CA1261757A - Compositions for treating acne vulgaris and methods of making and using same - Google Patents

Abstract

ABSTRACT
A facial mask composition for controlling and mitigating acne vulgaris which is capable of selectively penetrating the comedones while avoiding keratolytic and desquamating effects on the surrounding skin. The composition containing, in weight percent, from about 0.5 to about 10 percent benzoyl peroxide; from about 9 to about 13 percent of an inorganic thickening agent selected from the group consisting of magnesium aluminum silicate and bentonite; from about 20 to about 25 percent of an absorbent powder selected from the group consisting of kaolin and bentonite; from about 2.5 to about 15 percent of a humectant selected from the group consisting of glycerine, sorbital and propylene glycol, and q.s. of a solvent selected from the group consisting of distilled water, a lower alkyl alcohol and mixtures thereof.
A method of producing the facial mask composition is also provided.

Description

~L~6~7S7 OOMPOSITIONS ~R TREATING ACNE YULGARIS
~ND METHO~S OF MAKIN~ AND USING SAME

TEGHNICAL FIELD

The present invention relates to n~w and lmproved me~ns for tre~ting acne vulgaris; a unique faoial m~k containing benzoyl pero~ide as its essential active ingredient which is surprisingly compatible therewith and e~fective to eontrol and mitigate acne vulgaris in those individu~ls susceptible thereto; and ~ unique method for produclng a ch~nically and physi~ally stable mask composition which is efficacious in the treatment of acne vulgari~ and cosmetieally pleasing to use.

BACKGROUND ART

The cau3e of acne vulgaris is unknown but recent re~earGh ha~ provided insight into the pathogenesis of the : condition. Currently, there i5 general agreement that the relevant ~aotors are ~n individual's genetic predis-po~ition to ~ne, the size o~ un individual's sebaceous ~ gland (See: Cunliffe et al9 The Acnes: Clincial ~ . W. B. Saunders Co., London, pp 62, 66-67, 1975), the type and quantity of bacterla within the ~ollicle (See: M~rples et al, "Control o~ ~ree Fatty Acid in H~man Sur~ace Lipids . . ."
, 5~, 127-131, 1971;
Mill et ~ Acne Vulgari~ Orsl Therapy With Tetra~ycline dnd Topical Therapy . .n, ~, 106, 200-203, 1972), thc androgenic stimulation of sebum ~See:
~halita, "Acne Vulg~ris Current Concepts in Pathogenesi3 Treatmen~ International", Journal of Dermrtolo~ 15, 182-187, 1976), and alterations in the keratinization ~; process (See: Holms et al, "Pilosebaceous Duct Obstruction in Acnen, ~ , 87, 327-33).

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~26~7~i7 Benzoyl peroxide was first considered ~or the treatment of acne vulgaris in 1934 but was not fully Appreeiated until recently because of insufficient under~tanding of the role the vehicle plays in delivering the medication to the pilosebaceous apparatus.

The vehi~les heretofore attempted included cr~mes, lotion~ and hydroalcohol gels containing rom 2.5 to 2~ benzoyl peroxide. Sueh formulations reeeived wide acceptance mo~tly becau~e of the ability of benzoyl peroxide to inhibit P.acnes in vivoO

Purther, benzoyl peroxide was considered to be quite ver~atile since it achieved d~nonstrated success in treating all forms and grades of acne except acne ; conglobata, that is, grade 4 cystic acne. (See: Hurwitz et al, "How to Individualize Acne Therapy'~, Patient Care.
7, 133-167, 1983).

However these formulations were also found un~ble to avoid the keratolytic or desquamating ef~ect of benzoyl per- oxide ~9 d~monstrated by the irritation 2Q aCcompanying it3 use.

