U.S. patent application number 13/745326 was filed with the patent office on 2013-05-30 for solubilizing agents for active or functional organic compounds.
The applicant listed for this patent is Steven H. Bertz, Donna N. Laura, Ilya Makarovsky. Invention is credited to Steven H. Bertz, Donna N. Laura, Ilya Makarovsky.
Application Number | 20130136706 13/745326 |
Document ID | / |
Family ID | 38285785 |
Filed Date | 2013-05-30 |
United States Patent
Application |
20130136706 |
Kind Code |
A1 |
Bertz; Steven H. ; et
al. |
May 30, 2013 |
SOLUBILIZING AGENTS FOR ACTIVE OR FUNCTIONAL ORGANIC COMPOUNDS
Abstract
An active or functional organic compound is solubilized by an
ester of an aryl alcohol, e.g., phenethyl, benzyl or substituted
benzyl alcohol, and an alkyl or cycloalkyl carboxylic acid, or by a
carbonate of said aryl alcohol and an alkyl or cycloalkyl carbonic
acid.
Inventors: |
Bertz; Steven H.;
(Morristown, NJ) ; Makarovsky; Ilya; (Fair Lawn,
NJ) ; Laura; Donna N.; (Nutley, NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Bertz; Steven H.
Makarovsky; Ilya
Laura; Donna N. |
Morristown
Fair Lawn
Nutley |
NJ
NJ
NJ |
US
US
US |
|
|
Family ID: |
38285785 |
Appl. No.: |
13/745326 |
Filed: |
January 18, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12871202 |
Aug 30, 2010 |
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13745326 |
|
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11337857 |
Jan 23, 2006 |
7785573 |
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12871202 |
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Current U.S.
Class: |
424/59 |
Current CPC
Class: |
A61K 8/4966 20130101;
A61K 8/35 20130101; Y02P 20/582 20151101; A61Q 19/08 20130101; A61K
8/375 20130101; A61Q 17/04 20130101; A61K 8/37 20130101 |
Class at
Publication: |
424/59 |
International
Class: |
A61K 8/37 20060101
A61K008/37; A61Q 17/04 20060101 A61Q017/04 |
Claims
1-19. (canceled)
20. A sunscreen composition comprising a sunscreen active or
functional organic compound solubilized in an ester of (i) an aryl
alcohol and (ii) an alkyl or cycloalkyl carboxylic or carbonic acid
wherein the ester has one of the following named formulas:
##STR00004## ##STR00005## and wherein the ester is from 1 to 35% by
weight of the composition.
21. The sunscreen composition according to claim 20 wherein the
ester is from 2-20% by weight of the composition.
22. The sunscreen composition according to claim 21 wherein the
ester is from 10-20% by weight of the composition.
23. The sunscreen composition according to claim 21 wherein the
ester is 10% by weight of the composition.
24. The sunscreen composition according to claim 20 wherein the
ester is 2-phenylethyl pentanoate.
25. The sunscreen composition according to claim 20 wherein the
ester is 2-phenylethyl cyclohexanoate.
26. The sunscreen composition according to claim 20 wherein the
sunscreen active or functional organic compound is a solid.
27. The sunscreen composition according to claim 20 wherein the
sunscreen active or functional organic compound is solubilized in
an amount of at least 10 wt. %.
28. The sunscreen composition according to claim 20 wherein the
sunscreen active or functional organic compound is selected from
the group consisting of avobenzone, oxybenzone, 4-methylbenzylidene
camphor, ethylhexyl triazone or bis-ethylhexyloxyphenol
methoxyphenyl triazine, and mixtures thereof.
29. The sunscreen composition according to claim 20 in which said
active is selected from the group consisting of avobenzone,
benzophenone-3, benzophenone-4, benzophenone-5,4-methylbenzylidene
camphor, p-aminobenzoic acid (PABA), camphor benzalkonium
methosulfate, homosalate, phenylbenzimidazole sulfonic acid,
terephthalidene dicamphor sulfonic acid, benzylidene camphor
sulfonic acid, octocrylene, polyacrylamidomethyl benzylidene
camphor, ethylhexyl methoxycinnamate, PEG-25 PABA, isoamyl
p-methoxycinnamate, ethylhexyl triazone, drometrizole trisiloxane,
diethylhexyl butamido triazone, 3-benzylidene camphor, ethylhexyl
salicylate, ethylhexyl dimethyl PABA, methylene bis-benztriazolyl
tetramethylbutylphenol, disodium phenyl dibenzimidazole
tetrasulfonate, bis-ethylhexyloxyphenol methoxyphenyl triazine,
polysilicone-15, and mixtures thereof.
