CA2086259A1 - Topical treatment of acne - Google Patents

Abstract

The object of the invention is to provide methods and compositions for topically treating acne and acneiform dermal disorders by applying to the skin an amount of an antibiotic selected from the group consisting of ampicillin, amoxicillin, other aminopenicillins, and cephalosporin, and derivatives and analogs thereof, effective to treat the acne and acneiform dermal disorders. The antibiotic is blended with a carrier suitable for topical application to dermal tissues. The carrier includes at least one carrier ingredient selected from the group consisting of water and a water-miscible alcohol, wherein combined weight percents of said carrier ingredients is in a range spanning 3 % to 99.5 %.

Description

WO92/15299 P~T/US92/014~5 2~g2~9 TOPICA~ T~Ea~E~T OF A~

~ross-R~erence ~o Rel~ted APplication The present application is based on U.S.
patent application of the same inventors, Robinson et al, Ser. No. 07/664,7'35, filed on March 5, 1991, ~or TOPI Q L TREATMENT OF ACNE.

Techni~al Fi~ld The precent invention relates to the field of treating the skin condition known as acne. ~ore specifically, the present in~ention is conc~rned . .
with the prophylactic or therapeutic topical treatment of acne. Even more specifically, the present invention is concerned with the topical treatment of such skin disorders as acne vulgaris, other acneiform dermal conditions, e. g.
preadolescent acne, acne rosacea (now known as rosacea), premenstrual acne, acne venenata, acne cosmetica, pomade acne, acne detergicans, acne cosmetica, acne excoriee, gram negative acne, steroid acne, acne conglobata, or nodulocystic 20 acne. The present invention can also be used for .
topically treating certain types of dermatitis, e.
g. perioral dermatitis, seborrheic dermatitis, ;:
gram negative folliculitis, sebaceous gland :
dysfunction, hiddradenitis suppurativa, pseudo-folliculitis barbae, or folliculitis.
r~ `': '' Acne vulgaris is a com~on disease which :~
a~flicts approximately 90~ o~ all teenagers~ and, .
not uncommonly, affects ~en and women in their 30 twenties or thirties or may persist in adults for - ~
many years. Acne vulgaris most commonly occurs on ~ :
oily areas Or th~ skin wi~h high sebac~ous gland ;::oncentra~ion~ The areas o~ high sebaceous gland :

-~8~2~9 `

concentration are the face, ears, retroauricular area~ (e. g. behind the ears), chest, back, and occasionally the neck anld upper arms.
Acneiform eruptions can occur wherever there is a pilosebaceous unit or sebaceou~ follicle which does include the entire urface of the skin.

The basic lesion in acne is the comedo commonly known as the blackhead. The comedo is created by retention of layers of dead skin known as keratin in the lining of the follicles. In additions to hyperkeratosis (which is thickening or retentative layering of keratin), there is an accumulation of sebum which is the lipid-laden product of the sebaceous gland. The cells of the sebaceous glands in which sebum oriqinates are the sebocytes. The combination of the keratin and the sebum produces a plugging of the mouth or opening of the follicular canal, and papules are formed hy inflammation around the comedones (plural of :
comedo). Depending upon the degree of inflammation, pustules, cysts, nodules, granulomatous reactions, scars, and keloids may develop. Most typical forms of mild acne :
vulgaris demonstrate the predominance of comedones with the occasional pu~tule~. Pustules and papules predominate in ~ore severe cases. The~e ~ ;
can heal with scar formation; that is, fibrosis o~
the lesions which are are deep and penetrating.
In moderately active ca~3es, larger cystic lesions can develop.
Acnla vulgaris can appear in many clinical varietie~. The mildest case m3nifests comedone~
on oily ~3kin and i~3 called acns comedo.

, WO92/1529s PCT~US92/01405 2 ~

Papular acne is another variety of acne which has ma~y inflammatory papules. This form of acne is co~mon in adolescent ~kin, but it c~n be seen in all ages. ~he papulzlr inflammatory form of acne can progress to an indurated, deeper, and destructive form known ZIS acne indurata. These lesions can produce seve~re scarring and can be quite deep seated and destructive~
Steroid acne vulgaris can occur when oral corticosteroids or topical steroids are used and occurs as inflammatory follicular papules. When oral corticosteroids are ingested, the inflammatory papules are usually sudden in appearance and can cover the chest, back, arm, and face. When topical corticosteroids are ussd ~or more than two weeks, a localized infla~matory papular response can develop which can proceed to a granulomatous chronic reaction known as steroid acne rosacea.
Premenstrual acne can occur in a large number of menstruating women as a papular a~d pustular acne vulgaris, approximately one week prior to menstruation. There is a body of evidence that implicates a surge in progesterone as the mediator of premenstrual acne.
Preadolescent acne is divided into neonatal, infantile, and childhood ~orms of acne. The neonatal ~orm is-limited to the first few weeks of life. It usually develops a couple of days after birth. It more commonly afflicts male~ and reveals transient faci~l papules and pustules which can clear spontaneou~ly in a few days or weeks. The stimulation of neonat~l s~baceous glands by circulating maternal progesterone appears to be the cause, , ' ~

wos2/1s2ss PCT/US92/01405 ?~'3~2~!3 _4_ If the acne persists beyond the first month of life, the acne is ~alled infantile acne and can extend into chil~hood, adolescen~e, and adult li~e. The childhood acne can result from a persistent infantile acne or can develop de novo after age two. This form of acne is uncommion, but it has more of a male predeliction. It is characterized by comedone~s commonly in groups, papules, pustules, and, rarely, cysts. This condition can extend from a few weeks to several years and can develop into pubertal acne. -Acne venenata is by definitio~ a comedonal or papular acne which occurs a*ter exposure to chlorinated hydrocarbons (chloracne), cutting oils, petroleum oil, coal tar, and pitches.
Acne cosmetica is a persistent low grade comedonal and/or papular and pustular acne that occurs usually on the chin and cheeks of adult women due to oil-based cosmetics, i. e. foundations, facial creams, and sunscreens.
Pomade acne is a type of acne cosmetica which appears to occur almost exclusively in black persons who apply grease and oil to scalp hair and the face as a grooming aid. Tha lesions are predominately comedonal acne and can develop into inflammatory acne papules, depending upon the chronicity of the pomade usie.
Acne detergican~i occurs as a type of comedon~l acne in patients who use oil-based cleansing soaps. Acne excoriee, also known as pickers acne, starts out as mild form of papular or comedonal acne which is manipulated or picked and causes further inflammation, more papules, and sometimes scars, pitting, and atrophy of the ~kin.
'".

. : . ... . .

WO92/15~99 PCT/~92/014~5 .
~5~ ~ ? wg Gram negative acn~, sometimes called gram negative folliculitis when it extends to the neck, arm8, legs, and truck, is a ~orm of an inflammatory papular, ~ollicular, and pus~ular response to gram negative organisms including Enterobacter, Klebsiella, Escherichia, Pr~teus, Serratia, and Pseudomonas. The most characteristic lesion on the face is superficial pustules, or papulo-pustules (which is a combination of a papule and pustule). The face can show diffuse erythema and inflammation surrounding these pustules and juicy papules or papulo-pustules. The gram negative acne is usually highly resi~tant and usually occurs in patients who have ~ad inflammatory papular acne for long periods or who have been treated with long term oral administration of antibiotics such as tetracycline, erythromycin, or minocycline or topical anti~iotics such as topical clindamycin or topical erythromycin. Subsequent to the oral administration of t~tracycline or erythromycin, oral adminiætration of amoxicillin, ampicillin, and trimethoprim-sulfomethoxazole has been shown to be effective in treating this disease. (Poli, F., Pr~st, C., Revuz, J., Gram-negative Polliculitis, Ann. Dermatol. Venereol., 115:797-800, 1988).
In another rPference, Marks, R. and Ellis, J., "Comparativ~ effectivenes~ of tetraoycline and a~picillin in rosacean, Lancet, 1971, vol. 2, pages 1049~1052, there is a disclosure that a~pi~lllin has been used orally for treatment o~
rosacea. ~ore ~pecifically, orally administered ampicil:Lin was compar~d with orally administered tetracycline in the trea~ment of xosac~.

Wog2/ls2ss PCT/US92/01405 2 ~ 8 ~

Furthermore, in the personal experience of one of the invenkors, in his capacity as a practicing dermatologist, in treating well over 200 patients, that oral ampicillin taken in the form of an oral capsule ]between 500 mg and 1 gm each day for one month greatly improves this condition. Before treatment with ampicillin orally, the patients app~ar to have inflammatory papules and pustules present, and treatment of this clinical subset of acne vulgaris appears to have good success with the oral ampicillin.
However, unwanted side effects often occur with the oral administration of ampicillin (and amoxicillin). For example, unwanted side effects from oral administration o~ten include diarrhea, cramping, and nausea. It would be desirable, therefore, to pro~ide a treatment with ampicillin (and amoxicillin) which does not result in the unwanted side effects stated above.
Acne rosacea is an inflammatory eruption that is chronic and occurs on the face, especially on the nose as well as the scalp and neck, in some instances. It is-manifested by erythema, pustules, papules, telangiectasia (which is dilation of superficial capillaxies), and hypertrophy of sebaceous glands. The middle portions of the face are most frequently involved.
The eyes and eyelid~ ar~ not uncommonly involved and can produce inflam~ation and infection of th~
conjunctiva, eyelids, and hypertrophy o~ the meibomian glands. Acne rQsacea is often called simply rosacea and is most common in middle aged wome~ and men. Rosacea can go on to form a granulamatous ro cea which is characterized ~y wo92/l~2ss PCT/US9~/01~05 ~t~

resistant inflammatory papules which when biopsied reveal noncaseating epithelial cell granulomas.
Pseudofolliculiti~ barbae is a predominantly male affliction which i~ characterized by inflammatory papules and pustules on the bearded area of the faca most commonly in black persons, but all racial groups can be affected. The mechani~m is thought to be an inflammatory respon~e to the end of hair (usually curly beard facial hair) into the skin causing a foreign body inflammatory response.
Folliculitis is an inflammatory reaction around the hair follicule which can be bacterial or nonbacterial in nature. Predominately, folliculitis is caused by gram positive organisms such as Staphylococcus and Streptococcus, and less frequently by gram negative bacteria discussed hereinabove with respect to gram negative ~olliculitis.
Perioral dermatitis is a common papular inflammatory eruption which is confined around the mouth. It most commonly afflicts women in their early twenties to middle thirties, but it can be seen in adolescents and more mature adults.
~iddradenitis suppurativa is a suppurative ~chronic) and cystic disease of apocrine gland regions of the skin, including the axillae, perineal region and groin.
There is a gen~tic tendency to acna, in particular acne congoblata which is a de~p cystic and simls forming type of acne. This condition is essentizllly a deep, aggressive form of cystic acne occurring in the apocrine gland regions. Topical administ:ration of clindamyrin ha~ bee~ used to treat thi5 form of cystic acne.

., ' ~:
, WO92/15299 PCT/US92~01405 2 g~

The etiology of acne vulgaris and related disorders as discussed above is not completely known in every detail. However, what is known is that acne, in general, isi caused by a plurality of factors. In general, there are four main factors that cause acne: genetics; hormonal activity:
bacteria; and the inflammatory response.
Genetics is a prominent component as it is well known that several members of the same family can be affected with moderate to severe scarring acne~ The inheritance by some is thought to be autosomal dominant, but this has not been definitively proven. Furthermore, on the molecular level, there has not yet been discovered 15 a gene or group of genes that are responsible for `
the various forms of acne vulgaris.
Another key factor in the development of acne is hormonal. In adolescence, for example, it is thought that androgens can interact with receptors on the sebaceous glands and cause stimulation of the ~ebaceous gland, to hypertrophy and hence form more sebaceous production of lipids and free fatty acids which distend the follicular canal. More specifically, there is evidence for increased peripheral metabolic conver~iion of the androgen testosterone to dihydrotestosterone at the level of the skin in acne patients. It is further hypothesized that receptors on the sebaceous gland for the active androgen dihydrotestosterone ¢an exhibit various degrees of ~ensitivity, and that a - height~nled sensitiYity re6ponse may be partially or entirely genetically predetermined.
Another causitive factor in acne is the prasence o~ bact~ria in the follicular canal.
Within the follicular canal are bacteria which are :~.

WO92/15299 PCT/US92/01~05 _9~
indigenous to the follic:ular lining. They are anaerobic, gram positive! organisms called Proprionibacterium acnes. It is interesting to note that they are present in abundance in pathologically affected sites. They are reduced during oral antimicrobial treatment, and their absence from nonhuman animal skin is striking especially since anim~ls do not exhibit acne vulgaris.
Yet a~other causitive factor in acne is the inflammatory response manifested in the skin.
More specifically, it is thought that Proprionibacterium acnes lives in symbiosis on the keratin lined fo~licular canal.
Proprionibacterium acnes ingests the sebum produced from the sebocytes of the sebaceous glands. This nascen~ sebum is largely lipid in composition and also contains DNA, RNA, proteins, and other cellular components that result from the breakdown of sebocytes themselv~s. The Proprionibacterium acnes which are highly lipophilic, ~eed on the nascent sebum. It has been shown that Proprionibacterium acnes are found only in sebaceous rich areas. If the nutrients increase due to an ~ctive and large sebaceous system, then colonization and high growth rates of Proprionibacterium acnes will form. It has been shown that the resident bacterial flora will produce biologically active molecule~ such as histamine, extracellular enzymes, and peptides which may be responsible for the chemotaxis oP the inflammatory infiltrate in acne vulgaris. Since the ~ollicular lining in the pilosebaceous unit is intact, it has been theorized that if ~olonization of Proprionibacterium acnes occurs in sufficent .. .. .. . : .. . : . ~ . . .. . . .

W092/15299 PCT/USg2/01405 ,,_.
2 ~ 8 ~ o-numbers, they could produce initiating antigenic molecules that promote the initiakion of inflammation. Proprionibacteri~ acnes can produce proteinases, lipase, and hyaluronate lyase all of which may serve as the catalysts or initiator~ of the inflammatory infiltrate which has been shown to be composed of neutrophils and lymphocytes.
A number of treatments are presently known for treating acne, some more successful than others. Some modes of treatment have been mentioned above. There are two modes of treatment, topical and systemic.
Aside from treatments mentioned above, some additional systemic treatments for acne that are presently employed are: oral tetracycline; oral erythromycin: minocycline; doxycycline; oral trimethoprim-sulfamethoxazole and isotretinoin (ACCUTANE TR).
Those that have been suggested in the past and that are no longer generally employed include:
antibacterial vaccines; estrogen therapy; dietary restrictions; and vitamin therapy (e. g. oral ingestion of vitamin A~.
Some of the topical treatments that are presently employed are: topical erythromycin, clindamycin, benzoyl peroxide, 2% sulfur, 3%
resorcinol, a tetracycline derivative -(meclocycline sulfosalicylate 1~), 2% salicylic acid, and tretinoin (Retin-A TR).
Topical treatments that have been suggested in the past and that are no longer gen~rally employed include: x ray treatment; electric sparks; vitamin therapy; kreatment with a plant :

WO92/1s~ss PCT/US9~/0~405 extract as descri~ed in TJ. S. ~a~e~ No.
4,803,06~.
More specifically w:ith respect to the topical use of certain specific antibiotics, a topical solution, ointment, and gel cont~ining erythr~mycin is used. Also u~ed is a topical solution, gel, and lotion containing clindamycin, and a cream containing meclocycline sulfosalicylate 1% (a tetracycline derivative).
Some o the undesirable side effects of orally administered antibiotics are abdominal cramps, black tongue, cough, diarrhea, fatigue, irritation of the mouth, loss of appetite, nausea, vomiting, fever, hearing loss, jaundice, rash, rectal and vaginial itching, and superin~ection.
It is noted that erythromycin is produced by the bacterium Streptomyces erytheus and that erythromycin has a chemical structure ~hat is substantially unique to erythromycin and its derivatives. The molecular weight oE erythromycin A is 733.92. The empirical formula or erythromycin A is C~H6~N0~3 having a 60.55~ carbon content, a 9.20% hydrogen content, a 1.91% `
nitrogen content, and a 28.34% oxygen content.
Clindamycin has a chemical structure indicated by its chemical name which is methyl 7-chloro-6,7,8-trideoxy-6-t[(1-methyl-4-propyl-2-pyrrolidinyl)carbonyl]amino]-l-thio-L--threo-alpha-D-galacto-octopyranoside. The molecular weight of clindamycin is 424.98. The empirical formula for clind~mycin is Cl~H~7ClN20sS having a 50.87% carbon content, a 7.83% hydrogen content, a 8.34% chlorine content, a 6.59~ nitrogen content, . ~ .
a 18.82% oxygen content, and a 7.54~ ~ulfur content.