Yurthermore such commerical products have the tend~ncy to deliver benzoyl peroxide to syst~mic locations where it i~ not needed and in forms in which it is not act iYe-Thus a need exists for a product which can be u~ed to effectively treat the common forms of acne and expecially acne vulgaris, while avoiding the untoward side efiects and ineonvenience inherent in the prior art formulations and providing a readily applied, e~sily used, 3~ cosmetlcally pleasant and commercially acceptable product.

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SUMMARY OF IMVENTION

The present invention presents compositions and method3 of m~king and using same which co~mpositions are r~mark~bly use~ul for treating acne. The present invention is predicated upon the production of an uniquely comp~tible f~cial m~sk capable of containing as its essential active ingredient fr~m about 0.5 percent to about 10 percent by weight of benzoyl peroxide and which in use obtains a rem~rkably unexpected beneficial effect 0 QS sh~ll hereina~ter appear in greater detail-A¢cordingly, it is a prime object o~ the presentinvention to provide new and improved means and methods for deliverine benzoyl peroxide to acne sites which enhance the e~ectiveness of the active therapeutic agent while subst~ntially reducing the treatment period asso~iated with prior art products.

A further ob~ect of the present invention is to provide a new and improved product for the treatment of acne whi~h not only achieves direct therapeutic action but achieves a se~ond~ry benefit by attracting excess sebwm fron the situ~ thereby subst~ntially eliminating its influence on the ~urther replication of the aone condition.

Still ~nother object of the present invention is to provide improved means and methods for treating acne sites which tre~tment is of short duration and m~y be thereafter wa~hed off permitting the user to enga~e in normal social activity.

Still a further object of the present invention is to provide new and useful compositions and articles of manufaeture which contain benzoyl peroxide ~t levels e~ective to treat acne vulgaris.

~2~757 A still further object of the present invention is to provide a novel and unique mask composition which ;s physically and ch~nically stable when admixed with benzoyl peroxide at designated levels and which is effective in the treatment of acne vulgaris without degradation of active components or deterioration of the mask system.

These and still further objects as shall hereinafter appear are readily fulfilled by the present invention in a remarkably unexpected manner as will be 10 readily discerned from the following detailed description of an exemplary embodiment thereof.

The product of the present invention comprises a unique highly stable formulation in which from about 0.5 to about 10% by weight of benzoyl peroxide is strategically disposed throughout a specially formulated facial mask which is non-gritty and cosmetically pleasing to use.

The facial mask of the present invention 20 comprises a mixture of inorganic thickening agents, absorbent powders, and/or organic gelling agents, with or without alcohol. In practice, suitable inorganic thickening agents include Veegum*(magnesium aluminum silicate), and Bentonite. Suitable organic gelling agents include gelatin, starch, cellulosic gums, guar gum, alginates, and polyvinyl alcohols.

Other ingredients heretofore employed in the production of conventional facial masks may also be incorporated in the compositions of the present invention 30 so long as they do not affect the ultimate stability of the composition. Typical among such compatible additives * trad~ ~ark ~ .

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~26~57 are propylene glycol, which serves as a humectant, and methyl and ethyl paraben, which serve as microbial preservative~.

Thus the facial mask broadly contemplated hereby will contain 0.5 to about 10% by weight of ben~oyl peroxide thoroughly disposed throughout a blended mixture of an inorganic thickening agent, Qnd/or an organic gelling agent, Rnd an absorbent powder with or without ~lcohol. In a preferred ~orm oY this invention, excellent 10 result~ are obtained with a clay based ~acial mask composition.

