Method for treating acne vulgaris with a composition containing a stable, high purity, substantially anhydrous complex of PVP-H.sub.2 O.sub. 2

What is provided herein is a method for treating acne vulgaris with a composition containing a stable, high purity, substantially anhydrous complex of PVP and H.sub.2 O.sub.2 in which the constituents are present respectively in substantially a 1:1 molar ratio and the complex is a free-flowing, fine white powder.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to a method for reducing the microbial content of 
surfaces, and more particularly, to compositions containing a stable, high 
purity, free-flowing, substantially anhydrous complex of PVP-H.sub.2 
O.sub.2 for treating acne vulgaris. 
2. Description of the Prior Art 
Stabilized H.sub.2 O.sub.2 compositions have found wide utility in 
commercial and industrial applications, e.g. as antiseptics, 
disinfectants, sterilization agents, bleaching materials, washing 
concentrates, etchants, in cosmetic preparations, and as a catalyst in 
polymerizations requiring a free radical source. In biological 
applications which require an antiseptic, disinfectant or sterilization 
agent, such H.sub.2 O.sub.2 compositions require release of an effective 
amount of oxygen at a desired rate. 
Shiraeff, in U.S. Pat. Nos. 3,376,110 and 3,480,557, reacted hydrogen 
peroxide and PVP in an aqueous solution of the components. The process 
involved mixing predetermined amounts of PVP and a large excess of aqueous 
H.sub.2 O.sub.2, e.g. 50% aqueous solutions, and evaporating the solution 
to dryness. The Shiraeff composition was described as not necessarily 
anhydrous due to the hydrophilic nature of the PVP and the water present 
in the reaction solution. Shiraeff stated that water could be tolerated, 
however, if it did not affect the solid dry characteristics of the 
complexes. The H.sub.2 O.sub.2 content of the composition was given as 
being at least 2%, and preferably 4.5 to 70% by weight. Prolonged drying 
of the composition in an attempt to reduce the water content, however, 
resulted in loss of H.sub.2 O.sub.2 from the complex, forming a brittle, 
transparent, gummy, amorphous product of non-reproducible consistency. The 
resultant hard, brittle chips had a variable H.sub.2 O.sub.2 content 
ranging from about 3.20 to 18.07% by weight, depending upon the drying 
times, and a considerable amount of water. 
The Shiraeff PVP-H.sub.2 O.sub.2 material did not attain commercial success 
because the product (1) was not a free-flowing powder; (2) its water and 
peroxide content varied widely; (3) it had consistency and reproducibility 
problems; and (4) the aqueous laboratory process could not be scaled up 
due to great loss of H.sub.2 O.sub.2 during drying. 
Acne vulgaris is an inflammatory disease of the pilosebaceous glands 
characterized by an eruption of the skin, often pustular in nature but not 
suppurative. Acne is a common affliction of the adolescent and affects a 
small but significant percentage of the adult population. Acne lesions are 
of four basic types: comedones (blackheads or whiteheads), papules, 
pustules, and cysts (or nodules). Various topical agents are utilized in 
the treatment of acne and these include sulfur, resorcinol, salicylic 
acid, benzoyl peroxide, vitamin A acid and topical antibiotics. Acne 
involvement results in unslightly lesions, particularly on the face, and 
in some cases results in severe scarring. 
Accordingly, an object of the invention is to provide a method for treating 
acne vulgaris with a composition containing a stable, high purity, 
substantially anhydrous complex of PVP-H.sub.2 O.sub.2 in a defined molar 
ratio of 1:1 of constituents and which is a free-flowing, fine white 
powder. 
Another object of the invention is to provide a stick formulation of such 
composition for treating acne vulgaris in a commercial and 
consumer-acceptable manner. 
Still another object of the invention is to provide a method for reducing 
the microbial content of skin surfaces afflicted with acne vulgaris with a 
microbial amount of a 1:1 complex of PVP-H.sub.2 O.sub.2 having an H.sub.2 
O.sub.2 activity of at least 3%. 
SUMMARY OF THE INVENTION 
What is provided herein is a method for treating acne vulgaris with a 
composition containing a stable, high purity, substantially anhydrous 
complex PVP and H.sub.2 O.sub.2 in which the constituents are present 
respectively in substantially a 1:1 molar ratio, and the complex is a 
free-flowing, fine white powder. This result is accomplished herein in a 
preferred manner by contacting said surface with a stick formulation 
containing an antimicrobial amount of such complex.