.
~.i862~ 12-Other topical treatments for acne using antibiotics are descxibed in the following Great Britain patents: neomycin, G. B. Pat. No.
1,054,124; erythromycin, G. B. Pat. No. 1,587,428;
and erythromycin derivatives in conjunction with ~enzoyl peroxide, G. B. ]Pat. Nos. 2,088,717 and 2,090,135.
Still another topical treatment for acne, more specifically acne vulgaris, includes preparation of a hyaluronic acid derivative which is a bridged conjugate of hyaluronic acid (which is a linear polymer of N-acetyl glucosamine and glucuronic acid units) bonded to a bridging agent ;-(which is cyanogen bromide) which, in turn, is bonded to the amino-nitrogen atom o~ the aminopenicillin, ampicillin. Thus, with this hyaluronic acid derivative, the amino-nitrogen of the aminopenicillin is no longer in the form of a primary amino group. This hyaluronic acid d~rivative is disclosed in Great Britain Published Application 2,207,142.
The formulation disclosed in Great Britain Published Application 2,207,142 poses several significant problems. First, by reacting the bridging agent with the primary amino-nitrogen of the aminopenicillin, the effectiveness of the aminopenicillin may be severely reduced or even eliminated. More specifically, presently, all of the aminopenicillins that are approved for prescrib~ng in th~ practice of medicine in the United States include an amino-nitrogen which is in the form o~ a primary amino group (the nitrogen atom of the primary a~ino group being bonded to two hydrogen atoms~. Not one of these approved aminopen:icillins has its characteristic primary WO g2/15299 ~ /US92/01405 -13- ~ s'~?~
amino group ~odified so that it i5 no longer a primary amino group.
Another significant problem posed by the hyaluronic acid derivative in disclo~ed in Great ~ritain Published Application 2,207,142 is the fact that a very toxic bridging agent, cyanogen bromide, is disclosed. cyanogen br~mide can cause toxic effects similar to those of hydrogen cyanide. Hydrogen cyan~de may cause death from only a few minutes exposure to a concentration of approximat~ly 300 ppm. Lesser concentrations may cause headache, vertigo, nausea, and vomiting.
With these potentially serious toxic side effects of cyanogen bro~ide, it would be very risky to even employ the hyaluronic derivative disclosed in Great Britain Published Application 2,207,142.
More specifically, on page 5, lines 3-5 of Great Britain Published Application 2,207,142, there is a teaching that a stringy precipitate (of a bridged hyaluronic acid/cyanogen bromide/ampicillin conjugate) is washed several ~ :
times with absolute ethanol and dried in the air. :~
Then, as disclosed on page 5, lines 16-26, the bridged hyaluronic acid/cyanogen bromide/ampicillin conjugate, having been incorporated in a conventional medium, is applied .
directly to the skin to treat acne vulgaris. What is risky about using this bridged hyaluronic acid/cyanogen bromide/ampicillin conjugate is that 30 a quantity of unreacted cyanogen bromide remains ;:.
as a re~sidue the precipitate residue after several :~
rinses with absolute alcohol. Then, by applying some of this bridged hyaluronic acid/cyanog~n ~.
bromide/ampicillin conjugate directly to the skin of patients, one would then be applying a residue . .

WO9~/1529~ PCT/US92/01405 2 ~

of cyanogen bromide d~rectly to the skin of patients.
For the reasons ~tated above with respect to the bridged hyaluronic acid/cyanogen bromide/ampicillin conjugate disclosed in Great Britain Published Application 2,207,142, it is desirable to avoid using an ampicillin in which the characteristic amino^-nitrogen is not in the form of a primary amino group, and it is desirable to avoid using a material that may contain a toxic residue ~uch as the bridging agent cyanogen bromide.
Still other topical treatments for acne using antibacterials are described in the following U.
S. patents: an azole derivative in conjunction with benzoyl peroxide, U. S. Patent No. 4,446,145, incorporated herein by reference; and metronidazole in a sp~cial gel as described in U.
S. Patent No. 4,837,378, incorporated herein by reference.

Disclosure of Invention Accordingly, it is an object of the invention to provide a new topical treatment for acne and acneiform dermal disord~rs.
Another object of the invention is to provide a new topical treatment for acne which effectively adds to the armamentarium o~ physicians, and in particular dermatologists, to treat heretofore resistant forms o~ acne for which there was no 30 safe, mi~i~al side effect, and effective traatment . -available.
Another object o~ ~he invention is to provide a new topical treatment for acne which will avoid the unde~irable side effects of the currently WO92J15299 PCT/~S92/01405 f 2 ,! 1~ ~ 2 ~ ~
available oral antibiotics for the systemic treatment of acne and acneiform dermal disorders, such as diarrhea, abdominal cramping, nau~ea, vomiting, drug eruptions, photosensitvity, blood 5 dyscrasia~ ~e. g. depres~ion of white blood cell count and red blood cell count), drug induced hepatitis (elevation of liver functions), and teratogenicity, to name a ~ew. Another object o~ the invention is to provide a topical treatment for acne which uses an aminopenicillin whose characteristic amino group is in the form of a primary amino group.
Still another object of the invention is to provide a topical treatment for acne which uses an antibiotic that does not have the risk of bearing a toxic residu~ of a toxic bridging agent.
These and other objects are achieved by employing the principles of the invention wherein ampicillin, amoxicillin, ~nother aminopenicillin, or other penicillin-like derivativ~ is mixed with a carrier and applied topically to the skin of a patient suffering from acne and other acnei~orm dermal disorders. In accordance with the -invention described herein, the term aminopenicillin i5 understood to be an aminopenicillin whose characteristic amino group i5 in the form of a primary amino group. - `
Further in accoxdance with the invention, a cephalosporin or cephalosporin derivativ~ is mixed with a carrier and applied topically to the skin of a patient suffering from acne and other acneiform dermal disordar~. Suitable cephalosporins include ce~adroxil, cefazolin, cephalexin 9 cephalothin, cephapirin, cephradine, 35 cefaclor, ~efamandole, cefonicid, ceforanide, -.

:

. .
, :. .

Wog2/1529s PCT/US92/01405 2~ 9 -16-cefotetan (a cephamycin), cefoxitin (a cephamycin), cefuroxime, the l-acetyloxy ethyl estPr of cefuroxime (cefuroxime axetil), cefoperazone, cefotaxime, cePtazidime, ceftin, ceftizoxime, ceftriaxone, and moxalactam (a l-oxa-beta-lactam).
With the invention, ia variety of treatment regimens are contemplated.
In a first treatment rsgimen, topical compositions of the invention are used alone to treat the acne and acneiform dermal disorders. In this respect, the topical compositions of the invention can be used as a first line treatment for acne and acneiform dermal disorders.
In a second treat~ent regimen of the invention, an orally administer~d antibiotic and a topical composition of the invention are used in combination. There are a number of specific courses of treatment that can be carried out in this second treatment regimen. The oral antibiotic and the topical composition of th~
invention can be administered si~ultaneously from the beginning. Or, the oral admins~ation can be begun first, and the topical administration can then be begun. The oral administration can continue when the topical administration begins, or the oral administration can stop when the topical administration begins. Alternatively, the oral antibiotic and the topical composition of the invention can be administered sequentially.
~ith sequential administration, oral administration can tak~ place ~irst, and then topical a~ministration can be bequn.
In thi~ respect, after a conventional regi~en o~ ~reating a patient fox acne or acneiform dermal WO 92/15299 PCltUS92/014t)S

-17~ 9 disorders with an orally administered antibiotic, such as tetracycline, minocycline, doxycycline, erythromycin, wh~rein ~le patient develops resistance or no improvement, it is the teaching of this inv~ntion that an antibiotic selected from the group consisting of ampicillin, amoxicillin, another aminopenicillin, penicillin-like derivatives, and cephalosporin, and derivatives ~nd analogs thereof, is administered topically to the patient.
In a third treatment regimen of the invention, conventional topical medications and topical compositions of the invention can be administered simultaneously. The conventional topical medications which can be used include:
benzoyl peroxide and/or topical Retin-A (TM) (tretinoin) and/or any other topical agent currently used by physicians in the treatment of acne and acneiform dermal disorders. ;~
In a fourth treatment regimen of the invention, conventional oral medications, conventional topical medications, and topical compositions of the invention can be administered simultaneously. Still further in accordance with the invention, a treatment ~or ocular rosacea, blepharitis, bl~pharoconjunctivitis, giant papillary conjunctivitis, meibomian gland dysfunction, and infection by Acanthamoeba organi~ms is provided by topically administering to the eyelids and/or eyeballs a composition containing an ampicillin, amoxicillin, another aminopenicillin, other penicillin-like derivative, a cephalosporin, or derivative or analog ther~of, and a suitabl~ ophthalmological carrier selected from ~he group consisting of an aqueous liquid, an WO92/1529s PCTtUS92/01405 f arti~ a~2t~e'~r solution, a water soluble gel, an ointment base, petrolatum, a nonaqueous liquid base, a mineral oil base, a blend of mineral oil and petroleum, a suspension of solid particles in a liquid, and a suspension of an ion-exchange resin in water.
The a~picillin, amoxicillin, ano~her aminopenicillin, or other penicillin-like derivative, cephalosporin, or derivative or analog thereof can be administered alone or in conjunction with a nitroi~idazole, such as metronidazole, disclosed in U. S. Patent No.
4,957,918, incorporated herein by reference.
Furthermore, the ampicillin, amoxicillin, another aminopenicillin, or other penicillin-like derivative, cephalosporin, or derivative or analog thereo~ can be applied subsequent to treatment with the nitroimidazole compound.
Although the inventors are not bound by any theoretical explanation as to why the compositions and the methods of the invention are efficacious in treating acne and acneiform dermal disorders, presentation of certain theoxetical concepts may be of value.
For one thing, it is felt that the efficacy of the compositions and the methods of the invention is due in part to the antihiotic qualities of the compositions employed and the fact that a portion of the topically applied antibiotic is absorbed by the skin and enters the patient's bloodstream.
Another possible reason for the e~icacy o~
the compcsitions and the ~ethods of the inv~ntion is that the compositions of the invention exert an anti-inflammatory effect on the cells of ~he .

W092/15299 P~T/U~92/0~405 2~$~.lJ; 1~

sebaceous gland unit, thereby decreasing production of neutrophils and lymphocytes which contribute to inflammation. Still another possible reason for the efficacy of the topical compositions and methods of the invention is that the topically applied antibiotic is able to kill microorganisms that cannot be killed by an orally administered antibiotic. ~ore specifically, the topically applied antibiotic directly kills microorganisms in the sebaceous follicle that are shielded by a hydrophobic sebaceous film inside -the follicle from the effects of an antibiotic in the bloodstream. The bloodstream is essentially an aqueous medium, and the hydrophobic sebaceous film blocks the antibiotic in the bloodstream, from diffusing onto the microorganisms on the other side of the sebaceous film. However, the microorganism may produce products that are fat soluble and are able to cross through the sebaceous film and thereby irritate the cells lining the sebaceou~ follicle. Thus, the hydrophobic sebazeous film may allow passage, in one direction, of irritants from the microorganisms to the follicle walls, but the hydrophobic sebaceous film prevents passage of antibiotic in the bloodstream from di~fusing across the hydrophobic sebaceous film in the other direction to the microorganisms.

.
Mode for Carrvin~ Out ~he Invention -;
It is und~r~tcod herein that the term penicillin-like derivative is a compsu~d that contains the following chemical structural components: 6-~R-carbonyl)amino]-3,3-di-methyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic . . .... , . ,,, . . , .. . ... . .. , , . -, ~.. , ..... - . , . ., . . . . . . -WO92/15~99 PCT/US92/01405 acid, where R is a reactiv~ group substituted on the carbonyl carbon on tlle nitrogen atom of the 6-amino group.
Ampicillin is an am:inopenicillin. Generally, aminopenicillins are semisyn~hetic penicillin derivatives produced by acylation of 6-aminopenicillanic acid (6-APA). Aminopenicillins have a free amino group (a primary amino group) at the alpha-position on the penicillin nucleus which results in enhanced activity against gram-n~gative bacteria compared with natural penicillins and penicillinase-resistant penicillins. It is noted that ~or ampicillin there i5 a benzylamine group on the carbonyl carbon on the nitrogen atom of the 6-amino group. More specifically, for c~mpicillin, the 'IR'I in the formula for penicillin-like derivatives is a benzylamine group. Stated somewhat differently, for ampicillin specifically and for aminopenicillins generally, the R group includes a carbon atom bonded to the carbonyl-amino carbon atom, where a primary amino group is bonded to that carbon atom bonded to the carbonyl-amino carbon atom.
Other names for ampicillin include the terms ampicillin A, BRL 1341, P 50, Ay 6108, Adobacillin, Alpen, Amfip~n, Ampi-Bol, Bonapicillin, Grampenil, G~icitrina, Copharcilin, Nuvapen, Synpenin, Viccillin, Ultrabion, Ampipenin, Amplisom, Amimed, Ampy-Penyl, Totalciclina, Amipenix S, A~blosin, Ampicin, ~mplital, Austxapen, Binotal, Britacil, Doktacil:Lin, Marsilan, Pen-Bristol, Penbritin, Penbrock, Penicline, Pentrex, Pentrexyl, Ponecil, Polycillin, QI Damp, Toliocillin, Totacillin, and Totapen.
' -' . :

: : : - - -:: :: ~. . ~: ., .. ~.. . . ..... . . .. .. .. .. .. . . .

WO92/15299 PCT/US92/01~05 -21- 208~
Amoxicillin is ano~her aminopenicillin. It is also noted that for amoxicillin there a 4-hydroxybenzylamine group substituted on the carbonyl carbon on the n:Ltrogen atom of the 6-amino group. More specifically, for amoxicillinthe "R" in the formula for penicillin-like derivatives is a 4-hydro~benzylamine group.
Other names for amoxicillin include the terms amoxycillin, AMPC, Amolin, Amopenixin, Amoxi, Amoxipen, Anemolin, Aspenil! Bristamox, Delacillin, Efpenix, Ibiamox, Piramox, and sumox.

It is noted that both ampicillin and amoxicillin include "R" groups comprised of benzylamine and 4-hydroxybenzylamine groups, respectively. ~ore generically, in accordance with the invention, compositions containing penicillin-like derivatives where "R~ in the formula above is benzylamine and derivatives thereof. Stated somewhat differently, 20 compositions of the invention and the use thereof -~
include ampicillin and derivatives thereof and amoxicillin and derivatives thereof. Also, the -compositions of the invention and the use thereof include ampicillin, amoxicillin, or pharmaceutically acceptable salts or solvates thereof.
Suitable ~orm~ o~ ampicillin and amoxicillin can be selected from the group consisting of ampicillin; Empicillin, monohydrate; ampicilli~, potassi~Dm salt; ampicillin, ~esguihydrate;
ampicillin, trihydrate; ampicillin, anhydrous form; aDIpicillin, sodium salt; ampicillin, D(-)form, L(+)form, or DL-~orm; other suitable ampicillin derivatives; amoxicillin; amoxicillin .

, .
2~2~9 -22-trihydrate; amoxicillin hydrochloxide trihydrate;
amoxicillin beta-naphthalenesulfonate trihydrate;
and other suitable amoxicillin derivatives.
Other suitable aminopenicilli~s include bacampicillin and cyclacillin.
Suitable forms of ot:her penicillin-like derivatives or analogs ca,n be ~elected from the group consisting of azlocillin; acylureido penicillins related to azlocillin; carbenicillin;
carbenicillin, disodium salt; carbenicillin, indenyl; cloxacillin; dicloxacillin;
dicloxacillin, sodium salt; floxacillin;
isoxazolyl penicillins; hetacillin; methicillin;
methicillin, sodium; mezlocillin; mezlocillin, sodium salt; nafcillin oxacillin; oxacillin, sodium salt; penicillin BT; penicillin BT, procaine salt; penicillin G; penicillin G
benethamine; penicillin G benzathine; penicillin G
benzhydrylamine; penicillin G calcium; penicillin 20 G hydrabamine; penicillin G potassium; penicillin -G procaine; penicillin N; penicillin N, barium salt; penicillin O; penicillin O, 2-chloroprocaine salt monohydrate; penicillin O, potassium salt;
penicillin O, procaine salt; penicillin O, sodium salt; penicillin S potassium; penicillin V;
penicillin V, potas~ium salt; penicillin V, sodium salt; penicillin V, calcium salt; penicillin V
benzathine; penicillin V hydrabamine; and phenethicillin.
More speci~ic descriptions of some o~ the preferred penicillin-like derivatives or analogs are as ~ollows.
Ampicillin has a che~ical structure indicated by its chemical name which is 6-t(aminophenylacetyl)amino]-3,3-di-methyl-7-oxo-4-- ' . ' ~. :
~.

