99% by weight of the total
composition. For example distilled water can be added to the
composition in an amount of about 40% to about 99% by weight of the
total composition. In particular embodiments, distilled water can
be added to the composition in an amount of about 65% to about 80%
by weight of the total composition.
[0033] In embodiments, organic peroxide compositions in accordance
with the present disclosure are useful in the formation of
oil-in-water emulsion product forms. Accordingly, the compositions
may include an aqueous phase. Conventional emulsion formulation
typically requires mixing the aqueous phase ingredients and the
dispersant with heating until a uniform solution or dispersion is
obtained (optionally in several stages), mixing the organic phase
ingredients with heating until a uniform solution or dispersion is
obtained (also optionally in several stages), then adding the
aqueous phase to the organic phase with agitation (e.g. stirring or
other shearing or heating technique) to form an oil-in-water
emulsion of the two phases. However, heating steps are problematic
in that heat decomposes organic peroxides such as benzoyl peroxide.
The present compositions are capable of a low temperature blending
and shearing techniques that do not require an intensive heating
step. Accordingly, such blending can occur at room temperature.
[0034] In some emulsion embodiments, the aqueous phase constituting
the dispersion medium may include any suitable surfactant,
humectant, suspending agent, and/or buffer systems, and
combinations thereof suitable for combining with organic peroxide
compositions in accordance with the present disclosure.
[0035] Non-limiting examples of suitable surfactants include
natural compounds, such as phospholipids and cholates, or
nonnatural compounds such as: polysorbates, which are fatty acid
esters of polyethoxylated sorbitol; polyethylene glycol esters of
fatty acids from sources such as castor oil; polyethoxylated fatty
acid, e.g. stearic acid; octylphenolpoly(ethyleneglycolether);
polyethoxylated isooctylphenol/formaldehyde polymer; poloxamers,
e.g., poly(oxyethylene)poly(oxypropylene) block copolymers;
polyoxyethylene fatty alcohol ethers; polyoxyethylene nonylphenyl
ethers; polyoxyethylene isooctylphenyl ethers; SDS, and
combinations thereof.
[0036] In embodiments, non-limiting examples of suitable mixtures
of surfactant molecules, including mixtures of surfactants of
different chemical types, are acceptable. Surfactants should be
suitable for cosmetic or pharmaceutical administration and
compatible with the benzoyl peroxide to be delivered. Non-limiting
examples of surfactants include phospholipids such as
phosphatidylcholines (lecithins), including soy or egg lecithin.
Other suitable phospholipids include phosphatidylglycerol,
phosphatidylinositol, phosphatidylserine, phosphatidic acid,
cardiolipin, and phosphatidylethanolamine. The phospholipids may be
isolated from natural sources or prepared by synthesis.
[0037] Non-limiting examples of suitable suspending agents include
the following constituents: polyacrylamide, C13-14 isoparafin &
laureth 7; C13-14 isoparaffin, mineral oil, polyacrylate,
polyacrylamide and ethoxylated sorbitan ester; acrylamide/sodium
acryloyldimethyl taurate copolymer, isohexadecane and ethoxylated
sorbitan ester; and combinations thereof. However any cosmetically
or pharmaceutically acceptable suspending agent suitable for
combining with benzoyl peroxide may be used.
[0038] Non-limiting examples of suitable humectants include
glycerin, however any material capable of obtaining moisture may be
added provided it is stable with organic peroxide.
[0039] The products formulated with the present solutions can be
packaged in any type of container within the purview of those
skilled in the art, including, but not limited to bottles, tubes,
pump type, roll-ons, daubers, wipes, and the like.
[0040] The organic peroxide compositions in accordance with the
present disclosure can be topically applied to skin in need of
improvement in order to reduce or eliminate undesirable skin
conditions. As used herein the word "treat," "treating" or
"treatment" refers to using the compositions of the present
disclosure prophylactically to prevent outbreaks of undesirable
skin condition such as Acne Vulgaris, or therapeutically to
ameliorate an existing undesirable skin condition. A number of
different treatments are now possible, which reduce and/or
eliminate skin conditions such as Acne Vulgaris.
[0041] As used herein "skin condition" refers to any detectable
skin manifestations caused by one or more pathogens or microbes.
Such manifestations can be compounded due to a number of factors
such as, for example, chronological aging, environmental damage,
and/or other diseased or dysfunctional state. Non-limiting examples
of such manifestations include the development of skin lines,
crevices, bumps, comedones, craters, scaliness, flakiness and/or
other forms of skin unevenness, roughness, or mottled appearance.