30. A sunscreen composition comprising a sunscreen active or
functional organic compound solubilized in an ester of (i) a
phenylethyl alcohol and (ii) an alkyl or cycloalkyl carboxylic or
carbonic acid.
31. The composition according to claim 30 wherein the sunscreen
active or functional organic compound is selected from the group
consisting of avobenzone, benzophenone-3, benzophenone-4,
benzophenone-5,4-methylbenzylidene camphor, p-aminobenzoic acid
(PABA), camphor benzalkonium methosulfate, homosalate,
phenylbenzimidazole sulfonic acid, terephthalidene dicamphor
sulfonic acid, benzylidene camphor sulfonic acid, octocrylene,
polyacrylamidomethyl benzylidene camphor, ethylhexyl
methoxycinnamate, PEG-25 PABA, isoamyl p-methoxycinnamate,
ethylhexyl triazone, drometrizole trisiloxane, diethylhexyl
butamido triazone, 3-benzylidene camphor, ethylhexyl salicylate,
ethylhexyl dimethyl PABA, methylene bis-benztriazolyl
tetramethylbutylphenol, disodium phenyl dibenzimidazole
tetrasulfonate, bis-ethylhexyloxyphenol methoxyphenyl triazine,
polysilicone-15, and mixtures thereof.
32. The composition according to claim 30 wherein the ester is an
ester of 2-phenylethyl alcohol.
33. A composition consisting essentially of a sunscreen active or
functional organic compound solubilized in an ester selected from
the group consisting of ##STR00006## ##STR00007##
34. The composition according to claim 33 consisting of the
sunscreen active or functional organic compound and the ester.
35. The composition according to claim 33 wherein the sunscreen
active or functional organic compound has a solubility of at least
10 weight percent in the ester at 25 C.
36. The composition according to claim 33 wherein the sunscreen
active or functional organic compound has a solubility of at least
20 weight percent in the ester at 25 C.
37. The composition according to claim 33 wherein the sunscreen
active or functional organic compound has a solubility of at least
30 weight percent in the ester at 25 C.
38. The composition according to claim 33 wherein the sunscreen
active or functional organic compound is selected from the group
consisting of avobenzone, oxybenzone, 4-methylbenzylidene camphor,
ethylhexyl triazone or bis-ethylhexyloxyphenol methoxyphenyl
triazine, and mixtures thereof.
39. The sunscreen composition according to claim 33 wherein the
sunscreen active or functional organic compound is selected from
the group consisting of avobenzone, benzophenone-3, benzophenone-4,
benzophenone-5,4-methylbenzylidene camphor, p-aminobenzoic acid
(PABA), camphor benzalkonium methosulfate, homosalate,
phenylbenzimidazole sulfonic acid, terephthalidene dicamphor
sulfonic acid, benzylidene camphor sulfonic acid, octocrylene,
polyacrylamidomethyl benzylidene camphor, ethylhexyl
methoxycinnamate, PEG-25 PABA, isoamyl p-methoxycinnamate,
ethylhexyl triazone, drometrizole trisiloxane, diethylhexyl
butamido triazone, 3-benzylidene camphor, ethylhexyl salicylate,
ethylhexyl dimethyl PABA, methylene bis-benztriazolyl
tetramethylbutylphenol, disodium phenyl dibenzimidazole
tetrasulfonate, bis-ethylhexyloxyphenol methoxyphenyl triazine,
polysilicone-15, and mixtures thereof.
40. A method of preparing the sunscreen composition according to
claim 20 comprising solubilizing the sunscreen active or functional
organic compound in the ester.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser.