W~92/15299 PCT/US92/01~05 , . .
-23- 2 ~
thia-l-azabicyclo[3.2.o]heptane-2-aarboxylic acid.
The molecular weight of ampicillin is 349.42. The empirical formula for ampicillin is C16Hl~N304S
having a 55.0% carbon content, a 5.48% hydrogen content, a 12.02% nitrogen content, a 18.32 oxygen content, and a 9.18% sulfur content.
Amoxicillin has a c:hemical structure indicated by its chemical name which is 6-t[amino(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid. The molecular weight of amoxicillin is 365.41. The empirical formula for amoxi~illin is C,6H,~N305S having a 52.5g% carbon .
content, a 5.24% hydrogen content, a 11.50% -~
nitrogen content, a 21.89~ oxygen content, and a 8.77% sulfur content. :~
It is understood herein that the term cephalosporin derivative is a compound that contains the following chemical structural :
components: 3-[(acetyloxy)methyl]-7-[(R-)amino]~
8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene 2 carboxylic acid, whexe R is a reactive group ~.
substituted on the nitrogen of the 7-amino group.
It is noted that ~or cephalosporin C there is :~
25 a 5-amino-5-carboxy-1-oxopentyl group on the : -nitrogen of the 7-amino group. More specifically, for cephalosporin C, the "Rl' in the formula for cephalosporin derivativss is a 5-amino-5-carboxy-l-oxopentyl group.
It is noted ~hat for cephalothin there is a 2-thi~nyl5-a~ino-5-carboxy-1-oxopentyl group on the nit:rogen of the 7-amino group. More specifically, for cephalothin, the "R~l in the formula for cephalosporin derivati~es is a 5-amino-5--carboxy-1-oxopentyl group.

W092/15299 PCT/VS92/0]405 ?~ 4 Specific suitable cephalosporin derivatives are as follow~: cephalo~porin C; cephalospsrin C, sodium salt, dihydrate; cephalothin; cephalothin, sodium ~alt (al~o known as Averon-l, Ce~alotin, Cephation, Ceporacin, Cepovenin, Chephalotin, Coaxin, Keflin, Lospoven, Microtin, Synclotin, and Toricelocin); cephapirin sodium; cefadroxil;
cefazolin; cephalexin; c~!phalothin; cephapirin;
cephradine: cefaclor; cefamandole; cefonicid;
ceforanide; cefotetan ta cephamycin); cefoxitin ~a cephamycin); ceftin; cefuroxime; ~he l-acetyloxy ethyl ester of ce~uroxime (cefuroxime axetil);
cefoperazone; cefotaxime; ceftazidime;
ceftizoxime; ceftriaxone; and moxalactam (a 1 oxa- -beta-lactam~.
In addition, analogs of cephalosporin are also suitable for topical treatment of acne.
These cephalosporin analogs include:
cephalosporin Pl; cephamycins; cepharanthine; and cephradine~
Suitable carriers for the form of ampicillin, amoxicillin, or other penicillin-like derivative or cephalosporin or cephalosporin derivative or cephalosporin analog can be selected from the group consisting of: a petrolatum vehicle; a water soluble gel; a mineral oil base; a hlend of mineral oil and petrolatum; a suspension of an ion-exchange resin, e. g. Amberlite, in water; and other suitable pharmaceutical carriers, well known in the art.
By selection of a suitable vehicle, the ampicillin, amoxicillin, cephalosporin etc~ c~n be administered topically as a solution, a gel, a lotion, a cr~am, or an ointment.

wos2/ls2ss PCT/~S~2/01405 ( -25~ 2 ~
In addition to the ~orm of ampicillin, amoxicillin, another aminop~nicillin, or other penicillin like derivative or cephalosporin or cephalosporin derivative or cephalosporin analog that is employed as an active ingredient, another active ingredient, such as benzoyl peroxide can be used.
For a topical formulation, in addition to the form of ampicillin, amoxicillin, another ; .
aminopenicillin, or other penicillin-like derivative, ox cephalosporin or cephalosporin derivative or cephalosporin analog, the carrier, and possibly another active ingredient, the formulation can also include an agent which enhances penetration o~ an active ingredient through the skin. Exemplary a~ents which increase skin penetration are disclosed in the following U. .~
S. patents all o~ which are incorporated herein by -:
reference: U. S. Pate~t No. 4,537,776 (a binary 20 combination of N-(hydroxyethyl)pyrrolidone and a ..
cell-envelope disordering compound); U. S. Patent No. 4,130,667 (using a sugar ester in combination with a sulfoxide or pho~phine oxide); and U. S. :
Patent NoO 3,952,099 (using sucrose monooleate, .:
25 decyl methyl sulfoxide, and alcohol). -~
Other exemplary ~aterials that increase skin penetration are surfactants or wetting agents which include the following: polyoxyethylene sorbitan ~ono-oleoate (Polysorbate 80); sorbitan mono-oleate (Span 80): p-i~ooctyl polyoxyethylene-phensl polymer (Triton WR-1330); polyoxye~hylene sorbital- tri-ol~ate (T~een 85); dioctyl sodium sulphosuccinate; and sodium sarcosinate (Sarcosyl NL-97); and other pharmaceutically accepkable :~:
sur~actants.

W O 92/15299 P(~r/US~2/01405 , 2~ ~2 ~ -26-Although there i~ not a complete understanding of the det~iled theoretical mechanism upon which the efficacy of the topical dermatological compo~itions of the present invention which contain ampicillin, amoxicillin, another aminopenicillin, and other penicillin-like derivatives are founded, this lack of theoretical understanding in no way climinishes the benefits derived from employing the compositions and methods o~ the invention and in no way detracts from the utility of the invention as described herein.
Neverth~less, although not proven conclusively, it is felt that the topical use of ampicillin, amoxicillin, another aminopenicillin, and other penicillin-like derivatives or cephalosporin or cephalosporin derivative or cephalosporin analog of th~ invention help diminish the presence of Proprionibacterium acnes, and therefore diminish the e~fects on acne caused by the presence of Proprionibacterium acnes.
Furthermore, although not proven conclusively, it is felt that the topical use of ampicillin, amoxicillin, another aminopenicillin, and other penicillin-like derivatives or cephalo~porin or cephalosporin derivative or cephalosporin analog of the invention serv~s to inhibit the skin's in~lammatory response. More speci~ically, it is felt that by usiny the principles o~ the invention, thera is a decrease in chemotaxis of lymphocytes an~ neutrophils toward the pilosebaceous unit where in~lammation and follicular plugging, and sebaceous fluid are .
accumulating. It may be that the major effect of topical ampicillin and amoxicillin is this anti--27- ~J ~
chemotactic e~fect of neutrophils and lymphocytes.
A variety of suitable compositions of the invention are presented below in Examples 1-82.

Exam~le 1 A topical dermatological composition containing ampicillin is obtained as follows.
- Mix the following ingredi.ents in the amounts specified.
Innr~ient Weight Per Cent 10 Ethyl alcohol 42.0 Laureth-4 0.5 Isopropyl alcohol 6~0 Ampicillin 2.0 :;
Purified water 49.5 Citric acid can be used to adjust the pH to a ~:
desired level.
The composition in Example 1 contains approximately 2% ampicillin.
other suitable compositions can be made in accordance with Example 1 which include ampicillin in the following percent~ges: 0.5%, 1%, 3%, 4%, S%, and lO~.

Example 2 A topical dermatological composition 25 containing amoxicillin is obtained as follows. : .
Mix the following ingredients in the amounts -sp~cified. ;
Inqredient Weiqht Per Cent ~thyl alcohol ~2.0 30 Laureth-4 0.5 Isopropyl alcohol 6.0 Amoxicillin 2.O
Purified water 49,5 WO92/15299 PCT/US92/01~05 ~ '3 ~ if~

citric acid can be used to adju~t the pH to a desired level.
The composition in Example 2 contains approximately 2% amoxicillin.
Other suitable compositions can be made in accordance with Example 2 which include amoxicillin in the follo~wing percentages: O.5%, 1%, 3%, 4%, 5%, and lO~.

Example 3 A topical dermatological composition containing ampicillin is obtained as follows.
Mix the following ingredients in the amounts specified. i naredient Weiqht Per Cent l5 Ethyl alcohol 71.2 Propylene glycol 26.8 Ampicilli~ 2OO
The composition in Example 3 contains approximately 2~ ampicillin~

~o Examle 4 A topical dermatological composition containing amoxicillin is obtained as follows.
Mix the followin~ ingredients in the amounts specified, 25 .In~redien~ Weiaht Per Cent Ethyl alcohol 71.2 Propyl~ne glycol 26.8 :
~moxicillin 2.0 .
The composition in Example 4 contains 30 approxi~ately 2~ amoxicillin. : ~:
O~ler suitable co~positions can be made in accordarlc~ with Exampl~ 4 which include ::~
:~ ' j " ,:~. .

WO~2/15299 PCT/US92/01405 -29- ~ ~J(~S~ ~ ~
amoxicillin in the following percentages: 0.5%, 1%j 3%, 4%, 5%, and ~0%.

Other topical dermatological compositions are presented below.

Example 5 A formulation employing a water soluble gel as a carrier is obtained as ~ollows. More details of the gel carrier are described in U. S. Patent No. 4,837,378, incorporated herein by reference.
A 30 kilogram batch of a composition of the present invention containing ampicillin (as 0.75%
by weight) is prepared as follows. 180 grams of Carbopol 940 (TM) (0.6% by weight o~ the final weight of the composition) was dissolved in 16.5 liters of distilled water containing 15 grams of ethylenediaminetetraacetic acid (EDTA) disodium dihydrate. Suf~icient amount of 10 wt~ sodium hydroxid~ (NaOH) solution is added to bring the pH
value to about 5. This aqueous polymer solution 20 is called ~Part A". "Part B" is prepared by .-mixing 900 grams of propylene glycol (3% by weight of the final weight o~ the composition), 24 grams of methyl parabsn (0.08% by weight of the final weight of the composition), and 6.0 grams of propyl paraben (0.02% by weight o~ the final weight of the composition). The mixture is added to 225 g:rams of ampicillin dispersed in 11.4 liters O:e distilled water maintained at 50 degrees Centrigrad~. Part-~ A and B are then mixed ~horough:Ly and gelling of the composition results.
A cold a~ueou~ solution of NaOH is then used to adjust the final pH ~alue to approximately 5.25~ :
Distilled water is then add~d to give the desired , 3 i~ 2 ~

30 kilogram ~inal weight. The NaOH and water are thoroughly mixed into a viscou~ gel.
Other ~uitable compositions can be made in accordance with Example 5 which include ampicillin in the following percent~ges: 0.5%, 1%, 2%, 3%, 4%, 5%, and 10%.

ExamPl~ 6 A formulation employing a water soluble gel as a carrier is obtained as follows. ~ore details of the gel carrier are described in U. S. Patent No. 4,837,378, incorporated herein by reference.
A 30 kiloyram batch of a composition of the present invention containing amoxicillin (as 0.75%
by weight) is prepared as follows. 180 grams of Carbopol 940 (TM) (0.6% by weight of the final weight of the composition) was dissolved in 16.5 liters of distilled water containing 15 grams of ethylenediaminetetraacetic acid (EDTA) disodium dihydrate. Sufficient amount of 10 wt% sodium 20 hydroxide (NaOH) ~olution is added to bring the pH : .
value to about 5. This aqueous polymer solution ~:
is called "Part A". "Part B" is prepared by ::
~ixing 9OO grams o~ propylene glycol t3% by weight of the final weight of the composition), 24 grams - 25 of methyl paraben (0.08% by weight of the final ~eight of the composi~ion), and 6.0 grams of propyl para~en (0.02~ by weight of the final weight o~ the composition). The mixture i9 added to 225 gra~s of amoxicillin dispersed in 11.4 ~
30 liters of distilled water maintained at 50 degrees ~:
Centrigrade. Parts A and B are ~hen mixed thoroughly and gelling of the composition results.
A cold aqueous solution of NaO~ is then used to ::
adjust the ~inal pH value ~o approximately 5.25.

:' ..

-31- 2 5J 3 ~ rJ ^~ 9 Distilled water is then added to give the desired .-30 kilogram final weight. The NaOH and water are thoroughly mixed into a viscous gel.
Other suitable compc)sitions can be made in accordance with Example 6 which include amoxicillin in the following percentag~s: 0.5%, 1%, 2~, 3~, 4~, 5%, and 10~.

~xample 7 Another topical dermatological gel is obtained by mixing the following ingredients in suitable amounts: allantoin, carbomer 934P, methylparaben, polyethylene glycol 400, propylene glycol, sodium hydroxide, purified water and ampicillin.

Exam~e_8 Another topical dermatological gel is obtained by mixing the following ingredients in suitable amounts: allantoin, carbomer 934P, methylparaben, polyethylene glycol 400, propylene glycol, sodium hydroxide, purified water and amoxicillin.
' ' Exam~le 9 A dermatological lotion is obtained by mixing the following ingredients in the amounts s e~ified-P
In~redient Weiaht Per Cent Ethoxylated cetyl-stearyl alcohol 7 Cetyl alcohol 0.75 Isopropyl myristata 5 30 Butylat~d hydroxyanisole O.lO
Polyoxyl 40 stearate 0.25 - Water, deionized or distilled71.8 W092/1~299 PCT/US92/014~5 -2 sJ 8 ~t 2 5 ~ 3j_ Propylene glycol 3 Acetone 10 Dioctyl 60dium sulphosuccinate 0.1 Ampicillin 2 Other suitable compo~sitions can be made in accordance with Example 9 which include ampicillin in the following percentages: 0.5%, 1~, 3%, 4%, 5%, and 10%.

Example lO
A dermatological lotion is obtained by mixing the following ingredients in the amounts specified:
Inqredient Weiqht Per Cent Ethoxylated cetyl-stearyl alcohol 7 15 Cetyl alcohol 0.75 Isopropyl myristate 5 Butylated hydroxyanisole 0.10 Polyoxyl 40 stearate O.25 Wat~r, deionized or distilled71.8 .
20 Propylene glycol 3 Acetone 10 Dioctyl sodium sulphosuccinate0.1 . :
~moxicillin 2 Other suitable compositions can be made in accordance with Example 10 which include amoxicillin in the following percentages: 0.5%, 1%, 3~, 4%, 5%, and 10%.

ExamPle 11 ' .
A powdery composition is obtained as follows.
Mix the following ingredients in the amounts specified. ~ :
Inaredient Weiaht Per Cent Benzoyl peroxide (micronized)1 to 35 ~ . . :: : . '- ' . , . , ' ' , . ' ':
: ' ~ ';'. ' . ' : . ' '' : . . ' - . ' WO92/15299 PCT/U~92/0140~
2 ~ 9 Calcium phosphate 63 to 98.5 Ampicillin 0.5 to 5 ~2~plQ,12 A liquid composition is obtained as follows.
Mix the following ingredients in the amounts specified.
Inqredient Weiqht Per Cent Ampicillin 0,5 ~O 5 Benzoyl peroxide (micronized) l to 30 lO EthanolThe Balance to 100%

Example 13 A to~ical dermatological composition containing ampicillin is obtained as follows.
Mix the following ingredient~ in the amounts 15 specified.
InqredientWeiaht Per Cent Ethyl alcohol 44.0 Laureth-4 o.5 Isopropyl alcohol 6.0 20 Ampicillin 2.0 Purified water 49.5 Citric acid can be used to adjust the pH to a desired level.
The composition in Example 13 contains approximately 2~ ampicillin.
Other suitable compositions can be made in accordance with Example 13 which include :
ampicill:in in the following percentages: 0.5%, 1%, 3%, 4~, 5%, and 10%.