In one practice of the present invention benzoyl peroxide is blended into a master mask batch containing kaolin; a moisturizer, e.g., glycerine; SDA-40 alcohol; an inorganic thickening agent, e.g., Bentonite; and purified water USP to create a homogenous composition. The quantities o~ the several ingredients may vary depending on the viscositg, texture and drying properties desired in 20 the final mix. The ranges, in percent by weight, found ~ppropriate to create ~ commercially acceptable product are:

Ben~oyl Peroxide 2.0 - 10.0 Tltanlwm Dioxide 1.0 - 5.0 KRO1ln~ USPao.o - as.~
Gly~erine (96~SP) 2.5 - 15.0 SD~-40 Alcohol0.O - 10.0 Bentonite9.0 - 13.0 Purified water35.0 - 45.0 lt has been ~ound that the texture, appearan~e, and e~ficacy of the mask m~y be enhanced by a special manufacturing technique which produces an effica~ious and cosmetically elegan~ produ~t that is pleasing to use as will now be deseribed.

i26~757 In our new m~nu~acturing process, a pranix is prepared by combining a portion o~ the required water9 Benzoyl Peroxide, Glycerin U~P, Titanium Dioxide, and a portlon o~ the Kaolin USP~ These materials (in weight pereent o~ ~inal composition) are mixed into a slurry having the following proportions:

Puri~ied Water, USP 2a.0 Benzoyl Peroxide, USP 7.1 Glycerine, USP 12.5 Kaolin, USP 1.0 Titanium Dioxide 1.0 The resultant slurry is ground using conventional means and methods until it is essentialy non-gritty. Conventional grinding equipment such as ball mills, colloid mills, roller mills, homo mills, are suitable for use herein. The completeness oi the grinding operation can be quantified by e~amining particle size under a stand~rd microscope. A particle size o~ about 25 is asceptable.

Aiter grinding the slurry to the indicated particle size, the remainder o~ the ingredients are added step-wise using a conventional screw type mixer. Mixing is continued until the mixture is completely homogeneous, smooth and cre~my. Thereafter the product can be readily packaged in tube~ or jars for delivery to the consumer.

The pre~erred use of the product is accomplished once daily or as directed by the user's physician and comprises washing the affected areas thoroughly with a mild non-medicated cleanser and thereafter rinsing and pat drying the skin. Thereafter, using a circular motion, a thin layer of the mask formulation is applied evenly over the affected are~ and the mask is allowed to dry for 15 or 126~757 20 minutes. The f~ce is then rinsed thoroughly with warm w~ter to r~nove all cf the m~sk ~nd the f~ce is dried.

A~ will ~ppeflr ~ in order for benzoyl peroxide to be effective against ~cne, it must transit the vehi~le and penetrate into the seba~eous duct through the follicular opening. Earlier studies involving commercial ly aYai labl e vehicle3 indicated that benzoyl peroxide can penetrate the str~tum corneum but at that level is rapidly converted into benzoic a~id, an inactiYe form (See: Journal of the 10 Am~ ~ ' 4, 31-37, 1981; and ibid, 9, gao-924, 1983). As will hereina~ter appe~r, using the mask oi the present invention, penetration of the active reagent into the eomedone is achieved with demonstr~ted benefit.

; To ~urther aid In the understanding o~ the present invention, und not by way of limitation, the following examples ~re presented.

EXAMPLE I
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A faci~l m~sk i9 prepared using the ~ollowing procedure. A portion of the stated water is admixed with O.S to about 10% by weight (~inal formulation) of benzoyl peroxide, glycerine, titanium dioxide, and a portion of the absorbent powder to form a slurry. The slurry is then fine ~round to ~ as particle size. The bal~nce of the seYer~l ingredient~ is then sequentiQlly mixed into the ground slurry to produ¢e a homogeneous smooth and cre~my blend having the ~ollowing compositions in per~ent by weight.

