Stabilized benzoyl peroxide compositions

Benzoyl peroxide dispersed in an aqueous medium is stabilized by the presence of glycerol. Where the composition includes a finely dispersed and mild abrasive, together with a wetting agent and a thickener, the composition is suitable for use as a toothpaste. Where the composition includes a suitably large quantity of wetting agent and an appropriate soft abrasive, the composition is effective as a body scrub in preparation for surgery.

The subject matter of the present application is also related to my 
co-pending application Ser. No. 104,630 bearing the same title as the 
parent application and filed on the same date as the present application. 
BACKGROUND OF THE INVENTION 
As disclosed in the aforenoted parent application, glycerol stabilizes 
organic peroxides dispersed in an aqueous medium. The quantity of peroxide 
can vary from about 1% to about 30% by weight and the quantity of glycerol 
can vary from about 5 volume % to about 50 volume %. When combined with 
suitable thickener and alkali to bring the pH to a value between 3.5 and 
5.0, the composition is effective in the treatment of acne when applied 
topically. 
The effect of glycerol on the decomposition rate of organic peroxides was 
unexpected since monohydric alcohols and glycols by themselves do not 
stabilize the benzoyl peroxide. 
The present invention is concerned with benzoyl peroxide compositions 
useful for purposes other than the treatment of acne where the benzoyl 
peroxide is also stabilized by glycerol. 
SUMMARY OF THE INVENTION 
Compositions containing from 1 to 30 weight % of benzoyl peroxide, and 5 to 
50 volume % of glycerol in an aqueous medium are useful as a toothpaste 
and as a body scrub in preparation for surgery. Where the composition 
contains a pharmaceutically-acceptable wetting agent and a finely 
dispersed abrasive together with a thickener, the composition is effective 
for the removal of plaque from teeth. Where the composition contains a 
substantially greater content of wetting agent and granular polyethylene 
as abrasive, the composition is suitable for a body scrub. 
Accordingly, an object of the present invention is a composition containing 
benzoyl peroxide and sufficient glycerol to stabilize said benzoyl 
peroxide, in an aqueous medium. 
Another object of the present invention is a composition containing benzoyl 
peroxide, glycerol for stabilizing said benzoyl peroxide, and a thickener 
and mild abrasive in sufficient quantities so that said composition is a 
paste, said composition being useful as a toothpaste. 
A further object of the present invention is a composition comprising 
benzoyl peroxide and glycerol for stabilizing same, said composition 
containing a substantial quantity of a wetting agent and an extremely mild 
abrasive, such a composition being suitable as a body scrub in preparation 
for surgery. 
Still other objects and advantages of the invention will in part be obvious 
and will in part be apparent from the specification. 
The invention accordingly comprises a composition of matter possessing the 
characteristics, properties, and the relation of constituents which will 
be exemplified in the composition hereinafter described, and the scope of 
the invention will be indicated in the claims.

DESCRIPTION OF THE PREFERRED EMBODIMENTS 
Aqueous compositions containing from 1 to 30 weight % of benzoyl peroxide 
are stabilized by the incorporation of from 5 to 50 volume % of glycerol. 
The most useful compositions so far as toothpastes and body scrubs are 
concerned contain from 1 to 5 weight % of benzoyl peroxide and from 12 to 
30 volume % of glycerol. Where the composition is to be used as a 
toothpaste, the benzoyl peroxide content should be from about 1.2 to about 
1.8 weight % and the glycerol content should be from about 20 to about 30 
volume %. In addition, the composition should contain from 25 to 35 weight 
% of a mild abrasive and from 1 to about 3.5 volume % of a wetting agent. 
The preferred thickener is carboxyvinyl polymer having a molecular weight 
of about 4,000,000 and sold under the name of Carbopol 940 by B. F. 
Goodrich. The preferred wetting agent is sodium lauryl sulfonate. 
Optionally, up to about 0.7 weight % of sodium saccharin may be added as a 
sweetener and up to about 1 weight % of flavor. Also, up to about 0.05 
weight % of coloring material such as a dye may be added. Following are 
three toothpaste compositions exemplifying the present invention. 
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Formula #1 #2 #3 
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Water q.s. q.s. q.s. 
Glycerin 25% 25% 25% 
Dicalcium Phosphate 
30% 30% 30% 
Sodium Lauryl Sulfate 
2% 2.5% 2.5% 
Benzoyl Peroxide 1.5% 1.5% 2.5% 
Sodium Saccharin 0.15% 0.4% 0.4% 
Carboxyvinyl Polymer 
2.5% 6.0% 6.0% 
D & C Red #36 0.01% 0.01% 0.01% 
Flavor 0.47% 0.75% 0.75% 
Quantities of glycerol and sodium lauryl 
sulfonate in volume %. All other quantities 
in weight %. 