No. 11/337,857 filed on Jan. 23, 2006, the entire contents of which
are incorporated herein by reference.
[0002] This application is related to co-pending U.S. patent
application Ser. No. 11/007,744 filed on Dec. 8, 2004, which
described diaryl esters as solubilizing agents, the entire contents
of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0003] 1. Field of the Invention
[0004] This invention relates to compositions containing an active
or functional organic compound which requires solubilization, and
more particularly, to compositions which are effectively
solubilized by addition of an ester of an aryl alcohol, e.g.,
phenethyl, benzyl or substituted benzyl alcohol, and an alkyl or
cycloalkyl carboxylic or carbonic acid.
[0005] 2. Description of the Prior Art
[0006] Many commercial products such as personal care (e.g.,
sunscreens or UV filters), pharmaceutical, agricultural and
industrial compositions, contain active or functional materials
which require solubilization in the form of a solution, emulsion or
dispersion, in aqueous or non-aqueous fawn. For example, a
sunscreen formulation containing aromatic compounds such as
Avobenzone (Butyl methoxydibenzoylmethane, Escalol.RTM. 517) and/or
Oxybenzone (Benzophenone-3, Escalol.RTM. 567) as active UVA/UVB
absorbing ingredients requires a solubilizing agent to keep them in
an emulsion, i.e., to prevent crystallization. Several such
solubilizers are known, e.g., C.sub.12-15 alkyl benzoate
(Finsolv.RTM. TN); however, they are mediocre solubilizing agents
and/or have a "heavy" feel, which is undesirable in modern cosmetic
formulations.
[0007] H. Gers-Barlag et al. in U.S. Pat. No. 6,770,269 described a
solubilizing agent for triazine derivatives which was an ester of
an unbranched alkyl carboxylic acid and a mono- or polybranched
aliphatic alcohol, particularly hexyldecyl laurate, which was
derived from lauric acid and hexyldecyl alcohol. Previously, the
same authors in U.S. Pat. No. 6,703,001 had described a
solubilizing agent for triazine derivatives which was an ester of a
branched-chain carboxylic acid and a branched-chain alcohol,
particularly isodecyl neopentanoate, which was derived from
neopentanoic acid and isodecyl alcohol.
[0008] I. Walele et al. in U.S. Pat. No. 6,635,775 described a
process for "reduced odor esters" which improved the preparation of
established cosmetic esters such as C.sub.12-15 alkyl benzoates and
cetearyl octanoate.
[0009] We have previously disclosed in U.S. patent application Ser.
No. 11/007,744 that esters of aryl carboxylic acids and aryl
alcohols, particularly phenethyl benzoate, which was derived from
benzoic acid and 2-phenylethanol, are superior solvents for actives
such as sunscreens or UV filters. It was nevertheless surprising,
and it could not have been predicted by someone skilled in the art,
that combinations of actives with esters of alkyl (including
cycloalkyl) carboxylic acids and aryl alcohols would likewise be
superior solvents. Completely unprecedented was the discovery that
the cyclopropyl group, e.g., in 2-phenylethyl cyclopropanoate,
which was derived from cyclopropanecarboxylic acid and
2-phenylethanol, imparts remarkable solubilizing power for the
triazines, e.g., Ethylhexyl triazone and Bis-ethylhexyloxyphenol
methoxyphenyl triazine.
[0010] Accordingly, it is an object of this invention to provide a
composition including an active or functional organic compound
which is solubilized by a safe and effective organic ester or
carbonate as solvent, cosolvent or additive.
[0011] Another object is to provide a personal care composition,
e.g., a sunscreen or cosmetic composition, or a pharmaceutical,
agricultural or industrial composition, containing a solid active
or functional organic compound, which is effectively solubilized by
an ester of an aryl alcohol, e.g., phenethyl, benzyl or substituted
benzyl alcohol, and an alkyl or cycloalkyl carboxylic acid, or a
carbonate of an aryl alcohol and an alkyl or cycloalkyl carbonic
acid.
[0012] A specific object herein is to provide a sunscreen
composition containing active UVA and/or UVB compounds which are
effectively solubilized by the esters or carbonates of the
invention.
[0013] These and other objects and features of the invention will
be made apparent from the following description.