Composition A

Glycerine, 96% 5.0%
Propylene Glycol 5.0%

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Benzoyl Peroxide 3.4%
SDA-40 Alcohol 10 . 0%
Purified Water, USP43.~%
Bentoni t e, U~P11. 0%
KRolin, USP 21.0%
Titanium Dioxide 1.0%

Compo s i t i on B

Purified Water, USP42.77%
Chin~ Clay 42.17%
Bentonite 4.13%
Isopropyl Alcohol 3.78%
Benzoyl Peroxide, 78%7.0%

Composieion C

Glycerine, ~6% 10.0%
Benzoyl Peroxide 7.0%
SDA-40 Alcohol 3.0%
Puri~ied Water, U~P45.9%
Bentonite, USP 12.0 Kaolin, USP 21.0%
Tit~nium Dio~ide 1.0%

~XAMPLE II

A f~cial m~sks is prepared using the following pro~edure. A p~rt of the stated water is ~dmixed with methylcellulose, ben~oyl peroxide and a portion of the absorbent powder to form a slurry. The slurry is then ~ine ground to a 25 particle si~e. The balance of the several ingredient~ is then sequentially mixed into the gro~nd slurry to produce a homogeneous smooth and cre~my blend h~ving the ~ollowing compositions in percent by 30 weight.

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Composition D

Solulan 98 5.0%
Methyl Cellulose (400 cps) 1.5%
Benzoyl Peroxide 5.0%
SDA-40 Alcohol 5.0%
Purified Water, USP fi3.5%
Bentonite, USP 15.0%
- Zinc Oxide 5.U~
Titanium Dioxide 2.5%

EXAMPLE III

A facial mask is prepared using the following procedure. A portion of the stated w~ter is admixed with an organic gelling agent such as polyvinyl aleohol or gelatin and mixed until fully hydrated and homogeneolis. A
sep~rate slurry is prepared by combining benzoyl peroxide, glycerine and Tween 20 (if used). This slurry is then fine ground to a 25 particle si~e. The ground slurry and hydrated organic gellant ~re then combined and the r~naining ingredients are sequentially mixed to produce a homogeneous smooth and creamy blend having the ~ollowing compositions in percent by weight.

Composition E

Glycerine, 96% 5.0%
Benzoyl Peroxide 7.0%
SDA-40 Alcohol 8.0%
Purified Water, USP 64.0~
Polyvinyl Alcohol 15.0%
Tween 20 1.0%

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~6~757 Composition F

Glycerine, 96% 3.0%
Gelatin 4.0%
Benzoyl Peroxide 10.0~
Purified Water, USP 80.0%
Titanium Dioxide 3.0%

EXAMPLE IV

A facial maslc is prepared using tlle following procedure. A portion of the stated water is admixed with part of the veegum, benzoyl peroxide and titanium dioxide to form a slurry. The slurry is then fine ground to a 25 particle size. The balance of the several ingredients is then sequentially mixed into the ground slurry to produce a homogeneous smooth and creamy blend haYing the following compositions in percent by weight.

Composition G

Benzoyl Peroxide 10.0%
SDA-40 Alcohol 15.0%
Purified Water, USP 62.75%
Veegum* 10.0%
Methylparaben 0.25%
Titanium Divxide 2.0 EXAMPLE V

; Using the procedure of Example I, clay based facial masks were prepared having the following compositions in percent by weight:
Benzoyl Peroxide 2.0 - 10.0 Titanium Dioxide 1.0 - 5.0 Kaolin, USP 20.0 - 25.0 Glycerine (96%VSPj 2.5 - 15.0 ' * trad~ mark ~ 11 :
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SDA-~0 Alcohol0.0 - 10.0 Bentonite 9.0 - 13.0 ; Purified water3S.0 - 45.0 EX~MPLE VI

: A C1QY m~sk ~ccording to Example V contaiQing 5%
benzoyl p~roxide, U3P was prepnred in accordance with the procedure o~ Example II end applied to the right one-third forehead o~ twenty volunteers, from whi~h after tweney minute~, it w~ washed off with warm water. The left one-third forehead of e~ch subject was washed but without any mask applic~tion~ The center third forehead of each subiect wa~ ls~t untreated ~nd unwa~hed. Each test site was then extra¢ted for its lipid content and the qu~ntity of lipids was grav~netrieally determined and the composite result~ ~re shown in Table A below.