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The efficacy of benzoyl peroxide toothpaste, formulation No. 3, for the 
reduction of dental plaques and gingivitis was investigated, the Standard 
Plaque Index (PL I) and Gingival Inflammation Index (G I) being determined 
during a double-blind randomized comparison of: 
(A) Non-antibacterial toothpaste (Crest). 
(B) Toothpaste formulation No. 3. 
(C) Formulation No. 3 but minus benzoyl peroxide. 
The test was run on 36 adult male and female volunteers, minimum criteria 
for selection into the study requiring at least 16 healthy teeth without 
severe peridontal disease and absence of diabetes. None of the subjects 
were receiving antibiotic therapy or, in the case of females, were on oral 
contraceptives. 
On Day No. 1 of the 30-day pre-test period, all of the subjects were 
evaluated by the tooth surface stain scoring system using the labial 
surface of the 16 most anterior teeth. This involved both an area score 
and an intensity score developed after rinsing the mouth with disclosing 
solution. Following is the basis for the area score. 
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AREA SCORE 
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0 - No Stain 
1 - Specks of plaque at gingival margin 
2 - Continuous line of plaque at gingival margin 
3 - Plaque on gingival 1/3 of tooth surface 
4 - Plaque on gingival 2/3 of tooth surface 
5 - Plaque on more than 2/3 of tooth surface 
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The gingival status was monitored as to color, presence of edema, altered 
contour or bleeding on probing. 
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GINGIVAL SCORE 
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0 - Normal Gum 
1 - Mild inflammation with reddish discoloration 
2 - Mild inflammation with reddish discoloration, mild edema 
and bleeding on probing 
3 - Moderate inflammation with violaceous discoloration, 
edema and altered contour 
4 - Same as 3 but with additional bleeding on probing 
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Following evaluation on Day No. 1 of the study, patients were given a soft 
toothbrush and a non-antibacterial toothpaste and instructed to brush 
their teeth twice daily. The subjects were told to refrain from brushing 
their teeth on the morning of the 14th and 30th days to permit 
reevaluation. Those subjects with a stable score (30 subjects) were 
continued to Phase II. On Day No. 30 of the pre-test period (Phase II) the 
teeth of all participants were scaled and polished and the participants 
were again given toothbrushing instructions. 
Phase II 
The 30 remaining volunteers were randomly assigned to one of three groups 
(A), (B) and (C), and were given the appropriate toothpaste. The 
participants were instructed not to brush on Day No. 60, 90 or 120 of the 
study. On these days, the PL I and G I were again evaluated. The dental 
plaque score is shown in the FIGURE. As can be seen from the FIGURE, the 
participants initially had an average plaque index of about 2.5. After 
scaling, the plaque index reached almost to the initial level for Groups 
(A) and (C) in 60 days and then up to the initial level in 90 days. 
In contrast, the plaque index for the groups which had been brushing with 
the 2.5 weight % benzoyl peroxide toothpaste had a plaque index which was 
below 1. Since the members of Group (C) were tested with the toothpaste of 
the same composition as the members of Group (B) except for the benzoyl 
peroxide, it is evident that it is the benzoyl peroxide which is effective 
in lowering the plaque index. Moreover, after scaling, the gingival index 
also increased gradually in test Groups (A) and (C) but not in test Group 
(B). Also, the preparation is effective in eliminating gingival 
inflammation as none of the subjects in Group (B) showed gingival bleeding 
on probing. 
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GINGIVAL INDEX 
GROUP INDEX 
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A 2.1 
B 1.0 
C 2.5 
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With respect to body scrub solutions, these are conventionally used for 
"scrubbing-up" prior to surgery. Such solutions are used on the hands and 
arms of the surgeons who are about to participate in a surgical procedure 
and on the body of the subject. Compositions to be used as body scrubs 
comprise from 2 to 4 weight % of benzoyl peroxide, from 12 to 18 volume % 
of glycerol, up to 8 volume % of propylene glycol, from 1 to 4 weight % of 
thickener, from 12 to 20 volume % of wetting agent, and from 0.20 to 0.28 
weight % of alkali in an aqueous medium. The preferred wetting agent is a 
solution consisting essentially of 3 parts of ammonium lauryl sulfonate 
and 1 part of long chain imidazoline zwitterion. Also, the composition may 
contain up to 0.05 weight % of dye as coloring material, up to 1.5 weight 
% of ground mica for luster, up to 0.1% of perfume oil and up to 15 weight 
% of microthene (granular polyethylene) for abrasion. Following is a 
sample composition: 
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STABILIZED BENZOYL PEROXIDE SURGICAL SCRUB 
Percent Ingredient 
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3.5 Benzoyl Peroxide 78% 
14.8 Glycerin 
6.0 Propylene Glycol 
0.025 D & C Red #36 
1.2 Carbopol 940 (carboxyvinyl polymer) 
12.0 Ammonium Lauryl Sulfate 
4.0 Long Chain Imidazoline Zwitterion 
1.0 Pearl White Ground Mica 
0.24 Sodium Hydroxide 
0.05 Perfume Oil 
10.0 Microthene MA 778 Polyethylene 
Beads 
47.16 Purified Water 
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NOTE: 
Liquid content in volume % (1 ml taken as 1 
Solids content in weight % 
In both the toothpaste and the surgical scrub the quantity of alkali used 
is such as to bring the pH of the composition to from 3.5 to 5.0. 