SUMMARY OF THE INVENTION
[0014] What is described herein are effective solubilizing agents
for active or functional organic compounds, most particularly,
esters of an aryl alcohol, e.g., phenethyl, benzyl or substituted
benzyl alcohol, and an alkyl (linear or branched) or cycloalkyl
carboxylic acid, or carbonates of said aryl alcohol and an alkyl or
cycloalkyl carbonic acid. Preferred esters of the invention are
2-phenylethyl cyclopropanoate, 2-phenylethyl pentanoate and
2-phenylethyl cyclohexanoate, which are new solubilizers for UVA
and/or UVB sunscreens or filters.
DETAILED DESCRIPTION
[0015] General formulas for the solubilizers of the invention are
the following 1a and 1b:
##STR00001##
where R.sub.1-R.sub.12 are independently H or branched or
unbranched C.sub.1-C.sub.22 alkyl, C.sub.1-C.sub.22 alkoxy, or
hydroxy groups; a-e=0-8; and i=0-a, j=0-b, k=0-c, l=0-d and m=0-e;
X and Y are independently a heteroatom or CH.sub.2, and Z is a
heteroatom, H, or CH.sub.2; R' in 1b represents the alcohol-derived
moiety in 1a. While not explicitly shown in 1 b, we include bicyclo
and tricyclo compounds. When a=0, carbonates are included for
X.dbd.O. Other heteroatoms such as X,Y.dbd.N or S may be present,
and H, O or branched or unbranched C.sub.1-C.sub.22 alkyl groups
may also be attached said heteroatoms. Consistent with the rules of
structural organic chemistry, only one hydroxy group per C is
allowed.
[0016] Accordingly, representative solubilizers of the invention
are shown in Chart 1 and include 2-phenylethyl cyclopropanoate,
2-phenylethyl pentanoate and 2-phenylethyl cyclohexanoate.
##STR00002## ##STR00003##
[0017] Generally, the amount of the solubilizer of the invention in
the total weight of the composition is about 1-35 wt. %, preferably
2-20 wt. %.
[0018] The active or functional compound in the composition is
usually about 0.1-10 wt. % of the composition.
[0019] Invention Compositions
[0020] Formulations such as sunscreen compositions containing
active UVA and UVB compounds, e.g., Avobenzone (E-517), Oxybenzone
(E-567), 4-Methylbenzylidene camphor (MBC) Ethylhexyl triazone
(EHT), and Bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT),
were effectively solubilized by 2-phenylethyl cyclopropanoate or
the other compounds of the invention. Increased critical wavelength
and/or boosting of the SPF and/or enhancement of the UVA component
of the absorption spectrum relative to the UVB portion were
typically observed.
[0021] Other UV filter actives that may be employed in the present
inventive compositions (and solubilized in 2-phenylethyl
cyclopropanoate, 2-phenethyl pentanoate, 2-phenylethyl
cyclohexanoate, etc.) include but are not limited to p-Aminobenzoic
acid (PABA), Camphor benzalkonium methosulfate, Homosalate,
Phenylbenzimidazole sulfonic acid, Terephthalidene dicamphor
sulfonic acid, Benzylidene camphor sulfonic acid, Octocrylene,
Polyacrylamidomethyl benzylidene camphor, Ethylhexyl
methoxycinnamate, PEG-25 PABA, Isoamyl p-methoxycinnamate,
Drometrizole trisiloxane, Diethylhexyl butamido triazone,
3-Benzylidene camphor, Ethylhexyl salicylate, Ethylhexyl dimethyl
PABA, Benzophenone-4, Benzophenone-5, Methylene bis-benztriazolyl
tetramethylbutylphenol, Disodium phenyl dibenzimidazole
tetrasulfonate, and Polysilicone-15. Such compositions may include
one or more of the aforementioned UV filter actives, including
Avobenzone, Oxybenzone, 4-Methylbenzylidene camphor, Ethylhexyl
triazone and Bis-ethylhexyloxyphenol methoxyphenyl triazine.