TABLE A
Procedure Quantity of sebum r~na2ning (ug/cm ) 20 M~sk and wa~h 36.01 W~sh only 77.43 No tre~tment 208.93 The dat~ clearly demonstrated the lipid adsorbing capacity of the mask in that it r0noved signi~icantly (p~0.005) more sebwm than mere wa~hing.

XXAMPLE YII

:~ ~ clay m~sk preparation acording to Example V
containlng 5% benzoyl peroxide, USP was prep~red in : acoordance with the procedure of Example I. A panel of ~: 30 ten volunteer~ h~d the initi~l P. ~cnes level on each side `: of ~heir face measured by the method o~ Williamson ~nd .

1~6~75~i~
Kligman (Journal of Investigative Dermatology, 45t 492-503, 1965) and their initial fatty acid/triglyceride ratios were determined by the method of Downing (J.
Chrom ~ (38) 91-99, 1968). The clay mask prepared as indicated was applied one half of each volunteer's face once a day for twenty minutes per the specified regimen.
On the other side of each volunteer face was applied Desquam-X 5% gel twice per day per label instructions.
After one week, the P. acnes and free fatty 1O acid/triglyceride levels for each subject was repeated.
The eumulative reduction results in the respective levels of these accepted indicia of clinical efficacy are in Tables B and C.

TABLE B
P. acnes reduction (log/cm ) *

D-X gel Period Mask B.24 + 0.34 0 week 6.35 ~ 0.61 4.84 ~ 1.09 1 week 4.86 + 0.78 TABLE C

Free Fatty Acid/Tri~yceride Ratio D-X gel Period Mask 0.29 ~ 0.08 0 week 0.31 + 0.09 0.20 ~ 0.04 1 week 0.22 + 0.09 As evidence of the effectiveness of the benzoyl peroxide, all ten subjects showed significant reduction in both P. acnes and Free Fatty Acid level. Comparing the twice daily applications of a commercial gel with the single twenty minute application of the mask, it is readily seen that the degree of reduction induced are * trade mark 3 ,,~

~261757 equivalent while the mask required much less product, time and in¢onvenience to achieve that result.

EXAMPLE VIII

Using the n~n-invasive follicular biopsy technique described by Mills et al (~ee: Dermatolo~ca, 1_ , 57-63, 1983) and the direct measurement of drug levels by high pressuPe chromotography described by Wortzman et al (See: ~ , 82, 413, 1984), ~ half face study was conducted to compare benzoyl peroxide penetration from the facial mask o~
Example IV ~gainst the penetration obt~ined by a standard commercially Rvailable 5% gel.

The Yolunteers applied the mask to one side of their ~ace once ~ day and washed it off after t~enty minutes. On the other side, each volunteer applied a 5%
ben~oyl peroxide gel twice daily without washing, per its label direction~. A~ter one week, n follieular biopsy was taken and drug le~el~ determined. In addition, the reduct~on In P. acnes level was compared. The results are ~ 20 reported in TQbles D and E.
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TABLE D

; Microgr~m3 Micrograms BPO/Gomedone Benzoic Acid/Comedone Gel Ma~k Gel Mask 7.0 ~ 2.04.8 ~ 1.7 0.91 + .21 0.95 + .3 TABLE E

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Gel Mask 1.3 + .4 -1.0 + .4 , ~

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While the difference between the gel and the mask product are not statistical in all cases, they are significant to the baseline. Thus, the data do support the conclusion that ben~oyl peroxide transits through the clay mask and penetrates into the microcomedone at a sufficient concentration to suppress P. acnes levels to the same degree as a commerically available alcoholic gel such as Desquam-X-5.

EXAMPLE IX

To determine whether benzoyl peroxide exhibits a more selective penetration when delivered in a clay mask vehicle vis-a-vis an alcoholic gel9 standard ~ranz penetration chamber tests were conducted (See: J. Am Acad of ~ermatolo~, 9, 66-73, 1983).