DETAILED DESCRIPTION OF THE INVENTION 
The PVP-H.sub.2 O.sub.2 complexes of the invention may be prepared by 
several methods. According to one suitable process, PVP and anhydrous 
H.sub.2 O.sub.2 are reacted in predetermined molar ratios in suspension in 
an anhydrous organic solvent. The product is a uniform, free-flowing, fine 
white powder which is isolated by filtration from the solvent. 
Another method is a suspension process in which water-insoluble PVP is 
suspended in anhydrous ethyl acetate into which an aqueous, concentrated 
H.sub.2 O.sub.2 solution containing about 70 to 85% by weight H.sub.2 
O.sub.2 is slowly added, the amounts of PVP and H.sub.2 O.sub.2 thereby 
being reacted corresponding substantially to the desired 1:1 molar ratio 
in the complex, at a temperature of about 0.degree.-10.degree. C., under 
agitation. The precipitate obtained is a uniform, free-flowing, fine white 
powder, which is filtered and dried. 
In another method, a fluidized bed of PVP powders which is maintained at a 
reaction temperature of from about ambient temperature to 60.degree. C., 
preferably 35.degree.-40.degree. C., is contacted with finely divided 
droplets of a 30 to 85%, preferably 50-70%, by weight aqueous H.sub.2 
O.sub.2 solution. The feed rate for introduction of the H.sub.2 O.sub.2 
solution suitably is about 5-50 g/minute/kg PVP used, preferably about 
15-25 g/minute/kg PVP. 
The PVP polymeric starting materials used in the present invention are 
available commercially as a solid of varying molecular weight, water 
solubility or insolubility, and water content. Typical water soluble PVP 
polymers are PVP K-15, PVP C-15, PVP K-29-32, PVP K-30, K-90 and K-120 
(GAF Corp.), which contain less than 5% water. Crospovidone is an example 
of an available water-insoluble PVP material. Mixtures of water soluble 
and water insoluble PVP also may be used. Preferably water soluble PVP is 
used herein. 
Compositions of the invention suitably contain H.sub.2 O.sub.2 in an active 
amount of about 1-10% by weight level, preferably about 3-7%. The active 
peroxide is present in the 1:1 molar ratio PVP:H.sub.2 O.sub.2 complex 
powder in a compatible, non-aqueous, organic solvent, suitably an alcohol 
or polyol, such as ethanol, propylene glycol, glycerol and the like. 
Generally the PVP:H.sub.2 O.sub.2 powder is dissolved in the organic 
solvent up to the limit of its solubility, and then combined with a base 
to form the finished product. A stick formulation is preferred because it 
is easy to apply to the affected area of the skin, and further because it 
feels comfortable for the user. 
Typical active solutions of the 1:1 PVP:H.sub.2 O.sub.2 powder in the 
organic solvent include the following: 
______________________________________ 
ACTIVE COMPONENT OF COMPOSITION 
Ex. Constituent Amount (g) 
______________________________________ 
A 1:1 PVP:H.sub.2 O.sub.2 (23.4%) 
60 
Ethanol (100%) 40 
Active H.sub.2 O.sub.2 
14% 
B 1:1 PVP:H.sub.2 O.sub.2 (23.4%) 
50 
Propylene glycol 
50 
Active H.sub.2 O.sub.2 
12% 
C 1:1 PVP:H.sub.2 O.sub.2 (23.4%) 
25-30 
Glycerol 70-75 
Active H.sub.2 O.sub.2 
6-7 
______________________________________ 
A typical base formulation for a stick formulation is the following: 
______________________________________ 
Constituent Amount (g) 
______________________________________ 
PEG 4000 50. 
PEG 400 5. 
Stearic Acid 5. 
Cetyl alcohol 5. 
Synchrowax HRC 5. 
(glycerol tribenate) 
Crodavol PTC 20. 
(glycerol ester) 
Cyclomethicone DC 345 
5. 
Talc 15. 
100. 
______________________________________ 
Preferably the active component and the base are combined in amounts of 
about 40-60:60:40, respectively, although higher and lower ratios may be 
used as well, the result being a well-formulated stick which has an active 
peroxide content of about 1-10%. 
The preferred procedure for formulating the desired anti-acne product is 
the following: 
1. The base is prepared by melting all constituents except talc and 
cyclomethicone to about 10.degree. C. above their melting points, 
generally at about 75.degree. C., and blending until homogeneous. Then 
talc is sprinked in with agitation and the mixture is cooled to 
55.degree.-60.degree. C. Thereafter the active PVP-H.sub.2 O.sub.2 
solution is slowly added, followed by cyclomethicone, and the resultant 
mixture is quickly poured into molds to provide the stick products. 