[0022] Other actives such as personal care, cosmetic,
pharmaceutical, agricultural and industrial compounds are
effectively solubilized by the compounds of the invention,
including such actives as antibacterial and herbicidal (e.g.,
algaecidal) compounds, particularly to keep the active in emulsion
form without crystallizing or precipitating out of the emulsion,
and without requiring the use of large amounts of solvent. Examples
of such pharmaceutical compositions include but are not limited to
one or more of Furosemide, Lovastatin, Clarithromycin, Diclofenac,
Famotidine, Carbamaxepine, Dipridamole, Chlorthiazide,
Spironolactone, Dilantin, Imipranine, Mefloquine, Cyclosporine,
Glyburide, and Nimodipine. Compositions of the present invention
may also include combinations of active or functional organic
compounds such as, for example, a pharmaceutical (one or more
thereof) and a UV filter active (one or more thereof), as well.
[0023] The invention will now be illustrated more particularly by
the examples which follow:
Example 1
Preparation of 2-Phenylethyl Cyclopropanecarboxylate (2-Phenylethyl
Cyclopropanoate)
[0024] A 1-L, 4-neck, round-bottom flask, fitted with a
thermometer, mechanical stirrer, nitrogen inlet tube and Liebig
condenser/receiving flask, was charged with 258.3 g (3.00 mol, 1.00
equiv) of cyclopropanecarboxylic acid, 366.5 g (3.00 mol, 1.00
equiv) of 2-phenylethanol, and 1.14 g (0.2 wt. %) of tin oxalate
(Fascat.RTM. 2001). The air was removed with three cycles of
evacuation/nitrogen-fill using a mechanical vacuum pump (50-100
torr). The rate of stirring was set at ca. 200 rpm, the nitrogen
sparge was set at 0.05 scfh, and the reaction mixture was heated to
175.degree. C. After a 2-h hold, 78.0 g of distillate had been
collected. The temperature was increased to 180.degree. C. and held
for 1 h; an additional 9.6 g of distillate was collected. Finally,
the temperature was increased to 190.degree. C. and held for 2 h,
and an additional 8.6 g of distillate was collected. The acid
number was 5.30 mg KOH/g (98.3% conversion). The excess
2-phenylethanol (12.4% by GLC) and cyclopropanecarboxylic acid
(0.82% by GLC) were removed by vacuum distillation through a 15-cm
Vigreux column at 95-135.degree. C. (10 torr) in a 101-g forecut.
The crude product was distilled at 136-139.degree. C. (10 torr)
through a 15 cm Vigreux column to afford 410 g (72%) of
2-phenylethyl cyclopropanecarboxylate (99.1% pure by GLC): residual
alcohol, 0.6% (GLC); APHA color, 4.0; acid number, 0.14 mg KOH/g;
saponification number, 291 mg KOH/g (theor. 295 mg KOH/g). The
cyclopropanecarboxylic acid distilled out of the reaction mixture
with the water of reaction can be recycled to improve the
yield.
Example 2
Preparation of 2-Phenylethyl Pentanoate
[0025] A 2-L, 4-neck, round-bottom flask, fitted with a
thermometer, mechanical stirrer, nitrogen inlet tube and Liebig
condenser/receiving flask, was charged with 612.8 g (6.00 mol, 1.00
equiv) of pentanoic acid, 733.0 g (6.00 mol, 1.00 equiv) of
2-phenylethanol, and 2.50 g (0.2 wt. %) of tin oxalate (Fascat.RTM.
2001). The air was removed with three cycles of
evacuation/nitrogen-fill using a mechanical vacuum pump (50-100
torr). The rate of stirring was set at ca. 200 rpm, the nitrogen
sparge was set at 0.1 scfh, and the reaction mixture was heated to
170.degree. C. After a 1-h hold, 159.3 g of distillate had been
collected. It was not possible to get a clean separation;
therefore, the organic layer was not returned to the reaction
mixture. The temperature was increased to 180, 190, 200 and
210.degree. C. and held for 1 h at each; the amounts of distillate
were 21.4, 9.8, 4.9 and 2.2 g, respectively. The acid number was
2.88 mg KOH/g (99.0% conversion). The excess 2-phenylethanol (6.3%
by GLC) was removed by vacuum distillation through a 15-cm Vigreux
column at 140-165.degree. C. (15-20 torr). The crude product was
distilled at 150-155.degree. C. (10 torr, 0.5 scfh nitrogen sweep)
to afford 925 g (75%) of 2-phenylethyl pentanoate (99.3% pure by
GLC): residual alcohol, 0.3% (GLC); APHA color, 13; acid number,
0.06 mg KOH/g; saponification number, 271 mg KOH/g (theor. 272 mg
KOH/g).