WO92/1529s PCT/US92/01405 ExamPle 14 A lotion composition is obtained as follows.
~ix the following ingredients in the amounts specified.
5 Inqredient Wei~ht Per Cent Ethoxylated cetyl-stearyl alcohol 7 Cetyl alcohol 0.75 Isopropyl myristate 5 Butylated hydroxyanis~le 0O10 Polyoxyl 40 stearate 0.25 Water, deionized or distilled 66.8 Propylene glycol 3 Benzoyl peroxide (micronized) 5 Acetone 10 15 Dioctyl sodium sulphosuccinate 0.1 Ampicillin 2 Other suitable compositions can be made i~
accordance with Example 14 which include ampicillin in the following percentages: 0.5~, 1%, 3~, 4~, 5%, and 10%.

ExamDle 15 A cream composition is obtained as follows.
Nix the following ingredients in ~he amounts specified.
25 Inaredient Weiqht Per Cent Ethoxylated cetyl-stearyl alcohol lS :`
Cetyl alcohol 1.25 Isopropyl myristate 5 Butylated hydroxyanisole .o.lo Polyoxyl 40 stearate 0.25 Water, deionized or distilled 57.30 `
Propylene glycol 3 Benzoyl peroxidP (micronized) 5 Acetone 10 ~,.
,.~
,. . ,: . , .
:.:..

' ~
.

W092/15299 P~T/US92/01405 2 ~ 2 ~ ~

Dioctyl sodium sulphosuccinate 0.1 Ampicillin 3 other suitable compositions can be made in accordance with Example 15 which include ampicillin in the following percentages: 0.5~, 1%, 2%, 4~, 5%, and 10%.

x~mDle 16 A gel composition is obtained as follows.
Mix the following ingredients in the amounts specified.
InaredientWeiqht Per Cent Water, deionized or distilled 51.65 Butylated hydroxyanisoleO.10 Benzoyl peroxide (micronized) 5 Dioctyl sodium sulphosuccinate Colloidal Bentonite 2.5 Carboxy vinyl polymer ~acid form) Ethyl alcohol 35 Diisopropanolamine 0.75 20 ~mpicillin 3 Other suitable compositions can be made in ..
accordance with Example 16 which include ampicillin in the following percentages: 0.5%, 1~, 2~, 4%, 5~, and 10%.

25 Exam~le 17 A suspension composition is obtained as follows. Mix the following ingredients in the amounts specified.
Inqredient Wei ht Per ~ent :~
30 Water, deionized or distilled54.97 Butylated hydroxyan~sole O.lO
~enzoyl peroxide (micronized) 5 Dioctyl sodium sulphosuccinate , WO92/15299 PCT/US92/014~5 2 ~

Colloidal Bentonite 1.5 Carboxy vinyl polymer (acid form) - O.25 Ethyl alcohol 35 Diisopropanolamine 0O18 5 Ampicillin 2 Other suitable compositions can be made in accordance with Example 17 which include ampicillin in the followi.ng percentages: 0.5%, 1%, 3%, 4%, 5~, and 10%.
- .
~_mple 18 A powdery composition is obtained as follows. :
Mix the following ingredients in the amounts specified.
InaredientWeiqht Per Cent 15 Benzoyl peroxide (micronized) 1 to 35 Calcium phosphate63 to 98.5 Amoxicillin 0.5 to 5 . . ,:
Example 1~ ~ :
A liquid composition is obtained as follows. -~ix the following ingredient~ in the amounts specified.
IngredientWeiaht Per Cent ~:
Amoxicillin 0.5 to 5 ::
Benzoyl peroxide (micronized) 1 to 30 25 EthanolThe Balance to 100~
: .
Example Z0 A lotion composition is obtained as follows.
Mix the following ingredients in the amounts ;'~
specifie~d. `
30 Inqredien~ Weiq~_Per Cent : -Ethoxylated cetyl stearyl alcohol7 -~
Cetyl alcohol 0.75 , - .
2 ~ ~ 6~;3 Isopropyl myristate 5 Butylated hydroxyanisole 0.l0 Polyoxyl 40 stearate 0.25 Water, deionized or dist:Llled 66.8 5 Propylene glycol 3 Benzoyl peroxide (micron:ized~ 5 Acetone l0 Dioctyl sodium sulphosucs:inate 0.l Amoxicillin 2 Other suitable compositions can be made in accordance with Exampla 20 which include amoxicillin in the following percentages: 0.5~, 1%, 3%, 4%, 5%, and 10%.

Exam~le 2l A cream composition is obtained as follows.
Mix the ~ollowing ingredients in the amounts specified.
,Inaredient Weiqht Per Cent Ethoxylated cetyl~stearyl alcohol15 20 Cetyl alcohol l.25 Isopropyl myristate 5 ~utylated hydroxyanisole O.l0 Polyoxyl 40 stearate 0.25 Water, deionized or distilled 57.30 25 Propylene glycol 3 Benzoyl peroxide (micronized) 5 Acetone l0 Dioctyl sodium sulphosucci~ate O.l ~moxicillin 3 O~ier suitable compositions can be made in accorda~ce with Example 2l which include amoxicillin in the ~ollowing percentages: 0.5~, l~, 2~, 4%, 5%, and lO~.

WO92/15299 PCT/US92/0~405 ~ ~c~
3~-Example 22 A gel composition iS obtained as ~ollows.
Mix the following ingred:ients in the amounts specifi~d.
5 InqredientWeiqht Per Cent Water, deionized or dist:illed 51.65 Butylated hydroxyanisole 0.10 Benzoyl peroxide (micronized) 5 Dioctyl sodium sulphosuccinate 10 Colloidal Bentonite 2.5 Carboxy vinyl polymer (acid form) Ethyl alcohol 35 Diisopropanolamine 0.75 Amoxicillin 3 Other suitable compositions can be made in accordance with Example 22 which include amoxicillin in the following percentages: 0.5%, 1%, 2%, 4%, 5%, and 10%.
:' Exam~le 23 A suspension composition is obtained as :-follows. Mix the following ingredients in the amounts specified.
Inc-IredientWeicrht Par Cent ;`;
Water, deionized or distilled 54.97 ` .
25 Butylated hydroxyanisole0.10 Benzoyl peroxide (micronized) 5 Dioctyl sodium sulphosuccinate - Colloidal Bent~nite 1.5 Car~oxy vinyl polymer (acid form) 0.25 30 Ethyl alcohol 35 Diisopropanola~ine 0.18 Amoxicillin Other suitable compocitions can be made in accordance with Example 23 which include . . . . . .... , . . ., . , .. ... , . . - . . . - ~, . ~ . . . . - ~ ., . , . . . -WO 92/lS299 PCT/VS92/OlqO5 -39- h'~ 3..?~ ~.n amoxicillin in the following percentages: O.5%
1% 3~, 4% 5% and 10%.

Example_~4 An oil-in-water emulsion containing ampicillin in ointment fo:rm is obtained as follows.
Part A is comprised of a 3.33% at~eous solution of ampicillin.
Part B is an ointment base comprised of:
Inqredient Weiaht Per Cent viscid paraffin 35 white vafieline 35 cetylstearyl alcohol 30 A mixture is obtained as follows. Mix 60 ml.
of Part A is ~ixed with 40 ml. o~ Part B to provide an oil-in-water emulsion in ointment form containing approximately 2~ ampicillin.
Other suitable compositions can be made in accordance with Example 24 which include ampicillin in the following percentages: 0.5%, 1%, 3%, 4%, 5%, and 10%.

Example 25 A mineral-oil-based ampicillin ointme~t is obtained as follows.
Part A is comprised of a 6.66~ aqueous solution of a~picillin.
Part B is an ointment base comprised o~:
~nqredient Parts glycerin 5 30 isopropy:L alcohol, 96% 5 mineral oil 60 ~-A mixture is obtained as follows. ~ix 30 ml.
of Part A with 70 ml. of Part B to provide a wo92/1529s ~CT/US92/01405 ~f~ 'i s3 ~-mineral-oil-based ointment containing approximately 2~ a~picillin.
Other suitable compositions can be mad~ in accordance with Example 25 which include ampicillin in the following percentages: 0.5%, 1~, 3~, 4%/ 5%~ and 10%.
~ rom the volumes in ~his Example, it is easy to convert to approximate weight percents. To mak~ the conversion, the known densities of water, isspropyl alcohol, glycerin, and mineral oil are employed~ The known density of water is approximately 1 g/ml. The known density of water is approximately O.78 g/ml. The known density o~
glycerin is approximately 1.25 g/ml. The known density of mineral oil is approximately 0.85 g/ml~
The weight of the 30 ml. of part A is approximately 30 grams, in view of the fact that part A is predominantly water. By taking 30 ml.
of part A, approximately 2 grams of antibiotic (30 g. X 6.66% and approximately 28 grams of water (30 g. X g3.34%) are obtained.
- By taking 70 ml. o~ part B, approximately 3.9 grams of isopropyl alcohol (5 ml. X 0.78g/ml.), approximately 6.25 grams o~ glycerin (5 ml. X
1.25g/ml.), and approximately 51 grams o~ ~i~eral oil (60 ml. X 0.85g/ml.) are obtained. The weight of 70 ml. o~ part B is approximately 61.15 grams (3.9 g. + 6.25 ~. + 51 g.).
Therefore, the total weight of parts A and B
co~bined is approximately 91.15 grams (30 g. -~61.15 g~).
In the combination o~ parts A and B, the weight percents of th~ individual carrier components are as approximately as follows:
35 water, 3:L%: isopropyl alcohol, 4.3%; glycerin, , W092/15299 PCT/US~2/01405 .

-41- 2.~3~ 7j~

6.86~; and mineral oil, 55.95%. It is noted that the combined weight percentages of the water-miscible alcohols is approximately 11.2% (4.3~ +
6.86%). It is also noted that the combined weight perentages of the water and water-miscible alcohols is approximately 42.2% (31% ~ 11.2%).

Example 26 A topical dermatolo~ical composition containing cephalospori~ C is obtained as follows.

Mix the ~ollowing ingredients in the amounts specified.
Inqredient Weiaht Per Cent Ethyl alcohol 44.O
Laureth-4 O.5 15 Isopropyl alcohol 6.0 Cephalosporin C lo O
Purified water balance Citric acid can be used to adjust the pH ~o a desired level.
The composition in Example 26 contains approximately 1~ Cephalosporin C.
other suitable compositions can be made in accordance with Example 26 which include Cephalosporin C in the following p~rcentages:
25 0.5~, 2%, 3%, 4%, 5%, and 10%.

Example 27 A topical dermatological composition containing cephalosporin ~ is obtained as follows.

Mix the following ingredients in ~he amounts specified.

.

WO 92tl5299 PCI /VS92/~1405 ,,, 2 ~8~2~9 -~2-Inqredient Weiqht Per Cent Ethyl alcohol 71.2 Propylene glycol 26.8 Cephalosporin C 2.0 s The composition in E'xample 27 contains approximately 2% cephalosiporin c.
Other topical dermatological compositions are presenited below.
: ' ' Exam~le 28 A formulation employing a water sol~ble gel as a carrier is obtained as follows. More details of the gel carrier are described in U. S. Patent No. 4,837,378, incorporated herein by reference.
A 30 kilogram batch of a composition of the present invention containing cephalosporin C (as 0.75% by weight) is prepared as ~ollows. 180 grams of Carbopol 940 (TM) (0.6% by weight of the final weight of the composition) was dissolved in 16.5 liters of distilled water containing 15 grams of ethylenediaminetetraacetic acid (EDTA) disodium dihydrate. Sufficient amount ofi 10 wt% sodium hydroxide (NaOH) solution is added to bring the pH
value to about 5. This aqueous polymer solution -is called "Part A". "Part B" is prepared by mixing 900 graims of propylene glycol (3% by weight of the final weight of the composition), 24 grams of methyl paraben (0.08% by weight of tha final . .
weight of the composition), and 6.0 grams of propyl paraben (0.02% by wei~ht of the final ~eight of the composition). The mixture is added to 225 grams of cephalosporin C dispersed in 11.4 liters o~ distilled water maintained at 50 degrees Centrigrade. Parts A and B are then mixed thoroughly and gelling o~ the composition results.

~ 7~J~.j 2 ~ ~

A cold aqueous solution o~ NaOH is then used to adjust the final pH value to approximately 5.25.
Distilled water is then adlded to give the desired 30 kilogram ~inal weight. The NaOH and wat~r are thoroughly mixed into a viscous gel.
Other suitable compositions can be made in accordance with Example 28 which include cephalosporin C in the following percentages:
0.5%, 1%, 2~, 3%, 4%, 5%, and lO~.

Example 29 Another topical dermatolcgical gel is obtained by mixing the following ingredients in suitable amounts: allantoin, carbomer 934P, methylparaben, polyethylene glycol 400, propylene glycol, sodium hydroxide, purified water and cephalosporin C.

Example 30 A dermatological lotion containing ampicillin : :
is obtained by mixing the following ingredients in :
20 the amounts specified. The ingredients in . ~
Container A is blended with the ingredients in : :
Container B. :-In Container A:
Inqredient Weiqht Per Cent of inqredient in - .
overall lotion Ethoxylated cetyl-stearyl alcohol 7.00 Cetyl alcohol 0.75 Isopropyl myristate 5.00 :
30 Butylated hydroxyani~ole O.lO
Polyoxyl 40 fitearate O.25 Water, deionizad or distilled70.80 Propylene glycol 3.00 Acetone 7.00 ..

2~2~i~ f~`
-~4-Dioctyl sodium sulfosuccinate O.lO

In Container B:
Inqredient Weight_Per cent of inaredient in S overall lotion Acetone 3.00 ampicillin 3.00 Citric acid can be used t~ adjust the pH to a desired level.
To obtain the lotion co~position in Example ~0, the composition in Container A is prepared.
This composition in Container A is stable for long periods o~ time.
Container B can contain only ampicillin for a 15 long period of time. Just prior to forming the :
complete lotion composition, 3 grams of acetone are added to Container B to dissolve the ampicillin. Then, the contents of Container A and Container B are combined to form the complete ,-lotion composition of the invention.
The composition in Example 30 contains approximately 3% ampicillin.
Other suitable compositions can be made in accordance with Example 30 which include ampicillin in the following percentages: 0.5%, 1%, 2%, 4%, 5%, and 10%.
':
Exam~le 31 A powdery composition is sbtained as follows.
Mix the ~ollowing ingredients in the amounts specified.
Ilsrl~L~1t Weight~Per Cent Benzoyl peroxide (micronized) l to 35 Calcium phosphate 63 to 98.5 ~(R,fi~9 Cephalo~porin c 0.5 to 5 ExamPle 32 A liquid composition i5 obtained as follows.
Mix the following ingredilsnts in the amounts speci~ied.
Inqredient Wei~ht Per cent Cephalosporin C 0.5 to 5 Benzoyl peroxide (micronized) l to 30 EthanolThe Balance to 100%

Example 33 A lotion composition is obtained as follows.
Mix the following ingredients in the amounts specified.
InqE~edientWeiqht Per Cent .
15 Ethoxylated cetyl-stearyl alcohol 7 Cetyl alcohol 0.75 Isopropyl myristate 5 Butylated hydroxyanisole 0~10 Polyoxyl 40 stearate o.25 20 Water, deionized or distilled 66.8 Propylene glycol 3 Benzoyl peroxide (micronized) 5 Acetone lO
Dioctyl sodium sulphosuccinate 0.1 25 Cephalosporin C 2 Other suitable compositions can be made in accordance with Example 33 which includa cephalosporin C in the following percentages: -0~5%, 1%, 3%, 4%, 5%, and 10%. . -Example 34 A cream composition i5 obtained as follows.
Mix the following ingredients in the amounts specified.
Ing~e~ient Weiqht Per Cent 5 Ethoxylated cetyl-stearyl alcohol 15 Cetyl alcohol 1.25 Isopropyl myristate 5 Butylated hydroxyanisole 0.10 ~olyoxyl 40 stearate 0.25 10 Water, deionized or distilled 57.30 ..
Propylene glycol 3 -Benzoyl peroxide (micronized) 5 Acetone 10 Dioctyl sodium sulphosuccinate 0.1 15 Cephalosporin C 3 Other suitable compositions can be made in accordance wi~h Example 34 which include cephalosporin C in the following percentages:
0.5~, 1%, 2%, 4%, 5%, and lO~.

Example 35 A gel composition is obtained as follows.
Mix the following ingredients in the amounts :.
~pecified.
In~redlent Wei~h ~Per Cent 25 Water, deionized or distilled 51.65 Butylated hydroxyanisole O.lO
Benzoyl peroxide (micronized) 5 Dioctyl sodium sulphosuccinate Col~oidal Bentonite 2.5 30 Carboxy ~inyl pslymer (acid form~ 1 Ethyl alc:ohol 35 Diisopropanolamine 0.75 CephalosE10rin C 3 WO92/15~99 PCT/US92/01405 U ~ ~

Other suitable compositions can be made in accordance with Example 35 which include cephalosporin C in the following percentages:
0.5~ , 2%, 4%, 5~, and 10%.