Using excised hairless mouse skin which is "leakier" th~n human skin, test materials are applied and the amount that penetrates the epidermis and the papillary dermis is measured by high performance liquid chromatography.

The results shown in Table F demonstrate that while some benzoyl peroxide products cause penetration of as much as 30-40% of their applied dose, the acne mask of the present invention shows very little cutaneous penetration~ By implication, it is concluded that the mask promotes penetration almost exclusively into the follicle where the drug is effective. Thus, while the mask provides the same reductions P. acnes and free fatty acid/triglyceride ratio as the comnercially available gels, it allows much less benæoyl peroxide to be absorbed systemically or to be contained intradermally.

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~26;1~S7 TABL~ P

~ e Time Cl C2 C3 M~sk Hours% mg % mg % mg % mg 0.5 1.8053 1l0 3.17 115 2.67 25~ 2.g01~4 ~94 45

2.0 8.77 320 7.19 697 8.31413 1.33 fiS

3.0 12.8 ~371.79 87

4.0 30.~0 15.~1538 14.7 7301.8a ~1 6.0 39.21430 26.22541 23 41.11520 31.43045 Wherein : Cl = Cle~r by Design0 (2.5% BPO) C2 = Clsarasil~ (5% BPO) C3 = Oxycover~ (10% BPO).
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Pr~m the ~oregoing, it is readily ~pparent that impPoved eomposltion ~nd methods been herein described and illu~trated which ~ulfill ~ll of the aforestated ob~ct Ive8 in a r~n~rkably unexpected iashion. It is oi course under~tood that such modifications9 alterations Qnd ~ 20 ~daptatlo~s a~ m~y re~dily occur to the artisan conironted ; wlth thls disclosure are Intended withln the spirit oi this dlsclosure whieh i~ limited only by the scope oi t~e clalms ~pp~nded hereeo.

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Claims (5)

What is claimed is:

1. A facial mask composieion for controlling and mitigating aene vulgaris which is capable of selectively penetrating the comedones while avoiding keratolytic and desquamating effects on the surrounding skin, said composition containing, in weight percent) from about 0.5 to about 10 percent benzoyl peroxide; from about 9 to about 13 percent of an inorganic thickening agent selected from the group consisting of magnesium aluminum silicate and bentonite; from about 20 to about 25 percent of an absorbent powder selected from the group consisting of kaolin and bentonite; from about 2.5 to about 15 percent of a humectant selected from the group consisting of glycerine, sorbital and propylene glycol; and q.s. of a solvent selected from the group consisting of distilled water, a lower alkyl alcohol and mixtures thereof.

2. A facial mask composition according to claim 1 containing organic gelling agents selected from the group consisting of gelatin, starch, cellulosic gum, guar gum, alginate and polyvinyl alcohols.

3. A composition of matter according to claim 1 consisting of, in percent by weight: from about 5 to about 10 percent, benzoyl peroxide; from about 1 to about 5 percent, titanium dioxide; from about 20 to about 25 percent, kaolin; from about 2.5 to about 15 percent, glycerine; up to about 10 percent denatured ethyl alcohol; from about 9 to about 13 percent bentonite; and q.s distilled water.

4. A composition according to claim 3 consisting of, in percent by weight, 1 percent titanium dioxide; 21 percent kaolin, 12.5 percent glycerine; 2.75 percent ethyl alcohol; 11.5 percent bentonite, and 44 percent distilled water.

5. A method of producing a facial mask effective for the treatment oi aene vulgaris comprising the steps of: forming a slurry containing benzoyl peroxide, an inorganic thickening agent, an absorbent powder and a solvent selected frorn the group consisting of purified water, and mixture of purified water and a lower alkyl alcohol; grinding said slurry until the particles thereof are 25µ or less; admixing into said slurry sequentially whi1e continuing said grinding, additional amount of said thickening agent and said solvent to provide a homogeneous mixture; and collecting said homogeneous mixture into a container.