Example 3
Preparation of 2-Phenylethyl Cyclohexanecarboxylate (2-Phenylethyl
Cyclohexanoate)
[0026] A 1-L, 4-neck, round-bottom flask, fitted with a
thermometer, mechanical stirrer, nitrogen inlet tube and Liebig
condenser/receiving flask, was charged with 320.4 g (2.50 mol, 1.00
equiv) of cyclohexanecarboxylic acid, 335.9 g (2.75 mol, 1.10
equiv) of 2-phenylethanol, and 1.20 g (0.2 wt. %) of tin oxalate
(Fascat.RTM. 2001). The system was heated gently with slow stirring
(<50 rpm) until all the cyclohexanecarboxylic acid was in
solution. The air was removed with three cycles of
evacuation/nitrogen-fill using a mechanical vacuum pump (50-100
torr). The rate of stirring was increased to ca. 200 rpm, the
nitrogen sparge was set at 0.1 scfh, and the reaction mixture was
heated to 180.degree. C. After a 1-h hold, 36.7 g of distillate had
been collected. The alcohol (9.6 g) was separated and returned to
the reaction mixture. The temperature was increased to 190.degree.
C. and held for 1 h; an additional 14.0 g of distillate was
collected. The alcohol (2.5 g) was separated and returned. The
temperature was increased to 200.degree. C. and held for 1 h; an
additional 4.9 g of distillate was collected. The alcohol (1.0 g)
was separated and returned. The temperature was increased to
210.degree. C. and held for 1 h, and an additional 2.1 g of
distillate was collected; 0.3 g of alcohol was separated, but not
returned. The temperature was increased to 220.degree. C. and held
for 2 h, and an additional 1.3 g of distillate was collected; 0.4 g
of alcohol was separated, but not returned. The reaction mixture
was cooled to room temperature and sampled for analysis. The acid
number was 1.04 mg KOH/g (99.5% conversion). Triisodecylphosphite
(0.58 g) was added to the reaction mixture, and the excess
2-phenylethanol (3.9% by GLC) was removed by vacuum distillation at
165-170.degree. C. (10 torr, 0.5 scfh nitrogen sweep) for 1 h.
Activated carbon (17.4 g, 3 wt. %) was added, and the mixture was
heated at 75-80.degree. C. under vacuum (80 torr, 0.5 scfh nitrogen
sweep) for 1 h. The product was cooled to room temperature and
filtered through Celite.RTM. to afford 470 g (81%) of 2-phenylethyl
cyclohexanecarboxylate (99.5% pure by GLC): residual alcohol, 0.06%
(GLC); APHA color, 89; acid number, 0.21 mg KOH/g; saponification
number, 237 mg KOH/g (theor. 241 mg KOH/g).
Example 4
Solubility of Solid Organic Sunscreens in Solubilizers of the
Invention
[0027] Solutions (wt. %) of Avobenzone (E-517), Oxybenzone (E-567),
4-Methylbenzylidene camphor (MBC), Ethylhexyl triazone (EHT) or
Bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT) in each of
the solubilizers were prepared at 40-60.degree. C. such that the
total mass was 10.00 g. Upon cooling to 25.degree. C., a few seed
crystals (<10 mg) of the sunscreen were added to hasten
equilibration. The solutions were stored in the dark in a constant
temperature chamber at 25.degree. C. Each was sampled weekly, and
the ca. 0.1 g sample was filtered through a 0.45.mu. syringe filter
and analyzed by GLC or HPLC, calibrated using standard solutions,
until the value for wt. % of solute was constant.
[0028] As shown below in Table 1, the solubilizer of the invention
is effective in solubilizing at least 10 wt. %, preferably 20 wt.