Example 6 A suspension composition is obtained as follows. Mix the following ingredients in the amounts specified.
InqredientWeiqht Per Cent lO Water, deionized or distilled 54.97 Butylated hydroxyanisoleO.lO
Benzoyl peroxide (micronized) 5 : .
Dioctyl sodium sulphosuccinate Colloidal Bentonite 1.5 15 Carboxy vinyl polymer (acid for~) O.25 Ethyl alcohol 35 Diisopropanolamine 0.18 Cephalosporin C 2 Other suitable compositions can be made in accordance with Example 36 which include cephalosporin C in the following percentages:
0.5%, 1%, 3~, 4%, 5~, and lG%.

Exam~le 37 A topical dermatological composition -: -~5 containing amoxicillin is obtained as follows. ~ :
Mix the following ingredients in the amounts :
specified.
InaxedientWeiqht Per Cent Ethyl alcohol . 4~.0 30 Laureth-4 ~5 Isopropyl alcohol 6.0 A~oxicillin 2.O
Purified water 4~,5 : :

WO92/lS299 PCT/US92/01~05 2 ~ ~J~

Citric acid can be used to adjust the pH to a desired levelc The composition in Example 37 contains approximately 2% amoxicillin.
Other suitable compositions can be made in accordance with Example 37 which include amoxicillin in the following percentaaes: 0.5%, l~, 3%, 4%, 5%, and l0~.
: '-~x~mple 38 A topical dermatological composition containing ceftin is obtained as follows.
Mix the following ingredients in the amounts specified.
InaredientWei~ht Per Cent 15 Ethyl alcohol 44.0 Laureth-4 0,5 Isopropyl alcohol 6.0 Ceftin l.0 Purified water balance Citric acid can be used to adjust the pH to a desired level.
The composition in Example 38 contains approximately 1% Ceftin.
Other suitable compositions can be made in accordance with Example 38 which include Ceftin in the following percentages: 0.5%, 2~, 3~, 4~, 5~, and 10%. Example 37 Example 39 A dermatological lotion is obtained by mixing the following ingredien~s in suitable amounts:
ampicillin (approximately 1% by weight); and a carri~r which includes isopropyl alcohol (approxlmately 80% by weight), purified water W092/l5~99 PCT/US92/01~05 -49~ 9 (approximately 9% by weight), and propylen~ glycol (approximately 10% by weight).

Example 40 A dermatological lotion is obtained by mixing the following ingredients in suitable amounts:
amoxicillin tapproximataly 1~ by weight); and a carrier which includes isDpropyl alcohol (approximately 80~ by weight), purified water (approximately 9% by weight), and propylene glycol (approximately 10% by weight).

Exam~le 41 A ~ermatological lotion is obtained by mixing the following ingredients in suitable amounts:
cephalosporin C (approximately 1% by weight); and a carrier which includes isopropyl alcohol (approximately 80% by weight), purified water (approximately 9~ by weight), and propylene glycol (approximately 10% by weight).

Exam~le 42 A topical dermatological composition containing cephalexin is obtained as follows.
Mix the follo~ing ingredients in the amounts specified.
InqredientWeiqht Per Cent 25 Ethyl alcohol 42.0 La~reth-4 0,5 lsopropyl alcohol 6.0 Cephalexin 1.0 Purified water balance Citric acid can be used to adjust the pH to a desired level.
:

W09Z/l5299 PCT/V~92/OlqO5 The composition in Example 42 contains approximately 1% CephalexinO
Other suitable compositions can be made in accordance with Example 42 whlch include Cephalexin in the following percentages: O.5~, 2%, 3%, 4%, 5%, and lO~.

Exa~al~_~3 A topical dermatological composition containing cephalexin is obtained as follows.
Mix the following ingredients in the amounts specified.
Inare~ Wei~ht Per Cent Ethyl alcohol 48.0 Laureth-4 0.5 15 Isopropyl alcohol 4.0 Propylene glycol 10.0 Cephalexin 1.0 Purified water balance Citric acid can be used to adjust the pH to a desired level.
The composition in Example 43 contains approximately l~i Cephalexin.
Other suitable compositions can be made in accordance with Example 43 which include Cephalexin in the following percentages: 0.5%, 2%, 3~, 4%, 5%, and 10%.

Example 44 A topical dermatological composition containing ~ephalexin is obtained as follows.
~ix the Eollowing ingredients in the amounts specif i~d .
I~G~L~It Wei~ht Per cent E~hyl al~:ohol 44.o : . .

W092/15299 PCT/US92/01~05 , .
51- 2~ ?~
Laureth-4 o.5 Isopropyl alcohol 6.0 Cephalexin 1.0 Purified water balance Citric acid can be used to adjust the pH to a desired level.
The composition in Example 44 contains approximately 1% Cephalexin.
other suitable compositions can be made in accordance with Example 44 which include Cephalexin in the following percentages: 0.5%, 2~, 3%, 4%, 5%, and 10%.

Example 45 A topical dermatological composition containing cephalexin is obtained as follows.
Mix the following ingredients in the amounts specified.
In~redient Weiqht Per Cent Ethyl alcohol 48.0 20 Laureth-4 5 Isopropyl alcohol 4.0 Propylene glycol 10.0 Cephalexin 1.0 Puri~ied water balance .
Citric acid can be used to adjust the p~ to a decired level. ~ :
The composition in Example 45 contains ~ :
approximately 1~ Cephalexin.
Other suitable compositions can be made in accordance with Example 45 which include Cephalexin in the following per~entages: 0.5%, : ~
2%, 3~, 4%, 5%, and 10%. :

wog2/~52sg PCT/US92/OlqOS

~ 2~ 52- ~-Exam~le 46 A topical dermatological composition containing cefaclor is obtained as follows.
Mix the following ingredients in the amounts specified.
In~redient Weight Per Cent Ethyl alcohol 44.0 .
Laureth-4 0.5 Isopropyl alcohol 6.0 10 Cefaclor 2.0 Purified water balance Citric acid can be usad to adjust the pH to a desired level.
The composition in Example 46 contains approximately 2% Cefaclor.
Other suitable compositions can be made in accordance with Example 46 which include Ce~aclor in the following percentages: 0.5~ , 3~, 4%, 5%, and 10~.

Example 47 A topical dermatological composition containing cefaclor is obtained as ~ollows.
Nix the following ingredients in the amounts specified. .:~
25 Inqredient . Weiqht Per Cent Ethyl alcohol 48.0 Laureth-4 0.
Isopropyl alcohol 4.0 :
Propylene glycol 10.0 30 Cefaclox 1.0 Purified water balance Cit:ric acid can be used to adjust the pH to a desired level.

W092/15299 P~T/US92/01405 I!
_53~ Ji~ 2 ~j ~
The composition in Example 47 contains approximately 1% Cefaclor.
other suitable compositions can be made in accordance with Exa~ple 47 which include Cefaclor in the following percentages: 0.5%, 2~, 3%, 4%, 5%, and 10%.

le 48 A ~opical dermatological composition containing cefuroxime is obtained as follows.
lo Mix the following ingredisnts in the amounts specified.
InqredientWeiqht Per Cent Ethyl alcohol 44.0 Laureth-4 o.5 15 Isopropyl alcohol 6.0 Cefuroxime 1.0 Purified water balance .
Citric acid can be used to adjust the pH to a desired level.
The composition in Example 48 contains approximately 1% Cefuroxi~e~ -Other suitable compositions can be made in accordance with Example 48 which include Cefuroxime in the following percentages: 0.5%, .
25 2%, 3%, 4%, 5%, and 10%o ExamPle 49 A topical de~matological composition containing ~efuroxime is obtained as follows.
Mix the following ingredients in the amounts specified.
Inaredie~~ Weiaht Per Cent Ethyl alcohol 48.0 Laureth-4 0.5 WO92/lS299 PCT/VS92/0140~
2 ~ ~ 54_ Isopropyl alcohol 4.0 Propylene glycol lO.O
Cefuroxime l.o Purified water b~lance Citric acid can be u~;ed to adjust the pH to a desired level.
The composition in Example 49 contains approximately 1% Cefuroxi~le.
Other suitable compoE;itions can be made in accordance with Exa~ple 4~ which include Cefuroxime in the following percentages: 0.5%, 2~, 3%, 4~, 5~, and 10%.

Example_50 A topical dermatological composition containing cefuroxime axetil is obtained as follows. It is noted that cefuroxime axetil is th l-acetyloxy ethyl ester of cefuroxime.
Mix the following ingredients in the amounts specified.
20 Inqredient Wei~ht Per Cent Ethyl aloohol 44.0 Laureth-4 0.5 Isopropyl alcohol 6.0 Cefuroxime axetil l.O
25 Purified water balance Citric acid can be used to adjust the pH to a desired level.
The co~position in Example 50 contains approximately 1% Ce~uroxime axetil.
Other ~uitable compositions can be made in accordance with Example 50 which include Cefuroxime axetil in the following percentages: .
0.5~, 2%, 3%, 4%, 5%, and 10%, :

WO92/lS299 PCT/Ui~92/01405 _55~ t~ ~ r~ .~? ~ .9 Example 51 A topical dermatological composition containing cefuroxime axet:il is obtained as follows.
Mix the following ingredif!nts in the amounts specified.
In~redient ~ei~ht Per Cent Ethyl alcohol 48.0 Laureth-4 o.5 lO Isopropyl alcohol 4.0 Propylene glycol 10.0 Cefuroxime axetil 1.0 - -Puri~ied water balance Citric acid can be used to adjust the pH to a desired level.
The composition in Example 51 contains approximately 1~ Cefuroxime axetil.
Other suitable compositions can be made in .
accordance with Example 51 which include Cefuroxime axetil in the following percentages:
0.5%, 2~, 3~, 4%, 5%, and 10%.
. . :...
~xample 52 A topical dermatological composition containing cefoperazone is obtained as follows.
Mix the following ingredients in the amounts specified.
Inqredient Weiaht Per Cent Ethyl alcohol 44.0 Laureth-4 0.5 30 Isopropyl alcohol 6.0 Cefoperazone 1.0 Purified water balance Citric acid can be used to adjust the pH to a desired level.

, ; , ~ , , ,. :~

W~92/15299 PCT/USs2/o1qO5 $~ 56-The composition in Example 52 contains approximately 1% Cefopera2:0ne.
Other suitable co~po~;itions can be made in accordance with Example 52 which include Cefoperazone in ~he following percentages: O.5%, 2%, 3%, 4%, 5~, and lO~.

Example 53 A topical dermatological composition containing cefoperazone is obtained as follows.
Mix the following ingredients in the amo~nts specified.
InaredientWeiqht Per Cent Ethyl alcohol 48.0 ~aureth-4 0.5 15 Isopropyl alcohol 4.0 Propylene glycol lO.O
Cefoperazone l.O
Purified water balanc~
Citric acid can be used to adjust the pH to a desired levelO
The composition in Example 53 contains approxi~ately 1% Cefoperazone.
Other suitable compositions can be made in accordance with Example 53 which include 25 Cefoperazone in the following perce~tages: 0.5%, :
2~, 3%, 4%, 5~, and lO~.

Example 54 A topical dermatological composition containing ampicillin is obtained as follows.
~ix the following ingredients in the amounts specified. ~:
Inqredient Wei~ht Per Cent Ethyl alcohol 4800 ~.

W092/~5299 PCT/US92/01405 -57~ 9 Laureth-4 0.5 Isopropyl alcohol 4.0 Propylene glycol 10.0 Ampicillin l.O
5 Purified water balance Citric acid can be u~3ed to adjust ~he pH to a desired level.
The composition in Example 54 contains approximately 1% Ampicillln.
Other suitable compositions can be made in accordance with Example 54 which include Ampicillin in the following percentages: 0.5~, 2%, 3%, 4%, 5%, and 10%.
., ExamDle 55 A topical dermatological composition containing amoxicillin is obtained as follows.
Mix the following ingredients in the amounts specified.
nqredient Weiqht Per Cent - 20 Ethyl alcohol 48.0 Laureth-4 0.5 Isopropyl alcohol 4.0 Propylene glycol lO.0 Amoxicillin 1.0 25 Purified water balance Citric acid can be used to adjust the pH to a desired level.
The composition in Exa~ple 55 contains approximately 1% ~moxicillin.
Other suitable compositions can be made in accordanc:e with Example 55 which include Amoxirillin in the ~ollowing percentages: 0.5%, 2%, 3%, 4%, 5%, and 10%.

"."" .

W09Z/15299 PCT/US~2/01405 ,_ ~ r3 l~ -58-E~le 56 A topical dermatological composition containing ~eftin is obtai.ned as follows.
Mix the following ingredients in the amounts specified.
Inqredien~ Wei~ht Per Cent Ethyl alcohol 44.0 Laureth-4 0.5 Isopropyl alcohol 6.0 lO Ceftin l.O
Purified water balance Citric acid can be used to adjust the pH to a desired level.
The composition in Example 56 contains -15 approximately 1% Ceftin.
Other ~uitable compositions can be made in accordance with Example 56 which include Ceftin in the following percentages: 0.5~, 2~, 3%, 4%, 5%, and 10%. -~

Example 57 A topical dermatological composition containing ceftin is obtained as follows.
Mix the following ingredients in the amounts specified.
25 Inqredient Wei~ht Per Cent Ethyl alcohol ~8.Q
Laureth-4 0.5 Isopropyl alcohol 4 9 0 Propylene glycol lO.O
30 Ceftin l.O
Purified watex balance Citric acid can be used to adjust the pH to a desired level.

WO92/1s2ss PCT/US92/01405 2 ~

The composition in Example 57 contains approximately 1% ~eftin.
Other suitabla composition~ can be made in accordance with Example 57 which include Ceftin in the following percentages: 0.5~, 2~, 3%, 4~, 5%, and lO~o For ~xamples 58-60, reference is made to U. . .
S. Patent No. 4,497,794, incorporated hQrein by reference, in which topical gel compositions containing the antibiotic erythromycin and benzoyl peroxide in a gel carrier are disclosed. A number of topical gel compositions of the present invention can be made by simply replacing the erythromycin disclosed in the gel compositions in said patent with ampicillin, amoxicillin, or cephalosporin C, respecti~ely, to provide topical :.
gel compositions of the invention which contain benzoyl peroxide and the respective antibiotic o~ .
the invention.
The gel carrier or vehicle for Examples 58-60, prior to addition of the benzoyl peroxide and prior to addition of the respective antibiotic of :
the invention and, as explained below, the :.
approximately 3 ml. of ethyl alcohol used to dissolve th~ respective antibiotic for addition to the gel carrier to which benzoyl peroxide has been added, is comprised of the following ingredients :
in the approximate amounts specified.
Inaredient in qel carrier Weiqht Percnt in the Final Mixture ~:
contai~ina antibiot~c, benzovl peroxide. and ael carrler Butylated hydroxyani~ole 0.10 35 Colloidal Bentonite 2O50 Carboxy ~vinyl polymer (acid form) 1.00 ',' ''',: .",'..',.'' ' .'` "'" ' '~ ,"' ""

WO92/15299 PCT/Ui~92/01405 2 ~ 60-Water, deionized or distilled 54.55 DiiQopropanolamine O.75 Ethyl alcohol 32.00 Dioctyl sodium sulfosuccinate 1.00 Example 5i3 A topical dermatological gel composition con~aining ampicillin antibiotic and benzoyl peroxide in a gel carrier or vehicle is obtained as follows~
10 To a first container add the benzoyl peroxide and the gel carrier or vehicle ingredients (approximately 5 grams of benzoyl peroxide and approximately 89 grams of gel carrier or vehicle~.
To a second container add powdered ampicillin (approximately 3 grams of ampicillin). The contents o~ the first container and the con~ents of the second container are stable for long periods of time. When the topical composition containing ampicillin and benzoyl peroxide of the invention is to be made, a quantity of 70~ ethyl alcohol (e. g. 3 ml.) is added to the second container to dissolve the ampicillin and form an alcoholic solution thereof. Then the alcoholic solution of ampicillin is added to the first contain~r, and all the ingredients are mixed to ~orm the topical gel composition of the invention which contains both ampicillin and benzoyl peroxideO This composition of the invention is stable, under refrigeration, for approximately 3 months.
Mor~ specifically, the blended topical gel composition o~ the invention with contains ampicillin and benzoyl peroxide in a gel carrier WO92/15299 PCT/~S92/01405 ,.
-61- ~ n ~ 9 or vehicle has the following components in the approximate amounts specified.
In~redient Weiqht Per cent ampicillin 3.0 5 Benzoyl peroxide 5.0 Gel c~rriex or vehicle 92.0 Citric acid can be u~;ed to adjust the pH to a desired level.
The composition in Example 58 contains approximately 3% ampicillin.
Other suitable compositions can be made in accordance with Example 58 which include ampicillin in the following percentages: 0. 5%, 1%, 2%, 4%, 5%, and 10%.