The invention will now be illustrated by the following examples, which 
should be considered as representative but not limiting of the invention. 
PREATION OF STABLE, HIGH PURITY, SUBSTANTIALLY ANHYDROUS, FREE-FLOWING 
1:1 MOLAR RATIO PVP-H.sub.2 O.sub.2 COMPLEX (23.4% .sub.2 O.sub.2) 
Example 1 
PVP K-15 (GAF Corp. (4.5% water), 111 g., was suspended in 200 ml. of 
anhydrous ethyl acetate (0.01% H.sub.2 O), and the suspension was cooled 
to 0.degree. C. An anhydrous hydrogen peroxide solution in ethyl acetate 
was prepared by treating 200 g. of 50% aqueous hydrogen peroxide with 6 l. 
of ethyl acetate, and distilling in a rotary evaporator to remove 100 g. 
of water from the azeotrope solution. A 42.7% H.sub.2 O.sub.2 solution in 
anhydrous ethyl acetate was obtained. Then 100 g. of this solution was 
slowly added over a period of about 1 1/2 hours to the PVP suspension. A 
fine white precipitate formed which was filtered and dried in vacuo. The 
resultant water soluble complex contained 23.4% by weight H.sub.2 O.sub.2 
and 0.5% by weight water, upon drying at 50.degree. C. in vacuo for 2 
hours. 
Example 2 
200 g. of PVP (K-30) was suspended in 300 g. of anhydrous ethyl acetate. 
Then 424 g. of anhydrous H.sub.2 O.sub.2, (19.6% H.sub.2 O.sub.2 and 0.84% 
H.sub.2 O) in ethyl acetate was added in a 45 minutes period to the cooled 
(5.degree. C.) suspension of PVP/ethyl acetate. This suspension was 
stirred for an additional 45 minutes, filtered, and washed with anhydrous 
ethyl acetate. The resultant fine powder was dried under vacuum at 
40.degree.-50.degree. C. for 2 hours to recover residual ethyl acetate. 
The yield was 258.8 g. of water soluble PVP-H.sub.2 O.sub.2 complex 
containing 23.1% H.sub.2 O.sub.2 and 0.4% H.sub.2 O, which was a 
free-flowing, white powder. 
Example 3 
200 grams of crospovidone XL10 (water-insoluble, cross polymerized PVP) was 
suspended in 250 g. of anhydrous ethyl acetate. To this suspension 125 g. 
of anhydrous H.sub.2 O.sub.2 was added by using 28.1% H.sub.2 O.sub.2 in 
anhydrous ethyl acetate and during the addition cooling at 
0.degree.-5.degree. C. The resultant, cooled mixture was stirred for an 
additional 1 hour. The precipitate was filtered to provide 26.2 g. of a 
water-insoluble, PVP-H.sub.2 O.sub.2 complex containing 24.1% H.sub.2 
O.sub.2, and 0.5% water, after drying under vacuum at 40.degree. C. for 2 
hours. 
Stability of Complex of Example 1 
After 43 days at 60.degree. C. the complex of Example 1 lost only 15% of 
its H.sub.2 O.sub.2 activity, which demonstrates an excellent stability 
toward decomposition. At room temperature, decomposition was only 1.5% 
after 60 days. 
SUSPENSION PROCESS FOR THE PREATION OF FREE-FLOWING, FINE WHITE POWDERS 
OF 1:1 PVP-H.sub.2 O.sub.2 COMPLEX 
Example 4 
PVP-CI (K-30) (GAF Corporation) (4.5% water) was dried at 105.degree. C. in 
vacuo for 2 hours until it contained only 1.1% water. 160 g. of the dried, 
water-insoluble PVP was suspended in 450 g. of anhydrous ethyl acetate 
(0.01% water), and the suspension was cooled to 5.degree.-10.degree. C. 
while agitating the suspension. Then 55 ml. of 70% hydrogen peroxide 
solution in water (71 g. H.sub.2 O.sub.2) was added slowly over a period 
of 35 minutes to the agitated suspension keeping the temperature at 
5.degree.-10.degree. C. A fine, white precipitate was formed which was 
filtered to yield 312 g. of a wet product which was dried at 
40.degree.-50.degree. C. in vacuo for 4 hours. 200 g. of a free-flowing 
fine, white powder was obtained which contained 19.5% H.sub.2 O.sub.2 and 
2.9% water. Further drying under the same conditions for an additional 6 
hours reduced the water content to 0.5% while maintaining the H.sub.2 
O.sub.2 content at 18.5% and without affecting the free-flowing 
characteristic of the powder. 