The Standard Glove-Juice test was employed in a double-blind comparison to 
determine the efficacy of the surgical scrub. The materials tested were: 
A. Non-antibacterial soap (Ivory) 
B. Surgical Scrub with 2.5 weight % Benzoyl Peroxide 
C. Surgical Scrub without Benzoyl Peroxide 
D. Phisohex 
Twenty-four (24) adult male and female volunteers were selected for the 
test, one criterion for selection into the study being a bacterial count 
of 1.5-2.0.times.10.sup.4 per hand. In addition, individuals receiving 
antibiotic therapy or in the case of females on oral contraceptives, were 
excluded from the test. 
On Day No. 1 of a two-week pre-test period all subjects were instructed to 
use Ivory Soap and to avoid products containing anti-microbials. Subjects 
were also given rubber gloves to be worn during their normal daily 
routines to avoid contamination with germicidal agents. 
The baseline period for the study was the week following the two weeks of 
pre-conditioning. Baseline counts were performed three times during this 
period. In preparation for the counts, the hands were washed for thirty 
seconds with Ivory Soap, the washing extending 2/3 of the distance from 
wrist to elbow. Excess water was shaken from the hands and standard gloves 
were donned over the wet hands. Stripping solution was added to the gloves 
and the hands were massaged through the gloves for one minute. An aliquot 
was withdrawn from each glove and a bacterial count carried out. 
During the test period, both hands were scrubbed for six minutes and placed 
in sterile surgical gloves. One hand was immediately removed and stripping 
solution was added to the glove and the hand immediately rinsed with the 
solution; plate counts were performed at this time. The other hand was 
incubated in a glove for one, two, four and six hours. Stripping solution 
was added and plated. A different subject was used for each time period 
indicated. 
The stripping solution is a mixture of the detergent Triton X-100 at a 
concentration of 0.1% in the bacterial transfer medium called "Eugon's 
Broth". This material is injected into the surgical glove, massaged around 
the fingernails particularly, and then pipetted out. After dilution, it is 
applied to a plate. 
During the two-week pre-test period it was found that all subjects had 
stable counts. During the test period both hands were scrubbed with the 
solutions A, B, C or D. As a further refinement of the procedure, the 24 
volunteers were broken into four groups of 6 volunteers per group. It was 
found that the surgical scrub containing benzoyl peroxide was highly 
effective in reducing the bacteria count in the subjects tested, the test 
results clearly showing that the count remained low over the entire period 
of six hours. Further, the Ivory Soap test in Group A and the surgical 
scrub without benzoyl peroxide for Group C were relatively ineffective in 
reducing the bacterial count. Phisohex was found to be approximately half 
as effective as the surgical scrub with the benzoyl peroxide. 
As will be evident to those skilled in the art, a wide variety of wetting 
agents, thickeners and abrasives may be used in formulating both the 
toothpaste compositions and the surgical scrub compositions. In general, 
higher levels of benzoyl peroxide require higher levels of glycerol for 
effective stabilization and the quantity of thickener can be adjusted in 
accordance with the amount of abrasive to achieve appropriate viscosities 
for toothpaste on the one hand and for a surgical scrub on the other. 
As noted in my application having the Ser. No. 840,339, said application 
being incorporated herein by reference as if fully published, other 
suitable thickeners are magnesium aluminum silicate and finally divided 
silica. In general, in preparing formulations in accordance with the 
present invention, the benzoyl peroxide is added to the vehicle in a 
high-shear blender and agitated for several minutes until dispersion is 
complete and the product is uniform. The thickener is added to a small 
quantity of the vehicle and the resultant solution or dispersion is added 
to the benzoyl peroxide dispersion. Agitation is continued until the 
product is smooth, after which alkali, preferably in the form of a dilute 
solution, is added, blending same until the resultant gel or solution is 
homogenous. 
It will thus be seen that the objects set forth above, among those made 
apparent from the preceding description, are efficiently attained and, 
since certain changes made be made in the above composition of matter 
without departing from the spirit and scope of the invention, it is 
intended that all matter contained in the above description shall be 
interpreted as illustrative and not in a limiting sense.