15 Exam~le 59 A topical dexmatological gel composition containing amoxicillin antibiotic and benzoyl peroxide in a gel carrier or vehicle is obtained as follows.
To a first container add the benzoyl peroxide and the gel carrier or vehicle ingredients ;~
(approximately 5 grams of benzoyl peroxide and approximately 89 grams of gel carrier or vehicle).
To a second container add powd~red amoxicillin (approximately 3 grams of amoxicillin). The contents o~ the first container and th~ contents of the second container are stable for long periods of time. When the topical composition contzining amoxicillin and benzoyl peroxide of the invention is to be ~ade, a guantity of 70% ethyl alcohol (e. g. 3 ml.) is added to the second container to dissolve the amoxicillin and form a~
alcoholic solution thereo~. Then the alcoholic solution of amoxicillin is added to the ~irst ~ .
.

WO9~/15299 PCT/US92/OlqOS

'~ '3 8 ~ 62-contai~er, and all the ingredients are mixed to form th~ topical gel composition of the invention which contains both amoxicillin and benzoyl peroxide. This compo~ition of the invention is stable, under refrigeration, ~or approximately 3 month6.
More specifically, the blended topical gel composition of the invention with contains amoxicillin and benzoyl peroxide in a gel carrier or vehicle has the following components in the approxi~ate amounts specified.
InqredientWeight Per Cent amoxicillin 3.0 Benzoyl peroxide 5.0 15 Gel carrier or vehicle92.0 Citric acid can be used to adjust the pH to a desired level.
The composition in Example 59 contains approximately 3% amoxicillin.
Other suitable compositions can he made in accordance with Exa~mple 59 which include amoxicillin in the ~ollowing percentages: 0.5%, 1%, 2%, 4%, 5~, and lO~.

Example 60 A topical dermatological gel composition containing cephalosporin C antibiotic and benzoyl peroxide in a gel carrier or vehicle is obtained ~s follows.
To a first container add the benzoyl p~roxide and the gel carrier or vehicle ingredients (approximately 5 gra~ o~ benzoyl peroxide and approximaltely 89 grams o~ gel carrier or vehicle~.
To a second container add powdered cephalosporin C
( approximately 3 gra~s of cephalosporin C). The W092/15299 PCT/US92/01qO5 -63- 2 ~ ~ ~ 2 ~ ~
contents o~ the first container and ~he contents o~ the second container are stable for long periods of time. When the~ topical composition containing cephalosporin C and benzoyl peroxide of the invention is to be made, a quantity of 70%
ethyl alcohol (e. g. 3 mlO) is added to the second container to dissolve the cephalosporin C and form an alcoholic solution thereof. Then the alcoholic solution of cephalosporin C is added to the first container, and all the ingxedients are mixed to form the topical gel composition of the invention which contains both cephalosporin C and benzoyl peroxide. This composition o~ the invention is stable, under refrigeration, for approximately 3 `
months.
Nore specifically, the blended topical gel composition of the invention with contains cephalosporin C and benzoyl peroxide in a gel carrier or vehicle has the following components in 20 the approximate amounts specified.
Inq~edient Wei~ht Per Cent cephalosporin C 3.0 Benzoyl peroxide 5.0 Gel carrier or vehicle 92.0 Citric acid can be used to adjust the pH to a desired level.
The composition in Example 60 contains approximately 3~ cephalosporin C~
other suitable compositions can be made in accordance with Example 60 which include cephalosporin C in the following percentages~
0.5%, 1%, ~%, 4%, ~%, and ~0%.

WO92/1~299 PCT/U~92/014~5 , ~_ ~ ~ ~ 8 ~ 2 . ~ 64 Exa~ple 61 A dermatological lotion containing a~oxicillin i5 obtained by ~ixing the following ingredients in the amount~ specified. The ingredients in Container A is blended with the ingredients in Container E~.
In Container A:
Inqredient Weiqht Per Cent o~ ingredient in overall lo~on Ethoxylated cetyl-stearyl alcohol 7.00 Cetyl alcohol 0.75 Isopropyl myristate 5.00 Butylated hydroxyanisole 0.10 15 Polyoxyl 40 stearate 0.25 Water, deionized or distilled70.80 Propylene glycol 3.00 Acetone 7 0O
Dioctyl sodium sulfosuccinate0.10 In Container B:
Inqr~ n~ Weia~t~ Per Cent of in~redient in overall lotion Acetone 3.00 25 amcxicillin 3.00 Citric acid can be used to adjust the pH to a desired level.
To obtain the lotion composition in Example 61, the composition in Container A is preparad. ~ -This composition in Container A is stable for long periods Or time.
Container B can contain only amoxicillin ~or a long period of ti~e. Just prior to forming the -~
complete ].otion composition, 3 grams of acetone are added to Container B to dissolve the WO 92/lS299 PCT/US92/01405 i --65- 2~2~
amoxicillin. Then, the con~ents of Container A
and Container B are com~ined to form the complete lo~ion composition of the invention.
The composition in Example 61 contains approximately 3% amoxicillin.
~ th~r suitable compositions can be made in accordance with Example 61 which include amoxicillin in the following percentages: 0.5%, 1%, 2%, 4%, 5~, and 10%.

10 Example 62 .
A dermatological lotion containing cephalosporin C is obtained by mixing the following ingredients in the amounts specified.
The ingredients in Container A is blended with the 15 ingredients in Container B.
In Container A: -InqredientWei~ht Per Cent of in~redient in overall lo~ion 20 Ethoxylated cetyl-stearyl alcohol 7.00 Cetyl alcohol 0.75 Isopropyl myristate 5.00 Butylated hydroxyanisole 0.10 .
Polyoxyl 40 stearate 0.25 25 Water, deionized or distilled 70O80 ~ .
Propylene glycol 3.00 ~
Acetone 7.00 .
Dioctyl sodium sul~osuccinate 0.10 In Container B:
30 Inqredient Wei~ht~ent of in~aredient in overall lotion ~cetone 3.00 cephalosporin C 3.00 .
' : , ' ~'.
.

WO9~tl~299 PCT/~S~/OlqOS
. , ~

2~2~ -66-Citric acid can be used to ~djust the pH to a desired level.
To obtain the lotion composition in Example 62, the composition in Container A is prepared.
This composition in Container A is stable for long periods of time.
Container B can contain only cephalosporin C
for a long period of time. Just prior to forming the complete lotion composition, 3 grams of acetone are added to Container B to dissolve the cephalo~porin C. Then, the contents of Container A and Container B are combined to form the complete lotion composition of the invention.
The composition in Example 62 contains approximately 3% cephalosporin C.
Other suitable compositions can ba made in accordance with Example 62 which include cephalosporin C in the ~ollowing percentages:
0.5%, 1%, 2%, 4%, 5%, and 10%. .

Example 63 A dermatological lotion is obtained by mixing the following ingredients in ~he amounts specified:
Ingre~ient Weight Per Cent 25 Ethoxylat~d cetyl-stearyl alcohol 7 Cetyl alcohol 0.75 Isostearyl neopentanoate 5 Butylated hydroxyanisole o.~o Polyoxyl 40 stearate 0.25 30 Water, deionized or distilled 71.8 - Propylene glycol ` 3 Aceto~e 10 Dioctyl sodium sulphosuccinate 0.1 Ampicillin 2 W ~ 92/15299 PC~r/US92/01405 i -67~
Other suitable compositions can be made in accordance with Example 63 Which include ampicillin in the following percentages: 0.5%, 1%, 3%, 4%, 5%, and 10%.

Exam~le Ç4 A dermatological lotion is obtained by mixing the f~llowing ingredients; in ~he amounts specified:
InqredientWeiaht Per Cent 10 Ethoxylated cetyl-stearyl alcohol 7 Cetyl alcohol 0.75 Decyl ol~ate 5 Butylated hydroxyanisole0.10 Polyoxyl 40 stearate 0.25 15 Water, deionized or distilled 71.8 Propylene glycol 3 Acetone 10 Dioctyl sodium sulphosuccinate 0.1 Ampicillin 2 Other suitable compositions can be made in accordance with Example 64 which include ampicillin in the following percentages: 0.5%, 1%, 3%, 4%, 5%, and 10%.

Exam~le 65 A lotion compo~ition is obtained as follows.
Mix the following ingredients in the amounts specified.
InqredientWei~ht Per Cent Ethoxylated cetyl-stearyl alcohol 7 30 Cetyl alcohol 0.75 Isostearyl neopentanoate5 Butylated hydroxyanisole0.10 Polyo~yl 40 stearats 0.25 W092/t5~99 PCT/US92/OlqO5 , ~_ 2~2~ -6~-Water, deionized or distilled66~8 Propylene glycol 3 Benzoyl peroxide (micronized)5 Acetone 10 5 Dioctyl sodium sulphosucc:inate 0.1 Ampicillin 2 Other suitable compositions can be made in accordance with Example 65 which include ampicillin in the following percentages: 0.5~, 1%, 3%, 4~, 5%, and 10%.

Example ~6 A lotion composition is obtained as follows~
Mix the following ingredients in the amounts specified.
15 _naredient Weiaht Per Cent Ethoxylated cetyl-stearyl alcohol 7 Cetyl alcohol 0.75 Decyl oleate 5 Butylated hydroxyanisole 0~10 Polyoxyl 40 stearate 0.25 ..
Water, deionized or distilled66.8 Propylene glycol 3 Benzoyl peroxide (micronized)5 Acetone 10 25 Dioctyl sodium sulphosuccinate 0.1 .
Ampicilli~ 2 Oth~r suitable compositions can be made in accordance with Example 66 which include ampicillin in the following percentages: 0.5%, . -1%, 3~, 4%, 5%, and 10%. ~ .

WO92/1~99 PCT/US92/01405 -69- 2 ~ 3 ~
Example 67 A dermatological lot:ion is obtained by mixing the following ingredients; in the amounts specified:
5 Inqredient Weiaht Per cent Ethoxylated cetyl-stearyl alcohol 7 Cetyl alcohol 0.75 Isostearyl neopentanoate5 Butylated hydroxyanisole0.10 10 Polyoxyl 40 stearat~ 0.25 Water, deionized or distilled 71.8 Propylene glycol 3 Acetone 10 Dioctyl sodium sulphosuccinate O.1 15 Amoxicillin 2 Other suitable compositions can be made in accordance with Example 67 which include amoxicillin in the following percentages: 0.5~, 1%, 3~, 4%, 5%, and 10%.

Example 68 A dermatological lotion is obtained by mixing the following ingredients in the amounts specified:
In~redient Wei~ht Per Cent 25 Ethoxylated cetyl-stearyl alcohol 7 Cetyl alcohol 0.75 Decyl oleate 5 Butylated hydro~yanisoleO.10 Polyoxyl 40 stearate 0.~5 30 Water, cleionized or distilled 71.8 Propylene glycol 3 Acetone lO
Dioctyl sodium sulphosuccinate O.1 Amoxicillin 2 '' ' '. ' .,, ., .. '' , ' '''' ' ," ' . '' .: ., . , .' '` .. . ` ' ~' ' ', ,', ' ' . ' ' ... ' '"

WO92/15299 PCT/US92/014~5 2~7J~ 70-Other ~uitable compositions can be made in acoordance with Example 68 which include amoxicillin in the following percentages: 0.5~, l~, 3%, 4%, 5%, and 10%.

Example 69 A cream composition is obtained as follows.
Mix the following ingredients in the amounts specified.
Inqredie~ Weiqht Per ent l0 Ethoxylated cetyl-stearyl alcohol 15 Cetyl alcohol l.25 Isostearyl neopentanoate 5 Butylated hydroxyanisole 0.l0 Polyoxyl 40 stearate0.25 15 Water, deionized or distilled 57.30 Propylene glycol 3 Benzoyl peroxide (micronized) 5 Acetone l0 Dioctyl sodium sulphosuccinate 0.l .: .
20 Ampicillin 3 other suitable compositions can be made in accordance with Example 69 which include ampicillin in the following percentages: 0.5%, 1%, 2~, 4%, 5%, and l0~. ' 25 E~ample 70 : -A cream composition is obtained as follows.
Mix the following ingredients in the amounts specified.
InaredientWeiuht Per Cent 30 Ethoxylat~d cetyl-stearyl alcohol 15 : .
Cetyl alcohol l.25 Decyl oleat~ 5 Butylated hydroxyanisole 0.l0 ';
.

. . . . ~ . , .. . ., .. ~ . .. . . . . .. . . . .

W092/15299 PCT/US92/01~05 -71- ~ n ~
Polyo~yl 40 stearate O.25 Water, deionized or distilled57.30 Propylene glycol 3 Benzoyl peroxide (micronized)5 5 Acetone lO
Dioctyl sodium sulphosuccinate O.l Ampicillin 3 Other suitable compositions can be made in accordance with Example 70 which include ampicillin in the following percentages: 0.5%, 1%, 2~, 4~, 5%, and 10%.

Exam~le 71 A lotion composition is obtained as follows.
Mix the following ingredients in the amounts 15 specified.
Inqredient Weight Per Cent Ethoxylated cetyl-stearyl alcohol 7 Cetyl alcohol 0.75 Isostearyl neopentanoate 5 20 Butylated hydroxyanisole O.lO
Polyoxyl 40 stearate 0.25 Water, deionized or distilled 66.8 Propylene glycol 3 Benzoyl peroxide (micronized) 5 25 Acetone lO
Dioctyl sodium sulphosuccinate O.l Amoxicillin 2 other suitable compositions can be made in accordance with ~xa~ple 7l which include amoxicillin in the following percentages: 0.5~, 1%, 3%, 4~, 5%, and lO~.

2~2r~

Example 72 A lotion composition is o~tained as follows.
Mix the following ingredients in the amounts specified.
5 Inqredient Weiqht Per Cent Ethoxylated cetyl-stearyl alcohol 7 Cetyl alcohol 0.75 Decyl oleate 5 Butylated hydroxyanisole 0.10 Polyoxyl 40 stearate 0.25 Water, deionized or distilled S6.8 Propylene glycol 3 Benzoyl peroxide (micronized) 5 Acetone 10 15 Dioctyl sodium sulphosuccinate 0.1 Amoxicillin 2 Other suitable compositions can be made in ~ .
accordance with Example 72 which include amoxicillin in the following percentages: 0.5~, .
1~, 3~, 4~, 5%, and 10%.

Example 73 ~ cream composition is obtained as follows.
Mix the following ingredients in the amounts specified. ~ `
25 Inqredient Weight Per Cent Ethoxylated cetyl-stearyl alcohol 15 Cetyl alcohol 1.25 Isostearyl neopentanoate 5 Butylated hydroxyanisole 0.10 Polyoxyl 40 stearate 0.25 Water, deionized or distilled s7.30 ~ ~:
Propylene glycol 3 `
. Benzoyl peroxide (~icronized) 5 Acetone . 10 Wo92/ls2ss PCT/US92/01405 _73_ 2 ~
Dioctyl sodium sulphosuccinate 0.1 Amoxicillin 3 Other suitable compositions can be made in accordance with Example 73 which include amoxicillin in ~he following percentages: 0.5%, 1%, 2%, 4%, 5%, and 10%.

~xample 7~
A cream composition is o~tained as follows.
Mix the following ingredients in the amounts specified.
Inqredient Weiaht Per Cent Ethoxylated cetyl-stearyl alcohol 15 Cetyl alcohol 1.25 Decyl oleat~ 5 15 Butylated hydroxyanisole 0.10 Polyoxyl 40 stearate 0.25 Water, deionized or distilled 57.30 Propylene glycol 3 Benzoyl peroxide (micronized) 5 20 Acetone 10 Dioctyl sodium sulphosuccinate 0.1 Amoxicillin ` 3 Other suitable compositions can be made in accordance with Example 74 which i~clude amoxicillin in the following percentages: 0.5%, 1%, 2%, 4%, 5%, and 10~.