PROCESS FOR THE PRODUCTION OF 1:1 MOLAR RATIO PVP-H.sub.2 O.sub.2 COMPLEX 
USING A FLUIDIZED BED REACTOR AND VACUUM DRYING 
Example 5 
0.35 kg of polyvinylpyrrolidone (PVP K-30, CI grade) having particle sizes 
of predominantly 40-50 microns, and a moisture content of 2-3%, was 
introduced into a 0.4 liter fluid bed reactor. The PVP powders were 
fluidized by passing a stream of dry air upwardly through the charge. The 
bed temperature was set at 35.degree.-45.degree. C. Then an aqueous 
solution of 70% H.sub.2 O.sub.2 was metered through a spray nozzle with 
the assistance of an air stream and directed vertically onto the bed. The 
rate of addition of the solution was 15-25 g of solution/minute/kg PVP for 
20 minutes. Adsorption of the solution onto the bed produced a wet product 
containing 18% H.sub.2 O.sub.2 and 6% water. Subsequent downstream vacuum 
drying of the wet material at 25.degree.-35.degree. C. for 10 hours 
produced a free-flowing powder which had a 20-22% H.sub.2 O.sub.2 content 
and a water content therein at the same level as the PVP starting 
material. 
PROCESS FOR MAKING 1:1 PVP-H.sub.2 O.sub.2 PRODUCT USING FLUIDIZED BED 
DRYER 
Example 6 
3.6 kg of polyvinylpyrrolidone (PVP K-30, CI grade, having a particle size 
of 40-50 microns, was packed into a 22 liter fluidized bed dryer and 
fluidized at 35.degree.-45.degree. C. using a dry air stream. Then a 70% 
H.sub.2 O.sub.2 solution was introduced during 20 minutes at a feed rate 
of 10-15 g/minute/kg PVP. During the addition, water was being removed 
continuously from the product and the bed. Following completion of the 
H.sub.2 O.sub.2 addition, the resultant product was dried further for 10 
minutes. The resultant product was a free-flowing powdery complex of 
PVP-H.sub.2 O.sub.2 having a peroxide content of 20% and a moisture 
content of only 2%. 
Applications of the carrier and effective ingredient also are made to the 
face of acne patients 2 to 4 times daily with the result that open and 
closed comedones (blackheads and whiteheads) are markedly reduced within 
two weeks. The following examples illustrate the present invention. 
Example 7 
A 1% solution of the PVP-peroxide was prepared in an alcohol-propylene 
glycol carrier. Twice daily topical application of this solution were 
self-administered by a 26 year old female patient suffering from acne 
vulgaris. After two weeks of treatment the comedone count on the patient's 
face had declined from 28 to 15. 
Example 8 
A 20 year-old male applied 10% PVP-peroxide prepared in an alcohol gel 
containing 6% polyoxyethylene lauryl ether four times daily. After 10 days 
the number of comedones on his face had declined from 43 to 25 and by the 
end of four weeks of treatment he had only 18 comedones on his face. 
Example 9 
A 30 year-old female with acne vulgaris applied a 5% by volume solution of 
PVP-peroxide in a 70% ethyl alcohol and 30% propylene glycol carrier. The 
product was applied to all involved areas of the face and back twice 
daily. Before treatment this patient had 64 comedones on the face and back 
but after two weeks of treatment she had only 41 comedones in these areas. 
The preferred composition is clear and stable with 92% hydrogen peroxide 
remaining after six months' storage at room temperature. Moreover, said 
composition was found to be effective in reducing the P. Acne causing skin 
microflora when the composition was tested in a ten (10) day in-vivo 
antimicrobial study performed on three volunteers in which the composition 
was applied twice a day to the face area in half face fashion. Skin 
microflora was obtained on days 2, 3, 5 and 10 and after appropriate 
incubation under anaerobic conditions, the skin microflora was measured. 
The reduction in bacteria was determined by comparing the number of 
microorganisms between the treated and untreated sides of the faces. 
Acne is treated in patients by the topical application to the patient of an 
anti-acne effective amount of the clear stable compositions of this 
invention.