It is understood, that the listed skin conditions are non-limiting
and that only a portion of the skin conditions suitable for
treatment in accordance with the present disclosure are listed
herein.
[0042] In embodiments, compositions for use in accordance with the
present disclosure contain organic peroxide in an effective amount
to improve undesirable skin conditions. As used herein "effective
amount" refers to an amount of a compound or composition having
organic peroxide constituents in accordance with the present
disclosure that is sufficient to induce a particular positive
benefit to skin having a skin condition. The positive benefit can
be health-related, or it may be more cosmetic in nature, or it may
be a combination of the two. In embodiments, the positive benefit
is achieved by contacting skin with a combination of solvated
organic peroxide, and/or one or more antibiotic constituents, to
improve a skin condition such as Acne Vulgaris.
[0043] The particular organic peroxide concentration in the
compositions generally depends on the purpose for which the
composition is to be applied. For example, the dosage and frequency
of application can vary depending upon the type and severity of the
skin condition.
[0044] Treatments in accordance with the present disclosure contact
skin with organic peroxide in an effective amount to improve acne
related skin conditions. In embodiments, patients are treated by
topically applying to skin suffering from an acne related
condition, one or more organic peroxide compositions. The active
ingredient is applied until the treatment goals are obtained.
However, the duration of the treatment can vary depending on the
severity of the condition. For example, treatments can last several
weeks to months depending on whether the goal of treatment is to
reduce or eliminate an acne related skin condition.
[0045] As used herein the term "stable" or "stability" refers to
the ability of a material or composition to remain unchanged in the
presence of heat, moisture or air. With respect to shelf life the
terms further can refer to compositions that when in a closed
container, remain within the tolerances and limits set forth in US
Pharmacopoeia and/or the US FDA guidelines or monographs for
compositions containing organic peroxides. The entire US
Pharmacopoeia and collection of US FDA guidelines or monographs for
compositions containing any particular organic peroxide or
combination of active ingredients including at least one organic
peroxide are too voluminous to present in their entirety herein and
thus are instead incorporated in their entirety by this reference.
With respect to topical compositions, the tolerances and limits are
frequently presented relative to the labeled amount. With respect
to benzoyl peroxide cream, for example, the acceptable tolerance is
not less than 90.0 percent and not more than 125.0 percent of the
labeled amount of C.sub.14H.sub.10O.sub.4. Those skilled in the art
will readily be able to identify the tolerances and limits for
other compositions containing organic peroxides.
[0046] Treatments in accordance with the present disclosure contact
skin with a stable mixture of organic peroxide and antioxidant in
an effective amount to improve acne related skin conditions. In
embodiments, patients are treated by topically applying to skin
suffering from an acne related condition, one or more stable
mixtures of organic peroxide and antioxidant.
[0047] In embodiments, the stable organic peroxides/antioxidant
mixtures are applied for cosmetic purposes only.
[0048] In some embodiments, use of an antioxidant may be included
in the manufacture of organic peroxide medicament such as benzoyl
peroxide medicament for treatment of a skin condition. In some
embodiments, antioxidants include any antioxidant described in the
present disclosure. The organic peroxides include any organic
peroxides described in the present disclosure. In some embodiments,
the medicament include one or more stable mixtures of organic
peroxides and antioxidants in accordance with the present
disclosure. The medicament may include weight ratios of
antioxidants to organic peroxide as described in the present
disclosure.
[0049] The following non-limiting examples further illustrate
compositions, methods, and treatments in accordance with the
present disclosure. It should be noted that the disclosure is not
limited to the specific details embodied in the examples.
EXAMPLE 1
[0050] A solution of benzoyl peroxide ("BPO") was formulated in the
following manner to deliver 8% benzoyl peroxide in the finished
product. TABLE-US-00001 Ingredient Amount Benzoyl Peroxide 75% wet
with water 10.67 to carry in 8 parts dry BPO Benzoyl benzoate
40.00%
[0051] Benzoyl peroxide was dissolved into the benzyl benzoate. The
resulting solution/dispersion was then added to the following
materials. TABLE-US-00002 Ingredient Amount Ethoxydiglycol 10.00
parts Dimethyl Isosorbide 41.1 parts Butylated Hydroxytoluene (BHT)
(antioxidant) 0.40 parts Vitamin E Acetate (antioxidant) 0.50
parts
[0052] The above formulation results in a clear solution that has
pharmaceutical properties.
[0053] The thermal decomposition of benzoyl peroxide results in the
generation of carbon dioxide gas as well as free radicals. The
amount of carbon dioxide gas given off can be used as a relative
measurement of the stability of any two compositions in
relationship to each other.