Example 75 A lotion composition is obtained as follows.
Mix the following ingredients in the amounts specified.
Inqredient Weiqht Per Cent Ethoxylated cetyl-stearyl alcohol 7 Cetyl alcohol 0.75 WO 92/15299 PCI`/US92/0]405 , h~ ~ ~2r~ 7~-lsostearyl neopentanoate 5 Butylated hydroxyanisole0.10 Polyoxyl 40 stearate 0.25 water, deionized or distilled 66.8 5 Propylene glycol 3 Benzoyl peroxide ~micronized) 5 Acetone 10 Dioctyl sodium sulphosuccinate 0.1 Cephalosporin C 2 Other suitable compositions can be made in accordance with Example 75 which include cephalosporin C in the following percentages:
0.5%, 1~, 3%, 4%, 5%, and 10%.

xam~ 76 A lotion composition is obtained as follows.
Mix the following ingredients in the amounts speci~ied.
Inqredlen~ Weia~t Per Cent Ethoxylated cetyl-stearyl alcohol 7 20 Cetyl alcohol 0.75 Decyl oleate 5 Butylated hydroxyanisole 0.10 Polyoxyl 40 stearate 0.25 Water, deionized or distilled 66.8 25 Propylene glycol 3 Benzoyl peroxide ~micronized) 5 Acetone - 10 Dioctyl sodium sulphosuccin~te 0.1 Cephalosporin C 2 Other suitable compositions can be made in accordance with Example 76 which include cephalosporin C in the following percentages~
0.5%, 1%, 3%, 4%, 5%, and 10%.

, .. .
2 ~3 3 .~ ~ ~ {~
~75-ExamPle 77 A cream composition is obtained as follows.
~ix the following ingred:ients in the amounts specified.
5 Inqredient Wei~h~_Per_Cent Ethoxylated cetyl-steary:L alcohol 15 Cetyl alcohol 1.25 Isostearyl neopentanoate 5 Butylated hydroxyani~ole 0.10 Polyoxyl 40 stearate 0.25 ~ater, deionized or distilled57.30 Propylene glycol 3 Benzoyl peroxide (micronized) 5 Ac~tone 10 15 Dioctyl sodium sulphosuccinate 0.1 Cephalosporin C 3 Other suitable compositions can be made in accordance with Example 77 which include cephalosporin C in the following percentages: .
0.5%, 1%, 2%, 4%, 5%, and 10%.

Exam~le 78 A cream composition is obtained as follows.
~ix the following ingredients in the amounts specified.
25 Inqredient Weiqht Per Cent Ethoxylated cetyl-stearyl alcohol 15 Cetyl alcohol lo 25 Decyl oleate 5 .
Butylated hydroxyanisole 0.10 30 Polyoxyl 40 stearate O.25 Wat~r, deionized or distilled 57.30 Propylene glycol 3 ~ -Benzoyl peroxid.e (micronized) 5 A~etone 10 , '.-.

wo~2/l529s PCT/U~92/OlqO5 2~2~r)'3~{~ -76-Dioctyl sodium sulphosuccinate O.l Cephalosporin C 3 Other suitable compositions can be made in accordance with Example 78 which include cephalosporin C in the following percentages:
0.5%, 1%, 2~, 4%, 5%, and 10%.

Example 79 An oil-in-water emulsion containing amoxicillin in ointment form is obtained as follows.
Part A is comprised of a 3.33% aqueous solution of amoxicillin.
Part B is an ointment base comprisad of:
In~redient Weight Per Cent 15 viscid paraffin 35 white vaseline 35 cetylstearyl alcohol 30 A mixture is obtained as follows. Mix 60 ml.
of Part A is mixed with 40 ml. of Part B to provide an oil-in-water emulsion in ointment form containing approximately 2% amoxicillin.
Other suita~le compositions can be made in accordance with Example 79 which include amoxicillin in the following percentages: 0.5%, 1~, 3%, 4%, 5%, and 10~. -Exam~le 80 A mineral-oil-based amoxicillin ointment is obtained as follows.
Part A is comprised of a 6.66% agueous solution of amoxicillin.
Pa~: B is an ointment base comprised ofo 3 InqFedient Parts glycerln 5 - ~:

~: -. '.
,:, ' ' ' ~77~ ~ r~
isopropyl alcohol, 96% . 5 mineral oil 60 A mixture is obtained as follows. Mix 30 ml.
of Part A with 70 ml. of Part B to provide a mineral-oil-based ointment containing approximately 2% amoxicillin.
Other suitable compositions can be made in accordance with Example 80 which include amoxicillin in the following percentages: 0.5%, 1, 3%, 4%, 5%, and 10%. . .

Exam~le 81 An oil-in-water emulsion containing cephalosporin C in ointment form is obtained as follows.
Part A is comprised of a 3.33~ aqueous solution of cephalosporin C.
Part B is an ointment base compris~d of:
IngLredient Weiqht Per Cent viscid paraffin 35 .
20 white vaseline 35 cetylstearyl alcohol 30 :
A mixture is obtained as follows. Mix 60 ml.
of Part A is mixed with 40 ml. of Part B to provide an oil-in-water emulsion in ointment form containing approximately 2% cephalosporin C.
Other suitable compositions can be made in accordance with Example 81 which include cephalosporin C in the following percentages:
0.5~, 1%, 3%, 4%, 5%, and 10%.

ExamPle 82 A mineral-oil-based cephalosporin C ointment is obtai.ned as ~ollows.
.

.

Part A is comprised o~ a 6.66% aqueous solution o~ cephalosporin C
Part B is an ointment base comprised of:
Inqredie~t Parts 5 glycerin 5 isopropyl alcohol, 96% 5 mineral oil 60 A mixture is obtainecl as follows. Mix 30 ml.
of Part A with 70 ml. of Paxt B to provide a mineral-oil-based ointment containing approximately 2% cephalosporin C.
Other suitable compositions can be made in accordance with Example 82 which include cephalosporin C in the following percentages:
0.5%, 1%, 3~, 4%, 5%, and 10%.
A number of patients having acne vulgaris have been success~ully treated with 2~ topical ampicillin, and the case histories are described as follows.
Patient number one is a male and began .
treatment at the age of sixteen for acne vulgaris. :
Over the course of one year, he had been treated with the following agents in the order specified:
first, retin-A and Benzamycin gel topically:
second, oral ampicillin in conjunction with topical erythromycin solution and topical retin-A
(it is noted that therapeutic doses of oral ampicillin gave the patient diarrhea); third, low dose oral ampicillin ~250 mgm per day) in conjunction with topical retin-A and topical clindamycin solution; fourth, retin-A and clindamycin solution alone without any oral medication. Then the severity of the patisnt's a~ne worsened ., ~ " ,, ; ,, ! . ... . . . '.. ' , ; ' , :: . : . ' ' WOg2/15299 PCT/US92/01~05 _79 ~rQ~ ~?.I~
Then, photos were t:aken of the patient's right and left facial cheeksO The physical exam revealed on the face 2+ papules on a scale of 0-3+
and 2+ pustules on a sc2l1e of 0-3+. It is noted that the scale used for describing the symptoms of acne herein is an adaptation of the scale described on page 611 oi- Bleicher~ P., Charles, J., and Sober, A., "~opical Metronidazole Therapy for Rosacea", Ar~h De~ma~Ql, 1987, vol. 123, pages 609-614.
At this point topical clindamycin was discontinued, and 2% ampicillin in a vehicle known as "Neutrogena Vehicle N (mild)" made by :
Neutrogena Dermatologics Division of Neutrogena Corporation, Lo~ Angeles Corporation, (which contains approximately: ethyl alcohol (41.5% by weight), Laureth (0.5~ by weight), isopropyl . .
alcohol (6.0% by weight), ampicillin (2.0% by weight), and purified water (50.0% by we~ght)) was prescribed topically, in accordance with the invention, along with retin-A. Approximately seven weeks later, the patient subjectively indicated that his condition was improving.
Al~o, at this time, a physical examination was conducted which revealed on the face 1+ papules and only one pustule on the left cheek (0.5+
pustules). This constituted a 50% `i~provem~nt over a period of sevsn weeks with the i~vention in contrast to negligible improvement with prior art treatments over the course of more than one year.
Photos were again taken.
The second patient is a femal~, and at the tims of first treatment was 12 years old. She had acne vulgaris which was treated with the following combinations o~ treatments over a two year period ` ~ -80-in the order specified: first, a combination o~
topical retin-A and Benzamycin gel; second, oral ampicillin in conjunction with retin-A, topical clindamycin solution, and 1:opical benzoyl peroxide; third, topical c]Lindamycin and topical retin-~ and a 2% salicylic acid wash. At this point her acne vulgaris flared and on physical examination ~f her face, she had 2+ comedones on a scale of 0-3+, 2+ pustules on a scale of 0-3+, and 2+ papules on a scale of 0-3+.
At this point, photos were taken of her right and left facial cheeks. Then, in accordance with the invention, she was placed on 2~ topical ampicillin (as described above in the treatment of the first patient) twice daily to her face, and she continued with topical retin-A and salicylic acid wash.
Seven weeks later she was examined. The patient indicated that her acne cleared within a two and one-half to three week period after commencing the treatment with topical ampicillin.
On physical examination, her face revealed 1+
comedones, 0.5+ papules, and O pustules. The visual impression was a dramatic clearing tapproximately 75% reduction) of her acne vulgaris. Again, photos were taken. With the composition and method G~ the invention, there was - a 75% improvement over a period o~ a mere seven week in contrast to prior art treatments over a period of two years which resulted in only a negligible improvement. Photos were again taken.
The third patient i8 a female first see~ by the inventor at age 28 for the treat~ent of acne vulgaris. Prior to seeing the inventor, o~er a period of 12 years, she was treated for acne - ,.:,:-~. -.

:

W~92/1SZ99 PCT/VS9t/01405 !

vulgaris. Several months prior to seeing the inventor, for her facial ;acne, she was treated with topical retin-A, Benzamycin gel, and oral Bactrim (an oral sulfa dnag whose generic name is trimethoprim-sulfamethoxazole).
When the inventor first saw the third patient, she had l+ comedones, l+ pustules, and l+
papules. The inventor prescribed oral ampicillin and continued the other topical medications. Upon physical examination two months later, she had 1+
papules and 0+ comedones. She was improved.
This patient was to start taking a birth control pill (Orthonovum, 1~35) for oral contraception. Due to the possible side e~fects of oral antibiotic decreasing the ef~ectiveness o~
the birth control pill, the inventor and the patient elected to stop the oral ampicillin. The patient was placed on topical benzoyl peroxide, topical clindamycin gel, and continued on topical retin-A. Benzamycin gel was discontinued.
This patient was seen two months later, and upon physical examination, the patient exhibited l+ comedones and 0.5+ papules. The patient was continued on the above-mentioned topical medications; however, the xetin-A strength was increased. The patient called the inventor approximately six weeks later to report that her acne vulgaris ~as flaring, and the inventor placed the patient on oral a~picillin; and the topical medications were also continued.
Thii~i patient was seen by the inventor one - month later anid was not~d, on physical examination, to have 2+ comedones and 2+ papules.
At this point, ~he retin-A was increased to 0.1%
cream. All other topical medications were also .. ... . . . . .. ... , ~ .. . . . . . . .

W092/15299 PCT/V~92/01405 2 ~ 8 ~ .~ 3 ~

continued. The oral ampicillin was reduced to just one week out o~ ~he ~nonth.
Six weeks later, upon phy~ical examination, this patient exhibited 2+ pustules, o.5~ papules, and 1+ comedones. The patient's acne was flaring.
Again, due to the potential risk of decreasing the e~fectiv~ness of her oral contraceptive, the inventor wanted to discontinue the oral ampicillin and start her on a composition of the invention, namely 2~ topical ampicillin (as described above in the treatment of the first patient). A photo was taken prior to treatment with the topical ampicillin.
Upon treatment with the 2% ampicillin o~ the invention, the topical clindamycin was discontinued. The topical retin A and benzoyl peroxide were continued at their same doses.
Approximately seven weeks later, the patient remarked that her condition had improved with the topical ampicillin. On physical examination, the patient had on her face, 0.5l pustules on the right cheek and O pustules on the left cheek, 0.5+
papules, and 0.5+ comedones. The patient was approximately 50% improved clinically over the last seven weeks. Due to the success of the topical ampicillin, the patient el~cted to continue topical ampicillin. The other topical medications (retin-A a~d benzoyl peroxide) were continu~d as well. Photos were again taken.
The fourth patient is a male and began treatment at age 12 for acne vulgaris. He wa~
first treated with topical clindamycin gel and b~nzoyl peroxide. His acne vulgaris worsened by age 14 and required oral ampi~illin 1 gram a day, ?`

W092/15299 PCT/US92/014~

t~

topical retin-A, and Benzamycin gel. The severity of the acne worsened so ~uch by age 15 that oral ACCUTANE was discussed. The parents did not want to continue oral antibiotics or have their son take ACCUTANE due to si~e effects.
Then, photos were taken of the patient's right and left facial cheek~. The physical exam revealed 2+ comedones, 1+ papules and 1+ pustules.
In accordance with the invention, the patient wa~
started on topical 2% ampîcillin (as describe~
above in the treatment of the first patient) twice daily to his face, and continued on retin-A cream.
Approximately, 3 months later the patient returned. The patient indicated that his acne improved within one month and cleared by two months time. The physical exam revealed l+
comedones, 1 papule on his right cheek, O+ papules on his left cheek (which is a scor~ of O.5+
papules), and O+ pustules. This constituted a 75%
i~provement over a period of twelve weeks with the invention in contrast to resistance to prior oral treatments over the course of three and one half years. Photos were again taken.
The fiPth patient is male and began treatment at age 12 ~or acne vulgais. He had been treated with oral antibiotics including oral erythromycin, oral minocycline, topical retin-A, and benzoyl WO92/1529~ PCT/US92/01~05 ~ 2 ~ 9 -84-peroxid~ lotion. He failed this treatment regimen due to severe acne Yulgaris which necessitated treatment with oral ACCUTANE for 20 weeks. Even during his course of ACCUTANE, which is reserved for severe acne unresponsive to oral antibiotics, he ishowed resistance and u;pon discontinuance of this oral agent he required oral ampicillin, and topical retin-A.
At age 14, 7 months off oral ACCUTANE the pati~nt's acne was worsening despite oral ampicillin 500 mg twice daily and topical retin-A
cream. Then photos were taken of his facial cheeks and forehead. On physical exa~ on his forehead and facial cheeks were 2+ papules, 1+
pustules, and 2+ comedones. He was taken off of his oral ampicillin and in accordance with the invention he was placed on 2% topical ampicillin (as described above in the treatment of the first patient) twice daily to his face, and he was continued on topical retin-A.
Approximately 12 weeks later the pati~nt ~-returned :Eor examination. The patient indicated that he il~proved ~ithin the ~irst few weeks of therapy but ~orgot to get a new 2% topical ampicillin each month and used the same original topical a~picillin for the entir~ 3 monkhs. On physical exam of his forehead and facial cheek~ he ' ~ .
' . ', ' .: . .. .. . .

WO 92/15299 PCT/V~92/01405 ~ ~ 2~fi2a9 had 2+ comedones, 1+ pustules on his right cheek, 0.5+ pustules on his left cheek, and 1~ papules.
His acne was approximately 20% improved. The patient was educated to re~ill his prescription on a monthly basis to achieve better efficacy. He was continued on his topical ampicillin and his topical retin-A was increased. Photo~ were taken for documentation of his forehead and facial cheeks.
The sixth patient is a female, and at the time of first treatment was 13 years old. She had acne vulgaris which was treated with topical retin-A, topical clindamycin, and oral ~`
minocyoline. Her acne worsened and necessitated a change from minocycline to oral ampi~illin 1 gram a day, topical clinda~ycin, and topical retin-~.
Her acne improved only minimally on oral ampicillin, and her mother was concerned about her continuing on high doses of oral ampicillin.
Photos were taken of the patient's face. At this point on physical exam her face revealed 2 comedones, l+ pustules, l+ inflammatory papules.
Then, in accordance with the invention, she was placed Oll Z% topical ampicillin (as described above in the treatment of the first patient) twice daily to her face and she continued her oral W092/15299 PCT/US92/0~05 2~2~ 86-ampicillin and disrontinued her topical clindamycin.
Approximately 7 weeks later ~he was examined.
The patient indicated that her acne started to clear within 2 weeks of commencing treatment with topical 2% ampicillin. On physical examination, her face revealed l+ comedones, 0+ pustules, right cheek 0+ papules, left cheek 0.5+ papules. She was approximately 75% cleared from her previous examination seven weeks prior. Photos were again taXen.
The patients in these studies were all told to re~ill their topical ampicillin solution every one month and to keep their medication refrigerated.
The table below (Table I) illustrates in su~mary form the six patients treated with the invention 2% topical ampicillin:

, ., ~ .... .