%, most preferably 30 wt. % or more of at least one of the
sunscreens. In every case, the solubility of one or more of the
sunscreens is significantly higher in the solvent of the invention
than the industry standard for the class in question (e.g., esters)
or prior art. For example, benzyl lactate is significantly better
than C.sub.12-15 alkyl benzoate (Finsolv.RTM. TN) for Oxybenzone
(30 vs. 17%). Many of the esters are better across the board, e.g.,
2-phenylethyl cyclopropanoate, 2-phenylethyl pentanoate and
2-phenylethyl cyclohexanoate.
[0029] Triazines such as EHT and BEMT are particularly challenging
to dissolve, and we have discovered a number of solvents that are
significantly more effective than the industry standard or prior
art, e.g., 2-phenylethyl cyclopropanoate dissolved 16 wt. % of EHT
vs. 3 wt. % for isodecyl neopentanoate and 6% for C.sub.12-15 alkyl
benzoate. 2-Phenylethyl propionate (33 wt. %), 2-phenylethyl
cyclohexanoate (32 wt. %) and benzyl butyrate (32 wt. %) are at
least twice as effective as C.sub.12-15 alkyl benzoate (16 wt. %)
for dissolving BEMT.
[0030] Benzyl octyl carbonate is a significantly better solvent
than dioctyl carbonate (Cetiol.RTM. CC) for Avobenzone, Oxybenzone,
4-Methylbenzylidene camphor, and Bis-ethylhexyloxyphenol
methoxyphenyl triazine. The solubilities of Ethylhexyl triazone (6
vs. 7 wt. %, respectively) are the same to within experimental
uncertainty (.+-.1%). The differences are especially noteworthy for
Oxybenzone (27 vs. 16 wt. %) and BEMT (18 vs. 10 wt. %).
TABLE-US-00001 TABLE 1 Solubility data (25.degree. C.) for
sunscreen compounds in typical solubilizers of the invention.
Solubility (wt. %) Solvent E-517 E-567 MBC EHT BEMT 2-phenylethyl
acetate 26 44 44 14 26 2-phenylethyl propionate 25 40 44 12 33
1-phenylethyl propionate 23 38 44 10 26 2-phenylethyl 24 39 42 16
27 cyclopropanoate 2-phenylethyl pentanoate 22 35 41 10 27
2-phenylethyl neopentanoate 19 29 38 5 28 2-phenylethyl
cyclohexanoate 20 32 37 10 32 2-phenylethyl octanoate 19 27 36 8 23
2-phenylethyl 17 25 34 4 18 2-ethylhexanoate 2-phenoxyethyl
propionate 21 38 39 6 13 benzyl lactate 11 30 30 8 2 benzyl
butyrate 24 39 44 10 32 benzyl octyl carbonate 17 27 35 6 18
isodecyl neopentanoate 8 11 26 3 5 C.sub.12-15 alkyl benzoate 15 17
28 6 16 dioctyl carbonate 13 16 29 7 10
Example 5
Enhancement of UVA Absorption
[0031] Solutions containing 10 mg/L of sunscreen in selected
solvents were prepared, and their UV spectra were measured using a
Cary 1E UV-Visible spectrophotometer. The results in Table 2 show
that the molar extinction coefficients s are higher in
2-phenylethyl pentanoate than in C.sub.12-15 alkyl benzoate for all
five sunscreens. They are also higher in 2-phenylethyl
cyclohexanoate for Escalol 517 and Escalol 567. Generally speaking,
greater UVA protection is afforded by the composition with the
higher extinction coefficient.