[0054] The formula of Example 1 was placed on stability at elevated
temperatures of 40.degree. C. and 30.degree. C. versus the same
formula without the two antioxidants. The samples were placed in
glass bottles with eye droppers. When samples are first made the
dropper is completely empty of liquid, due to the seal of the bulb
onto the bottle. Carbon dioxide gas, if any, generated by the
benzoyl peroxide decomposition raises pressure in the bottle. As
the pressure raises the glass dropper will fill with liquid,
eventually filling the dropper and finally forcing the liquid into
the dropper bulb. In extreme cases, the bulb will expand and then
finally rupture if great pressures are present. Lack of liquid
being forced into the dropper is considered an indication of very
low levels of decomposition.
[0055] During the test period of a month at 40.degree. C., the
samples with the antioxidants had significantly less gas generated
than the control sample, in which the liquid had pushed up into the
bulb and eventually destroyed it. The test product dropper had only
just filled and remained at bottle liquid height.
[0056] Many experiments were performed utilizing this procedure of
comparing the formulas with and without individual as well as
combinations of antioxidants. This test was sensitive enough to be
able to pick up differences in solvent systems stability, the level
of benzoyl peroxide, type antioxidant versus efficacy, temperature
of storage, and levels of antioxidant in the samples. Conventional
analytical testing confirmed the actual concentration of the
remaining benzoyl peroxide.
EXAMPLE 2
[0057] A toner composition shown below was tested using the
procedure described in Example 1. TABLE-US-00003 Ingredient Amount
Benzoyl Peroxide 75% wet with water 3.33% to carry in 2.5% BPO dry
Ethoxydiglycol 25.00% Benzyl benzoate 42.47% Dimethyl isosorbide
21.6% Benzoic acid 5.00% Salicylic acid 2.00% Vitamin E Acetate
0.2% Butylated hydroxyl toluene 0.4%
[0058] The test formula above was placed on stability at elevated
temperatures of 40.degree. C. and 30.degree. C. versus a control
formulation (the same formula above without the two antioxidants).
The samples were placed in glass bottles with eye droppers and
checked for the amount of gas that was generated. After a month at
40.degree. C. the control samples (the same formula above without
the two antioxidants) had filled up into the rubber bulb and
pressure was evident via bulb expansion. In the case of the test
formula, the droppers were empty and liquid had not moved into
bulb. For the 30.degree. C. samples the control had completely
filled the dropper and was present in the bulb. The dropper of the
above test formula was completely empty of fluid at 30.degree. C.
The results of Example 2 where less dramatic than Example 1 (where
the bulb was destroyed) because Example 2 had lower levels of
benzyl peroxide in the toner formula.
EXAMPLE 3
[0059] Another formulation in accordance with the present
disclosure is as follows: TABLE-US-00004 Ingredient Amount Benzoyl
Peroxide 6.25% Benzoyl benzoate 42.45% Dimethyl isosorbide 40.00%
Vitamin E Acetate 0.5% BHT 0.8% Ethoxy diglycol 10.0% fumed silica
0-10%
EXAMPLE 4
[0060] An emulsion formulation in accordance with the present
disclosure is prepared by combining the following two phases A and
B: TABLE-US-00005 Phase A Ingredients Amount Benzoyl Peroxide 75%
wet with water 8.68% Benzyl Benzoate 10.00% BHT 0.4% Vitamin E
Acetate 0.5% Dimethyl Isosorbide 3.00%
[0061] Phase A is made by adding benzoyl peroxide to container with
the Benzyl Benzoate, BHT and Vitamin E Acetate and mixing for 30
minutes. The dimethyl isosorbide is then added with mixing for an
additional ten minutes. TABLE-US-00006 Phase B Ingredients Amount
DI Water 74.22% Phenoxyethanol 0.1% EDTA disodium salt 0.1%
Simulgel NS* 3.0% *(Hydroxyethyl acrylate/sodium acryloyidimethyl
taurate copolymer, squalane and polysorbate 60.)
[0062] The phase B ingredients are added together and mixed. Phase
A is added to Phase B under high shear mixing until uniform
emulsion (oil-in-water) is formed. Other materials with desired
properties may be added, provided they are stabile with organic
peroxide.
[0063] It will be understood that various modifications may be made
to the embodiments disclosed herein. Therefore, the above
description should not be construed as limiting, but merely as
exemplifications of embodiments. Those skilled in art will envision
other modifications within the scope and spirit of the claims
appended hereto.
* * * * *