W0~2/15299 PCT/US92/01405 ( -87- ~ 2 ~ ~

~abla I Patients treat~d with tGpical ampicillin ____~_ Baseline exam Follo~ -up Time in ~eeks ~ set faee - start e~a~ - face bet~een baseline exam P t~one ~c Sox o~ ~cn~ Z~ tDp. c~picillin i~ top. ~pic~ n cnd Follc~ Up ox~
1 ~ 16 2~ pDpule~1~ popules 7 we~ks 2t pustulos ~.5~ pu~tul~s 2 F 12 2t p~pules0.51 pDpules 7 ~e~ks 2~ pustule~ 0~ pustults 2~ comcdbne~ 1~ co~edcnc~
3 F 16 0.5~ popules0.5~ pspu~es 7 ~eeks 2~ pustules 0.5~ pustules 1~ comedones û.5~ comedbnes 12 1~ popules0.5~ p~pules ' 12 ~eeks 1~ pustules 0~ pustules 2t co7ecbnes 1~ c ~ s ~ 12 2~ pDpUles2~ p~pules 12 ~ce~s 1~ pustulcs 1~ pustulcs Ri~ht cheek 0.5~ pustules Loft chcek 2~ com~dones 2~ comedbnc~
6 F 13 1~ popules 0~ popule5 Right cheek 7 ~ee~8 0.51 papuleq Left cheek 1~ pus~ules 0~ pu~tules 2I comcdcnes 1~ come~onos .
From the description of the treatment of the patients and the composition examples set forth h~reinabove, the weight percent of ethyl alcohol spans 35~ to 93.5%. More specifically, the weight percents of ethyl alcohol ara as ~ollows: 35.0%
in Example 17; 35~0% in Example 16i 41.5% for the treated Patients; 41.0% in Example 1; 44.0~ in Example 13; 48.0% in Example 54; 65% in Example - 12; 71.2% in Examp}e 3; and 98.5~ in Example 120 , i~ -88-Similarly, from the description of the treatment of the patients and the compsotiion example~ set forth hereina;bove, the weight percent of isopropyl alcohol spans 4~ to 80%. More specifically, the weight plercents of isopropyl alcohol are as follows: 4.0% in Example 54; 4.3%
in Example 25; 6~0% for the trsated Patients; 6.0 in Exaple 13; and 80.0~ in Example 39.
Similarly, from the description o~f the treatment of the patients and the composition examples set forth hereinabove, the weight parcent of propylene glycol spans 3% to 26.8%. More :-specifically, the weight percents of propylene glycol are ~s follows: 3.0% in Example 6; 3.0% in 15 Example 9; 3.0% in Example 30; lO.0% in Example 54; lO.0% in Example 39; and 26.8~ in Example 3. .
Similarly, from the description of the composition examples set ~orth hereinabove, the :~
weight percent of glycerin is 6.9% in Example 25.
It is well known that ethyl alcohol, -isopropyl alcohol, propylene ylycol, and glycerin are water-miscible alcohols that can be applied .
topically to the skin. ``
It i~s seen in Example 12, that the carrier .
25 ingredients for the antibiotic can be one water- .
miscible ~solvent (ethyl alcohol) without th~
presence of water. More generally, the lowest WO92~15299 ~CT/US92/01405 i -89- 2~2a9 weight percent for a wat~r-misci~le alcohol used in a carrier for the antibiotic is 3% as disclosied in Examples 6, 9 and 30 which disclose 3%
propylene glycol.
It is seen in Examp:Le 3 that the carrier ingredients for the antibiotic can be two water-miscibl~ solents (ethyl alcohol and propylene glycol) without the presence of water.
It is seen in Examples 1, 14, 25, 39 and 54 10 that the carrier ingredients for the antibiotic ~:
can be two or more water-miscible solvents in the presence of water. The highest weight percent for two or more water-miscible solvents in the presence of water as carriers for the antibiotic is 99.5% disclosed in Example 13.
Thus, the widest range for a water-miscible alcohol either alone, or in combination with another water-miscible alcohol or water, in weight percent, is 3% to 99.5%.
Similarly, from the description of the treatment of the patie~ts and the composition examples set ~oth hereinabov~, the s~ms of the wsight percents of the water-miscible alcohols (ethyl alcohol, i50propyl alcohol, propylene glycol, and glyc~rin) span 11.2% to 90%. ~ore specifically, the sum~ o~ the weight percents of the water-miscible alcohols are as follows: 11.2%

2~C~[3~ _ in Example 25; 47.5~ for the treated Patients;
50.0% in Exampl~ 13; 62.0'~ in Example 54; and 90.0% in Example 39.
Similarly, from the description of the treatment of the patients and the composition examples set forth hereinab~ve, the sums of the weight percents of the water-miscible alcohols (ethyl alcohol, isopropyl alcohol, propylene glycol, and glycerin) and water spans 42.4~ to 99.5%. More specifically, tha sums of the weight percents of *he water-miscible alcohols and water are as follows: 42.2% in Example 25; 73~8$ in Example 30; 74.8% in Example 9: 86.6% in Example :
16: 90.0% in Exa~ple 17: 97.5% for the treated Patients; 98.0~ in Example 6; 98.5~ in Example 54;
99.O~ in Example 39; and 99.5% in Example 13.
The foregoing description of the invention has been presented for purposes of illustration and description. It is not intended to be 2~ exhaustive or to li~it ~he invention to the pr~cise forms disclo~d. Obvious ~odifications or variations of the ~ethods and compositions of the invention are possible in light of the above teaching.q. The embodiments were chosen and described in ord~r to best illus~rate the principles of the invention and its practical ~:
application to thereby enable one of ordinary WO92/15299 PCT/~S92/0140~

skill in the art to best utilize the invention in various embodiments and with various modifications as are suited to the part:icular use contemplated.
It is intended that the scope of the invention be defined by the claims appended hereto.

Claims (39)

Claims

1. A method of treating a human being for acne and acneiform dermal disorders which comprises administering to the human being an amount of a composition consisting essentially of an antibiotic and a carrier, the composition applied topically directly to affected dermal tissues, the composition being effective to treat the acne and acneiform dermal disorders, wherein the antibiotic is selected from the group consisting of aminopenicillins and cephalosporins, and wherein the carrier includes at least one carrier ingredient selected from the group consisting of water and a water-miscible alcohol, wherein combined weight percents of said carrier ingredients is in a range spanning 3% to 99.5%.

2. The method described in claim 1 wherein the aminopenicillin is selected from the group consisting of ampicillin and amoxicillin, and derivatives and analogs thereof.

3. The method described in claim 1 wherein an aminopenicillin is selected from the group consisting of ampicillin and amoxicillin known by the following names: ampicillin; amoxicillin;
bacampicillin; cyclacillin; ampicillin A; BRL
1341: P 50; Ay 6108; Adobacillin: Alpen: Amfipen;

Ampi-Bol; Bonapicillin; Grampenil; Guicitrina;
Copharcilin; Nuvapen; Synpenin; Viccillin;
Ultrabion; Ampipenin; Amplisom; Amimed; Ampy-Penyl; Totalciclina; Amipenix S; Amblosin;
Ampicin; Amplital; Austrapen; Binotal; Britacil;
Doktacillin; Marsilan; Pen-Bristol; Penbritin;
Penbrock; Penicline; Pentrex; Pentrexyl; Ponecil;
Polycillin; QI Damp; Toliocillin; Totacillin;
Totapen; ampicillin, monohydrate; ampicillin, potassium salt; ampicillin, sesquihydrate;
ampicillin, trihydrate; ampicillin, anhydrous form; ampicillin, sodium salt; ampicillin, D(-)form, L(+)form, or DL-form; amoxycillin; AMPC;
Amolin; Amopenixin; Amoxi; Amoxipen; Anemolin;
Aspenil: Bristamox; Delacillin; Efpenix; Ibiamox;
Piramox; Sumox; amoxicillin; amoxicillin trihydrate; amoxicillin hydrochloride trihydrate;
and amoxicillin beta-naphthalenesulfonate trihydrate.

4. The method described in claim 1 wherein the cephalosporin antibiotic is selected from the group consisting of cephalosporin C; cephalosporin C, sodium salt, dihydrate; cephalothin;
cephalothin, sodium salt (also known as Averon-1, Cefalotin, Cephation, Ceporacin, Cepovenin, Chephalotin, Coaxin, Keflin, Lospoven, Microtin, Synclotin, and Toricelocin); cephapirin sodium;

cefadroxil; cefazolin; cephalexin; cephalothin;
cephapirin; cephradine; cefaclor; cefamandole;
cefonicid; ceforanide; cefotetan (a cephamycin);
cefoxitin (a cephamycin); cefuroxime;
cefoperazone: cefotaxime; ceftazidime: ceftin;
ceftizoxime; the 1-acetyloxy ethyl ester of cefuroxime (cefuroxime axetil); ceftriaxone; and moxalactam (a 1-oxa-beta-lactam).

5. The method described in claim 1 wherein the antibiotic is an ampicillin.

6. The method described in claim 1 wherein the antibiotic is an amoxicillin.

7. The method described in claim 1 wherein the antibiotic is a cephalosporin.

8. The method described in claim 1 wherein the antibiotic is present in a range of from 0.5 to 10% by weight of the composition.

9. The method described in claim 1 wherein the antibiotic is applied in a carrier which includes at least one carrier ingredient selected from the group consisting of water and a water-miscible alcohol, wherein combined weight percents of said carrier ingredients is in a range spanning 3% to 99.5%.

10. The method described in claim 1 wherein the antibiotic is applied in a water-miscible carrier including at least one water-miscible alcohol, wherein the weight percent of the at least one water-miscible alcohol is in a range spanning 11.2% to 90%.

11. The method described in claim 1 wherein the antibiotic is applied in a water-miscible carrier including at least two water-miscible alcohols, wherein the sum of the weight percents of the at least two water-miscible alcohols is in a range spanning 11.2% to 90%.

12. The method described in claim 1 wherein the antibiotic is present in an amount of 2% by weight and is applied in a carrier comprised of:

ethyl alcohol, 41.5% by weight, Laureth-4, 0.5% by weight, isopropyl alcohol, 6% by weight, and water, 50% by weight.

13. A method of treating a human being for acne and acneiform dermal disorders which comprises administering to the human being an amount of an antibiotic selected from the group consisting of ampicillin, amoxicillin, and cephalosporin, and derivatives and analogs thereof, applied directly to affected dermal tissues, effective to treat the acne and acneiform dermal disorders, wherein the antibiotic is applied in a carrier including at least one carrier ingredient selected from the group consisting of water and a water-miscible alcohol, wherein combined weight percents of said carrier ingredients is in a range spanning 3% to 99.5%.

14. The method described in claim 13 wherein the carrier is present in a weight percent range spanning 42.2% to 99.5%.

15. The method described in claim 13 wherein the carrier is present in a weight percent range spanning 42.2% to 99.5% and includes water, ethyl alcohol, and isopropyl alcohol.

16. The method described in claim 13 wherein the carrier includes ethyl alcohol in a weight percent range spanning 35% to 98.5%.

17. The method described in claim 13 wherein the carrier includes isopropyl alcohol in a weight percent range spanning 4% to 80%.

18. The method described in claim 13 wherein the carrier includes propylene glycol in a weight percent range spanning 3% to 26.8%.

19. The method described in claim 13 wherein the carrier includes water in a weight percent range spanning 9% to 95%.

20. The method described in claim 13 wherein the carrier includes at least one water-miscible alcohol in a weight percent range spanning 11.2%
to 90%.

21. The method described in claim 13 wherein the carrier includes water, at least one water-miscible alcohol, and mineral oil.

22. The method described in claim 13 wherein the carrier is present in a weight percent range spanning 42.2% to 99.5% and includes water in a weight percent range spanning 9% to 95%, ethyl alcohol in a weight percent range spanning 35% to 98.5%, and isopropyl alcohol in a weight percent range spanning 4% to 80%.

23. A method of treating a human being for acne and acneiform dermal disorders which comprises the step of;
topically administering to affected dermal areas of the human being an amount of a composition comprised of benzoyl peroxide and an antibiotic selected from the group consisting of aminopenicillins and cephalosporin and derivatives and analogs thereof, effective to treat the acne and acneiform dermal disorders, wherein the composition is applied in a carrier which includes at least one carrier ingredient selected from the group consisting of water and a water-miscible alcohol, wherein combined weight percents of said carrier ingredients is in a range spanning 3% to 99.5%.

24. The method described in claim 23 wherein:
the antibiotic is present in a range spanning 0.5% to 10% by weight; and the benzoyl peroxide is present in a range spanning 1% to 30% by weight.

25. The method described in claim 23 wherein the antibiotic is an aminopenicillin.

26. The method described in claim 23 wherein the aminopenicillin antibiotic is selected from the group consisting of ampicillin and amoxicillin.

27. The method described in claim 23 wherein the aminopenicillin antibiotic is an ampicillin.

28. The method described in claim 23 wherein the antibiotic is a cephalosporin.

29. A method of treating a human being for acne and acneiform dermal disorders which comprises administering to the human being an amount of a composition comprising an antibiotic, benzoyl peroxide, and a carrier, the composition applied topically directly to affected dermal tissues, the composition being effective to treat the acne and acneiform dermal disorders, wherein the antibiotic is selected from the group consisting of aminopenicillins and cephalosporins, and wherein the carrier includes at least one carrier ingredient selected from the group consisting of water and a water-miscible alcohol, wherein combined weight percents of said carrier ingredients is in a range spanning 3% to 99.5%.

30. The method described in claim 29 wherein:
the antibiotic is present in an amount of 3%
by weight;
the benzoyl peroxide is present in an amount of 5% by weight; and the carrier is a gel vehicle present in an amount of 92% by weight.

31. The method described in claim 30 wherein the gel vehicle is comprised as follows:

.

32. A pharmaceutical composition, comprising:
an amount of an antibiotic selected from the group consisting of an aminopenicillin and a cephalosporin and derivatives and analogs thereof, effective to treat acne and acneiform dermal disorders in a human patient; and a carrier for said antibiotic, said carrier suitable for topical application to dermal tissues, and said carrier is present in a weight percent range spanning 42.2% to 99.5% and includes water in a weight percent range spanning 9% to 95%, ethyl alcohol in a weight percent range spanning 35% to 98.5%, and isopropyl alcohol in a weight percent range spanning 4% to 80%.

33. The composition described in claim 32 wherein said antibiotic is present in an amount of 2% by weight and is present in a carrier comprised of:
ethyl alcohol, 41.5% by weight, Laureth-4, 0.5% by weight, isopropyl alcohol, 6% by weight, and water, 50% by weight.

34. The composition described in claim 32 wherein said antibiotic is ampicillin.

35. A pharmaceutical composition, comprising:
an amount of an antibiotic selected from the group consisting of an aminopenicillin and a cephalosporin and derivatives and analogs thereof, effective to treat acne and acneiform dermal disorders in a human patient;
an amount of a conventionally topically applied anti-acne medication selected from the group consisting of benzoyl peroxide, sulfur, resorcinol, salicylic acid, and tretinoin; and a carrier for said antibiotic and said conventionally topically applied medication, said carrier suitable for topical application to dermal tissues, and said carrier being present in a weight percent range spanning 42.2% to 99.5% and and said carrier including water in a weight percent range spanning 9% to 95%, ethyl alcohol in a weight percent range spanning 35% to 98.5%, and isopropyl alcohol in a weight percent range spanning 4% to 80%.

36. The composition described in claim 35 wherein said conventionally topically applied anti-acne medication is benzoyl peroxide.

37. A pharmaceutical composition, comprising:
an amount of an antibiotic selected from the group consisting of aminopenicillins and cephalosporins, and derivatives and analogs thereof, benzoyl peroxide, and a carrier, applied directly to affected dermal tissues, effective to treat the acne and acneiform dermal disorders, wherein:
the antibiotic is present in an amount of 3%
by weight, the benzoyl peroxide is present in an amount of 5% by weight, and the carrier is a gel vehicle present in an amount of 92% by weight.

38. The composition described in claim 37 wherein the gel vehicle is comprised as follows:

.

39. The composition described in claim 37 wherein the antibiotic is ampicillin.