TABLE-US-00002 TABLE 2 UV Absorption Data, .lamda..sub.max
(.epsilon.). .lamda..sub.max (.epsilon.) Solvent E-517 E-567 MBC
EHT BEMT C.sub.12- 15 alkyl 358 328 N/A N/A 347 benzoate (33,400)
(9,260) (N/A) (N/A) (43,800) N/A 298 301 313 313 (N/A) (9,310)
(22,000) (117,000) (40,800) 2- 359 327 N/A N/A 345 phenylethyl
(34,100) (9,600) (N/A) (N/A) (48,000) pentanoate N/A 287 298 312
312 (N/A) (14,300) (23,600) (123,000) (42,900) 2- 359 326 N/A N/A
345 phenylethyl (34,500) (12,100) (N/A) (N/A) (49,000) cyclo- N/A
N/A 317 317 N/A hexanoate (N/A) (N/A) (10,400) (47,300) (N/A)
Example 6
Broad Spectrum UVA/UVB Sunscreen Formulations
[0032] The "anti-aging" formulations in Table 3 were examined for
critical wavelength, a measure of UVA protection, using an
Optometrics SPF 290 analyzer, shortly after preparation and after
five freeze-thaw cycles or 1 month of storage at 45.degree. C. The
higher the critical wavelength, the greater the UVA protection. As
can be seen in Table 4, the formulation containing 2-phenylethyl
cyclohexanoate was superior to the other formulations containing
Finsolv.RTM. TN, Eldew.RTM. SL-205, Finsoly.RTM. TPP, or
Elefac.RTM. I-205.
TABLE-US-00003 TABLE 3 Anti-aging cream formulations. Formulation 1
2 3 4 5 Ingredient Wt. % Wt. % Wt. % Wt. % Wt. % Phase A Deionized
water 57.35 57.35 57.35 57.35 57.35 Stabileze .RTM. QM 0.50 0.50
0.50 0.50 0.50 Butylene glycol 3.00 3.00 3.00 3.00 3.00 Disodium
EDTA 0.10 0.10 0.10 0.10 0.10 Phase B Cerasynt .RTM. 840 1.50 1.50
1.50 1.50 1.50 Cerasynt .RTM. 945 2.00 2.00 2.00 2.00 2.00 Escalol
.RTM. 517 3.00 3.00 3.00 3.00 3.00 Escalol .RTM. 557 7.50 7.50 7.50
7.50 7.50 Escalol .RTM. 567 2.00 2.00 2.00 2.00 2.00 Escalol .RTM.
587 5.00 5.00 5.00 5.00 5.00 Phenethyl 10.00 0.00 0.00 0.00 0.00
cyclohexanoate Finsolv .RTM. TN 0.00 10.00 0.00 0.00 0.00 Eldew
.RTM. SL-205 0.00 0.00 10.00 0.00 0.00 Finsolv .RTM. TPP 0.00 0.00
0.00 10.00 0.00 Elefac .RTM. I-205 0.00 0.00 0.00 0.00 10.00 Phase
C Sodium hydroxide, 1.30 1.30 1.30 1.30 1.30 10 wt. % Deionized
water 5.00 5.00 5.00 5.00 5.00 Phase D Liquapar .RTM. Optima 1.25
1.25 1.25 1.25 1.25 Liquapar .RTM. Oil 0.40 0.40 0.40 0.40 0.40
Phase E Glycacil .RTM.-L 0.10 0.10 0.10 0.10 0.10 100.00 100.00
100.00 100.00 100.00
[0033] Typical Preparation: For Phase A, a beaker was charged with
water, butylene glycol and disodium EDTA. Mixing was begun, and
Stabileze.RTM. QM was slowly sifted into it. The batch was heated
to 80.degree. C. with mixing and held for 45 min. In a separate
beaker, the ingredients for Phase B were combined, mixed and heated
to 75.degree. C. Phase C was slowly added to Phase A, and the batch
was mixed until clarity was obtained. Phase B was added, and the
batch was cooled to 45.degree. C. with mixing. Phase D was added
and mixed thoroughly. Phase E was added and mixed thoroughly. After
qs for water loss, the batch was packaged.
TABLE-US-00004 TABLE 4 Critical wavelength data. Critical
wavelength (nm) Formulation initial freeze-thaw 45.degree.
C.-storage 1 377.6 377.7 376.8 2 375.0 374.7 373.3 3 375.0 374.3
374.1 4 374.8 373.9 373.8 5 373.1 373.7 372.5
[0034] While the invention has been described with particular
reference to certain embodiments thereof, it will be understood
that changes and modifications may be made which are within the
skill of the art. Accordingly, it is intended to be bound only by
the following claims.
* * * * *